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Sample records for adenoviruses persistently shed

  1. Isolation and characterization of adenoviruses persistently shed from the gastrointestinal tract of non-human primates.

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    Soumitra Roy

    2009-07-01

    Full Text Available Adenoviruses are important human pathogens that have been developed as vectors for gene therapies and genetic vaccines. Previous studies indicated that human infections with adenoviruses are self-limiting in immunocompetent hosts with evidence of some persistence in adenoid tissue. We sought to better understand the natural history of adenovirus infections in various non-human primates and discovered that healthy populations of great apes (chimpanzees, bonobos, gorillas, and orangutans and macaques shed substantial quantities of infectious adenoviruses in stool. Shedding in stools from asymptomatic humans was found to be much less frequent, comparable to frequencies reported before. We purified and fully sequenced 30 novel adenoviruses from apes and 3 novel adenoviruses from macaques. Analyses of the new ape adenovirus sequences (as well as the 4 chimpanzee adenovirus sequences we have previously reported together with 22 complete adenovirus genomes available from GenBank revealed that (a the ape adenoviruses could clearly be classified into species corresponding to human adenovirus species B, C, and E, (b there was evidence for intraspecies recombination between adenoviruses, and (c the high degree of phylogenetic relatedness of adenoviruses across their various primate hosts provided evidence for cross species transmission events to have occurred in the natural history of B and E viruses. The high degree of asymptomatic shedding of live adenovirus in non-human primates and evidence for zoonotic transmissions warrants caution for primate handling and housing. Furthermore, the presence of persistent and/or latent adenovirus infections in the gut should be considered in the design and interpretation of human and non-human primate studies with adenovirus vectors.

  2. Isolation and Characterization of Adenoviruses Persistently Shed from the Gastrointestinal Tract of Non-Human Primates

    OpenAIRE

    Roy, Soumitra; Vandenberghe, Luk H.; Kryazhimskiy, Sergey; Grant, Rebecca; Calcedo, Roberto; Yuan, Xin; Keough, Martin; Sandhu, Arbans; Wang, Qiang; Medina-Jaszek, C. Angelica; Plotkin, Joshua B.; Wilson, James M.

    2009-01-01

    Adenoviruses are important human pathogens that have been developed as vectors for gene therapies and genetic vaccines. Previous studies indicated that human infections with adenoviruses are self-limiting in immunocompetent hosts with evidence of some persistence in adenoid tissue. We sought to better understand the natural history of adenovirus infections in various non-human primates and discovered that healthy populations of great apes (chimpanzees, bonobos, gorillas, and orangutans) and m...

  3. Isolation and characterization of adenoviruses persistently shed from the gastrointestinal tract of non-human primates.

    OpenAIRE

    Soumitra Roy; Vandenberghe, Luk H.; Sergey Kryazhimskiy; Rebecca Grant; Roberto Calcedo; Xin Yuan; Martin Keough; Arbans Sandhu; Qiang Wang; C Angelica Medina-Jaszek; Plotkin, Joshua B.; Wilson, James M.

    2009-01-01

    Adenoviruses are important human pathogens that have been developed as vectors for gene therapies and genetic vaccines. Previous studies indicated that human infections with adenoviruses are self-limiting in immunocompetent hosts with evidence of some persistence in adenoid tissue. We sought to better understand the natural history of adenovirus infections in various non-human primates and discovered that healthy populations of great apes (chimpanzees, bonobos, gorillas, and orangutans) and m...

  4. The Coxsackievirus and Adenovirus Receptor (CAR undergoes ectodomain shedding and regulated intramembrane proteolysis (RIP.

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    Nadia Houri

    Full Text Available The Coxsackievirus and Adenovirus Receptor (CAR is a cell adhesion molecule originally characterized as a virus receptor but subsequently shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumour suppression. Proteolysis of cell adhesion molecules and a wide variety of other cell surface proteins serves as a mechanism for protein turnover and, in some cases, cell signaling. Metalloproteases such as A Disintegrin and Metalloprotease (ADAM family members cleave cell surface receptors to release their substrates' ectodomains, while the presenilin/ɣ-secretase complex mediates regulated intramembrane proteolysis (RIP, releasing intracellular domain fragments from the plasma membrane. In the case of some substrates such as Notch and amyloid precursor protein (APP, the released intracellular domains enter the nucleus to modulate gene expression. We report that CAR ectodomain is constitutively shed from glioma cells and developing neurons, and is also shed when cells are treated with the phorbol ester phorbol 12-myristate 13-acetate (PMA and the calcium ionophore ionomycin. We identified ADAM10 as a sheddase of CAR using assays involving shRNA knockdown and rescue, overexpression of wild-type ADAM10 and inhibition of ADAM10 activity by addition of its prodomain. In vitro peptide cleavage, mass spectrometry and mutagenesis revealed the amino acids M224 to L227 of CAR as the site of ADAM10-mediated ectodomain cleavage. CAR also undergoes RIP by the presenilin/γ-secretase complex, and the intracellular domain of CAR enters the nucleus. Ectodomain shedding is a prerequisite for RIP of CAR. Thus, CAR belongs to the increasing list of cell surface molecules that undergo ectodomain shedding and that are substrates for ɣ-secretase-mediated RIP.

  5. Host Immune Responses to Chronic Adenovirus Infections in Human and Nonhuman Primates ▿ †

    OpenAIRE

    Calcedo, Roberto; Vandenberghe, Luk H.; Roy, Soumitra; Somanathan, Suryanarayan; Wang, Lili; Wilson, James M.

    2008-01-01

    Recent studies indicate that great apes and macaques chronically shed adenoviruses in the stool. Shedding of adenovirus in the stool of humans is less prevalent, although virus genomes persist in gut-associated lymphoid tissue in the majority of individual samples. Chimpanzees have high levels of broadly reactive neutralizing antibodies to adenoviruses in serum, with very low frequencies of adenovirus-specific T cells in peripheral blood. A similar situation exists in macaques; sampling of gu...

  6. Avian influenza in ovo vaccination with replication defective recombinant adenovirus in chickens: vaccine potency, antibody persistence, and maternal antibody transfer.

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    Mesonero, Alexander; Suarez, David L; van Santen, Edzard; Tang, De-Chu C; Toro, Haroldo

    2011-06-01

    Protective immunity against avian influenza (AI) can be elicited in chickens in a single-dose regimen by in ovo vaccination with a replication-competent adenovirus (RCA)-free human adenovirus serotype 5 (Ad)-vector encoding the AI virus (AIV) hemagglutinin (HA). We evaluated vaccine potency, antibody persistence, transfer of maternal antibodies (MtAb), and interference between MtAb and active in ovo or mucosal immunization with RCA-free recombinant Ad expressing a codon-optimized AIV H5 HA gene from A/turkey/WI/68 (AdTW68.H5(ck)). Vaccine coverage and intrapotency test repeatability were based on anti-H5 hemagglutination inhibition (HI) antibody levels detected in in ovo vaccinated chickens. Even though egg inoculation of each replicate was performed by individuals with varying expertise and with different vaccine batches, the average vaccine coverage of three replicates was 85%. The intrapotency test repeatability, which considers both positive as well as negative values, varied between 0.69 and 0.71, indicating effective vaccination. Highly pathogenic (HP) AIV challenge of chicken groups vaccinated with increasing vaccine doses showed 90% protection in chickens receiving > or = 10(8) ifu (infectious units)/bird. The protective dose 50% (PD50) was determined to be 10(6.5) ifu. Even vaccinated chickens that did not develop detectable antibody levels were effectively protected against HP AIV challenge. This result is consistent with previous findings ofAd-vector eliciting T lymphocyte responses. Higher vaccine doses significantly reduced viral shedding as determined by AIV RNA concentration in oropharyngeal swabs. Assessment of antibody persistence showed that antibody levels of in ovo immunized chickens continued to increase until 12 wk and started to decline after 18 wk of age. Intramuscular (IM) booster vaccination with the same vaccine at 16 wk of age significantly increased the antibody responses in breeder hens, and these responses were maintained at high

  7. Impact of the shedding level on transmission of persistent infections in Mycobacterium avium subspecies paratuberculosis (MAP).

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    Slater, Noa; Mitchell, Rebecca Mans; Whitlock, Robert H; Fyock, Terry; Pradhan, Abani Kumar; Knupfer, Elena; Schukken, Ynte Hein; Louzoun, Yoram

    2016-01-01

    Super-shedders are infectious individuals that contribute a disproportionate amount of infectious pathogen load to the environment. A super-shedder host may produce up to 10,000 times more pathogens than other infectious hosts. Super-shedders have been reported for multiple human and animal diseases. If their contribution to infection dynamics was linear to the pathogen load, they would dominate infection dynamics. We here focus on quantifying the effect of super-shedders on the spread of infection in natural environments to test if such an effect actually occurs in Mycobacterium avium subspecies paratuberculosis (MAP). We study a case where the infection dynamics and the bacterial load shed by each host at every point in time are known. Using a maximum likelihood approach, we estimate the parameters of a model with multiple transmission routes, including direct contact, indirect contact and a background infection risk. We use longitudinal data from persistent infections (MAP), where infectious individuals have a wide distribution of infectious loads, ranging upward of three orders of magnitude. We show based on these parameters that the effect of super-shedders for MAP is limited and that the effect of the individual bacterial load is limited and the relationship between bacterial load and the infectiousness is highly concave. A 1000-fold increase in the bacterial contribution is equivalent to up to a 2-3 fold increase in infectiousness. PMID:26925966

  8. Amplified and Persistent Immune Responses Generated by Single-Cycle Replicating Adenovirus Vaccines

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    Crosby, Catherine M.; Nehete, Pramod; Sastry, K. Jagannadha

    2014-01-01

    ABSTRACT Replication-competent adenoviral (RC-Ad) vectors generate exceptionally strong gene-based vaccine responses by amplifying the antigen transgenes they carry. While they are potent, they also risk causing adenovirus infections. More common replication-defective Ad (RD-Ad) vectors with deletions of E1 avoid this risk but do not replicate their transgene and generate markedly weaker vaccine responses. To amplify vaccine transgenes while avoiding production of infectious progeny viruses, we engineered “single-cycle” adenovirus (SC-Ad) vectors by deleting the gene for IIIa capsid cement protein of lower-seroprevalence adenovirus serotype 6. In mouse, human, hamster, and macaque cells, SC-Ad6 still replicated its genome but prevented genome packaging and virion maturation. When used for mucosal intranasal immunization of Syrian hamsters, both SC-Ad and RC-Ad expressed transgenes at levels hundreds of times higher than that of RD-Ad. Surprisingly, SC-Ad, but not RC-Ad, generated higher levels of transgene-specific antibody than RD-Ad, which notably climbed in serum and vaginal wash samples over 12 weeks after single mucosal immunization. When RD-Ad and SC-Ad were tested by single sublingual immunization in rhesus macaques, SC-Ad generated higher gamma interferon (IFN-γ) responses and higher transgene-specific serum antibody levels. These data suggest that SC-Ad vectors may have utility as mucosal vaccines. IMPORTANCE This work illustrates the utility of our recently developed single-cycle adenovirus (SC-Ad6) vector as a new vaccine platform. Replication-defective (RD-Ad6) vectors produce low levels of transgene protein, which leads to minimal antibody responses in vivo. This study shows that replicating SC-Ad6 produces higher levels of luciferase and induces higher levels of green fluorescent protein (GFP)-specific antibodies than RD in a permissive Syrian hamster model. Surprisingly, although a replication-competent (RC-Ad6) vector produces more luciferase

  9. Structure of human adenovirus

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    Nemerow, Glen R.; Stewart, Phoebe L.; Reddy, Vijay S. (Scripps); (Vanderbilt)

    2012-07-11

    A detailed structural analysis of the entire human adenovirus capsid has been stymied by the complexity and size of this 150 MDa macromolecular complex. Over the past 10 years, the steady improvements in viral genome manipulation concomitant with advances in crystallographic techniques and data processing software has allowed structure determination of this virus by X-ray diffraction at 3.5 {angstrom} resolution. The virus structure revealed the location, folds, and interactions of major and minor (cement proteins) on the inner and outer capsid surface. This new structural information sheds further light on the process of adenovirus capsid assembly and virus-host cell interactions.

  10. Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016.

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    Barzon, Luisa; Pacenti, Monia; Franchin, Elisa; Lavezzo, Enrico; Trevisan, Marta; Sgarabotto, Dino; Palù, Giorgio

    2016-08-11

    We describe the dynamics of Zika virus (ZIKV) infection in a man in his early 40s who developed fever and rash after returning from Haiti to Italy, in January 2016. Follow-up laboratory testing demonstrated detectable ZIKV RNA in plasma up to day 9 after symptom onset and in urine and saliva up to days 15 and 47, respectively. Notably, persistent shedding of ZIKV RNA was demonstrated in semen, still detectable at 181 days after onset. PMID:27542178

  11. Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016

    Science.gov (United States)

    Barzon, Luisa; Pacenti, Monia; Franchin, Elisa; Lavezzo, Enrico; Trevisan, Marta; Sgarabotto, Dino; Palù, Giorgio

    2016-01-01

    We describe the dynamics of Zika virus (ZIKV) infection in a man in his early 40s who developed fever and rash after returning from Haiti to Italy, in January 2016. Follow-up laboratory testing demonstrated detectable ZIKV RNA in plasma up to day 9 after symptom onset and in urine and saliva up to days 15 and 47, respectively. Notably, persistent shedding of ZIKV RNA was demonstrated in semen, still detectable at 181 days after onset. PMID:27542178

  12. Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding.

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    Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

    2014-01-01

    Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2-8 dpi. Viral ribonucleic acid was detected from 1-15 days post inoculation from the oral route and 1-24 days post inoculation from the cloacal route (cycle threshold Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection.

  13. Mouse adenovirus type 1 infection of macrophages

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    Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.

    2009-01-01

    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

  14. Mouse Adenovirus Type 1 Infection of Macrophages

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    Ashley, Shanna L.; Welton, Amanda R.; Harwood, Kirsten M.; van Rooijen, Nico; Spindler, Katherine R.

    2009-01-01

    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus. Here we determined the extent and functional importance of macrophage infection by MAV-1. Bone marrow-derived macrophages expressed MAV-1 mRNAs and proteins upon ex vivo infection. Adherent perito...

  15. Presence of adenovirus species C in infiltrating lymphocytes of human sarcoma.

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    Karin Kosulin

    Full Text Available Human adenoviruses are known to persist in T-lymphocytes of tonsils, adenoids and intestinal tract. The oncogenic potential of different adenovirus types has been widely studied in rodents, in which adenovirus inoculation can induce multiple tumors such as undifferentiated sarcomas, adenocarcinomas and neuroectodermal tumors. However, the oncogenic potential of this virus has never been proven in human subjects. Using a highly sensitive broad-spectrum qRT-PCR, we have screened a set of different human sarcomas including leiomyosarcoma, liposarcoma and gastro intestinal stroma tumors. Primers binding the viral oncogene E1A and the capsid-coding gene Hexon were used to detect the presence of adenovirus DNA in tumor samples. We found that 18% of the tested leiomyosarcomas and 35% of the liposarcomas were positive for the presence of adenovirus DNA, being species C types the most frequently detected adenoviruses. However, only in one sample of the gastro intestinal stroma tumors the virus DNA could be detected. The occurrence of adenovirus in the tumor sections was confirmed by subsequent fluorescence in-situ-hybridization analysis and co-staining with the transcription factor Bcl11b gives evidence for the presence of the virus in infiltrating T-lymphocytes within the tumors. Together these data underline, for the first time, the persistence of adenovirus in T-lymphocytes infiltrated in muscular and fatty tissue tumor samples. If an impaired immune system leads to the viral persistence and reactivation of the virus is involved in additional diseases needs further investigation.

  16. Frequent detection of human adenovirus from the lower gastrointestinal tract in men who have sex with men.

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    Marcel E Curlin

    Full Text Available BACKGROUND: The association between baseline seropositivity to human adenovirus (HAdV type 5 and increased HIV acquisition in the Step HIV Vaccine Study has raised questions concerning frequency of acquired and/or persistent Adenovirus infections among adults at high risk of HIV-1 infection. METHODOLOGY: To evaluate the frequency and pattern of HAdV shedding from the lower GI tract, we retrospectively tested rectal swabs for HAdVs in a cohort of 20 HSV-2 positive HIV-positive Peruvian men who have sex with men (MSM undergoing rectal swabbing three times/week for 18 consecutive weeks, in a prospective study of HSV-2 suppression in HIV infection. Viral DNA was extracted and amplified using a sensitive multiplex PCR assay that detects all currently recognized HAdV types. Molecular typing of viruses was performed on selected samples by hexon gene sequencing. Baseline neutralizing antibody titers to HAdVs -5, -26, -35 and -48 were also assessed. PRINCIPAL FINDINGS: 15/20 individuals had HAdV detected during follow up. The median frequency of HAdV detection was 30% of samples (range 2.0% to 64.7%. HAdV shedding typically occurred on consecutive days in clustered episodes lasting a median of 4 days (range 1 to 9 days separated by periods without shedding, suggesting frequent new infections or reactivation of latent infections over time. 8 of the 15 shedders had more than one type detected in follow-up. 20 HAdV types from species B, C, and D were identified, including HAdV-5, -26 and -48, HAdV types under development as potential vaccine candidates. 14/20 subjects were seropositive for HAdV-5; 15/20 for HAdV-26; 3/20 for HAdV-35; and 2/20 for HAdV-48. HAdV shedding did not correlate with CD4 count, plasma HIV-1 viral load, or titers to HAdV-5 or HAdV-35. The sole individual with HAdV-5 shedding was HAdV-5 seropositive. CONCLUSIONS: HAdV shedding was highly prevalent and diverse, including types presently under consideration as HIV vaccine vectors

  17. Adenovirus (For Parents)

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    ... respiratory tract as well, causing bronchiolitis , croup , or viral pneumonia, which is less common but can cause serious illness in infants. Adenovirus can also produce a dry, harsh cough that can resemble whooping cough (pertussis) . Gastroenteritis is an inflammation of the stomach and the ...

  18. Excreção e transmissão do vírus da diarréia viral bovina por bezerros persistentemente infectados Shedding and transmission of bovine viral diarrhea virus by persistently infected calves

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    Sandra Arenhart

    2009-09-01

    /48 (16,6% foram soropositivos para anticorpos no dia 10, 26/48 (54,1% no dia 40 e 37/48 (77% haviam soroconvertido no dia 100, quando encerrou-se o monitoramento. Estes resultados demonstram que a viremia e excreção viral contínua em altos títulos por animais PI assegura a transmissão rápida do BVDV a animais mantidos em contato, sendo a transmissão notadamente mais rápida em condições intensivas e de alta densidade animal.Persistently infected (PI calves born to cows infected with non-cytopathic bovine virus diarrhea virus (BVDV represent the main reservoir of the virus in nature. We herein report an investigation on the patterns of virus shedding and transmission by five PI calves produced experimentally through inoculation of pregnant cows with Brazilian BVDV isolates. Five calves that survived intrauterine infection were born healthy, lacking neutralizing antibodies to BVDV and harboring virus in the blood. After weaning - and following the disappearance of colostral antibodies - PI calves were monitored for virus in serum and body secretions (ocular, oral, nasal and genital at weekly intervals for up to 150 days. For each animal, the virus titers in serum showed minor variations throughout the collections (with one exception that presented an increase late in infection, yet the titers varied widely among animals (from 10² to 10(6TCID50/mL. Virus shedding in secretions was detected steadily during all the observation period with minor titer variations for each particular animal. The highest titers were generally detected in nasal and ocular secretions (titers 10(4 to 10(6TCID50mL whereas genital and oral secretions usually contained low amount of virus (10² to 10³TCID50mL. To evaluate the kinetics of virus transmission by these animals, one PI was introduced on a group of 10 seronegative calves maintained with a high animal density simulating the conditions of an intensive management. All 10 contact calves seroconverted to BVDV by day 30. Another PI calf

  19. Human adenovirus type identification

    OpenAIRE

    Banik U; Adhikary AK

    2015-01-01

    Urmila Banik,1 Arun Kumar Adhikary21Unit of Pathology, 2Unit of Microbiology, Faculty of Medicine, AIMST University, Bedong, Kedah, MalaysiaThe published paper in your journal entitling “Human adenovirus type 8 epidemic keratoconjunctivitis with large corneal epithelial full-layer detachment: an endemic outbreak with uncommon manifestations” has come into our attention.1 The article provides interesting clinical presentation of corneal epithelial layer detachment among 25%...

  20. New Adenovirus in Bats, Germany

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    Sonntag, Michael; Mühldorfer, Kristin; Speck, Stephanie; Wibbelt, Gudrun; Kurth, Andreas

    2009-01-01

    We tested 55 deceased vespertilionid bats of 12 species from southern Germany for virus infections. A new adenovirus was isolated from tissue samples of 2 Pipistrellus pipistrellus bats, which represents the only chiropteran virus isolate found in Europe besides lyssavirus (rabies virus). Evidence was found for adenovirus transmission between bats.

  1. In a buffalo shed

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    Macfarlane, Alan

    2004-01-01

    Sitting in a buffalo shed under a village house, Alan Macfarlane reflects on the origins of settled agriculture and the role of animals and technology. He also considers some of the effects of growing wealth on equality and work.

  2. Adenovirus infection in immunocompromised patients

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    Sylwia Rynans

    2013-09-01

    Full Text Available Human adenoviruses belong to the Adenoviridae family and they are divided into seven species, including 56 types. Adenoviruses are common opportunistic pathogens that are rarely associated with clinical symptoms in immunocompetent patients. However, they are emerging pathogens causing morbidity and mortality in recipients of hematopoietic stem cell and solid organ transplants, HIV infected patients and patients with primary immune deficiencies. Clinical presentation ranges from asymptomatic viraemia to respiratory and gastrointestinal disease, haemorrhagic cystitis and severe disseminated illness. There is currently no formally approved therapy for the treatment of adenovirus infections.This article presents current knowledge about adenoviruses, their pathogenicity and information about available methods to diagnose and treat adenoviral infections.

  3. Tracking adenovirus infections in reptiles

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    Ball, Inna

    2015-01-01

    The purpose of this project was to screen reptiles for the presence of adenovirus (AdV) infection, develop serological tests for the detection of antibodies against AdVs in squamate reptiles and to examine the serological relationships between lizard and snake AdVs, helping to ensure the establishment and maintenance of healthy populations. An additional aim of the project was the establishment of an agamid cell line and isolation of adenoviruses from bearded dragons (Pogona vitticeps). A...

  4. An adenovirus 4 outbreak amongst staff in a pediatric ward manifesting as keratoconjunctivitis-a possible failure of contact and aerosol infection control.

    Science.gov (United States)

    Hoyle, Elizabeth; Erez, Joanne C; Kirk-Granger, Helen R; Collins, Elizabeth; Tang, Julian W

    2016-05-01

    An adenovirus serotype 4 outbreak was identified on a pediatric ward involving 4 members of the health care staff. Two inpatients on the ward at the time (1 immunocompromised) were shedding this virus from their respiratory tracts and could have acted as independent index cases for the staff infections. Significantly, upon investigation, it was found that staff members were unaware that adenoviruses are not completely eliminated by alcohol gel handrubs and that soap and water handwashing is also required. PMID:26804304

  5. Shedding skin and tears.

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    Hammlerschlag, Carl A

    2007-06-01

    I am a purported expert in change and personal growth; that's the work I do with patients, and what I lecture and write about. I say that growth has nothing to do with adding on; it's always about letting go. Alas, it's always easier to tell others how to welcome shedding their skins than it is for me to do it myself. Letting go of the old and familiar is a necessary prerequisite for growth, but it's hard to do because no matter how much we may know, we have to move on. It always makes us feel vulnerable, which can inspire fear.

  6. Oncolytic Adenoviruses in Cancer Treatment

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    Ramon Alemany

    2014-02-01

    Full Text Available The therapeutic use of viruses against cancer has been revived during the last two decades. Oncolytic viruses replicate and spread inside tumors, amplifying their cytotoxicity and simultaneously reversing the tumor immune suppression. Among different viruses, recombinant adenoviruses designed to replicate selectively in tumor cells have been clinically tested by intratumoral or systemic administration. Limited efficacy has been associated to poor tumor targeting, intratumoral spread, and virocentric immune responses. A deeper understanding of these three barriers will be required to design more effective oncolytic adenoviruses that, alone or combined with chemotherapy or immunotherapy, may become tools for oncologists.

  7. Polymerase chain reaction detection of adenovirus DNA sequences in human lymphocytes

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    Araújo Aufra A.

    2001-01-01

    Full Text Available Human lymphoid cells frequently carry adenoviruses and DNA sequences have been identified in peripheral blood lymphocytes by Southern blot and PCR, although these cells are not permissive for virus replication, suggesting persistence of the viral genome. In order to investigate this phenomenon we screened non-symptomatic volunteers for adenovirus DNA presence and E1A gene expression. DNA samples extracted from peripheral blood mononuclear cells of 51 volunteers were submitted to PCR using primers for a conserved hexon sequence, followed by nested PCR. Adenovirus sequences were detected in 27 samples (52.9%. After more than one year, new samples of these positive volunteers were analyzed and in 70.8% of the cases the result was maintained. Since this could be due to a possible persistence we checked if the early gene E1A was involved analyzing its expression by RT-PCR. For that purpose we developed a pair of primers to target a conserved region in the E1A gene. The RT-PCR results for E1A were negative for all samples. Using these primers it was possible to detect adenovirus sequences directly by PCR in DNA samples and we found 84% agreement in comparison to the hexon analysis. Our data suggest a high occurrence and persistence of adenovirus genome sequences in human lymphoid cells, and an indication that a region other than E1A is involved in persistence. We also can say that E1A gene is a good choice for amplification as a tool in adenovirus detection, avoiding the high risk of contamination in the nested PCR procedure necessary for hexon detection.

  8. Latest Insights on Adenovirus Structure and Assembly

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    Carmen San Martín

    2012-05-01

    Full Text Available Adenovirus (AdV capsid organization is considerably complex, not only because of its large size (~950 Å and triangulation number (pseudo T = 25, but also because it contains four types of minor proteins in specialized locations modulating the quasi-equivalent icosahedral interactions. Up until 2009, only its major components (hexon, penton, and fiber had separately been described in atomic detail. Their relationships within the virion, and the location of minor coat proteins, were inferred from combining the known crystal structures with increasingly more detailed cryo-electron microscopy (cryoEM maps. There was no structural information on assembly intermediates. Later on that year, two reports described the structural differences between the mature and immature adenoviral particle, starting to shed light on the different stages of viral assembly, and giving further insights into the roles of core and minor coat proteins during morphogenesis [1,2]. Finally, in 2010, two papers describing the atomic resolution structure of the complete virion appeared [3,4]. These reports represent a veritable tour de force for two structural biology techniques: X-ray crystallography and cryoEM, as this is the largest macromolecular complex solved at high resolution by either of them. In particular, the cryoEM analysis provided an unprecedented clear picture of the complex protein networks shaping the icosahedral shell. Here I review these latest developments in the field of AdV structural studies.

  9. Adeno-associated virus Rep78 restricts adenovirus E1B55K-mediated p53 nuclear exportation

    Institute of Scientific and Technical Information of China (English)

    Jingjing Wang; Wenjuan Li; Ran Wang; Jinglun Xue; Jinzhong Chen

    2013-01-01

    Inactivation of p53 is needed during adenovirus type 5 DNA replication.E1B55K,an adenovirus early protein,has been reported to interact with p53 and inhibit p53 transactivation.Previous studies have shown that adenoassociated virus (AAV) type 2 could reduce the transforming potential of adenovirus by rescuing p53 from adenovirus-mediated degradation,but the details are not clear yet.We detected the Rep78-p53 interaction by co-immunoprecipitation assay.The co-localization assay revealed that Rep78 inhibits E1B55K-mediated p53 nuclear exportation.However,Rep78 did not detectably influence p53 stability and could not relieve the transcriptional inactivation of p53,as E1B55K could not be replaced from the p53-E1B55K complex by Rep78.Our results reveal a new possible mechanism that AAV-2 Rep78 inhibits adenovirus 5 by relocalizing p53 in the nucleus,which may shed some light on the regulatory mechanism of AAV-2 on its helper virus,adenovirus.

  10. Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children.

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    Legrand, F; Berrebi, D; Houhou, N; Freymuth, F; Faye, A; Duval, M; Mougenot, J F; Peuchmaur, M; Vilmer, E

    2001-03-01

    Adenovirus infection remains an important cause of mortality after bone marrow transplantation (BMT). Currently no efficient antiviral treatment is known. Thus, testing new modalities of early diagnosis and treatment is a crucial objective. Adenovirus infection is defined by the combination of symptoms and the isolation of virus from the source of clinical symptoms. The involvement of two or more organs and the presence of virus in blood cultures define disseminated disease. Seven children with a median age of 7 years received bone marrow transplantation for leukemia. All received an unrelated graft without T cell depletion. Adenovirus was sought in blood, urine and biopsy specimens using PCR and culture. Analysis of biopsy specimens included systematic immunohistochemistry. Cidofovir treatment was initiated as soon as biopsy revealed the histopathological signs of adenovirus. Cidofovir was given at 5 mg/kg once weekly for 3 weeks then every 2 weeks. Six patients had diarrhoea and one patient had cystitis. Adenovirus infection and disseminated disease were diagnosed in four cases and three cases, respectively. In six cases, serotype A31 was isolated from gastrointestinal biopsy and in two cases serotypes B2 and C6 were detected in blood and urine. Cidofovir treatment was associated with clinical improvement of diarrhoea, cystitis and fever in five patients, in whom the virus became undetectable in cultures and PCR analyses despite the persistence of immunodeficiency. The median follow-up was 360 days after BMT (240-570). One child died of invasive aspergillosis and another of disseminated adenovirus after interruption of cidofovir therapy. Further studies in immunocompromised patients will be needed to extend these promising results concerning the role of cidofovir in adenovirus infection.

  11. Pandemic influenza virus 2009 H1N1 and adenovirus in a high risk population of young adults: epidemiology, comparison of clinical presentations, and coinfection.

    Directory of Open Access Journals (Sweden)

    Heather C Yun

    Full Text Available BACKGROUND: In 2009, pandemic H1N1 influenza virus (2009 H1N1 emerged worldwide, causing morbidity and mortality that disproportionately affected young adults. Upper respiratory infection (URI, largely due to adenovirus, is an endemic cause of morbidity in military training. Whether clinical presentations differ or excess morbidity results from coinfection is unclear. METHODS: The Center for Advanced Molecular Detection evaluates epidemiology and rapid diagnostics of respiratory pathogens in trainees with URI. From May 1, 2009, to November 30, 2009, demographic, clinical, and PCR data from throat and nasal specimens for adenovirus and 2009 H1N1 were prospectively collected. RESULTS: 375 trainees with URI enrolled and were tested for both adenovirus and 2009 H1N1 by PCR (median age 20; 89% male. Adenovirus PCR was positive in 72% (96% serotype E-4 and 2009 H1N1 in 20%. Males were more likely to have adenovirus and females more likely to have 2009 H1N1 (p  =  0.047. Subjects with 2009 H1N1 presented an average of 1 week earlier in training, had shorter illness duration before enrollment, less sore throat, diarrhea, and fewer abnormal findings on throat exam. Coryza and cough were more common with 2009 H1N1 compared to adenovirus. Subjects with 2009 H1N1 were less likely to have adenovirus than those without, despite persistently high frequencies of adenovirus detections during peak 2009 H1N1 weeks (15% vs. 83%, p < 0.01. Coinfection with adenovirus and 2009 H1N1 was rare (4%. Rates of hospitalization and pneumonia did not differ between the adenovirus, 2009 H1N1, or coinfected groups. CONCLUSION: Military trainees with 2009 H1N1 vs. adenovirus have differing clinical presentations, and males are more likely to have adenovirus. Despite high frequencies of adenovirus infection, coinfection with adenovirus and 2009 H1N1 is rare and apparently does not result in increased morbidity.

  12. Adenoviruses in Côte d`Ivoire: investigation of diversity and interspecies transmission

    OpenAIRE

    Pauly, Maude

    2015-01-01

    Sub-Saharan Africa is considered to be a hotspot for emerging infectious diseases (EID) and the majority of these EID in humans originated from animal hosts and many are caused by viruses. In this first study on Adenovirus (AdV) in humans and domestic animals in Côte d`Ivoire, not only the prevalence and diversity of AdV shedding was assessed, but also the zoonotic and recombination potential of AdV was elucidated. The study region is situated next to the Taï National Park, the largest tropic...

  13. Enfermedad neurologica por adenovirus Neurologic disease due to adenovirus infection

    Directory of Open Access Journals (Sweden)

    Cristina L. Lema

    2005-06-01

    Full Text Available El objetivo de este trabajo fue determinar la prevalencia de adenovirus (ADV en las infecciones del sistema nervioso central (SNC. Se analizaron 108 muestras de líquido cefalorraquídeo (LCR provenientes de 79 casos de encefalitis, 7 meningitis y 22 de otras patologías neurológicas, recibidas en el período 2000-2002. Cuarenta y nueve (47.35% se obtuvieron de pacientes inmunocomprometidos. La presencia de ADV se investigó mediante reacción en cadena de la polimerasa en formato anidado (Nested-PCR. La identificación del genogrupo se realizó mediante análisis filogenético de la secuencia nucleotídica parcial de la región que codifica para la proteína del hexón. Se detectó la presencia de ADV en 6 de 108 (5.5% muestras de LCR analizadas. Todos los casos positivos pertenecieron a pacientes con encefalitis que fueron 79, (6/79, 7.6%. No se observó diferencia estadísticamente significativa entre los casos de infección por ADV en pacientes inmunocomprometidos e inmunocompetentes (p>0.05. Las cepas de ADV detectadas se agruparon en los genogrupos B1 y C. En conclusión, nuestros resultados describen el rol de los ADV en las infecciones neurológicas en Argentina. La información presentada contribuye al conocimiento de su epidemiología, en particular en casos de encefalitis.The aim of this study was to assess the prevalence of adenovirusm (ADV infections in neurological disorders. A total of 108 cerebrospinal fluid (CSF samples from 79 encephalitis cases, 7 meningitis and 22 other neurological diseases analysed in our laboratory between 2000 and 2002 were studied. Forty nine (47.4% belonged to immunocompromised patients. Viral genome was detected using nested polymerase chain reaction (Nested-PCR and ADV genotypes were identified using partial gene sequence analysis of hexon gene. Adenovirus were detected in 6 of 108 (5.5% CSF samples tested. All of these were from encephalitis cases, 6/79, representing 7.6% of them. No statistically

  14. Fatal adenovirus 32 infection in a bone marrow transplant recipient.

    OpenAIRE

    Charles, A K; Caul, E. O.; Porter, H J; Oakhill, A

    1995-01-01

    A case of disseminated adenovirus type 32 infection causing severe hepatitis, gastrointestinal ulceration and also with respiratory involvement is reported in a bone marrow transplant recipient. Typical viral inclusions were seen in the postmortem histological sections and adenovirus infection was confirmed using in situ hybridisation and isolation of adenovirus type 32 from separate organs at necropsy. This is the first case in which adenovirus 32 was the cause of fatal disseminated disease ...

  15. Components of Adenovirus Genome Packaging

    Science.gov (United States)

    Ahi, Yadvinder S.; Mittal, Suresh K.

    2016-01-01

    Adenoviruses (AdVs) are icosahedral viruses with double-stranded DNA (dsDNA) genomes. Genome packaging in AdV is thought to be similar to that seen in dsDNA containing icosahedral bacteriophages and herpesviruses. Specific recognition of the AdV genome is mediated by a packaging domain located close to the left end of the viral genome and is mediated by the viral packaging machinery. Our understanding of the role of various components of the viral packaging machinery in AdV genome packaging has greatly advanced in recent years. Characterization of empty capsids assembled in the absence of one or more components involved in packaging, identification of the unique vertex, and demonstration of the role of IVa2, the putative packaging ATPase, in genome packaging have provided compelling evidence that AdVs follow a sequential assembly pathway. This review provides a detailed discussion on the functions of the various viral and cellular factors involved in AdV genome packaging. We conclude by briefly discussing the roles of the empty capsids, assembly intermediates, scaffolding proteins, portal vertex and DNA encapsidating enzymes in AdV assembly and packaging. PMID:27721809

  16. THE PERSISTENCE OF INSURERS PROFITABILITY

    Directory of Open Access Journals (Sweden)

    Maja Pervan

    2013-02-01

    Full Text Available Most of the academic researches have analyzed the persistence of profit for the manufacturing and (non-financial services sector. These studies were mainly conducted in advance market economies. In order to shed some light on the issue of persistence in corporate rates of return, this research aims to examine the persistence of profitability of financial entities i.e. non-life insurance companies operating in an emerging market economy, Croatia. In order to determine persistence of insurers’ profitability, a Markov Chains stochastic process is applied on the profitability classes that were formulated based on the changes of insurers’ ROA (return on assets indicator during the period from 2002 to 2011. The empirical results showed that profit persistence was more likely to occur within moderate profit classes/states.

  17. Rapid generation of fowl adenovirus 9 vectors.

    Science.gov (United States)

    Pei, Yanlong; Griffin, Bryan; de Jong, Jondavid; Krell, Peter J; Nagy, Éva

    2015-10-01

    Fowl adenoviruses (FAdV) have the largest genomes of any fully sequenced adenovirus genome, and are widely considered as excellent platforms for vaccine development and gene therapy. As such, there is a strong need for stream-lined protocols/strategies for the generation of recombinant adenovirus genomes. Current genome engineering strategies rely upon plasmid based homologous recombination in Escherichia coli BJ5183. This process is time-consuming, involves multiple cloning steps, and low efficiency recombination. This report describes a novel system for the more rapid generation of recombinant fowl adenovirus genomes using the lambda Red recombinase system in E. coli DH10B. In this strategy, PCR based amplicons with around 50 nt long homologous arms, a unique SwaI site and a chloramphenicol resistance gene fragment (CAT cassette), are introduced into the FAdV-9 genome in a highly efficient and site-specific manner. To demonstrate the efficacy of this system we generated FAdV-9 ORF2, and FAdV-9 ORF11 deleted, CAT marked and unmarked FAdV-9 infectious clones (FAdmids), and replaced either ORF2 or ORF11, with an EGFP expression cassette or replaced ORF2 with an EGFP coding sequence via the unique SwaI sites, in approximately one month. All recombinant FAdmids expressed EGFP and were fully infectious in CH-SAH cells. PMID:26238923

  18. Deaths from Adenovirus in the US Military

    Centers for Disease Control (CDC) Podcasts

    2012-03-26

    Dr. Joel Gaydos, science advisor for the Armed Forces Health Surveillance Center, and Dr. Robert Potter, a research associate for the Armed Forces Medical Examiner System, discuss deaths from adenovirus in the US military.  Created: 3/26/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 3/29/2012.

  19. Adenovirus-based vaccine against Listeria monocytogenes

    DEFF Research Database (Denmark)

    Jensen, Søren; Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech;

    2013-01-01

    The use of replication-deficient adenoviruses as vehicles for transfer of foreign genes offers many advantages in a vaccine setting, eliciting strong cellular immune responses involving both CD8(+) and CD4(+) T cells. Further improving the immunogenicity, tethering of the inserted target Ag to MHC...

  20. Employment persistence

    OpenAIRE

    Fleischman, Charles A.; Joshua H. Gallin

    2001-01-01

    The recent U.S. expansion has provided employment experience to individuals at tail of the skill distribution. Will these opportunities bestow persistent benefits in the form of greater future employability? Using synthetic cohorts constructed from the CPS, this paper estimates the degree of persistence in cohort-level employment rates in excess of persistence in aggregate macroeconomic conditions. This approach is in some ways superior to testing for hysteresis in the aggregate unemployment ...

  1. Adenovirus serotype 5 hexon mediates liver gene transfer.

    Science.gov (United States)

    Waddington, Simon N; McVey, John H; Bhella, David; Parker, Alan L; Barker, Kristeen; Atoda, Hideko; Pink, Rebecca; Buckley, Suzanne M K; Greig, Jenny A; Denby, Laura; Custers, Jerome; Morita, Takashi; Francischetti, Ivo M B; Monteiro, Robson Q; Barouch, Dan H; van Rooijen, Nico; Napoli, Claudio; Havenga, Menzo J E; Nicklin, Stuart A; Baker, Andrew H

    2008-02-01

    Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. However, targeting of liver cells by adenoviruses compromises their potential efficacy. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor (CAR) to bind cells. Paradoxically, following intravascular delivery, CAR is not used for liver transduction, implicating alternate pathways. Recently, we demonstrated that coagulation factor (F)X directly binds adenovirus leading to liver infection. Here, we show that FX binds to the Ad5 hexon, not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surface. Binding occurs in multiple human adenovirus serotypes. Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo. PMID:18267072

  2. Protection of adenovirus from neutralizing antibody by cationic PEG derivative ionically linked to adenovirus

    Directory of Open Access Journals (Sweden)

    Sun X

    2012-02-01

    Full Text Available Qin Zeng, Jianfeng Han, Dong Zhao, Tao Gong, Zhirong Zhang, Xun SunKey Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of ChinaBackground: The generation of anti-adenovirus neutralizing antibody (NAb in humans severely restricts the utilization of recombinant adenovirus serotype 5 (Ad5 vectors in gene therapy for a wide range of clinical trials. To overcome this limitation, we ionically complexed Ad5 with a newly synthesized copolymer, which we called APC, making an adenovirus shielded from NAb.Methods: APC, a cationic polyethylene glycol derivative, was synthesized via two steps of ring-opening copolymerization of ethylene oxide and allyl glycidyl ether, followed by the addition of 2-mercaptoethylamine. The copolymer or the control PEI-2k was ionically complexed to anionic Ad5 in 5% glucose, and in vitro transduction assays were carried out in coxsackievirus and adenovirus receptor-positive cells (A549 and coxsackievirus and adenovirus receptor-negative cells (B16 and SKOV3. The physical properties and morphology of adenovirus alone or the complexes were investigated respectively by zeta potential, size distribution, and transmission electron microscopy image. Then cytotoxicity of APC was examined using 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assays. Finally, the ability of APC to protect adenovirus from NAb was evaluated by transfection assays after a neutralizing effect.Results: APC was successfully synthesized and showed a low cytotoxicity. Positively charged Ad5/APC exhibited slightly increased diameter (130.2 ± 0.60 nm than naked Ad5 (115.6 ± 5.46 nm while Ad5/PEI-2k showed severe aggregation (1382 ± 79.9 nm. Ad5/APC achieved a gene transfection level as high as Ad5/PEI-2k in A549 or B16 cells, and significantly higher than Ad5/PEI-2k in SKOV3 cells. Most importantly, after the exposure to the neutralizing

  3. Adenovirus: an emerging factor in red squirrel Sciurus vulgaris conservation

    OpenAIRE

    Everest, David J.; Shuttleworth, Craig M.; Stidworthy, Mark F.; Sylvia S Grierson; Duff, J. Paul; Kenward, Robert E.

    2014-01-01

    1. Adenovirus is an emerging threat to red squirrel Sciurus vulgaris conservation, but confirming clinically significant adenovirus infections in red squirrels is challenging. Rapid intestinal autolysis after death in wild animals frequently obscures pathology characteristic of the disease in animals found dead. 2. We review the available literature to determine current understanding of both subclinical and clinically significant adenovirus infections in free-living wild and captive red sq...

  4. [Persistent diarrhea

    Science.gov (United States)

    Andrade, J A; Moreira, C; Fagundes Neto, U

    2000-07-01

    INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and mortality rates in developing countries. Several studies have shown that 3 to 20% of acute diarrheal episodes in children under 5 years of age become persistent. DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14 days. ETIOLOGY: The most important agents isolated in persistent diarrhea are: Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC), Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical characteristics of patients with persistent diarrhea do not change with the pathogenic agent. Persistent diarrhea seems to represent the final result of a several insults a infant suffers that predisposes to a more severe episode of diarrhea due to a combination of host factors and high rates of enviromental contamination. Therefore, efforts should be made to promptly treat all episodes of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to restore hydroelectrolytic deficits and to replace losses until the diarrheal ceases. It is possible in the majority of the cases, using oral rehydration therapy and erly an appropriate type of diet. PREVENTION: It is imperative that management strategies also focus on preventive aspects. The most effective diarrheal prevention strategy in young infants worldwide is promotion of exclusive breast feeding. PMID:14676915

  5. Isolation and Epidemiology of Falcon Adenovirus

    OpenAIRE

    Oaks, J. Lindsay; Schrenzel, Mark; Rideout, Bruce; Sandfort, Cal

    2005-01-01

    An adenovirus was detected by electron microscopy in tissues from falcons that died during an outbreak of inclusion body hepatitis and enteritis that affected neonatal Northern aplomado (Falco femoralis septentrionalis) and peregrine (Falco peregrinus anatum) falcons. Molecular characterization has identified the falcon virus as a new member of the aviadenovirus group (M. Schrenzel, J. L. Oaks, D. Rotstein, G. Maalouf, E. Snook, C. Sandfort, and B. Rideout, J. Clin. Microbiol. 43:3402-3413, 2...

  6. Coacervate microspheres as carriers of recombinant adenoviruses.

    Science.gov (United States)

    Kalyanasundaram, S; Feinstein, S; Nicholson, J P; Leong, K W; Garver, R I

    1999-01-01

    The therapeutic utility of recombinant adenoviruses (rAds) is limited in part by difficulties in directing the viruses to specific sites and by the requirement for bolus administration, both of which limit the efficiency of target tissue infection. As a first step toward overcoming these limitations, rAds were encapsulated in coacervate microspheres comprised of gelatin and alginate followed by stabilization with calcium ions. Ultrastructural evaluation showed that the microspheres formed in this manner were 0.8-10 microM in diameter, with viruses evenly distributed. The microspheres achieved a sustained release of adenovirus with a nominal loss of bioactivity. The pattern of release and the total amount of virus released was modified by changes in microsphere formulation. Administration of the adenovirus-containing microspheres to human tumor nodules engrafted in mice showed that the viral transgene was transferred to the tumor cells. It is concluded that coacervate microspheres can be used to encapsulate bioactive rAd and release it in a time-dependent manner.

  7. ADENOVIRUS INTERACTION WITH ITS CELLULAR RECEPTOR CAR.

    Energy Technology Data Exchange (ETDEWEB)

    HOWITT,J.; ANDERSON,C.W.; FREIMUTH,P.

    2001-08-01

    The mechanism of adenovirus attachment to the host cell plasma membrane has been revealed in detail by research over the past 10 years. It has long been known that receptor binding activity is associated with the viral fibers, trimeric spike proteins that protrude radially from the vertices of the icosahedral capsid (Philipson et al. 1968). In some adenovirus serotypes, fiber and other virus structural proteins are synthesized in excess and accumulate in the cell nucleus during late stages of infection. Fiber protein can be readily purified from lysates of cells infected with subgroup C viruses, for example Ad2 and Ad5 (Boulanger and Puvion 1973). Addition of purified fiber protein to virus suspensions during adsorption strongly inhibits infection, indicating that fiber and intact virus particles compete for binding sites on host cells (Philipson et al. 1968; Hautala et al. 1998). Cell binding studies using purified radiolabeled fiber demonstrated that fiber binds specifically and with high affinity to the cell plasma membrane, and that cell lines typically used for laboratory propagation of adenovirus have approximately 10{sup 4} high-affinity receptor sites per cell (Persson et al. 1985; Freimuth 1996). Similar numbers of high-affinity binding sites for radiolabeled intact virus particles also were observed (Seth et al. 1994).

  8. LIGHT induces distinct signals to clear an AAV-expressed persistent antigen in the mouse liver and to induce liver inflammation.

    Directory of Open Access Journals (Sweden)

    Michael L Washburn

    Full Text Available BACKGROUND: Infection with adeno-associated virus (AAV vector with liver tropism leads to persistent expression of foreign antigens in the mouse liver, with no significant liver inflammation or pathology. This provides a model to investigate antigen persistence in the liver and strategies to modulate host immunity to reduce or clear the foreign antigen expressed from AAV vector in the liver. METHODS/PRINCIPAL FINDINGS: We showed that expressing LIGHT with an adenovirus vector (Ad in mice with established AAV in the liver led to clearance of the AAV. Ad-LIGHT enhanced CD8 effector T cells in the liver, correlated with liver inflammation. LTbetaR-Ig proteins blocked Ad-LIGHT in clearing AAV. Interestingly, in LTbetaR-null mice, Ad-LIGHT still cleared AAV but caused no significant liver inflammation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that LIGHT interaction with the LTbetaR plays a critical role in liver inflammation but is not required for LIGHT-mediated AAV clearance. These findings will shed light on developing novel immuno-therapeutics in treating people chronically infected with hepato-tropic viruses.

  9. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident...... characteristic of architectural practice. But the persistence in persistent modelling can also be understood to apply in other ways, reflecting and anticipating extended roles for representation. This book identifies three principle areas in which these extensions are becoming apparent within contemporary....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....

  10. 猴腺病毒研究进展%The Research Progress of Simian Adenovirus

    Institute of Scientific and Technical Information of China (English)

    张荣建; 贺争鸣

    2011-01-01

    Simian adenovirus( SAdV), as common viral agent persistent in respiratory and gastrointestinal tract of non-human primates, can cause pneumonia, gastroenteritis and conjunctivitis and spread mainly by Fecal-oral way. SadV can infect macaques, chimpanzees, baboons, etal belonging to genus Mastadenovirus . Some resarchers agured that SadV had strict species specificity. Other reports suggested that cross species transmission may be a common occurance and is zoonotic transmission. No report says SadV can infect human, but found a novel adenovirus serotype that may be recombination with a human adenovirus. SadV and HadV are close, casuing similar clinical symptoms, which make it a good model for adenovirus research. To date, the goal of developing a non-human primate adenovirus model has been made to study the mechanisms of infection and promote progress on gene therapies and genetic vaccines with adenovirus vector. However,little is known about the prevalence of adenovirus infection in non-human primates. This article reviewed discovery and classification, biological characterization, and detection of SAdV so as to provide some useful insights for researchers.%猴腺病毒(simian adenovirus,SAdV)是猴类呼吸道和消化道的常在病毒之一,可引起肺炎、咽炎、肠胃炎、结膜炎等以粪口途径传播为主,主要感染猕猴、非洲绿猴、黑猩猩和狒狒等[1]属腺病毒科,哺乳动物腺病毒属.有学者认为SAdV感染有严格的种属特异性[1],也有报道认为其种间交叉传播在非人灵长类中可能普遍发生,是动物传染病似的感染[2,3].SAdV是否感染人类尚未见报道,但已从猴的分泌物中发现了可能和人腺病毒(human adenovius,HAdV)发生重组的新型腺病毒[4].SAdV与HAdV亲缘关系很近,感染引起的临床症状也相似,是人腺病毒研究的理想模型.目前已经制定了研发猴腺病毒模型的目标,用于研究感染机制,促进腺病毒基因治

  11. A novel adenovirus in Chinstrap penguins (Pygoscelis antarctica) in Antarctica.

    Science.gov (United States)

    Lee, Sook-Young; Kim, Jeong-Hoon; Park, Yon Mi; Shin, Ok Sarah; Kim, Hankyeom; Choi, Han-Gu; Song, Jin-Won

    2014-05-07

    Adenoviruses (family Adenoviridae) infect various organ systems and cause diseases in a wide range of host species. In this study, we examined multiple tissues from Chinstrap penguins (Pygoscelis antarctica), collected in Antarctica during 2009 and 2010, for the presence of novel adenoviruses by PCR. Analysis of a 855-bp region of the hexon gene of a newly identified adenovirus, designated Chinstrap penguin adenovirus 1 (CSPAdV-1), showed nucleotide (amino acid) sequence identity of 71.8% (65.5%) with South Polar skua 1 (SPSAdV-1), 71% (70%) with raptor adenovirus 1 (RAdV-1), 71.4% (67.6%) with turkey adenovirus 3 (TAdV-3) and 61% (61.6%) with frog adenovirus 1 (FrAdV-1). Based on the genetic and phylogenetic analyses, CSPAdV-1 was classified as a member of the genus, Siadenovirus. Virus isolation attempts from kidney homogenates in the MDTC-RP19 (ATCC® CRL-8135™) cell line were unsuccessful. In conclusion, this study provides the first evidence of new adenovirus species in Antarctic penguins.

  12. Adaptive load shedding and regional protection

    Energy Technology Data Exchange (ETDEWEB)

    Ford, J.J.; Ledwich, G. [School of Engineering Systems, Queensland University of Technology, Brisbane, Qld 4001 (Australia); Bevrani, H. [Department of Electrical and Computer Engineering, University of Kurdistan Sanandaj, Kurdistan (Iran)

    2009-11-15

    The requirement for improved efficiency whilst maintaining system security necessitates the development of improved system analysis approaches and the development of advanced emergency control technologies. Load shedding is a type of emergency control that is designed to ensure system stability by curtailing system load to match generation supply. This paper presents a new adaptive load shedding scheme that provides emergency protection against excess frequency decline, whilst minimizing the risk of line overloading. The proposed load shedding scheme uses the local frequency rate information to adapt the load shedding behaviour to suit the size and location of the experienced disturbance. The proposed scheme is tested in simulation on a 3-region, 10-generator sample system and shows good performance. (author)

  13. Vortex shedding by a Savonius rotor

    Science.gov (United States)

    Botrini, M.; Beguier, C.; Chauvin, A.; Brun, R.

    1984-05-01

    A series of flow visualizations was performed to characterize the wake vortices of a Savonius rotor. The trials were undertaken in an attempt to account for discrepancies between theoretical and experimentally-derived power coefficients. The Savonius examined was two-bladed with a center offset. All tests were made in a water tunnel. Dye injection provided the visualization, and average velocities and velocity fluctuations were measured using a laser Doppler anemometer. A system of three vortices was found to be periodically shed by the rotor. Flow velocity fluctuation intensity peaked as a vortex was shed. The vortex shedding alternated from blade to blade, so that one was shed from a blade moving upstream.

  14. Vortex Shedding From a Flexible Hydrofoil

    CERN Document Server

    Dreyer, Matthieu

    2011-01-01

    Video of vortex shedding in the wake of a Naca0009 hydrofoil made of polyoxymethylene type C (POM C). This video was submitted as part of the Gallery of Fluid Motion 2011 which is showcase of fluid dynamics videos.

  15. PEGylated Adenoviruses: From Mice to Monkeys

    Directory of Open Access Journals (Sweden)

    Piyanuch Wonganan

    2010-02-01

    Full Text Available Covalent modification with polyethylene glycol (PEG, a non-toxic polymer used in food, cosmetic and pharmaceutical preparations for over 60 years, can profoundly influence the pharmacokinetic, pharmacologic and toxciologic profile of protein and peptide-based therapeutics. This review summarizes the history of PEGylation and PEG chemistry and highlights the value of this technology in the context of the design and development of recombinant viruses for gene transfer, vaccination and diagnostic purposes. Specific emphasis is placed on the application of this technology to the adenovirus, the most potent viral vector with the most highly characterized toxicity profile to date, in several animal models.

  16. Investigation of gene therapy of adenovirus in immune suppression

    Institute of Scientific and Technical Information of China (English)

    Xi XIA; Beibei WANG; Li CAO; Gang CHEN; Peng WU; Yunping LU; Jianfeng ZHOU; Ding MA

    2008-01-01

    The aim of this paper is to investigate the safety of reconstructed adenovirus in immunosuppressive ther-apeutics and to explore the role of ciclosporin A in ant-agonizing the elimination of the vector. Several rats were given retroperitoneal injection of purified ADV-TK in order to obtain models. After 14 days' treatment of ciclos-porin A, samples of different periods were obtained, then stained with hematoxylin-eosin (HE) to detect inflam-mation reactions. Immunohistochemistry was used to examine the expression of adenovirus in organs. The results are as follows: (1) In HE stained sections of the organs, some transitory and reversible inflammation was detected. (2) In immunohistochemistry assay, recon-structed adenovirus decreased gradually as time went by in the control group, while it did not happen in the experi-mental group in which the adenovirus showed a relative increase compared with their counterparts (P<0.05). (3) The distributions of adenovirus in the liver, spleen and lung were higher than those in the other organs detected. Reconstructed adenovirus as a vector is definitely safe in immunosuppressive therapeutics, and ciclosporin A, to some extent, is able to consequently inhibit the immune response of the rats and prolong the existing period of adenovirus.

  17. Adrenal gland infection by serotype 5 adenovirus requires coagulation factors.

    Directory of Open Access Journals (Sweden)

    Lucile Tran

    Full Text Available Recombinant, replication-deficient serotype 5 adenovirus infects the liver upon in vivo, systemic injection in rodents. This infection requires the binding of factor X to the capsid of this adenovirus. Another organ, the adrenal gland is also infected upon systemic administration of Ad, however, whether this infection is dependent on the cocksackie adenovirus receptor (CAR or depends on the binding of factor X to the viral capsid remained to be determined. In the present work, we have used a pharmacological agent (warfarin as well as recombinant adenoviruses lacking the binding site of Factor X to elucidate this mechanism in mice. We demonstrate that, as observed in the liver, adenovirus infection of the adrenal glands in vivo requires Factor X. Considering that the level of transduction of the adrenal glands is well-below that of the liver and that capsid-modified adenoviruses are unlikely to selectively infect the adrenal glands, we have used single-photon emission computed tomography (SPECT imaging of gene expression to determine whether local virus administration (direct injection in the kidney could increase gene transfer to the adrenal glands. We demonstrate that direct injection of the virus in the kidney increases gene transfer in the adrenal gland but liver transduction remains important. These observations strongly suggest that serotype 5 adenovirus uses a similar mechanism to infect liver and adrenal gland and that selective transgene expression in the latter is more likely to be achieved through transcriptional targeting.

  18. Regulation of Human Adenovirus Replication by RNA Interference.

    Science.gov (United States)

    Nikitenko, N A; Speiseder, T; Lam, E; Rubtsov, P M; Tonaeva, Kh D; Borzenok, S A; Dobner, T; Prassolov, V S

    2015-01-01

    Adenoviruses cause a wide variety of human infectious diseases. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are commonly associated with human species D adenoviruses. Currently, there is no sufficient or appropriate treatment to counteract these adenovirus infections. Thus, there is an urgent need for new etiology-directed therapies with selective activity against human adenoviruses. To address this problem, the adenoviral early genes E1A and E2B (viral DNA polymerase) seem to be promising targets. Here, we propose an effective approach to downregulate the replication of human species D adenoviruses by means of RNA interference. We generated E1A expressing model cell lines enabling fast evaluation of the RNA interference potential. Small interfering RNAs complementary to the E1A mRNA sequences of human species D adenoviruses mediate significant suppression of the E1A expression in model cells. Furthermore, we observed a strong downregulation of replication of human adenoviruses type D8 and D37 by small hairpin RNAs complementary to the E1A or E2B mRNA sequences in primary human limbal cells. We believe that our results will contribute to the development of efficient anti-adenoviral therapy.

  19. Structure of adenovirus bound to cellular receptor car

    Science.gov (United States)

    Freimuth, Paul I.

    2007-01-02

    Disclosed is a mutant CAR-DI-binding adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have a significantly weakened binding affinity for CAR-DI relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type.

  20. Habit persistence

    DEFF Research Database (Denmark)

    Vinther Møller, Stig

    2009-01-01

    This paper uses an iterated GMM approach to estimate and test the consumption based habit persistence model of Campbell and Cochrane (1999) on the US stock market. The empirical evidence shows that the model is able to explain the size premium, but fails to explain the value premium. Further, the......, the state variable of the model - the surplus consumption ratio - explains counter-cyclical time-varying expected returns on stocks. The model also produces plausible low real risk-free rates despite high relative risk aversion....

  1. Improved Production of Gutted Adenovirus in Cells Expressing Adenovirus Preterminal Protein and DNA Polymerase

    OpenAIRE

    Hartigan-O’Connor, Dennis; Amalfitano, Andrea; Chamberlain, Jeffrey S.

    1999-01-01

    Production of gutted, or helper-dependent, adenovirus vectors by current methods is inefficient. Typically, a plasmid form of the gutted genome is transfected with helper viral DNA into 293 cells; the resulting lysate is serially passaged to increase the titer of gutted virions. Inefficient production of gutted virus particles after cotransfection is likely due to suboptimal association of replication factors with the abnormal origins found in these plasmid substrates. To test this hypothesis...

  2. Development of Smart Underfrequency Load Shedding System

    OpenAIRE

    Čuvičins, V; Petričenko, R

    2012-01-01

    Paper describes possibility to apply innovation technology of Smart Grid for power system emergency automation. Operational characteristics of existing emergency automation and new suggested one are compared in the paper. The method for liquidation of drawback of existing automation is suggested. Paper describes developed mathematical model of intellectual underfrequency load shedding system and its operational algorithms.

  3. Clinical characteristics analysis of adult human adenovirus type 7 infection

    Institute of Scientific and Technical Information of China (English)

    张乃春

    2014-01-01

    Objective To investigate the clinical characteristics of patients infected with human adenovirus type 7 and to provide guidance for early diagnosis and timely control of the outbreak.Methods A total of 301 patients infected with the human adenoviruses who were quarantined in hospital from December 2012 to February 2013 were observed.Epidemiological questionnaires were used to collect data of clinical features of the disease including

  4. New Adenovirus Species Found in a Patient Presenting with Gastroenteritis▿

    OpenAIRE

    Jones, Morris Saffold; Harrach, Balázs; Ganac, Robert D.; Gozum, Mary M. A.; Dela Cruz, Wilfred P.; Riedel, Brian; Pan, Chao; Delwart, Eric L.; David P Schnurr

    2007-01-01

    An unidentified agent was cultured in primary monkey cells at the Los Angeles County Public Health Department from each of five stool specimens submitted from an outbreak of gastroenteritis. Electron microscopy and an adenovirus-specific monoclonal antibody confirmed this agent to be an adenovirus. Since viral titers were too low, complete serotyping was not possible. Using the DNase-sequence-independent viral nucleic acid amplification method, we identified several nucleotide sequences with ...

  5. Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus

    Directory of Open Access Journals (Sweden)

    Amr Matoq

    2016-01-01

    Full Text Available Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection.

  6. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    OpenAIRE

    Wold, William S.M.; Toth, Karoly

    2013-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  7. Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus.

    Science.gov (United States)

    Matoq, Amr; Salahuddin, Asma

    2016-01-01

    Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection. PMID:27340581

  8. Vaccine Design: Replication-Defective Adenovirus Vectors.

    Science.gov (United States)

    Zhou, Xiangyang; Xiang, Zhiquan; Ertl, Hildegund C J

    2016-01-01

    Replication-defective adenovirus (Ad) vectors were initially developed for gene transfer for correction of genetic diseases. Although Ad vectors achieved high levels of transgene product expression in a variety of target cells, expression of therapeutic proteins was found to be transient as vigorous T cell responses directed to components of the vector as well as the transgene product rapidly eliminate Ad vector-transduced cells. This opened the use of Ad vectors as vaccine carriers and by now a multitude of preclinical as well as clinical studies has shown that Ad vectors induce very potent and sustained transgene product-specific T and B cell responses. This chapter provides guidance on developing E1-deleted Ad vectors based on available viral molecular clones. Specifically, it describes methods for cloning, viral rescue and purification as well as quality control studies. PMID:27076309

  9. Proteome analysis of adenovirus using mass spectrometry.

    Science.gov (United States)

    Lind, Sara Bergström; Artemenko, Konstantin A; Pettersson, Ulf

    2014-01-01

    Analysis of proteins and their posttranslational modifications is important for understanding different biological events. For analysis of viral proteomes, an optimal protocol includes production of a highly purified virus that can be investigated with a high-resolving analytical method. In this Methods in Molecular Biology paper we describe a working strategy for how structural proteins in the Adenovirus particle can be studied using liquid chromatography-high-resolving mass spectrometry. This method provides information on the chemical composition of the virus particle. Further, knowledge about amino acids carrying modifications that could be essential for any part of the virus life cycle is collected. We describe in detail alternatives available for preparation of virus for proteome analysis as well as choice of mass spectrometric instrumentation suitable for this kind of analysis.

  10. Adenovirus-Vectored Drug-Vaccine Duo as a Rapid-Response Tool for Conferring Seamless Protection against Influenza

    OpenAIRE

    Jianfeng Zhang; E Bart Tarbet; Tsungwei Feng; Zhongkai Shi; Van Kampen, Kent R; Tang, De-chu C

    2011-01-01

    Few other diseases exert such a huge toll of suffering as influenza. We report here that intranasal (i.n.) administration of E1/E3-defective (ΔE1E3) adenovirus serotype 5 (Ad5) particles rapidly induced an anti-influenza state as a means of prophylactic therapy which persisted for several weeks in mice. By encoding an influenza virus (IFV) hemagglutinin (HA) HA1 domain, an Ad5-HA1 vector conferred rapid protection as a prophylactic drug followed by elicitation of sustained protective immunity...

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

    OpenAIRE

    Gallaher, Sean D.; Berk, Arnold J.

    2013-01-01

    Adenoviruses are employed in the study of cellular processes and as expression vectors used in gene therapy. The success and reproducibility of these studies is dependent in part on having accurate and meaningful titers of replication competent and helper-dependent adenovirus stocks, which is problematic due to the use of varied and divergent titration protocols. Physical titration methods, which quantify the total number of viral particles, are used by many, but are poor at estimating activi...

  12. ADENO-ASSOCIATED SATELLITE VIRUS INTERFERENCE WITH THE REPLICATION OF ITS HELPER ADENOVIRUS

    Science.gov (United States)

    Parks, Wade P.; Casazza, Anna M.; Alcott, Judith; Melnick, Joseph L.

    1968-01-01

    Adeno-associated satellite virus type 4 interferes with the replication of its helper adenovirus. No interferon-like soluble substance could be detected in satellite-infected cultures and other DNA- and RNA-containing viruses were not inhibited by coinfection with satellite virus under conditions which reduced adenovirus yields by more than 90% in monkey cells. Altering the concentration of adenovirus in the presence of constant amounts of satellite resulted in a constant degree of interference over a wide range of adenovirus inocula and suggested that adenovirus concentration was not a significant factor in the observed interference. The interference with adenovirus replication was abolished by pretreating satellite preparations with specific antiserum, ultraviolet light or heating at 80°C for 30 min. This suggested that infectious satellite virus mediated the interference. Satellite virus concentration was found to be a determinant of interference and studies indicated that the amount of interference with adenovirus was directly proportional to the concentration of satellite virus. 8 hr after adenovirus infection, the replication of adenovirus was no longer sensitive to satellite interference. This was true even though the satellite virus was enhanced as effectively as if the cells were infected simultaneously with both viruses. Interference with adenovirus infectivity was accompanied by reduced yields of complement-fixing antigen and of virus particles which suggested that satellite virus interfered with the formation and not the function of adenovirus products. When cells were infected either with adenovirus alone or with adenovirus plus satellite, the same proportion of cells plated as adenovirus infectious centers. However, the number of plaque-forming units of adenovirus formed per cell in the satellite-infected cultures was reduced by approximately 90%, the same magnitude of reduction noted in whole cultures coinfected with satellite and adenovirus. This

  13. Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anti-carcinoembryonic antigen bispecific adapter.

    Science.gov (United States)

    Li, Hua-Jung; Everts, Maaike; Pereboeva, Larisa; Komarova, Svetlana; Idan, Anat; Curiel, David T; Herschman, Harvey R

    2007-06-01

    Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.g., colon, lung, and breast) express carcinoembryonic antigen (CEA). To block the natural hepatic tropism of adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE-23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in the liver by >90% following systemic vector administration. Moreover, sCAR-MFE can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture, in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific adapter should, therefore, be a powerful agent to retarget adenovirus vectors to epithelial tumor metastases.

  14. Rejection of adenovirus infection is independent of coxsackie and adenovirus receptor expression in cisplatin-resistant human lung cancer cells.

    Science.gov (United States)

    Zhang, Nian-Hua; Peng, Rui-Qing; Ding, Ya; Zhang, Xiao-Shi

    2016-08-01

    The adenovirus vector-based cancer gene therapy is controversial. Low transduction efficacy is believed to be one of the main barriers for the decreased expression of coxsackie and adenovirus receptor (CAR) on tumor cells. However, the expression of CAR on primary tumor tissue and tumor tissue survived from treatment has still been not extensively studied. The present study analyzed the adenovirus infection rates and CAR expression in human lung adenocarcinoma cell line A549 and its cisplatin-resistant subline A549/DDP. The results showed that although the CAR expression in A549 and A549/DDP was not different, compared with the A549, A549/DDP appeared obviously to reject adenovirus infection. Moreover, we modified CAR expression in the two cell lines with proteasome inhibitor MG-132 and histone deacetylase inhibitor trichostatin A (TSA), and analyzed the adenovirus infection rates after modifying agent treatments. Both TSA and MG-132 pretreatments could increase the CAR expression in the two cell lines, but the drug pretreatments could only make A549 cells more susceptible to adenovirus infectivity. PMID:27373420

  15. On Level persistence (Relevant level persistence numbers)

    OpenAIRE

    Du, Dong

    2014-01-01

    The purpose of this note is to describe of a new set of numerical invariants, the relevant level persistence numbers, and make explicit their relationship with the four types of bar codes, a more familiar set of complete invariants for level persistence. The paper provides the opportunity to compare level persistence with the persistence introduced by Edelsbrunner- Letscher-Zomorodian called in this paper, as sub-level persistence.

  16. Superhydrophobic porous networks for enhanced droplet shedding

    Science.gov (United States)

    Liu, Yahua; Wang, Zuankai

    2016-09-01

    Recent research has shown that the use of submillimeter-scale tapered post arrays could generate the so-called pancake bouncing, which is characterized by the fast shedding of impinging drops from the surface in a pancake shape without undergoing the retraction stage as observed on conventional superhydrophobic surfaces. Despite this exciting discovery, the fabrication of this unique superhydrophobic surface with tapered post arrays involves complex processes, hindering its wide applications in practical sectors. Here, we report on the facile strategy to prepare a new hierarchical multilayered superhydrophobic surface directly from commercially available porous matrix that allows for efficient drop shedding. Further study shows that the enhanced drop mobility observed on such a surface is attributed to the synergistic cooperation of hierarchical structures endowing an adequate energy storage and effective energy release. The facile fabrication of superhydrophobic surface with enhanced drop mobility may find many practical applications including anti-icing, dropwise condensation and self-cleaning.

  17. Shedding further light on late globalization

    DEFF Research Database (Denmark)

    Turcan, Romeo V.

    2016-01-01

    In his opening essay on ‘What and/or Who is Late’, Nikhilesh Dholakia delineated inter alia “stage-setting contexts” or levels of analysis which could shed light on the phenomenon of late globalization, including its causes and effects. Indeed, these, especially the effects in contemporary context......, are less understood and researched. To stimulate research on late globalization, Nikhilesh essay is a rich source for conceiving research questions. Herein I will try to do that....

  18. Periodic cavitation shedding in a cylindrical orifice

    Energy Technology Data Exchange (ETDEWEB)

    Stanley, C.; Barber, T.; Milton, B.; Rosengarten, G. [University of New South Wales, School of Mechanical and Manufacturing Engineering, Sydney (Australia)

    2011-11-15

    Cavitation structures in a large-scale (D = 8.25 mm), plain orifice style nozzle within a unique experimental rig are investigated using high-speed visualisation and digital image processing techniques. Refractive index matching with an acrylic nozzle is achieved using aqueous sodium iodide for the test fluid. Cavitation collapse length, unsteady shedding frequency and spray angles are measured for cavitation conditions from incipient to supercavitation for a range of Reynolds numbers, for a fixed L/D ratio of 4.85. Periodic cavitation shedding was shown to occur with frequencies between 500 and 2,000 Hz for conditions in which cavitation occupied less than 30% of the nozzle length. A discontinuity in collapse length was shown to occur once the cavitation exceeded this length, coinciding with a loss of periodic shedding. A mechanism for this behaviour is discussed. Peak spray angles of approximately {theta} {approx} 14 were recorded for supercavitation conditions indicating the positive influence of cavitation bubble collapse on the jet atomisation process. (orig.)

  19. Vaccination with recombinant adenoviruses expressing the peste des petits ruminants virus F or H proteins overcomes viral immunosuppression and induces protective immunity against PPRV challenge in sheep.

    Directory of Open Access Journals (Sweden)

    José M Rojas

    Full Text Available Peste des petits ruminants (PPR is a highly contagious disease of small ruminants caused by the Morbillivirus peste des petits ruminants virus (PPRV. Two recombinant replication-defective human adenoviruses serotype 5 (Ad5 expressing either the highly immunogenic fusion protein (F or hemagglutinin protein (H from PPRV were used to vaccinate sheep by intramuscular inoculation. Both recombinant adenovirus vaccines elicited PPRV-specific B- and T-cell responses. Thus, neutralizing antibodies were detected in sera from immunized sheep. In addition, we detected a significant antigen specific T-cell response in vaccinated sheep against two different PPRV strains, indicating that the vaccine induced heterologous T cell responses. Importantly, no clinical signs and undetectable virus shedding were observed after virulent PPRV challenge in vaccinated sheep. These vaccines also overcame the T cell immunosuppression induced by PPRV in control animals. The results indicate that these adenovirus constructs could be a promising alternative to current vaccine strategies for the development of PPRV DIVA vaccines.

  20. Polyinosinic acid enhances delivery of adenovirus vectors in vivo by preventing sequestration in liver macrophages

    NARCIS (Netherlands)

    Haisma, Hidde J.; Kamps, Jan A. A. M.; Plantinga, Josee A.; Rots, Marianne G.; Bellu, Anna Rita; Kamps, Grietina

    2008-01-01

    Adenovirus is among the preferred vectors for gene therapy because of its superior in vivo gene-transfer efficiency. However, upon systemic administration, adenovirus is preferentially sequestered by the liver, resulting in reduced adenovirus-mediated transgene expression in targeted tissues. In the

  1. Viability of human adenovirus from hospital fomites.

    Science.gov (United States)

    Ganime, Ana Carolina; Carvalho-Costa, Filipe A; Santos, Marisa; Costa Filho, Rubens; Leite, José Paulo G; Miagostovich, Marize P

    2014-12-01

    The monitoring of environmental microbial contamination in healthcare facilities may be a valuable tool to determine pathogens transmission in those settings; however, such procedure is limited to bacterial indicators. Viruses are found commonly in those environments and are rarely used for these procedures. The aim of this study was to assess distribution and viability of a human DNA virus on fomites in an Adult Intensive Care Unit of a private hospital in Rio de Janeiro, Brazil. Human adenoviruses (HAdV) were investigated in 141 fomites by scraping the surface area and screening by quantitative PCR (qPCR) using TaqMan® System (Carlsbad, CA). Ten positive samples were selected for virus isolation in A549 and/or HEp2c cell lines. A total of 63 samples (44.7%) were positive and presented viral load ranging from 2.48 × 10(1) to 2.1 × 10(3) genomic copies per millilitre (gc/ml). The viability was demonstrated by integrated cell culture/nested-PCR in 5 out of 10 samples. Nucleotide sequencing confirmed all samples as HAdV and characterized one of them as specie B, serotype 3 (HAdV-3). The results indicate the risk of nosocomial transmission via contaminated fomites and point out the use of HAdV as biomarkers of environmental contamination.

  2. Increasing the Efficacy of Oncolytic Adenovirus Vectors

    Directory of Open Access Journals (Sweden)

    William S. M. Wold

    2010-08-01

    Full Text Available Oncolytic adenovirus (Ad vectors present a new modality to treat cancer. These vectors attack tumors via replicating in and killing cancer cells. Upon completion of the vector replication cycle, the infected tumor cell lyses and releases progeny virions that are capable of infecting neighboring tumor cells. Repeated cycles of vector replication and cell lysis can destroy the tumor. Numerous Ad vectors have been generated and tested, some of them reaching human clinical trials. In 2005, the first oncolytic Ad was approved for the treatment of head-and-neck cancer by the Chinese FDA. Oncolytic Ads have been proven to be safe, with no serious adverse effects reported even when high doses of the vector were injected intravenously. The vectors demonstrated modest anti-tumor effect when applied as a single agent; their efficacy improved when they were combined with another modality. The efficacy of oncolytic Ads can be improved using various approaches, including vector design, delivery techniques, and ancillary treatment, which will be discussed in this review.

  3. Adenovirus 36 and Obesity: An Overview

    Directory of Open Access Journals (Sweden)

    Eleonora Ponterio

    2015-07-01

    Full Text Available There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36. Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed.

  4. Adenovirus hexon modifications influence in vitro properties of pseudotyped human adenovirus type 5 vectors.

    Science.gov (United States)

    Solanki, Manish; Zhang, Wenli; Jing, Liu; Ehrhardt, Anja

    2016-01-01

    Commonly used human adenovirus (HAdV)-5-based vectors are restricted by their tropism and pre-existing immunity. Here, we characterized novel HAdV-5 vectors pseudotyped with hypervariable regions (HVRs) and surface domains (SDs) of other HAdV types. Hexon-modified HAdV-5 vectors (HV-HVR5, HV-HVR12, HV-SD12 and HV-SD4) could be reconstituted and amplified in human embryonic kidney cells. After infection of various cell lines, we measured transgene expression levels by performing luciferase reporter assays or coagulation factor IX (FIX) ELISA. Dose-dependent studies revealed that luciferase expression levels were comparable for HV-HVR5, HV-SD12 and HV-SD4, whereas HV-HVR12 expression levels were significantly lower. Vector genome copy numbers (VCNs) from genomic DNA and nuclear extracts were then determined by quantitative real-time PCR. Surprisingly, determination of cell- and nuclear fraction-associated VCNs revealed increased VCNs for HV-HVR12 compared with HV-SD12 and HV-HVR5. Increased nuclear fraction-associated HV-HVR12 DNA molecules and decreased transgene expression levels were independent of the cell line used, and we observed the same effect for a hexon-modified high-capacity adenoviral vector encoding canine FIX. In conclusion, studying hexon-modified adenoviruses in vitro demonstrated that HVRs but also flanking hexon regions influence uptake and transgene expression of adenoviral vectors. PMID:26519158

  5. Full genome sequence analysis of a novel adenovirus of rhesus macaque origin indicates a new simian adenovirus type and species

    Directory of Open Access Journals (Sweden)

    Daniel Malouli

    2014-09-01

    Full Text Available Multiple novel simian adenoviruses have been isolated over the past years and their potential to cross the species barrier and infect the human population is an ever present threat. Here we describe the isolation and full genome sequencing of a novel simian adenovirus (SAdV isolated from the urine of two independent, never co-housed, late stage simian immunodeficiency virus (SIV-infected rhesus macaques. The viral genome sequences revealed a novel type with a unique genome length, GC content, E3 region and DNA polymerase amino acid sequence that is sufficiently distinct from all currently known human- or simian adenovirus species to warrant classifying these isolates as a novel species of simian adenovirus. This new species, termed Simian mastadenovirus D (SAdV-D, displays the standard genome organization for the genus Mastadenovirus containing only one copy of the fiber gene which sets it apart from the old world monkey adenovirus species HAdV-G, SAdV-B and SAdV-C.

  6. Infecciones por adenovirus en Cuba (2000-2008)

    OpenAIRE

    González Muñoz, Grehete

    2013-01-01

    Las infecciones por adenovirus causan un variado espectro clínico en el hombre, con un rango que incluye desde la infección asintomática hasta la enfermedad diseminada con peligro para la vida. En el presente estudio, se analizó el comportamiento de las infecciones por adenovirus en síndromes de etiología viral como la infección respiratoria aguda, la miocarditis viral, la conjuntivitis hemorrágica y el síndrome neurológico infeccioso. Además, se estudió la participación de estos agentes en l...

  7. Comparative study of adenoviruses with monoclonal antibodies Estudo comparativo de diferentes tipos de adenovirus através de anticorpos monoclonais

    OpenAIRE

    Terezinha Maria de Paiva; Sueko Takimoto; María Akíko Ishida; María Candida Oliveira de Souza; Tuneo Ishimaru; Jorge Neumann; Jorge Kalil

    1992-01-01

    The obtainment of monoclonal antibodies for adenovirus species 4(Ad4) is described.The specificities of selected monoclonal antibodies were determined by means of viral neutralization test in cell culture, immunofluorescence and Enzyme-Linked Immunosorbent Assay (ELISA), in the presence of the following species of human adenovirus: 1, 2, 5 (subgenus C), 4 (subgenus E), 7 and 16 (subgenus B) and 9 (subgenus D). Two monoclonal antibodies species specific to adenovirus 4 (1CIII and 3DIII) and on...

  8. Identification and characterization of a novel adenovirus in the cloacal bursa of gulls

    Energy Technology Data Exchange (ETDEWEB)

    Bodewes, R.; Bildt, M.W.G. van de; Schapendonk, C.M.E. [Department of Viroscience, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE Rotterdam (Netherlands); Leeuwen, M. van [Viroclinics Biosciences, Marconistraat 16, 3029 AK Rotterdam (Netherlands); Boheemen, S. van [Department of Viroscience, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE Rotterdam (Netherlands); Jong, A.A.W. de [Department of Pathology, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE Rotterdam (Netherlands); Osterhaus, A.D.M.E.; Smits, S.L. [Department of Viroscience, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE Rotterdam (Netherlands); Viroclinics Biosciences, Marconistraat 16, 3029 AK Rotterdam (Netherlands); Kuiken, T., E-mail: t.Kuiken@erasmusmc.nl [Department of Viroscience, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE Rotterdam (Netherlands)

    2013-05-25

    Several viruses of the family of Adenoviridae are associated with disease in birds. Here we report the detection of a novel adenovirus in the cloacal bursa of herring gulls (Larus argentatus) and lesser black-backed gulls (Larus fuscus) that were found dead in the Netherlands in 2001. Histopathological analysis of the cloacal bursa revealed cytomegaly and karyomegaly with basophilic intranuclear inclusions typical for adenovirus infection. The presence of an adenovirus was confirmed by electron microscopy. By random PCR in combination with deep sequencing, sequences were detected that had the best hit with known adenoviruses. Phylogenetic analysis of complete coding sequences of the hexon, penton and polymerase genes indicates that this novel virus, tentatively named Gull adenovirus, belongs to the genus Aviadenovirus. The present study demonstrates that birds of the Laridae family are infected by family-specific adenoviruses that differ from known adenoviruses in other bird species. - Highlights: ► Lesions typical for adenovirus infection detected in cloacal bursa of dead gulls. ► Confirmation of adenovirus infection by electron microscopy and deep sequencing. ► Sequence analysis indicates that it is a novel adenovirus in the genus Aviadenovirus. ► The novel (Gull) adenovirus was detected in multiple organs of two species of gulls.

  9. Transport of human adenoviruses in porous media

    Science.gov (United States)

    Kokkinos, Petros; Syngouna, Vasiliki I.; Tselepi, Maria A.; Bellou, Maria; Chrysikopoulos, Constantinos V.; Vantarakis, Apostolos

    2015-04-01

    Groundwater may be contaminated with infective human enteric viruses from various wastewater discharges, sanitary landfills, septic tanks, agricultural practices, and artificial groundwater recharge. Coliphages have been widely used as surrogates of enteric viruses, because they share many fundamental properties and features. Although a large number of studies focusing on various factors (i.e. pore water solution chemistry, fluid velocity, moisture content, temperature, and grain size) that affect biocolloid (bacteria, viruses) transport have been published over the past two decades, little attention has been given toward human adenoviruses (hAdVs). The main objective of this study was to evaluate the effect of pore water velocity on hAdV transport in water saturated laboratory-scale columns packed with glass beads. The effects of pore water velocity on virus transport and retention in porous media was examined at three pore water velocities (0.39, 0.75, and 1.22 cm/min). The results indicated that all estimated average mass recovery values for hAdV were lower than those of coliphages, which were previously reported in the literature by others for experiments conducted under similar experimental conditions. However, no obvious relationship between hAdV mass recovery and water velocity could be established from the experimental results. The collision efficiencies were quantified using the classical colloid filtration theory. Average collision efficiency, α, values decreased with decreasing flow rate, Q, and pore water velocity, U, but no significant effect of U on α was observed. Furthermore, the surface properties of viruses and glass beads were used to construct classical DLVO potential energy profiles. The results revealed that the experimental conditions of this study were unfavorable to deposition and that no aggregation between virus particles is expected to occur. A thorough understanding of the key processes governing virus transport is pivotal for public

  10. Identification and characterization of a novel adenovirus in the cloacal bursa of gulls.

    Science.gov (United States)

    Bodewes, R; van de Bildt, M W G; Schapendonk, C M E; van Leeuwen, M; van Boheemen, S; de Jong, A A W; Osterhaus, A D M E; Smits, S L; Kuiken, T

    2013-05-25

    Several viruses of the family of Adenoviridae are associated with disease in birds. Here we report the detection of a novel adenovirus in the cloacal bursa of herring gulls (Larus argentatus) and lesser black-backed gulls (Larus fuscus) that were found dead in the Netherlands in 2001. Histopathological analysis of the cloacal bursa revealed cytomegaly and karyomegaly with basophilic intranuclear inclusions typical for adenovirus infection. The presence of an adenovirus was confirmed by electron microscopy. By random PCR in combination with deep sequencing, sequences were detected that had the best hit with known adenoviruses. Phylogenetic analysis of complete coding sequences of the hexon, penton and polymerase genes indicates that this novel virus, tentatively named Gull adenovirus, belongs to the genus Aviadenovirus. The present study demonstrates that birds of the Laridae family are infected by family-specific adenoviruses that differ from known adenoviruses in other bird species.

  11. Vortex shedding by matched asymptotic vortex method

    Science.gov (United States)

    Guo, Xinjun; Mandre, Shreyas

    2014-11-01

    An extension of the Kutta condition, using matched asymptotic expansion applied to the Navier-Stokes equations, is presented for flow past a smooth body at high Reynolds number. The goal is to study the influence of unsteady fluid dynamical effects like leading edge vortex, unsteady boundary layer separation, etc. In order to capture accurately the location and strength of vortex shedding, the simplified Navier-Stokes equations in the form of boundary layer approximation are solved in the thin inner region close to the solid body. In the outer region far from the structure, the vortex methods are applied, which significantly reduces the computational cost compared to CFD in the whole domain. With this method, the flow past an airfoil with two degrees of freedom, pitching and heaving, is investigated.

  12. Bioaccumulation of animal adenoviruses in the pink shrimp

    Directory of Open Access Journals (Sweden)

    Roger B. Luz

    2015-09-01

    Full Text Available Adenoviruses are among the most promising viral markers of fecal contamination. They are frequently found in the water, sediment and soil of regions impacted by human activity. Studies of the bioaccumulation of enteric viruses in shrimp are scarce. The cities located in the northern coast of the lake systems in Southern Brazil have high urbanization and intensive farming rates, and poor sewage collection and treatment. One hundred (n = 100 Farfantepenaeus paulensis pink-shrimp specimens and 48 water samples were collected from coastal lagoons between June 2012 and May 2013. Water samples were concentrated and the shrimp, mashed. After DNA extraction, samples were analyzed by real time polymerase chain reaction (qPCR in order to detect and quantify viral genomes. Thirty-five percent of shrimp samples were positive for contamination, predominantly by avian adenoviruses. A total of 91.7% of water samples contained adenoviruses DNA, with the human form being the most frequent. Our results provided evidence of significant bioaccumulation of adenoviruses in shrimp, showing the extent of the impact of fecal pollution on aquatic ecosystems.

  13. Adenovirus infection reverses the antiviral state induced by human interferon.

    Science.gov (United States)

    Feduchi, E; Carrasco, L

    1987-04-01

    HeLa cells treated with human lymphoblastoid interferon do not synthesize poliovirus proteins. The antiviral state against poliovirus is reversed if cells are previously infected with adenovirus type 5. A late gene product seems to be involved in this reversion, since no effect is observed at early stages of infection or in the presence of aphidicolin.

  14. Recombinant adenovirus vectors with knobless fibers for targeted gene transfer

    NARCIS (Netherlands)

    van Beusechem, VW; van Rijswijk, ALCT; van Es, HHG; Haisma, HJ; Pinedo, HM; Gerritsen, WR

    2000-01-01

    Adenoviral vector systems for gene therapy can be much improved by targeting vectors to specific cell types. This requires both the complete ablation of native adenovirus tropism and the introduction of a novel binding affinity in the viral capsid. We reasoned that these requirements could be fulfil

  15. Localization of adenovirus DNA replication in KB cells

    NARCIS (Netherlands)

    Vlak, J.M.; Rozijn, Th.H.; Spies, F.

    1975-01-01

    The localization of adenovirus type 5 DNA replication has been investigated by both fractionation of isolated nuclei and electron-microscope autoradiography. Nuclear fractionation by means of the M-band-technique of Tremblay et al. (Tremblay, G. Y., Daniels, M. J., and Schaechter, M. (1969). J. Mol.

  16. Pharmacological Interventions for Improving Adenovirus Usage in Gene Therapy

    NARCIS (Netherlands)

    Haisma, Hidde J.; Bellu, Anna Rita

    2011-01-01

    Gene therapy may be an innovative and promising new treatment strategy for cancer but is limited due to a low efficiency and specificity of gene delivery to the target cells. Adenovirus is the preferred gene therapy vector for systemic delivery because of its unparalleled in vivo transduction effici

  17. Targeting species D adenoviruses replication to counteract the epidemic keratoconjunctivitis.

    Science.gov (United States)

    Nikitenko, Natalia A; Speiseder, Thomas; Groitl, Peter; Spirin, Pavel V; Prokofjeva, Maria M; Lebedev, Timofey D; Rubtsov, Petr M; Lam, Elena; Riecken, Kristoffer; Fehse, Boris; Dobner, Thomas; Prassolov, Vladimir S

    2015-06-01

    Human adenoviruses are non-enveloped DNA viruses causing various infections; their pathogenicity varies dependent on virus species and type. Although acute infections can sometimes take severe courses, they are rarely fatal in immune-competent individuals. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are hyperacute and highly contagious infections of the eye caused by human adenovirus types within species D. Currently there is no causal treatment available to counteract these diseases effectively. The E2B region of the adenovirus genome encodes for the viral DNA polymerase, which is required for adenoviral DNA replication. Here we propose novel model systems to test this viral key factor, DNA polymerase, as a putative target for the development of efficient antiviral therapy based on RNA interference. Using our model cell lines we found that different small interfering RNAs mediate significant suppression (up to 90%) of expression levels of viral DNA polymerase upon transfection. Moreover, permanent expression of short hairpin RNA based on the most effective small interfering RNA led to a highly significant, more than tenfold reduction in replication for different human group D adenoviruses involved in ocular infections.

  18. Avian influenza shedding patterns in waterfowl: implications for surveillance, environmental transmission, and disease spread

    Science.gov (United States)

    Viviane Henaux; Samuel, Michael D.

    2011-01-01

    Despite the recognized importance of fecal/oral transmission of low pathogenic avian influenza (LPAI) via contaminated wetlands, little is known about the length, quantity, or route of AI virus shed by wild waterfowl. We used published laboratory challenge studies to evaluate the length and quantity of low pathogenic (LP) and highly pathogenic (HP) virus shed via oral and cloacal routes by AI-infected ducks and geese, and how these factors might influence AI epidemiology and virus detection. We used survival analysis to estimate the duration of infection (from virus inoculation to the last day virus was shed) and nonlinear models to evaluate temporal patterns in virus shedding. We found higher mean virus titer and longer median infectious period for LPAI-infected ducks (10–11.5 days in oral and cloacal swabs) than HPAI-infected ducks (5 days) and geese (7.5 days). Based on the median bird infectious dose, we found that environmental contamination is two times higher for LPAI- than HPAI-infectious ducks, which implies that susceptible birds may have a higher probability of infection during LPAI than HPAI outbreaks. Less environmental contamination during the course of infection and previously documented shorter environmental persistence for HPAI than LPAI suggest that the environment is a less favorable reservoir for HPAI. The longer infectious period, higher virus titers, and subclinical infections with LPAI viruses favor the spread of these viruses by migratory birds in comparison to HPAI. Given the lack of detection of HPAI viruses through worldwide surveillance, we suggest monitoring for AI should aim at improving our understanding of AI dynamics (in particular, the role of the environment and immunity) using long-term comprehensive live bird, serologic, and environmental sampling at targeted areas. Our findings on LPAI and HPAI shedding patterns over time provide essential information to parameterize environmental transmission and virus spread in predictive

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

    OpenAIRE

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

    2013-01-01

    Adenovirus (Ad) derived vectors have been widely used for short or long-term gene transfer, both for gene therapy and vaccine applications. Because of the frequent pre-existing immunity against the classically used human adenovirus type 5, canine adenovirus type 2 (CAV2) has been proposed as an alternative vector for human gene transfer. The well-characterized biology of CAV2, together with its ease of genetic manipulation, offer major advantages, notably for gene transfer into the central ne...

  20. Genomic variation of adenovirus type 5 isolates recovered from bone marrow transplant recipients.

    OpenAIRE

    Webb, D H; Shields, A. F.; Fife, K H

    1987-01-01

    We characterized the genomic variation of adenovirus type 5 isolates recovered from bone marrow transplant recipients in Seattle between 1976 and 1982. By restriction endonuclease analysis, we identified three new adenovirus genomic variants, each associated with a single invasive adenovirus infection. In addition, we were able to obtain suggestive evidence for a nosocomial spread of a particular group of isolates within this population. This study demonstrates that the technique of restricti...

  1. Incidence of enteric adenoviruses among children in Thailand and the significance of these viruses in gastroenteritis.

    OpenAIRE

    Herrmann, J E; Blacklow, N R; Perron-Henry, D M; Clements, E; Taylor, D N; Echeverria, P

    1988-01-01

    In countries with temperate climates, enteric adenoviruses have been shown to be a substantial cause of pediatric gastroenteritis. To determine the incidence of adenovirus infection in a tropical climate, stools were collected from children under age 7 during a 1-year period at an outpatient clinic in Bangkok, Thailand. Stools from 1,114 children with gastroenteritis and from 947 children without gastroenteritis were tested. Each stool was tested for adenovirus group antigen and for specific ...

  2. The frequency of rotavirus and enteric adenovirus in children with acute gastroenteritis in Mardin

    OpenAIRE

    Alicem Tekin

    2010-01-01

    Objectives: Infectious gastroenteritis is one of most important causes of morbidity and mortality in children. Rotavirus and enteric adenoviruses are the most important agents of infectious gastroenteritis. Little is known about the epide-miology of rotavirus and enteric adenovirus gastroenteritis in our region. This study was aimed to determine the fre-quency of rotavirus and enteric adenovirus gastroenteritis in pediatric patients admitted to our hospital.Materials and Methods: Fresh stool ...

  3. Nucleotide sequence analysis of regions of adenovirus 5 DNA containing the origins of DNA replication

    International Nuclear Information System (INIS)

    The purpose of the investigations described is the determination of nucleotide sequences at the molecular ends of the linear adenovirus type 5 DNA. Knowledge of the primary structure at the termini of this DNA molecule is of particular interest in the study of the mechanism of replication of adenovirus DNA. The initiation- and termination sites of adenovirus DNA replication are located at the ends of the DNA molecule. (Auth.)

  4. TheQ1 Influence of Innate and Pre-Existing Immunity on Adenovirus Therapy

    OpenAIRE

    Zaiss, Anne K.; Machado, Hidevaldo B.; Herschman, Harvey R.

    2009-01-01

    Recombinant adenovirus serotype 5 (Ad5) vectors have been studied extensively in preclinical gene therapy models and in a range of clinical trials. However, innate immune responses to adenovirus vectors limit effectiveness of Ad5 based therapies. Moreover, extensive pre-existing Ad5 immunity in human populations will likely limit the clinical utility of adenovirus vectors, unless methods to circumvent neutralizing antibodies that bind virus and block target cell transduction can be developed;...

  5. Host Cell Autophagy Modulates Early Stages of Adenovirus Infections in Airway Epithelial Cells

    OpenAIRE

    Zeng, Xuehuo; Carlin, Cathleen R

    2013-01-01

    Human adenoviruses typically cause mild infections in the upper or lower respiratory tract, gastrointestinal tract, or ocular epithelium. However, adenoviruses may be life-threatening in patients with impaired immunity and some serotypes cause epidemic outbreaks. Attachment to host cell receptors activates cell signaling and virus uptake by endocytosis. At present, it is unclear how vital cellular homeostatic mechanisms affect these early steps in the adenovirus life cycle. Autophagy is a lys...

  6. First detection of adenovirus in the vampire bat (Desmodus rotundus) in Brazil.

    Science.gov (United States)

    Lima, Francisco Esmaile de Sales; Cibulski, Samuel Paulo; Elesbao, Felipe; Carnieli Junior, Pedro; Batista, Helena Beatriz de Carvalho Ruthner; Roehe, Paulo Michel; Franco, Ana Cláudia

    2013-10-01

    This paper describes the first detection of adenovirus in a Brazilian Desmodus rotundus bat, the common vampire bat. As part of a continuous rabies surveillance program, three bat specimens were captured in Southern Brazil. Total DNA was extracted from pooled organs and submitted to a nested PCR designed to amplify a 280 bp long portion of the DNA polymerase gene of adenoviruses. One positive sample was subjected to nucleotide sequencing, confirming that this DNA fragment belongs to a member of the genus Mastadenovirus. This sequence is approximately 25 % divergent at the nucleotide level from equine adenovirus 1 and two other recently characterized bat adenoviruses. PMID:23828618

  7. E1A genes of adenovirus type 2 and type 5 are expressed at different levels

    DEFF Research Database (Denmark)

    Moritz, Constanze; Dobbelstein, Matthias

    2006-01-01

    Adenoviruses are an extensively studied system for modeling oncogenesis and for experimental cancer therapy. The most commonly analyzed virus types are 2 and 5, and little distinction has been made between them in past studies. Adenoviruses used for therapeutic purposes are frequently hybrids...... region. We found that the hybrid viruses replicated with considerably lower efficiency than their type 5 counterparts in H1299 cells (dl309:WtD = 3-4, dl338:dl1520 > 10). Moreover, adenovirus type 2 E1A expression from the hybrid viruses was strongly reduced in comparison to adenovirus type 5 E1A...

  8. ENTERIC ADENOVIRUS INFECTION IN INFANTS AND YOUNG CHILDREN WITH ACUTE GASTROENTERITIS IN TEHRAN

    Directory of Open Access Journals (Sweden)

    F. Jam-Afzon S. Modarres

    2006-09-01

    Full Text Available Adenoviruses are one of the most important etiological agents of serious gastroenteritis among infants and young children. Fecal specimens from patients with an acute gastroenteritis were evaluated for the presence of adenovirus (Ad40, 41 from April 2002 to February 2004. During the study, 1052 samples were collected from children under the age of 5 years in six educational and therapeutic pediatric centers. The specimens were tested for adenovirus (Ad40, 41 by EIA technique in the Virology Department of Pasteur Institute of Iran. Adenoviruses (Ad40, 41 were detected from 27(2.6% samples, but were not detected in 150 samples of healthy control group. In this study the highest rate of adenovirus was found in children aged 6 to 12 months (40.7%, but the male to female ratio inpatients was approximately equal. Adenovirus (Ad40, 41 infections peaked in the winter as 48.1% was detected from December to March. There were a statistically significant difference between age and infection (P < 0.001, also between season with adenovirus (Ad40, 41 infection (P = 0.005. Breast-feeding had a protective action against adenovirus (Ad40, 41 infection. This study revealed that enteric adenovirus (Ad40, 41 is an etiological agent of acute gastroenteritis among children in Tehran.

  9. Optimization and evaluation of a method to detect adenoviruses in river water

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset includes the recoveries of spiked adenovirus through various stages of experimental optimization procedures. This dataset is associated with the...

  10. Vortex shedding patterns in flow past inline oscillating elliptical cylinders

    Directory of Open Access Journals (Sweden)

    Huang Li-Zhong

    2012-01-01

    Full Text Available Vortex shedding patterns in flow past inline oscillating elliptical cylinder are simulated by lattice Boltzmann and direct forcing/fictitious domain method which is validated by finite volume method when this cylinder is fixed. The modes of vortex shedding are analyzed in detail by changing the amplitude and the frequency of oscillation by using the first method in this paper.

  11. Dielectrophoresis and dielectrophoretic impedance detection of adenovirus and rotavirus

    Science.gov (United States)

    Nakano, Michihiko; Ding, Zhenhao; Suehiro, Junya

    2016-01-01

    The aim of this study is the electrical detection of pathogenic viruses, namely, adenovirus and rotavirus, using dielectrophoretic impedance measurement (DEPIM). DEPIM consists of two simultaneous processes: dielectrophoretic trapping of the target and measurement of the impedance change and increase in conductance with the number of trapped targets. This is the first study of applying DEPIM, which was originally developed to detect bacteria suspended in aqueous solutions, to virus detection. The dielectric properties of the viruses were also investigated in terms of their dielectrophoretic behavior. Although their estimated dielectric properties were different from those of bacteria, the trapped viruses increased the conductance of the microelectrode in a manner similar to that in bacteria detection. We demonstrated the electrical detection of viruses within 60 s at concentrations as low as 70 ng/ml for adenovirus and 50 ng/ml for rotavirus.

  12. Novel bat adenoviruses with an extremely large E3 gene.

    Science.gov (United States)

    Tan, Bing; Yang, Xing-Lou; Ge, Xing-Yi; Peng, Cheng; Zhang, Yun-Zhi; Zhang, Li-Biao; Shi, Zheng-Li

    2016-07-01

    Bats carry diverse RNA viruses, some of which are responsible for human diseases. Compared to bat-borne RNA viruses, relatively little information is known regarding bat-borne DNA viruses. In this study, we isolated and characterized three novel bat adenoviruses (BtAdV WIV9-11) from Rhinolophus sinicus. Their genomes, which are highly similar to each other but distinct from those of previously sequenced adenoviruses (AdVs), are 37 545, 37 566 and 38 073 bp in size, respectively. An unusually large E3 gene was identified in their genomes. Phylogenetic and taxonomic analyses suggested that these isolates represent a distinct species of the genus Mastadenovirus. Cell susceptibility assays revealed a broad cell tropism for these isolates, indicating that they have a potentially wide host range. Our results expand the understanding of genetic diversity of bat AdVs. PMID:27032099

  13. Synergistic Antitumor Efficacy of Oncolytic Adenovirus Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    LI Yue-min; QIAN Qi-jun; SONG San-tai; JIANG Ze-fei; ZHANG Qi; QU Yi-mei; SU Chang-qing; ZHAO Chuan-hua; LI Zhi-qiang; GE Fei-jiao

    2007-01-01

    Objective: Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK300 can mediate selective antitumor efficacy and produce synergistic cytotoxicity with chemotherapy on HER-2 over-expressing breast cancer. Methods: We engineered the telomerase-dependent replicative adenovirus CNHK300 by placing the E1A gene under the control of the human hTERT promoter. By analysis of E1A expression, we proved the fidelity of hTERT promoter in adenovirus genome and the selective expression of E1A in telomerase-positive breast cancer cells but not in normal fibroblast cells. By proliferation test, we further showed efficient replication of CNHK300 in breast cancer cells with apparently attenuated proliferation in normal fibroblast cells. Finally, we demonstrated by MTT methods that CNHK300 virus caused potent cytolysis and produced synergistic cytotoxicity with chemotherapy in breast cancer cells with attenuated cytotoxicity on normal cells. Results: In this virus, the E1A gene is successfully placed under the control of the human hTERT promoter. CNHK300 virus replicated as efficiently as the wild-type adenovirus and caused intensive cell killing in HER-2 over-expressing breast cancer cells in vitro. In contrast, telomerase-negative normal fibroblast cells, which expressed no hTERT activity, were not able to support CNHK300 replication. Combined treatment of CNHK300 with paclitaxel improved cytotoxicity on cancer cells. Conclusion: We conclude that CNHK300 can produce selective antitumor efficacy and enhance the in vitro response of chemotherapy on HER-2 overexpressing breast cancer.

  14. Oncolytic adenovirus-mediated therapy for prostate cancer.

    Science.gov (United States)

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy) prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen-androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting local-ized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support future systemic delivery of oncolytic adenoviruses. PMID:27579296

  15. Reassessing culture media and critical metabolites that affect adenovirus production.

    Science.gov (United States)

    Shen, Chun Fang; Voyer, Robert; Tom, Roseanne; Kamen, Amine

    2010-01-01

    Adenovirus production is currently operated at low cell density because infection at high cell densities still results in reduced cell-specific productivity. To better understand nutrient limitation and inhibitory metabolites causing the reduction of specific yields at high cell densities, adenovirus production in HEK 293 cultures using NSFM 13 and CD 293 media were evaluated. For cultures using NSFM 13 medium, the cell-specific productivity decreased from 3,400 to 150 vp/cell (or 96% reduction) when the cell density at infection was increased from 1 to 3 x 10(6) cells/mL. In comparison, only 50% of reduction in the cell-specific productivity was observed under the same conditions for cultures using CD 293 medium. The effect of medium osmolality was found critical on viral production. Media were adjusted to an optimal osmolality of 290 mOsm/kg to facilitate comparison. Amino acids were not critical limiting factors. Potential limiting nutrients including vitamins, energy metabolites, bases and nucleotides, or inhibitory metabolites (lactate and ammonia) were supplemented to infected cultures to further investigate their effect on the adenovirus production. Accumulation of lactate and ammonia in a culture infected at 3 x 10(6) cells/mL contributed to about 20% reduction of the adenovirus production yield, whereas nutrient limitation appeared primarily responsible for the decline in the viral production when NSFM 13 medium was used. Overall, the results indicate that multiple factors contribute to limiting the specific production yield at cell densities beyond 1 x 10(6) cells/mL and underline the need to further investigate and develop media for better adenoviral vector productions.

  16. Oncolytic adenovirus-mediated therapy for prostate cancer

    Science.gov (United States)

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy) prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen–androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting local-ized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support future systemic delivery of oncolytic adenoviruses. PMID:27579296

  17. Brain tumors induced in rats by human adenovirus type 12

    Directory of Open Access Journals (Sweden)

    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  18. A novel and simple method for construction of recombinant adenoviruses.

    Science.gov (United States)

    Tan, Rong; Li, Chunhua; Jiang, Sijing; Ma, Lixin

    2006-07-19

    Recombinant adenoviruses have been widely used for various applications, including protein expression and gene therapy. We herein report a new and simple cloning approach to an efficient and robust construction of recombinant adenoviral genomes based on the mating-assisted genetically integrated cloning (MAGIC) strategy. The production of recombinant adenovirus serotype 5-based vectors was greatly facilitated by the use of the MAGIC procedure and the development of the Adeasy adenoviral vector system. The recombinant adenoviral plasmid can be generated by a direct and seamless substitution, which replaces the stuff fragment in a full-length adenoviral genome with the gene of interest in a small plasmid in Escherichia coli. Recombinant adenoviral plasmids can be rapidly constructed in vivo by using the new method, without manipulations of the large adenoviral genome. In contrast to other traditional systems, it reduces the need for multiple in vitro manipulations, such as endonuclease cleavage, ligation and transformation, thus achieving a higher efficiency with negligible background. This strategy has been proven to be suitable for constructing an adenoviral cDNA expression library. In summary, the new method is highly efficient, technically less demanding and less labor-intensive for constructing recombinant adenoviruses, which will be beneficial for functional genomic and proteomic researches in mammalian cells.

  19. Evaluating contribution of the cellular and humoral immune responses to the control of shedding of Mycobacterium avium spp. paratuberculosis in cattle

    NARCIS (Netherlands)

    Ganusov, Vitaly V.; Klinkenberg, D.; Bakker, D.; Koets, A.P.

    2015-01-01

    Mycobacterium avium spp. paratuberculosis (MAP) causes a persistent infection and chronic inflammation of the gut in ruminants leading to bacterial shedding in feces in many infected animals. Although there are often strong MAP-specific immune responses in infected animals, immunological correlates

  20. August 2007 FIFRA Scientific Advisory Panel Recommendations for SHEDS-Dietary and SHEDS-Residential Modules (Summarized) and EPA Responses

    Science.gov (United States)

    Over the past ten years, the Agency has requested the Panel to review several probabilistic dietary exposure software models. These have included DEEM-FCID™, Calendex-FCID, CARES™, LifeLine™, and an earlier (specialized) version of SHEDS (SHEDS-Wood) designed to assess exposure...

  1. Stochastic oscillations induced by vortex shedding in wind

    DEFF Research Database (Denmark)

    Christensen, Claus

    1997-01-01

    As a fluid flows past a circular cylinder,vortices are shed alternately from each side at most values of the Reynolds number. Over a certain range of windspeeds, the periodicity in the wake is synchronized or captured by the mechanical system. The shedding abruptly deviates from the linear Strouhal...... in the wake is synchronized or captured by the mechanical system. The shedding abruptly deviates from the linear Strouhal dependence and stays constant at the mechanical natural frequency. This coupling between the velocity field and the motion of the mechanical system is referred to as the lock-in phenomenon...

  2. The effects of exposure of susceptible alpacas to alpacas persistently infected with bovine viral diarrhea virus

    OpenAIRE

    Byers, Stacey R.; Evermann, James F.; Bradway, Daniel S; Grimm, Amanda L.; Ridpath, Julia F.; Parish, Steven M.; Tibary, Ahmed; Barrington, George M.

    2011-01-01

    Reports of bovine viral diarrhea virus (BVDV) infections in alpacas have been increasing in recent years but much is still unknown about the mechanisms of disease in this species. This report characterizes the transmission of BVDV from persistently infected (PI) alpacas to BVDV naïve alpacas, documents shedding patterns, and characterizes the disease effects in both PI and transiently infected alpacas. Two PI alpacas shed BVDV Type 1b virus in most body fluids, and commonly available diagnost...

  3. Presence of protein at the termini of intracellular adenovirus type 5 DNA

    NARCIS (Netherlands)

    Wielink, P.S. van; Naaktgeboren, N.; Sussenbach, J.S.

    1979-01-01

    Adenovirus type 5 contains linear double-stranded DNA with protein covalently attached to the ends of the molecules. The presence of protein at the termini of intracellular viral DNA in adenovirus type 5-infected cells was investigated at different stages during the replication process. The intracel

  4. Interspecies differences in virus uptake versus cardiac function of the coxsackievirus and adenovirus receptor.

    NARCIS (Netherlands)

    Freiberg, F.; Sauter, M.; Pinkert, S.; Govindarajan, T.; Kaldrack, J.; Thakkar, M.; Fechner, H.; Klingel, K.; Gotthardt, M.

    2014-01-01

    The coxsackievirus and adenovirus receptor (CAR) is a cell contact protein with an important role in virus uptake. Its extracellular immunoglobulin domains mediate the binding to coxsackievirus and adenovirus as well as homophilic and heterophilic interactions between cells. The cytoplasmic tail lin

  5. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Science.gov (United States)

    2010-01-01

    ... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing cell... hepatitis, the test is inconclusive and may be repeated. (B) If at least 19 of the 20 vaccinates do...

  6. Marketing researcher sheds new light on rewards programs

    OpenAIRE

    Ho, Sookhan

    2010-01-01

    A new study by Rajesh Bagchi, assistant professor of marketing in the Pamplin College of Business, sheds new light on loyalty or rewards programs, used by airlines, hotels, and other businesses to promote customer allegiance.

  7. Guam Power Authority automatic underfrequency load shedding study

    Energy Technology Data Exchange (ETDEWEB)

    Wong, H.H. [Hawaiian Electric Co., Honolulu, HI (United States); Flores, J.C.; Fang, Y.; Baldevia, R.P. Jr. [Guam Power Authority, Agana (Guam)

    1995-12-31

    This paper describes the development of a new automatic underfrequency load shedding scheme on the Guam Power Authority`s (GPA) system using a transient stability simulation program. The new scheme strives to minimize the amount of load shed by selecting frequency settings based on the severity of generation or load unbalance and the availability of spinning reserves. The fast speed of frequency decay due to loss of generation is shown to be particularly pronounced in an island system, requiring more careful design of any load shedding scheme than large interconnected systems. The use of a well-prepared transient stability study model allows the simulation of specific contingencies and the fine-tuning of load shedding strategies for optimality. The trade-off between equipment protection, customer service availability, and practical operating issues, such as, synchronization of generators to the grid, are discussed.

  8. Guam Power Authority automatic underfrequency load shedding study

    Energy Technology Data Exchange (ETDEWEB)

    Wong, H.H. [Hawaiian Electric Co., Inc., Honolulu, HI (United States); Flores, J.C.; Fang, Y.; Baldevia, R.P. [Guam Power Authority, Agana (Guam)

    1995-12-31

    Guam Power Authority (GPA) has developed an automatic underfrequency load shedding scheme using a transient stability simulation program. This scheme strives to minimize the amount of load shed by selecting frequency settings based on the severity of generation or load imbalance and the availability of spinning reserves. The fast speed of frequency decay due to loss of generation is shown to be particularly pronounced in an island system, requiring more careful design of any load shedding scheme than large interconnected systems. The use of a well prepared transient stability study model allows the simulation of specific contingencies and the fine-tuning of load shedding strategies for optimality. The development of the scheme is described, and trade-off between equipment protection, customer service availability, and practical operating issues, such as synchronization of generators to the grid, are discussed. (author). 9 figs., 6 refs.

  9. Insulation Characteristics of Bushing Shed at Cryogenic Temperature

    Science.gov (United States)

    Kim, W. J.; Kim, Y. J.; Kim, S. H.

    2014-05-01

    In the development of high-Tc superconducting(HTS) devices, the bushing for HTS devices (HTS bushing) is the core technology, the need to because of supply high voltage to the cable or the winding of the transformer. The lower part of the bushing is exposed to the liquid nitrogen (LN2), and it has many sheds. In particular, the insulation body with sheds and electrical insulation at cryogenic temperature have attracted a great deal of interest from the view point of the size, weight and efficiency of bushing. This study has mainly investigated the shed and insulation body by comparing glass fiber reinforced plastics (GFRP) in LN2. We investigated the surface discharge characteristics according to insulating materials, width and height of the shed.

  10. SHED: Stem cells from human exfoliated deciduous teeth

    OpenAIRE

    Miura, Masako; Gronthos, Stan; Zhao, Mingrui; Lu, Bai; Fisher, Larry W.; Robey, Pamela Gehron; Shi, Songtao

    2003-01-01

    To isolate high-quality human postnatal stem cells from accessible resources is an important goal for stem-cell research. In this study we found that exfoliated human deciduous tooth contains multipotent stem cells [stem cells from human exfoliated deciduous teeth (SHED)]. SHED were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. After in vivo transplantation, ...

  11. Capacity building in indigenous men's groups and sheds across Australia.

    Science.gov (United States)

    Southcombe, Amie; Cavanagh, Jillian; Bartram, Timothy

    2015-09-01

    This article presents an investigation into capacity building, at the community level, in Aboriginal and Torres Strait Islander Men's Groups and Sheds. As safe men's spaces, Men's Groups and Sheds represent an ever-growing social, and health and well-being community service across Australia. The study is qualitative and employs 'yarning circles' (focus groups), semi-structured interviews and observations to gather data from 15 Groups/Sheds involving 45 men from urban, regional and remote communities. We found that capacity building is primarily about securing relationships between Group Leaders/Shed Co-ordinators and Government services. Capacity building establishes links to services such as Centrelink, Medicare, Department of Housing, Probation and Control, and positive outcomes such as Indigenous men securing housing and Centrelink payments. Capacity building results in better health outcomes and, educates and empowers men to improve their social, cultural, emotional and economic well-being. It helps men to better connect with family and community. The current research paves the way for countries worldwide to explore the conceptual and empirical approach of capacity building applicable to other Indigenous [and non-Indigenous] Men's Groups/Sheds. We recommend feasibilities studies, on approaches to capacity building in Indigenous Groups/Sheds, be carried out within urban, regional and remote regions across the country.

  12. Asymptomatic Herpes Simplex Virus Shedding in STI Patients

    Institute of Scientific and Technical Information of China (English)

    叶兴东; 颜景兰; 朱慧兰; 张莉; 佟菊贞

    2002-01-01

    Objective: This study examined Herpes Simplex Virus(HSV) subclinical shedding in the genital tract of patients withgenital herpes (GH) or non-gonoccal urethritis (NGU). Method: Swabs were collected after exposure to rash andgenital tract during GH relapse or remission on a weekly basisfor four to six weeks. NGU patients with negative chlamydiaand mycoplasma tests were also swabbed for a similarduration. All swabs underwent HSV DNA detection withquantitative PCR. Result: There was a significant difference in the rate ofasymptomatic HSV shedding in urinary tracts comparing GHand the control group and comparing NGU and the controlgroup (P<0.05). The rate of HSV shedding was 22%, 9.8%and 3.3% for GH, NGU and control groups respectively. Therate of HSV shedding was 21.7% (20/92) for patients withactive GH and 23% for those in remission. The HSV positiverate was significantly higher in the group with patients whohad more than six relapses within one year compared to thegroup of patients with less than six GH relapses. Conclusion: There is HSV subclinical shedding in theirgenital tract during active GH and remission. SubclinicalHSV shedding is more common in patients with more than sixGH relapses per year compared to GH patients with fewerrelapses. Approximately 9.9% of NGU patients with negativechlamydia, mycoplasma testing was found to have subclinicalHSV infection.

  13. Capacity building in indigenous men's groups and sheds across Australia.

    Science.gov (United States)

    Southcombe, Amie; Cavanagh, Jillian; Bartram, Timothy

    2015-09-01

    This article presents an investigation into capacity building, at the community level, in Aboriginal and Torres Strait Islander Men's Groups and Sheds. As safe men's spaces, Men's Groups and Sheds represent an ever-growing social, and health and well-being community service across Australia. The study is qualitative and employs 'yarning circles' (focus groups), semi-structured interviews and observations to gather data from 15 Groups/Sheds involving 45 men from urban, regional and remote communities. We found that capacity building is primarily about securing relationships between Group Leaders/Shed Co-ordinators and Government services. Capacity building establishes links to services such as Centrelink, Medicare, Department of Housing, Probation and Control, and positive outcomes such as Indigenous men securing housing and Centrelink payments. Capacity building results in better health outcomes and, educates and empowers men to improve their social, cultural, emotional and economic well-being. It helps men to better connect with family and community. The current research paves the way for countries worldwide to explore the conceptual and empirical approach of capacity building applicable to other Indigenous [and non-Indigenous] Men's Groups/Sheds. We recommend feasibilities studies, on approaches to capacity building in Indigenous Groups/Sheds, be carried out within urban, regional and remote regions across the country. PMID:24399032

  14. Persistence of Innovation: Stylised Facts and Panel Data Evidence

    OpenAIRE

    Peters, Bettina

    2005-01-01

    This paper investigates whether firms innovate persistently or discontinuously over time using an innovation panel data set on German manufacturing and service firms for the period 1994–2002. It turns out that innovation behaviour is permanent at the firm–level to a very large extent. Using a dynamic random effects discrete choice model and a new estimator recently proposed by Wooldrigde (2005), I further shed some light on the driving forces for this phenomenon. The econometric results show ...

  15. Severe Community-Acquired Pneumonia Caused by Human Adenovirus in Immunocompetent Adults: A Multicenter Case Series.

    Directory of Open Access Journals (Sweden)

    Dingyu Tan

    Full Text Available Severe community-acquired pneumonia (CAP caused by human adenovirus (HAdV, especially HAdV type 55 (HAdV-55 in immunocompetent adults has raised increasing concerns. Clinical knowledge of severe CAP and acute respiratory distress syndrome induced by HAdV-55 is still limited, though the pathogen has been fully characterized by whole-genome sequencing.We conducted a multicentre retrospective review of all consecutive patients with severe CAP caused by HAdV in immunocompetent adults admitted to the Emergency Department Intensive Care Unit of two hospitals in Northern China between February 2012 and April 2014. Clinical, laboratory, radiological characteristics, treatments and outcomes of these patients were collected and analyzed.A total of 15 consecutive severe CAP patients with laboratory-confirmed adenovirus infections were included. The median age was 30 years and all cases were identified during the winter and spring seasons. HAdV-55 was the most frequently (11/15 detected HAdV type. Persistent high fever, cough and rapid progression of dyspnea were typically reported in these patients. Significantly increased pneumonia severity index (PSI, respiratory rate, and lower PaO2/FiO2, hypersensitive CRP were reported in non-survivors compared to survivors (P = 0.013, 0.022, 0.019 and 0.026, respectively. The rapid development of bilateral consolidations within 10 days after illness onset were the most common radiographic finding, usually accompanied by adjacent ground glass opacities and pleural effusions. Total mortality was 26.7% in this study. Corticosteroids were prescribed to 14 patients in this report, but the utilization rate between survivors and non-survivors was not significant.HAdV and the HAdV-55 sub-type play an important role among viral pneumonia pathogens in hospitalized immunocompetent adults in Northern China. HAdV should be tested in severe CAP patients with negative bacterial cultures and a lack of response to antibiotic

  16. HSF1 overexpression enhances oncolytic effect of replicative adenovirus

    Directory of Open Access Journals (Sweden)

    Deng Youwen

    2010-05-01

    Full Text Available Abstract Background E1B55kD deleted oncolytic adenovirus was designed to achieve cancer-specific cytotoxicity, but showed limitations in clinical study. To find a method to increase its efficacy, we investigated the correlation between oncolytic effect of such oncolytic adenovirus Adel55 and intracellular heat shock transcription factor 1 (HSF1 activity. Methods In the present study, human breast cancer cell line Bcap37 was stably transfected with constitutively active HSF1 (cHSF1 or HSF1 specific siRNA (HSF1i to establish increased or decreased HSF1 expression levels. Cytotoxicity of Adel55 was analyzed in these cell lines in vitro and in vivo. Furthermore, Adel55 incorporated with cHSF1 (Adel55-cHSF1 was used to treat various tumor xenografts. Results Adel55 could achieve more efficient oncolysis in cHSF1 transfected Bcap37 cells, both in vitro and in vivo. However, inhibition of HSF1 expression by HSF1i could rescue Bcap37 cell line from oncolysis by Adel55. A time course study of viral replication established a correlation between higher replication of Adel55 and cytolysis or tumor growth inhibition. Then, we constructed Adel55-cHSF1 for tumor gene therapy and demonstrated that it is more potent than Adel55 itself in oncolysis and replication in both Bcap37 and SW620 xenografts. Conclusions cHSF1 enhances the Adel55 cell-killing potential through increasing the viral replication and is a potential therapeutic implication to augment the potential of E1B55kD deleted oncolytic adenovirus by increasing its burst.

  17. Adenovirus vaccine vectors expressing hepatitis B surface antigen: importance of regulatory elements in the adenovirus major late intron.

    Science.gov (United States)

    Mason, B B; Davis, A R; Bhat, B M; Chengalvala, M; Lubeck, M D; Zandle, G; Kostek, B; Cholodofsky, S; Dheer, S; Molnar-Kimber, K

    1990-08-01

    Adenovirus types 4 and 7 are currently used as live oral vaccines for prevention of acute respiratory disease caused by these adenovirus serotypes. To investigate the concept of producing live recombinant vaccines using these serotypes, adenovirus types 4 (Ad4) and 7 (Ad7) were constructed that produce HBsAg upon infection of cell cultures. Ad4 recombinants were constructed that express HBsAg from a cassette inserted 135 bp from the right-hand terminus of the viral genome. The cassette contained the Ad4 major late promoter followed by leader 1 of the tripartite leader, the first intervening sequence between leaders 1 and 2, leaders 2 and 3, the HBsAg gene, and tandem polyadenylation signals from the Ad4 E3B and hexon genes. Using this same cassette, a series of Ad4 recombinants expressing HBsAg were constructed with deletions in the intervening sequence between leaders 1 and 2 to evaluate the contribution of the downstream control elements more precisely. Inclusion of regions located between +82 and +148 as well as +148 and +232 resulted in increases in expression levels of HBsAg in A549-infected cells by 22-fold and 44-fold, respectively, over the levels attained by an adenovirus recombinant retaining only sequences from +1 to +82, showing the importance of these elements in the activation of the major late promoter during the course of a natural Ad4 viral infection. Parallel increases were also observed in steady-state levels of cytoplasmic HBsAg-specific mRNA. When similar Ad7 recombinant viruses were constructed, these viruses also expressed 20-fold more HBsAg due to the presence of the intron. All Ad4 and Ad7 recombinants produced HBsAg particles containing gp27 and p24 which were secreted in the medium. When dogs were immunized intratracheally with one of these Ad7 recombinants, they seroconverted to both Ad7 and HBsAg to a high level. PMID:2371766

  18. Qubit persistence probability

    International Nuclear Information System (INIS)

    In this work, I formulate the persistence probability for a qubit device as the probability of measuring its computational degrees of freedom in the unperturbed state without the decoherence arising from environmental interactions. A decoherence time can be obtained from the persistence probability. Drawing on recent work of Garg, and also Palma, Suomine, and Ekert, I apply the persistence probability formalism to a generic single-qubit device coupled to a thermal environment, and also apply it to a trapped-ion quantum register coupled to the ion vibrational modes. (author)

  19. IMPROVEMENT OF HUMAN ISLET FUNCTION BY ADENOVIRUS MEDIATED HO-1 GENE TRANSFER

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate in vitro heme oxygenase-1 gene (HO-1) delivery to human pancreatic islets by adenovirus vectors. Methods Recombinant adenovirus containing HO-1 or enhanced green fluorescent protein gene(EGFP) was generated by using the AdEasy System. The purified human pancreatic islets were infected with recombinant adenovirus vectors at various multiplicity of infection (MOI). Transduction was confirmed by fluorescence photographs and Western blot. Glucose-stimulated insulin secretion was detected by using Human insulin radioimmunoassay kits and was used to assess the function of human islets infected by recombinant adenovirus.Results Viral titers of Ad-hHO-1 and Ad-EGFP were 1.96×109 and 1.99×109 pfu/mL, respectively. Human pancreatic islets were efficiently infected by recombinant adenovirus vectors in vitro. Transfection of human islets at an MOI of 20 did not inhibit islet function. Recombinant adenovirus mediated HO-1gene transfer significantly improved the islet function of insulin release when simulated by high level glucose. Conclusion Recombinant adenovirus is efficient to deliver exogenous gene into human pancreatic islets in vitro. HO-1 gene transfection can improve human islet function.

  20. Combined use of chemotherapeutics and oncolytic adenovirus in treatment of AFP-expressing hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chen-Yu Mao; Han-Ju Hua; Ping Chen; De-Chao Yu; Jiang Cao; Li-Song Teng

    2009-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) which is always refractory to most chemotherapeutic agents may result in poor survival of patients with advanced HCC. Oncolytic adenovirus is a new form for cancer gene therapy via its ability to replicate and kill tumor cells in a tumor-speciifc manner. In order to eradicate tumors effectively, the combination of chemotherapeutic agents and oncolytic adenovirus has been considered. This study aimed to systematically analyze the possibility of synergistic cytotoxicity of oncolytic adenoviruses in combination with chemotherapeutic agents. METHODS: Several types of human HCC cell lines were used to determine the speciifcity and cytotoxicity of oncolytic adenovirus Ad5-HC and Ad5-AFP (IRES) by measuring cell viabilityin vitro and antitumor efifciency in vivo. The cytotoxicity of Ad5-HC and Ad5-AFP (IRES) combined with chemotherapeutic agents were also assessed by the methyl thiazolyl tetrazolium assay. RESULTS: Both Ad5-HC and Ad5-AFP (IRES) were signiifcantly cytotoxic to HCC cells with great speciifcity in vitro andin vivo. The combination of oncolytic adenovirus with 5-FU, doxorubicin, and paclitaxel was synergistically effective for the killing of HCC cells. CONCLUSIONS: These data suggest that oncolytic adenovirus sensitize tumors to chemotherapy and the combination therapy of chemotherapeutic agents and oncolytic adenovirus has an enhanced antitumor effect on HCC cells.

  1. CRISP. Intelligent load shedding. Deliverable 1.5

    International Nuclear Information System (INIS)

    Load shedding has been used to mitigate the consequences of large disturbances in electric power systems, since the beginning of the electrification era. The way to execute the load shedding, i.e. open a circuit breaker, has hardly developed at all for a 100-year period. The modern society dependence on reliable electricity supply is continuously increasing. This means that the consequences of traditional load shedding are not acceptable. In the meantime computer and communication technology has developed tremendously. There is also a trend to use more and more intelligent control and less hardware, such as lines and generators, to provide the required level of reliability for the electric supply. Especially in power systems, and parts of power systems, comprising distributed generation, there seems to be a great potential to improve the overall cost/benefit-ratio for the desired level of reliability, by the use of intelligent load shedding. Intelligent load shedding is a means to improve power system stability, by providing an adapted load control along the distribution network, in situations where the power system otherwise would go unstable. The work with intelligent load shedding in this work package results in various technical principles of dedicated algorithms. These algorithms intend to bring a support tool for the operating system during critical situations. The main aspects are evaluating the right amount and location of power response for a given disturbance, and evaluating the right time response expected in order to comply with an acceptable stability recover. This time response is a main object in order to define appropriate ICT network enabling such a reliable implementation. A main problem of the intelligent load shedding is how to choose load to shed conveniently and quickly. There is a technical problem of finding the right level and location of the load to shed, and also an economical problem of giving incentives in order to have enough remote

  2. Adenovirus gene transfer to amelogenesis imperfecta ameloblast-like cells.

    Directory of Open Access Journals (Sweden)

    Anton V Borovjagin

    Full Text Available To explore gene therapy strategies for amelogenesis imperfecta (AI, a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5 vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including "pK7" and/or "RGD" motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3 fiber "knob" domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both α(vβ3/α(vβ5 integrins and heparan sulfate proteoglycans (HSPGs highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI.

  3. Non-Replicating Adenovirus-Vectored Anthrax Vaccine

    International Nuclear Information System (INIS)

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

  4. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, Eric A. [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Camacho, Zenaido T. [Department of Cell Biology, Department of Natural Sciences, Western New Mexico University, Silver City, NM 88062 (United States); Hillestad, Matthew L. [Nephrology Training Program, Mayo Clinic, Rochester, MN 55902 (United States); Crosby, Catherine M.; Turner, Mallory A.; Guenzel, Adam J.; Fadel, Hind J. [Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902 (United States); Mercier, George T. [Department of Physics, University of Houston, Houston, TX 77004 (United States); Barry, Michael A., E-mail: mab@mayo.edu [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Department of Immunology and Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902 (United States)

    2015-08-15

    We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. When wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.

  5. A novel adenovirus of Western lowland gorillas (Gorilla gorilla gorilla

    Directory of Open Access Journals (Sweden)

    Ludwig Carsten

    2010-11-01

    Full Text Available Abstract Adenoviruses (AdV broadly infect vertebrate hosts including a variety of primates. We identified a novel AdV in the feces of captive gorillas by isolation in cell culture, electron microscopy and PCR. From the supernatants of infected cultures we amplified DNA polymerase (DPOL, preterminal protein (pTP and hexon gene sequences with generic pan primate AdV PCR assays. The sequences in-between were amplified by long-distance PCRs of 2 - 10 kb length, resulting in a final sequence of 15.6 kb. Phylogenetic analysis placed the novel gorilla AdV into a cluster of primate AdVs belonging to the species Human adenovirus B (HAdV-B. Depending on the analyzed gene, its position within the cluster was variable. To further elucidate its origin, feces samples of wild gorillas were analyzed. AdV hexon sequences were detected which are indicative for three distinct and novel gorilla HAdV-B viruses, among them a virus nearly identical to the novel AdV isolated from captive gorillas. This shows that the discovered virus is a member of a group of HAdV-B viruses that naturally infect gorillas. The mixed phylogenetic clusters of gorilla, chimpanzee, bonobo and human AdVs within the HAdV-B species indicate that host switches may have been a component of the evolution of human and non-human primate HAdV-B viruses.

  6. Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever.

    Science.gov (United States)

    Warimwe, George M; Gesharisha, Joseph; Carr, B Veronica; Otieno, Simeon; Otingah, Kennedy; Wright, Danny; Charleston, Bryan; Okoth, Edward; Elena, Lopez-Gil; Lorenzo, Gema; Ayman, El-Behiry; Alharbi, Naif K; Al-dubaib, Musaad A; Brun, Alejandro; Gilbert, Sarah C; Nene, Vishvanath; Hill, Adrian V S

    2016-01-01

    Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A 'One Health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs. PMID:26847478

  7. Suppression of vortex shedding around a square cylinder using blowing

    Indian Academy of Sciences (India)

    Arun K Saha; Ankit Shrivastava

    2015-05-01

    Direct numerical simulation (DNS) of flow past a square cylinder at a Reynolds number of 100 has been carried out to explore the effect of blowing in the form of jet(s) on vortex shedding. Higher order spatial as well as temporal discretization has been employed for the discretization of governing equations. The varying number of jets, jet velocity profiles and different blowing velocities are studied to investigate the characteristics of vortex shedding. The parabolic velocity profile has been found to be more effective in suppressing the vortex shedding as compared to the uniform velocity. Complete suppression of vortex shedding along with remarkable reduction in drag coefficient has been achieved for both jet velocity profiles but at different velocities. The corresponding values for uniform and parabolic jet profiles are 0.87 and 0.6, respectively at a mass flux of 0.120. The study also reveals that there is considerable effect of the number of jets on the vortex shedding phenomena.

  8. Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.

    Science.gov (United States)

    Miner, Jonathan J; Sene, Abdoulaye; Richner, Justin M; Smith, Amber M; Santeford, Andrea; Ban, Norimitsu; Weger-Lucarelli, James; Manzella, Francesca; Rückert, Claudia; Govero, Jennifer; Noguchi, Kevin K; Ebel, Gregory D; Diamond, Michael S; Apte, Rajendra S

    2016-09-20

    Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye. PMID:27612415

  9. Persistent depressive disorder

    Science.gov (United States)

    PDD; Chronic depression; Depression - chronic ... The exact cause of persistent depressive disorder (PDD) is unknown. It tends to run in families. PDD occurs more often in women. Most people with PDD will also ...

  10. Is Inflation Persistence Over?

    Directory of Open Access Journals (Sweden)

    Fernando N. de Oliveira

    2014-09-01

    Full Text Available We analyze inflation persistence in several industrial and emerging countries in the recent past by implementing unit root tests in the presence of unknown structural breaks and by estimating reduced-form models of inflation dynamics. We select a very representative group of 23 industrial and 17 emerging economies. Our sample period is comprised of quarterly data and differs for each country. Our results indicate that inflation persistence is decreasing over time for the great majority of industrial economies. Many emerging economies, however, show increasing persistence and even a few have highly persistent inflationary processes. We also observe structural breaks in all inflation processes we study with the exception of the inflation processes of Germany and Austria. Our results are robust to different reduced forms of the inflation processes and different econometric techniques.

  11. Orthogonal Persistence Revisited

    CERN Document Server

    Dearle, Alan; Morrison, Ron

    2010-01-01

    The social and economic importance of large bodies of programs and data that are potentially long-lived has attracted much attention in the commercial and research communities. Here we concentrate on a set of methodologies and technologies called persistent programming. In particular we review programming language support for the concept of orthogonal persistence, a technique for the uniform treatment of objects irrespective of their types or longevity. While research in persistent programming has become unfashionable, we show how the concept is beginning to appear as a major component of modern systems. We relate these attempts to the original principles of orthogonal persistence and give a few hints about how the concept may be utilised in the future.

  12. Molecular detection of two adenoviruses associated with disease in Australian lizards.

    Science.gov (United States)

    Hyndman, T; Shilton, C M

    2011-06-01

    We give the first published description of the pathology and molecular findings associated with adenovirus infection in lizards in Australia. A central netted dragon (Ctenophorus nuchalis) exhibited severe necrotising hepatitis with abundant intranuclear inclusion bodies within hepatocytes and rarely within intestinal epithelial cells. Polymerase chain reaction (PCR) using pooled tissues yielded an amplicon that shared strong nucleotide identity with an agamid adenovirus (EU914203). PCR on the liver of a bearded dragon (Pogona minor minor) with illthrift, coccidiosis, nematodiasis and hepatic lipidosis yielded an amplicon with strong nucleotide identity to a helodermatid adenovirus (EU914207). PMID:21595645

  13. Molecular characterization of adenovirus circulating in Central and South America during the 2006–2008 period

    Science.gov (United States)

    García, Josefina; Sovero, Merly; Laguna‐Torres, Victor Alberto; Gomez, Jorge; Chicaiza, Wilson; Barrantes, Melvin; Sanchez, Felix; Jimenez, Mirna; Comach, Guillermo; De Rivera, Ivette L.; Agudo, Roberto; Arango, Ana E.; Barboza, Alma; Aguayo, Nicolas; Kochel, Tadeusz J.

    2009-01-01

    Background  Human Adenoviruses are recognized pathogens, causing a broad spectrum of diseases. Serotype identification is critical for epidemiological surveillance, detection of new strains and understanding of HAdvs pathogenesis. Little data is available about HAdvs subtypes in Latin America. Methods  In this study, we have molecularly characterized 213 adenoviruses collected from ILI presenting patients, during 2006‐08, in Central and South America. Results  Our results indicate that 161(76%) adenoviruses belong to subgroup C, 45 (21%) to subgroup B and 7 (3%) to subtype E4. PMID:19903214

  14. Elites and institutional persistence

    OpenAIRE

    Robinson, James A.

    2010-01-01

    Particular sets of institutions, once they become established in a society, have a strong tendency to persist. In this paper I argue that understanding how elites form and reproduce is key to understanding the persistence of institutions over time. I illustrate this idea with a simple political economy theory of institutions and through examples from Liberia, the US, South Africa and Germany I show how elites influence institutions. To change institutions requires having an understanding of h...

  15. Rapid and sustained CD4(+) T-cell-independent immunity from adenovirus-encoded vaccine antigens

    DEFF Research Database (Denmark)

    Holst, Peter J; Bartholdy, Christina; Buus, Anette Stryhn;

    2007-01-01

    Many novel vaccine strategies rely on recombinant viral vectors for antigen delivery, and adenovirus vectors have emerged among the most potent of these. In this report, we have compared the immune response induced through priming with adenovirus vector-encoded full-length viral protein...... to that elicited with an adenovirus-encoded minimal epitope covalently linked to beta(2)-microglobulin. We demonstrate that the beta(2)-microglobulin-linked epitope induced an accelerated and augmented CD8(+) T-cell response. Furthermore, the immunity conferred by vaccination with beta(2)-microglobulin...... in the absence of CD4(+) T-cell help were sustained in the long term and able to expand and control a secondary challenge with LCMV. Our results demonstrate that modifications to the antigen used in adenovirus vaccines may be used to improve the induced T-cell response. Such a strategy for CD4(+) T...

  16. [Downregulation of Human Adenovirus DNA Polymerase Gene by Modified siRNAs].

    Science.gov (United States)

    Nikitenko, N A; Speiseder, T; Chernolovskaya, E L; Zenkova, M A; Dobner, T; Prassolov, V S

    2016-01-01

    Human adenoviruses, in particular D8, D19, and D37, cause ocular infections. Currently, there is no available causally directed treatment, which efficiently counteracts adenoviral infectious diseases. In our previous work, we showed that gene silencing by means of RNA interference is an effective approach for downregulation of human species D adenoviruses replication. In this study, we compared the biological activity of siRNAs and their modified analogs targeting human species D adenoviruses DNA polymerase. We found that one of selectively 2'-O-methyl modified siRNAs mediates stable and long-lasting suppression of the target gene (12 days post transfection). We suppose that this siRNA can be used as a potential therapeutic agent against human species D adenoviruses.

  17. Immune-Complexed Adenovirus Induce AIM2-Mediated Pyroptosis in Human Dendritic Cells

    Science.gov (United States)

    Eichholz, Karsten; Bru, Thierry; Tran, Thi Thu Phuong; Fernandes, Paulo; Mennechet, Franck J. D.; Manel, Nicolas; Alves, Paula; Perreau, Matthieu

    2016-01-01

    Human adenoviruses (HAdVs) are nonenveloped proteinaceous particles containing a linear double-stranded DNA genome. HAdVs cause a spectrum of pathologies in all populations regardless of health standards. Following repeat exposure to multiple HAdV types, we develop robust and long-lived humoral and cellular immune responses that provide life-long protection from de novo infections and persistent HAdV. How HAdVs, anti-HAdV antibodies and antigen presenting cells (APCs) interact to influence infection is still incompletely understood. In our study, we used physical, pharmacological, biochemical, fluorescence and electron microscopy, molecular and cell biology approaches to dissect the impact of immune-complexed HAdV (IC-HAdV) on human monocyte-derived dendritic cells (MoDCs). We show that IC-HAdV generate stabilized complexes of ~200 nm that are efficiently internalized by, and aggregate in, MoDCs. By comparing IC-HAdV, IC-empty capsid, IC-Ad2ts1 (a HAdV-C2 impaired in endosomal escape due to a mutation that impacts protease encapsidation) and IC-AdL40Q (a HAdV-C5 impaired in endosomal escape due to a mutation in protein VI), we demonstrate that protein VI-dependent endosomal escape is required for the HAdV genome to engage the DNA pattern recognition receptor AIM2 (absent in melanoma 2). AIM2 engagement induces pyroptotic MoDC death via ASC (apoptosis-associated speck protein containing a caspase activation/recruitment domain) aggregation, inflammasome formation, caspase 1 activation, and IL-1β and gasdermin D (GSDMD) cleavage. Our study provides mechanistic insight into how humoral immunity initiates an innate immune response to HAdV-C5 in human professional APCs. PMID:27636895

  18. Role of coxsackievirus and adenovirus receptor in the pathogenesis of dilated cardiomyopathy and its influencing factor

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shuo; JIA Hai-bo; GONG Bin-sheng; ZHANG Shao-jun; LI Xia; YU Bo

    2008-01-01

    Background Although clinical treatment for heart failure and sudden death has been improved over the last few decades, the morbidity and mortality of dilated cardiomyopathy (DCM) have increased. So a better understanding of the underlying molecular events leading to DCM is urgent. Persistent viral infection (especially coxsackievirus group B) of the myocardium in viral myocarditis and DCM has never been neglected by experts. Recent data indicate that the up-regulation of coxsackievirus and adenovirus receptor (CAR) in viral cardiomyopathy contributes to viral infection as a key factor in the pathogenesis of this disease. This study aimed to investigate the role and regulatory mechanism of CAR in DCM by the bioinformatic method.Methods We identified the clusters of genes co-expressed with CAR by clustering algorithm based on the public available microarray dataset of DCM (Kittleson, et al. 2005), and mapped these genes into the protein-protein interaction networks to investigate the interaction relationship to each other at the protein level after confirming that the samples are characterized by the cluster of genes in correctly partitioning.Results The gene cluster GENESET 11 containing 33 genes including CAR with similar expression pattem was identified by cluster algorithm, of which 19 genes were found to have interaction information of the protein encoded by them in the current human protein interaction database. Especially, 12 genes present as critical nodes (called HUB node) at the protein level are involved in energy metabolism, signal transduction, viral infection, immuno-response, cell apoptosis, cell proliferation, tissue repair, etc.Conclusions The genes in GENESET 11 together with CAR may play a pathogenic role in the development of DCM, mainly involved in the mechanism of energy metabolism, signal transduction, viral infection, immuno-response, cell apoptosis and tissue repair.

  19. Inactivation of adenovirus, reovirus and bacteriophages in fecal sludge by pH and ammonia.

    Science.gov (United States)

    Magri, Maria Elisa; Fidjeland, Jørgen; Jönsson, Håkan; Albihn, Ann; Vinnerås, Björn

    2015-07-01

    The aim of this study was to evaluate the inactivation of adenovirus, reovirus and bacteriophages (MS2, ΦX174, 28B) in a fecal sludge. We conducted two experiments. In the first, we tested different compositions of the fecal sludge by mixing different amounts of water, feces and urine, totaling nine combinations which were kept at temperatures between 10 and 28°C. In the second study, urea was added to the mixtures, which were kept at temperatures from 5 to 33°C. The inactivation was based on a combination of temperature, pH and uncharged ammonia concentration. The increase in pH and ammonia was provided mainly by urine content (Experiment 1) and by urine and added urea (Experiment 2). The inactivation of bacteriophages was slower than the AdV and ReV. At 23°C and 28°, reasonable treatment times were obtained when pH was higher than 8.9 and NH3 concentrations were higher than 35 and 55 mM respectively. With those conditions, the maximum time for a 3 log reduction in viruses, according to this study, would be 35 days (23°C) and 21 days (28°C). However, in most applications where helminth eggs are present, the treatment time and NH3 for sanitization will be the scaling criteria, as they are more persistent. Concerning the sanitization of effluents from latrines, vacuum toilets or dry toilets in developing countries with tropical and sub-tropical climates, the use of intrinsic ammonia combined with high pH can be effective in producing a safe and highly valuable liquid that can be used as a fertilizer. In the case of the fecal sludge with very intrinsic ammonia concentration (<20 mM), sanitization could still be achieved by the addition of urea.

  20. Weight-Loss Surgery Sheds Pounds Long Term

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160719.html Weight-Loss Surgery Sheds Pounds Long Term 10-year follow- ... 31, 2016 WEDNESDAY, Aug. 31, 2016 (HealthDay News) -- Weight-loss surgery helps people drop a significant amount of ...

  1. Vortex shedding flow meter performance at high flow velocities

    Science.gov (United States)

    Siegwarth, J. D.

    1986-01-01

    In some of the ducts of the Space Shuttle Main Engine (SSME), the maximum liquid oxygen flow velocities approach 10 times those at which liquid flow measurements are normally made. The hydrogen gas flow velocities in other ducts exceed the maximum for gas flow measurement by more than a factor of 3. The results presented here show from water flow tests that vortex shedding flow meters of the appropriate design can measure water flow to velocities in excess of 55 m/s, which is a Reynolds number of about 2 million. Air flow tests have shown that the same meter can measure flow to a Reynolds number of at least 22 million. Vortex shedding meters were installed in two of the SSME ducts and tested with water flow. Narrow spectrum lines were obtained and the meter output frequencies were proportional to flow to + or - 0.5% or better over the test range with no flow conditioning, even though the ducts had multiple bends preceeding the meter location. Meters with the shedding elements only partially spanning the pipe and some meters with ring shaped shedding elements were also tested.

  2. Developing of the EV charging and parking shed of BIPV

    Institute of Scientific and Technical Information of China (English)

    Wu Shaobo; Wei Chuanchuan; Yu Jiang

    2013-01-01

    Building-integrated photovoltaic (BIPV) is an important application way of solar photovoltaic power. The electric vehicle (EV) charging and parking shed of BIPV is the regeneration energy intellectual integration demonstration application system collection of photovoltaic (PV) grid power,PV off-grid power,EV charging and parking shed,and any part of the functions and their combination will be engaged in practical application on demand. The paper describes the PV shed system structure and design in detail with the present of its actual photos. The shed is 50 m long and 5.5 m wide and capable of parking 18 cars. Under the control of system intellectual con-troller,the power produced by PV from sunlight will charge the parking EV car prior to charging the storage bat-tery,charging the storage battery prior to grid power,grid power at last,and charge the EV by utility grid when it is a cloudy or rainy day.

  3. The transmembrane domain of TACE regulates protein ectodomain shedding

    Institute of Scientific and Technical Information of China (English)

    Xiaojin Li; Liliana Pérez; Zui Pan; Huizhou Fan

    2007-01-01

    Numerous membrane proteins are cleaved by tumor necrosis factor-α converting enzyme (TACE), which causes the release of their ectodomains. An ADAM (a disintegrin and metalloprotease domain) family member, TACE contains several noncatalytic domains whose roles in ectodomain shedding have yet to be fully resolved. Here, we have explored the function of the transmembrane domain (TM) of TACE by coupling molecular engineering and functional analysis. A TM-free TACE construct that is anchored to the plasma membrane by a glycosylphosphatidylino-sitol (GPI)-binding polypeptide failed to restore shedding of transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α) and L-selectin in cells lacking endogenous TACE activity. Substitution of the TACE TM with that of the prolactin receptor or platelet-derived growth factor receptor (PDGFR) also resulted in severe loss of TGF-α shedding, but had no effects on the cleavage of TNF-α and L-selectin. Replacement of the TM in TGF-a with that of L-selectin enabled TGF-a shedding by the TACE mutants carrying the TM of prolactin receptor and PDGFR. Taken together, our observations suggest that anchorage of TACE to the lipid bilayer through a TM is required for efficient cleavage of a broad spectrum of substrates, and that the amino-acid sequence of TACE TM may play a role in regulatory specificity among TACE substrates.

  4. Development of resource shed delineation in aquatic ecosystems.

    Science.gov (United States)

    Raikow, David F; Atkinson, Joseph F; Croley Ii, Thomas E

    2010-01-01

    We apply a concept derived from food web ecology to large-scale spatial patterns of material supply within and between watersheds and coasts by generalizing the definition "resource shed" to source areas for materials supplied to a receptor (e.g., a point location) over a specified time interval. Independent hydrologic and hydrodynamic models, coupled with a particle tracking model, were used to delimit resource shed total spatial extent and relative contributory importance for selected receptors in Lake Erie (North America) over varying time intervals. One resource shed was extended into the Maumee River watershed (OH) by integrating the lake and hydrologic models. Model validation was achieved through comparison with data from the 2005 International Field Years on Lake Erie (IFYLE) study. Resource shed size, orientation, and internal structure varied with receptor location, in-lake circulation, terrestrial precipitation, time interval, and season. River plume extent and interaction were illustrated, and model integration revealed the relative contributory importance of subwatershed catchments to an off-shore receptor. PMID:19958021

  5. Vortex Shedding from Tapered Cylinders at high Reynolds Numbers

    DEFF Research Database (Denmark)

    Johansson, Jens; Andersen, Michael Styrk; Christensen, Silas Sverre;

    2015-01-01

    percent for strakes of circular cross section. The present paper argues that this height can be reduced for structures where the critical wind velocity for vortex shedding is in the Supercritical Reynolds number regime. The present investigations are aimed for suppressing VIV on offshore wind turbine...

  6. A Robust Load Shedding Strategy for Microgrid Islanding Transition

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Guodong [ORNL; Xiao, Bailu [ORNL; Starke, Michael R [ORNL; Ceylan, Oguzhan [ORNL; Tomsovic, Kevin [University of Tennessee, Knoxville (UTK)

    2016-01-01

    A microgrid is a group of interconnected loads and distributed energy resources. It can operate in either gridconnected mode to exchange energy with the main grid or run autonomously as an island in emergency mode. However, the transition of microgrid from grid-connected mode to islanded mode is usually associated with excessive load (or generation), which should be shed (or spilled). Under this condition, this paper proposes an robust load shedding strategy for microgrid islanding transition, which takes into account the uncertainties of renewable generation in the microgrid and guarantees the balance between load and generation after islanding. A robust optimization model is formulated to minimize the total operation cost, including fuel cost and penalty for load shedding. The proposed robust load shedding strategy works as a backup plan and updates at a prescribed interval. It assures a feasible operating point after islanding given the uncertainty of renewable generation. The proposed algorithm is demonstrated on a simulated microgrid consisting of a wind turbine, a PV panel, a battery, two distributed generators (DGs), a critical load and a interruptible load. Numerical simulation results validate the proposed algorithm.

  7. USEPA SHEDS MODEL: METHODOLOGY FOR EXPOSURE ASSESSMENT FOR WOOD PRESERVATIVES

    Science.gov (United States)

    A physically-based, Monte Carlo probabilistic model (SHEDS-Wood: Stochastic Human Exposure and Dose Simulation model for wood preservatives) has been applied to assess the exposure and dose of children to arsenic (As) and chromium (Cr) from contact with chromated copper arsenat...

  8. 25 CFR 247.15 - May I reserve a campsite or drying shed?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false May I reserve a campsite or drying shed? 247.15 Section... RIVER TREATY FISHING ACCESS SITES § 247.15 May I reserve a campsite or drying shed? No. You may not reserve a campsite, drying shed, or other facility. (a) You must use campsites, drying sheds, and...

  9. Efficient manipulation of the human adenovirus genome as an infectious yeast artificial chromosome clone.

    OpenAIRE

    Ketner, G; Spencer, F; Tugendreich, S; C. Connelly; Hieter, P

    1994-01-01

    A yeast artificial chromosome (YAC) containing a complete human adenovirus type 2 genome was constructed, and viral DNA derived from the YAC was shown to be infectious upon introduction into mammalian cells. The adenovirus YAC could be manipulated efficiently using homologous recombination-based methods in the yeast host, and mutant viruses, including a variant that expresses the human analog of the Saccharomyces cerevisiae CDC27 gene, were readily recovered from modified derivatives of the Y...

  10. Neoplastic transformation of chimpanzee cells induced by adenovirus type 12--simian virus 40 hybrid virus.

    OpenAIRE

    Rhim, J S; Trimmer, R; Arnstein, P; Huebner, R J

    1981-01-01

    The adenovirus 12--simian virus 40 hybrid virus produced neoplastic transformation of chimpanzee skin fibroblasts in vitro. The transformed fibroblasts showed morphological alteration and became permanent lines. The transformed cells contained both adenovirus 12 and simian virus 40 large tumor antigens and were virus producers. However at passage 9, one line (WES) was found to be a nonproducer, producing neither infectious virus nor virus-specific antigen detectable by the complement fixation...

  11. Construction and Expression of Human PTEN Tumor Suppressor Gene Recombinant Adenovirus Vector

    Institute of Scientific and Technical Information of China (English)

    CHEN Qingyong; WANG Chunyou; CHEN Daoda; CHEN Jianying; JIANG Chunfang; ZHENG Hai

    2006-01-01

    The recombinant defective adenovirus vector carrying human PTEN tumor suppres sor gene was constructed by using AdEasy-1 system and its expression was detected in human breast cancer cell line MDA-MB-468. Human PTEN cDNA was cloned into adenovirus shuttle plasmid pAdTrack-CMV to generate a recombinant plasmid pAdTrack-CMV-PTEN, then homologeous recombination was carried out in the E. coli BJ5183 by contransforming linearized shuttle vector with adenovirus backbone plasmid pAdEasy-1. The newly recombined defective adenovirus vector AdPTEN containing green fluorescent protein (GFP) was packaged and propagated in 293 cells. After being purified by cesium chloride gradient centrifugation, the adenovirus was transfected into human breast cancer cell line MDA-MB-468 in vitro. The expression of PTEN mRNA and protein in infected human breast cancer cell line MDA-MB-468 was detected by RT-PCR and Western blot respectively. The recombinant defective adenovirus vector carrying PTEN gene was constructed successfully. The viral titer of purified adenovirus was 2.5×1010 pfu/mL, and about 70 % breast cancer cells were infected with Ad PTEN when multiplicity of infection (MOI) reached 50. The exogenous PTEN mRNA and protein were expressed in MDA-MB-468 cells infected with Ad-PTEN by RT-PCR and Western blot. The recombinant defective adenovirus vector of PTEN gene was constructed successfully using AdEasy-1 system rapidly, which paved a sound foundation for gene study of breast cancer.

  12. Frequency of Rotavirus and Adenovirus Gastroenteritis Among Children in Shiraz, Iran

    OpenAIRE

    Motamedifar, Mohammad; Amini, Elham; Talezadeh Shirazi, Pedram

    2013-01-01

    Background Viral pathogens are the main cause of acute gastroenteritis in developed and developing countries. Rotavirus and adenovirus are the two important agents associated with hospitalization for diarrhea especially in children. Limitation and control of diarrhea as a costly disease must be considered in national health programs. Objectives Epidemiological studies on viral diarrhea and collecting data for rotavirus and adenovirus prevalence, as two important viral agents of gastroenteriti...

  13. A retrospective investigation of canine adenovirus (CAV) infection in adult dogs in Turkey : article

    OpenAIRE

    Gur, S; A. Acar

    2009-01-01

    Canine adenovirus (CAV) type 1 and 2, respectively, cause infectious canine hepatitis and infectious canine laryngotracheitis in members of the families Canidae and Ursidae worldwide. Both of these infections are acute diseases, especially in young dogs. The aim of this study was to conduct a serological investigation of canine adenovirus infection. For this purpose, serumsamples were collected from native pure-bred Kangal (n = 11), and Akbash dogs (n = 17) and Turkish Greyhounds (n=15) in Es...

  14. Mutation in fiber of adenovirus serotype 5 gene therapy vector decreases liver tropism

    OpenAIRE

    Wang, Zhen; Wang, Baoming; Lou, Junfang; Yan, Jingyi; Gao, Lei; Geng, Ranshen; Yu, Bin

    2014-01-01

    Recombinant adenovirus (Ad) vectors are widely used for both in vitro and in vivo gene transfer. However, intravenous administration of Ad vectors results mainly in hepatocyte transduction and subsequent hepatotoxicity. Coxsackie-adenovirus receptor (CAR) and αvβ integrins, which are functional receptors for the fiber and penton proteins, respectively, are the tropism determinants of Ad type 5 (Ad5). We previously developed a system for rapid construction of fiber-modified Ad5 vectors. We als...

  15. Detection of adenovirus in nasopharyngeal specimens by radioactive and nonradioactive DNA probes.

    OpenAIRE

    Hyypiä, T

    1985-01-01

    The presence of adenovirus DNA in clinical specimens was analyzed by nucleic acid hybridization assays by both radioactive and enzymatic detection systems. The sensitivity of the hybridization tests was in the range of 10 to 100 pg of homologous adenovirus DNA. Minimal background was noticed with unrelated viral and nonviral DNA. Twenty-four nasopharyngeal mucus aspirate specimens, collected from children with acute respiratory infection, were assayed in the hybridization tests and also by an...

  16. Ad 2.0: a novel recombineering platform for high-throughput generation of tailored adenoviruses

    OpenAIRE

    Mück-Häusl, Martin; Solanki, Manish; Zhang, Wenli; Ruzsics, Zsolt; Ehrhardt, Anja

    2015-01-01

    Recombinant adenoviruses containing a double-stranded DNA genome of 26–45 kb were broadly explored in basic virology, for vaccination purposes, for treatment of tumors based on oncolytic virotherapy, or simply as a tool for efficient gene transfer. However, the majority of recombinant adenoviral vectors (AdVs) is based on a small fraction of adenovirus types and their genetic modification. Recombineering techniques provide powerful tools for arbitrary engineering of recombinant DNA. Here, we ...

  17. A Study of Single Mothers' Experience of Persistence at a Four-Year Public University

    Science.gov (United States)

    Hayes Nelson, Geraldine

    2009-01-01

    The overall purpose of this study was to uncover and describe the barriers that low-income, single mothers between the ages of 17-24 experience and the strategies they adopt in their efforts to persist through year one to year three of college at a four-year public university. Adult education scholarship has shed light on the obstacles to college…

  18. Visual persistence and cinema?

    Science.gov (United States)

    Galifret, Yves

    2006-01-01

    In Faraday and Plateau's days, both apparent motion and the fusion of intermittent lights, two phenomena that are hardly connected, were explained by retinal persistence. The works of Exner and of the 'Gestalt' psychologists, as well as the modern works on 'sampled' motion and smooth motion, disregarded retinal persistence. One tried, originally, to measure this persistence using intermittent stimulation, but under the pressure of practical concern, what was established in 1902 was the logarithmic relation between fusion frequency and the intensity of the stimulation. One had to wait until the 1950s for the use of harmonic analysis to finally allow a renewal in which many problems that, for decades, had only given rise to discussions that led nowhere and to groundless assertions, were correctly stated and easily solved.

  19. Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding.

    Science.gov (United States)

    Basagiannis, Dimitris; Christoforidis, Savvas

    2016-08-01

    VEGFR2 plays a fundamental role in blood vessel formation and in life threatening diseases, such as cancer angiogenesis and cardiovascular disorders. Although inactive growth factor receptors are mainly localized at the plasma membrane, VEGFR2 undergoes constitutive endocytosis (in the absence of ligand) and recycling. Intriguingly, the significance of these futile transport cycles of VEGFR2 remains unclear. Here we found that, unexpectedly, the function of constitutive endocytosis of VEGFR2 is to protect the receptor against plasma membrane cleavage (shedding), thereby preserving the functional state of the receptor until the time of activation by VEGF. Inhibition of constitutive endocytosis of VEGFR2, by interference with the function of clathrin, dynamin, or Rab5, increases dramatically the cleavage/shedding of VEGFR2. Shedding of VEGFR2 produces an N-terminal soluble fragment (100 kDa, s100), which is released in the extracellular space, and a residual C-terminal part (130 kDa, p130) that remains integrated at the plasma membrane. The released soluble fragment (s100) co-immunoprecipitates with VEGF, in line with the topology of the VEGF-binding domain at the N terminus of VEGFR2. Increased shedding of VEGFR2 (via inhibition of constitutive endocytosis) results in reduced response to VEGF, consistently with the loss of the VEGF-binding domain from the membrane remnant of VEGFR2. These data suggest that constitutive internalization of VEGFR2 protects the receptor against shedding and provides evidence for an unprecedented mechanism via which endocytosis can regulate the fate and activity of growth factor receptors. PMID:27298320

  20. Construction of adenovirus vectors encoding the lumican gene by gateway recombinant cloning technology

    Science.gov (United States)

    Wang, Gui-Fang; Qi, Bing; Tu, Lei-Lei; Liu, Lian; Yu, Guo-Cheng; Zhong, Jing-Xiang

    2016-01-01

    AIM To construct adenovirus vectors of lumican gene by gateway recombinant cloning technology to further understand the role of lumican gene in myopia. METHODS Gateway recombinant cloning technology was used to construct adenovirus vectors. The wild-type (wt) and mutant (mut) forms of the lumican gene were synthesized and amplified by polymerase chain reaction (PCR). The lumican cDNA fragments were purified and ligated into the adenovirus shuttle vector pDown-multiple cloning site (MCS)-/internal ribozyme entry site (IRES)/enhanced green fluorescent protein (EGFP). Then the desired DNA fragments were integrated into the destination vector pAV.Des1d yielding the final expression constructs pAV.Ex1d-cytomegalovirus (CMV)>wt-lumican/IRES/EGFP and pAV.Ex1d-CMV>mut-lumican/IRES /EGFP, respectively. RESULTS The adenovirus plasmids pAV.Ex1d-CMV>wt-lumican/IRES/EGFP and pAV.Ex1d-CMV>mut-lumican/IRES/EGFP were successfully constructed by gateway recombinant cloning technology. Positive clones identified by PCR and sequencing were selected and packaged into recombinant adenovirus in HEK293 cells. CONCLUSION We construct adenovirus vectors containing the lumican gene by gateway recombinant cloning technology, which provides a basis for investigating the role of lumican gene in the pathogenesis of high myopia. PMID:27672590

  1. A molecular epidemiology survey of respiratory adenoviruses circulating in children residing in Southern Palestine.

    Directory of Open Access Journals (Sweden)

    Lina Qurei

    Full Text Available A molecular epidemiology survey was performed in order to establish and document the respiratory adenovirus pathogen profiles among children in Southern Palestine. Three hundred and thirty-eight hospitalized pediatric cases with adenovirus-associated respiratory tract infections were analyzed. Forty four cases out of the 338 were evaluated in more detail for the adenoviruses types present. All of the children resided in Southern Palestine, that is, in city, village and refugee camp environments within the districts of Hebron and Bethlehem. Human adenoviruses circulated throughout 2005-2010, with major outbreaks occurring in the spring months. A larger percent of the children diagnosed with adenoviral infections were male infants. DNA sequence analysis of the hexon genes from 44 samples revealed that several distinct adenovirus types circulated in the region; these were HAdV-C1, HAdV-C2, HAdV-B3 and HAdV-C5. However, not all of these types were detected within each year. This is the first study ever conducted in Palestine of the genetic epidemiology of respiratory adenovirus infections.

  2. Intratracheal administration of recombinant adenovirus containing IL-18 gene in treatment of experimental metastatic lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    CHEN Ji-quan; GAO Xue-tao; XIU Qing-yu; YU Yi-zhi; LUO Wen-tong

    2001-01-01

    To study the treatment of experimental metastatic lung carcinoma by intratracheal injection of IL-18 gene recombinant adenovirus. Methods: (1)The mouse IL-18 mRNA was detected by RT-PCR, and the concentration of IL-18 and associated cytokines in lung lavages and blood were determined by ELISA at different time points after intratracheal injection of IL-18 recombinant adenovirus. (2)The lung metastasis nodes, mouse survival periods and survival rates were evaluated. NK activity and CTL activity were determined by 51Cr 4 h release method. Results: (1)IL-18 mRNA was detectable in lung tissue 6 h after intratracheal use of IL-18 recombinant adenovirus, and the concentration of IL-18 in lung lavage was higher than that in pelipheral blood. Neither IL-18 mRNA nor IL-18 was detectable in control group. (2) Intratracheal use of IL-18 recombinant adenovirus resulted in increased CTL and NK activity, longer survival time and higher survival rates compared with the control group, showing significant therapeutic effect on experimental lung metastasis. Conclusion: Intratracheal use of adenovirus vector containing IL-18 gene has therapeutic effect on the lung metastasis, denoting that gene therapy of lung diseases could be applied through airway directly with recombinant adenovirus.

  3. Financial Markets and Persistence

    CERN Document Server

    Jain, S

    2005-01-01

    Persistence is studied in a financial context by mapping the time evolution of the values of the shares quoted on the London Financial Times Stock Exchange 100 index (FTSE 100) onto Ising spins. By following the time dependence of the spins, we find evidence for power law decay of the proportion of shares that remain either above or below their ` starting\\rq values. As a result, we estimate a persistence exponent for the underlying financial market to be $\\theta_f\\sim 0.5$.

  4. PERSISTENT LEFT SUPERIOR VENACAVA

    Directory of Open Access Journals (Sweden)

    Devinder Singh

    2014-05-01

    Full Text Available A Persistent Left Superior Venacava (PLSVC is the most common variation of the thoracic venous system and rare congenital vascular anomaly and is prevalent in 0.3% of the population. It may be associated with other cardiovascular abnormalities including atrial septal defect, bicuspid aortic valve, coarctation of aorta, coronary sinus ostial atresia, and cor triatriatum. Incidental rotation of a dilated coronary sinus on echocardiography should raise the suspicion of PLSVC. The diagnosis should be confirmed by saline contrast echocardiography. Condition is usually asymptomatic. Here we present a rare case of persistent left superior vena cava presented in OPD with dyspnoea & palpitations.

  5. Van Yöresinde Gözlenen Gastroenteritlerde Rotavirus ve Adenovirus Sıklığı

    OpenAIRE

    Gültepe, Bilge; Güdücüoğlu, Hüseyin; Çıkman, Aytekin; PARLAK, Mehmet; Berktaş, Mustafa

    2013-01-01

    Objectives: Infectious gastroenteritis is one of most important causes of morbidity and mortality in children. Rotavirus and enteric adenoviruses are the most important agents of infectious gastroenteritis. The epidemiology of rotavirus and enteric adenovirus gastroenteritis is not well known in our region. This study was aimed to determine the frequency of rotavirus and enteric adenovirus gastroenteritis in pediatric patients admitted to our hospital.Materials and Methods: Fresh stool spec...

  6. Contributions to Persistence Theory

    Directory of Open Access Journals (Sweden)

    Du Dong

    2014-12-01

    Full Text Available Persistence theory discussed in this paper is an application of algebraic topology (Morse Theory [29] to Data Analysis, precisely to qualitative understanding of point cloud data, or PCD for short. PCD can be geometrized as a filtration of simplicial complexes (Vietoris-Rips complex [25] [36] and the homology changes of these complexes provide qualitative information about the data. Bar codes describe the changes in homology with coefficients in a fixed field. When the coefficient field is ℤ2, the calculation of bar codes is done by ELZ algorithm (named after H. Edelsbrunner, D. Letscher, and A. Zomorodian [20]. When the coefficient field is ℝ, we propose an algorithm based on the Hodge decomposition [17]. With Dan Burghelea and Tamal K. Dey we developed a persistence theory which involves level sets discussed in Section 4. We introduce and discuss new computable invariants, the “relevant level persistence numbers” and the “positive and negative bar codes”, and explain how they are related to the bar codes for level persistence. We provide enhancements and modifications of ELZ algorithm to calculate such invariants and illustrate them by examples.

  7. Persistent organic pollutants

    NARCIS (Netherlands)

    Dungen, van den M.W.

    2016-01-01

    Fish wild caught in polluted areas, may contain high levels of persistent organic pollutants (POPs). In the Netherlands, especially eel from the main rivers have high POP levels. Health concerns led to a ban on eel fishing in 2011 due to health concerns. We showed that men consuming eel from the hig

  8. Introduction: Persistent Modelling

    DEFF Research Database (Denmark)

    Ayres, Phil

    2012-01-01

    , familiar contemporary and, perhaps, not so familiar emerging manifestations of this relation. What persists from this probing, fully intact, is that representation and the represented remain inextricably related in our contemporary and emerging practices. What comes into focus is that the nature...

  9. Persistent Trigeminal Artery

    Directory of Open Access Journals (Sweden)

    Dijo T George

    2015-04-01

    Full Text Available Trigeminal artery is the commonest of the four primitive anastomoses between the carotid and vertebrobasilar system that may rarely persist in adults, with an angiographic incidence of 0.1 - 0.6%. We present the CT and MR angiograms of a patient who presented with a minor stroke and was detected to have this anomaly and briefly discuss the significance

  10. Chilly Ties Persist

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Sino-Japanese relations seem unlikely to improve under the leadership of Shinzo Abe The deteriorating state of relations between China and Japan may persist under the government of Shinzo Abe, who won the presidential election of the ruling Liberal Democratic Party (LDP) on September 20 and was

  11. Up-regulation of integrin β3 in radioresistant pancreatic cancer impairs adenovirus-mediated gene therapy

    International Nuclear Information System (INIS)

    Adenovirus-mediated gene therapy is a promising approach for the treatment of pancreatic cancer. We previously reported that radiation enhanced adenovirus-mediated gene expression in pancreatic cancer, suggesting that adenoviral gene therapy might be more effective in radioresistant pancreatic cancer cells. In the present study, we compared the transduction efficiency of adenovirus-delivered genes in radiosensitive and radioresistant cells, and investigated the underlying mechanisms. We used an adenovirus expressing the hepatocyte growth factor antagonist, NK4 (Ad-NK4), as a representative gene therapy. We established two radioresistant human pancreatic cancer cell lines using fractionated irradiation. Radiosensitive and radioresistant pancreatic cancer cells were infected with Ad-NK4, and NK4 levels in the cells were measured. In order to investigate the mechanisms responsible for the differences in the transduction efficiency between these cells, we measured expression of the genes mediating adenovirus infection and endocytosis. The results revealed that NK4 levels in radioresistant cells were significantly lower (P<0.01) than those in radiosensitive cells, although there were no significant differences in adenovirus uptake between radiosensitive cells and radioresistant cells. Integrin β3 was up-regulated and the Coxsackie virus and adenovirus receptor was down-regulated in radioresistant cells, and inhibition of integrin β3 promoted adenovirus gene transfer. These results suggest that inhibition of integrin β3 in radioresistant pancreatic cancer cells could enhance adenovirus-mediated gene therapy. (author)

  12. Construction and expression of SET gene and siRNA recombinant adenovirus vectors

    Institute of Scientific and Technical Information of China (English)

    Xu Bo-qun; Lu Pin-hong; Li Ying; Xue Kai; Li Mei; Ma Xiang; Diao Fei-yan; Cui Yu-gui; Liu Jia-yin

    2010-01-01

    Objective: To construct SET gene recombinant adenovirus vector and SET gene small interfering RNA (SiRNA) recombinant adenovirus vector for over-expression or knock-down of SET levels.Methods: The cDNA sequence of SET was cloned by reverse transcriptive polymerase chain reaction (RT-PCR) and the SET gene fragment was subcloned into adenovirus shuttle plasmid pAdTrack-CMV to construct the shuttle plasmid pAdTrack-SET. The shuttle plasmid pAdtrack-SET was transformed into BJ5183 cells with the adenoviral backbone pAdEasy-1 to obtain the homologous recombinant Ad-CMV-SET and the recombinant Ad-CMV-SET was packaged and amplified in the AD293 cells. The expression of SET in AD293 cells was detected by Western blot. In addition, we constructed SET gene SiRNA recombinant adenovirus vector (Ad-H1-SiRNA/SET) and its efficacy of knockdown of SET protein was detected in infected GC-2spd(ts) cells by Western blot. Results: The recombinant adenovirus vectors, both SET gene recombinant adenovirus vector Ad-CMV-SET and SET gene SiRNA recombinant adenovirus vector Ad-H1-SiRNA/SET, were proven to be constructed successfully by the evidence of endonulease digestion and sequencing. AD293 cells infected with either recombinant adenovirus vector of Ad-CMV-SET or Ad-H1-SiRNA/SET were observed to express GFP. The expression of SET protein was up-regulated significantly in AD293 cells infected with SET gene recombinant adenovirus vector. On the contrast, SET protein was significantly down-regulated in the GC-2spd(ts) cells infected with Ad-H1-SiRNA/SET (P<0.05) and the knockdown efficiency was approximately 50%-70%. Conclusion: The recombinant adenovirus vector Ad-CMV-SET and Ad-H1-SiRNA/SET were successfully constructed and effectively expressed in germ cells and somatic cells. It provides an experimental tool for further study of SET gene in the physiological and pathophysiological mechanism of reproduction-related diseases.

  13. Persistent primitive trigeminal artery associated with monocular blindness and external carotid-vertebral artery anastomosis

    Science.gov (United States)

    Yin, Suo; Zhang, Hong T.; Zhang, Dao P.; Zhang, Shu L.

    2015-01-01

    In this paper, we present 2 rare cases of persistent embryonic anastomoses. In one case, the patient presented with persistent trigeminal artery along with multiple foci of cerebral infarction as well as central retinal artery thrombosis. In the other case, the patient had direct anastomosis of the vertebral artery with ipsilateral external carotid artery as well as pontine infarction, aneurysm, and unilateral hypoplasia of the vertebral artery. The findings in these cases may shed light on the clinical presentation of such persistent anastomoses and aid their detection in clinical settings. PMID:25935186

  14. Persistent primitive trigeminal artery associated with monocular blindness and external carotid-vertebral artery anastomosis.

    Science.gov (United States)

    Yin, Suo; Zhang, Hong T; Zhang, Dao P; Zhang, Shu L

    2015-05-01

    In this paper, we present 2 rare cases of persistent embryonic anastomoses. In one case, the patient presented with persistent trigeminal artery along with multiple foci of cerebral infarction as well as central retinal artery thrombosis. In the other case, the patient had direct anastomosis of the vertebral artery with ipsilateral external carotid artery as well as pontine infarction, aneurysm, and unilateral hypoplasia of the vertebral artery. The findings in these cases may shed light on the clinical presentation of such persistent anastomoses and aid their detection in clinical settings. PMID:25935186

  15. Vortex shedding flowmeters for liquids at high flow velocities

    Science.gov (United States)

    Siegwarth, J. D.

    1985-01-01

    A number of vortex shedding flowmeter designs for flow measurements in liquid oxygen ducts on the space shuttle main engines have been tested in a high head water flow test facility. The results have shown that a vortex shedding element or vane spanning the duct can give a linear response to an average flow velocity of 46 m/s (150 ft/s) in a 1 1/2 inch nominal (41 mm actual) diameter duct while a vane partially spanning the duct can give a linear response to velocities exceeding 55 m/s (180 ft/s). The maximum pressure drops across the flow sensing elements extrapolate to less than 0.7 MPa (100 psi) at 56 m/s (184 ft/s) for liquid oxygen. The test results indicate that the vanes probably cannot be scaled up with pipe size, at least not linearly.

  16. Birds shed RNA-viruses according to the pareto principle.

    Science.gov (United States)

    Jankowski, Mark D; Williams, Christopher J; Fair, Jeanne M; Owen, Jennifer C

    2013-01-01

    A major challenge in disease ecology is to understand the role of individual variation of infection load on disease transmission dynamics and how this influences the evolution of resistance or tolerance mechanisms. Such information will improve our capacity to understand, predict, and mitigate pathogen-associated disease in all organisms. In many host-pathogen systems, particularly macroparasites and sexually transmitted diseases, it has been found that approximately 20% of the population is responsible for approximately 80% of the transmission events. Although host contact rates can account for some of this pattern, pathogen transmission dynamics also depend upon host infectiousness, an area that has received relatively little attention. Therefore, we conducted a meta-analysis of pathogen shedding rates of 24 host (avian) - pathogen (RNA-virus) studies, including 17 bird species and five important zoonotic viruses. We determined that viral count data followed the Weibull distribution, the mean Gini coefficient (an index of inequality) was 0.687 (0.036 SEM), and that 22.0% (0.90 SEM) of the birds shed 80% of the virus across all studies, suggesting an adherence of viral shedding counts to the Pareto Principle. The relative position of a bird in a distribution of viral counts was affected by factors extrinsic to the host, such as exposure to corticosterone and to a lesser extent reduced food availability, but not to intrinsic host factors including age, sex, and migratory status. These data provide a quantitative view of heterogeneous virus shedding in birds that may be used to better parameterize epidemiological models and understand transmission dynamics.

  17. Post-Modernising the Museum: The Ration Shed

    OpenAIRE

    Carly Smith

    2014-01-01

    The application of postmodern critical theory to the essentially modernist construct of the museum has significantly impacted the role of the contemporary museum within society. This article briefly describes the movement toward a ‘new museology’ and the subsequent emergence of the ‘post-museum’. It then presents a case study of the Ration Shed Museum in the historical precinct of Cherbourg, Queensland, as an example of this new ‘post-museum’. Through its application of postmodern critical th...

  18. Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding.

    Science.gov (United States)

    Newman, K L; Moe, C L; Kirby, A E; Flanders, W D; Parkos, C A; Leon, J S

    2016-06-01

    Noroviruses (NoV) are the most common cause of epidemic gastroenteritis world-wide. NoV infections are often asymptomatic, although individuals still shed large amounts of NoV in their stool. Understanding the differences between asymptomatic and symptomatic individuals would help in elucidating mechanisms of NoV pathogenesis. Our goal was to compare the serum cytokine responses and faecal viral RNA titres of asymptomatic and symptomatic NoV-infected individuals. We tested serum samples from infected subjects (n = 26; 19 symptomatic, seven asymptomatic) from two human challenge studies of GI.1 NoV for 16 cytokines. Samples from prechallenge and days 1-4 post-challenge were tested for these cytokines. Cytokine levels were compared to stool NoV RNA titres quantified previously by reverse transcription-polymerase chain reaction (RT-qPCR). While both symptomatic and asymptomatic groups had similar patterns of cytokine responses, the symptomatic group generally exhibited a greater elevation of T helper type 1 (Th1) and Th2 cytokines and IL-8 post-challenge compared to the asymptomatic group (all P viral RNA titre was associated positively with daily IL-6 concentration and negatively with daily IL-12p40 concentration (all P viral RNA titre, duration of viral shedding or cumulative shedding. Symptomatic individuals, compared to asymptomatic, have greater immune system activation, as measured by serum cytokines, but they do not have greater viral burden, as measured by titre and shedding, suggesting that symptoms may be immune-mediated in NoV infection. PMID:26822517

  19. Autotransfusion of shed mediastinal blood after open heart surgery

    Institute of Scientific and Technical Information of China (English)

    赵康丽; 许建屏; 胡盛寿; 吴清玉; 魏以桢; 刘迎龙

    2003-01-01

    Objective To determine the safety and effectiveness of autotransfusion of shed mediastinal blood after open heart surgery. Methods Sixty patients undergoing coronary artery bypass grafting (CABG) were selected randomly to receive either nonwashed shed mediastinal blood (Group 1, n=30) or banked blood (Group 2, n=30). Drainage and transfusion volume were determined after the operation. Hb, RBC, HCT and PLT were detected immediately before and after the operation, as well as 24 hours and 7 days after the operation. Data were analyzed using Fisher's exact test. A P0.05). In the two groups, no significant difference in the mean blood loss was observed during 24 hours after the operation (660±300 ml in Group 1 and 655±280 ml in Group 2, P>0.05). In Group 1, the mean volume autotransfused was 280±160 ml, and the patients required 360±80 ml banked blood compared with 660±120 ml in Group 2. In other words, the banked blood requirement in Group 1 was 40% lower. Conclusions Autotransfusion of shed mediastinal blood after an open heart operation is safe and effective.

  20. Vortex shedding from two surface-mounted cubes in tandem

    International Nuclear Information System (INIS)

    Periodic vortex shedding from two surface-mounted cubes, of height H, in tandem arrangement placed in a thin boundary layer is investigated for a spacing 2H using phase-averaged Laser Doppler Velocimetry. Tests were conducted for a Reynolds number of 22,000, based on H and the freestream velocity, and an approximately 0.07H thick laminar boundary layer. For obstacle separations between 1.5H and 2.5H, the shedding frequency scales inversely with the obstacle spacing, S, such that the Strouhal number based on S is constant or geometrically locked. In this locked regime, periodic shedding is triggered by the interference between a vertical flow stream along the front face of the downstream obstacle and the vortex in the inter-obstacle cavity. This three-dimensional mechanism is not observed for two-dimensional geometries and helps explain why a locked regime cannot be observed for square cylinders in tandem arrangement. Furthermore, it is shown that the structure of the turbulent field in the cavity region differs significantly from that in the base region of a two-dimensional obstacle

  1. Globally shed wakes for three distinct retracting foil geometries

    Science.gov (United States)

    Steele, Stephanie; Triantafyllou, Michael

    2015-11-01

    In quickly retracting foils at an angle of attack, the boundary layer vorticity along with the added mass energy is immediately and globally shed from the body into the surrounding fluid. The deposited vorticity quickly reforms into lasting vortex structures, which could be used for purposes such as manipulating or exploiting the produced flow structures by additional bodies in the fluid. The globally shed wake thus entrains the added mass energy provided by the initially moving body, reflected by the value of the circulation left in the wake. In studying experimentally as well as numerically this phenomenon, we find that the three different tested geometries leave behind distinct wakes. Retracting a square-ended foil is undesirable because the deposited wake is complicated by three-dimensional ring vorticity effects. Retracting a tapered, streamlined-tipped foil is also undesirable because the shape-changing aspect of the foil geometry actually induces energy recovery back to the retracting foil, leaving a less energetic globally shed wake. Finally, a retracting hollow foil geometry avoids both of these detrimental effects, leaving relatively simple, yet energetic, vortex structures in the wake.

  2. A CD46-binding chimpanzee adenovirus vector as a vaccine carrier.

    Science.gov (United States)

    Tatsis, Nia; Blejer, Ariella; Lasaro, Marcio O; Hensley, Scott E; Cun, Ann; Tesema, Lello; Li, Yan; Gao, Guang-Ping; Xiang, Zhi Q; Zhou, Dongming; Wilson, James M; Ertl, Hildegund C J

    2007-03-01

    A replication-defective chimeric vector based on the chimpanzee adenovirus serotype C1 was developed and tested as a vaccine carrier in mice. The AdC1 virus is closely related to human adenoviruses of subgroup B2 and uses CD46 for cell attachment. To overcome poor growth of E1-deleted AdC1 vectors on cell lines that provide the E1 of adenovirus of the human serotype 5 (AdHu5) virus in trans, the inverted terminal repeats and some of the early genes of AdC1 were replaced with those from AdC5, a chimpanzee origin adenovirus of subfamily E. The chimeric AdC1/C5 vector efficiently transduces CD46-expressing mouse dendritic cells (DCs) in vitro and initiates their maturation. Transduction of DCs in vivo is inefficient in CD46 transgenic mice. The AdC1/C5 vector induces transgene product-specific B- and CD8(+) T-cell responses in mice. Responses are slightly higher in wild-type mice than in CD46 transgenic mice. Transgene product-specific T-cell responses elicited by the AdC1/C5 vector can be increased by priming or boosting with a heterologous adenovirus vector. Pre-existing immunity to adenovirus of the common human serotype 5 does not affect induction of cell-mediated immune responses by the AdC1/C5 vector. This vector provides an additional tool in a repertoire of adenovirus-based vaccine vectors. PMID:17228314

  3. Persistent Hiccups Following Stapedectomy

    Directory of Open Access Journals (Sweden)

    Aidonis I

    2010-10-01

    Full Text Available Objective: We report a case of a 37 year-old man who developed persistent hiccups after elective stapedectomy. Method and Results: The diagnostic approach is discussed as well as the non-pharmacologic and pharmacologic treatments and overall management. The aim is to stress that there is a variety of potential factors that can induce hiccups perioperatively and in cases like this a step by step approach must be taken. Conclusion: Persistent hiccups are very rare following stapedectomy, control of them is crucial for the successful outcome. The trigger may be more than one factors and the good response to treatment may be due to dealing successfully with more than one thing.

  4. Genetic and Molecular Epidemiological Characterization of a Novel Adenovirus in Antarctic Penguins Collected between 2008 and 2013

    Science.gov (United States)

    Lee, Sook-Young; Kim, Jeong-Hoon; Seo, Tae-Kun; No, Jin Sun; Kim, Hankyeom; Kim, Won-keun; Choi, Han-Gu; Kang, Sung-Ho; Song, Jin-Won

    2016-01-01

    Antarctica is considered a relatively uncontaminated region with regard to the infectious diseases because of its extreme environment, and isolated geography. For the genetic characterization and molecular epidemiology of the newly found penguin adenovirus in Antarctica, entire genome sequencing and annual survey of penguin adenovirus were conducted. The entire genome sequences of penguin adenoviruses were completed for two Chinstrap penguins (Pygoscelis antarctica) and two Gentoo penguins (Pygoscelis papua). The whole genome lengths and G+C content of penguin adenoviruses were found to be 24,630–24,662 bp and 35.5–35.6%, respectively. Notably, the presence of putative sialidase gene was not identified in penguin adenoviruses by Rapid Amplification of cDNA Ends (RACE-PCR) as well as consensus specific PCR. The penguin adenoviruses were demonstrated to be a new species within the genus Siadenovirus, with a distance of 29.9–39.3% (amino acid, 32.1–47.9%) in DNA polymerase gene, and showed the closest relationship with turkey adenovirus 3 (TAdV-3) in phylogenetic analysis. During the 2008–2013 study period, the penguin adenoviruses were annually detected in 22 of 78 penguins (28.2%), and the molecular epidemiological study of the penguin adenovirus indicates a predominant infection in Chinstrap penguin population (12/30, 40%). Interestingly, the genome of penguin adenovirus could be detected in several internal samples, except the lymph node and brain. In conclusion, an analysis of the entire adenoviral genomes from Antarctic penguins was conducted, and the penguin adenoviruses, containing unique genetic character, were identified as a new species within the genus Siadenovirus. Moreover, it was annually detected in Antarctic penguins, suggesting its circulation within the penguin population. PMID:27309961

  5. Genetic and Molecular Epidemiological Characterization of a Novel Adenovirus in Antarctic Penguins Collected between 2008 and 2013.

    Directory of Open Access Journals (Sweden)

    Sook-Young Lee

    Full Text Available Antarctica is considered a relatively uncontaminated region with regard to the infectious diseases because of its extreme environment, and isolated geography. For the genetic characterization and molecular epidemiology of the newly found penguin adenovirus in Antarctica, entire genome sequencing and annual survey of penguin adenovirus were conducted. The entire genome sequences of penguin adenoviruses were completed for two Chinstrap penguins (Pygoscelis antarctica and two Gentoo penguins (Pygoscelis papua. The whole genome lengths and G+C content of penguin adenoviruses were found to be 24,630-24,662 bp and 35.5-35.6%, respectively. Notably, the presence of putative sialidase gene was not identified in penguin adenoviruses by Rapid Amplification of cDNA Ends (RACE-PCR as well as consensus specific PCR. The penguin adenoviruses were demonstrated to be a new species within the genus Siadenovirus, with a distance of 29.9-39.3% (amino acid, 32.1-47.9% in DNA polymerase gene, and showed the closest relationship with turkey adenovirus 3 (TAdV-3 in phylogenetic analysis. During the 2008-2013 study period, the penguin adenoviruses were annually detected in 22 of 78 penguins (28.2%, and the molecular epidemiological study of the penguin adenovirus indicates a predominant infection in Chinstrap penguin population (12/30, 40%. Interestingly, the genome of penguin adenovirus could be detected in several internal samples, except the lymph node and brain. In conclusion, an analysis of the entire adenoviral genomes from Antarctic penguins was conducted, and the penguin adenoviruses, containing unique genetic character, were identified as a new species within the genus Siadenovirus. Moreover, it was annually detected in Antarctic penguins, suggesting its circulation within the penguin population.

  6. An annoying persistent cough

    OpenAIRE

    Francesco Cipollini

    2007-01-01

    Chronic cough is a stressful condition and can lead to extensive investigations. We report a case of a 48-year-old woman who had suffered from persistent chronic cough for more than 3 months. She had been treated with cough suppressant. However, her cough was not alleviated by these treatments, and the patient was referred to our hospital. She did not exhibit typical gastroesophageal reflux disease (GERD) symptoms heartburn and regurgitation. Esophagoscopy did not disclose reflux esophagitis....

  7. Intergenerational Top Income Persistence

    DEFF Research Database (Denmark)

    Munk, Martin D.; Bonke, Jens; Hussain, M. Azhar

    2016-01-01

    In this paper, we investigate intergenerational top earnings and top income mobility in Denmark. Access to administrative registers allowed us to look at very small fractions of the population. We find that intergenerational mobility is lower in the top when including capital income in the income...... measure— for the rich top 0.1% fathers and sons the elasticity is 0.466. Compared with Sweden, however, the intergenerational top income persistence is about half the size in Denmark....

  8. Persistence in corporate networks

    OpenAIRE

    Milaković, Mishael; Raddant, Matthias; Birg, Laura

    2014-01-01

    We examine the bipartite graphs of German corporate boards in 1993, 1999 and 2005, and identify cores of directors who are highly central in the entire network while being densely connected among themselves. The novel feature of this paper is the focus on the dynamics of these networks. Germany's corporate governance has experienced significant changes during this time, and there is substantial turnover in the identity of core members, yet we observe the persistent presence of a network core,...

  9. Detection and Analysis of Six Lizard Adenoviruses by Consensus Primer PCR Provides Further Evidence of a Reptilian Origin for the Atadenoviruses

    OpenAIRE

    Wellehan, James F. X.; Johnson, April J.; Harrach, Balázs; Benkö, Mária; Pessier, Allan P.; Johnson, Calvin M.; Garner, Michael M.; Childress, April; Jacobson, Elliott R.

    2004-01-01

    A consensus nested-PCR method was designed for investigation of the DNA polymerase gene of adenoviruses. Gene fragments were amplified and sequenced from six novel adenoviruses from seven lizard species, including four species from which adenoviruses had not previously been reported. Host species included Gila monster, leopard gecko, fat-tail gecko, blue-tongued skink, Tokay gecko, bearded dragon, and mountain chameleon. This is the first sequence information from lizard adenoviruses. Phyloge...

  10. Genomic and Bioinformatics Analysis of HAdV-4, a Human Adenovirus Causing Acute Respiratory Disease: Implications for Gene Therapy and Vaccine Vector Development

    OpenAIRE

    Purkayastha, Anjan; Ditty, Susan E.; Su, Jing; McGraw, John; Hadfield, Ted L.; Tibbetts, Clark; Seto, Donald

    2005-01-01

    Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and...

  11. Comparative study of adenoviruses with monoclonal antibodies Estudo comparativo de diferentes tipos de adenovirus através de anticorpos monoclonais

    Directory of Open Access Journals (Sweden)

    Terezinha Maria de Paiva

    1992-02-01

    Full Text Available The obtainment of monoclonal antibodies for adenovirus species 4(Ad4 is described.The specificities of selected monoclonal antibodies were determined by means of viral neutralization test in cell culture, immunofluorescence and Enzyme-Linked Immunosorbent Assay (ELISA, in the presence of the following species of human adenovirus: 1, 2, 5 (subgenus C, 4 (subgenus E, 7 and 16 (subgenus B and 9 (subgenus D. Two monoclonal antibodies species specific to adenovirus 4 (1CIII and 3DIII and one monoclonal antibody that cross reacted with adenovirus species 4 and 7 (2HIII were obtained.O estudo relata a obtenção de anticorpos monoclonais para o adenovirus tipo (espécie 4. A especificidade dos anticorpos monoclonais, selecionados nesse experimento, foi determinada testando-os frente às diferentes espécies de adenovírus: 1, 2, 5 (subgênero C, 4 (subgênero E, 7 e 16 (subgênero B e 9 (subgênero D, pelas técnicas de neutralização em cultura de células, imunofluorescência e ensaio imunoenzimático (ELISA. Os resultados demonstram a obtenção de anticorpos monoclonais que reagiram de maneira específica para o adenovírus 4 (1CIII e 3DIII e anticorpo monoclonal apresentando reação cruzada com as espécies de adenovírus 4 e 7 (2HIII.

  12. Isoform-specific regulation and localization of the coxsackie and adenovirus receptor in human airway epithelia.

    Directory of Open Access Journals (Sweden)

    Katherine J D A Excoffon

    Full Text Available Adenovirus is an important respiratory pathogen. Adenovirus fiber from most serotypes co-opts the Coxsackie-Adenovirus Receptor (CAR to bind and enter cells. However, CAR is a cell adhesion molecule localized on the basolateral membrane of polarized epithelia. Separation from the lumen of the airways by tight junctions renders airway epithelia resistant to inhaled adenovirus infection. Although a role for CAR in viral spread and egress has been established, the mechanism of initial respiratory infection remains controversial. CAR exists in several protein isoforms including two transmembrane isoforms that differ only at the carboxy-terminus (CAR(Ex7 and CAR(Ex8. We found low-level expression of the CAR(Ex8 isoform in well-differentiated human airway epithelia. Surprisingly, in contrast to CAR(Ex7, CAR(Ex8 localizes to the apical membrane of epithelia where it augments adenovirus infection. Interestingly, despite sharing a similar class of PDZ-binding domain with CAR(Ex7, CAR(Ex8 differentially interacts with PICK1, PSD-95, and MAGI-1b. MAGI-1b appears to stoichiometrically regulate the degradation of CAR(Ex8 providing a potential mechanism for the apical localization of CAR(Ex8 in airway epithelial. In summary, apical localization of CAR(Ex8 may be responsible for initiation of respiratory adenoviral infections and this localization appears to be regulated by interactions with PDZ-domain containing proteins.

  13. Expression of adenovirus-mediated neurotrophin-3 gene in Schwann cells of sciatic nerve in rats

    Institute of Scientific and Technical Information of China (English)

    朱锦宇; 黄耀添; 朱庆生; 吕荣

    2003-01-01

    Objective: To investigate the expression of neurotrophin-3 (NT-3) gene in Schwann cells of rat sciatic nerve introduced by an adenovirus vector in vivo. Methods: A recombinant adenovirus vector for NT-3 (Ad-NT-3) was propagated in 293 packaging cells and titered with tissue culture infectious dose50 (TCID50). Ad-NT-3 was injected directly into the rat sciatic nerve after transection and immediate repair. Immunohistochemical staining was employed to determine the expression of NT-3 in Schwann cells in rat sciatic nerve and the expressive intensity of the tissue slices of the sciatic nerve was measured with LEICA M550 image analysis system. Results: On the 2nd day after injection of Ad-NT-3, positive stain in the Schwann cells was apparent in the vicinity of anastomosis. NT-3 expression increased significantly on the 7th day (P0.05). Compared with the 2nd day group, the 14th and 28th day groups still maintained a relatively high level of NT-3 (P<0.01). Intact and repaired nerves, which were injected with adenovirus encoding LacZ genes (Ad-LacZ) or physiological saline served as controls, showed no NT-3-positive Schwann cells. Conclusions: An adenovirus vector can be used to induce efficiently the expression of NT-3 gene in Schwann cells of rat peripheral nerves following nerve injury and repair, which suggests that neurotrophic factors can be introduced into Schwann cells with an adenovirus vector to promote peripheral nerve regeneration.

  14. Technical aspects of using human adenovirus as a viral water quality indicator.

    Science.gov (United States)

    Rames, Emily; Roiko, Anne; Stratton, Helen; Macdonald, Joanne

    2016-06-01

    Despite dramatic improvements in water treatment technologies in developed countries, waterborne viruses are still associated with many of cases of illness each year. These illnesses include gastroenteritis, meningitis, encephalitis, and respiratory infections. Importantly, outbreaks of viral disease from waters deemed compliant from bacterial indicator testing still occur, which highlights the need to monitor the virological quality of water. Human adenoviruses are often used as a viral indicator of water quality (faecal contamination), as this pathogen has high UV-resistance and is prevalent in untreated domestic wastewater all year round, unlike enteroviruses and noroviruses that are often only detected in certain seasons. Standard methods for recovering and measuring adenovirus numbers in water are lacking, and there are many variations in published methods. Since viral numbers are likely under-estimated when optimal methods are not used, a comprehensive review of these methods is both timely and important. This review critically evaluates how estimates of adenovirus numbers in water are impacted by technical manipulations, such as during adenovirus concentration and detection (including culturing and polymerase-chain reaction). An understanding of the implications of these issues is fundamental to obtaining reliable estimation of adenovirus numbers in water. Reliable estimation of HAdV numbers is critical to enable improved monitoring of the efficacy of water treatment processes, accurate quantitative microbial risk assessment, and to ensure microbiological safety of water. PMID:27065054

  15. Nitrogen Gas Plasma Generated by a Static Induction Thyristor as a Pulsed Power Supply Inactivates Adenovirus.

    Science.gov (United States)

    Sakudo, Akikazu; Toyokawa, Yoichi; Imanishi, Yuichiro

    2016-01-01

    Adenovirus is one of the most important causative agents of iatrogenic infections derived from contaminated medical devices or finger contact. In this study, we investigated whether nitrogen gas plasma, generated by applying a short high-voltage pulse to nitrogen using a static induction thyristor power supply (1.5 kilo pulse per second), exhibited a virucidal effect against adenoviruses. Viral titer was reduced by one log within 0.94 min. Results from detection of viral capsid proteins, hexon and penton, by Western blotting and immunochromatography were unaffected by the plasma treatment. In contrast, analysis using the polymerase chain reaction suggested that plasma treatment damages the viral genomic DNA. Reactive chemical products (hydrogen peroxide, nitrate, and nitrite), ultraviolet light (UV-A) and slight temperature elevations were observed during the operation of the gas plasma device. Viral titer versus intensity of each potential virucidal factor were used to identify the primary mechanism of disinfection of adenovirus. Although exposure to equivalent levels of UV-A or heat treatment did not inactivate adenovirus, treatment with a relatively low concentration of hydrogen peroxide efficiently inactivated the virus. Our results suggest the nitrogen gas plasma generates reactive chemical products that inactivate adenovirus by damaging the viral genomic DNA.

  16. Recombinant adenovirus of human p66Shc inhibits MCF-7 cell proliferation.

    Science.gov (United States)

    Yang, Xiaoshan; Xu, Rong; Lin, Yajun; Zhen, Yongzhan; Wei, Jie; Hu, Gang; Sun, Hongfan

    2016-01-01

    The aim of this work was to construct a human recombinant p66Shc adenovirus and to investigate the inhibition of recombinant p66Shc adenovirus on MCF-7 cells. The recombinant adenovirus expression vector was constructed using the Adeno-X Adenoviral System 3. Inhibition of MCF-7 cell proliferation was determined by MTT. Intracellular ROS was measured by DCFH-DA fluorescent probes, and 8-OHdG was detected by ELISA. Cell apoptosis and the cell cycle were assayed by flow cytometry. Western blot were used to observe protein expression. p66Shc expression was upregulated in 4 cell lines after infection. The inhibitory effect of p66Shc recombinant adenovirus on MCF-7 cells was accompanied by enhanced ROS and 8-OHdG. However, no significant differences were observed in the cell apoptosis rate. The ratio of the cell cycle G2/M phase showed a significant increase. Follow-up experiments demonstrated that the expressions of p53, p-p53, cyclin B1 and CDK1 were upregulated with the overexpression of p66Shc. The Adeno-X Adenoviral System 3 can be used to efficiently construct recombinant adenovirus containing p66Shc gene, and the Adeno-X can inhibit the proliferation of MCF-7 cells by inducing cell cycle arrest at the G2/M phase. These results suggested that p66Shc may be a key target for clinical cancer therapy. PMID:27530145

  17. Nitrogen Gas Plasma Generated by a Static Induction Thyristor as a Pulsed Power Supply Inactivates Adenovirus.

    Science.gov (United States)

    Sakudo, Akikazu; Toyokawa, Yoichi; Imanishi, Yuichiro

    2016-01-01

    Adenovirus is one of the most important causative agents of iatrogenic infections derived from contaminated medical devices or finger contact. In this study, we investigated whether nitrogen gas plasma, generated by applying a short high-voltage pulse to nitrogen using a static induction thyristor power supply (1.5 kilo pulse per second), exhibited a virucidal effect against adenoviruses. Viral titer was reduced by one log within 0.94 min. Results from detection of viral capsid proteins, hexon and penton, by Western blotting and immunochromatography were unaffected by the plasma treatment. In contrast, analysis using the polymerase chain reaction suggested that plasma treatment damages the viral genomic DNA. Reactive chemical products (hydrogen peroxide, nitrate, and nitrite), ultraviolet light (UV-A) and slight temperature elevations were observed during the operation of the gas plasma device. Viral titer versus intensity of each potential virucidal factor were used to identify the primary mechanism of disinfection of adenovirus. Although exposure to equivalent levels of UV-A or heat treatment did not inactivate adenovirus, treatment with a relatively low concentration of hydrogen peroxide efficiently inactivated the virus. Our results suggest the nitrogen gas plasma generates reactive chemical products that inactivate adenovirus by damaging the viral genomic DNA. PMID:27322066

  18. Characterizing clearance of helper adenovirus by a clinical rAAV1 manufacturing process.

    Science.gov (United States)

    Thorne, Barbara A; Quigley, Paulene; Nichols, Gina; Moore, Christine; Pastor, Eric; Price, David; Ament, Jon W; Takeya, Ryan K; Peluso, Richard W

    2008-01-01

    Recombinant adeno-associated viral vectors (rAAV) are being developed as gene therapy delivery vehicles and as genetic vaccines, and some of the most scaleable manufacturing methods for rAAV use live adenovirus to induce production. One aspect of establishing safety of rAAV products is therefore demonstrating adequate and reliable clearance of this helper virus by the vector purification process. The ICH Q5A regulatory guidance on viral safety provides recommendations for process design and characterization of viral clearance for recombinant proteins, and these principles were adapted to a rAAV serotype 1 purification process for clinical vectors. Specific objectives were to achieve overall adenovirus clearance factors significantly greater than input levels by using orthogonal separation and inactivation methods, and to segregate adenovirus from downstream operations by positioning a robust clearance step early in the process. Analytical tools for process development and characterization addressed problematic in-process samples, and a viral clearance validation study was performed using adenovirus and two non-specific model viruses. Overall clearance factors determined were >23 LRV for adenovirus, 11 LRV for BVDV, and >23 LRV for AMuLV.

  19. On URL and content persistence

    OpenAIRE

    Gomes, Daniel; Silva, Mário J

    2005-01-01

    This report presents a study of URL and content persistence among 51 million pages from a national web harvested 8 times over almost 3 years. This study differs from previous ones because it describes the evolution of a large set of web pages for several years, studying in depth the characteristics of persistent data. We found that the persistence of URLs and contents follows a logarithmic distribution. We characterized persistent URLs and contents, and identified reasons for URL death. We fo...

  20. Poverty persistence and poverty dynamics

    OpenAIRE

    Biewen, Martin

    2014-01-01

    A considerable part of the poverty that is measured in a single period is transitory rather than persistent. In most countries, only a portion of people who are currently poor are persistently poor. People who are persistently poor or who cycle into and out of poverty should be the main focus of anti-poverty policies. Understanding the characteristics of the persistently poor, and the circumstances and mechanisms associated with entry into and exit from poverty, can help to inform governments...

  1. 'Inflation Targeting and Inflation Persistence'

    OpenAIRE

    George J. Bratsiotis; Jakob Madsen; Christopher Martin

    2015-01-01

    This paper argues that the adoption of an inflation target reduces the persistence of inflation. We develop the theoretical literature on inflation persistence by introducing a Taylor rule for monetary policy into a model of persistence and showing that inflation targets reduce inflation persistence. We investigate changes in the time series properties of inflation in seven countries that introduced inflation targets in the late 1980s or early 1990s. We find that the persistenc...

  2. Characterization of fastidious adenovirus types 40 and 41 by DNA restriction enzyme analysis and by neutralizing monoclonal antibodies.

    NARCIS (Netherlands)

    H.G.A.M. van der Avoort (Harrie); A.G. Wermenbol; T.P.L. Zomerdijk (Timo); J.A.F.W. Kleijne; J.A.A.M. van Asten (Jack); P. Jensma; A.D.M.E. Osterhaus (Ab); A.H. Kidd; J.C. de Jong (Jan)

    1989-01-01

    textabstractThe DNA of 48 strains of adenovirus type 40 (Ad40) and of 128 strains of adenovirus type 41 (Ad41), isolated between 1971 and 1986 from various countries, was characterized by restriction enzyme analysis using nine and ten restriction endonucleases respectively. Five new DNA variants of

  3. Fiber-chimeric adenoviruses expressing fibers from serotype 16 and 50 improve gene transfer to human pancreatic adenocarcinoma

    NARCIS (Netherlands)

    Kuhlmann, K.F.D.; Geer, M.A. van; Bakker, C.T.; Dekker, J.E.M.; Havenga, M.J.E.; Oude Elferink, R.P.J.; Gouma, D.J.; Bosma, P.J.; Wesseling, J.G.

    2009-01-01

    Survival of patients with pancreatic cancer is poor. Adenoviral (Ad) gene therapy employing the commonly used serotype 5 reveals limited transduction efficiency due to the low amount of coxsackie-adenovirus receptor on pancreatic cancer cells. To identify fiber-chimeric adenoviruses with improved ge

  4. The photobinding of 5,7-dimethoxycoumarin to adenovirus type-2 DNA. A method for in vitro mutagenesis

    International Nuclear Information System (INIS)

    The photobinding of 5,7-dimethoxycoumarin to isolated adenovirus-type 2 DNA has been investigated with respect to the influence of the ionic environment, and varying molar ratios of DNAsub(p): 5,7-dimethyoxycoumarin. In particular, the ultraviolet radiation-induced covalent addition of 5,7-dimethoxycoumarin to adenovirus DNA was increased by reducing the concentration of Na+. The maximum photobinding of 5,7-[3H]dimethoxycoumarin to adenovirus DNA under the given ionic condition was one 5,7-dimethoxycoumarin per 101 nucleotides. Moreover, restriction enzyme analysis of the 5,7-dimethoxycoumarin-DNA photoadduct versus unmodified viral DNA, suggested that the sequence d(A-T) is the preferential site for intercalation and subsequent photobinding of 5,7-dimethoxycoumarin. This susceptibility of d(A-T) sequences to 5,7-dimethoxycoumarin interaction has a corresponding influence on the survival of adenovirus because of the A-T-rich sequences that occur in some of the early gene regions of the adenovirus genome. Specifically, 5,7-dimethoxycoumarin per 800 nucleotides in adenovirus DNA reduced the surviving fraction of adenovirus to a value of 0.1 after DNA infectivity (transfection) into human 293 cells. Results suggest that 5,7-dimethoxycoumarin may be used for generating a limited 'library' of mutations in each of the five early gene regions of the adenovirus genome. (Auth.)

  5. Recombinant adenovirus containing hyper-interleukin-6 and hepatocyte growth factor ameliorates acute-on-chronic liver failure in rats

    OpenAIRE

    Gao, Dan-Dan; Fu, Jia; Qin, Bo; Huang, Wen-Xiang; Yang, Chun; Jia, Bei

    2016-01-01

    AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF).

  6. BS69 : A novel adenovirus E1A-associated protein that inhibits E1A transactivation

    NARCIS (Netherlands)

    Hateboer, G.; Gennissen, A.M.C.; Ramos, Y.F.M.; Kerkhoven, R.; Sonntag-Buck, V.; Stunnenberg, H.G.; Bernards, R.A.

    1995-01-01

    The adenovirus ElA gene products are nuclear phosphoproteins that can transactivate the other adenovirus early genes as well as several cellular genes, and can transform primary rodent cells in culture. Transformation and transactivation by ElA proteins is most likely to be mediated through binding

  7. Application of mesenchymal stem cells as a vehicle to deliver replication-competent adenovirus for treating malignant glioma

    Institute of Scientific and Technical Information of China (English)

    Cui Hai; Yong-Min Jin; Wen-Biao Jin; Zhe-Zhu Han; Mei-Nv Cui; Xue-Zhe Piao; Xiong-Hu Shen; Song-Nan Zhang; Hong-Hua Sun

    2012-01-01

    Although gene therapy was regarded as a promising approach for glioma treatment,its therapeutic efficacy was often disappointing because of the lack of efficient drug delivery systems.Mesenchymal stem cells (MSCs) have been reported to have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy.Therefore,in this study,we attempted to treat glioma by using MSCs as a vehicle for delivering replication-competent adenovirus.We firstly compared the infectivity of type 3,type 5,and type 35 fiber-modified adenoviruses in MSCs.We also determined suitable adenovirus titer in vitro and then used this titer to analyze the ability of MSCs to deliver replication-competent adenovirus into glioma in vivo.Our results indicated that type 35 fiber-modified adenovirus showed higher infectivity than did naked type 3 or type 5 fiber-modified adenovirus.MSCs carrying replication-competent adenovirus significantly inhibited tumor growth in vivo compared with other control groups.In conclusion,MSCs are an effective vehicle that can successfully transport replication-competent adenovirus into glioma,making it a potential therapeutic strategy for treating malignant glioma.

  8. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  9. Prevalence of neutralising antibodies against adenoviruses in lizards and snakes.

    Science.gov (United States)

    Ball, Inna; Ofner, Sabine; Funk, Richard S; Griffin, Chris; Riedel, Ulf; Möhring, Jens; Marschang, Rachel E

    2014-10-01

    Adenoviruses (AdVs) are relatively common in lizards and snakes, and several genetically distinct AdVs have been isolated in cell culture. The aims of this study were to examine serological relationships among lizard and snake AdVs and to determine the frequency of AdV infections in these species. Isolates from a boa constrictor (Boa constrictor), a corn snake (Pantherophis gutattus) and a central bearded dragon (Pogona vitticeps), and two isolates from helodermatid lizards (Heloderma horridum and H. suspectum) were used in neutralisation tests for the detection of antibodies in plasma from 263 lizards from seven families (including 12 species) and from 141 snakes from four families (including 28 species) from the USA and Europe. Most lizard and snake samples had antibodies against a range of AdV isolates, indicating that AdV infection is common among these squamates. Neutralisation tests with polyclonal antibodies raised in rabbits demonstrated serological cross-reactivity between both helodermatid lizard isolates. However, squamate plasma showed different reactions to each of these lizard isolates in neutralisation tests. PMID:25163614

  10. Non-classical export of an adenovirus structural protein.

    Science.gov (United States)

    Trotman, Lloyd C; Achermann, Dominik P; Keller, Stephan; Straub, Monika; Greber, Urs F

    2003-06-01

    The icosahedral capsids of Adenoviruses (Ads) consist of the hexon and stabilizing proteins building the facettes, and of the vertex protein penton base (Pb) anchoring the protruding fibers. The fibers bind to the Coxsackie virus B Ad cell surface receptor (CAR) and Pb to integrins. Here we describe a novel property of the Ad2 Pb. Pb was found to leave the infected cell and, upon exit, it attached to the surrounding noninfected cells forming a radial gradient with highest Pb levels on cells adjacent to the infected cell. The producer cells remained intact until at least 30 h post infection. At this point, Pb was not recovered from the extracellular medium, suggesting that its cell-cell spread might not involve free Pb. When viral particles were released at late stages of infection, soluble Pb was found in the extracellular medium and it randomly bound to noninfected cells. Nonlytic export of Pb occurred upon transient transfection with plasmid DNA, but plasmid-encoded fiber was not exported, indicating that cell-cell spread of Pb is autonomous of infection. Pb export was not affected by Brefeldin A-induced disruption of the Golgi apparatus, suggesting that it occurred via a nonclassical mechanism. Interestingly, the coexpression of Pb and fiber leads to both Pb and fiber export, termed 'protein abduction'. We suggest that fiber abduction might support viral dissemination in infected tissues by interfering with tissue integrity.

  11. Prevalence of neutralising antibodies against adenoviruses in lizards and snakes.

    Science.gov (United States)

    Ball, Inna; Ofner, Sabine; Funk, Richard S; Griffin, Chris; Riedel, Ulf; Möhring, Jens; Marschang, Rachel E

    2014-10-01

    Adenoviruses (AdVs) are relatively common in lizards and snakes, and several genetically distinct AdVs have been isolated in cell culture. The aims of this study were to examine serological relationships among lizard and snake AdVs and to determine the frequency of AdV infections in these species. Isolates from a boa constrictor (Boa constrictor), a corn snake (Pantherophis gutattus) and a central bearded dragon (Pogona vitticeps), and two isolates from helodermatid lizards (Heloderma horridum and H. suspectum) were used in neutralisation tests for the detection of antibodies in plasma from 263 lizards from seven families (including 12 species) and from 141 snakes from four families (including 28 species) from the USA and Europe. Most lizard and snake samples had antibodies against a range of AdV isolates, indicating that AdV infection is common among these squamates. Neutralisation tests with polyclonal antibodies raised in rabbits demonstrated serological cross-reactivity between both helodermatid lizard isolates. However, squamate plasma showed different reactions to each of these lizard isolates in neutralisation tests.

  12. Magnesium-Dependent Interaction of PKR with Adenovirus VAI

    Energy Technology Data Exchange (ETDEWEB)

    K Launer -Felty; C Wong; A Wahid; G Conn; J Cole

    2011-12-31

    Protein kinase R (PKR) is an interferon-induced kinase that plays a pivotal role in the innate immunity pathway for defense against viral infection. PKR is activated to undergo autophosphorylation upon binding to RNAs that contain duplex regions. Activated PKR phosphorylates the {alpha}-subunit of eukaryotic initiation factor 2, thereby inhibiting protein synthesis in virus-infected cells. Viruses have evolved diverse PKR-inhibitory strategies to evade the antiviral response. Adenovirus encodes virus-associated RNA I (VAI), a highly structured RNA inhibitor that binds PKR but fails to activate. We have characterized the stoichiometry and affinity of PKR binding to define the mechanism of PKR inhibition by VAI. Sedimentation velocity and isothermal titration calorimetry measurements indicate that PKR interactions with VAI are modulated by Mg{sup 2+}. Two PKR monomers bind in the absence of Mg{sup 2+}, but a single monomer binds in the presence of divalent ion. Known RNA activators of PKR are capable of binding multiple PKR monomers to allow the kinase domains to come into close proximity and thus enhance dimerization. We propose that VAI acts as an inhibitor of PKR because it binds and sequesters a single PKR in the presence of divalent cation.

  13. ADENOVIRUS-MEDIATED WILD-TYPE P53 EXPRESSION SUPPRESSES GROWTH OF LUNG ADENOCARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    Li Jian; Xia Yongjing; Jiang Lei; Li Hongxia; Hu Yajun; Yi Lin; Hu Shixue; Xu Hongji

    1998-01-01

    Objective: To study the growth suppression of lung adenocarcinoma cell by the introduction of wild-type P53gene and explore a gene therapy approach for lung adenocarcinoma. Methods: A replication-deficient adenovirus vector encoding a wild-type P53 was constructed and transfected into the cultured human lung adenocarcinoma cell line GLC-82. The efficiency of gene transfection and expression was detected by immunochemical staining and polymerase chain reaction. The cell growth rate and cell cycle were analysed by cell-counting and flow cytometry. Results: Wild-type P53 gene could be quickly and effectively transfected into the cells by adenovirus vector. Wild-type P53 expression could inhibit GLC-82 cell proliferation and induce apoptosis.Conclusion: The results indicated that recombinant adenovirus expressing wild-type P53 might be useful vector for gene therapy of human lung adenocarcinoma.

  14. Protection of non-human primates against rabies with an adenovirus recombinant vaccine

    International Nuclear Information System (INIS)

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protects against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus

  15. Adenovirus-mediated transfection with glucose transporter 3 suppresses PC12 cell apoptosis following ischemic injury

    Institute of Scientific and Technical Information of China (English)

    Junliang Li; Xinke Xu; Shanyi Zhang; Meiguang Zheng; Zhonghua Wu; Yinlun Weng; Leping Ouyang; Jian Yu; Fangcheng Li

    2012-01-01

    In this study, we investigated the effects of adenovirus-mediated transfection of PC12 cells with glucose transporter 3 after ischemic injury. The results of flow cytometry and TUNEL showed that exogenous glucose transporter 3 significantly suppressed PC12 cell apoptosis induced by ischemic injury. The results of isotopic scintiscan and western blot assays showed that, the glucose uptake rate was significantly increased and nuclear factor kappaB expression was significantly decreased after adenovirus-mediated transfection of ischemic PC12 cells with glucose transporter 3. These results suggest that adenovirus-mediated transfection of cells with glucose transporter 3 elevates the energy metabolism of PC12 cells with ischemic injury, and inhibits cell apoptosis.

  16. Mislocalization of the MRN complex prevents ATR signaling during adenovirus infection

    DEFF Research Database (Denmark)

    Carson, Christian T; Orazio, Nicole I; Lee, Darwin V;

    2009-01-01

    replication centres, but there is minimal ATR activation. We show that the Mre11/Rad50/Nbs1 (MRN) complex is recruited to viral centres only during infection with adenoviruses lacking the early region E4 and ATR signaling is activated. This suggests a novel requirement for the MRN complex in ATR activation......The protein kinases ataxia-telangiectasia mutated (ATM) and ATM-Rad3 related (ATR) are activated in response to DNA damage, genotoxic stress and virus infections. Here we show that during infection with wild-type adenovirus, ATR and its cofactors RPA32, ATRIP and TopBP1 accumulate at viral...... for immobilization of the MRN complex and show that this prevents ATR signaling during adenovirus infection. We propose that immobilization of the MRN damage sensor by E4orf3 protein prevents recognition of viral genomes and blocks detrimental aspects of checkpoint signaling during virus infection....

  17. Crystal Structure of Human Adenovirus at 3.5 Å Resolution

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Vijay S.; Natchiar, S. Kundhavai; Stewart, Phoebe L.; Nemerow, Glen R. (Scripps); (Vanderbilt)

    2010-09-27

    Rational development of adenovirus vectors for therapeutic gene transfer is hampered by the lack of accurate structural information. Here, we report the x-ray structure at 3.5 angstrom resolution of the 150-megadalton adenovirus capsid containing nearly 1 million amino acids. We describe interactions between the major capsid protein (hexon) and several accessory molecules that stabilize the capsid. The virus structure also reveals an altered association between the penton base and the trimeric fiber protein, perhaps reflecting an early event in cell entry. The high-resolution structure provides a substantial advance toward understanding the assembly and cell entry mechanisms of a large double-stranded DNA virus and provides new opportunities for improving adenovirus-mediated gene transfer.

  18. Protection of non-human primates against rabies with an adenovirus recombinant vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Z.Q. [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Greenberg, L. [Centers for Disease Control and Prevention, Atlanta, GA (United States); Ertl, H.C., E-mail: ertl@wistar.upenn.edu [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Rupprecht, C.E. [The Global Alliance for Rabies Control, Manhattan, KS (United States); Ross University School of Veterinary Medicine, Basseterre (Saint Kitts and Nevis)

    2014-02-15

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protects against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus.

  19. Genetic and Antigenic Analysis of Adenovirus Type 3 Strains Showing Intermediate Behavior in Standard Seroneutralization Test

    Directory of Open Access Journals (Sweden)

    Márcia TB Moraes

    1998-03-01

    Full Text Available During an epidemiological survey of acute respiratory infection in Rio de Janeiro, among 208 adenovirus isolates, we found two strains that we were not able, by a standard neutralization procedure, to distinguish between type 3 or 7. However, DNA restriction pattern for the two strains with different enzymes were analyzed and showed a typical Ad3h profile. Using a cross-neutralization test in which both Ad3p and Ad7p antisera were used in different concentration against 100 TCID50 of each adenovirus standard and both isolates, we were able to confirm that the two isolates belong to serotype 3. An hemagglutination inhibition test also corroborated the identification of both strains as adenovirus type 3. Comparing Ad3h and Ad3p genome, we observed 16 different restriction enzyme sites, three of which were located in genomic regions encoding polypeptides involved in neutralization sites

  20. Inflation Targeting and Inflation Persistence

    Institute of Scientific and Technical Information of China (English)

    GEORGE; J.BRATSIOTIS; JAKOB; MADSEN; CHRISTOPHER; MARTIN

    2015-01-01

    This paper argues that the adoption of an inflation target reduces the persistence of inflation.We develop the theoretical literature on inflation persistence by introducing a Taylor Rule for monetary policy into a model of persistence and showing that inflation targets reduce inflation persistence.We investigate changes in the time series properties of inflation in seven countries that introduced inflation targets in the late 1980s or early 1990s.We find that the persistence of inflation is greatly reduced or eliminated following the introduction of inflation targets.

  1. Persistence of airline accidents.

    Science.gov (United States)

    Barros, Carlos Pestana; Faria, Joao Ricardo; Gil-Alana, Luis Alberiko

    2010-10-01

    This paper expands on air travel accident research by examining the relationship between air travel accidents and airline traffic or volume in the period from 1927-2006. The theoretical model is based on a representative airline company that aims to maximise its profits, and it utilises a fractional integration approach in order to determine whether there is a persistent pattern over time with respect to air accidents and air traffic. Furthermore, the paper analyses how airline accidents are related to traffic using a fractional cointegration approach. It finds that airline accidents are persistent and that a (non-stationary) fractional cointegration relationship exists between total airline accidents and airline passengers, airline miles and airline revenues, with shocks that affect the long-run equilibrium disappearing in the very long term. Moreover, this relation is negative, which might be due to the fact that air travel is becoming safer and there is greater competition in the airline industry. Policy implications are derived for countering accident events, based on competition and regulation.

  2. Hellbender genome sequences shed light on genomic expansion at the base of crown salamanders.

    Science.gov (United States)

    Sun, Cheng; Mueller, Rachel Lockridge

    2014-07-01

    Among animals, genome sizes range from 20 Mb to 130 Gb, with 380-fold variation across vertebrates. Most of the largest vertebrate genomes are found in salamanders, an amphibian clade of 660 species. Thus, salamanders are an important system for studying causes and consequences of genomic gigantism. Previously, we showed that plethodontid salamander genomes accumulate higher levels of long terminal repeat (LTR) retrotransposons than do other vertebrates, although the evolutionary origins of such sequences remained unexplored. We also showed that some salamanders in the family Plethodontidae have relatively slow rates of DNA loss through small insertions and deletions. Here, we present new data from Cryptobranchus alleganiensis, the hellbender. Cryptobranchus and Plethodontidae span the basal phylogenetic split within salamanders; thus, analyses incorporating these taxa can shed light on the genome of the ancestral crown salamander lineage, which underwent expansion. We show that high levels of LTR retrotransposons likely characterize all crown salamanders, suggesting that disproportionate expansion of this transposable element (TE) class contributed to genomic expansion. Phylogenetic and age distribution analyses of salamander LTR retrotransposons indicate that salamanders' high TE levels reflect persistence and diversification of ancestral TEs rather than horizontal transfer events. Finally, we show that relatively slow DNA loss rates through small indels likely characterize all crown salamanders, suggesting that a decreased DNA loss rate contributed to genomic expansion at the clade's base. Our identification of shared genomic features across phylogenetically distant salamanders is a first step toward identifying the evolutionary processes underlying accumulation and persistence of high levels of repetitive sequence in salamander genomes. PMID:25115007

  3. Efficient construction of recombinant adenovirus expression vector of the Qinchuan cattle LYRM1 gene.

    Science.gov (United States)

    Li, Y K; Fu, C Z; Zhang, Y R; Zan, L S

    2015-01-01

    In this study, we cloned the coding DNA sequence (CDS) region of Qinchuan cattle LYR motif-containing 1 (LYRM1) and constructed a recombinant adenovirus expression vector to examine the function of LYRM1 on the cellular level. Total RNA was extracted from the adipose tissue of Qinchuan cattle, cDNA was obtained by reverse transcription, and polymerase chain reaction was used to amplify the CDS region of the LYRM1 gene. The CDS-containing fragment was inserted into the shuttle vector pAdTrack-CMV to construct pAdTrack-CMV-LYRM1 vector. After linearization of pAdTrack-CMV-LYRM1 and the negative control vector pAdTrack-CMV by restriction endonuclease PmeI, the vectors were transformed into Escherichia coli BJ5183 containing pAdEasy-1 to obtain the recombinant adenovirus vector pAd-LYRM1 and pAd-CMV through homologous recombination. pAd-LYRM1 and pAd-CMV were then digested by PacI and transfected into the 293A cell line. The recombinant adenovirus Ad-LYRM1 and Ad-CMV was obtained at a concentration of 7 x 108 and 1.3 x 109 green fluorescent units/mL, respectively. Preadipocytes derived from Qinchuan cattle were separately infected with Ad-LYRM1 and Ad- CMV. Quantitative real-time polymerase chain reaction demonstrated that the expression of LYRM1 was increased by approximate 28,000-folds after the infection with recombinant adenovirus for 48 h. In conclusion, we successfully cloned the CDS region of the Qinchuan cattle LYRM1 gene, constructed the recombinant adenovirus expression vector, and obtained the adenovirus with high titer, providing valuable materials for studying the function of LYRM1 at the cellular level. PMID:26345880

  4. CCL21/IL21-armed oncolytic adenovirus enhances antitumor activity against TERT-positive tumor cells.

    Science.gov (United States)

    Li, Yang; Li, Yi-Fei; Si, Chong-Zhan; Zhu, Yu-Hui; Jin, Yan; Zhu, Tong-Tong; Liu, Ming-Yuan; Liu, Guang-Yao

    2016-07-15

    Multigene-armed oncolytic adenoviruses are capable of efficiently generating a productive antitumor immune response. The chemokine (C-C motif) ligand 21 (CCL21) binds to CCR7 on naïve T cells and dendritic cells (DCs) to promote their chemoattraction to the tumor and resultant antitumor activity. Interleukin 21 (IL21) promotes survival of naïve T cells while maintaining their CCR7 surface expression, which increases their capacity to transmigrate in response to CCL21 chemoattraction. IL21 is also involved in NK cell differentiation and B cell activation and proliferation. The generation of effective antitumor immune responses is a complex process dependent upon coordinated interactions of various subsets of effector cells. Using the AdEasy system, we aimed to construct an oncolytic adenovirus co-expressing CCL21 and IL21 that could selectively replicate in TERTp-positive tumor cells (Ad-CCL21-IL21 virus). The E1A promoter of these oncolytic adenoviruses was replaced by telomerase reverse transcriptase promoter (TERTp). Ad-CCL21-IL21 was constructed from three plasmids, pGTE-IL21, pShuttle-CMV-CCL21 and AdEasy-1 and was homologously recombined and propagated in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293, respectively. Our results showed that our targeted and armed oncolytic adenoviruses Ad-CCL21-IL21 can induce apoptosis in TERTp-positive tumor cells to give rise to viral propagation, in a dose-dependent manner. Importantly, we confirm that these modified oncolytic adenoviruses do not replicate efficiently in normal cells even under high viral loads. Additionally, we investigate the role of Ad-CCL21-IL21 in inducing antitumor activity and tumor specific cytotoxicity of CTLs in vitro. This study suggests that Ad-CCL21-IL21 is a promising targeted tumor-specific oncolytic adenovirus. PMID:27157859

  5. Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.

    Science.gov (United States)

    José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

  6. Bacterial persistence: a winning strategy?

    CERN Document Server

    Schinazi, Rinaldo B

    2011-01-01

    It has long been known that antibiotic treatment will not completely kill off a bacteria population. For many species a small fraction of bacteria is not sensitive to antibiotics. These bacteria are said to persist. Recently it has been shown that persistence is not a permanent state and that in fact a bacterium can switch back and forth between persistent and non persistent states. We introduce two stochastic models for bacteria persistence. In both models there are mass killings of non persistent bacteria at certain times. The first model has deterministic killing times and the second one has random killing times. Both models suggest that persistence may be a successful strategy for a wide range of parameter values.

  7. Detection and Analysis of Six Lizard Adenoviruses by Consensus Primer PCR Provides Further Evidence of a Reptilian Origin for the Atadenoviruses

    Science.gov (United States)

    Wellehan, James F. X.; Johnson, April J.; Harrach, Balázs; Benkö, Mária; Pessier, Allan P.; Johnson, Calvin M.; Garner, Michael M.; Childress, April; Jacobson, Elliott R.

    2004-01-01

    A consensus nested-PCR method was designed for investigation of the DNA polymerase gene of adenoviruses. Gene fragments were amplified and sequenced from six novel adenoviruses from seven lizard species, including four species from which adenoviruses had not previously been reported. Host species included Gila monster, leopard gecko, fat-tail gecko, blue-tongued skink, Tokay gecko, bearded dragon, and mountain chameleon. This is the first sequence information from lizard adenoviruses. Phylogenetic analysis indicated that these viruses belong to the genus Atadenovirus, supporting the reptilian origin of atadenoviruses. This PCR method may be useful for obtaining templates for initial sequencing of novel adenoviruses. PMID:15542689

  8. Detection and analysis of six lizard adenoviruses by consensus primer PCR provides further evidence of a reptilian origin for the atadenoviruses.

    Science.gov (United States)

    Wellehan, James F X; Johnson, April J; Harrach, Balázs; Benkö, Mária; Pessier, Allan P; Johnson, Calvin M; Garner, Michael M; Childress, April; Jacobson, Elliott R

    2004-12-01

    A consensus nested-PCR method was designed for investigation of the DNA polymerase gene of adenoviruses. Gene fragments were amplified and sequenced from six novel adenoviruses from seven lizard species, including four species from which adenoviruses had not previously been reported. Host species included Gila monster, leopard gecko, fat-tail gecko, blue-tongued skink, Tokay gecko, bearded dragon, and mountain chameleon. This is the first sequence information from lizard adenoviruses. Phylogenetic analysis indicated that these viruses belong to the genus Atadenovirus, supporting the reptilian origin of atadenoviruses. This PCR method may be useful for obtaining templates for initial sequencing of novel adenoviruses. PMID:15542689

  9. Detection of human adenoviruses in organic fresh produce using molecular and cell culture-based methods.

    Science.gov (United States)

    Marti, Elisabet; Barardi, Célia Regina Monte

    2016-08-01

    The consumption of organic fresh produce has increased in recent years due to consumer demand for healthy foods without chemical additives. However, the number of foodborne outbreaks associated with fresh produce has also increased. Contamination of food with enteric viruses is a major concern because the viruses have a low infectious dose and high persistence in the environment. Human adenovirus (HAdV) has been proposed as a good marker of faecal contamination. Therefore, the aim of this study was to evaluate the efficiency of the plaque assay (PA), real time PCR (qPCR) and integrated cell culture-RT-qPCR (ICC-RT-qPCR) for the recovery of HAdV from artificially and naturally contaminated fresh produce. Organic lettuce, strawberries and green onions were selected because these fresh products are frequently associated with foodborne outbreaks. The virus extraction efficiencies from artificially contaminated samples varied from 2.8% to 32.8% depending on the food matrix and the quantification method used. Although the HAdV recoveries determined by qPCR were higher than those determined by PA and ICC-RT-qPCR, PA was defined as the most reproducible method. The qPCR assays were more sensitive than the PA and ICC-RT-qPCR assays; however, this technique alone did not provide information about the viability of the pathogen. ICC-RT-qPCR was more sensitive than PA for detecting infectious particles in fresh produce samples. HAdV genome copies were detected in 93.3% of the analysed naturally contaminated samples, attesting to the common faecal contamination of the fresh produce tested. However, only 33.3% of the total samples were positive for infectious HAdV particles based on ICC-RT-qPCR. In conclusion, this study reported that HAdV can be an efficient viral marker for fresh produce contamination. Good detection of infectious HAdV was obtained with the ICC-RT-qPCR and PA assays. Thus, we suggest that the ICC-RT-qPCR and PA assays should be considered when quantitative

  10. Detection of human adenoviruses in organic fresh produce using molecular and cell culture-based methods.

    Science.gov (United States)

    Marti, Elisabet; Barardi, Célia Regina Monte

    2016-08-01

    The consumption of organic fresh produce has increased in recent years due to consumer demand for healthy foods without chemical additives. However, the number of foodborne outbreaks associated with fresh produce has also increased. Contamination of food with enteric viruses is a major concern because the viruses have a low infectious dose and high persistence in the environment. Human adenovirus (HAdV) has been proposed as a good marker of faecal contamination. Therefore, the aim of this study was to evaluate the efficiency of the plaque assay (PA), real time PCR (qPCR) and integrated cell culture-RT-qPCR (ICC-RT-qPCR) for the recovery of HAdV from artificially and naturally contaminated fresh produce. Organic lettuce, strawberries and green onions were selected because these fresh products are frequently associated with foodborne outbreaks. The virus extraction efficiencies from artificially contaminated samples varied from 2.8% to 32.8% depending on the food matrix and the quantification method used. Although the HAdV recoveries determined by qPCR were higher than those determined by PA and ICC-RT-qPCR, PA was defined as the most reproducible method. The qPCR assays were more sensitive than the PA and ICC-RT-qPCR assays; however, this technique alone did not provide information about the viability of the pathogen. ICC-RT-qPCR was more sensitive than PA for detecting infectious particles in fresh produce samples. HAdV genome copies were detected in 93.3% of the analysed naturally contaminated samples, attesting to the common faecal contamination of the fresh produce tested. However, only 33.3% of the total samples were positive for infectious HAdV particles based on ICC-RT-qPCR. In conclusion, this study reported that HAdV can be an efficient viral marker for fresh produce contamination. Good detection of infectious HAdV was obtained with the ICC-RT-qPCR and PA assays. Thus, we suggest that the ICC-RT-qPCR and PA assays should be considered when quantitative

  11. Post-Modernising the Museum: The Ration Shed

    Directory of Open Access Journals (Sweden)

    Carly Smith

    2014-06-01

    Full Text Available The application of postmodern critical theory to the essentially modernist construct of the museum has significantly impacted the role of the contemporary museum within society. This article briefly describes the movement toward a ‘new museology’ and the subsequent emergence of the ‘post-museum’. It then presents a case study of the Ration Shed Museum in the historical precinct of Cherbourg, Queensland, as an example of this new ‘post-museum’. Through its application of postmodern critical theory, the Ration Shed Museum has détourned the construct of the modernist museum and applied its cultural logics in order to meet the specific needs of its local community. This museum presents a history previously overlooked by western grand narratives and offers insight into a contemporary local indigenous community on its own terms. It presents a public pedagogy where the agency of both the viewer and the museum itself is embraced, and promotes active engagement – a form of dialogue – between the viewer, the community and the museum’s curators.

  12. Some effects of vortex shedding in grid-generated turbulence

    Science.gov (United States)

    Melina, Gianfrancesco; Bruce, Paul J. K.; Vassilicos, John Christos

    2015-11-01

    We perform hot-wire measurements in a wind tunnel downstream of different types of turbulence-generating grids: a regular grid (RG60), a fractal square grid (FSG17) and a single square grid (SSG). We characterize the flow highlighting similarities and differences between the grids and between the production and the decay regions of turbulence. We focus on the effects of vortex shedding from the bars of the grids. For this purpose we design a novel 3D configuration formed by the SSG and a set of four splitter plates detached from the grid. We show that, by placing the splitter plates, the peak of turbulence intensity on the centerline is reduced and its location is moved downstream. We compare data from the different turbulence generators and find that a reduction of vortex shedding energy correlates with an increase in the magnitudes of the skewness and flatness of the turbulent velocity fluctuations in the production region. The authors acknowledge support form the EU through the FP7 Marie Curie MULTISOLVE project (grant agreement No. 317269).

  13. Measurement on the cavitating vortex shedding behind rectangular obstacles

    Energy Technology Data Exchange (ETDEWEB)

    Hegedus, F; Hos, C; Pandula, Z; Kullmann, L, E-mail: hegedusf@hds.bme.h [Department of Hydrodynamic Systems, Budapest University of Technology and Economics Muegyetem rkp. 1, Budapest 1111 (Hungary)

    2010-08-15

    Measurement results on the cavitating vortex shedding behind sharp-edged rectangular bodies are presented, intended to provide benchmark cases for the validation of unsteady cavitation models of CFD codes. Rectangular bodies of increasing aspect ratio (1, 2, 3 and 4) were used with a constant 25mm height (12.5% blockage ratio). The water velocity in the 0.2x0.05m test section of the channel was varied between 1 and 12 m/s resulting in a Reynolds number in the range of (0.4-3.5)x105. Pressure signals were measured at several locations, notably in the wake. Dominant frequencies and Strouhal numbers are reported from cavitation-free flow (classic von Karman vortex shedding) up to supercavitation as a function of the free-stream Reynolds number. The results are in good agreement with the literature in case of the square cylinder. We experienced a slight increase of the dominant Strouhal number with increasing aspect ratio. This result is somewhat inconsistent with the literature, in which a fall of the Strouhal number can be observed at side ratio 2. This may be the consequence of the different ranges of Reynolds numbers. It was also found that between the inception of cavitation and the formation of supercavitation the Strouhal number is not affected by cavitation.

  14. Modulation of breast cancer resistance protein mediated atypical multidrug resistance using RNA interference delivered by adenovirus

    Institute of Scientific and Technical Information of China (English)

    LI Wen-tong; ZHOU Geng-yin; WANG Chun-ling; GUO Cheng-hao; SONG Xian-rang; CHI Wei-ling

    2005-01-01

    @@ Clinical multidrug resistance (MDR) of malignancies to many antineoplastic agents is the major obstacle in the successful treatment of cancer. The emergence of breast cancer resistance protein (BCRP), a member of the adenosine triphosphate (ATP) binding cassette (ABC) transporter family, has necessitated the development of antagonists. To overcome the BCRP-mediated atypical MDR, RNA interference (RNAi) delivered by adenovirus targeting BCRP mRNA was used to inhibit the atypical MDR expression by infecting MCF-7/MX100 cell lines with constructed RNAi adenovirus.

  15. Oncolytic adenovirus SG600-IL24 selectively kills hepatocellular carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the effect of oncolytic adenovirus SG600-IL24 and replication-incompetent adenovirus Ad.IL-24 on hepatocellular carcinoma (HCC) cell lines and normal liver cell line. METHODS: HCC cell lines (HepG2, Hep3B and MHCC97L) and normal liver cell line (L02) with a different p53 status were infected with SG600-IL24 and Ad.IL-24, respectively. Melanoma differentiation-associated (MDA)-7/interleukin (IL)-24 mRNA and protein expressions in infected cells were detected by reverse transcription-polym...

  16. Shedding a Tier: Flattening Organisational Structures and Employee Empowerment.

    Science.gov (United States)

    Powell, Loraine

    2002-01-01

    Surveyed United Kingdom business people and secondary school educators working in organizations with a flatter structure about organizational climate, job meaningfulness, communications, work intensity, and personal motivation. Found that old hierarchical attitudes persist and that an investment in changing the culture is required in order to…

  17. Salmonella enterica serovar enteritidis antimicrobial peptide resistance genes aid in defense against chicken innate immunity, fecal shedding, and egg deposition.

    Science.gov (United States)

    McKelvey, Jessica A; Yang, Ming; Jiang, Yanhua; Zhang, Shuping

    2014-12-01

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is a major etiologic agent of nontyphoid salmonellosis in the United States. S. Enteritidis persistently and silently colonizes the intestinal and reproductive tract of laying hens, resulting in contaminated poultry products. The consumption of contaminated poultry products has been identified as a significant risk factor for human salmonellosis. To understand the mechanisms S. Enteritidis utilizes to colonize and persist in laying hens, we used selective capture of transcribed sequences to identify genes overexpressed in the HD11 chicken macrophage cell line and in primary chicken oviduct epithelial cells. From the 15 genes found to be overexpressed in both cell types, we characterized the antimicrobial peptide resistance (AMPR) genes, virK and ybjX, in vitro and in vivo. In vitro, AMPR genes were required for natural morphology, motility, secretion, defense against detergents such as EDTA and bile salts, and resistance to antimicrobial peptides polymyxin B and avian β-defensins. From this, we inferred the AMPR genes play a role in outer membrane stability and/or modulation. In the intestinal tract, AMPR genes were involved in early intestinal colonization and fecal shedding. In the reproductive tract, virK was required in early colonization whereas a deletion of ybjX caused prolonged ovary colonization and egg deposition. Data from the present study indicate that AMPR genes are differentially utilized in various host environments, which may ultimately assist S. Enteritidis in persistent and silent colonization of chickens.

  18. Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears

    Directory of Open Access Journals (Sweden)

    Jonathan J. Miner

    2016-09-01

    Full Text Available Zika virus (ZIKV is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl−/−, Mertk−/−, and Axl−/−Mertk−/− double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye.

  19. Anti-HBV activity of TRL mediated by recombinant adenovirus

    Institute of Scientific and Technical Information of China (English)

    Wei-Dong Gong; Ya Zhao; Jun Yi; Jin Ding; Jun Liu; Cai-Fang Xue

    2005-01-01

    AIM: To investigate the inhibitive effect of hepatitis B virus (HBV)-TRL on HBV replication. METHODS: Based on previously constructed pcDNA3.1 (-)/TRL, TR, TRmut, HBV core protein (HBVc) and hEDN, interest gene sequences TRL, TR, HBVc and hEDN were inserted into adenovirus shuttle plasmid pDC316 respectively and co-transfected HEK293 cells with rescue plasmid pBHGlox(delta)E1,3Cre to acquire RAd/TRL, TR, HBVcand hEDN. And then RAds were identified, amplified and the titers in HEK293 cells were determined. RAd/TRL and TR were named as the experimental groups, and others were control ones. After HepG2.2.15 cells were infected, RAd/TRL expression was identified by indirect immunofluorescence staining. Supernatant HBV-DNA content was determined by fluorescent quantification PCR. Meanwhile, metabolism of HepG2.2.15 cells was evaluated by MTT colorimetry.RESULTS: RAd vectors with distinct interest gene sequence were successfully constructed. Effective expression of RAd/TRL in HepG2.2.15 cells resulted in a significant decrease of supernatant HBV-DNA content compared to RAd/TR (0.63±0.14 vs 1.60±0.47, P = 0.0266, <0.05) andother control groups (0.63±0.14 vs 8.50±2.78, 8.25±2.26,8.25±2.29, 8.50±1.51, 8.57±1.63, P<0.01). MTT assaysuggested that there were no significant differences in cell metabolic activity between groups (P>0.05).CONCLUSION: The construction and expression of RAd/TRL has been achieved and it could inhibit HBV replication successfully, which has laid the foundation for further research on anti-HBV activity in vivo.

  20. Experimental study of Human Adenoviruses interactions with clays

    Science.gov (United States)

    Bellou, Maria; Syngouna, Vasiliki; Paparrodopoulos, Spyros; Vantarakis, Apostolos; Chrysikopoulos, Constantinos

    2014-05-01

    Clays are used to establish low permeability liners in landfills, sewage lagoons, water retention ponds, golf course ponds, and hazardous waste sites. Human adenoviruses (HAdVs) are waterborne viruses which have been used as viral indicators of fecal pollution. The objective of this study was to investigate the survival of HAdV in static and dynamic clay systems. The clays used as a model were crystalline aluminosilicates: kaolinite and bentonite. The adsorption and survival of HAdVs onto these clays were characterized at two different controlled temperatures (4 and 25o C) under static and dynamic batch conditions. Control tubes, in the absence of clay, were used to monitor virus inactivation due to factors other than adsorption to clays (e.g. inactivation or sorption onto the tubes walls). For both static and dynamic batch experiments, samples were collected for a maximum period of seven days. This seven day time - period was determined to be sufficient for the virus-clay systems to reach equilibrium. To infer the presence of infectious HAdV particles, all samples were treated with Dnase and the extraction of viral nucleid acid was performed using a commercial viral RNA kit. All samples were analyzed by Real - Time PCR which was used to quantify viral particles in clays. Samples were also tested for virus infectivity by A549 cell cultures. Exposure time intervals in the range of seven days (0.50-144 hours) resulted in a load reduction of 0.74 to 2.96 logs for kaolinite and a reduction of 0.89 to 2.92 for bentonite. Furthermore, virus survival was higher onto bentonite than kaolinite (p

  1. Caliber-Persistent Artery

    Directory of Open Access Journals (Sweden)

    Sabrina Araújo Pinho Costa

    2015-01-01

    Full Text Available Caliber-persistent artery (CPLA of the lip is a common vascular anomaly in which a main arterial branch extends to the surface of the mucous tissue with no reduction in its diameter. It usually manifests as pulsatile papule, is easily misdiagnosed, and is observed more frequently among older people, suggesting that its development may involve a degenerative process associated with aging; CPLA is also characterized by the loss of tone of the adjacent supporting connective tissue. Although the diagnosis is clinical, high-resolution Doppler ultrasound is a useful noninvasive tool for evaluating the lesion. This report describes the case of a 58-year-old male patient who complained of a lesion of the lower lip with bleeding and recurrent ulceration. The patient was successfully treated in our hospital after a diagnosis of CPLA and is currently undergoing a clinical outpatient follow-up with no complaints.

  2. An annoying persistent cough

    Directory of Open Access Journals (Sweden)

    Francesco Cipollini

    2007-03-01

    Full Text Available Chronic cough is a stressful condition and can lead to extensive investigations. We report a case of a 48-year-old woman who had suffered from persistent chronic cough for more than 3 months. She had been treated with cough suppressant. However, her cough was not alleviated by these treatments, and the patient was referred to our hospital. She did not exhibit typical gastroesophageal reflux disease (GERD symptoms heartburn and regurgitation. Esophagoscopy did not disclose reflux esophagitis. The patient was treated with a proton-pump inhibitor, which markedly alleviated her cough. Chronic cough due to GERD was diagnosed. Although the diagnosis of chronic cough due to GERD is not easy when traditionally symptoms are not present, our case report underscores the importance of this association to the differential diagnosis of chronic cough. In these cases a relatively simple test as high dose proton pump-inhibitors trial may be useful to confirm GERD related cough.

  3. Persistent Aerial Tracking

    KAUST Repository

    Mueller, Matthias

    2016-04-13

    In this thesis, we propose a new aerial video dataset and benchmark for low altitude UAV target tracking, as well as, a photo-realistic UAV simulator that can be coupled with tracking methods. Our benchmark provides the rst evaluation of many state of-the-art and popular trackers on 123 new and fully annotated HD video sequences captured from a low-altitude aerial perspective. Among the compared trackers, we determine which ones are the most suitable for UAV tracking both in terms of tracking accuracy and run-time. We also present a simulator that can be used to evaluate tracking algorithms in real-time scenarios before they are deployed on a UAV "in the field", as well as, generate synthetic but photo-realistic tracking datasets with free ground truth annotations to easily extend existing real-world datasets. Both the benchmark and simulator will be made publicly available to the vision community to further research in the area of object tracking from UAVs. Additionally, we propose a persistent, robust and autonomous object tracking system for unmanned aerial vehicles (UAVs) called Persistent Aerial Tracking (PAT). A computer vision and control strategy is applied to a diverse set of moving objects (e.g. humans, animals, cars, boats, etc.) integrating multiple UAVs with a stabilized RGB camera. A novel strategy is employed to successfully track objects over a long period, by \\'handing over the camera\\' from one UAV to another. We integrate the complete system into an off-the-shelf UAV, and obtain promising results showing the robustness of our solution in real-world aerial scenarios.

  4. The Role of Collaborative Learning on Training and Development Practices within the Australian Men's Shed Movement: A Study of Five Men's Sheds

    Science.gov (United States)

    Cavanagh, Jillian; Southcombe, Amie; Bartram, Tim

    2014-01-01

    This study examines the role and impact of collaborative learning on training and development practices in Australian Men's Sheds. We use a case study approach, underpinned by Peters and Armstrong's theoretical framework of collaborative learning in adult education, to investigate five Men's Sheds. Semi-structured interviews were…

  5. Leading-edge vortex shedding from rotating wings

    CERN Document Server

    Kolomenskiy, Dmitry; Schneider, Kai

    2014-01-01

    The paper presents a numerical investigation of the leading-edge vortices generated by rotating triangular wings at Reynolds number $Re=250$. A series of three-dimensional numerical simulations have been carried out using a Fourier pseudo-spectral method with volume penalization. The transition from stable attachment of the leading-edge vortex to periodic vortex shedding is explored, as a function of the wing aspect ratio and the angle of attack. It is found that, in a stable configuration, the spanwise flow in the recirculation bubble past the wing is due to the centrifugal force, incompressibility and viscous stresses. For the flow outside of the bubble, an inviscid model of spanwise flow is presented.

  6. Leading-edge vortex shedding from rotating wings

    Energy Technology Data Exchange (ETDEWEB)

    Kolomenskiy, Dmitry [Centre de Recherches Mathématiques (CRM), Department of Mathematics and Statistics, McGill University, 805 Sherbrooke W., Montreal, QC H3A 0B9 (Canada); Elimelech, Yossef [Faculty of Aerospace Engineering, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Schneider, Kai, E-mail: dkolom@gmail.com [M2P2–CNRS, Université d' Aix-Marseille, 39, rue Frédéric Joliot-Curie, F-13453 Marseille Cedex 13 (France)

    2014-06-01

    This paper presents a numerical investigation of the leading-edge vortices generated by rotating triangular wings at Reynolds number Re = 250. A series of three-dimensional numerical simulations have been carried out using a Fourier pseudo-spectral method with volume penalization. The transition from stable attachment of the leading-edge vortex to periodic vortex shedding is explored, as a function of the wing aspect ratio and the angle of attack. It is found that, in a stable configuration, the spanwise flow in the recirculation bubble past the wing is due to the centrifugal force, incompressibility and viscous stresses. For the flow outside of the bubble, an inviscid model of spanwise flow is presented. (papers)

  7. Shedding light on restoring respiratory function after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Warren J Alilain

    2009-10-01

    Full Text Available Loss of respiratory function is one of the leading causes of death following spinal cord injury. Because of this, much work has been done in studying ways to restore respiratory function following SCI - including pharmacological and regeneration strategies. With the emergence of new and powerful tools from molecular neuroscience, new therapeutically relevant alternatives to these approaches have become available, including expression of light sensitive proteins called channelrhodopsins. In this article we briefly review the history of various attempts to restore breathing after C2 hemisection, and focus on our recent work using the activation of light sensitive channels to restore respiratory function after experimental spinal cord injury. We also discuss how such light induced activity can help shed light on the inner workings of the central nervous system respiratory circuitry that controls diaphragmatic function.

  8. Nocturnal drainage wind characteristics in two converging air sheds

    International Nuclear Information System (INIS)

    During the short experimental period in the Grants Basin of Northeastern New Mexico a survey was conducted on the complex meteorology of this area. Emphasis was placed on the nocturnal drainage flow because of the potential hazards to the populated areas of Milan and Grants from the effluents of the uranium mining and milling operation in this area. This investigation has shown that the nocturnal drainage flow patterns agree with the winds predicted on the basis of the complex terrain of the area. Because of the surface cooling at night (over 250C during summer and about 200C during winter), air from elevated surrounding areas flows to the low lying regions consequently setting up a nocturnal drainage flow. This regime exists over 60% of the time during summer months and over 65% of the time during winter months with a depth generally less than 200 m. In the San Mateo air shed the drainage flow is east northeast, and in the Ambrosia Lake air shed it is from northwest. The confluence of these two air flows contributes mainly to the drainage flow through the channel formed by La Ja Mesa and Mesa Montanosa. The analysis of data collected by the recording Flats Station confirms the prediction that although the area south of the channel region broadens considerably causing a reduction in flow speed, contributions from the southside of La Jara Mesa and Mesa Montanosa partly compensate for this reduction. The position of this recording station is 15 to 20 km from the populated towns of Milan and Grants. A drainage flow speed of approximately 2.2 m s-1 and the duration of over 11 hours as recorded by this station indicates that air from the San Mateo and Ambrosia Lake regions may be transported southwards to these population centers during a nocturnal period. In order to test this prediction, a series of multi-atmospheric tracer experiments were conducted in the Grants Basin

  9. Random Sampling of Squamate Reptiles in Spanish Natural Reserves Reveals the Presence of Novel Adenoviruses in Lacertids (Family Lacertidae) and Worm Lizards (Amphisbaenia)

    Science.gov (United States)

    Szirovicza, Leonóra; López, Pilar; Kopena, Renáta; Benkő, Mária; Martín, José; Pénzes, Judit J.

    2016-01-01

    Here, we report the results of a large-scale PCR survey on the prevalence and diversity of adenoviruses (AdVs) in samples collected randomly from free-living reptiles. On the territories of the Guadarrama Mountains National Park in Central Spain and of the Chafarinas Islands in North Africa, cloacal swabs were taken from 318 specimens of eight native species representing five squamate reptilian families. The healthy-looking animals had been captured temporarily for physiological and ethological examinations, after which they were released. We found 22 AdV-positive samples in representatives of three species, all from Central Spain. Sequence analysis of the PCR products revealed the existence of three hitherto unknown AdVs in 11 Carpetane rock lizards (Iberolacerta cyreni), nine Iberian worm lizards (Blanus cinereus), and two Iberian green lizards (Lacerta schreiberi), respectively. Phylogeny inference showed every novel putative virus to be a member of the genus Atadenovirus. This is the very first description of the occurrence of AdVs in amphisbaenian and lacertid hosts. Unlike all squamate atadenoviruses examined previously, two of the novel putative AdVs had A+T rich DNA, a feature generally deemed to mirror previous host switch events. Our results shed new light on the diversity and evolution of atadenoviruses. PMID:27399970

  10. Random Sampling of Squamate Reptiles in Spanish Natural Reserves Reveals the Presence of Novel Adenoviruses in Lacertids (Family Lacertidae and Worm Lizards (Amphisbaenia.

    Directory of Open Access Journals (Sweden)

    Leonóra Szirovicza

    Full Text Available Here, we report the results of a large-scale PCR survey on the prevalence and diversity of adenoviruses (AdVs in samples collected randomly from free-living reptiles. On the territories of the Guadarrama Mountains National Park in Central Spain and of the Chafarinas Islands in North Africa, cloacal swabs were taken from 318 specimens of eight native species representing five squamate reptilian families. The healthy-looking animals had been captured temporarily for physiological and ethological examinations, after which they were released. We found 22 AdV-positive samples in representatives of three species, all from Central Spain. Sequence analysis of the PCR products revealed the existence of three hitherto unknown AdVs in 11 Carpetane rock lizards (Iberolacerta cyreni, nine Iberian worm lizards (Blanus cinereus, and two Iberian green lizards (Lacerta schreiberi, respectively. Phylogeny inference showed every novel putative virus to be a member of the genus Atadenovirus. This is the very first description of the occurrence of AdVs in amphisbaenian and lacertid hosts. Unlike all squamate atadenoviruses examined previously, two of the novel putative AdVs had A+T rich DNA, a feature generally deemed to mirror previous host switch events. Our results shed new light on the diversity and evolution of atadenoviruses.

  11. Downmodulation of El A Protein Expression as a Novel Strategy to Design Cancer-Selective Adenoviruses

    Directory of Open Access Journals (Sweden)

    Hong Jiang

    2005-08-01

    Full Text Available Oncolytic adenoviruses are being tested as potential therapies for human malignant tumors, including gliomas. Here we report for the first time that a mutation in the E1A gene results in low levels of ElA protein, conditioning the replication of mutant adenoviruses specifically to cancer cells. In this study, we compared the oncolytic potencies of three mutant adenoviruses encompassing deletions within the CRi (Delta-39, CR2 (Delta-24 regions, or both regions (Delta-24/39 of the ElA protein. Delta-39, Delta-24 induced a cytopathic effect with similar efficiency in glioma cells, a comparable capacity for replication. Importantly, the activity of Delta-39 was significantly attenuated compared to Delta-24 in proliferating normal human astrocytes. Direct analyses of the activation of E2F-1 promoter demonstrated the inability of Delta-39 to induce S-phase-related transcriptional activity in normal cells. Interestingly, ElA protein levels in cells infected with Delta-39 were remarkably downmodulated. Furthermore, protein stability studies revealed enhanced degradation of CRi mutant ElA proteins, inhibition of the proteasome activity resulted in the striking rescue of ElA levels. We conclude that the level of ElA protein is a critical determinant of oncolytic phenotype, we propose a completely novel strategy for the design, construction of conditionally replicative adenoviruses.

  12. Ad 2.0: a novel recombineering platform for high-throughput generation of tailored adenoviruses.

    Science.gov (United States)

    Mück-Häusl, Martin; Solanki, Manish; Zhang, Wenli; Ruzsics, Zsolt; Ehrhardt, Anja

    2015-04-30

    Recombinant adenoviruses containing a double-stranded DNA genome of 26-45 kb were broadly explored in basic virology, for vaccination purposes, for treatment of tumors based on oncolytic virotherapy, or simply as a tool for efficient gene transfer. However, the majority of recombinant adenoviral vectors (AdVs) is based on a small fraction of adenovirus types and their genetic modification. Recombineering techniques provide powerful tools for arbitrary engineering of recombinant DNA. Here, we adopted a seamless recombineering technology for high-throughput and arbitrary genetic engineering of recombinant adenoviral DNA molecules. Our cloning platform which also includes a novel recombination pipeline is based on bacterial artificial chromosomes (BACs). It enables generation of novel recombinant adenoviruses from different sources and switching between commonly used early generation AdVs and the last generation high-capacity AdVs lacking all viral coding sequences making them attractive candidates for clinical use. In combination with a novel recombination pipeline allowing cloning of AdVs containing large and complex transgenes and the possibility to generate arbitrary chimeric capsid-modified adenoviruses, these techniques allow generation of tailored AdVs with distinct features. Our technologies will pave the way toward broader applications of AdVs in molecular medicine including gene therapy and vaccination studies. PMID:25609697

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

    Science.gov (United States)

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

    2013-01-01

    Adenovirus (Ad) derived vectors have been widely used for short or long-term gene transfer, both for gene therapy and vaccine applications. Because of the frequent pre-existing immunity against the classically used human adenovirus type 5, canine adenovirus type 2 (CAV2) has been proposed as an alternative vector for human gene transfer. The well-characterized biology of CAV2, together with its ease of genetic manipulation, offer major advantages, notably for gene transfer into the central nervous system, or for inducing a wide range of protective immune responses, from humoral to cellular immunity. Nowadays, CAV2 represents one of the most appealing nonhuman adenovirus for use as a vaccine vector. This protocol describes a simple method to construct, produce and titer recombinant CAV2 vectors. After cloning the expression cassette of the gene of interest into a shuttle plasmid, the recombinant genomic plasmid is obtained by homologous recombination in the E. coli BJ5183 bacterial strain. The resulting genomic plasmid is then transfected into canine kidney cells expressing the complementing CAV2-E1 genes (DK-E1). A viral amplification enables the production of a large viral stock, which is purified by ultracentrifugation through cesium chloride gradients and desalted by dialysis. The resulting viral suspension routinely has a titer of over 10(10) infectious particles per ml and can be directly administrated in vivo. PMID:24326926

  14. Fatal Fulminant Hepatic Failure from Adenovirus in Allogeneic Bone Marrow Transplant Patients

    OpenAIRE

    Jatin M Vyas; Marasco, Wayne A.

    2012-01-01

    We report two cases of fatal hepatic failure in patients who received matched unrelated bone marrow transplantation. Both patients presented with high fevers, abnormal liver functions tests, and hypodense lesions in the liver by CT scan. Histologic examination of postmortem liver samples demonstrated extensive necrosis, and immunohistochemistry was positive for adenovirus.

  15. Transcriptional activation by the E1A regions of adenovirus types 40 and 41

    NARCIS (Netherlands)

    Loon, A.E. van; Gilardi, P.; Perricaudet, M.; Rozijn, Th. H.; Sussenbach, J.S.

    1987-01-01

    In order to establish whether the poor growth of the two fastidious adenoviruses types 40 and 41 (Ad40 and Ad41) in HeLa cells is due to a reduced trans-activation by the early region to (E1A), we have determined the trans-activating effect of this region on the expression of the chloramphenicol ace

  16. The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies

    DEFF Research Database (Denmark)

    Nielsen, Trine Skov; Hansen, Jakob; Nielsen, Lars Peter;

    2014-01-01

    of adenovirus, enterovirus, and parvovirus B19 (PVB) in myocardial autopsy samples from myocarditis related deaths and in non-inflamed control hearts in an effort to clarify their significance as the causes of myocarditis in a forensic material. METHODS: We collected all autopsy cases diagnosed with myocarditis...

  17. Adenovirus-mediated interteukin-13 gene therapy attenuates acute kidney allograft injury

    NARCIS (Netherlands)

    Sandovici, Maria; Deelmani, Leo E.; van Goor, Harry; Helfrich, Wijnand; de Zeeuw, Dick; Henning, Robert H.

    2007-01-01

    Background Kidney transplantation is possible by virtue of systemic immunosuppression, which is in turn accompanied by serious side effects. The search for novel therapeutic agents and strategies is ongoing. Here we investigate the effects of adenovirus-mediated gene therapy with interleukin (IL)-13

  18. Adenovirus DNA replication in vitro is stimulated by RNA from uninfected HeLa cells

    NARCIS (Netherlands)

    Vliet, P.C. van der; Dam, D. van; Kwant, M.M.

    1984-01-01

    Adenovirus DNA replication was studied in a partially reconstituted system consisting of purified viral proteins (DNA-binding protein, precursor terminal protein and Ad DNA polymerase) and a nuclear extract from uninfected HeLa cells. Optimal DNA replication required the presence of a heat-stable, r

  19. Effects of hCD80-Adenovirus on B16-F10 Cells

    Institute of Scientific and Technical Information of China (English)

    田长富; 李殿俊; 刘旭

    2002-01-01

    @@ To study the biological characteristics of B16-F10 cells transduced with hCD80 gene in vitro, a kind of replication-deficient recombinant adenovirus bearing hCD80 gene (hCD80-rAd) was constructed and several means were utilized to observe the changes of biological characteristics after gene transduced.

  20. Studies on the mechanism of replication of adenovirus DNA. IV. Discontinuous DNA chain propagation

    NARCIS (Netherlands)

    Vlak, J.M.; Rozijn, Th.H.; Sussenbach, J.S.

    1975-01-01

    The replication of adenovirus type 5 DNA occurs by discontinuous chain propagation via short pieces of DNA. These pieces accumulate if the infected cells are treated with hydroxyurea. They have a sedimentation coefficient of 11 S corresponding to a molecular weight of about 700,000, and they contain

  1. Valganciclovir Inhibits Human Adenovirus Replication and Pathology in Permissive Immunosuppressed Female and Male Syrian Hamsters

    Directory of Open Access Journals (Sweden)

    Karoly Toth

    2015-03-01

    Full Text Available Adenovirus infections of immunocompromised pediatric hematopoietic stem cell transplant patients can develop into serious and often deadly multi-organ disease. There are no drugs approved for adenovirus infections. Cidofovir (an analog of 2-deoxycytidine monophosphate is used at times but it can be nephrotoxic and its efficacy has not been proven in clinical trials. Brincidofovir, a promising lipid-linked derivative of cidofovir, is in clinical trials. Ganciclovir, an analog of 2-deoxyguanosine, has been employed occasionally but with unknown efficacy in the clinic. In this study, we evaluated valganciclovir against disseminated adenovirus type 5 (Ad5 infection in our permissive immunosuppressed Syrian hamster model. We administered valganciclovir prophylactically, beginning 12 h pre-infection or therapeutically starting at Day 1, 2, 3, or 4 post-infection. Valganciclovir significantly increased survival, reduced viral replication in the liver, and mitigated the pathology associated with Ad5 infection. In cultured cells, valganciclovir inhibited Ad5 DNA replication and blocked the transition from early to late stage of infection. Valganciclovir directly inhibited Ad5 DNA polymerase in vitro, which may explain, at least in part, its mechanism of action. Ganciclovir and valganciclovir are approved to treat infections by certain herpesviruses. Our results support the use of valganciclovir to treat disseminated adenovirus infections in immunosuppressed patients.

  2. [The complexes of adenovirus and anionic liposomes: preparation and in vitro characterization].

    Science.gov (United States)

    Zhong, Zhi-Rong; Wan, Yu; Shi, San-Jun; Zhang, Zhi-Rong; Sun, Xun

    2012-01-01

    This study is to report the preparation of complexes of Ad5 and anionic liposomes (AL-Ad5), the amplification of adenoviruses with enhanced green fluorescent protein (eGFP) reporter gene performed by HEK 293 cells, the adenoviral vectors purified by cesium chloride gradient centrifugation, and the titer of adenovirus determined by cytopathic effect (CPE) method, hexon capsid immunoassay and quantitative-PCR (Q-PCR), separately. The prescription and experiment conditions were optimized by central composite design (CCD). The complexes of Ad5 and AL-Ad5 were formulated by the calcium-induced phase change method. The morpholopy, particle size and zeta potential were detected by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. Additionally, the bicolourable fluoresce-labeled complexes (F(labeled)-AL-Ad5) were prepared and their intracellular location in MDCK cells was detected by confocal laser scanning microscopy (CLSM). The results indicate that the complexes of AL-Ad5 exhibited a uniform distribution with a particle size of 211 +/- 10 nm and a zeta potential of -41.2 +/- 2.2 mV. The result of CLSM demonstrates that the intracellular location of red fluoresce-labeled adenovirus was consistent with that of green fluoresce-labeled liposomes suggesting that the naked adenovirus was well encapsulated by the anionic liposomes in complexes of AL-Ad5. PMID:22493816

  3. Effect of organic carbon on sorption of human adenovirus to soil particles and laboratory containers

    Science.gov (United States)

    A key factor controlling the relationship between virus release and human exposure is how virus particles interact with soils, sediments and other solid particles in the environment and in engineered treatment systems. Finding no previous investigations of human adenovirus (HAdV)...

  4. High expression level of soluble SARS spike protein mediated by adenovirus in HEK293 cells

    Institute of Scientific and Technical Information of China (English)

    Fei Zhong; Zhen-Yu Zhong; Shuang Liang; Xiu-Jin Li

    2006-01-01

    AIM: To develop a highly efficacious method for preparation of soluble SARS S-protein using adenovirus vector to meet the requirement for S-protein investigation.METHODS: The human adenovirus vector was used to express the soluble S-protein (corresponding to 1~1190 amino acids) fused with Myc/His tag using codon-optimized gene construct in HEK239 cells. The recombinant adenovirus bearing S-protein gene was generated by ligation method. The expressed S-protein with Myc/His tag was purified from culture medium with Ni-NTA agarose beads followed by dialysis. The S-protein was detected by Western blot and its biologic activity was analyzed by binding to Vero cells.RESULTS: Under the conditions of infection dose (MOI of 50) and expression time (48 h), the high-level expression of S-protein was obtained. The expression level was determined to be approximately 75 μg/106cells after purification. Purified soluble S-protein was readily detected by Western blot with anti-Myc antibody and showed the ability to bind to surface of Vero cells,demonstrating that the soluble S-protein could remain the biologic activity in the native molecule.CONCLUSION: The high-level expression of S-protein in HEK293 cells mediated by adenovirus can be achieved under the optimized expression conditions. The proteins possess the biologic activity, which lays a foundation for further investigation of S-protein biological function.

  5. Detection of adenovirus hexon sequence in a cat by polymerase chain reaction(short communication)

    NARCIS (Netherlands)

    Horzinek, M.C.; Lakatos, B.; Farkas, J.; Egberink, H.F.; Vennema, H.; Benko, M.

    1999-01-01

    Adenoviral nucleic acid was detected by polymerase chain reaction (PCR) in pharyngeal and rectal swab samples of a cat seropositive for adenovirus and suffering from transient hepatic failure. The samples were taken at a one-year interval, and both faecal samples as well as the second pharyngeal sam

  6. Adenovirus serotype 5 vectored foot-and-mouth disease subunit vaccines: the first decade

    Science.gov (United States)

    Here we present the results of the first decade of development of a replication-defective human adenovirus (Ad5) containing the capsid and 3C protease coding regions of foot-and-mouth disease virus (FMDV) as a vaccine candidate. In proof-of concept studies we demonstrated that a single inoculation w...

  7. Fatal Fulminant Hepatic Failure from Adenovirus in Allogeneic Bone Marrow Transplant Patients

    Directory of Open Access Journals (Sweden)

    Jatin M. Vyas

    2012-01-01

    Full Text Available We report two cases of fatal hepatic failure in patients who received matched unrelated bone marrow transplantation. Both patients presented with high fevers, abnormal liver functions tests, and hypodense lesions in the liver by CT scan. Histologic examination of postmortem liver samples demonstrated extensive necrosis, and immunohistochemistry was positive for adenovirus.

  8. Intravenous delivery of adenovirus-mediated soluble FLT-1 results in liver toxicity

    NARCIS (Netherlands)

    Mahasreshti, P.J.; Kataram, M.; Wang, Miao; Stockard, C.R.; Grizzle, W.E.; Carey, D.; Siegal, G.P.; Haisma, H.J.; Alvarez, R.D.; Curiel, D.T.

    2003-01-01

    Purpose: Vascular endothelial growth factor (VEGF) is a potent angiogenic agent and plays a major role in tumor growth and metastases. We have previously reported the locoregional (i.p.) delivery of adenovirus-mediated antiangiogenic soluble FLT-1 (sFLT-1; a naturally encoded potent VEGF antagonist)

  9. Analysis of the expression of coxsackievirus and adenovirus receptor in five colon cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the expression of coxsackievirus and adenovirus receptor (CAR) and adenovirus-mediated reporter gene transfer in five human colon cancer cell lines.METHODS: Expression of CAR-specific mRNA and protein was analyzed by reverse transcriptase polymerase chain reaction and Western blotting, respectively. Adenovirusbased gene delivery was evaluated by infection of cells with adenoviral vector carrying the green fluorescent protein (GFP) gene.RESULTS: All the colon cancer cell lines examined (HT29,LS180, SW480, SW948 and SW1116) expressed CAR full-length mRNA and an alternatively-spliced variant that lacks the transmembrane coding exon. All cell lines were detected as CAR-positive by Western blot analysis.Further, all cells we examined were efficiently infected with adenoviral vector-GFP.CONCLUSION: The data indicated that the five colon cancer cell lines tested expressed adenovirus primary receptor and could be efficiently infected by adenoviral vectors. Therefore, these cell lines will be useful for adenovirus-based gene transfer and research.

  10. An Adenovirus Vector Incorporating Carbohydrate Binding Domains Utilizes Glycans for Gene Transfer

    NARCIS (Netherlands)

    Kim, Julius W.; Glasgow, Joel N.; Nakayama, Masaharu; Ak, Ferhat; Ugai, Hideyo; Curiel, David T.

    2013-01-01

    Background: Vectors based on human adenovirus serotype 5 (HAdV-5) continue to show promise as delivery vehicles for cancer gene therapy. Nevertheless, it has become clear that therapeutic benefit is directly linked to tumor-specific vector localization, highlighting the need for tumor-targeted gene

  11. Crystallographic Structure of Porcine Adenovirus Type 4 Fiber Head and Galectin Domains▿

    Science.gov (United States)

    Guardado-Calvo, Pablo; Muñoz, Eva M.; Llamas-Saiz, Antonio L.; Fox, Gavin C.; Kahn, Richard; Curiel, David T.; Glasgow, Joel N.; van Raaij, Mark J.

    2010-01-01

    Adenovirus isolate NADC-1, a strain of porcine adenovirus type 4, has a fiber containing an N-terminal virus attachment region, shaft and head domains, and a C-terminal galectin domain connected to the head by an RGD-containing sequence. The crystal structure of the head domain is similar to previously solved adenovirus fiber head domains, but specific residues for binding the coxsackievirus and adenovirus receptor (CAR), CD46, or sialic acid are not conserved. The structure of the galectin domain reveals an interaction interface between its two carbohydrate recognition domains, locating both sugar binding sites face to face. Sequence evidence suggests other tandem-repeat galectins have the same arrangement. We show that the galectin domain binds carbohydrates containing lactose and N-acetyl-lactosamine units, and we present structures of the galectin domain with lactose, N-acetyl-lactosamine, 3-aminopropyl-lacto-N-neotetraose, and 2-aminoethyl-tri(N-acetyl-lactosamine), confirming the domain as a bona fide galectin domain. PMID:20686025

  12. Pathways of Student Persistence at RSC (Includes Persistence of Matriculants).

    Science.gov (United States)

    Fredericksen, Marlene

    In 1991, a study was conducted of semester-to-semester persistence patterns at Rancho Santiago College (RSC). The study involved tracking the attendance patterns of all RSC students entering as new students in fall 1983 and each subsequent fall until 1990; and comparing the persistence rates of matriculated and non-matriculated students in the…

  13. Isolation and identification of Adenovirus in hospitalized children, under five years, with acute respiratory disease, in Havana, Cuba

    Directory of Open Access Journals (Sweden)

    Tania Pumariega

    2000-12-01

    Full Text Available Nine Adenovirus (Ad strains isolated in Cuba, from 128 nasopharingeal swab specimens of children below five years old, with acute respiratory diseases, during 1996 and 1997, were studied by restriction enzyme analysis of genomic DNA with two endonucleases BamH I and Sma I. All different fragment patterns were compared with the respective prototypes. The identified adenoviruses were Ad 1 (n=4, Ad 2 (n=1 and Ad 6 (n=4. Males were more frequently infected than females. The analysis of the occurrence of these Adenovirus strains of subgenus C revealed that Ad 1 and Ad 6 were the predominant serotypes in 1996 and in 1997, respectively.

  14. Adenovirus, calicivirus and astrovirus detection in fecal samples of hospitalized children with acute gastroenteritis from Campo Grande, MS, Brazil

    Directory of Open Access Journals (Sweden)

    Marcia Sueli Assis Andreasi

    2008-11-01

    Full Text Available We analyzed fecal samples from hospitalized children up to three years of age with acute gastroenteritis at Campo Grande, Mato Grosso do Sul, Brazil, from May 2000-January 2004. Astrovirus and calicivirus were detected by Reverse Transcription-Polymerase Chain Reaction and adenovirus was detected using the Rotavirus and Adenovirus combined immunoenzyme assay. Astrovirus, adenovirus and calicivirus were detected at rates of 3.1%, 3.6% and 7.6%, respectively. These results re-emphasize the need for the establishment of regional vigilance systems to evaluate the impact of enteric viruses on viral gastroenteritis.

  15. Assessment of Chlamydia psittaci Shedding and Environmental Contamination as Potential Sources of Worker Exposure throughout the Mule Duck Breeding Process.

    Science.gov (United States)

    Hulin, V; Bernard, P; Vorimore, F; Aaziz, R; Cléva, D; Robineau, J; Durand, B; Angelis, L; Siarkou, V I; Laroucau, K

    2015-12-28

    Chlamydia psittaci is an obligate intracellular bacterium responsible for avian chlamydiosis, otherwise known as psittacosis, a zoonotic disease that may lead to severe atypical pneumonia. This study was conducted on seven mule duck flocks harboring asymptomatic birds to explore the circulation and persistence of C. psittaci during the entire breeding process and assess the potential sources of worker exposure. Cloacal swabs and air samples were taken on each occasion requiring humans to handle the birds. In parallel, environmental samples, including dust, water, and soil, were collected. Specific real-time PCR analyses revealed the presence of C. psittaci in all flocks but with three different shedding patterns involving ducks about the age of 4, 8, and 12 weeks with heavy, moderate, and low excretion levels, respectively. Air samples were only positive in flocks harboring heavy shedders. Dust in flocks with heavy or moderate shedders carried chlamydial loads strongly associated with the loads detected in avian and soil samples. Environmental contamination, significantly correlated with shedding dynamics, was considered to be the most probable source of exposure. The high prevalence of bacteriophage Chp1 in all flocks, mostly jointly present with chlamydia, suggests an important factor in C. psittaci persistence, thus creating a greater risk for humans. A survey conducted in these flocks regarding farming practices and activities showed that disinfection seems to be the most promising practice for reducing C. psittaci prevalence in ducks and that the place and the duration of action during operations seem to be potential risk factors. Strict adherence to good practices is strongly recommended.

  16. Caveolin-1 associated adenovirus entry into human corneal cells.

    Directory of Open Access Journals (Sweden)

    Mohammad A Yousuf

    Full Text Available The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection. Epidemic keratoconjunctivitis (EKC, caused by viruses within human adenovirus species D (HAdV-D, is a severe, ocular surface infection associated with corneal inflammation. Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types. However, HAdV-D endocytosis into corneal cells has not been extensively studied. Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts. Cholesterol depletion using methyl-β-cyclodextrin (MβCD profoundly reduced viral infection. When replenished with soluble cholesterol, the effect of MβCD was reversed, allowing productive viral infection. HAdV-D37 DNA was identified in caveolin-1 rich endosomal fractions after infection. Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/- mice corneas compared to wild type mice. siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/- mouse corneas showed reduced cellular entry of HAdV-D37. As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism. Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry. Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with

  17. Analysis and Prediction of Ice Shedding for a Full-Scale Heated Tail Rotor

    Science.gov (United States)

    Kreeger, Richard E.; Work, Andrew; Douglass, Rebekah; Gazella, Matthew; Koster, Zakery; Turk, Jodi

    2016-01-01

    When helicopters are to fly in icing conditions, it is necessary to consider the possibility of ice shed from the rotor blades. In 2013, a series of tests were conducted on a heated tail rotor at NASA Glenn's Icing Research Tunnel (IRT). The tests produced several shed events that were captured on camera. Three of these shed events were captured at a sufficiently high frame rate to obtain multiple images of the shed ice in flight that had a sufficiently long section of shed ice for analysis. Analysis of these shed events is presented and compared to an analytical Shedding Trajectory Model (STM). The STM is developed and assumes that the ice breaks off instantly as it reaches the end of the blade, while frictional and viscous forces are used as parameters to fit the STM. The trajectory of each shed is compared to that predicted by the STM, where the STM provides information of the shed group of ice as a whole. The limitations of the model's underlying assumptions are discussed in comparison to experimental shed events.

  18. A role for the non-canonical Wnt-ß-Catenin and TGF-ß signaling pathways in the induction of tolerance during the establishment of a Salmonella enterica serovar Enteritidis persistent cecal infection in chickens

    Science.gov (United States)

    Non-typhoidal Salmonella enterica induce an early pro-inflammatory response in chickens. However, the response is short-lived, asymptomatic of disease, resulting in a persistent colonization of the ceca, and fecal shedding of bacteria. The underlying mechanisms that control this persistent infecti...

  19. High efficient generation of replication-defective adenoviruses containing thymidine kinase by homogeneous recombination in bacteria

    Institute of Scientific and Technical Information of China (English)

    CONG Tie-chuan; LU Zhe-ming; LI Yong; ZHENG Li; QIN Yong

    2007-01-01

    Background Suicide gene therapy is a widely used molecular treatment for head and neck cancer. In this study, we try to use the method of homogenous recombination in bacteria to clone thymidine kinase gene (tk)-a kind of suicide gene to adenovirus backbone vectors for the construction of replication-defective adenoviruses.Methods pAdTrack-CMV/tk was constructed through subclone of a restriction endonuclease fragment including thymidine kinase gene from plasmid pCMV-tk to another plasmid pAdTrack-CMV, and then co-transfected with supercoiled pAdEasy-1, which was an adenoviral backbone vector except for deletions of E1 and E3, to competent E.coli BJ5183 for homogenous recombination using electroporation procedure. With the same method, pAdTrack-CMV was also co-transformed with pAdEasy-1 for homogenous recombination in BJ5183. Identified with restriction endonuclease Pacl and polymerase chain reaction (PCR), plasmids pAd-GFP/tk and pAd-GFP were successfully constructed. Each of them was digested with Pacl and sequently transfected into human embryo kidney 293 cells (HEK293) using Lipofectamine 2000.Results Comet-like adenovirus-producing foci of Ad-GFP/tk and Ad-GFP were observed after 5 to 7 days of cell culture.After twelve days of packaging, the replication-defective adenoviruses were collected. Identified with PCR, thymidine kinase gene was successfully constructed into Ad-GFP/tk.Conclusion The replication-defective adenoviruses containing thymidine kinase can be constructed more easily by homogenous recombination in bacteria than conventional techniques.

  20. Adenovirus-mediated short hairpin RNA interference against p75 neurotrophin receptor in pheochromocytoma cells

    Institute of Scientific and Technical Information of China (English)

    Dongxu Feng; Haopeng Li; Siyue Xu; Yu Liu; Xiaofei Hou

    2011-01-01

    Previous studies have confirmed that motor neuron apoptosis in the anterior horn of the lumbosacral spinal cord is positively correlated with p75 neurotrophin receptor (p75NTR) expression in rat models of cauda equina syndrome. This study used adenovirus to carry a short hairpin RNA (shRNA) for p75NTR gene silencing, to reduce p75NTR expression in the damaged phase and to decrease motor neuron apoptosis. Three p75 siRNA template oligonucleotide segments (shRNA) were designed, and cloned into the 1.0 CMV shuttle vector. HEK293 cells were cotransfected with shuttle vector (carrying shRNA) and an adenovirus vector framework expressing enhanced green fluorescent protein. Thus, this study successfully obtained adenovirus carrying p75shRNA. The obtained viruses were named Ad.shRNA1, Ad.shRNA2, and Ad.shRNA3. The recombinant adenoviruses were separately used to infect cultured pheochromocytoma cells (PC12). Forty-eight hours later, p75NTR mRNA and total protein were analyzed from the PC12 cells. Compared with the negative controls, RNA interference rates were separately 98.49±0.68%, 95.08±1.79% and 96.60±1.14% at the mRNA level, and 72.89±2.17%, 58.83±1.15% and 59.88±0.44% at the protein level in the Ad.shRNA1, Ad.shRNA2, and Ad.shRNA3 groups, respectively. Thus, recombinant adenovirus shRNA-mediated gene silencing successfully suppressed p75NTR expression.

  1. [Stability of the structure and antigenic determinants of adenovirus type 1 native hexon to proteases].

    Science.gov (United States)

    Kiseleva, E K; Khil'ko, S N; Grigor'ev, V G; Diachenko, N S; Vantsak, N P

    1986-08-01

    Hexon capsomers of human adenovirus type 1 (h1) labeled by iodine 125 were digested in a native state (trimers) by trypsin, chymotrypsin or papain, and the resulting hydrolysates were analyzed by SDS-PAGE. In each case, a discrete and temporally stable pattern of relatively large fragments was revealed. The degree of hexon polypeptide hydrolysis was maximal for papain, intermediate for chymotrypsin and minimal for trypsin, the largest fragments in the digest being 32, 40 and 80 kD, respectively. At room temperature, all the electrophoretically discernible hexon proteolytical fragments were held together in structures resembling intact hexon trimers and could be regarded as "hexon cores", of which papain hexon cores were the most stable during SDS-PAGE. Radioimmunoprecipitation analysis revealed a complete absence of native hexon antigenicity in thermodenaturated fragments of hexon protease digests, while native trypsin, chymotrypsin and papain hexon cores could be precipitated by hexon-specific antibodies. The immunoprecipitated material contained all of the hexon fragments found in appropriate hexon cores and retained the structure of the original cores. Trypsin, chymotrypsin and papain hexon cores were shown to possess at least part of native Ad h1 hexon antigenic determinants of each of the following specificities: species-specific (epsilon), cross-reactive with hexon of human adenoviruses (h3 and h6), simian adenovirus (sim 16), bovine adenoviruses (bos 3 and bos 7) and avian adenovirus (Aviadenovirus gal 1 or CELO). Thus, the full spectrum of known hexon antigenic determinants (species-specific to intergenus-crossreactive) is at least portly stable against protease attack of native hexon capsomers.

  2. The Revolution in Viral Genomics as Exemplified by the Bioinformatic Analysis of Human Adenoviruses

    Directory of Open Access Journals (Sweden)

    Sarah Torres

    2010-06-01

    Full Text Available Over the past 30 years, genomic and bioinformatic analysis of human adenoviruses has been achieved using a variety of DNA sequencing methods; initially with the use of restriction enzymes and more currently with the use of the GS FLX pyrosequencing technology. Following the conception of DNA sequencing in the 1970s, analysis of adenoviruses has evolved from 100 base pair mRNA fragments to entire genomes. Comparative genomics of adenoviruses made its debut in 1984 when nucleotides and amino acids of coding sequences within the hexon genes of two human adenoviruses (HAdV, HAdV–C2 and HAdV–C5, were compared and analyzed. It was determined that there were three different zones (1-393, 394-1410, 1411-2910 within the hexon gene, of which HAdV–C2 and HAdV–C5 shared zones 1 and 3 with 95% and 89.5% nucleotide identity, respectively. In 1992, HAdV-C5 became the first adenovirus genome to be fully sequenced using the Sanger method. Over the next seven years, whole genome analysis and characterization was completed using bioinformatic tools such as blastn, tblastx, ClustalV and FASTA, in order to determine key proteins in species HAdV-A through HAdV-F. The bioinformatic revolution was initiated with the introduction of a novel species, HAdV-G, that was typed and named by the use of whole genome sequencing and phylogenetics as opposed to traditional serology. HAdV bioinformatics will continue to advance as the latest sequencing technology enables scientists to add to and expand the resource databases. As a result of these advancements, how novel HAdVs are typed has changed. Bioinformatic analysis has become the revolutionary tool that has significantly accelerated the in-depth study of HAdV microevolution through comparative genomics.

  3. The persistence of depression score

    NARCIS (Netherlands)

    Spijker, J.; de Graaf, R.; Ormel, J.; Nolen, W. A.; Grobbee, D. E.; Burger, H.

    2006-01-01

    Objective: To construct a score that allows prediction of major depressive episode (MDE) persistence in individuals with MDE using determinants of persistence identified in previous research. Method: Data were derived from 250 subjects from the general population with new MDE according to DSM-III-R.

  4. Metabolic aspects of bacterial persisters

    Directory of Open Access Journals (Sweden)

    Marcel ePrax

    2014-10-01

    Full Text Available Persister cells form a multi-drug tolerant subpopulation within an isogenic culture of bacteria that are genetically susceptible to antibiotics. Studies with different Gram negative and Gram positive bacteria have identified a large number of genes associated with the persister state. In contrast, the revelation of persister metabolism has only been addressed recently. We here summarize metabolic aspects of persisters, which includes an overview about the bifunctional role of selected carbohydrates as both triggers for the exit from the drug tolerant state and metabolites which persisters feed on. Also alarmones as indicators for starvation have been shown to influence persister levels via different signaling cascades involving the activation of toxin-antitoxin systems and other regulatory factors. Finally, recent data obtained by 13C-isotopologue profiling demonstrated an active amino acid anabolism in Staphylococcus aureus cultures challenged with high drug concentrations. Understanding the metabolism of persister cells poses challenges but also paves the way for the development of anti-persister compounds.

  5. Biodistribution and Toxicological Safety of Adenovirus Type 5 and Type 35 Vectored Vaccines Against Human Immunodeficiency Virus-1 (HIV-1), Ebola, or Marburg Are Similar Despite Differing Adenovirus Serotype Vector, Manufacturer's Construct, or Gene Inserts

    OpenAIRE

    Sheets, Rebecca L.; Stein, Judith; Bailer, Robert T.; Koup, Richard A.; Andrews, Charla; Nason, Martha; He, Bin; Koo, Edward; Trotter, Holly; Duffy, Chris; Manetz, T. Scott; Gomez, Phillip

    2008-01-01

    The Vaccine Research Center has developed vaccine candidates for different diseases/infectious agents (including HIV-1, Ebola, and Marburg viruses) built on an adenovirus vector platform, based on adenovirus type 5 or 35. To support clinical development of each vaccine candidate, pre-clinical studies were performed in rabbits to determine where in the body they biodistribute and how rapidly they clear, and to screen for potential toxicities (intrinsic and immunotoxicities). The vaccines biodi...

  6. Use of adenovirus vector expressing the mouse full estrogen receptor alpha gene to infect mouse primary neurons

    Institute of Scientific and Technical Information of China (English)

    Xiao HU; Lei Lou; Jun Yuan; Xing Wan; Jianyi Wang; Xinyue Qin

    2010-01-01

    Estrogen plays important regulatory and protective roles in the central nervous system through estrogen receptor a mediation.Previous studies applied eukaryotic expression and lentiviral vectors carrying estrogen receptor a to clarify the undedying mechanisms,in the present study,an adenovirus vector expressing the mouse full estrogen receptor a gene was constructed to identify biological characteristics of estrogen receptor a recombinant adenovirus infecting nerve cells.Primary cultured mouse nerve cells were first infected with estrogen receptor a recombinant adenovirus at various multiplicities of infection,followed by 100 multiplicity of infection.Results showed overexpression of estrogen receptor a mRNA and protein in the infected nerve cells.Estrogen receptor a recombinant adenovirus at 100 multiplicity of infection successfully infected neurons and upregulated estrogen receptor a mRNA and protein expression.

  7. The evaluation of hollow-fiber ultrafiltration and celite concentration of enteroviruses, adenoviruses and bacteriophage from different water matrices

    Data.gov (United States)

    U.S. Environmental Protection Agency — The data to support the evaluation of hollow-fiber ultrafiltration and celite concentration of enteroviruses, adenoviruses and bacteriophage from different water...

  8. DETECTION OF INFECTIOUS ADENOVIRUS IN TERTIARY TREATED AND UV DISINFECTED WASTEWATER DURING A UV DISINFECTION PILOT STUDY

    Science.gov (United States)

    An infectious enteric adenovirus was isolated from urban wastewater receiving tertiary treatment and ultraviolet (UV) disinfection. A pilot study was undertaken to investigate the efficacy of UV disinfection (low pressure, high intensity radiation) of total and fecal coliform bac...

  9. Demand Response an Alternative Solution to Prevent Load Shedding Triggering

    Directory of Open Access Journals (Sweden)

    K. Mollah

    2014-12-01

    Full Text Available This paper investigates an alternative solution to prevent Load Shedding (LS triggering during underfrequency and proposes a new technique to restore the frequency during emergency events. Demand response (DR is considered as one of the most promising Smart Grid concepts that can be used to support the peak demand, whereas, LS is an existing last resort method during emergency grid situations. Both schemes aim to balance the load and generation in real-time and restore the frequency very quickly. This paper incorporates integrating Incentive based Demand Response (IDR with spinning reserve for smaller underfrequency events to manage the system peak demand. It also introduces a new frequency band for an Emergency Demand Response (EDR as an alternative inexpensive solution that can replace costly spinning reserves and help to prevent LS. An energy index factor is used to identify the consumption pattern of consumers to enable them to participate in IDR. An illustrative example of the performance of the proposed scheme on a modified 15 bus test system is shown. Simulation results on different scenarios confirm that the proposed method is effective to improve the frequency restoration process along with enabling participation of new services.

  10. CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis

    Science.gov (United States)

    Lopes-Pacheco, Miquéias

    2016-01-01

    Cystic fibrosis (CF) is the most common life-threatening monogenic disease afflicting Caucasian people. It affects the respiratory, gastrointestinal, glandular and reproductive systems. The major cause of morbidity and mortality in CF is the respiratory disorder caused by a vicious cycle of obstruction of the airways, inflammation and infection that leads to epithelial damage, tissue remodeling and end-stage lung disease. Over the past decades, life expectancy of CF patients has increased due to early diagnosis and improved treatments; however, these patients still present limited quality of life. Many attempts have been made to rescue CF transmembrane conductance regulator (CFTR) expression, function and stability, thereby overcoming the molecular basis of CF. Gene and protein variances caused by CFTR mutants lead to different CF phenotypes, which then require different treatments to quell the patients’ debilitating symptoms. In order to seek better approaches to treat CF patients and maximize therapeutic effects, CFTR mutants have been stratified into six groups (although several of these mutations present pleiotropic defects). The research with CFTR modulators (read-through agents, correctors, potentiators, stabilizers and amplifiers) has achieved remarkable progress, and these drugs are translating into pharmaceuticals and personalized treatments for CF patients. This review summarizes the main molecular and clinical features of CF, emphasizes the latest clinical trials using CFTR modulators, sheds light on the molecular mechanisms underlying these new and emerging treatments, and discusses the major breakthroughs and challenges to treating all CF patients. PMID:27656143

  11. Correlates of HIV-1 genital shedding in Tanzanian women.

    Directory of Open Access Journals (Sweden)

    Clare Tanton

    Full Text Available BACKGROUND: Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo in Tanzania. METHODOLOGY: Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load. PRINCIPAL FINDINGS: Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load. CONCLUSIONS: RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services.

  12. Dairy shed effluent treatment and recycling: Effluent characteristics and performance.

    Science.gov (United States)

    Fyfe, Julian; Hagare, Dharma; Sivakumar, Muttucumaru

    2016-09-15

    Dairy farm milking operations produce considerable amounts of carbon- and nutrient-rich effluent that can be a vital source of nutrients for pasture and crops. The study aim was to characterise dairy shed effluent from a commercial farm and examine the changes produced by treatment, storage and recycling of the effluent through a two-stage stabilisation pond system. The data and insights from the study are broadly applicable to passive pond systems servicing intensive dairy and other livestock operations. Raw effluent contained mostly poorly biodegradable particulate organic material and organically bound nutrients, as well as a large fraction of fixed solids due to effluent recycling. The anaerobic pond provided effective sedimentation and biological treatment, but hydrolysis of organic material occurred predominantly in the sludge and continually added to effluent soluble COD, nutrients and cations. Sludge digestion also suppressed pH in the pond and increased salt levels through formation of alkalinity. High sludge levels significantly impaired pond treatment performance. In the facultative pond, BOD5 concentrations were halved; however smaller reductions in COD showed the refractory nature of incoming organic material. Reductions in soluble N and P were proportional to reductions in respective particulate forms, suggesting that respective removal mechanisms were not independent. Conditions in the ponds were unlikely to support biological nutrient removal. Recycling caused conservative inert constituents to accumulate within the pond system. Material leaving the system was mostly soluble (86% TS) and inert (65% TS), but salt concentrations remained below thresholds for safe land application. PMID:27213866

  13. Cryogenic transmission electron microscopy nanostructural study of shed microparticles.

    Directory of Open Access Journals (Sweden)

    Liron Issman

    Full Text Available Microparticles (MPs are sub-micron membrane vesicles (100-1000 nm shed from normal and pathologic cells due to stimulation or apoptosis. MPs can be found in the peripheral blood circulation of healthy individuals, whereas elevated concentrations are found in pregnancy and in a variety of diseases. Also, MPs participate in physiological processes, e.g., coagulation, inflammation, and angiogenesis. Since their clinical properties are important, we have developed a new methodology based on nano-imaging that provides significant new data on MPs nanostructure, their composition and function. We are among the first to characterize by direct-imaging cryogenic transmitting electron microscopy (cryo-TEM the near-to-native nanostructure of MP systems isolated from different cell types and stimulation procedures. We found that there are no major differences between the MP systems we have studied, as most particles were spherical, with diameters from 200 to 400 nm. However, each MP population is very heterogeneous, showing diverse morphologies. We investigated by cryo-TEM the effects of standard techniques used to isolate and store MPs, and found that either high-g centrifugation of MPs for isolation purposes, or slow freezing to -80 °C for storage introduce morphological artifacts, which can influence MP nanostructure, and thus affect the efficiency of these particles as future diagnostic tools.

  14. Rotavirus vaccines: viral shedding and risk of transmission.

    Science.gov (United States)

    Anderson, Evan J

    2008-10-01

    Rotavirus causes gastroenteritis in almost all children by 5 years of age. Immunity to rotavirus is incomplete, with potential for recurrent infections occurring throughout life. Live rotavirus vaccines have been developed for the protection of children from severe wildtype rotavirus infections. Transmission of vaccine virus strains from vaccinated children to unvaccinated contacts harbours the potential for herd immunity, but also the risk of vaccine-derived disease in immunocompromised contacts. A review of rotavirus vaccine prelicensure studies shows that viral shedding and transmission were higher with the old tetravalent rhesus rotavirus vaccine than with the current human attenuated monovalent rotavirus vaccine and the pentavalent bovine-human reassortant vaccine. Immunocompromised contacts should be advised to avoid contact with stool from the immunised child if possible, particularly after the first vaccine dose for at least 14 days. Since the risk of vaccine transmission and subsequent vaccine-derived disease with the current vaccines is much less than the risk of wildtype rotavirus disease in immunocompromised contacts, vaccination should be encouraged.

  15. Persistence, resistance, resonance

    Science.gov (United States)

    Tsadka, Maayan

    form of musical consumption and experience. The three pieces draw lines connecting different aspects of persistence, resistance, and resonance.

  16. Community-based Men's Sheds: promoting male health, wellbeing and social inclusion in an international context.

    Science.gov (United States)

    Cordier, Reinie; Wilson, Nathan J

    2014-09-01

    Males experience greater mortality and morbidity than females in most Western countries. The Australian and Irish National Male Health Policies aim to develop a framework to address this gendered health disparity. Men's Sheds have a distinct community development philosophy and are thus identified in both policies as an ideal location to address social isolation and positively impact the health and wellbeing of males who attend. The aim of this international cross-sectional survey was to gather information about Men's Sheds, the people who attend Men's Sheds, the activities at Men's Sheds, and the social and health dimensions of Men's Sheds. Results demonstrate that Men's Sheds are contributing a dual health and social role for a range of male subgroups. In particular, Men's Sheds have an outward social focus, supporting the social and mental health needs of men; health promotion and health literacy are key features of Men's Sheds. Men's Sheds have an important role to play in addressing the gendered health disparity that males face. They serve as an exemplar to health promotion professionals of a community development context where the aims of male health policy can be actualized as one part of a wider suite of global initiatives to reduce the gendered health disparity.

  17. Acoustic interaction with vortex structures shed by an obstacle in a closed cavity

    Science.gov (United States)

    Biron, D.; Hebrard, P.; Pauzin, S.; Garnier, F.; Labegorre, B.; Laverdant, A.

    CERT-DERMES has created an experimental set-up for studying the interaction between acoustics and coherent structures. The set-up comprises a subsonic diffuser, a rectangular wind tunnel with a square prismatic obstacle placed at an incidence to shed vortices, and a converging-diverging nozzle. The sound waves are observed to be amplified when the acoustic triggering and vortex shedding frequencies are close to one another. A numerical simulation using an adapted version of the KIVA code developed at Los Alamos replicated experimental vortex shedding with particle dyes. The experimental and numerical Strouhal numbers for the vortex shedding behind the obstacle are in good agreement with previously published results.

  18. Efficient generation of double heterologous promoter controlled oncolytic adenovirus vectors by a single homologous recombination step in Escherichia coli

    OpenAIRE

    Wildner Oliver; Hoffmann Dennis

    2006-01-01

    Abstract Background Oncolytic adenoviruses are promising agents for the multimodal treatment of cancer. However, tumor-selectivity is crucial for their applicability in patients. Recent studies by several groups demonstrated that oncolytic adenoviruses with tumor-/tissue-specific expression of the E1 and E4 genes, which are pivotal for adenoviral replication, have a specificity profile that is superior to viruses that solely target the expression of E1 or E4 genes. Presently the E1 and E4 reg...

  19. Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus.

    OpenAIRE

    Lubeck, M D; Davis, A R; Chengalvala, M; Natuk, R J; Morin, J E; Molnar-Kimber, K; Mason, B. B.; Bhat, B M; Mizutani, S; Hung, P P

    1989-01-01

    As a major cause of acute and chronic liver disease as well as hepatocellular carcinoma, hepatitis B virus (HBV) continues to pose significant health problems world-wide. Recombinant hepatitis B vaccines based on adenovirus vectors have been developed to address global needs for effective control of hepatitis B infection. Although considerable progress has been made in the construction of recombinant adenoviruses that express large amounts of HBV gene products, preclinical immunogenicity and ...

  20. Molecular epidemiological study of adenovirus infecting western lowland gorillas and humans in and around Moukalaba-Doudou National Park (Gabon).

    Science.gov (United States)

    Nkogue, Chimène Nze; Horie, Masayuki; Fujita, Shiho; Ogino, Michiko; Kobayashi, Yuki; Mizukami, Keijiro; Masatani, Tatsunori; Ezzikouri, Sayeh; Matsuu, Aya; Mizutani, Tetsuya; Ozawa, Makoto; Yamato, Osamu; Ngomanda, Alfred; Yamagiwa, Juichi; Tsukiyama-Kohara, Kyoko

    2016-10-01

    Adenoviruses are widespread in human population as well as in great apes, although the data about the naturally occurring adenovirus infections remain rare. We conducted the surveillance of adenovirus infection in wild western lowland gorillas in Moukalaba-Doudou National Park (Gabon), in order to investigate naturally occurring adenovirus in target gorillas and tested specifically a possible zoonotic transmission with local people inhabiting the vicinity of the park. Fecal samples were collected from western lowland gorillas and humans, and analyzed by PCR. We detected adenoviral genes in samples from both gorillas and the local people living around the national park, respectively: the overall prevalence rates of adenovirus were 24.1 and 35.0 % in gorillas and humans, respectively. Sequencing revealed that the adenoviruses detected in the gorillas were members of Human mastadenovirus B (HAdV-B), HAdV-C, or HAdV-E, and those in the humans belonged to HAdV-C or HAdV-D. Although HAdV-C members were detected in both gorillas and humans, phylogenetic analysis revealed that the virus detected in gorillas are genetically distinct from those detected in humans. The HAdV-C constitutes a single host lineage which is compatible with the host-pathogen divergence. However, HAdV-B and HAdV-E are constituted by multiple host lineages. Moreover, there is no evidence of zoonotic transmission thus far. Since the gorilla-to-human transmission of adenovirus has been shown before, the current monitoring should be continued in a broader scale for getting more insights in the natural history of naturally occurring adenoviruses and for the safe management of gorillas' populations.

  1. A pRb-responsive, RGD-modified, and Hyaluronidase-armed Canine Oncolytic Adenovirus for Application in Veterinary Oncology

    OpenAIRE

    Laborda, Eduardo; Puig-Saus, Cristina; Rodriguez-García, Alba; Moreno, Rafael; Cascalló, Manel; Pastor, Josep; Alemany, Ramon

    2014-01-01

    Human and canine cancer share similarities such as genetic and molecular aspects, biological complexity, tumor epidemiology, and targeted therapeutic treatment. Lack of good animal models for human adenovirotherapy has spurred the use of canine adenovirus 2-based oncolytic viruses. We have constructed a canine oncolytic virus that mimics the characteristics of our previously published human adenovirus ICOVIR17: expression of E1a controlled by E2F sites, deletion of the pRb-binding site of E1a...

  2. Molecular epidemiological study of adenovirus infecting western lowland gorillas and humans in and around Moukalaba-Doudou National Park (Gabon).

    Science.gov (United States)

    Nkogue, Chimène Nze; Horie, Masayuki; Fujita, Shiho; Ogino, Michiko; Kobayashi, Yuki; Mizukami, Keijiro; Masatani, Tatsunori; Ezzikouri, Sayeh; Matsuu, Aya; Mizutani, Tetsuya; Ozawa, Makoto; Yamato, Osamu; Ngomanda, Alfred; Yamagiwa, Juichi; Tsukiyama-Kohara, Kyoko

    2016-10-01

    Adenoviruses are widespread in human population as well as in great apes, although the data about the naturally occurring adenovirus infections remain rare. We conducted the surveillance of adenovirus infection in wild western lowland gorillas in Moukalaba-Doudou National Park (Gabon), in order to investigate naturally occurring adenovirus in target gorillas and tested specifically a possible zoonotic transmission with local people inhabiting the vicinity of the park. Fecal samples were collected from western lowland gorillas and humans, and analyzed by PCR. We detected adenoviral genes in samples from both gorillas and the local people living around the national park, respectively: the overall prevalence rates of adenovirus were 24.1 and 35.0 % in gorillas and humans, respectively. Sequencing revealed that the adenoviruses detected in the gorillas were members of Human mastadenovirus B (HAdV-B), HAdV-C, or HAdV-E, and those in the humans belonged to HAdV-C or HAdV-D. Although HAdV-C members were detected in both gorillas and humans, phylogenetic analysis revealed that the virus detected in gorillas are genetically distinct from those detected in humans. The HAdV-C constitutes a single host lineage which is compatible with the host-pathogen divergence. However, HAdV-B and HAdV-E are constituted by multiple host lineages. Moreover, there is no evidence of zoonotic transmission thus far. Since the gorilla-to-human transmission of adenovirus has been shown before, the current monitoring should be continued in a broader scale for getting more insights in the natural history of naturally occurring adenoviruses and for the safe management of gorillas' populations. PMID:27290717

  3. Epidemiology and transmission characteristics of human adenovirus type 7 caused acute respiratory disease outbreak in military trainees in East China

    OpenAIRE

    Cheng, Jun; Qi, Xiaoping; Chen, Dawei; Xu, Xujian; Wang, Guozheng; Dai, Yuzhu; Cui, Dawei; Chen, Qingyong; Fan, Ping; Ni, Liuda; Liu, Miao; Zhu, Feiyan; Yang, Mei; Wang, Changjun; Li, Yuexi

    2016-01-01

    Background: Human adenovirus type 7 (HAdV7) is globally attracting great concern as its high morbidity and severity in respiratory diseases, especially in Asia. Objective: To investigate the clinical and epidemiologic characteristics of HAdV7 infection outbreak in East China. Methods: The clinical samples were collected from the patients of an ARD outbreak in East Chinafor the detection of causative pathogens by multiplex PCR. The molecular type of human adenovirus isolates were identified by...

  4. Combined transductional untargeting/retargeting and transcriptional restriction enhance adenovirus gene targeting and therapy for hepatic colorectal cancer tumors

    OpenAIRE

    Li, Hua-Jung; Everts, Maaike; Yamamoto, Masato; Curiel, David T.; Herschman, Harvey R.

    2009-01-01

    Unresectable hepatic colorectal cancer (CRC) metastases are a leading cause of cancer mortality. These tumors, and other epithelial tumors, often express both cyclooxygenase 2 (COX-2) and carcinoembryonic antigen (CEA). Because adenovirus vectors infect liver and lack tumor tropism, they cannot be utilized for systemic therapy of hepatic metastases. We used COX-2 transcriptional restriction, in combination with transductional adenovirus hepatic untargeting and tumor retargeting by a bispecifi...

  5. Energy landscapes and persistent minima

    International Nuclear Information System (INIS)

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests

  6. Energy landscapes and persistent minima

    Energy Technology Data Exchange (ETDEWEB)

    Carr, Joanne M.; Wales, David J., E-mail: dw34@cam.ac.uk [University Chemical Laboratories, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Mazauric, Dorian; Cazals, Frédéric, E-mail: frederic.cazals@inria.fr [Inria Sophia Antipolis Méditerranée, 2004 route des Lucioles, F-06902 Sophia Antipolis (France)

    2016-02-07

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests.

  7. Smallpox vaccine, ACAM2000: Sites and duration of viral shedding and effect of povidone iodine on scarification site shedding and immune response.

    Science.gov (United States)

    Pittman, Phillip R; Garman, Patrick M; Kim, Sung-Han; Schmader, Trevor J; Nieding, William J; Pike, Jason G; Knight, Ryan; Johnston, Sara C; Huggins, John W; Kortepeter, Mark G; Korman, Lawrence; Ranadive, Manmohan; Quinn, Xiaofei; Meyers, Mitchell S

    2015-06-12

    The U.S. Department of Defense vaccinates personnel deployed to high-risk areas with the vaccinia virus (VACV)-based smallpox vaccine. Autoinoculations and secondary and tertiary transmissions due to VACV shedding from the vaccination site continue to occur despite education of vaccinees on the risks of such infections. The objectives of this study were to investigate, in naïve smallpox vaccinees, (a) whether the vaccination site can remain contagious after the scab separates and (b) whether the application of povidone iodine ointment (PIO) to the vaccination site inactivates VACV without affecting the immune response. These objectives were tested in 60 individuals scheduled to receive smallpox vaccine. Thirty individuals (control) did not receive PIO; 30 subjects (treatment) received PIO starting on post-vaccination day 7. Counter to current dogma, this study showed that VACV continues to shed from the vaccination site after the scab separates. Overall viral shedding levels in the PIO group were significantly lower than those in the control group (p=0.0045), and PIO significantly reduced the duration of viral shedding (median duration 14.5 days and 21 days in the PIO and control groups, respectively; p=0.0444). At least 10% of control subjects continued to shed VACV at day 28, and 3.4% continued to shed the virus at day 42. PIO reduced the proportion of subjects shedding virus from the vaccination site from day 8 until days 21-23 compared with control subjects. Groups did not differ significantly in the proportion of subjects mounting an immune response, as measured by neutralizing antibodies, IgM, IgG, and interferon-gamma enzyme-linked immunospot assay. When applied to the vaccination site starting on day 7, PIO reduced viral shedding without altering the immune response. The use of PIO in addition to a semipermeable dressing may reduce the rates of autoinoculation and contact transmission originating from the vaccination site in smallpox-vaccinated individuals.

  8. [MOLECULAR ASPECTS OF BRUCELLA PERSISTENCE].

    Science.gov (United States)

    Kulakov Yu K

    2016-01-01

    Brucellosis is a dangerous zoonotic disease of animals and humans caused by bacteria of the genus Brucella, which are able to survive, multiply, and persist in host cells. The review is devoted to the Brucella species persistence connected to the molecular mechanisms of escape from innate and adaptive immunity of the host and active interaction of effector proteins of the type IV secretion system with the host's signaling pathways. Understanding of the molecular mechanisms used by Brucella for the intracellular persistence in the host organism can allow us to develop new and effective means for the prevention and treatment of chronic brucellosis infection.

  9. Construction and identification of recombinant adenovirus-mediated gene transfer system for rat vascular endothelial growth factor

    Institute of Scientific and Technical Information of China (English)

    Hongyu Yang; Hong Qi; Junjie Zou; Xiwei Zhang

    2008-01-01

    Objective: To construct the recombinant adenovirus vector carrying rat vascular endothelial growth factor(VEGF), as preparation for genetic transfection that follows. Methods: Rat VEGF was obtained by using RT-PCR amplification and then cloned into the shutter plasmid pDC316. Subsequently, this newly constructed plasmid pDC316-VEGF, after identification by nuclease digestion analysis and sequencing analysis, was transfected into human embryonic kidney cells HEK293 by Lipofectamine 2000 mediation, together with adenovirus-packaging plasmid pBHGE3. Based on the homologous recombination of the two plasmids within HEK293 cells, the recombinant adenovirus vector carrying VEGF and VDC316-VEGF was created. VDC316-VEGF was subsequently identified using PCR, purified using repeated plaque passages, proliferated using freezing and melting within HEK293 cells, and titrated using 50% Tissue Culture Infective Dose(TCID50) assay. Results:The newly constructed recombinant adenovirus was confirmed to carry rat VEGF based on PCR results, and its titration value determined based on TCID50 assay was 3×109 pfu/ml. Conclusion:The recombinant adenovirus carrying rat VEGF was successfully constructed. The newly constructed adenovirus can produce a sufficiently high titration value within HEK293 cells, providing a reliable tool for genetic transfection in further gene therapy researches.

  10. Identification of a nonstructural DNA-binding protein (DBP as an antigen with diagnostic potential for human adenovirus.

    Directory of Open Access Journals (Sweden)

    Li Guo

    Full Text Available BACKGROUND: Human adenoviruses (HAdVs have been implicated as important agents in a wide range of human illnesses. To date, 58 distinct HAdV serotypes have been identified and can be grouped into six species. For the immunological diagnosis of adenoviruses, the hexon protein, a structural protein, has been used. The potential of other HAdV proteins has not been fully addressed. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a nonstructural antigenic protein, the DNA binding protein (DBP of human adenovirus 5 and 35 (Ad5, Ad35 - was identified using immunoproteomic technology. The expression of Ad5 and Ad35 DBP in insect cells could be detected by rhesus monkey serum antibodies and healthy adult human serum positive for Ad5 and Ad35. Recombinant DBPs elicited high titer antibodies in mice. Their conserved domain displayed immunological cross-reactions with heterologous DBP antibodies in Western blot assays. DBP-IgM ELISA showed higher sensitivity adenovirus IgM detection than the commercial Adenovirus IgM Human ELISA Kit. A Western blot method developed based on Ad5 DBP was highly consistent with (χ(2 = 44.9, P<0.01 the Western blot assay for the hexon protein in the detection of IgG, but proved even more sensitive. CONCLUSIONS/SIGNIFICANCE: The HAdV nonstructural protein DBP is an antigenic protein that could serve as an alternative common antigen for adenovirus diagnosis.

  11. Construction of Rat Calcineurin A α cDNA Recombinant Adenovirus Vector and Its Identification

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Rat calcineurin (CaN) A α isoform (Ppp3ca) cDNA recombinant adenovirus vector was constructed in order to explore the effect of CaN on the myocardium apoptosis induced by ischemiareperfusion injury. Total RNA was isolated from the heart of the adult Wistar rat, and Ppp3ca CDS segment of approximate 1.59 kb size was amplified by reverse transcriptional PCR method. Ppp3ca cDNA segment was cloned into pMD18-T Simple vector for sequencing, and the right clone was named T-Ppp3ca. Ppp3ca cDNA segment obtained from T-Ppp3ca was ligated with pShuttle2-IRES-EGFP to construct a recombinant plasmid pShuttle2-Ppp3ca-IRES-EGFP. Ppp3ca-IRES-EG-FP expression cassette containing CMV, Ppp3ca-IRES-EGFP and SV40 polyA DNA fragment (3.97 kb) obtained from pShuttle2-Ppp3ca-IRES-EGFP was connected with pAdeno-X backbone sequence to construct a recombinant plasmid pAdeno-Ppp3ca. After being identified by PCR and enzyme digestion, recombinant plasmid pAdeno-Ppp3ca was packaged in HEK293 cells. Supernatant of adenovirus from HEK293 cells was collected after a visible cytopathic effect (CPE) appeared.The DNA of the recombinant adenovirus was extracted with the standard method. The presence of the recombinant adenovirus was verified by PCR. The results showed that sequencing results veri fied that the PCR product of Ppp3ca gene was identical to GenBank. Agarose electrophoresis showed the bands of recombined plasmid pAdeno-Ppp3ca and the recombinant adenovirus identified by enzyme digestion and PCR were in the right range corresponding with expectation. It was concluded that the recombinant adenovirus carrying rat calcineurin A α (Ppp3ca) cDNA as well as a report gene-enhancer green fluorescent protein gene was successfully constructed in this experiment.

  12. A novel psittacine adenovirus identified during an outbreak of avian chlamydiosis and human psittacosis: zoonosis associated with virus-bacterium coinfection in birds.

    OpenAIRE

    To, Kelvin K. W.; Herman Tse; Wan-Mui Chan; Choi, Garnet K. Y.; Zhang, Anna J. X.; Siddharth Sridhar; Wong, Sally C. Y.; Chan, Jasper F. W.; Chan, Andy S. F.; Woo, Patrick C. Y.; Susanna K P Lau; Lo, Janice Y. C.; Kwok-Hung Chan; Cheng, Vincent C. C.; Kwok-Yung Yuen

    2014-01-01

    Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1) was most closely related to Du...

  13. Comparison of three nonlinear models to describe long-term tag shedding by lake trout

    Science.gov (United States)

    Fabrizio, Mary C.; Swanson, Bruce L.; Schram, Stephen T.; Hoff, Michael H.

    1996-01-01

    We estimated long-term tag-shedding rates for lake trout Salvelinus namaycush using two existing models and a model we developed to account for the observed permanence of some tags. Because tag design changed over the course of the study, we examined tag-shedding rates for three types of numbered anchor tags (Floy tags FD-67, FD-67C, and FD-68BC) and an unprinted anchor tag (FD-67F). Lake trout from the Gull Island Shoal region, Lake Superior, were double-tagged, and subsequent recaptures were monitored in annual surveys conducted from 1974 to 1992. We modeled tag-shedding rates, using time at liberty and probabilities of tag shedding estimated from fish released in 1974 and 1978–1983 and later recaptured. Long-term shedding of numbered anchor tags in lake trout was best described by a nonlinear model with two parameters: an instantaneous tag-shedding rate and a constant representing the proportion of tags that were never shed. Although our estimates of annual shedding rates varied with tag type (0.300 for FD-67, 0.441 for FD-67C, and 0.656 for FD-68BC), differences were not significant. About 36% of tags remained permanently affixed to the fish. Of the numbered tags that were shed (about 64%), two mechanisms contributed to tag loss: disintegration and dislodgment. Tags from about 11% of recaptured fish had disintegrated, but most tags were dislodged. Unprinted tags were shed at a significant but low rate immediately after release, but the long-term, annual shedding rate of these tags was only 0.013. Compared with unprinted tags, numbered tags dislodged at higher annual rates; we hypothesized that this was due to the greater frictional drag associated with the larger cross-sectional area of numbered tags.

  14. Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors

    Directory of Open Access Journals (Sweden)

    Chandhoke Vikas

    2006-02-01

    Full Text Available Abstract Background It has been recently reported that major pathogens Staphylococcus aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface syndecan-1 (Synd1 ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if acceleration of Synd1 shedding takes place in vitro upon treatment of epithelial cells with B. anthracis hemolysins, as well as in vivo during anthrax infection in mice. Results The isolated anthrax hemolytic proteins AnlB (sphingomyelinase and AnlO (cholesterol-binding pore-forming factor, as well as ClnA (B. cereus homolog of B. anthracis phosphatidyl choline-preferring phospholipase C cause accelerated shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial barrier integrity within a few hours. In comparison with hemolysins in a similar range of concentrations, anthrax lethal toxin (LT also accelerates shedding albeit at slower rate. Individual components of LT, lethal factor and protective antigen are inactive with regard to shedding. Inhibition experiments favor a hypothesis that activities of tested bacterial shedding inducers converge on the stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK signaling pathways, while JNK pathway seems to be irrelevant to accelerated shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged with Bacillus anthracis (Sterne spores. Elevated levels of shed ectodomain are readily detectable in circulation after 24 h. Conclusion The concerted acceleration of shedding by several virulence factors could represent a new pathogenic mechanism contributing to disruption of epithelial or endothelial integrity, hemorrhage, edema and abnormal cell signaling during anthrax infection.

  15. Object-oriented persistent homology

    Science.gov (United States)

    Wang, Bao; Wei, Guo-Wei

    2016-01-01

    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  16. A study on the frictional response of reptilian shed skin

    International Nuclear Information System (INIS)

    Deterministic surfaces are constructs of which profile, topography and textures are integral to the function of the system they enclose. They are designed to yield a predetermined tribological response. Developing such entities relies on controlling the structure of the rubbing interface so that, not only the surface is of optimized topography, but also is able to self-adjust its tribological behaviour according to the evolution of sliding conditions. In seeking inspirations for such designs, many engineers are turning toward the biological world to study the construction and behaviour of bio-analogues, and to probe the role surface topography assumes in conditioning of frictional response. That is how a bio-analogue can self-adjust its tribological response to adapt to habitat constraints. From a tribological point of view, Squamate Reptiles, offer diverse examples where surface texturing, submicron and nano-scale features, achieves frictional regulation. In this paper, we study the frictional response of shed skin obtained from a snake (Python regius). The study employed a specially designed tribo-acoustic probe capable of measuring the coefficient of friction and detecting the acoustical behavior of the skin in vivo. The results confirm the anisotropy of the frictional response of snakes. The coefficient of friction depends on the direction of sliding: the value in forward motion is lower than that in the backward direction. Diagonal and side winding motion induces a different value of the friction coefficient. We discuss the origin of such a phenomenon in relation to surface texturing and study the energy constraints, implied by anisotropic friction, on the motion of the reptile.

  17. Human Capital Persistence and Development

    OpenAIRE

    Rocha, Rudi; Ferraz, Claudio; Soares, Rodrigo R.

    2015-01-01

    This paper examines the role of human capital persistence in explaining long-term development. We exploit variation induced by a state-sponsored settlement policy that attracted a pool of immigrants with higher levels of schooling to particular regions of Brazil in the late 19th and early 20th century. We show that municipalities that received settlements experienced increases in schooling that persisted over time. One century after the policy, localities that received state-sponsored settlem...

  18. Teriparatide Induced Delayed Persistent Hypercalcemia

    Directory of Open Access Journals (Sweden)

    Nirosshan Thiruchelvam

    2014-01-01

    Full Text Available Teriparatide, a recombinant PTH, is an anabolic treatment for osteoporosis that increases bone density. Transient hypercalcemia is a reported side effect of teriparatide that is seen few hours following administration of teriparatide and resolves usually within 16 hours of drug administration. Persistent hypercalcemia, although not observed in clinical trials, is rarely reported. The current case describes a rare complication of teriparatide induced delayed persistent hypercalcemia.

  19. Population Dynamics of Bacterial Persistence

    OpenAIRE

    Patra, Pintu; Klumpp, Stefan

    2013-01-01

    Persistence is a prime example of phenotypic heterogeneity, where a microbial population splits into two distinct subpopulations with different growth and survival properties as a result of reversible phenotype switching. Specifically, persister cells grow more slowly than normal cells under unstressed growth conditions, but survive longer under stress conditions such as the treatment with bactericidal antibiotics. We analyze the population dynamics of such a population for several typical ex...

  20. : Socioeconomic position and depression persistence.

    OpenAIRE

    Melchior, Maria; Chastang, Jean-François; Leclerc, Annette; Ribet, Céline; Rouillon, Frédéric

    2010-01-01

    International audience Research examining the association between socioeconomic position and depression course has yielded inconsistent results. We tested the association between low socioeconomic position and 7-year depression persistence among 298 community-based individuals with depression (subset of the GAZEL cohort study based in France). Data were analyzed using Generalized Estimating Equation (GEE models). Low socioeconomic position predicted depression persistence (men: low vs. int...

  1. Assessment of the Incidence of Enteric Adenovirus Species and Serotypes in Surface Waters in the Eastern Cape Province of South Africa: Tyume River as a Case Study

    Directory of Open Access Journals (Sweden)

    Timothy Sibanda

    2012-01-01

    Full Text Available TaqMan real-time PCR was used for the detection and quantitation of adenoviruses in Tyume River water samples over a 12-month period. A total of 72 samples were analysed, and 22 samples were positive for adenovirus. Of the positive samples, 18 were collected from downstream sampling points. Among the downstream sampling points, adenovirus detection rate increased with distance downstream, being 28%, 33%, and 39% for Alice, Drayini, and Manqulweni, respectively. The Alice sampling site had the highest concentrations of adenovirus ranging between 6.54×103 genome copies/L and 8.49×104 genome copies/L. The observed trend could have been expected considering the level of anthropogenic activities in areas along the lower stretch of Tyume River, with the major one being the effluent of treated and semi treated sewage from wastewater treatment facilities. Adenovirus detection was sporadic at most sampling sites. Multiplex conventional PCR was used for the detection of clinically important adenovirus species B, C, and F and their serotypes. Species C and F adenoviruses were detected in 77% and 18% of the samples, respectively. Most adenovirus positive samples were obtained from areas of increased population densities. The presence of adenoviruses may confirm the risk of its transmission to the human population.

  2. Unusual properties of adenovirus E2E transcription by RNA polymerase III.

    Science.gov (United States)

    Huang, Wenlin; Flint, S J

    2003-04-01

    In adenovirus type 5-infected cells, RNA polymerase III transcription of a gene superimposed on the 5' end of the E2E RNA polymerase II transcription unit produces two small (chase method appear to account for their limited accumulation. The transcription of E2E sequences by RNA polymerase II and III in cells infected by recombinant adenoviruses carrying ectopic E2E-CAT (chloramphenicol transferase) reporter genes with mutations in E2E promoter sequences was also examined. The results of these experiments indicate that recognition of the E2E promoter by the RNA polymerase II transcriptional machinery in infected cells limits transcription by RNA polymerase III, and vice versa. Such transcriptional competition and the properties of E2E RNAs made by RNA polymerase III suggest that the function of this viral RNA polymerase III transcription unit is unusual. PMID:12634361

  3. Establishment of an agamid cell line and isolation of adenoviruses from central bearded dragons (Pogona vitticeps).

    Science.gov (United States)

    Ball, Inna; Hoferer, Marc; Marschang, Rachel E

    2014-03-01

    A cell line was established from whole 6-8-week-old central bearded dragon (Pogona vitticeps) embryos. Cells were mid-sized and showed an elongated and polymorphic form. The cell line grew in a monolayer and has been serially passaged for 17 passages at time of publication. This cell line has been used with samples from adenovirus polymerase chain reaction (PCR)-positive bearded dragons, and 2 virus isolates have been obtained so far. The isolates show a clear cytopathic effect in inoculated cells. Both virus isolates have been serially passaged on this cell line, and have been identified by PCR amplification and sequencing of a portion of the DNA-dependent DNA polymerase gene and show 100% nucleotide identity to the corresponding region of an agamid adenovirus. Electron microscopic examination of supernatant from infected cells demonstrated the presence of nonenveloped particles, with a diameter of approximately 80 nm in both virus isolates. PMID:24569225

  4. Acute respiratory distress syndrome in adenovirus type 4 pneumonia: A case report.

    Science.gov (United States)

    Narra, R; Bono, P; Zoccoli, A; Orlandi, A; Piconi, S; Grasselli, G; Crotti, S; Girello, A; Piralla, A; Baldanti, F; Lunghi, G

    2016-08-01

    Human adenoviruses (HAdVs) cause a wide spectrum of clinical syndromes, depending on species and types, from mild respiratory infections to deadly pneumonia: in particular, severe infections occur in immunocompromised patients. In this report, we describe the case of a 36 years-old woman admitted to our intensive care unit (ICU) with severe respiratory distress syndrome caused by adenovirus pneumonia, that required invasive respiratory support (mechanical ventilation and extracorporeal membrane oxygenation). Molecular assays detected the virus in respiratory and plasma specimen and sequencing procedure identified HAdV type 4. Patient improved after cidofovir administration. Leukopenia and subsequent bacterial infection occurred, but the patient recovered completely and was discharged from the hospital after 54days. PMID:27354307

  5. Inhibitory Effect of Pulmonary Carcinoma by Adenovirus-Mediated CD/UPRT Gene

    Institute of Scientific and Technical Information of China (English)

    HUANG Qi; CHEN Dayu; FU Xiangning; ZU Yukun

    2006-01-01

    The cell killing effects and bystander effects of double suicide gene on pulmonary carcinoma cells were explored. Lung adenocarcinoma cells (A549) were transfected with different titers of adenovirus vector and followed with different concentrations of 5-FC after a recombinant adenovirus vector carrying CD/UPRT gene (Ad-CD/UPRT) was constructed. The cell viability was measured by MTT assay 4 days later. The cell viability was dropped to 30.57 %-8.62 % after 10 MOI of Ad-CD/UPRT transfected and 5-FC (10-1000 μg/mL) administration. Furthermore, Ad-CD/UPRT-infected A549 cells showed a profound neighbor cell killing effect in the same methods. These results suggested that Ad-CD/UPRT/5-FC system can effectively suppress growth of lung adenocarcinoma cells, which may provide a novel and powerful candidate for lung cancer gene therapy strategies.

  6. Adenovirus-mediated transfer of RA538 gene and its antitumor effect

    Institute of Scientific and Technical Information of China (English)

    程金科; 林晨; 隗玥; 张雪艳; 邢嵘; 牟巨伟; 王秀琴; 吴旻

    1999-01-01

    The RA538 cDNA was transferred into human ovarian cancer cell line SK-OV-3 and human melanoma cell line WM-983A by its recombinant adenoviral vector constructed through homologous recombination. It was demonstrated that the recombinant adenovirus could transfer RA538 gene with high efficiency, and could obviously inhibit tumor growth, with the inhibiting rates of 85% and 73% respectively, at the same time greatly repress the colony forming ability of the cells. The therapeutic experiments on transplanted subcutaneous tumor model in nude mice demonstrated that RA538 could significantly inhibit tumor growth. Flow cytometry and DNA fragmentation analysis indicated that RA538 could induce the cell cycle G1 arrest/apoptosis of the tumor cells. The expression of cmyc gene was found pronouncedly reduced by Western blot analysis. These results suggest that the RA538 recombinant adenovirus could be a promising drug in cancer gene therapy.

  7. Inclusion body hepatitis (IBH outbreak associated with fowl adenovirus type 8b in broilers

    Directory of Open Access Journals (Sweden)

    Zadravec M.

    2013-01-01

    Full Text Available The causative agent of inclusion body hepatitis (IBH was identified as fowl adenovirus (FAdV type 8b, a member of the Fowl adenovirus E species, based on PCR results of adenoviral polymerase and the hexon gene in an outbreak of acute mortality that affected a broiler flock of 12,000 animals. In two waves of elevated mortality rate, a total of 264 chickens were found dead. Affected birds showed ruffled feathers, depression, watery droppings and limping. The most common pathological lesions seen on necropsy were pale, swollen and friable livers. On histological examination, acute hepatitis characterized by necrosis of hepatocytes, with large basophilic intranuclear inclusion bodies, were observed. In addition, infectious bursal disease virus and infectious bronchitis virus were detected in the same flock.

  8. A retrospective investigation of canine adenovirus (CAV infection in adult dogs in Turkey : article

    Directory of Open Access Journals (Sweden)

    S. Gur

    2009-05-01

    Full Text Available Canine adenovirus (CAV type 1 and 2, respectively, cause infectious canine hepatitis and infectious canine laryngotracheitis in members of the families Canidae and Ursidae worldwide. Both of these infections are acute diseases, especially in young dogs. The aim of this study was to conduct a serological investigation of canine adenovirus infection. For this purpose, serumsamples were collected from native pure-bred Kangal (n = 11, and Akbash dogs (n = 17 and Turkish Greyhounds (n=15 in Eskisehir and Konya provinces. None ofthe dogs were previously vaccinated against CAV types. Indirect ELISA detected 88.2 %, 93.3 % and 100 % prevalences in Akbash, Greyhound and Kangal dogs, respectively. The remainder of the samples (n = 51 were collected at the Afyonkarahisar Municipality Shelter. Fourty-two of these dogs (82.3 % were detected as seropositive. In total, 82 of 94 dogs (87.2 % were found to be positive for CAV serum antibodies.

  9. A retrospective investigation of canine adenovirus (CAV) infection in adult dogs in Turkey.

    Science.gov (United States)

    Gür, S; Acar, A

    2009-06-01

    Canine adenovirus (CAV) type 1 and 2, respectively, cause infectious canine hepatitis and infectious canine laryngotracheitis in members of the families Canidae and Ursidae worldwide. Both of these infections are acute diseases, especially in young dogs. The aim of this study was to conduct a serological investigation of canine adenovirus infection. For this purpose, serum samples were collected from native pure-bred Kangal(n = 11), and Akbash dogs (n = 17) and Turkish Greyhounds (n = 15) in Eskişehir and Konya provinces. None of the dogs were previously vaccinated against CAV types. Indirect ELISA detected 88.2%, 93.3% and 100% prevalences in Akbash, Greyhound and Kangal dogs, respectively. The remainder of the samples (n = 51) were collected at the Afyonkarahisar Municipality Shelter. Fourty-two of these dogs (82.3%) were detected as seropositive. In total, 82 of 94 dogs (87.2%) were found to be positive for CAV serum antibodies. PMID:19831268

  10. Activating Ras mutations fail to ensure efficient replication of adenovirus mutants lacking VA-RNA

    DEFF Research Database (Denmark)

    Schümann, Michael; Dobbelstein, Matthias

    2006-01-01

    Adenoviruses lacking their PKR-antagonizing VA RNAs replicate poorly in primary cells. It has been suggested that these virus recombinants still replicate efficiently in tumor cells with Ras mutations and might therefore be useful in tumor therapy. The ability of interferon-sensitive viruses...... to grow in Ras-mutant tumor cells is generally ascribed to a postulated inhibitory effect of mutant Ras on PKR. We have constructed a set of isogenic adenoviruses that lack either or both VA RNA species, and tested virus replication in a variety of cell species with different Ras status. In tendency, VA......-less viruses replicated with higher efficiency in Ras-mutant cells, as compared to cell lines without Ras mutation. However, several exceptions to this rule were observed, arguing against a direct inhibition of PKR by mutant Ras. Phosphorylation of the PKR-substrate eIF2alpha was observed regardless of the Ras...

  11. Strongyle egg shedding consistency in horses on farms using selective therapy in Denmark

    DEFF Research Database (Denmark)

    Nielsen, Martin Krarup; Haaning, Niels; Olsen, Susanne Nautrup

    2006-01-01

    Knowledge of horses that shed the same number of strongyle eggs over time can lead to the optimization of parasite control strategies. This study evaluated shedding of strongyle eggs in 424 horses on 10 farms whan a selective anthelmintic treatment regime was used over a 3-year period....

  12. Application of computational intelligence techniques for load shedding in power systems: A review

    International Nuclear Information System (INIS)

    Highlights: • The power system blackout history of last two decades is presented. • Conventional load shedding techniques, their types and limitations are presented. • Applications of intelligent techniques in load shedding are presented. • Intelligent techniques include ANN, fuzzy logic, ANFIS, genetic algorithm and PSO. • The discussion and comparison between these techniques are provided. - Abstract: Recent blackouts around the world question the reliability of conventional and adaptive load shedding techniques in avoiding such power outages. To address this issue, reliable techniques are required to provide fast and accurate load shedding to prevent collapse in the power system. Computational intelligence techniques, due to their robustness and flexibility in dealing with complex non-linear systems, could be an option in addressing this problem. Computational intelligence includes techniques like artificial neural networks, genetic algorithms, fuzzy logic control, adaptive neuro-fuzzy inference system, and particle swarm optimization. Research in these techniques is being undertaken in order to discover means for more efficient and reliable load shedding. This paper provides an overview of these techniques as applied to load shedding in a power system. This paper also compares the advantages of computational intelligence techniques over conventional load shedding techniques. Finally, this paper discusses the limitation of computational intelligence techniques, which restricts their usage in load shedding in real time

  13. Influence of thermal inhibitor position and temperature on vortex-shedding-driven pressure oscillations

    Institute of Scientific and Technical Information of China (English)

    Su Wanxing; Li Shipeng; Zhang Qiao; Li Junwei; Ye Qingqing; Wang Ningfei

    2013-01-01

    Vortex-acoustic coupling is one of the most important potential sources of combustion instability in solid rocket motors (SRMs).Based on the Von Karman Institute for Fluid Dynamics (VKI) experimental motor,the influence of the thermal inhibitor position and temperature on vortex-shedding-driven pressure oscillations is numerically studied via the large eddy simulation (LES)method.The simulation results demonstrate that vortex shedding is a periodic process and its accurate frequency can be numerically obtained.Acoustic modes could be easily excited by vortex shedding.The vortex shedding frequency and second acoustic frequency dominate the pressure oscillation characteristics in the chamber.Thermal inhibitor position and gas temperature have little effect on vortex shedding frequency,but have great impact on pressure oscillation amplitude.Pressure amplitude is much higher when the thermal inhibitor locates at the acoustic velocity anti-nodes.The farther the thermal inhibitor is to the nozzle head,the more vortex energy would be dissipated by the turbulence.Therefore,the vortex shedding amplitude at the second acoustic velocity antinode near 3/4L (L is chamber length) is larger than those of others.Besides,the natural acoustic frequencies increase with the gas temperature.As the vortex shedding frequency departs from the natural acoustic frequency,the vortex-acoustic feedback loop is decoupled.Consequently,both the vortex shedding and acoustic amplitudes decrease rapidly.

  14. Proteoglycans in health and disease: the multiple roles of syndecan shedding

    DEFF Research Database (Denmark)

    Manon-Jensen, Tina; Itoh, Yoshifumi; Couchman, John R

    2010-01-01

    dynamics and generates soluble ectodomains that can function as paracrine or autocrine effectors, or competitive inhibitors. It is known that the family of syndecans can be shed by a variety of matrix proteinase, including many metzincins. Shedding is particularly active in proliferating and invasive cells...

  15. Efficient directional cloning of recombinant adenovirus vectors using DNA-protein complex.

    OpenAIRE

    Okada, T; Ramsey, W J; Munir, J; Wildner, O.; Blaese, R M

    1998-01-01

    We describe an efficient cloning system utilizing adenoviral DNA-protein complexes which allows the directional cloning of genes into adenoviral expression vectors in a single step. DNA-protein complexes derived from a recombinant adenovirus (AVC2.null) were isolated by sequential use of CsCl step gradients followed by isopycnic centrifugation in a mixture of CsCl and guanidine HCl. AVC2.null is an adenoviral expression vector containing unique restriction sites between the human CMV-IE promo...

  16. Armoring CRAds with p21/Waf-1 shRNAs: the next generation of oncolytic adenoviruses

    OpenAIRE

    Höti, N; Chowdhury, WH; Mustafa, S.; Ribas, J; Castanares, M; Johnson, T.; Liu, M.; Lupold, SE; Rodriguez, R.

    2010-01-01

    Conditionally replicating adenoviruses (CRAds) represent a promising modality for the treatment of neoplastic diseases, including Prostate Cancer. Selectively replicating viruses can be generated by placing a tissue or cancer-specific promoter upstream of one or more of the viral genes required for replication (for example, E1A, E1B). We have previously reported multiple cellular processes that can attenuate viral replication, which in turn compromises viral oncolysis and tumor kill. In this ...

  17. Bicalutamide Activated Oncolytic Adenovirus for the Adjuvant Therapy of High Risk Prostate Cancer

    OpenAIRE

    Johnson, Tamara Jane; Hoti, Naser Uddin; Liu, Chunyan; Chowdhury, Wasim H.; Ying LI; Zhang, Yonggang; Lupold, Shawn E.; DeWeese, Theodore; Rodriguez, Ronald

    2013-01-01

    Conditionally replicating adenoviruses (CRAds) utilize tissue specific promoters to control the expression of the early genes, E1A and E1B, to preferentially replicate and lyse tumor cells (oncolysis). Previous CRAds used in prostate cancer gene therapy require androgens to activate prostate specific promoters and induce viral replication. Unfortunately, these CRAds have reduced activity in patients on androgen suppressive therapy. We describe a novel prostate specific CRAd generated by fusin...

  18. Triple-controlled oncolytic adenovirus expressing melittin to exert inhibitory efficacy on hepatocellular carcinoma

    OpenAIRE

    Qian, Chun-Yu; Wang, Kai-Li; Fang, Fan-Fu; Gu, Wei; Huang, Feng; Wang, Fu-Zhe; Li, Bai; Wang, Li-Na

    2015-01-01

    Hepatocellular carcinoma (HCC) is a highly malignant disease, and its outcome of routine therapies is poor. Comprehensive treatment including gene therapy is an important way to improve patients’ prognosis and survival. In this study, we successfully constructed a triple-controlled cancer-selective oncolytic adenovirus, QG511-HA-Melittin, carrying melittin gene, in which the hybrid promoter, hypoxia-response element (HRE)-AFP promoter, was used to control viral E1a expression targeting AFP-po...

  19. Inhibition of adenovirus replication by a trisubstituted piperazin-2-one derivative

    OpenAIRE

    Sanchez-Cespedes, Javier; Moyer, Crystal L.; Whitby, Landon R.; Boger, Dale L.; Nemerow, Glen R.

    2014-01-01

    The number of disseminated adenovirus (Ad) infections continues to increase mostly due to the growing use of immunosuppressive treatments. Recipients of solid organ or hematopoietic stem cell transplants, mainly in pediatric units, exhibit a high morbidity and mortality due to these infections. Unfortunately, there are no Ad-specific antiviral drugs currently approved for medical use. To address this situation, we used high-throughput screening (HTS) of synthetic small molecule libraries to i...

  20. The p53 Protein Does Not Facilitate Adenovirus Type 5 Replication in Normal Human Cells

    OpenAIRE

    Chahal, Jasdave S.; Flint, S J

    2013-01-01

    Although several adenovirus type 5 (Ad5) proteins prevent deleterious consequences of activation of p53, it has been reported that viral replication proceeds more efficiently when human tumor cells produce wild-type compared to mutant p53. We have now exploited RNA interference and lentiviral vectors to achieve essentially complete knockdown of p53 in normal human cells: no effects on the kinetics or efficiency of viral gene expression or production of infectious particles were observed.

  1. Expression and function of DMT1 without IRE in C6 cells mediated by recombinant adenovirus

    Institute of Scientific and Technical Information of China (English)

    Xixun DU; Huamin XU; Hong JIANG; Jun WANG; Lei WANG; Junxia XIE

    2009-01-01

    Divalent metal transporter 1 (DMT1) is a ferrous iron import protein. The improper expression of DMT1 is involved in neurodegenerative diseases. In the present study, we constructed a recombinant adenovirus containing the gene of DMT1 without the iron response element (DMT1-IRE) and investigated its expression and function in the C6 glioma cell line. The DMTI-IRE gene, obtained by RT-PCR, was cloned into the shuttle plasmid-ing pAdTrack-CMV containing green fluorescent protein (GFP) reporter gene. Linearized plasmid pAdTrack-CMV-DMTI-IRE was subsequently co-transformed into Escher-iehia coli (E. coli) BJ5183 cells along with an adenoviral backbone plasmid pAdEasy-1 after digestion with Pme I. Pac I-digested pAdEasy 1-DMT 1-IRE was then transfected into El-transformed human embryonic kidney cells (HEK293 cells), in which recombinant adenoviruses were generated within 7 to 10 days. The results demon-strated that we obtained the DMTI-IRE gene. pAdEasyl-DMT1-IRE yielded a large fragment, plus a smaller fragment of 4.5kb after digestion with Pac I. PCR confirmed pAdEasy1-DMT1-IRE contained gene DMT1-IRE, indicating the successful construction of recombi-nant adenovirus plasmid containing DMT1-IRE. GFP fluorescence further confirmed the generation of recombi-nant AdDMTI-IRE adenovirus. AdDMTI-IRE could efficiently infect C6 glioma cells. And cell viability decreased in AdDMT1-IRE infected cells after iron overload compared to the control. These results suggest that the over expressed DMT1-IRE can aggravate the iron induced cell death due to its iron influx function.

  2. Frequency of Rotavirus and Enteric Adenoviruses among children with acute gastroenteritis in a district hospital

    OpenAIRE

    Özer, Türkan Toka; Yula, Erkan; Deveci, Özcan; Tekin, Alicem; Durmaz, Süleyman; Gülenç, Mustafa; Yanık, Keramettin

    2011-01-01

    Objective: Rotavirus and Enteric Adenoviruses (EA) are most important viral enteric agents which cause acute infectious gastroenteritis. Little is known about the epidemiology of Rotavirus and EA gastroenteritis in our city. In this study, it was purposed to determine of the frequency of Rotavirus, EA, and to detect of the seasonal distribution among pediatric patients with acute gastroenteritis in Kiziltepe General Hospital, Mardin-Turkey. Materials and methods: The records of acute infe...

  3. Investigation of rotavirus and adenovirus antigens in patients with acute gastroenteritis

    OpenAIRE

    Hatice Türk Dağı,; Duygu Fındık

    2014-01-01

    Objective: Nowadays, viruses are the most common agents of acute gastroenteritis all over the world. Acute gastroenteritis, especially in children, is an important cause of mortality and morbidity. Both the lack of effective treatments as well as due to the unnecessary use of antibiotics, detection of viral agents in stool is important in terms of the epidemiology and monitoring of the disease. The purpose of this study is to determine the frequency of rotavirus and adenovirus in patients wit...

  4. Genetic Diversity of Human Adenovirus in Children with Acute Gastroenteritis, Albania, 2013–2015

    OpenAIRE

    La Rosa, G.; Della Libera, S.; S. Petricca; M. Iaconelli; D. Donia; Saccucci, P.; Cenko, F.; Xhelilaj, G.; Divizia, M.

    2015-01-01

    The objectives of the present study were to assess the occurrence of human adenoviruses (HAdVs) in paediatric patients with gastroenteritis in Albania and to characterize HAdV strains. Faecal specimens from children admitted with acute gastroenteritis to the Paediatric Hospital in Tirana were screened for HAdV, using broad-range primers targeting the hexon gene, in combination with species-specific primers targeting the fiber gene. Phylogenetic analysis was then performed to assess the geneti...

  5. Frequency of Rotavirus and Enteric Adenoviruses among children with acute gastroenteritis in a district hospital

    OpenAIRE

    Süleyman Durmaz; Mustafa Gülenç; Alicem Tekin; Keramettin Yanık; Türkan Toka Özer; Özcan Deveci; Erkan Yula

    2011-01-01

    Objective: Rotavirus and Enteric Adenoviruses (EA) are most important viral enteric agents which cause acute infectious gastroenteritis. Little is known about the epidemiology of Rotavirus and EA gastroenteritis in our city. In this study, it was purposed to determine of the frequency of Rotavirus, EA, and to detect of the seasonal distribution among pediatric patients with acute gastroenteritis in Kiziltepe General Hospital, Mardin-Turkey.Materials and methods: The records of acute infectiou...

  6. Prevalence of Rotavirus, Adenovirus, and Astrovirus Infections Among Patients with Acute Gastroenteritis in, Northern Iran

    OpenAIRE

    R Savad-Koohi; A Pakfetrat; AA Poor-Babaei; S Vaziri; L Adibi; Jalilvand, S; K Nourijelyani; Noroozi, M.; Y Yahyapour; Hamkar, R

    2010-01-01

    Background: The aim of the study was to determine the incidence of non-bacterial acute gastroenteritis associated with diarrheal diseases in Mazandaran Province, northern Iran. Methods: A total of 400 symptomatic cases from patients with acute gastroenteritis from Mazandaran Province in Iran were screened using EIA method for the presence of rotavirus, adenovirus and astrovirus during 2005–2006. Chi-square tests were used for testing relationships between different variables. Results: Rotavir...

  7. Phylogenetic analysis of the genomes of two strains of human adenovirus type 3

    Institute of Scientific and Technical Information of China (English)

    RONG ZHOU; XIAO Bo SU; QI WEI ZIIANG; QI YI ZENG; BING ZHU; CHU Yu ZHANG; Hou Bo WU; ZAO HE WU; SI TANG GONG

    2007-01-01

    Human adenovirus type 3 (HAdV-3) is widely prevalent all over the world, especially in Asia. The objective of this study is to carry out complete genomic DNA sequencing and the phylogenetic analysis for two strains (Guangzhou01 and Guangzhou02) of HAdV-3 wild virus isolated from South China. Nasopharyngeal secretion aspirate specimens of sick children were inoculated into HEp-2 and HeLa culture tubes, and the cultures were identified by neutralization assay with type-specific reference rabbit antisermn. Type-specific primers were also utilized to confirm the serotype. The restriction fragments of HAdV genome DNA were cloned into pBlueScript SK ( + ) vectors and sequenced, and the 5' and 3'ends of the linear HAdV-3 genome were directly sequenced with double purified genomic DNA as templates. General features of the HAdV-3 genome sequences were explored by using several bio-software.Phylogenetic analysis was done with MEGA 3.0 software. The genomic sequences of Guangzhou01 and Guangzhou02 possess the same 4 early regions and 5 late regions and have 39 ceding sequences and two RNA coding sequences. Other non-ceding regions are conservative. Inverted repeats and palindromes were identified in the genome sequences. The genomes of group B human adenovirus as well as HAdV-3have close phylogenetic relationship with that of chimpanzee adenovirus type 21. The genomie lengths of these two isolated strains are 35 273 bp and 35 269 bp, respectively. The phylogenetie analysis showed that HAdV-B species has some relationship with eertain types of chimpanzee adenovirus.

  8. Targeting Mesothelioma Using an Infectivity Enhanced Survivin-Conditionally Replicative Adenoviruses

    OpenAIRE

    ZHU, Zeng B.; Makhija, Sharmila K.; Lu, Baogen; Wang, Minghui; Wang, Shuyi; Takayama, Koichi; Siegal, Gene P.; Reynolds, Paul N.; Curiel, David T.

    2006-01-01

    Mesothelioma is a highly malignant neoplasm with no effective treatment. Conditionally replicative adenoviruses (CRAds) represent a promising new modality for the treatment of cancer in general. A key contribution in this regard is the introduction of tumor-selective viral replication for amplification of the initial inoculum in the neoplastic cell population. Under ideal conditions following cellular infection, the viruses replicate selectively in the infected tumor cells and kill the cells ...

  9. Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus

    OpenAIRE

    Koob, George; Hicks, Martin J.; Wee, Sunmee; Rosenberg, Jonathan B; De, Bishnu P.; Kaminksy, Stephen M.; Moreno, Amira; Kim D. Janda; Crystal, Ronald G.

    2011-01-01

    The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on t...

  10. Novel adenoviruses in wild primates: a high level of genetic diversity and evidence of zoonotic transmissions.

    OpenAIRE

    Wevers, Diana; Metzger, Sonja; Babweteera, Fred; Bieberbach, Marc; Boesch, Christophe; Cameron, Kenneth; Couacy-Hymann, Emmanuel; Cranfield, Mike; Gray, Maryke; Harris, Laurie A.; Head, Josephine; Jeffery, Kathryn; Knauf, Sascha; Lankester, Felix; Siv Aina J. Leendertz

    2011-01-01

    Adenoviruses (AdVs) broadly infect vertebrate hosts, including a variety of nonhuman primates (NHPs). In the present study, we identified AdVs in NHPs living in their natural habitats, and through the combination of phylogenetic analyses and information on the habitats and epidemiological settings, we detected possible horizontal transmission events between NHPs and humans. Wild NHPs were analyzed with a pan-primate AdV-specific PCR using a degenerate nested primer set that targets the highly...

  11. Effect of recombinant adenovirus vector mediated human interleukin-24 gene transfection on pancreatic carcinoma growth

    Institute of Scientific and Technical Information of China (English)

    PAN Xin-ting; ZHU Qing-yun; LI De-chun; YANG Ji-cheng; ZHANG Zi-xiang; ZHU Xing-guo; ZHAO Hua

    2008-01-01

    Background Pancreatic cancer is a highly malignant tumor affecting an ever increasing number of patients with a mean 5-year survival rate below 4%. Therefore, gene therapy for cancer has become a potential novel therapeutic modality. In this study we sought to determine the inhibitory effects of adenovirus-mediated human interleukin-24 (AdhlL-24) on pancreatic cancer.Methods Human interleukin-24 gene was cloned into replication-defective adenovirus specific for patu8988 tumor cells by virus recombination technology. Reverse transcription-polymerase chain reaction and Western blotting analysis were used to determine the expression of human interleukin-24 mRNA in patu8988 cells in vitro. Induction of apoptosis by overexpression of human interleukin-24 in patu8988 cells was determined by flow cytometry. In vivo efficacy of adenoviral delivery of human interleukin-24 was assessed in nude mice (n=10 for each group) bearing patu8988 pancreatic cancer cell lines by determining inhibition of tumor growth, endothelial growth factor and CD34 expression, and intratumoral microvessel density (MVD).Results The recombinant adenovirus vector AdVGFP/IL-24 was constructed with a packaged recombinant retrovirus titer of 1.0x1010 pfu/ml and successfully expressed of both mRNA and protein in patu8988 cells. The AdVGFP/IL-24 induced apoptosis of patu8988 tumor cells in vitro and significantly inhibited tumor growth in vivo (P <0.05). The intratumoral MVD decreased significantly in the treated tumors (P <0.05).Conclusion The recombinant adenovirus AdGFP/IL-24 can effectively express biologically active human interleukin-24, which results in inhibition of pancreatic cancer growth.

  12. Association of Human Adenovirus-36 With Dyslipidemia in Tehranian Children and Adolescent; TLGS

    OpenAIRE

    Zarkesh; Sadat Daneshpour; Ehsandar; Bandehpour; Alfadhli; Azizi; Hedayati

    2015-01-01

    Background The human adenovirus-36 (Adv36) has been associated with obesity and lipid disorders in some countries. The primary dyslipidemia related to obesity is characterized by increased TG, decreased HDL levels and abnormal LDL composition. Childhood obesity is a major public health problem in most developing countries. Objectives The aim of this study was to investigate the association between Adv36 and lipid disorders in Tehr...

  13. Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.

    Directory of Open Access Journals (Sweden)

    Marko T Ahonen

    Full Text Available BACKGROUND: Adenoviruses are attractive vectors for gene therapy because of their stability in vivo and the possibility of production at high titers. Despite exciting preclinical data with various approaches, there are only a few examples of clear efficacy in clinical trials. Effective gene delivery to target cells remains the key variable determining efficacy and thus enhanced transduction methods are important. METHODS/RESULTS: We found that heated serum could enhance adenovirus 5 mediated gene delivery up to twentyfold. A new protein-level interaction was found between fiber knob and serum transthyretin, but this was not responsible for the observed effect. Instead, we found that heating caused the calcium and phosphate present in the serum mix to precipitate, and this was responsible for enhanced gene delivery. This finding could have relevance for designing preclinical experiments with adenoviruses, since calcium and phosphate are present in many solutions. To translate this into an approach potentially testable in patients, we used calcium gluconate in phosphate buffered saline, both of which are clinically approved, to increase adenoviral gene transfer up to 300-fold in vitro. Gene transfer was increased with or without heating and in a manner independent from the coxsackie-adenovirus receptor. In vivo, in mouse studies, gene delivery was increased 2-, 110-, 12- and 13-fold to tumors, lungs, heart and liver and did not result in increased pro-inflammatory cytokine induction. Antitumor efficacy of a replication competent virus was also increased significantly. CONCLUSION: In summary, adenoviral gene transfer and antitumor efficacy can be enhanced by calcium gluconate in phosphate buffered saline.

  14. Calcium Gluconate in Phosphate Buffered Saline Increases Gene Delivery with Adenovirus Type 5

    Science.gov (United States)

    Ahonen, Marko T.; Diaconu, Iulia; Pesonen, Sari; Kanerva, Anna; Baumann, Marc; Parviainen, Suvi T.; Spiller, Brad

    2010-01-01

    Background Adenoviruses are attractive vectors for gene therapy because of their stability in vivo and the possibility of production at high titers. Despite exciting preclinical data with various approaches, there are only a few examples of clear efficacy in clinical trials. Effective gene delivery to target cells remains the key variable determining efficacy and thus enhanced transduction methods are important. Methods/Results We found that heated serum could enhance adenovirus 5 mediated gene delivery up to twentyfold. A new protein-level interaction was found between fiber knob and serum transthyretin, but this was not responsible for the observed effect. Instead, we found that heating caused the calcium and phosphate present in the serum mix to precipitate, and this was responsible for enhanced gene delivery. This finding could have relevance for designing preclinical experiments with adenoviruses, since calcium and phosphate are present in many solutions. To translate this into an approach potentially testable in patients, we used calcium gluconate in phosphate buffered saline, both of which are clinically approved, to increase adenoviral gene transfer up to 300-fold in vitro. Gene transfer was increased with or without heating and in a manner independent from the coxsackie-adenovirus receptor. In vivo, in mouse studies, gene delivery was increased 2-, 110-, 12- and 13-fold to tumors, lungs, heart and liver and did not result in increased pro-inflammatory cytokine induction. Antitumor efficacy of a replication competent virus was also increased significantly. Conclusion In summary, adenoviral gene transfer and antitumor efficacy can be enhanced by calcium gluconate in phosphate buffered saline. PMID:20927353

  15. Binding of Adenovirus Capsid to Dipalmitoyl Phosphatidylcholine Provides a Novel Pathway for Virus Entry

    OpenAIRE

    Balakireva, Larissa; Schoehn, Guy; Thouvenin, Eric; Chroboczek, Jadwiga

    2003-01-01

    Adenovirus (Ad) is an airborne, nonenveloped virus infecting respiratory epithelium. To study the mechanism of Ad entry, we used alveolar adenocarcinoma A549 cells, which have retained the ability of alveolar epithelial type II cells to synthesize the major component of pulmonary surfactant, disaturated phosphatidylcholine. Stimulation of phosphatidylcholine secretion by calcium ionophore or phorbol ester augmented the susceptibility of these cells to Ad. Both Ad infection and recombinant-Ad-...

  16. Impact of Adenovirus infection in host cell metabolism evaluated by (1)H-NMR spectroscopy.

    Science.gov (United States)

    Silva, Ana Carina; P Teixeira, Ana; M Alves, Paula

    2016-08-10

    Adenovirus-based vectors are powerful vehicles for gene transfer applications in vaccination and gene therapy. Although highly exploited in the clinical setting, key aspects of the adenovirus biology are still not well understood, in particular the subversion of host cell metabolism during viral infection and replication. The aim of this work was to gain insights on the metabolism of two human cell lines (HEK293 and an amniocyte-derived cell line, 1G3) after infection with an adenovirus serotype 5 vector (AdV5). In order to profile metabolic alterations, we used (1)H-NMR spectroscopy, which allowed the quantification of 35 metabolites in cell culture supernatants with low sample preparation and in a relatively short time. Significant differences between both cell lines in non-infected cultures were identified, namely in glutamine and acetate metabolism, as well as by-product secretion. The main response to AdV5 infection was an increase in glucose consumption and lactate production rates. Moreover, cultures performed with or without glutamine supplementation confirmed the exhaustion of this amino acid as one of the main causes of lower AdV5 production at high cell densities (10- and 1.5-fold less specific yields in HEK293 and 1G3 cells, respectively), and highlighted different degrees of glutamine dependency of adenovirus replication in each cell line. The observed metabolic alterations associated with AdV5 infection and specificity of the host cell line can be useful for targeted bioprocess optimization. PMID:27215342

  17. Enzyme immunoassay for direct detection of influenza type A and adenovirus antigens in clinical specimens.

    OpenAIRE

    Harmon, M W; Pawlik, K M

    1982-01-01

    Detection of viral antigens in specimens without prior cultivation in cell culture provides the most rapid method for specific viral diagnosis. A solid-phase, double-antibody enzyme immunoassay was developed for this purpose and tested with clinical specimens containing influenza type A and adenovirus. Polystyrene microtiter wells were the solid phase and were coated with virus-specific guinea pig immunoglobulins. Specimens were added, and bound viral antigens were detected by addition of vir...

  18. Bankruptcy Problem Approach to Load-Shedding in Agent-Based Microgrid Operation

    Science.gov (United States)

    Kim, Hak-Man; Kinoshita, Tetsuo; Lim, Yujin; Kim, Tai-Hoon

    Research, development, and demonstration projects on microgrids have been progressed in many countries. Furthermore, microgrids are expected to introduce into power grids as eco-friendly small-scale power grids in the near future. Load-shedding is a problem not avoided to meet power balance between power supply and power demand to maintain specific frequency such as 50 Hz or 60 Hz. Load-shedding causes consumers inconvenience and therefore should be performed minimally. Recently, agent-based microgrid operation has been studied and new algorithms for their autonomous operation including load-shedding has been required. The bankruptcy problem deals with distribution insufficient sources to claimants. In this paper, we approach the load-shedding problem as a bankruptcy problem and adopt the Talmud rule as an algorithm. Load-shedding using the Talmud rule is tested in islanded microgrid operation based on a multiagent system.

  19. Clinical data analysis of 19 cases of community-acquired adenovirus pneumonia in immunocompetent adults.

    Science.gov (United States)

    Yu, Hong-Xia; Zhao, Mao-Mao; Pu, Zeng-Hui; Wang, Yun-Qiang; Liu, Yan

    2015-01-01

    The aim of this study was to investigate the characteristics of clinical manifestations, laboratory tests and imaging changes of community-acquired adenovirus pneumonia in immunocompetent adults. A retrospective study was performed on 19 adult community-acquired adenovirus pneumonia cases in Yantai, whereby the clinical data were collected and analyzed. Of 19 cases, 14 (73.68%) had fever and 17 (89.47%) had cough symptoms. Moreover, 14 cases (73.68%) had normal white blood cell counts, while 11 cases (57.89%) exhibited a reduction in lymphocyte proportion. Among the 19 cases, 17 cases exhibited lesions in a single lung, while 2 cases involved bilateral lungs. The lesions predominantly exhibited ground glass-like changes. The clinical manifestations of adult community-acquired adenovirus pneumonia patients with normal immune functions were mild, with such presenting symptoms as fever, cough, and sputum; most patients did not exhibit high levels of white blood cells or low lymphocyte counts, and the imaging features (ground glass-like effusion) were indicative of single-lung involvement.

  20. An armed oncolytic adenovirus system,ZD55-gene,demonstrating potent antitumoral efficacy

    Institute of Scientific and Technical Information of China (English)

    ZI LAI ZHANG; WEI GUO ZOU; CHUN XIA LUO; BING HUA LI; JIN HUI WANG; LAN YING SUN; QI JUN QIAN; XIN YUAN LIU

    2003-01-01

    ONYXONYX-015 is an attractive therapeutic adenovirus for cancer because it can selectively replicate in tumor cells and kill them.To date,clinicaltrials of this adenovirus have demonstrated marked safety but not potent enough when it was used alone.In this paper,we put forward a novel concept of Gene-Viro Therapy strategy and in this way,we constructed an armed therapeutic onco1ytic adenovirus system,ZD55-gene,whichis not only deleted of E1B 55-kD gene similar to ONYX-015,but also armed with foreign antitumor gene.ZD55-gene exhibited similar cytopathic effects and replication Kinetics to that of ONYX-015 in vitro.Importantly,the carried gene 1s expressed and the expression level can increase with the replication of virus.Consequently,a significant antitumoral efficacy was observed when ZD55-CD/5-FU was used as an example in nude mice with subcutaneous human SW620 colon cancer.Our data demonstratedthat ZD55-gene,which utilizingthe Gene-ViroTherapy strategy,is more efficacious than each individual component in vivo.

  1. Stimulation of innate immunity by in vivo cyclic di-GMP synthesis using adenovirus.

    Science.gov (United States)

    Koestler, Benjamin J; Seregin, Sergey S; Rastall, David P W; Aldhamen, Yasser A; Godbehere, Sarah; Amalfitano, Andrea; Waters, Christopher M

    2014-11-01

    The bacterial second messenger cyclic di-GMP (c-di-GMP) stimulates inflammation by initiating innate immune cell recruitment and triggering the release of proinflammatory cytokines and chemokines. These properties make c-di-GMP a promising candidate for use as a vaccine adjuvant, and numerous studies have demonstrated that administration of purified c-di-GMP with different antigens increases protection against infection in animal models. Here, we have developed a novel approach to produce c-di-GMP inside host cells as an adjuvant to exploit a host-pathogen interaction and initiate an innate immune response. We have demonstrated that c-di-GMP can be synthesized in vivo by transducing a diguanylate cyclase (DGC) gene into mammalian cells using an adenovirus serotype 5 (Ad5) vector. Expression of DGC led to the production of c-di-GMP in vitro and in vivo, and this was able to alter proinflammatory gene expression in murine tissues and increase the secretion of numerous cytokines and chemokines when administered to animals. Furthermore, coexpression of DGC modestly increased T-cell responses to a Clostridium difficile antigen expressed from an adenovirus vaccine, although no significant differences in antibody titers were observed. This adenovirus c-di-GMP delivery system offers a novel method to administer c-di-GMP as an adjuvant to stimulate innate immunity during vaccination.

  2. Adenovirus KH901 promotes 5-FU antitumor efficacy and S phase in LoVo cells.

    Science.gov (United States)

    Peng, Wei; Li, Jin; Yin, X G; Xu, J F; Cheng, L Z

    2012-06-01

    A combination of oncolytic and chemotherapeutic agents has been used to kill cancer cells. However, the effect of oncolytic adenoviruses on the cell cycle remains to be determined. Cytotoxicity assays were performed to determine cell death in cells treated with 5-fluorouracil (5-FU) alone or in combination with the oncolytic adenovirus KH901. Dynamic changes in the cell cycle, cell proliferation, and apoptosis-related proteins including p-AKT, Bcl-2, Bax, and caspase 3 were investigated after treatment with 5-FU with or without KH901. A higher proportion of S-phase cells were observed after treatment with KH901 and 5-FU than with 5-FU alone. p-AKT, Bcl-2, and Bax expression was increased upon treatment with KH901, whereas the expression of caspase-3 was not induced upon treatment with KH901 with or without 5-FU. KH901 exhibited significant potential as an oncolytic adenovirus and increased cell death in combination with 5-FU in LoVo cells, as compared to 5-FU alone. In conclusion, KH901 stimulates LoVo cells to enter the S-phase by activation of p-AKT, which could partly explain its synergistic effect with 5-FU on LoVo cell cytotoxicity.

  3. Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice

    Directory of Open Access Journals (Sweden)

    Zhao Yarui

    2011-01-01

    Full Text Available Abstract Background Sphingomyelin synthase 2 (SMS2 contributes to de novo sphingomyelin (SM biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis. Methods The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR and protein level examination (SMS activity assay. Result We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2 or GFP cDNA (AdV-GFP. On day six after intravenous infusion of 2 × 1011 particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p Conclusions Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis.

  4. Serologic study on the outbreak of acute upper respiratory tract Infections caused by adenovirus 3

    Institute of Scientific and Technical Information of China (English)

    JIANG Lufang; JU Liwen; JIANG Renjie; LIN Yuzun; ZHOU Liandi; YU Shunzhang; JIANG Qingwu

    2007-01-01

    From April to June,2004,an outbreak of acute upper respiratory tract infections(AURTI)occurred in the north area of Jiangsu Province,China.Twenty throat swabs were collected with 13 of them presenting an adenovirus (Ad)-like cytopathogenic effect on HEp-2.These were verified as Ad by the electron microscope,direct immunofluorescence assay and Ad primer-mediated PCR.Moreover,they were identified as adenovirus type 3(Ad3)by type-specific PCR and sequencing of the amplification products.Subsequent serologic studies were carried out to finally diagnose and document the outbreak.The neutralization test of paired serum of six in nine cases show obviously increased antibodies titers.The positive rate of IgM,IgG and recovery phase neutralization antibodies of the cases were 3.7%,44.4%and 59.5%respectively while those of the controls were 0%,8.3%and 33.3%respectively.The Pvalues of Chi-Square were 0.510,0.018 and 0.226 respectively.The concordance between IgG detected by ELISA and neutralization antibodies detected by the neutralization test was 61.4%and the Pvalue of Kappa was 0.070.By the serologic study,we can definitively diagnose that this outbreak of acute respiratory infections was caused by Adenovirus 3.

  5. Antitumor bioactivity of adenovirus-mediated p27mt in colorectal cancer cell line SW480

    Institute of Scientific and Technical Information of China (English)

    Ze-Qun sun; Chang-Sheng Deng; Shao-Yong Xu; Yong Du

    2008-01-01

    AIM: To explore the antitumor bioactivity of adenovirus-mediated mutant type p27kip1 gene in a colorectal cancer cell line SW480.METHODS: We constructed recombinant adenovirus vector expressing a mutant type p27kip1 gene (ad-p27mt), with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC), and transduced into SW480 cells. Then we detected expression of p27, Bcl-2 and Bax protein in the transductants by Western blotting, cell cycle of transductants by a digital flow cytometric system, migrating potential with Boyden Chamber end SW480 tumor cell growth inhibition in vitro and in vivo.RESULTS: We found that a recombinant adenovirus vector of expressing ad-p27mt, with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC) has potent inhibition of SW480 tumor cell growth in vitro and in vivo. Furthermore, ed-p27mt induced cell apoptosis via regulating bax and bcl-2 expressions, and G1/S arrest in SW480 cells and inhibited celt migration.CONCLUSION: ad-p27mt has a strong anti-tumor bioactivity and has the potential to develop into new therapeutic agents for colorectal cancer.

  6. E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

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    Turner, Roberta L. [Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Wilkinson, John C., E-mail: john.wilkinson@ndsu.edu [Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Ornelles, David A., E-mail: ornelles@wakehealth.edu [Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States)

    2014-05-15

    Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4ORF3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4ORF3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. - Highlights: • E1B-55K or E4orf3 prevents nuclear fragmentation. • Nuclear fragmentation requires AIF and PARP-1 activity. • Adenovirus DNA replication activates PARP-1. • E1B-55K or E4orf3 proteins alter the distribution of PAR.

  7. Canine adenovirus type 2 vector generation via I-Sce1-mediated intracellular genome release.

    Directory of Open Access Journals (Sweden)

    Sandy Ibanes

    Full Text Available When canine adenovirus type 2 (CAdV-2, or also commonly referred to as CAV-2 vectors are injected into the brain parenchyma they preferentially transduce neurons, are capable of efficient axonal transport to afferent regions, and allow transgene expression for at last >1 yr. Yet, translating these data into a user-friendly vector platform has been limited because CAV-2 vector generation is challenging. Generation of E1-deleted adenovirus vectors often requires transfection of linear DNA fragments of >30 kb containing the vector genome into an E1-transcomplementing cell line. In contrast to human adenovirus type 5 vector generation, CAV-2 vector generation is less efficient due, in part, to a reduced ability to initiate replication and poor transfectibility of canine cells with large, linear DNA fragments. To improve CAV-2 vector generation, we generated an E1-transcomplementing cell line expressing the estrogen receptor (ER fused to I-SceI, a yeast meganuclease, and plasmids containing the I-SceI recognition sites flanking the CAV-2 vector genome. Using transfection of supercoiled plasmid and intracellular genome release via 4-OH-tamoxifen-induced nuclear translocation of I-SceI, we improved CAV-2 vector titers 1,000 fold, and in turn increased the efficacy of CAV-2 vector generation.

  8. Nucleotide sequence determination of the region in adenovirus 5 DNA involved in cell transformation

    International Nuclear Information System (INIS)

    A description is given of investigations into the primary structure of the transforming region of adenovirus type 5 DNA. The phenomenon of cell transformation is discussed in general terms and the principles of a number of fairly recent techniques, which have been in use for DNA sequence determination since 1975 are dealt with. A few of the author's own techniques are described which deal both with nucleotide sequence analysis and with the determination of DNA cleavage sites of restriction endonucleases. The results are given of the mapping of cleavage sites in the HpaI-E fragment of adenovirus DNA of HpaII, HaeIII, AluI, HinfI and TaqI and of the determination of the nucleotide sequence in the transforming region of adenovirus type 5 DNA. The results of the sequence determination of the Ad5 HindIII-G fragment are discussed in relation with the investigation on the transforming proteins isolated from in vitro and in vivo synthesizing systems. Labelling procedures of DNA are described including the exonuclease III/DNA polymerase 1 method and TA polynucleotide kinase labelling of DNA fragments. (Auth.)

  9. Bovine adenovirus serotype 3 utilizes sialic acid as a cellular receptor for virus entry.

    Science.gov (United States)

    Li, Xiaoxin; Bangari, Dinesh S; Sharma, Anurag; Mittal, Suresh K

    2009-09-30

    Bovine adenovirus serotype 3 (BAd3) and porcine adenovirus serotype 3 (PAd3) entry into the host cells is independent of Coxsackievirus adenovirus receptor and integrins. The role of sialic acid in BAd3 and PAd3 entry was investigated. Removal of sialic acid by neuraminidase, or blocking sialic acid by wheat germ agglutinin lectin significantly inhibited BAd3, but not PAd3, transduction of Madin-Darby bovine kidney cells. Maackia amurensis agglutinin or Sambucus nigra (elder) agglutinin treatment efficiently blocked BAd3 transduction suggesting that BAd3 utilized alpha(2,3)-linked and alpha(2,6)-linked sialic acid as a cell receptor. BAd3 transduction of MDBK cells was sensitive to sodium periodate, bromelain, or trypsin treatment indicating that the receptor sialoconjugate was a glycoprotein rather than a ganglioside. To determine sialic acid-containing cell membrane proteins that bind to BAd3, virus overlay protein binding assay (VOPBA) was performed and showed that sialylated cell membrane proteins in size of approximately 97 and 34 kDa bind to BAd3. The results suggest that sialic acid serves as a primary receptor for BAd3.

  10. THE ROLE OF RECOMBINANT Rb GENE ADENOVIRUS VECTOR IN THE GROWTH OF LUNG ADENOCARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    Li Jian; Jiang Lei; Xia Yongjing; Li Hongxia; Hu Yajun; Hu Shixue; Xu Hongji

    1998-01-01

    Objective:To study the role of the most extensively studied tumor suppressor gene, retinoblastoma (Rb) gene,on the growth of lung adenocarcinoma cell line GLC-82 and explore a gene therapy approach for lung adenocarcinoma. Methods: The recombinant Rb gene adenovirus vector was constructed, the control virus which carries LacZ gene was producted by the same method. Infection effects were detected by biochemical staining of β-gal and immunohistochemical analysis of Rb protein. The Rb cDNA of infected cells were determined by PCR. The cell growth rate and cell cycle were observed by cell-counting and flow cytometry. Results: The constructed recombinant adenovirus vector could infect effectively the cells with high level expression of Rb cDNA and Rb protein. The transfection of wild-type Rb gene could suppress GLC-82 cell proliferation and decrease the cellular DNA synthesis. Conclusions: These results showed the possibility of using recombinant Rb gene adenovirus vector in the gene therapy of cancer to inhibit the growth of cancer.

  11. EXPRESSION AND GLYCOSYLATION OF ROTAVIRUS STRAIN SAIl VP4 PROTEIN IN A RECOMBINANT ADENOVIRUS

    Institute of Scientific and Technical Information of China (English)

    孙茂盛; 昝云红; 马雁冰; 张光明; 杜秋江; 戴长柏

    2001-01-01

    Objective. Using a recombinant human adenovirus to express modified VP4 gene of rotavirus SA11 strain. Methods. A whole VP4 gene was obtained with PCR and induced the signal peptide at the gene N terminal.The chimera gene Was cloned into pCMV plasmid that consists of human cytomegalovirus promoter, and then the gene was cloned to the transfer vector of human adenovirus type 5. Homologous recombination was performed by co-transfection to 293 cell lines with recombinant plasmid and viral genome using CaPO4 precipitation. Results. No mutation was found in the whole VP4 gene sequence of 2362 base pair. The expressed productin recombinant adenovirus was confirmed to be specific and more antigenicity by indirect immunofluorescence as-say. Both the Western blot and immunoprecipitation assay showed that the molecular mass of the expressed protein was higher than the wild type VP4 protein, and that the modified product was corresponding to a glycosyla-tion of VP4 protein. Conclusion. To modify the target gene might be an effective method to enhance the stability, antigenicityand immunogenicity of expressed protein.

  12. EXPRESSION AND GLYCOSYLATION OF ROTAVIRUS STRAIN SA11 VP4 PROTEIN IN A RECOMBINANT ADENOVIRUS

    Institute of Scientific and Technical Information of China (English)

    孙茂盛; 昝云红; 马雁冰; 张光明; 杜秋江; 戴长柏

    2001-01-01

    Objective. Using a recombinant human adenovirus to express modified VP4 gene of rotavirus SA11 strain.``Methods. A whole VP4 gene was obtained with PCR and induced the signal peptide at the gene N terninal.``The chimera gene was cloned into pCMV plasmid that consists of human cytomegalovirus promoter, and then the gene was cloned to the transfer vector of human adenovirus type 5. Homologous recombination was performed by co-transfection to 293 cell lines with recombinant plasmid and viral genome using CaPO4 precipitation.``Results. No mutation was found in the whole VP4 gene sequence of 2362 base pair. The expressed product in recombinant adenovirus was confirmed to be specific and more antigenicity by indirect immunofluorescence assay. Both the Western blot and immunoprecipitation assay showed that the molecular mass of the expressed protein was higher than the wild type VP4 protein, and that the modified product was corresponding to a glycosylation of VP4 protein.``Conclusion. To modify the target gene might be an effective method to enhance the stability, antigenicity and immunogenicity of expressed protein.``

  13. Viral capsid is a pathogen-associated molecular pattern in adenovirus keratitis.

    Directory of Open Access Journals (Sweden)

    Ashish V Chintakuntlawar

    2010-04-01

    Full Text Available Human adenovirus (HAdV infection of the human eye, in particular serotypes 8, 19 and 37, induces the formation of corneal subepithelial leukocytic infiltrates. Using a unique mouse model of adenovirus keratitis, we studied the role of various virus-associated molecular patterns in subsequent innate immune responses of resident corneal cells to HAdV-37 infection. We found that neither viral DNA, viral gene expression, or viral replication was necessary for the development of keratitis. In contrast, empty viral capsid induced keratitis and a chemokine profile similar to intact virus. Transfected viral DNA did not induce leukocyte infiltration despite CCL2 expression similar to levels in virus infected corneas. Mice without toll-like receptor 9 (Tlr9 signaling developed clinical keratitis upon HAdV-37 infection similar to wild type mice, although the absolute numbers of activated monocytes in the cornea were less in Tlr9(-/- mice. Virus induced leukocytic infiltrates and chemokine expression in mouse cornea could be blocked by treatment with a peptide containing arginine glycine aspartic acid (RGD. These results demonstrate that adenovirus infection of the cornea induces chemokine expression and subsequent infiltration by leukocytes principally through RGD contact between viral capsid and the host cell, possibly through direct interaction between the viral capsid penton base and host cell integrins.

  14. Construction and in vitro Study of an E1B-Defective Adenovirus

    Institute of Scientific and Technical Information of China (English)

    Xue Feng; Joshua Mallam Nock; Zhu Hua-bin; Dong Chang-yuan; Qi Yi-peng

    2004-01-01

    An E1B-defective adenovirus named r1/Ad was constructed by homologous recombination. The construction, selection and propagation of recombinant virus was done in the human embryonic kidney 293 cells (HEK293). The in vitro study demonstrated that the recombinant virus has the ability to replicate in and lyse some p53-deficient human tumor cells such as the human glioblastoma tumor cells (U251) and human bladder tumer cells (EJ) but not in the normal cells with functional p53 such as the human fibroblast cells (MRC-5). Also, based on the cytopathic effect (CPE), it was demonstrated that the U251 cells were more sensitive to the infection of r1/Ad than that of EJ cells under identical conditions. In this paper, it was found that r1/Ad could be very useful in studying the in vitro selective replication of E1B-defective adenovirus. This may help to determine the safety of using any E1B-defective adenoviruses in cancer gene therapy.

  15. Experimental Investigation on Cavitating Flow Shedding over an Axisymmetric Blunt Body

    Institute of Scientific and Technical Information of China (English)

    HU Changli; WANG Guoyu; HUANG Biao

    2015-01-01

    Nowadays, most researchers focus on the cavity shedding mechanisms of unsteady cavitating flows over different objects, such as 2D/3D hydrofoils, venturi-type section, axisymmetric bodies with different headforms, and so on. But few of them pay attention to the differences of cavity shedding modality under different cavitation numbers in unsteady cavitating flows over the same object. In the present study, two kinds of shedding patterns are investigated experimentally. A high speed camera system is used to observe the cavitating flows over an axisymmetric blunt body and the velocity fields are measured by a particle image velocimetry (PIV) technique in a water tunnel for different cavitation conditions. The U-type cavitating vortex shedding is observed in unsteady cavitating flows. When the cavitation number is 0.7, there is a large scale cavity rolling up and shedding, which cause the instability and dramatic fluctuation of the flows, while at cavitation number of 0.6, the detached cavities can be conjunct with the attached part to induce the break-off behavior again at the tail of the attached cavity, as a result, the final shedding is in the form of small scale cavity and keeps a relatively steady flow field. It is also found that the interaction between the re-entrant flow and the attached cavity plays an important role in the unsteady cavity shedding modality. When the attached cavity scale is insufficient to overcome the re-entrant flow, it deserves the large cavity rolling up and shedding just as that at cavitation number of 0.7. Otherwise, the re-entrant flow is defeated by large enough cavity to induce the cavity-combined process and small scale cavity vortexes shedding just as that of the cavitation number of 0.6. This research shows the details of two different cavity shedding modalities which is worthful and meaningful for the further study of unsteady cavitation.

  16. Persistent symptoms in mild to moderate traumatic brain injury associated with executive dysfunction.

    Science.gov (United States)

    Hartikainen, Kaisa M; Waljas, Minna; Isoviita, Tuulia; Dastidar, Prasun; Liimatainen, Suvi; Solbakk, Anne-Kristin; Ogawa, Keith H; Soimakallio, Seppo; Ylinen, Aarne; Ohman, Juha

    2010-08-01

    In order to improve detection of subtle cognitive dysfunction and to shed light on the etiology of persistent symptoms after mild-to-moderate traumatic brain injury (TBI), we employed an experimental executive reaction time (RT) test, standardized neuropsychological tests, and diffusion tensor imaging (DTI). The Executive RT-Test, an Executive Composite Score from standardized neuropsychological tests, and DTI-indices in the midbrain differentiated between patients with persistent symptoms from those fully recovered after mild-to-moderate TBI. We suggest that persistent symptoms in mild-to-moderate TBI may reflect disrupted fronto-striatal network involved in executive functioning, and the Executive RT-Test provides an objective and novel method to detect it. PMID:20198531

  17. Effects of Persistent Organic Pollutants on the Immune System: The Case of Dioxins

    Directory of Open Access Journals (Sweden)

    M Ebtekar

    2004-10-01

    Full Text Available Persistent organic pollutants can be traced in air, water, soil and biota in industrialized and non industrialized regions. Although the production of these chemicals has been banned since 1980's when their toxicity was proven, their use, trade and disposal as well as persistence due to previous use, continues to contaminate the environment and threaten human health. Recent studies on the immunological consequences of dioxin contamination and exposure indicate that these compounds and specifically 2, 3, 7, 8- Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor on lymphocytes. This activation results in an array of effects on T, B and APC cells, biological mediators of the immune response and thereby results in suppression or remodelling of the immune response. This review attempts to shed light on the recent research developments in this field and to provide insight into the vast and long term health consequences of persistent organic pollutants.

  18. Reprogramming of Yersinia from virulent to persistent mode revealed by complex in vivo RNA-seq analysis.

    Directory of Open Access Journals (Sweden)

    Kemal Avican

    2015-01-01

    Full Text Available We recently found that Yersinia pseudotuberculosis can be used as a model of persistent bacterial infections. We performed in vivo RNA-seq of bacteria in small cecal tissue biopsies at early and persistent stages of infection to determine strategies associated with persistence. Comprehensive analysis of mixed RNA populations from infected tissues revealed that Y. pseudotuberculosis undergoes transcriptional reprogramming with drastic down-regulation of T3SS virulence genes during persistence when the pathogen resides within the cecum. At the persistent stage, the expression pattern in many respects resembles the pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes and invA. These findings are expected to have impact on future rationales to identify suitable bacterial targets for new antibiotics. Other genes that are up-regulated during persistence are genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress, which indicates the influence of different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades influence the pattern of bacterial gene expression during persistence. Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our findings suggest a model for the life cycle of this enteropathogen with reprogramming from a virulent to an adapted phenotype capable of persisting and spreading by fecal shedding.

  19. Construction of a recombinant adenovirus Vector of human papillomavirus type 16 L1_E7c

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Human papillomaviruses are closely associated with human cervical cancer, especially HPV types 16 and 18. At present, HPV can not be produced in large quantity; it also has tumorgenicity and these properties of HPV have seriously hampered the development of HPV vaccine. HPV type 16 L1 proteins can assembled into virus-like particles (VLP), which are morphologically identical to the nature virion. In order to develop the recombinant adenovirus vectors of HPV, we constructed a recombinant adenovirus shuttle plasmid pCA14 L1-E7c. Methods: Human papillomavirus type 16 L1 open reading frame without terminator codon (TAA) (5559- 7152) and E7c (682- 855) were amplified using PCR. The L1 and E7c fragments were inserted into pGEM-T easy vectors by T- A strategy, named pTAL1 and pTAE7c. pTAL1 was cut with Hind III and BglII, the pTAE7c with BamHI and ClaI. The L1 DNA fragment, E7c and pBluesscript SK were ligated together using T4 DNA ligase. pBSL1-E7c and pBSL1-E7c was digested with Hind III and Xhol. The L1-E7c fragment was inserted into adenovirus shuttle plasmids pCAl4, named pCAl4L1-E7c. DNA sequence results indicated that The L1-E7c DNA fragment can encode the HPV16L1-E7 fusion protein correctly. Results: The L1 and E7c DNA fragments were amplified by PCR and recombinant plasmid pTAL1, pTAE7c, pBSL1-E7c and pCA14L1-E7c were constructed correctly. The pCAl4L1-E7c can be used in the further research work, cotransfected the 293 cell with the parent adenovirus pBHG10. Conclusion: Our results indicated that we have constructed a HPV16L1-E7 fusion DNA fragments and the adenovirus shuttle plasmids pCALl-E7c for the further research.

  20. Dynamics of African swine fever virus shedding and excretion in domestic pigs infected by intramuscular inoculation and contact transmission.

    Science.gov (United States)

    Guinat, Claire; Reis, Ana Luisa; Netherton, Christopher L; Goatley, Lynnette; Pfeiffer, Dirk U; Dixon, Linda

    2014-09-26

    African swine fever virus (ASFV) is a highly virulent swine pathogen that has spread across Eastern Europe since 2007 and for which there is no effective vaccine or treatment available. The dynamics of shedding and excretion is not well known for this currently circulating ASFV strain. Therefore, susceptible pigs were exposed to pigs intramuscularly infected with the Georgia 2007/1 ASFV strain to measure those dynamics through within- and between-pen transmission scenarios. Blood, oral, nasal and rectal fluid samples were tested for the presence of ASFV by virus titration (VT) and quantitative real-time polymerase chain reaction (qPCR). Serum was tested for the presence of ASFV-specific antibodies. Both intramuscular inoculation and contact transmission resulted in development of acute disease in all pigs although the experiments indicated that the pathogenesis of the disease might be different, depending on the route of infection. Infectious ASFV was first isolated in blood among the inoculated pigs by day 3, and then chronologically among the direct and indirect contact pigs, by day 10 and 13, respectively. Close to the onset of clinical signs, higher ASFV titres were found in blood compared with nasal and rectal fluid samples among all pigs. No infectious ASFV was isolated in oral fluid samples although ASFV genome copies were detected. Only one animal developed antibodies starting after 12 days post-inoculation. The results provide quantitative data on shedding and excretion of the Georgia 2007/1 ASFV strain among domestic pigs and suggest a limited potential of this isolate to cause persistent infection.

  1. Chicken-specific kinome array reveals that Salmonella enterica serovar Enteritidis modulates host immune signaling pathways in the cecum to establish a persistence infection

    Science.gov (United States)

    Non-typhoidal Salmonella enterica induce an early, short-lived, pro-inflammatory response in chickens that is asymptomatic of clinical disease and results in a persistent colonization of the gastrointestinal (GI) tract that transmits infections to naïve hosts via fecal shedding of bacteria. The und...

  2. The Transition from Thick to Thin Plate Wake Physics: Whither Vortex Shedding?

    Science.gov (United States)

    Rai, Man Mohan

    2016-01-01

    The near and very near wake of a flat plate with a circular trailing edge is investigated with data from direct numerical simulations. Computations were performed for six different combinations of the Reynolds numbers based on plate thickness (D) and boundary layer momentum thickness upstream of the trailing edge (theta). Unlike the case of the cylinder, these Reynolds numbers are independent parameters for the flat plate. The separating boundary layers are turbulent in all the cases investigated. One objective of the study is to understand the changes in the wake vortex shedding process as the plate thickness is reduced (increasing theta/D). The value of D varies by a factor of 16 and that of theta by approximately 5 in the computations. Vortex shedding is vigorous in the low theta/D cases with a substantial decrease in shedding intensity in the large theta/D cases. Other shedding characteristics are also significantly altered with increasing theta/D. A visualization of the shedding process in the different cases is provided and discussed. The basic shedding mechanism is explored in depth. The effect of changing theta/D on the time-averaged, near-wake velocity statistics is also discussed. A functional relationship between the shedding frequency and the Reynolds numbers mentioned above is obtained.

  3. Numerical simulation of terrain-induced vortex/wave shedding at the Hong Kong International Airport

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lei; Zhang, Li-Jie; Mao, Hui [Shenzhen National Climate Observatory, Meteorological Bureau of Shenzhen Municipality (China); Chan, P.W. [Hong Kong Observatory (China)

    2013-10-15

    The present study aims at simulating the shedding of vortex/wave from a mountain nearby the Hong Kong International Airport using a computational fluid dynamics model by employing high resolution terrain data without smoothing. The successful simulation of this shedding would have an important application in the short-term forecasting of the chance of occurrence of terrain-induced windshear at an operating airport. Two typical cases of vortex/wave shedding are considered, namely, in neutral atmosphere associated with the passage of a typhoon, and in stably stratified atmosphere in spring-time easterly flow with continental origin. The model is found to successfully capture the salient features of the shedding. The simulated radial velocity fields of weather radar/LIDAR compare well with actual observations. In particular, the creation and the propagation of the vortex/wave through shedding from a mountain nearby the airport are captured well in the model simulation. The shedding periods are also reproduced. From the limited number of cases studied in this paper, it appears that the model has the capability of forecasting the occurrence of vortex/wave shedding by coupling with a mesoscale meteorological model. (orig.)

  4. Numerical simulation of terrain-induced vortex/wave shedding at the Hong Kong International Airport

    Directory of Open Access Journals (Sweden)

    Li Lei

    2013-07-01

    Full Text Available The present study aims at simulating the shedding of vortex/wave from a mountain nearby the Hong Kong International Airport using a computational fluid dynamics model by employing high resolution terrain data without smoothing. The successful simulation of this shedding would have an important application in the short-term forecasting of the chance of occurrence of terrain-induced windshear at an operating airport. Two typical cases of vortex/wave shedding are considered, namely, in neutral atmosphere associated with the passage of a typhoon, and in stably stratified atmosphere in spring-time easterly flow with continental origin. The model is found to successfully capture the salient features of the shedding. The simulated radial velocity fields of weather radar/LIDAR compare well with actual observations. In particular, the creation and the propagation of the vortex/wave through shedding from a mountain nearby the airport are captured well in the model simulation. The shedding periods are also reproduced. From the limited number of cases studied in this paper, it appears that the model has the capability of forecasting the occurrence of vortex/wave shedding by coupling with a mesoscale meteorological model.

  5. Kinetics of viral shedding provide insights into the epidemiology of viral hemorrhagic septicemia in Pacific herring

    Science.gov (United States)

    Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Courtney; Collins, Rachael

    2010-01-01

    Losses from infectious diseases are an important component of natural mortality among marine fish species, but factors controlling the ecology of these diseases and their potential responses to anthropogenic changes are poorly understood. We used viral hemorrhagic septicemia virus (VHSV) and a laboratory stock of Pacific herring Clupea pallasii to investigate the kinetics of viral shedding and its effect on disease transmission and host mortality. Outbreaks of acute disease, accompanied by mortality and viral shedding, were initiated after waterborne exposure of herring to concentrations of VHSV as low as 101 plaque-forming units (pfu) ml–1. Shed virus in flow-through tanks was first detected 4 to 5 d post-exposure, peaked after 6 to 10 d, and was no longer detected after 16 d. Shedding rates, calculated from density, flow and waterborne virus titer reached 1.8 to 5.0 × 108 pfu fish–1 d–1. Onset of viral shedding was dose-dependent and preceded initial mortality by 2 d. At 21 d, cumulative mortality in treatment groups ranged from 81 to 100% and was dependent not on challenge dose, but on the kinetics and level of viral shedding by infected fish in the tank. Possible consequences of the viral shedding and disease kinetics are discussed in the context of epizootic initiation and perpetuation among populations of wild Pacific herring.

  6. Energy Savings Lifetimes and Persistence

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Ian M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schiller, Steven R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Todd, Annika [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Billingsley, Megan A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Goldman, Charles A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schwartz, Lisa C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-02-01

    This technical brief explains the concepts of energy savings lifetimes and savings persistence and discusses how program administrators use these factors to calculate savings for efficiency measures, programs and portfolios. Savings lifetime is the length of time that one or more energy efficiency measures or activities save energy, and savings persistence is the change in savings throughout the functional life of a given efficiency measure or activity. Savings lifetimes are essential for assessing the lifecycle benefits and cost effectiveness of efficiency activities and for forecasting loads in resource planning. The brief also provides estimates of savings lifetimes derived from a national collection of costs and savings for electric efficiency programs and portfolios.

  7. Clinical and epidemiological aspects related to the detection of adenovirus or respiratory syncytial virus in infants hospitalized for acute lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Eduardo A. Ferone

    2014-01-01

    Full Text Available OBJECTIVE: To characterize and compare clinical, epidemiological, and laboratory aspects ofinfants with acute lower respiratory infection (ALRI associated with the detection of adenovirus(ADV or respiratory syncytial virus (RSV. METHODS: A preliminary respiratory infection surveillance study collected samples of nasopharyngeal aspirate (NPA for viral research, linked to the completion of a standard protocol, from children younger than two years admitted to a university hospital with ALRI, between March of 2008 and August of 2011. Polymerase chain reaction (PCR was used for eight viruses: ADV, RSV, metapneumovirus, Parainfluenza 1, 2, and 3, and Influenza A and B. Cases with NPA collectedduring the first 24 hours of admission, negative results of blood culture, and exclusive detection of ADV (Gadv group or RSV (Grsv group were selected for comparisons. RESULTS: The preliminary study included collection of 1,121 samples of NPA, 813 collected in thefirst 24 hours of admission, of which 50.3% were positive for at least one virus; RSV was identifiedin 27.3% of cases surveyed, and ADV was identified in 15.8%. Among the aspects analyzed inthe Gadv (n = 58 and Grsv (n = 134 groups, the following are noteworthy: the higher meanage, more frequent prescription of antibiotics, and the highest median of total white blood cellcount and C-reactive protein values in Gadv. CONCLUSIONS: PCR can detect persistent/latent forms of ADV, an aspect to be considered wheninterpreting results. Additional studies with quantitative diagnostic techniques could elucidatethe importance of the high frequency observed.

  8. Characterization of persistent and transient Escherichia coli isolates recovered from clinical mastitis episodes in dairy cows.

    Science.gov (United States)

    Fairbrother, Julie-Hélène; Dufour, Simon; Fairbrother, John Morris; Francoz, David; Nadeau, Éric; Messier, Serge

    2015-03-23

    Escherichia coli usually cause transient intramammary infections in dairy cows, but persistent intramammary infections have been observed. The objective of the study was to compare antimicrobial resistance and virulence genes found in persistent and transient E. coli isolated from clinical mastitis cases in a cohort of 91 Canadian dairy herds monitored over a 2-year period. Antimicrobial susceptibility was determined by broth microdilution and the presence of 27 virulence genes associated with extra-intestinal E. coli infections was determined by colony hybridization. Proportion of resistance in persistent E. coli ranged from 0.0% (enrofloxacin) to 27.8% (ampicillin and tetracycline). Proportion of resistance in transient E. coli ranged from 0.0% (enrofloxacin) to 16.8% (tetracycline). Odds of being classified as a persistent isolate increased by a factor of 1.6 (95% CI: 1.1, 2.4) for each aditional resistance observed (e.g. isolates resistant to four antimicrobial agents had 1.6 times higher odds of belonging to the persistent groups compared to isolates demonstrating resistance to three agents). Persistency was associated with higher odds of resistance to ampicillin (OR: 9.8, Pcoli isolates is associated with certain traits. Findings concerning iron-acquisition shed new light on the mechanisms of intramammary survival.

  9. Lipids shed into the culture medium by trypomastigotes of Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Agusti Rosalia

    2000-01-01

    Full Text Available Trypomastigote forms of Trypanosoma cruzi were metabolically labeled with [14C]-ethanolamine and [3H]-palmitic acid. Lipids shed to the culture medium were analyzed and compared with the parasite components. Phosphatidylcholine and lysophosphatidylcholine accounted for 53% of the total incorporated precursor. Interestingly, phosphatidylethanolamine and its lyso derivative lysophosphatidylethanolamine, although present in significant amounts in the parasites, could not be detected in the shed material. Shed lipids were highly enriched in the desaturated fatty acids C16:1 and C18:1 when compared to the total fatty acid pool isolated from the parasites.

  10. Detection, typing and subtyping of enteric adenoviruses 40 and 41 in fecal samples, and observation of changing incidences of infections with these types and subtypes.

    NARCIS (Netherlands)

    J.C. de Jong (Jan); K. Bijlsma; A.G. Wermenbol; M.W. Verweij-Uijterwaal; H.G.A.M. van der Avoort (Harrie); D.J. Wood; A.S. Bailey; A.D.M.E. Osterhaus (Albert)

    1993-01-01

    textabstractMonoclonal antibody (MAb) preparations specific for the enteric adenoviruses of subgenus F (AdF) were generated and evaluated as typing reagents in virus neutralization tests and enzyme-linked immunosorbent assays (ELISAs). A panel of 11 genome types of adenovirus 40 (Ad40), 24 genome ty

  11. Evaluation of a rapid immunochromatographic assay for the detection of rotavirus, norovirus and adenovirus from children hospitalized with acute watery diarrhea.

    Science.gov (United States)

    Kas, Monalisa P; Maure, Tobias; Soli, Kevin W; Umezaki, Masahiro; Morita, Ayako; Bebes, Sauli; Jonduo, Marinjho H; Larkins, Jo-Ann; Luang-Suarkia, Dagwin; Siba, Peter M; Greenhill, Andrew R; Horwood, Paul F

    2013-01-01

    We evaluated the IP-Triple I immunochromatographic rapid test for the detection of rotavirus, norovirus and adenovirus using stool samples from children with diarrhoea. The detection of norovirus and adenovirus was poor compared to polymerase chain reaction assays. However, high sensitivity (92%) and specificity (99%) were obtained for the detection of rotavirus.

  12. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge.

    Science.gov (United States)

    Schutta, Christopher; Barrera, José; Pisano, Melia; Zsak, Laszlo; Grubman, Marvin J; Mayr, Gregory A; Moraes, Mauro P; Kamicker, Barbara J; Brake, David A; Ettyreddy, Damodar; Brough, Douglas E; Butman, Bryan T; Neilan, John G

    2016-06-01

    The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0×10(8) to 2.1×10(11) particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R(2)=0.97) and viremia (R(2)=0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R(2)=0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge. PMID:26707216

  13. On persistently positively expansive maps

    Directory of Open Access Journals (Sweden)

    Alexander Arbieto

    2010-06-01

    Full Text Available In this paper, we prove that any C¹-persistently positively expansive map is expanding. This improves a result due to Sakai (Sakai 2004.Neste artigo, mostramos que todo mapa C¹-persistentemente positivamente expansivo e expansor. Isto melhora um resultado devido a Sakai (Sakai 2004.

  14. Persistence length of dendronized polymers

    NARCIS (Netherlands)

    Mikhailov, I.V.; Darinskii, A.A.; Zhulina, E.B.; Borisov, O.V.; Leermakers, F.A.M.

    2015-01-01

    We present numerical results for the thermodynamic rigidity and induced persistence length of dendronized polymers with systematically varied topology of their grafts obtained by the Scheutjens-Fleer self-consistent field method. The results were compared to predictions of an analytical mean-fiel

  15. Persistent postoperative hiccups: a review

    DEFF Research Database (Denmark)

    Hansen, B J; Rosenberg, J

    1993-01-01

    . Numerous treatment modalities have been tried but with questionable success. Valproate has proven effective in two trials investigating persistent non-surgical hiccups. The simple application of a nasogastric tube may successfully treat the hiccups, possibly because of an alteration of the activity...

  16. Molecular Mechanisms Underlying Bacterial Persisters

    DEFF Research Database (Denmark)

    Maisonneuve, Etienne; Gerdes, Kenn

    2014-01-01

    technological advances in microfluidics and reporter genes have improved this scenario. Here, we summarize recent progress in the field, revealing the ubiquitous bacterial stress alarmone ppGpp as an emerging central regulator of multidrug tolerance and persistence, both in stochastically and environmentally...

  17. Microfluidic isolation of cancer-cell-derived microvesicles from hetergeneous extracellular shed vesicle populations.

    Science.gov (United States)

    Santana, Steven M; Antonyak, Marc A; Cerione, Richard A; Kirby, Brian J

    2014-12-01

    Extracellular shed vesicles, including exosomes and microvesicles, are disseminated throughout the body and represent an important conduit of cell communication. Cancer-cell-derived microvesicles have potential as a cancer biomarker as they help shape the tumor microenvironment to promote the growth of the primary tumor and prime the metastatic niche. It is likely that, in cancer cell cultures, the two constituent extracellular shed vesicle subpopulations, observed in dynamic light scattering, represent an exosome population and a cancer-cell-specific microvesicle population and that extracellular shed vesicle size provides information about provenance and cargo. We have designed and implemented a novel microfluidic technology that separates microvesicles, as a function of diameter, from heterogeneous populations of cancer-cell-derived extracellular shed vesicles. We measured cargo carried by the microvesicle subpopulation processed through this microfluidic platform. Such analyses could enable future investigations to more accurately and reliably determine provenance, functional activity, and mechanisms of transformation in cancer. PMID:25342569

  18. Power System Stability Using Decentralized Under Frequency and Voltage Load Shedding

    DEFF Research Database (Denmark)

    Hoseinzadeh, Bakhtyar; Silva, Filipe Faria Da; Bak, Claus Leth

    2014-01-01

    Load shedding (LS) is the last emergency control action against voltage and frequency instability or even system blackout. In conventional Under Frequency Load Shedding (UFLS) relays, LS is carried out by curtailing a fixed amount of load when the frequency declines below a set of predefined...... of disturbance location. In this paper, to aim adaptive performance of the relays, the amount of load shed in each stage is determined proportional to the measured Rate of Change of Frequency (ROCOF). In order to localize the LS scheme close to the disturbance place, this scheme utilizes the voltage drop...... information to shed the loads with higher voltage decay first. Therefore, this approach deals with coordination of voltage and frequency information instead of independent methods. Numerical simulations which are carried out in DigSilent PowerFactory software confirm the efficiency of proposed methodology...

  19. Prevalence of human herpesvirus-8 salivary shedding in HIV increases with CD4 count.

    Science.gov (United States)

    Gandhi, M; Koelle, D M; Ameli, N; Bacchetti, P; Greenspan, J S; Navazesh, M; Anastos, K; Greenblatt, R M

    2004-08-01

    Human herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), which occurs in epidemic form in human immunodeficiency virus(HIV)-infected individuals. Saliva is the only mucosal fluid in which infectious HHV-8 has been identified, although factors associated with HHV-8 salivary shedding remain unclear. Our study performed PCR analysis for HHV-8 DNA in saliva (and other body fluids) in 66 HIV- and HHV-8-co-infected women without KS so that we could examine predictors for HHV-8 DNA detection. CD4 count was the most significant predictor of HHV-8 salivary shedding, with increased prevalence of HHV-8 salivary DNA at higher CD4 counts. The odds of salivary HHV8 shedding at CD4 counts > = 350 cells/microL was 63 times the odds of shedding at CD4 200. Analysis of these data suggests an increased potential for HHV-8 transmission early in HIV infection, with implications for HHV-8 prevention.

  20. Preparation of a novel adenovirus formulation with artificial envelope of multilayer polymer-coatings: therapeutic effect on metastatic ovarian cancer.

    Science.gov (United States)

    Yoshihara, Chieko; Hamada, Katsuyuki; Koyama, Yoshiyuki

    2010-03-01

    Layer-by-layer deposition of the ionic polymers onto adenovirus particles afforded the multilayer-coated virus vectors. The infectivity of the virus in the presence of anti-adenovirus antibody increased as the layer number and the viruses with five or six polymer layers allowed relatively high efficiency of reporter gene expression in vitro. Therapeutic effect of the intraperitoneal injection of the oncolytic adenovirus with quintal polymer multilayers on the mice bearing intraperitoneal metastatic ovarian cancer was examined. All the control mice injected with PBS died within 21 days after the tumor inoculation. On the other hand, the mice injected with the multilayer-coated oncolytic virus lived much longer and seven eighths of them lived >60 days without apparent accumulation of ascites. These approaches would open a new way to create a novel, safe and efficient viral gene therapy. PMID:20127013

  1. Nucleic acid sequences encoding D1 and D1/D2 domains of human coxsackievirus and adenovirus receptor (CAR)

    Science.gov (United States)

    Freimuth, Paul I.

    2010-04-06

    The invention provides recombinant human CAR (coxsackievirus and adenovirus receptor) polypeptides which bind adenovirus. Specifically, polypeptides corresponding to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2 are provided. In another aspect, the invention provides nucleic acid sequences encoding these domains and expression vectors for producing the domains and bacterial cells containing such vectors. The invention also includes an isolated fusion protein comprised of the D1 polypeptide fused to a polypeptide which facilitates folding of D1 when expressed in bacteria. The functional D1 domain finds application in a therapeutic method for treating a patient infected with a CAR D1-binding virus, and also in a method for identifying an antiviral compound which interferes with viral attachment. The invention also provides a method for specifically targeting a cell for infection by a virus which binds to D1.

  2. Adenovirus-induced alterations in host cell gene expression prior to the onset of viral gene expression.

    Science.gov (United States)

    Granberg, Fredrik; Svensson, Catharina; Pettersson, Ulf; Zhao, Hongxing

    2006-09-15

    In this report, we have studied gene expression profiles in human primary lung fibroblasts (IMR-90) during the very early phase of an adenovirus infection. Eight out of twelve genes with known functions encoded transcription factors linked to two major cellular processes; inhibition of cell growth (ATF3, ATF4, KLF4, KLF6 and ELK3) and immune response (NR4A1 and CEBPB), indicating that the earliest consequences of an adenovirus infection are growth arrest and induction of an immune response. A time course analysis showed that the induction of these immediate-early response genes was transient and suppressed after the onset of the adenovirus early gene expression. PMID:16860366

  3. Persistence

    DEFF Research Database (Denmark)

    Hansen, Kis Boisen

    2012-01-01

    The note shows an example of an architure for buildin g stand-alone program, where the programming language is object oriented and the databas system is a relational database system. Together with the notes is an example program.......The note shows an example of an architure for buildin g stand-alone program, where the programming language is object oriented and the databas system is a relational database system. Together with the notes is an example program....

  4. Persistent Bovine Viral Diarrhea Virus Infection in Domestic and Wild Small Ruminants and Camelids Including the Mountain Goat (Oreamnos americanus)

    OpenAIRE

    Nelson, Danielle D.; Duprau, Jennifer L.; Wolff, Peregrine L.; Evermann, James F.

    2016-01-01

    Bovine viral diarrhea virus (BVDV) is a pestivirus best known for causing a variety of disease syndromes in cattle, including gastrointestinal disease, reproductive insufficiency, immunosuppression, mucosal disease, and hemorrhagic syndrome. The virus can be spread by transiently infected individuals and by persistently infected animals that may be asymptomatic while shedding large amounts of virus throughout their lifetime. BVDV has been reported in over 40 domestic and free-ranging species,...

  5. Bovine coronavirus in naturally and experimentally exposed calves; viral shedding and the potential for transmission

    OpenAIRE

    Oma, Veslemøy Sunniva; Tråvén, Madeleine; Alenius, Stefan; Myrmel, Mette; Stokstad, Maria

    2016-01-01

    Background Bovine coronavirus (BCoV) is a widely distributed pathogen, causing disease and economic losses in the cattle industry worldwide. Prevention of virus spread is impeded by a lack of basic knowledge concerning viral shedding and transmission potential in individual animals. The aims of the study were to investigate the duration and quantity of BCoV shedding in feces and nasal secretions related to clinical signs, the presence of virus in blood and tissues and to test the hypothesis t...

  6. Microfluidic isolation of cancer-cell-derived microvesicles from hetergeneous extracellular shed vesicle populations

    OpenAIRE

    Santana, Steven M.; Antonyak, Marc A.; Cerione, Richard A.; Kirby, Brian J.

    2014-01-01

    Extracellular shed vesicles, including exosomes and microvesicles, are disseminated throughout the body and represent an important conduit of cell communication. Cancer-cell-derived microvesicles have potential as a cancer biomarker as they help shape the tumor microenvironment to promote the growth of the primary tumor and prime the metastatic niche. It is likely that, in cancer cell cultures, the two constituent extracellular shed vesicle subpopulations, observed in dynamic light scattering...

  7. Neumonectomía en atelectasia masiva post infección por adenovirus Pneumonectomy in massive atelectasis post adenovirus infection

    OpenAIRE

    Andrés Koppmann A; Ana María Escobar C; Isabel Valdés I

    2006-01-01

    Se describen las características clínicas, la imagenología torácica y función pulmonar de tres pacientes (edades actuales: 8-14 años). Todos ellos cursaron con una neumonía grave por adenovirus en el período de lactante y cuya evolución se agravó por una atelectasia pulmonar masiva refractaria al tratamiento que determinó la indicación de neumonectomía. En los tres casos, el pulmón resecado presentaba atelectasia, bronquiectasias y fibrosis. Dos niños mejoraron su condición clínica posterior ...

  8. Double-detargeted oncolytic adenovirus shows replication arrest in liver cells and retains neuroendocrine cell killing ability.

    Directory of Open Access Journals (Sweden)

    Justyna Leja

    Full Text Available BACKGROUND: We have previously developed an oncolytic serotype 5 adenovirus (Ad5 with chromogranin-A (CgA promoter-controlled E1A expression, Ad[CgA-E1A], with the intention to treat neuroendocrine tumors, including carcinoids. Since carcinoids tend to metastasize to the liver it is important to fully repress viral replication in hepatocytes to avoid adenovirus-related liver toxicity. Herein, we explore miRNA-based regulation of E1A expression as a complementary mechanism to promoter-based transcriptional control. METHODOLOGY/PRINCIPAL FINDINGS: Ad[CgA-E1A-miR122], where E1A expression is further controlled by six tandem repeats of the target sequence for the liver-specific miR122, was constructed and compared to Ad[CgA-E1A]. We observed E1A suppression and replication arrest of the miR122-detargeted adenovirus in normal hepatocytes, while the two viruses killed carcinoid cells to the same degree. Repeated intravenous injections of Ad[CgA-E1A] induced liver toxicity in mice while Ad[CgA-E1A-miR122] injections did not. Furthermore, a miR122-detargeted adenovirus with the wild-type E1A promoter showed reduced replication in hepatic cells compared to wild-type Ad5 but not to the same extent as the miR122-detargeted adenovirus with the neuroendocrine-selective CgA promoter. CONCLUSIONS/SIGNIFICANCE: A combination of transcriptional (promoter and post-transcriptional (miRNA target regulation to control virus replication may allow for the use of higher doses of adenovirus for efficient tumors treatment without liver toxicity.

  9. Single-step concentration and purification of adenoviruses by coxsackievirus-adenovirus receptor-binding capture and elastin-like polypeptide-mediated precipitation.

    Science.gov (United States)

    Wu, Qian; Liu, Wenjun; Xu, Bi; Zhang, Xinyu; Xia, Xiaoli; Sun, Huaichang

    2016-02-01

    A single-step method for quick concentration and purification of adenoviruses (Ads) was established by combining coxsackievirus and adenovirus receptor (CAR)-binding capture with elastin-like polypeptide (ELP)-mediated precipitation. The soluble ELP-CAR fusion protein was expressed in vector-transformed E. coli and purified to high purity by two rounds of inverse transition cycling (ITC). After demonstration of the specific binding of fusion protein, a recombinant Ad (rAd), namely rAd/GFP, was pulled down from the culture medium and extract of rAd-transduced cells using ELP-CAR protein, with recovery of 76.2 % and 73.3 %, respectively. The rAd was eluted from the ELP-CAR protein and harvested by one round of ITC, with recoveries ranging from 30.6 % to 34.5 % (virus titration assay). Both ELP-CAR-bound and eluted rAds were able to transduce CAR-positive cells, but not CAR-negative cells (fluorescent microscopy). A further viral titration assay showed that the ELP-CAR-bound rAd/GFP had significantly lower transduction efficiency than the eluted rAd, and there was less of a decrease when tested in the presence of fetal bovine serum. In addition, rAd/GFP was efficiently recovered from the "spiked" PBS and tap water with recovery of ~74 % or ~60 %. This work demonstrates the usefulness of the ELP-CAR-binding capture method for concentration and/or purification of Ads in cellular and environmental samples.

  10. Development of a screening method to identify regulators of MICA shedding.

    Science.gov (United States)

    Kishikawa, Takahiro; Otsuka, Motoyuki; Ohno, Motoko; Yoshikawa, Takeshi; Sato, Masaya; Koike, Kazuhiko

    2015-10-01

    Immune cells, such as natural killer (NK) cells, recognize virally infected and transformed cells, and eliminate them through the interaction between NKG2D receptors on NK cells and NKG2D ligands on pathogenic cells. Shedding of NKG2D ligands is thought to be a type of counter-mechanism employed by pathogenic cells to evade from NKG2D-mediated immune surveillance. MHC class I polypeptide-related sequence A (MICA) is a prototypical NKG2D ligand. We previously reported that, in soluble form, MICA expression levels are significantly associated with hepatitis virus-induced hepatocellular carcinoma. Here, we report a MICA shedding assay that utilizes membrane-bound MICA tagged at its N-terminus with a nano-luciferase reporter to quantify MICA shedding into culture media. Using this method, we screened a compound library and identified putative regulators of MICA shedding that have the potential to enhance the immune reaction by simultaneously increasing cell surface MICA levels and decreasing soluble MICA levels. This shedding assay may be useful for screening regulators of cell surface molecule shedding.

  11. Cone outer segment shedding in the goldfish retina characterized with the 3H-fucose technique

    International Nuclear Information System (INIS)

    After an intravitreal injection of 3H-fucose, red- and blue-sensitive cone outer segments (OSs) in the goldfish retina became heavily labeled, green-sensitive cone OSs showed light labeling, and rod OSs showed virtually no labeling. Fish were maintained in white light (light/dark: 12 hr/12 hr; 6 to 10 weeks) and were injected with 3H-fucose 24 hr before sacrifice. After light onset, only phagosomes with no label were found in the retinal pigment epithelium (RPE); after light offset, phagosomes with heavy, light, or no label were found in the RPE. A broad peak of cone OS shedding derived from all cone types was found beginning 2 hr after light offset and returning to baseline levels after 12 hr, with a maximum at 4 to 6 hr. When the white light was replaced with red light during the final 24 hr (irradiance matched to the white light at 625 nm), the green cones showed a reduction in shedding by 62%, the rods showed a 48% reduction in shedding, and the number of heavily labeled phagosomes was reduced by 24% (a value that may reflect normal and red cone shedding and a reduction in blue cone shedding). The results suggest that chromatic stimulation during the light period may influence the shedding response of a given class of cone OS. Finally, the 3H-fucose technique is useful for determination of the photoreceptor OS from which a given phagosome in the RPE originates in this species

  12. A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Isabela Resende Pereira

    2015-01-01

    Full Text Available Chagas disease (CD, caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd carrying sequences of amastigote surface protein-2 (rAdASP2 and trans-sialidase (rAdTS T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi, when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFNγ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi and the boost (analysis at 180 and 230 dpi. Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28, CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells

  13. Avian Adenoviruses Infections with Special Attention to Inclusion Body Hepatitis/ Hydropericardium Syndrome and Egg Drop Syndrome

    Directory of Open Access Journals (Sweden)

    Hafez Mohamed Hafez*

    2011-04-01

    Full Text Available The first avian adenovirus (AAV associated with clinical disease was isolated from an outbreak of respiratory disease in quail in 1950 (Olson, 1950. Since that time, AAVs have been found in all types and breeds of chickens and from a variety of other avian species. The infections may be asymptomatic or associated with several clinical and pathological conditions. Vertical transmission via the egg is the most common way of transmission. Also horizontal transmission through faeces, contaminated egg trays, crates and trucks play a role in the infection route. Studies have demonstrated the presence of antibodies in healthy poultry, and viruses have been isolated from normal birds. Avian adenoviruses in chickens are the etiological agents of 2 diseases known as inclusion body hepatitis (IBH and hydropericardium syndrome (HP. In some cases each condition is observed separately, however, recently the 2 conditions have frequently been observed as a single entity; therefore, the name hepatitis hydropericardium has been widely used to describe the pathologic condition. The syndrome is an acute disease of young chickens associated with anemia, haemorrhagic disorders, hydropericardium and high mortality. Egg-Drop-Syndrome (EDS is caused also by an adenovirus. The disease is characterised by a severe drop in egg production as well as the production of shell-less, thin-shelled, discoloured or misshapen eggs in apparently healthy birds. Ducks and geese are the natural host of the EDS virus. It was first described in chickens in the 1970s and spread to several countries world wide. The birds usually do not show any other signs of disease, and mortality is not expected. There is no specific treatment of the AAV infections. Active immunization by vaccination using an inactivated is wide spread.

  14. Effects of adenovirus-mediated human cyclooxygenase-2 antisense RNA on the growth of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hu Wang; Sheng-Bao Li; Qiang Tong; Guo-Jian Xie; Qing-Ming Wu

    2005-01-01

    AIM: To investigate the relation between the expression of cyclooxygenase-2 (COX-2) and liver cancer, to construct the recombinant adenovirus encoding human COX-2antisense RNA, and to explore its effects on liver cancer cell proliferation.METHODS: We studied the expression of COX-2 in 34cases of hepatocellular carcinoma (HCC) and SMMC7402and SMMC7721 by immunohistochemical technique.Recombinant adenovirus Ad-AShcox-2 was constructed and transfected into human HCC cell lines SMMC7402and SMMC7721, and its effects on COX-2 expression, cell apoptosis and cell cycle were analyzed by flow cytometry.Cell proliferation was determined by colony-forming efficiency.RESULTS: We observed COX-2 expression in 82.4% of HCC and SMMC7402 cells, but no COX-2 expression in SMMC7721 cells. In addition, recombinant adenovirus encoding antisense COX-2 fragment Ad-AShcox-2 was obtained with the titer of 1.06× 1012 PFU/mL. Ad-AShcox-2 could reduce the expression of COX-2 and enhance the percentage of cells in G1/G0 phase in SMMC7402 cell line.The difference of apoptotic index between the Ad-AShcox2 group and control group was statistically significant(tcontrol group= 32.62 and tAd-LacZ= 10.93, P<0.001) in SMMC7402 but not in SMMC7721. Similarly, colony-forming rates of SMMC7402 and SMMC7721 cell lines, after the transfer of Ad-AShcox-2, were (2.7±0.94)% and(33.6±4.24)%, respectively.CONCLUSION: Reduction in the expression of COX-2 can inhibit COX-2 expressing HCC cells.

  15. Systemic Delivery of an Oncolytic Adenovirus Expressing Decorin for the Treatment of Breast Cancer Bone Metastases.

    Science.gov (United States)

    Yang, Yuefeng; Xu, Weidong; Neill, Thomas; Hu, Zebin; Wang, Chi-Hsiung; Xiao, Xianghui; Stock, Stuart R; Guise, Theresa; Yun, Chae-Ok; Brendler, Charles B; Iozzo, Renato V; Seth, Prem

    2015-12-01

    The development of novel therapies for breast cancer bone metastasis is a major unmet medical need. Toward that end, we have constructed an oncolytic adenovirus, Ad.dcn, and a nonreplicating adenovirus, Ad(E1-).dcn, both containing the human decorin gene. Our in vitro studies showed that Ad.dcn produced high levels of viral replication and the decorin protein in the breast tumor cells. Ad(E1-).dcn-mediated decorin expression in MDA-MB-231 cells downregulated the expression of Met, β-catenin, and vascular endothelial growth factor A, all of which are recognized decorin targets and play pivotal roles in the progression of breast tumor growth and metastasis. Adenoviral-mediated decorin expression inhibited cell migration and induced mitochondrial autophagy in MDA-MB-231 cells. Mice bearing MDA-MB-231-luc skeletal metastases were systemically administered with the viral vectors, and skeletal tumor growth was monitored over time. The results of bioluminescence imaging and X-ray radiography indicated that Ad.dcn and Ad(E1-).dcn significantly inhibited the progression of bone metastases. At the terminal time point, histomorphometric analysis, micro-computed tomography, and bone destruction biomarkers showed that Ad.dcn and Ad(E1-).dcn reduced tumor burden and inhibited bone destruction. A nonreplicating adenovirus Ad(E1-).luc expressing the luciferase 2 gene had no significant effect on inhibiting bone metastases, and in several assays, Ad.dcn and Ad(E1-).dcn were better than Ad.luc, a replicating virus expressing the luciferase 2 gene. Our data suggest that adenoviral replication coupled with decorin expression could produce effective antitumor responses in a MDA-MB-231 bone metastasis model of breast cancer. Thus, Ad.dcn could potentially be developed as a candidate gene therapy vector for treating breast cancer bone metastases.

  16. Mitogenic activity of the adenovirus type 12 E1A gene induced by hormones in rat cells.

    OpenAIRE

    Oda, K.; Masuda-Murata, M; Shiroki, K; Handa, H.

    1986-01-01

    Several lines of rat 3Y1 cells in which expression of the adenovirus type 12 E1A gene can be regulated by dexamethasone were established by introduction of recombinant vector DNA containing the adenovirus type 12 E1A gene placed downstream of the hormone-inducible promoter of mouse mammary tumor virus. These cell lines (gMA cells) produced low basal levels of the E1A transcripts and proteins in normal medium and much higher levels upon addition of dexamethasone to the medium. When dexamethaso...

  17. Identification and Typing of Respiratory Adenoviruses in Guangzhou,Southern China Using a Rapid and Simple Method

    Institute of Scientific and Technical Information of China (English)

    Guiyuan Han; Hongling Niu; Suhui Zhao; Bing Zhu; Changbing Wang; Yungang Liu; Mingjie Zhang

    2013-01-01

    Human adenoviruses (HAdVs),especially HAdV-B3,-E4 and-B7,are associated with Acute Respiratory Disease in Chinese children,and occasionally in adults.In order to establish and document the profiles of the respiratory adenovirus pathogen among children in Guangzhou,Southern China,a rapid,simple and practical method for identification and typing of respiratory adenoviruses was developed and evaluated.One pair of universal PCR primers was designed according to the conserved region of the hexon gene,which can detect not only HAdV-B3,-E4 and-B7,but also HAdV-B14,-F40 and-F41,with a specific 300bp PCR product.Three pairs of type-specific PCR primers were also designed according to the hypervariable regions of the hexon gene to type HAdV-B3,-E4 and-B7 by three independent PCR reactions,making it easy to optimize the PCR conditions.By using this method,one hundred throat swab specimens collected during Oct 2010 to Dec 2011 and suspected of being positive for adenoviral infection were identified and typed for adenoviruses.Of these samples,fifty-five were adenovirus-positive.The most common HAdV type was HAdV-B3,identified in 92.7% of samples,which is not only consistent with the data reported in 2004-2006,but also consistent with the recent report in Hangzhou,eastern China,indicating that HAdV-B3 has been circulating in Guangzhou,and maybe in eastern China,for many years.The method for the respiratory adenovirus identification and typing we developed is rapid,simple and practical,which has a potential in the real-time surveillance of circulating adenovirus strains and also to provide etiological evidence for the adenovirus-relative disease control and prevention in China.

  18. A broadly applicable method to characterize large DNA viruses and adenoviruses based on the DNA polymerase gene

    Directory of Open Access Journals (Sweden)

    Montgomery Roy D

    2006-04-01

    Full Text Available Abstract Background Many viral pathogens are poorly characterized, are difficult to culture or reagents are lacking for confirmatory diagnoses. We have developed and tested a robust assay for detecting and characterizing large DNA viruses and adenoviruses. The assay is based on the use of degenerate PCR to target a gene common to these viruses, the DNA polymerase, and sequencing the products. Results We evaluated our method by applying it to fowl adenovirus isolates, catfish herpesvirus isolates, and largemouth bass ranavirus (iridovirus from cell culture and lymphocystis disease virus (iridovirus and avian poxvirus from tissue. All viruses with the exception of avian poxvirus produced the expected product. After optimization of extraction procedures, and after designing and applying an additional primer we were able to produce polymerase gene product from the avian poxvirus genome. The sequence data that we obtained demonstrated the simplicity and potential of the method for routine use in characterizing large DNA viruses. The adenovirus samples were demonstrated to represent 2 types of fowl adenovirus, fowl adenovirus 1 and an uncharacterized avian adenovirus most similar to fowl adenovirus 9. The herpesvirus isolate from blue catfish was shown to be similar to channel catfish virus (Ictalurid herpesvirus 1. The case isolate of largemouth bass ranavirus was shown to exactly match the type specimen and both were similar to tiger frog virus and frog virus 3. The lymphocystis disease virus isolate from largemouth bass was shown to be related but distinct from the two previously characterized lymphocystis disease virus isolates suggesting that it may represent a distinct lymphocystis disease virus species. Conclusion The method developed is rapid and broadly applicable to cell culture isolates and infected tissues. Targeting a specific gene for in the large DNA viruses and adenoviruses provide a common reference for grouping the newly identified

  19. Immunostimulatory activities of dendritic cells loaded with adenovirus vector carrying HBcAg/HBsAg

    OpenAIRE

    Jia, Hongyu; Li, Chunling; Zhang, Yimin; Yu, Liang; Xiang, Dairong; Liu, Jun; Chen, Fengzhe; Han, Xiaochun

    2015-01-01

    Objective: This study is to investigate the immunostimulatory activities of dendritic cells (DCs) transfected with HBcAg and/or HBsAg recombinant adenovirus (rAd). Methods: DCs were transfected with rAd (DC/Ad-C+Ad-S, DC/Ad-C, and DC/Ad-S), or pulsed with HBcAg antigen (DC/HBcAg). Flow cytometry was used to detect the phenotype of DCs and the cytokine production of T lymphocytes. Mice were vaccinated with DCs transfected with rAd or pulsed with antigen, and DNA vaccine. Mixed lymphocyte react...

  20. A non-enteric adenovirus A12 gastroenteritis outbreak in Rio de Janeiro, Brazil

    OpenAIRE

    Silvana Augusta Rodrigues Portes; Eduardo de Mello Volotão; Monica Simões Rocha; Maria Cristina Rebelo; Maria da Penha Trindade Pinheiro Xavier; Rosane Maria de Assis; Tatiana Lundgren Rose; Marize Pereira Miagostovich; José Paulo Gagliardi Leite; Filipe Anibal Carvalho-Costa

    2016-01-01

    A gastroenteritis outbreak that occurred in 2013 in a low-income community in Rio de Janeiro was investigated for the presence of enteric viruses, including species A rotavirus (RVA), norovirus (NoV), astrovirus (HAstV), bocavirus (HBoV), aichivirus (AiV), and adenovirus (HAdV). Five of nine stool samples (83%) from patients were positive for HAdV, and no other enteric viruses were detected. Polymerase chain reaction products were sequenced and subjected to phylogenetic analysis, which reveal...

  1. Inhibition of KIT RNAi mediated with adenovirus in gastrointestinal stromal tumor xenograft

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate a therapeutic method for gastrointestinal stromal tumor (GIST) based on KIT RNA interference (RNAi) with AdMax adenovirus. METHODS: KIT short hairpin RNA (shRNA), whose lateral sides were decorated with restriction endonuclease sequences, was designed. T 4 DNA ligase catalyzed the joint of the KIT shRNA and the green fluorescent protein-containing PDC316-EGFP-U6 to form PDC316EGFP-U6-KIT. Homologous recombination of AdEGFPU6-KIT was performed with the AdMax system. Heterotopically transp...

  2. Isolation, identification, and complete genome sequence of a bovine adenovirus type 3 from cattle in China

    Directory of Open Access Journals (Sweden)

    Zhu Yuan-Mao

    2011-12-01

    Full Text Available Abstract Background Bovine adenovirus type 3 (BAV-3 belongs to the Mastadenovirus genus of the family Adenoviridae and is involved in respiratory and enteric infections of calves. The isolation of BAV-3 has not been reported prior to this study in China. In 2009, there were many cases in cattle showing similar clinical signs to BAV-3 infection and a virus strain, showing cytopathic effect in Madin-Darby bovine kidney cells, was isolated from a bovine nasal swab collected from feedlot cattle in Heilongjiang Province, China. The isolate was confirmed as a bovine adenovirus type 3 by PCR and immunofluorescence assay, and named as HLJ0955. So far only the complete genome sequence of prototype of BAV-3 WBR-1 strain has been reported. In order to further characterize the Chinese isolate HLJ0955, the complete genome sequence of HLJ0955 was determined. Results The size of the genome of the Chinese isolate HLJ0955 is 34,132 nucleotides in length with a G+C content of 53.6%. The coding sequences for gene regions of HLJ0955 isolate were similar to the prototype of BAV-3 WBR-1 strain, with 80.0-98.6% nucleotide and 87.5-98.8% amino acid identities. The genome of HLJ0955 strain contains 16 regions and four deletions in inverted terminal repeats, E1B region and E4 region, respectively. The complete genome and DNA binding protein gene based phylogenetic analysis with other adenoviruses were performed and the results showed that HLJ0955 isolate belonged to BAV-3 and clustered within the Mastadenovirus genus of the family Adenoviridae. Conclusions This is the first study to report the isolation and molecular characterization of BAV-3 from cattle in China. The phylogenetic analysis performed in this study supported the use of the DNA binding protein gene of adenovirus as an appropriate subgenomic target for the classification of different genuses of the family Adenoviridae on the molecular basis. Meanwhile, a large-scale pathogen and serological epidemiological

  3. Tumor promoters alter the temporal program of adenovirus replication in human cells.

    OpenAIRE

    Fisher, P B; Young, C S; Weinstein, I B; Carter, T. H.

    1981-01-01

    In this study we evaluated the effect of phorbol ester tumor promoters on the kinetics of adenovirus type 5 (Ad5) replication in human cells. When added at the time of infection, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) accelerated the appearance of an early virus antigen (72,000-molecular-weight [72K] deoxyribonucleic acid-binding protein), the onset of viral deoxyribonucleic acid synthesis, and the production of infectious virus. The appearance of an Ad5-specific cytopathic effect (CPE) ...

  4. Multiple phenotypes in adult mice following inactivation of the Coxsackievirus and Adenovirus Receptor (Car gene.

    Directory of Open Access Journals (Sweden)

    Ahmad Pazirandeh

    Full Text Available To determine the normal function of the Coxsackievirus and Adenovirus Receptor (CAR, a protein found in tight junctions and other intercellular complexes, we constructed a mouse line in which the CAR gene could be disrupted at any chosen time point in a broad spectrum of cell types and tissues. All knockouts examined displayed a dilated intestinal tract and atrophy of the exocrine pancreas with appearance of tubular complexes characteristic of acinar-to-ductal metaplasia. The mice also exhibited a complete atrio-ventricular block and abnormal thymopoiesis. These results demonstrate that CAR exerts important functions in the physiology of several organs in vivo.

  5. ZEB1 limits adenoviral infectability by transcriptionally repressing the Coxsackie virus and Adenovirus Receptor

    Directory of Open Access Journals (Sweden)

    Lacher Markus D

    2011-07-01

    Full Text Available Abstract Background We have previously reported that RAS-MEK (Cancer Res. 2003 May 1;63(9:2088-95 and TGF-β (Cancer Res. 2006 Feb 1;66(3:1648-57 signaling negatively regulate coxsackie virus and adenovirus receptor (CAR cell-surface expression and adenovirus uptake. In the case of TGF-β, down-regulation of CAR occurred in context of epithelial-to-mesenchymal transition (EMT, a process associated with transcriptional repression of E-cadherin by, for instance, the E2 box-binding factors Snail, Slug, SIP1 or ZEB1. While EMT is crucial in embryonic development, it has been proposed to contribute to the formation of invasive and metastatic carcinomas by reducing cell-cell contacts and increasing cell migration. Results Here, we show that ZEB1 represses CAR expression in both PANC-1 (pancreatic and MDA-MB-231 (breast human cancer cells. We demonstrate that ZEB1 physically associates with at least one of two closely spaced and conserved E2 boxes within the minimal CAR promoter here defined as genomic region -291 to -1 relative to the translational start ATG. In agreement with ZEB1's established role as a negative regulator of the epithelial phenotype, silencing its expression in MDA-MB-231 cells induced a partial Mesenchymal-to-Epithelial Transition (MET characterized by increased levels of E-cadherin and CAR, and decreased expression of fibronectin. Conversely, knockdown of ZEB1 in PANC-1 cells antagonized both the TGF-β-induced down-regulation of E-cadherin and CAR and the reduction of adenovirus uptake. Interestingly, even though ZEB1 clearly contributes to the TGF-β-induced mesenchymal phenotype of PANC-1 cells, TGF-β did not seem to affect ZEB1's protein levels or subcellular localization. These findings suggest that TGF-β may inhibit CAR expression by regulating factor(s that cooperate with ZEB1 to repress the CAR promoter, rather than by regulating ZEB1 expression levels. In addition to the negative E2 box-mediated regulation the minimal

  6. Impaired antiviral response of adenovirus-transformed cell lines supports virus replication.

    Science.gov (United States)

    Bachmann, Mandy; Breitwieser, Theresa; Lipps, Christoph; Wirth, Dagmar; Jordan, Ingo; Reichl, Udo; Frensing, Timo

    2016-02-01

    Activation of the innate immune response represents one of the most important cellular mechanisms to limit virus replication and spread in cell culture. Here, we examined the effect of adenoviral gene expression on the antiviral response in adenovirus-transformed cell lines; HEK293, HEK293SF and AGE1.HN. We demonstrate that the expression of the early region protein 1A in these cell lines impairs their ability to activate antiviral genes by the IFN pathway. This property may help in the isolation of newly emerging viruses and the propagation of interferon-sensitive virus strains.

  7. Persistence, Perseverance, and Success (PPS

    Directory of Open Access Journals (Sweden)

    Lewis Madhlangobe

    2014-07-01

    Full Text Available The purpose of this qualitative study was to describe motivational factors that increased open distance learning (ODL students’ capacity to successfully graduate with master’s and doctoral credentials. Study background revealed that Zimbabwe Open University (ZOU persistently experiences increased levels of student dropout and competition from conventional universities that introduce ODL through “block-release” programs. We used a descriptive qualitative research approach to collect and analyze data—hence, data collection through audio-recorded open-ended semi-structured interviews helped to maintain accurate accounts of data. We presented data through themed reporting enhanced by direct quotes from participants. Our research broadly concluded that once participants registered to study, perceived attention from various social angles created immense motivational factors ranging from institution motivators, personal factors, and social-generated motivators such as fear of what society would think of them all motivated them to persist and graduate with proposed credentials.

  8. Population dynamics of bacterial persistence.

    Directory of Open Access Journals (Sweden)

    Pintu Patra

    Full Text Available Persistence is a prime example of phenotypic heterogeneity, where a microbial population splits into two distinct subpopulations with different growth and survival properties as a result of reversible phenotype switching. Specifically, persister cells grow more slowly than normal cells under unstressed growth conditions, but survive longer under stress conditions such as the treatment with bactericidal antibiotics. We analyze the population dynamics of such a population for several typical experimental scenarios, namely a constant environment, shifts between growth and stress conditions, and periodically switching environments. We use an approximation scheme that allows us to map the dynamics to a logistic equation for the subpopulation ratio and derive explicit analytical expressions for observable quantities that can be used to extract underlying dynamic parameters from experimental data. Our results provide a theoretical underpinning for the study of phenotypic switching, in particular for organisms where detailed mechanistic knowledge is scarce.

  9. Persistent Homology of Collaboration Networks

    Directory of Open Access Journals (Sweden)

    C. J. Carstens

    2013-01-01

    Full Text Available Over the past few decades, network science has introduced several statistical measures to determine the topological structure of large networks. Initially, the focus was on binary networks, where edges are either present or not. Thus, many of the earlier measures can only be applied to binary networks and not to weighted networks. More recently, it has been shown that weighted networks have a rich structure, and several generalized measures have been introduced. We use persistent homology, a recent technique from computational topology, to analyse four weighted collaboration networks. We include the first and second Betti numbers for the first time for this type of analysis. We show that persistent homology corresponds to tangible features of the networks. Furthermore, we use it to distinguish the collaboration networks from similar random networks.

  10. Coping with persistent environmental problems

    DEFF Research Database (Denmark)

    Varjopuro, Riku; Andrulewicz, Eugeniusz; Brandt, Urs Steiner;

    2014-01-01

    involved in the implementation are keys to improve understanding of the systemic delays. The improved understanding is necessary for the adaptive management of a persistent environmental problem. In addition to the state of the environment, the monitoring and analysis should be targeted also......ABSTRACT In this paper we focus on systemic delays in the Baltic Sea that cause the problem of eutrophication to persist. These problems are demonstrated in our study by addressing three types of delays: (1) decision delay: the time it takes for an idea or perceived need to be launched as a policy...... is to analyze these systemic delays and especially to discuss how the critical delays can be better addressed in marine protection policies by strengthening the adaptive capacity of marine protection. We conclude that the development of monitoring systems and reflexive, participatory analysis of dynamics...

  11. Persistent Monitoring Platforms Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, C L

    2007-02-22

    This project was inspired and motivated by the need to provide better platforms for persistent surveillance. In the years since the inception of this work, the need for persistence of surveillance platforms has become even more widely appreciated, both within the defense community and the intelligence community. One of the most demanding technical requirements for such a platform involves the power plant and energy storage system, and this project concentrated almost exclusively on the technology associated with this system for a solar powered, high altitude, unmanned aircraft. An important realization for the feasibility of such solar powered aircraft, made at the outset of this project, was that thermal energy may be stored with higher specific energy density than for any other known practical form of rechargeable energy storage. This approach has proved to be extraordinarily fruitful, and a large number of spin-off applications of this technology were developed in the course of this project.

  12. The role of metabolism in bacterial persistence

    Directory of Open Access Journals (Sweden)

    Stephanie M. Amato

    2014-03-01

    Full Text Available Bacterial persisters are phenotypic variants with extraordinary tolerances toward antibiotics. Persister survival has been attributed to inhibition of essential cell functions during antibiotic stress, followed by reversal of the process and resumption of growth upon removal of the antibiotic. Metabolism plays a critical role in this process, since it participates in the entry, maintenance, and exit from the persister phenotype. Here, we review the experimental evidence that demonstrates the importance of metabolism to persistence, highlight the successes and potential for targeting metabolism in the search for anti-persister therapies, and discuss the current methods and challenges to understand persister physiology.

  13. Mentoring at Men's Sheds: an international survey about a community approach to health and well-being.

    Science.gov (United States)

    Cordier, Reinie; Wilson, Nathan J

    2014-05-01

    Men's Sheds are named within the Australian and Irish National Male Health Policies as an exemplar of male health and well-being and offer a range of formal and informal mentoring to counter the known consequences of social exclusion. The study aimed to report on whether Men's Sheds undertake mentoring programmes, and if so, who is being mentored; are mentors being trained, and if so by whom; and the perceived effectiveness of the mentoring programme. Furthermore, the study aimed to explore associations between sheds with a mentoring programme and factors that reflect an inclusive and a health-focused environment. All known Men's Sheds were invited to participate in the survey; of those, 324 (42.8%) Men's Sheds in Australia and 59 (48.0%) International sheds participated in the study between April and August 2012. Overall, 39.2% (n = 127) of Australian sheds and 23.7% (n = 14) of International sheds undertook formal mentoring. Youth was the most common group being mentored in both Australia (60.6%; n = 77) and Internationally (71.4%; n = 10). Over half of Australian shed co-ordinators rated their mentoring programme as moderately effective (52.8%; n = 67) and over a third as highly effective (36.2%; n = 46), while half of International shed co-ordinators rated theirs as highly effective (50.0%; n = 7). The findings from this paper support the notion that a large number of Men's Sheds offer formal mentoring programmes targeting a range of disadvantaged sub-populations, thus supporting social inclusion. Inter-generational mentoring is the most frequently occurring type of mentoring programme. While training mentors occurs at some sheds, the efficacy of this training and programme outcomes are unknown. A typology of shed types appears to be emerging based on a divergence of sheds with a more utilitarian focus and sheds that appear to embrace a health and well-being focus.

  14. Long memory and changing persistence

    DEFF Research Database (Denmark)

    Kruse, Robinson; Sibbertsen, Philipp

    We study the empirical behaviour of semi-parametric log-periodogram estimation for long memory models when the true process exhibits a change in persistence. Simulation results confirm theoretical arguments which suggest that evidence for long memory is likely to be found. A recently proposed test...... by Sibbertsen and Kruse (2009) is shown to exhibit noticeable power to discriminate between long memory and a structural change in autoregressive parameters....

  15. Persistent Authentication in Smart Environments

    DEFF Research Database (Denmark)

    Hansen, Mads Syska; Kirschmeyer, Martin; Jensen, Christian D.

    2008-01-01

    present a proof-of-concept implementation of the proposed mechanism, which employs camera based tracking with a single stationary 3D camera that uses the "time of flight" principle. A preliminary evaluation of the proposed mechanism indicates that persistent authentication is technically possible...... with the proposed hardware. The proposed model is sufficiently general to allow the addition of more cameras or supplemental tracking technologies, which will improve the robustness and scalability of the proposed mechanism....

  16. Understanding poverty persistence in Spain

    OpenAIRE

    Aylloón, Sara

    2013-01-01

    The aim of this paper is to study the mechanisms behind poverty persistence in Spain. We examine the importance of past poverty experiences for explaining current poverty as opposed to observed and unobserved individual heterogeneity. Our results are based on the model proposed by Cappellari and Jenkins (J Appl Econometr 19:593-610, 2004a) that estimates poverty transitions while simultaneously controlling for attrition and initial conditions. We find that about 50% of aggregate state depende...

  17. Coagulation-induced shedding of platelet glycoprotein VI mediated by factor Xa.

    Science.gov (United States)

    Al-Tamimi, Mohammad; Grigoriadis, George; Tran, Huy; Paul, Eldho; Servadei, Patricia; Berndt, Michael C; Gardiner, Elizabeth E; Andrews, Robert K

    2011-04-01

    This study evaluated shedding of the platelet collagen receptor, glycoprotein VI (GPVI) in human plasma. Collagen or other ligands induce metalloproteinase-mediated GPVI ectodomain shedding, generating approximately 55-kDa soluble GPVI (sGPVI) and approximately 10-kDa platelet-associated fragments. In the absence of GPVI ligands, coagulation of platelet-rich plasma from healthy persons induced GPVI shedding, independent of added tissue factor, but inhibitable by metalloproteinase inhibitor, GM6001. Factor Xa (FXa) common to intrinsic and tissue factor-mediated coagulation pathways was critical for sGPVI release because (1) shedding was strongly blocked by the FXa-selective inhibitor rivaroxaban but not FIIa (thrombin) inhibitors dabigatran or hirudin; (2) Russell viper venom that directly activates FX generated sGPVI, with complete inhibition by enoxaparin (inhibits FXa and FIIa) but not hirudin; (3) impaired GPVI shedding during coagulation of washed platelets resuspended in FX-depleted plasma was restored by adding purified FX; and (4) purified FXa induced GM6001-inhibitable GPVI shedding from washed platelets. In 29 patients with disseminated intravascular coagulation, mean plasma sGPVI was 53.9 ng/mL (95% confidence interval, 39.9-72.8 ng/mL) compared with 12.5 ng/mL (95% confidence interval, 9.0-17.3 ng/mL) in thrombocytopenic controls (n = 36, P coagulation-induced GPVI shedding via FXa down-regulates GPVI under procoagulant conditions. FXa inhibitors have an unexpected role in preventing GPVI down-regulation.

  18. Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

    Directory of Open Access Journals (Sweden)

    Ngama Mwanajuma

    2010-01-01

    Full Text Available Abstract Background Our understanding of the transmission dynamics of respiratory syncytial virus (RSV infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months, 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25 equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3, with a median duration of shedding of 4 days (IQR 2-6, range 1-14. Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86. The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community.

  19. Role of ADAM10 and ADAM17 in CD16b Shedding Mediated by Different Stimulators

    Institute of Scientific and Technical Information of China (English)

    Sha Guo; Min Peng; Qing Zhao; Wei Zhang

    2012-01-01

    Objective To investigate the main proteinases responsible for CD16b shedding under different stimulators.Methods HEK293 cell line stably expressing CD16b was constructed by lentivirus system.The cell line was then overexpressed with a disintegrin and metalloproteinase 10 (ADAM10) or ADAM17,suppressed with short hairpin RNA of ADAM10 or ADAM17,and reconstituted with ADAMi0 or ADAM17,respectively.After each treatment,the cell line was stimulated with ionomycin or phorbol 12-myristate13-acetate (PMA) for 12 hours.The soluble CD 16b released from cell membrane was detected by immunoprecipition and immtmoblot.Quantitation was then implemented to compare the amount of soluble CD 16b in cell supernatant after stimulation.Results HEK293 cell line stably expressing CD16b was successfully established.When CD16b expressing cell line was overexpressed with ADAM1 0,shedding of CD 16b was increased after stimulation with ionomycin but not PMA; when the cell line overexpressed with ADAM 17,shedding of CD 16b was increased after stimulation with PMA but not ionomycin.Similarly,when ADAM10 was suppressed by short hairpin RNA,CD16b shedding was decreased after stimulation with ionomycin; when ADAM17 was suppressed by short hairpin RNA,CD16b shedding was decreased after stimulation with PMA.The shedding of CD16b was increased again when CD16b expressing cell line was reconstituted with ADAM10 and stimulated by ionomycin or reconstituted with ADAM 17 and stimulated by PMA.Conclusions Both ADAM10 and ADAM17 could shed CD16b,but they possess differed preferences.ADAM10 is the main sheddase under stimulation of ionomycin,while ADAM17 is the main sheddase under stimulation of PMA.

  20. Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus).

    Science.gov (United States)

    Voutilainen, Liina; Sironen, Tarja; Tonteri, Elina; Bäck, Anne Tuiskunen; Razzauti, Maria; Karlsson, Malin; Wahlström, Maria; Niemimaa, Jukka; Henttonen, Heikki; Lundkvist, Åke

    2015-06-01

    The knowledge of viral shedding patterns and viraemia in the reservoir host species is a key factor in assessing the human risk of zoonotic viruses. The shedding of hantaviruses (family Bunyaviridae) by their host rodents has widely been studied experimentally, but rarely in natural settings. Here we present the dynamics of Puumala hantavirus (PUUV) shedding and viraemia in naturally infected wild bank voles (Myodes glareolus). In a monthly capture-mark-recapture study, we analysed 18 bank voles for the presence and relative quantity of PUUV RNA in the excreta and blood from 2 months before up to 8 months after seroconversion. The proportion of animals shedding PUUV RNA in saliva, urine and faeces peaked during the first month after seroconversion, but continued throughout the study period with only a slight decline. The quantity of shed PUUV in reverse transcription quantitative PCR (RT-qPCR) positive excreta was constant over time. In blood, PUUV RNA was present for up to 7 months but both the probability of viraemia and the virus load declined with time. Our findings contradict the current view of a decline in virus shedding after the acute phase and a short viraemic period in hantavirus infection - an assumption widely adopted in current epidemiological models. We suggest the life-long shedding as a means of hantaviruses to survive over host population bottlenecks, and to disperse in fragmented habitats where local host and/or virus populations face temporary extinctions. Our results indicate that the kinetics of pathogens in wild hosts may differ considerably from those observed in laboratory settings. PMID:25701819

  1. Beyond Technical Competence: A Passion for Persistence.

    Science.gov (United States)

    Scarnati, James T.

    1998-01-01

    Persistence is a characteristic of leadership that enables successful individuals to pursue a goal despite setbacks. Achievements are as much an act of persistence as they are an expression of technical competence or intelligence. (SK)

  2. MOOCs and Persistence: Definitions and Predictors

    Science.gov (United States)

    Evans, Brent J.; Baker, Rachel B.

    2016-01-01

    The chapter argues for redefining the term "persistence" as it relates to MOOCs and considers how different measures produce different results in the research; it closes with a review of research on persistence in MOOCs.

  3. Gene therapy for allergic rhinitis with recombinant adenovirus vector containing CTLA4Ig in mice

    Institute of Scientific and Technical Information of China (English)

    朱瑾; 吴军; 陈希炜; 易绍萱; 罗高兴; 贺伟峰

    2003-01-01

    Objective: To examine the role of recombinant adenovirus vector containing CTLA4Ig gene(Ad-CTLA4Ig) in the treatment of induced allergic rhinitis in mice.Methods: Allergic rhinitis was induced by sensitizing and challenging with ovalbumin(OVA).Ad-CTLA4Ig was intraperitoneally injected 30 min before OVA challenge.Adenovirus vector without inserted CTLA4Ig cDNA served as the control.The symptoms and morphological changes of nasal mucosa of each group were observed, and the serum levels of IgE against OVA were detected with ELISA.Results: There were no obvious symptoms and pathological changes in Ad-CTLA4Ig treated group, in which the serum OVA-specific IgE levels were significantly lower than that in control groups(P< 0.05).Conclusion: Ad-CTLA4Ig prevents and treats allergic rhinitis of mice,implying the possibility of the usage of Ad-CTLA4Ig against allergic rhinitis in clinic in future.

  4. A regenerating ultrasensitive electrochemical impedance immunosensor for the detection of adenovirus.

    Science.gov (United States)

    Lin, Donghai; Tang, Thompson; Harrison, D Jed; Lee, William E; Jemere, Abebaw B

    2015-06-15

    We report on the development of a regenerable sensitive immunosensor based on electrochemical impedance spectroscopy for the detection of type 5 adenovirus. The multi-layered immunosensor fabrication involved successive modification steps on gold electrodes: (i) modification with self-assembled layer of 1,6-hexanedithiol to which gold nanoparticles were attached via the distal thiol groups, (ii) formation of self-assembled monolayer of 11-mercaptoundecanoic acid onto the gold nanoparticles, (iii) covalent immobilization of monoclonal anti-adenovirus 5 antibody, with EDC/NHS coupling reaction on the nanoparticles, completing the immunosensor. The immunosensor displayed a very good detection limit of 30 virus particles/ml and a wide linear dynamic range of 10(5). An electrochemical reductive desorption technique was employed to completely desorb the components of the immunosensor surface, then re-assemble the sensing layer and reuse the sensor. On a single electrode, the multi-layered immunosensor could be assembled and disassembled at least 30 times with 87% of the original signal intact. The changes of electrode behavior after each assembly and desorption processes were investigated by cyclic voltammetry, electrochemical impedance spectroscopy and X-ray photoelectron spectroscopy techniques. PMID:25562739

  5. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

    Directory of Open Access Journals (Sweden)

    Debrah A Fine

    Full Text Available The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT.

  6. Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

    Science.gov (United States)

    Padi, Megha; Korkhin, Anna; James, Robert L.; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A.; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A.; Hill, David E.; Cusick, Michael E.; Vidal, Marc; Florens, Laurence; Washburn, Michael P.; Litovchick, Larisa; DeCaprio, James A.

    2012-01-01

    The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. PMID:23093934

  7. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

    Science.gov (United States)

    Fine, Debrah A; Rozenblatt-Rosen, Orit; Padi, Megha; Korkhin, Anna; James, Robert L; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A; Hill, David E; Cusick, Michael E; Vidal, Marc; Florens, Laurence; Washburn, Michael P; Litovchick, Larisa; DeCaprio, James A

    2012-01-01

    The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. PMID:23093934

  8. Generation of an adenovirus-parvovirus chimera with enhanced oncolytic potential.

    Science.gov (United States)

    El-Andaloussi, Nazim; Bonifati, Serena; Kaufmann, Johanna K; Mailly, Laurent; Daeffler, Laurent; Deryckère, François; Nettelbeck, Dirk M; Rommelaere, Jean; Marchini, Antonio

    2012-10-01

    In this study, our goal was to generate a chimeric adenovirus-parvovirus (Ad-PV) vector that combines the high-titer and efficient gene transfer of adenovirus with the anticancer potential of rodent parvovirus. To this end, the entire oncolytic PV genome was inserted into a replication-defective E1- and E3-deleted Ad5 vector genome. As we found that parvoviral NS expression inhibited Ad-PV chimera production, we engineered the parvoviral P4 early promoter, which governs NS expression, by inserting into its sequence tetracycline operator elements. As a result of these modifications, P4-driven expression was blocked in the packaging T-REx-293 cells, which constitutively express the tetracycline repressor, allowing high-yield chimera production. The chimera effectively delivered the PV genome into cancer cells, from which fully infectious replication-competent parvovirus particles were generated. Remarkably, the Ad-PV chimera exerted stronger cytotoxic activities against various cancer cell lines, compared with the PV and Ad parental viruses, while being still innocuous to a panel of tested healthy primary human cells. This Ad-PV chimera represents a novel versatile anticancer agent which can be subjected to further genetic manipulations in order to reinforce its enhanced oncolytic capacity through arming with transgenes or retargeting into tumor cells.

  9. Coinfection of a bearded dragon, Pogona vitticeps, with adenovirus- and dependovirus-like viruses.

    Science.gov (United States)

    Jacobson, E R; Kopit, W; Kennedy, F A; Funk, R S

    1996-05-01

    Four neonate bearded dragons, Pogona vitticeps, from two collections became ill and died. Multiple tissues were collected and processed for light microscopy. In hematoxylin and eosin-stained sections of liver of one lizard, numerous basophilic intranuclear inclusions were observed. In three lizards, intranuclear inclusions were primarily seen within enterocytes in the small intestine. A portion of paraffin-embedded liver of one lizard and small intestine of a second lizard were removed, deparaffinized, and examined by electron microscopy. For the most part, inclusions in the liver consisted of nonenveloped viral particles 60-66 nm in diameter. Smaller nonenveloped virions 15-17 nm in diameter were occasionally seen in association with these particles. In the intestine, inclusions consisted only of 60-70 nm particles. Based on morphology and location, the larger particles were consistent with an adenovirus. Based on size and presence within nuclei of host cells coinfected with the adenovirus-like virus, the smaller viral agent was consistent with members of the genus Dependovirus. PMID:8740710

  10. Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication

    Directory of Open Access Journals (Sweden)

    Natascha Krömmelbein

    2016-02-01

    Full Text Available The human cytomegalovirus (HCMV replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production.

  11. Cryo-EM structures of two bovine adenovirus type 3 intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Lingpeng; Huang, Xiaoxing; Li, Xiaomin [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Xiong, Wei [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Luo-jia-shan, Wuhan, Hubei 430072 (China); Sun, Wei; Yang, Chongwen; Zhang, Kai; Wang, Ying [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Liu, Hongrong [College of Physics and Information Science, Hunan Normal University, Changsha, Hunan 410081 (China); Huang, Xiaojun; Ji, Gang; Sun, Fei [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Zheng, Congyi, E-mail: cctcc202@whu.edu.cn [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Luo-jia-shan, Wuhan, Hubei 430072 (China); Zhu, Ping, E-mail: zhup@ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

    2014-02-15

    Adenoviruses (Ads) infect hosts from all vertebrate species and have been investigated as vaccine vectors. We report here near-atomic structures of two bovine Ad type 3 (BAd3) intermediates obtained by cryo-electron microscopy. A comparison between the two intermediate structures reveals that the differences are localized in the fivefold vertex region, while their facet structures are identical. The overall facet structure of BAd3 exhibits a similar structure to human Ads; however, BAd3 protein IX has a unique conformation. Mass spectrometry and cryo-electron tomography analyses indicate that one intermediate structure represents the stage during DNA encapsidation, whilst the other intermediate structure represents a later stage. These results also suggest that cleavage of precursor protein VI occurs during, rather than after, the DNA encapsidation process. Overall, our results provide insights into the mechanism of Ad assembly, and allow the first structural comparison between human and nonhuman Ads at backbone level. - Highlights: • First structure of bovine adenovirus type 3. • Some channels are located at the vertex of intermediate during DNA encapsidation. • Protein IX exhibits a unique conformation of trimeric coiled–coiled structure. • Cleavage of precursor protein VI occurs during the DNA encapsidation process.

  12. Construction and Identification of Recombinant Adenovirus Vector Containing the hVEGF165 Gene

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To construct the recombinant adenovirus vector containing the cDNA for human vascular endothelial growth factor (hVEGF165), the cDNA for hVEGF165 was subcloned into pACCMV·pLpA. Subsequently, this recombinant pACCMV·hVEGF was co-transfected into 293 cells together with pJM17 to obtain the replication-deficient recombinant adenovirus containing hVEGF gene-AdCMV·hVEGF. The VEGF gene expression was detected by using RT-PCR and Western blot in rabbit aorta vascular smooth muscle cells (VSMC) infected with AdCMV·hVEGF. Cultured human umbilical vein endothelial cells (HUVEC) were incubated with the conditioned medium (CM) from above mentioned VSMC infected with AdCMV·hVEGF to observe the effect of VEGF on proliferation of HUVEC. 48 h after the infection with AdCMV·hVEGF, VSMC demonstrated VEGF expression, and the expressed VEGF could stimulate the proliferation of HUVEC in vitro. Successfully prepared AdCMV·hVEGF165 could express biologically active VEGF in infected VSMC, and stimulate proliferation of HUVEC.

  13. Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity.

    Science.gov (United States)

    Garofalo, Mariangela; Iovine, Barbara; Kuryk, Lukasz; Capasso, Cristian; Hirvinen, Mari; Vitale, Andrea; Yliperttula, Marjo; Bevilacqua, Maria Assunta; Cerullo, Vincenzo

    2016-04-01

    Oncolytic viruses are able to specifically replicate, infect, and kill only cancer cells. Their combination with chemotherapeutic drugs has shown promising results due to the synergistic action of virus and drugs; the combinatorial therapy is considered a potential clinically relevant approach for cancer. In this study, we optimized a strategy to absorb peptides on the viral capsid, based on electrostatic interaction, and used this strategy to deliver an active antitumor drug. We used L-carnosine, a naturally occurring histidine dipeptide with a significant antiproliferative activity. An ad hoc modified, positively charged L-carnosine was combined with the capsid of an oncolytic adenovirus to generate an electrostatic virus-carnosine complex. This complex showed enhanced antitumor efficacy in vitro and in vivo in different tumor models. In HCT-116 colorectal and A549 lung cancer cell lines, the complex showed higher transduction ratio and infectious titer compared with an uncoated oncolytic adenovirus. The in vivo efficacy of the complex was tested in lung and colon cancer xenograft models, showing a significant reduction in tumor growth. Importantly, we investigated the molecular mechanisms underlying the effects of complex on tumor growth reduction. We found that complex induces apoptosis in both cell lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in future studies also for delivery of other bioactive drugs. Mol Cancer Ther; 15(4); 651-60. ©2016 AACR. PMID:26861248

  14. Attachment and Detachment Behavior of Human Adenovirus and Surrogates in Fine Granular Limestone Aquifer Material.

    Science.gov (United States)

    Stevenson, Margaret E; Sommer, Regina; Lindner, Gerhard; Farnleitner, Andreas H; Toze, Simon; Kirschner, Alexander K T; Blaschke, Alfred P; Sidhu, Jatinder P S

    2015-09-01

    The transport of human adenovirus, nanoparticles, and PRD1 and MS2 bacteriophages was tested in fine granular limestone aquifer material taken from a borehole at a managed aquifer recharge site in Adelaide, South Australia. Comparison of transport and removal of virus surrogates with the pathogenic virus is necessary to understand the differences between the virus and surrogate. Because experiments using pathogenic viruses cannot be done in the field, laboratory tests using flow-through soil columns were used. Results show that PRD1 is the most appropriate surrogate for adenovirus in an aquifer dominated by calcite material but not under high ionic strength or high pH conditions. It was also found that straining due to size and the charge of the colloid were not dominant removal mechanisms in this system. Implications of this study indicate that a certain surrogate may not represent a specific pathogen solely based on similar size, morphology, and/or surface charge. Moreover, if a particular surrogate is representative of a pathogen in one aquifer system, it may not be the most appropriate surrogate in another porous media system. This was apparent in the inferior performance of MS2 as a surrogate, which is commonly used in virus transport studies. PMID:26436257

  15. Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/low cells.

    Science.gov (United States)

    Eriksson, Minna; Guse, Kilian; Bauerschmitz, Gerd; Virkkunen, Pekka; Tarkkanen, Maija; Tanner, Minna; Hakkarainen, Tanja; Kanerva, Anna; Desmond, Renee A; Pesonen, Sari; Hemminki, Akseli

    2007-12-01

    Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44(+)CD24(-/low) population. The use of oncolytic adenoviruses presents an attractive anti-tumor approach for eradication of these cells because their entry occurs through infection and they are, therefore, not susceptible to those mechanisms that commonly render stem cells resistant to many drugs. We isolated CD44(+)CD24(-/low) cells from patient pleural effusions and confirmed stem cell-like features including oct4 and sox2 expression and Hoechst 33342 exclusion. CD44(+)CD24(-/low) cells, including the Hoechst excluding subpopulation, could be effectively killed by oncolytic adenoviruses Ad5/3-Delta24 and Ad5.pk7-Delta24. In mice, CD44(+)CD24(-/low) cells formed orthotopic breast tumors but virus infection prevented tumor formation. Ad5/3-Delta24 and Ad5.pk7-Delta24 were effective against advanced orthotopic CD44(+)CD24(-/low)-derived tumors. In summary, Ad5/3-Delta24 and Ad5.pk7-Delta24 can kill CD44(+)CD24(-/low), and also committed breast cancer cells, making them promising agents for treatment of breast cancer. PMID:17848962

  16. Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model.

    Science.gov (United States)

    Simão, D; Pinto, C; Fernandes, P; Peddie, C J; Piersanti, S; Collinson, L M; Salinas, S; Saggio, I; Schiavo, G; Kremer, E J; Brito, C; Alves, P M

    2016-01-01

    Gene therapy is a promising approach with enormous potential for treatment of neurodegenerative disorders. Viral vectors derived from canine adenovirus type 2 (CAV-2) present attractive features for gene delivery strategies in the human brain, by preferentially transducing neurons, are capable of efficient axonal transport to afferent brain structures, have a 30-kb cloning capacity and have low innate and induced immunogenicity in preclinical tests. For clinical translation, in-depth preclinical evaluation of efficacy and safety in a human setting is primordial. Stem cell-derived human neural cells have a great potential as complementary tools by bridging the gap between animal models, which often diverge considerably from human phenotype, and clinical trials. Herein, we explore helper-dependent CAV-2 (hd-CAV-2) efficacy and safety for gene delivery in a human stem cell-derived 3D neural in vitro model. Assessment of hd-CAV-2 vector efficacy was performed at different multiplicities of infection, by evaluating transgene expression and impact on cell viability, ultrastructural cellular organization and neuronal gene expression. Under optimized conditions, hd-CAV-2 transduction led to stable long-term transgene expression with minimal toxicity. hd-CAV-2 preferentially transduced neurons, whereas human adenovirus type 5 (HAdV5) showed increased tropism toward glial cells. This work demonstrates, in a physiologically relevant 3D model, that hd-CAV-2 vectors are efficient tools for gene delivery to human neurons, with stable long-term transgene expression and minimal cytotoxicity.

  17. Adenovirus-mediated expression of an elastase-specific inhibitor (elafin): a comparison of different promoters.

    Science.gov (United States)

    Sallenave, J M; Xing, Z; Simpson, A J; Graham, F L; Gauldie, J

    1998-03-01

    This report describes the design and construction of three recombinant adenoviruses of serotype 5 (Ad5) expressing elafin (EL), also called elastase-specific inhibitor. Three promoters were chosen to drive the synthesis of elafin: the small (380 bp) human cytomegalovirus promoter (HCMV), the Ad2 major late promoter (MLP) and the mouse cytomegalovirus (MCMV) promoter. Human alveolar epithelial cells (A549), as well as rat and human primary pulmonary fibroblasts were infected with Ad5-HCMV-EL, Ad5-MLP-EL, Ad5-MCMV-EL and with the control Ad5-dl70/3. The MCMV promoter was the most efficient promoter in all cells studied. MLP was the least efficient promoter Intermediate between MCMV and MLP was HCMV which was able to induce significant amounts of elafin, particularly in human A549 cells. When compared in vivo in rat lungs, results were similar; MCMV was the only promoter which induced significant amounts of elafin as assessed by Northern blot analysis and ELISA, even with a low dose of virus (3 x 10(8) p.f.u.). Our data indicate that the MCMV promoter is the promoter of choice for the strong induction of adenovirus-mediated transgenes in the lung and suggest its suitability both in rodent experimental models and in humans for investigative and therapeutic purposes. PMID:9614555

  18. Degradation and inactivation of adenovirus in water by photo-electro-oxidation.

    Science.gov (United States)

    Monteiro, G S; Staggemeier, R; Klauck, C R; Bernardes, A M; Rodrigues, M A S; Spilki, F R

    2015-12-01

    The present study analyzed the efficiency of the photo-electro-oxidation process as a method for degradation and inactivation of adenovirus in water. The experimental design employed a solution prepared from sterile water containing 5.107 genomic copies/L (gc/L) of a standard strain of human adenovirus type 5 (HAdV-5) divided into two equal parts, one to serve as control and one treated by photo-electro-oxidation (PEO) for 3 hours and with a 5A current. Samples collected throughout the exposure process were analyzed by real-time polymerase chain reaction (qPCR) for viral genome identification and quantitation. Prior to gene extraction, a parallel DNAse treatment step was carried out to assess the integrity of viral particles. Integrated cell culture (ICC) analyses assessed the viability of infection in a cell culture. The tested process proved effective for viral degradation, with a 7 log10 reduction in viral load after 60 minutes of treatment. The DNAse-treated samples exhibited complete reduction of viral load after a 75 minute exposure to the process, and ICC analyses showed completely non-viable viral particles at 30 minutes of treatment. PMID:26628240

  19. Alpha interferon-induced antiviral response noncytolytically reduces replication defective adenovirus DNA in MDBK cells.

    Science.gov (United States)

    Guo, Ju-Tao; Zhou, Tianlun; Guo, Haitao; Block, Timothy M

    2007-12-01

    Although alpha interferon (IFN-alpha) is of benefit in the treatment of viral hepatitis B, HBV replication has been refractory to the cytokine in commonly used hepatocyte-derived cell lines. In search for a cell culture system to study the mechanism by which IFN-alpha inhibits HBV replication, we infected a variety of cell lines with an adenoviral vector containing a replication competent 1.3-fold genome length HBV DNA (AdHBV) and followed by incubation with IFN-alpha. We found that IFN-alpha efficiently decreased the level of HBV DNA replicative intermediates in AdHBV infected Madin-Darby bovine kidney (MDBK) cells. Further analysis revealed, surprisingly, that IFN-alpha did not directly inhibit HBV replication, rather the amount of adenovirus DNA in the nuclei of MDBK cells was reduced. As a consequence, HBV RNA transcription and DNA replication were inhibited. Experiments with adenoviral vector expressing a green fluorescent protein (GFP) further supported the notion that IFN-alpha treatment noncytolytically eliminated adenovirus DNA, but did not kill the vector infected MDBK cells. Our data suggest that IFN-alpha-induced antiviral program is able to discriminate host cellular DNA from episomal viral DNA and might represent a novel pathway of interferon mediate innate defense against DNA virus infections.

  20. Immunological effects of a tumor necrosis factor alpha-armed oncolytic adenovirus.

    Science.gov (United States)

    Hirvinen, Mari; Rajecki, Maria; Kapanen, Mika; Parviainen, Suvi; Rouvinen-Lagerström, Noora; Diaconu, Iulia; Nokisalmi, Petri; Tenhunen, Mikko; Hemminki, Akseli; Cerullo, Vincenzo

    2015-03-01

    For long it has been recognized that tumor necrosis factor alpha (TNFa) has anticancer characteristics, and its use as a cancer therapeutic was proposed already in the 1980s. However, its systemic toxicity has limited its usability. Oncolytic viruses, selectively cancer-killing viruses, have shown great potency, and one of their most useful aspects is their ability to produce high amounts of transgene products locally, resulting in high local versus systemic concentrations. Therefore, the overall magnitude of tumor cell killing results from the combination of oncolysis, transgene-mediated direct effect such as TNFa-mediated apoptosis, and, perhaps most significantly, from activation of the host immune system against the tumor. We generated a novel chimeric oncolytic adenovirus expressing human TNFa, Ad5/3-D24-hTNFa, whose efficacy and immunogenicity were tested in vitro and in vivo. The hTNFa-expressing adenovirus showed increased cancer-eradicating potency, which was shown to be because of elevated apoptosis and necrosis rates and induction of various immune responses. Interestingly, we saw increase in immunogenic cell death markers in Ad5/3-d24-hTNFa-treated cells. Moreover, tumors treated with Ad5/3-D24-hTNFa displayed enhanced presence of OVA-specific cytotoxic T cells. We thus can conclude that tumor eradication and antitumor immune responses mediated by Ad5/3-d24-hTNFa offer a new potential drug candidate for cancer therapy.

  1. Derivation of a myeloid cell-binding adenovirus for gene therapy of inflammation.

    Directory of Open Access Journals (Sweden)

    Michael O Alberti

    Full Text Available The gene therapy field is currently limited by the lack of vehicles that permit efficient gene delivery to specific cell or tissue subsets. Native viral vector tropisms offer a powerful platform for transgene delivery but remain nonspecific, requiring elevated viral doses to achieve efficacy. In order to improve upon these strategies, our group has focused on genetically engineering targeting domains into viral capsid proteins, particularly those based on adenovirus serotype 5 (Ad5. Our primary strategy is based on deletion of the fiber knob domain, to eliminate broad tissue specificity through the human coxsackie-and-adenovirus receptor (hCAR, with seamless incorporation of ligands to re-direct Ad tropism to cell types that express the cognate receptors. Previously, our group and others have demonstrated successful implementation of this strategy in order to specifically target Ad to a number of surface molecules expressed on immortalized cell lines. Here, we utilized phage biopanning to identify a myeloid cell-binding peptide (MBP, with the sequence WTLDRGY, and demonstrated that MBP can be successfully incorporated into a knob-deleted Ad5. The resulting virus, Ad.MBP, results in specific binding to primary myeloid cell types, as well as significantly higher transduction of these target populations ex vivo, compared to unmodified Ad5. These data are the first step in demonstrating Ad targeting to cell types associated with inflammatory disease.

  2. Suppression of gastric cancer growth by adenovirus-mediated transfer of the PTEN gene

    Institute of Scientific and Technical Information of China (English)

    Ying Hang; Yong-Chen Zheng; Yan Cao; Qing-Shan Li; Yu-Jie Sui

    2005-01-01

    AIM: To investigate the tumor-suppressive effect of the phosphatase and tensin homologue deleted from chromosome (PTEN) in human gastric cancer cells th atwere wild type for PTEN.METHODS: Adenoviruses expressing PTEN or luciferase as a control were introduced into gastric cancer cells.The effect of exogenous PTEN gene on the growth and apoptosis of gastric cancer cells that are wtPTEN were examined in vitro and in vivo.RESULTS: Adenovirus-mediated transfer of PTEN (AdPTEN) suppressed cell growth and induced apoptosis significantly in gastric cancer cells (MGC-803, SGC-7901)carrying wtPTEN in comparison with that in normal gastric epithelial cells (GES-1) carrying wtPTEN. This suppression was induced through downregulation of the Akt/PKB pathway, dephosphorylation of focal adhesion kinase and mitogen-activated protein kinase and cell-cycle arrest at the G2/M phase but not at the G1 phase. Furthermore,treatment of human gastric tumor xenografts (MGC-803,SGC-7901) with Ad-PTEN resulted in a significant (P<0.01)suppression of tumor growth.CONCLUSION: These results indicate a significant tumorsuppressive effect of Ad-PTEN against human gastric cancer cells. Thus, Ad-PTEN may be used as a potential therapeutic strategy for treatment of gastric cancers.

  3. An adenovirus vector incorporating carbohydrate binding domains utilizes glycans for gene transfer.

    Directory of Open Access Journals (Sweden)

    Julius W Kim

    Full Text Available BACKGROUND: Vectors based on human adenovirus serotype 5 (HAdV-5 continue to show promise as delivery vehicles for cancer gene therapy. Nevertheless, it has become clear that therapeutic benefit is directly linked to tumor-specific vector localization, highlighting the need for tumor-targeted gene delivery. Aberrant glycosylation of cell surface glycoproteins and glycolipids is a central feature of malignant transformation, and tumor-associated glycoforms are recognized as cancer biomarkers. On this basis, we hypothesized that cancer-specific cell-surface glycans could be the basis of a novel paradigm in HAdV-5-based vector targeting. METHODOLOGY/PRINCIPAL FINDINGS: As a first step toward this goal, we constructed a novel HAdV-5 vector encoding a unique chimeric fiber protein that contains the tandem carbohydrate binding domains of the fiber protein of the NADC-1 strain of porcine adenovirus type 4 (PAdV-4. This glycan-targeted vector displays augmented CAR-independent gene transfer in cells with low CAR expression. Further, we show that gene transfer is markedly decreased in cells with genetic glycosylation defects and by inhibitors of glycosylation in normal cells. CONCLUSIONS/SIGNIFICANCE: These data provide the initial proof-of-concept for HAdV-5 vector-mediated gene delivery based on the presence of cell-surface carbohydrates. Further development of this new targeting paradigm could provide targeted gene delivery based on vector recognition of disease-specific glycan biomarkers.

  4. Adenovirus Mediated BIMS Transfer Induces Growth Supression and Apoptosis in Raji Lymphoma Cells

    Institute of Scientific and Technical Information of China (English)

    ZHAO Ya Ning; LI Qiang

    2014-01-01

    Objective To transfer pro-apoptotic BIM directly into tumor cells bypass the complicated biological processes of BIM activation so as to reverse the chemoresistance of cancer cells. Methods BIMS was specifically amplified from HL-60 cells by RT-PCR, confirmed to be correct by sequencing and cloned into shuttle vector pAdTrack-CMV carrying a green fluorescence protein gene to generate a recombinant plasmid pAdTrack-CMV-BIMS. This plasmid and adenovirus backbone plasmid pAdEasy-1 were linearized and electroporated into E.coli BJ5183 host bacteria to mediate homologous recombination. The positive clone was identified by restrict endonuclease digestion. The recombinant pAdEasy-CMV-BIMS was transferred into HEK293 cells for packaging and amplification. The successful construction of recombinant human BIMS adenovirus (Ad-BIMS) was demonstrated by Western blot. To test whether Ad-BIMS has the capability of inducing apoptosis of tumor cells, Ad-BIMS was used to infect GC resistant Burkitt lymphoma Raji cells. Results After infected for 2-5 days, BIMS expression in Raji cells was detected by RT-PCR and Western blot. The significant growth retardation and apoptosis of Raji cells were also observed by MTT and flow cytometry. Conclusion These results indicated that BIMS might be a potential candidate of gene therapy for chemoresistant tumor cells.

  5. A Grounded Theory of Adult Student Persistence

    Science.gov (United States)

    Capps, Rosemary

    2010-01-01

    This grounded theory study investigates adult student persistence at a community college. Student persistence in college is a prerequisite for degree achievement, which correlates with higher earnings and overall better quality of life. Persistence rates remain low for adult students, who combine their college endeavors with responsibilities to…

  6. Quantitative profiling of the shedding rate of the three Marek's disease virus (MDV) serotypes reveals that challenge with virulent MDV markedly increases shedding of vaccinal viruses.

    Science.gov (United States)

    Islam, Aminul; Walkden-Brown, Stephen W

    2007-08-01

    The shedding profile of Marek's disease virus serotype 1 (MDV1, virulent), serotype 2 (MDV2, vaccinal) and herpesvirus of turkeys (HVT, vaccinal) in commercial broiler chickens was determined by measuring the daily rate of production of feather dander from chickens housed in isolators and by quantifying the viral load of each of these serotypes in the dander using quantitative real-time PCR (qPCR). MDV1 and HVT viruses were detectable in dander filtered from isolator exhaust air from day 7 and MDV2 from day 12 after infection and thereafter until the end of the experiment at 61 days of age of the chickens. There was no difference in shedding rate among the three MDV1 isolates. Daily shedding of MDV1 increased sharply between days 7 and 28 and stabilized thereafter at about 10(9) virus copies per chicken per day, irrespective of vaccination status. Challenge with the three different MDV1 isolates markedly increased shedding of the vaccinal viruses HVT and MDV2 in dander by 38- and 75-fold, respectively. These results demonstrate the utility of qPCR for the differentiation and quantification of different MDV serotypes in feather dander and have significant implications for the routine monitoring of Marek's disease using qPCR assays of dust, for epidemiological modelling of the behaviour and spread of MDVs in chicken populations and for studies into the evolution of virulence in MDV1 in the face of blanket vaccination with imperfect vaccines that ameliorate disease but do not prevent infection and replication of virulent virus.

  7. Simulated browsing affects leaf shedding phenology and litter quality of oak and birch saplings.

    Science.gov (United States)

    Palacio, S; Hester, A J; Maestro, M; Millard, P

    2013-04-01

    Herbivore effects on leaf litter can have a strong impact on ecosystem nutrient cycling. Although such effects are well described for insect herbivory, research on the impacts of browsing by mammalian herbivores on leaf litter dynamics and nutrient cycling has been more limited, particularly at the level of the individual plant. Clipping treatments (66% shoot removal twice, plus unclipped) were applied to analyse the effect of browsing on the phenology (start date and pattern of leaf shedding) and leaf litter quality (nitrogen (N), soluble sugars, starch and total non-structural carbohydrate concentrations, plus C : N ratios) of Betula pubescens Ehrh. and Quercus petraea [Matt.] Liebl. saplings. Clipping decreased leaf litter biomass and delayed leaf senescence and shedding, but did not change the phenological timing of litterfall between senescence and shedding. The quality of leaf litter of both species was increased by simulated browsing, through an increase in N and carbohydrate concentrations (mainly soluble sugars) and a decreased C : N ratio. This is the first evidence we are aware of that browsing may cause changes in leaf shedding phenology, delaying the process without altering its pattern. Our results also indicate that simulated browsing increases the quality of leaf litter. However, the potential positive effect of browsing on N cycling through litter quality may be offset by its negative impact on the amount of N shed per tree.

  8. The Influence of Load Shedding on the Productivity of Hotel Staff in Cape Town, South Africa

    Directory of Open Access Journals (Sweden)

    Henriëtte STEENKAMP

    2016-07-01

    Full Text Available In South Africa, ESCOM is the country’s main electricity supplier. Since 2008, Eskom has implemented load shedding on an ongoing basis as a result of insufficient electricity supply to meet the demands of all its customers. Owing to the fact that many organisations across South Africa are depended on electricity in order to function, previous research studies show that the wide-spread impact of load shedding has had an adverse on the sustainability of many of these organisations. Among these organisations are those based in the hospitality industry – imperative in relation to the stimulation of the national economy; directly related to tourism. Albeit the aforementioned, the sustainability of organisations in the hospitality industry is also heavily dependent on the productivity of their employees. For this research study the influence of load shedding on the productivity of the staff in the hospitality industry was investigated within one particular hotel (Hotel X based in Cape Town. Empirical research was deployed, making use of a mixed methods approach to obtain both quantitative data and qualitative data from respondents. Stemming from the findings it was found that load shedding did have an adverse influence on the productivity of staff in Hotel X, despite the fact that affordable measures were put in place to mitigate the disruptions caused by load shedding. Moreover, the latter dispensation was found to have an inadvertently adverse influence on the overall sustainability of Hotel X on the long run.

  9. An Experimental Study of the Effect of Vortex Shedding on Solar Collector Performance

    Directory of Open Access Journals (Sweden)

    Alaulddin Abdulqader Kadim

    2015-07-01

    Full Text Available In this work, the effect of vortex shedding on the solar collector performance of the parabolic trough solar collector (PTSC was estimated experimentally. The effect of structure oscillations due to wind vortex shedding on solar collector performance degradation was estimated. The performance of PTSC is evaluated by using the useful heat gain and the thermal instantaneous efficiency. Experimental work to simulate the vortex shedding excitation was done. The useful heat gain and the thermal efficiency of the parabolic trough collector were calculated from experimental measurements with and without vortex loading. The prototype of the collector was fabricated for this purpose. The effect of vortex shedding at different operation conditions was examined. The variation of angles of attack and wind velocity leads to different values of vortex loading coefficients and shedding frequencies. The relation between the dynamic characteristics and solar collector performance was evaluated. The finite element method was used to estimate the dynamic characteristic of the solar collector in addition to experimental work to evaluate the relation between the dynamic behavior of the collector and its performance.

  10. Oral and systemic health correlates of HIV-1 shedding in saliva.

    Science.gov (United States)

    Navazesh, M; Mulligan, R; Kono, N; Kumar, S K S; Nowicki, M; Alves, M; Mack, W J

    2010-10-01

    The relationship among oral and systemic health and HIV shedding in saliva is not well-understood. We hypothesized that oral and systemic health are associated with HIV shedding in saliva of HIV-infected women. Saliva from 127 participants enrolled in the Women's Interagency HIV Study (WIHS) was collected at repeated visits over a 5½-year study period (October 1998 through March 2004) and was evaluated for HIV-1 RNA. Demographic, lifestyle, and systemic and oral health characteristics were evaluated as possible correlates of salivary HIV-1 shedding. Multivariate models showed significantly increased risk of HIV-1 shedding in saliva as blood levels of CD4 cell counts decreased (p < 0.0001) and HIV RNA increased (p < 0.0001). Diabetes (p = 0.002) and a high proportion of gingival bleeding sites (p = 0.01) were associated with increased likelihood, while anti-retroviral therapy (p = 0.0003) and higher levels of stimulated saliva flow rates (p = 0.02) were associated with a lower likelihood of HIV-1 RNA shedding in saliva.

  11. First report of human salivirus/klassevirus in respiratory specimens of a child with fatal adenovirus infection.

    Science.gov (United States)

    Pei, Na; Zhang, Jiaosheng; Ma, Jinmin; Li, Liqiang; Li, Meng; Li, Jiandong; Sun, Yisuo; Ji, Jingkai; Jiang, Hui; Hou, Yong; Xu, Fengping; Lu, Haorong; Zhang, Ruimu; Wei, Xuemei; Xu, Xun; Deng, Jikui

    2016-10-01

    Adenovirus is a leading cause of respiratory infection in children. Salivirus/klassevirus was first identified as an etiologic agent of gastroenteritis and was never reported in respiratory infection cases. The case being discussed here caught our attention because, although it is a common respiratory infection, it was fatal, while similar cases were mild. In order to find potential causes in the fatal case, we describe the clinical diagnosis and treatment, the sequencing analysis of the salivirus/klassevirus, and the co-infectious adenovirus. Metagenomics sequencing was conducted on the samples from a nasopharyngeal swab of the children with adenovirus infection. Sequences were assembled using IDBA-ud (1.1.1); phylogenetic analysis was performed using MEGA 5.2. RT-PCR and quantitative PCR were performed to verify the existence of the virus in the samples. A nearly full genome of this new virus strain was obtained with 7633 nt encoding a polyprotein of 2331 aa. Meanwhile, it was detected specifically in the nasopharyngeal swab by RT-PCR. Further, homology analysis indicated that the virus has a closer relationship with Salivirus A strain in Shanghai (GU245894). Our study reports the first case of Human salivirus/klassevirus in respiratory specimens of a child with fatal adenovirus infection in Shenzhen, China. The finding and investigation of the virus will provide more useful information for the clinical diagnosis of unexplained lethal infection and expand our knowledge of the new family, salivirus/klassevirus in picornavirus. PMID:27314269

  12. The binding of in vitro synthesized adenovirus DNA binding protein to single-stranded DNA is stimulated by zinc ions

    NARCIS (Netherlands)

    Vos, H.L.; Lee, F.M. van der; Sussenbach, J.S.

    1988-01-01

    We have synthesized wild type DNA binding protein (DBP) of adenovirus type 5 (Ad5) and several truncated forms of this protein by a combination of in vitro transcription and translation. The proteins obtained were tested for binding to a single-stranded DNA-cellulose column. It could be shown that f

  13. Immunogenic comparison of chimeric adenovirus 5/35 vector carrying optimized human immunodeficiency virus clade C genes and various promoters.

    Science.gov (United States)

    Shoji, Masaki; Yoshizaki, Shinji; Mizuguchi, Hiroyuki; Okuda, Kenji; Shimada, Masaru

    2012-01-01

    Adenovirus vector-based vaccine is a promising approach to protect HIV infection. However, a recent phase IIb clinical trial using the vector did not show its protective efficacy against HIV infection. To improve the vaccine, we explored the transgene protein expression and its immunogenicity using optimized codon usage, promoters and adaptors. We compared protein expression and immunogenicity of adenovirus vector vaccines carrying native or codon usage-optimized HIV-1 clade C gag and env genes expression cassettes driven by different promoters (CMV, CMVi, and CA promoters) and adapters (IRES and F2A). The adenovirus vector vaccine containing optimized gag gene produced higher Gag protein expression and induced higher immune responses than the vector containing native gag gene in mice. Furthermore, CA promoter generated higher transgene expression and elicited higher immune responses than other two popularly used promoters (CMV and CMVi). The second gene expression using F2A adaptor resulted in higher protein expression and immunity than that of using IRES and direct fusion protein. Taken together, the adenovirus vector containing the expression cassette with CA promoter, optimized HIV-1 clade C gene and an F2A adaptor produced the best protein expression and elicited the highest transgene-specific immune responses. This finding would be promising for vaccine design and gene therapy.

  14. Comparison of polystyrene nanoparticles and UV-inactivated antigen-displaying adenovirus for vaccine delivery in mice

    Science.gov (United States)

    2013-01-01

    Background Inert nanoparticles are attracting attention as carriers for protein-based vaccines. Here we evaluate the immunogenicity of the model antigen ovalbumin delivered on polystyrene particles and directly compare particulate delivery with adenovirus-based immunization. Findings Mice were vaccinated with soluble ovalbumin, ovalbumin-coated polystyrene particles of different sizes, or an adenovirus-based expression-display vector that encodes and displays a pIX-ovalbumin fusion protein. Antibody responses were clearly higher when ovalbumin was administered on polystyrene particles compared to soluble protein administration, regardless of the particle size. Compared to adenovirus-based immunization, antibody levels were lower if an equivalent amount of protein was delivered, and no cellular immune response was detectable. Conclusions We demonstrate in a side-by-side comparison that inert nanoparticles allow for the reduction of the administered antigen amount compared to immunization with soluble protein and induce strongly enhanced antibody responses, but responses are lower compared to adenovirus-based immunization. PMID:23560981

  15. Electrostatic Interactions between Complement Regulator CD46(SCR1-2 and Adenovirus Ad11/Ad21 Fiber Protein Knob

    Directory of Open Access Journals (Sweden)

    Carl Z. Chen

    2015-01-01

    Full Text Available Adenoviruses bind to a variety of human cells to cause infection. Both the B2 adenovirus 11 and B1 adenovirus 21 use protein knobs to bind to complement regulator CD46(SCR1-2 in order to gain entry into host cells. In each complex, the two proteins are highly negatively charged but bind to each other at an interface with oppositely charged surface patches. We computationally generated single-alanine mutants of charged residues in the complexes CD46(SCR1-2-Ad11k and CD46(SCR1-2-Ad21k. We used electrostatic clustering and Poisson-Boltzmann free energy calculations to propose a hypothesis on the role of electrostatics in association. Our results delineate specific interfacial electrostatic interactions that are critical for association in both CD46(SCR1-2-Ad11k and CD46(SCR1-2-Ad21k. These results will serve as a predictive tool in the selection of mutants with desired binding affinity in experimental mutagenesis studies. This study will also serve as a foundation for the design of inhibitors to treat adenovirus infections.

  16. Human Adenovirus Type 7 Infection Associated with Severe and Fatal Acute Lower Respiratory Illness and Nosocomial Transmission

    OpenAIRE

    Cui, Xianyan; Wen, Liang; Zhihao WU; Liu, Nan; Yang, Chaojie; Liu, Wei; Ba, Zhongwei; Wang, Jian; Yi, Shengjie; Li, Hao; Liang, Beibei; Li, Peng; Jia, Leili; Hao, Rongzhang; Wang, Ligui

    2014-01-01

    A 23-year-old male died of severe pneumonia and respiratory failure in a tertiary hospital in Beijing, and 4 out of 55 close contacts developed fever. Molecular analysis confirmed human adenovirus type 7 (HAdV7) as the causative agent. We highlight the importance of early diagnosis and treatment and proper transmission control of HAdV7.

  17. Human Adenovirus Type 7 Infection Associated with Severe and Fatal Acute Lower Respiratory Illness and Nosocomial Transmission

    Science.gov (United States)

    Cui, Xianyan; Wen, Liang; Wu, Zhihao; Liu, Nan; Yang, Chaojie; Liu, Wei; Ba, Zhongwei; Wang, Jian; Yi, Shengjie; Li, Hao; Liang, Beibei; Li, Peng; Jia, Leili; Hao, Rongzhang; Wang, Ligui; Hua, Yuejin; Wang, Yong

    2014-01-01

    A 23-year-old male died of severe pneumonia and respiratory failure in a tertiary hospital in Beijing, and 4 out of 55 close contacts developed fever. Molecular analysis confirmed human adenovirus type 7 (HAdV7) as the causative agent. We highlight the importance of early diagnosis and treatment and proper transmission control of HAdV7. PMID:25520444

  18. Cellular Changes Induced by Adenovirus Vaccine Vectors Expressing Foot-and-Mouth Disease Virus Structural and Nonstructural Proteins

    Science.gov (United States)

    Foot-and-mouth disease virus (FMDV) is the most contagious pathogen of cloven-hoofed animals including swine and bovines. The emergency control of outbreaks is dependent on rapid protection and prevention of virus spread. Adenovirus-based FMD subunit vaccines containing the coding region of viral ca...

  19. Coxsackie and adenovirus receptor is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia.

    NARCIS (Netherlands)

    Marsman, R.F.; Bezzina, C.R.; Freiberg, F.; Verkerk, A.O.; Adriaens, M.E.; Podliesna, S.; Chen, C.; Purfurst, B.; Spallek, B.; Koopmann, T.T.; Baczko, I.; Remedios, C.G. Dos; George AL, J.r.; Bishopric, N.H.; Lodder, E.M.; Bakker, J.M. de; Fischer, R.; Coronel, R.; Wilde, A.A.; Gotthardt, M.; Remme, C.A.

    2014-01-01

    OBJECTIVES: The aim of this study was to investigate the modulatory effect of the coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. BACKGROUND: A heritable component in the risk of ventricular fibrillation during myo

  20. Poly ICLC increases the potency of a replication-defective human adenovirus vectored foot-and-mouth disease vaccine

    Science.gov (United States)

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have previously demonstrated that a replication-defective human adenovirus 5 vector carrying the FMDV capsid coding region of serotype A24 Cruzeiro (Ad5-CI-A24-2B) protects swine and cattle against FM...