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Sample records for tumor viruses conference

  1. Functional and structural analysis of the DNA sequence conferring glucocorticoid inducibility to the mouse mammary tumor virus gene

    International Nuclear Information System (INIS)

    Skroch, P.

    1987-05-01

    In the first part of my thesis I show that the DNA element conferring glucocorticoid inducibility to the Mouse Mammary Tumor Virus (HRE) has enhancer properties. It activates a heterologous promoter - that of the β-globin gene, independently of distance, position and orientation. These properties however have to be regarded in relation to the remaining regulatory elements of the activated gene as the recombinants between HRE and the TK gene have demonstrated. In the second part of my thesis I investigated the biological significance of certain sequence motifs of the HRE, which are remarkable by their interaction with transacting factors or sequence homologies with other regulatory DNA elements. I could confirm the generally postulated modular structure of enhancers for the HRE and bring the relevance of the single subdomains for the function of the element into relationship. (orig.) [de

  2. FASEB Science Research Conference on Virus Structure and Assembly

    Science.gov (United States)

    2017-10-24

    Report: FASEB Science Research Conference on Virus Structure and Assembly The views, opinions and/or findings contained in this report are those of the...Title: FASEB Science Research Conference on Virus Structure and Assembly Report Term: 0-Other Email: srcgrants@faseb.org Distribution Statement...support for the 2016 FASEB Science Research Conference on Virus Structure and Assembly which was held July 24-29, 2016 in Steamboat Springs, CO. This

  3. Transgenic strategies to confer resistance against viruses in rice plants

    Directory of Open Access Journals (Sweden)

    Takahide eSasaya

    2014-01-01

    Full Text Available Rice (Oryza sativa L. is cultivated in more than 100 countries and supports nearly half of the world’s population. Developing efficient methods to control rice viruses is thus an urgent necessity because viruses cause serious losses in rice yield. Most rice viruses are transmitted by insect vectors, notably planthoppers and leafhoppers. Viruliferous insect vectors can disperse their viruses over relatively long distances, and eradication of the viruses is very difficult once they become widespread. Exploitation of natural genetic sources of resistance is one of the most effective approaches to protect crops from virus infection; however, only a few naturally occurring rice genes confer resistance against rice viruses. In an effort to improve control, many investigators are using genetic engineering of rice plants as a potential strategy to control viral diseases. Using viral genes to confer pathogen-derived resistance against crops is a well-established procedure, and the expression of various viral gene products has proved to be effective in preventing or reducing infection by various plant viruses since the 1990s. RNA-interference (RNAi, also known as RNA silencing, is one of the most efficient methods to confer resistance against plant viruses on their respective crops. In this article, we review the recent progress, mainly conducted by our research group, in transgenic strategies to confer resistance against tenuiviruses and reoviruses in rice plants. Our findings also illustrate that not all RNAi constructs against viral RNAs are equally effective in preventing virus infection and that it is important to identify the viral Achilles’ heel gene to target for RNAi attack when engineering plants.

  4. GADD45ß, an anti-tumor gene, inhibits avian leukosis virus subgroup J replication in chickens

    Science.gov (United States)

    Avian leukosis virus subgroup J (ALV-J) is a retrovirus that induces neoplasia, hepatomegaly, immunosuppression and poor performance in chickens. The tumorigenic and pathogenic mechanisms of ALV-J remain a hot topic. To explore anti-tumor genes that confer genetic resistance to ALV-J infection in ch...

  5. Oncolytic Viruses-Interaction of Virus and Tumor Cells in the Battle to Eliminate Cancer.

    Science.gov (United States)

    Howells, Anwen; Marelli, Giulia; Lemoine, Nicholas R; Wang, Yaohe

    2017-01-01

    Oncolytic viruses (OVs) are an emerging treatment option for many cancer types and have recently been the focus of extensive research aiming to develop their therapeutic potential. The ultimate aim is to design a virus which can effectively replicate within the host, specifically target and lyse tumor cells and induce robust, long lasting tumor-specific immunity. There are a number of viruses which are either naturally tumor-selective or can be modified to specifically target and eliminate tumor cells. This means they are able to infect only tumor cells and healthy tissue remains unharmed. This specificity is imperative in order to reduce the side effects of oncolytic virotherapy. These viruses can also be modified by various methods including insertion and deletion of specific genes with the aim of improving their efficacy and safety profiles. In this review, we have provided an overview of the various virus species currently being investigated for their oncolytic potential and the positive and negative effects of a multitude of modifications used to increase their infectivity, anti-tumor immunity, and treatment safety, in particular focusing on the interaction of tumor cells and OVs.

  6. ONCOLYTIC VIRUS-MEDIATED REVERSAL OF IMPAIRED TUMOR ANTIGEN PRESENTATION

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    Shashi Ashok Gujar

    2014-04-01

    Full Text Available Anti-tumor immunity can eliminate existing cancer cells and also maintain a constant surveillance against possible relapse. Such an antigen-specific adaptive response begins when tumor-specific T cells become activated. T cell activation requires two signals on antigen presenting cells (APCs: antigen presentation through MHC molecules and co-stimulation. In the absence of one or both of these signals, T cells remain inactivated or can even become tolerized. Cancer cells and their associated microenvironment strategically hinder the processing and presentation of tumor antigens and consequently prevent the development of anti-tumor immunity. Many studies, however, demonstrate that interventions that overturn tumor-associated immune evasion mechanisms can establish anti-tumor immune responses of therapeutic potential. One such intervention is oncolytic virus (OV-based anti-cancer therapy. Here we discuss how OV-induced immunological events override tumor-associated antigen presentation impairment and promote appropriate T cell:APC interaction. Detailed understanding of this phenomenon is pivotal for devising the strategies that will enhance the efficacy of OV-based anti-cancer therapy by complementing its inherent oncolytic

  7. Modulation of Autophagy-Like Processes by Tumor Viruses

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    Karl Munger

    2012-06-01

    Full Text Available Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection. However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks. Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved.

  8. No association between Epstein-Barr Virus and Mouse Mammary Tumor Virus with Breast Cancer in Mexican Women

    Science.gov (United States)

    Morales-Sánchez, Abigail; Molina-Muñoz, Tzindilú; Martínez-López, Juan L. E.; Hernández-Sancén, Paulina; Mantilla, Alejandra; Leal, Yelda A.; Torres, Javier; Fuentes-Pananá, Ezequiel M.

    2013-10-01

    Breast cancer is the most frequent malignancy affecting women worldwide. It has been suggested that infection by Epstein Barr Virus (EBV), Mouse Mammary Tumor Virus or a similar virus, MMTV-like virus (MMTV-LV), play a role in the etiology of the disease. However, studies looking at the presence of these viruses in breast cancer have produced conflicting results, and this possible association remains controversial. Here, we used polymerase chain reaction assay to screen specific sequences of EBV and MMTV-LV in 86 tumor and 65 adjacent tissues from Mexican women with breast cancer. Neither tumor samples nor adjacent tissue were positive for either virus in a first round PCR and only 4 tumor samples were EBV positive by a more sensitive nested PCR. Considering the study's statistical power, these results do not support the involvement of EBV and MMTV-LV in the etiology of breast cancer.

  9. Targeting an Oncolytic Influenza A Virus to Tumor Tissue by Elastase

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    Irina Kuznetsova

    2017-12-01

    Full Text Available Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA, which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site. We chose this cleavage site because elastase is expressed in the tumor microenvironment. Moreover, the exchange of the cleavage site previously has been shown to attenuate viral growth in lungs. Newly generated elastase-activated influenza viruses (AE viruses grew to similar titers in tumor cells as the trypsin-activated counterparts (AT viruses. Intratumoral injection of AE viruses into syngeneic B16f1 melanoma-derived tumors in mice reduced tumor growth similar to AT viruses and had a better therapeutic effect in heterologous human PANC-1-derived tumors. Therefore, the introduction of the attenuation marker “elastase cleavage site” in viral HA allows for safe, effective oncolytic virus therapy.

  10. Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein-Barr Virus (EBV).

    Science.gov (United States)

    Lawson, James S; Salmons, Brian; Glenn, Wendy K

    2018-01-01

    Although the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma viruses (HPVs), and Epstein-Barr virus (EBV-also known as human herpes virus type 4). Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence. MMTV and human breast cancer-the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer-the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer-the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer-the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal. The influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

  11. Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV, Bovine Leukemia Virus (BLV, Human Papilloma Virus (HPV, and Epstein–Barr Virus (EBV

    Directory of Open Access Journals (Sweden)

    James S. Lawson

    2018-01-01

    Full Text Available BackgroundAlthough the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV, bovine leukemia virus (BLV, human papilloma viruses (HPVs, and Epstein–Barr virus (EBV-also known as human herpes virus type 4. Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence.The evidenceMMTV and human breast cancer—the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer—the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer—the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer—the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal.ConclusionThe influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

  12. Final report [FASEB Summer Research Conference ''Virus Assembly''--agenda and attendee list

    Energy Technology Data Exchange (ETDEWEB)

    Feiss, Michael

    2001-01-31

    The conference brought together researchers working on virus structure and virus assembly in diverse systems. Information was integrated from many viral systems, including plant bacterial and eukaryotic viruses, and many techniques such as biophysical approaches of x-ray diffraction, electron microscopy and spectroscopy, along with molecular biological and molecular genetic analysis.

  13. Pericentriolar Targeting of the Mouse Mammary Tumor Virus GAG Protein.

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    Guangzhi Zhang

    Full Text Available The Gag protein of the mouse mammary tumor virus (MMTV is the chief determinant of subcellular targeting. Electron microscopy studies show that MMTV Gag forms capsids within the cytoplasm and assembles as immature particles with MMTV RNA and the Y box binding protein-1, required for centrosome maturation. Other betaretroviruses, such as Mason-Pfizer monkey retrovirus (M-PMV, assemble adjacent to the pericentriolar region because of a cytoplasmic targeting and retention signal in the Matrix protein. Previous studies suggest that the MMTV Matrix protein may also harbor a similar cytoplasmic targeting and retention signal. Herein, we show that a substantial fraction of MMTV Gag localizes to the pericentriolar region. This was observed in HEK293T, HeLa human cell lines and the mouse derived NMuMG mammary gland cells. Moreover, MMTV capsids were observed adjacent to centrioles when expressed from plasmids encoding either MMTV Gag alone, Gag-Pro-Pol or full-length virus. We found that the cytoplasmic targeting and retention signal in the MMTV Matrix protein was sufficient for pericentriolar targeting, whereas mutation of the glutamine to alanine at position 56 (D56/A resulted in plasma membrane localization, similar to previous observations from mutational studies of M-PMV Gag. Furthermore, transmission electron microscopy studies showed that MMTV capsids accumulate around centrioles suggesting that, similar to M-PMV, the pericentriolar region may be a site for MMTV assembly. Together, the data imply that MMTV Gag targets the pericentriolar region as a result of the MMTV cytoplasmic targeting and retention signal, possibly aided by the Y box protein-1 required for the assembly of centrosomal microtubules.

  14. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis.

    Science.gov (United States)

    Kuss-Duerkop, Sharon K; Westrich, Joseph A; Pyeon, Dohun

    2018-02-13

    Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus-host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  15. Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors.

    Science.gov (United States)

    Groner, B; Hynes, N E

    1980-01-01

    The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. Images PMID:6245257

  16. Effect of a mouse mammary tumor virus-derived protein vaccine on primary tumor development in mice

    NARCIS (Netherlands)

    Creemers, P.; Ouwehand, J.; Bentveizen, P.

    1978-01-01

    The vaccines used in this study were derived from purified murine mammary tumor virus (MuMTV) preparations. Approximately 60% of the protein fractions consisted of the major viral membrane glycoprotein gp52. Inoculation sc of 10 pg MuMTV-S-derived vaccine significantly delayed the appearance of

  17. SSAT State-of-the-Art Conference: Current Surgical Management of Gastric Tumors.

    Science.gov (United States)

    Norton, Jeffrey A; Kim, Teresa; Kim, Joseph; McCarter, Martin D; Kelly, Kaitlyn J; Wong, Joyce; Sicklick, Jason K

    2018-01-01

    The current era of gastric surgery is marked by low morbidity and mortality rates, innovative strategies to approach resections with a minimally invasive fashion or hyperthermic intraperitoneal chemotherapy (HIPEC), as well as improved understanding of the biology of sporadic and hereditary stromal, neuroendocrine, and epithelial malignancies. In 2017, the Society for Surgery of the Alimentary Tract convened a State-of-the-Art Conference on Current Surgical Management of Gastric Tumors with both international experts and emerging leaders in the field of gastric surgery. Martin D. McCarter, MD of the University of Colorado discussed the current management of gastric gastrointestinal stromal tumors (GIST). Kaitlyn J. Kelly, MD of the University of California, San Diego discussed the management of gastric carcinoid tumors. Jeffrey A. Norton of Stanford University discussed recent advances in the management of gastric adenocarcinoma including a focus on hereditary diffuse gastric cancer (HDGC). Joseph Kim, MD of Stony Brook University discussed a systematic approach to minimally invasive gastrectomy for cancer. Joyce Wong, MD of Pennsylvania State University discussed the role for cytoreductive surgery (CRS) and HIPEC for gastric adenocarcinoma. This review provides gastrointestinal surgeons with a concise update on the current surgical management of gastric tumors.

  18. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis

    Directory of Open Access Journals (Sweden)

    Sharon K. Kuss-Duerkop

    2018-02-01

    Full Text Available Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus–host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  19. Expression of artificial microRNAs in transgenic Arabidopsis thaliana confers virus resistance.

    Science.gov (United States)

    Niu, Qi-Wen; Lin, Shih-Shun; Reyes, Jose Luis; Chen, Kuan-Chun; Wu, Hui-Wen; Yeh, Shyi-Dong; Chua, Nam-Hai

    2006-11-01

    Plant microRNAs (miRNAs) regulate the abundance of target mRNAs by guiding their cleavage at the sequence complementary region. We have modified an Arabidopsis thaliana miR159 precursor to express artificial miRNAs (amiRNAs) targeting viral mRNA sequences encoding two gene silencing suppressors, P69 of turnip yellow mosaic virus (TYMV) and HC-Pro of turnip mosaic virus (TuMV). Production of these amiRNAs requires A. thaliana DICER-like protein 1. Transgenic A. thaliana plants expressing amiR-P69(159) and amiR-HC-Pro(159) are specifically resistant to TYMV and TuMV, respectively. Expression of amiR-TuCP(159) targeting TuMV coat protein sequences also confers specific TuMV resistance. However, transgenic plants that express both amiR-P69(159) and amiR-HC-Pro(159) from a dimeric pre-amiR-P69(159)/amiR-HC-Pro(159) transgene are resistant to both viruses. The virus resistance trait is displayed at the cell level and is hereditable. More important, the resistance trait is maintained at 15 degrees C, a temperature that compromises small interfering RNA-mediated gene silencing. The amiRNA-mediated approach should have broad applicability for engineering multiple virus resistance in crop plants.

  20. Cordycepin enhances Epstein-Barr virus lytic infection and Epstein-Barr virus-positive tumor treatment efficacy by doxorubicin.

    Science.gov (United States)

    Du, Yinping; Yu, Jieshi; Du, Li; Tang, Jun; Feng, Wen-Hai

    2016-07-01

    The consistent latent presence of Epstein-Barr virus (EBV) in tumor cells offers potential for virus-targeted therapies. The switch from the latent form of EBV to the lytic form in tumor cells can lead to tumor cell lysis. In this study, we report that a natural small molecule compound, cordycepin, can induce lytic EBV infection in tumor cells. Subsequently, we demonstrate that cordycepin can enhance EBV reactivating capacity and EBV-positive tumor cell killing ability of low dose doxorubicin. The combination of cordycepin and doxorubicin phosphorylates CCAAT/enhancer binding protein β (C/EBPβ) through protein kinase C (PKC)-p38 mitogen activated protein kinases (p38 MAPK) signaling pathway, and C/EBPβ is required for the activation of lytic EBV infection. Most importantly, an in vivo experiment demonstrates that the combination of cordycepin and doxorubicin is more effective in inhibiting tumor growth in SCID mice than is doxorubicin alone. Our findings establish that cordycepin can enhance the efficacy of conventional chemotherapy for treatment of EBV-positive tumors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Role of the ubiquitin system and tumor viruses in AIDS-related cancer

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    Pagano Joseph S

    2007-11-01

    Full Text Available Abstract Tumor viruses are linked to approximately 20% of human malignancies worldwide. This review focuses on examples of human oncogenic viruses that manipulate the ubiquitin system in a subset of viral malignancies; those associated with AIDS. The viruses include Kaposi's sarcoma herpesvirus, Epstein-Barr virus and human papilloma virus, which are causally linked to Kaposi's sarcoma, certain B-cell lymphomas and cervical cancer, respectively. We discuss the molecular mechanisms by which these viruses subvert the ubiquitin system and potential viral targets for anti-cancer therapy from the perspective of this system. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com.

  2. Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus.

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    Yonatan Y Mahller

    Full Text Available Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers.Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice.These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

  3. Tenth International Foamy Virus Conference 2014–Achievements and Perspectives

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    Magdalena Materniak

    2015-03-01

    Full Text Available For the past two decades, scientists from around the world, working on different aspects of foamy virus (FV research, have gathered in different research institutions almost every two years to present their recent results in formal talks, to discuss their ongoing studies informally, and to initiate fruitful collaborations. In this report we review the 2014 anniversary conference to share the meeting summary with the virology community and hope to arouse interest by other researchers to join this exciting field. The topics covered included epidemiology, virus molecular biology, and immunology of FV infection in non-human primates, cattle, and humans with zoonotic FV infections, as well as recent findings on endogenous FVs. Several topics focused on virus replication and interactions between viral and cellular proteins. Use of FV in biomedical research was highlighted with presentations on using FV vectors for gene therapy and FV proteins as scaffold for vaccine antigen presentation. On behalf of the FV community, this report also includes a short tribute to commemorate Prof. Axel Rethwilm, one of the leading experts in the field of retrovirology and foamy viruses, who passed away 29 July 2014.

  4. Zika virus infection confers protection against West Nile virus challenge in mice.

    Science.gov (United States)

    Vázquez-Calvo, Ángela; Blázquez, Ana-Belén; Escribano-Romero, Estela; Merino-Ramos, Teresa; Saiz, Juan-Carlos; Martín-Acebes, Miguel A; Jiménez de Oya, Nereida

    2017-09-20

    Flaviviruses are RNA viruses that constitute a worrisome threat to global human and animal health. Zika virus (ZIKV), which was initially reported to cause a mild disease, recently spread in the Americas, infecting millions of people. During this recent epidemic, ZIKV infection has been linked to serious neurological diseases and birth defects, specifically Guillain-Barrè syndrome (GBS) and microcephaly. Because information about ZIKV immunity remains scarce, we assessed the humoral response of immunocompetent mice to infection with three viral strains of diverse geographical origin (Africa, Asia and America). No infected animals showed any sign of disease or died after infection. However, specific neutralizing antibodies were elicited in all infected mice. Considering the rapid expansion of ZIKV throughout the American continent and its co-circulation with other medically relevant flaviviruses, such as West Nile virus (WNV), the induction of protective immunity between ZIKV and WNV was analyzed. Remarkably, protection after challenge with WNV was observed in mice previously infected with ZIKV, as survival rates were significantly higher than in control mice. Moreover, previous ZIKV infection enhanced the humoral immune response against WNV. These findings may be relevant in geographical areas where both ZIKV and WNV co-circulate, as well as for the future development of broad-spectrum flavivirus vaccines.

  5. Naturally selected hepatitis C virus polymorphisms confer broad neutralizing antibody resistance.

    Science.gov (United States)

    Bailey, Justin R; Wasilewski, Lisa N; Snider, Anna E; El-Diwany, Ramy; Osburn, William O; Keck, Zhenyong; Foung, Steven K H; Ray, Stuart C

    2015-01-01

    For hepatitis C virus (HCV) and other highly variable viruses, broadly neutralizing mAbs are an important guide for vaccine development. The development of resistance to anti-HCV mAbs is poorly understood, in part due to a lack of neutralization testing against diverse, representative panels of HCV variants. Here, we developed a neutralization panel expressing diverse, naturally occurring HCV envelopes (E1E2s) and used this panel to characterize neutralizing breadth and resistance mechanisms of 18 previously described broadly neutralizing anti-HCV human mAbs. The observed mAb resistance could not be attributed to polymorphisms in E1E2 at known mAb-binding residues. Additionally, hierarchical clustering analysis of neutralization resistance patterns revealed relationships between mAbs that were not predicted by prior epitope mapping, identifying 3 distinct neutralization clusters. Using this clustering analysis and envelope sequence data, we identified polymorphisms in E2 that confer resistance to multiple broadly neutralizing mAbs. These polymorphisms, which are not at mAb contact residues, also conferred resistance to neutralization by plasma from HCV-infected subjects. Together, our method of neutralization clustering with sequence analysis reveals that polymorphisms at noncontact residues may be a major immune evasion mechanism for HCV, facilitating viral persistence and presenting a challenge for HCV vaccine development.

  6. Construction of a molecular clone of ovine enzootic nasal tumor virus.

    Science.gov (United States)

    Walsh, Scott R; Gerpe, María Carla Rosales; Wootton, Sarah K

    2016-12-30

    Enzootic nasal tumor virus (ENTV-1) is an ovine betaretrovirus that has been linked to enzootic nasal adenocarcinoma (ENA), a contagious tumor of the ethmoid turbinates of sheep. Transmission experiments performed using virus isolated from cell free nasal tumor homogenates suggest that ENTV-1 is the causative agent of ENA; however, this etiological relationship has not been conclusively proven due to the fact that the virus cannot be propagated in vitro nor is there an infectious molecular clone of the virus. Here we report construction of a molecular clone of ENTV-1 and demonstrate that transfection of this molecular clone into HEK 293T cells produces mature virus particles. Analysis of recombinant virus particles derived from the initial molecular clone revealed a defect in the proteolytic processing of Gag; however, this defect could be corrected by co-expression of the Gag-Pro-Pol polyprotein from the highly related Jaagsiekte sheep retrovirus (JSRV) suggesting that the polyprotein cleavage sites in the ENTV-1 molecular clone were functional. Mutagenesis of the molecular clone to correct amino acid variants identified within the pro gene did not restore proteolytic processing; whereas deletion of one proline residue from a polyproline tract located in variable region 1 (VR1) of the matrix resulted in production of CA protein of the mature (cleaved) size strongly suggesting that normal virion morphogenesis and polyprotein cleavage took place. Finally, electron microscopy revealed the presence of spherical virus particles with an eccentric capsid and an average diameter of about 100 nm. In summary, we have constructed the first molecular clone of ENTV-1 from which mature virus particles can be produced. Future experiments using virus produced from this molecular clone can now be conducted to fulfill Koch's postulates and demonstrate that ENTV-1 is necessary and sufficient to induce ENA in sheep.

  7. PENELITIAN PENULARAN VIRUS TUMOR MAMMA (MTV PADA MENCIT C3H

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    Dodo Djuanda

    2012-09-01

    Full Text Available Cancer has been caused by several factors, such as : Virus             :  biological factorRadiation      : physical factorCarcinogenic chemical compound : chemical factor. The study of the transmission of MTV on experimental animals and its descendants has been tried since 1963. Several strains of mice have been bred successfully, one of which is the C3H strain. This strain is known to'have a high mammary tumor incidence due to the high content of the MTV (Bittner virus in mother's milk. The transmission of MTV can be observed by foster nursing or reciprocal crossing between strains with high and low mammary tumor incidence. All females used in this experiment were force bred and observed for the appearance of a tumor until the age of one year. Some conclusions from this experiment are that: MTV was transmitted through mother's milk.Other strains (Balb/c and AJ could develop mammary tumor when infected by MTV.There is a different susceptibility between Balb/c and AJ to MTV. The transmission of MTV from parent to off spring is -called the vertical transmission. This virus has been known as Bittner virus and it can be identifed by the electrone microscope, immunodiffusion test (Ouchterlony or immunofluorescence test. The result of this experiment may be useful for studying the problem of Cancer tumor in human beings.

  8. Selective Killing of Prostate Tumor Cells by Cytocidal Viruses

    National Research Council Canada - National Science Library

    Lyles, Douglas

    2003-01-01

    .... The novelty in our approach is our ability to enhance the selectivity of killing of tumor cells versus normal cells by manipulating the viral genes that control the antiviral interferon response...

  9. Selective Killing of Prostate Tumor Cells by Cytocidal Viruses

    National Research Council Canada - National Science Library

    Lyles, Douglas

    2004-01-01

    .... The novelty in our approach is our ability to enhance the selectivity of killing of tumor cells versus normal cells by manipulating the viral genes that control the antiviral interferon response...

  10. Selective Killing of Prostate Tumor Cells by Cytocidal Viruses

    National Research Council Canada - National Science Library

    Lyles, Douglas S

    2005-01-01

    ...). The novelty in our approach is our ability to enhance the selectivity of VSV-induced killing of tumor cells versus normal cells by manipulating the viral genes that control the antiviral interferon response...

  11. Research update: Avian Disease and Oncology Laboratory avian tumor viruses

    Science.gov (United States)

    Genomics and Immunogenetics Use of genomics to identify QTL, genes, and proteins associated with resistance to Marek’s disease. Marek’s disease (MD), a lymphoproliferative disease caused by the highly oncogenic herpesvirus Marek's disease virus (MDV), continues to be a major disease concern to the p...

  12. Virus vector-mediated genetic modification of brain tumor stromal cells after intravenous delivery.

    Science.gov (United States)

    Volak, Adrienn; LeRoy, Stanley G; Natasan, Jeya Shree; Park, David J; Cheah, Pike See; Maus, Andreas; Fitzpatrick, Zachary; Hudry, Eloise; Pinkham, Kelsey; Gandhi, Sheetal; Hyman, Bradley T; Mu, Dakai; GuhaSarkar, Dwijit; Stemmer-Rachamimov, Anat O; Sena-Esteves, Miguel; Badr, Christian E; Maguire, Casey A

    2018-05-16

    The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively. Delivery of transgenes encoding secreted, anti-tumor proteins to tumor stromal cells may provide a more stable and localized reservoir of therapy as they are more differentiated than fast-dividing tumor cells. Reactive astrocytes and tumor-associated macrophage/microglia (TAMs) are stromal cells that comprise a large portion of the tumor mass and are associated with tumorigenesis. In mouse models of GBM, we used IV delivery of exosome-associated AAV vectors driving green fluorescent protein expression by specific promoters (NF-κB-responsive promoter and a truncated glial fibrillary acidic protein promoter), to obtain targeted transduction of TAMs and reactive astrocytes, respectively, while avoiding transgene expression in the periphery. We used our approach to express the potent, yet toxic anti-tumor cytokine, interferon beta, in tumor stroma of a mouse model of GBM, and achieved a modest, yet significant enhancement in survival compared to controls. Noninvasive genetic modification of tumor microenvironment represents a promising approach for therapy against cancers. Additionally, the vectors described here may facilitate basic research in the study of tumor stromal cells in situ.

  13. [Identification of occult disseminated tumor cells by recombinant herpes simplex virus expressing GFP (HSV(GFP))].

    Science.gov (United States)

    Han, Xiang-ping; Shi, Gui-lan; Wang, Cheng-feng; Li, Jie; Zhang, Jian-wei; Zhang, Yu; Zhang, Shu-ren; Liu, Bin-lei

    2012-12-01

    To develop a novel rapid protocol for the detection of occult disseminated tumor cells by a recombinant herpes simplex virus expressing GFP (HSV(GFP)). Tumor cells of seven cell lines were exposed to HSV(GFP) and then examined for GFP expression by fluorescence microscopy. Various numbers of tumor cells (10, 100, 1000, 10 000) were mixed into 2 ml human whole blood, separated with lymphocytes separation medium, exposed to HSV(GFP), incubated at 37°C for 6 - 24 h and then counted for the number of green cells under the fluorescence microscope. Some clinical samples including peripheral blood, pleural effusion, ascites, spinal fluid from tumor-bearing patients were screened using this protocol in parallel with routine cytological examination. HSV(GFP) was able to infect all 7 tumor cell lines indicating that the HSV(GFP) can be used to detect different types of tumor cells. The detection sensitivity was 10 cancer cells in 2 ml whole blood. In the clinical samples, there were 4/15 positive by routine cytological examination but 11/15 positive by HSV(GFP), indicating a higher sensitivity of this new protocol. Recombinant herpes simplex virus-mediated green fluorescence is a simple and sensitive technique for the identification of occult disseminated cancer cells including circulating tumor cells (CTCs).

  14. Infektion mit Epstein-Barr-Virus und Tumor-Entstehung beim Menschen

    Science.gov (United States)

    Kirchner, H.

    1981-08-01

    The Epstein-Barr Virus (EBV) is the only infectious agent for which a close association with human malignant tumors has been clearly demonstrated. These tumors are one type of nasopharyngeal carcinoma which is frequent in parts of East Asia and the Burkitt lymphoma which predominantly occurs in parts of Africa and New Guinea. Nonetheless, the EBV is the causative agent of infectious mononucleosis (IM), a benign, self-limiting lymphoproliferative disease of adolescents. The major difference between the countries in which the EBV-induced tumors occur and those in which IM occurs is the late primary EBV infection in the latter, whereas primary infection with EBV occurs in the first year of life in the former. All theories of viral carcinogenesis have to explain the long latency period between primary infection and tumor growth and how an ubiquitous virus may be oncogenic. Thus, invariably, one has to assume a role of cofactors, which may be of cytogenetic nature or may be represented by additional infections or by chemical agents. Since most modern theories of carcinogenesis consider a multi-step development of tumors, the theory that infection with an ubiquitous virus at the right time of life represents one step to carcinogenesis seems to be tenable.

  15. Filaggrin gene polymorphism associated with Epstein-Barr virus-associated tumors in China.

    Science.gov (United States)

    Yang, Yang; Liu, Wen; Zhao, Zhenzhen; Zhang, Yan; Xiao, Hua; Luo, Bing

    2017-08-01

    Mutations of filaggrin gene (FLG) have been identified as the cause of ichthyosis vulgaris, while recently FLG mutations were found to be associated with gastric cancer. This study aimed to investigate the association of filaggrin polymorphism with Epstein-Barr virus-associated tumors in China. A total of 200 patients with three types of tumors and 117 normal control samples were genotyped at three common FLG mutation loci (rs3126085, K4671X, R501X) by using Sequenom MassARRAY technique. The χ 2 test was used to evaluate the relationship between the mutation and the three kinds of tumors. A two-sided P value of Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), respectively. Furthermore, allele distributions in EBVaGC and EBVnGC were verified to be different in both SNP loci.

  16. Reporting and Staging of Testicular Germ Cell Tumors: The International Society of Urological Pathology (ISUP) Testicular Cancer Consultation Conference Recommendations.

    Science.gov (United States)

    Verrill, Clare; Yilmaz, Asli; Srigley, John R; Amin, Mahul B; Compérat, Eva; Egevad, Lars; Ulbright, Thomas M; Tickoo, Satish K; Berney, Daniel M; Epstein, Jonathan I

    2017-06-01

    The International Society of Urological Pathology held a conference devoted to issues in testicular and penile pathology in Boston in March 2015, which included a presentation and discussion led by the testis microscopic features working group. This conference focused on controversies related to staging and reporting of testicular tumors and was preceded by an online survey of the International Society of Urological Pathology members. The survey results were used to initiate discussions, but decisions were made by expert consensus rather than voting. A number of recommendations emerged from the conference, including that lymphovascular invasion (LVI) should always be reported and no distinction need be made between lymphatic or blood invasion. If LVI is equivocal, then it should be regarded as negative to avoid triggering unnecessary therapy. LVI in the spermatic cord is considered as category pT2, not pT3, unless future studies provide contrary evidence. At the time of gross dissection, a block should be taken just superior to the epididymis to define the base of the spermatic cord, and direct invasion of tumor in this block indicates a category of pT3. Pagetoid involvement of the rete testis epithelium must be distinguished from rete testis stromal invasion, with only the latter being prognostically useful. Percentages of different tumor elements in mixed germ cell tumors should be reported. Although consensus was reached on many issues, there are still areas of practice that need further evidence on which to base firm recommendations.

  17. Dynamics of melanoma tumor therapy with vesicular stomatitis virus: explaining the variability in outcomes using mathematical modeling.

    Science.gov (United States)

    Rommelfanger, D M; Offord, C P; Dev, J; Bajzer, Z; Vile, R G; Dingli, D

    2012-05-01

    Tumor selective, replication competent viruses are being tested for cancer gene therapy. This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable, even when studies utilize highly inbred strains of mice and the same cell line and virus. Recognizing that virotherapy is an exercise in population dynamics, we utilize mathematical modeling to understand the variable outcomes observed when B16ova malignant melanoma tumors are treated with vesicular stomatitis virus in syngeneic, fully immunocompetent mice. We show how variability in the initial tumor size and the actual amount of virus delivered to the tumor have critical roles on the outcome of therapy. Virotherapy works best when tumors are small, and a robust innate immune response can lead to superior tumor control. Strategies that reduce tumor burden without suppressing the immune response and methods that maximize the amount of virus delivered to the tumor should optimize tumor control in this model system.

  18. Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma.

    Science.gov (United States)

    Starrett, Gabriel J; Marcelus, Christina; Cantalupo, Paul G; Katz, Joshua P; Cheng, Jingwei; Akagi, Keiko; Thakuria, Manisha; Rabinowits, Guilherme; Wang, Linda C; Symer, David E; Pipas, James M; Harris, Reuben S; DeCaprio, James A

    2017-01-03

    Merkel cell polyomavirus is the primary etiological agent of the aggressive skin cancer Merkel cell carcinoma (MCC). Recent studies have revealed that UV radiation is the primary mechanism for somatic mutagenesis in nonviral forms of MCC. Here, we analyze the whole transcriptomes and genomes of primary MCC tumors. Our study reveals that virus-associated tumors have minimally altered genomes compared to non-virus-associated tumors, which are dominated by UV-mediated mutations. Although virus-associated tumors contain relatively small mutation burdens, they exhibit a distinct mutation signature with observable transcriptionally biased kataegic events. In addition, viral integration sites overlap focal genome amplifications in virus-associated tumors, suggesting a potential mechanism for these events. Collectively, our studies indicate that Merkel cell polyomavirus is capable of hijacking cellular processes and driving tumorigenesis to the same severity as tens of thousands of somatic genome alterations. A variety of mutagenic processes that shape the evolution of tumors are critical determinants of disease outcome. Here, we sequenced the entire genome of virus-positive and virus-negative primary Merkel cell carcinomas (MCCs), revealing distinct mutation spectra and corresponding expression profiles. Our studies highlight the strong effect that Merkel cell polyomavirus has on the divergent development of viral MCC compared to the somatic alterations that typically drive nonviral tumorigenesis. A more comprehensive understanding of the distinct mutagenic processes operative in viral and nonviral MCCs has implications for the effective treatment of these tumors. Copyright © 2017 Starrett et al.

  19. Oncolytic Herpes Simplex Virus Vectors Fully Retargeted to Tumor- Associated Antigens.

    Science.gov (United States)

    Uchida, Hiroaki; Hamada, Hirofumi; Nakano, Kenji; Kwon, Heechung; Tahara, Hideaki; Cohen, Justus B; Glorioso, Joseph C

    2018-01-01

    Oncolytic virotherapy is a novel therapeutic modality for malignant diseases that exploits selective viral replication in cancer cells. Herpes simplex virus (HSV) is a promising agent for oncolytic virotherapy due to its broad cell tropism and the identification of mutations that favor its replication in tumor over normal cells. However, these attenuating mutations also tend to limit the potency of current oncolytic HSV vectors that have entered clinical studies. As an alternative, vector retargeting to novel entry receptors has the potential to achieve tumor specificity at the stage of virus entry, eliminating the need for replication-attenuating mutations. Here, we summarize the molecular mechanism of HSV entry and recent advances in the development of fully retargeted HSV vectors for oncolytic virotherapy. Retargeted HSV vectors offer an attractive platform for the creation of a new generation of oncolytic HSV with improved efficacy and specificity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Engineered Herpes Simplex Viruses for the Treatment of Malignant Peripheral Nerve Sheath Tumors

    Science.gov (United States)

    2015-11-01

    lines). This is an entry receptor usually limited to lymphoid cells has not been previously identified in neuroectodermal tissue. Year 3: As a... innate and adaptive immune 327 response. However, resistance is common in vitro and therefore, to the extent that tumor cell lines 328 maintain the...Handgretinger R, et al. Innate immune 461 defense defines susceptibility of sarcoma cells to measles vaccine virus-based oncolysis. J Virol. 462 2013;87

  1. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016

    DEFF Research Database (Denmark)

    Lugli, Alessandro; Kirsch, Richard; Ajioka, Yoichi

    2017-01-01

    to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: Tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1......%). Intratumoral budding exists in colorectal cancer and has been shown to be related to lymph node metastasis (22/22, 100%). Tumor budding is assessed in one hotspot (in a field measuring 0.785 mm 2) at the invasive front (22/22, 100%). A three-tier system should be used along with the budding count in order...

  2. Efficacy of the multidisciplinary tumor board conference in gynecologic oncology: A prospective study.

    Science.gov (United States)

    Lee, Banghyun; Kim, Kidong; Choi, Jin Young; Suh, Dong Hoon; No, Jae Hong; Lee, Ho-Young; Eom, Keun-Yong; Kim, Haeryoung; Hwang, Sung Il; Lee, Hak Jong; Kim, Yong Beom

    2017-12-01

    Evidence has shown that multidisciplinary tumor board conferences (MTBCs) improve patient management for various cancer types. However, few retrospective studies have investigated MTBC efficacy for patients with gynecologic cancers. Here, we prospectively aimed to evaluate how MTBCs influence patient management in gynecologic oncology. This prospective study included 85 consecutive cases that were presented at gynecologic oncology MTBCs in our tertiary university hospital between January 2015 and April 2016. The primary endpoint was treatment plan change rate, which included both major and minor changes. Major changes were defined as exchange, addition, or subtraction of treatment modality. Minor changes included all other, such as intramodality changes or treatment time changes. The secondary endpoints were the change rates of diagnosis, diagnostic work-up, and radiological and pathological findings.The treatment plan change rate, irrespective of changes in diagnostic work-up, was 27.1%, which included 10.6% major and 16.5% minor changes. Among the treatment plan changes, changes in the treatment plan change rate alone were noted in 16.5% of cases, and changes in diagnosis and radiological findings occurred in 7.1% and 3.5% of cases, respectively. Diagnosis and radiological findings, irrespective of changes in diagnostic work-up, were also changed in 9.4% and 10.6% of cases, respectively. However, there were no changes in pathological findings. Moreover, there was a change of diagnostic method for further work-up in 23.5% of cases. The implementation rate of MTBC-determined treatment changes was 91.8%. Gynecologic oncology MTBCs resulted in considerable changes in treatment plans. Diagnosis, diagnostic work-up, and radiological findings were influenced by MTBCs. The data emphasize the importance of adopting a multidisciplinary team approach for gynecologic cancer management.

  3. JST Thesaurus Headwords and Synonyms: mouse mammary tumor virus [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term mouse mammary tumor virus 名詞 一般 *... * * * マウス乳癌ウイルス マウスニュウガンウイルス マウスニューガンウイルス Thesaurus2015 200906026078109489 C LS07 UNKNOWN_2 mouse mammary tumor virus

  4. The Epstein-Barr virus encoded BART miRNAs potentiate tumor growth in vivo.

    Directory of Open Access Journals (Sweden)

    Jin Qiu

    2015-01-01

    Full Text Available The human herpes virus Epstein-Barr virus (EBV latently infects and drives the proliferation of B lymphocytes in vitro and is associated with several forms of lymphoma and carcinoma in vivo. The virus encodes ~30 miRNAs in the BART region, the function of most of which remains elusive. Here we have used a new mouse xenograft model of EBV driven carcinomagenesis to demonstrate that the BART miRNAs potentiate tumor growth and development in vivo. No effect was seen on invasion or metastasis, and the growth promoting activity was not seen in vitro. In vivo tumor growth was not associated with the expression of specific BART miRNAs but with up regulation of all the BART miRNAs, consistent with previous observations that all the BART miRNAs are highly expressed in all of the EBV associated cancers. Based on these observations, we suggest that deregulated expression of the BART miRNAs potentiates tumor growth and represents a general mechanism behind EBV associated oncogenesis.

  5. Immunization with plasmid DNA encoding the hemagglutinin and the nucleoprotein confers robust protection against a lethal canine distemper virus challenge.

    Science.gov (United States)

    Dahl, Lotte; Jensen, Trine Hammer; Gottschalck, Elisabeth; Karlskov-Mortensen, Peter; Jensen, Tove Dannemann; Nielsen, Line; Andersen, Mads Klindt; Buckland, Robin; Wild, T Fabian; Blixenkrone-Møller, Merete

    2004-09-09

    We have investigated the protective effect of immunization of a highly susceptible natural host of canine distemper virus (CDV) with DNA plasmids encoding the viral nucleoprotein (N) and hemagglutinin (H). The combined intradermal and intramuscular routes of immunization elicited high virus-neutralizing serum antibody titres in mink (Mustela vison). To mimic natural exposure, we also conducted challenge infection by horizontal transmission from infected contact animals. Other groups received a lethal challenge infection by administration to the mucosae of the respiratory tract and into the muscle. One of the mink vaccinated with N plasmid alone developed severe disease after challenge. In contrast, vaccination with the H plasmid together with the N plasmid conferred solid protection against disease and we were unable to detect CDV infection in PBMCs or in different tissues after challenge. Our findings show that DNA immunization by the combined intradermal and intramuscular routes can confer solid protective immunity against naturally transmitted morbillivirus infection and disease.

  6. Tumor Necrosis Factor-Mediated Survival of CD169+ Cells Promotes Immune Activation during Vesicular Stomatitis Virus Infection

    DEFF Research Database (Denmark)

    Shinde, Prashant V; Xu, Haifeng C; Maney, Sathish Kumar

    2018-01-01

    Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169(+) cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169(+) cells during viral infections remain...... stomatitis virus infection, phagocytes produce tumor necrosis factor (TNF) which signals via TNFR1 and promote "enforced virus replication" in CD169(+) macrophages. Consequently, lack of TNF or TNFR1 resulted in defective immune activation and VSV clearance....

  7. Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of radiation therapy (Conference Presentation)

    Science.gov (United States)

    Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Shang, Yu; Li, Xingzhe; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2016-03-01

    Radiation therapy is a principal modality for head and neck cancers and its efficacy depends on tumor hemodynamics. Our laboratory developed a hybrid diffuse optical instrument allowing for simultaneous measurements of tumor blood flow and oxygenation. In this study, the clinically involved cervical lymph node was monitored by the hybrid instrument once a week over the treatment period of seven weeks. Based on treatment outcomes within one year, patients were classified into a complete response group (CR) and an incomplete response group (IR) with remote metastasis and/or local recurrence. A linear mixed models was used to compare tumor hemodynamic responses to the treatment between the two groups. Interestingly, we found that human papilloma virus (HPV-16) status largely affected tumor hemodynamic responses. For HPV-16 negative tumors, significant differences in blood flow index (BFI, p = 0.007) and reduced scattering coefficient (μs', p = 0.0005) were observed between the two groups; IR tumors exhibited higher μs' values and a continuous increase in BFI over the treatment period. For HPV-16 positive tumors, oxygenated hemoglobin concentration ([HbO2]) and blood oxygen saturation (StO2) were significant different (p = 0.003 and 0.01, respectively); IR group showed lower [HbO2] and StO2. Our results imply HPV-16 negative tumors with higher density of vasculature (μs') and higher blood flow show poor responses to radiotherapy and HPV-16 positive tumors with lower tissue oxygenation level (lower StO2 and [HbO2]) exhibit poor treatment outcomes. Our diffuse optical measurements show the great potential for early prediction of radiotherapy in head and neck cancers.

  8. Cellular expression of gH confers resistance to herpes simplex virus type-1 entry

    International Nuclear Information System (INIS)

    Scanlan, Perry M.; Tiwari, Vaibhav; Bommireddy, Susmita; Shukla, Deepak

    2003-01-01

    Entry of herpes simplex virus-1 (HSV-1) into cells requires a concerted action of four viral glycoproteins gB, gD, and gH-gL. Previously, cell surface expression of gD had been shown to confer resistance to HSV-1 entry. To investigate any similar effects caused by other entry glycoproteins, gB and gH-gL were coexpressed with Nectin-1 in Chinese hamster ovary (CHO) cells. Interestingly, cellular expression of gB had no effect on HSV-1(KOS) entry. In contrast, entry was significantly reduced in cells expressing gH-gL. This effect was further analyzed by expressing gH and gL separately. Cells expressing gL were normally susceptible, whereas gH-expressing cells were significantly resistant. Further experiments suggested that the gH-mediated interference phenomenon was not specific to any particular gD receptor and was also observed in gH-expressing HeLa cells. Moreover, contrary to a previous report, gL-independent cell surface expression of gH was detected in stably transfected CHO cells, possibly implicating cell surface gH in the interference phenomenon. Thus, taken together these findings indicate that cellular expression of gH interferes with HSV-1 entry

  9. Reduced H3K27me3 expression in Merkel cell polyoma virus-positive tumors.

    Science.gov (United States)

    Busam, Klaus J; Pulitzer, Melissa P; Coit, Daniel C; Arcila, Maria; Leng, Danielle; Jungbluth, Achim A; Wiesner, Thomas

    2017-06-01

    Merkel cell carcinoma is a primary cutaneous neuroendocrine carcinoma, which once metastatic is difficult to treat. Recent mutation analyses of Merkel cell carcinoma revealed a low number of mutations in Merkel cell polyomavirus-associated tumors, and a high number of mutations in virus-negative combined squamous cell and neuroendocrine carcinomas of chronically sun-damaged skin. We speculated that the paucity of mutations in virus-positive Merkel cell carcinoma may reflect a pathomechanism that depends on derangements of chromatin without alterations in the DNA sequence (epigenetic dysregulation). One central epigenetic regulator is the Polycomb repressive complex 2 (PRC2), which silences genomic regions by trimethylating (me3) lysine (K) 27 of histone H3, and thereby establishes the histone mark H3K27me3. Recent experimental research data demonstrated that PRC2 loss in mice skin results in the formation of Merkel cells. Prompted by these findings, we explored a possible contribution of PRC2 loss in human Merkel cell carcinoma. We examined the immunohistochemical expression of H3K27me3 in 35 Merkel cell carcinomas with pure histological features (22 primary and 13 metastatic lesions) and in 5 combined squamous and neuroendocrine carcinomas of the skin. We found a strong reduction of H3K27me3 staining in tumors with pure histologic features and virus-positive Merkel cell carcinomas. Combined neuroendocrine carcinomas had no or only minimal loss of H3K27me3 labeling. Our findings suggest that a PRC2-mediated epigenetic deregulation may play a role in the pathogenesis of virus-positive Merkel cell carcinomas and in tumors with pure histologic features.

  10. Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

    Science.gov (United States)

    Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

    2013-02-01

    The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

  11. In Vitro Synergistic Enhancement of Newcastle Disease Virus to 5-Fluorouracil Cytotoxicity against Tumor Cells

    Directory of Open Access Journals (Sweden)

    Ahmed M. Al-Shammari

    2016-01-01

    Full Text Available Background: Chemotherapy is one of the antitumor therapies used worldwide in spite of its serious side effects and unsatisfactory results. Many attempts have been made to increase its activity and reduce its toxicity. 5-Fluorouracil (5-FU is still a widely-used chemotherapeutic agent, especially in combination with other chemotherapies. Combination therapy seems to be the best option for targeting tumor cells by different mechanisms. Virotherapy is a promising agent for fighting cancer because of its safety and selectivity. Newcastle disease virus is safe, and it selectively targets tumor cells. We previously demonstrated that Newcastle disease virus (NDV could be used to augment other chemotherapeutic agents and reduce their toxicity by halving the administered dose and replacing the eliminated chemotherapeutic agents with the Newcastle disease virus; the same antitumor activity was maintained. Methods: In the current work, we tested this hypothesis on different tumor cell lines. We used the non-virulent LaSota strain of NDV in combination with 5-FU, and we measured the cytotoxicity effect. We evaluated this combination using Chou–Talalay analysis. Results: NDV was synergistic with 5-FU at low doses when used as a combination therapy on different cancer cells, and there were very mild effects on non-cancer cells. Conclusion: The combination of a virulent, non-pathogenic NDV–LaSota strain with a standard chemotherapeutic agent, 5-FU, has a synergistic effect on different tumor cells in vitro, suggesting this combination could be an important new adjuvant therapy for treating cancer.

  12. Quantitative multi-target RNA profiling in Epstein-Barr virus infected tumor cells.

    Science.gov (United States)

    Greijer, A E; Ramayanti, O; Verkuijlen, S A W M; Novalić, Z; Juwana, H; Middeldorp, J M

    2017-03-01

    Epstein-Barr virus (EBV) is etiologically linked to multiple acute, chronic and malignant diseases. Detection of EBV-RNA transcripts in tissues or biofluids besides EBV-DNA can help in diagnosing EBV related syndromes. Sensitive EBV transcription profiling yields new insights on its pathogenic role and may be useful for monitoring virus targeted therapy. Here we describe a multi-gene quantitative RT-PCR profiling method that simultaneously detects a broad spectrum (n=16) of crucial latent and lytic EBV transcripts. These transcripts include (but are not restricted to), EBNA1, EBNA2, LMP1, LMP2, BARTs, EBER1, BARF1 and ZEBRA, Rta, BGLF4 (PK), BXLF1 (TK) and BFRF3 (VCAp18) all of which have been implicated in EBV-driven oncogenesis and viral replication. With this method we determine the amount of RNA copies per infected (tumor) cell in bulk populations of various origin. While we confirm the expected RNA profiles within classic EBV latency programs, this sensitive quantitative approach revealed the presence of rare cells undergoing lytic replication. Inducing lytic replication in EBV tumor cells supports apoptosis and is considered as therapeutic approach to treat EBV-driven malignancies. This sensitive multi-primed quantitative RT-PCR approach can provide broader understanding of transcriptional activity in latent and lytic EBV infection and is suitable for monitoring virus-specific therapy responses in patients with EBV associated cancers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models

    Directory of Open Access Journals (Sweden)

    Fabrice Le Boeuf

    2017-09-01

    Full Text Available The reovirus fusion-associated small transmembrane (FAST proteins are the smallest known viral fusogens (∼100–150 amino acids and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant encoding the p14 FAST protein (VSV-p14 was compared with a similar construct encoding GFP (VSV-GFP in cell culture and syngeneic BALB/c tumor models. Compared with VSV-GFP, VSV-p14 exhibited increased oncolytic activity against MCF-7 and 4T1 breast cancer spheroids in culture and reduced primary 4T1 breast tumor growth in vivo. VSV-p14 prolonged survival in both primary and metastatic 4T1 breast cancer models, and in a CT26 metastatic colon cancer model. As with VSV-GFP, VSV-p14 preferentially replicated in vivo in tumors and was cleared rapidly from other sites. Furthermore, VSV-p14 increased the numbers of activated splenic CD4, CD8, natural killer (NK, and natural killer T (NKT cells, and increased the number of activated CD4 and CD8 cells in tumors. FAST proteins may therefore provide a multi-pronged approach to improving oncolytic virotherapy via syncytium formation and enhanced immune stimulation.

  14. Protection against polyoma virus-induced tumors is perforin-independent

    International Nuclear Information System (INIS)

    Byers, Anthony M.; Hadley, Annette; Lukacher, Aron E.

    2007-01-01

    CD8 T cells are necessary for controlling tumors induced by mouse polyoma virus (PyV), but the effector mechanism(s) responsible have not been determined. We examined the PyV tumorigenicity in C57BL/6 mice mutated in Fas or carrying targeted disruptions in the perforin gene or in both TNF receptor type I and type II genes. Surprisingly, none of these mice developed tumors. Perforin/Fas double-deficient radiation bone marrow chimeric mice were also resistant to PyV-induced tumors. Anti-PyV CD8 T cells in perforin-deficient mice were found not to differ from wild type mice with respect to phenotype, capacity to produce cytokines or maintenance of memory T cells, indicating that perforin does not modulate the PyV-specific CD8 T cell response. In addition, virus was cleared and persisted to similar extents in wild type and perforin-deficient mice. In summary, perforin/granzyme exocytosis is not an essential effector pathway for protection against PyV infection or tumorigenesis

  15. Live attenuated measles virus vaccine therapy for locally established malignant glioblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Al-Shammari AM

    2014-05-01

    Full Text Available Ahmed M Al-Shammari,1 Farah E Ismaeel,2 Shahlaa M Salih,2 Nahi Y Yaseen11Experimental Therapy Department, Iraqi Center for Cancer and Medical Genetic Researches, Mustansiriya University, 2Departments of Biotechnology, College of Science, Al-Nahrain University, Baghdad, IraqAbstract: Glioblastoma multiforme is the most aggressive malignant primary brain tumor in humans, with poor prognosis. A new glioblastoma cell line (ANGM5 was established from a cerebral glioblastoma multiforme in a 72-year-old Iraqi man who underwent surgery for an intracranial tumor. This study was carried out to evaluate the antitumor effect of live attenuated measles virus (MV Schwarz vaccine strain on glioblastoma multiforme tumor cell lines in vitro. Live attenuated MV Schwarz strain was propagated on Vero, human rhabdomyosarcoma, and human glioblastoma-multiform (ANGM5 cell lines. The infected confluent monolayer appeared to be covered with syncytia with granulation and vacuolation, as well as cell rounding, shrinkage, and large empty space with cell debris as a result of cell lysis and death. Cell lines infected with virus have the ability for hemadsorption to human red blood cells after 72 hours of infection, whereas no hemadsorption of uninfected cells is seen. Detection of MV hemagglutinin protein by monoclonal antibodies in infected cells of all cell lines by immunocytochemistry assay gave positive results (brown color in the cytoplasm of infected cells. Cell viability was measured after 72 hours of infection by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results showed a significant cytotoxic effect for MV (P≤0.05 on growth of ANGM5 and rhabdomyosarcoma cell lines after 72 hours of infection. Induction of apoptosis by MV was assessed by measuring mitochondrial membrane potentials in tumor cells after 48, 72, and 120 hours of infection. Apoptotic cells were counted, and the mean percentage of dead cells was significantly higher after 48, 72

  16. A cell culture-derived whole virus influenza A vaccine based on magnetic sulfated cellulose particles confers protection in mice against lethal influenza A virus infection.

    Science.gov (United States)

    Pieler, Michael M; Frentzel, Sarah; Bruder, Dunja; Wolff, Michael W; Reichl, Udo

    2016-12-07

    Downstream processing and formulation of viral vaccines employs a large number of different unit operations to achieve the desired product qualities. The complexity of individual process steps involved, the need for time consuming studies towards the optimization of virus yields, and very high requirements regarding potency and safety of vaccines results typically in long lead times for the establishment of new processes. To overcome such obstacles, to enable fast screening of potential vaccine candidates, and to explore options for production of low cost veterinary vaccines a new platform for whole virus particle purification and formulation based on magnetic particles has been established. Proof of concept was carried out with influenza A virus particles produced in suspension Madin Darby canine kidney (MDCK) cells. The clarified, inactivated, concentrated, and diafiltered virus particles were bound to magnetic sulfated cellulose particles (MSCP), and directly injected into mice for immunization including positive and negative controls. We show here, that in contrast to the mock-immunized group, vaccination of mice with antigen-loaded MSCP (aMSCP) resulted in high anti-influenza A antibody responses and full protection against a lethal challenge with replication competent influenza A virus. Antiviral protection correlated with a 400-fold reduced number of influenza nucleoprotein gene copies in the lungs of aMSCP immunized mice compared to mock-treated animals, indicating the efficient induction of antiviral immunity by this novel approach. Thus, our data proved the use of MSCP for purification and formulation of the influenza vaccine to be fast and efficient, and to confer protection of mice against influenza A virus infection. Furthermore, the method proposed has the potential for fast purification of virus particles directly from bioreactor harvests with a minimum number of process steps towards formulation of low-cost veterinary vaccines, and for screening

  17. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

    Science.gov (United States)

    Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

    2006-04-11

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

  18. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

    Science.gov (United States)

    Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

    2006-01-01

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

  19. Myristoylation drives dimerization of matrix protein from mouse mammary tumor virus

    Czech Academy of Sciences Publication Activity Database

    Doležal, Michal; Zábranský, Aleš; Dostál, Jiří; Vaněk, O.; Brynda, Jiří; Lepšík, Martin; Hadravová, Romana; Pichová, Iva

    2016-01-01

    Roč. 13, Jan 5 (2016), č. článku 2. ISSN 1742-4690 R&D Projects: GA MŠk LO1302; GA MŠk(CZ) LO1304; GA ČR GBP208/12/G016 Institutional support: RVO:61388963 Keywords : dimerization * matrix protein * MMTV * molecular dynamics * mouse mammary tumor virus * myristoylation Subject RIV: CE - Biochemistry Impact factor: 3.867, year: 2016 http://retrovirology.biomedcentral.com/articles/10.1186/s12977-015-0235-8

  20. Mutations Conferring Resistance to Viral DNA Polymerase Inhibitors in Camelpox Virus Give Different Drug-Susceptibility Profiles in Vaccinia Virus

    Czech Academy of Sciences Publication Activity Database

    Duraffour, S.; Andrei, G.; Topalis, D.; Krečmerová, Marcela; Crance, J. M.; Garin, D.; Snoeck, R.

    2012-01-01

    Roč. 86, č. 13 (2012), s. 7310-7325 ISSN 0022-538X Institutional support: RVO:61388963 Keywords : camelpox virus * CMLV * vaccinia virus VACV * acyclic nucleoside phosphonates * HPMPDAP * cidofovir * drug resistance Subject RIV: CC - Organic Chemistry Impact factor: 5.076, year: 2012

  1. Conference on Hamiltonian Systems and Celestial Mechanics 2014 & Workshop on Virus Dynamics and Evolution : Extended Abstracts Spring 2014

    CERN Document Server

    Cors, Josep; Llibre, Jaume; Korobeinikov, Andrei

    2015-01-01

    The two parts of the present volume contain extended conference abstracts corresponding to selected talks given by participants at the "Conference on Hamiltonian Systems and Celestial Mechanics 2014" (HAMSYS2014) (15 abstracts) and at the "Workshop on Virus Dynamics and Evolution" (12 abstracts), both held at the Centre de Recerca Matemàtica (CRM) in Barcelona from June 2nd to 6th, 2014, and from June 23th to 27th, 2014, respectively. Most of them are brief articles, containing preliminary presentations of new results not yet published in regular research journals. The articles are the result of a direct collaboration between active researchers in the area after working in a dynamic and productive atmosphere. The first part is about Central Configurations, Periodic Orbits and Hamiltonian Systems with applications to Celestial Mechanics – a very modern and active field of research. The second part is dedicated to mathematical methods applied to viral dynamics and evolution. Mathematical modelling of biologi...

  2. Murine mammary tumor virus pol-related sequences in human DNA: characterization and sequence comparison with the complete murine mammary tumor virus pol gene

    International Nuclear Information System (INIS)

    Deen, K.C.; Sweet, R.W.

    1986-01-01

    Sequences in the human genome with homology to the murine mammary tumor virus (MMTV) pol gene were isolated from a human phage library. Ten clones with extensive pol homology were shown to define five separate loci. These loci share common sequences immediately adjacent to the pol-like segments and, in addition, contain a related repeat element which bounds this region. This organization is suggestive of a proviral structure. The authors estimate that the human genome contains 30 to 40 copies of these pol-related sequences. The pol region of one of the cloned segments (HM16) and the complete MMTV pol gene were sequenced and compared. The nucleotide homology between these pol sequences is 52% and is concentrated in the terminal regions. The MMTV pol gene contains a single long open reading frame encoding 899 amino acids and is demarcated from the partially overlapping putative gag gene by termination codons and a shift in translational reading frame. The pol sequence of HM16 is multiply terminated but does contain open reading frames which encode 370, 105, and 112 amino acids residues in separate reading frames. The authors deduced a composite pol protein sequence for HM16 by aligning it to the MMTV pol gene and then compared these sequences with other retroviral pol protein sequences. Conserved sequences occur in both the amino and carboxyl regions which lie within the polymerase and endonuclease domains of pol, respectively

  3. Induction of mouse mammary tumor virus RNA in mammary tumors of BALB/c mice treated with urethane, x-irradiation, and hormones

    International Nuclear Information System (INIS)

    Michalides, R.; van Deemter, L.; Nusse, R.; Hageman, P.

    1979-01-01

    The involvement of mouse mammary tumor virus (MTV) in the development of mammary tumors of nonviral etiology in BALB/c mice was studied by measuring the levels of MTV RNA, MTV DNA, and MTV proteins in spontaneously arising and hormally, chemically, and/or physically induced mammary tumors of BALB/c females. The following results were obtained: (1) spontaneous mammary tumors contained very low levels of MTV RNA; 4 x 10 -6 % of the cytoplasmic RNA was MTV RNA. No MTV proteins could be demonstrated by using sensitive radioimmunoassays for MTV proteins p27 and gp52. (2) Mammary tumors induced by treatments with urethane or x-irradiation alone contained higher levels of MTV RNA; these tumors contained 3- and 19-fold more MTV RNA, respectively, compared with spontaneous mammary tumors. (3) Mammary tumors induced by combined treatment with urethane and x-irradiation expressed high levels of MTV RNA in the mammary tumors; a 1,724-fold increase in MTV RNA content compared with spontaneous mammary tumors was observed. However, very low levels of MTV proteins gp52 and p27 were detected, suggesting some kind of impairment at the translation of MTV RNA. MTV RNA was also induced by this treatment in mammary glands and spleens, but not in the livers of tumor-bearing animals. (4) BALB/c females continuously exposed to prolactin contained high levels of MTV RNA and MTV proteins in stimulated mammary glands and in the hormonally induced mammary tumors. These findings suggest that MTV is not responsible for the maintenance and probably also not for the development of all murine mammary cancers

  4. An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge.

    Science.gov (United States)

    Ma, Ji-Hong; Yang, Fu-Ru; Yu, Hai; Zhou, Yan-Jun; Li, Guo-Xin; Huang, Meng; Wen, Feng; Tong, Guangzhi

    2013-07-09

    Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses. Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds' adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus. Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.

  5. Autofluorescence lifetime imaging during transoral robotic surgery: a clinical validation study of tumor detection (Conference Presentation)

    Science.gov (United States)

    Lagarto, João. L.; Phipps, Jennifer E.; Unger, Jakob; Faller, Leta M.; Gorpas, Dimitris; Ma, Dinglong M.; Bec, Julien; Moore, Michael G.; Bewley, Arnaud F.; Yankelevich, Diego R.; Sorger, Jonathan M.; Farwell, Gregory D.; Marcu, Laura

    2017-02-01

    Autofluorescence lifetime spectroscopy is a promising non-invasive label-free tool for characterization of biological tissues and shows potential to report structural and biochemical alterations in tissue owing to pathological transformations. In particular, when combined with fiber-optic based instruments, autofluorescence lifetime measurements can enhance intraoperative diagnosis and provide guidance in surgical procedures. We investigate the potential of a fiber-optic based multi-spectral time-resolved fluorescence spectroscopy instrument to characterize the autofluorescence fingerprint associated with histologic, morphologic and metabolic changes in tissue that can provide real-time contrast between healthy and tumor regions in vivo and guide clinicians during resection of diseased areas during transoral robotic surgery. To provide immediate feedback to the surgeons, we employ tracking of an aiming beam that co-registers our point measurements with the robot camera images and allows visualization of the surgical area augmented with autofluorescence lifetime data in the surgeon's console in real-time. For each patient, autofluorescence lifetime measurements were acquired from normal, diseased and surgically altered tissue, both in vivo (pre- and post-resection) and ex vivo. Initial results indicate tumor and normal regions can be distinguished based on changes in lifetime parameters measured in vivo, when the tumor is located superficially. In particular, results show that autofluorescence lifetime of tumor is shorter than that of normal tissue (p robot assisted cancer removal interventions.

  6. Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells

    DEFF Research Database (Denmark)

    Zhang, Wen; Bao, Li; Yang, Shaoxing

    2016-01-01

    Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase......-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326...

  7. Towards intraoperative assessment of tumor margins in breast surgery using optical coherence elastography (Conference Presentation)

    Science.gov (United States)

    Kennedy, Brendan F.; Wijesinghe, Philip; Allen, Wes M.; Chin, Lixin; Latham, Bruce; Saunders, Christobel M.; Sampson, David D.

    2016-03-01

    Surgical excision of tumor is a critical factor in the management of breast cancer. The most common surgical procedure is breast-conserving surgery. The surgeon's goal is to remove the tumor and a rim of healthy tissue surrounding the tumor: the surgical margin. A major issue in breast-conserving surgery is the absence of a reliable tool to guide the surgeon in intraoperatively assessing the margin. A number of techniques have been proposed; however, the re-excision rate remains high and has been reported to be in the range 30-60%. New tools are needed to address this issue. Optical coherence elastography (OCE) shows promise as a tool for intraoperative tumor margin assessment in breast-conserving surgery. Further advances towards clinical translation are limited by long scan times and small fields of view. In particular, scanning over sufficient areas to assess the entire margin in an intraoperative timeframe has not been shown to be feasible. Here, we present a protocol allowing ~75% of the surgical margins to be assessed within 30 minutes. To achieve this, we have incorporated a 65 mm-diameter (internal), wide-aperture annular piezoelectric transducer, allowing the entire surface of the excised tumor mass to be automatically imaged in an OCT mosaic comprised of 10 × 10 mm tiles. As OCT is effective in identifying adipose tissue, our protocol uses the wide-field OCT to selectively guide subsequent local OCE scanning to regions of solid tissue which often present low contrast in OCT images. We present promising examples from freshly excised human breast tissue.

  8. Conjunctival tumor caused by Epstein-Barr virus-related infectious mononucleosis: Case report and review of literature.

    Science.gov (United States)

    Vaivanijkul, Juntarut; Boonsiri, Kreopun

    2017-04-01

    The conjunctival tumor associated with Epstein-Barr virus related infectious mononucleosis is a rare ocular manifestation. Only a few cases have been reported in the literature. We reported this rare condition that presented in a 5-year-old boy.

  9. Activation of human T cells by a tumor vaccine infected with recombinant Newcastle disease virus producing IL-2

    NARCIS (Netherlands)

    Janke, M.; Peeters, B.; Zhao, H.; Leeuw, O.; Moormann, R.J.M.; Arnold, A.; Ziouta, Y.; Fournier, P.; Schirrmacher, V.

    2008-01-01

    A new recombinant (rec) Newcastle disease virus (NDV) with incorporated human interleukin 2 (IL-2) as foreign therapeutic gene [rec(IL-2)] will be described. The foreign gene in rec(IL-2) did not affect the main features of NDV replication nor its tumor selectivity. Biologically active IL-2 was

  10. Tumor necrosis factor alpha selectively sensitizes human immunodeficiency virus-infected cells to heat and radiation

    International Nuclear Information System (INIS)

    Wong, G.H.; McHugh, T.; Weber, R.; Goeddel, D.V.

    1991-01-01

    We report here that infection of the human T-cell line HUT-78 with human immunodeficiency virus (HIV) increases its sensitivity to heat and radiation toxicity. A possible explanation for this result may be the reduced expression of manganous superoxide dismutase (MnSOD) in HIV-infected cells compared to uninfected cells. Tumor necrosis factor alpha (TNF-alpha) further sensitizes HIV-infected cells but not uninfected cells to heat and radiation. This is consistent with the ability of TNF-alpha to induce the expression of MnSOD in uninfected but not in HIV-infected cells. HIV-infected HUT-78 cell lines engineered to overexpress MnSOD are more resistant to heat and radiation than HIV-infected cells that do not overexpress MnSOD. However, treatment with TNF-alpha still sensitizes these cells to heat and radiation

  11. Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4+ T Cells

    Science.gov (United States)

    Muraro, Elena; Merlo, Anna; Martorelli, Debora; Cangemi, Michela; Dalla Santa, Silvia; Dolcetti, Riccardo; Rosato, Antonio

    2017-01-01

    CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors. PMID:28289418

  12. Real-time temperature feedback for nanoparticles based tumor thermal treatment (Conference Presentation)

    Science.gov (United States)

    Steinberg, Idan; Tamir, Gil; Gannot, Israel

    2017-02-01

    Systemic hyperthermia therapy exploits the fact that cancer cells are more sensitive to elevated temperatures than healthy tissue. Systemic application of hyperthermia externally usually leads to low efficiency treatment. Recently, our group and others have proposed an antibody conjugated magnetic nanoparticles (MNPs) approach to overcome the limitation of systemic hyperthermia. MNPs can bind specifically to the tumor sites, thus delivering internal highly effective targeted hyperthermia. However, such internal mechanism requires more complicated controls and monitoring. This current work presents a deep tissue temperature monitoring method to control hyperthermia effectiveness and minimize collateral damage to surrounding tissues. A low-frequency narrowband modulation of the RF field used for MNP heating leads to the generation of diffused thermal waves which propagate to the tissue surface and captured by a thermal camera. A Fourier domain, analytical heat transfer model is used for temperature monitoring algorithm. The ill-posed thermal inverse problem is solved efficiently by iterating over the source power until both the amplitude and phase match the recorded thermal image sequence. The narrow bandwidth thermal stimulation enables acquiring deep signals with high SNR. We show that thermal transverse resolution improves as the stimulation frequency increases even slightly above DC, enabling better heat source transverse separation and margin identification in the case of distributed tumors. These results can be used as a part of an overall image and treat system for efficient detection of tumors, manipulation of MNPs and monitoring MNP based hyperthermia.

  13. Laser-induced immune modulation inhibits tumor growth in vivo (Conference Presentation)

    Science.gov (United States)

    Ottaviani, Giulia; Martinelli, Valentina; Rupel, Katia; Caronni, Nicoletta; Naseem, Asma; Zandonà, Lorenzo; Perinetti, Giuseppe; Gobbo, Margherita; Di Lenarda, Roberto; Bussani, Rossana; Benvenuti, Federica; Giacca, Mauro; Biasotto, Matteo; Zacchigna, Serena

    2017-02-01

    Photobiomodulation stands as a recommended therapy for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. We assessed cancer cell metabolism and proliferation in vitro and in vivo after exposure to different laser protocols. We exploited both ectopic melanoma and a more physiological oral carcinogenesis mouse model, followed by molecular, histological and immunohistochemical characterization. Laser irradiation resulted in a slightly increase in cell metabolism and proliferation in vitro, albeit each protocol exerted a difference response. Of notice, in vivo laser light reduced tumour growth and invasiveness, indicating e beneficial effect on tumor microenvironment. Laser-treated tumors were surrounded and infiltrated by immune cells, mainly lymphocytes and dendritic cells, paralleled by an enhanced secretion of type I interferons. In contrast, the number of pro-angiogenic macrophages was reduced in response to laser irradiation, with consequent normalization of the tumor vasculature. Based on these finding we have also started exploring the effect of photobiomodulation on lymphocyte response in an experimental model of vaccination. Preliminary data indicate that laser light induced antigen-specific CD8+ and CD4+ T cell responses. In conclusion, our data point toward photobiomodulation as an effective strategy to boost the immune response in vivo, with relevant, therapeutic activities in both cancer and vaccination experimental models. These results support the safe use of laser light on cancer patients and open the way to innovative therapeutic opportunities.

  14. Transcriptional Inhibition of the Human Papilloma Virus Reactivates Tumor Suppressor p53 in Cervical Carcinoma Cells

    Science.gov (United States)

    Kochetkov, D. V.; Ilyinskaya, G. V.; Komarov, P. G.; Strom, E.; Agapova, L. S.; Ivanov, A. V.; Budanov, A. V.; Frolova, E. I.; Chumakov, P. M.

    2009-01-01

    Inactivation of tumor suppressor p53 accompanies the majority of human malignancies. Restoration of p53 function causes death of tumor cells and is potentially suitable for gene therapy of cancer. In cervical carcinoma, human papilloma virus (HPV) E6 facilitates proteasomal degradation of p53. Hence, a possible approach to p53 reactivation is the use of small molecules suppressing the function of viral proteins. HeLa cervical carcinoma cells (HPV-18) with a reporter construct containing the b-galactosidase gene under the control of a p53-responsive promoter were used as a test system to screen a library of small molecules for restoration of the transcriptional activity of p53. The effect of the two most active compounds was studied with cell lines differing in the state of p53-dependent signaling pathways. The compounds each specifically activated p53 in cells expressing HPV-18 and, to a lesser extent, HPV-16 and exerted no effect on control p53-negative cells or cells with the intact p53-dependent pathways. Activation of p53 in cervical carcinoma cells was accompanied by induction of p53-dependent CDKN1 (p21), inhibition of cell proliferation, and induction of apoptosis. In addition, the two compounds dramatically decreased transcription of the HPV genome, which was assumed to cause p53 reactivation. The compounds were low-toxic for normal cells and can be considered as prototypes of new anticancer drugs. PMID:17685229

  15. Tumor Suppressor p53 Stimulates the Expression of Epstein-Barr Virus Latent Membrane Protein 1.

    Science.gov (United States)

    Wang, Qianli; Lingel, Amy; Geiser, Vicki; Kwapnoski, Zachary; Zhang, Luwen

    2017-10-15

    Epstein-Barr virus (EBV) is associated with multiple human malignancies. EBV latent membrane protein 1 (LMP1) is required for the efficient transformation of primary B lymphocytes in vitro and possibly in vivo The tumor suppressor p53 plays a seminal role in cancer development. In some EBV-associated cancers, p53 tends to be wild type and overly expressed; however, the effects of p53 on LMP1 expression is not clear. We find LMP1 expression to be associated with p53 expression in EBV-transformed cells under physiological and DNA damaging conditions. DNA damage stimulates LMP1 expression, and p53 is required for the stimulation. Ectopic p53 stimulates endogenous LMP1 expression. Moreover, endogenous LMP1 blocks DNA damage-mediated apoptosis. Regarding the mechanism of p53-mediated LMP1 expression, we find that interferon regulatory factor 5 (IRF5), a direct target of p53, is associated with both p53 and LMP1. IRF5 binds to and activates a LMP1 promoter reporter construct. Ectopic IRF5 increases the expression of LMP1, while knockdown of IRF5 leads to reduction of LMP1. Furthermore, LMP1 blocks IRF5-mediated apoptosis in EBV-infected cells. All of the data suggest that cellular p53 stimulates viral LMP1 expression, and IRF5 may be one of the factors for p53-mediated LMP1 stimulation. LMP1 may subsequently block DNA damage- and IRF5-mediated apoptosis for the benefits of EBV. The mutual regulation between p53 and LMP1 may play an important role in EBV infection and latency and its related cancers. IMPORTANCE The tumor suppressor p53 is a critical cellular protein in response to various stresses and dictates cells for various responses, including apoptosis. This work suggests that an Epstein-Bar virus (EBV) principal viral oncogene is activated by cellular p53. The viral oncogene blocks p53-mediated adverse effects during viral infection and transformation. Therefore, the induction of the viral oncogene by p53 provides a means for the virus to cope with infection and

  16. Needle-based polarization-sensitive OCT of breast tumor (Conference Presentation)

    Science.gov (United States)

    Villiger, Martin; Lorenser, Dirk; McLaughlin, Robert A.; Quirk, Bryden C.; Kirk, Rodney W.; Bouma, Brett E.; Sampson, David D.

    2016-03-01

    OCT imaging through miniature needle probes has extended the range of OCT and enabled structural imaging deep inside breast tissue, with the potential to assist in the intraoperative assessment of tumor margins. However, in many situations, scattering contrast alone is insufficient to clearly identify and delineate malignant areas. Here, we present a portable, depth-encoded polarization-sensitive OCT system, connected to a miniature needle probe. From the measured polarization states we constructed the tissue Mueller matrix at each sample location and improved the accuracy of the measured polarization states through incoherent averaging before retrieving the depth-resolved tissue birefringence. With the Mueller matrix at hand, additional polarization properties such as depolarization are readily available. We then imaged freshly excised breast tissue from a patient undergoing lumpectomy. The reconstructed local retardation highlighted regions of connective tissue, which exhibited birefringence due to the abundance of collagen fibers, and offered excellent contrast to areas of malignant tissue, which exhibited less birefringence due to their different tissue composition. Results were validated against co-located histology sections. The combination of needle-based imaging with the complementary contrast provided by polarization-sensitive analysis offers a powerful instrument for advanced tissue imaging and has potential to aid in the assessment of tumor margins during the resection of breast cancer.

  17. Low Tumor Infiltrating Mast Cell Density Confers Prognostic Benefit and Reflects Immunoactivation in Colorectal Cancer.

    Science.gov (United States)

    Mao, Yihao; Feng, Qingyang; Zheng, Peng; Yang, Liangliang; Zhu, Dexiang; Chang, Wenju; Ji, Meiling; He, Guodong; Xu, Jianmin

    2018-06-06

    The role of mast cells (MCs) in colorectal cancer (CRC) progression was controversial. Thus, this study was designed to evaluate the prognostic value of MCs as well as their correlation with immune microenvironment. A retrospective cohort of CRC patients of stage I-IV was enrolled in this study. 854 consecutive patients were divided into training set (427 patients) and validation set (427 patients) randomly. The findings were further validated in a GEO cohort, GSE39582 (556 patients). The mast cell density (MCD) was measured by immunohistochemical staining of tryptase or by CIBERSORT algorithm. Low MCD predicted prolonged overall survival (OS) in training and validation set. Moreover, MCD was identified as an independent prognostic indicator in both sets. Better stratification for CRC prognosis can be achieved by building a MCD based nomogram. The prognostic role of MCD was further validated in GSE39582. In addition, MCD predicted improved survival in stage II and III CRC patients receiving adjuvant chemotherapy (ACT). Multiple immune pathways were enriched in low MCD group while cytokines/chemokines promoting anti-tumor immunity were highly expressed in such group. Furthermore, MCD was negatively correlated with CD8+ T cells infiltration. In conclusion, MCD was identified as an independent prognostic factor, as well as a potential biomarker for ACT benefit in stage II and III CRC. Better stratification of CRC prognosis could be achieved by building a MCD based nomogram. Moreover, immunoactivation in low MCD tumors may contributed to improved prognosis. This article is protected by copyright. All rights reserved. © 2018 UICC.

  18. Accessory genes confer a high replication rate to virulent feline immunodeficiency virus.

    Science.gov (United States)

    Troyer, Ryan M; Thompson, Jesse; Elder, John H; VandeWoude, Sue

    2013-07-01

    Feline immunodeficiency virus (FIV) is a lentivirus that causes AIDS in domestic cats, similar to human immunodeficiency virus (HIV)/AIDS in humans. The FIV accessory protein Vif abrogates the inhibition of infection by cat APOBEC3 restriction factors. FIV also encodes a multifunctional OrfA accessory protein that has characteristics similar to HIV Tat, Vpu, Vpr, and Nef. To examine the role of vif and orfA accessory genes in FIV replication and pathogenicity, we generated chimeras between two FIV molecular clones with divergent disease potentials: a highly pathogenic isolate that replicates rapidly in vitro and is associated with significant immunopathology in vivo, FIV-C36 (referred to here as high-virulence FIV [HV-FIV]), and a less-pathogenic strain, FIV-PPR (referred to here as low-virulence FIV [LV-FIV]). Using PCR-driven overlap extension, we produced viruses in which vif, orfA, or both genes from virulent HV-FIV replaced equivalent genes in LV-FIV. The generation of these chimeras is more straightforward in FIV than in primate lentiviruses, since FIV accessory gene open reading frames have very little overlap with other genes. All three chimeric viruses exhibited increased replication kinetics in vitro compared to the replication kinetics of LV-FIV. Chimeras containing HV-Vif or Vif/OrfA had replication rates equivalent to those of the virulent HV-FIV parental virus. Furthermore, small interfering RNA knockdown of feline APOBEC3 genes resulted in equalization of replication rates between LV-FIV and LV-FIV encoding HV-FIV Vif. These findings demonstrate that Vif-APOBEC interactions play a key role in controlling the replication and pathogenicity of this immunodeficiency-inducing virus in its native host species and that accessory genes act as mediators of lentiviral strain-specific virulence.

  19. Detection of polyomavirus simian virus 40 tumor antigen DNA in AIDS-related systemic non-Hodgkin lymphoma

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    Vilchez, Regis A.; Lednicky, John A.; Halvorson, Steven J.; White, Zoe S.; Kozinetz, Claudia A.; Butel, Janet S.

    2002-01-01

    Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV infection, and it is hypothesized that infectious agents may be involved in the etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related S-NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play a role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from HIV-negative patients, peripheral blood leukocytes from HIV-infected and -uninfected patients without NHL, and lymph nodes without tumors from HIV-infected patients. Specimens were examined by polymerase chain reaction analysis with use of primers specific for an N-terminal region of the oncoprotein large tumor antigen ( T-ag ) gene conserved among all three polyomaviruses (simian virus 40 [SV40], JC virus, and BK virus). Polyomavirus T-ag DNA sequences, proven to be SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of 26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs. 0 of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10; p =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16). Sequences of C-terminal T-ag DNA from SV40 were amplified from two AIDS-related S-NHL samples. Epstein-Barr virus DNA sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples, 50% (5 of 10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of the S-NHL samples were positive for both Epstein-Barr virus DNA and SV40 DNA. Further studies of the possible role of SV40 in the pathogenesis of S-NHL are warranted.

  20. A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus.

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    Yoshimi Tsuda

    2011-08-01

    Full Text Available Human outbreaks of Ebola virus (EBOV are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes.We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a 'proof-of-concept' for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV vector expressing a CD8+ T cell epitope from the nucleoprotein (NP of Zaire ebolavirus (ZEBOV (MCMV/ZEBOV-NP(CTL. MCMV/ZEBOV-NP(CTL induced high levels of long-lasting (>8 months CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection.This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for 'disseminating' CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations.

  1. Hairpin RNA Targeting Multiple Viral Genes Confers Strong Resistance to Rice Black-Streaked Dwarf Virus

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    Fangquan Wang

    2016-05-01

    Full Text Available Rice black-streaked dwarf virus (RBSDV belongs to the genus Fijivirus in the family of Reoviridae and causes severe yield loss in rice-producing areas in Asia. RNA silencing, as a natural defence mechanism against plant viruses, has been successfully exploited for engineering virus resistance in plants, including rice. In this study, we generated transgenic rice lines harbouring a hairpin RNA (hpRNA construct targeting four RBSDV genes, S1, S2, S6 and S10, encoding the RNA-dependent RNA polymerase, the putative core protein, the RNA silencing suppressor and the outer capsid protein, respectively. Both field nursery and artificial inoculation assays of three generations of the transgenic lines showed that they had strong resistance to RBSDV infection. The RBSDV resistance in the segregating transgenic populations correlated perfectly with the presence of the hpRNA transgene. Furthermore, the hpRNA transgene was expressed in the highly resistant transgenic lines, giving rise to abundant levels of 21–24 nt small interfering RNA (siRNA. By small RNA deep sequencing, the RBSDV-resistant transgenic lines detected siRNAs from all four viral gene sequences in the hpRNA transgene, indicating that the whole chimeric fusion sequence can be efficiently processed by Dicer into siRNAs. Taken together, our results suggest that long hpRNA targeting multiple viral genes can be used to generate stable and durable virus resistance in rice, as well as other plant species.

  2. Hairpin RNA Targeting Multiple Viral Genes Confers Strong Resistance to Rice Black-Streaked Dwarf Virus.

    Science.gov (United States)

    Wang, Fangquan; Li, Wenqi; Zhu, Jinyan; Fan, Fangjun; Wang, Jun; Zhong, Weigong; Wang, Ming-Bo; Liu, Qing; Zhu, Qian-Hao; Zhou, Tong; Lan, Ying; Zhou, Yijun; Yang, Jie

    2016-05-11

    Rice black-streaked dwarf virus (RBSDV) belongs to the genus Fijivirus in the family of Reoviridae and causes severe yield loss in rice-producing areas in Asia. RNA silencing, as a natural defence mechanism against plant viruses, has been successfully exploited for engineering virus resistance in plants, including rice. In this study, we generated transgenic rice lines harbouring a hairpin RNA (hpRNA) construct targeting four RBSDV genes, S1, S2, S6 and S10, encoding the RNA-dependent RNA polymerase, the putative core protein, the RNA silencing suppressor and the outer capsid protein, respectively. Both field nursery and artificial inoculation assays of three generations of the transgenic lines showed that they had strong resistance to RBSDV infection. The RBSDV resistance in the segregating transgenic populations correlated perfectly with the presence of the hpRNA transgene. Furthermore, the hpRNA transgene was expressed in the highly resistant transgenic lines, giving rise to abundant levels of 21-24 nt small interfering RNA (siRNA). By small RNA deep sequencing, the RBSDV-resistant transgenic lines detected siRNAs from all four viral gene sequences in the hpRNA transgene, indicating that the whole chimeric fusion sequence can be efficiently processed by Dicer into siRNAs. Taken together, our results suggest that long hpRNA targeting multiple viral genes can be used to generate stable and durable virus resistance in rice, as well as other plant species.

  3. Targeted therapy of animal eyes with tumors by laser-generated focused ultrasound (Conference Presentation)

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    Lee, Taehwa; Luo, Wei; Demirci, Hakan; Guo, L. Jay

    2016-03-01

    Cavitation therapy based on high-amplitude focused ultrasound (e.g., Histotripsy) has shown great promise in clinical trials. The technique realizes localized treatments of tissues and diseased cells by controlling cavitation zones, which can be even smaller than its acoustic spot sizes. Also, the short pressure pulse used in the technique can minimize the unwanted heat accumulation, which the conventional piezoelectric transducers suffer from due to low operating frequencies and relatively long acoustic pulses. However, this modality requires bulky system composed of array of piezoelectric elements and electric amplifiers in order to obtain high pressure amplitude. Moreover, especially when treating an area much smaller than the acoustic spot size, this approach may be vulnerable to nucleation sites within the focal volume, which can potentially induce cavitation and thus enlarge the total treatment area. Here, we show targeted cell-level therapy by using laser generated ultrasound. By employing a concave lens coated by a carbon nanotube (CNT)-polymer composite, high-amplitude acoustic pressure can be obtained at a tight focal spot (small focal spot, comparable to cavitation zone, lead to controlled cavitation treatment. Such feature can be exploited for treating intraocular tumors but without harming other parts of the eye (e.g. healthy retina and choroid) and therefore preserve the vision of the patients. We demonstrate that the localized disruption effects can be used for cell-level surgery to remove cells and to kill cells. Some experimental examples are shown using animal eyeballs.

  4. Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

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    Rodríguez-Padilla Cristina

    2011-09-01

    Full Text Available Abstract Background Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like env gene sequences. Results The MMTV-like env gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number AY161347. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the env sequences exhibited disruption of the reading frame due to mutations. Conclusion In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18% of the lung carcinomas and 1 out of 7 (14% of acute inflamatory lung infiltrate specimens studied of a Mexican Population.

  5. Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection

    International Nuclear Information System (INIS)

    Konnai, Satoru; Usui, Tatsufumi; Ikeda, Manabu; Kohara, Junko; Hirata, Toh-ichi; Okada, Kosuke; Ohashi, Kazuhiko; Onuma, Misao

    2005-01-01

    Previously, we found an up-regulation of tumor necrosis factor alpha (TNF)-α and an imbalance of TNF receptors in sheep experimentally infected with bovine leukemia virus (BLV). In order to investigate the different TNF-α-induced responses, in this study we examined the TNF-α-induced proliferative response and the expression levels of two distinct TNF receptors on peripheral blood mononuclear cells (PBMC) derived from BLV-uninfected cattle and BLV-infected cattle that were aleukemic (AL) or had persistent lymphocytosis (PL). The proliferative response of PBMC isolated from those cattle with PL in the presence of recombinant bovine TNF-α (rTNF-α) was significantly higher than those from AL cattle and uninfected cattle and the cells from PL cattle expressed significantly higher mRNA levels of TNF receptor type II (TNF-RII) than those from AL and BLV-uninfected cattle. No difference was found in TNF-RI mRNA levels. Most cells expressing TNF-RII in PL cattle were CD5 + or sIgM + cells and these cells showed resistance to TNF-α-induced apoptosis. Additionally, there were significant positive correlations between the changes in provirus load and TNF-RII mRNA levels, and TNF-α-induced proliferation and TNF-RII mRNA levels. These data suggest that imbalance in the expression of TNF receptors could at least in part contribute to the progression of lymphocytosis in BLV infection

  6. Biothechnology conferences held in Cuba. Cuba no biotechnology gakkai ni sankashite

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    Murata, M. (Ajinomoto Co. Inc., Tokyo, (Japan))

    1990-04-25

    Three biotechnology conferences including Cuba International Interferon Conference were held at Havana in April 1989, and the author participated in them. The number of participants was about 3,000. Most of them were from the Middle and the Central America, but there were also those from Europe, the USSR and the USA. The three conferences were composed of 16 symposiums and they covered a wide range of field such as medical science, agriculture and industry. High leveled reports were read in the conferences: on the application of interferons to medical treatments, curing effects of infections caused by herpes virus and B type hepatitis virus, anti-tumor effects, and anti-virus effects against AIDS virus; on the production of protein and vaccini by gene engineering, large quantity production of interleukin and epithelium cell multiplication genes. Especially impressing were the efforts the whole nation of Cuba makes to promote biotechnology and its modern facilities. 3 figs.

  7. Oncolytic Herpes Virus rRp450 Shows Efficacy in Orthotopic Xenograft Group 3/4 Medulloblastomas and Atypical Teratoid/Rhabdoid Tumors

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    Adam W. Studebaker

    2017-09-01

    Full Text Available Pediatric brain tumors including medulloblastoma and atypical teratoid/rhabdoid tumor are associated with significant mortality and treatment-associated morbidity. While medulloblastoma tumors within molecular subgroups 3 and 4 have a propensity to metastasize, atypical teratoid/rhabdoid tumors frequently afflict a very young patient population. Adjuvant treatment options for children suffering with these tumors are not only sub-optimal but also associated with many neurocognitive obstacles. A potentially novel treatment approach is oncolytic virotherapy, a developing therapeutic platform currently in early-phase clinical trials for pediatric brain tumors and recently US Food and Drug Administration (FDA-approved to treat melanoma in adults. We evaluated the therapeutic potential of the clinically available oncolytic herpes simplex vector rRp450 in cell lines derived from medulloblastoma and atypical teratoid/rhabdoid tumor. Cells of both tumor types were supportive of virus replication and virus-mediated cytotoxicity. Orthotopic xenograft models of medulloblastoma and atypical teratoid/rhabdoid tumors displayed significantly prolonged survival following a single, stereotactic intratumoral injection of rRp450. Furthermore, addition of the chemotherapeutic prodrug cyclophosphamide (CPA enhanced rRp450’s in vivo efficacy. In conclusion, oncolytic herpes viruses with the ability to bioactivate the prodrug CPA within the tumor microenvironment warrant further investigation as a potential therapy for pediatric brain tumors.

  8. Modulation of the tumor microenvironment by Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma.

    Science.gov (United States)

    Yoshizaki, Tomokazu; Kondo, Satoru; Endo, Kazuhira; Nakanishi, Yosuke; Aga, Mitsuharu; Kobayashi, Eiji; Hirai, Nobuyuki; Sugimoto, Hisashi; Hatano, Miyako; Ueno, Takayoshi; Ishikawa, Kazuya; Wakisaka, Naohiro

    2018-02-01

    Latent membrane protein 1 (LMP1) is a primary oncogene encoded by the Epstein-Barr virus, and various portions of LMP1 are detected in nasopharyngeal carcinoma (NPC) tumor cells. LMP1 has been extensively studied since the discovery of its transforming property in 1985. LMP1 promotes cancer cell growth during NPC development and facilitates the interaction of cancer cells with surrounding stromal cells for invasion, angiogenesis, and immune modulation. LMP1 is detected in 100% of pre-invasive NPC tumors and in approximately 50% of advanced NPC tumors. Moreover, a small population of LMP1-expressing cells in advanced NPC tumor tissue is proposed to orchestrate NPC tumor tissue maintenance and development through cancer stem cells and progenitor cells. Recent studies suggest that LMP1 activity shifts according to tumor development stage, but it still has a pivotal role during all stages of NPC development. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  9. Multiplicações celulares e tumores induzidos por virus: o cancer como infecção

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    F. Rocha Lagôa

    1953-12-01

    Full Text Available Após terem sido apreciadas, à luz de fatos experimentais, as principais causas determinantes das multiplicações celulares normais e aquelas responsabilidades pelas multiplicações anormais, encontradas nos tumores blastomatosos, foram analisados os tumores animais que reconhecidamente são causados por virus tais como: o sarcoma e o epitelioma das galinhas; o papiloma e o mixoma dos coelhos; os carcinomas de ratos e rãs, e finalmente, o papiloma oral e o linfo-sarcoma venéreo dos cães. Em seguida, foram focalizadas as várias propriedades em comum existentes entre os vírus indutores dêsses tumores como: capacidade de determinar multiplicações anormais nos tecidos atacados; elevada especificidade para as espécies sensíveis; existência de diminuição do poder infeccioso à medida que aumenta a capacidade de estimular a formação de tumores e, as afinidades existentes entre êles e os gens, principalmente àquelas referentes à sensibilidade aos raios X. Finalmente, foi aventada a hipótese da possível existência de elementos patogênicos ainda não identificados, situados entre os virus citocinéticos conhecidos e os gens, com poder infeccioso mínimo, exigindo por isso, condições de susceptibilidade ainda não totalmente conhecidas e controladas, possuidores de elevado poder de induzir multiplicações anormais nos tecidos atacados e possìvelmente responsáveis pelos tumores neoplásicos humanos.After being analysed, upon experimental facts, the principal determinant causes of the normal cellular multiplication, and of the abnormal, found in the tumors, were studied the animal tumors caused by viruses like chicken sarcoma and epithelioma, rabbit, papiloma and infectious myxomatosis, rat and frog carcinoma and also oral papiloma and venereal lympho-sarcoma of dog. After words there was focused the various common properties existing between the induction viruses of such tumors like that of abnormal cellular multiplication in

  10. Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D

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    M.O. Diniz

    2011-05-01

    Full Text Available Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5 expressing three proteins (E7, E6, and E5 of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose induced a strong activation of E7-specific interferon-γ (INF-γ-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.

  11. A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection.

    Science.gov (United States)

    Yoshikawa, Rokusuke; Izumi, Taisuke; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Ren, Fengrong; Carpenter, Michael A; Ikeda, Terumasa; Münk, Carsten; Harris, Reuben S; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

    2016-01-01

    Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) DNA cytosine deaminases can be incorporated into progeny virions and inhibit lentiviral replication. On the other hand, viral infectivity factor (Vif) of lentiviruses antagonizes A3-mediated antiviral activities by degrading A3 proteins. It is known that domestic cat (Felis catus) APOBEC3Z3 (A3Z3), the ortholog of human APOBEC3H, potently suppresses the infectivity of vif-defective feline immunodeficiency virus (FIV). Although a recent report has shown that domestic cat encodes 7 haplotypes (hap I to hap VII) of A3Z3, the relevance of A3Z3 polymorphism in domestic cats with FIV Vif has not yet been addressed. In this study, we demonstrated that these feline A3Z3 variants suppress vif-defective FIV infectivity. We also revealed that codon 65 of feline A3Z3 is a positively selected site and that A3Z3 hap V is subject to positive selection during evolution. It is particularly noteworthy that feline A3Z3 hap V is resistant to FIV Vif-mediated degradation and still inhibits vif-proficient viral infection. Moreover, the side chain size, but not the hydrophobicity, of the amino acid at position 65 determines the resistance to FIV Vif-mediated degradation. Furthermore, phylogenetic analyses have led to the inference that feline A3Z3 hap V emerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hap V may have been selected for escape from an ancestral FIV. This is the first evidence for an evolutionary "arms race" between the domestic cat and its cognate lentivirus. Gene diversity and selective pressure are intriguing topics in the field of evolutionary biology. A direct interaction between a cellular protein and a viral protein can precipitate an evolutionary arms race between host and virus. One example is primate APOBEC3G, which potently restricts the replication of primate lentiviruses (e.g., human immunodeficiency virus type 1 [HIV-1] and simian

  12. Impact of Plasma Epstein-Barr Virus-DNA and Tumor Volume on Prognosis of Locally Advanced Nasopharyngeal Carcinoma

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    Meng Chen

    2015-01-01

    Full Text Available This retrospective study aims to examine the association of plasma Epstein-Barr virus- (EBV- DNA levels with the tumor volume and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC. A total of 165 patients with newly diagnosed locally advanced NPC were identified from September 2011 to July 2012. EBV-DNA was detected using fluorescence quantitative polymerase chain reaction (PCR amplification. The tumor volume was calculated by the systematic summation method of computer software. The median copy number of plasma EBV-DNA before treatment was 3790 copies/mL. The median gross tumor volume of the primary nasopharyngeal tumor (GTVnx, the lymph node lesions (GTVnd, and the total GTV before treatment were 72.46, 23.26, and 106.25 cm3, respectively; the EBV-DNA levels were significantly correlated with the GTVnd and the total GTV (P<0.01. The 2-year overall survival (OS rates in patients with positive and negative pretreatment plasma EBV-DNA were 100% and 98.4% (P=1.000, and the disease-free survival (DFS rates were 94.4% and 80.8% (P=0.044, respectively. These results indicate that high pretreatment plasma EBV-DNA levels in patients with locally advanced NPC are associated with the degree of lymph node metastasis, tumor burden, and poor prognosis.

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

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    Laura Evgin

    2016-01-01

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

  14. Polymicrobial infection and bacterium-mediated epigenetic modification of DNA tumor viruses contribute to pathogenesis.

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    Doolittle, J M; Webster-Cyriaque, J

    2014-04-29

    ABSTRACT The human body plays host to a wide variety of microbes, commensal and pathogenic. In addition to interacting with their host, different microbes, such as bacteria and viruses, interact with each other, sometimes in ways that exacerbate disease. In particular, gene expression of a number of viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV), is known to be regulated by epigenetic modifications induced by bacteria. These viruses establish latent infection in their host cells and can be reactivated by bacterial products. Viral reactivation has been suggested to contribute to periodontal disease and AIDS. In addition, bacterium-virus interactions may play a role in cancers, such as Kaposi's sarcoma, gastric cancer, and head and neck cancer. It is important to consider the effects of coexisting bacterial infections when studying viral diseases in vivo.

  15. Two avirulent, lentogenic strains of Newcastle disease virus are cytotoxic for some human pancreatic tumor lines in vitro.

    Science.gov (United States)

    Walter, Robert J; Attar, Bashar M; Rafiq, Asad; Delimata, Megan; Tejaswi, Sooraj

    2012-09-10

    Pancreatic cancer is the fourth leading cause of cancer death in the U.S. Highly infectious Newcastle disease virus (NDV) strains are known to be very cytotoxic for an array of human tumor cell types in vitro and in vivo but the effects of these and avirulent NDV strains on pancreatic neoplasms are little known. Here, the direct cytolytic effects of the avirulent Hitchner-B1 (B1) and Ulster (U) NDV strains on 7 human pancreatic tumor cell lines and 4 normal human cell lines were studied. Cytotoxicity assays used serially diluted NDV to determine minimum cytotoxic plaque forming unit (PFU) doses. For NDV-B1, normal human cells were killed only by relatively high doses (range: 471-3,724 PFU) whereas NDV-U killed these cells at low PFU (range: 0.32-1.60 PFU). Most pancreatic cancer cell types were killed by much lower NDV-B1 doses (range: 0.40-2.60 PFU) while NDV-U killed Capan-1 and SU.86.86 cultures at very low doses (0.00041 PFU and 0.0034 PFU, respectively). On average, 1,555 times more NDV-B1 was needed to kill normal cells than most pancreatic tumor cells and 558 times more NDV-U to kill the two most sensitive pancreatic cancer lines. These innately-targeted lentogenic viruses may have meaningful potential in treating pancreatic cancer.

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

    Science.gov (United States)

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

    2016-11-01

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

  17. Coupled Transcriptome and Proteome Analysis of Human Lymphotropic Tumor Viruses: Insights on the Detection and Discovery of Viral Genes

    Energy Technology Data Exchange (ETDEWEB)

    Dresang, Lindsay R.; Teuton, Jeremy R.; Feng, Huichen; Jacobs, Jon M.; Camp, David G.; Purvine, Samuel O.; Gritsenko, Marina A.; Li, Zhihua; Smith, Richard D.; Sugden, Bill; Moore, Patrick S.; Chang, Yuan

    2011-12-20

    Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. Results The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. Conclusions This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

  18. Tumor virus induction: a model for studying gene derepression by light radiation and chemicals

    International Nuclear Information System (INIS)

    Hellman, K.B.

    1981-01-01

    Cells of most, if not all, animal species contain information for type C retraviruses. This information is normally repressed, but may be derepressed after cellular exposure to a variety of agents. This phenomenon of virus induction can be utilized to investigate the phenomenon of gene derepression, since control of type C virus induction is thought to be under regulatory processes affecting cellular genes. Properties of type C retraviruses, results of virus induction studies, and discussion of a possible mechanism(s) for virus induction are presented in this review. Utilizing the Al-2 nonproducer cell line, originally derived from cells of the BALB/c mouse, quantitative and kinetic dose-response data have been obtained for type C virus induction by uv radiation, chemicals, and biological agents. Studies showing that protease inhibitors suppress induction suggest the presence of a common mechanism for controlling virus induction; i.e., a protein repressor(s) which acts to control virus gene derepression. Since protease inhibitors suppress induction of prophage in E. coli, similar processes may control virus induction in animal and bacterial systems

  19. Biological activity of cloned mammary tumor virus DNA fragments that bind purified glucocorticoid receptor protein in vitro

    International Nuclear Information System (INIS)

    Yamamoto, K.R.; Payvar, F.; Firestone, G.L.; Maler, B.A.; Wrange, O.; Carlstedt-Duke, J.; Gustafsson, J.A.; Chandler, V.L.; Karolinska Institutet, Stockholm, Sweden)

    1983-01-01

    To test whether high-affinity receptor:DNA interactions can be correlated with receptor effects on promoter function in vivo, we have mapped in greater detail the receptor-binding regions on murine mammary tumor virus DNA, using both nitrocellulose-filter binding and electron microscopy. Recombinant plasmids bearing these receptor-binding domains have been transfected into cultured cells, and the expression of the plasmid sequences has been monitored for hormonal regulation. The results are considered in terms of a speculative proposal that the glucocorticoid receptor may effect changes in promoter activity via specific alteration of chromatin and/or DNA structure. 37 references, 6 figures, 2 tables

  20. A rare case of anal carcinosarcoma with human papilloma virus infection in both biphasic tumor elements: An immunohistochemical, molecular and ultrastructural study

    Directory of Open Access Journals (Sweden)

    Richard A. Hickman

    2016-12-01

    Full Text Available Carcinosarcoma of the anus is rare and has yet to be reportedly associated with the keratinocyte-specific Human Papilloma Virus (HPV. We describe a case of anal carcinosarcoma with HPV infection in both the epithelial and mesenchymal components of the tumor by immunohistochemistry, chromogenic in-situ hybridization (CISH and further supported by electron microscopy (EM. Microscopic examination of the tumor showed nests of poorly-differentiated invasive squamous cell carcinoma with basaloid features intermixed with a hypercellular, atypical spindle cell proliferation. Immunohistochemistry demonstrated that the epithelial component was positive for AE1/AE3, p63, CK5/6 and p16, whilst the mesenchymal component was positive for smooth muscle actin, vimentin, and focally positive for desmin and p16, consistent with carcinosarcoma. The tumor was negative for GATA-3, CK7 and CK20. CISH demonstrated that the tumor was positive for high risk HPV (subtype 16/18 in both tumor components. EM further supported the presence of intracellular virus particles (~50 nm that is compatible with HPV infection. Infection of both epithelial and mesenchymal tumor components by HPV has not been previously observed in the gastrointestinal tract. This finding may represent initial epithelial HPV infection with subsequent divergent tumoral differentiation and suggests the presence of viral replication in both biphasic tumor components. Keywords: Carcinosarcoma, Human Papilloma Virus, Gastrointestinal

  1. Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma.

    Science.gov (United States)

    Jiang, De-Ke; Sun, Jielin; Cao, Guangwen; Liu, Yao; Lin, Dongxin; Gao, Yu-Zhen; Ren, Wei-Hua; Long, Xi-Dai; Zhang, Hongxing; Ma, Xiao-Pin; Wang, Zhong; Jiang, Wei; Chen, Tao-Yang; Gao, Yong; Sun, Liang-Dan; Long, Ji-Rong; Huang, Hui-Xing; Wang, Dan; Yu, Hongjie; Zhang, Pengyin; Tang, Li-Sha; Peng, Bo; Cai, Hao; Liu, Ting-Ting; Zhou, Ping; Liu, Fang; Lin, Xiaoling; Tao, Sha; Wan, Bo; Sai-Yin, He-Xi Ge; Qin, Lun-Xiu; Yin, Jianhua; Liu, Li; Wu, Chen; Pei, Yan; Zhou, Yuan-Feng; Zhai, Yun; Lu, Pei-Xin; Tan, Aihua; Zuo, Xian-Bo; Fan, Jia; Chang, Jiang; Gu, Xiaoli; Wang, Neng-Jin; Li, Yang; Liu, Yin-Kun; Zhai, Kan; Zhang, Hongwei; Hu, Zhibin; Liu, Jun; Yi, Qing; Xiang, Yongbing; Shi, Rong; Ding, Qiang; Zheng, Wei; Shu, Xiao-Ou; Mo, Zengnan; Shugart, Yin Yao; Zhang, Xue-Jun; Zhou, Gangqiao; Shen, Hongbing; Zheng, S Lilly; Xu, Jianfeng; Yu, Long

    2013-01-01

    To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).

  2. Capsid proteins from field strains of foot-and-mouth disease virus confer a pathogenic phenotype in cattle on an attenuated, cell-culture-adapted virus

    DEFF Research Database (Denmark)

    Bøtner, Anette; Kakker, Naresh K.; Barbezange, Cyril

    2011-01-01

    Chimeric foot-and-mouth disease viruses (FMDVs) have been generated from plasmids containing full-length FMDV cDNAs and characterized. The parental virus cDNA was derived from the cell-culture-adapted O1Kaufbeuren B64 (O1K B64) strain. Chimeric viruses, containing capsid coding sequences derived...... cells than the rescued parental O1K B64 virus. The two chimeric viruses displayed the expected antigenicity in serotype-specific antigen ELISAs. Following inoculation of each virus into cattle, the rescued O1K B64 strain proved to be attenuated whereas, with each chimeric virus, typical clinical signs...... region within the O1K B64 strain that inhibits replication in cattle. These chimeric infectious cDNA plasmids provide a basis for the analysis of FMDV pathogenicity and characterization of receptor utilization in vivo....

  3. Polyomavirus-Negative Merkel Cell Carcinoma: A More Aggressive Subtype Based on Analysis of 282 Cases Using Multimodal Tumor Virus Detection.

    Science.gov (United States)

    Moshiri, Ata S; Doumani, Ryan; Yelistratova, Lola; Blom, Astrid; Lachance, Kristina; Shinohara, Michi M; Delaney, Martha; Chang, Oliver; McArdle, Susan; Thomas, Hannah; Asgari, Maryam M; Huang, Meei-Li; Schwartz, Stephen M; Nghiem, Paul

    2017-04-01

    Previous studies have reached conflicting conclusions regarding the proportion of Merkel cell carcinomas (MCCs) that contain the Merkel cell polyomavirus (MCPyV) and the clinical significance of tumor viral status. To address these controversies, we detected MCPyV large T antigen using immunohistochemistry with two distinct antibodies and MCPyV DNA using quantitative PCR. Tumors were called MCPyV-positive if two or more of these three assays indicated presence of this virus. A total of 53 of 282 (19%) MCC tumors in this cohort were virus-negative using this multimodal system. Immunohistochemistry with the CM2B4 antibody had the best overall performance (sensitivity = 0.882, specificity = 0.943) compared with the multimodal classification. Multivariate analysis including age, sex, and immunosuppression showed that, relative to MCC patients with virus-positive tumors, virus-negative MCC patients had significantly increased risk of disease progression (hazard ratio = 1.77, 95% confidence interval = 1.20-2.62) and death from MCC (hazard ratio = 1.85, 95% confidence interval = 1.19-2.89). We confirm that approximately 20% of MCCs are not driven by MCPyV and that such virus-negative MCCs, which can be quite reliably identified by immunohistochemistry using the CM2B4 antibody alone, represent a more aggressive subtype that warrants closer clinical follow-up. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Single Amino Acid Insertion in Loop 4 Confers Amphotropic Murine Leukemia Virus Receptor Function upon Murine Pit1

    DEFF Research Database (Denmark)

    Lundorf, Mikkel D.; Pedersen, Finn Skou; O'Hara, Bryan

    1998-01-01

    Pit1 is the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related human protein Pit2 is a receptor for amphotropic murine leukemia virus (A-MuLV). The A-MuLV-related isolate 10A1 can utilize both Pit1 and Pit2 as receptors. A stretch...

  5. Efficient Production of an Engineered Apoptin from Chicken Anemia Virus in a Recombinant E. coli for Tumor Therapeutic Applications

    Directory of Open Access Journals (Sweden)

    Lee Meng-Shiou

    2012-06-01

    Full Text Available Abstract Background Apoptin, a nonstructural protein encoded by the VP3 gene of chicken anemia virus (CAV, has been shown to not only induce apoptosis when introduced into the precursors of chicken thymocytes, but has been found to specifically kill human cancer cells, tumor cell and transformed cells without affecting the proliferation of normal cells. This tumor-specific apoptotic characteristic of the protein potentially may allow the development of a protein drug that has applications in tumor therapy. However, several major problems, which include poor expression and poor protein solubility, have hampered the production of apoptin in bacteria. Results Significantly increased expression of recombinant full-length apoptin that originated from chicken anemia virus was demonstrated using an E. coli expression system. The CAV VP3 gene was fused with a synthetic sequence containing a trans-acting activator of transcription (TAT protein transduction domain (PTD. The resulting construct was cloned into various different expression vectors and these were then expressed in various E. coli strains. The expression of the TAT-Apoptin in E. coli was significantly increased when TAT-Apoptin was fused with GST-tag rather than a His-tag. When the various rare amino acid codons of apoptin were optimized, the expression level of the GST-TAT-Apoptinopt in E. coli BL21(DE3 was significantly further increased. The highest protein expression level obtained was 8.33 g/L per liter of bacterial culture after induction with 0.1 mM IPTG for 4 h at 25 °C. Moreover, approximately 90% of the expressed GST-TAT-Apoptinopt under these conditions was soluble. After purification by GST affinity chromatography, the purified recombinant TAT-Apoptinopt protein was used to evaluate the recombinant protein’s apoptotic activity on tumor cells. The results demonstrated that the E. coli-expressed GST-TAT-apoptinopt showed apoptotic activity and was able to induce human

  6. Enhanced tumor control of human Glioblastoma Multiforme xenografts with the concomitant use of radiotherapy and an attenuated herpes simplex-1 virus (ASTRO research fellowship)

    International Nuclear Information System (INIS)

    Song, Paul Y.; Sibley, Gregory S.; Advani, Sunil; Hallahan, Dennis; Hyland, John; Kufe, Donald W.; Chou, Joany; Roizman, Bernard; Weichselbaum, Ralph R.

    1996-01-01

    Purpose: Glioblastoma Multiforme remains one of the most incurable of human tumors. The current treatment outcomes are dismal. There are several recent reports which suggest that some human glioblastoma xenografts implanted in the brains of athymic mice may be potentially cured with the use of an attenuated herpes simplex-1 virus alone. We have chosen a replication competent, non-neurovirulent HSV-1 mutant, designated R3616 to determine whether there is an interactive cell killing and enhanced tumor control with radiotherapy in the treatment of a human glioblastoma xenograft. Materials and Methods: In vivo, 1 mm 3 pieces of U-87 human glioblastoma cell line xenografts were implanted into the right hind limb of athymic mice and grown to > 200 mm 3 . A total of 112 mice were then equally distributed within four treatment arms (see chart below) based upon tumor volume. Xenografts selected to receive virus as part of the therapy were inoculated with three injections of 2 x 10 7 plaque forming units (PFU) of R3616 virus given on day 1, 2, and 3 for a total dose of 6 x 10 7 PFU. R3616 is a non-neurovirulent HSV-1 mutant created by the deletion of the γ 34.5 gene. Local field irradiation was delivered on day 2 (20 Gy) and day 3 (25 Gy). The mice were then followed for 60 days during which time the xenografts were measured twice weekly. A clinically non-palpable tumor (< 10% original volume) was scored as a cure. In addition percent-fractional tumor volume (FTV) and mean tumor volume (MTV) were calculated for each group. Results: Conclusion: While our tumor control with R3616 alone is similar to that reported in the literature, we have seen significantly enhanced tumor control and cell killing with the addition of RT suggesting a synergistic interaction between an oncolytic virus and radiation in the treatment of human glioblastoma multiforme xenografts

  7. Recombinant Vaccinia Viruses Coding Transgenes of Apoptosis-Inducing Proteins Enhance Apoptosis But Not Immunogenicity of Infected Tumor Cells

    Science.gov (United States)

    Tkachenko, Anastasiya; Richter, Vladimir

    2017-01-01

    Genetic modifications of the oncolytic vaccinia virus (VV) improve selective tumor cell infection and death, as well as activation of antitumor immunity. We have engineered a double recombinant VV, coding human GM-CSF, and apoptosis-inducing protein apoptin (VV-GMCSF-Apo) for comparing with the earlier constructed double recombinant VV-GMCSF-Lact, coding another apoptosis-inducing protein, lactaptin, which activated different cell death pathways than apoptin. We showed that both these recombinant VVs more considerably activated a set of critical apoptosis markers in infected cells than the recombinant VV coding GM-CSF alone (VV-GMCSF-dGF): these were phosphatidylserine externalization, caspase-3 and caspase-7 activation, DNA fragmentation, and upregulation of proapoptotic protein BAX. However, only VV-GMCSF-Lact efficiently decreased the mitochondrial membrane potential of infected cancer cells. Investigating immunogenic cell death markers in cancer cells infected with recombinant VVs, we demonstrated that all tested recombinant VVs were efficient in calreticulin and HSP70 externalization, decrease of cellular HMGB1, and ATP secretion. The comparison of antitumor activity against advanced MDA-MB-231 tumor revealed that both recombinants VV-GMCSF-Lact and VV-GMCSF-Apo efficiently delay tumor growth. Our results demonstrate that the composition of GM-CSF and apoptosis-inducing proteins in the VV genome is very efficient tool for specific killing of cancer cells and for activation of antitumor immunity. PMID:28951871

  8. A rare case of anal carcinosarcoma with human papilloma virus infection in both biphasic tumor elements: An immunohistochemical, molecular and ultrastructural study.

    Science.gov (United States)

    Hickman, Richard A; Bradshaw, Azore-Dee; Cassai, Nicholas; Neto, Antonio Galvao; Zhou, David; Fu, Tinghao; Lee, Peng; Pei, Zhiheng; Wieczorek, Rosemary

    2016-12-01

    Carcinosarcoma of the anus is rare and has yet to be reportedly associated with the keratinocyte-specific Human Papilloma Virus (HPV). We describe a case of anal carcinosarcoma with HPV infection in both the epithelial and mesenchymal components of the tumor by immunohistochemistry, chromogenic in-situ hybridization (CISH) and further supported by electron microscopy (EM). Microscopic examination of the tumor showed nests of poorly-differentiated invasive squamous cell carcinoma with basaloid features intermixed with a hypercellular, atypical spindle cell proliferation. Immunohistochemistry demonstrated that the epithelial component was positive for AE1/AE3, p63, CK5/6 and p16, whilst the mesenchymal component was positive for smooth muscle actin, vimentin, and focally positive for desmin and p16, consistent with carcinosarcoma. The tumor was negative for GATA-3, CK7 and CK20. CISH demonstrated that the tumor was positive for high risk HPV (subtype 16/18) in both tumor components. EM further supported the presence of intracellular virus particles (~50 nm) that is compatible with HPV infection. Infection of both epithelial and mesenchymal tumor components by HPV has not been previously observed in the gastrointestinal tract. This finding may represent initial epithelial HPV infection with subsequent divergent tumoral differentiation and suggests the presence of viral replication in both biphasic tumor components.

  9. A virus-like particle based bivalent vaccine confers dual protection against enterovirus 71 and coxsackievirus A16 infections in mice.

    Science.gov (United States)

    Ku, Zhiqiang; Liu, Qingwei; Ye, Xiaohua; Cai, Yicun; Wang, Xiaoli; Shi, Jinping; Li, Dapeng; Jin, Xia; An, Wenqi; Huang, Zhong

    2014-07-23

    Enterovirus 71(EV71) and coxsackievirus A16 (CA16) are responsible for hand, foot and mouth disease which has been prevalent in Asia-Pacific regions, causing significant morbidity and mortality in young children. Co-circulation of and co-infection by both viruses underscores the importance and urgency of developing vaccines against both viruses simultaneously. Here we report the immunogenicity and protective efficacy of a bivalent combination vaccine comprised of EV71 and CA16 virus-like particles (VLPs). We show that monovalent EV71- or CA16-VLPs-elicited serum antibodies exhibited potent neutralization effect on the homotypic virus but little or no effect on the heterotypic one, whereas the antisera against the bivalent vaccine formulation were able to efficiently neutralize both EV71 and CA16, indicating there is no immunological interference between the two antigens with respect to their ability to induce virus-specific neutralizing antibodies. Passive immunization with monovalent VLP vaccines protected mice against a homotypic virus challenge but not heterotypic infection. Surprisingly, antibody-dependent enhancement (ADE) of disease was observed in mice passively transferred with mono-specific anti-CA16 VLP sera and subsequently challenged with EV71. In contrast, the bivalent VLP vaccine conferred full protection against lethal challenge by either EV71 or CA16, thus eliminating the potential of ADE. Taken together, our results demonstrate for the first time that the bivalent VLP approach represents a safe and efficacious vaccine strategy for both EV71 and CA16. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

    Science.gov (United States)

    Iwase, Y; Takemura, Y; Ju-ichi, M; Ito, C; Furukawa, H; Kawaii, S; Yano, M; Mou, X Y; Takayasu, J; Tokuda, H; Nishino, H

    2000-06-01

    To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

  11. Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumor burden, and metabolic activity in advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Ma, Brigette; King, Ann; Lo, Y.M. Dennis; Yau, Y.Y.; Zee, Benny; Hui, Edwin P.; Leung, Sing F.; Mo, Frankie; Kam, Michael K.; Ahuja, Anil; Kwan, Wing H.; Chan, Anthony

    2006-01-01

    Purpose: Plasma Epstein-Barr virus DNA (pEBV DNA) is an important prognostic marker in nasopharyngeal carcinoma (NPC). This study tested the hypotheses that pEBV DNA reflects tumor burden and metabolic activity by evaluating its relationship with tumor volume and 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake in NPC. Methods and Materials: Pre-treatment pEBV DNA analysis, 18 F-FDG positron emission tomography-computed tomography scan (PET-CT) and magnetic resonance imaging (MRI) of the head and neck were performed in 57 patients. Net volume (cm 3 ) of the primary tumor (T vol ) and regional nodes (N vol ) were quantified on MRI. 18 F-FDG uptake was expressed as the maximum standardized uptake value (SUV max ) at the primary tumor (T suv ) and regional nodes (N suv ). Lesions with SUV max ≥ 2.5 were considered malignant. Relationship between SUV max , natural logarithm (log) of pEBV DNA, and square root (sq) of MRI volumes was analyzed using the Wilcoxon test. A linear regression model was constructed to test for any interaction between variables and disease stage. Results: Log-pEBV DNA showed significant correlation with sq-T vol (r = 0.393), sq-N vol (r = 0.452), total tumor volume (sq-Total vol = T vol + N vol , r = 0.554), T suv (r = 0.276), N suv (r = 0.434), and total SUV max (Total suv = T suv + N suv , r = 0.457). Likewise, sq-T vol was correlated to T suv (r 0.426), and sq-N vol with N suv (r = 0.651). Regression analysis showed that only log-pEBV DNA was significantly associated with sq-Total vol (p vol was significantly associated with T suv (p = 0.002; parameter estimate = 3.923; 95% confidence interval = 1.498-6.348). Conclusion: This study supports the hypothesis that cell-free plasma EBV DNA is a marker of tumor burden in EBV-related NPC

  12. IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

    Science.gov (United States)

    Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

    2016-10-27

    Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8 + T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8 + T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated with

  13. Expression of self-complementary hairpin RNA under the control of the rolC promoter confers systemic disease resistance to plum pox virus without preventing local infection.

    Science.gov (United States)

    Pandolfini, Tiziana; Molesini, Barbara; Avesani, Linda; Spena, Angelo; Polverari, Annalisa

    2003-06-25

    Homology-dependent selective degradation of RNA, or post-transcriptional gene silencing (PTGS), is involved in several biological phenomena, including adaptative defense mechanisms against plant viruses. Small interfering RNAs mediate the selective degradation of target RNA by guiding a multicomponent RNAse. Expression of self-complementary hairpin RNAs within two complementary regions separated by an intron elicits PTGS with high efficiency. Plum pox virus (PPV) is the etiological agent of sharka disease in Drupaceae, although it can also be transmitted to herbaceous species (e.g. Nicotiana benthamiana). Once inside the plant, PPV is transmitted via plasmodesmata from cell to cell, and at longer distances, via phloem. The rolC promoter drives expression in phloem cells. RolC expression is absent in both epidermal and mesophyll cells. The aim of the present study was to confer systemic disease resistance without preventing local viral infection. In the ihprolC-PP197 gene (intron hair pin rolC PPV 197), a 197 bp sequence homologous to the PPV RNA genome (from base 134 to 330) was placed as two inverted repeats separated by the DNA sequence of the rolA intron. This hairpin construct is under the control of the rolC promoter.N. benthamiana plants transgenic for the ihprolC-PP197 gene contain siRNAs homologous to the 197 bp sequence. The transgenic progeny of ihprolC-PP197 plants are resistant to PPV systemic infection. Local infection is unaffected. Most (80%) transgenic plants are virus free and symptomless. Some plants (20%) contain virus in uninoculated apical leaves; however they show only mild symptoms of leaf mottling. PPV systemic resistance cosegregates with the ihprolC-PP197 transgene and was observed in progeny plants of all independent transgenic lines analyzed. SiRNAs of 23-25 nt homologous to the PPV sequence used in the ihprolC-PP197 construct were detected in transgenic plants before and after inoculation. Transitivity of siRNAs was observed in

  14. Expression of self-complementary hairpin RNA under the control of the rolC promoter confers systemic disease resistance to plum pox virus without preventing local infection

    Directory of Open Access Journals (Sweden)

    Spena Angelo

    2003-06-01

    Full Text Available Abstract Background Homology-dependent selective degradation of RNA, or post-transcriptional gene silencing (PTGS, is involved in several biological phenomena, including adaptative defense mechanisms against plant viruses. Small interfering RNAs mediate the selective degradation of target RNA by guiding a multicomponent RNAse. Expression of self-complementary hairpin RNAs within two complementary regions separated by an intron elicits PTGS with high efficiency. Plum pox virus (PPV is the etiological agent of sharka disease in Drupaceae, although it can also be transmitted to herbaceous species (e.g. Nicotiana benthamiana. Once inside the plant, PPV is transmitted via plasmodesmata from cell to cell, and at longer distances, via phloem. The rolC promoter drives expression in phloem cells. RolC expression is absent in both epidermal and mesophyll cells. The aim of the present study was to confer systemic disease resistance without preventing local viral infection. Results In the ihprolC-PP197 gene (intron hair pin rolC PPV 197, a 197 bp sequence homologous to the PPV RNA genome (from base 134 to 330 was placed as two inverted repeats separated by the DNA sequence of the rolA intron. This hairpin construct is under the control of the rolC promoter.N. benthamiana plants transgenic for the ihprolC-PP197 gene contain siRNAs homologous to the 197 bp sequence. The transgenic progeny of ihprolC-PP197 plants are resistant to PPV systemic infection. Local infection is unaffected. Most (80% transgenic plants are virus free and symptomless. Some plants (20% contain virus in uninoculated apical leaves; however they show only mild symptoms of leaf mottling. PPV systemic resistance cosegregates with the ihprolC-PP197 transgene and was observed in progeny plants of all independent transgenic lines analyzed. SiRNAs of 23–25 nt homologous to the PPV sequence used in the ihprolC-PP197 construct were detected in transgenic plants before and after inoculation

  15. Early Increases in Superantigen-Specific Foxp3+ Regulatory T Cells during Mouse Mammary Tumor Virus Infection▿ †

    Science.gov (United States)

    Cabrera, Gabriel; Burzyn, Dalia; Mundiñano, Juliana; Courreges, M. Cecilia; Camicia, Gabriela; Lorenzo, Daniela; Costa, Héctor; Ross, Susan R.; Nepomnaschy, Irene; Piazzon, Isabel

    2008-01-01

    Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. Here, we show in a natural model of MMTV infection that the virus causes early and progressive increases in superantigen (SAg)-specific Foxp3+ regulatory T cells (Treg) in Peyer's patches (PP). These increases were shown to be dependent on the presence of dendritic cells. CD4+ CD25+ T cells from the PP of infected mice preferentially suppress the proliferative response of T cells to SAg-expressing antigen-presenting cells ex vivo. We investigated the influence of the depletion of CD25+ cells at different stages of the infection. When CD25+ cells were depleted before MMTV infection, an increase in the number of PP SAg-cognate Foxp3− T cells was found at day 6 of infection. Since the SAg response is associated with viral amplification, the possibility exists that Treg cells attenuate the increase in viral load at the beginning of the infection. In contrast, depletion of CD25+ cells once the initial SAg response has developed caused a lower viral load, suggesting that at later stages Treg cells may favor viral persistence. Thus, our results indicated that Treg cells play an important and complex role during MMTV infection. PMID:18495774

  16. Epstein-Barr virus patterns in US Burkitt lymphoma tumors from the SEER residual tissue repository during 1979-2009.

    Science.gov (United States)

    Mbulaiteye, Sam M; Pullarkat, Sheeja T; Nathwani, Bharat N; Weiss, Lawrence M; Rao, Nagesh; Emmanuel, Benjamin; Lynch, Charles F; Hernandez, Brenda; Neppalli, Vishala; Hawes, Debra; Cockburn, Myles G; Kim, Andre; Williams, Makeda; Altekruse, Sean; Bhatia, Kishor; Goodman, Marc T; Cozen, Wendy

    2014-01-01

    Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein-Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV-encoded RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi-squared statistics, and Student's t-test. Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0-19, 20-34, 35-59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age group 0-19 to 55% in age group 20-34, and fell to 25% in age group 60+ years, p = 0.08); with race (56% in Blacks/Hispanics vs 21% in Whites/Asians/Pacific Islanders, p = 0.006); and by HIV status (64% in HIV positive vs 22% in HIV negative cases, p = 0.03). EBER positivity was demonstrated in about one-third of tumors and it was strongly associated with race and HIV status, and marginally with age-group. © 2013 APMIS Published by Blackwell Publishing Ltd.

  17. Search for virus-related genetic information in human tumors DNA by the transfection method

    Energy Technology Data Exchange (ETDEWEB)

    Knyazev, P G; Perevozchikov, A P; Korobitsyn, L P; Zhudina, A I; Kuznetsov, O K; Savost' yanov, G A; Dyad' kova, A M; Sejts, I F [Nauchno-Issledovatel' skij Inst. Onkologii, Leningrad (USSR)

    1979-01-01

    DNA preparations from the blood cells of a patient suffering from acute myeloid leukemia, from tissues of polymorphous cell rhabdomyosarcoma, synovial sarcoma and neurinoma were studied. The production of virus-like RNA-containing particles (according to radioisotope analysis and the content of reverse transcriptase in these particles) was observed in cultures of embryonic human cells treated with DNA from the cells of leukemia patient.

  18. Canine distemper virus induces apoptosis in cervical tumor derived cell lines

    Directory of Open Access Journals (Sweden)

    Rajão Daniela S

    2011-06-01

    Full Text Available Abstract Apoptosis can be induced or inhibited by viral proteins, it can form part of the host defense against virus infection, or it can be a mechanism for viral spread to neighboring cells. Canine distemper virus (CDV induces apoptotic cells in lymphoid tissues and in the cerebellum of dogs naturally infected. CDV also produces a cytopathologic effect, leading to apoptosis in Vero cells in tissue culture. We tested canine distemper virus, a member of the Paramyxoviridae family, for the ability to trigger apoptosis in HeLa cells, derived from cervical cancer cells resistant to apoptosis. To study the effect of CDV infection in HeLa cells, we examined apoptotic markers 24 h post infection (pi, by flow cytometry assay for DNA fragmentation, real-time PCR assay for caspase-3 and caspase-8 mRNA expression, and by caspase-3 and -8 immunocytochemistry. Flow cytometry showed that DNA fragmentation was induced in HeLa cells infected by CDV, and immunocytochemistry revealed a significant increase in the levels of the cleaved active form of caspase-3 protein, but did not show any difference in expression of caspase-8, indicating an intrinsic apoptotic pathway. Confirming this observation, expression of caspase-3 mRNA was higher in CDV infected HeLa cells than control cells; however, there was no statistically significant change in caspase-8 mRNA expression profile. Our data suggest that canine distemper virus induced apoptosis in HeLa cells, triggering apoptosis by the intrinsic pathway, with no participation of the initiator caspase -8 from the extrinsic pathway. In conclusion, the cellular stress caused by CDV infection of HeLa cells, leading to apoptosis, can be used as a tool in future research for cervical cancer treatment and control.

  19. Circular RNA alterations are involved in resistance to avian leukosis virus subgroup-J-induced tumor formation in chickens.

    Science.gov (United States)

    Zhang, Xinheng; Yan, Yiming; Lei, Xiaoya; Li, Aijun; Zhang, Huanmin; Dai, Zhenkai; Li, Xinjian; Chen, Weiguo; Lin, Wencheng; Chen, Feng; Ma, Jingyun; Xie, Qingmei

    2017-05-23

    Avian leukosis virus subgroup (ALV-J) is an oncogenic neoplasm-inducing retrovirus that causes significant economic losses in the poultry industry. Recent studies have demonstrated circular RNAs (circRNAs) are implicated in pathogenic processes; however, no research has indicated circRNAs are involved in resistance to disease. In this study, over 1800 circRNAs were detected by circRNA sequencing of liver tissues from ALV-J-resistant (n = 3) and ALV-J-susceptible chickens (n = 3). 32 differentially expressed circRNAs were selected for analyzing including 12 upregulated in ALV-J-resistant chickens and 20 upregulated in ALV-J-susceptible chickens, besides, the top five microRNAs (miRNAs) for 12 upregulated circRNAs in ALV-J-resistant chickens were analyzed. Gene ontology and KEGG pathway analyses were performed for miRNA target genes, the predicted genes were mainly involved in immune pathways. This study provides the first evidence that circRNA alterations are involved in resistance to ALV-J-induced tumor formation. We propose circRNAs may help to mediate tumor induction and development in chickens.

  20. Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Joseph Kwong

    2009-06-01

    Full Text Available In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.

  1. Improved protection conferred by vaccination with a recombinant vaccinia virus that incorporates a foreign antigen into the extracellular enveloped virion

    International Nuclear Information System (INIS)

    Kwak, Heesun; Mustafa, Waleed; Speirs, Kendra; Abdool, Asha J.; Paterson, Yvonne; Isaacs, Stuart N.

    2004-01-01

    Recombinant poxviruses have shown promise as vaccine vectors. We hypothesized that improved cellular immune responses could be developed to a foreign antigen by incorporating it as part of the extracellular enveloped virion (EEV). We therefore constructed a recombinant vaccinia virus that replaced the cytoplasmic domain of the B5R protein with a test antigen, HIV-1 Gag. Mice immunized with the virus expressing Gag fused to B5R had significantly better primary CD4 T-cell responses than recombinant virus expressing HIV-Gag from the TK-locus. The CD8 T-cell responses were less different between the two groups. Importantly, although we saw differences in the immune response to the test antigen, the vaccinia virus-specific immune responses were similar with both constructs. When groups of vaccinated mice were challenged 30 days later with a recombinant Listeria monocytogenes that expresses HIV-Gag, mice inoculated with the virus that expresses the B5R-Gag fusion protein had lower colony counts of Listeria in the liver and spleen than mice vaccinated with the standard recombinant. Thus, vaccinia virus expressing foreign antigen incorporated into EEV may be a better vaccine strategy than standard recombinant vaccinia virus

  2. Anti-tumoral effect of recombinant vaccinia virus through US guided injection in a rabbit model of hepatic VX2 carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jong Young; Park, Byeong Ho; Kang, Myong Jin; Cho, Jin Han; Choi, Jong Cheol; Choi, Sun Seob; Nam, Kyung Jin; Hwang, Tae Ho; Jeong, Jin Sook [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2006-02-15

    The purpose of this study was to evaluate the anti-tumoral effect of recombinant vaccinia virus (rVV) (Thymidine kinase (-)/GM-CSF (+)) that was administered as a US guided intratumoral injection in a rabbit model of hepatic VX2 carcinoma. VX2 carcinoma was implanted in the livers of 12 rabbits. US was performed at every week interval to detect hepatic mass after the implantation of VX2 carcinoma. The accurate tumor size and volume was evaluated with CT when the tumor was detected on US. US guided injection of rVV (10{sup 9} pfu/ml) was preformed in three rabbits, intravenous injection of the same dose of rVV was done in two rabbits and another seven rabbits that were without any treatment were selected as a control group. We evaluated the change of the hepatic tumor size and extrahepatic metastasis on serial CT. Tumor specimens were harvested from rabbits that were killed at 8 weeks after VX2 implantation. These tissues were histoimmuopathologically compared to each other (the virus injection group and the control group). The differences between these groups were statistically assessed with student t-tests. Tumor growth was significantly suppressed in the US guided injection group compared with the intravenous injection group or the control group ({rho} < 0.01). The intravenous injection group showed statistically significant tumor suppression compared to the control group ({rho} < 0.01) until 2 weeks after virus injection. Quantification of the pulmonary metastatic nodules was performed in view of both the number and volume. The average number or volume of the pulmonary metastatic nodules in the US injection group was much smaller than these in the control group. Histopathologically, the tumors of the US guided injection group showed less extensive necrosis than those of the control group. Immunohistochemically, the tumor of the US guided injection group showed more prominent infiltration of CD4 (+) and CD8 (+) lymphocytes than did the tumors of the other group

  3. Miniaturizing 3D assay for high-throughput drug and genetic screens for small patient-derived tumor samples (Conference Presentation)

    Science.gov (United States)

    Rotem, Asaf; Garraway, Levi; Su, Mei-Ju; Basu, Anindita; Regev, Aviv; Struhl, Kevin

    2017-02-01

    Three-dimensional growth conditions reflect the natural environment of cancer cells and are crucial to be performed at drug screens. We developed a 3D assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the 50-year old benchmark assay-soft agar. Using GILA, we performed high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. This phenotypic approach is complementary to our genetic approach that utilizes single-cell RNA-sequencing of a patient sample to identify putative oncogenes that confer sensitivity to drugs designed to specifically inhibit the identified oncoprotein. Currently, we are dealing with a big challenge in our field- the limited number of cells that might be extracted from a biopsy. Small patient-derived samples are hard to test in the traditional multiwell plate and it will be helpful to minimize the culture area and the experimental system. We managed to design a suitable microfluidic device for limited number of cells and perform the assay using image analysis. We aim to test drugs on tumor cells, outside of the patient body- and recommend on the ideal treatment that is tailored to the individual. This device will help to minimize biopsy-sampling volumes and minimize interventions in the patient's tumor.

  4. Recessive resistance to Bean common mosaic virus conferred by the bc-1 and bc-2 genes in common bean (Phaseolus vulgaris L.) affects long distance movement of the virus.

    Science.gov (United States)

    Feng, Xue; Orellana, Gardenia; Myers, James; Karasev, Alexander V

    2018-04-12

    Recessive resistance to Bean common mosaic virus (BCMV) in common bean (Phaseolus vulgaris L.) is governed by four genes that include one strain-nonspecific helper gene bc-u, and three strain-specific genes bc-1, bc-2, and bc-3. The bc-3 gene was identified as an eIF4E translation initiation factor gene mediating resistance through disruption of the interaction between this protein and the VPg protein of the virus. The mode of action of bc-1 and bc-2 in expression of BCMV resistance is unknown, although bc-1 gene was found to affect systemic spread of a related potyvirus, Bean common mosaic necrosis virus. To investigate the possible role of both bc-1 and bc-2 genes in replication, cell-to-cell, and long distance movement of BCMV in P. vulgaris, we tested virus spread of eight BCMV isolates representing pathogroups I, IV, VI, VII, and VIII, in a set of bean differentials expressing different combinations of six resistance alleles including bc-u, bc-1, bc-1 2 , bc-2, bc-2 2 , and bc-3. All studied BCMV isolates were able to replicate and spread in inoculated leaves of bean cultivars harboring bc-u, bc-1, bc-1 2 , bc-2, and bc-2 2 alleles and their combinations, while no BCMV replication was found in inoculated leaves of 'IVT7214' carrying the bc-u, bc-2 and bc-3 genes, except for isolate 1755a capable of overcoming the resistance conferred by bc-2 and bc-3. In contrast, the systemic spread of all BCMV isolates from pathogroups I, IV,VI, VII, and VIII was impaired in common bean cultivars carrying bc-1, bc-1 2 , bc-2, and bc-2 2 alleles. The data suggest that bc-1 and bc-2 recessive resistance genes have no effect on the replication and cell-to-cell movement of BCMV, but affect systemic spread of BCMV in common bean. The BCMV resistance conferred by bc-1 and bc-2 and affecting systemic spread was found only partially effective when these two genes were expressed singly. The efficiency of the restriction of the systemic spread of the virus was greatly enhanced when

  5. Thy1+ NK [corrected] cells from vaccinia virus-primed mice confer protection against vaccinia virus challenge in the absence of adaptive lymphocytes.

    Directory of Open Access Journals (Sweden)

    Geoffrey O Gillard

    2011-08-01

    Full Text Available While immunological memory has long been considered the province of T- and B-lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now show that an innate memory immune response is generated in mice following infection with vaccinia virus, a poxvirus for which no cognate germline-encoded receptor has been identified. This immune response results in viral clearance in the absence of classical adaptive T and B lymphocyte populations, and is mediated by a Thy1(+ subset of natural killer (NK cells. We demonstrate that immune protection against infection from a lethal dose of virus can be adoptively transferred with memory hepatic Thy1(+ NK cells that were primed with live virus. Our results also indicate that, like classical immunological memory, stronger innate memory responses form in response to priming with live virus than a highly attenuated vector. These results demonstrate that a defined innate memory cell population alone can provide host protection against a lethal systemic infection through viral clearance.

  6. Hantaan Virus Nucleocapsid Protein Binds to Importin alpha Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B

    Science.gov (United States)

    2008-11-19

    Microbiology . All Rights Reserved. Hantaan Virus Nucleocapsid Protein Binds to Importin Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced...Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702,1 and Department of Microbiology , Mount Sinai...34–36. 32. Prescott , J., C. Ye, G. Sen, and B. Hjelle. 2005. Induction of innate immune response genes by Sin Nombre hantavirus does not require

  7. Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus-Driven Production of a Bispecific T-cell Engager.

    Science.gov (United States)

    Wing, Anna; Fajardo, Carlos Alberto; Posey, Avery D; Shaw, Carolyn; Da, Tong; Young, Regina M; Alemany, Ramon; June, Carl H; Guedan, Sonia

    2018-05-01

    T cells expressing chimeric antigen receptors (CART) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors. We report that CART cells targeting the folate receptor alpha (FR-α) successfully infiltrated preestablished xenograft tumors but failed to induce complete responses, presumably due to the presence of antigen-negative cancer cells. We demonstrated that OAd-BiTE-mediated oncolysis significantly improved CART-cell activation and proliferation, while increasing cytokine production and cytotoxicity, and showed an in vitro favorable safety profile compared with EGFR-targeting CARTs. BiTEs secreted from infected cells redirected CART cells toward EGFR in the absence of FR-α, thereby addressing tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T cells found in CART-cell preparations toward tumor cells. The combinatorial approach improved antitumor efficacy and prolonged survival in mouse models of cancer when compared with the monotherapies, and this was the result of an increased BiTE-mediated T-cell activation in tumors. Overall, these results demonstrated that the combination of a BiTE-expressing oncolytic virus with adoptive CART-cell therapy overcomes key limitations of CART cells and BiTEs as monotherapies in solid tumors and encourage its further evaluation in human trials. Cancer Immunol Res; 6(5); 605-16. ©2018 AACR . ©2018 American Association for Cancer Research.

  8. Inability of Kaplan radiation leukemia virus to replicate on mouse fibroblasts is conferred by its long terminal repeat

    International Nuclear Information System (INIS)

    Rassart, E.; Paquette, Y.; Jolicoeur, P.

    1988-01-01

    The molecularly cloned infectious Kaplan radiation leukemia virus has previously been shown to be unable to replicate on mouse fibroblasts. To map the viral sequences responsible for this, we constructed chimeric viral DNA genomes in vitro with parental cloned infectious viral DNAs from the nonfibrotropic (F-) BL/VL3 V-13 radiation leukemia virus and the fibrotropic (F+) endogenous BALB/c or Moloney murine leukemia viruses (MuLV). Infectious chimeric MuLVs, recovered after transfection of Ti-6 lymphocytes with these recombinant DNAs, were tested for capacity to replicate on mouse fibroblasts in vitro. We found that chimeric MuLVs harboring the long terminal repeat (LTR) of a fibrotropic MuLV replicated well on mouse fibroblasts. Conversely, chimeric MuLVs harboring the LTR of a nonfibrotropic MuLV were restricted on mouse fibroblasts. These results indicate that the LTR of BL/VL3 radiation leukemia virus harbors the primary determinant responsible for its inability to replicate on mouse fibroblasts in vitro. Our results also show that the primary determinant allowing F+ MuLVs (endogenous BALB/c and Moloney MuLVs) to replicate on mouse fibroblasts in vitro resides within the LTR

  9. Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV): consequences of deficient interferon-dependent antiviral defense

    International Nuclear Information System (INIS)

    Echchgadda, Ibtissam; Chang, Te-Hung; Sabbah, Ahmed; Bakri, Imad; Ikeno, Yuji; Hubbard, Gene B; Chatterjee, Bandana; Bose, Santanu

    2011-01-01

    Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human respiratory syncytial virus (RSV) is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells. The present study extends the result to androgen-dependent prostate cancer, and explores the underlying mechanism that triggers RSV-induced oncolysis of prostate cancer cells. The oncolytic effect of RSV on androgen-sensitive LNCaP human prostate cancer cells and on androgen-independent RM1 murine prostate cancer cells was studied in vitro in culture and in vivo in a xenograft or allograft tumor model. In vitro, cell viability, infectivity and apoptosis were monitored by MTT assay, viral plaque assay and annexin V staining, respectively. In vivo studies involved virus administration to prostate tumors grown in immune compromised nude mice and in syngeneic immune competent C57BL/6J mice. Anti-tumorogenic oncolytic activity was monitored by measuring tumor volume, imaging bioluminescent tumors in live animals and performing histopathological analysis and TUNEL assay with tumors We show that RSV imposes a potent oncolytic effect on LNCaP prostate cancer cells. RSV infectivity was markedly higher in LNCaP cells compared to the non-tumorigenic RWPE-1 human prostate cells. The enhanced viral burden led to LNCaP cell apoptosis and growth inhibition of LNCaP xenograft tumors in nude mice. A functional host immune response did not interfere with RSV-induced oncolysis, since growth of xenograft tumors in syngeneic C57BL/6J mice from murine RM1 cells was inhibited upon RSV administration. LNCaP cells failed to activate the type-I interferon (IFNα/β)-induced transcription factor STAT-1, which is required for antiviral gene expression, although these cells could produce IFN in response to RSV infection. The essential role of IFN in restricting infection was further

  10. Precise gene editing of chicken Na+/H+ exchange type 1 (chNHE1) confers resistance to avian leukosis virus subgroup J (ALV-J).

    Science.gov (United States)

    Lee, Hong Jo; Lee, Kyung Youn; Jung, Kyung Min; Park, Kyung Je; Lee, Ko On; Suh, Jeong-Yong; Yao, Yongxiu; Nair, Venugopal; Han, Jae Yong

    2017-12-01

    Avian leukosis virus subgroup J (ALV-J), first isolated in the late 1980s, has caused economic losses to the poultry industry in many countries. As all chicken lines studied to date are susceptible to ALV infection, there is enormous interest in developing resistant chicken lines. The ALV-J receptor, chicken Na + /H + exchange 1 (chNHE1) and the critical amino acid sequences involved in viral attachment and entry have already been characterized. However, there are no reported attempts to induce resistance to the virus by targeted genome modification of the receptor sequences. In an attempt to induce resistance to ALV-J infection, we used clustered regularly interspaced short palindromic repeats (CRISPR)-associated (CRISPR/Cas9)-based genome editing approaches to modify critical residues of the chNHE1 receptor in chicken cells. The susceptibility of the modified cell lines to ALV-J infection was examined using enhanced green fluorescent protein (EGFP)-expressing marker viruses. We showed that modifying the chNHE1 receptor by artificially generating a premature stop codon induced absolute resistance to viral infection, with mutations of the tryptophan residue at position 38 (Trp38) being very critical. Single-stranded oligodeoxynucleotide (ssODN)-mediated targeted recombination of the Trp38 region revealed that deletions involving the Trp38 residue were most effective in conferring resistance to ALV-J. Moreover, protein structure analysis of the chNHE1 receptor sequence suggested that its intrinsically disordered region undergoes local conformational changes through genetic alteration. Collectively, these results demonstrate that targeted mutations on chNHE1 alter the susceptibility to ALV-J and the technique is expected to contribute to develop disease-resistant chicken lines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Tumor necrosis factor-α-induced protein 1 and immunity to hepatitis B virus

    Science.gov (United States)

    Lin, Marie C; Lee, Nikki P; Zheng, Ning; Yang, Pai-Hao; Wong, Oscar G; Kung, Hsiang-Fu; Hui, Chee-Kin; Luk, John M; Lau, George Ka-Kit

    2005-01-01

    AIM: To compare the gene expression profile in a pair of HBV-infected twins. METHODS: The gene expression profile was compared in a pair of HBV-infected twins. RESULTS: The twins displayed different disease outcomes. One acquired natural immunity against HBV, whereas the other became a chronic HBV carrier. Eighty-eight and forty-six genes were found to be up- or down-regulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-αIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RT-PCR. However, upon HBV core antigen stimulation, TNF-αIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+ channel tetramerization domain in TNF-αIP1 that shares a significant homology with some human, mouse, and C elegan proteins. CONCLUSION: TNF-αIP1 may play a role in the innate immunity against HBV. PMID:16437679

  12. Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Fogg, Mark; Murphy, John R.; Lorch, Jochen; Posner, Marshall; Wang, Fred

    2013-01-01

    Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. - Highlights: • Viral proteins are tumor antigens in Epstein–Barr virus associated Nasopharyngeal Carcinoma. • CD8+ T cell responses against EBV proteins EBNA-1 and LMP2 are suppressed in NPC patients. • T regulatory cells are responsible for suppressing EBV immunity in NPC patients. • Depletion of Tregs with Ontak can rescue EBV-specific CD8+ T cell responses in NPC patients. • This clinically approved drug may be effective for enhancing anti-tumor immunity in NPC patients

  13. Mouse Mammary Tumor Virus Promoter-Containing Retroviral Promoter Conversion Vectors for Gene-Directed Enzyme Prodrug Therapy are Functional in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Reinhard Klein

    2008-01-01

    Full Text Available Gene directed-enzyme prodrug therapy (GDEPT is an approach for sensitization of tumor cells to an enzymatically activated, otherwise nontoxic, prodrug. Cytochrome P450 2B1 (CYP2B1 metabolizes the prodrugs cyclophosphamide (CPA and ifosfamide (IFA to produce the cytotoxic substances phosphoramide mustard and isophosphoramide mustard as well as the byproduct acrolein. We have constructed a retroviral promoter conversion (ProCon vector for breast cancer GDEPT. The vector allows expression of CYP2B1 from the mouse mammary tumor virus (MMTV promoter known to be active in the mammary glands of transgenic animals. It is anticipated to be used for the generation of encapsulated viral vector producing cells which, when placed inside or close to a tumor, will act as suppliers of the therapeutic CYP2B1 protein as well as of the therapeutic vector itself. The generated vector was effectively packaged by virus producing cells and allowed the production of high levels of enzymatically active CYP2B1 in infected cells which sensitized them to killing upon treatment with both IFA and CPA. Determination of the respective IC50 values demonstrated that the effective IFA dose was reduced by sixteen folds. Infection efficiencies in vivo were determined using a reporter gene-bearing vector in a mammary cancer cell-derived xenograft tumor mouse model.

  14. Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fogg, Mark [Department of Medicine, Brigham and Women' s Hospital (United States); Murphy, John R. [Departments of Medicine and Microbiology, Boston University School of Medicine, Boston, MA 02118 (United States); Lorch, Jochen; Posner, Marshall [Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Wang, Fred, E-mail: fwang@research.bwh.harvard.edu [Department of Medicine, Brigham and Women' s Hospital (United States); Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 (United States)

    2013-07-05

    Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. - Highlights: • Viral proteins are tumor antigens in Epstein–Barr virus associated Nasopharyngeal Carcinoma. • CD8+ T cell responses against EBV proteins EBNA-1 and LMP2 are suppressed in NPC patients. • T regulatory cells are responsible for suppressing EBV immunity in NPC patients. • Depletion of Tregs with Ontak can rescue EBV-specific CD8+ T cell responses in NPC patients. • This clinically approved drug may be effective for enhancing anti-tumor immunity in NPC patients.

  15. Mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low pH compartment and infect cells

    International Nuclear Information System (INIS)

    Wang Enxiu; Obeng-Adjei, Nyamekye; Ying Qihua; Meertens, Laurent; Dragic, Tanya; Davey, Robert A.; Ross, Susan R.

    2008-01-01

    Mouse mammary tumor virus (MMTV) is a pH-dependent virus that uses mouse transferrin receptor 1 (TfR1) for entry into cells. Previous studies demonstrated that MMTV could induce pH 5-dependent fusion-from-with of mouse cells. Here we show that the MMTV envelope-mediated cell-cell fusion requires both the entry receptor and low pH (pH 5). Although expression of the MMTV envelope and TfR1 was sufficient to mediate low pH-dependent syncytia formation, virus infection required trafficking to a low pH compartment; infection was independent of cathepsin-mediated proteolysis. Human TfR1 did not support virus infection, although envelope-mediated syncytia formation occurred with human cells after pH 5 treatment and this fusion depended on TfR1 expression. However, although the MMTV envelope bound human TfR1, virus was only internalized and trafficked to a low pH compartment in cells expressing mouse TfR1. Thus, while human TfR1 supported cell-cell fusion, because it was not internalized when bound to MMTV, it did not function as an entry receptor. Our data suggest that MMTV uses TfR1 for all steps of entry: cell attachment, induction of the conformational changes in Env required for membrane fusion and internalization to an appropriate acidic compartment

  16. A Role for Protein Phosphatase 2A in Regulating p38 Mitogen Activated Protein Kinase Activation and Tumor Necrosis Factor-Alpha Expression during Influenza Virus Infection

    Directory of Open Access Journals (Sweden)

    Anna H. Y. Law

    2013-04-01

    Full Text Available Influenza viruses of avian origin continue to pose pandemic threats to human health. Some of the H5N1 and H9N2 virus subtypes induce markedly elevated cytokine levels when compared with the seasonal H1N1 virus. We previously showed that H5N1/97 hyperinduces tumor necrosis factor (TNF-alpha through p38 mitogen activated protein kinase (MAPK. However, the detailed mechanisms of p38MAPK activation and TNF-alpha hyperinduction following influenza virus infections are not known. Negative feedback regulations of cytokine expression play important roles in avoiding overwhelming production of proinflammatory cytokines. Here we hypothesize that protein phosphatases are involved in the regulation of cytokine expressions during influenza virus infection. We investigated the roles of protein phosphatases including MAPK phosphatase-1 (MKP-1 and protein phosphatase type 2A (PP2A in modulating p38MAPK activation and downstream TNF-alpha expressions in primary human monocyte-derived macrophages (PBMac infected with H9N2/G1 or H1N1 influenza virus. We demonstrate that H9N2/G1 virus activated p38MAPK and hyperinduced TNF-alpha production in PBMac when compared with H1N1 virus. H9N2/G1 induced PP2A activity in PBMac and, with the treatment of a PP2A inhibitor, p38MAPK phosphorylation and TNF-alpha production were further increased in the virus-infected macrophages. However, H9N2/G1 did not induce the expression of PP2A indicating that the activation of PP2A is not mediated by p38MAPK in virus-infected PBMac. On the other hand, PP2A may not be the targets of H9N2/G1 in the upstream of p38MAPK signaling pathways since H1N1 also induced PP2A activation in primary macrophages. Our results may provide new insights into the control of cytokine dysregulation.

  17. Isolation of an attenuated myxoma virus field strain that can confer protection against myxomatosis on contacts of vaccinates.

    Science.gov (United States)

    Bárcena, J; Pagès-Manté, A; March, R; Morales, M; Ramírez, M A; Sánchez-Vizcaíno, J M; Torres, J M

    2000-01-01

    Twenty MV strains obtained from a survey of field strains currently circulating throughout Spain were analyzed for their virulence and horizontal spreading among rabbits by contact transmission. A virus strain with suitable characteristics to be used as a potential vaccine against myxomatosis in wild rabbit populations was selected. Following inoculation, the selected MV strain elicited high levels of MV specific antibodies and induced protection of rabbits against a virulent MV challenge. Furthermore, the attenuated MV was transmitted to 9 out of 16 uninoculated rabbits by contact, inducing protection against myxomatosis.

  18. Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1.

    Science.gov (United States)

    El-Diwany, Ramy; Cohen, Valerie J; Mankowski, Madeleine C; Wasilewski, Lisa N; Brady, Jillian K; Snider, Anna E; Osburn, William O; Murrell, Ben; Ray, Stuart C; Bailey, Justin R

    2017-02-01

    Broadly-neutralizing monoclonal antibodies (bNAbs) may guide vaccine development for highly variable viruses including hepatitis C virus (HCV), since they target conserved viral epitopes that could serve as vaccine antigens. However, HCV resistance to bNAbs could reduce the efficacy of a vaccine. HC33.4 and AR4A are two of the most potent anti-HCV human bNAbs characterized to date, binding to highly conserved epitopes near the amino- and carboxy-terminus of HCV envelope (E2) protein, respectively. Given their distinct epitopes, it was surprising that these bNAbs showed similar neutralization profiles across a panel of natural HCV isolates, suggesting that some viral polymorphisms may confer resistance to both bNAbs. To investigate this resistance, we developed a large, diverse panel of natural HCV envelope variants and a novel computational method to identify bNAb resistance polymorphisms in envelope proteins (E1 and E2). By measuring neutralization of a panel of HCV pseudoparticles by 10 μg/mL of each bNAb, we identified E1E2 variants with resistance to one or both bNAbs, despite 100% conservation of the AR4A binding epitope across the panel. We discovered polymorphisms outside of either binding epitope that modulate resistance to both bNAbs by altering E2 binding to the HCV co-receptor, scavenger receptor B1 (SR-B1). This study is focused on a mode of neutralization escape not addressed by conventional analysis of epitope conservation, highlighting the contribution of extra-epitopic polymorphisms to bNAb resistance and presenting a novel mechanism by which HCV might persist even in the face of an antibody response targeting multiple conserved epitopes.

  19. Murine polyomavirus virus-like particles carrying full-length human PSA protect BALB/c mice from outgrowth of a PSA expressing tumor.

    Directory of Open Access Journals (Sweden)

    Mathilda Eriksson

    Full Text Available Virus-like particles (VLPs consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV VLPs carrying the entire human Prostate Specific Antigen (PSA (PSA-MPyVLPs for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs. Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4(+ and CD8(+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4(+ and CD8(+ cells with a low induction of anti-VLP antibodies.

  20. Murine Polyomavirus Virus-Like Particles Carrying Full-Length Human PSA Protect BALB/c Mice from Outgrowth of a PSA Expressing Tumor

    Science.gov (United States)

    Eriksson, Mathilda; Andreasson, Kalle; Weidmann, Joachim; Lundberg, Kajsa; Tegerstedt, Karin

    2011-01-01

    Virus-like particles (VLPs) consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV) VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs). Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4+ and CD8+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4+ and CD8+ cells with a low induction of anti-VLP antibodies. PMID:21858228

  1. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and anti-tumor effects

    Science.gov (United States)

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

    2013-01-01

    We recently demonstrated that Venezuelan equine encephalitis (VEE) virus-based replicon particles (VRP) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP expressing Interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and anti-tumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)) and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12 and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing anti-tumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted. PMID:22488274

  2. Analysis of the selective advantage conferred by a C-E1 fusion protein synthesized by rubella virus DI RNAs

    International Nuclear Information System (INIS)

    Claus, Claudia; Tzeng, W.-P.; Liebert, Uwe Gerd; Frey, Teryl K.

    2007-01-01

    During serial passaging of rubella virus (RUB) in cell culture, the dominant species of defective-interfering RNA (DI) generated contains an in-frame deletion between the capsid protein (C) gene and E1 glycoprotein gene resulting in production of a C-E1 fusion protein that is necessary for the maintenance of the DI [Tzeng, W.P., Frey, T.K. (2006). C-E1 fusion protein synthesized by rubella virus DI RNAs maintained during serial passage. Virology 356 198-207.]. A BHK cell line stably expressing the RUB structural proteins was established which was used to package DIs into virus particles following transfection with in vitro transcripts from DI infectious cDNA constructs. Packaging of a DI encoding an in-frame C-GFP-E1 reporter fusion protein corresponding to the C-E1 fusion protein expressed in a native DI was only marginally more efficient than packaging of a DI encoding GFP, indicating that the C-E1 fusion protein did not function by enhancing packaging. However, infection with the DI encoding the C-GFP-E1 fusion protein (in the absence of wt RUB helper virus) resulted in formation of clusters of GFP-positive cells and the percentage of GFP-positive cells in the culture following infection remained relatively constant. In contrast, a DI encoding GFP did not form GFP-positive clusters and the percentage of GFP-positive cells declined by roughly half from 2 to 4 days post-infection. Cluster formation and sustaining the percentage of infected (GFP-positive) cells required the C part of the fusion protein, including the downstream but not the upstream of two arginine clusters (both of which are associated with RNA binding and association with mitochondrial p32 protein) and the E1 part through the transmembrane sequence, but not the C-terminal cytoplasmic tail. Among a collection of mutant DI constructs, cluster formation and sustaining infected cell percentage correlated with maintenance during serial passage with wt RUB. We hypothesize that cluster formation and

  3. Preparation for emergence of an Eastern European porcine reproductive and respiratory syndrome virus (PRRSV) strain in Western Europe: Immunization with modified live virus vaccines or a field strain confers partial protection.

    Science.gov (United States)

    Renson, P; Fablet, C; Le Dimna, M; Mahé, S; Touzain, F; Blanchard, Y; Paboeuf, F; Rose, N; Bourry, O

    2017-05-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) causes huge economic losses for the swine industry worldwide. In the past several years, highly pathogenic strains that lead to even greater losses have emerged. For the Western European swine industry, one threat is the possible introduction of Eastern European PRRSV strains (example Lena genotype 1.3) which were shown to be more virulent than common Western resident strains under experimental conditions. To prepare for the possible emergence of this strain in Western Europe, we immunized piglets with a Western European PRRSV field strain (Finistere: Fini, genotype 1.1), a new genotype 1 commercial modified live virus (MLV) vaccine (MLV1) or a genotype 2 commercial MLV vaccine (MLV2) to evaluate and compare the level of protection that these strains conferred upon challenge with the Lena strain 4 weeks later. Results show that immunization with Fini, MLV1 or MLV2 strains shortened the Lena-induced hyperthermia. In the Fini group, a positive effect was also demonstrated in growth performance. The level of Lena viremia was reduced for all immunized groups (significantly so for Fini and MLV2). This reduction in Lena viremia was correlated with the level of Lena-specific IFNγ-secreting cells. In conclusion, we showed that a commercial MLV vaccine of genotype 1 or 2, as well as a field strain of genotype 1.1 may provide partial clinical and virological protection upon challenge with the Lena strain. The cross-protection induced by these immunizing strains was not related with the level of genetic similarity to the Lena strain. The slightly higher level of protection established with the field strain is attributed to a better cell-mediated immune response. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Biological effects of a de novo designed myxoma virus peptide analogue: evaluation of cytotoxicity on tumor cells.

    Directory of Open Access Journals (Sweden)

    Taghrid S Istivan

    Full Text Available BACKGROUND: The Resonant Recognition Model (RRM is a physico-mathematical model that interprets protein sequence linear information using digital signal processing methods. In this study the RRM concept was employed for structure-function analysis of myxoma virus (MV proteins and the design of a short bioactive therapeutic peptide with MV-like antitumor/cytotoxic activity. METHODOLOGY/PRINCIPAL FINDINGS: The analogue RRM-MV was designed by RRM as a linear 18 aa 2.3 kDa peptide. The biological activity of this computationally designed peptide analogue against cancer and normal cell lines was investigated. The cellular cytotoxicity effects were confirmed by confocal immunofluorescence microscopy, by measuring the levels of cytoplasmic lactate dehydrogenase (LDH and by Prestoblue cell viability assay for up to 72 hours in peptide treated and non-treated cell cultures. Our results revealed that RRM-MV induced a significant dose and time-dependent cytotoxic effect on murine and human cancer cell lines. Yet, when normal murine cell lines were similarly treated with RRM-MV, no cytotoxic effects were observed. Furthermore, the non-bioactive RRM designed peptide RRM-C produced negligible cytotoxic effects on these cancer and normal cell lines when used at similar concentrations. The presence/absence of phosphorylated Akt activity in B16F0 mouse melanoma cells was assessed to indicate the possible apoptosis signalling pathway that could be affected by the peptide treatment. So far, Akt activity did not seem to be significantly affected by RRM-MV as is the case for the original viral protein. CONCLUSIONS/SIGNIFICANCE: Our findings indicate the successful application of the RRM concept to design a bioactive peptide analogue (RRM-MV with cytotoxic effects on tumor cells only. This 2.345 kDa peptide analogue to a 49 kDa viral protein may be suitable to be developed as a potential cancer therapeutic. These results also open a new direction to the rational

  5. Proinflammatory response during Ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily.

    Science.gov (United States)

    Hensley, Lisa E; Young, Howard A; Jahrling, Peter B; Geisbert, Thomas W

    2002-03-01

    Ebola virus (EBOV) infections are characterized by dysregulation of normal host immune responses. Insight into the mechanism came from recent studies in nonhuman primates, which showed that EBOV infects cells of the mononuclear phagocyte system (MPS), resulting in apoptosis of bystander lymphocytes. In this study, we evaluated serum levels of cytokines/chemokines in EBOV-infected nonhuman primates, as possible correlates of this bystander apoptosis. Increased levels of interferon (IFN)-alpha, IFN-beta, interleukin (IL)-6, IL-18, MIP-1alpha, and MIP-1beta were observed in all EBOV-infected monkeys, indicating the occurrence of a strong proinflammatory response. To investigate the mechanism(s) involved in lymphoid apoptosis, soluble Fas (sFas) and nitrate accumulation were measured. sFas was detected in 4/9 animals, while, elevations of nitrate accumulation occurred in 3/3 animals. To further evaluate the potential role of these factors in the observed bystander apoptosis and intact animals, in vitro cultures were prepared of adherent human monocytes/macrophages (PHM), and monocytes differentiated into immature dendritic cells (DC). These cultures were infected with EBOV and analyzed for cytokine/chemokine induction and expression of apoptosis-related genes. In addition, the in vitro EBOV infection of peripheral blood mononuclear cells (PBMC) resulted in strong cytokine/chemokine induction, a marked increase in lactate dehydrogenase (LDH) activity, and an increase in the number of apoptotic lymphocytes examined by electron microscopy. Increased levels of sFAS were detected in PHM cultures, although, 90% of EBOV-infected PHM were positive for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by immunohistochemistry, RNA analysis, and flow cytometry. Inactivated EBOV also effected increased TRAIL expression in PHM, suggesting that the TNF receptor superfamily may be involved in apoptosis of the host lymphoid cells, and that induction may occur

  6. CD47 expression in Epstein-Barr virus-associated gastric carcinoma: coexistence with tumor immunity lowering the ratio of CD8+/Foxp3+ T cells.

    Science.gov (United States)

    Abe, Hiroyuki; Saito, Ruri; Ichimura, Takashi; Iwasaki, Akiko; Yamazawa, Sho; Shinozaki-Ushiku, Aya; Morikawa, Teppei; Ushiku, Tetsuo; Yamashita, Hiroharu; Seto, Yasuyuki; Fukayama, Masashi

    2018-04-01

    Epstein-Barr virus-associated gastric carcinoma (EBVaGC) frequently harbors dense lymphocytic infiltration, suggesting a specific microenvironment allowing coexistence with tumor immunity. CD47, which mediates the "do not eat me" signal in innate immunity, is also important in adaptive anti-tumor immunity. We investigated the significance of CD47 in EBVaGC compared with EBV-negative gastric cancer and the correlation with various immune cells. By immunohistochemistry of CD47, high, low, and negative expression was observed in 24, 63, and 12% of EBVaGC (n = 41), while 11, 49, and 39% of EBV-negative gastric cancer (n = 262), respectively, indicating that high expression of CD47 in cancer cells was significantly frequent and increased in EBVaGC (P = 0.043). In contrast to EBV-negative gastric carcinoma in which no significant correlation was observed between CD47 and survival, high expression of CD47 correlated significantly with worse disease-specific survival (P = 0.011) and overall survival (P = 0.013) in EBVaGC. To further clarify the role of CD47 expression in EBVaGC, digital image analysis of immune cell infiltration revealed that high CD47 expression was correlated with a lower ratio of CD8 + /Foxp3 + T cells (P = 0.021), a sensitive indicator of tumor immunity. Thus, CD47 lowers anti-tumor immunity in EBVaGC by finely tuning profile of infiltrating T cells, suggesting that CD47 is an additional target for cancer immunotherapy against this virus-driven gastric cancer.

  7. Antibodies to parvovirus, distemper virus and adenovirus conferred to household dogs using commercial combination vaccines containing Leptospira bacterin.

    Science.gov (United States)

    Taguchi, M; Namikawa, K; Maruo, T; Lynch, J; Sahara, H

    2010-12-11

    To examine how the inclusion (+) or exclusion (-) of inactivated Leptospira antigens in a vaccine for canine parvovirus type 2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type 2 (CAdV-2) affects antibody titres to CPV-2, CDV and CAdV-1 antigens, household dogs were vaccinated with commercially available vaccines from one of three manufacturers. CPV-2, CDV and CAdV-1 antibody titres were measured 11 to 13 months later and compared within three different age groups and three different bodyweight groups. There were significant differences between CPV-2 antibody titres in dogs vaccinated with (+) vaccine and those vaccinated with (-) vaccine for two products in the two-year-old group and for one product in the greater than seven-year-old group; no significant differences were seen that could be attributed to bodyweight. No differences in CDV antibody titres were observed within age groups, but a significant difference was seen in the 11 to 20 kg weight group for one product. Significant differences in CAdV-1 antibody titres were seen for one product in both the two-year-old group and the ≤10 kg weight group.

  8. Epstein–Barr virus nuclear antigen 3C interact with p73: Interplay between a viral oncoprotein and cellular tumor suppressor

    International Nuclear Information System (INIS)

    Sahu, Sushil Kumar; Mohanty, Suchitra; Kumar, Amit; Kundu, Chanakya N.; Verma, Subhash C.; Choudhuri, Tathagata

    2014-01-01

    The p73 protein has structural and functional homology with the tumor suppressor p53, which plays an important role in cell cycle regulation, apoptosis, and DNA repair. The p73 locus encodes both a tumor suppressor (TAp73) and a putative oncogene (ΔNp73). p73 May play a significant role in p53-deficient lymphomas infected with Epstein–Barr virus (EBV). EBV produces an asymptomatic infection in the majority of the global population, but it is associated with several human B-cell malignancies. The EBV-encoded Epstein–Barr virus nuclear antigen 3C (EBNA3C) is thought to disrupt the cell cycle checkpoint by interacting directly with p53 family proteins. Doxorubicin, a commonly used chemotherapeutic agent, induces apoptosis through p53 and p73 signaling such that the lowΔNp73 level promotes the p73-mediated intrinsic pathway of apoptosis. In this report, we investigated the mechanism by which EBV infection counters p73α-induced apoptosis through EBNA3C. - Highlights: • EBV-encoded EBNA3C suppresses doxorubicin-induced apoptosis in B-cell lymphomas. • EBNA3C binds to p73 to suppress its apoptotic effect. • EBNA3C maintains latency by regulating downstream mitochondrial pathways

  9. Epstein–Barr virus nuclear antigen 3C interact with p73: Interplay between a viral oncoprotein and cellular tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Sushil Kumar; Mohanty, Suchitra; Kumar, Amit [Division of Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023 (India); Kundu, Chanakya N. [School of Biotechnology, KIIT University, Bhubaneswar (India); Verma, Subhash C. [Department of Microbiology and Immunology, University of Nevada, School of Medicine, Reno, NV 89557 (United States); Choudhuri, Tathagata, E-mail: tatha@ils.res.in [Division of Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023 (India); Department of Biotechnology, Siksha Bhavana, Visva Bharati, Santiniketan, Bolpur (India)

    2014-01-05

    The p73 protein has structural and functional homology with the tumor suppressor p53, which plays an important role in cell cycle regulation, apoptosis, and DNA repair. The p73 locus encodes both a tumor suppressor (TAp73) and a putative oncogene (ΔNp73). p73 May play a significant role in p53-deficient lymphomas infected with Epstein–Barr virus (EBV). EBV produces an asymptomatic infection in the majority of the global population, but it is associated with several human B-cell malignancies. The EBV-encoded Epstein–Barr virus nuclear antigen 3C (EBNA3C) is thought to disrupt the cell cycle checkpoint by interacting directly with p53 family proteins. Doxorubicin, a commonly used chemotherapeutic agent, induces apoptosis through p53 and p73 signaling such that the lowΔNp73 level promotes the p73-mediated intrinsic pathway of apoptosis. In this report, we investigated the mechanism by which EBV infection counters p73α-induced apoptosis through EBNA3C. - Highlights: • EBV-encoded EBNA3C suppresses doxorubicin-induced apoptosis in B-cell lymphomas. • EBNA3C binds to p73 to suppress its apoptotic effect. • EBNA3C maintains latency by regulating downstream mitochondrial pathways.

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

    Science.gov (United States)

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

    2002-04-01

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

  11. Vectorization in an oncolytic vaccinia virus of an antibody, a Fab and a scFv against programmed cell death -1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition.

    Science.gov (United States)

    Kleinpeter, Patricia; Fend, Laetitia; Thioudellet, Christine; Geist, Michel; Sfrontato, Nathalie; Koerper, Véronique; Fahrner, Catherine; Schmitt, Doris; Gantzer, Murielle; Remy-Ziller, Christelle; Brandely, Renée; Villeval, Dominique; Rittner, Karola; Silvestre, Nathalie; Erbs, Philippe; Zitvogel, Laurence; Quéméneur, Eric; Préville, Xavier; Marchand, Jean-Baptiste

    2016-01-01

    We report here the successful vectorization of a hamster monoclonal IgG (namely J43) recognizing the murine Programmed cell death-1 (mPD-1) in Western Reserve (WR) oncolytic vaccinia virus. Three forms of mPD-1 binders have been inserted into the virus: whole antibody (mAb), Fragment antigen-binding (Fab) or single-chain variable fragment (scFv). MAb, Fab and scFv were produced and assembled with the expected patterns in supernatants of cells infected by the recombinant viruses. The three purified mPD-1 binders were able to block the binding of mPD-1 ligand to mPD-1 in vitro . Moreover, mAb was detected in tumor and in serum of C57BL/6 mice when the recombinant WR-mAb was injected intratumorally (IT) in B16F10 and MCA 205 tumors. The concentration of circulating mAb detected after IT injection was up to 1,900-fold higher than the level obtained after a subcutaneous (SC) injection (i.e., without tumor) confirming the virus tropism for tumoral cells and/or microenvironment. Moreover, the overall tumoral accumulation of the mAb was higher and lasted longer after IT injection of WR-mAb1, than after IT administration of 10 µg of J43. The IT injection of viruses induced a massive infiltration of immune cells including activated lymphocytes (CD8 + and CD4 + ). Interestingly, in the MCA 205 tumor model, WR-mAb1 and WR-scFv induced a therapeutic control of tumor growth similar to unarmed WR combined to systemically administered J43 and superior to that obtained with an unarmed WR. These results pave the way for next generation of oncolytic vaccinia armed with immunomodulatory therapeutic proteins such as mAbs.

  12. Glycans Flanking the Hypervariable Connecting Peptide between the A and B Strands of the V1/V2 Domain of HIV-1 gp120 Confer Resistance to Antibodies That Neutralize CRF01_AE Viruses

    Science.gov (United States)

    O’Rourke, Sara M.; Sutthent, Ruengpung; Phung, Pham; Mesa, Kathryn A.; Frigon, Normand L.; To, Briana; Horthongkham, Navin; Limoli, Kay; Wrin, Terri; Berman, Phillip W.

    2015-01-01

    Understanding the molecular determinants of sensitivity and resistance to neutralizing antibodies is critical for the development of vaccines designed to prevent HIV infection. In this study, we used a genetic approach to characterize naturally occurring polymorphisms in the HIV envelope protein that conferred neutralization sensitivity or resistance. Libraries of closely related envelope genes, derived from virus quasi-species, were constructed from individuals infected with CRF01_AE viruses. The libraries were screened with plasma containing broadly neutralizing antibodies, and neutralization sensitive and resistant variants were selected for sequence analysis. In vitro mutagenesis allowed us to identify single amino acid changes in three individuals that conferred resistance to neutralization by these antibodies. All three mutations created N-linked glycosylation sites (two at N136 and one at N149) proximal to the hypervariable connecting peptide between the C-terminus of the A strand and the N-terminus of the B strand in the four-stranded V1/V2 domain β-sheet structure. Although N136 has previously been implicated in the binding of broadly neutralizing monoclonal antibodies, this glycosylation site appears to inhibit the binding of neutralizing antibodies in plasma from HIV-1 infected subjects. Previous studies have reported that the length of the V1/V2 domain in transmitted founder viruses is shorter and possesses fewer glycosylation sites compared to viruses isolated from chronic infections. Our results suggest that vaccine immunogens based on recombinant envelope proteins from clade CRF01_AE viruses might be improved by inclusion of envelope proteins that lack these glycosylation sites. This strategy might improve the efficacy of the vaccines used in the partially successful RV144 HIV vaccine trial, where the two CRF01_AE immunogens (derived from the A244 and TH023 isolates) both possessed glycosylation sites at N136 and N149. PMID:25793890

  13. Mouse mammary tumor viruses expressed by RIII/Sa mice with a high incidence of mammary tumors interact with the Vβ-2- and Vβ-8-specific T cells during viral infection

    International Nuclear Information System (INIS)

    Uz-Zaman, Taher; Ignatowicz, Leszek; Sarkar, Nurul H.

    2003-01-01

    The mouse mammary tumor viruses (MMTVs) that induce mammary adenocarcinomas in mice are transmitted from mother to offspring through milk. MMTV infection results in the deletion of specific T cells as a consequence of interaction between the MMTV-encoded superantigen (Sag) and specific Vβ chains of the T cell receptor. The specificity and kinetics of T cell deletion for a number of highly oncogenic MMTVs, such as C3H- and GR-MMTVs, have been studied in great detail. Some work has also been done with the MMTVs expressed in two substrains of RIII mice, BR6 and RIIIS/J, but the nature of the interaction between T cells and the virus(es) that the parental RIII-strain of mice express has not been investigated. Since RIII mice (designated henceforth as RIII/Sa) have a very high incidence (90-98%) of mammary tumors, and they have been extensively used in studies of the biology of mammary tumor development, we have presently determined the pattern of Vβ-T cell deletion caused by RIII/Sa-MMTV-Sag(s) during viral infection. T cells were isolated from lymph nodes and thymus of young RIII/Sa mice, as well as from BALB/c (BALB/cfRIII/Sa), C57BL (C57BLfRIII/Sa), and RIIIS/J (RIIIS/JfRIII/Sa) mice after they were infected with RIII/Sa-MMTV(s) by foster nursing. The composition of the T cells was analyzed by FACS using a panel of monoclonal antibodies specific to a variety of Vβs. Our results show that milk-borne RIII/Sa-MMTV(s) infection leads to the deletion of CD4 + Vβ-2, and to a lesser extent Vβ-8 bearing peripheral and central T cells in RIII/Sa, RIIIS/J, BALB/c, and C57BL mice. Our results are in contrast to the findings that C3H-, GR-, and BR6-MMTVs delete Vβ-14- and/or Vβ-15-specific T cells

  14. Sequences within both the 5' UTR and Gag are required for optimal in vivo packaging and propagation of mouse mammary tumor virus (MMTV genomic RNA.

    Directory of Open Access Journals (Sweden)

    Farah Mustafa

    Full Text Available BACKGROUND: This study mapped regions of genomic RNA (gRNA important for packaging and propagation of mouse mammary tumor virus (MMTV. MMTV is a type B betaretrovirus which preassembles intracellularly, a phenomenon distinct from retroviruses that assemble the progeny virion at cell surface just before budding such as the type C human and feline immunodeficiency viruses (HIV and FIV. Studies of FIV and Mason-Pfizer monkey virus (MPMV, a type D betaretrovirus with similar intracellular virion assembly processes as MMTV, have shown that the 5' untranslated region (5' UTR and 5' end of gag constitute important packaging determinants for gRNA. METHODOLOGY: Three series of MMTV transfer vectors containing incremental amounts of gag or 5' UTR sequences, or incremental amounts of 5' UTR in the presence of 400 nucleotides (nt of gag were constructed to delineate the extent of 5' sequences that may be involved in MMTV gRNA packaging. Real time PCR measured the packaging efficiency of these vector RNAs into MMTV particles generated by co-transfection of MMTV Gag/Pol, vesicular stomatitis virus envelope glycoprotein (VSV-G Env, and individual transfer vectors into human 293T cells. Transfer vector RNA propagation was monitored by measuring transduction of target HeLaT4 cells following infection with viral particles containing a hygromycin resistance gene expression cassette on the packaged RNA. PRINCIPAL FINDINGS: MMTV requires the entire 5' UTR and a minimum of ~120 nucleotide (nt at the 5' end of gag for not only efficient gRNA packaging but also propagation of MMTV-based transfer vector RNAs. Vector RNAs without the entire 5' UTR were defective for both efficient packaging and propagation into target cells. CONCLUSIONS/SIGNIFICANCE: These results reveal that the 5' end of MMTV genome is critical for both gRNA packaging and propagation, unlike the recently delineated FIV and MPMV packaging determinants that have been shown to be of bipartite nature.

  15. HoxD10 gene delivery using adenovirus/adeno-associate hybrid virus inhibits the proliferation and tumorigenicity of GH4 pituitary lactotrope tumor cells

    International Nuclear Information System (INIS)

    Cho, Mi Ae; Yashar, Parham; Kim, Suk Kyoung; Noh, Taewoong; Gillam, Mary P.; Lee, Eun Jig; Jameson, J. Larry

    2008-01-01

    Prolactinoma is one of the most common types of pituitary adenoma. It has been reported that a variety of growth factors and cytokines regulating cell growth and angiogenesis play an important role in the growth of prolactinoma. HoxD10 has been shown to impair endothelial cell migration, block angiogenesis, and maintain a differentiated phenotype of cells. We investigated whether HoxD10 gene delivery could inhibit the growth of prolactinoma. Rat GH4 lactotrope tumor cells were infected with adenovirus/adeno-associated virus (Ad/AAV) hybrid vectors carrying the mouse HoxD10 gene (Hyb-HoxD10) or the β-galactosidase gene (Hyb-Gal). Hyb-HoxD10 expression inhibited GH4 cell proliferation in vitro. The expression of FGF-2 and cyclin D2 was inhibited in GH4 cells infected with Hyb-HoxD10. GH4 cells transduced with Hyb-HoxD10 did not form tumors in nude mice. These results indicate that the delivery of HoxD10 could potentially inhibit the growth of PRL-secreting tumors. This approach may be a useful tool for targeted therapy of prolactinoma and other neoplasms

  16. "Cancer tumor".

    Science.gov (United States)

    Bronshtehn, V. A.

    The title is a phrase borrowed from a speech by a Leningrad pressman, V. E. Lvov, who called upon those attending a theoretical conference on ideological issues in astronomy held by the Leningrad Branch of the All-Union Astronomic and Geodetic Society (13 - 4 December 1948), "to make a more radical emphasis on the negative role of relativistic cosmology which is a cancer tumor disintegrating the contemporary astronomy theory, and a major ideological enemy of a materialist astronomy".

  17. Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor

    NARCIS (Netherlands)

    Lilly, Cameron L.; Villa, Nancy Y.; Lemos de Matos, Ana; Ali, Haider M.; Dhillon, Jess-Karan S.; Hofland, Tom; Rahman, Masmudur M.; Chan, Winnie; Bogen, Bjarne; Cogle, Christopher; McFadden, Grant

    2017-01-01

    Allogeneic stem cell transplant-derived T cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma virus (MYXV) exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (MM) and can arm transplant-derived T cells

  18. Spatially selective depleting tumor-associated negative regulatory T-(Treg) cells with near infrared photoimmunotherapy (NIR-PIT): A new cancer immunotherapy (Conference Presentation)

    Science.gov (United States)

    Kobayashi, Hisataka

    2017-02-01

    Near infrared photoimmunotherapy (NIR-PIT) is a new type of molecularly-targeted photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IR700, to a monoclonal antibody (MAb) targeting target-specific cell-surface molecules. When exposed to NIR light, the conjugate rapidly induces a highly-selective cell death only in receptor-positive, MAb-IR700-bound cells. Current immunotherapies for cancer seek to modulate the balance among different immune cell populations, thereby promoting anti-tumor immune responses. However, because these are systemic therapies, they often cause treatment-limiting autoimmune adverse effects. It would be ideal to manipulate the balance between suppressor and effector cells within the tumor without disturbing homeostasis elsewhere in the body. CD4+CD25+Foxp3+ regulatory T cells (Tregs) are well-known immune-suppressor cells that play a key role in tumor immuno-evasion and have been the target of systemic immunotherapies. We used CD25-targeted NIR-PIT to selectively deplete Tregs, thus activating CD8+ T and NK cells and restoring local anti-tumor immunity. This not only resulted in regression of the treated tumor but also induced responses in separate untreated tumors of the same cell-line derivation. We conclude that CD25-targeted NIR-PIT causes spatially selective depletion of Tregs, thereby providing an alternative approach to cancer immunotherapy that can treat not only local tumors but also distant metastatic tumors.

  19. Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules

    Czech Academy of Sciences Publication Activity Database

    Němečková, Š.; Šmahel, M.; Hainz, P.; Macková, J.; Zurková, K.; Gabriel, P.; Indrová, Marie; Kutinová, L.

    2007-01-01

    Roč. 54, č. 4 (2007), s. 326-333 ISSN 0028-2685 R&D Projects: GA MZd NR8004 Institutional research plan: CEZ:AV0Z50520514 Keywords : vaccinia virus MVA expressing GM- CSF * DNA vaccine * HPV16 induced tumors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.208, year: 2007

  20. Mouse Mammary Tumor Virus Signal Peptide Uses a Novel p97-Dependent and Derlin-Independent Retrotranslocation Mechanism To Escape Proteasomal Degradation

    Directory of Open Access Journals (Sweden)

    Hyewon Byun

    2017-03-01

    Full Text Available Multiple pathogens, including viruses and bacteria, manipulate endoplasmic reticulum-associated degradation (ERAD to avoid the host immune response and promote their replication. The betaretrovirus mouse mammary tumor virus (MMTV encodes Rem, which is a precursor protein that is cleaved into a 98-amino-acid signal peptide (SP and a C-terminal protein (Rem-CT. SP uses retrotranslocation for ER membrane extraction and yet avoids ERAD by an unknown mechanism to enter the nucleus and function as a Rev-like protein. To determine how SP escapes ERAD, we used a ubiquitin-activated interaction trap (UBAIT screen to trap and identify transient protein interactions with SP, including the ERAD-associated p97 ATPase, but not E3 ligases or Derlin proteins linked to retrotranslocation, polyubiquitylation, and proteasomal degradation of extracted proteins. A dominant negative p97 ATPase inhibited both Rem and SP function. Immunoprecipitation experiments indicated that Rem, but not SP, is polyubiquitylated. Using both yeast and mammalian expression systems, linkage of a ubiquitin-like domain (UbL to SP or Rem induced degradation by the proteasome, whereas SP was stable in the absence of the UbL. ERAD-associated Derlin proteins were not required for SP activity. Together, these results suggested that Rem uses a novel p97-dependent, Derlin-independent retrotranslocation mechanism distinct from other pathogens to avoid SP ubiquitylation and proteasomal degradation.

  1. A single immunization with a recombinant canine adenovirus expressing the rabies virus G protein confers protective immunity against rabies in mice

    International Nuclear Information System (INIS)

    Li Jianwei; Faber, Milosz; Papaneri, Amy; Faber, Marie-Luise; McGettigan, James P.; Schnell, Matthias J.; Dietzschold, Bernhard

    2006-01-01

    Rabies vaccines based on live attenuated rabies viruses or recombinant pox viruses expressing the rabies virus (RV) glycoprotein (G) hold the greatest promise of safety and efficacy, particularly for oral immunization of wildlife. However, while these vaccines induce protective immunity in foxes, they are less effective in other animals, and safety concerns have been raised for some of these vaccines. Because canine adenovirus 2 (CAV2) is licensed for use as a live vaccine for dogs and has an excellent efficacy and safety record, we used this virus as an expression vector for the RVG. The recombinant CAV2-RV G produces virus titers similar to those produced by wild-type CAV2, indicating that the RVG gene does not affect virus replication. Comparison of RVG expressed by CAV2-RV G with that of vaccinia-RV G recombinant virus (V-RG) revealed similar amounts of RV G on the cell surface. A single intramuscular or intranasal immunization of mice with CAV2-RVG induced protective immunity in a dose-dependent manner, with no clinical signs or discomfort from the virus infection regardless of the route of administration or the amount of virus

  2. Advances in virus research. Volume 29

    International Nuclear Information System (INIS)

    Lauffer, M.A.; Maramorosch, K.

    1984-01-01

    This book contains nine chapters. Some of the titles are: Molecular Biology of Wound Tumor Virus; The Application of Monoclonal Antibodies in the Study of Viruses; Prions: Novel Infectious Pathogens; and Monoclonal Antibodies Against Plant Viruses

  3. Vesicular stomatitis virus modified with single chain IL-23 exhibits oncolytic activity against tumor cells in vitro and in vivo

    OpenAIRE

    Reiss, Carol Shoshkes

    2010-01-01

    James M Miller1, Sarah McNulty Bidula1,5, Troels Mygind Jensen1,6, Carol Shoshkes Reiss1,2,3,41Department of Biology, New York University, New York, NY, USA; 2Center for Neural Science, NYU; 3NYU Cancer Institute; 4Departments of Microbiology, NYU School of Medicine and Mt Sinai School of Medicine, New York, NY, USA; 5Present address Graduate Program, University of Pittsburgh School of Medicine, Pittsburgh, PA,USA 6Present address: Univercity of Copenhagen, Copenhagen, DenmarkAbstract: Viruse...

  4. Acquisition of a novel eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site confers intracellular cleavage of an H7N7 influenza virus hemagglutinin

    International Nuclear Information System (INIS)

    Hamilton, Brian S.; Sun, Xiangjie; Chung, Changik; Whittaker, Gary R.

    2012-01-01

    A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.

  5. Acquisition of a novel eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site confers intracellular cleavage of an H7N7 influenza virus hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Brian S.; Sun, Xiangjie; Chung, Changik [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States); Whittaker, Gary R., E-mail: grw7@cornell.edu [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States)

    2012-12-05

    A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.

  6. Rift valley fever virus lacking the NSs and NSm genes is highly attenuated, confers protective immunity from virulent virus challenge, and allows for differential identification of infected and vaccinated animals.

    Science.gov (United States)

    Bird, Brian H; Albariño, César G; Hartman, Amy L; Erickson, Bobbie Rae; Ksiazek, Thomas G; Nichol, Stuart T

    2008-03-01

    Rift Valley fever (RVF) virus is a mosquito-borne human and veterinary pathogen associated with large outbreaks of severe disease throughout Africa and more recently the Arabian peninsula. Infection of livestock can result in sweeping "abortion storms" and high mortality among young animals. Human infection results in self-limiting febrile disease that in approximately 1 to 2% of patients progresses to more serious complications including hepatitis, encephalitis, and retinitis or a hemorrhagic syndrome with high fatality. The virus S segment-encoded NSs and the M segment-encoded NSm proteins are important virulence factors. The development of safe, effective vaccines and tools to screen and evaluate antiviral compounds is critical for future control strategies. Here, we report the successful reverse genetics generation of multiple recombinant enhanced green fluorescent protein-tagged RVF viruses containing either the full-length, complete virus genome or precise deletions of the NSs gene alone or the NSs/NSm genes in combination, thus creating attenuating deletions on multiple virus genome segments. These viruses were highly attenuated, with no detectable viremia or clinical illness observed with high challenge dosages (1.0 x 10(4) PFU) in the rat lethal disease model. A single-dose immunization regimen induced robust anti-RVF virus immunoglobulin G antibodies (titer, approximately 1:6,400) by day 26 postvaccination. All vaccinated animals that were subsequently challenged with a high dose of virulent RVF virus survived infection and could be serologically differentiated from naïve, experimentally infected animals by the lack of NSs antibodies. These rationally designed marker RVF vaccine viruses will be useful tools for in vitro screening of therapeutic compounds and will provide a basis for further development of RVF virus marker vaccines for use in endemic regions or following the natural or intentional introduction of the virus into previously unaffected areas.

  7. Cerebral gumma mimicking a brain tumor in a human immunodeficiency virus-negative patient: A case report

    International Nuclear Information System (INIS)

    Baek, Hye Jin; Kim, Woo Jin

    2013-01-01

    Syphilis has a broad spectrum of clinical manifestations, and the cerebral gumma is a kind of neurosyphilis which is rare and can be cured by appropriate antibiotic treatments. However, in clinical practices, diagnosis of cerebral syphilitic gumma is often difficult because imaging and laboratory findings revealed elusive results. Herein, we present a rare case of neurosyphilis presenting as cerebral gumma confirmed by histopathological examination, and positive serologic and cerebrospinal fluid analyses. This case report suggests that cerebral gumma should be considered as possible diagnosis for human immunodeficiency virus-negative patients with space-occupying lesion of the brain. And this case also provides importance of clinical suspicions in diagnosing neurosyphilis because syphilis serology is not routinely tested on patients with neurologic symptoms.

  8. Cerebral gumma mimicking a brain tumor in a human immunodeficiency virus-negative patient: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Hye Jin; Kim, Woo Jin [Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2013-09-15

    Syphilis has a broad spectrum of clinical manifestations, and the cerebral gumma is a kind of neurosyphilis which is rare and can be cured by appropriate antibiotic treatments. However, in clinical practices, diagnosis of cerebral syphilitic gumma is often difficult because imaging and laboratory findings revealed elusive results. Herein, we present a rare case of neurosyphilis presenting as cerebral gumma confirmed by histopathological examination, and positive serologic and cerebrospinal fluid analyses. This case report suggests that cerebral gumma should be considered as possible diagnosis for human immunodeficiency virus-negative patients with space-occupying lesion of the brain. And this case also provides importance of clinical suspicions in diagnosing neurosyphilis because syphilis serology is not routinely tested on patients with neurologic symptoms.

  9. A baculovirus dual expression system-based vaccine confers complete protection against lethal challenge with H9N2 avian influenza virus in mice

    Directory of Open Access Journals (Sweden)

    Ye Yu

    2011-06-01

    Full Text Available Abstract Background Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. Results The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice. Conclusion BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection.

  10. Mutations to PB2 and NP proteins of an avian influenza virus combine to confer efficient growth in primary human respiratory cells.

    Science.gov (United States)

    Danzy, Shamika; Studdard, Lydia R; Manicassamy, Balaji; Solorzano, Alicia; Marshall, Nicolle; García-Sastre, Adolfo; Steel, John; Lowen, Anice C

    2014-11-01

    Influenza pandemics occur when influenza A viruses (IAV) adapted to other host species enter humans and spread through the population. Pandemics are relatively rare due to host restriction of IAV: strains adapted to nonhuman species do not readily infect, replicate in, or transmit among humans. IAV can overcome host restriction through reassortment or adaptive evolution, and these are mechanisms by which pandemic strains arise in nature. To identify mutations that facilitate growth of avian IAV in humans, we have adapted influenza A/duck/Alberta/35/1976 (H1N1) (dk/AB/76) virus to a high-growth phenotype in differentiated human tracheo-bronchial epithelial (HTBE) cells. Following 10 serial passages of three independent lineages, the bulk populations showed similar growth in HTBE cells to that of a human seasonal virus. The coding changes present in six clonal isolates were determined. The majority of changes were located in the polymerase complex and nucleoprotein (NP), and all isolates carried mutations in the PB2 627 domain and regions of NP thought to interact with PB2. Using reverse genetics, the impact on growth and polymerase activity of individual and paired mutations in PB2 and NP was evaluated. The results indicate that coupling of the mammalian-adaptive mutation PB2 E627K or Q591K to selected mutations in NP further augments the growth of the corresponding viruses. In addition, minimal combinations of three (PB2 Q236H, E627K, and NP N309K) or two (PB2 Q591K and NP S50G) mutations were sufficient to recapitulate the efficient growth in HTBE cells of dk/AB/76 viruses isolated after 10 passages in this substrate. Influenza A viruses adapted to birds do not typically grow well in humans. However, as has been seen recently with H5N1 and H7N9 subtype viruses, productive and virulent infection of humans with avian influenza viruses can occur. The ability of avian influenza viruses to adapt to new host species is a consequence of their high mutation rate that

  11. A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets and monkeys

    Science.gov (United States)

    A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of HP A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (...

  12. Memory T Cells Generated by Prior Exposure to Influenza Cross React with the Novel H7N9 Influenza Virus and Confer Protective Heterosubtypic Immunity

    Science.gov (United States)

    McMaster, Sean R.; Gabbard, Jon D.; Koutsonanos, Dimitris G.; Compans, Richard W.; Tripp, Ralph A.; Tompkins, S. Mark; Kohlmeier, Jacob E.

    2015-01-01

    Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic. PMID:25671696

  13. Memory T cells generated by prior exposure to influenza cross react with the novel H7N9 influenza virus and confer protective heterosubtypic immunity.

    Directory of Open Access Journals (Sweden)

    Sean R McMaster

    Full Text Available Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic.

  14. Resistance to Two Heterologous Neurotropic Oncolytic Viruses, Semliki Forest Virus and Vaccinia Virus, in Experimental Glioma

    Science.gov (United States)

    Le Boeuf, Fabrice; Lemay, Chantal; De Silva, Naomi; Diallo, Jean-Simon; Cox, Julie; Becker, Michelle; Choi, Youngmin; Ananth, Abhirami; Sellers, Clara; Breton, Sophie; Roy, Dominic; Falls, Theresa; Brun, Jan; Hemminki, Akseli; Hinkkanen, Ari; Bell, John C.

    2013-01-01

    Attenuated Semliki Forest virus (SFV) may be suitable for targeting malignant glioma due to its natural neurotropism, but its replication in brain tumor cells may be restricted by innate antiviral defenses. We attempted to facilitate SFV replication in glioma cells by combining it with vaccinia virus, which is capable of antagonizing such defenses. Surprisingly, we found parenchymal mouse brain tumors to be refractory to both viruses. Also, vaccinia virus appears to be sensitive to SFV-induced antiviral interference. PMID:23221568

  15. The nucleoprotein of newly emerged H7N9 influenza A virus harbors a unique motif conferring resistance to antiviral human MxA.

    Science.gov (United States)

    Riegger, David; Hai, Rong; Dornfeld, Dominik; Mänz, Benjamin; Leyva-Grado, Victor; Sánchez-Aparicio, Maria T; Albrecht, Randy A; Palese, Peter; Haller, Otto; Schwemmle, Martin; García-Sastre, Adolfo; Kochs, Georg; Schmolke, Mirco

    2015-02-01

    Interferon-induced Mx proteins show strong antiviral activity against influenza A viruses (IAVs). We recently demonstrated that the viral nucleoprotein (NP) determines resistance of seasonal and pandemic human influenza viruses to Mx, while avian isolates retain Mx sensitivity. We identified a surface-exposed cluster of amino acids in NP of pandemic A/BM/1/1918 (H1N1), comprising isoleucine-100, proline-283, and tyrosine-313, that is essential for reduced Mx sensitivity in cell culture and in vivo. This cluster has been maintained in all descendant seasonal strains, including A/PR/8/34 (PR/8). Accordingly, two substitutions in the NP of PR/8 [PR/8(mut)] to the Mx-sensitive amino acids (P283L and Y313F) led to attenuation in Mx1-positive mice. Serial lung passages of PR/8(mut) in Mx1 mice resulted in a single exchange of tyrosine to asparagine at position 52 in NP (in close proximity to the amino acid cluster at positions 100, 283, and 313), which partially compensates loss of Mx resistance in PR/8(mut). Intriguingly, the NP of the newly emerged avian-origin H7N9 virus also contains an asparagine at position 52 and shows reduced Mx sensitivity. N52Y substitution in NP results in increased sensitivity of the H7N9 virus to human Mx, indicating that this residue is a determinant of Mx resistance in mammals. Our data strengthen the hypothesis that the human Mx protein represents a potent barrier against zoonotic transmission of avian influenza viruses. However, the H7N9 viruses overcome this restriction by harboring an NP that is less sensitive to Mx-mediated host defense. This might contribute to zoonotic transmission of H7N9 and to the severe to fatal outcome of H7N9 infections in humans. The natural host of influenza A viruses (IAVs) are aquatic birds. Occasionally, these viruses cross the species barrier, as in early 2013 when an avian H7N9 virus infected humans in China. Since then, multiple transmissions of H7N9 viruses to humans have occurred, leaving experts

  16. A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4

    International Nuclear Information System (INIS)

    Hanley, Kathryn A.; Manlucu, Luella R.; Gilmore, Lara E.; Blaney, Joseph E.; Hanson, Christopher T.; Murphy, Brian R.; Whitehead, Stephen S.

    2003-01-01

    An acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Δ30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host

  17. Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection.

    Science.gov (United States)

    Ferrari, Roberto; Gou, Dawei; Jawdekar, Gauri; Johnson, Sarah A; Nava, Miguel; Su, Trent; Yousef, Ahmed F; Zemke, Nathan R; Pellegrini, Matteo; Kurdistani, Siavash K; Berk, Arnold J

    2014-11-12

    Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGF-β, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Structural Analysis of a Viral Ovarian Tumor Domain Protease from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded Ubiquitin

    Energy Technology Data Exchange (ETDEWEB)

    Capodagli, Glenn C.; McKercher, Marissa A.; Baker, Erica A.; Masters, Emily M.; Brunzelle, Joseph S.; Pegan, Scott D. (Denver); (NWU)

    2014-10-02

    Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(-)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage of posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 {angstrom}, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.

  19. Tofacitinib induces G1 cell-cycle arrest and inhibits tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells.

    Science.gov (United States)

    Ando, Shotaro; Kawada, Jun-Ichi; Watanabe, Takahiro; Suzuki, Michio; Sato, Yoshitaka; Torii, Yuka; Asai, Masato; Goshima, Fumi; Murata, Takayuki; Shimizu, Norio; Ito, Yoshinori; Kimura, Hiroshi

    2016-11-22

    Epstein-Barr virus (EBV) infects not only B cells, but also T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoma. These lymphoid malignancies are refractory to conventional chemotherapy. We examined the activation of the JAK3/STAT5 pathway in EBV-positive and -negative B, T and NK cell lines and in cell samples from patients with EBV-associated T cell lymphoma. We then evaluated the antitumor effects of the selective JAK3 inhibitor, tofacitinib, against these cell lines in vitro and in a murine xenograft model. We found that all EBV-positive T and NK cell lines and patient samples tested displayed activation of the JAK3/STAT5 pathway. Treatment of these cell lines with tofacitinib reduced the levels of phospho-STAT5, suppressed proliferation, induced G1 cell-cycle arrest and decreased EBV LMP1 and EBNA1 expression. An EBV-negative NK cell line was also sensitive to tofacitinib, whereas an EBV-infected NK cell line was more sensitive to tofacitinib than its parental line. Tofacitinib significantly inhibited the growth of established tumors in NOG mice. These findings suggest that tofacitinib may represent a useful therapeutic agent for patients with EBV-associated T and NK cell lymphoma.

  20. Liver cancer-derived hepatitis C virus core proteins shift TGF-beta responses from tumor suppression to epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Serena Battaglia

    Full Text Available BACKGROUND: Chronic hepatitis C virus (HCV infection and associated liver cirrhosis represent a major risk factor for hepatocellular carcinoma (HCC development. TGF-beta is an important driver of liver fibrogenesis and cancer; however, its actual impact in human cancer progression is still poorly known. The aim of this study was to investigate the role of HCC-derived HCV core natural variants on cancer progression through their impact on TGF-beta signaling. PRINCIPAL FINDINGS: We provide evidence that HCC-derived core protein expression in primary human or mouse hepatocyte alleviates TGF-beta responses in terms or growth inhibition or apoptosis. Instead, in these hepatocytes TGF-beta was still able to induce an epithelial to mesenchymal transition (EMT, a process that contributes to the promotion of cell invasion and metastasis. Moreover, we demonstrate that different thresholds of Smad3 activation dictate the TGF-beta responses in hepatic cells and that HCV core protein, by decreasing Smad3 activation, may switch TGF-beta growth inhibitory effects to tumor promoting responses. CONCLUSION/SIGNIFICANCE: Our data illustrate the capacity of hepatocytes to develop EMT and plasticity under TGF-beta, emphasize the role of HCV core protein in the dynamic of these effects and provide evidence for a paradigm whereby a viral protein implicated in oncogenesis is capable to shift TGF-beta responses from cytostatic effects to EMT development.

  1. Use of anti-tumor necrosis factor biologics in the treatment of rheumatoid arthritis does not change human T-lymphotropic virus type 1 markers: a case series.

    Science.gov (United States)

    Umekita, Kunihiko; Umeki, Kazumi; Miyauchi, Shunichi; Ueno, Shiro; Kubo, Kazuyoshi; Kusumoto, Norio; Takajo, Ichiro; Nagatomo, Yasuhiro; Okayama, Akihiko

    2015-09-01

    Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.

  2. Conference summaries

    International Nuclear Information System (INIS)

    1991-01-01

    This volume contains conference summaries for the 31. annual conference of the Canadian Nuclear Association and the 12. annual conference of the Canadian Nuclear Society. Topics of discussion include: reactor physics; thermalhydraulics; industrial irradiation; computer applications; fuel channel analysis; small reactors; severe accidents; fuel behaviour under accident conditions; reactor components, safety related computer software; nuclear fuel management; fuel behaviour and performance; reactor safety; reactor engineering; nuclear waste management; and, uranium mining and processing

  3. INTERCARTO CONFERENCES

    OpenAIRE

    Vladimir Tikunov

    2010-01-01

    The InterCarto conferences are thematically organized to target one of the most pressing problems of modern geography—creation and use of geographical information systems (GISs) as effective tools for achieving sustainable development of territories. Over the years, from 1994 to 2009, 1872 participants from 51 countries and 156 cities, who made 1494 reports, attended the conferences. There were 1508 participants from 49 regions of Russia making 1340 presentations. The conferences hosted 31 di...

  4. In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses

    Science.gov (United States)

    Schmier, Sonja; Mostafa, Ahmed; Haarmann, Thomas; Bannert, Norbert; Ziebuhr, John; Veljkovic, Veljko; Dietrich, Ursula; Pleschka, Stephan

    2015-06-01

    Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.

  5. Increased pulmonary secretion of tumor necrosis factor-alpha in calves experimentally infected with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Rontved, C. M.; Tjørnehøj, Kirsten; Viuff, B.

    2000-01-01

    , of which 23 were experimentally infected with BRSV and five were given a mock inoculum. The presence of the cytokine tumor necrosis factor alpha (TNF-alpha) in the BAL fluids was detected and quantified by a capture ELISA. TNF-alpha was detected in 21 of the infected animals. The amount of TNF-alpha...... in the BAL fluid of calves killed post inoculation day (PID) 2 and 4 was at the same very low level as in the uninfected control animals. Large amounts of TNF-alpha were detected on PID 6, maximum levels of TNF-alpha were reached on PID 7, and smaller amounts of TNF-alpha were seen on PID 8. The high levels...... of TNF-alpha appeared on the days where severe lung lesions and clinical signs were obvious and the amounts of BRSV-antigen were at their greatest. Although Pasteurellaceae were isolated from some of the BRSV-infected calves, calves treated with antibiotics before and through the whole period...

  6. Exosomes isolated from cancer patients' sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells.

    Science.gov (United States)

    Abdouh, Mohamed; Hamam, Dana; Gao, Zu-Hua; Arena, Vincenzo; Arena, Manuel; Arena, Goffredo Orazio

    2017-08-30

    Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients' sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients' sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients' sera or cancer patients' sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts' membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Cells treated with exosomes isolated from cancer patients' sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression

  7. The synergistic effect of chemical carcinogens enhances Epstein-Barr virus reactivation and tumor progression of nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Fang, Chih-Yeu; Huang, Sheng-Yen; Wu, Chung-Chun; Hsu, Hui-Yu; Chou, Sheng-Ping; Tsai, Ching-Hwa; Chang, Yao; Takada, Kenzo; Chen, Jen-Yang

    2012-01-01

    Seroepidemiological studies imply a correlation between Epstein-Barr virus (EBV) reactivation and the development of nasopharyngeal carcinoma (NPC). N-nitroso compounds, phorbols, and butyrates are chemicals found in food and herb samples collected from NPC high-risk areas. These chemicals have been reported to be risk factors contributing to the development of NPC, however, the underlying mechanism is not fully understood. We have demonstrated previously that low dose N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 0.1 µg/ml) had a synergistic effect with 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate (SB) in enhancing EBV reactivation and genome instability in NPC cells harboring EBV. Considering that residents in NPC high-risk areas may contact regularly with these chemical carcinogens, it is vital to elucidate the relation between chemicals and EBV and their contributions to the carcinogenesis of NPC. In this study, we constructed a cell culture model to show that genome instability, alterations of cancer hallmark gene expression, and tumorigenicity were increased after recurrent EBV reactivation in NPC cells following combined treatment of TPA/SB and MNNG. NPC cells latently infected with EBV, NA, and the corresponding EBV-negative cell, NPC-TW01, were periodically treated with MNNG, TPA/SB, or TPA/SB combined with MNNG. With chemically-induced recurrent reactivation of EBV, the degree of genome instability was significantly enhanced in NA cells treated with a combination of TPA/SB and MNNG than those treated individually. The Matrigel invasiveness, as well as the tumorigenicity in mouse, was also enhanced in NA cells after recurrent EBV reactivation. Expression profile analysis by microarray indicates that many carcinogenesis-related genes were altered after recurrent EBV reactivation, and several aberrations observed in cell lines correspond to alterations in NPC lesions. These results indicate that cooperation between chemical carcinogens can

  8. Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV).

    Science.gov (United States)

    Aktar, Suriya J; Vivet-Boudou, Valérie; Ali, Lizna M; Jabeen, Ayesha; Kalloush, Rawan M; Richer, Delphine; Mustafa, Farah; Marquet, Roland; Rizvi, Tahir A

    2014-11-14

    two MMTV RNAs, leading to gRNA dimerization and its subsequent encapsidation into the assembling virus particles. The results presented here enhance our understanding of the MMTV gRNA dimerization and packaging processes and the role of structural motifs with respect to RNA-RNA and possibly RNA-protein interactions that might be taking place during MMTV life cycle.

  9. Conference summaries

    International Nuclear Information System (INIS)

    1986-01-01

    This volume contains conference summaries of the international conference on radioactive waste management of the Canadian Nuclear Society. Topics of discussion include: storage and disposal; hydrogeology and geochemistry; transportation; buffers and backfill; public attitudes; tailings; site investigations and geomechanics; concrete; economics; licensing; matrix materials and container design; durability of fuel; biosphere modelling; radioactive waste processing; and, future options

  10. Development of reliable techniques for the differential diagnosis of avian tumor viruses by immunohistochemistry and polymerase chain reaction from formalin-fixed paraffin-embedded tissue sections

    Science.gov (United States)

    In the past, several techniques have been developed as diagnostic tools for the differential diagnosis of tumours produced by Marek’s disease virus (MDV) from those induced by avian leukosis virus (ALV) and reticuloendotheliosis virus (REV). However, most current techniques are unreliable using form...

  11. FasL and FADD delivery by a glioma-specific and cell cycle-dependent HSV-1 amplicon virus enhanced apoptosis in primary human brain tumors

    Directory of Open Access Journals (Sweden)

    Lam Paula Y

    2010-10-01

    Full Text Available Abstract Background Glioblastoma multiforme is the most malignant cancer of the brain and is notoriously difficult to treat due to the highly proliferative and infiltrative nature of the cells. Herein, we explored the combination treatment of pre-established human glioma xenograft using multiple therapeutic genes whereby the gene expression is regulated by both cell-type and cell cycle-dependent transcriptional regulatory mechanism conferred by recombinant HSV-1 amplicon vectors. Results We demonstrated for the first time that Ki67-positive proliferating primary human glioma cells cultured from biopsy samples were effectively induced into cell death by the dual-specific function of the pG8-FasL amplicon vectors. These vectors were relatively stable and exhibited minimal cytotoxicity in vivo. Intracranial implantation of pre-transduced glioma cells resulted in better survival outcome when compared with viral vectors inoculated one week post-implantation of tumor cells, indicating that therapeutic efficacy is dependent on the viral spread and mode of viral vectors administration. We further showed that pG8-FasL amplicon vectors are functional in the presence of commonly used treatment regimens for human brain cancer. In fact, the combined therapies of pG8-FasL and pG8-FADD in the presence of temozolomide significantly improved the survival of mice bearing intracranial high-grade gliomas. Conclusion Taken together, our results showed that the glioma-specific and cell cycle-dependent HSV-1 amplicon vector is potentially useful as an adjuvant therapy to complement the current gene therapy strategy for gliomas.

  12. Constitutive expression of interferon-induced human MxA protein in transgenic tobacco plants does not confer resistance to a variety of RNA viruses

    NARCIS (Netherlands)

    Frese, M.; Prins, M.; Ponten, A.; Goldbach, R.W.; Haller, O.; Zeltz, P.

    2000-01-01

    MxA is a key component in the interferon-induced antiviral defense in humans. After viral infections, MxA is rapidly induced and accumulates in the cytoplasm. The multiplication of many RNA viruses,including all bunyaviruses tested so far, is inhibited by MxA. These findings prompted us to express

  13. INTERCARTO CONFERENCES

    Directory of Open Access Journals (Sweden)

    Vladimir Tikunov

    2010-01-01

    Full Text Available The InterCarto conferences are thematically organized to target one of the most pressing problems of modern geography—creation and use of geographical information systems (GISs as effective tools for achieving sustainable development of territories. Over the years, from 1994 to 2009, 1872 participants from 51 countries and 156 cities, who made 1494 reports, attended the conferences. There were 1508 participants from 49 regions of Russia making 1340 presentations. The conferences hosted 31 different sections, most popular of which were Environmental GIS-Projects: Development and Experience, Sustainable Development and Innovative Projects, GIS: the Theory and Methodology, Projects for Russia and Regions, and GIS-Technologies and Digital Mapping. The next annual InterCarto-InterGIS conference will take place in December 2011. The Russian component of the conference will be held in the Altay Kray followed by another meeting on Bali, Indonesia

  14. Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells

    Science.gov (United States)

    Takachi, Takayuki; Takahashi, Masahiko; Takahashi-Yoshita, Manami; Higuchi, Masaya; Obata, Miki; Mishima, Yukio; Okuda, Shujiro; Tanaka, Yuetsu; Matsuoka, Masao; Saitoh, Akihiko; Green, Patrick L; Fujii, Masahiro

    2015-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia (ATL), which is an aggressive form of T-cell malignancy. HTLV-1 oncoproteins, Tax and HBZ, play crucial roles in the immortalization of T-cells and/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that HTLV-1-infected T-cells have reduced expression of the BCL11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral transduction of Tax in a human T-cell line repressed the expression of BCL11B at both the protein and mRNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF-κB, CREB or PDZ protein pathways still showed a reduced expression of the BCL11B protein, thereby implicating a different function of Tax in BCL11B downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL-derived cell lines, showed reduced BCL11B mRNA and protein expression relative to an uninfected T-cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of HTLV-1-infected T-cells. PMID:25613934

  15. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas

    International Nuclear Information System (INIS)

    Glaser, R.; Zhang, Haizhang; Yao, Kaitai; Zhu, Hecheng; Wang, Fuxi; Li, Guiyuan; Wen, Dongseng; Li, Yingping

    1989-01-01

    Two epithelia tumor cell lines were established from biopsy specimens of nasopharyngeal carcinomas (NPC). The specimens were taken from poorly differentiated squamous cell carcinomas of the nasopharynx. The tissues were prepared for cell culture and eventually two continuous epithelia cell lines were obtained and designated HONE-1 and HNE-1. Light and electron microscopic examination of these two cell lines demonstrated cells with an epithelial morphology including the presence of desmosomes. It was found that early-passage uncloned HNE-1 cells (passage 23) could be superinfected with B95-8 and NPC-EBV isolates as demonstrated by the induction of Epstein-Barr virus (EBV)-specific early antigen(s) in a small percentage of the cells; HONE-1 cells could also be superinfected with EBV. Southern blot analysis detected EBV DNA in samples from uncloned HNE-1 cells at passages 12, 17, 21, 27, and 35. However, by passage 45, EBV DNA could no longer be detected in HNE-1 cells by Southern blot analysis. The EBV genome was detected in parental HONE-1 cells at subculture 9 and in clone 40 cells up to passage 40 thus far. The data suggest that EBV genome-positive HNE-1 and HONE-1 cells were lost as the cells were cultivated in vitro and that cloning the cells at an early passage level may be critical in maintaining EBV genome-positive epithelial NPC cells. These EBV genome-positive epithelia NPC cell lines will be useful for studying the association of EBV and NPC

  16. Human T-cell lymphotropic virus type 1-infected T lymphocytes impair catabolism and uptake of glutamate by astrocytes via Tax-1 and tumor necrosis factor alpha.

    Science.gov (United States)

    Szymocha, R; Akaoka, H; Dutuit, M; Malcus, C; Didier-Bazes, M; Belin, M F; Giraudon, P

    2000-07-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of a chronic progressive myelopathy called tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In this disease, lesions of the central nervous system (CNS) are associated with perivascular infiltration by lymphocytes. We and others have hypothesized that these T lymphocytes infiltrating the CNS may play a prominent role in TSP/HAM. Here, we show that transient contact of human or rat astrocytes with T lymphocytes chronically infected by HTLV-1 impairs some of the major functions of brain astrocytes. Uptake of extracellular glutamate by astrocytes was significantly decreased after transient contact with infected T cells, while the expression of the glial transporters GLAST and GLT-1 was decreased. In two-compartment cultures avoiding direct cell-to-cell contact, similar results were obtained, suggesting possible involvement of soluble factors, such as cytokines and the viral protein Tax-1. Recombinant Tax-1 and tumor necrosis factor alpha (TNF-alpha) decreased glutamate uptake by astrocytes. Tax-1 probably acts by inducing TNF-alpha, as the effect of Tax-1 was abolished by anti-TNF-alpha antibody. The expression of glutamate-catabolizing enzymes in astrocytes was increased for glutamine synthetase and decreased for glutamate dehydrogenase, the magnitudes of these effects being correlated with the level of Tax-1 transcripts. In conclusion, Tax-1 and cytokines produced by HTLV-1-infected T cells impair the ability of astrocytes to manage the steady-state level of glutamate, which in turn may affect neuronal and oligodendrocytic functions and survival.

  17. Conference summaries

    International Nuclear Information System (INIS)

    1988-01-01

    This volume contains conference summaries of the 28. annual conference of the Canadian Nuclear Association, and the 9. annual conference of the Canadian Nuclear Society. Topics of discussion include: power reactors; fuel cycles; nuclear power and public understanding; future trends; applications of nuclear technology; CANDU reactors; operational enhancements; design of small reactors; accident behaviour in fuel channels; fuel storage and waste management; reactor commissioning/decommissioning; nuclear safety experiments and modelling; the next generation reactors; advances in nuclear engineering education in Canada; safety of small reactors; current position and improvements of fuel channels; current issues in nuclear safety; and radiation applications - medical and industrial

  18. Seasonal influenza split vaccines confer partial cross-protection against heterologous influenza virus in ferrets when combined with the CAF01 adjuvant

    DEFF Research Database (Denmark)

    Christensen, Dennis; Christensen, Jan P.; Korsholm, Karen S.

    2018-01-01

    Influenza epidemics occur annually, and estimated 5-10% of the adult population and 20-30% of children will become ill from influenza infection. Seasonal vaccines primarily work through the induction of neutralizing antibodies against the principal surface antigen hemagglutinin (HA). This important...... role of HA-specific antibodies explains why previous pandemics have emerged when new HAs have appeared in circulating human viruses. It has long been recognized that influenza virus-specific CD4(+) T cells are important in protection from infection through direct effector mechanisms or by providing...... help to B cells and CD8(+) T cells. However, the seasonal influenza vaccine is poor at inducing CD4(+) T-cell responses and needs to be combined with an adjuvant facilitating this response. In this study, we applied the ferret model to investigate the cross-protective efficacy of a heterologous...

  19. Mucosal immunity induced by adenovirus-based H5N1 HPAI vaccine confers protection against a lethal H5N2 avian influenza virus challenge

    International Nuclear Information System (INIS)

    Park, Ki Seok; Lee, Jiyeung; Ahn, So Shin; Byun, Young-Ho; Seong, Baik Lin; Baek, Yun Hee; Song, Min-Suk; Choi, Young Ki; Na, Yun Jeong; Hwang, Inhwan; Sung, Young Chul; Lee, Chang Geun

    2009-01-01

    Development of effective vaccines against highly pathogenic avian influenza (HPAI) H5N1 viruses is a global public health priority. Considering the difficulty in predicting HPAI H5N1 pandemic strains, one strategy used in their design includes the development of formulations with the capacity of eliciting broad cross-protective immunity against multiple viral antigens. To this end we constructed a replication-defective recombinant adenovirus-based avian influenza virus vaccine (rAdv-AI) expressing the codon-optimized M2eX-HA-hCD40L and the M1-M2 fusion genes from HPAI H5N1 human isolate. Although there were no significant differences in the systemic immune responses observed between the intramuscular prime-intramuscular boost regimen (IM/IM) and the intranasal prime-intramuscular boost regimen (IN/IM), IN/IM induced more potent CD8 + T cell and antibody responses at mucosal sites than the IM/IM vaccination, resulting in more effective protection against lethal H5N2 avian influenza (AI) virus challenge. These findings suggest that the strategies used to induce multi-antigen-targeted mucosal immunity, such as IN/IM delivery of rAdv-AI, may be a promising approach for developing broad protective vaccines that may be more effective against the new HPAI pandemic strains.

  20. Viruses and Breast Cancer

    Science.gov (United States)

    Lawson, James S.; Heng, Benjamin

    2010-01-01

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix. PMID:24281093

  1. Viruses and Breast Cancer

    International Nuclear Information System (INIS)

    Lawson, James S.; Heng, Benjamin

    2010-01-01

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix

  2. Viruses and Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lawson, James S., E-mail: james.lawson@unsw.edu.au; Heng, Benjamin [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney (Australia)

    2010-04-30

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

  3. Virus-Vectored Influenza Virus Vaccines

    Science.gov (United States)

    Tripp, Ralph A.; Tompkins, S. Mark

    2014-01-01

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

  4. Inhibition of transient receptor potential vanilloid-1 confers neuroprotection, reduces tumor necrosis factor-alpha, and increases IL-10 in a rat stroke model.

    Science.gov (United States)

    Hakimizadeh, Elham; Shamsizadeh, Ali; Roohbakhsh, Ali; Arababadi, Mohammad Kazemi; Hajizadeh, Mohammad R; Shariati, Mehdi; Rahmani, Mohammad R; Allahtavakoli, Mohammad

    2017-08-01

    Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  5. Pancreatic gross tumor volume contouring on computed tomography (CT) compared with magnetic resonance imaging (MRI): Results of an international contouring conference.

    Science.gov (United States)

    Hall, William A; Heerkens, Hanne D; Paulson, Eric S; Meijer, Gert J; Kotte, Alexis N; Knechtges, Paul; Parikh, Parag J; Bassetti, Michael F; Lee, Percy; Aitken, Katharine L; Palta, Manisha; Myrehaug, Sten; Koay, Eugene J; Portelance, Lorraine; Ben-Josef, Edgar; Erickson, Beth A

    Accurate identification of the gross tumor volume (GTV) in pancreatic adenocarcinoma is challenging. We sought to understand differences in GTV delineation using pancreatic computed tomography (CT) compared with magnetic resonance imaging (MRI). Twelve attending radiation oncologists were convened for an international contouring symposium. All participants had a clinical and research interest in pancreatic adenocarcinoma. CT and MRI scans from 3 pancreatic cases were used for contouring. CT and MRI GTVs were analyzed and compared. Interobserver variability was compared using Dice's similarity coefficient (DSC), Hausdorff distances, and Jaccard indices. Mann-Whitney tests were used to check for significant differences. Consensus contours on CT and MRI scans and constructed count maps were used to visualize the agreement. Agreement regarding the optimal method to determine GTV definition using MRI was reached. Six contour sets (3 from CT and 3 from MRI) were obtained and compared for each observer, totaling 72 contour sets. The mean volume of contours on CT was significantly larger at 57.48 mL compared with a mean of 45.76 mL on MRI, P = .011. The standard deviation obtained from the CT contours was significantly larger than the standard deviation from the MRI contours (P = .027). The mean DSC was 0.73 for the CT and 0.72 for the MRI (P = .889). The conformity index measurement was similar for CT and MRI (P = .58). Count maps were created to highlight differences in the contours from CT and MRI. Using MRI as a primary image set to define a pancreatic adenocarcinoma GTV resulted in smaller contours compared with CT. No differences in DSC or the conformity index were seen between MRI and CT. A stepwise method is recommended as an approach to contour a pancreatic GTV using MRI. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  6. Loss of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 Confers Resistance to the Antiatherogenic Effects of Tumor Necrosis Factor-α Inhibition.

    Science.gov (United States)

    Zhu, Lin; Giunzioni, Ilaria; Tavori, Hagai; Covarrubias, Roman; Ding, Lei; Zhang, Youmin; Ormseth, Michelle; Major, Amy S; Stafford, John M; Linton, MacRae F; Fazio, Sergio

    2016-08-01

    Antiatherosclerotic effects of tumor necrosis factor-α (TNF-α) blockade in patients with systemic inflammatory states are not conclusively demonstrated, which suggests that effects depend on the cause of inflammation. Macrophage LRP1 (low-density lipoprotein receptor-related protein 1) and apoE contribute to inflammation through different pathways. We studied the antiatherosclerosis effects of TNF-α blockade in hyperlipidemic mice lacking either LRP1 (MΦLRP1(-/-)) or apoE from macrophages. Lethally irradiated low-density lipoprotein receptor (LDLR)(-/-) mice were reconstituted with bone marrow from either wild-type, MΦLRP1(-/-), apoE(-/-) or apoE(-/-)/MΦLRP1(-/-)(DKO) mice, and then treated with the TNF-α inhibitor adalimumab while fed a Western-type diet. Adalimumab reduced plasma TNF-α concentration, suppressed blood ly6C(hi) monocyte levels and their migration into the lesion, and reduced lesion cellularity and inflammation in both wild-type→LDLR(-/-) and apoE(-/-)→LDLR(-/-) mice. Overall, adalimumab reduced lesion burden by 52% to 57% in these mice. Adalimumab reduced TNF-α and blood ly6C(hi) monocyte levels in MΦLRP1(-/-)→LDLR(-/-) and DKO→LDLR(-/-) mice, but it did not suppress ly6C(hi) monocyte migration into the lesion or atherosclerosis progression. Our results show that TNF-α blockade exerts antiatherosclerotic effects that are dependent on the presence of macrophage LRP1. © 2016 American Heart Association, Inc.

  7. Intranasal immunization of baculovirus displayed hemagglutinin confers complete protection against mouse adapted highly pathogenic H7N7 reassortant influenza virus.

    Directory of Open Access Journals (Sweden)

    Subaschandrabose Rajesh Kumar

    Full Text Available BACKGROUND: Avian influenza A H7N7 virus poses a pandemic threat to human health because of its ability for direct transmission from domestic poultry to humans and from human to human. The wide zoonotic potential of H7N7 combined with an antiviral immunity inhibition similar to pandemic 1918 H1N1 and 2009 H1N1 influenza viruses is disconcerting and increases the risk of a putative H7N7 pandemic in the future, underlining the urgent need for vaccine development against this virus. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we developed a recombinant vaccine by expressing the H7N7-HA protein on the surface of baculovirus (Bac-HA. The protective efficacy of the live Bac-HA vaccine construct was evaluated in a mouse model by challenging mice immunized intranasally (i.n. or subcutaneously (s.c. with high pathogenic mouse adapted H7N7 reassorted strain. Although s.c. injection of live Bac-HA induced higher specific IgG than i.n. immunization, the later resulted in an elevated neutralization titer. Interestingly, 100% protection from the lethal viral challenge was only observed for the mice immunized intranasally with live Bac-HA, whereas no protection was achieved in any other s.c. or i.n. immunized mice groups. In addition, we also observed higher mucosal IgA as well as increased IFN-γ and IL-4 responses in the splenocytes of the surviving mice coupled with a reduced viral titer and diminished histopathological signs in the lungs. CONCLUSION: Our results indicated that protection from high pathogenic H7N7 (NL/219/03 virus requires both mucosal and systemic immune responses in mice. The balance between Th1 and Th2 cytokines is also required for the protection against the H7N7 pathogen. Intranasal administration of live Bac-HA induced all these immune responses and protected the mice from lethal viral challenge. Therefore, live Bac-HA is an effective vaccine candidate against H7N7 viral infections.

  8. Superior Orbital Fissure Syndrome and Ophthalmoplegia Caused by Varicella Zoster Virus with No Skin Eruption in a Patient Treated with Tumor Necrosis Alpha Inhibitor

    DEFF Research Database (Denmark)

    Jensen, Helene; Thomsen, Sidsel Thorup; Hansen, Stine Scott

    2015-01-01

    Varicella zoster virus lies dormant in the dorsal root ganglia after symptomatic chicken pox infection, usually in childhood. If the virus reactivates in the trigeminal ganglia, it can cause varicella zoster ophthalmicus, which can have severe ocular complications. We report a case of a 73-year...

  9. La depleción de las células T regulatorias aumenta el número de las células CD8 durante la infección con el virus del tumor mamario murino

    OpenAIRE

    Gabriel Cabrera; Juliana Mundiñano; Gabriela Camicia; Héctor Costa; Irene Nepomnaschy; Isabel Piazzon

    2011-01-01

    El virus del tumor mamario murino (MMTV) es un retrovirus que se transmite durante la lactancia y que ha desarrollado estrategias para explotar y subvertir el sistema inmune. En un modelo de infección natural con MMTV hemos mostrado previamente que la infección causa incrementos tempranos y progresivos de células T regulatorias (Treg) CD4+CD25+Foxp3+ específicas para el superantígeno (Sag) viral en las placas de Peyer (PP). En este trabajo se evaluó si la depleción de las células Treg influen...

  10. The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Lotte M E Berghauser Pont

    Full Text Available A phase I/II trial for glioblastoma with the oncolytic adenovirus Delta24-RGD was recently completed. Delta24-RGD conditionally replicates in cells with a disrupted retinoblastoma-pathway and enters cells via αvβ3/5 integrins. Glioblastomas are differentially sensitive to Delta24-RGD. HDAC inhibitors (HDACi affect integrins and share common cell death pathways with Delta24-RGD. We studied the combination treatment effects of HDACi and Delta24-RGD in patient-derived glioblastoma stem-like cells (GSC, and we determined the most effective HDACi.SAHA, Valproic Acid, Scriptaid, MS275 and LBH589 were combined with Delta24-RGD in fourteen distinct GSCs. Synergy was determined by Chou Talalay method. Viral infection and replication were assessed using luciferase and GFP encoding vectors and hexon-titration assays. Coxsackie adenovirus receptor and αvβ3 integrin levels were determined by flow cytometry. Oncolysis and mechanisms of cell death were studied by viability, caspase-3/7, LDH and LC3B/p62, phospho-p70S6K. Toxicity was studied on normal human astrocytes. MGMT promotor methylation status, TCGA classification, Rb-pathway and integrin gene expression levels were assessed as markers of responsiveness.Scriptaid and LBH589 acted synergistically with Delta24-RGD in approximately 50% of the GSCs. Both drugs moderately increased αvβ3 integrin levels and viral infection in responding but not in non-responding GSCs. LBH589 moderately increased late viral gene expression, however, virus titration revealed diminished viral progeny production by both HDACi, Scriptaid augmented caspase-3/7 activity, LC3B conversion, p62 and phospho-p70S6K consumption, as well as LDH levels. LBH589 increased LDH and phospho-p70S6K consumption. Responsiveness correlated with expression of various Rb-pathway genes and integrins. Combination treatments induced limited toxicity to human astrocytes.LBH589 and Scriptaid combined with Delta24-RGD revealed synergistic anti-tumor

  11. Tumor features and correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer with Yin deficiency

    Directory of Open Access Journals (Sweden)

    YANG Zhiyun

    2016-03-01

    Full Text Available ObjectiveTo investigate the tumor features and the correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer (PLC with yin deficiency. MethodsA total of 148 PLC patients who were treated in Beijing Ditan Hospital, Capital Medical University, from July 2013 to February 2015 were enrolled and divided into yin-deficiency PLC group (52 patients and non-yin-deficiency PLC group (96 patients. The patients′ general information and laboratory markers were collected, including oncological parameters (alpha-fetoprotein, carcinoembryonic antigen (CEA, and carbohydrate antigen 199 (CA19-9, virological parameter (HBsAg, gross type (nodular type, massive type, bulky type, and diffuse type, radiological features (main portal vein diameter, portal vein tumor thrombus, and extrahepatic metastasis, biochemical parameters (Model for End-Stage Liver Disease (MELD score, white blood cell, red blood cell, platelet (PLT, alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBil, gamma-glutamyl transpeptidase, alkaline phosphatase, albumin, cholinesterase, prothrombin time (PT, and prothrombin time activity (PTA, and lymphocyte count. The t-test was applied for comparison of normally distributed continuous data between groups, and the Pearson correlation analysis was applied for correlation analysis. The Mann-Whitney U test was applied for comparison of non-normally distributed continuous data between groups, and the Spearman correlation analysis was applied for correlation analysis. The chi-square test was applied for comparison of categorical data between groups. ResultsHBsAg showed a significant difference between the two groups (χ2=5.658, P=0.017. Compared with the non-yin-deficiency PLC group, the yin-deficiency PLC group had significantly increased CEA and CA19-9 (U=-2.200 and -2.194, both P<0.05, significantly increased MELD score, TBil, and PT (t=2.2, U=-2.0, U=-2

  12. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  13. La depleción de las células T regulatorias aumenta el número de las células CD8 durante la infección con el virus del tumor mamario murino Regulatory T cell depletion increases the number of CD8 cells during mouse mammary tumor virus infection

    Directory of Open Access Journals (Sweden)

    Gabriel Cabrera

    2011-06-01

    Full Text Available El virus del tumor mamario murino (MMTV es un retrovirus que se transmite durante la lactancia y que ha desarrollado estrategias para explotar y subvertir el sistema inmune. En un modelo de infección natural con MMTV hemos mostrado previamente que la infección causa incrementos tempranos y progresivos de células T regulatorias (Treg CD4+CD25+Foxp3+ específicas para el superantígeno (Sag viral en las placas de Peyer (PP. En este trabajo se evaluó si la depleción de las células Treg influencia la población de células CD8+ durante la infección con MMTV a través del amamantamiento. La depleción de las células Treg al día 6 de infección causó incrementos en el porcentaje y número absoluto de las células CD8+ en los ganglios y provocó un incremento en la intensidad de fluorescencia media del marcador de activación CD44 en esas células. Los incrementos en el número absoluto de las células CD8 se observaron en células con cadenas variables Vβ del receptor de las células T (TCR tanto reactivas como no reactivas al Sag. Previamente habíamos demostrado que la depleción de las células Treg al día 6 de infección disminuye la carga viral. Los resultados presentados en este trabajo sugieren que, al menos a partir del día 6 de infección con MMTV, las células Treg podrían tener un rol inhibiendo la generación de una respuesta CD8 antiviral.Mouse mammary tumor virus (MMTV is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. We have shown in a natural model of MMTV infection that the virus causes early and progressive increases in superantigen (Sag-specific CD4+ CD25+ Foxp3+ regulatory T cells (Treg in Peyer's patches. Herein, we evaluated whether the depletion of Treg cells affects the CD8+ population during milk-borne MMTV infection. At day 6 of infection, the depletion of Treg cells increased the percentage and absolute number of CD8+ cells in lymph nodes as well as the

  14. Mendel conference

    CERN Document Server

    2015-01-01

    This book is a collection of selected accepted papers of Mendel conference that has been held in Brno, Czech Republic in June 2015. The book contents three chapters which represent recent advances in soft computing including intelligent image processing and bio-inspired robotics.: Chapter 1: Evolutionary Computing, and Swarm intelligence, Chapter 2: Neural Networks, Self-organization, and Machine Learning, and Chapter3: Intelligent Image Processing, and Bio-inspired Robotics. The Mendel conference was established in 1995, and it carries the name of the scientist and Augustinian priest Gregor J. Mendel who discovered the famous Laws of Heredity. In 2015 we are commemorating 150 years since Mendel's lectures, which he presented in Brno on February and March 1865. The main aim of the conference was to create a periodical possibility for students, academics and researchers to exchange their ideas and novel research methods.  .

  15. A tetravalent virus-like particle vaccine designed to display domain III of dengue envelope proteins induces multi-serotype neutralizing antibodies in mice and macaques which confer protection against antibody dependent enhancement in AG129 mice.

    Directory of Open Access Journals (Sweden)

    Viswanathan Ramasamy

    2018-01-01

    Full Text Available Dengue is one of the fastest spreading vector-borne diseases, caused by four antigenically distinct dengue viruses (DENVs. Antibodies against DENVs are responsible for both protection as well as pathogenesis. A vaccine that is safe for and efficacious in all people irrespective of their age and domicile is still an unmet need. It is becoming increasingly apparent that vaccine design must eliminate epitopes implicated in the induction of infection-enhancing antibodies.We report a Pichia pastoris-expressed dengue immunogen, DSV4, based on DENV envelope protein domain III (EDIII, which contains well-characterized serotype-specific and cross-reactive epitopes. In natural infection, <10% of the total neutralizing antibody response is EDIII-directed. Yet, this is a functionally relevant domain which interacts with the host cell surface receptor. DSV4 was designed by in-frame fusion of EDIII of all four DENV serotypes and hepatitis B surface (S antigen and co-expressed with unfused S antigen to form mosaic virus-like particles (VLPs. These VLPs displayed EDIIIs of all four DENV serotypes based on probing with a battery of serotype-specific anti-EDIII monoclonal antibodies. The DSV4 VLPs were highly immunogenic, inducing potent and durable neutralizing antibodies against all four DENV serotypes encompassing multiple genotypes, in mice and macaques. DSV4-induced murine antibodies suppressed viremia in AG129 mice and conferred protection against lethal DENV-4 virus challenge. Further, neither murine nor macaque anti-DSV4 antibodies promoted mortality or inflammatory cytokine production when passively transferred and tested in an in vivo dengue disease enhancement model of AG129 mice.Directing the immune response to a non-immunodominant but functionally relevant serotype-specific dengue epitope of the four DENV serotypes, displayed on a VLP platform, can help minimize the risk of inducing disease-enhancing antibodies while eliciting effective tetravalent

  16. Berkeley Conference

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-10-15

    To a regular observer at annual international meetings, progress in particle physics from one year to the next sometimes might seem ponderously slow. But shift the timescale and the result is startling. Opening his summary of the 1986 International Conference on High Energy Physics, held in Berkeley, California, from 16-23 July, Steve Weinberg first recalled the 1966 Conference, also held in Berkeley. Then the preoccupations were current algebra, hadron resonances and the interpretation of scattering in terms of Regge poles, and the theory of weak interactions. Physics certainly has moved.

  17. Berkeley Conference

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    To a regular observer at annual international meetings, progress in particle physics from one year to the next sometimes might seem ponderously slow. But shift the timescale and the result is startling. Opening his summary of the 1986 International Conference on High Energy Physics, held in Berkeley, California, from 16-23 July, Steve Weinberg first recalled the 1966 Conference, also held in Berkeley. Then the preoccupations were current algebra, hadron resonances and the interpretation of scattering in terms of Regge poles, and the theory of weak interactions. Physics certainly has moved

  18. Conference proceedings

    African Journals Online (AJOL)

    ebutamanya

    2016-02-29

    Feb 29, 2016 ... In addition, there are persistent problems with leadership and planning, vaccine stock management, supply chain capacity and quality, provider-parent communication, and financial sustainability. The conference delegates agreed to move from talking to taking concrete actions around children's health, and ...

  19. Glasgow conference

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Gordon

    1994-10-15

    The biennial 'Rochester' International Conferences on High Energy Physics which tick the rhythm of high energy physics progress reflect the dominance of the 'Standard Model' - the picture of electroweak and quark/gluon interactions in a simple framework of six weaklyinteracting particles (leptons) and six quarks. Despite its limited intellectual appeal, after a decade of intense probing the Standard Model still refuses to budge.

  20. Conference summary

    International Nuclear Information System (INIS)

    Clark, D.J.

    1975-10-01

    A brief review is given of the main results presented at the International Conference on Heavy Ion Sources, October 27--30, 1975. The sections are as follows: highlights, general observations, fundamental processes in sources, positive ion sources, negative ion sources, beam formation and emittance measurements, stripping, accelerators and experiments, and future prospects

  1. Lisbon Conference

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    Although no major physics discoveries were announced, the European Physical Society's International Conference on High Energy Physics, held in Lisbon from 9-15 July, was significant in that it showed the emerging pattern of physics for the 1980s

  2. Conference report

    African Journals Online (AJOL)

    Tamara Shefer

    Bloomberg Philanthropies. The conference theme “from research to implementation” emphasised the importance of connecting knowledge around violence with injury prevention, while stressing the need to address the multitude of transnational public health challenges. In speaking to this theme, the. Tampere Declaration ...

  3. Conference Planning.

    Science.gov (United States)

    Carter, Richard

    1982-01-01

    Presents an overview of the management planning technique known as Break Even Analysis and outlines its use as a tool in financial planning for organizations intending to conduct or sponsor a conference, seminar, or workshop. Three figures illustrating Break Even Analysis concepts and a Break Even Analysis worksheet are included. (JL)

  4. Conference proceedings

    African Journals Online (AJOL)

    abp

    2015-08-07

    Aug 7, 2015 ... Conference was organized in June 2-6, 2014 at the Yaoundé Mont Febe Hotel, in Cameroon. Under the theme«Practice .... while the implementation of family planning in African HIV programs will favor safe contraception ... equipment. The WHO-stepwise approach for the global strategy for the prevention ...

  5. Conference summaries

    International Nuclear Information System (INIS)

    1983-01-01

    The papers presented at this conference cover the fields of thermalhydraulics, nuclear plant design and operation, licensing, decontamination, restoration and dismantling of nuclear power facilities, services to the nuclear industry, new applications of nuclear technology, reactor physics and fuel cycles, accelerator-breeders, fusion research and lasers

  6. Characterization and Comparison of the Structural Features, Immune-Modulatory and Anti-Avian Influenza Virus Activities Conferred by Three Algal Sulfated Polysaccharides

    Science.gov (United States)

    Song, Lin; Chen, Xiaolin; Liu, Xiaodong; Zhang, Fubo; Hu, Linfeng; Yue, Yang; Li, Kecheng; Li, Pengcheng

    2015-01-01

    Three marine macroalgae, i.e., Grateloupia filicina, Ulva pertusa and Sargassum qingdaoense, were selected as the deputies of Rhodophyta, Chlorophyta and Ochrophyta for comparative analysis of the molecular structures and biological activities of sulfated polysaccharides (SP). The ratio of water-soluble polysaccharides, the monosaccharide composition and the sulfated contents of three extracted SPs were determined, and their structures were characterized by Fourier transformation infrared spectroscopy. In addition, biological activity analysis showed that all three SPs had immune-modulatory activity both in vitro and in vivo, and SPs from S. qingdaoense had the best effect. Further bioassays showed that three SPs could not only enhance the immunity level stimulated by inactivated avian influenza virus (AIV) in vivo but also significantly inhibited the activity of activated AIV (H9N2 subtype) in vitro. G. filicina SP exhibited the strongest anti-AIV activity. These results revealed the variations in structural features and bioactivities among three SPs and indicated the potential adjuvants for immune-enhancement and anti-AIV. PMID:26729137

  7. La dicotomía de los virus polioma: ¿Infección lítica o inducción de neoplasias? The paradox of polyomaviruses Lytic infection or tumor induction?

    Directory of Open Access Journals (Sweden)

    Norberto A. Sanjuan

    2004-02-01

    Full Text Available Los virus Polioma murinos provocan infecciones líticas en cultivos de células de ratón y transforman in vitro células de rata a través de la interacción de su oncogén mT con diversos reguladores celulares. Luego de su inoculación en ratones neonatos inducen neoplasias epiteliales y mesenquimáticas. Se ha propuesto que las cepas de polioma más oncogénicas son aquellas que previamente replican más en el ratón. Sin embargo, a nivel de una sola célula la infección lítica y la transformación deberían ser mutuamente excluyentes. En cada neoplasia han sido descriptos 3 tipos celulares según expresen el DNA viral solo o concomitantemente con la proteína mayor de la cápside VP1, o que no contengan DNA viral ni VP-1. En nuestro laboratorio detectamos la existencia de un cuarto tipo celular en las neoplasias, en el que se expresa la totalidad del genoma viral pero no ocurre el ensamblaje, probablemente por alteraciones en la fosforilación de VP-1. Se discuten los mecanismos de migración intracelular de Polioma, la diseminación en el ratón y los factores que podrían estar involucrados en la inducción de neoplasias o en la infección lítica inducidas por el virus.Murine polyomaviruses can produce lytic infections in mouse cell cultures or transform in vitro rat fibroblasts through a complex interaction with key cellular regulators. After infection of newborn mice, some strains of polyomavirus induce epithelial and mesenchymal tumors. It has been described that there is a direct relationship between viral dissemination in the mouse and tumor induction. However, at a single cell level lytic infection and transformation would not be able to coexist. The existence of 3 distinct cell populations in polyoma-induced tumors, classified according to the presence or absence of viral DNA and viral capsid protein VP-1 have been described. We have reported a fourth type of cell in the neoplasms, that can express the early and the late viral

  8. A genetic variant in microRNA-122 regulatory region confers risk for chronic hepatitis B virus infection and hepatocellular carcinoma in Han Chinese.

    Science.gov (United States)

    Liu, Yao; Xie, Kaipeng; Wen, Juan; Deng, Min; Li, Jianming; Hu, Zhibin

    2014-10-01

    miR-122 plays a vital role in the development of chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). Based on data from the Encyclopedia of DNA Elements (ENCODE), two single nucleotide polymorphisms (SNPs), rs4309483 and rs4503880, were identified in the upstream regulatory region of miR-122. A case-control study consisting of 1,300 HBV-positive HCC cases, 1,344 HBV carriers, and 1,344 persons who cleared HBV naturally was carried out to test the association between the two SNPs and the risk for chronic HBV infection and HCC. The CA/AA genotypes of rs4309483 were associated with significantly increased risk for HCC [adjusted odds ratio (OR) = 1.21, 95% confidence intervals (CIs) = 1.02-1.43, P = 0.025] compared with HBV carriers, but decreased risk for chronic HBV infection (adjusted OR = 0.82, 95% CIs = 0.70-0.97, P = 0.017) compared with persons who cleared HBV naturally. The genotype-expression correlation between rs4309483 and the expression of primary or mature miR-122 expression was investigated in 29 pairs of HBV positive HCC and noncancerous liver tissues. In noncancerous liver tissues, subjects carrying the CA genotype exhibited significantly lower expression level of pri-miR-122 than those carrying the CC genotype. In addition, positive or inverse correlation between the expression levels of pri-miR-122 and mature miR-122 were observed in HCC tissues or noncancerous tissues, respectively. These findings indicate that the C to A base change of rs4309483 may alter the expression of miR-122, thus providing protective effect from chronic HBV infection but an increased risk for HCC in HBV carriers. © 2014 Wiley Periodicals, Inc.

  9. Molecular and genetic characterization of the Ry adg locus on chromosome XI from Andigena potatoes conferring extreme resistance to potato virus Y.

    Science.gov (United States)

    Herrera, María Del Rosario; Vidalon, Laura Jara; Montenegro, Juan D; Riccio, Cinzia; Guzman, Frank; Bartolini, Ida; Ghislain, Marc

    2018-05-31

    We have elucidated the Andigena origin of the potato Ry adg gene on chromosome XI of CIP breeding lines and developed two marker assays to facilitate its introgression in potato by marker-assisted selection. Potato virus Y (PVY) is causing yield and quality losses forcing farmers to renew periodically their seeds from clean stocks. Two loci for extreme resistance to PVY, one on chromosome XI and the other on XII, have been identified and used in breeding. The latter corresponds to a well-known source of resistance (Solanum stoloniferum), whereas the one on chromosome XI was reported from S. stoloniferum and S. tuberosum group Andigena as well. To elucidate its taxonomic origin in our breeding lines, we analyzed the nucleotide sequences of tightly linked markers (M45, M6) and screened 251 landraces of S. tuberosum group Andigena for the presence of this gene. Our results indicate that the PVY resistance allele on chromosome XI in our breeding lines originated from S. tuberosum group Andigena. We have developed two marker assays to accelerate the introgression of Ry adg gene into breeding lines by marker-assisted selection (MAS). First, we have multiplexed RYSC3, M6 and M45 DNA markers flanking the Ry adg gene and validated it on potato varieties with known presence/absence of the Ry adg gene and a progeny of 6,521 individuals. Secondly, we developed an allele-dosage assay particularly useful to identify multiplex Ry adg progenitors. The assay based on high-resolution melting analysis at the M6 marker confirmed Ry adg plex level as nulliplex, simplex and duplex progenitors and few triplex progenies. These marker assays have been validated and can be used to facilitate MAS in potato breeding.

  10. Conference Proceedings

    International Nuclear Information System (INIS)

    1998-01-01

    National and international aspects of climate change were the central concern of this conference organized by the Alliance for Responsible Environmental Alternatives (AREA). AREA is a coalition of industry, labour and municipalities from across Canada which was created to reflect the views and represent the interests of Canadians in the Climate Change Debate. Ways and means of optimizing Canada's response to the Global Climate Change Challenge were discussed. Discussions emphasized issues regarding the effectiveness of voluntary mechanisms to reduce greenhouse gases, as opposed to government-mandated actions for achieving climate change targets. The issue of how a differentiated system for emission reduction targets and timetables can be implemented was also debated. The economic implications of climate change were outlined. Canada's national agenda and the likely outcomes of the Conference of Parties (COP 4) in Buenos Aires also received much attention. tabs., figs

  11. SIGEF Conference

    CERN Document Server

    Terceño-Gómez, Antonio; Ferrer-Comalat, Joan; Merigó-Lindahl, José; Linares-Mustarós, Salvador

    2015-01-01

    This book is a collection of selected papers presented at the SIGEF conference, held at the Faculty of Economics and Business of the University of Girona (Spain), 06-08 July, 2015. This edition of the conference has been presented with the slogan “Scientific methods for the treatment of uncertainty in social sciences”. There are different ways for dealing with uncertainty in management. The book focuses on soft computing theories and their role in assessing uncertainty in a complex world. It gives a comprehensive overview of quantitative management topics and discusses some of the most recent developments in all the areas of business and management in soft computing including Decision Making, Expert Systems and Forgotten Effects Theory, Forecasting Models, Fuzzy Logic and Fuzzy Sets, Modelling and Simulation Techniques, Neural Networks and Genetic Algorithms and Optimization and Control. The book might be of great interest for anyone working in the area of management and business economics and might be es...

  12. Conference summaries

    International Nuclear Information System (INIS)

    1987-01-01

    This volume contains summaries of 28 papers presented at the 27. conference of the Canadian Nuclear Association. These papers discuss the general situation of the Canadian nuclear industry and the CANDU reactor; dialogue with the public; the International Atomic Energy Agency; and economic goals and operating lessons. It also contains summaries of 70 papers presented at the 8. conference of the Canadian Nuclear Society, which discuss plant life extension; safety and the environment; reactor physics; thermalhydraulics; risk assessment; the CANDU spacer location and repositioning project; CANDU operations; safety research after Chernobyl; fuel channels; and nuclear technology developments. The individual papers are also available in INIS-mf--13673 (CNA), and INIS-mf--12909 (CNS). (L.L.)

  13. Glasgow conference

    International Nuclear Information System (INIS)

    Fraser, Gordon

    1994-01-01

    The biennial 'Rochester' International Conferences on High Energy Physics which tick the rhythm of high energy physics progress reflect the dominance of the 'Standard Model' - the picture of electroweak and quark/gluon interactions in a simple framework of six weaklyinteracting particles (leptons) and six quarks. Despite its limited intellectual appeal, after a decade of intense probing the Standard Model still refuses to budge

  14. Washington Conference

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    The 1981 Particle Accelerator Conference was held in Washington from 11-13 March. It was the ninth in the series of meetings organized in the USA which differ from the 'International' meetings in their coverage of the full range of accelerator engineering and technology, including applications outside e field of high energy physics. The Conference took place under the cloud of further budget cuts for Fiscal Year 1982 in the USA which the Department of Energy has applied in line with the financial policy of the new administration. Coming on top of many years of budget trimming which have reduced the number of high energy physics Laboratories funded by the DOE to three (Brookhaven, Fermilab, Stanford - Cornell is funded by the National Science Foundation) and reduced the exploitation of these Laboratories to less than half of their potential, the new cuts did not exactly help to boost morale. Nevertheless, the huge amount of tailed work in accelerator physics and technology which was presented at the Conference showed how alive the field is

  15. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  16. The temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus PB2, PB1, and NP genes are influenced by the species of origin of the PB2 gene in reassortant viruses derived from influenza A/California/07/2009 and A/WSN/33 viruses.

    Science.gov (United States)

    Broadbent, Andrew J; Santos, Celia P; Godbout, Rachel A; Subbarao, Kanta

    2014-11-01

    Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (≥ 100-fold) replication at 39 °C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391 E, 581 G, and 661 T), PB2 (265 S), and NP (34 G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04(ts sig) and CA07(ts sig) viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39 °C, but the replication of WSN(ts sig) was restricted ≥ 100-fold compared to that at 33 °C. Reassortant CA07(ts sig) viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication ≥ 100-fold at 39 °C. In ferrets, the CA07(ts sig) virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07(ts sig) virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses. Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our

  17. Ebola Virus and Marburg Virus

    Science.gov (United States)

    Ebola virus and Marburg virus Overview Ebola virus and Marburg virus are related viruses that cause hemorrhagic fevers — illnesses marked by severe bleeding (hemorrhage), organ failure and, in many ...

  18. Prostate-Specific and Tumor-Specific Targeting of an Oncolytic HSV-1 Amplicon/Helper Virus for Prostate Cancer Treatment

    Science.gov (United States)

    2009-11-01

    regulation HSV-1 amplicon and recombinant viruses Molecular cloning Cell culture/gene transfection Xenograft mouse model Histology 20...no herpetic lesions were seen in CMV-ICP4-143T–treated and CMV-ICP4-145T– treated animals, although some gastritis developed 28 days after the viral

  19. Conference summaries

    International Nuclear Information System (INIS)

    Phillips, G.J.

    1985-01-01

    The 113 papers presented at this conference covered the areas of 1) fuel design, development and production; 2) nuclear plant safety; 3) nuclear instrumentation; 4) public and regulatory matters; 5) developments and opportunities in fusion; 6) fuel behaviour under normal operating conditions; 7) nuclear plant design and operations; 8) materials science and technology; 9) nuclear power issues; 10) fusion technology; 11) fuel behaviour under accident conditions; 12) large scale fuel channel replacement programs; 13) thermalhydraulics experimental studies; 14) reactor physics and analysis; 15) applications of accelerators; 16) fission product release and severe fuel damage under accident conditions; 17) thermalhydraulics modeling and assessments; 18) waste management and the environment; and 20) new reactor concepts

  20. Predictive value of CpG island methylator phenotype for tumor recurrence in hepatitis B virus-associated hepatocellular carcinoma following liver transplantation

    Directory of Open Access Journals (Sweden)

    Zheng Shu-Sen

    2010-08-01

    Full Text Available Abstract Background CpG island methylator phenotype (CIMP, in which multiple genes concordantly methylated, has been demonstrated to be associated with progression, recurrence, as well as overall survival in some types of cancer. Methods We examined the promoter methylation status of seven genes including P16, CDH1, GSTP1, DAPK, XAF1, SOCS1 and SYK in 65 cases of HCC treated with LT by methylation-specific PCR. CIMP+ was defined as having three or more genes that are concordantly methylated. The relationship between CIMP status and clinicopathological parameters, as well as tumor recurrence was further analyzed. Results CIMP+ was more frequent in HCC with AFP > 400 ng/ml than those with AFP ≤ 400 ng/ml (P = 0.017. In addition, patients with CIMP+ were prone to have multiple tumor numbers than those with CIMP- (P = 0.007. Patients with CIMP+ tumors had significantly worse recurrence-free survival (RFS than patients with CIMP-tumors by Kaplan-Meier estimates (P = 0.004. Multivariate analysis also revealed that CIMP status might be a novel independent prognostic factor of RFS for HCC patients treated with LT (HR: 3.581; 95% CI: 1.473-8.710, P = 0.005. Conclusion Our results suggested that CIMP could serve as a new prognostic biomarker to predict the risk of tumor recurrence in HCC after transplantation.

  1. Predictive value of CpG island methylator phenotype for tumor recurrence in hepatitis B virus-associated hepatocellular carcinoma following liver transplantation

    International Nuclear Information System (INIS)

    Wu, Li-Ming; Zhang, Feng; Zhou, Lin; Yang, Zhe; Xie, Hai-Yang; Zheng, Shu-Sen

    2010-01-01

    CpG island methylator phenotype (CIMP), in which multiple genes concordantly methylated, has been demonstrated to be associated with progression, recurrence, as well as overall survival in some types of cancer. We examined the promoter methylation status of seven genes including P16, CDH1, GSTP1, DAPK, XAF1, SOCS1 and SYK in 65 cases of HCC treated with LT by methylation-specific PCR. CIMP+ was defined as having three or more genes that are concordantly methylated. The relationship between CIMP status and clinicopathological parameters, as well as tumor recurrence was further analyzed. CIMP+ was more frequent in HCC with AFP > 400 ng/ml than those with AFP ≤ 400 ng/ml (P = 0.017). In addition, patients with CIMP+ were prone to have multiple tumor numbers than those with CIMP- (P = 0.007). Patients with CIMP+ tumors had significantly worse recurrence-free survival (RFS) than patients with CIMP-tumors by Kaplan-Meier estimates (P = 0.004). Multivariate analysis also revealed that CIMP status might be a novel independent prognostic factor of RFS for HCC patients treated with LT (HR: 3.581; 95% CI: 1.473-8.710, P = 0.005). Our results suggested that CIMP could serve as a new prognostic biomarker to predict the risk of tumor recurrence in HCC after transplantation

  2. Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential

    Science.gov (United States)

    Watanabe, Tokiko; Zhong, Gongxun; Russell, Colin A.; Nakajima, Noriko; Hatta, Masato; Hanson, Anthony; McBride, Ryan; Burke, David F.; Takahashi, Kenta; Fukuyama, Satoshi; Tomita, Yuriko; Maher, Eileen A.; Watanabe, Shinji; Imai, Masaki; Neumann, Gabriele; Hasegawa, Hideki; Paulson, James C.; Smith, Derek J.; Kawaoka, Yoshihiro

    2014-01-01

    Summary Wild birds harbor a large gene pool of influenza A viruses that have the potential to cause influenza pandemics. Foreseeing and understanding this potential is important for effective surveillance. Our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. To assess this risk, we generated and characterized a virus composed of avian influenza viral segments with high homology to the 1918 virus. This virus exhibited higher pathogenicity in mice and ferrets than an authentic avian influenza virus. Further, acquisition of seven amino acid substitutions in the viral polymerases and the hemagglutinin surface glycoprotein conferred respiratory droplet transmission to the 1918-like avian virus in ferrets, demonstrating that contemporary avian influenza viruses with 1918 virus-like proteins may have pandemic potential. PMID:24922572

  3. NATO Conference

    CERN Document Server

    Lynn, W

    1975-01-01

    The contents of this volume involve selection, emendation and up-dating of papers presented at the NATO Conference "Mathe­ matical Analysis of Decision problems in Ecology" in Istanbul, Turkey, July 9-13, 1973. It was sponsored by the System Sciences Division of NATO directed by Dr. B. Bayraktar with local arrange­ ments administered by Dr. Ilhami Karayalcin, professor of the Department of Industrial Engineering at the Technical University of Istanbul. It was organized by A. Charnes, University professor across the University of Texas System, and Walter R.Lynn, Di­ rector of the School of Civil and Environmental Engineering at Cornell Unjversity. The objective of the conference was to bring together a group of leading researchers from the major sciences involved in eco­ logical problems and to present the current state of progress in research of a mathematical nature which might assist in the solu­ tion of these problems. Although their presentations are not herein recorded, the key­ note address of Dr....

  4. EGC Conferences

    CERN Document Server

    Ritschard, Gilbert; Pinaud, Bruno; Venturini, Gilles; Zighed, Djamel; Advances in Knowledge Discovery and Management

    This book is a collection of representative and novel works done in Data Mining, Knowledge Discovery, Clustering and Classification that were originally presented in French at the EGC'2012 Conference held in Bordeaux, France, on January 2012. This conference was the 12th edition of this event, which takes place each year and which is now successful and well-known in the French-speaking community. This community was structured in 2003 by the foundation of the French-speaking EGC society (EGC in French stands for ``Extraction et Gestion des Connaissances'' and means ``Knowledge Discovery and Management'', or KDM). This book is intended to be read by all researchers interested in these fields, including PhD or MSc students, and researchers from public or private laboratories. It concerns both theoretical and practical aspects of KDM. The book is structured in two parts called ``Knowledge Discovery and Data Mining'' and ``Classification and Feature Extraction or Selection''. The first part (6 chapters) deals with...

  5. Munich conference

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1988-10-15

    'The Standard Model has survived impact for another year', declared Don Perkins of Oxford, summarizing the 24th International Conference on High Energy Physics held in Munich from 4-10 August. 'But is this a triumph or a frustration for physics?' he added. The twin pillars of the Standard Model, the electroweak unification of electromagnetism and the weak nuclear force, and the field theory (quantum chromodynamics) of the quark-gluon interactions responsible for the strong nuclear force, have not trembled since the electroweak unification went to the textbooks in 1983, but from time to time small cracks have appeared which might have gone on to shake the theory severely, if not undermine it. Major conference summarizers have got used to singing the praises of the Standard Model, but this year at Munich even detailed examination failed to reveal any serious cracks, while looking deeper into physics even some anomalous results hinting at gaps in understanding have either gone away or have diminished credibility.

  6. Munich conference

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    'The Standard Model has survived impact for another year', declared Don Perkins of Oxford, summarizing the 24th International Conference on High Energy Physics held in Munich from 4-10 August. 'But is this a triumph or a frustration for physics?' he added. The twin pillars of the Standard Model, the electroweak unification of electromagnetism and the weak nuclear force, and the field theory (quantum chromodynamics) of the quark-gluon interactions responsible for the strong nuclear force, have not trembled since the electroweak unification went to the textbooks in 1983, but from time to time small cracks have appeared which might have gone on to shake the theory severely, if not undermine it. Major conference summarizers have got used to singing the praises of the Standard Model, but this year at Munich even detailed examination failed to reveal any serious cracks, while looking deeper into physics even some anomalous results hinting at gaps in understanding have either gone away or have diminished credibility

  7. In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells.

    Science.gov (United States)

    Sales, Natiely S; Silva, Jamile R; Aps, Luana R M M; Silva, Mariângela O; Porchia, Bruna F M M; Ferreira, Luís Carlos S; Diniz, Mariana O

    2017-12-19

    In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8 + T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8 + T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Elevated Dengue Virus Nonstructural Protein 1 Serum Levels and Altered Toll-Like Receptor 4 Expression, Nitric Oxide, and Tumor Necrosis Factor Alpha Production in Dengue Hemorrhagic Fever Patients

    Directory of Open Access Journals (Sweden)

    Denise Maciel Carvalho

    2014-01-01

    Full Text Available Background. During dengue virus (DV infection, monocytes produce tumor necrosis factor alpha (TNF-α and nitric oxide (NO which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1 on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1 serum levels and innate immune response (TLR4 expression and TNF-α/NO production of DV infected patients presenting different clinical outcomes. Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA, TNF-α production by peripheral blood mononuclear cells (PBMCs, and TLR4 expression on CD14+ cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF was detected compared to patients with dengue hemorrhagic fever (DHF. Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-α production when compared to DF patients. Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes.

  9. Title - EFARS - Conference (Uninvited)

    OpenAIRE

    Lohrey, MC; Lawrence, AS

    2016-01-01

    Abstract - EFARS - Conference (Uninvited) "Notes" - EFARS - Conference (Uninvited) In preparation (Publication status) Yes, full paperYes, abstract onlyNo (Peer reviewed?) "Add a comment" - EFARS - Conference - Uninvited

  10. Prime/boost immunotherapy of HPV16-induced tumors with E7 protein delivered by Bordetella adenylate cyclase and modified vaccinia virus Ankara

    Czech Academy of Sciences Publication Activity Database

    Macková, J.; Stasíková, J.; Kutinová, L.; Mašín, Jiří; Hainz, P.; Šimšová, Marcela; Gabriel, P.; Šebo, Peter; Němečková, P.

    2006-01-01

    Roč. 55, - (2006), s. 39-46 ISSN 0340-7004 R&D Projects: GA AV ČR IBS5020311; GA ČR GA310/04/0004; GA MZd NR8004 Grant - others:GA MZd NC6570 Institutional research plan: CEZ:AV0Z50200510 Keywords : vaccine * hpv-e7 * vaccinia virus Subject RIV: EE - Microbiology, Virology Impact factor: 4.313, year: 2006

  11. Phase I Trial of Intratumoral Administration of NIS-Expressing Strain of Measles Virus in Unresectable or Recurrent Malignant Peripheral Nerve Sheath Tumor

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0115 TITLE: Phase I Trial of Intratumoral Administration of NIS-Expressing Strain of Measles Virus in Unresectable or...Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited REPORT DOCUMENTATION PAGE Form...Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time

  12. Conference Proceedings

    International Nuclear Information System (INIS)

    2002-01-01

    This volume contains the unedited proceedings of the Second Annual Conference on Managing Electricity Price Volatility. There were a total of eleven papers presented, dealing with a variety of issues affecting price volatility. Subjects treated included: new power generation development in Alberta; an analysis of electricity supply and demand to predict future price volatility; the effect of government intervention in the Alberta electricity market; risk management in volatile energy markets; an analysis of Alberta's capacity to supply its own internal electric power needs; the impact of increased electricity import and export capacity on price fluctuation in Alberta; improving market liquidity in Alberta; using weather derivatives to offset price risk; the impact of natural gas prices on electricity price volatility; capitalizing on advancements in online trading; and strategies for businesses to keep operating through times of price volatility. In most cases only overhead viewgraphs are available

  13. MUSME Conference

    CERN Document Server

    Martinez, Eusebio

    2015-01-01

    This volume contains the Proceedings of MUSME 2014, held at Huatulco in Oaxaca, Mexico, October 2014. Topics include analysis and synthesis of mechanisms; dynamics of multibody systems; design algorithms for mechatronic systems; simulation procedures and results; prototypes and their performance; robots and micromachines; experimental validations; theory of mechatronic simulation; mechatronic systems; and control of mechatronic systems. The MUSME symposium on Multibody Systems and Mechatronics was held under the auspices of IFToMM, the International Federation for Promotion of Mechanism and Machine Science, and FeIbIM, the Iberoamerican Federation of Mechanical Engineering. Since the first symposium in 2002, MUSME events have been characterised by the way they stimulate the integration between the various mechatronics and multibody systems dynamics disciplines, present a forum for facilitating contacts among researchers and students mainly in South American countries, and serve as a joint conference for the ...

  14. Cairo conference.

    Science.gov (United States)

    McMichael, A J

    1994-09-03

    The United Nations Conference on Population and Development in Cairo in September, 1994, will evoke criticism of the inability of governments to act quickly enough to avert demographic and environmental crises. Rapid population growth has clear implications for public health. Globally there now occur anthropogenic changes in atmospheric composition, the degradation of fertile lands and ocean fisheries, an accelerating loss of biodiversity, and the social and ecological problems of massive urbanization. In the future, per capita consumption levels will increase in burgeoning populations of developing countries, thus adding to the environmental impacts of overconsuming rich countries. By the end of the decade there will be over six billion people, of whom one half will live in cities. These demographic and environmental trends, if translated into climatic change, regional food shortages, and weakened ecosystems, would adversely affect human health. The World Health Organization is likely to concentrate only on accessible family planning and promotion of health for women and families. Continuing asymmetric child-saving aid, unaccompanied by substantial aid to help mobilize the social and economic resources needed to reduce fertility, may delay the demographic transition in poor countries and potentiate future public health disasters. As a result of recent reductions in fertility, even in Sub-Saharan Africa, average family sizes have been halved. Yet the demographic momentum will double population by 2050. The biosphere is a complex of ecosystems and, if unsustained, it could not fulfill the productive, cleansing, and protective functions on which life depends. The Cairo conference must therefore recognize that sustaining human health is a prime reason for concern about population growth and models of economic development.

  15. New frontiers in oncolytic viruses: optimizing and selecting for virus strains with improved efficacy

    Directory of Open Access Journals (Sweden)

    Lundstrom K

    2018-02-01

    Full Text Available Kenneth Lundstrom PanTherapeutics, Lutry, Switzerland Abstract: Oncolytic viruses have demonstrated selective replication and killing of tumor cells. Different types of oncolytic viruses – adenoviruses, alphaviruses, herpes simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and vaccinia viruses – have been applied as either naturally occurring or engineered vectors. Numerous studies in animal-tumor models have demonstrated substantial tumor regression and prolonged survival rates. Moreover, clinical trials have confirmed good safety profiles and therapeutic efficacy for oncolytic viruses. Most encouragingly, the first cancer gene-therapy drug – Gendicine, based on oncolytic adenovirus type 5 – was approved in China. Likewise, a second-generation oncolytic herpes simplex virus-based drug for the treatment of melanoma has been registered in the US and Europe as talimogene laherparepvec. Keywords: immunotherapy, viral vectors, clinical trials, drug approval

  16. Conference summaries

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, Tim [Inta Communication Limited for European Service Network/ DG Research, Trillium House, 32 New Street, St. Neots, Cambridge PE19 1AJ (United Kingdom)

    2004-07-01

    The summaries were derived from presentations, interviews and discussions at the conference. The summaries are given at two levels, overall for the conference and for specific sessions as follows: 1) Overall Conference: 'A Sound Scientific Basis for Serious Decisions; 2) Sessions on EC Policy and Socio-Political Issues: 'Promoting Safety and Protecting Society'; 3) Session on P and T: 'Partitioning and Transmutation: A Technical Fix or Technical Training?'; 4) Sessions on Geological Disposal and Research Networking: 'No Technical Barriers to Geological Disposal'. First an overall summary of Euradwaste '04 is presented. Significant progress was made on the technical and scientific basis for geological disposal of radioactive waste during the European Commission's Fifth EURATOM Framework Programme for Research (FP5). Deep geological disposal is technically feasible now and can demonstrate the guarantees of long-term isolation and protection of the public. In parallel, socio-political studies have produced methodologies for constructive dialogue with potential host communities that reflect the honesty and openness expected by a democratic society. A harmonized legislative framework for nuclear safety and waste disposal across the enlarged European Union is currently being discussed. Disposal in deep (> 300 metre) geological repositories, the favoured strategy in Europe for long-lived high-level radioactive waste, is now possible. The Sessions on EC Policy and Socio-Political Issues are summarized as follows. The opening day of Euradwaste '04 focused on European Commission policy, including the proposed Directives on disposal of radioactive waste and nuclear safety and socio-political aspects including governance and decision making, public perception/acceptance of waste disposal and its sustainability. A decision on the proposed package will now be made after Union enlargement. Public agreement on the siting of

  17. Conference Papers

    International Nuclear Information System (INIS)

    2003-01-01

    A total of 18 papers were presented at the 2003 Annual Executive Conference of the Canadian Gas Association held at St. Andrews, NB, from June 25th to June 28th. Titles of the presentations were as follows: (1) 'Positioning natural gas in a transforming world' by Pierre Marcel Desjardins; (2) 'Positioning natural gas in a transforming world' by Jean-Paul Theoret; (3) 'Perceptions of natural gas' by Noel Sampson; (4) 'Energy efficiency as an opportunity for the natural gas industry' by Peter Love; (5) 'Natural gas R and D - NRCan perspective' by Graham R. Campbell; (6) 'Impact of earned media on corporate perceptions in the gas industry' by Michael Coates; (7) 'Moving forward with an initiative for natural gas technology innovation' by Emmanuel Morin; (8) 'Natural gas R and D - No more dodging the issue' by Chuck Szmurlo; (9) 'Meeting the technology needs of the gas industry and the gas consumer' by Stanley S. Borys; (10) 'Market signals' by John Wellard; (11) 'Future sources of Canadian natural gas' by Rick Hyndman; (12) 'The state of supply: Northeast U.S. perspective' by Tom Kiley; (13) 'AGA's priorities and perspectives' by Dick Reiten; (14) 'Global energy issues: Recent development in policy and business' by Gerald Doucet; (15) 'Keeping the distribution cart behind the horse: Why finding more offshore gas is much more important than completing the natural gas grid, including for New Brunswick' by Brian Lee Crowley; (16) 'Environmental opportunities and challenges for the gas industry' by Manfred Klein; (17) 'The potential for natural gas demand destruction' by Timothy Partridge; and (18) 'Pushing the envelope on gas supply' by Roland R. George. In most instances only speaking notes and view graphs are available

  18. Sinus Tumors

    Science.gov (United States)

    ... RESOURCES Medical Societies Patient Education About this Website Font Size + - Home > CONDITIONS > Sinus Tumors Adult Sinusitis Pediatric ... and they vary greatly in location, size and type. Care for these tumors is individualized to each ...

  19. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  20. Wilms tumor

    Science.gov (United States)

    ... suggested. Alternative Names Nephroblastoma; Kidney tumor - Wilms Images Kidney anatomy Wilms tumor References Babaian KN, Delacroix SE, Wood CG, Jonasch E. Kidney cancer. In: Skorecki K, Chertow GM, Marsden PA, ...

  1. Detection of Secondary Liver Tumors in Patients with Colorectal Carcinoma by Using Tumor Markers

    Czech Academy of Sciences Publication Activity Database

    Holubec jr., L.; Topolčan, O.; Třeška, V.; Holubec sen., L.; Pecen, Ladislav; Pikner, R.; Finek, J.; Visokai, V.; Lipská, L.

    2002-01-01

    Roč. 17, č. 3 (2002), s. 134-135 ISSN 0886-3849. [International Conference on Human Tumor Markers /19./. 25.08.2002-29.08.2002, Velje] Institutional research plan: AV0Z1030915 Keywords : tumor markers * colorectal CA Subject RIV: BA - General Mathematics

  2. Designing herpes viruses as oncolytics

    Directory of Open Access Journals (Sweden)

    Cole Peters

    Full Text Available Oncolytic herpes simplex virus (oHSV was one of the first genetically-engineered oncolytic viruses. Because HSV is a natural human pathogen that can cause serious disease, it is incumbent that it can be genetically-engineered or significantly attenuated for safety. Here, we present a detailed explanation of the functions of HSV-1 genes frequently mutated to endow oncolytic activity. These genes are nonessential for growth in tissue culture cells but are important for growth in postmitotic cells, interfering with intrinsic antiviral and innate immune responses or causing pathology, functions dispensable for replication in cancer cells. Understanding the function of these genes leads to informed creation of new oHSVs with better therapeutic efficacy. Virus infection and replication can also be directed to cancer cells through tumor-selective receptor binding and transcriptional- or post-transcriptional miRNA-targeting, respectively. In addition to the direct effects of oHSV on infected cancer cells and tumors, oHSV can be “armed” with transgenes that are: reporters, to track virus replication and spread; cytotoxic, to kill uninfected tumor cells; immune modulatory, to stimulate antitumor immunity; or tumor microenvironment altering, to enhance virus spread or to inhibit tumor growth. In addition to HSV-1, other alphaherpesviruses are also discussed for their oncolytic activity.

  3. Designing herpes viruses as oncolytics

    Science.gov (United States)

    Peters, Cole; Rabkin, Samuel D

    2015-01-01

    Oncolytic herpes simplex virus (oHSV) was one of the first genetically-engineered oncolytic viruses. Because HSV is a natural human pathogen that can cause serious disease, it is incumbent that it can be genetically-engineered or significantly attenuated for safety. Here, we present a detailed explanation of the functions of HSV-1 genes frequently mutated to endow oncolytic activity. These genes are nonessential for growth in tissue culture cells but are important for growth in postmitotic cells, interfering with intrinsic antiviral and innate immune responses or causing pathology, functions dispensable for replication in cancer cells. Understanding the function of these genes leads to informed creation of new oHSVs with better therapeutic efficacy. Virus infection and replication can also be directed to cancer cells through tumor-selective receptor binding and transcriptional- or post-transcriptional miRNA-targeting, respectively. In addition to the direct effects of oHSV on infected cancer cells and tumors, oHSV can be “armed” with transgenes that are: reporters, to track virus replication and spread; cytotoxic, to kill uninfected tumor cells; immune modulatory, to stimulate antitumor immunity; or tumor microenvironment altering, to enhance virus spread or to inhibit tumor growth. In addition to HSV-1, other alphaherpesviruses are also discussed for their oncolytic activity. PMID:26462293

  4. Epstein-barr virus latent membrane protein 1 (EBV-LMP1) and tumor proliferation rate as predictive factors of nasopharyngeal cancer (NPC) radiation response

    Energy Technology Data Exchange (ETDEWEB)

    Gondhowiardjo, S. [Univ. of Indonesia, Jakarta (Indonesia). Faculty of Medicine

    2000-05-01

    Irradiation is still the treatment of choice in NPC treatment as one of highest malignancy in Indonesia as well as in Southeast Asia. Up to now there is no accurate predictor on radiation response, since that the similar histo-morphological pattern, as a well-known prognostic factor can revealed a wide range of treatment outcomes. Purpose of the study is to established the influence of EBV-LMP 1 as the most important protein expressed by EBV oncogenes in cellular behavior such as proliferation rate, tumor aggressivity in NPC and to find out the role of both, proliferation rate and EBV-LMP1 expression as a predictor on NPC radiation response. One-hundred seventy-two paraffin-embedded biopsy specimens from NPC patients were analysed flow-cytometrically to obtain the S-phase fraction value as the proliferation parameter. From this group of patients, 81 fresh specimen biopsies could be collected, and the EBV-LMP 1 expression were detected by western blotting technique (mAB S12-Karolinska Institute) could be done. Several variables such as clinical stage, pathology pattern and radiation response were also collected. The radiation responses were established clinically (by nasopharyngoscopy), by CT scanning and pathologically. Sixty-five percent of our patients belong to the T3 and T4, whereby the N2-3 group consists 75% of them. Fourteen percent of the patients are Hsu type I, 48% are Hs type II and the rest belong to Hsu type III. Our study revealed that the mean SPF value was 14.62% (10.18%, which correlated (p<0.05) with the tumor and nodal sizes). The rate of positive expression of the EBV-LMP1 was 50%, and did not show a correlation with the proliferation activity as well as the radiation response. However, it showed a significant correlation with the tumor and nodal size. There was a significant correlation between this proliferation value with the radiation response calculated by both, bivariate as well as by multivariate analysis. The complete and incomplete

  5. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  6. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  7. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  8. ECHO virus

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001340.htm ECHO virus To use the sharing features on this page, please enable JavaScript. Enteric cytopathic human orphan (ECHO) viruses are a group of viruses that can lead ...

  9. Engineering resistance against Tomato yellow leaf curl virus via the CRISPR/Cas9 system in tomato

    KAUST Repository

    Mahfouz, Magdy M.; Tashkandi, Manal; Ali, Zahir; Aljedaani, Fatimah R.; Shami, Ashwag

    2017-01-01

    CRISPR/Cas systems confer molecular immunity against phages and conjugative plasmids in prokaryotes. Recently, CRISPR/Cas9 systems have been used to confer interference against eukaryotic viruses. Here, we engineered Nicotiana benthamiana and tomato

  10. INFCE plenary conference documents

    International Nuclear Information System (INIS)

    This document consists of the reports to the First INFCE Plenary Conference (November 1978) by the Working Groups a Plenary Conference of its actions and decisions, the Communique of the Final INFCE Plenary Conference (February 1980), and a list of all documents in the IAEA depository for INFCE

  11. Conferences are like swans

    OpenAIRE

    Corker, Chris

    2012-01-01

    Chris Corker was the lead on bringing the 2011 Higher Education Research Scholarship Group Conference to fruition, both in the months preceding the event and on the day. In this viewpoint, Chris shares his experiences of conference administration and delivery, and explores how conferences and swans have more in common that you would imagine.

  12. COAL Conference Poster

    OpenAIRE

    Brown, Taylor Alexander; McGibbney, Lewis John

    2017-01-01

    COAL Conference Poster This archive contains the COAL conference poster for the AGU Fall Meeting 2017 by Taylor Alexander Brown. The Inkscape SVG source is available at https://github.com/capstone-coal/coal-conference-poster/ under the Creative Commons Attribution-ShareAlike 4.0 International license.

  13. Overcoming tumor resistance by heterologous adeno-poxvirus combination therapy

    Directory of Open Access Journals (Sweden)

    Markus Vähä-Koskela

    2014-01-01

    Full Text Available Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.

  14. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  15. Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter.

    Directory of Open Access Journals (Sweden)

    Jianqing Pan

    Full Text Available Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373. Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement.

  16. Tumor-Associated Macrophages in Oncolytic Virotherapy: Friend or Foe?

    Directory of Open Access Journals (Sweden)

    Nicholas L. Denton

    2016-07-01

    Full Text Available Cancer therapy remains a challenge due to toxicity limitations of chemotherapy and radiation therapy. Oncolytic viruses that selectively replicate and destroy cancer cells are of increasing interest. In addition to direct cell lysis, these vectors stimulate an anti-tumor immune response. A key regulator of tumor immunity is the tumor-associated macrophage population. Macrophages can either support oncolytic virus therapy through pro-inflammatory stimulation of the anti-tumor response at the cost of hindering direct oncolysis or through immunosuppressive protection of virus replication at the cost of hindering the anti-tumor immune response. Despite similarities in macrophage interaction between adult and pediatric tumors and the abundance of research supporting macrophage modulation in adult tumors, there are few studies investigating macrophage modulation in pediatric cancers or modulation of immunotherapy. We review the current state of knowledge regarding macrophages in cancers and their influence on oncolytic virotherapy.

  17. International Conference on Physics

    CERN Document Server

    2016-01-01

    OMICS International, (conference series) the World Class Open Access Publisher and Scientific Event Organizer is hosting “International Conference on physics” which is going to be the biggest conference dedicated to Physics. The theme “Highlighting innovations and challenges in the field of Physics” and it features a three day conference addressing the major breakthroughs, challenges and the solutions adopted. The conference will be held during June 27-29, 2016 at New Orleans, USA. Will be published in: http://physics.conferenceseries.com/

  18. Facilitating Learning at Conferences

    DEFF Research Database (Denmark)

    Ravn, Ib; Elsborg, Steen

    2011-01-01

    The typical conference consists of a series of PowerPoint presentations that tend to render participants passive. Students of learning have long abandoned the transfer model that underlies such one-way communication. We propose an al-ternative theory of conferences that sees them as a forum...... for learning, mutual inspiration and human flourishing. We offer five design principles that specify how conferences may engage participants more and hence increase their learning. In the research-and-development effort reported here, our team collaborated with conference organizers in Denmark to introduce...... and facilitate a variety of simple learning techniques at thirty one- and two-day conferences of up to 300 participants each. We present ten of these techniques and data evaluating them. We conclude that if conference organizers allocate a fraction of the total conference time to facilitated processes...

  19. AIDS and Cancer Virus Program (ACVP)

    Data.gov (United States)

    Federal Laboratory Consortium — Researchers from the AIDS and Cancer Virus Program (ACVP) work to improve the diagnosis, prevention, and treatment of HIV infection, AIDS, and AIDS-related tumors,...

  20. Hypervariable region 1 deletion and required adaptive envelope mutations confer decreased dependency on scavenger receptor class B type I and low-density lipoprotein receptor for hepatitis C virus

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Serre, Stéphanie B N; Ramirez, Santseharay

    2014-01-01

    -deleted viruses. Apolipoprotein E (ApoE)-specific HCV neutralization was similar for H77, J6, and S52 viruses with and without HVR1. In conclusion, HVR1 and HVR1-related adaptive envelope mutations appeared to be involved in LDLr and SR-BI dependency, respectively. Also, LDLr served Apo....../S733F), S52(ΔHVR1/A369V), and S52(A369V), but not for J6(ΔHVR1). Low-density lipoprotein receptor (LDLr) dependency was decreased for HVR1-deleted viruses, but not for H77(N476D/S733F) and S52(A369V). Soluble LDLr neutralization revealed strong inhibition of parental HCV but limited effect against HVR1...

  1. Tumor targeted gene therapy

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2006-01-01

    Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

  2. AINSE's 40th anniversary conference. Conference handbook

    International Nuclear Information System (INIS)

    1998-01-01

    Highlights of 40 years of activity of the Australian Institute of Nuclear Science and Engineering (AINSE) were the main focus of this conference. Topics covered include nuclear physics, plasma physics, radiation chemistry, radiation biology, neutron diffraction, nuclear techniques of analysis and other relevant aspects of nuclear science and technology. The conference handbook contains the summaries of the 78 papers and posters presented and the list of participants

  3. Oncolytic viruses as anticancer vaccines

    Directory of Open Access Journals (Sweden)

    Norman eWoller

    2014-07-01

    Full Text Available Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

  4. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

    Direct tumor tracers are subdivided in the following categories:metabolite tracers, antitumoral tracers, radioactive proteins and cations. Use of 67 Ga-citrate as a clinically important tumoral tracer is emphasized and gallium-67 whole-body scintigraphy is discussed in detail. (M.A.) [pt

  5. 76 FR 64083 - Reliability Technical Conference; Notice of Technical Conference

    Science.gov (United States)

    2011-10-17

    ... Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, November 29, 2011, from 1 p.m. to 5 p.m. and... reliability that were identified in earlier Commission technical conferences. The conference also will discuss...

  6. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  7. International Cryocooler Conference

    CERN Document Server

    Cryocoolers 13

    2005-01-01

    This is the 13th volume in the conference series. Over the years the International Cryocoolers Conference has become the preeminent worldwide conference for the presentation of the latest developments and test experiences with cryocoolers. The typical applications of this technology include cooling space and terrestrial infrared focal plane arrays, space x-ray detectors, medical applications, and a growing number of high-temperature super-capacitor applications.

  8. CONFERENCE: Computers and accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1984-01-15

    In September of last year a Conference on 'Computers in Accelerator Design and Operation' was held in West Berlin attracting some 160 specialists including many from outside Europe. It was a Europhysics Conference, organized by the Hahn-Meitner Institute with Roman Zelazny as Conference Chairman, postponed from an earlier intended venue in Warsaw. The aim was to bring together specialists in the fields of accelerator design, computer control and accelerator operation.

  9. Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells

    Directory of Open Access Journals (Sweden)

    Benencia Fabian

    2008-04-01

    Full Text Available Abstract Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV B radiation using a convenient tumor model expressing human papilloma virus (HPV E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

  10. Conference proceedings ISES 2014

    DEFF Research Database (Denmark)

    Christensen, Janne Winther; Peerstrup Ahrendt, Line; Malmkvist, Jens

    The 10th Internatinal Equitation Science Conference is held i Denmark from August 6th - 9th 2014. This book of proceedings contaions abstracts of 35 oral and 57 poster presentations within the conference themes Equine Stress, Learning and Training as well as free papers.......The 10th Internatinal Equitation Science Conference is held i Denmark from August 6th - 9th 2014. This book of proceedings contaions abstracts of 35 oral and 57 poster presentations within the conference themes Equine Stress, Learning and Training as well as free papers....

  11. Changes in Tumor Marker Values with Patients with Beginning Disease Git. Detection of Secondary Liver Tumors in Patients with Colorectal Carcinoma by using Tumor Markers

    Czech Academy of Sciences Publication Activity Database

    Holubec jr., L.; Topolčan, O.; Pašková, H.; Holubec sen., L.; Pecen, Ladislav; Třeška, L.; Finek, J.; Pikner, R.; Visokai, V.; Lipská, V.; Svobodová, S.

    2002-01-01

    Roč. 17, č. 3 (2002), s. 133-134 ISSN 0886-3849. [International Conference on Human Tumor Markers /19./. 25.08.2002-29.08.2002, Velje] Institutional research plan: AV0Z1030915 Keywords : tumor markers * GIT cancers Subject RIV: BA - General Mathematics

  12. Second international conference on isotopes. Conference proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, C J [ed.

    1997-10-01

    The Second International Conference on Isotopes (2ICI) was hosted by the Australian Nuclear Association in Sydney, NSW, Australia. The Theme of the Second Conference: Isotopes for Industry, Health and a Better Environment recognizes that isotopes have been used in these fields successfully for many years and offer prospects for increasing use in the future. The worldwide interest in the use of research reactors and accelerators and in applications of stable and radioactive isotopes, isotopic techniques and radiation in industry, agriculture, medicine, environmental studies and research in general, was considered. Other radiation issues including radiation protection and safety were also addressed. International and national overviews and subject reviews invited from leading experts were included to introduce the program of technical sessions. The invited papers were supported by contributions accepted from participants for oral and poster presentation. A Technical Exhibition was held in association with the Conference. This volume contains the full text or extended abstracts of papers number 61- to number 114

  13. Radiation`96. Conference handbook

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    The conference program includes eight invited lectures which cover a range of contemporary topics in radiation science and technology. In addition, thirty-two oral papers were presented, along with forty-five posters. The conference handbook contains one-page precis or extended abstracts of all presentations, and is a substantial compendium of current radiation research in Australia.

  14. Multiphoton processes: conference proceedings

    International Nuclear Information System (INIS)

    Lambropoulos, P.; Smith, S.J.

    1984-01-01

    The chapters of this volume represent the invited papers delivered at the conference. They are arranged according to thermatic proximity beginning with atoms and continuing with molecules and surfaces. Section headings include multiphoton processes in atoms, field fluctuations and collisions in multiphoton process, and multiphoton processes in molecules and surfaces. Abstracts of individual items from the conference were prepared separately for the data base

  15. Radiation`96. Conference handbook

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    The conference program includes eight invited lectures which cover a range of contemporary topics in radiation science and technology. In addition, thirty-two oral papers were presented, along with forty-five posters. The conference handbook contains one-page precis or extended abstracts of all presentations, and is a substantial compendium of current radiation research in Australia.

  16. FPGAworld CONFERENCE2009 SEPTEMBER

    OpenAIRE

    2009-01-01

    The FPGAworld Conference addresses aspects of digital and hardware/software system engineering on FPGA technology. It is a discussion and network forum for students, researchers and engineers working on industrial and research projects, state-of-the-art investigations, development and applications. The book contains some presentations; for more information see (www.fpgaworld.com/conference).

  17. Major Biomass Conference

    Science.gov (United States)

    Top Scientists, Industry and Government Leaders to Gather for Major Biomass Conference America, South America and Europe will focus on building a sustainable, profitable biomass business at the Third Biomass Conference of the Americas in Montreal. Scheduled presentations will cover all biomass

  18. Hamburg Accelerator Conference (2)

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Edmund J.N. [CERN Accelerator School (Switzerland)

    1992-11-15

    From 20-24 July, Hamburg welcomed the Fifteenth International Conference on High Energy Accelerators (HEACC). The HEACC Conference traditionally reviews the status of all major accelerator projects whether they are already running like clockwork, still in the construction phase, or waiting impatiently for financial approval.

  19. Program of the Conference

    International Nuclear Information System (INIS)

    2006-01-01

    The International Conference SES 2006 (Secure Energy Supply, Bezpecna dodavka energie) was realised in Bratislava, during September 26 - 29, 2006 in the hotel Crowne Plaza and deals with most important problems of world and Slovak energetics. Objective of this Conference was discussion of experience and information concerning strategic aspects of energy supply safety and the development of the Slovak and European Energy Industry

  20. Vehicular Networking Conference (VNC)

    NARCIS (Netherlands)

    Altintas, O.; Chen, W.; Heijenk, Geert; Dressler, F.; Ekici, E.; Kargl, Frank; Shigeno, H.; Dietzel, Stefan

    2011-01-01

    On behalf of the Organizing Committee, we would like to welcome you to the third edition of the IEEE Vehicular Networking Conference (IEEE VNC 2011) in Amsterdam, the Netherlands. IEEE VNC is a unique conference sponsored by both the IEEE Communications Society and the IEEE Intelligent

  1. Radiation'96. Conference handbook

    International Nuclear Information System (INIS)

    1996-01-01

    The conference program includes eight invited lectures which cover a range of contemporary topics in radiation science and technology. In addition, thirty-two oral papers were presented, along with forty-five posters. The conference handbook contains one-page precis or extended abstracts of all presentations, and is a substantial compendium of current radiation research in Australia

  2. Hamburg Accelerator Conference (2)

    International Nuclear Information System (INIS)

    Wilson, Edmund J.N.

    1992-01-01

    From 20-24 July, Hamburg welcomed the Fifteenth International Conference on High Energy Accelerators (HEACC). The HEACC Conference traditionally reviews the status of all major accelerator projects whether they are already running like clockwork, still in the construction phase, or waiting impatiently for financial approval

  3. Chikungunya virus

    Science.gov (United States)

    Chikungunya virus infection; Chikungunya ... Where Chikungunya is Found Before 2013, the virus was found in Africa, Asia, Europe, and the Indian and Pacific oceans. In late 2013, outbreaks occurred for the first time in the ...

  4. Zika Virus

    Science.gov (United States)

    ... through blood transfusions. There have been outbreaks of Zika virus in the United States, Africa, Southeast Asia, the ... not travel to areas where there is a Zika virus outbreak. If you do decide to travel, first ...

  5. Zika Virus

    Science.gov (United States)

    ... Funding CDC Activities For Healthcare Providers Clinical Evaluation & Disease Sexual Transmission HIV Infection & Zika Virus Testing for Zika Test Specimens – At Time of Birth Diagnostic Tests Understanding Zika Virus Test Results ...

  6. The microarray detecting six fruit-tree viruses

    Czech Academy of Sciences Publication Activity Database

    Lenz, Ondřej; Petrzik, Karel; Špak, Josef

    2009-01-01

    Roč. 148, July (2009), s. 27 ISSN 1866-590X. [International Conference on Virus and other Graft Transmissible Diseases of Fruit Crops /21./. 05.07.2009-10.07.2009, Neustadt] R&D Projects: GA MŠk OC 853.001 Institutional research plan: CEZ:AV0Z50510513 Keywords : microarray * detection * virus Subject RIV: EE - Microbiology, Virology

  7. Pituitary Tumors

    Science.gov (United States)

    ... Association (ABTA) International RadioSurgery Association National Brain Tumor Society National Institute of Child Health and Human Development ... Definition The pituitary is a small, bean-sized gland ...

  8. Hypothalamic tumor

    Science.gov (United States)

    ... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

  9. Threats, protests greet conference.

    Science.gov (United States)

    Struck, D

    1994-09-04

    In preparation for the 1994 International Conference on Population and Development, Egypt has deployed 14,000 police to protect participants from threatened violence. The Vatican has joined forces with Muslim fundamentalists to condemn the conference as a vehicle for imposing Western ideals, particularly abortion, on Third world countries. In addition, the opposition is raising the specter of a descent of homosexuals onto Cairo and Muslim fundamentalists have threatened to murder Western representatives. A suit filed by Islamic lawyers, aimed at stopping the conference, failed. Sudan and Saudi Arabia plan to boycott the conference, and it remains uncertain whether Libya will be represented. Conference organizers have not been deterred by the threats and note that the controversy has drawn public attention to the central issues under debate.

  10. Malignant renal tumors in pediatrics

    International Nuclear Information System (INIS)

    Pena, C.; Torterolo, J.; Irigoyen, B.; Bel, M.; Elias, E.

    2004-01-01

    Introduction: Professionals who work in pediatric oncology, we see childhood cancer as a common disease, but in fact constitutes about 2% of all cancers diagnosed worldwide. Wilms tumor accounts for 6% of all childhood tumors and presentation bilateral accounts for 4-6% of all Wilms tumors diagnosed. Theoretical Framework: In the period between the year 1994-2003 period were attended in the Pediatric Hematology-Oncology Center, a total of 29 cases of malignant renal tumors, corresponding to 86% (25 cases) to Wilms tumor or nephroblastoma tumor. The Wilms is of embryonic origin, capable of metastatic spread, (85% lungs 15% liver). Very sensitive to chemotherapy and radiotherapy, which confers high cure rates (85%); having a multidisciplinary treatment model, combining surgery, chemotherapy, and radiotherapy. The role of nursing in comprehensive cancer care child is essential in the prevention and early detection of side effects or complications. Case report: S.D. currently 10 years old. In 10/1994, at 8 months of age, was diagnosed with bilateral Wilms tumor. On admission her weight was 8200gr with abdominal circumference 50cm. Conducted pre-operative MDT and 02/1995 nephrectomy of the left kidney and right kidney lumpectomy (tumor nodule 420gr. and a 250gr.). MDT begins in 03/1995 01/1996 ending. 09/2003 with abdominal pain and vomiting, and kidney failure. 10/2003 lumpectomy biopsy (sclerotic nodule associated with maturation nephroblastoma). Currently severe renal insufficiency plan enters dialysis. Nursing process: Objectives: 1) To prepare the child and family to the side effects and possible complications of chemotherapy and / or radiotherapy 2) Prevent and minimize related complications tumor and / or treatment. Care Plan comprises four stages: A) rating and customer income. B) Implement care chemotherapy C) post-operative Care D) Implement radiation care

  11. La depleción de las células T regulatorias aumenta el número de las células CD8 durante la infección con el virus del tumor mamario murino

    Directory of Open Access Journals (Sweden)

    Gabriel Cabrera

    2011-06-01

    Full Text Available El virus del tumor mamario murino (MMTV es un retrovirus que se transmite durante la lactancia y que ha desarrollado estrategias para explotar y subvertir el sistema inmune. En un modelo de infección natural con MMTV hemos mostrado previamente que la infección causa incrementos tempranos y progresivos de células T regulatorias (Treg CD4+CD25+Foxp3+ específicas para el superantígeno (Sag viral en las placas de Peyer (PP. En este trabajo se evaluó si la depleción de las células Treg influencia la población de células CD8+ durante la infección con MMTV a través del amamantamiento. La depleción de las células Treg al día 6 de infección causó incrementos en el porcentaje y número absoluto de las células CD8+ en los ganglios y provocó un incremento en la intensidad de fluorescencia media del marcador de activación CD44 en esas células. Los incrementos en el número absoluto de las células CD8 se observaron en células con cadenas variables Vβ del receptor de las células T (TCR tanto reactivas como no reactivas al Sag. Previamente habíamos demostrado que la depleción de las células Treg al día 6 de infección disminuye la carga viral. Los resultados presentados en este trabajo sugieren que, al menos a partir del día 6 de infección con MMTV, las células Treg podrían tener un rol inhibiendo la generación de una respuesta CD8 antiviral.

  12. The MC160 Protein Expressed by the Dermatotropic Poxvirus Molluscum Contagiosum Virus Prevents Tumor Necrosis Factor Alpha-Induced NF-κB Activation via Inhibition of I Kappa Kinase Complex Formation

    Science.gov (United States)

    Nichols, Daniel Brian; Shisler, Joanna L.

    2006-01-01

    The pluripotent cytokine tumor necrosis factor alpha (TNF-α) binds to its cognate TNF receptor I (TNF-RI) to stimulate inflammation via activation of the NF-κB transcription factor. To prevent the detrimental effects of TNF-α in keratinocytes infected with the molluscum contagiosum virus (MCV), this poxvirus is expected to produce proteins that block at least one step of the TNF-RI signal transduction pathway. One such product, the MC160 protein, is predicted to interfere with this cellular response because of its homology to other proteins that regulate TNF-RI-mediated signaling. We report here that expression of MC160 molecules did significantly reduce TNF-α-mediated NF-κB activation in 293T cells, as measured by gene reporter and gel mobility shift assays. Since we observed that MC160 decreased other NF-κB activation pathways, namely those activated by receptor-interacting protein, TNF receptor-associated factor 2, NF-κB-inducing kinase, or MyD88, we hypothesized that the MC160 product interfered with I kappa kinase (IKK) activation, an event common to multiple signal transduction pathways. Indeed, MC160 protein expression was associated with a reduction in in vitro IKK kinase activity and IKK subunit phosphorylation. Further, IKK1-IKK2 interactions were not detected in MC160-expressing cells, under conditions demonstrated to induce IKK complex formation, but interactions between the MC160 protein and the major IKK subunits were undetectable. Surprisingly, MC160 expression correlated with a decrease in IKK1, but not IKK2 levels, suggesting a mechanism for MC160 disruption of IKK1-IKK2 interactions. MCV has probably retained its MC160 gene to inhibit NF-κB activation by interfering with signaling via multiple biological mediators. In the context of an MCV infection in vivo, MC160 protein expression may dampen the cellular production of proinflammatory molecules and enhance persistent infections in host keratinocytes. PMID:16378960

  13. High Stromal Carbonic Anhydrase IX Expression Is Associated With Decreased Survival in p16-Negative Head-and-Neck Tumors

    International Nuclear Information System (INIS)

    Brockton, Nigel; Dort, Joseph; Lau, Harold; Hao, Desiree; Brar, Sony; Klimowicz, Alexander; Petrillo, Stephanie; Diaz, Roman; Doll, Corinne; Magliocco, Anthony

    2011-01-01

    Purpose: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. Alcohol use and tobacco use are the most established risk factors; however, human papilloma virus (HPV) infection is a major risk factor for a subset of HNSCCs. Although HPV-positive tumors typically present at a more advanced stage at diagnosis, they are associated with a better prognosis. Tumor hypoxia confers poor prognosis and treatment failure, but direct tumor oxygen measurement is challenging. Endogenous markers of hypoxia (EMHs) have been proposed but have not replicated the prognostic utility of direct oxygen measurement. The expression of endogenous markers of hypoxia may be influenced by oxygen-independent factors, such as the HPV status of the tumor. Methods and Materials: Consecutive cases of locally advanced HNSCC, treated with a uniform regimen of combined radiotherapy and chemotherapy, were identified. Tissue microarrays were assembled from triplicate 0.6-mm cores of archived tumor tissue. HPV status was inferred from semiquantitative p16 immunostaining and directly measured by use of HPV-specific chromogenic in situ hybridization and polymerase chain reaction. Automated quantitative fluorescent immunohistochemistry was conducted to measure epithelial and stromal expression of carbonic anhydrase IX (CAIX) and glucose transporter 1 (GLUT1). Results: High stromal CAIX expression was associated with significantly reduced overall survival (p = 0.03) in patients with p16-negative tumors. Conclusions: This is the first study to use quantitative immunohistochemistry to examine endogenous markers of hypoxia stratified by tumor p16/HPV status. Assessment of CAIX expression in p16-negative HNSCC could identify patients with the least favorable prognosis and inform therapeutic strategies.

  14. Second international conference on isotopes. Conference proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, C J [ed.

    1997-10-01

    The Second International Conference on Isotopes (2ICI) was hosted by the Australian Nuclear Association in Sydney, NSW, Australia. The Theme of the Second Conference: Isotopes for Industry, Health and a Better Environment recognizes that isotopes have been used in these fields successfully for many years and offer prospects for increasing use in the future. The worldwide interest in the use of research reactors and accelerators and in applications of stable and radioactive isotopes, isotopic techniques and radiation in industry, agriculture, medicine, environmental studies and research in general, was considered. Other radiation issues including radiation protection and safety were also addressed. International and national overviews and subject reviews invited from leading experts were included to introduce the program of technical sessions. The invited papers were supported by contributions accepted from participants for oral and poster presentation. A Technical Exhibition was held in association with the Conference. This volume contains the foreword, technical program, the author index and of the papers (1-60) presented at the conference.

  15. Second international conference on isotopes. Conference proceedings

    International Nuclear Information System (INIS)

    Hardy, C.J.

    1997-10-01

    The Second International Conference on Isotopes (2ICI) was hosted by the Australian Nuclear Association in Sydney, NSW, Australia. The Theme of the Second Conference: Isotopes for Industry, Health and a Better Environment recognizes that isotopes have been used in these fields successfully for many years and offer prospects for increasing use in the future. The worldwide interest in the use of research reactors and accelerators and in applications of stable and radioactive isotopes, isotopic techniques and radiation in industry, agriculture, medicine, environmental studies and research in general, was considered. Other radiation issues including radiation protection and safety were also addressed. International and national overviews and subject reviews invited from leading experts were included to introduce the program of technical sessions. The invited papers were supported by contributions accepted from participants for oral and poster presentation. A Technical Exhibition was held in association with the Conference. This volume contains the foreword, technical program, the author index and of the papers (1-60) presented at the conference

  16. To conference or not to conference

    African Journals Online (AJOL)

    can travel throughout the world, from Cape to Cairo, from Jakarta to. Istanbul, from San ... Is there any real advantage of going to conferences in the era of electronic ... to register and travel, and the time off work, are justified, although we are.

  17. Virus and Infections 2010 - BIT's first world congress.

    Science.gov (United States)

    Garkavenko, Olga

    2010-10-01

    The World Congress of Virus and Infections, held in Busan, South Korea, included topics reviewing the field of zoonoses. This conference report highlights selected presentations on surveillance, epidemiology and measures for the control and prevention of zoonotic diseases. Topics discussed include human factors influencing zoonoses, the molecular epidemiology of Crimean-Congo hemorrhagic fever, the emerging Nipah virus, and the re-emergence of cowpox virus.

  18. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    ... May cause excessive secretion of hormones Common among men and women in their 50s-80s Accounts for about 13 percent of all brain tumors Symptoms Headache Depression Vision loss Nausea or vomiting Behavioral and cognitive ...

  19. French Society of Microscopy, 10. conference

    International Nuclear Information System (INIS)

    Thibault-Penisson, J.; Cremer, Ch.; Susini, J.; Kirklanda, A.I.; Rigneault, H.; Renault, O.; Bailly, A.; Zagonel, L.F.; Barrett, N.; Bogner, A.; Gauthier, C.; Jouneau, P.H.; Thollet, G.; Fuchs, G.; Basset, D.; Deconihout, B.; Vurpillot, F.; Vella, A.; Matthieu, G.; Cadel, E.; Bostel, A.; Blavette, D.; Baumeister, W.; Usson, Y.; Zaefferer, St.; Laffont, L.; Weyland, M.; Thomas, J.M.; Midgley, P.; Benlekbir, S.; Epicier, Th.; Diop, B.N.; Roux, St.; Ou, M.; Perriat, P.; Bausach, M.; Aouine, M.; Berhault, G.; Idrissi, H.; Cottevieille, M.; Jonic, S.; Larquet, E.; Svergun, D.; Vannoni, M.A.; Boisset, N.; Ersena, O.; Werckmann, J.; Ulhaq, C.; Hirlimann, Ch.; Tihay, F.; Cuong, Pham-Huu; Crucifix, C.; Schultz, P.; Jornsanoha, P.; Thollet, G.; Masenelli-Varlot, K.; Gauthier, C.; Ludwig, W.; King, A.; Johnson, G.; Gonzalves-Hoennicke, M.; Reischig, P.; Messaoudi, C.; Ibrahim, R.; Marco, S.; Klie, R.F.; Zhao, Y.; Yang, G.; Zhu, Y.; Hue, F.; Hytch, M.; Hartmann, J.M.; Bogumilowicz, Y.; Claverie, A.; Klein, H.; Alloyeau, D.; Ricolleau, C.; Langlois, C.; Le Bouar, Y.; Loiseau, A.; Colliex, C.; Stephan, O.; Kociak, M.; Tence, M.; Gloter, A.; Imhoff, D.; Walls, M.; Nelayah, J.; March, K.; Couillard, M.; Ailliot, C.; Bertin, F.; Cooper, D.; Rivallin, P.; Dumelie, N.; Benhayoune, H.; Balossier, G.; Cheynet, M.; Pokrant, S.; Tichelaar, F.; Rouviere, J.L.; Cooper, D.; Truche, R.; Chabli, A.; Debili, M.Y.; Houdellier, F.; Warot-Fonrose, B.; Hytch, M.J.; Snoeck, E.; Calmels, L.; Serin, V.; Schattschneider, P.; Jacob, D.; Cordier, P.

    2007-01-01

    This document gathers the resumes of some of the presentations made at this conference whose aim was to present the last developments and achievements of the 3 complementary microscopies: optical microscopy, electron microscopy and X-ray microscopy. The contributions have been organized around the following 12 topics: 1) new technical developments, 2) 3-dimensional imaging, 3) quantitative microscopy, 4) technical progress in photon microscopy, 5) synchrotron radiation, 6) measurements of patterns, deformations and strains, 7) materials for energy and transports, 8) nano-structures, 9) virus: structure and infection mechanisms, 10) 3-dimensional imaging for molecules, cells and cellular tissues, 11) nano-particles and colloids, and 12) liquid crystals

  20. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

    Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

  1. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  2. Otto Toeplitz Memorial Conference

    International Nuclear Information System (INIS)

    Ball, J.A.

    1981-01-01

    A conference in operator theory and its applications commemorating the 100th anniversary of the birth of the distinguished German mathematician Otto Toeplitz, organized by the University of Tel Aviv together with German Mathematical Society, took place in Tel Aviv, Israel, from May 11th to 15th, 1981. I give here a broad very subjective overview of the proceedings of the conference for the benefit of readers of TTSP; for those interested in further details, a forthcoming volume in the Birkhaeuser series Operator Theory: Advances and Applications will consist of expanded written versions of most of the talks given at the conference

  3. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  4. Imaging of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gaensler, E H.L. [California Univ., San Francisco, CA (United States). Dept. of Radiology

    1996-12-31

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.).

  5. Neuraminidase inhibitor susceptibility profile of human influenza viruses during the 2016-2017 influenza season in Mainland China.

    Science.gov (United States)

    Huang, Weijuan; Cheng, Yanhui; Li, Xiyan; Tan, Minju; Wei, Hejiang; Zhao, Xiang; Xiao, Ning; Dong, Jie; Wang, Dayan

    2018-06-01

    To understand the current situation of antiviral-resistance of influenza viruses to neuraminidase inhibitors (NAIs) in Mainland China, The antiviral-resistant surveillance data of the circulating influenza viruses in Mainland China during the 2016-2017 influenza season were analyzed. The total 3215 influenza viruses were studied to determine 50% inhibitory concentration (IC 50 ) for oseltamivir and zanamivir using a fluorescence-based assay. Approximately 0.3% (n = 10) of viruses showed either highly reduced inhibition (HRI) or reduced inhibition (RI) against at least one NAI. The most common neuraminidase (NA) amino acid substitution was H275Y in A (H1N1)pdm09 virus, which confers HRI by oseltamivir. Two A (H1N1)pdm09 viruses contained a new NA amino acid substitution respectively, S110F and D151E, which confers RI by oseltamivir or/and zanamivir. Two B/Victoria-lineage viruses harbored a new NA amino acid substitution respectively, H134Q and S246P, which confers RI by zanamivir. One B/Victoria-lineage virus contained dual amino acid substitution NA P124T and V422I, which confers HRI by zanamivir. One B/Yamagata-lineage virus was a reassortant virus that haemagglutinin (HA) from B/Yamagata-lineage virus and NA from B/Victoria-lineage virus, defined as B/Yamagata-lineage virus confers RI by oseltamivir, but as B/Victoria-lineage virus confers normal inhibition by oseltamivir. All new substitutions that have not been reported before, the correlation of these substitutions and observed changes in IC 50 should be further assessed. During the 2016-2017 influenza season in Mainland China the majority tested viruses were susceptible to oseltamivir and zanamivir. Hence, NAIs remain the recommended antiviral for treatment and prophylaxis of influenza virus infections. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. The 26. CLI national conference. Conference proceedings

    International Nuclear Information System (INIS)

    Chevet, Pierre-Franck; Niel, Jean-Christophe; Legrand, Henri; Dumont, Jean-Jacques; Lachaume, Jean-Luc; Delalonde, Jean-Claude; Sene, Monique; Le Deaut, Jean Yves; Charles, Thierry; Sasseigne, Philippe; Fournier, Nicolas; Murith, Christophe; Rivasi, Michele; Perissat, Frederic; KESSLER, Emmanuel

    2014-12-01

    This document gathers contributions presented during a conference held in December 2014. After introduction speeches and a focus of some updates by ANCCLI and ASN representatives, this conference comprised two round tables. The first one addressed the continuation of nuclear reactor operation after their fourth safety re-examination, with contributions by representatives of the ASN, of the ANCCLI, of the IRSN, and of EDF. The second one addressed the issue of a European harmonisation regarding actions of protection of populations in case of a nuclear accident, with interventions of representatives of a CLI, of the ASN, of the Swiss federal office for public health, of an NGO (Nuclear Transparency Watch), and of a departmental prefect

  7. The learning conference

    DEFF Research Database (Denmark)

    Ravn, Ib

    little support amongst serious students of learning. The professional conference as a forum for knowledge sharing is in dire need of a new learning theory and a more enlightened practice. The notion of human flourishing is offered as basis for theory, and four simple design principles for the so......The typical one-day conference attended by managers or professionals in search of inspiration is packed with PowerPoint presentations and offers little opportunity for involvement or knowledge sharing. Behind the conventional conference format lurks the transfer model of learning, which finds......-called “learning conference” are proposed: People go to conferences to 1. get concise input, 2. interpret it in the light of their ongoing concerns, 3. talk about their current projects and 4. meet the other attendees and be inspired by them. Six practical techniques that induce attendees to do these things...

  8. EVOLVE 2014 International Conference

    CERN Document Server

    Tantar, Emilia; Sun, Jian-Qiao; Zhang, Wei; Ding, Qian; Schütze, Oliver; Emmerich, Michael; Legrand, Pierrick; Moral, Pierre; Coello, Carlos

    2014-01-01

    This volume encloses research articles that were presented at the EVOLVE 2014 International Conference in Beijing, China, July 1–4, 2014.The book gathers contributions that emerged from the conference tracks, ranging from probability to set oriented numerics and evolutionary computation; all complemented by the bridging purpose of the conference, e.g. Complex Networks and Landscape Analysis, or by the more application oriented perspective. The novelty of the volume, when considering the EVOLVE series, comes from targeting also the practitioner’s view. This is supported by the Machine Learning Applied to Networks and Practical Aspects of Evolutionary Algorithms tracks, providing surveys on new application areas, as in the networking area and useful insights in the development of evolutionary techniques, from a practitioner’s perspective. Complementary to these directions, the conference tracks supporting the volume, follow on the individual advancements of the subareas constituting the scope of the confe...

  9. DNA sequencing conference, 2

    Energy Technology Data Exchange (ETDEWEB)

    Cook-Deegan, R.M. [Georgetown Univ., Kennedy Inst. of Ethics, Washington, DC (United States); Venter, J.C. [National Inst. of Neurological Disorders and Strokes, Bethesda, MD (United States); Gilbert, W. [Harvard Univ., Cambridge, MA (United States); Mulligan, J. [Stanford Univ., CA (United States); Mansfield, B.K. [Oak Ridge National Lab., TN (United States)

    1991-06-19

    This conference focused on DNA sequencing, genetic linkage mapping, physical mapping, informatics and bioethics. Several were used to study this sequencing and mapping. This article also discusses computer hardware and software aiding in the mapping of genes.

  10. Conference on radioecology

    International Nuclear Information System (INIS)

    1989-12-01

    32 abstracts of contributions presented at the conference and covering all aspects of radioecology are included. The lecturers were mainly from Czechoslovakia; contributions from the USSR, France, Belgium, Hungary, Bulgaria, etc., however, were also presented. (P.A.)

  11. Ranking Operations Management conferences

    NARCIS (Netherlands)

    Steenhuis, H.J.; de Bruijn, E.J.; Gupta, Sushil; Laptaned, U

    2007-01-01

    Several publications have appeared in the field of Operations Management which rank Operations Management related journals. Several ranking systems exist for journals based on , for example, perceived relevance and quality, citation, and author affiliation. Many academics also publish at conferences

  12. Photos of the conference

    Directory of Open Access Journals (Sweden)

    Birgitta Åhman

    1984-05-01

    Full Text Available Birgitta  Åhman is the photographer of the series of pictures from the conference, also for the cover photo of the full paper edition showing Kongsvold Mountain Hut and Biological Station.

  13. Virus-Specific T Cells for the Immunocompromised Patient

    Directory of Open Access Journals (Sweden)

    Amy Houghtelin

    2017-10-01

    Full Text Available While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST, which are not only effective but also confer protection in 70–90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo.

  14. Virus-Specific T Cells for the Immunocompromised Patient.

    Science.gov (United States)

    Houghtelin, Amy; Bollard, Catherine M

    2017-01-01

    While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs) is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST), which are not only effective but also confer protection in 70-90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo .

  15. Japan Accelerator Conference

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    At the international level, the high energy accelerator scene evolves rapidly and the International Conference on High Energy Accelerators is where its strong pulse can best be felt. This year, the Conference was held for the first time in Japan, with the 14th meeting in the series having been hosted in August by the Japanese KEK National Laboratory for High Energy Physics, Tsukuba. The venue was a recognition of the premier accelerator physics and technology status achieved by this diligent nation

  16. 2nd SUMO Conference

    CERN Document Server

    Weber, Melanie

    2015-01-01

    This contributed volume contains the conference proceedings of the Simulation of Urban Mobility (SUMO) conference 2014, Berlin. The included research papers cover a wide range of topics in traffic planning and simulation, including open data, vehicular communication, e-mobility, urban mobility, multimodal traffic as well as usage approaches. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.  

  17. Multiphoton processes: conference proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Lambropoulos, P.; Smith, S.J. (eds.)

    1984-01-01

    The chapters of this volume represent the invited papers delivered at the conference. They are arranged according to thermatic proximity beginning with atoms and continuing with molecules and surfaces. Section headings include multiphoton processes in atoms, field fluctuations and collisions in multiphoton process, and multiphoton processes in molecules and surfaces. Abstracts of individual items from the conference were prepared separately for the data base. (GHT)

  18. Japan Accelerator Conference

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1989-11-15

    At the international level, the high energy accelerator scene evolves rapidly and the International Conference on High Energy Accelerators is where its strong pulse can best be felt. This year, the Conference was held for the first time in Japan, with the 14th meeting in the series having been hosted in August by the Japanese KEK National Laboratory for High Energy Physics, Tsukuba. The venue was a recognition of the premier accelerator physics and technology status achieved by this diligent nation.

  19. Conference Report: The BPS Annual Conference 2004

    Directory of Open Access Journals (Sweden)

    Irina Roncaglia

    2004-05-01

    Full Text Available In this article I will review four papers presented at the British Psychological Society Annual Conference held this year in London held over a 3 day period. The Conference included a variety of scientific presentations and discussions through symposia, roundtable discussions, single papers and poster sessions. Although numerous papers took an experimental approach, few applied any type of qualitative methodology. The topics covered within the different psychological disciplines spanned from early childhood through old age; I have chosen four papers that covered a life course perspective and took into consideration clinical issues as well. The first paper discusses a grounded theory approach used to analyse a play therapy session between therapist and child. The second review reports some recent findings in the way the brains of people on the autistic spectrum disorder might function. The third paper discusses positive psychology and how such an emerging movement has influenced new research in the field. The last paper reviewed will discuss the issue of the ageing process, and I will present some arguments related to the useful application of qualitative methodologies within this area of research. In conclusion, I will highlight some personal reflections on the Conference and the need for a greater balance between qualitative and quantitative methodologies to be used in collaboration rather than as antagonists. URN: urn:nbn:de:0114-fqs0402176

  20. Conference scene: DGVS spring conference 2009.

    Science.gov (United States)

    Kolligs, Frank Thomas

    2009-10-01

    The 3rd annual DGVS Spring Conference of the German Society for Gastroenterology (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten) was held at the Seminaris Campus Hotel in Berlin, Germany, on 8-9 May, 2009. The conference was organized by Roland Schmid and Matthias Ebert from the Technical University of Munich, Germany. The central theme of the meeting was 'translational gastrointestinal oncology: towards personalized medicine and individualized therapy'. The conference covered talks on markers for diagnosis, screening and surveillance of colorectal cancer, targets for molecular therapy, response prediction in clinical oncology, development and integration of molecular imaging in gastrointestinal oncology and translational research in clinical trial design. Owing to the broad array of topics and limitations of space, this article will focus on biomarkers, response prediction and the integration of biomarkers into clinical trials. Presentations mentioned in this summary were given by Matthias Ebert (Technical University of Munich, Germany), Esmeralda Heiden (Epigenomics, Berlin, Germany), Frank Kolligs (University of Munich, Germany), Florian Lordick (University of Heidelberg, Germany), Hans Jorgen Nielsen (University of Copenhagen, Denmark), Anke Reinacher-Schick (University of Bochum, Germany), Christoph Röcken (University of Berlin, Germany), Wolff Schmiegel (University of Bochum, Germany) and Thomas Seufferlein (University of Halle, Germany).

  1. World Energy Conference

    International Nuclear Information System (INIS)

    Ott, G.; Schilling, H.D.

    1979-01-01

    After making some general remarks about goals, tasks, and works of the World Energy Conference the topics and the frame of the 11th World Energy Conference which will take place in Munich from 8th to 12th September 1980 are outlined. This conference is held under the general topic 'energy for our world' and deals with the reciprocal relation between energy supply, environment, and society. The main part of the publication presented here is the German version of the most important sections of the investigation 'World Energy-Looking Ahead to 2020' by the Conservation Commission (CC) of the World Energy Conference. Added to this is the German original brief version of a report by the Mining-Research Company (Bergbau-Forschung GmbH) to the CC which deals with the estimation of the world's coal resources and their future availability. This report was presented on the 10th World Energy Conference in Istanbul together with the corresponding reports concerning the other energy sources. Finally, an introduction to the technical programme for the 11th World Energy Conference 1980 is given. (UA) [de

  2. Bone tumors

    International Nuclear Information System (INIS)

    Moylan, D.J.; Yelovich, R.M.

    1991-01-01

    Primary bone malignancies are relatively rare with less than 4,000 new cases per year. Multiple myeloma (more correctly a hematologic malignancy) accounts for 40%; osteosarcomas, 28%; chondrosarcomas, 13%; fibrosarcomas arising in bone, 4%; and Ewing's sarcoma, 7%. The authors discuss various treatments for bone tumors, including radiotherapy, chemotherapy and surgery

  3. Wilms Tumor

    Science.gov (United States)

    ... a child's general health and to detect any adverse side effects (such as low red or white blood cell ... medicine needed, which helps reduce long-term side effects. The most common ... can be completely removed by surgery. About 41% of all Wilms tumors are stage ...

  4. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  5. Microbial Regulation of p53 Tumor Suppressor.

    Directory of Open Access Journals (Sweden)

    Alexander I Zaika

    2015-09-01

    Full Text Available p53 tumor suppressor has been identified as a protein interacting with the large T antigen produced by simian vacuolating virus 40 (SV40. Subsequent research on p53 inhibition by SV40 and other tumor viruses has not only helped to gain a better understanding of viral biology, but also shaped our knowledge of human tumorigenesis. Recent studies have found, however, that inhibition of p53 is not strictly in the realm of viruses. Some bacterial pathogens also actively inhibit p53 protein and induce its degradation, resulting in alteration of cellular stress responses. This phenomenon was initially characterized in gastric epithelial cells infected with Helicobacter pylori, a bacterial pathogen that commonly infects the human stomach and is strongly linked to gastric cancer. Besides H. pylori, a number of other bacterial species were recently discovered to inhibit p53. These findings provide novel insights into host-bacteria interactions and tumorigenesis associated with bacterial infections.

  6. 2nd Bozeman Conference

    CERN Document Server

    Lund, John

    1991-01-01

    This volume contains a collection of papers delivered by the partici­ pants at the second Conference on Computation and Control held at Mon­ tana State University in Bozeman, Montana from August 1-7, 1990. The conference, as well as this proceedings, attests to the vitality and cohesion between the control theorist and the numerical analyst that was adver­ tised by the first Conference on Computation and Control in 1988. The proceedings of that initial conference was published by Birkhiiuser Boston as the first volume of this same series entitled Computation and Control, Proceedings of the Bozeman Conference, Bozeman, Montana, 1988. Control theory and numerical analysis are both, by their very nature, interdisciplinary subjects as evidenced by their interaction with other fields of mathematics and engineering. While it is clear that new control or es­ timation algorithms and new feedback design methodologies will need to be implemented computationally, it is likewise clear that new problems in computation...

  7. Phytophthora viruses.

    Science.gov (United States)

    Cai, Guohong; Hillman, Bradley I

    2013-01-01

    Phytophthora sp. is a genus in the oomycetes, which are similar to filamentous fungi in morphology and habitat, but phylogenetically more closely related to brown algae and diatoms and fall in the kingdom Stramenopila. In the past few years, several viruses have been characterized in Phytophthora species, including four viruses from Phytophthora infestans, the late blight pathogen, and an endornavirus from an unnamed Phytophthora species from Douglas fir. Studies on Phytophthora viruses have revealed several interesting systems. Phytophthora infestans RNA virus 1 (PiRV-1) and PiRV-2 are likely the first members of two new virus families; studies on PiRV-3 support the establishment of a new virus genus that is not affiliated with established virus families; PiRV-4 is a member of Narnaviridae, most likely in the genus Narnavirus; and Phytophthora endornavirus 1 (PEV1) was the first nonplant endornavirus at the time of reporting. Viral capsids have not been found in any of the above-mentioned viruses. PiRV-1 demonstrated a unique genome organization that requires further examination, and PiRV-2 may have played a role in late blight resurgence in 1980s-1990s. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Schmallenberg Virus

    Indian Academy of Sciences (India)

    IAS Admin

    explore the potential of this infection crossing the species barrier and thereby .... The virus targets mainly the brain of the unborn animal resulting in neurological ... The virus is located in the blood of the adult infected animal or in the central ...

  9. Zika Virus

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Zika Virus Credit: NIAID A female Aedes mosquito. This type of mosquito can transmit Zika, ... transmitted to humans through the bite of infected Aedes aegypti mosquitoes. Zika virus can be transmitted from an infected pregnant woman ...

  10. CHANDIPURA VIRUS

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. CHANDIPURA VIRUS. First isolated from a village called Chandipura near Nagpur in 1965 in India. Belongs to rhabdoviridae family. Used as a Model System to study RNA virus multiplication in the infected cell at molecular level. Notes:

  11. Genetic susceptibility to and presence of endogenous avian leukosis viruses impose no significant impact on survival days of chickens challenged with very virulent plus Marek's disease virus

    Science.gov (United States)

    Chicks of distinct genotypes at the tumor virus B locus (TVB) in combination with presence or absence of endogenous avian leukosis virus ev21 gene in their genomes were examined for survival day patterns after challenge with very virulent plus Marek’s disease virus (vv+MDV) in three consecutive tria...

  12. Conferences and Family Reunions

    Directory of Open Access Journals (Sweden)

    Sarah Sutherland

    2012-12-01

    Full Text Available Professional associations and conferences have similarities with and differences from families and family reunions. This comparison can illustrate some ways professional associations can approach the integration of new members and the planning of conferences in order to facilitate membership development and leadership renewal. Unlike family reunions, professional conferences are not closed events that require a shared culture in order to fully participate; they are events that should show the constant change and development of practice that is representative of the profession – for both members and non-members. Some of the topics explored in the article are: making it easy for outsiders to contribute, considering the tastes of new members, making it easy to volunteer in a meaningful way, and remembering who the future of the organization is. These simple considerations will assist in opening professional associations to new participants and help them to maintain their relevance and vitality over time.

  13. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  14. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  15. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  16. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  17. Low Energy Conference 2009

    Energy Technology Data Exchange (ETDEWEB)

    2009-07-01

    11 of the 19 presentations have been indexed for the database. The following national organisations jointly organised the Low-energy Conference 2009: The Norwegian Society for the Conservation of Nature, the Norwegian Society of Engineers and Technologists, Norwegian Technology, the Federation of Norwegian Industries and the Low-Energy Program. Energy efficiency is often given little attention in the ongoing debates concerning different initiatives in order to reduce greenhouse emissions. The aim of the conference was to set energy efficiency on the agenda as an important environmental instrument. Both the Intergovernmental Panel on Climate Change - IPCC and the International Energy Agency - IEA regard energy efficiency as one of the fastest and most effective ways of reducing greenhouse emissions. Despite of this little is done. Many countries are ahead of Norway - why are we lagging behind? The Low-Energy conference has a broad approach: Nigel Jollands from the International Energy Agency -IEA puts energy efficiency in a global perspective. Soeren Rise from Teqniq in Denmark informs about the Danes' energy saving agreement, which appears to have been a success. The conference increased the competencies on concrete energy efficiency solutions, how to speed up the marketing of energy-friendly buildings and technologies, possibilities through industry and the impact of EU-directives and other instruments in order to trigger the potential. The conference closed with a discussion panel of leading energy politicians. The conference contributed to raise the debate in advance of the General election in Norway and the climate negotiations in Copenhagen during the autumn 2009. (EW)

  18. CONFERENCE: Nuclear visions

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    Last summer, four hundred visitors of about 30 different nationalities descended on the ancient town of Visby on the Swedish island of Gotland for the Second International Conference on Nucleus-Nucleus Collisions. For the conference itself, sessions were organized not according to conventional topics like low, intermediate and high energy reactions, but along phenomena-related lines that brought listeners together instead of splitting them up. Examples were 'phase transitions', 'new facilities' and 'breaking nuclear matter into pieces'

  19. VMEbus in physics conference

    International Nuclear Information System (INIS)

    1986-01-01

    The first conference ''VMEbus in Physics'' was held at CERN on 7th and 8th October 1985. The conference surveyed the applications of the VMEbus standards in physics, with special emphasis on particle physics and accelerator control. Developments in the definition of the standards and in the formation of users groups were discussed. Manufacturer's representatives were given the opportunity to appreciate the requirements of the fast-growing VMEbus market in the physics community. These proceedings contain the unedited text of the oral and poster presentations given on that occasion. (orig.)

  20. CONFERENCE: Linacs at Seeheim

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1984-07-15

    The 12th Linear Accelerator Conference, organized by GSI Darmstadt, was held from 8-11 May at the Lufthansa Schulungszentrum in Seeheim, West Germany. It was the first of this series of Linac Accelerator Conferences - started in 1961 with 20 participants and 17 contributions at Brookhaven - held outside North America. In Seeheim, 32 invited talks, 11 oral and 98 poster papers were presented to more than 250 participants from the USA, Canada, Europe, Japan, the USSR and China, representing 39 research institutions and 12 industrial laboratories.

  1. International conference, ICPRAM 2012

    CERN Document Server

    Sánchez, J; Fred, Ana; Pattern recognition : applications and methods : revised selected papers

    2013-01-01

    This edited book includes extended and revised versions of a set of selected papers from the First International Conference on Pattern Recognition (ICPRAM 2012), held in Vilamoura, Algarve, Portugal, from 6 to 8 February, 2012, sponsored by the Institute for Systems and Technologies of Information Control and Communication (INSTICC) and held in cooperation with the Association for the Advancement of Artificial Intelligence (AAAI) and Pattern Analysis, Statistical Modelling and Computational Learning (PASCAL2). The conference brought together researchers, engineers and practitioners interested on the areas of Pattern Recognition, both from theoretical and application perspectives.

  2. Internet conferences in glycobiology.

    Science.gov (United States)

    Hardy, B J; Doughty, S W; Parretti, M F; Tennison, J; Wilson, I

    1997-09-01

    In this article we describe recent activities in the use of electronic conferencing in glycobiology focusing on our experiences with the organization and development of the Second Electronic Glycoscience Conference (EGC-2), which was held on the Internet and World Wide Web in September 1996. EGC-2 involved the presentation and discussion of scientific research results in a virtual conferencing environment which incorporated virtual replicas of many activities usually observed at a physical conference in addition to features unique to the electronic medium. Highlights of the scientific program and technical developments in the design and use of these facilities are briefly described. EGC-3 will be held in October 1997.

  3. The learning conference

    DEFF Research Database (Denmark)

    Ravn, Ib

    2007-01-01

    /methodology/approach: A typical full-day conference is analyzed. It has six hours of podium talk and twenty-five minutes for delegates to become involved. What model of learning can possibly lie behind this? The transfer model, which assumes learners to be empty vessels. An alternative view is that conference delegates...... are described: Individual reflection, the buzz dyad, ?You have won two consultants, free of charge?, facilitated group work, the knowledge exchange, and lunch with gaffer tape. Originality/value: This paper introduces modern learning theory and techniques into an educational context which has resisted...

  4. CONFERENCE: Linacs at Seeheim

    International Nuclear Information System (INIS)

    Anon.

    1984-01-01

    The 12th Linear Accelerator Conference, organized by GSI Darmstadt, was held from 8-11 May at the Lufthansa Schulungszentrum in Seeheim, West Germany. It was the first of this series of Linac Accelerator Conferences - started in 1961 with 20 participants and 17 contributions at Brookhaven - held outside North America. In Seeheim, 32 invited talks, 11 oral and 98 poster papers were presented to more than 250 participants from the USA, Canada, Europe, Japan, the USSR and China, representing 39 research institutions and 12 industrial laboratories

  5. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

    2015-09-15

    Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

  6. Veterans in Society Conference 2014: Humanizing the Discourse (Conference Program)

    OpenAIRE

    Virginia Tech. Department of English. Center for the Study of Rhetoric in Society; Virginia Tech. Veterans Studies Group

    2014-01-01

    This program lists the daily sessions, presentations, and events that took place during the 2014 Veterans in Society Conference, which was held from April 27-28, 2014 at the Hotel Roanoke in Roanoke, VA. This program also includes speaker and presenter bios, descriptions of unrecorded conference events, and a letter from conference co-chair Jim Dubinsky, the director of Virginia Tech's Center for the Study of Rhetoric in Society. The 2014 Veterans in Society Conference: Humanizing the Discour...

  7. Genomic profiling of tumor necrosis factor alpha (TNF-alpha) receptor and interleukin-1 receptor knockout mice reveals a link between TNF-alpha signaling and increased severity of 1918 pandemic influenza virus infection

    Science.gov (United States)

    The influenza pandemic of 1918-1919 was one of the worst global pandemics in recent history. The highly pathogenic nature of the 1918 virus is thought to be mediated in part by a dysregulation of the host response, including an exacerbated pro-inflammatory cytokine response. In the present study, we...

  8. 78 FR 27963 - Reliability Technical Conference; Notice of Technical Conference

    Science.gov (United States)

    2013-05-13

    ... Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, July 9, 2013 from 9:00 a.m. to 5:00 p.m. This... technical support for webcasts and offers the option of listening to the meeting via phone-bridge for a fee...

  9. Testis tumors

    International Nuclear Information System (INIS)

    White, R.L.; Maier, J.G.

    1987-01-01

    Clinical trials are evaluating new combinations of drugs with the goal of diminishing the toxicity associated with the current regimens while not compromising the chance for cure. The evolution of information and staging studies such as tumor markers, CT scanning and MR scanning has made possible the detection of residual metastatic disease while obviating the need for surgical staging procedures. This has made less treatment possible for a large number of patients. The regularity of follow-up studies has made early detection of recurrences a possibility, so that effective and curative treatment is generally possible

  10. Viral exploitation of the MEK/ERK pathway - A tale of vaccinia virus and other viruses.

    Science.gov (United States)

    Bonjardim, Cláudio A

    2017-07-01

    The VACV replication cycle is remarkable in the sense that it is performed entirely in the cytoplasmic compartment of vertebrate cells, due to its capability to encode enzymes required either for regulating the macromolecular precursor pool or the biosynthetic processes. Although remarkable, this gene repertoire is not sufficient to confer the status of a free-living microorganism to the virus, and, consequently, the virus relies heavily on the host to successfully generate its progeny. During the complex virus-host interaction, viruses must deal not only with the host pathways to accomplish their temporal demands but also with pathways that counteract viral infection, including the inflammatory, innate and acquired immune responses. This review focuses on VACV and other DNA or RNA viruses that stimulate the MEK (MAPK - Mitogen Activated Protein Kinase)/ERK- Extracellular signal-Regulated Kinase) pathway as part of their replication cycle. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Interaction of Human Enteric Viruses with Microbial Compounds: Implication for Virus Persistence and Disinfection Treatments.

    Science.gov (United States)

    Waldman, Prunelle; Meseguer, Alba; Lucas, Françoise; Moulin, Laurent; Wurtzer, Sébastien

    2017-12-05

    Although the interaction between phages and bacteria has already been well described, it only recently emerged that human viruses also interact with bacteria in the mammalian gut. We studied whether this interaction could occur in tap water and thus confer enteric viruses protection against temperature and the classical disinfection treatments used in drinking water production. We demonstrated that the addition of lipopolysaccharide or peptidoglycan of bacterial origin to enterovirus provides thermal protection through stabilization of the viral capsid. This interaction plays a role when viruses are exposed to disinfection that targets the capsid, but less so when the virus genome is directly targeted. The interaction seems to be serotype-specific, suggesting that the capsid protein sequence could be important. The protection is linked to a direct association between viral particles and bacterial compounds as observed by microscopy. These results show that bacterial compounds present in the environment can affect virus inactivation.

  12. Teratoid Wilms′ tumor - A rare renal tumor

    Directory of Open Access Journals (Sweden)

    Biswanath Mukhopadhyay

    2011-01-01

    Full Text Available Teratoid Wilms′ tumor is an extremely rare renal tumor. We report a case of unilateral teratoid Wilms′ tumor in a 4-year-old girl. The patient was admitted with a right-sided abdominal mass. The mass was arising from the right kidney. Radical nephrectomy was done and the patient had an uneventful recovery. Histopathology report showed teratoid Wilms′ tumor.

  13. Santa Fe Accelerator Conference

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    The 10th USA National Particle Accelerator Conference was hosted this year by the Los Alamos National Laboratory in Santa Fe from 21-23 March. It was a resounding success in emphasizing the ferment of activity in the accelerator field. About 900 people registered and about 500 papers were presented in invited and contributed talks and poster sessions

  14. Annual Conference Abstracts

    Science.gov (United States)

    Journal of Engineering Education, 1972

    1972-01-01

    Includes abstracts of papers presented at the 80th Annual Conference of the American Society for Engineering Education. The broad areas include aerospace, affiliate and associate member council, agricultural engineering, biomedical engineering, continuing engineering studies, chemical engineering, civil engineering, computers, cooperative…

  15. International Nuclear Physics Conference

    CERN Document Server

    2016-01-01

    We are pleased to announce that the 26th International Nuclear Physics Conference (INPC2016) will take place in Adelaide (Australia) from September 11-16, 2016. The 25th INPC was held in Firenze in 2013 and the 24th INPC in Vancouver, Canada, in 2010. The Conference is organized by the Centre for the Subatomic Structure of Matter at the University of Adelaide, together with the Australian National University and ANSTO. It is also sponsored by the International Union of Pure and Applied Physics (IUPAP) and by a number of organisations, including AUSHEP, BNL, CoEPP, GSI and JLab. INPC 2016 will be held in the heart of Adelaide at the Convention Centre on the banks of the River Torrens. It will consist of 5 days of conference presentations, with plenary sessions in the mornings, up to ten parallel sessions in the afternoons, poster sessions and a public lecture. The Conference will officially start in the evening of Sunday 11th September with Registration and a Reception and will end late on the afternoon of Fri...

  16. Hamburg Accelerator Conference

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Edmund J.N. [CERN Accelerator School (Switzerland)

    1992-10-15

    From 20-24 July, Hamburg welcomed the Fifteenth International Conference on High Energy Accelerators (HEACC). A natural highlight was the recent commissioning success of the HERA electron-proton collider at Hamburg's DESY Laboratory and its first high energy electron-proton collision data. This gave the meeting the feel of a family event celebrating a newborn.

  17. BEAUTY'99 Conference Summary

    International Nuclear Information System (INIS)

    Eerola, Paula

    2000-01-01

    Investigations of B hadrons are expected to break new ground in measuring CP-violation effects. This series of BEAUTY conferences, originating from the 1993 conference in Liblice, has contributed significantly in developing ideas of CP-violation measurements using B hadrons and formulating and comparing critically the B-physics experiments. In the '99 conference in Bled we saw the ripening of the field and the first fruit emerging - Tevatron have produced beautiful B-physics results and more are expected to come with the next run, while the B-physics experiments at DESY, SLAC and KEK are starting their operation. The longer-term projects at LHC and Tevatron have taken their shape and detailed prototyping work is going on. Meanwhile, on the phenomenological side, there has been impressive theoretical progress in understanding deeper the 'standard' measurements and proposing new signatures. In this summary, I will highlight the status of the field as presented in the conference, concentrating on signatures, experiments and R and D programmes

  18. Bioenergy 93 conference

    International Nuclear Information System (INIS)

    1993-01-01

    In this report the presentations given in the Bioenergy 93 Conference are published. The papers are grouped as follows: Opening addresses, biomass implementation strategies, nordic bioenergy research programs, production, handling and conversion of biofuels, combustion technology of biofuels and bioenergy visions

  19. Leader Training Conference Report.

    Science.gov (United States)

    Michigan-Ohio Regional Educational Lab., Inc., Detroit.

    The purpose of this conference was to prepare key people in the field of education to function as inservice education leaders in their respective settings. It called for participants to learn what the MOREL inservice education program is and what it hopes to accomplish, to identify the role and functions of the inservice education leader, and to…

  20. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  1. Vienna wirechamber conference 98

    International Nuclear Information System (INIS)

    1998-02-01

    This volume of the Vienna wirechamber conference 1998 contains abstracts of lectures and abstracts of poster sessions of the following topics: high energy physics, gaseous detectors, radiation detectors, calorimetry, drift chambers, wire spark chambers, tracking chambers, neutron detectors, particle detection, muon spectrometry, nuclear medicine. (Suda)

  2. CONFERENCE: Quark matter 88

    International Nuclear Information System (INIS)

    Jacob, Maurice

    1988-01-01

    The 'Quark Matter' Conference caters for physicists studying nuclear matter under extreme conditions. The hope is that relativistic (high energy) heavy ion collisions allow formation of the long-awaited quark-gluon plasma, where the inter-quark 'colour' force is no longer confined inside nucleon-like dimensions

  3. Transactions: student conference, 1982

    International Nuclear Information System (INIS)

    1982-01-01

    Papers presented at this conference covered the topics of CANDU reactor physics, control systems and steam generators; imaging in neutron radiography; cooling systems for a SLOWPOKE reactor; accelerator breeders; the investigation of point defects using positrons; neutron and gamma detectors; fusion reaction kinetics; and heavy ion fusion

  4. International waste management conference

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    This book contains the proceedings of the international waste management conference. Topics covered include: Quality assurance in the OCR WM program; Leading the spirit of quality; Dept. of Energy hazardous waste remedial actions program; management of hazardous waste projects; and System management and quality assurance

  5. Microbicides 2006 conference

    Directory of Open Access Journals (Sweden)

    McGowan Ian

    2006-10-01

    Full Text Available Abstract Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition. The biannual Microbicides conference took place in Cape Town, South Africa from 23–26 April 2006. The conference was held for the first time on the African continent, the region worst affected by the HIV/AIDS pandemic. The conference brought together a record number of 1,300 scientists, researchers, policy makers, healthcare workers, communities and advocates. The conference provided an opportunity for an update on microbicide research and development as well as discussions around key issues such as ethics, acceptability, access and community involvement. This report discusses the current status of microbicide research and development, encompassing basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities.

  6. Hamburg Accelerator Conference

    International Nuclear Information System (INIS)

    Wilson, Edmund J.N.

    1992-01-01

    From 20-24 July, Hamburg welcomed the Fifteenth International Conference on High Energy Accelerators (HEACC). A natural highlight was the recent commissioning success of the HERA electron-proton collider at Hamburg's DESY Laboratory and its first high energy electron-proton collision data. This gave the meeting the feel of a family event celebrating a newborn

  7. Grammar! A Conference Report.

    Science.gov (United States)

    King, Lid, Ed.; Boaks, Peter, Ed.

    Papers from a conference on the teaching of grammar, particularly in second language instruction, include: "Grammar: Acquisition and Use" (Richard Johnstone); "Grammar and Communication" (Brian Page); "Linguistic Progression and Increasing Independence" (Bernardette Holmes); "La grammaire? C'est du bricolage!" ("Grammar? That's Hardware!") (Barry…

  8. Wire chamber conference

    International Nuclear Information System (INIS)

    Bartl, W.; Neuhofer, G.; Regler, M.

    1986-02-01

    This booklet contains program and the abstracts of the papers presented at the conference, most of them dealing with performance testing of various types of wire chambers. The publication of proceedings is planned as a special issue of 'Nuclear instruments and methods' later on. All abstracts are in English. An author index for the book of abstracts is given. (A.N.)

  9. Santa Fe Linac Conference

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    The 1981 Linear Accelerator Conference, organized by Los Alamos National Laboratory, was held from 19-23 October in Santa Fe, New Mexico. The surroundings were superb and helped to ensure a successful meeting. There were more than two hundred and twenty participants, with good representation from Japan and Western Europe

  10. Oncolytic viruses: a step into cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Pol JG

    2011-12-01

    Full Text Available Jonathan G Pol, Julien Rességuier, Brian D LichtyMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, CanadaAbstract: Oncolytic virotherapy is currently under investigation in phase I–III clinical trials for approval as a new cancer treatment. Oncolytic viruses (OVs selectively infect, replicate in, and kill tumor cells. For a long time, the therapeutic efficacy was thought to depend on the direct viral oncolysis (virocentric view. The host immune system was considered as a brake that impaired virus delivery and spread. Attention was paid primarily to approaches enhancing virus tumor selectivity and cytotoxicity and/or that limited antiviral responses. Thinking has changed over the past few years with the discovery that OV therapy was also inducing indirect oncolysis mechanisms. Among them, induction of an antitumor immunity following OV injection appeared to be a key factor for an efficient therapeutic activity (immunocentric view. Indeed, tumor-specific immune cells persist post-therapy and can search and destroy any tumor cells that escape the OVs, and thus immune memory may prevent relapse of the disease. Various strategies, which are summarized in this manuscript, have been developed to enhance the efficacy of OV therapy with a focus on its immunotherapeutic aspects. These include genetic engineering and combination with existing cancer treatments. Several are currently being evaluated in human patients and already display promising efficacy.Keywords: oncolytic virus, cancer immunotherapy, tumor antigen, cancer vaccine, combination strategies

  11. Generation and characterization of P gene-deficient rabies virus

    International Nuclear Information System (INIS)

    Shoji, Youko; Inoue, Satoshi; Nakamichi, Kazuo; Kurane, Ichiro; Sakai, Takeo; Morimoto, Kinjiro

    2004-01-01

    Rabies virus (RV) deficient in the P gene was generated by reverse genetics from cDNA of HEP-Flury strain lacking the entire P gene. The defective virus was propagated and amplified by rescue of virus, using a cell line that complemented the functions of the deficient gene. The P gene-deficient (def-P) virus replicated its genome and produced progeny viruses in the cell lines that constitutively expressed the P protein, although it grew at a slightly retarded rate compared to the parental strain. In contrast, no progeny virus was produced in the infected host when the def-P virus-infected cells that did not express the P protein. However, we found that the def-P virus had the ability to perform primary transcription (by the virion-associated polymerase) in the infected host without de novo P protein synthesis. The def-P virus was apathogenic in adult and suckling mice, even when inoculated intracranially. Inoculation of def-P virus in mice induced high levels of virus-neutralizing antibody (VNA) and conferred protective immunity against a lethal rabies infection. These results demonstrate the potential utility of gene-deficient virus as a novel live attenuated rabies vaccine

  12. Indico CONFERENCE: Define the Programme

    CERN Multimedia

    CERN. Geneva; Ferreira, Pedro

    2017-01-01

    In this tutorial you are going to learn how to define the programme of a conference in Indico. The program of your conference is divided in different “tracks”. Tracks represent the subject matter of the conference, such as “Online Computing”, “Offline Computing”, and so on.

  13. Cancer-associated adipocytes promotes breast tumor radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Bochet, Ludivine; Meulle, Aline [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Imbert, Sandrine [CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Salles, Bernard [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Valet, Philippe [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Muller, Catherine, E-mail: muller@ipbs.fr [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France)

    2011-07-22

    Highlights: {yields} Tumor-surrounding adipocytes contribute to breast cancer progression. {yields} Breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance. {yields} Increased in Chk1 phosphorylation is observed in irradiated co-cultivated tumor cells. {yields} IL-6 is over-expressed in tumor cells co-cultivated with adipocytes. {yields} IL-6 exposure confers increased Chk1 phosphorylation and radioresistance in tumor cells. -- Abstract: Mature adipocytes are excellent candidates to influence tumor behavior through heterotypic signaling processes since these cells produce hormones, growth factors, cytokines and other molecules, a heterogeneous group of molecules named adipokines. Using a 2D coculture system, we demonstrate that breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance and an earlier and higher increase in the effector kinase Chk1, a phenotype that was associated with decreased cell death as compared to tumor cells grown alone. Interestingly, the adipocytes-induced tumor changes taking place during the coculture time preceding the exposure to IR were sufficient to confer the radioresistant effect. Notorious among the changes brought by adipocytes was the significant increase of IL-6 expression in tumor cells, whose activity may well account for the observed tumor cell protection from IR toxicity. Indeed, our data confirmed the protective role of this cytokine as tumor cells incubated after irradiation with recombinant IL-6 exhibit an increased in Chk1 phosphorylation and a radioresistant phenotype, thus far recapitulating the effects observed in the presence of adipocytes. Our current study sheds light on a new role of tumor-surrounding adipocytes in fostering a radioresistant phenotype in breast tumors, a finding that might have important clinical implications in obese patients that frequently exhibit aggressive diseases.

  14. Conference summaries. Canadian Nuclear Association 29. annual conference; Canadian Nuclear Society 10. annual conference

    International Nuclear Information System (INIS)

    1989-01-01

    Separate abstracts were prepared for 15 papers from the twenty-ninth Annual Conference of the Canadian Nuclear Association. Abstracts were also prepared for the 102 papers from the tenth Annual Conference of the Canadian Nuclear Society

  15. Conference summaries. Canadian Nuclear Association 29. annual conference; Canadian Nuclear Society 10. annual conference

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1990-12-31

    Separate abstracts were prepared for 15 papers from the twenty-ninth Annual Conference of the Canadian Nuclear Association. Abstracts were also prepared for the 102 papers from the tenth Annual Conference of the Canadian Nuclear Society.

  16. Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge.

    Science.gov (United States)

    Mooney, Alaina J; Gabbard, Jon D; Li, Zhuo; Dlugolenski, Daniel A; Johnson, Scott K; Tripp, Ralph A; He, Biao; Tompkins, S Mark

    2017-12-01

    Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) viruses along with other emerging influenza viruses continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enable the evasion of virus-inhibiting antibody responses, resulting in vaccine failure. The neuraminidase (NA) surface glycoprotein, while diverse, has a conserved enzymatic site and presents an appealing target for priming broadly effective antibody responses. Here we show that vaccination with parainfluenza virus 5 (PIV5), a promising live viral vector expressing NA from avian (H5N1) or pandemic (H1N1) influenza virus, elicited NA-specific antibody and T cell responses, which conferred protection against homologous and heterologous influenza virus challenges. Vaccination with PIV5-N1 NA provided cross-protection against challenge with a heterosubtypic (H3N2) virus. Experiments using antibody transfer indicate that antibodies to NA have an important role in protection. These findings indicate that PIV5 expressing NA may be effective as a broadly protective vaccine against seasonal influenza and emerging pandemic threats. IMPORTANCE Seasonal influenza viruses cause considerable morbidity and mortality annually, while emerging viruses pose potential pandemic threats. Currently licensed influenza virus vaccines rely on the antigenic match of hemagglutinin (HA) for vaccine strain selection, and most vaccines rely on HA inhibition titers to determine efficacy, despite the growing

  17. Oncolytic viruses for cancer therapy II. Cell-internal factors for conditional growth in neoplastic cells.

    Science.gov (United States)

    Campbell, Stephanie A; Gromeier, Matthias

    2005-04-01

    Recent advances in our understanding of virus-host interactions have fueled new studies in the field of oncolytic viruses. The first part of this review explained how cell-external factors, such as cellular receptors, influence tumor tropism and specificity of oncolytic virus candidates. In the second part of this review, we focus on cellinternal factors that mediate tumor-specific virus growth. An oncolytic virus must be able to replicate within cancerous cells and kill them without collateral damage to healthy surrounding cells. This desirable property is inherent to some proposed oncolytic viral agents or has been achieved by genetic manipulation in others.

  18. NIH Consensus Conference. Acupuncture.

    Science.gov (United States)

    1998-11-04

    To provide clinicians, patients, and the general public with a responsible assessment of the use and effectiveness of acupuncture to treat a variety of conditions. A nonfederal, nonadvocate, 12-member panel representing the fields of acupuncture, pain, psychology, psychiatry, physical medicine and rehabilitation, drug abuse, family practice, internal medicine, health policy, epidemiology, statistics, physiology, biophysics, and the representatives of the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 1200. Presentations and discussions were divided into 3 phases over 2 1/2 days: (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that were part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of the third. The conference was organized and supported by the Office of Alternative Medicine and the Office of Medical Applications of Research, National Institutes of Health, Bethesda, Md. The literature, produced from January 1970 to October 1997, was searched through MEDLINE, Allied and Alternative Medicine, EMBASE, and MANTIS, as well as through a hand search of 9 journals that were not indexed by the National Library of Medicine. An extensive bibliography of 2302 references was provided to the panel and the conference audience. Expert speakers prepared abstracts of their own conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in the open forum and scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience

  19. Tumor Macroenvironment and Metabolism

    OpenAIRE

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organ...

  20. Use of hygiene protocols to control the spread of viruses in a hotel.

    Science.gov (United States)

    Sifuentes, Laura Y; Koenig, David W; Phillips, Ronnie L; Reynolds, Kelly A; Gerba, Charles P

    2014-09-01

    The goals of this study were to observe the spread of viruses in a hotel setting and to assess the effectiveness of a hygiene intervention in reducing their spread. Selected fomites in one hotel room were inoculated with bacteriophage ϕx-174, and fomites in a conference center within the same hotel were inoculated using bacteriophage MS2. Cleaning of the contaminated room resulted in the spread of viruses to other rooms by the housekeeping staff. Furthermore, viruses were transferred by hotel guests to the conference center and a communal kitchen area. Additionally, conference attendees transferred viruses from the conference center to their hotel rooms and a communal kitchen area. This study demonstrated how viruses can be spread throughout a hotel setting by both housekeepers and guests. A hygiene intervention, which included providing hand hygiene products and facial tissues to the guests and disinfecting solutions with disposable wipes to the housekeeping staff, was successful in reducing the spread of viruses between the hotel guest rooms and conference center. The hygiene intervention resulted in significantly reduced transfer of the ϕx-174 between the contaminated hotel room and other hotel rooms, communal areas, and the conference center (p = 0.02).

  1. Ganjam virus.

    Science.gov (United States)

    Sudeep, A B; Jadi, R S; Mishra, A C

    2009-11-01

    Ganjam virus (GANV), a member of genus Nairovirus of family Bunyavirdae is of considerable veterinary importance in India. Though, predominantly tick borne, GANV was also isolated from mosquitoes, man and sheep. Neutralizing and complement fixing antibodies to GANV have been detected in animal and human sera collected from different parts of the country. Thirty three strains of GANV have been isolated from India, mainly from Haemaphysalis ticks. The virus replicated in certain vertebrate and mosquito cell lines and found pathogenic to laboratory animals. One natural infection and five laboratory-acquired infections in men were also reported. GANV is antigenically related to Nairobi sheep disease virus (NSDV) of Africa, which is highly pathogenic for sheep and goats causing 70-90 per cent mortality among the susceptible population. Recent molecular studies have demonstrated that GANV is an Asian variant of NSDV and both these viruses are related to the dreaded Crimean Congo haemorrhagic fever (CCHF) group viruses. The versatility of the virus to replicate in different arthropod species, its ability to infect sheep, goat and man makes it an important zoonotic agent.

  2. Wake Conference 2017

    International Nuclear Information System (INIS)

    2017-01-01

    The 52 papers in this volume constitute the proceedings of the 2017 Wake Conference, held in Visby on the island of Gotland, Sweden. The Wake Conference series began in Visby, where it was held in 2009 and 2011. In 2013 the conference took place in Copenhagen where it was combined with the International Conference on Offshore Wind Energy and Ocean Energy. In 2015 it went back to where it started, Visby, and this time it once again takes place at Uppsala University’s Gotland campus, May 30 th - June 1 st . Modern wind turbines are today clustered in large farms with a total production capacity reaching those of a nuclear power plant. When placed in a wind farm, the turbines will be fully or partially influenced by the wake of upstream turbines. This wake interaction results in a decreased power production, caused by the lower kinetic energy in the wind, and an increase in the turbulence intensity. Therefore, understanding the physical nature of vortices and their dynamics in the wake of a turbine is important for the optimal design of wind farms. The increased importance and interest in the field of wake and wind farm aerodynamics can be seen in the increased number of scientific articles on the subject. For example, on the Web of Science citation index, the number citations on the topic ‘wind turbine wakes’ increased from about 50 in 2006 to more than 3800 in 2016. This citation growth essentially shows that the growth in the global production of electrical energy has become a scientific problem to be solved by scientists and engineers. In order to make a substantial impact on one of the most significant challenges of our time, global climate change, the wind industry’s growth must continue. A part of making this growth possible will require research into the physics of wind turbine wakes and wind farms. This conference is aimed at scientists and PhD students working in the field of wake dynamics. The conference covers the following subject areas: Wake and

  3. Computational Intelligence : International Joint Conference

    CERN Document Server

    Rosa, Agostinho; Cadenas, José; Dourado, António; Madani, Kurosh; Filipe, Joaquim

    2016-01-01

    The present book includes a set of selected extended papers from the sixth International Joint Conference on Computational Intelligence (IJCCI 2014), held in Rome, Italy, from 22 to 24 October 2014. The conference was composed by three co-located conferences:  The International Conference on Evolutionary Computation Theory and Applications (ECTA), the International Conference on Fuzzy Computation Theory and Applications (FCTA), and the International Conference on Neural Computation Theory and Applications (NCTA). Recent progresses in scientific developments and applications in these three areas are reported in this book. IJCCI received 210 submissions, from 51 countries, in all continents. After a double blind paper review performed by the Program Committee, 15% were accepted as full papers and thus selected for oral presentation. Additional papers were accepted as short papers and posters. A further selection was made after the Conference, based also on the assessment of presentation quality and audience in...

  4. Powassan (POW) Virus Basics

    Science.gov (United States)

    ... Health Professionals Related Topics For International Travelers Powassan Virus Disease Basics Download this fact sheet formatted for ... Virus Disease Fact Sheet (PDF) What is Powassan virus? Powassan virus is a tickborne flavivirus that is ...

  5. The raccoon polyomavirus genome and tumor antigen transcription are stable and abundant in neuroglial tumors.

    Science.gov (United States)

    Brostoff, Terza; Dela Cruz, Florante N; Church, Molly E; Woolard, Kevin D; Pesavento, Patricia A

    2014-11-01

    Raccoon polyomavirus (RacPyV) is associated with 100% of neuroglial tumors in free-ranging raccoons. Other tumor-associated polyomaviruses (PyVs), including simian virus 40 (SV40), murine PyV, and Merkel cell PyV, are found integrated in the host genome in neoplastic cells, where they constitutively express splice variants of the tumor antigen (TAg) gene. We have previously reported that RacPyV exists only as an episome (nonintegrated) in neuroglial tumors. Here, we have investigated TAg transcription in primary tumor tissue by transcriptome analysis, and we identified the alternatively spliced TAg transcripts for RacPyV. We also determined that TAg was highly transcribed relative to host cellular genes. We further colocalized TAg DNA and mRNA by in situ hybridization and found that the majority of tumor cells showed positive staining. Lastly, we examined the stability of the viral genome and TAg transcription by quantitative reverse transcriptase PCR in cultured tumor cells in vitro and in a mouse xenograft model. When tumor cells were cultured in vitro, TAg transcription increased nearly 2 log-fold over that of parental tumor tissue by passage 17. Both episomal viral genome and TAg transcription were faithfully maintained in culture and in tumors arising from xenotransplantation of cultured cells in mice. This study represents a minimal criterion for RacPyV's association with neuroglial tumors and a novel mechanism of stability for a polyomavirus in cancer. The natural cycle of polyomaviruses in mammals is to persist in the host without causing disease, but they can cause cancer in humans or in other animals. Because this is an unpredictable and rare event, the oncogenic potential of polyomavirus is primarily evaluated in laboratory animal models. Recently, raccoon polyomavirus (RacPyV) was identified in neuroglial tumors of free-ranging raccoons. Viral copy number was consistently high in these tumors but was low or undetectable in nontumor tissue or in

  6. Indico CONFERENCE tutorial

    CERN Multimedia

    CERN. Geneva; Manzoni, Alex Marc

    2017-01-01

    This short tutorial explains how to create a CONFERENCE in indico and how to handle abstracts and registration forms, in detail: Timestamps: 1:01 - Programme  2:28 - Call for abstracts  11:50 - Abstract submission  13:41 - Abstract Review 15:41 - The Judge's Role 17:23 - Registration forms' creation 23:34 - Candidate participant's registration/application 25:54 - Customisation of Indico pages - Layout 28:08 - Customisation of Indico pages - Menus 29:47 - Configuring Event reminders and import into calendaring tools   See HERE a recent presentation by Pedro about the above steps in the life of an indico CONFERENCE event.

  7. 7th IAASS Conference

    CERN Document Server

    Rongier, Isabelle

    2015-01-01

    The 7th IAASS Conference, “Space Safety is No Accident” is an invitation to reflect and exchange information on a number of topics in space safety and sustainability of national and international interest. The conference is also a forum to promote mutual understanding, trust and the widest possible international cooperation in such matters. The once exclusive “club” of nations with autonomous sub-orbital and orbital space access capabilities is becoming crowded with fresh and ambitious new entrants. New commercial spaceports are starting operations and others are being built. In the manned spaceflight arena a commercial market is becoming a tangible reality with suborbital spaceflights and government use of commercial services for cargo and crew transportation to orbit. Besides the national ambitions in space, the international cooperation both civil and commercial is also gaining momentum. In the meantime robotic space exploration will accelerate and with it the need to internationally better regulat...

  8. Annual conference SAEE 2009

    International Nuclear Information System (INIS)

    2009-01-01

    The role of economical support instruments in the successful and efficient propagation of renewable forms of energy was the issue addressed by the 2009 conference of the Swiss Association for Energy Economics. Topics covered include production conditions, resource annuities and remuneration for the feeding-in of power generated from renewable forms of energy, a review of instruments for the encouragement of the use of renewable forms of energy from the economics point of view and the appraisal of support instruments from the economic policy point of view. Contributions presented in the second session include a review of global and national potentials for the use of renewable forms of energy, a review of instruments and their effect on the market from the point of view of an energy utility active at national and European levels, and, finally, the question if economic instruments are needed to support investments in renewable forms of energy is posed. A podium session concluded the conference

  9. UKSG Annual Conference 2012

    Directory of Open Access Journals (Sweden)

    Gopal Dutta

    2012-07-01

    Full Text Available UKSG offered four free places for students to attend the 2012 Conference, made possible with generous support from Elsevier, whose contribution is very much appreciated. Those eligible to apply were students enrolled on Library & Information and Publishing degree courses, and the successful applicants were (Ieft to right as photographed against the River Clyde: Stuart Lawson (University of Brighton, Jennifer Lovatt (Oxford Brookes University, Gopal Dutta (University of Sheffield and Lydia Lantzsch (Oxford Brookes University. The four have allowed us to take a peek at the diaries they kept during the conference. The extracts below give us a flavour of the event including the plenary and breakout sessions, the debates and the stamina of those who kept the dancing going!

  10. Mississippi Climate & Hydrology Conference

    Energy Technology Data Exchange (ETDEWEB)

    Lawford, R.; Huang, J.

    2002-05-01

    The GEWEX Continental International Project (GCIP), which started in 1995 and completed in 2001, held its grand finale conference in New Orleans, LA in May 2002. Participants at this conference along with the scientists funded through the GCIP program are invited to contribute a paper to a special issue of Journal of Geophysical Research (JGR). This special JGR issue (called GCIP3) will serve as the final report on scientific research conducted by GCIP investigators. Papers are solicited on the following topical areas, but are not limited to, (1) water energy budget studies; (2) warm season precipitation; (3) predictability and prediction system; (4) coupled land-atmosphere models; (5) climate and water resources applications. The research areas cover observations, modeling, process studies and water resources applications.

  11. 2013 APPLEPIES Conference

    CERN Document Server

    2014-01-01

    This book provides a thorough overview of cutting-edge research on electronics applications relevant to industry, the environment, and society at large. A wide spectrum of application domains are covered, from automotive to space and from health to security, and special attention is devoted to the use of embedded devices and sensors for imaging, communication, and control. The book is based on the 2013 APPLEPIES Conference, held in Rome, which brought together researchers and stakeholders to consider the most significant current trends in the field of applied electronics and to debate visions for the future. Areas covered by the conference included information communication technology; biotechnology and biomedical imaging; space; secure, clean, and efficient energy; the environment; and smart, green, and integrated transport. As electronics technology continues to develop apace, constantly meeting previously unthinkable targets, further attention needs to be directed toward the electronics applications and th...

  12. The third Geneva Conference

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1964-12-15

    Full text: On 31 August 1964, the Third United Nations International Conference on the Peaceful Uses of Atomic Energy (more familiarly known as the 'Third Geneva') was opened at the Palais des Nations in Geneva by the Secretary-General of the United Nations, U Thant. It was somewhat narrower in scope than the previous conferences held in 1935 and 1958, the emphasis being on nuclear power and closely related topics; the conference showed that recent progress in this field had provided more than ample material for a major international gathering. All three conferences have been organized by the United Nations, but on this occasion responsibility for the scientific aspects was delegated to IAEA. The UN Scientific Advisory Committee provided advice and guidance on the scientific side. Under the presidency of Professor V. S. Emelyanov (USSR) the conference sat from 31 August to 9 September, to deal with a programme divided into eight general sessions and 36 technical sessions, for which a total of nearly 750 papers were presented. About 1800 delegates and advisers, representing 75 countries as well as UN agencies, attended; in addition there were some 2000 observers. The central theme of the conference was experience in the construction and operation of power reactors and recent advances in power technology, together with forecasts of future developments. Nuclear fuels and reactor materials, health and safety, waste disposal, and economics of nuclear power figured largely. Technical sessions were devoted to such subjects as the technical and economic aspects of the power reactor systems currently in operation or being built, and the main lines of development towards more advanced systems and development of the fast breeder. Parallel lines of development of alternative systems were also considered - some, such as organic reactors, having already been the subject of extensive trials, while others are in the conceptual stage. 'Package' power plants designed for easy

  13. IEEE conference record -- Abstracts

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    This conference covers the following areas: computational plasma physics; vacuum electronic; basic phenomena in fully ionized plasmas; plasma, electron, and ion sources; environmental/energy issues in plasma science; space plasmas; plasma processing; ball lightning/spherical plasma configurations; plasma processing; fast wave devices; magnetic fusion; basic phenomena in partially ionized plasma; dense plasma focus; plasma diagnostics; basic phenomena in weakly ionized gases; fast opening switches; MHD; fast z-pinches and x-ray lasers; intense ion and electron beams; laser-produced plasmas; microwave plasma interactions; EM and ETH launchers; solid state plasmas and switches; intense beam microwaves; and plasmas for lighting. Separate abstracts were prepared for 416 papers in this conference

  14. Metabolic Engineering VII Conference

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  15. The third Geneva Conference

    International Nuclear Information System (INIS)

    1964-01-01

    Full text: On 31 August 1964, the Third United Nations International Conference on the Peaceful Uses of Atomic Energy (more familiarly known as the 'Third Geneva') was opened at the Palais des Nations in Geneva by the Secretary-General of the United Nations, U Thant. It was somewhat narrower in scope than the previous conferences held in 1935 and 1958, the emphasis being on nuclear power and closely related topics; the conference showed that recent progress in this field had provided more than ample material for a major international gathering. All three conferences have been organized by the United Nations, but on this occasion responsibility for the scientific aspects was delegated to IAEA. The UN Scientific Advisory Committee provided advice and guidance on the scientific side. Under the presidency of Professor V. S. Emelyanov (USSR) the conference sat from 31 August to 9 September, to deal with a programme divided into eight general sessions and 36 technical sessions, for which a total of nearly 750 papers were presented. About 1800 delegates and advisers, representing 75 countries as well as UN agencies, attended; in addition there were some 2000 observers. The central theme of the conference was experience in the construction and operation of power reactors and recent advances in power technology, together with forecasts of future developments. Nuclear fuels and reactor materials, health and safety, waste disposal, and economics of nuclear power figured largely. Technical sessions were devoted to such subjects as the technical and economic aspects of the power reactor systems currently in operation or being built, and the main lines of development towards more advanced systems and development of the fast breeder. Parallel lines of development of alternative systems were also considered - some, such as organic reactors, having already been the subject of extensive trials, while others are in the conceptual stage. 'Package' power plants designed for easy

  16. XIX Edoardo Amaldi Conference

    CERN Document Server

    Abousahl, Said; Plastino, Wolfango

    2016-01-01

    This book, comprising contributions presented at the XIX Edoardo Amaldi Conference, examines important aspects of international cooperation aimed at enhancing nuclear safety, security, safeguards (the “3S”), and non-proliferation, thereby assisting in the development and maintenance of the verification regime and progress toward a nuclear weapon-free world. The Conference served as a forum where eminent scientists, diplomats, and policymakers could compare national perspectives and update international collaborations. The book opens by addressing the political, institutional, and legal dimensions of the 3S and non-proliferation; current challenges are discussed and attempts made to identify possible solutions and future improvements. Subsequent sections consider scientific developments that can contribute to increased effectiveness in the implementation of international regimes, particularly in critical areas, technology foresight, and the ongoing evaluation of current capabilities. The closing sections d...

  17. Vienna Wire Chamber Conference

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    After those of 1978 and 1980, a third Wire Chamber Conference was held from 15-18 February in the Technical University of Vienna. Eight invited speakers covered the field from sophisticated applications in biology and medicine, via software, to the state of the art of gaseous detectors. In some forty other talks the speakers tackled in more detail the topics of gaseous detectors, calorimetry and associated electronics and software

  18. Vancouver Accelerator Conference

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1985-06-15

    Anyone who contends that particle physics is conducted in an ivory tower, not contributing to other fields of science or to humanity at large, should have attended the 1985 Particle Accelerator Conference in Vancouver. Over a thousand participants contributed 781 papers and only a fraction were actually related to accelerators for high energy physics. The majority of present developments are in the service of other fields of science, for alternative power sources, for medicine, for industrial applications, etc.

  19. Computing Conference at Bologna

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    From 9-12 September a Europhysics Conference on Computing in High Energy and Nuclear Physics, organized by the Computational Physics Group of the European Physical Society, was held in Bologna, attracting some 150 participants. Its purpose was contact and exchange of information between experimental physicists (from both fields of research) and computer experts (on whom the successful outcome of the research has become increasingly dependent)

  20. CONFERENCE: Nordic physics

    International Nuclear Information System (INIS)

    Anon.

    1984-01-01

    Around 80 physicists from eleven countries fought heavy snowstorms and 20-below temperatures at the winter resort of Spåtind, Norway, for the 8th Nordic Meeting on Elementary Particle Physics in January. This biennial conference is a traditional meeting place for Nordic particle physicists, and especially for the young research students, but also draws participants from other countries. This year's meeting was organized by the Division of Particle Physics of the Swedish Physical Society

  1. Incineration conference 1990

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    This book contains the proceedings of the 1990 incineration conference. The proceedings are organized under the following headings: Regulations- international comparison, Current trends in facility design, Oxygen enhancement, Metals, Off-gas treatment, Operating experience: transportable, Materials, Operating experience: R/A and mixed, Incineration of specific wastes, Medical waste management, Ash qualification, Ash solidification/ immobilization, Innovative technologies, Operating experience : medical waste, Instrumentation and monitoring, process control and modeling, Risk assessment/management, Operating considerations

  2. Vancouver Accelerator Conference

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    Anyone who contends that particle physics is conducted in an ivory tower, not contributing to other fields of science or to humanity at large, should have attended the 1985 Particle Accelerator Conference in Vancouver. Over a thousand participants contributed 781 papers and only a fraction were actually related to accelerators for high energy physics. The majority of present developments are in the service of other fields of science, for alternative power sources, for medicine, for industrial applications, etc

  3. Interan '82 conference

    International Nuclear Information System (INIS)

    Obrusnik, I.

    1982-01-01

    The conference was held on September 20 to 23, 1982, in Karlovy Vary and was devoted to analytical problems related to the determination of water and air pollution. Some of the papers presented in session ''Water'' dealt with the analysis of water contaminated by nuclear power plants, and the use of tracer techniques. The session devoted to the atmosphere heard several papers devoted to the use of neutron activation analysis for analyzing air pollution. (Ha)

  4. Chicago particle accelerator conference

    International Nuclear Information System (INIS)

    Southworth, Brian

    1989-01-01

    Naturally, emphasis at the Particle Accelerator Conference in Chicago in March was on work in the US, just as the newly instituted European Particle Accelerator Conference places emphasis on work in the 'old continent'. All will come together at the international conference in Japan in August. The proposed US Superconducting Supercollider (SSC) was highlighted in the opening talk at Chicago. Progress on this inchoate project to explore the TeV (1000 GeV) energy region by colliding 20 TeV proton beams was reported by the recently-appointed Director of the SSC Laboratory, Roy Schwitters. He reviewed the physics challenges and described progress and plans towards full authorization of construction.This year, the SSC conceptual design will be transformed into a 'site specific' report, now that the location at Waxahachie in Ellis County, Texas, has been selected. The Central Design Group, based in Berkeley for the past few years, will soon move to the Waxahachie region. The top management structure is taking shape and an International Advisory Committee is being formed

  5. International Conference Medical Radiations

    International Nuclear Information System (INIS)

    2010-01-01

    Full text : The second edition of the international conference Medical radiation : research and applications which took place in Marrakech (Morocco) from 7 to 9 April 2010, was designed to bring together researchers and physicians from different countries who dedicated their talents and time to this endeavour. The conference's program defined goals were is to identify the most reliable techniques among the several tested so far and to establish the most practical standardized methodologies, taking into account such recent technological development in radiation medical research. The scientific objectives of this conference are as follows : present the state of the art of the various topics of the congress, give a progress report on the impact of the interaction of the various scientific and technical disciplinary fields (Medicine, Biology, Mathematics, Physics,..) on the applications of radiations in medicine, promote the interdisciplinary efforts of research among researchers, present new technologies and research and development tasks prepared in the field of medical radiations, contribute to the emergence of new ideas of research and development of new collaborations [fr

  6. Conference on Logical Methods

    CERN Document Server

    Remmel, Jeffrey; Shore, Richard; Sweedler, Moss; Progress in Computer Science and Applied Logic

    1993-01-01

    The twenty-six papers in this volume reflect the wide and still expanding range of Anil Nerode's work. A conference on Logical Methods was held in honor of Nerode's sixtieth birthday (4 June 1992) at the Mathematical Sciences Institute, Cornell University, 1-3 June 1992. Some of the conference papers are here, but others are from students, co-workers and other colleagues. The intention of the conference was to look forward, and to see the directions currently being pursued, in the development of work by, or with, Nerode. Here is a brief summary of the contents of this book. We give a retrospective view of Nerode's work. A number of specific areas are readily discerned: recursive equivalence types, recursive algebra and model theory, the theory of Turing degrees and r.e. sets, polynomial-time computability and computer science. Nerode began with automata theory and has also taken a keen interest in the history of mathematics. All these areas are represented. The one area missing is Nerode's applied mathematica...

  7. Chicago particle accelerator conference

    Energy Technology Data Exchange (ETDEWEB)

    Southworth, Brian

    1989-06-15

    Naturally, emphasis at the Particle Accelerator Conference in Chicago in March was on work in the US, just as the newly instituted European Particle Accelerator Conference places emphasis on work in the 'old continent'. All will come together at the international conference in Japan in August. The proposed US Superconducting Supercollider (SSC) was highlighted in the opening talk at Chicago. Progress on this inchoate project to explore the TeV (1000 GeV) energy region by colliding 20 TeV proton beams was reported by the recently-appointed Director of the SSC Laboratory, Roy Schwitters. He reviewed the physics challenges and described progress and plans towards full authorization of construction.This year, the SSC conceptual design will be transformed into a 'site specific' report, now that the location at Waxahachie in Ellis County, Texas, has been selected. The Central Design Group, based in Berkeley for the past few years, will soon move to the Waxahachie region. The top management structure is taking shape and an International Advisory Committee is being formed.

  8. 2004 Mutagenesis Gordon Conference

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Sue Jinks-Robertson

    2005-09-16

    Mutations are genetic alterations that drive biological evolution and cause many, if not all, human diseases. Mutation originates via two distinct mechanisms: ''vertical'' variation is de novo change of one or few bases, whereas ''horizontal'' variation occurs by genetic recombination, which creates new mosaics of pre-existing sequences. The Mutagenesis Conference has traditionally focused on the generation of mutagenic intermediates during normal DNA synthesis or in response to environmental insults, as well as the diverse repair mechanisms that prevent the fixation of such intermediates as permanent mutations. While the 2004 Conference will continue to focus on the molecular mechanisms of mutagenesis, there will be increased emphasis on the biological consequences of mutations, both in terms of evolutionary processes and in terms of human disease. The meeting will open with two historical accounts of mutation research that recapitulate the intellectual framework of this field and thereby place the current research paradigms into perspective. The two introductory keynote lectures will be followed by sessions on: (1) mutagenic systems, (2) hypermutable sequences, (3) mechanisms of mutation, (4) mutation avoidance systems, (5) mutation in human hereditary and infectious diseases, (6) mutation rates in evolution and genotype-phenotype relationships, (7) ecology, mutagenesis and the modeling of evolution and (8) genetic diversity of the human population and models for human mutagenesis. The Conference will end with a synthesis of the meeting as the keynote closing lecture.

  9. The value of oncolysis virus in treating liver cancer

    International Nuclear Information System (INIS)

    Xiong Zhuang; Wang Jianhua

    2007-01-01

    The effect of traditional therapy is limited for liver cancer, gene therapy gets more and more recognition in recent years. Oncolysis virus is a kind of conditionally replicating virus, with special reproductivity in cancer cells, and then kills them. Gene agents are usually introduced into tumor tissue by intra-tumor and intra-arterial injection, and the technique of interventional therapy is able to satisfy the demand excellently. So, some breakthrough is expected in treating liver cancer by skillfully combining oncolysis virus and interventional technique. (authors)

  10. PREFACE: Wake Conference 2015

    Science.gov (United States)

    Barney, Andrew; Nørkær Sørensen, Jens; Ivanell, Stefan

    2015-06-01

    The 44 papers in this volume constitute the proceedings of the 2015 Wake Conference, held in Visby on the island of Gotland in Sweden. It is the fourth time this conference has been held. The Wake Conference series started in Visby, where it was held in 2009 and 2011. In 2013 it took place in Copenhagen where it was combined with the International Conference on Offshore Wind Energy and Ocean Energy. In 2015 it is back where it started in Visby, where it takes place at Uppsala University Campus Gotland, June 9th-11th. The global yearly production of electrical energy by wind turbines has grown tremendously in the past decade and it now comprises more than 3% of the global electrical power consumption. Today the wind power industry has a global annual turnover of more than 50 billion USD and an annual average growth rate of more than 20%. State-of-the-art wind turbines have rotor diameters of up to 150 m and 8 MW installed capacity. These turbines are often placed in large wind farms that have a total production capacity corresponding to that of a nuclear power plant. In order to make a substantial impact on one of the most significant challenges of our time, global warming, the industry's growth has to continue for a decade or two yet. This in turn requires research into the physics of wind turbine wakes and wind farms. Modern wind turbines are today clustered in wind farms in which the turbines are fully or partially influenced by the wake of upstream turbines. As a consequence, the wake behind the wind turbines has a lower mean wind speed and an increased turbulence level, as compared to the undisturbed flow outside the farm. Hence, wake interaction results in decreased total production of power, caused by lower kinetic energy in the wind, and an increase in the turbulence intensity. Therefore, understanding the physical nature of the vortices and their dynamics in the wake of a turbine is important for the optimal design of a wind farm. This conference is aimed

  11. Biopsy techniques for intraocular tumors

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2016-01-01

    Full Text Available Biopsy involves the surgical removal of a tissue specimen for histopathologic evaluation. Most intraocular tumors are reliably diagnosed based on the clinical evaluation or with noninvasive diagnostic techniques. However, accurately diagnosing a small percentage of tumors can be challenging. A tissue biopsy is thus needed to establish a definitive diagnosis and plan the requisite treatment. From fine-needle aspiration biopsy (FNAB to surgical excision, all tissue collection techniques have been studied in the literature. Each technique has its indications and limitations. FNAB has been reported to provide for 88-95% reliable and safe ophthalmic tumor diagnosis and has gained popularity for prognostic purposes and providing eye conserving treatment surgeries. The technique and instrumentation for biopsy vary depending upon the tissue involved (retina, choroid, subretinal space, vitreous, and aqueous, suspected diagnosis, size, location, associated retinal detachment, and clarity of the media. The cytopathologist confers a very important role in diagnosis and their assistance plays a key role in managing and planning the treatment for malignancies.

  12. First survey on blueberry viruses and phytoplasma in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Špak, Josef; Kubelková, Darina; Přibylová, Jaroslava; Špaková, Vlastimila; Petrzik, Karel

    2009-01-01

    Roč. 148, July (2009), s. 48-49 ISSN 1866-590X. [International Conference on Virus and other Graft Transmissible Diseases of Fruit Crops /21./. 05.07.2009-10.07.2009, Neustadt] R&D Projects: GA MŠk OC09022 Institutional research plan: CEZ:AV0Z50510513 Keywords : Vaccinium * viruses * phytoplasma Subject RIV: EE - Microbiology, Virology

  13. Architecture of conference control functions

    Science.gov (United States)

    Kausar, Nadia; Crowcroft, Jon

    1999-11-01

    Conference control is an integral part in many-to-many communications that is used to manage and co-ordinate multiple users in conferences. There are different types of conferences which require different types of control. Some of the features of conference control may be user invoked while others are for internal management of a conference. In recent years, ITU (International Telecommunication Union) and IETF (Internet Engineering Task Force) have standardized two main models of conferencing, each system providing a set of conference control functionalities that are not easily provided in the other one. This paper analyzes the main activities appropriate for different types of conferences and presents an architecture for conference control called GCCP (Generic Conference Control Protocol). GCCP interworks different types of conferencing and provides a set of conference control functions that can be invoked by users directly. As an example of interworking, interoperation of IETF's SIP and ITU's H.323 call control functions have been examined here. This paper shows that a careful analysis of a conferencing architecture can provide a set of control functions essential for any group communication model that can be extensible if needed.

  14. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  15. Brain Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Brain Tumors KidsHealth / For Parents / Brain Tumors What's in ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  16. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  17. Malignant bone tumors

    International Nuclear Information System (INIS)

    Zedgenidze, G.A.; Kishkovskij, A.N.; Elashov, Yu.G.

    1984-01-01

    Clinicoroentgenologic semiotics of malignant bone tumors as well as metastatic bone tumors are presented. Diagnosis of malignant and metastatic bone tumors should be always complex, representing a result of cooperation of a physician, roentgenologist, pathoanatomist

  18. Tumors and Pregnancy

    Science.gov (United States)

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  19. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 01/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  20. Conference Report: The First ATLAS.ti User Conference

    Directory of Open Access Journals (Sweden)

    Jeanine C. Evers

    2014-01-01

    Full Text Available This report on the First ATLAS.ti User Conference shares our impressions and experiences as longstanding ATLAS.ti users and trainers about the First ATLAS.ti User Conference in Berlin 2013. The origins, conceptual principles and development of the program are outlined, the conference themes discussed and experiences shared. Finally, the future of the program is discussed. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1401197

  1. Ebola Virus

    Directory of Open Access Journals (Sweden)

    Anusha Rangare Lakshman

    2015-09-01

    Full Text Available The disease Ebola takes its name from the Ebola River situated near a village in the Democratic Republic of Congo, where the disease first appeared in 1976. It is caused by a virus from the Filoviridae family (filovirus. The present outbreak of Ebola Virus Disease (EVD concerns four countries in West Africa, namely Guinea, Liberia, Sierra Leone and Nigeria till date. Further to widespread transmission of the disease, it has been declared as a Public Health Emergency of International Concern by the World Health Organisation on 8 August 2014. As of 4 August 2014, countries have reported 1,711 cases (1,070 confirmed, 436 probable, 205 suspect, including 932 deaths. This review paper enlightens about the awareness of Ebola virus and its preventive measures. [Archives Medical Review Journal 2015; 24(3.000: 296-305

  2. [Meeting Report: 20 years after the First International Symposium on hepatitis C virus and related viruses].

    Science.gov (United States)

    Carnero, Elena; Díez, Juana; Fortes, Purificación; Gastaminza, Pablo; Majano, Pedro; Martínez, Miguel Angel; Pérez-del-Pulgar, Sofía; Quer, Josep; López-Labrador, F Xavier

    2013-12-01

    The hepatitis C virus (HCV) was discovered by the team of Michael Houghton at Chiron Corporation in 1989 and the first symposium on HCV and related viruses was held in Venice, Italy, shortly after, in 1992. This conference was organized to advance knowledge on what then was a mysterious virus responsible for most cases of «non-A, non-B» hepatitis. During the 20 years since the first conference, the scientific quality of presentations has steadily increased, together with the tremendous advances in basic and clinical research and epidemiology. What started as a small conference on a new virus, about which there were very few data, has today become a first-in-class congress: a meeting place for basic researchers, clinicians, epidemiologists, public health experts, and industry members to present the most important advances and their application to HCV treatment and control. The nineteenth HCV symposium was held in September 2012, once again in Venice. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  3. Migratory birds and West Nile virus

    Czech Academy of Sciences Publication Activity Database

    Rappole, J. H.; Hubálek, Zdeněk

    2003-01-01

    Roč. 94, s1 (2003), s. 47-58 ISSN 1364-5072. [Conference of Society for Applied Microbiology (U.K.) "Pathogens in the Environment and Changing Ecosystems". Nottingham, 08.07.2002-11.07.2002] Institutional research plan: CEZ:AV0Z6093917 Keywords : West Nile virus * bird migration Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 1.743, year: 2003

  4. Peripheral epithelial odontogenic tumor

    International Nuclear Information System (INIS)

    Carzoglio, J.; Tancredi, N.; Capurro, S.; Ravecca, T.; Scarrone, P.

    2006-01-01

    A new case of peripheral epithelial odontogenic tumor (Pindborg tumor) is reported. It is localized in the superior right gingival region, a less frequent site, and has the histopathological features previously reported. Immunochemical studies were performed, revealing a differential positive stain to cytokeratins in tumor cells deeply seated in the tumor mass, probably related to tumoral cell heterogeneity.Interestingly, in this particular case S-100 protein positive reactivity was also detected in arborescent cells intermingled with tumoral cells, resembling Langerhans cells. Even though referred in the literature in central Pindborg tumors, no references were found about their presence in peripheral tumors, like the one that is presented here

  5. Computational Intelligence : International Joint Conference

    CERN Document Server

    Dourado, António; Rosa, Agostinho; Filipe, Joaquim; Kacprzyk, Janusz

    2016-01-01

    The present book includes a set of selected extended papers from the fifth International Joint Conference on Computational Intelligence (IJCCI 2013), held in Vilamoura, Algarve, Portugal, from 20 to 22 September 2013. The conference was composed by three co-located conferences:  The International Conference on Evolutionary Computation Theory and Applications (ECTA), the International Conference on Fuzzy Computation Theory and Applications (FCTA), and the International Conference on Neural Computation Theory and Applications (NCTA). Recent progresses in scientific developments and applications in these three areas are reported in this book. IJCCI received 111 submissions, from 30 countries, in all continents. After a double blind paper review performed by the Program Committee, only 24 submissions were accepted as full papers and thus selected for oral presentation, leading to a full paper acceptance ratio of 22%. Additional papers were accepted as short papers and posters. A further selection was made after ...

  6. Joint US/German Conference

    CERN Document Server

    Gulledge, Thomas; Jones, Albert

    1993-01-01

    This proceedings volume contains selected and refereed contributions that were presented at the conference on "Recent Developments and New Perspectives of Operations Research in the Area of Production Planning and Control" in Hagen/Germany, 25. - 26. June 1992. This conference was organized with the cooperation of the FernuniversiHit Hagen and was jointly hosted by the "Deutsche Gesellschaft fur Operations Research (DGOR)" and the "Manufacturing Special Interest Group of the Operations Research Society of America (ORSA-SIGMA)". For the organization of the conference we received generous financial support from the sponsors listed at the end of this volume. We wish to express our appreciation to all supporters for their contributions. This conference was the successor of the JOInt ORSA/DGOR-conference in Gaithersburg/Maryland, USA, on the 30. and 31. July 1991. Both OR-societies committed themselves in 1989 to host joint conferences on special topics of interest from the field of operations research. This goal ...

  7. The Impact of Human Papilloma Viruses, Matrix Metallo-Proteinases and HIV Protease Inhibitors on the Onset and Progression of Uterine Cervix Epithelial Tumors: A Review of Preclinical and Clinical Studies

    Directory of Open Access Journals (Sweden)

    Giovanni Barillari

    2018-05-01

    Full Text Available Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN. CIN lesions may regress, persist or progress to invasive cervical carcinoma (CC, a leading cause of death worldwide. CIN is particularly frequent and aggressive in women infected by both HPV and the Human Immunodeficiency Virus (HIV, as compared to the general female population. In these individuals, however, therapeutic regimens employing HIV protease inhibitors (HIV-PI have reduced CIN incidence and/or clinical progression, shedding light on the mechanism(s of its development. This article reviews published work concerning: (i the role of HPV proteins (including HPV-E5, E6 and E7 and of matrix-metalloproteinases (MMPs in CIN evolution into invasive CC; and (ii the effect of HIV-PI on events leading to CIN progression such as basement membrane and extracellular matrix invasion by HPV-positive CIN cells and the formation of new blood vessels. Results from the reviewed literature indicate that CIN clinical progression can be monitored by evaluating the expression of MMPs and HPV proteins and they suggest the use of HIV-PI or their derivatives for the block of CIN evolution into CC in both HIV-infected and uninfected women.

  8. Vancouver Cyclotron Conference

    International Nuclear Information System (INIS)

    Clark, David J.

    1993-01-01

    Although no longer on the high energy frontier, the cyclotron field is still a major scientific growth area. Its progress is highlighted at the international conference on cyclotron design, development and utilization held at intervals of about three years, under the auspices of the International Union of Pure and Applied Physics (IUPAP). Vancouver, surrounded by mountains, water and some cyclotrons, provided a pleasant setting for the 13th Conference, held last summer. With over 200 cyclotrons in operation around the world, the attendance, 241 delegates and 26 industrial exhibitors, was a near record, reflecting the flourishing state of the field. The early sessions covered the initial operation of new or upgraded cyclotron facilities. Major facilities completed since the previous Conference in Berlin in May 1989 included the 400 MeV ring cyclotron at Osaka, the U400M cyclotron at Dubna which will be coupled to the U400 to give 20 MeV nucléon uranium beams, the 130 MeV cyclotron at Jyvaskyla (in Finland, the furthest north!), the 110 MeV JAERI machine in Japan, and the 65 MeV proton therapy cyclotron in Nice. Among the facility upgrades were the KFA cyclotron at Julich which will inject the 2.5 GeV storage ring COSY, and the addition of an FM mode to the K=200 CW mode at Uppsala to give protons up to 180 MeV. The impressive current of 1.5 mA at 72 MeV obtained from the PSI Injector II will soon be injected into the 590 MeV ring

  9. 15th International Cryocooler Conference

    CERN Document Server

    Ross, Ronald G

    2009-01-01

    This is the 15th volume in the conference series. Over the years the International Cryocooler Conference has become the preeminent worldwide conference for the presentation of the latest developments and test experiences with cryocoolers. The typical applications of this technology include cooling space and terrestrial infrared focal plane arrays, space x-ray detectors, medical applications, and a growing number of high-temperature superconductor applications.

  10. 14th International Cryocooler Conference

    CERN Document Server

    Ross, Ronald G

    2007-01-01

    This is the 14th volume in the conference series. Over the years the International Cryocoolers Conference has become the preeminent worldwide conference for the presentation of the latest developments and test experiences with cryocoolers. The typical applications of this technology include cooling space and terrestrial infrared focal plane arrays, space x-ray detectors, medical applications, and a growing number of high-temperature superconductor applications.

  11. International conference on string theory

    CERN Document Server

    2017-01-01

    The Strings 2017 conference is part of the "Strings" series of annual conferences, that bring the entire string theory community together. It will include reviews of major developments in the field, and specialized talks on specific topics. There will also be several public lectures given by conference participants, a pre-Strings school at the Technion, and a post-Strings workshop at the Weizmann Institute.

  12. Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors

    Directory of Open Access Journals (Sweden)

    Shanawaz Mohammed Ghouse

    2018-01-01

    Full Text Available Summary: High numbers of mast cells populate the stroma of many types of neoplasms, including human papilloma virus-induced benign and malignant tumors in man and mouse. Equipped with numerous pattern recognition receptors and capable of executing important pro-inflammatory responses, mast cells are considered innate sentinels that significantly impact tumor biology. Mast cells were reported to promote human papilloma virus (HPV-induced epithelial hyperproliferation and neo-angiogenesis in an HPV-driven mouse model of skin cancer. We analyzed HPV-induced epithelial hyperplasia and squamous cell carcinoma formation, as well as growth of tumors inoculated into the dermis, in mice lacking skin mast cells. Unexpectedly, the absence of mast cells had no effect on HPV-induced epithelial growth or angiogenesis, on growth kinetics of inoculated tumors, or on the immunological tumor micro-milieu. Thus, the conspicuous recruitment of mast cells into tumor tissues cannot necessarily be equated with important mast cell functions in tumor growth. : Mast cells accumulate in high numbers in many human tumors, and they are widely viewed as important promoters of tumor growth. Ghouse et al. show that growth, angiogenesis, and the immunological micro-milieu of tumors growing in mice genetically deficient for mast cells are unchanged compared to control tumors. Keywords: mast cells, HPV-induced skin cancer, tumor angiogenesis, tumor micro-milieu

  13. National Physics Conference

    International Nuclear Information System (INIS)

    Oancea, Margareta; Sandu, Doina; Calboreanu, Rodica

    2000-01-01

    The National Physics Conference organized annually by the Romanian Physical Society has been held in Constanta, Romania on September 21-23, 2000. It covered the following 12 sections: - 1. Astrophysics and High Energy (9 reports); - 2. Atomic and Molecular Physics (20 reports); - 3. Nuclear Physics (18 reports); - 4. Technical and Engineering Physics (34 reports); - 5. Condensed Matter Physics (67 reports); - 6. Optics and Quantum Electronics (12 reports); - 7. Plasma Physics (27 reports); - 8. Biophysics (30 reports); - 9. Physics for Energy (17 reports); - 10. Mathematical and Computational Physics (20 reports); -11. Physics and Education (8 reports); - 12. Earth and Environmental Physics (16 reports). The proceedings contains mainly short communications

  14. Proceedings: pellet fuels conference

    Energy Technology Data Exchange (ETDEWEB)

    1995-12-31

    The conference brought together professionals from the process- engineered-fuels (PEF), utility, paper, plastics, and boiler industries. Although the last two decades have produced technical breakthroughs, efforts to advance PEF must now focus on increasing commercial breakthroughs. Successful commercialization will depend on increasing supplier, consumer, and regulator confidence and support by demonstrating the performance and value of PEF products. Speakers provided updates on how PEF technology is evolving with respect to technical, economic, and regulatory challenges. Actions critical toward full commercialization of PEF were then considered. Discussion groups addressed materials sourcing, fuel processing and transportation, combustion, and ash handling.

  15. 2nd UNet conference

    CERN Document Server

    Menasche, Daniel; Sabir, Essaïd; Pellegrini, Francesco; Benjillali, Mustapha

    2017-01-01

    This volume offers the proceedings of the 2nd UNet conference, held in Casablanca May 30 - June 1, 2016. It presents new trends and findings in hot topics related to ubiquitous computing/networking, covered in three tracks and three special sessions: Main Track 1: Context-Awareness and Autonomy Paradigms Track Main Track 2: Mobile Edge Networking and Virtualization Track Main Track 3: Enablers, Challenges and Applications Special Session 1: Smart Cities and Urban Informatics for Sustainable Development Special Session 2: Unmanned Aerial Vehicles From Theory to Applications Special Session 3: From Data to Knowledge: Big Data applications and solutions.

  16. Dynamical Systems Conference

    CERN Document Server

    Gils, S; Hoveijn, I; Takens, F; Nonlinear Dynamical Systems and Chaos

    1996-01-01

    Symmetries in dynamical systems, "KAM theory and other perturbation theories", "Infinite dimensional systems", "Time series analysis" and "Numerical continuation and bifurcation analysis" were the main topics of the December 1995 Dynamical Systems Conference held in Groningen in honour of Johann Bernoulli. They now form the core of this work which seeks to present the state of the art in various branches of the theory of dynamical systems. A number of articles have a survey character whereas others deal with recent results in current research. It contains interesting material for all members of the dynamical systems community, ranging from geometric and analytic aspects from a mathematical point of view to applications in various sciences.

  17. LEAP 1992: Conference summary

    International Nuclear Information System (INIS)

    Dover, C.B.

    1992-12-01

    We present a summary of the many new results in antiproton (bar p) physics presented at the LEAP '92 conference, in the areas of meson spectroscopy, bar NN scattering, annihilation and spin observables, strangeness and charm production, bar N annihilation in nuclei, atomic physics with very low energy bar p's, the exploration of fundamental symmetries and interactions with bar p (CP, T, CPT, gravitation), and the prospects for new bar p facilities at ultralow energies or energies above the LEAR regime (≥ 2 GeV/c)

  18. CONFERENCE: Muon spin rotation

    Energy Technology Data Exchange (ETDEWEB)

    Karlsson, Erik

    1986-11-15

    An international physics conference centred on muons without a word about leptons, weak interactions, EMC effects, exotic decay modes or any other standard high energy physics jargon. Could such a thing even have been imagined ten years ago? Yet about 120 physicists and chemists from 16 nations gathered at the end of June in Uppsala (Sweden) for their fourth meeting on Muon Spin Rotation, Relaxation and Resonance, without worrying about the muon as an elementary particle. This reflects how the experimental techniques based on the muon spin interactions have reached maturity and are widely recognized by condensed matter physicists and specialized chemists as useful tools.

  19. Aerospace Environmental Technology Conference

    Science.gov (United States)

    Whitaker, A. F. (Editor)

    1995-01-01

    The mandated elimination of CFC's, Halons, TCA, and other ozone depleting chemicals and specific hazardous materials has required changes and new developments in aerospace materials and processes. The aerospace industry has been involved for several years in providing product substitutions, redesigning entire production processes, and developing new materials that minimize or eliminate damage to the environment. These activities emphasize replacement cleaning solvents and their application verifications, compliant coatings including corrosion protection systems, and removal techniques, chemical propulsion effects on the environment, and the initiation of modifications to relevant processing and manufacturing specifications and standards. The Executive Summary of this Conference is published as NASA CP-3297.

  20. MICHIGAN: Cyclotron conference

    International Nuclear Information System (INIS)

    Anon.

    1984-01-01

    A sense of excitement was in the air as cyclotron physicists and engineers from 17 countries convened on 30 April for the opening of the Tenth International Conference on Cyclotrons and Their Applications. Some 50 years after its invention, the redoubtable cyclotron remains a topic of compelling current interest. Cyclotron experts gathered at Michigan State University's Kellogg Center to hear of latest developments, of progress and successes on new machines which had come into operation, of new projects which were underway, and of dreams which lay ahead

  1. MICHIGAN: Cyclotron conference

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1984-10-15

    A sense of excitement was in the air as cyclotron physicists and engineers from 17 countries convened on 30 April for the opening of the Tenth International Conference on Cyclotrons and Their Applications. Some 50 years after its invention, the redoubtable cyclotron remains a topic of compelling current interest. Cyclotron experts gathered at Michigan State University's Kellogg Center to hear of latest developments, of progress and successes on new machines which had come into operation, of new projects which were underway, and of dreams which lay ahead.

  2. Quark search conference

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    In spite of (or perhaps because of) the present doctrine of total quark confinement held by the majority of particle theorists, experimental searches for free fractional charge and other anomalous stable particles in ordinary matter have been increasing in number during recent years, using a range of techniques of increasing sophistication and sensitivity. As a result, researchers in this area had a conference to themselves in June. About 40 participants and 150 observers gathered at San Francisco State University to report progress and discuss future plans, with representatives present from almost every group involved in quark searches

  3. 17th International Cryocooler Conference

    CERN Document Server

    Ross, Ronald G

    2012-01-01

    Cryocoolers 17 archives developments and performance measurements in the field of cryocoolers based on the contributions of leading international experts at the 17th International Cryocooler Conference that was held in Los Angeles, California, on July 9-12, 2012. The program of this conference consisted of 94 papers; of these, 71 are published here. Over the years the International Cryocoolers Conference has become the preeminent worldwide conference for the presentation of the latest developments and test experiences with cryocoolers. The typical applications of this technology include cooling space and terrestrial infrared focal plane arrays, space x-ray detectors, medical applications, and a growing number of high-temperature superconductor applications.

  4. 16th International Cryocooler Conference

    CERN Document Server

    Ross, Ronald G

    2011-01-01

    Cryocoolers 16 archives developments and performance measurements in the field of cryocoolers based on the contributions of leading international experts at the 16th International Cryocooler Conference that was held in Atlanta, Georgia, on May 17-20, 2010. The program of this conference consisted of 116 papers; of these, 89 are published here. Over the years the International Cryocoolers Conference has become the preeminent worldwide conference for the presentation of the latest developments and test experiences with cryocoolers. The typical applications of this technology include cooling space and terrestrial infrared focal plane arrays, space x-ray detectors, medical applications, and a growing number of high-temperature superconductor applications.

  5. 4th International Cryocoolers Conference

    CERN Document Server

    Patton, George; Knox, Margaret

    1987-01-01

    The Cryocoolers 4 proceedings archives the contributions of leading international experts at the 4th International Cryocooler Conference that was held in Easton, Maryland on September 25-26, 1986. About 170 people attended the conference representing 11 countries, 14 universities, 21 government laboratories and 60 industrial companies. Thirty-one papers were presented describing advancements and applications of cryocoolers in the temperature range below 80K. This year's conference was sponsored by the David Taylor Naval Ship Research and Development Center of Annapolis, Maryland, and the conference proceedings reproduced here was published by them.

  6. Radiological diagnostics of skeletal tumors

    International Nuclear Information System (INIS)

    Uhl, M.; Herget, G.W.

    2008-01-01

    The book contains contributions concerning the following topics: 1. introduction and fundamentals: WHO classification of bone tumors, imaging diagnostics and their function; localization, typical clinical and radiological criteria, TNM classification and status classification, invasive tumor diagnostics; 2. specific tumor diagnostics: chondrogenic bone tumors, osseous tumors, connective tissue bony tumors, osteoclastoma, osteomyelogenic bone tumors, vascular bone tumors, neurogenic bone tumors, chordoma; adamantinoma of the long tubular bone; tumor-like lesions, bony metastases, bone granulomas, differential diagnostics: tumor-like lesions

  7. The Influence of Diabetes on Prevalence of Various Tumor Diseases

    Czech Academy of Sciences Publication Activity Database

    Topolčan, O.; Pecen, Ladislav; Steinerová, A.; Vlasák, J.; Gajewski, I.; Pavelka, V.; Svobodová, S.; Pikner, R.; Holubec, L.

    2000-01-01

    Roč. 15, č. 1 (2000), s. 56-57 ISSN 0886-3849. [International Conference on Human Tumor Markers /17./. 23.03.2000-24.03.2000, Hong Kong] Grant - others:IGA MZ ČR(CZ) NC4780; IGA MZ ČR(CZ) NC4746 Institutional research plan: AV0Z1030915

  8. Epidemiology of Pancreatic Tumor in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Svobodová, S.; Topolčan, O.; Pecen, Ladislav; Koukalová, H.; Novák, J.; Široký, P.; Roušarová, M.; Pikner, R.; Holubec, L.

    2000-01-01

    Roč. 15, č. 1 (2000), s. 58 ISSN 0886-3849. [International Conference on Human Tumor Markers /17./. 23.03.2000-24.03.2000, Hong Kong] Grant - others:IGA MZ ČR(CZ) NC4780; IGA MZ ČR(CZ) NC4746 Institutional research plan: AV0Z1030915

  9. SARS virus

    Indian Academy of Sciences (India)

    ... consequence.Protein spike similar. HE gene absent. 2787 nucleotides. Largest genome. Jumps species by genetic deletion. < 300 compounds screened. Glycyrrhizin (liquorics/mullatha) seems attractive. Antivirals not effective. Vaccines – animal model only in monkeys. Killed corona or knockout weakened virus as targets.

  10. Changes in Values of Tumor Markers with Pregnant Women in their IInd Trimester

    Czech Academy of Sciences Publication Activity Database

    Topolčan, O.; Holubec jr., L.; Pecen, Ladislav; Pikner, R.; Svobodová, S.

    2002-01-01

    Roč. 17, č. 3 (2002), s. 121-123 ISSN 0886-3849. [International Conference on Human Tumor Markers /19./. 25.08.2002-29.08.2002, Velje] Institutional research plan: AV0Z1030915 Keywords : tumor markers * pregrancy Subject RIV: BA - General Mathematics

  11. Human papilloma virus: a new risk factor in a subset of head and neck cancers.

    Science.gov (United States)

    Bisht, Manisha; Bist, Sampan Singh

    2011-01-01

    Head and neck cancer is the sixth most common malignancy worldwide. Tobacco smoking and alcohol consumption are two well known behavioral risk factors associated with head and neck cancer. Recently, evidence is mounting that infection with human papilloma virus, most commonly human papilloma virus-16 is responsible for a subset of head and neck squamous cell carcinoma especially tumors of tonsillar origin. The molecular pathway used by human papilloma virus to trigger malignant transformation of tissue is different from that of other well known risk factors, i.e. smoking and alcohol, associated with squamous cell carcinoma. Apparently, these subsets of patients with human papilloma virus positive tumor are more likely to have a better prognosis than human papilloma virus negative tumor. Considering this fact, the human papilloma virus infection should be determined in all oropharyngeal cancers since it can have a major impact on the decision making process of the treatment.

  12. Immune cells: more than simple carriers for systemic delivery of oncolytic viruses

    Directory of Open Access Journals (Sweden)

    Eisenstein S

    2014-11-01

    Full Text Available Samuel Eisenstein,1 Shu-Hsia Chen,2 Ping-Ying Pan21Department of Surgery, 2Department of Oncological Sciences and Tisch Cancer Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, USAAbstract: Oncolytic virotherapy on its own has numerous drawbacks, including an inability of the virus to actively target tumor cells and systemic toxicities at the high doses necessary to effectively treat tumors. Addition of immune cell-based carriers of oncolytic viruses holds promise as a technique in which oncolytic virus can be delivered directly to tumors in smaller and less toxic doses. Interestingly, the cell carriers themselves have also demonstrated antitumor effects, which can be augmented further by tailoring the appropriate oncolytic virus to the appropriate cell type. This review discusses the multiple factors that go into devising an effective, cell-based delivery system for oncolytic viruses.Keywords: oncolytic virus, cell carrier, immune cells, cancer therapy, myeloid-derived suppressor cells

  13. Crisis or Conference! Master List for Conference Planners.

    Science.gov (United States)

    Carey, Tony

    This conference organizer's guide contains 42 lists of ideas, reminders, things to check, and questions to ask when a person is planning an event such as a conference, workshop, or training session. Written from a British point of view, the guide is organized into four parts in chronological order: preplanning, planning, onsite, and…

  14. 20. AINSE plasma science and technology conference. Conference handbook

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    The 20th AINSE plasma science and technology conference was held at Flinders University of South Australia on 13-14 February 1995. Topics under discussion included plasma physics studies, current status of rotamak devices, plasma processing and material studies. The handbook contains the conference program, 54 abstracts and a list of participants.

  15. 20. AINSE plasma science and technology conference. Conference handbook

    International Nuclear Information System (INIS)

    1995-01-01

    The 20th AINSE plasma science and technology conference was held at Flinders University of South Australia on 13-14 February 1995. Topics under discussion included plasma physics studies, current status of rotamak devices, plasma processing and material studies. The handbook contains the conference program, 54 abstracts and a list of participants

  16. Annual conference SAEE 2008

    International Nuclear Information System (INIS)

    2008-01-01

    Technical and economic challenges of a 1 t CO 2 society was the topic addressed by the 2008 annual conference of the Swiss Association for Energy Economics. One tonne of carbon dioxide per head and year as a long-term energy strategy is the theme of a presentation made by professor Konstantin Boulouchos from the Swiss Federal Institute of Technology ETH in Zurich, Switzerland. Professor Dr. Rainhard Madlener from the Institute for Future Energy Consumer Needs and Behaviour in Aachen, Germany, took a look at the one-ton CO 2 vision as a focus for technical development. Professor Thomas F. Rutherford from the ETH presented an economic analysis of one-ton CO 2 scenarios. Eduard Schumacher, former Chairman of the Board at the IWB utility in Basel, Switzerland, presented examples of how energy policy can be implemented, using the IWB's activities as an example. Hansruedi Kunz, Head of the Energy Department in the Building Department of the Canton of Zurich discussed the chances offered and the problems posed by the implementation of measures that are to lead to the meeting of energy visions for the year 2050. A podium and discussion session completed the conference

  17. 24. CLI national conference

    International Nuclear Information System (INIS)

    Niel, Jean-Christophe; Jamet, Philippe; Delalonde, Jean-Claude; Revol, Henri; Lallier, Michel; Gaillard, Pierre; Jeffroy, Francois; Miniere, Dominique; Moulin, Ludovic; Charre, Jean-Pierre; Andrieux, Jean-Luc; Dubuis, Thierry; Giusti, Charles; Quintin, Christophe; Riviere, Emmanuel

    2012-12-01

    This document gathers contributions presented during a conference held in December 2012. After introduction speeches, a focus of some updates and an assessment of ANCCLI activities, this conference comprised two round tables. The first one addressed social, organisational and human factors in the nuclear field. It comprised a presentation of works performed by a CLI on these issues and of how CLIs address these issues, a presentation on the evolution of the notion of human factor with a progressive integration of organisational and societal dimensions, with a presentation of ASN actions in this respect (creation of a dialogue structure). Debates have been an occasion to discuss issues like staff and abilities turnover within EDF, subcontracting, and the culture of doubt. The second round table addressed the perception of risks and public information in the case of a nuclear incident or accident which does not require an emergency plan. Beside a presentation on an accident which occurred in the Centraco plant in 2011, the participants discussed how to organise information, the perception of the notion of nuclear safety in France, the difficulty to accept the 'small risk', an initiative of automatic information implemented by industrials in Dunkirk

  18. History of NAMES Conferences

    Science.gov (United States)

    Filippov, Lev

    2013-03-01

    -Russian International Centre was demonstrated. By the high standards of the reports presented, as well as by its overall organization, the second Seminar met the standards of an international conference. Reviews of state-of-the-art developments in materials science were given by leading scientists from Moscow and from the Lorraine region. The three days of the seminar were structured into four main themes: Functional Materials Coatings, Films and Surface Engineering Nanomaterials and Nanotechnologies The Environment and three Round Table discussions: Defining practical means of carrying out Franco-Russian collaborations in technology transfer and innovation Materials science ARCUS: Lorraine-Russian collaboration in materials science and the environment 32 oral and 25 poster presentations within four sections were given by a total of 110 participants. NAMES 2007, the 3rd Franco-Russian Seminar on New Achievements in Materials and Environmental Sciences, took place in Metz, France on 7-9 November 2007. The conference highlights fundamentals and development of the five main themes connected to the Lorraine-Russia ARCUS project with possible extension to other topics. The five main subjects included in the ARCUS project are: Bulk-surface-interface material sciences Nanomaterials and nanotechnologies Environment and natural resources Plasma physics—ITER project Vibrational dynamics The first, second and third NAMES conferences were financially supported by the following organizations: Ambassade de France à Moscou Communauté Urbaine du Grand Nancy Région Lorraine Conseil Général de Meurthe et Moselle Institut National Polytechnique de Lorraine Université de Metz Université Henry Poincaré CNRS ANVAR Federal Agency on Science and Innovations of the Ministry of Education and Science of the Russian Federation Moscow Committee on Science and Technologies Moscow Institute of Steel and Alloys (Technological University) The 4th conference is supported by the Ministry of Foreign Affairs of

  19. Hepatitis C virus expressing reporter tagged NS5A protein

    DEFF Research Database (Denmark)

    2014-01-01

    Hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A were developed. A deletion upstream of the inserted reporter gene sequence conferred favorable...... growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. JFH1-based intergenotypic recombinants with genotype specific homotypic 5'UTR, or heterotypic 5'UTR (either of genotype 1a (strain H...

  20. 2008 Gordon Research Conference on Catalysis [Conference summary report

    Energy Technology Data Exchange (ETDEWEB)

    Soled, Stuart L.; Gray, Nancy Ryan

    2009-01-01

    The GRC on Catalysis is one of the most prestigious catalysis conferences as it brings together leading researchers from around the world to discuss their latest, most exciting work in catalysis. The 2008 conference will continue this tradition. The conference will cover a variety of themes including new catalytic materials, theoretical and experimental approaches to improve understanding of kinetics and transport phenomena, and state of the art nanoscale characterization probes to monitor active sites. The conference promotes interactions among established researchers and young scientists. It provides a venue for students to meet, talk to and learn from some of the world leading researchers in the area. It also gives them a platform for displaying their own work during the poster sessions. The informal nature of the meeting, excellent quality of the presentations and posters, and ability to meet many outstanding colleagues makes this an excellent conference.

  1. Liver Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Liver Tumors KidsHealth / For Parents / Liver Tumors What's in this article? Types of Tumors ... Cancerous) Tumors Symptoms Diagnosis Treatment Coping Print The liver is the body's largest solid organ. Lying next ...

  2. Molecular and genetic aspects of odontogenic tumors: a review.

    Science.gov (United States)

    Garg, Kavita; Chandra, Shaleen; Raj, Vineet; Fareed, Wamiq; Zafar, Muhammad

    2015-06-01

    Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/conttrollers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors.

  3. Molecular and genetic aspects of odontogenic tumors: a review

    Directory of Open Access Journals (Sweden)

    Kavita Garg

    2015-06-01

    Full Text Available Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/controllers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors.

  4. Targeting Nanomedicine to Brain Tumors: Latest Progress and Achievements.

    Science.gov (United States)

    Van't Root, Moniek; Lowik, Clemens; Mezzanotte, Laura

    2017-01-01

    Targeting nanomedicine to brain tumors is hampered by the heterogeneity of brain tumors and the blood brain barrier. These represent the main reasons of unsuccessful treatments. Nanomedicine based approaches hold promise for improved brain tissue distribution of drugs and delivery of combination therapies. In this review, we describe the recent advancements and latest achievements in the use of nanocarriers, virus and cell-derived nanoparticles for targeted therapy of brain tumors. We provide successful examples of nanomedicine based approaches for direct targeting of receptors expressed in brain tumor cells or modulation of pathways involved in cell survival as well as approaches for indirect targeting of cells in the tumor stroma and immunotherapies. Although the field is at its infancy, clinical trials involving nanomedicine based approaches for brain tumors are ongoing and many others will start in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses

    DEFF Research Database (Denmark)

    Mordstein, M; Kochs, G; Dumoutier, L

    2008-01-01

    Virus-infected cells secrete a broad range of interferon (IFN) subtypes which in turn trigger the synthesis of antiviral factors that confer host resistance. IFN-alpha, IFN-beta and other type I IFNs signal through a common universally expressed cell surface receptor, whereas IFN-lambda uses....... Mice lacking functional IFN-lambda receptors were only slightly more susceptible to influenza virus than wild-type mice. However, mice lacking functional receptors for both IFN-alpha/beta and IFN-lambda were hypersensitive and even failed to restrict usually non-pathogenic influenza virus mutants...

  6. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  7. Engineering resistance against Tomato yellow leaf curl virus via the CRISPR/Cas9 system in tomato

    KAUST Repository

    Mahfouz, Magdy M.

    2017-12-22

    CRISPR/Cas systems confer molecular immunity against phages and conjugative plasmids in prokaryotes. Recently, CRISPR/Cas9 systems have been used to confer interference against eukaryotic viruses. Here, we engineered Nicotiana benthamiana and tomato (Solanum lycopersicum) plants with the CRISPR/Cas9 system to confer immunity against the Tomato yellow leaf curl virus (TYLCV). Targeting the TYLCV genome with Cas9-single guide RNA at the sequences encoding the coat protein (CP) or replicase (Rep) resulted in efficient virus interference, as evidenced by low accumulation of the TYLCV DNA genome in the transgenic plants. The CRISPR/Cas9-based immunity remained active across multiple generations in the N. benthamiana and tomato plants. Together, our results confirmed the efficiency of the CRISPR/Cas9 system for stable engineering of TYLCV resistance in N. benthamiana and tomato, and opens the possibilities of engineering virus resistance against single and multiple infectious viruses in other crops.

  8. Building Bridges through Scientific Conferences

    DEFF Research Database (Denmark)

    Zierath, Juleen R

    2016-01-01

    Getting together to exchange ideas, forge collaborations, and disseminate knowledge is a long-standing tradition of scientific communities. How conferences are serving the community, what their current challenges are, and what is in store for the future of conferences are the topics covered...

  9. Conference summary: Theory and phoneymenology

    International Nuclear Information System (INIS)

    Close, F. E.

    1998-01-01

    This is a written version of the talk that I gave at the end of the Conference. It concentrates on the status of light flavoured hadrons with emphasis on gluonic excitations. The experimental aspects of the conference are summarized by E. Klempt

  10. Organization and planning of conferences

    International Nuclear Information System (INIS)

    Hudson, S.R.

    1976-05-01

    The author uses as an example of conference planning The First International Topical Conference on Electron Beam Research and Technology which was held in Albuquerque, New Mexico, November 3-6, 1975. Guidelines are given through all phases of planning up to and during the meeting

  11. International conference on plasma physics

    International Nuclear Information System (INIS)

    Silin, V.P.; Sitenko, A.G.

    1985-01-01

    A brief report on the 6th International conference on plasma physics and on the 6th International Congress on plasma waves and plasma instabilities, which have taken place in summer 1984 in Losanne, is presented. Main items of the conference are enlightened, such as the general theory of a plasma, laboratory plasma, thermonuclear plasma, cosmic plasma and astrophysics

  12. The Writing Conference as Performance.

    Science.gov (United States)

    Newkirk, Thomas

    1995-01-01

    Provides an overview of the conversational roles taken on by students and teachers during college-level writing conferences. Uses the performative theory of Erving Goffman to analyze these role patterns. Illuminates the specific performative demands presented by writing conferences on both students and teachers. (HB)

  13. CT of abdominal tumor

    International Nuclear Information System (INIS)

    Endo, Satoshi; Yamada, Kenji; Ito, Masatoshi; Ito, Hisao; Yamaura, Harutsugu

    1981-01-01

    CT findings in 33 patients who had an abdominal tumor were evaluated. CT revealed a tumor in 31 cases. The organ from which the tumor originated was correctly diagnosed in 18 patients. Whether the tumor was solid or cystic was correctly predicted in 28 patients. The diagnosis malignant or benign nature of tumor was correct, incorrect and impossible, in 23, 3, and five patiens, respectively. (Kondo, M.)

  14. 2017 Gordon Conference on Superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Chubukov, Andrey [Univ. of Minnesota, Twin Cities, MN (United States)

    2017-11-14

    The DOE award was for a 2017 Gordon Research conference on Superconductivity (GRC). The objective of GRC is to interchange the information about the latest theoretical and experimental developments in the area of superconductivity and to select most perspective directions for future research in this area.The goal of the Gordon Conference on Superconductivity is to present and discuss the latest results in the field of modern superconductivity, discuss new ideas and new directions of research in the area. It is a long-standing tradition of the Gordon conference on Superconductivity that the vast majority of participants are junior scientists. Funding for the conference would primarily be used to support junior researchers, particularly from under-represented groups. We had more 10 female speakers, some of them junior researchers, and some funding was used to support these speakers. The conference was held together with Gordon Research Seminar on Superconductivity, where almost all speakers and participants were junior scientists.

  15. 4th European Turbulence Conference

    CERN Document Server

    1993-01-01

    The European Turbulence Conferences have been organized under the auspices of the European Mechanics Committee (Euromech) to provide a forum for discussion and exchange of recent and new results in the field of turbulence. The first conference was organized in Lyon in 1986 with 152 participants. The second and third conferences were held in Berlin (1988) and Stockholm (1990) with 165 and 172 participants respectively. The fourth was organized in Delft from 30 June to 3 July 1992 by the J.M. Burgers Centre. There were 214 participants from 22 countries. This steadily growing number of participants demonstrates both the success and need for this type of conference. The main topics of the Fourth European Turbulence Conference were: Dynamical Systems and Transition; Statistical Physics and Turbulence; Experiments and Novel Experimental Techniques; Particles and Bubbles in Turbulence; Simulation Methods; Coherent Structures; Turbulence Modelling and Compressibility Effects. In addition a special session was held o...

  16. 28th Linear Accelerator Conference

    CERN Document Server

    Facco, Alberto; McCausey, Amy; Schaa, Volker R W

    2017-01-01

    The 28th Linear Accelerator Conference, LINAC 16, to take place at the Kellogg Hotel and Conference Center in East Lansing, Michigan, on 25-30 September 2016. This conference is the main bi-yearly gathering for the world-wide community of linac specialists. It provides a unique opportunity to hear about the latest advances of projects and developments concerning hadron and lepton linacs, and their applications. In the tradition of previous LINAC conferences, plenary sessions including invited speakers are scheduled every day. Poster sessions will be held on Monday, Tuesday and Thursday afternoons. There will also be two special events on Sunday, 25 September 2016, namely a student poster session and an evening reception for registrants and their companions at the Kellogg Hotel and Conference Center. Participants are also warmly invited to join an outing to Lake Michigan and the beautiful surroundings on Wednesday afternoon, and to visit the Facility for Rare Isotope Beams on Friday afternoon, after the formal...

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

    Science.gov (United States)

    Wool-Lewis, R J; Bates, P

    1998-04-01

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

  18. Istanbul Bridge Conference 2014

    CERN Document Server

    Gülkan, Polat; Mahmoud, Khaled

    2016-01-01

      The book includes peer-reviewed contributions selected from presentations given at the Istanbul Bridge Conference 2014, held from August 11 – 13 in Istanbul, Turkey. It reports on the current challenges in bridge engineering faced by professionals around the globe, giving a special emphasis to recently developed techniques, innovations and opportunities. The book covers key topics in the field, including modeling and analysis methods; construction and erection techniques; design for extreme events and condition assessment and structural health monitoring. There is a balanced presentation of theory, research and practice. This book, which provides the readers with a comprehensive and timely reference guide on current practices in bridge engineering, is intended for professionals, academic researchers and students alike.

  19. International Logistics Science Conference

    CERN Document Server

    Hompel, Michael; Meier, J

    2014-01-01

    The importance of logistics in all its variations is still increasing. New technologies emerge, new planning methods and algorithms are developed, only to face a market with a growing complexity and the need of weighting monetary costs against ecological impact. Mastering these challenges requires a scientific viewpoint on logistics, but always with applications in mind. This volume presents up-to-date logistics research in all its diversity and interconnectedness. It grew out of the “International Logistics Science Conference” (ILSC) held in Dortmund in September 2013, bringing together leading scientists and young academics from nine different countries. The conference was jointly organized by the “Efficiency Cluster Logistics” and the “Fraunhofer Institute for Material Flow and Logistics”. The Program Committee used a double blind review process to choose the 12 strongest contributions, which were then grouped in four areas: - Sustainability logistics, including electric mobility, smart inform...

  20. 11th radiochemical conference

    International Nuclear Information System (INIS)

    Prasil, Z.

    1987-01-01

    The conference met in four sesions which discussed: Separation methods, Radioanalytical methods, Labelled compounds and Miscellaneous. The first session discussed extraction methods, ion exchange and chromatographic separation of radioisotopes. The second session heard papers on the application of these methods, e.g., in geochemistry, on the use of radioactive tracers in radiochemical analysis and the use of activation analysis in the determination of trace elements. The third session heard papers on the preparation of labelled organic compounds with isotopes 3 H, 14 C, radioiodine and 32 P, on the preparation of RIA kits and on the chemistry and radiopharmacology of technetium compounds. The other contributions which could not be heard in any of the three sessions discussed, e.g., the preparation of elements on the cyclotron and microtron, the production of a new 99m Tc-generator, the participation of the IAEA in processing low- and medium-level radioactive wastes, etc. (E.S.)