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  1. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

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    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  2. Intragastric administration of Lactobacillus plantarum and AT-2-inactivated SIV does not protect Indian rhesus macaques from intra-rectal SIV challenge nor reduce virus replication after transmission.

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    Carnathan, Diane G; Mackel, Joseph J; Sweat, Shelby L; Enemuo, Chiamaka A; Gebru, Etse H; Dhadvai, Pallavi; Gangadhara, Sailaja; Hicks, Sakeenah; Vanderford, Thomas H; Amara, Rama R; Esparza, José; Lu, Wei; Andrieu, Jean-Marie; Silvestri, Guido

    2018-02-28

    for acquisition of HIV. An alternative strategy could involve induction of a tolerizing response that limits the availability of activated CD4+ T cells, thus limiting the ability of virus to establish infection. In this regard, exciting results were obtained in Chinese-origin rhesus macaques by using a "tolerogenic" vaccine consisting of intra-gastric administration of Lactobacillus plantarum and AT-2-inactivated SIV (iSIV+LP) which showed highly significant protection from virus transmission. Here, we administered iSIV+LP immunizations to Indian-origin rhesus macaques, and failed to observe any protective effect from virus acquisition in this experimental setting. This work is important as it contributes to the overall assessment of the clinical potential of a new candidate AIDS vaccine platform based on the iSIV+LP. Copyright © 2018 American Society for Microbiology.

  3. Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL-21.

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    Suresh Pallikkuth

    Full Text Available In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs, preferential depletion of CD4⁺ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8⁺ T cells, and differentiation of memory B cells and antibody-secreting plasma cells. We hypothesized that administration of IL-21 will improve mucosal function in the context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12 RMs with SIV(mac239 and at day 14 post-infection treated six of them with rhesus rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or systemic immune activation. Compared to untreated animals, IL-21-treated RMs showed (i higher expression of perforin and granzyme B in total and SIV-specific CD8⁺ T cells and (ii higher levels of intestinal Th17 cells. Remarkably, increased levels of Th17 cells were associated with reduced levels of intestinal T cell proliferation, microbial translocation and systemic activation/inflammation in the chronic infection. In conclusion, IL-21-treatment in SIV-infected RMs improved mucosal immune function through enhanced preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted to test its potential use during chronic infection in conjunction with antiretroviral therapy.

  4. Rhesus macaque IFITM3 gene polymorphisms and SIV infection.

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    Michael Winkler

    Full Text Available Interferon-induced transmembrane proteins (IFITMs have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV and human immunodeficiency virus (HIV infection, respectively. Rhesus macaques (Macaca mulatta are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals.

  5. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

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    Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

  6. SIV Infection of Lung Macrophages.

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    Yue Li

    Full Text Available HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.

  7. Traveling waves for two SIV models

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    REN Jingli

    2015-06-01

    Full Text Available The existence of traveling waves is established for a diffusive SIV system with constant total population. The approach used is the geometric singular perturbation method. The same result is suitable to another SIV system with exponential input.

  8. Conditionally replicating HIV and SIV variants

    NARCIS (Netherlands)

    Das, Atze T.; Berkhout, Ben

    2016-01-01

    Conditionally replicating human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) variants that can be switched on and off at will are attractive tools for HIV and SIV research. We constructed HIV and SIV variants in which the natural transcription control mechanism was replaced

  9. Immunotherapy of Congenital SIV Infection.

    Science.gov (United States)

    1996-10-01

    Yudi n Hs these infants do not die of opportunistic with nef-deleted SIV (18). Tl.d, all adult Robert A. Rasmussen infections in our biocontainment... Zhang YJ, Putkonen P, Albert J, et al.: Stable biological and anti- genic characteristics of HIV-2sBt" 69 in nonpathogenic infection of macaques

  10. Protection of rhesus macaques from SIV infection by immunization with different experimental SIV vaccines.

    NARCIS (Netherlands)

    P. de Vries (Petra); J.L. Heeney (Jonathan); J. Boes (Jolande); M.E.M. Dings (Marlinda); E.G.J. Hulskotte (Ellen); R. Dubbes (Rob); W. Koornstra (Willem); P. ten Haaft (Peter); L. Akerblom; S. Eriksson (Sigrid); B. Morein (Bror); S. Norley (Steve); A.D.M.E. Osterhaus (Albert)

    1994-01-01

    textabstractThe immunogenicity and efficacy of an inactivated whole SIVmac (32H) preparation adjuvanted with muramyl dipeptide (SIV-MDP) and a gp120-enriched SIVmac (32H) ISCOM preparation (SIV-ISCOM), were compared by immunizing four rhesus macaques (Macaca mulatta) four times with SIV-MDP and four

  11. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

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    Chie Sugimoto

    Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

  12. Myocarditis in CD8-depleted SIV-infected rhesus macaques after short-term dual therapy with nucleoside and nucleotide reverse transcriptase inhibitors.

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    Lakshmanan Annamalai

    2010-12-01

    Full Text Available Although highly active antiretroviral therapy (HAART has dramatically reduced the morbidity and mortality associated with HIV infection, a number of antiretroviral toxicities have been described, including myocardial toxicity resulting from the use of nucleotide and nucleoside reverse transcriptase inhibitors (NRTIs. Current treatment guidelines recommend the use of HAART regimens containing two NRTIs for initial therapy of HIV-1 positive individuals; however, potential cardiotoxicity resulting from treatment with multiple NRTIs has not been addressed.We examined myocardial tissue from twelve CD8 lymphocyte-depleted adult rhesus macaques, including eight animals infected with simian immunodeficiency virus, four of which received combined antiretroviral therapy (CART consisting of two NRTIs [(9-R-2-Phosphonomethoxypropyl Adenine (PMPA and (+/--beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine (RCV] for 28 days. Multifocal infiltrates of mononuclear inflammatory cells were present in the myocardium of all macaques that received CART, but not untreated SIV-positive animals or SIV-negative controls. Macrophages were the predominant inflammatory cells within lesions, as shown by immunoreactivity for the macrophage markers Iba1 and CD68. Heart specimens from monkeys that received CART had significantly lower virus burdens than untreated animals (p<0.05, but significantly greater quantities of TNF-α mRNA than either SIV-positive untreated animals or uninfected controls (p<0.05. Interferon-γ (IFN-γ, IL-1β and CXCL11 mRNA were upregulated in heart tissue from SIV-positive monkeys, independent of antiretroviral treatment, but CXCL9 mRNA was only upregulated in heart tissue from macaques that received CART.These results suggest that short-term treatment with multiple NRTIs may be associated with myocarditis, and demonstrate that the CD8-depleted SIV-positive rhesus monkey is a useful model for studying the cardiotoxic effects of combined antiretroviral

  13. Natural SIV hosts: showing AIDS the door.

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    Chahroudi, Ann; Bosinger, Steven E; Vanderford, Thomas H; Paiardini, Mirko; Silvestri, Guido

    2012-03-09

    Many species of African nonhuman primates are naturally infected with simian immunodeficiency viruses (SIVs) in the wild and in captivity. In contrast to HIV-infected humans, these natural SIV hosts typically do not develop AIDS, despite chronic infection with a highly replicating virus. In this Review, we discuss the most recent advances on the mechanisms of protection from disease progression in natural SIV hosts, with emphasis on how they differ from pathogenic HIV/SIV infections of humans and rhesus macaques. These mechanisms include: (i) resolution of immune activation after acute infection, (ii) restricted pattern of target cell infection, and (iii) protection from mother-to-infant transmission. We highlight the areas that should be pursued in future studies, focusing on potential applications for the treatment and prevention of HIV infection.

  14. Cytotoxic Capacity of SIV-Specific CD8+ T Cells against Primary Autologous Targets Correlates with Immune Control in SIV-Infected Rhesus Macaques

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    Mendoza, Daniel; Migueles, Stephen A.; Rood, Julia E.; Peterson, Bennett; Johnson, Sarah; Doria-Rose, Nicole; Schneider, Douglas; Rakasz, Eva; Trivett, Matthew T.; Trubey, Charles M.; Coalter, Vicky; Hallahan, Claire W.; Watkins, David; Franchini, Genoveffa; Lifson, Jeffrey D.; Connors, Mark

    2013-01-01

    Although the study of non-human primates has resulted in important advances for understanding HIV-specific immunity, a clear correlate of immune control over simian immunodeficiency virus (SIV) replication has not been found to date. In this study, CD8+ T-cell cytotoxic capacity was examined to determine whether this function is a correlate of immune control in the rhesus macaque (RM) SIV infection model as has been suggested in chronic HIV infection. SIVmac251-infected human reverse transcriptase (hTERT)-transduced CD4+ T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4+ T-cell elimination (ICE). Twenty-three SIV-infected rhesus macaques with widely varying plasma viral RNA levels were evaluated in a blinded fashion. Nineteen of 23 subjects (83%) were correctly classified as long-term nonprogressor/elite controller (LTNP/EC), slow progressor, progressor or SIV-negative rhesus macaques based on measurements of ICE (weighted Kappa 0.75). LTNP/EC had higher median ICE than progressors (67.3% [22.0–91.7%] vs. 23.7% [0.0–58.0%], p = 0.002). In addition, significant correlations between ICE and viral load (r = −0.57, p = 0.01), and between granzyme B delivery and ICE (r = 0.89, pspecific CD8+ T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans. Therefore, such measurements appear to represent a correlate of control of viral replication in chronic SIV infection and their role as predictors of immunologic control in the vaccine setting should be evaluated. PMID:23468632

  15. Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions

    International Nuclear Information System (INIS)

    Devitt, Gerard; Emerson, Vanessa; Holtkotte, Denise; Pfeiffer, Tanya; Pisch, Thorsten; Bosch, Valerie

    2007-01-01

    Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767 stop , which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752 N750K ) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752 N750K exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses

  16. Stability of the Gorilla Microbiome Despite SIV Infection

    OpenAIRE

    Moeller, Andrew H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H.; Ochman, Howard

    2015-01-01

    Simian Immunodeficiency Viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in fecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. He...

  17. Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

    International Nuclear Information System (INIS)

    Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

    2013-01-01

    Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication

  18. Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

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    Félicien Moukambi

    2015-12-01

    Full Text Available Follicular T helper cells (Tfh, a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

  19. Increases in NKG2C Expression on T Cells and Higher Levels of Circulating CD8+B Cells Are Associated with Sterilizing Immunity Provided by a Live Attenuated SIV Vaccine.

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    Hodara, Vida L; Parodi, Laura M; Keckler, M Shannon; Giavedoni, Luis D

    Vaccines based on live attenuated viruses are highly effective immunogens in the simian immunodeficiency virus (SIV)/rhesus macaque animal model and offer the possibility of studying correlates of protection against infection with virulent virus. We utilized a tether system for studying, in naive macaques and animals vaccinated with a live-attenuated vaccine, the acute events after challenge with pathogenic SIV. This approach allowed for the frequent sampling of small blood volumes without sedation or restraining of the animals, thus reducing the confounding effect of sampling stress. Before challenge, vaccinated animals presented significantly higher levels of proliferating and activated B cells than naive macaques, which were manifested by high expression of CD8 on B cells. After SIV challenge, the only changes observed in protected vaccinated macaques were significant increases in expression of the NK marker NKG2C on CD4 and CD8 T cells. We also identified that infection of naive macaques with SIV resulted in a transient peak of expression of CD20 on CD8 T cells and a constant rise in the number of B cells expressing CD8. Finally, analysis of a larger cohort of vaccinated animals identified that, even when circulating levels of vaccine virus are below the limit of detection, live attenuated vaccines induce systemic increases of IP-10 and perforin. These studies indicate that components of both the innate and adaptive immune systems of animals inoculated with a live-attenuated SIV vaccine respond to and control infection with virulent virus. Persistence of the vaccine virus in tissues may explain the elevated cytokine and B-cell activation levels. In addition, our report underpins the utility of the tether system for the intensive study of acute immune responses to viral infections.

  20. Dynamics of immune escape during HIV/SIV infection.

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    Christian L Althaus

    Full Text Available Several studies have shown that cytotoxic T lymphocytes (CTLs play an important role in controlling HIV/SIV infection. Notably, the observation of escape mutants suggests a selective pressure induced by the CTL response. However, it remains difficult to assess the definite role of the cellular immune response. We devise a computational model of HIV/SIV infection having a broad cellular immune response targeting different viral epitopes. The CTL clones are stimulated by viral antigen and interact with the virus population through cytotoxic killing of infected cells. Consequently, the virus population reacts through the acquisition of CTL escape mutations. Our model provides realistic virus dynamics and describes several experimental observations. We postulate that inter-clonal competition and immunodominance may be critical factors determining the sequential emergence of escapes. We show that even though the total killing induced by the CTL response can be high, escape rates against a single CTL clone are often slow and difficult to estimate from infrequent sequence measurements. Finally, our simulations show that a higher degree of immunodominance leads to more frequent escape with a reduced control of viral replication but a substantially impaired replicative capacity of the virus. This result suggests two strategies for vaccine design: Vaccines inducing a broad CTL response should decrease the viral load, whereas vaccines stimulating a narrow but dominant CTL response are likely to induce escape but may dramatically reduce the replicative capacity of the virus.

  1. CD40L-adjuvanted DNA/modified vaccinia virus Ankara simian immunodeficiency virus SIV239 vaccine enhances SIV-specific humoral and cellular immunity and improves protection against a heterologous SIVE660 mucosal challenge.

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    Kwa, Suefen; Lai, Lilin; Gangadhara, Sailaja; Siddiqui, Mariam; Pillai, Vinod B; Labranche, Celia; Yu, Tianwei; Moss, Bernard; Montefiori, David C; Robinson, Harriet L; Kozlowski, Pamela A; Amara, Rama Rao

    2014-09-01

    It remains a challenge to develop a successful human immunodeficiency virus (HIV) vaccine that is capable of preventing infection. Here, we utilized the benefits of CD40L, a costimulatory molecule that can stimulate both dendritic cells (DCs) and B cells, as an adjuvant for our simian immunodeficiency virus (SIV) DNA vaccine in rhesus macaques. We coexpressed the CD40L with our DNA/SIV vaccine such that the CD40L is anchored on the membrane of SIV virus-like particle (VLP). These CD40L containing SIV VLPs showed enhanced activation of DCs in vitro. We then tested the potential of DNA/SIV-CD40L vaccine to adjuvant the DNA prime of a DNA/modified vaccinia virus Ankara (MVA) vaccine in rhesus macaques. Our results demonstrated that the CD40L adjuvant enhanced the functional quality of anti-Env antibody response and breadth of anti-SIV CD8 and CD4 T cell responses, significantly delayed the acquisition of heterologous mucosal SIV infection, and improved viral control. Notably, the CD40L adjuvant enhanced the control of viral replication in the gut at the site of challenge that was associated with lower mucosal CD8 immune activation, one of the strong predictors of disease progression. Collectively, our results highlight the benefits of CD40L adjuvant for enhancing antiviral humoral and cellular immunity, leading to enhanced protection against a pathogenic SIV. A single adjuvant that enhances both humoral and cellular immunity is rare and thus underlines the importance and practicality of CD40L as an adjuvant for vaccines against infectious diseases, including HIV-1. Despite many advances in the field of AIDS research, an effective AIDS vaccine that can prevent infection remains elusive. CD40L is a key stimulator of dendritic cells and B cells and can therefore enhance T cell and antibody responses, but its overly potent nature can lead to adverse effects unless used in small doses. In order to modulate local expression of CD40L at relatively lower levels, we expressed

  2. Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines, and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge.

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    Demberg, Thorsten; Boyer, Jean D; Malkevich, Nina; Patterson, L Jean; Venzon, David; Summers, Ebonita L; Kalisz, Irene; Kalyanaraman, V S; Lee, Eun Mi; Weiner, David B; Robert-Guroff, Marjorie

    2008-11-01

    Previously, combination DNA/nonreplicating adenovirus (Ad)- or poxvirus-vectored vaccines have strongly protected against SHIV(89.6P), DNAs expressing cytokines have modulated immunity elicited by DNA vaccines, and replication-competent Ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (SIV) challenge. Here we evaluated a vaccine strategy composed of these promising components. Seven rhesus macaques per group were primed twice with multigenic SIV plasmid DNA with or without interleukin-12 (IL-12) DNA or IL-15 DNA. After a multigenic replicating Ad-SIV immunization, all groups received two booster immunizations with SIV gp140 and SIV Nef protein. Four control macaques received control DNA plasmids, empty Ad vector, and adjuvant. All vaccine components were immunogenic, but the cytokine DNAs had little effect. Macaques that received IL-15-DNA exhibited higher peak anti-Nef titers, a more rapid anti-Nef anamnestic response postchallenge, and expanded CD8(CM) T cells 2 weeks postchallenge compared to the DNA-only group. Other immune responses were indistinguishable between groups. Overall, no protection against intrarectal challenge with SIV(mac251) was observed, although immunized non-Mamu-A*01 macaques as a group exhibited a statistically significant 1-log decline in acute viremia compared to non-Mamu-A*01 controls. Possible factors contributing to the poor outcome include administration of cytokine DNAs to sites different from the Ad recombinants (intramuscular and intratracheal, respectively), too few DNA priming immunizations, a suboptimal DNA delivery method, failure to ensure delivery of SIV and cytokine plasmids to the same cell, and instability and short half-life of the IL-15 component. Future experiments should address these issues to determine if this combination approach is able to control a virulent SIV challenge.

  3. The significance of sensory appeal for reduced meat consumption.

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    Tucker, Corrina A

    2014-10-01

    Reducing meat (over-)consumption as a way to help address environmental deterioration will require a range of strategies, and any such strategies will benefit from understanding how individuals might respond to various meat consumption practices. To investigate how New Zealanders perceive such a range of practices, in this instance in vitro meat, eating nose-to-tail, entomophagy and reducing meat consumption, focus groups involving a total of 69 participants were held around the country. While it is the damaging environmental implications of intensive farming practices and the projected continuation of increasing global consumer demand for meat products that has propelled this research, when asked to consider variations on the conventional meat-centric diet common to many New Zealanders, it was the sensory appeal of the areas considered that was deemed most problematic. While an ecological rationale for considering these 'meat' alternatives was recognised and considered important by most, transforming this value into action looks far less promising given the recurrent sensory objections to consuming different protein-based foods or of reducing meat consumption. This article considers the responses of focus group participants in relation to each of the dietary practices outlined, and offers suggestions on ways to encourage a more environmentally viable diet. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Significantly reducing registration time in IGRT using graphics processing units

    DEFF Research Database (Denmark)

    Noe, Karsten Østergaard; Denis de Senneville, Baudouin; Tanderup, Kari

    2008-01-01

    Purpose/Objective For online IGRT, rapid image processing is needed. Fast parallel computations using graphics processing units (GPUs) have recently been made more accessible through general purpose programming interfaces. We present a GPU implementation of the Horn and Schunck method...... respiration phases in a free breathing volunteer and 41 anatomical landmark points in each image series. The registration method used is a multi-resolution GPU implementation of the 3D Horn and Schunck algorithm. It is based on the CUDA framework from Nvidia. Results On an Intel Core 2 CPU at 2.4GHz each...... significant reduction of the registration time due to the parallelized architecture of the GPU. Considering the slice spacing we find the registration result acceptable. The accuracy is comparable to previous results for the Demons algorithm in the POPI model (Vandemeulenboucke et al, ICCR 2007...

  5. Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps

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    Oguz Kayiran

    2013-01-01

    Full Text Available Introduction: Numerous pharmacological agents have been used to enhance the viability of flaps. Ischemia reperfusion (I/R injury is an unwanted, sometimes devastating complication in reconstructive microsurgery. Tadalafil, a specific inhibitor of phosphodiesterase type 5 is mainly used for erectile dysfunction, and acts on vascular smooth muscles, platelets and leukocytes. Herein, the protective and therapeutical effect of tadalafil in I/R injury in rat skin flap model is evaluated. Materials and Methods: Sixty epigastric island flaps were used to create I/R model in 60 Wistar rats (non-ischemic group, ischemic group, medication group. Biochemical markers including total nitrite, malondialdehyde (MDA and myeloperoxidase (MPO were analysed. Necrosis rates were calculated and histopathologic evaluation was carried out. Results: MDA, MPO and total nitrite values were found elevated in the ischemic group, however there was an evident drop in the medication group. Histological results revealed that early inflammatory findings (oedema, neutrophil infiltration, necrosis rate were observed lower with tadalafil administration. Moreover, statistical significance (P < 0.05 was recorded. Conclusions: We conclude that tadalafil has beneficial effects on epigastric island flaps against I/R injury.

  6. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients

    Science.gov (United States)

    Kuo, Ming-Chun; Chang, Shun-Jen; Hsieh, Ming-Chia

    2015-01-01

    Abstract Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77–0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout. PMID:26683907

  7. Innate Lymphoid Cells in HIV/SIV Infections

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    Spandan V. Shah

    2017-12-01

    Full Text Available Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  8. Comparison of protection from homologous cell-free vs cell-associated SIV challenge afforded by inactivated whole SIV vaccines.

    NARCIS (Netherlands)

    J.L. Heeney (Jonathan); P. de Vries (Petra); R. Dubbes (Rob); W. Koornstra (Willem); H. Niphuis; P. ten Haaft (Peter); J. Boes (Jolande); M.E.M. Dings (Marlinda); B. Morein (Bror); A.D.M.E. Osterhaus (Albert)

    1992-01-01

    textabstractThis study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8)

  9. 'Omics investigations of HIV and SIV pathogenesis and innate immunity.

    Science.gov (United States)

    Palermo, Robert E; Fuller, Deborah H

    2013-01-01

    In the 30 years since the advent of the AIDS epidemic, the biomedical community has put forward a battery of molecular therapies that are based on the accumulated knowledge of a limited number of viral targets. Despite these accomplishments, the community still confronts unanswered foundational questions about HIV infection. What are the cellular or biomolecular processes behind HIV pathogenesis? Can we elucidate the characteristics that distinguish those individuals who are naturally resistant to either infection or disease progression? The discovery of simian immunodeficiency viruses (SIVs) and the ensuing development of in vivo, nonhuman primate (NHP) infection models was a tremendous advance, especially in abetting the exploration of vaccine strategies. And while there have been numerous NHP infection models and vaccine trials performed, fundamental questions remain regarding host-virus interactions and immune correlates of protection. These issues are, perhaps, most starkly illustrated with the appreciation that many species of African nonhuman primates are naturally infected with strains of SIV that do not cause any appreciable disease while replicating to viral loads that match or exceed those seen with pathogenic SIV infections in Asian species of nonhuman primates. The last decade has seen the establishment of high-throughput molecular profiling tools, such as microarrays for transcriptomics, SNP arrays for genome features, and LC-MS techniques for proteins or metabolites. These provide the capacity to interrogate a biological model at a comprehensive, systems level, in contrast to historical approaches that characterized a few genes or proteins in an experiment. These methods have already had revolutionary impacts in understanding human diseases originating within the host genome such as genetic disorders and cancer, and the methods are finding increasing application in the context of infectious disease. We will provide a review of the use of such 'omics

  10. Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

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    Marx Preston

    2006-12-01

    Full Text Available Abstract Background Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1 is a major obstacle to successful antiretroviral therapy (ART in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV. Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. Results Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Δnef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Δnef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4+ T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Δnef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8+ T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055. Conclusion

  11. Role of Monocyte/Macrophages during HIV/SIV Infection in Adult and Pediatric Acquired Immune Deficiency Syndrome

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    Kristen M. Merino

    2017-12-01

    Full Text Available Monocytes/macrophages are a diverse group of cells that act as first responders in innate immunity and then as mediators for adaptive immunity to help clear infections. In performing these functions, however, the macrophage inflammatory responses can also contribute to pathogenesis. Various monocyte and tissue macrophage subsets have been associated with inflammatory disorders and tissue pathogeneses such as occur during HIV infection. Non-human primate research of simian immunodeficiency virus (SIV has been invaluable in better understanding the pathogenesis of HIV infection. The question of HIV/SIV-infected macrophages serving as a viral reservoir has become significant for achieving a cure. In the rhesus macaque model, SIV-infected macrophages have been shown to promote pathogenesis in several tissues resulting in cardiovascular, metabolic, and neurological diseases. Results from human studies illustrated that alveolar macrophages could be an important HIV reservoir and humanized myeloid-only mice supported productive HIV infection and viral persistence in macrophages during ART treatment. Depletion of CD4+ T cells is considered the primary cause for terminal progression, but it was reported that increasing monocyte turnover was a significantly better predictor in SIV-infected adult macaques. Notably, pediatric cases of HIV/SIV exhibit faster and more severe disease progression than adults, yet neonates have fewer target T cells and generally lack the hallmark CD4+ T cell depletion typical of adult infections. Current data show that the baseline blood monocyte turnover rate was significantly higher in neonatal macaques compared to adults and this remained high with disease progression. In this review, we discuss recent data exploring the contribution of monocytes and macrophages to HIV/SIV infection and progression. Furthermore, we highlight the need to further investigate their role in pediatric cases of infection.

  12. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers.

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    Benjamin B Policicchio

    2016-09-01

    Full Text Available Viruses that persist despite seemingly effective antiretroviral treatment (ART and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35-50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml peaking at 5-12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control

  13. Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2.

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    Bin Jia

    2009-05-01

    Full Text Available Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host-cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the SIV(smm/mac/HIV-2 lineage do not have a vpu gene, this activity has likely been assumed by other viral gene products. We found that deletion of the SIV(mac239 nef gene significantly impaired virus release in cells expressing rhesus macaque tetherin. Virus release could be restored by expressing Nef in trans. However, Nef was unable to facilitate virus release in the presence of human tetherin. Conversely, Vpu enhanced virus release in the presence of human tetherin, but not in the presence of rhesus tetherin. In accordance with the species-specificity of Nef in mediating virus release, SIV Nef downregulated cell-surface expression of rhesus tetherin, but did not downregulate human tetherin. The specificity of SIV Nef for rhesus tetherin mapped to four amino acids in the cytoplasmic domain of the molecule that are missing from human tetherin, whereas the specificity of Vpu for human tetherin mapped to amino acid differences in the transmembrane domain. Nef alleles of SIV(smm, HIV-2 and HIV-1 were also able to rescue virus release in the presence of both rhesus macaque and sooty mangabey tetherin, but were generally ineffective against human tetherin. Thus, the ability of Nef to antagonize tetherin from these Old World primates appears to be conserved among the primate lentiviruses. These results identify Nef as the viral gene product of SIV that opposes restriction by tetherin in rhesus macaques and sooty mangabeys, and reveal species-specificity in the activities of both Nef and Vpu in overcoming tetherin in their respective hosts.

  14. The Earthquake‐Source Inversion Validation (SIV) Project

    KAUST Repository

    Mai, Paul Martin

    2016-04-27

    Finite-fault earthquake source inversions infer the (time-dependent) displacement on the rupture surface from geophysical data. The resulting earthquake source models document the complexity of the rupture process. However, multiple source models for the same earthquake, obtained by different research teams, often exhibit remarkable dissimilarities. To address the uncertainties in earthquake-source inversion methods and to understand strengths and weaknesses of the various approaches used, the Source Inversion Validation (SIV) project conducts a set of forward-modeling exercises and inversion benchmarks. In this article, we describe the SIV strategy, the initial benchmarks, and current SIV results. Furthermore, we apply statistical tools for quantitative waveform comparison and for investigating source-model (dis)similarities that enable us to rank the solutions, and to identify particularly promising source inversion approaches. All SIV exercises (with related data and descriptions) and statistical comparison tools are available via an online collaboration platform, and we encourage source modelers to use the SIV benchmarks for developing and testing new methods. We envision that the SIV efforts will lead to new developments for tackling the earthquake-source imaging problem.

  15. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load.

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    Collin R Diedrich

    2010-03-01

    Full Text Available HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb infection are at significantly greater risk of reactivation tuberculosis (TB than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV. Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection.

  16. Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection.

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    Haiying Li

    2014-12-01

    Full Text Available HIV/SIV infections break down the integrity of the gastrointestinal mucosa and lead to chronic immune activation and associated disease progression. Innate lymphoid cells (ILCs, distinguishable by high expression of NKp44 and RORγt, play key roles in mucosal defense and homeostasis, but are depleted from gastrointestinal (GI tract large bowel during chronic SIV infection. However, less is known about the kinetics of ILC loss, or if it occurs systemically. In acute SIV infection, we found a massive, up to 8-fold, loss of NKp44+ILCs in all mucosae as early as day 6 post-infection, which was sustained through chronic disease. Interestingly, no loss of ILCs was observed in mucosa-draining lymph nodes. In contrast, classical NK cells were not depleted either from gut or draining lymph nodes. Both ILCs and NK cells exhibited significantly increased levels of apoptosis as measured by increased Annexin-V expression, but while classical NK cells also showed increased proliferation, ILCs did not. Interestingly, ILCs, which are normally noncytolytic, dramatically upregulated cytotoxic functions in acute and chronic infection and acquired a polyfunctional phenotype secreting IFN-γ, MIP1-β, and TNF-α, but decreased production of the prototypical cytokine, IL-17. Classical NK cells had less dramatic functional change, but upregulated perforin expression and increased cytotoxic potential. Finally, we show that numerical and functional loss of ILCs was due to increased apoptosis and ROR γt suppression induced by inflammatory cytokines in the gut milieu. Herein we demonstrate the first evidence for acute, systemic, and permanent loss of mucosal ILCs during SIV infection associated with reduction of IL-17. The massive reduction of ILCs involves apoptosis without compensatory de novo development/proliferation, but the full mechanism of depletion and the impact of functional change so early in infection remain unclear.

  17. Plasmon resonance enhanced temperature-dependent photoluminescence of Si-V centers in diamond

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Shaoheng [State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012 (China); State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China); Song, Jie; Wang, Qiliang; Liu, Junsong; Li, Hongdong, E-mail: hdli@jlu.edu.cn [State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012 (China); Zhang, Baolin [State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China)

    2015-11-23

    Temperature dependent optical property of diamond has been considered as a very important factor for realizing high performance diamond-based optoelectronic devices. The photoluminescence feature of the zero phonon line of silicon-vacancy (Si-V) centers in Si-doped chemical vapor deposited single crystal diamond (SCD) with localized surface plasmon resonance (LSPR) induced by gold nanoparticles has been studied at temperatures ranging from liquid nitrogen temperature to 473 K, as compared with that of the SCD counterpart in absence of the LSPR. It is found that with LSPR the emission intensities of Si-V centers are significantly enhanced by factors of tens and the magnitudes of the redshift (width) of the emissions become smaller (narrower), in comparison with those of normal emissions without plasmon resonance. More interestingly, these strong Si-V emissions appear remarkably at temperatures up to 473 K, while the spectral feature was not reported in previous studies on the intrinsic Si-doped diamonds when temperatures are higher than room temperature. These findings would lead to reaching high performance diamond-based devices, such as single photon emitter, quantum cryptography, biomarker, and so forth, working under high temperature conditions.

  18. Defining HIV and SIV Reservoirs in Lymphoid Tissues

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    Claire Deleage

    2016-06-01

    Full Text Available A primary obstacle to an HIV-1 cure is long-lived viral reservoirs, which must be eliminated or greatly reduced. Cure strategies have largely focused on monitoring changes in T cell reservoirs in peripheral blood (PB, even though the lymphoid tissues (LT are primary sites for viral persistence. To track and discriminate viral reservoirs within tissue compartments we developed a specific and sensitive next-generation in situ hybridization approach to detect vRNA, including vRNA+ cells and viral particles (“RNAscope”, vDNA+ cells (“DNAscope” and combined vRNA and vDNA with immunohistochemistry to detect and phenotype active and latently infected cells in the same tissue section. RNAscope is highly sensitive with greater speed of analysis compared to traditional in situ hybridization. Highly sensitive and specific DNAscope detected SIV/HIV vDNA+ cells, including duplexed detection of vDNA and vRNA or immunophenotypic markers in the same section. Analysis of LT samples from macaques prior to and during combination antiretroviral therapy demonstrated that B cell follicles are an important anatomical compartment for both latent and active viral persistence during treatment. These new tools should allow new insights into viral reservoir biology and evaluation of cure strategies.

  19. Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIV(mac251).

    Science.gov (United States)

    Zhou, Qifeng; Hidajat, Rachmat; Peng, Bo; Venzon, David; Aldrich, M Kristine; Richardson, Ersell; Lee, Eun Mi; Kalyanaraman, V S; Grimes, George; Gómez-Román, V Raúl; Summers, L Ebonita; Malkevich, Nina; Robert-Guroff, Marjorie

    2007-11-19

    Oral, replication-competent Ad-HIV vaccines are advancing to human trials. Previous evaluation of protective efficacy in non-human primates has primarily followed upper respiratory tract administrations. Here we compared sequential oral (O/O) versus intranasal/oral (I/O) priming of rhesus macaques with Ad5 host range mutant-SIV recombinants expressing SIV env/rev, gag, and nef genes followed by boosting with SIV gp120 protein. Cellular immune responses in PBMC were stronger and more frequent after I/O administration. Both groups developed mucosal immunity, including memory cells in bronchial alveolar lavage, and gut-homing receptors on PBMC. Following intrarectal SIV(mac251) challenge, both groups exhibited equivalent, significant protection and robust post-challenge cellular immunity. Our results illustrate the promise of oral replication-competent Ad-recombinant vaccines. Pre-challenge PBMC ELISPOT and proliferative responses did not predict protection in the O/O group, highlighting the need for simple, non-invasive methods to reliably assess mucosal immunity.

  20. Mapping the small RNA content of simian immunodeficiency virions (SIV.

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    Markus Brameier

    Full Text Available Recent evidence indicates that regulatory small non-coding RNAs are not only components of eukaryotic cells and vesicles, but also reside within a number of different viruses including retroviral particles. Using ultra-deep sequencing we have comprehensively analyzed the content of simian immunodeficiency virions (SIV, which were compared to mock-control preparations. Our analysis revealed that more than 428,000 sequence reads matched the SIV mac239 genome sequence. Among these we could identify 12 virus-derived small RNAs (vsRNAs that were highly abundant. Beside known retrovirus-enriched small RNAs, like 7SL-RNA, tRNA(Lys3 and tRNA(Lys isoacceptors, we also identified defined fragments derived from small ILF3/NF90-associated RNA snaR-A14, that were enriched more than 50 fold in SIV. We also found evidence that small nucleolar RNAs U2 and U12 were underrepresented in the SIV preparation, indicating that the relative number or the content of co-isolated exosomes was changed upon infection. Our comprehensive atlas of SIV-incorporated small RNAs provides a refined picture of the composition of retrovirions, which gives novel insights into viral packaging.

  1. B-Cell-Activating Factor and the B-Cell Compartment in HIV/SIV Infection

    Science.gov (United States)

    Borhis, Gwenoline; Trovato, Maria; Chaoul, Nada; Ibrahim, Hany M.; Richard, Yolande

    2017-01-01

    With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing antibodies, which arise in a fraction of HIV-infected people. Apart from identifying new vulnerability sites in the viral envelope proteins, these studies have shown that a fraction of these antibodies are produced by self/poly-reactive B-cells. These findings prompted us to revisit the B-cell differentiation and selection process during HIV/SIV infection and to consider B-cells as active players possibly shaping the helper T-cell program within germinal centers (GCs). In this context, we paid a particular attention to B-cell-activating factor (BAFF), a key cytokine in B-cell development and immune response that is overproduced during HIV/SIV infection. As it does in autoimmune diseases, BAFF excess might contribute to the abnormal rescue of self-reactive B-cells at several checkpoints of the B-cell development and impair memory B-cell generation and functions. In this review, we first point out what is known about the functions of BAFF/a proliferation-inducing ligand and their receptors [B-cell maturation, transmembrane activator and CAML interactor (TACI), and BAFF-R], in physiological and pathophysiological settings, in mice and humans. In particular, we highlight recent results on the previously underappreciated regulatory functions of TACI and on the highly regulated production of soluble TACI and BAFF-R that act as decoy receptors. In light of recent data on BAFF, TACI, and BAFF-R, we then revisit the altered phenotypes and functions of B-cell subsets during the acute and chronic phase of HIV/SIV infection. Given the atypical phenotype and reduced functions of memory B-cells in HIV/SIV infection, we particularly discuss the GC reaction, a key checkpoint where self-reactive B-cells are eliminated and pathogen-specific memory B-cells and plasmablasts/cells are generated in physiological settings. Through its capacity to differentially bind and process BAFF-R and

  2. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

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    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  3. CD4 depletion in SIV-infected macaques results in macrophage and microglia infection with rapid turnover of infected cells.

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    Luca Micci

    2014-10-01

    Full Text Available In rhesus macaques (RMs, experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes. In this study we used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigate the sources of the increased viral burden and the lifespan of productively infected cells. CD4-depleted animals showed (i set-point viral load two-logs higher than controls; (ii macrophages constituting 80% of all SIV vRNA+ cells in lymph node and mucosal tissues; (iii substantial expansion of pro-inflammatory monocytes; (iv aberrant activation and infection of microglial cells; and (v lifespan of productively infected cells significantly longer in comparison to controls, but markedly shorter than previously estimated for macrophages. The net effect of CD4+ T-cell depletion is an inability to control SIV replication and a shift in the tropism of infected cells to macrophages, microglia, and, potentially, other CD4-low cells which all appear to have a shortened in vivo lifespan. We believe these findings have important implications for HIV eradication studies.

  4. Stability of the Gorilla Microbiome Despite SIV Infection

    Science.gov (United States)

    Moeller, Andrew H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H.; Ochman, Howard

    2015-01-01

    Simian Immunodeficiency Viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in fecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1 infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune-system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority. PMID:25545295

  5. Collapse of Cytolytic Potential in SIV-Specific CD8+ T Cells Following Acute SIV Infection in Rhesus Macaques.

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    Emily R Roberts

    2016-12-01

    Full Text Available Poor maintenance of cytotoxic factor expression among HIV-specific CD8+ T cells, in part caused by dysregulated expression of the transcription factor T-bet, is associated with HIV disease progression. However, the precise evolution and context in which CD8+ T cell cytotoxic functions become dysregulated in HIV infection remain unclear. Using the rhesus macaque (RM SIV infection model, we evaluated the kinetics of SIV-specific CD8+ T cell cytolytic factor expression in peripheral blood, lymph node, spleen, and gut mucosa from early acute infection through chronic infection. We identified rapid acquisition of perforin and granzyme B expression in SIV-specific CD8+ T cells in blood, secondary lymphoid tissues and gut mucosa that collapsed rapidly during the transition to chronic infection. The evolution of this expression profile was linked to low expression of T-bet and occurred independent of epitope specificity, viral escape patterns and tissue origin. Importantly, during acute infection SIV-specific CD8+ T cells that maintained T-bet expression retained the ability to express granzyme B after stimulation, but this relationship was lost in chronic infection. Together, these data demonstrate the loss of cytolytic machinery in SIV-specific CD8+ T cells in blood and at tissue sites of viral reservoir and active replication during the transition from acute to chronic infection. This phenomenon occurs despite persistent high levels of viremia suggesting that an inability to maintain properly regulated cytotoxic T cell responses in all tissue sites enables HIV/SIV to avoid immune clearance, establish persistent viral reservoirs in lymphoid tissues and gut mucosa, and lead ultimately to immunopathogenesis and death.

  6. CTLA-4+PD-1-Memory CD4+T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques.

    Science.gov (United States)

    McGary, Colleen S; Deleage, Claire; Harper, Justin; Micci, Luca; Ribeiro, Susan P; Paganini, Sara; Kuri-Cervantes, Leticia; Benne, Clarisse; Ryan, Emily S; Balderas, Robert; Jean, Sherrie; Easley, Kirk; Marconi, Vincent; Silvestri, Guido; Estes, Jacob D; Sekaly, Rafick-Pierre; Paiardini, Mirko

    2017-10-17

    Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1 + follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4 + PD-1 - memory CD4 + T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus. In contrast to PD-1 + Tfh cells, SIV-enriched CTLA-4 + PD-1 - CD4 + T cells were found outside the B cell follicle of the LN, predicted the size of the persistent viral reservoir during ART, and significantly increased their contribution to the SIV reservoir with prolonged ART-mediated viral suppression. We have shown that CTLA-4 + PD-1 - memory CD4 + T cells are a previously unrecognized component of the SIV and HIV reservoir that should be therapeutically targeted for a functional HIV-1 cure. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Sodium-Reduced Meat and Poultry Products Contain a Significant Amount of Potassium from Food Additives.

    Science.gov (United States)

    Parpia, Arti Sharma; Goldstein, Marc B; Arcand, JoAnne; Cho, France; L'Abbé, Mary R; Darling, Pauline B

    2018-01-06

    counterparts (mean difference [95% CI]: 486 [334-638]; Padditives appearing on the product label ingredient list, did not significantly differ between the two groups. Potassium additives are frequently added to sodium-reduced MPPs in amounts that significantly contribute to the potassium load for patients with impaired renal handling of potassium caused by chronic kidney disease and certain medications. Patients requiring potassium restriction should be counseled to be cautious regarding the potassium content of sodium-reduced MPPs and encouraged to make food choices accordingly. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  8. Characterization of founder viruses in very early SIV rectal transmission.

    Science.gov (United States)

    Yuan, Zhe; Ma, Fangrui; Demers, Andrew J; Wang, Dong; Xu, Jianqing; Lewis, Mark G; Li, Qingsheng

    2017-02-01

    A better understanding of HIV-1 transmission is critical for developing preventative strategies. To that end, we analyzed 524 full-length env sequences of SIVmac251 at 6 and 10 days post intrarectal infection of rhesus macaques. There was no tissue compartmentalization of founder viruses across plasma, rectal and distal lymphatic tissues for most animals; however one animal has evidence of virus tissue compartmentalization. Despite identical viral inoculums, founder viruses were animal-specific, primarily derived from rare variants in the inoculum, and have a founder virus signature that can distinguish dominant founder variants from minor founder or untransmitted variants in the inoculum. Importantly, the sequences of post-transmission defective viruses were phylogenetically associated with competent viral variants in the inoculum and were mainly converted from competent viral variants by frameshift rather than APOBEC mediated mutations, suggesting the converting the transmitted viruses into defective viruses through frameshift mutation is an important component of rectal transmission bottleneck. Anorectal receptive intercourse is a common route of HIV-1 transmission and a better understanding of the transmission mechanisms is critical for developing HIV-1 preventative strategies. Here, we report that there is no tissue compartmentalization of founder viruses during very early rectal transmission of SIV in the majority of rhesus macaques and founder viruses are preferentially derived from rare variant in the inoculum. We also found that founder viruses are animal-specific despite identical viral inoculums. After viruses cross the mucosal barriers, the host further reduces viral diversity by converting some of the transmitted functional viruses into defective viruses through frameshift rather than APOBEC derived mutations. To our knowledge, this is the first study of founder viruses at multiple tissue sites during very early rectal transmission. Copyright © 2016

  9. Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.

    Science.gov (United States)

    Byrareddy, Siddappa N; Kallam, Brianne; Arthos, James; Cicala, Claudia; Nawaz, Fatima; Hiatt, Joseph; Kersh, Ellen N; McNicholl, Janet M; Hanson, Debra; Reimann, Keith A; Brameier, Markus; Walter, Lutz; Rogers, Kenneth; Mayne, Ann E; Dunbar, Paul; Villinger, Tara; Little, Dawn; Parslow, Tristram G; Santangelo, Philip J; Villinger, Francois; Fauci, Anthony S; Ansari, Aftab A

    2014-12-01

    α4β7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4β7 reduces mucosal transmission of SIV in macaques.

  10. Vaccination and timing influence SIV immune escape viral dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Liyen Loh

    2008-01-01

    Full Text Available CD8+ cytotoxic T lymphocytes (CTL can be effective at controlling HIV-1 in humans and SIV in macaques, but their utility is partly offset by mutational escape. The kinetics of CTL escape and reversion of escape mutant viruses upon transmission to MHC-mismatched hosts can help us understand CTL-mediated viral control and the fitness cost extracted by immune escape mutation. Traditional methods for following CTL escape and reversion are, however, insensitive to minor viral quasispecies. We developed sensitive quantitative real-time PCR assays to track the viral load of SIV Gag164-172 KP9 wild-type (WT and escape mutant (EM variants in pigtail macaques. Rapid outgrowth of EM virus occurs during the first few weeks of infection. However, the rate of escape plateaued soon after, revealing a prolonged persistence of WT viremia not detectable by standard cloning and sequencing methods. The rate of escape of KP9 correlated with levels of vaccine-primed KP9-specific CD8+ T cells present at that time. Similarly, when non-KP9 responder (lacking the restricting Mane-A*10 allele macaques were infected with SHIVmn229 stock containing a mixture of EM and WT virus, rapid reversion to WT was observed over the first 2 weeks following infection. However, the rate of reversion to WT slowed dramatically over the first month of infection. The serial quantitation of escape mutant viruses evolving during SIV infection shows that rapid dynamics of immune escape and reversion can be observed in early infection, particularly when CD8 T cells are primed by vaccination. However, these early rapid rates of escape and reversion are transient and followed by a significant slowing in these rates later during infection, highlighting that the rate of escape is significantly influenced by the timing of its occurrence.

  11. [Heart rate variability is significantly reduced in non-diabetic patients with hypertension].

    Science.gov (United States)

    Nagy, Krisztina; Sipos, Evelin; El Hadj Othmane, Taha

    2014-06-01

    Heart rate variability is reduced among patients with hypertension and/or with diabetes mellitus. Hypertension and diabetes show frequent co-morbidity, but it is still not entirely clear whether heart rate variability is reduced in non-diabetic patients with hypertension. The aim of the authors was to evaluate the heart rate variability in hypertensive patients with and without diabetes and in control subjects. 130 patients with hypertension, 48 patients with hypertension and type 2 diabetes mellitus, and 87 control subjects were involved in the study. Minimum, mean and maximum heart rate, and parameters of heart rate variability were measured. The mean of minimum heart rate did not differ significantly between the three groups. However, all other parameters were significantly reduced in patients with hypertension with and without diabetes as compared to the control group. No significant differences were observed between hypertensive patients with and without diabetes mellitus. Heart rate variability is significantly reduced in non-diabetic patients with hypertension. It seems that type 2 diabetes results in no further significant reduction of heart rate variability in patients with hypertension.

  12. Aged Chinese-origin rhesus macaques infected with SIV develop marked viremia in absence of clinical disease, inflammation or cognitive impairment.

    Science.gov (United States)

    Bissel, Stephanie J; Gurnsey, Kate; Jedema, Hank P; Smith, Nicholas F; Wang, Guoji; Bradberry, Charles W; Wiley, Clayton A

    2018-02-01

    Damage to the central nervous system during HIV infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND). There is no clear consensus regarding the neuropathological or cellular basis of HAND. We sought to study the potential contribution of aging to the pathogenesis of HAND. Aged (range = 14.7-24.8 year) rhesus macaques of Chinese origin (RM-Ch) (n = 23) were trained to perform cognitive tasks. Macaques were then divided into four groups to assess the impact of SIVmac251 infection (n = 12) and combined antiretroviral therapy (CART) (5 infected; 5 mock-infected) on the execution of these tasks. Aged SIV-infected RM-Ch demonstrated significant plasma viremia and modest CSF viral loads but showed few clinical signs, no elevations of systemic temperature, and no changes in activity levels, platelet counts or weight. Concentrations of biomarkers of acute and chronic inflammation such as soluble CD14, CXCL10, IL-6 and TNF-α are known to be elevated following SIV infection of young adult macaques of several species, but concentrations of these biomarkers did not shift after SIV infection in aged RM-Ch and remained similar to mock-infected macaques. Neither acute nor chronic SIV infection or CART had a significant impact on accuracy, speed or percent completion in a sensorimotor test. Viremia in the absence of a chronic elevated inflammatory response seen in some aged RM-Ch is reminiscent of SIV infection in natural disease resistant hosts. The absence of cognitive impairment during SIV infection in aged RM-Ch might be in part attributed to diminishment of some facets of the immunological response. Additional study encompassing species and age differences is necessary to substantiate this hypothesis.

  13. Identification of Unequally Represented Founder Viruses Among Tissues in Very Early SIV Rectal Transmission

    Directory of Open Access Journals (Sweden)

    Jian Chen

    2018-03-01

    Full Text Available Characterizing the transmitted/founder (T/F viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission. We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 104 TCID50 and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA. All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses was unequally represented in different tissues. This cluster of rare T/F viruses phylogenetically related to the non-dominant SIV variants in the inoculum and was not detected in any rectum tissues, but could be identified in the descending colon, jejunum, spleen, or plasma. In 2 out of 6 macaques, identical SIVmac251 variants belonging to this cluster were detected simultaneously in descending colon/jejunum and the inoculum. We also demonstrated that the average CG dinucleotide frequency of these rare T/F viruses found in tissues, as well as non-dominant variants in the inoculum, was significantly higher than the dominant T/F viruses in tissues and the inoculum. Collectively, these findings suggest that descending colon/jejunum might be more susceptible than rectum to SIV in the very early phase of infection. And host CG suppression, which was previously shown to inhibit HIV replication in vitro, may also contribute to the bottleneck selection during in vivo transmission.

  14. Decreased number of CD4+ and CD8+ T cells that express the interleukin-7 receptor in blood and tissues of SIV-infected macaques

    International Nuclear Information System (INIS)

    Moniuszko, Marcin; Edghill-Smith, Yvette; Venzon, David; Stevceva, Liljana; Nacsa, Janos; Tryniszewska, Elzbieta; Tsai, Wen-Po; Franchini, Genoveffa

    2006-01-01

    Acute HIV/SIV (human/simian immunodeficiency virus) infection results in severe CD4 + T cell depletion in lymphoid compartments. During the chronic phase of infection, CD4 + T cell numbers rebound in blood but remain low in the gut-associated lymphoid tissue (GALT), even when viral replication is suppressed by antiretroviral therapy (ART). Thus, strategies to repopulate lymphoid compartments may ameliorate the clinical outcome of HIV/SIV infection. Interleukin (IL)-7 is a key cytokine for the maintenance of homeostatic proliferation of T cells. In HIV/SIV infection, IL-7 expression is increased, likely to compensate for T cell loss, suggesting that supraphysiological administration of IL-7 could provide additional benefit. However, the ability of T cells to respond to IL-7 is dependent on the level of expression of the IL-7 receptor (IL-7R) in T cells in various body compartments. In here, we investigated the proportion of IL-7R + T cells in blood, spleen, gut, and genitourinary tract of healthy and SIV-infected macaques with various degrees of CD4 + T cell depletion. We found that the percentage of T cells expressing IL-7R was significantly lower in both CD4 + and CD8 + T cell subsets in SIV-infected macaques than in healthy animals and this decrease directly correlated with the CD4 + T cell number. Importantly, the proportion of CD4 + and CD8 + T cells expressing IL-7R in blood paralleled that found in tissues. IL-7R + T cells within the SIV-specific CD8 + T cells varied and were lowest in most tissues of viremic macaques, likely reflecting continuous antigen stimulation of effector cells

  15. Defibrillator charging before rhythm analysis significantly reduces hands-off time during resuscitation

    DEFF Research Database (Denmark)

    Hansen, L. K.; Folkestad, L.; Brabrand, M.

    2013-01-01

    tachycardia and asystole were presented randomly to all participants in a simulation setting. A manikin (Resusci Anne; Laerdal Scandinavia A/S, Stavanger, Norway) and a defibrillator (LIFEPACK 12; Physio-Control, Inc, Redmond, WA, USA) were used. In ALT, chest compressions were only interrupted...... was observed in either of the asystole scenarios. CONCLUSION: In a simulation setting, we demonstrated that charging of the defibrillator before rhythm analysis significantly reduced hands-off time compared with the ERC 2005 and ERC 2010 guidelines....

  16. Thrombolysis significantly reduces transient myocardial ischaemia following first acute myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H; Pless, P; Nielsen, J R

    1992-01-01

    In order to investigate whether thrombolysis affects residual myocardial ischaemia, we prospectively performed a predischarge maximal exercise test and early out-of-hospital ambulatory ST segment monitoring in 123 consecutive men surviving a first acute myocardial infarction (AMI). Seventy...... less than 0.02). Thrombolysis resulted in a non-significant reduction in exercise-induced ST segment depression: prevalence 43% vs 62% in controls. However, during ambulatory monitoring the duration of transient myocardial ischaemia was significantly reduced in thrombolysed patients: 322 min vs 1144...... myocardial ischaemia. This may explain the improvement in myocardial function during physical activities, which was also observed in this study....

  17. Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV vaccines compared to live-attenuated SIV.

    Science.gov (United States)

    Van Rompay, Koen K A; Abel, Kristina; Earl, Patricia; Kozlowski, Pamela A; Easlick, Juliet; Moore, Joseph; Buonocore-Buzzelli, Linda; Schmidt, Kimberli A; Wilson, Robert L; Simon, Ian; Moss, Bernard; Rose, Nina; Rose, John; Marthas, Marta L

    2010-02-10

    In a previously developed infant macaque model mimicking HIV infection by breast-feeding, we demonstrated that intramuscular immunization with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins provided partial protection against infection following oral inoculation with virulent SIV. In an attempt to further increase systemic but also local antiviral immune responses at the site of viral entry, we tested the immunogenicity of different orally administered, replicating vaccines. One group of newborn macaques received an oral prime immunization with a recombinant vesicular stomatitis virus expressing SIVmac239 gag, pol and env (VSV-SIVgpe), followed 2 weeks later by an intramuscular boost immunization with MVA-SIV. Another group received two immunizations with live-attenuated SIVmac1A11, administered each time both orally and intravenously. Control animals received mock immunizations or non-SIV VSV and MVA control vectors. Analysis of SIV-specific immune responses in blood and lymphoid tissues at 4 weeks of age demonstrated that both vaccine regimens induced systemic antibody responses and both systemic and local cell-mediated immune responses. The safety and immunogenicity of the VSV-SIVgpe+MVA-SIV immunization regimen described in this report provide the scientific incentive to explore the efficacy of this vaccine regimen against virulent SIV exposure in the infant macaque model. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  18. Transcription Profiling Reveals Potential Mechanisms of Dysbiosis in the Oral Microbiome of Rhesus Macaques with Chronic Untreated SIV Infection

    Science.gov (United States)

    Ocon, Susan; Murphy, Christina; Dang, Angeline T.; Sankaran-Walters, Sumathi; Li, Chin-Shang; Tarara, Ross; Borujerdpur, Niku; Dandekar, Satya; Paster, Bruce J.; George, Michael D.

    2013-01-01

    A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and “macaque versions” of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides. PMID:24312248

  19. Partial protection of SIV-infected rhesus monkeys against superinfection with a heterologous SIV isolate

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory

    2009-01-01

    Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virus for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4(+) T-cell count, CD4(+) memory T-cell subsets, cytokine production by virus-specific CD8(+) or CD4(+) cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4(+) T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.

  20. Properties of Si:V Annealed under Enhanced Hydrostatic Pressure

    International Nuclear Information System (INIS)

    Misiuk, A.; Wierzchowski, W.; Wieteska, K.; Barcz, A.; Bak-Misiuk, J.; Chow, L.; Vanfleet, R.; Prujszczyk, M.

    2011-01-01

    It is known that processing of silicon implanted with vanadium, Si:V, at high temperature-pressure, HT-HP, can lead to magnetic ordering within the V-enriched area. New data concerning structure of Si:V (prepared using V + doses, D = (1-5) x 10 15 cm -2 , and energy, E = 200 keV), as implanted and processed for up to 10 h at HT ≤ 1400 K under enhanced hydrostatic pressure, HP ≤ 1.1 GPa, are presented. In effect of implantation, amorphous (a-Si) area is produced near range of implanted species. Transmission electron microscopy, secondary ion mass spectrometry, X-ray, and synchrotron methods were used for sample characterisation. At HT-HP the a-Si layer is subjected to solid phase epitaxial re-growth. Depending on HP, distinct solid phase epitaxial re-growth and formation of VSi 2 are observed at HT ≥ 720 K. HP applied at processing results in the improved solid phase epitaxial re-growth in Si:V. This can be related, among others, to the effect of HP on diffusivity of V + and of implantation-induced point defects. Our results can be useful for development of the new family of diluted magnetic semiconductors. (author)

  1. Expansion of Simian Immunodeficiency Virus (SIV)-Specific CD8 T Cell Lines from SIV-Naive Mauritian Cynomolgus Macaques for Adoptive Transfer.

    Science.gov (United States)

    Mohns, Mariel S; Greene, Justin M; Cain, Brian T; Pham, Ngoc H; Gostick, Emma; Price, David A; O'Connor, David H

    2015-10-01

    CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). However, the specific qualities and characteristics of an effective CD8 T cell response remain unclear. Although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with HIV control, further investigation is needed to determine the precise contributions of these various attributes to CD8 T cell efficacy. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques (MCM). These cells exhibited an effector memory phenotype, produced cytokines in response to cognate antigen, and suppressed viral replication in vitro. We further cultured cell lines specific for four SIV-derived epitopes, Nef103-111 RM9, Gag389-394 GW9, Env338-346 RF9, and Nef254-262 LT9. These cell lines were up to 94.4% pure, as determined by major histocompatibility complex (MHC) tetramer analysis. After autologous transfer into two MCM recipients, expanded CD8 T cells persisted in peripheral blood and lung tissue for at least 24 weeks and trafficked to multiple extralymphoid tissues. However, these cells did not impact the acute-phase SIV load after challenge compared to historic controls. The expansion and autologous transfer of SIV-specific T cells into naive animals provide a unique model for exploring cellular immunity and the control of SIV infection and facilitate a systematic evaluation of therapeutic adoptive transfer strategies for eradication of the latent reservoir. CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Autologous adoptive transfer studies followed by SIV challenge may help define the critical elements of an effective T cell response to HIV and SIV infection. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus

  2. A Chimpanzee Recognizes Synthetic Speech With Significantly Reduced Acoustic Cues to Phonetic Content

    Science.gov (United States)

    Heimbauer, Lisa A.; Beran, Michael J.; Owren, Michael J.

    2011-01-01

    Summary A long-standing debate concerns whether humans are specialized for speech perception [1–7], which some researchers argue is demonstrated by the ability to understand synthetic speech with significantly reduced acoustic cues to phonetic content [2–4,7]. We tested a chimpanzee (Pan troglodytes) that recognizes 128 spoken words [8,9], asking whether she could understand such speech. Three experiments presented 48 individual words, with the animal selecting a corresponding visuo-graphic symbol from among four alternatives. Experiment 1 tested spectrally reduced, noise-vocoded (NV) synthesis, originally developed to simulate input received by human cochlear-implant users [10]. Experiment 2 tested “impossibly unspeechlike” [3] sine-wave (SW) synthesis, which reduces speech to just three moving tones [11]. Although receiving only intermittent and non-contingent reward, the chimpanzee performed well above chance level, including when hearing synthetic versions for the first time. Recognition of SW words was least accurate, but improved in Experiment 3 when natural words in the same session were rewarded. The chimpanzee was more accurate with NV than SW versions, as were 32 human participants hearing these items. The chimpanzee's ability to spontaneously recognize acoustically reduced synthetic words suggests that experience rather than specialization is critical for speech-perception capabilities that some have suggested are uniquely human [12–14]. PMID:21723125

  3. A chimpanzee recognizes synthetic speech with significantly reduced acoustic cues to phonetic content.

    Science.gov (United States)

    Heimbauer, Lisa A; Beran, Michael J; Owren, Michael J

    2011-07-26

    A long-standing debate concerns whether humans are specialized for speech perception, which some researchers argue is demonstrated by the ability to understand synthetic speech with significantly reduced acoustic cues to phonetic content. We tested a chimpanzee (Pan troglodytes) that recognizes 128 spoken words, asking whether she could understand such speech. Three experiments presented 48 individual words, with the animal selecting a corresponding visuographic symbol from among four alternatives. Experiment 1 tested spectrally reduced, noise-vocoded (NV) synthesis, originally developed to simulate input received by human cochlear-implant users. Experiment 2 tested "impossibly unspeechlike" sine-wave (SW) synthesis, which reduces speech to just three moving tones. Although receiving only intermittent and noncontingent reward, the chimpanzee performed well above chance level, including when hearing synthetic versions for the first time. Recognition of SW words was least accurate but improved in experiment 3 when natural words in the same session were rewarded. The chimpanzee was more accurate with NV than SW versions, as were 32 human participants hearing these items. The chimpanzee's ability to spontaneously recognize acoustically reduced synthetic words suggests that experience rather than specialization is critical for speech-perception capabilities that some have suggested are uniquely human. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Expression of IL-18 by SIV does not modify the outcome of the antiviral immune response.

    Science.gov (United States)

    Giavedoni, Luis D; Velasquillo, M Cristina; Parodi, Laura M; Hubbard, Gene B; Hodara, Vida L

    2002-11-25

    Interleukin 18 (IL-18) is a proinflammatory cytokine expressed by several cell types, including activated dendritic cells and macrophages, that acts in synergy with IL-12 as an important amplifying factor for IFN-gamma production and Th1 development. To study the immunological and virological effects of IL-18 expression in the context of a lentiviral infection, we inoculated rhesus macaques with a high dose of replication-competent simian immunodeficiency virus (SIV) vectors carrying the rhesus IL-18 gene in the sense (SIV(IL-18)) or antisense (SIV(FIGI)) orientation. Both vectors behaved as attenuated viruses, resulting in low viral loads, induction of low and transient levels of inflammatory cytokines, no CD4(+) T cell depletion, and mild activation of T lymphocytes. Although IL-18-expressing virus could be isolated from some SIV(IL18)-infected macaques for 12 weeks postinfection, the anti-SIV humoral and cellular immune responses of macaques inoculated with SIV(IL18) and SIV(FIGI) were similar to each other, with the exception of an early IFN-gamma response in animals infected with SIV(IL18). In summary, expression of IL-18 during the acute phase of SIV infection does not increase viral replication or influence the outcome of the antiviral immune response.

  5. Reduced content of chloroatranol and atranol in oak moss absolute significantly reduces the elicitation potential of this fragrance material.

    Science.gov (United States)

    Andersen, Flemming; Andersen, Kirsten H; Bernois, Armand; Brault, Christophe; Bruze, Magnus; Eudes, Hervé; Gadras, Catherine; Signoret, Anne-Cécile J; Mose, Kristian F; Müller, Boris P; Toulemonde, Bernard; Andersen, Klaus Ejner

    2015-02-01

    Oak moss absolute, an extract from the lichen Evernia prunastri, is a valued perfume ingredient but contains extreme allergens. To compare the elicitation properties of two preparations of oak moss absolute: 'classic oak moss', the historically used preparation, and 'new oak moss', with reduced contents of the major allergens atranol and chloroatranol. The two preparations were compared in randomized double-blinded repeated open application tests and serial dilution patch tests in 30 oak moss-sensitive volunteers and 30 non-allergic control subjects. In both test models, new oak moss elicited significantly less allergic contact dermatitis in oak moss-sensitive subjects than classic oak moss. The control subjects did not react to either of the preparations. New oak moss is still a fragrance allergen, but elicits less allergic contact dermatitis in previously oak moss-sensitized individuals, suggesting that new oak moss is less allergenic to non-sensitized individuals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Significantly improved photocurrent response of ZnS-reduced graphene oxide composites

    International Nuclear Information System (INIS)

    Sookhakian, M.; Amin, Y.M.; Zakaria, R.; Basirun, W.J.; Mahmoudian, M.R.; Nasiri-Tabrizi, B.; Baradaran, S.; Azarang, Majid

    2015-01-01

    Highlights: • ZnS/reduced graphene oxide nanoparticles by hydrothermal method. • ZnS nanoparticles in a gelatin medium without agglomeration. • Support of ZnS shows efficient photocurrent response. • The fabricated solar cell electrode improved in the presence of reduced graphene oxide. - Abstract: ZnS-nanoparticles (NPs) reduced graphene oxide (rGO) composites with a high degree of crystallinity and high dispersity were successfully synthesized via a facile solvothermal method in the gelatin medium, during which the formation of ZnS NPs, reduction of graphene oxide and loading of ZnS NPs into the rGO surface occur simultaneously. Gelatin, as a natural capping agent, plays a significant role in controlling the degree of dispersion and coverage of ZnS NPs. The effect of rGO on the crystalline structure and optical properties of ZnS NPs were determined via X-ray diffraction, UV–visible diffused reflectance spectroscopy and photoluminescence spectroscopy. The ZnS–rGO composites exhibit excellent potential for photocurrent generation compared with pure ZnS NPs under visible light irradiation, provided that efficient photoinduced charge separation and transportation can be achieved at the interface. The maximum photocurrent response was obtained for ZnS–rGO composite with a 3% mass fraction of rGO, which is 2 times that achieved on pure ZnS NPs

  7. Significantly improved photocurrent response of ZnS-reduced graphene oxide composites

    Energy Technology Data Exchange (ETDEWEB)

    Sookhakian, M., E-mail: m.sokhakian@gmail.com [Department of Physics, Faculty of Science, University of Malaya, Kuala Lumpur 50603 (Malaysia); Amin, Y.M. [Department of Physics, Faculty of Science, University of Malaya, Kuala Lumpur 50603 (Malaysia); Zakaria, R. [Department of Physics, Faculty of Science, University of Malaya, Kuala Lumpur 50603 (Malaysia); Photonics Research Centre, Faculty of Science, University of Malaya, Kuala Lumpur 50603 (Malaysia); Basirun, W.J. [Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603 (Malaysia); Institute of Nanotechnology & Catalysis Research (NanoCat), University Malaya, Kuala Lumpur 50603 (Malaysia); Mahmoudian, M.R. [Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603 (Malaysia); Nasiri-Tabrizi, B.; Baradaran, S. [Department of Mechanical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603 (Malaysia); Azarang, Majid [Department of Physics, Faculty of Science, University of Malaya, Kuala Lumpur 50603 (Malaysia)

    2015-05-25

    Highlights: • ZnS/reduced graphene oxide nanoparticles by hydrothermal method. • ZnS nanoparticles in a gelatin medium without agglomeration. • Support of ZnS shows efficient photocurrent response. • The fabricated solar cell electrode improved in the presence of reduced graphene oxide. - Abstract: ZnS-nanoparticles (NPs) reduced graphene oxide (rGO) composites with a high degree of crystallinity and high dispersity were successfully synthesized via a facile solvothermal method in the gelatin medium, during which the formation of ZnS NPs, reduction of graphene oxide and loading of ZnS NPs into the rGO surface occur simultaneously. Gelatin, as a natural capping agent, plays a significant role in controlling the degree of dispersion and coverage of ZnS NPs. The effect of rGO on the crystalline structure and optical properties of ZnS NPs were determined via X-ray diffraction, UV–visible diffused reflectance spectroscopy and photoluminescence spectroscopy. The ZnS–rGO composites exhibit excellent potential for photocurrent generation compared with pure ZnS NPs under visible light irradiation, provided that efficient photoinduced charge separation and transportation can be achieved at the interface. The maximum photocurrent response was obtained for ZnS–rGO composite with a 3% mass fraction of rGO, which is 2 times that achieved on pure ZnS NPs.

  8. Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector.

    Science.gov (United States)

    Zhang, Xinsheng; Wallace, Olivia; Wright, Kevin J; Backer, Martin; Coleman, John W; Koehnke, Rebecca; Frenk, Esther; Domi, Arban; Chiuchiolo, Maria J; DeStefano, Joanne; Narpala, Sandeep; Powell, Rebecca; Morrow, Gavin; Boggiano, Cesar; Zamb, Timothy J; Richter King, C; Parks, Christopher L

    2013-11-01

    We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert designs. Vectors containing a gene inserted between the CDV H and L genes, which encoded Env lacking most of its cytoplasmic tail, propagated efficiently in Vero cells, expressed the immunogen on the cell surface, and incorporated the SIV glycoprotein into progeny virus particles. When ferrets were vaccinated intranasally, there were no signs of distress, vector replication was observed in the gut-associated lymphoid tissues, and the animals produced anti-SIV Env antibodies. These data show that live CDV-SIV Env vectors can safely induce anti-Env immune responses following intranasal vaccination. © 2013 Elsevier Inc. All rights reserved.

  9. Aluminum sulfate significantly reduces the skin test response to common allergens in sensitized patients

    Directory of Open Access Journals (Sweden)

    Grier Thomas J

    2006-02-01

    Full Text Available Abstract Background Avoidance of allergens is still recommended as the first and best way to prevent allergic illnesses and their comorbid diseases. Despite a variety of attempts there has been very limited success in the area of environmental control of allergic disease. Our objective was to identify a non-invasive, non-pharmacological method to reduce indoor allergen loads in atopic persons' homes and public environments. We employed a novel in vivo approach to examine the possibility of using aluminum sulfate to control environmental allergens. Methods Fifty skin test reactive patients were simultaneously skin tested with conventional test materials and the actions of the protein/glycoprotein modifier, aluminum sulfate. Common allergens, dog, cat, dust mite, Alternaria, and cockroach were used in the study. Results Skin test reactivity was significantly reduced by the modifier aluminum sulfate. Our studies demonstrate that the effects of histamine were not affected by the presence of aluminum sulfate. In fact, skin test reactivity was reduced independent of whether aluminum sulfate was present in the allergen test material or removed prior to testing, indicating that the allergens had in some way been inactivated. Conclusion Aluminum sulfate was found to reduce the in vivo allergic reaction cascade induced by skin testing with common allergens. The exact mechanism is not clear but appears to involve the alteration of IgE-binding epitopes on the allergen. Our results indicate that it may be possible to diminish the allergenicity of an environment by application of the active agent aluminum sulfate, thus producing environmental control without complete removal of the allergen.

  10. Four-phonon scattering significantly reduces intrinsic thermal conductivity of solids

    Science.gov (United States)

    Feng, Tianli; Lindsay, Lucas; Ruan, Xiulin

    2017-10-01

    For decades, the three-phonon scattering process has been considered to govern thermal transport in solids, while the role of higher-order four-phonon scattering has been persistently unclear and so ignored. However, recent quantitative calculations of three-phonon scattering have often shown a significant overestimation of thermal conductivity as compared to experimental values. In this Rapid Communication we show that four-phonon scattering is generally important in solids and can remedy such discrepancies. For silicon and diamond, the predicted thermal conductivity is reduced by 30% at 1000 K after including four-phonon scattering, bringing predictions in excellent agreement with measurements. For the projected ultrahigh-thermal conductivity material, zinc-blende BAs, a competitor of diamond as a heat sink material, four-phonon scattering is found to be strikingly strong as three-phonon processes have an extremely limited phase space for scattering. The four-phonon scattering reduces the predicted thermal conductivity from 2200 to 1400 W/m K at room temperature. The reduction at 1000 K is 60%. We also find that optical phonon scattering rates are largely affected, being important in applications such as phonon bottlenecks in equilibrating electronic excitations. Recognizing that four-phonon scattering is expensive to calculate, in the end we provide some guidelines on how to quickly assess the significance of four-phonon scattering, based on energy surface anharmonicity and the scattering phase space. Our work clears the decades-long fundamental question of the significance of higher-order scattering, and points out ways to improve thermoelectrics, thermal barrier coatings, nuclear materials, and radiative heat transfer.

  11. Distinct phenotype, longitudinal changes of numbers and cell-associated virus in blood dendritic cells in SIV-infected CD8-lymphocyte depleted macaques.

    Directory of Open Access Journals (Sweden)

    Caroline Soulas

    Full Text Available Loss of circulating CD123+ plasmacytoid dendritic cells (pDCs during HIV infection is well established. However, changes of myeloid DCs (mDCs are ambiguous since they are studied as a homogeneous CD11c+ population despite phenotypic and functional heterogeneity. Heterogeneity of CD11c+ mDCs in primates is poorly described in HIV and SIV infection. Using multiparametric flow cytometry, we monitored longitudinally cell number and cell-associated virus of CD123+ pDCs and non-overlapping subsets of CD1c+ and CD16+ mDCs in SIV-infected CD8-depleted rhesus macaques. The numbers of all three DC subsets were significantly decreased by 8 days post-infection. Whereas CD123+ pDCs were persistently depleted, numbers of CD1c+ and CD16+ mDCs rebounded. Numbers of CD1c+ mDCs significantly increased by 3 weeks post-infection while numbers of CD16+ mDCs remained closer to pre-infection levels. We found similar changes in the numbers of all three DC subsets in CD8 depleted animals as we found in animals that were SIV infected animals that were not CD8 lymphocyte depleted. CD16+ mDCs and CD123+ pDCs but not CD1c+ mDCs were significantly decreased terminally with AIDS. All DC subsets harbored SIV RNA as early as 8 days and then throughout infection. However, SIV DNA was only detected in CD123+ pDCs and only at 40 days post-infection consistent with SIV RNA, at least in mDCs, being surface-bound. Altogether our data demonstrate that SIV infection differently affects CD1c+ and CD16+ mDCs where CD16+ but not CD1c+ mDCs are depleted and might be differentially regulated in terminal AIDS. Finally, our data underline the importance of studying CD1c+ and CD16+ mDCs as discrete populations, and not as total CD11c+ mDCs.

  12. Solar light irradiation significantly reduced cytotoxicity and disinfection byproducts in chlorinated reclaimed water.

    Science.gov (United States)

    Lv, Xiao-Tong; Zhang, Xue; Du, Ye; Wu, Qian-Yuan; Lu, Yun; Hu, Hong-Ying

    2017-11-15

    Chlorinated reclaimed water is widely used for landscaping and recreational purposes, resulting in human exposure to toxic disinfection byproducts. Although the quality of chlorinated reclaimed water might be affected by sunlight during storage, the effects of solar light irradiation on the toxicity remain unknown. This study investigated the changes in cytotoxicity and total organic halogen (TOX) of chlorinated reclaimed water exposed to solar light. Irradiation with solar light for 12 h was found to significantly reduce the cytotoxicity of chlorinated reclaimed water by about 75%, with ultraviolet light being responsible for the majority of this reduction. Chlorine residual in reclaimed water tended to increase the cytotoxicity, and the synergy between solar light and free chlorine could not enhance the reduction of cytotoxicity. Adding hydroxyl radical scavengers revealed that the contribution of hydroxyl radical to cytotoxicity reduction was limited. Solar light irradiation concurrently reduced TOX. The low molecular weight (cytotoxicity and TOX in chlorinated reclaimed water. Detoxification of the low molecular weight fraction by light irradiation was mainly a result of TOX dehalogenation, while detoxification of the high molecular weight (>1 kDa) fraction was probably caused by photoconversion from high toxic TOX to low toxic TOX. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Nano-CL-20/HMX Cocrystal Explosive for Significantly Reduced Mechanical Sensitivity

    Directory of Open Access Journals (Sweden)

    Chongwei An

    2017-01-01

    Full Text Available Spray drying method was used to prepare cocrystals of hexanitrohexaazaisowurtzitane (CL-20 and cyclotetramethylene tetranitramine (HMX. Raw materials and cocrystals were characterized using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, Raman spectroscopy, and Fourier transform infrared spectroscopy. Impact and friction sensitivity of cocrystals were tested and analyzed. Results show that, after preparation by spray drying method, microparticles were spherical in shape and 0.5–5 µm in size. Particles formed aggregates of numerous tiny plate-like cocrystals, whereas CL-20/HMX cocrystals had thicknesses of below 100 nm. Cocrystals were formed by C–H⋯O bonding between –NO2 (CL-20 and –CH2– (HMX. Nanococrystal explosives exhibited drop height of 47.3 cm, and friction demonstrated explosion probability of 64%. Compared with raw HMX, cocrystals displayed significantly reduced mechanical sensitivity.

  14. Incorporation of catalytic dehydrogenation into fischer-tropsch synthesis to significantly reduce carbon dioxide emissions

    Science.gov (United States)

    Huffman, Gerald P.

    2012-11-13

    A new method of producing liquid transportation fuels from coal and other hydrocarbons that significantly reduces carbon dioxide emissions by combining Fischer-Tropsch synthesis with catalytic dehydrogenation is claimed. Catalytic dehydrogenation (CDH) of the gaseous products (C1-C4) of Fischer-Tropsch synthesis (FTS) can produce large quantities of hydrogen while converting the carbon to multi-walled carbon nanotubes (MWCNT). Incorporation of CDH into a FTS-CDH plant converting coal to liquid fuels can eliminate all or most of the CO.sub.2 emissions from the water-gas shift (WGS) reaction that is currently used to elevate the H.sub.2 level of coal-derived syngas for FTS. Additionally, the FTS-CDH process saves large amounts of water used by the WGS reaction and produces a valuable by-product, MWCNT.

  15. An enhanced recovery program for bariatric surgical patients significantly reduces perioperative opioid consumption and postoperative nausea.

    Science.gov (United States)

    King, Adam B; Spann, Matthew D; Jablonski, Patrick; Wanderer, Jonathan P; Sandberg, Warren S; McEvoy, Matthew D

    2018-02-13

    Patients frequently remain in the hospital after bariatric surgery due to pain, nausea, and inability to tolerate oral intake. Enhanced recovery after surgery (ERAS) concepts address these perioperative complications and therefore improve length of stay for bariatric surgery patients. To determine if ERAS concepts increase the proportion of patients discharged on postoperative day 1. Secondary objectives included mean length of stay, perioperative opioid use, emergency department visits, and readmissions. A large metropolitan university tertiary hospital. A quantitative before and after study was conducted for patients undergoing bariatric surgical patients. Data were collected surrounding length of stay, perioperative opioid consumption, antiemetic therapy requirements postoperatively, multimodal analgesia compliance, emergency department visits, and hospital readmission rates. Wilcoxon rank-sum and χ 2 test were used to compare continuous and categorical variables, respectively. A secondary analysis was performed using Aligned Rank Transformation and Cochran-Mantel-Haenszel χ 2 tests to account for an increase in sleeve gastrectomies in the intervention group. The 2 groups had clinically similar baseline characteristics. Comparison group (N = 366) and ERAS group (N = 715) patients underwent a primary bariatric surgery procedure. There was an increase in the number of patients undergoing a laparoscopic sleeve gastrectomy in the intervention group. After accounting for this increase, the percentage of patients discharged on postoperative day 1 was unchanged (79.8% non-ERAS versus 83.1% ERAS, P = .52). ERAS length of stay was statistically significantly lower for gastric bypass (P<.001) and robotic gastric bypass (P = .01). Perioperative opioid consumption was reduced (41.0 versus 16.2 morphine equivalents, P<0.001), and fewer ERAS patients required postoperative antiemetics (68.8% versus 46.2%, P<.001). Emergency department visits at 7 days were reduced (6

  16. Induction-heating MOCVD reactor with significantly improved heating efficiency and reduced harmful magnetic coupling

    Science.gov (United States)

    Li, Kuang-Hui; Alotaibi, Hamad S.; Sun, Haiding; Lin, Ronghui; Guo, Wenzhe; Torres-Castanedo, Carlos G.; Liu, Kaikai; Valdes-Galán, Sergio; Li, Xiaohang

    2018-04-01

    In a conventional induction-heating III-nitride metalorganic chemical vapor deposition (MOCVD) reactor, the induction coil is outside the chamber. Therefore, the magnetic field does not couple with the susceptor well, leading to compromised heating efficiency and harmful coupling with the gas inlet and thus possible overheating. Hence, the gas inlet has to be at a minimum distance away from the susceptor. Because of the elongated flow path, premature reactions can be more severe, particularly between Al- and B-containing precursors and NH3. Here, we propose a structure that can significantly improve the heating efficiency and allow the gas inlet to be closer to the susceptor. Specifically, the induction coil is designed to surround the vertical cylinder of a T-shaped susceptor comprising the cylinder and a top horizontal plate holding the wafer substrate within the reactor. Therefore, the cylinder coupled most magnetic field to serve as the thermal source for the plate. Furthermore, the plate can block and thus significantly reduce the uncoupled magnetic field above the susceptor, thereby allowing the gas inlet to be closer. The results show approximately 140% and 2.6 times increase in the heating and susceptor coupling efficiencies, respectively, as well as a 90% reduction in the harmful magnetic flux on the gas inlet.

  17. Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy

    International Nuclear Information System (INIS)

    Braam, Petra M.; Terhaard, Chris H.J. M.D.; Roesink, Judith M.; Raaijmakers, Cornelis P.J.

    2006-01-01

    Purpose: Xerostomia is a severe complication after radiotherapy for oropharyngeal cancer, as the salivary glands are in close proximity with the primary tumor. Intensity-modulated radiotherapy (IMRT) offers theoretical advantages for normal tissue sparing. A Phase II study was conducted to determine the value of IMRT for salivary output preservation compared with conventional radiotherapy (CRT). Methods and Materials: A total of 56 patients with oropharyngeal cancer were prospectively evaluated. Of these, 30 patients were treated with IMRT and 26 with CRT. Stimulated parotid salivary flow was measured before, 6 weeks, and 6 months after treatment. A complication was defined as a stimulated parotid flow rate <25% of the preradiotherapy flow rate. Results: The mean dose to the parotid glands was 48.1 Gy (SD 14 Gy) for CRT and 33.7 Gy (SD 10 Gy) for IMRT (p < 0.005). The mean parotid flow ratio 6 weeks and 6 months after treatment was respectively 41% and 64% for IMRT and respectively 11% and 18% for CRT. As a result, 6 weeks after treatment, the number of parotid flow complications was significantly lower after IMRT (55%) than after CRT (87%) (p = 0.002). The number of complications 6 months after treatment was 56% for IMRT and 81% for CRT (p = 0.04). Conclusions: IMRT significantly reduces the number of parotid flow complications for patients with oropharyngeal cancer

  18. Induction-heating MOCVD reactor with significantly improved heating efficiency and reduced harmful magnetic coupling

    KAUST Repository

    Li, Kuang-Hui

    2018-02-23

    In a conventional induction-heating III-nitride metalorganic chemical vapor deposition (MOCVD) reactor, the induction coil is outside the chamber. Therefore, the magnetic field does not couple with the susceptor well, leading to compromised heating efficiency and harmful coupling with the gas inlet and thus possible overheating. Hence, the gas inlet has to be at a minimum distance away from the susceptor. Because of the elongated flow path, premature reactions can be more severe, particularly between Al- and B-containing precursors and NH3. Here, we propose a structure that can significantly improve the heating efficiency and allow the gas inlet to be closer to the susceptor. Specifically, the induction coil is designed to surround the vertical cylinder of a T-shaped susceptor comprising the cylinder and a top horizontal plate holding the wafer substrate within the reactor. Therefore, the cylinder coupled most magnetic field to serve as the thermal source for the plate. Furthermore, the plate can block and thus significantly reduce the uncoupled magnetic field above the susceptor, thereby allowing the gas inlet to be closer. The results show approximately 140% and 2.6 times increase in the heating and susceptor coupling efficiencies, respectively, as well as a 90% reduction in the harmful magnetic flux on the gas inlet.

  19. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

    Science.gov (United States)

    Tuero, Iskra; Mohanram, Venkatramanan; Musich, Thomas; Miller, Leia; Vargas-Inchaustegui, Diego A; Demberg, Thorsten; Venzon, David; Kalisz, Irene; Kalyanaraman, V S; Pal, Ranajit; Ferrari, Maria Grazia; LaBranche, Celia; Montefiori, David C; Rao, Mangala; Vaccari, Monica; Franchini, Genoveffa; Barnett, Susan W; Robert-Guroff, Marjorie

    2015-08-01

    Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males) was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males) received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC) in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized) remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC and ADCP

  20. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

    Directory of Open Access Journals (Sweden)

    Iskra Tuero

    2015-08-01

    Full Text Available Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC

  1. Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Hongzhao Li

    Full Text Available Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10, respectively (PCS peptides, and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

  2. High expression levels of BLyS/BAFF by blood dendritic cells and granulocytes are associated with B-cell dysregulation in SIV-infected rhesus macaques.

    Science.gov (United States)

    Poudrier, Johanne; Soulas, Caroline; Chagnon-Choquet, Josiane; Burdo, Tricia; Autissier, Patrick; Oskar, Kathryn; Williams, Kenneth C; Roger, Michel

    2015-01-01

    Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). In recent longitudinal studies involving HIV-1-infected individuals with different rates of disease progression, we have shown that DCs were altered in number and phenotype in the context of HIV-1 disease progression and B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs) in rapid and classic progressors but not in HIV-1-elite controllers (EC). Suggesting that the extent to which HIV-1 disease progression is controlled may be linked to BLyS/BAFF expression status and the capacity to orchestrate B-cell responses. Herein, longitudinal analyses of simian immunodeficiency virus (SIV)-infected rhesus macaques also revealed increased expression of BLyS/BAFF by blood mDCs as soon as day 8 and throughout infection. Strikingly, granulocytes presented the highest BLyS/BAFF expression profile in the blood of SIV-infected macaques. BLyS/BAFF levels were also increased in plasma and correlated with viral loads. Consequently, these SIV-infected animals had plasma hyperglobulinemia and reduced blood B-cell numbers with altered population frequencies. These data underscore that BLyS/BAFF is associated with immune dysregulation in SIV-infected rhesus macaques and suggest that BLyS/BAFF is a key regulator of immune activation that is highly conserved among primates. These findings emphasize the potential importance of this SIV-infected primate model to test whether blocking excess BLyS/BAFF has an effect on the overall inflammatory burden and immune restoration.

  3. High expression levels of BLyS/BAFF by blood dendritic cells and granulocytes are associated with B-cell dysregulation in SIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Johanne Poudrier

    Full Text Available Dendritic cells (DCs modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF. In recent longitudinal studies involving HIV-1-infected individuals with different rates of disease progression, we have shown that DCs were altered in number and phenotype in the context of HIV-1 disease progression and B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs in rapid and classic progressors but not in HIV-1-elite controllers (EC. Suggesting that the extent to which HIV-1 disease progression is controlled may be linked to BLyS/BAFF expression status and the capacity to orchestrate B-cell responses. Herein, longitudinal analyses of simian immunodeficiency virus (SIV-infected rhesus macaques also revealed increased expression of BLyS/BAFF by blood mDCs as soon as day 8 and throughout infection. Strikingly, granulocytes presented the highest BLyS/BAFF expression profile in the blood of SIV-infected macaques. BLyS/BAFF levels were also increased in plasma and correlated with viral loads. Consequently, these SIV-infected animals had plasma hyperglobulinemia and reduced blood B-cell numbers with altered population frequencies. These data underscore that BLyS/BAFF is associated with immune dysregulation in SIV-infected rhesus macaques and suggest that BLyS/BAFF is a key regulator of immune activation that is highly conserved among primates. These findings emphasize the potential importance of this SIV-infected primate model to test whether blocking excess BLyS/BAFF has an effect on the overall inflammatory burden and immune restoration.

  4. Significantly reduced radiation exposure to operators during kyphoplasty and vertebroplasty procedures: methods and techniques.

    Science.gov (United States)

    Ortiz, A O; Natarajan, V; Gregorius, D R; Pollack, S

    2006-05-01

    Vertebroplasty and kyphoplasty can be associated with significant radiation exposure to the operator. We compared the exposure levels to an operator performing vertebral fracture augmentation with vertebroplasty and kyphoplasty, to assess a cement injection and a monitoring technique designed to reduce this exposure. A neuroradiologist performed 189 consecutive vertebral augmentation procedures in 135 patients with osteoporotic compression fractures by using a bilateral approach with biplane pulse fluoroscopy at 7.5 pulses/second. Cement delivery was performed with intermittent fluoroscopy with kyphoplasty and vertebroplasty by using syringes or continuous fluoroscopic monitoring with a cement delivery system (CDS). Data collection included time and operator exposure parameters. A total of 87 kyphoplasty procedures, 82 vertebroplasty procedures with a CDS (VP-CDS), and 20 vertebroplasty procedures with syringes (VP-S) were safely performed. Mean fluoroscopy time for device positioning was 4.3 minutes for each procedure type. Mean fluoroscopy time (minutes) for cement delivery was significantly different for the 3 procedure types; 2.1 for kyphoplasty, 3.7 for VP-CDS, and 1.5 for VP-S (P exposure rates (microsieverts/minute) were 0.8 for kyphoplasty, 1.1 for VP-CDS, and 0.3 for VP-S during device-positioning and 1.7 for kyphoplasty, 2.9 for VP-CDS, and 0.2 for VP-S during cement injection (P technique and intermittent fluoroscopy with kyphoplasty and vertebroplasty with syringes results in a significantly lower operator exposure rate compared with vertebroplasty with a CDS.

  5. Expression of myeloperoxidase in swine influenza virus (SIV)-infected neutrophils in lungs from pigs experimentally infected with SIV subtype H1N2.

    Science.gov (United States)

    Kim, Bongtae; Shin, Jeoung Hwa; Han, Kiwon; Seo, Hwi Won; Oh, Yeonsu; Kang, Ikjae; Park, Changhoon; Lee, Bog-Hieu; Jang, Jin Sil; Kim, Sung-Hoon; Chae, Chanhee

    2011-10-01

    The expression of myeloperoxidase (MPO) was examined in the swine influenza virus (SIV)-infected neutrophils in the lungs of pigs experimentally infected with swine influenza virus (SIV) subtype H1N2 by immunohistochemistry. Five pigs each from the infected and non-infected group were euthanized 1, 3, 5, 7, and 10 days post-inoculation (dpi). Immunohistochemical reactivity was mainly seen in neutrophils. The score for pulmonary histopathological lesions correlated with the score for MPO immunohistochemical reactivity (r ( s ) = 0.962, P < 0.01). In addition, the score for in situ hybridization of SIV nucleic acid correlated with the score for MPO immunohistochemical reactivity (r ( s ) = 0.976, P < 0.01). These results suggest neutrophils are one of the primary effector cells in the early phase of SIV infection in pigs.

  6. Sensitive method for the determination of different S(IV) species in cloud and fog water.

    Science.gov (United States)

    Lammel, G

    1996-08-01

    Suppressed ion chromatography has been applied to the determination of S(IV) species in cloud and fog water in the range 0.012-2.4 mg S(IV)-S/L. The samples have been preserved prior to storage and S(IV) species have been determined as hydroxy methanesulfonate (HMS) together with the low molecular weight carboxylic acid anions, formate and acetate. Samples have been divided and treated differently such that total S(IV) as well as the non-oxidizable fraction of S(IV) (as given by the reactivity with H(2)O(2), added in surplus) could be determined. The difference between the two corresponds to the S(IV) fraction subjected to oxididation, which is of paramount interest in cloud and fogwater chemistry.

  7. Physician Education on Controllable Costs Significantly Reduces Cost of Laparoscopic Hysterectomy.

    Science.gov (United States)

    Croft, Katherine; Mattingly, Patricia J; Bosse, Patrick; Naumann, R Wendel

    2017-01-01

    To determine whether educating surgeons about their controllable instrumentation costs by providing cost data on total laparoscopic hysterectomy (LH) would reduce the cost of this procedure. Prospective cohort study (Canadian Task Force classification III). Academic-affiliated community hospital. Patients who underwent LH between April 2014 and March 2015 with surgeons who performed at least 10 LHs during that time period, along with a second group who underwent LH with the same cohort of surgeons between July 2015 and September 2015. The cost of LH was calculated for all surgeons who performed more than 10 LHs between April 2014 and March 2015. Itemized cost data were collected. The individual costs, as well as a summary of the data, were shared with all of the physicians to highlight areas of potential cost savings. The costs were then measured for 3 months after the educational intervention (July-September 2015) to gauge the impact of physician cost education. Thirteen surgeons met the criteria for inclusion in this analysis. Together, they performed 271 hysterectomies, with an average instrumentation cost of $1539.47 ± $294.16 and an average operating room time of 178 ± 26 minutes. Bipolar instrument choice represented 37% of the baseline costs, followed by 10% for trocar, 9% for cuff closure, and 8% for uterine manipulator. This same group of surgeons performed a total of 69 hysterectomies in the 3-month follow-up period of July-September 2015, with an average instrumentation cost of $1282.62 ± $235.03 and an average operating room time of 163 ± 50 minutes. There was statistically significant cost reduction of $256.85 ± $190.69 (p = .022), with no significant change in operating room time. Bipolar instrument cost decreased significantly, by $130.02 ± $125.02 (p = .021), representing 51% of the total cost savings. Trocar, cuff closure, and uterine manipulator costs were not significant sources of cost savings on average, but did represent

  8. Intriguing model significantly reduces boarding of psychiatric patients, need for inpatient hospitalization.

    Science.gov (United States)

    2015-01-01

    As new approaches to the care of psychiatric emergencies emerge, one solution is gaining particular traction. Under the Alameda model, which has been put into practice in Alameda County, CA, patients who are brought to regional EDs with emergency psychiatric issues are quickly transferred to a designated emergency psychiatric facility as soon as they are medically stabilized. This alleviates boarding problems in area EDs while also quickly connecting patients with specialized care. With data in hand on the model's effectiveness, developers believe the approach could alleviate boarding problems in other communities as well. The model is funded by through a billing code established by California's Medicaid program for crisis stabilization services. Currently, only 22% of the patients brought to the emergency psychiatric facility ultimately need to be hospitalized; the other 78% are able to go home or to an alternative situation. In a 30-day study of the model, involving five community hospitals in Alameda County, CA, researchers found that ED boarding times were as much as 80% lower than comparable ED averages, and that patients were stabilized at least 75% of the time, significantly reducing the need for inpatient hospitalization.

  9. Significantly reduced hypoxemic events in morbidly obese patients undergoing gastrointestinal endoscopy: Predictors and practice effect

    Directory of Open Access Journals (Sweden)

    Basavana Gouda Goudra

    2014-01-01

    Full Text Available Background: Providing anesthesia for gastrointestinal (GI endoscopy procedures in morbidly obese patients is a challenge for a variety of reasons. The negative impact of obesity on the respiratory system combined with a need to share the upper airway and necessity to preserve the spontaneous ventilation, together add to difficulties. Materials and Methods: This retrospective cohort study included patients with a body mass index (BMI >40 kg/m 2 that underwent out-patient GI endoscopy between September 2010 and February 2011. Patient data was analyzed for procedure, airway management technique as well as hypoxemic and cardiovascular events. Results: A total of 119 patients met the inclusion criteria. Our innovative airway management technique resulted in a lower rate of intraoperative hypoxemic events compared with any published data available. Frequency of desaturation episodes showed statistically significant relation to previous history of obstructive sleep apnea (OSA. These desaturation episodes were found to be statistically independent of increasing BMI of patients. Conclusion: Pre-operative history of OSA irrespective of associated BMI values can be potentially used as a predictor of intra-procedural desaturation. With suitable modification of anesthesia technique, it is possible to reduce the incidence of adverse respiratory events in morbidly obese patients undergoing GI endoscopy procedures, thereby avoiding the need for endotracheal intubation.

  10. Significantly reduced hypoxemic events in morbidly obese patients undergoing gastrointestinal endoscopy: Predictors and practice effect.

    Science.gov (United States)

    Goudra, Basavana Gouda; Singh, Preet Mohinder; Penugonda, Lakshmi C; Speck, Rebecca M; Sinha, Ashish C

    2014-01-01

    Providing anesthesia for gastrointestinal (GI) endoscopy procedures in morbidly obese patients is a challenge for a variety of reasons. The negative impact of obesity on the respiratory system combined with a need to share the upper airway and necessity to preserve the spontaneous ventilation, together add to difficulties. This retrospective cohort study included patients with a body mass index (BMI) >40 kg/m(2) that underwent out-patient GI endoscopy between September 2010 and February 2011. Patient data was analyzed for procedure, airway management technique as well as hypoxemic and cardiovascular events. A total of 119 patients met the inclusion criteria. Our innovative airway management technique resulted in a lower rate of intraoperative hypoxemic events compared with any published data available. Frequency of desaturation episodes showed statistically significant relation to previous history of obstructive sleep apnea (OSA). These desaturation episodes were found to be statistically independent of increasing BMI of patients. Pre-operative history of OSA irrespective of associated BMI values can be potentially used as a predictor of intra-procedural desaturation. With suitable modification of anesthesia technique, it is possible to reduce the incidence of adverse respiratory events in morbidly obese patients undergoing GI endoscopy procedures, thereby avoiding the need for endotracheal intubation.

  11. Endoscopic Sleeve Gastroplasty Significantly Reduces Body Mass Index and Metabolic Complications in Obese Patients.

    Science.gov (United States)

    Sharaiha, Reem Z; Kumta, Nikhil A; Saumoy, Monica; Desai, Amit P; Sarkisian, Alex M; Benevenuto, Andrea; Tyberg, Amy; Kumar, Rekha; Igel, Leon; Verna, Elizabeth C; Schwartz, Robert; Frissora, Christina; Shukla, Alpana; Aronne, Louis J; Kahaleh, Michel

    2017-04-01

    Endoscopic sleeve gastroplasty (ESG) is an incisionless, minimally invasive bariatric procedure that reduces the length and width of the gastric cavity to facilitate weight loss. We performed a prospective study to evaluate the effects of ESG on total body weight loss and obesity-related comorbidities. We collected data from 91 consecutive patients (mean age, 43.86 ± 11.26 years; 68% female) undergoing ESG from August 2013 through March 2016. All patients had a body mass index (BMI) greater than 30 kg/m 2 and had failed noninvasive weight-loss measures or had a BMI greater than 40 kg/m 2 and were not considered as surgical candidates or refused surgery. All procedures were performed with a cap-based flexible endoscopic suturing system to facilitate a triangular pattern of sutures to imbricate the greater curvature of the stomach. Patients were evaluated after 6 months (n = 73), 12 months (n = 53), and 24 months (n = 12) for anthropometric features (BMI, weight, waist circumference, blood pressure) and underwent serologic (hemoglobin A1c), lipid panel, serum triglycerides, and liver function tests. The primary outcomes were total body weight loss at 6, 12, and 24 months. Secondary outcomes were the effects of ESG on metabolic factors (blood pressure, diabetes, hyperlipidemia, steatohepatitis) and safety. The patients' mean BMI before the procedure was 40.7 ± 7.0 kg/m 2 . Patients had lost 14.4% of their total body weight at 6 months (80% follow-up rate), 17.6% at 12 months (76% follow-up rate), and 20.9% at 24 months (66% follow-up rate) after ESG. At 12 months after ESG, patients had statistically significant reductions in levels of hemoglobin A1c (P = .01), systolic blood pressure (P = .02), waist circumference (P ESG (P = .79). There was one serious adverse event (1.1%) (perigastric leak) that occurred that was managed non-operatively. ESG is a minimally invasive and effective endoscopic weight loss intervention. In addition to sustained total body weight

  12. Synergy in Sulfur Cycle: The Biogeochemical Significance of Sulfate Reducing Bacteria in Syntrophic Associations

    Digital Repository Service at National Institute of Oceanography (India)

    LokaBharathi, P.A.

    ). The first oxidation product of sulfide, elemental sulphur appears outside the cells of green sulfur bacteria and can therefore be oxidized further to sulfate or reduced by sulphur reducing bacteria. In defined syntrophic cocultures of acetate... carrying capacity of an environment in question. Sytrophic associations between suphate reducing and sulfur oxidizing bacteria could be gainfully used in the bioremediation of oil wells polluted by sulfide production (Loka Bharathi et al., 1997). While...

  13. Reduced content of chloroatranol and atranol in oak moss absolute significantly reduces the elicitation potential of this fragrance material

    DEFF Research Database (Denmark)

    Andersen, Flemming; Andersen, Kirsten H; Bernois, Armand

    2015-01-01

    subjects. RESULTS: In both test models, new oak moss elicited significantly less allergic contact dermatitis in oak moss-sensitive subjects than classic oak moss. The control subjects did not react to either of the preparations. CONCLUSIONS: New oak moss is still a fragrance allergen, but elicits less...

  14. Environmental program with operational cases to reduce risk to the marine environment significantly

    International Nuclear Information System (INIS)

    Cline, J.T.; Forde, R.

    1991-01-01

    In this paper Amoco Norway Oil Company's environmental program is detailed, followed by example operational programs and achievements aimed to minimize environmental risks to the marine environment at Valhall platform. With a corporate goal to be a leader in protecting the environment, the appropriate strategies and policies that form the basis of the environmental management system are incorporated in the quality assurance programs. Also, included in the program are necessary organizational structures, responsibilities of environmental affairs and line organization personnel, compliance procedures and a waste task force obliged to implement operations improvements. An internal environmental audit system has been initiated, in addition to corporate level audits, which, when communicated to the line organization closes the environmental management loop through experience feed back. Environmental projects underway are significantly decreasing the extent and/or risk of pollution from offshore activities. The cradle to grave responsibility is assumed with waste separated offshore and onshore followed by disposal in audited sites. A $5 MM program is underway to control produced oily solids and reduce oil in produced water aiming to less than 20 ppm. When oil-based mud is used in deeper hole sections, drill solids disposed at sea average less than 60 g oil/kg dry cuttings using appropriate shaker screens, and a washing/centrifuge system to remove fines. Certain oily liquid wastes are being injected down hole whereas previously they were burned using a mud burner. Finally, a program is underway with a goal to eliminate sea discharge of oil on cuttings through injection disposal of oily wastes, drilling with alternative muds such as a cationic water base mud, and/or proper onshore disposal of oily wastes

  15. Sulfide-driven autotrophic denitrification significantly reduces N2O emissions.

    Science.gov (United States)

    Yang, Weiming; Zhao, Qing; Lu, Hui; Ding, Zhi; Meng, Liao; Chen, Guang-Hao

    2016-03-01

    The Sulfate reduction-Autotrophic denitrification-Nitrification Integrated (SANI) process build on anaerobic carbon conversion through biological sulfate reduction and autotrophic denitrification by using the sulfide byproduct from the previous reaction. This study confirmed extra decreases in N2O emissions from the sulfide-driven autotrophic denitrification by investigating N2O reduction, accumulation, and emission in the presence of different sulfide/nitrate (S/N) mass ratios at pH 7 in a long-term laboratory-scale granular sludge autotrophic denitrification reactor. The N2O reduction rate was linearly proportional to the sulfide concentration, which confirmed that no sulfide inhibition of N2O reductase occurred. At S/N = 5.0 g-S/g-N, this rate resulted by sulfide-driven autotrophic denitrifying granular sludge (average granule size = 701 μm) was 27.7 mg-N/g-VSS/h (i.e., 2 and 4 times greater than those at 2.5 and 0.8 g-S/g-N, respectively). Sulfide actually stimulates rather than inhibits N2O reduction no matter what granule size of sulfide-driven autotrophic denitrifying sludge engaged. The accumulations of N2O, nitrite and free nitrous acid (FNA) with average granule size 701 μm of sulfide-driven autotrophic denitrifying granular sludge engaged at S/N = 5.0 g-S/g-N were 4.7%, 11.4% and 4.2% relative to those at 3.0 g-S/g-N, respectively. The accumulation of FNA can inhibit N2O reduction and increase N2O accumulation during sulfide-driven autotrophic denitrification. In addition, the N2O gas emission level from the reactor significantly increased from 14.1 ± 0.5 ppmv (0.002% of the N load) to 3707.4 ± 36.7 ppmv (0.405% of the N load) as the S/N mass ratio in the influent decreased from 2.1 to 1.4 g-S/g-N over the course of the 120-day continuous monitoring period. Sulfide-driven autotrophic denitrification may significantly reduce greenhouse gas emissions from biological nutrient removal when sulfur conversion processes are applied

  16. Conserved molecular signatures in gp120 are associated with the genetic bottleneck during simian immunodeficiency virus (SIV), SIV-human immunodeficiency virus (SHIV), and HIV type 1 (HIV-1) transmission.

    Science.gov (United States)

    Gonzalez, Mileidy W; DeVico, Anthony L; Lewis, George K; Spouge, John L

    2015-04-01

    Human immunodeficiency virus (HIV) transmission typically results from infection by a single transmitted/founder (T/F) variant. Are T/F variants chosen uniformly at random from the donor pool, or are they selected based on advantageous traits facilitating transmission? Finding evidence for selection during transmission is of particular interest, because it would indicate that phenotypic and/or genetic properties of the viruses might be harnessed as potential vaccine targets or immunotherapies. Here, we systematically evaluated the differences between the Env proteins of simian immunodeficiency virus/simian HIV (SIV/SHIV) stock and T/F variants in search of "signature" sites of transmission. We also surveyed residue preferences in HIV at the SIV/SHIV signature sites. Four sites of gp120 showed significant selection, and an additional two sites showed a similar trend. Therefore, the six sites clearly differentiate T/F viruses from the majority of circulating variants in the stocks. The selection of SIV/SHIV could be inferred reasonably across both vaccinated and unvaccinated subjects, with infections resulting from vaginal, rectal, and intravenous routes of transmission and regardless of viral dosage. The evidence for selection in SIV and SHIV T/F variants is strong and plentiful, and in HIV the evidence is suggestive though commensurate with the availability of suitable data for analysis. Two of the signature residues are completely conserved across the SIV, SHIV, and HIV variants we examined. Five of the signature residues map to the C1 region of gp120 and one to the signal peptide. Our data raise the possibility that C1, while governing the association between gp120 and gp41, modulates transmission efficiency, replicative fitness, and/or host cell tropism at the level of virus-cell attachment and entry. The present study finds significant evidence of selection on gp120 molecules of SIV/SHIV T/F viruses. The data provide ancillary evidence suggesting the same sites

  17. Simple Mathematical Models Do Not Accurately Predict Early SIV Dynamics

    Directory of Open Access Journals (Sweden)

    Cecilia Noecker

    2015-03-01

    Full Text Available Upon infection of a new host, human immunodeficiency virus (HIV replicates in the mucosal tissues and is generally undetectable in circulation for 1–2 weeks post-infection. Several interventions against HIV including vaccines and antiretroviral prophylaxis target virus replication at this earliest stage of infection. Mathematical models have been used to understand how HIV spreads from mucosal tissues systemically and what impact vaccination and/or antiretroviral prophylaxis has on viral eradication. Because predictions of such models have been rarely compared to experimental data, it remains unclear which processes included in these models are critical for predicting early HIV dynamics. Here we modified the “standard” mathematical model of HIV infection to include two populations of infected cells: cells that are actively producing the virus and cells that are transitioning into virus production mode. We evaluated the effects of several poorly known parameters on infection outcomes in this model and compared model predictions to experimental data on infection of non-human primates with variable doses of simian immunodifficiency virus (SIV. First, we found that the mode of virus production by infected cells (budding vs. bursting has a minimal impact on the early virus dynamics for a wide range of model parameters, as long as the parameters are constrained to provide the observed rate of SIV load increase in the blood of infected animals. Interestingly and in contrast with previous results, we found that the bursting mode of virus production generally results in a higher probability of viral extinction than the budding mode of virus production. Second, this mathematical model was not able to accurately describe the change in experimentally determined probability of host infection with increasing viral doses. Third and finally, the model was also unable to accurately explain the decline in the time to virus detection with increasing viral

  18. Soil nitrate reducing processes – drivers, mechanisms for spatial variation, and significance for nitrous oxide production

    Science.gov (United States)

    Giles, Madeline; Morley, Nicholas; Baggs, Elizabeth M.; Daniell, Tim J.

    2012-01-01

    The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for the loss of nitrate (NO3−) and production of the potent greenhouse gas, nitrous oxide (N2O). A number of factors are known to control these processes, including O2 concentrations and moisture content, N, C, pH, and the size and community structure of nitrate reducing organisms responsible for the processes. There is an increasing understanding associated with many of these controls on flux through the nitrogen cycle in soil systems. However, there remains uncertainty about how the nitrate reducing communities are linked to environmental variables and the flux of products from these processes. The high spatial variability of environmental controls and microbial communities across small sub centimeter areas of soil may prove to be critical in determining why an understanding of the links between biotic and abiotic controls has proved elusive. This spatial effect is often overlooked as a driver of nitrate reducing processes. An increased knowledge of the effects of spatial heterogeneity in soil on nitrate reduction processes will be fundamental in understanding the drivers, location, and potential for N2O production from soils. PMID:23264770

  19. Reducing dysfunctional beliefs about sleep does not significantly improve insomnia in cognitive behavioral therapy.

    Science.gov (United States)

    Okajima, Isa; Nakajima, Shun; Ochi, Moeko; Inoue, Yuichi

    2014-01-01

    The present study examined to examine whether improvement of insomnia is mediated by a reduction in sleep-related dysfunctional beliefs through cognitive behavioral therapy for insomnia. In total, 64 patients with chronic insomnia received cognitive behavioral therapy for insomnia consisting of 6 biweekly individual treatment sessions of 50 minutes in length. Participants were asked to complete the Athens Insomnia Scale and the Dysfunctional Beliefs and Attitudes about Sleep scale both at the baseline and at the end of treatment. The results showed that although cognitive behavioral therapy for insomnia greatly reduced individuals' scores on both scales, the decrease in dysfunctional beliefs and attitudes about sleep with treatment did not seem to mediate improvement in insomnia. The findings suggest that sleep-related dysfunctional beliefs endorsed by patients with chronic insomnia may be attenuated by cognitive behavioral therapy for insomnia, but changes in such beliefs are not likely to play a crucial role in reducing the severity of insomnia.

  20. The characteristic of reduced form exciting factors of governing mineralization in hydrothermal uranium deposits and its prospecting significance

    International Nuclear Information System (INIS)

    Liu Guangqing; Lou Xianhong; Li Zhenqiu

    2008-01-01

    Reduced form exciting factors of governing mineralization are discussed. It is indicated that metallogenic conditions of hydrothermal uranium deposits of reduced form exciting factors governing mineralization are ore-forming solution flow into metallogenic space; Eh decreases significantly, and reach reducing condition of mineral deposit. The exciting factors of governing mineralization are divided into internal reduction subclass and environment reduction subclass. Then emphases on the classification, characteristic, formation condition, representative deposits and prospecting significance in this paper. The environment reduction index is put forward to evaluate reducing power of surrounding rock. (authors)

  1. The Evolution of Polymer Composition during PHA Accumulation: The Significance of Reducing Equivalents

    Science.gov (United States)

    Montano-Herrera, Liliana; Laycock, Bronwyn; Werker, Alan; Pratt, Steven

    2017-01-01

    This paper presents a systematic investigation into monomer development during mixed culture Polyhydroxyalkanoates (PHA) accumulation involving concurrent active biomass growth and polymer storage. A series of mixed culture PHA accumulation experiments, using several different substrate-feeding strategies, was carried out. The feedstock comprised volatile fatty acids, which were applied as single carbon sources, as mixtures, or in series, using a fed-batch feed-on-demand controlled bioprocess. A dynamic trend in active biomass growth as well as polymer composition was observed. The observations were consistent over replicate accumulations. Metabolic flux analysis (MFA) was used to investigate metabolic activity through time. It was concluded that carbon flux, and consequently copolymer composition, could be linked with how reducing equivalents are generated. PMID:28952499

  2. The Evolution of Polymer Composition during PHA Accumulation: The Significance of Reducing Equivalents

    Directory of Open Access Journals (Sweden)

    Liliana Montano-Herrera

    2017-03-01

    Full Text Available This paper presents a systematic investigation into monomer development during mixed culture Polyhydroxyalkanoates (PHA accumulation involving concurrent active biomass growth and polymer storage. A series of mixed culture PHA accumulation experiments, using several different substrate-feeding strategies, was carried out. The feedstock comprised volatile fatty acids, which were applied as single carbon sources, as mixtures, or in series, using a fed-batch feed-on-demand controlled bioprocess. A dynamic trend in active biomass growth as well as polymer composition was observed. The observations were consistent over replicate accumulations. Metabolic flux analysis (MFA was used to investigate metabolic activity through time. It was concluded that carbon flux, and consequently copolymer composition, could be linked with how reducing equivalents are generated.

  3. Mindfulness significantly reduces self-reported levels of anxiety and depression

    DEFF Research Database (Denmark)

    Würtzen, Hanne; Dalton, Susanne Oksbjerg; Elsass, Peter

    2013-01-01

    INTRODUCTION: As the incidence of and survival from breast cancer continue to raise, interventions to reduce anxiety and depression before, during and after treatment are needed. Previous studies have reported positive effects of a structured 8-week group mindfulness-based stress reduction program...... (MBSR) among patients with cancer and other conditions. PURPOSE: To test the effect of such a programme on anxiety and depression among women with breast cancer in a population-based randomised controlled study. METHODS: A total of 336 women who had been operated on for breast cancer (stage I-III) were...... randomised to usual care or MBSR+usual care. Questionnaires including the Symptom Checklist-90r anxiety and depression subscales and the Center for Epidemiological Studies-Depression scale were administered before randomisation and immediately, 6 and 12 months after the intervention. RESULTS: Intention...

  4. Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions

    NARCIS (Netherlands)

    Manoussaka, Maria S.; Berry, Neil; Ferguson, Deborah; Stebbings, Richard; Robinson, Mark; Ham, Claire; Page, Mark; Li, Bo; Das, Atze T.; Berkhout, Ben; Almond, Neil; Cranage, Martin P.

    2013-01-01

    Live attenuated SIV induces potent protection against superinfection with virulent virus; however the mechanism of this vaccine effect is poorly understood. Such knowledge is important for the development of clinically acceptable vaccine modalities against HIV. Using a novel, doxycycline dependent,

  5. Sealing of the hepatic resection area using fibrin glue reduces significant amount of postoperative drain fluid.

    Science.gov (United States)

    Eder, Frank; Meyer, Frank; Nestler, Gerd; Halloul, Zuhir; Lippert, Hans

    2005-10-14

    To investigate whether the routine use of fibrin glue applied onto the hepatic resection area can diminish postoperative volume of bloody or biliary fluids drained via intraoperatively placed perihepatic tubes and can thus lower the complication rate. Two groups of consecutive patients with a comparable spectrum of recent hepatic resections were compared: (1) 13 patients who underwent application of fibrin glue immediately after resection of liver parenchyma; (2) 12 patients who did not. Volumes of postoperative drainage fluid were determined in 4-h intervals through 24 h indicating the intervention caused bloody and biliary segregation. Through the first 8 h postoperatively, there was a tendency of higher amounts of fluids in patients with no additional application of fibrin glue while through the following intervals, a significant increase of drainage volumes was documented in comparison with the first two 4-h intervals, e.g., after 12 h, 149.6 mL +/-110 mL vs 63.2 mL +/-78 mL. Using fibrin glue, postoperative fluid amounts were significantly lower through the postoperative observation period of 24 h (851 mL +/-715 mL vs 315 mL +/-305 mL). For hepatic resections, the use of fibrin glue appears to be advantageous in terms of a significant decrease of surgically associated segregation of blood or bile out of the resection area. This might result in a better outcome.

  6. Factor Xa inhibition by rivaroxaban in the trough steady state can significantly reduce thrombin generation.

    Science.gov (United States)

    Horinaka, Shigeo; Sugawara, Rie; Yonezawa, Yutaka; Ishimitsu, Toshihiko

    2018-01-01

    The aim of the present study was to demonstrate evidence of reduced thrombin generation at the trough plasma rivaroxaban concentration. A single-centre, prospective, nonrandomized, drug-intervention, self-controlled study was conducted in 51 anticoagulation therapy-naïve patients with nonvalvular atrial fibrillation. Plasma rivaroxaban concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and the anti-factor Xa chromogenic assay. Partial thrombin time (PT), protein C activity, and protein S antigen, prothrombin fragment 1 + 2 (F1 + 2), D-dimer, thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasminogen activator inhibitor-1 (PAI-1) and tissue factor pathway inhibitor (TFPI) levels were also measured at the trough steady state after 4 weeks of rivaroxaban treatment and compared with baseline. Plasma concentrations obtained by the LC-MS/MS and anti-Xa assays were correlated (r = 0.841, P steady state was 23.6 ng ml -1 , at which F1 + 2, TAT and D-dimer had decreased from the baseline values (P steady state in the first to third quartile groups (+0.79 pg ml -1 , P = 0.048). By contrast, PAI-1, protein C activity, protein S antigen and TM remained within the normal range at the trough steady state. Residual plasma rivaroxaban at the trough steady state may explain the antithrombin effect of rivaroxaban in patients with nonvalvular atrial fibrillation. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  7. A case of gastric endocrine cell carcinoma which was significantly reduced in size by radiotherapy

    International Nuclear Information System (INIS)

    Azakami, Kiyoshi; Nishida, Kouji; Tanikawa, Ken

    2016-01-01

    In 2010, the World Health Organization classified gastric neuroendocrine tumors (NETs) into three types: NET grade (G) 1, NET G2 and neuroendocrine carcinoma (NEC). NECs are associated with a very poor prognosis. The patient was an 84-year-old female who was initially diagnosed by gastrointestinal endoscope with type 3 advanced gastric cancer with stenosis of the gastric cardia. Her overall status and performance status did not allow for operations or intensive chemotherapy. Palliative radiotherapy was performed and resulted in a significant reduction in the size of the tumor as well as the improvement of the obstructive symptoms. She died 9 months after radiotherapy. An autopsy provided a definitive diagnosis of gastric endocrine cell carcinoma, and the effectiveness of radiotherapy was pathologically-confirmed. Palliative radiotherapy may be a useful treatment option for providing symptom relief, especially for old patients with unresectable advanced gastric neuroendocrine carcinoma. (author)

  8. HIV/SIV infection primes monocytes and dendritic cells for apoptosis.

    Directory of Open Access Journals (Sweden)

    Mireille Laforge

    2011-06-01

    Full Text Available Subversion or exacerbation of antigen-presenting cells (APC death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of pro-apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1 and FLIP proteins. To assess the relevance of these observations in the context of an experimental model of HIV infection, we investigated the death of APC during pathogenic SIV-infection in rhesus macaques (RMs. We demonstrated increased apoptosis, during the acute phase, of both peripheral blood DCs and monocytes (CD14(+ from SIV(+RMs, associated with a dysregulation in the balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death receptors antagonists prevented apoptosis of APCs from SIV(+RMs. Furthermore, increased levels of FasL in the sera of pathogenic SIV(+RMs were detected, compared to non-pathogenic SIV infection of African green monkey. We suggest that inappropriate apoptosis of antigen-presenting cells may contribute to dysregulation of cellular immunity early in the process of HIV/SIV infection.

  9. An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

    Science.gov (United States)

    Beck, Sarah E; Queen, Suzanne E; Metcalf Pate, Kelly A; Mangus, Lisa M; Abreu, Celina M; Gama, Lucio; Witwer, Kenneth W; Adams, Robert J; Zink, M Christine; Clements, Janice E; Mankowski, Joseph L

    2018-04-01

    Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

  10. Social networking strategies that aim to reduce obesity have achieved significant although modest results.

    Science.gov (United States)

    Ashrafian, Hutan; Toma, Tania; Harling, Leanne; Kerr, Karen; Athanasiou, Thanos; Darzi, Ara

    2014-09-01

    The global epidemic of obesity continues to escalate. Obesity accounts for an increasing proportion of the international socioeconomic burden of noncommunicable disease. Online social networking services provide an effective medium through which information may be exchanged between obese and overweight patients and their health care providers, potentially contributing to superior weight-loss outcomes. We performed a systematic review and meta-analysis to assess the role of these services in modifying body mass index (BMI). Our analysis of twelve studies found that interventions using social networking services produced a modest but significant 0.64 percent reduction in BMI from baseline for the 941 people who participated in the studies' interventions. We recommend that social networking services that target obesity should be the subject of further clinical trials. Additionally, we recommend that policy makers adopt reforms that promote the use of anti-obesity social networking services, facilitate multistakeholder partnerships in such services, and create a supportive environment to confront obesity and its associated noncommunicable diseases. Project HOPE—The People-to-People Health Foundation, Inc.

  11. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients: A 12-Year Cohort Study.

    Science.gov (United States)

    Kuo, Ming-Chun; Chang, Shun-Jen; Hsieh, Ming-Chia

    2015-12-01

    Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77-0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout.

  12. Strong mucosal immune responses in SIV infected macaques contribute to viral control and preserved CD4+ T-cell levels in blood and mucosal tissues.

    Science.gov (United States)

    Schultheiss, Tina; Schulte, Reiner; Sauermann, Ulrike; Ibing, Wiebke; Stahl-Hennig, Christiane

    2011-04-11

    Since there is still no protective HIV vaccine available, better insights into immune mechanism of persons effectively controlling HIV replication in the absence of any therapy should contribute to improve further vaccine designs. However, little is known about the mucosal immune response of this small unique group of patients. Using the SIV-macaque-model for AIDS, we had the rare opportunity to analyze 14 SIV-infected rhesus macaques durably controlling viral replication (controllers). We investigated the virological and immunological profile of blood and three different mucosal tissues and compared their data to those of uninfected and animals progressing to AIDS-like disease (progressors). Lymphocytes from blood, bronchoalveolar lavage (BAL), and duodenal and colonic biopsies were phenotypically characterized by polychromatic flow cytometry. In controllers, we observed higher levels of CD4+, CD4+CCR5+ and Gag-specific CD8+ T-cells as well as lower immune activation in blood and all mucosal sites compared to progressors. However, we could also demonstrate that immunological changes are distinct between these three mucosal sites.Intracellular cytokine staining demonstrated a significantly higher systemic and mucosal CD8+ Gag-specific cellular immune response in controllers than in progressors. Most remarkable was the polyfunctional cytokine profile of CD8+ lymphocytes in BAL of controllers, which significantly dominated over their blood response. The overall suppression of viral replication in the controllers was confirmed by almost no detectable viral RNA in blood and all mucosal tissues investigated. A strong and complex virus-specific CD8+ T-cell response in blood and especially in mucosal tissue of SIV-infected macaques was associated with low immune activation and an efficient suppression of viral replication. This likely afforded a repopulation of CD4+ T-cells in different mucosal compartments to almost normal levels. We conclude, that a robust SIV

  13. Comparative analysis of immune activation markers of CD8+ T cells in lymph nodes of different origins in SIV-infected Chinese rhesus macaques

    Directory of Open Access Journals (Sweden)

    Jinbiao Liu

    2016-09-01

    Full Text Available Altered T-cell homeostasis, such as expansion of CD8+ T cells to the secondary lymphatic compartments has been suggested as a mechanism of HIV/SIV-pathogenesis. However, the role of immune activation of CD8+ T cells in the CD4/CD8 turnover and viral replication in these tissues is not completely understood. In the present study, we compared the expression of immune activation markers (CD69 and HLA-DR on CD8+ T cells in the peripheral blood and lymph nodes (LNs of SIV-infected/uninfected Chinese rhesus macaques. SIV-infected macaques had significantly higher percentages of CD8+CD69+ and CD8+HLA-DR+ T cells in all these anatomical compartments than uninfected macaques except for CD8+HLA-DR+ T cells in peripheral blood. LNs that located close to the gastrointestinal (GI tract (colon, mesenteric and iliac LNs of SIV-infected macaques had profoundly lower numbers of CD4+ T cells, but no significantly difference in expression of activation marker (CD8+CD69+ and CD8+HLA-DR+ as compared with the peripheral lymphatic tissues (axillary and inguinal LNs. The CD4/CD8 ratios were negatively correlated with the activation of CD8 T cells in the overall LNs, with further associations with CD8+HLA-DR+ in GI LNs while CD8+CD69+ in peripheral LNs. These observations demonstrate that the increase of CD8+ T cell activation is a contributing factor for the decline of CD4/CD8 ratios in GI system.

  14. Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

    Directory of Open Access Journals (Sweden)

    Sama Adnan

    2016-12-01

    Full Text Available Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.

  15. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

    Directory of Open Access Journals (Sweden)

    Kevin R McCarthy

    Full Text Available In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm. Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac and pig-tailed macaques (SIVmne have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

  16. Simian Immunodeficiency Virus (SIV-Specific Chimeric Antigen Receptor-T Cells Engineered to Target B Cell Follicles and Suppress SIV Replication

    Directory of Open Access Journals (Sweden)

    Kumudhini Preethi Haran

    2018-03-01

    Full Text Available There is a need to develop improved methods to treat and potentially cure HIV infection. During chronic HIV infection, replication is concentrated within T follicular helper cells (Tfh located within B cell follicles, where low levels of virus-specific CTL permit ongoing viral replication. We previously showed that elevated levels of simian immunodeficiency virus (SIV-specific CTL in B cell follicles are linked to both decreased levels of viral replication in follicles and decreased plasma viral loads. These findings provide the rationale to develop a strategy for targeting follicular viral-producing (Tfh cells using antiviral chimeric antigen receptor (CAR T cells co-expressing the follicular homing chemokine receptor CXCR5. We hypothesize that antiviral CAR/CXCR5-expressing T cells, when infused into an SIV-infected animal or an HIV-infected individual, will home to B cell follicles, suppress viral replication, and lead to long-term durable remission of SIV and HIV. To begin to test this hypothesis, we engineered gammaretroviral transduction vectors for co-expression of a bispecific anti-SIV CAR and rhesus macaque CXCR5. Viral suppression by CAR/CXCR5-transduced T cells was measured in vitro, and CXCR5-mediated migration was evaluated using both an in vitro transwell migration assay, as well as a novel ex vivo tissue migration assay. The functionality of the CAR/CXCR5 T cells was demonstrated through their potent suppression of SIVmac239 and SIVE660 replication in in vitro and migration to the ligand CXCL13 in vitro, and concentration in B cell follicles in tissues ex vivo. These novel antiviral immunotherapy products have the potential to provide long-term durable remission (functional cure of HIV and SIV infections.

  17. 26 CFR 54.4980F-1 - Notice requirements for certain pension plan amendments significantly reducing the rate of future...

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Notice requirements for certain pension plan amendments significantly reducing the rate of future benefit accrual. 54.4980F-1 Section 54.4980F-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980...

  18. High-throughput profiling of anti-glycan humoral responses to SIV vaccination and challenge.

    Directory of Open Access Journals (Sweden)

    Christopher T Campbell

    Full Text Available Recent progress toward an HIV vaccine highlights both the potential of vaccines to end the AIDS pandemic and the need to boost efficacy by incorporating additional vaccine strategies. Although many aspects of the immune response can contribute to vaccine efficacy, the key factors have not been defined fully yet. A particular area that may yield new insights is anti-glycan immune responses, such as those against the glycan shield that HIV uses to evade the immune system. In this study, we used glycan microarray technology to evaluate anti-glycan antibody responses induced by SIV vaccination and infection in a non-human primate model of HIV infection. This comprehensive profiling of circulating anti-glycan antibodies found changes in anti-glycan antibody levels after both vaccination with the Ad5hr-SIV vaccine and SIV infection. Notably, SIV infection produced generalized declines in anti-glycan IgM antibodies in a number of animals. Additionally, some infected animals generated antibodies to the Tn antigen, which is a cryptic tumor-associated antigen exposed by premature termination of O-linked glycans; however, the Ad5hr-SIV vaccine did not induce anti-Tn IgG antibodies. Overall, this study demonstrates the potential contributions that glycan microarrays can make for HIV vaccine development.

  19. Capabilities of optical SIV technique in measurements of flow velocity vector field dynamics

    Science.gov (United States)

    Mikheev, N. I.; Dushin, N. S.; Saushin, I. I.

    2017-11-01

    The main difference between Smoke Image Velocimetry (SIV) technique and the conventional PIV is that higher concentration of tracer particles typical of smoke visualization techniques is used in SIV. Not separate particles but smoke structures with continuous pixel intensity are visible in the recorded images. Owing to better smoke reflectivity, higher spatial and temporal resolution is obtained in the case when relatively simple equipment (camera and laser) is used. It is simple enough to perform SIV measurements of velocity vector field dynamics at the frequency exceeding 15000 Hz, which offers new opportunities in unsteady flow examination. The paper describes fundamentals of SIV technique and gives some new results obtained using this method for the measurements that require high spatial and temporal resolution. The latter include frequency spectra of turbulent velocity fluctuations, turbulence dissipation profiles in the boundary layer and higher-order moments of velocity fluctuations. It has been shown that SIV technique considerably extends the potential of experimental studies of turbulence and flow structure in high-speed processes.

  20. Mechanisms of CD8+ T cell-mediated suppression of HIV/SIV replication.

    Science.gov (United States)

    McBrien, Julia Bergild; Kumar, Nitasha A; Silvestri, Guido

    2018-02-10

    In this article, we summarize the role of CD8 + T cells during natural and antiretroviral therapy (ART)-treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8 + T cell-based HIV cure strategies. Evidence suggests that CD8 + T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8 + T cells is responsible for control of viremia. However, it has been proposed that CD8 + T cells also use non-cytolytic mechanisms to control SIV infection. More recently, CD8 + T cells were shown to be required to fully suppress virus production in ART-treated SIV-infected macaques, suggesting that CD8 + T cells are involved in the control of virus transcription in latently infected cells that persist under ART. A better understanding of the complex antiviral activities of CD8 + T cells during HIV/SIV infection will pave the way for immune interventions aimed at harnessing these functions to target the HIV reservoir. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Serum capacity to inhibit reverse transcriptase in vitro distinguishes HIV-1 infection from HIV-2 or SIV infection

    NARCIS (Netherlands)

    Wolfs, T. F.; Geelen, J. L.; Schellekens, H.; Barin, F.; Dekker, J. T.; Goudsmit, J.

    1989-01-01

    The inhibition of HIV-1 and SIV reverse transcriptase by human and rhesus macaque serum positive for HIV-1 or HIV-2/SIV antibodies was studied. The domain to which reverse transcriptase-inhibiting antibodies were elicited appeared to be highly antigenic. A total of 67% (48 of 72) of individuals had

  2. Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection

    DEFF Research Database (Denmark)

    Muenchhoff, Maximilian; Adland, Emily; Karimanzira, Owen

    2016-01-01

    Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preven...... over thousands of years in natural SIV hosts than those operating in HIV-infected adults.......Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors...... preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-Age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26...

  3. [Genetic diversity and phylogeographic distribution of SIV: how to understand the origin of HIV].

    Science.gov (United States)

    Peeters, Martine; Chaix, Marie-Laure; Delaporte, Eric

    2008-01-01

    Emergence of human immunodeficiency viruses HIV-1 and HIV-2 results from interspecies transmission from simian viruses SIV. SIVcpzPtt infecting chimpanzees, and from which the HIV-1 (subgroups M and N) is derived is still found in the Pan troglodytes troglodytes population of south Cameroon chimpanzees. The ancestor of HIV-1 group O, is found in the Gorilla residing in Western Africa, but chimpanzees are in fact the initial reservoir of the SIV viruses SIVgor, and it is still unclear whether the group O HIV-1 has been transmitted to humans by gorillas and/or chimpanzees. At least eight interspecies transmissions between and humans implicating SIVsmm (from sooty mangabey monkeys) have occurred, corresponding to the eight VIH-2 groups. Since habits of hunting and meat preparation in the bush still persistently expose humans in Africa to SIV infection, new interspecies transmission of these viruses remains a possibility.

  4. [Electron microscopic investigation of CD4+ lymphocyte cell line C8166 after infection with simian immunodeficiency virus (SIV)].

    Science.gov (United States)

    Kaup, F J; Bingger, K; Mätz-Rensing, K; Stahl-Hennig, C; Schneider, T; Hofmann, P

    2003-04-01

    The SIV infection of rhesus macaques (Macaca mulatta) is the most appropriate animal model in HIV research. The permanent human T-cell line C8166 is used for in vitro SIV propagation. This paper describes ultrastructural features of the cells after infection with SIVmac. The C8166 cells are ultrastructurally characterized by a heterogenous morphology which is independent of the infection. SIV induced cell syncytia are observed 18 hours after infection. Viral particles and budding occur 48 hours p.i with a peak at the day 8. Viral particles present the typical lentiviral morphology. Using the monoclonal antibody anti SIVp28 and ultra small (0.8 nm) immunogold-silver enhancement technique, we are able to demonstrate SIV antigen immunoelectron microscopically. Therefore, this ultrastructural method is suitable to detect SIV antigen in in vivo experiments with C8166 cells from day 8 p.i. serving as positive control.

  5. Interaction between FOXO1A-209 Genotype and Tea Drinking is Significantly Associated with Reduced Mortality at Advanced Ages

    DEFF Research Database (Denmark)

    Zeng, Yi; Chen, Huashuai; Ni, Ting

    2016-01-01

    Based on the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality...... at advanced ages. Such significant association is replicated in two independent Han Chinese CLHLS cohorts (p =0.028-0.048 in the discovery and replication cohorts, and p =0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers...... of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably...

  6. Validation of SIV measurements of turbulent characteristics in the separation region

    Science.gov (United States)

    Dushin, N. S.; Mikheev, N. I.; Dushina, O. A.; Zaripov, D. I.; Aslaev, A. K.

    2017-11-01

    Temporally and spatially resolved 2D measurements are important for the studies of complex turbulent flows. The recently developed SIV technique (Smoke Image Velocimetry), which is superior to PIV in some cases, can be used for this purpose. SIV validation results are presented for the steady turbulent backward-facing step flow measurements. Velocity profiles and Reynolds stress profiles are given for the regions of oncoming flow, reverse flow, flow reattachment and relaxation. The Reynolds number based on the step height and oncoming flow velocity at the boundary layer edge was Reh = 4834. The obtained data have been compared to LDA measurements and DNS.

  7. A Recombinant Multi-Stage Vaccine against Paratuberculosis Significantly Reduces Bacterial Level in Tissues without Interference in Diagnostics

    DEFF Research Database (Denmark)

    Jungersen, Gregers; Thakur, Aneesh; Aagaard, C.

    A new (FET11) recombinant vaccine against paratuberculosis was developed based on recombinant antigens from acute and latent stages of Mycobacterium avium subsp. paratuberculosis (Map) infection. In two experiments 28 calves and 15 goats were orally inoculated with live Map in their third week...... of life and post-exposure vaccinated at different times after inoculation or with different vaccine constructs. In contrast to common whole-cells vaccination, the FET11 vaccine did not interfere with tests for paratuberculosis or bovine tuberculosis as no measurable antibody responses by ID Screen® ELISA...... PCR and revealed significantly reduced levels of Map and reduced histopathology. Diagnostic tests for antibody responses and cell-mediated immune responses, used as surrogates of infection, corroborated the observed vaccine efficacy: Five of seven non‐vaccinated calves seroconverted in ID Screen...

  8. Low dose rectal inoculation of rhesus macaques by SIV SME660 or SIV MAC251 recapitulates human mucosal infection by HIV-1

    Energy Technology Data Exchange (ETDEWEB)

    Koraber, Bette [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory; Hraber, Peter [Los Alamos National Laboratory; Giorgi, E [Los Alamos National Laboratory; Bhattacharya, T [Los Alamos National Laboratory

    2009-01-01

    Recently, we developed a novel approach to the identification of transmitted or early founder HIV -1 genomes in acutely infected humans based on single genome amplification and sequencing. Here we tested this approach in 18 acutely infected Indian rhesus macaques to determine the molecular features of SIV transmission. Animals were inoculated intrarectally (IR) or intravenously (IV) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV -1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA one to five weeks after infection. IR inoculation was followed by productive infection by one or few viruses (median 1; range 1-5) that diversified randomly with near star-like phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or few nuc1eotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder virus( es). IV infection was approximately 10,000-fold more efficient than IR infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV -1.

  9. Use of chlorhexidine chewing gum significantly reduces dental plaque formation compared to use of similar xylitol and sorbitol products.

    Science.gov (United States)

    Tellefsen, G; Larsen, G; Kaligithi, R; Zimmerman, G J; Wikesjö, M E

    1996-03-01

    A double-blind 3-treatment crossover design employing a 6-day trial period with out mechanical oral hygiene measures was used to compare dental plaque formation following use of chlorhexidine (CHX) acetate-, xylitol-, and sorbitol-containing chewing gum. Fourteen dental students were assigned a random ordering of the chewing gum products and received professional tooth cleaning at the start of trial periods. For each trial period, subjects were instructed to use 5 pieces of the unlabeled chewing gum daily (containing 5.0 mg CHX acetate/piece; 0.8 xylitol/piece; or 1.0 g sorbitol/piece). Two pieces of chewing gum were used following each morning and evening meal and one piece following the noon meal. The subjects were instructed to use the products for 20 minutes at each occasion. A 7-day washout-period between trial periods was used. The Turesky modification of the Quigley and Hein index was used to assess plaque formation. Differences between treatments were evaluated using a repeated measures ANOVA with Newman-Keuls multiple comparisons. The CHX-containing chewing gum showed significantly reduced plaque values (0.7 +/- 0.4) compared to the sorbitol-(2.7 +/- 0.4; P product (1.7 +/- 0.3; P product significantly reduced plaque levels compared to the study subjects' regular plaque control routines (1.3 +/- 0.04; P product exhibited significantly lower plaque-values than the sorbitol-product (P control dental plaque formation.

  10. Angiotensin 1-7 significantly reduces diabetes-induced leukocyte recruitment both in vivo and in vitro.

    Science.gov (United States)

    Bossi, Fleur; Bernardi, Stella; De Nardo, Daniele; Bramante, Alessandra; Candido, Riccardo; Carretta, Renzo; Fischetti, Fabio; Fabris, Bruno

    2016-01-01

    Recent studies have demonstrated that Ang1-7 has anti-inflammatory effects. Since the formation of Ang1-7 is significantly altered in the setting of diabetes, here we aimed to evaluate whether Ang1-7 infusion could ameliorate diabetes-induced leukocyte recruitment. Wild-type male Wistar rats were randomly allocated to the following groups: control + saline, control + Ang1-7, diabetes + saline, diabetes + Ang1-7. Diabetes was induced by streptozotocin. Saline and Ang1-7 (576 μg/kg/day) were injected intraperitoneally daily. After 4 weeks leukocyte trafficking was studied in vivo by intravital microscopy in the mesenteric bed, where the expression of pro-oxidative, proinflammatory, and profibrotic molecules was also assessed. In parallel in vitro studies, HUVEC were grown in 5 mM, 22 mM, 30 mM, 40 mM, 50 mM, and 75 mM glucose media for 48 h, 72 h and 6 days and were treated either with placebo, or with Ang1-7, or with Ang1-7 and its inhibitor A779 in order to evaluate the expression of ICAM-1 and VCAM-1. We further studied leukocytes recruitment in vitro by evaluating PMN-HUVEC adhesion. Ang1-7 prevented in vivo diabetes-induced leukocyte adhesion and extravasation, and it significantly reduced vascular hypertrophy and the other molecular changes due to diabetes. Ang 1-7 prevented also in vitro the hyperglycemia-induced increase of ICAM-1 and VCAM-1 as well as the hyperglycemia-induced PMN adhesion. A779 inhibited Ang 1-7 effects. Ang1-7 significantly reduced diabetes-induced leukocyte recruitment both in vivo and in vitro. These findings emphasize the potential utility of ACE2/Ang1-7/Mas repletion as a strategy to reduce diabetes-induced atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Lime and Phosphate Amendment Can Significantly Reduce Uptake of Cd and Pb by Field-Grown Rice

    Directory of Open Access Journals (Sweden)

    Rongbo Xiao

    2017-03-01

    Full Text Available Agricultural soils are suffering from increasing heavy metal pollution, among which, paddy soil polluted by heavy metals is frequently reported and has elicited great public concern. In this study, we carried out field experiments on paddy soil around a Pb-Zn mine to study amelioration effects of four soil amendments on uptake of Cd and Pb by rice, and to make recommendations for paddy soil heavy metal remediation, particularly for combined pollution of Cd and Pb. The results showed that all the four treatments can significantly reduce the Cd and Pb content in the late rice grain compared with the early rice, among which, the combination amendment of lime and phosphate had the best remediation effects where rice grain Cd content was reduced by 85% and 61%, respectively, for the late rice and the early rice, and by 30% in the late rice grain for Pb. The high reduction effects under the Ca + P treatment might be attributed to increase of soil pH from 5.5 to 6.7. We also found that influence of the Ca + P treatment on rice production was insignificant, while the available Cd and Pb content in soil was reduced by 16.5% and 11.7%, respectively.

  12. Stable multi-infection of splenocytes during SIV infection - the basis for continuous recombination

    Directory of Open Access Journals (Sweden)

    Schultz Anke

    2012-04-01

    Full Text Available Abstract Background Recombination is an important mechanism in the generation of genetic diversity of the human (HIV and simian (SIV immunodeficiency viruses. It requires the co-packaging of divergent RNA genomes into the same retroviral capsid and subsequent template switching during the reverse transcription reaction. By HIV-specific fluorescence in situ hybridization (FISH, we have previously shown that the splenocytes from 2 chronically infected patients with Castelman's disease were multi-infected and thus fulfill the in vivo requirements to generate genetic diversity by recombination. In order to analyze when multi-infection first occurs during a lentivirus infection and how the distribution of multi-infection evolves during the disease course, we now determined the SIV copy numbers from splenocytes of 11 SIVmac251-infected rhesus macaques cross-sectionally covering the time span of primary infection throughout to end-stage immunodeficiency. Results SIV multi-infection of single splenocytes was readily detected in all monkeys and all stages of the infection. Single-infected cells were more frequent than double- or triple- infected cells. There was no strong trend linking the copy number distribution to plasma viral load, disease stage, or CD4 cell counts. Conclusions SIV multi-infection of single cells is already established during the primary infection phase thus enabling recombination to affect viral evolution in vivo throughout the disease course.

  13. High Rate of Simian Immunodeficiency Virus (SIV Infections in Wild Chimpanzees in Northeastern Gabon

    Directory of Open Access Journals (Sweden)

    Vanina Boué

    2015-09-01

    Full Text Available The emergence of HIV-1 groups M, N, O, and P is the result of four independent cross-species transmissions between chimpanzees (cpz and gorillas (gor from central/south Cameroon and humans respectively. Although the first two SIVcpz were identified in wild-born captive chimpanzees in Gabon in 1989, no study has been conducted so far in wild chimpanzees in Gabon. To document the SIVcpz infection rate, genetic diversity, and routes of virus transmission, we analyzed 1458 faecal samples collected in 16 different locations across the country, and we conducted follow-up missions in two of them. We found 380 SIV antibody positive samples in 6 different locations in the north and northeast. We determined the number of individuals collected by microsatellite analysis and obtained an adjusted SIV prevalence of 39.45%. We performed parental analysis to investigate viral spread between and within communities and found that SIVs were epidemiologically linked and were transmitted by both horizontal and vertical routes. We amplified pol and gp41 fragments and obtained 57 new SIVcpzPtt strains from three sites. All strains, but one, clustered together within a specific phylogeographic clade. Given that these SIV positive samples have been collected nearby villages and that humans continue to encroach in ape’s territories, the emergence of a new HIV in this area needs to be considered.

  14. Lipopolysaccharide induces immune activation and SIV replication in rhesus macaques of Chinese origin.

    Directory of Open Access Journals (Sweden)

    Rong Bao

    Full Text Available BACKGROUND: Chronic immune activation is a hallmark of progressive HIV infection and a key determinant of immunodeficiency in HIV-infected individuals. Bacterial lipopolysaccharide (LPS in the circulation has been implicated as a key factor in HIV infection-related systemic immune activation. We thus investigate the impact of LPS on systemic immune activation in simian immunodeficiency virus (SIV-infected rhesus macaques of Chinese origin. METHODS: The animals were inoculated intravenously with SIVmac239. The levels of plasma viral load and host inflammatory cytokines in PBMC were measured by real-time RT-PCR. CD4/CD8 ratio and systemic immune activation markers were examined by flow cytometric analysis of PBMCs. White blood cell and neutrophil counts and C Reactive Protein levels were determined using biochemistry analyzer. The plasma levels of LPS were determined by Tachypleus Amebocyte Lysate (TAL test. RESULTS: The animals inoculated with SIVmac239 became infected as evidenced by the increased plasma levels of SIV RNA and decreased CD4/CD8 ratio. LPS administration of SIV-infected animals induced a transient increase of plasma SIV RNA and immune activation, which was indicated by the elevated expression of the inflammatory cytokines and CD4+HLA-DR+ T cells in PBMCs. CONCLUSIONS: These data support the concept that LPS is a driving factor in systemic immune activation of HIV disease.

  15. Smoking cessation programmes in radon affected areas: can they make a significant contribution to reducing radon-induced lung cancers?

    International Nuclear Information System (INIS)

    Denman, A.R.; Groves-Kirkby, C.J.; Timson, K.; Shield, G.; Rogers, S.; Phillips, P.S.

    2008-01-01

    Domestic radon levels in parts of the UK are sufficiently high to increase the risk of lung cancer in the occupants. Public health campaigns in Northamptonshire, a designated radon affected area with 6.3% of homes having average radon levels over the UK action level of 200 Bq m -3 , have encouraged householders to test for radon and then to carry out remediation in their homes, but have been only partially successful. Only 40% of Northamptonshire houses have been tested, and only 15% of householders finding raised levels proceed to remediate. Of those who did remediate, only 9% smoked, compared to a countywide average of 28.8%. This is unfortunate, since radon and smoking combine to place the individual at higher risk by a factor of around 4, and suggests that current strategies to reduce domestic radon exposure are not reaching those most at risk. During 2004-5, the NHS Stop Smoking Services in Northamptonshire assisted 2,808 smokers to quit to the 4-week stage, with some 30% of 4-week quitters remaining quitters at 1 year. We consider whether smoking cessation campaigns make significant contributions to radon risk reduction on their own, by assessing individual occupants' risk of developing lung cancer from knowledge of their age, gender, and smoking habits, together with he radon level in their house. The results demonstrate that smoking cessation programmes have significant added value in radon affected areas, and contribute a greater health benefit than reducing radon levels in the smokers' homes, whilst they remain smokers. Additionally, results are presented from a questionnaire-based survey of quitters, addressing their reasons for seeking help in quitting smoking, and whether knowledge of radon risks influenced this decision. The impact of these findings on future public health campaigns to reduce the impact of radon and smoking are discussed. (author)

  16. Lipid Replacement Therapy Drink Containing a Glycophospholipid Formulation Rapidly and Significantly Reduces Fatigue While Improving Energy and Mental Clarity

    Directory of Open Access Journals (Sweden)

    Robert Settineri

    2011-08-01

    Full Text Available Background: Fatigue is the most common complaint of patients seeking general medical care and is often treated with stimulants. It is also important in various physical activities of relatively healthy men and women, such as sports performance. Recent clinical trials using patients with chronic fatigue have shown the benefit of Lipid Replacement Therapy in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Methods: Lipid Replacement Therapy was administered for the first time as an all-natural functional food drink (60 ml containing polyunsaturated glycophospholipids but devoid of stimulants or herbs to reduce fatigue. This preliminary study used the Piper Fatigue Survey instrument as well as a supplemental questionnaire to assess the effects of the glycophospholipid drink on fatigue and the acceptability of the test drink in adult men and women. A volunteer group of 29 subjects of mean age 56.2±4.5 years with various fatigue levels were randomly recruited in a clinical health fair setting to participate in an afternoon open label trial on the effects of the test drink. Results: Using the Piper Fatigue instrument overall fatigue among participants was reduced within the 3-hour seminar by a mean of 39.6% (p<0.0001. All of the subcategories of fatigue showed significant reductions. Some subjects responded within 15 minutes, and the majority responded within one hour with increased energy and activity and perceived improvements in cognitive function, mental clarity and focus. The test drink was determined to be quite acceptable in terms of taste and appearance. There were no adverse events from the energy drink during the study.Functional Foods in Health and Disease 2011; 8:245-254Conclusions: The Lipid Replacement Therapy functional food drink appeared to be a safe, acceptable and potentially useful new method to reduce fatigue, sustain energy and improve perceptions of mental function.

  17. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  18. Estimating the impact of vaccination in acute SHIV-SIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ruy [Los Alamos National Laboratory

    2008-01-01

    Human Immunodeficiency Virus (HIV) infects approxmately 0.5% of the world population, and is a major cause of morbidity and mortality worldwide. A vaccine for HIV is urgently required, and a variety of vaccine modalities have been tested in animal models of infection. A number of these studies have shown protection in monkey models of infection, although the ability of the vaccine to protect appears to vary with the viral strain and animal model used. The recent failure of a large vaccine study in humans suggests that further understanding of the basic dynamics of infection and impact of vaccination are required, in order to understand the variable efficacy of vaccination in different infections. The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio (R{sub 0}) of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, in the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in Simian Human Immunodeficiency Virus (SHIV) and Simian Immunodeficiency Virus (SIV) infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3 and 2 fold respectively. This method allows the comparison of vaccination efficacy amongst different viral strains and animal models in vivo.

  19. Reducing eating disorder onset in a very high risk sample with significant comorbid depression: A randomized controlled trial.

    Science.gov (United States)

    Taylor, C Barr; Kass, Andrea E; Trockel, Mickey; Cunning, Darby; Weisman, Hannah; Bailey, Jakki; Sinton, Meghan; Aspen, Vandana; Schecthman, Kenneth; Jacobi, Corinna; Wilfley, Denise E

    2016-05-01

    Eating disorders (EDs) are serious problems among college-age women and may be preventable. An indicated online eating disorder (ED) intervention, designed to reduce ED and comorbid pathology, was evaluated. 206 women (M age = 20 ± 1.8 years; 51% White/Caucasian, 11% African American, 10% Hispanic, 21% Asian/Asian American, 7% other) at very high risk for ED onset (i.e., with high weight/shape concerns plus a history of being teased, current or lifetime depression, and/or nonclinical levels of compensatory behaviors) were randomized to a 10-week, Internet-based, cognitive-behavioral intervention or waitlist control. Assessments included the Eating Disorder Examination (EDE, to assess ED onset), EDE-Questionnaire, Structured Clinical Interview for DSM Disorders, and Beck Depression Inventory-II. ED attitudes and behaviors improved more in the intervention than control group (p = .02, d = 0.31); although ED onset rate was 27% lower, this difference was not significant (p = .28, NNT = 15). In the subgroup with highest shape concerns, ED onset rate was significantly lower in the intervention than control group (20% vs. 42%, p = .025, NNT = 5). For the 27 individuals with depression at baseline, depressive symptomatology improved more in the intervention than control group (p = .016, d = 0.96); although ED onset rate was lower in the intervention than control group, this difference was not significant (25% vs. 57%, NNT = 4). An inexpensive, easily disseminated intervention might reduce ED onset among those at highest risk. Low adoption rates need to be addressed in future research. (c) 2016 APA, all rights reserved).

  20. Reducing Eating Disorder Onset in a Very High Risk Sample with Significant Comorbid Depression: A Randomized Controlled Trial

    Science.gov (United States)

    Taylor, C. Barr; Kass, Andrea E.; Trockel, Mickey; Cunning, Darby; Weisman, Hannah; Bailey, Jakki; Sinton, Meghan; Aspen, Vandana; Schecthman, Kenneth; Jacobi, Corinna; Wilfley, Denise E.

    2015-01-01

    Objective Eating disorders (EDs) are serious problems among college-age women and may be preventable. An indicated on-line eating disorder (ED) intervention, designed to reduce ED and comorbid pathology, was evaluated. Method 206 women (M age = 20 ± 1.8 years; 51% White/Caucasian, 11% African American, 10% Hispanic, 21% Asian/Asian American, 7% other) at very high risk for ED onset (i.e., with high weight/shape concerns plus a history of being teased, current or lifetime depression, and/or non-clinical levels of compensatory behaviors) were randomized to a 10-week, Internet-based, cognitive-behavioral intervention or wait-list control. Assessments included the Eating Disorder Examination (EDE to assess ED onset), EDE-Questionnaire, Structured Clinical Interview for DSM Disorders, and Beck Depression Inventory-II. Results ED attitudes and behaviors improved more in the intervention than control group (p = 0.02, d = 0.31); although ED onset rate was 27% lower, this difference was not significant (p = 0.28, NNT = 15). In the subgroup with highest shape concerns, ED onset rate was significantly lower in the intervention than control group (20% versus 42%, p = 0.025, NNT = 5). For the 27 individuals with depression at baseline, depressive symptomatology improved more in the intervention than control group (p = 0.016, d = 0.96); although ED onset rate was lower in the intervention than control group, this difference was not significant (25% versus 57%, NNT = 4). Conclusions An inexpensive, easily disseminated intervention might reduce ED onset among those at highest risk. Low adoption rates need to be addressed in future research. PMID:26795936

  1. A standardized education protocol significantly reduces traumatic injuries and syncope recurrence: an observational study in 316 patients with vasovagal syncope.

    Science.gov (United States)

    Aydin, M Ali; Mortensen, Kai; Salukhe, Tushar V; Wilke, Iris; Ortak, Michelle; Drewitz, Imke; Hoffmann, Boris; Müllerleile, Kai; Sultan, Arian; Servatius, Helge; Steven, Daniel; von Kodolitsch, Yskert; Meinertz, Thomas; Ventura, Rodolfo; Willems, Stephan

    2012-03-01

    The aim of this study was to assess the role of a non-pharmacological approach on the frequency of traumatic injuries and syncope recurrence in patients with vasovagal syncope and normal hearts. We report the experience in our syncope centre with a standardized education and teaching protocol for patients with vasovagal syncope. The treatment of vasovagal syncope is often complex and discouraging. Besides medical options, behaviour modification is a main component of therapy but has no statistical evidence to support its use. Between January 1999 and September 2006, we prospectively enrolled all patients with vasovagal syncope. The patients were counselled about the benign nature of their disease. Specific recommendations were made according to a standardized education protocol established at our syncope centre. A pre-/post-study was conducted to investigate the effectiveness of our approach on syncope recurrence and frequency of injury as the study endpoints. Complete follow-up data were available from 85% of the study population (316 of 371) after a mean time of 710 ± 286 days (mean age 50 years; standard deviation ± 18 years, 160 female). Eighty-seven patients (27.5%) had a syncope recurrence with 22 suffering an injury during syncope. During the follow-up period, the syncope burden per month was significantly reduced from 0.35 ± 0.03 at initial presentation to 0.08 ± 0.02 (Psyncope was significantly lower at the time of recurrence compared with the initial presentation (25 vs. 42%; McNemar's test P= 0.02). A standardized education protocol significantly reduces traumatic injuries and syncope recurrence in patients with vasovagal syncope.

  2. A field study on chemistry, S(IV) oxidation rates and vertical transport during fog conditions

    Science.gov (United States)

    Joos, F.; Baltensperger, U.

    An extensive fog study was carried out in the central plateu of Switzerland. Ninety-seven fog samples were collected along with aerosol filter and cascade impactor samples, and measurements of O 3, SO 2, NO, NO x, PAN, temperature, and wind speed and direction. Maximum levels in fogwater were 4.3, 4.4., 0.033, 1.7, 0.5, 0.024 and 9.2 mmol ℓ -1 for Cl -, NO 3-, NO 2-, SO 42-, S(IV), oxalate and NH 4+, respectively. pH varied between 2.9 and 7.1. Sixteen additional elements were determined in the fog samples by ICP. The sum of the concentrations of SO 42- and S(IV) agreed very with the total sulfur concentration as determined by ICP. A substantial excess of S(IV) (up to 0.2 mmol ℓ -1) compared to Henry and acid-base equilibrium calculations was found, which can probably be attributed to complex formations with aldehydes. S(IV) oxidation rates of up to 650 nmol ℓ -1 s -1 with ozone and of up to 100 nmol ℓ -1 s -1 with NO 2 were calculated. S(IV) oxidation due to PAN, NO 2- and Fe(III) was of minor importance. A substantial fraction of the major ions was present in the intersitial aerosol (aerosol particles < 4 μm) even during fog conditions. High correlations were found for NH 4+, NO 32-. From their ratios in the fog water and the aerosol (< 4 μm) it could be concluded that at least 40% of NO 3- and 20% of NH 4+ in fog water was due to gas phase scavenging. Increasing concentrations in fog water were found during fog dissipation. Concentrations decreased with increasing height. A vertical transport model including turbulent diffusion and droplet sedimentation is introduced, which matches the experimental data of this vertical profile.

  3. One-Step Ball Milling Preparation of Nanoscale CL-20/Graphene Oxide for Significantly Reduced Particle Size and Sensitivity

    Science.gov (United States)

    Ye, Baoyun; An, Chongwei; Zhang, Yuruo; Song, Changkun; Geng, Xiaoheng; Wang, Jingyu

    2018-02-01

    A one-step method which involves exfoliating graphite materials (GIMs) off into graphene materials (GEMs) in aqueous suspension of CL-20 and forming CL-20/graphene materials (CL-20/GEMs) composites by using ball milling is presented. The conversion of mixtures to composite form was monitored by scanning electron microscopy (SEM) and powder X-ray diffraction (XRD). The impact sensitivities of CL-20/GEM composites were contrastively investigated. It turned out that the energetic nanoscale composites based on CL-20 and GEMs comprising few layers were accomplished. The loading capacity of graphene (reduced graphene oxide, rGO) is significantly less than that of graphene oxide (GO) in CL-20/GEM composites. The formation mechanism was proposed. Via this approach, energetic nanoscale composites based on CL-20 and GO comprised few layers were accomplished. The resulted CL-20/GEM composites displayed spherical structure with nanoscale, ɛ-form, equal thermal stabilities, and lower sensitivities.

  4. Reduced frontal and occipital lobe asymmetry on the CT-scans of schizophrenic patients. Its specificity and clinical significance

    International Nuclear Information System (INIS)

    Falkai, P.; Schneider, T.; Greve, B.; Klieser, E.; Bogerts, B.

    1995-01-01

    Frontal and occipital lobe widths were determined in the computed tomographic (CT) scans of 135 schizophrenic patients, 158 neuro psychiatrically healthy and 102 psychiatric control subjects, including patients with affective psychosis, neurosis and schizoaffective psychosis. Most healthy right-handed subjects demonstrate a relative enlargement of the right frontal as well as left occipital lobe compared to the opposite hemisphere. These normal frontal and occipital lobe asymmetries were selectively reduced in schizophrenics (f.: 5%, p < .0005; o.: 3%, p < .05), irrespective of the pathophysiological subgroup. Schizophrenic neuroleptic non-responders revealed a significant reduction of frontal lobe asymmetry (3%, p < .05), while no correlation between BPRS-sub scores and disturbed cerebral laterality could be detected. In sum the present study demonstrates the disturbed cerebral lateralisation in schizophrenic patients supporting the hypothesis of interrupted early brain development in schizophrenia. (author)

  5. Lactobacillus reuteri DSM 17938 and a placebo both significantly reduced symptoms in children with functional abdominal pain.

    Science.gov (United States)

    Maragkoudaki, M; Chouliaras, G; Orel, R; Horvath, A; Szajewska, H; Papadopoulou, A

    2017-11-01

    Lactobacillus reuteri is a Gram-positive bacterium that naturally inhabits the human intestinal tract. This study assessed how effectively the probiotic L. reuteri DSM 17938 managed childhood functional abdominal pain (FAP). We recruited 54 children with a mean age 9.1 ± 3.8 years, who were diagnosed with FAP in the outpatient clinics of three university hospitals in Greece, Slovenia and Poland, according to the Rome III criteria, from January 2013 to December 2015. They were randomly assigned to receive either 2 × 10 8 colony-forming units of L. reuteri (n = 27) or a placebo (n = 27) for four weeks. Both L. reuteri and the placebo significantly reduced the frequency and intensity of abdominal pain episodes at four and eight weeks compared to baseline (all p L. reuteri decreased the use of pain relieving drugs at four weeks and the number of child school and adult work absences at four and eight weeks, unlike the placebo, which achieved nonsignificant results. However, the difference between the groups did not reach significance. No side effects were recorded. Both L. reuteri and the placebo were effective in alleviating pain in children with FAP, but only L. reuteri improved the child's and family's normal activities. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  6. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Hashimoto, Takeshi; Yokokawa, Takumi; Endo, Yuriko; Iwanaka, Nobumasa; Higashida, Kazuhiko; Taguchi, Sadayoshi

    2013-01-01

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O 2 for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  7. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Yokokawa, Takumi; Endo, Yuriko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Iwanaka, Nobumasa [Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Higashida, Kazuhiko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Faculty of Sport Science, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192 (Japan); Taguchi, Sadayoshi [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan)

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  8. Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail

    Directory of Open Access Journals (Sweden)

    Takeo eKuwata

    2013-05-01

    Full Text Available The role of antibodies in protecting the host from human immunodeficiency virus type 1 (HIV-1 infection is of considerable interest, particularly because the RV144 trial results suggest that antibodies contribute to protection. Although infection of nonhuman primates with simian immunodeficiency virus (SIV is commonly used as an animal model of HIV-1 infection, the viral epitopes that elicit potent and broad neutralizing antibodies to SIV have not been identified. We isolated a monoclonal antibody (MAb B404 that potently and broadly neutralizes various SIV strains. B404 targets a conformational epitope comprising the V3 and V4 loops of Env that intensely exposed when Env binds CD4. B404-resistant variants were obtained by passaging viruses in the presence of increasing concentration of B404 in PM1/CCR5 cells. Genetic analysis revealed that the Q733stop mutation, which truncates the cytoplasmic tail of gp41, was the first major substitution in Env during passage. The maximal inhibition by B404 and other MAbs were significantly decreased against a recombinant virus with a gp41 truncation compared with the parental SIVmac316. This indicates that the gp41 truncation was associated with resistance to antibody-mediated neutralization. The infectivities of the recombinant virus with the gp41 truncation were 7900-fold, 1000-fold, and 140-fold higher than those of SIVmac316 in PM1, PM1/CCR5, and TZM-bl cells, respectively. Immunoblotting analysis revealed that the gp41 truncation enhanced the incorporation of Env into virions. The effect of the gp41 truncation on infectivity was not obvious in the HSC-F macaque cell line, although the resistance of viruses harboring the gp41 truncation to neutralization was maintained. These results suggest that viruses with a truncated gp41 cytoplasmic tail were selected by increased infectivity in human cells and by acquiring resistance to neutralizing antibody.

  9. A pilot study: Horticulture-related activities significantly reduce stress levels and salivary cortisol concentration of maladjusted elementary school children.

    Science.gov (United States)

    Lee, Min Jung; Oh, Wook; Jang, Ja Soon; Lee, Ju Young

    2018-04-01

    The effects of three horticulture-related activities (HRAs), including floral arranging, planting, and flower pressing were compared to see if they influenced changes on a stress scale and on salivary cortisol concentrations (SCC) in maladjusted elementary school children. Twenty maladjusted elementary school children were randomly assigned either to an experimental or control group. The control group carried out individual favorite indoor activities under the supervision of a teacher. Simultaneously, the ten children in the experimental group participated in a HRA program consisting of flower arrangement (FA), planting (P), and flower pressing (PF) activities, in which the other ten children in the control group did not take part. During nine sessions, the activities were completed as follows: FA-FA-FA, P-P-P, and PF-PF-PF; each session lasted 40 min and took place once a week. For the quantitative analysis of salivary cortisol, saliva was collected from the experimental group one week before the HRAs and immediately after the activities for 9 consecutive weeks at the same time each session. In the experimental group, stress scores of interpersonal relationship, school life, personal problems, and home life decreased after the HRAs by 1.3, 1.8, 4.2, and 1.3 points, respectively. In particular, the stress score of school life was significantly reduced (P < 0.01). In addition, from the investigation of the SCCs for the children before and after repeating HRAs three times, it was found that flower arrangement, planting, and flower pressing activities reduced the SCCs by ≥37% compared to the SCCs prior to taking part in the HRAs. These results indicate that HRAs are associated with a reduction in the stress levels of maladjusted elementary school children. Copyright © 2018. Published by Elsevier Ltd.

  10. Evaluación de la estructura factorial del Cuestionario de Valores Interpersonales (SIV

    Directory of Open Access Journals (Sweden)

    César Merino Soto

    2013-09-01

    Full Text Available El artículo evalúa la estructura factorial bajo los efectos del método ipsativo de respuesta, estudiados en el nivel de las subescalas del Cuestionario de Valores Interpersonales de Gordon (SIV, y las relaciones entre ellas, en una muestra de adolescentes entre 15 y 17 años de ambos sexos y procedentes de un colegio privado y estatal, representativos de los niveles socioeconómicos medio y bajo. Aunque el SIV ha sido una herramienta extensamente utilizada, no se reportado previamente un análisis de su estructura factorial en muestras Latinoamericanas. Mediante el análisis de componentes principales y el análisis factorial con un enfoque confirmatorio, se han identificado relaciones bipolares entre Independencia y Benevolencia, y Soporte y Conformidad. Se obtuvo también la confirmación del modelo de valores interpersonales propuesto por L. V. Gordon. En el análisis se consideró un aspecto que artificialmente puede haber influido en el patrón de correlaciones entre los componentes, esto es el método ipsativo de las preguntas del SIV. Finalmente, se discute sobre las medidas ipsativas y sus consecuencias en la interpretación de sus resultados. The present study evaluates the factorial structure, in the level of the subscales, of the Survey of Interpersonal Values (SIV, and the relationships among them, in a sample of adolescents between 15 and 17 years old of both sexes and from a private and public school, representative of low and middle socioeconomic levels. Although the SIV has been a widely used tool, there is no report of an analysis of its factorial structure in Latin-American samples. By means of the principal components analysis and the factorial analysis with a confirmatory approach, bipolar relationships have been identified between Independence and Benevolence, and Support and Conformity. The confirmation of the pattern of interpersonal values proposed by L. V. Gordon was also accomplished. An aspect considered in the

  11. Significant change of local atomic configurations at surface of reduced activation Eurofer steels induced by hydrogenation treatments

    Energy Technology Data Exchange (ETDEWEB)

    Greculeasa, S.G.; Palade, P.; Schinteie, G. [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania); Kuncser, A.; Stanciu, A. [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania); University of Bucharest, Faculty of Physics, 77125, Bucharest-Magurele (Romania); Lungu, G.A. [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania); Porosnicu, C.; Lungu, C.P. [National Institute for Laser, Plasma and Radiation Physics, 77125, Bucharest-Magurele (Romania); Kuncser, V., E-mail: kuncser@infim.ro [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania)

    2017-04-30

    Highlights: • Engineering of Eurofer slab properties by hydrogenation treatments. • Hydrogenation modifies significantly the local atomic configurations at the surface. • Hydrogenation increases the expulsion of the Cr atoms toward the very surface. • Approaching binomial atomic distribution by hydrogenation in the next surface 100 nm. - Abstract: Reduced-activation steels such as Eurofer alloys are candidates for supporting plasma facing components in tokamak-like nuclear fusion reactors. In order to investigate the impact of hydrogen/deuterium insertion in their crystalline lattice, annealing treatments in hydrogen atmosphere have been applied on Eurofer slabs. The resulting samples have been analyzed with respect to local structure and atomic configuration both before and after successive annealing treatments, by X-ray diffractometry (XRD), scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS) and conversion electron Mössbauer spectroscopy (CEMS). The corroborated data point out for a bcc type structure of the non-hydrogenated alloy, with an average alloy composition approaching Fe{sub 0.9}Cr{sub 0.1} along a depth of about 100 nm. EDS elemental maps do not indicate surface inhomogeneities in concentration whereas the Mössbauer spectra prove significant deviations from a homogeneous alloying. The hydrogenation increases the expulsion of the Cr atoms toward the surface layer and decreases their oxidation, with considerable influence on the surface properties of the steel. The hydrogenation treatment is therefore proposed as a potential alternative for a convenient engineering of the surface of different Fe-Cr based alloys.

  12. Site-specific integration and expression of an anti-malarial gene in transgenic Anopheles gambiae significantly reduces Plasmodium infections.

    Directory of Open Access Journals (Sweden)

    Janet M Meredith

    2011-01-01

    Full Text Available Diseases transmitted by mosquitoes have a devastating impact on global health and this is worsening due to difficulties with existing control measures and climate change. Genetically modified mosquitoes that are refractory to disease transmission are seen as having great potential in the delivery of novel control strategies. Historically the genetic modification of insects has relied upon transposable elements which have many limitations despite their successful use. To circumvent these limitations the Streptomyces phage phiC31 integrase system has been successfully adapted for site-specific transgene integration in insects. Here, we present the first site-specific transformation of Anopheles gambiae, the principal vector of human malaria. Mosquitoes were initially engineered to incorporate the phiC31 targeting site at a defined genomic location. A second phase of genetic modification then achieved site-specific integration of Vida3, a synthetic anti-malarial gene. Expression of Vida3, specifically in the midgut of bloodfed females, offered consistent and significant protection against Plasmodium yoelii nigeriensis, reducing average parasite intensity by 85%. Similar protection was observed against Plasmodium falciparum in some experiments, although protection was inconsistent. In the fight against malaria, it is imperative to establish a broad repertoire of both anti-malarial effector genes and tissue-specific promoters for their expression, enabling those offering maximum effect with minimum fitness cost to be identified. In the future, this technology will allow effective comparisons and informed choices to be made, potentially leading to complete transmission blockade.

  13. Optical trapping of nanoparticles with significantly reduced laser powers by using counter-propagating beams (Presentation Recording)

    Science.gov (United States)

    Zhao, Chenglong; LeBrun, Thomas W.

    2015-08-01

    Gold nanoparticles (GNP) have wide applications ranging from nanoscale heating to cancer therapy and biological sensing. Optical trapping of GNPs as small as 18 nm has been successfully achieved with laser power as high as 855 mW, but such high powers can damage trapped particles (particularly biological systems) as well heat the fluid, thereby destabilizing the trap. In this article, we show that counter propagating beams (CPB) can successfully trap GNP with laser powers reduced by a factor of 50 compared to that with a single beam. The trapping position of a GNP inside a counter-propagating trap can be easily modulated by either changing the relative power or position of the two beams. Furthermore, we find that under our conditions while a single-beam most stably traps a single particle, the counter-propagating beam can more easily trap multiple particles. This (CPB) trap is compatible with the feedback control system we recently demonstrated to increase the trapping lifetimes of nanoparticles by more than an order of magnitude. Thus, we believe that the future development of advanced trapping techniques combining counter-propagating traps together with control systems should significantly extend the capabilities of optical manipulation of nanoparticles for prototyping and testing 3D nanodevices and bio-sensing.

  14. Carbon dioxide insufflation can significantly reduce toilet use after colonoscopy: a double-blind randomized controlled trial.

    Science.gov (United States)

    Hsu, Wen-Feng; Hu, Wen-Hao; Chen, Yen-Nien; Lai, Ho-Hsien; Chen, Meng-Kan; Chang, Li-Chun; Tu, Chia-Hong; Chou, Chu-Kuang; Wang, Hsiu-Po; Wu, Ming-Shiang; Chiu, Han-Mo

    2014-03-01

    Carbon dioxide (CO2) insufflation during colonoscopy can significantly decrease abdominal pain and bloating after the procedure, but its impact on the frequency and duration of toilet use remains unknown. The aim of this study was to assess the impact of CO2 insufflation on toilet use after screening colonoscopy. From 138 average-risk individuals who underwent screening colonoscopy during March to August 2013, 120 were enrolled and randomized to receive either CO2 or air insufflation at colonoscopy. Both the colonoscopist and participant were blinded to the type of gas used. Abdominal pain and distension were assessed using a visual analog scoring system. The frequency and duration of toilet visits during a 2-hour postcolonoscopy period were recorded using a radiofrequency identification system. Baseline characteristics were similar in both groups in terms of age, sex, and procedure time. In the 2 hours after colonoscopy, 50 participants (83 %) in the air group and 18 participants (30 %) in the CO2 group (P toilet at least once. The mean (± SD) duration of each toilet visit was 5.93 ± 4.65 minutes in the air group and 1.53 ± 2.84 minutes in the CO2 group (P toilet use after colonoscopy. Use of this technique may help reduce patient burden and allow more efficient use of space in the endoscopy unit. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Analysis of the functional compatibility of SIV capsid sequences in the context of the FIV gag precursor.

    Directory of Open Access Journals (Sweden)

    César A Ovejero

    Full Text Available The formation of immature lentiviral particles is dependent on the multimerization of the Gag polyprotein at the plasma membrane of the infected cells. One key player in the virus assembly process is the capsid (CA domain of Gag, which establishes the protein-protein interactions that give rise to the hexagonal lattice of Gag molecules in the immature virion. To gain a better understanding of the functional equivalence between the CA proteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively, we generated a series of chimeric FIV Gag proteins in which the CA-coding region was partially or totally replaced by its SIV counterpart. All the FIV Gag chimeras were found to be assembly-defective; however, all of them are able to interact with wild-type SIV Gag and be recruited into extracellular virus-like particles, regardless of the SIV CA sequences present in the chimeric FIV Gag. The results presented here markedly contrast with our previous findings showing that chimeric SIVs carrying FIV CA-derived sequences are assembly-competent. Overall, our data support the notion that although the SIV and FIV CA proteins share 51% amino acid sequence similarity and exhibit a similar organization, i.e., an N-terminal domain joined by a flexible linker to a C-terminal domain, their functional exchange between these different lentiviruses is strictly dependent on the context of the recipient Gag precursor.

  16. Fluoroscopy integrated 3D mapping significantly reduces radiation exposure during ablation for a wide spectrum of cardiac arrhythmias.

    Science.gov (United States)

    Christoph, Marian; Wunderlich, Carsten; Moebius, Stefanie; Forkmann, Mathias; Sitzy, Judith; Salmas, Jozef; Mayer, Julia; Huo, Yan; Piorkowski, Christopher; Gaspar, Thomas

    2015-06-01

    Despite the use of established 3D-mapping systems, invasive electrophysiological studies and catheter ablation require high radiation exposure of patients and medical staff. This study investigated whether electroanatomic catheter tracking in prerecorded X-ray images on top of an existing 3D-mapping system has any impact on radiation exposure. Two hundred and ninety-five consecutive patients were either ablated with the guidance of the traditional CARTO-3 system (c3) or with help of the CARTO-UNIVU system (cU): [typical atrial flutter (AFL) n = 58, drug refractory atrial fibrillation (AF) n = 81, ectopic atrial tachycardia (EAT) n = 37, accessory pathways (APs) n = 22, symptomatic, idiopathic premature ventricular complexes (PVCs) n = 56, ventricular tachycardias (VTs) n = 41]. The CARTO-UNIVU allowed a reduction in radiation exposure: fluoroscopy time: AFL c3: 8.6 ± 0.8 min vs. cU: 2.9 ± 0.3 min, P fluoroscopy time the fluoroscopy dose was also reduced significantly. These advantages were not at the cost of increased procedure times, periprocedural complications, or decreased acute ablation success rates. In a wide spectrum of cardiac arrhythmias, and especially in AF and VT ablation, fluoroscopy integrated 3D mapping contributed to a dramatic reduction in radiation exposure without prolonging procedure times and compromising patient's safety. That effect, however, could not be maintained in patients with APs and PVCs. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  17. New scanning technique using Adaptive Statistical lterative Reconstruction (ASIR) significantly reduced the radiation dose of cardiac CT

    International Nuclear Information System (INIS)

    Tumur, Odgerel; Soon, Kean; Brown, Fraser; Mykytowycz, Marcus

    2013-01-01

    The aims of our study were to evaluate the effect of application of Adaptive Statistical Iterative Reconstruction (ASIR) algorithm on the radiation dose of coronary computed tomography angiography (CCTA) and its effects on image quality of CCTA and to evaluate the effects of various patient and CT scanning factors on the radiation dose of CCTA. This was a retrospective study that included 347 consecutive patients who underwent CCTA at a tertiary university teaching hospital between 1 July 2009 and 20 September 2011. Analysis was performed comparing patient demographics, scan characteristics, radiation dose and image quality in two groups of patients in whom conventional Filtered Back Projection (FBP) or ASIR was used for image reconstruction. There were 238 patients in the FBP group and 109 patients in the ASIR group. There was no difference between the groups in the use of prospective gating, scan length or tube voltage. In ASIR group, significantly lower tube current was used compared with FBP group, 550mA (450–600) vs. 650mA (500–711.25) (median (interquartile range)), respectively, P<0.001. There was 27% effective radiation dose reduction in the ASIR group compared with FBP group, 4.29mSv (2.84–6.02) vs. 5.84mSv (3.88–8.39) (median (interquartile range)), respectively, P<0.001. Although ASIR was associated with increased image noise compared with FBP (39.93±10.22 vs. 37.63±18.79 (mean ±standard deviation), respectively, P<001), it did not affect the signal intensity, signal-to-noise ratio, contrast-to-noise ratio or the diagnostic quality of CCTA. Application of ASIR reduces the radiation dose of CCTA without affecting the image quality.

  18. Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

    Directory of Open Access Journals (Sweden)

    W David Wick

    Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

  19. Significantly Reduced Health Burden from Ambient Air Pollution in the United States under Emission Reductions from 1990 to 2016

    Science.gov (United States)

    Zhang, Y.; West, J. J.; Mathur, R.; Xing, J.; Hogrefe, C.; Roselle, S. J.; Bash, J. O.; Pleim, J. E.; Gan, C. M.; Wong, D. C.; Tong, D.; van Donkelaar, A.; Martin, R.

    2017-12-01

    mortality burden would have increased by 61% if the O3 concentration had stayed at the 1990 level. Our preliminary results suggest that air quality improvements have significantly reduced the health burden over the past two decades.

  20. Oxidation of naturally reduced uranium in aquifer sediments by dissolved oxygen and its potential significance to uranium plume persistence

    Science.gov (United States)

    Davis, J. A.; Smith, R. L.; Bohlke, J. K.; Jemison, N.; Xiang, H.; Repert, D. A.; Yuan, X.; Williams, K. H.

    2015-12-01

    The occurrence of naturally reduced zones is common in alluvial aquifers in the western U.S.A. due to the burial of woody debris in flood plains. Such reduced zones are usually heterogeneously dispersed in these aquifers and characterized by high concentrations of organic carbon, reduced mineral phases, and reduced forms of metals, including uranium(IV). The persistence of high concentrations of dissolved uranium(VI) at uranium-contaminated aquifers on the Colorado Plateau has been attributed to slow oxidation of insoluble uranium(IV) mineral phases found in association with these reducing zones, although there is little understanding of the relative importance of various potential oxidants. Four field experiments were conducted within an alluvial aquifer adjacent to the Colorado River near Rifle, CO, wherein groundwater associated with the naturally reduced zones was pumped into a gas-impermeable tank, mixed with a conservative tracer (Br-), bubbled with a gas phase composed of 97% O2 and 3% CO2, and then returned to the subsurface in the same well from which it was withdrawn. Within minutes of re-injection of the oxygenated groundwater, dissolved uranium(VI) concentrations increased from less than 1 μM to greater than 2.5 μM, demonstrating that oxygen can be an important oxidant for uranium in such field systems if supplied to the naturally reduced zones. Dissolved Fe(II) concentrations decreased to the detection limit, but increases in sulfate could not be detected due to high background concentrations. Changes in nitrogen species concentrations were variable. The results contrast with other laboratory and field results in which oxygen was introduced to systems containing high concentrations of mackinawite (FeS), rather than the more crystalline iron sulfides found in aged, naturally reduced zones. The flux of oxygen to the naturally reduced zones in the alluvial aquifers occurs mainly through interactions between groundwater and gas phases at the water table

  1. Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

    Science.gov (United States)

    Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

    2016-03-01

    Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

  2. In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain

    Directory of Open Access Journals (Sweden)

    Joo Chan-Gyu

    2009-06-01

    Full Text Available Abstract Background In vivo proton magnetic resonance spectroscopy (1H-MRS studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection. Results Changes in the N-acetylaspartate (NAA, choline (Cho, myo-inositol (MI, creatine (Cr and glutamine/glutamate (Glx resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi. At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions. Conclusion These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.

  3. Reduced joint counts misclassify patients with oligoarticular psoriatic arthritis and miss significant numbers of patients with active disease.

    Science.gov (United States)

    Coates, Laura C; FitzGerald, Oliver; Gladman, Dafna D; McHugh, Neil; Mease, Philip; Strand, Vibeke; Helliwell, Philip S

    2013-06-01

    To evaluate joint counts in patients with oligoarticular psoriatic arthritis (PsA) for their correlation with treatment decisions and to determine the proportion of patients in whom active disease was missed using reduced joint counts. The international Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise cohort was used for this study. Oligoarthritis was defined as count (TJC) using 68 joints and a swollen joint count (SJC) using 66 joints (66/68-joint counts) were assessed. Reduced joint counts designed for use in rheumatoid arthritis (RA), including 28- and 44-joint counts, were analyzed. In addition, the following proposed joint counts for PsA were tested: the PsA-44 (which includes elbows, wrists, metacarpophalangeal joints, finger proximal interphalangeal [PIP] joints, distal interphalangeal joints, knees, and metatarsophalangeal joints) and the PsA-56 (which includes the same joints as those assessed for the PsA-44 plus ankles and toe PIP joints). Receiver operating characteristic (ROC) curve analysis was used to assess whether joint counts predict treatment changes. The proportion of patients in whom active disease was missed using reduced joint counts designed for RA was also assessed. Among 503 patients recruited to the study, 266 (53%) had oligoarthritis. ROC curve analysis revealed that no TJC or active joint count (AJC), even a 66/68-joint count, predicted treatment change (for the TJC, area under the curve [AUC] 0.57, P = 0.125; for the AJC, AUC 0.56, P = 0.159). Use of the SJC in 66 joints did predict treatment change (AUC 0.62, P = 0.006), as did the SJC using the PsA-44 and the PsA-56 (P counts designed for RA predicted treatment change. A 28-joint count designed for RA missed 21% of patients with tender joints (n = 29) and 27% of patients with swollen joints (n = 23). The PsA-44 and PsA-56 joint counts missed tender joints in 25 patients and 13 patients, respectively, and missed swollen joints in 11 patients

  4. Revisiting a quarter of a century of simian immunodeficiency virus (SIV-associated cardiovascular diseases at the German Primate Center

    Directory of Open Access Journals (Sweden)

    M. Mietsch

    2017-06-01

    Full Text Available Human immunodeficiency virus (HIV comorbidities have become clinically more important due to antiretroviral therapy. Although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. The simian immunodeficiency virus (SIV-infected rhesus macaque (Macaca mulatta represents a valuable model for the investigation of SIV-associated diseases. Although cardiovascular (CV changes are common in HIV-infected patients, there are only a few reports on the incidence of CV findings in SIV-infected animals. In addition, potential associations between pathohistological findings and hematological parameters are still unclear. We therefore conducted a retrospective analysis of 195 SIV-infected rhesus macaques that were euthanized with AIDS-related symptoms at the German Primate Center, Goettingen, over a 25-year period. Pathological findings were correlated with hematological data. The main findings included myocarditis (12.8 %, endocarditis (9.7 %, and arteriopathy (10.3 % in various organs. Thrombocytopenia occurred more frequently in macaques with endocarditis or arteriopathy than in macaques without CV disease (80 % in animals with endocarditis, 60 % in animals with arteriopathy, p < 0. 0001 and p = 0. 0016, respectively. Further investigations of the interaction between coagulation markers, proinflammatory cytokines, and biomarkers associated with endothelial dysfunction (e.g., D-dimers and histological data (vascular wall structure may unravel the mechanisms underlying HIV/SIV-associated CV comorbidities.

  5. Collagen hemostat significantly reduces time to hemostasis compared with cellulose: COBBANA, a single-center, randomized trial.

    Science.gov (United States)

    Qerimi, Bekim; Baumann, Petra; Hüsing, Johannes; Knaebel, Hanns-Peter; Schumacher, Hardy

    2013-06-01

    This single-center, randomized trial compares the hemostatic effectiveness of microfibrillar collagen and oxidized cellulose in arterial bypass surgery. In patients undergoing arterial bypass surgery, 2 hemostats, microfibrillar collagen and oxidized cellulose, were randomly used to achieve hemostasis. The primary endpoint was the time to hemostasis. The secondary endpoints were the complication rate, mortality, number of hemostats required, handling, and adhesion. Collagen achieved hemostasis significantly faster than cellulose, with considerably less hemostats. In addition, its ease of use was rated substantially better. In arterial bypass surgery, microfibrillar collagen is more effective than oxidized cellulose in achieving hemostasis. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. ClusterSignificance: A bioconductor package facilitating statistical analysis of class cluster separations in dimensionality reduced data

    DEFF Research Database (Denmark)

    Serviss, Jason T.; Gådin, Jesper R.; Eriksson, Per

    2017-01-01

    Summary Multi-dimensional data generated via high-throughput experiments is increasingly used in conjunction with dimensionality reduction methods to ascertain if resulting separations of the data correspond with known classes. This is particularly useful to determine if a subset of the variables......, e.g. genes in a specific pathway, alone can separate samples into these established classes. Despite this, the evaluation of class separations is often subjective and performed via visualization. Here we present the ClusterSignificance package; a set of tools designed to assess the statistical...

  7. Bacteriophage treatment significantly reduces viable Clostridium difficile and prevents toxin production in an in vitro model system.

    Science.gov (United States)

    Meader, Emma; Mayer, Melinda J; Gasson, Michael J; Steverding, Dietmar; Carding, Simon R; Narbad, Arjan

    2010-12-01

    Clostridium difficile is primarily a nosocomial pathogen, causing thousands of cases of antibiotic-associated diarrhoea in the UK each year. In this study, we used a batch fermentation model of a C. difficile colonised system to evaluate the potential of a prophylactic and a remedial bacteriophage treatment regime to control the pathogen. It is shown that the prophylaxis regime was effective at preventing the growth of C. difficile (p = viable C. difficile cells (p = <0.0001), but still resulted in a lower level of toxin production relative to the control. The numbers of commensal bacteria including total aerobes and anaerobes, Bifidobacterium sp., Bacteroides sp., Lactobacillus sp., total Clostridium sp., and Enterobacteriaceae were not significantly decreased by this therapy, whereas significant detrimental effects were observed with metronidazole treatment. Our study indicates that phage therapy has potential to be used for the control of C. difficile; it highlights the main benefits of this approach, and some future challenges. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Combination of infliximab with thiopurines significantly reduces white cell and neutrophil counts in inflammatory bowel disease patients.

    Science.gov (United States)

    Parihar, V; Maceneaney, O; Maguire, S; Garry, C; O'Sullivan, M; Kennedy, M; Safaya, K; Smyth, C; Farrell, R

    2017-05-01

    The effects of thiopurines on white cell count are well documented. We compared the effects of infliximab 5 mg/kg monotherapy and combination of infliximab with thiopurines on the total and differential white cell count (WBC). 13 IBD patients treated with infliximab monotherapy and 18 IBD patients treated with a combination of infliximab and thiopurines were included in the study. Using retrospective data, cell counts were examined prior to induction of infliximab, and at 6 weeks and 1 year post-induction. The patients on combination therapy had an absolute WBC at 52 weeks of 5.7 whereas that of patients on Infliximab monotherapy at the same time point was 8.3 with comparable neutrophil count of 3.4 and 5.4. The results showed a significant reduction in white cell count and neutrophils at 6 weeks which persisted at 52 weeks in both groups (p infliximab and thiopurine (p Infliximab monotherapy. There was no significant change in the lymphocyte count. Full blood counts should be closely monitored in all patients starting infliximab therapy, in particular patients receiving concomitant thiopurines.

  9. Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys.

    Science.gov (United States)

    Letvin, Norman L; Rao, Srinivas S; Montefiori, David C; Seaman, Michael S; Sun, Yue; Lim, So-Yon; Yeh, Wendy W; Asmal, Mohammed; Gelman, Rebecca S; Shen, Ling; Whitney, James B; Seoighe, Cathal; Lacerda, Miguel; Keating, Sheila; Norris, Philip J; Hudgens, Michael G; Gilbert, Peter B; Buzby, Adam P; Mach, Linh V; Zhang, Jinrong; Balachandran, Harikrishnan; Shaw, George M; Schmidt, Stephen D; Todd, John-Paul; Dodson, Alan; Mascola, John R; Nabel, Gary J

    2011-05-04

    The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights the importance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and genetic mechanisms of protection against mucosal infection by the simian immunodeficiency virus (SIV). A plasmid DNA prime/recombinant adenovirus serotype 5 (rAd5) boost vaccine regimen was evaluated for its ability to protect monkeys from infection by SIVmac251 or SIVsmE660 isolates after repeat intrarectal challenges. Although this prime-boost vaccine regimen failed to protect against SIVmac251 infection, 50% of vaccinated monkeys were protected from infection with SIVsmE660. Among SIVsmE660-infected animals, there was about a one-log reduction in peak plasma virus RNA in monkeys expressing the major histocompatibility complex class I allele Mamu-A*01, implicating cytotoxic T lymphocytes in the control of SIV replication once infection is established. Among Mamu-A*01-negative monkeys challenged with SIVsmE660, no CD8(+) T cell response or innate immune response was associated with protection against virus acquisition. However, low levels of neutralizing antibodies and an envelope-specific CD4(+) T cell response were associated with vaccine protection in these monkeys. Moreover, monkeys that expressed two TRIM5 alleles that restrict SIV replication were more likely to be protected from infection than monkeys that expressed at least one permissive TRIM5 allele. This study begins to elucidate the mechanisms of vaccine protection against immunodeficiency viruses and highlights the need to analyze these immune and genetic correlates of protection in future trials of HIV vaccine strategies.

  10. Wind Erosion Caused by Land Use Changes Significantly Reduces Ecosystem Carbon Storage and Carbon Sequestration Potentials in Grassland

    Science.gov (United States)

    Li, P.; Chi, Y. G.; Wang, J.; Liu, L.

    2017-12-01

    Wind erosion exerts a fundamental influence on the biotic and abiotic processes associated with ecosystem carbon (C) cycle. However, how wind erosion under different land use scenarios will affect ecosystem C balance and its capacity for future C sequestration are poorly quantified. Here, we established an experiment in a temperate steppe in Inner Mongolia, and simulated different intensity of land uses: control, 50% of aboveground vegetation removal (50R), 100% vegetation removal (100R) and tillage (TI). We monitored lateral and vertical carbon flux components and soil characteristics from 2013 to 2016. Our study reveals three key findings relating to the driving factors, the magnitude and consequence of wind erosion on ecosystem C balance: (1) Frequency of heavy wind exerts a fundamental control over the severity of soil erosion, and its interaction with precipitation and vegetation characteristics explained 69% variation in erosion intensity. (2) With increases in land use intensity, the lateral C flux induced by wind erosion increased rapidly, equivalent to 33%, 86%, 111% and 183% of the net ecosystem exchange of the control site under control, 50R, 100R and TI sites, respectively. (3) After three years' treatment, erosion induced decrease in fine fractions led to 31%, 43%, 85% of permanent loss of C sequestration potential in the surface 5cm soil for 50R, 100R and TI sites. Overall, our study demonstrates that lateral C flux associated with wind erosion is too large to be ignored. The loss of C-enriched fine particles not only reduces current ecosystem C content, but also results in irreversible loss of future soil C sequestration potential. The dynamic soil characteristics need be considered when projecting future ecosystem C balance in aeolian landscape. We also propose that to maintain the sustainability of grassland ecosystems, land managers should focus on implementing appropriate land use rather than rely on subsequent managements on degraded soils.

  11. Influence of microwave plasma parameters on light emission from SiV color centers in nanocrystalline diamond films

    Directory of Open Access Journals (Sweden)

    Himics László

    2014-11-01

    Full Text Available Zero phonon line (ZPL shape, position and integral intensity of SiV defect center in diamond is presented for nanocrystalline diamond (NCD films grown at different conditions, NCD films of average grain sizes from ~50 nm up to ~180 nm have been deposited onto c-Si wafer at substrate temperature of 700 and 850oC from mixture with different CH4 and H2 ratios using MWCVD process. Light emission of SiV defect center and Raman scattering properties of NCD samples were measured on a Renishaw micro-Raman spectrometer with 488 nm excitation. Scanning electron microscopy images were used for monitoring surface morphology and for the analysis of the average grain sizes. Sample thickness was determined by in situ laser reflection interferometry. Characteristics of SiV ZPL are discussed in light of the morphology, bonding structure and average grain size of NCD films.

  12. A novel multi-stage subunit vaccine against paratuberculosis induces significant immunity and reduces bacterial burden in tissues (P4304)

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, Claus; Riber, Ulla

    2013-01-01

    Effective control of paratuberculosis is hindered by lack of a vaccine preventing infection, transmission and without diagnostic interference with tuberculosis. We have developed a novel multi-stage recombinant subunit vaccine in which a fusion of four early expressed MAP antigens is combined...... with a MAP protein expressed in latent infection (FET11 vaccine). FET11 vaccine proteins were formulated with CAF01 adjuvant and injected to MAP challenged calves at two different ages. 28 calves divided into two FET11 vaccine groups, a commercial vaccine and a control group were used in the study...... and followed for a year. The FET11 vaccine induced a significant T cell response against constituent vaccine proteins characterized by a high percentage of CD4+ T cells and participation of polyfunctional CD4+ T cells. Of the two different age groups, late FET11 vaccination conferred protective immunity...

  13. [Intra-Articular Application of Tranexamic Acid Significantly Reduces Blood Loss and Transfusion Requirement in Primary Total Knee Arthroplasty].

    Science.gov (United States)

    Lošťák, J; Gallo, J; Špička, J; Langová, K

    2016-01-01

    PURPOSE OF THE STUDY The aim of this prospective study was to investigate the effect of topical application of tranexamic acid (TXA, Exacyl) on the amount of post-operative blood loss, and blood transfusion requirement in patients undergoing primary total knee arthroplasty (TKA). Attention was paid to early complications potentially associated with TXA administration, such as haematoma, wound exudate, or knee swelling. In addition, the economic benefit of TXA treatment was also taken into account. MATERIAL AND METHODS The study included 238 patients (85 men and 153 women) who underwent primary total knee arthroplasty (TKA) at our department between January 2013 and November 2015. A group of 119 patients (41 men and 78 women) received intraarticular TXA injections according to the treatment protocol (TXA group). A control group matched in basic characteristics to the TXA group also consisted of 119 patients. The average age in the TXA group was 69.8 years, and the most frequent indication for TKA surgery was primary knee osteoarthritis (81.5%). In each patient, post-operative volume of blood lost from drains and total blood loss including hidden blood loss were recorded, as well as post-operative haemoglobin and haematocrit levels. On discharge of each patient from hospital, the size and site of a haematoma; wound exudate, if present after post-operative day 4; joint swelling; range of motion and early revision surgery, if performed, were evaluated. Requirements of analgesic drugs after surgery were also recorded. RESULTS In the TXA group, blood losses from drains were significantly lower than in the control group (456.7 ± 270.8 vs 640.5 ±448.2; p = 0.004). The median value for blood losses from drains was lower by 22% and the average value for total blood loss, including hidden losses, was also lower than in the control group (762.4 ± 345.2 ml vs 995.5 ± 457.3 ml). The difference in the total amount of blood loss between the two groups was significant (p = 0

  14. Activated charcoal significantly reduces the amount of colchicine released from Gloriosa superba in simulated gastric and intestinal media.

    Science.gov (United States)

    Zawahir, Shukry; Gawarammana, Indika; Dargan, Paul I; Abdulghni, Mahfoudh; Dawson, Andrew H

    2017-09-01

    Poisoning with Gloriosa superba, a plant containing colchicine, is common in Sri Lanka. This study was to estimate release of colchicine from 5 g of different parts of Gloriosa superba in simulated gastric and intestinal media, and examine the binding efficacy of activated charcoal (AC) to colchicine within this model. A USP dissolution apparatus-II was used to prepare samples for analysis of colchicine using HPLC. Cumulative colchicine release from tuber in gastric media at 120 minutes was significantly higher (2883 μg/g) than in intestinal media (1015 μg/g) (p colchicine concentration over 2 hours from tuber, leaves and trunk in gastric medium was 2883.15 ± 1295.63, 578.25 ± 366.26 and 345.60 ± 200.08 μg/g respectively and the release in intestinal media was 1014.75 ± 268.16, 347.40 ± 262.61 and 251.55 ± 285.72 μg/g respectively. Introduction of 50 g of AC into both media made colchicine undetectable (colchicine. The colchicine release and elapse time to achieve saturated, equilibrium dissolution mainly depends on physicochemical properties of plant part. Significant in vitro binding of colchicine to AC suggests that AC has a role in decontamination of patients presenting to hospital after ingestion of Gloriosa superba.

  15. Significance of surface functionalization of Gold Nanorods for reduced effect on IgG stability and minimization of cytotoxicity

    International Nuclear Information System (INIS)

    Alex, Sruthi Ann; Rajiv, Sundaramoorthy; Chakravarty, Sujay; Chandrasekaran, N.; Mukherjee, Amitava

    2017-01-01

    side effect of AuNRs by modifying capping. • Polymer-coated AuNRs safe for in vitro assays, but hamper protein functioning. • PEG-AuNRs reduced toxicity to lymphocyte cells and lesser effect on IgG. • Highlights importance of neutral PEGylated particles for theranostic applications.

  16. Experimental Oral Herpes Simplex Virus-1 (HSV-1 Co-infection in Simian Immunodeficiency Virus (SIV-Infected Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Meropi Aravantinou

    2017-12-01

    Full Text Available Herpes simplex virus 1 and 2 (HSV-1/2 similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

  17. Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate and elicit durable immune responses in rhesus macaques

    Science.gov (United States)

    2013-01-01

    Background Live attenuated viruses are among our most potent and effective vaccines. For human immunodeficiency virus, however, a live attenuated strain could present substantial safety concerns. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express SIV and HIV vaccine antigens because its safety and immunogenicity have been demonstrated in millions of children. One dose protects for life against rubella infection. In previous studies, rubella vectors replicated to high titers in cell culture while stably expressing SIV and HIV antigens. Their viability in vivo, however, as well as immunogenicity and antibody persistence, were unknown. Results This paper reports the first successful trial of rubella vectors in rhesus macaques, in combination with DNA vaccines in a prime and boost strategy. The vectors grew robustly in vivo, and the protein inserts were highly immunogenic. Antibody titers elicited by the SIV Gag vector were greater than or equal to those elicited by natural SIV infection. The antibodies were long lasting, and they were boosted by a second dose of replication-competent rubella vectors given six months later, indicating the induction of memory B cells. Conclusions Rubella vectors can serve as a vaccine platform for safe delivery and expression of SIV and HIV antigens. By presenting these antigens in the context of an acute infection, at a high level and for a prolonged duration, these vectors can stimulate a strong and persistent immune response, including maturation of memory B cells. Rhesus macaques will provide an ideal animal model for demonstrating immunogenicity of novel vectors and protection against SIV or SHIV challenge. PMID:24041113

  18. Guanine polynucleotides are self-antigens for human natural autoantibodies and are significantly reduced in the human genome

    Science.gov (United States)

    Fattal, Ittai; Shental, Noam; Ben-Dor, Shifra; Molad, Yair; Gabrielli, Armando; Pokroy-Shapira, Elisheva; Oren, Shirly; Livneh, Avi; Langevitz, Pnina; Zandman-Goddard, Gisele; Sarig, Ofer; Margalit, Raanan; Gafter, Uzi; Domany, Eytan; Cohen, Irun R

    2015-01-01

    In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170 000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome. PMID:26227667

  19. Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV.

    Directory of Open Access Journals (Sweden)

    Jordan Wilkins

    Full Text Available Interferon-induced transmembrane (IFITM proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis.

  20. Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV.

    Science.gov (United States)

    Wilkins, Jordan; Zheng, Yi-Min; Yu, Jingyou; Liang, Chen; Liu, Shan-Lu

    2016-01-01

    Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis.

  1. Viral RNA levels and env variants in semen and tissues of mature male rhesus macaques infected with SIV by penile inoculation.

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    Francis Fieni

    Full Text Available HIV is shed in semen but the anatomic site of virus entry into the genital secretions is unknown. We determined viral RNA (vRNA levels and the envelope gene sequence in the SIVmac 251 viral populations in the genital tract and semen of 5 adult male rhesus monkeys (Macaca mulatta that were infected after experimental penile SIV infection. Paired blood and semen samples were collected from 1-9 weeks after infection and the monkeys were necropsied eleven weeks after infection. The axillary lymph nodes, testes, epididymis, prostate, and seminal vesicles were collected and vRNA levels and single-genome analysis of the SIVmac251 env variants was performed. At the time of semen collection, blood vRNA levels were between 3.09 and 7.85 log10 vRNA copies/ml plasma. SIV RNA was found in the axillary lymph nodes of all five monkeys and in 3 of 5 monkeys, all tissues examined were vRNA positive. In these 3 monkeys, vRNA levels (log10 SIVgag copies/ug of total tissue RNA in the axillary lymph node (6.48 ± 0.50 were significantly higher than in the genital tract tissues: testis (3.67 ± 2.16; p<0.05, epididymis (3.08 ± 1.19; p<0.0001, prostate (3.36 ± 1.30; p<0.01, and seminal vesicle (2.67 ± 1.50; p<0.0001. Comparison of the SIVmac251 env viral populations in blood plasma, systemic lymph node, and genital tract tissues was performed in two of the macaques. Visual inspection of the Neighbor-Joining phylograms revealed that in both animals, all the sequences were generally distributed evenly among all tissue compartments. Importantly, viral populations in the genital tissues were not distinct from those in the systemic tissues. Our findings demonstrate striking similarity in the viral populations in the blood and male genital tract tissues within 3 months of penile SIV transmission.

  2. The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid

    Directory of Open Access Journals (Sweden)

    Aiken Christopher

    2004-06-01

    Full Text Available Abstract Background Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-O-{3',3'-dimethylsuccinyl}-betulinic acid (DSB specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction in Pr55Gag. By contrast, SIVmac239 replicates efficiently in the presence of high concentrations of DSB. To determine whether sequence differences in the CA-SP1 junction can fully account for the differential sensitivity of HIV-1 and SIV to DSB, we engineered mutations in this region of two viruses and tested their sensitivity to DSB in replication assays using activated human primary CD4+ T cells. Results Substitution of the P2 and P1 residues of HIV-1 by the corresponding amino acids of SIV resulted in strong resistance to DSB, but the mutant virus replicated with reduced efficiency. Conversely, replication of an SIV mutant containing three amino acid substitutions in the CA-SP1 cleavage site was highly sensitive to DSB, and the mutations resulted in delayed cleavage of the CA-SP1 junction in the presence of the drug. Conclusions These results demonstrate that the CA-SP1 junction in Pr55Gag represents the primary viral target of DSB. They further suggest that the therapeutic application of DSB will be accompanied by emergence of mutant viruses that are highly resistant to the drug but which exhibit reduced fitness relative to wild type HIV-1.

  3. From meatless Mondays to meatless Sundays: motivations for meat reduction among vegetarians and semi-vegetarians who mildly or significantly reduce their meat intake.

    Science.gov (United States)

    De Backer, Charlotte J S; Hudders, Liselot

    2014-01-01

    This study explores vegetarians' and semi-vegetarians' motives for reducing their meat intake. Participants are categorized as vegetarians (remove all meat from their diet); semi-vegetarians (significantly reduce meat intake: at least three days a week); or light semi-vegetarians (mildly reduce meat intake: once or twice a week). Most differences appear between vegetarians and both groups of semi-vegetarians. Animal-rights and ecological concerns, together with taste preferences, predict vegetarianism, while an increase in health motives increases the odds of being semi-vegetarian. Even within each group, subgroups with different motives appear, and it is recommended that future researchers pay more attention to these differences.

  4. Bacteriophage cocktail significantly reduces Escherichia coli O157: H7 contamination of lettuce and beef, but does not protect against recontamination.

    Science.gov (United States)

    Carter, Chandi D; Parks, Adam; Abuladze, Tamar; Li, Manrong; Woolston, Joelle; Magnone, Joshua; Senecal, Andre; Kropinski, Andrew M; Sulakvelidze, Alexander

    2012-07-01

    Foods contaminated with Escherichia coli O157:H7 cause more than 63,000 foodborne illnesses in the United States every year, resulting in a significant economic impact on medical costs and product liabilities. Efforts to reduce contamination with E. coli O157:H7 have largely focused on washing, application of various antibacterial chemicals, and gamma-irradiation, each of which has practical and environmental drawbacks. A relatively recent, environmentally-friendly approach proposed for eliminating or significantly reducing E. coli O157:H7 contamination of foods is the use of lytic bacteriophages as biocontrol agents. We found that EcoShield™, a commercially available preparation composed of three lytic bacteriophages specific for E. coli O157:H7, significantly (p < 0.05) reduced the levels of the bacterium in experimentally contaminated beef by ≥ 94% and in lettuce by 87% after a five minute contact time. The reduced levels of bacteria were maintained for at least one week at refrigerated temperatures. However, the one-time application of EcoShield™ did not protect the foods from recontamination with E. coli O157:H7. Our results demonstrate that EcoShield™ is effective in significantly reducing contamination of beef and lettuce with E. coli O157:H7, but does not protect against potential later contamination due to, for example, unsanitary handling of the foods post processing.

  5. Role of Occult and Post-acute Phase Replication in Protective Immunity Induced with a Novel Live Attenuated SIV Vaccine

    NARCIS (Netherlands)

    Berry, Neil; Manoussaka, Maria; Ham, Claire; Ferguson, Deborah; Tudor, Hannah; Mattiuzzo, Giada; Klaver, Bep; Page, Mark; Stebbings, Richard; Das, Atze T.; Berkhout, Ben; Almond, Neil; Cranage, Martin P.

    2016-01-01

    In order to evaluate the role of persisting virus replication during occult phase immunisation in the live attenuated SIV vaccine model, a novel SIVmac239Δnef variant (SIVrtTA) genetically engineered to replicate in the presence of doxycycline was evaluated for its ability to protect against

  6. Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection.

    Science.gov (United States)

    Glavan, T W; Gaulke, C A; Santos Rocha, C; Sankaran-Walters, S; Hirao, L A; Raffatellu, M; Jiang, G; Bäumler, A J; Goulart, L R; Dandekar, S

    2016-05-01

    HIV targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. However, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (PRRs) during HIV infection and disease progression are not well defined. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we found a robust increase in PRRs and inflammatory cytokine gene expression during the acute SIV infection in both peripheral blood and gut mucosa, coinciding with viral replication. PRR expression remained elevated in peripheral blood following the transition to chronic SIV infection. In contrast, massive dampening of PRR expression was detected in the gut mucosa, despite the presence of detectable viral loads. Exceptionally, expression of Toll-like receptor 4 (TLR4) and TLR8 was downmodulated and diverged from expression patterns for most other TLRs in the gut. Decreased mucosal PRR expression was associated with increased abundance of several pathogenic bacterial taxa, including Pasteurellaceae members, Aggregatibacter and Actinobacillus, and Mycoplasmataceae family. Early antiretroviral therapy led to viral suppression but only partial maintenance of gut PRRs and cytokine gene expression. In summary, SIV infection dampens mucosal innate immunity through PRR dysregulation and may promote immune activation, gut microbiota changes, and ineffective viral clearance.

  7. Association of activating KIR copy number variation of NK cells with containment of SIV replication in rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Ina Hellmann

    2011-12-01

    Full Text Available While the contribution of CD8⁺ cytotoxic T lymphocytes to early containment of HIV-1 spread is well established, a role for NK cells in controlling HIV-1 replication during primary infection has been uncertain. The highly polymorphic family of KIR molecules expressed on NK cells can inhibit or activate these effector cells and might therefore modulate their activity against HIV-1-infected cells. In the present study, we investigated copy number variation in KIR3DH loci encoding the only activating KIR receptor family in rhesus monkeys and its effect on simian immunodeficiency virus (SIV replication during primary infection in rhesus monkeys. We observed an association between copy numbers of KIR3DH genes and control of SIV replication in Mamu-A*01⁻ rhesus monkeys that express restrictive TRIM5 alleles. These findings provide further evidence for an association between NK cells and the early containment of SIV replication, and underscore the potential importance of activating KIRs in stimulating NK cell responses to control SIV spread.

  8. Kunstimuuseumi Kumu püsiväljapanek = Permanent exhibition at the Kumu Art Museum of Estonia

    Index Scriptorium Estoniae

    2007-01-01

    siväljapanekute "Eesti kunsti klassika 18. sajandi algusest kuni 1944. aastani" (kujundus Liina Siib) ja "Eesti kunst 1945-1991" (kujundus Terje Kallast ja Urmas Luure) näitusekujundusest, kujundajatest, nende tähtsamad tööd näituse kujundajatena. 8 värv. vaadet, fotod L. Siibist ja T. Kallastist

  9. Low dose rectal inoculation of rhesus macaques by SIV smE660 or SIVmac251 recapitulates

    Energy Technology Data Exchange (ETDEWEB)

    Hraber, Peter [Los Alamos National Laboratory; Giorgi, Elena E [Los Alamos National Laboratory; Keele, Brandon [UNIV OF ALABAMA; Li, Hui [UNIV OF ALABAMA; Learn, Gerald [UNIV OF ALABAMA

    2008-01-01

    We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1--5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1--5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research.

  10. Mucosal vaccination with heterologous viral vectored vaccine targeting subdominant SIV accessory antigens strongly inhibits early viral replication

    DEFF Research Database (Denmark)

    Xu, Huanbin; Andersson, Anne-Marie Carola; Ragonnaud, Emeline

    2017-01-01

    Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat...

  11. Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion

    Directory of Open Access Journals (Sweden)

    Durand-Gasselin Lucie

    2010-09-01

    Full Text Available Abstract Background HIV reservoirs are rapidly established after infection, and the effect of HAART initiated very early during acute infection on HIV reservoirs remains poorly documented, particularly in tissue known to actively replicate the virus. In this context, we used the model of experimental infection of macaques with pathogenic SIV to assess in different tissues: (i the effect of a short term HAART initiated at different stages during acute infection on viral dissemination and replication, and (ii the local concentration of antiviral drugs. Results Here, we show that early treatment with AZT/3TC/IDV initiated either within 4 hours after intravenous infection of macaques with SIVmac251 (as a post exposure prophylaxis or before viremia peak (7 days post-infection [pi], had a strong impact on SIV production and dissemination in all tissues but did not prevent infection. When treatment was initiated after the viremia peak (14 days pi or during early chronic infection (150 days pi, significant viral replication persists in the peripheral lymph nodes and the spleen of treated macaques despite a strong effect of treatment on viremia and gut associated lymphoid tissues. In these animals, the level of virus persistence in tissues was inversely correlated with local concentrations of 3TC: high concentrations of 3TC were measured in the gut whereas low concentrations were observed in the secondary lymphoid tissues. IDV, like 3TC, showed much higher concentration in the colon than in the spleen. AZT concentration was below the quantification threshold in all tissues studied. Conclusions Our results suggest that limited antiviral drug diffusion in secondary lymphoid tissues may allow persistent viral replication in these tissues and could represent an obstacle to HIV prevention and eradication.

  12. Fragmentation of SIV-gag vaccine induces broader T cell responses.

    Directory of Open Access Journals (Sweden)

    Adel Benlahrech

    Full Text Available High mutation rates of human immunodeficiency virus (HIV allows escape from T cell recognition preventing development of effective T cell vaccines. Vaccines that induce diverse T cell immune responses would help overcome this problem. Using SIV gag as a model vaccine, we investigated two approaches to increase the breadth of the CD8 T cell response. Namely, fusion of vaccine genes to ubiquitin to target the proteasome and increase levels of MHC class I peptide complexes and gene fragmentation to overcome competition between epitopes for presentation and recognition.three vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes were cloned into a replication defective adenovirus vector and immunogenicity assessed in an in vitro human priming system. The breadth of the CD8 T cell response, defined by the number of distinct epitopes, was assessed by IFN-γ-ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry. We observed an increase of two- to six-fold in the number of epitopes recognised in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag. In contrast, although proteasomal targeting was achieved, there was a marked reduction in the number of epitopes recognised in the ubiquitin-fused full-length gag compared to the full-length unmodified gene, but there were no differences in the number of epitope responses induced by non-ubiquitinated full-length gag and the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T cell memory differentiation and polyfunctionality, though most responses were directed against the Ad5 vector.Fragmentation but not fusion with ubiquitin increases the breadth of the CD8 T vaccine response against SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise

  13. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Martin Cranage

    2008-08-01

    Full Text Available The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT inhibitor tenofovir (PMPA, 9-[(R-2-(phosphonomethoxy propyl] adenine monohydrate, a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV in a well-established and standardised macaque model.A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50 of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC, quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA load by sensitive quantitative competitive (qc RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6 or had

  14. Photoluminescence excitation spectroscopy of SiV- and GeV- color center in diamond

    Science.gov (United States)

    Häußler, Stefan; Thiering, Gergő; Dietrich, Andreas; Waasem, Niklas; Teraji, Tokuyuki; Isoya, Junichi; Iwasaki, Takayuki; Hatano, Mutsuko; Jelezko, Fedor; Gali, Adam; Kubanek, Alexander

    2017-06-01

    Color centers in diamond are important quantum emitters for a broad range of applications ranging from quantum sensing to quantum optics. Understanding the internal energy level structure is of fundamental importance for future applications. We experimentally investigate the level structure of an ensemble of few negatively charged silicon-vacancy (SiV-) and germanium-vacancy (GeV-) centers in bulk diamond at room temperature by photoluminescence (PL) and excitation (PLE) spectroscopy over a broad wavelength range from 460 to 650 {nm} and perform power-dependent saturation measurements. For SiV- our experimental results confirm the presence of a higher energy transition at ˜ 2.31 {eV}. By comparison with detailed theoretical simulations of the imaginary dielectric function we interpret the transition as a dipole-allowed transition from {}2{E}g-state to {}2{A}2u-state where the corresponding a 2u -level lies deeply inside the diamond valence band. Therefore, the transition is broadened by the diamond band. At higher excitation power of 10 {mW} we indicate signs of a parity-conserving transition at ˜ 2.03 {eV} supported by saturation measurements. For GeV- we demonstrate that the PLE spectrum is in good agreement with the mirror image of the PL spectrum of the zero-phonon line. Experimentally we do not observe a higher lying energy level up to a transition wavelength of 460 {nm}. The observed PL spectra are identical, independent of excitation wavelength, suggesting a rapid decay to {}2{E}u excited state and followed by optical transition to {}2{E}g ground state. Our investigations convey important insights for future quantum optics and quantum sensing experiments based on SiV--center and GeV--center in diamond.

  15. Intra-articular (IA) ropivacaine microparticle suspensions reduce pain, inflammation, cytokine, and substance p levels significantly more than oral or IA celecoxib in a rat model of arthritis.

    Science.gov (United States)

    Rabinow, Barrett; Werling, Jane; Bendele, Alison; Gass, Jerome; Bogseth, Roy; Balla, Kelly; Valaitis, Paul; Hutchcraft, Audrey; Graham, Sabine

    2015-02-01

    Current therapeutic treatment options for osteoarthritis entail significant safety concerns. A novel ropivacaine crystalline microsuspension for bolus intra-articular (IA) delivery was thus developed and studied in a peptidoglycan polysaccharide (PGPS)-induced ankle swelling rat model. Compared with celecoxib controls, both oral and IA, ropivacaine IA treatment resulted in a significant reduction of pain upon successive PGPS reactivation, as demonstrated in two different pain models, gait analysis and incapacitance testing. The reduction in pain was attended by a significant reduction in histological inflammation, which in turn was accompanied by significant reductions in the cytokines IL-18 and IL-1β. This may have been due to inhibition of substance P, which was also significantly reduced. Pharmacokinetic analysis indicated that the analgesic effects outlasted measurable ropivacaine levels in either blood or tissue. The results are discussed in the context of pharmacologic mechanisms both of local anesthetics as well as inflammatory arthritis.

  16. Eight weeks of omeprazole 20 mg significantly reduces both laryngopharyngeal reflux and comorbid chronic rhinosinusitis signs and symptoms: Randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Anzić, S A; Turkalj, M; Župan, A; Labor, M; Plavec, D; Baudoin, T

    2018-04-01

    Gastroesophageal reflux recommended treatment (dose and duration) with proton-pump inhibitor (PPI) compared to placebo significantly reduces the signs and symptoms of laryngopharyngeal reflux (LPR) and comorbid chronic rhinosinusitis (CRS). Double-blind randomised placebo-controlled trial. Eight weeks of treatment with omeprazole 20 mg once daily (OD). Sixty patients (28 women, aged 19-87 years) with diagnosed LPR and comorbid CRS. Significant reduction in signs and symptoms (reflux symptom index (RSI) score as subjective, and reflux finding score (RFS) as objective measure) of LPR after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo. Secondary objectives were significant reduction in signs and symptoms of comorbid CRS after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo and the association of the severity of signs and symptoms of LPR with the ones of CRS. RSI and RFS decreased significantly more in the active treatment group after 8 weeks compared to placebo (P < .001 for both). CRS and endoscopy scoring decreased both significantly more in the active group after 8 weeks compared to placebo (P < .001 for both). CRS scoring significantly correlated with RSI (R = 0.312, P = .015) but not with RFS (R = 0.199, P = .127). The results of our trial suggest that omeprazole 20 mg OD for 8 weeks was effective in reducing signs and symptoms of both LPR and CRS, although in most patients still present at the end of the trial. © 2017 John Wiley & Sons Ltd.

  17. An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy.

    Science.gov (United States)

    Lakritz, Jessica R; Yalamanchili, Samshita; Polydefkis, Michael J; Miller, Andrew D; McGrath, Michael S; Williams, Kenneth C; Burdo, Tricia H

    2017-08-01

    Peripheral neuropathy (PN) is a major comorbidity of HIV infection that is caused in part by chronic immune activation. HIV-PN is associated with infiltration of monocytes/macrophages to the dorsal root ganglia (DRG) causing neuronal loss and formation of Nageotte nodules. Here, we used an oral form of methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine biosynthesis inhibitor, to specifically reduce activation of myeloid cells. MGBG is selectively taken up by monocyte/macrophages in vitro and inhibits HIV p24 expression and DNA viral integration in macrophages. Here, MGBG was administered to nine SIV-infected, CD8-depleted rhesus macaques at 21 days post-infection (dpi). An additional nine SIV-infected, CD8-depleted rhesus macaques were used as untreated controls. Cell traffic to tissues was measured by in vivo BrdU pulse labeling. MGBG treatment significantly diminished DRG histopathology and reduced the number of CD68+ and CD163+ macrophages in DRG tissue. The number of recently trafficked BrdU+ cells in the DRG was significantly reduced with MGBG treatment. Despite diminished DRG pathology, intraepidermal nerve fiber density (IENFD) did not recover after treatment with MGBG. These data suggest that MGBG alleviated DRG pathology and inflammation.

  18. Measuring turnover of SIV DNA in resting CD4+ T cells using pyrosequencing: implications for the timing of HIV eradication therapies.

    Directory of Open Access Journals (Sweden)

    Jeanette C Reece

    Full Text Available Resting CD4+ T cells are a reservoir of latent HIV-1. Understanding the turnover of HIV DNA in these cells has implications for the development of eradication strategies. Most studies of viral latency focus on viral persistence under antiretroviral therapy (ART. We studied the turnover of SIV DNA resting CD4+ T cells during active infection in a cohort of 20 SIV-infected pigtail macaques. We compared SIV sequences at two Mane-A1*084:01-restricted CTL epitopes using serial plasma RNA and resting CD4+ T cell DNA samples by pyrosequencing, and used a mathematical modeling approach to estimate SIV DNA turnover. We found SIV DNA turnover in resting CD4+ T cells was slow in animals with low chronic viral loads, consistent with the long persistence of latency seen under ART. However, in animals with high levels of chronic viral replication, turnover was high. SIV DNA half-life within resting CD4 cells correleated with viral load (p = 0.0052 at the Gag KP9 CTL epitope. At a second CTL epitope in Tat (KVA10 there was a trend towards an association of SIV DNA half-life in resting CD4 cells and viral load (p = 0.0971. Further, we found that the turnover of resting CD4+ T cell SIV DNA was higher for escape during early infection than for escape later in infection (p = 0.0084. Our results suggest viral DNA within resting CD4 T cells is more labile and may be more susceptible to reactivation/eradication treatments when there are higher levels of virus replication and during early/acute infection.

  19. Compartmentalization of SIV Replication Within Secondary Lymphoid Tissues of Rhesus Macaques is Linked to Disease Stage and Inversely Related to Localization of Virus-Specific CTL1 2

    Science.gov (United States)

    Connick, Elizabeth; Folkvord, Joy M.; Lind, Katherine T.; Rakasz, Eva G.; Miles, Brodie; Wilson, Nancy A.; Santiago, Mario L.; Schmitt, Kimberly; Stephens, Edward B.; Kim, Hyeon O.; Wagstaff, Reece; Li, Shengbin; Abdelaal, Hadia M.; Kemp, Nathan; Watkins, David I.; MaWhinney, Samantha; Skinner, Pamela J.

    2014-01-01

    We previously demonstrated that HIV replication is concentrated in lymph node B cell follicles during chronic infection and that HIV-specific CTL fail to accumulate in large numbers at those sites. It is unknown whether these observations can be generalized to other secondary lymphoid tissues, or whether virus compartmentalization occurs in the absence of CTL. We evaluated these questions in SIVmac239-infected rhesus macaques by quantifying SIV RNA+ cells and SIV-specific CTL in situ in spleen, lymph nodes and intestinal tissues obtained at several stages of infection. During chronic asymptomatic infection prior to simian AIDS (SAIDS), SIV-producing cells were more concentrated in follicular compared to extrafollicular regions of secondary lymphoid tissues. At day 14 of infection, when CTL have minimal impact on virus replication, there was no compartmentalization of SIV-producing cells. Virus compartmentalization was diminished in animals with SAIDS, which often have low frequency CTL responses. SIV-specific CTL were consistently more concentrated within extrafollicular regions of lymph node and spleen in chronically infected animals regardless of epitope specificity. Frequencies of SIV-specific CTL within follicular and extrafollicular compartments predicted SIV RNA+ cells within these compartments in a mixed model. Few SIV-specific CTL expressed the follicular homing molecule CXCR5 in the absence of the extrafollicular retention molecule CCR7, possibly accounting for the paucity of follicular CTL. These findings bolster the hypothesis that B cell follicles are immune privileged sites and suggest that strategies to augment CTL in B cell follicles could lead to improved viral control and possibly a functional cure for HIV infection. PMID:25362178

  20. Humoral immunity induced by mucosal and/or systemic SIV-specific vaccine platforms suggest novel combinatorial approaches for enhancing responses

    OpenAIRE

    Vargas-Inchaustegui, Diego A.; Tuero, Iskra; Mohanram, Venkatramanan; Musich, Thomas; Pegu, Poonam; Valentin, Antonio; Sui, Yongjun; Rosati, Margherita; Bear, Jenifer; Venzon, David J.; Kulkarni, Viraj; Alicea, Candido; Pilkington, Guy R.; Liyanage, Namal P.M.; Demberg, Thorsten

    2014-01-01

    Combinatorial HIV/SIV vaccine approaches targeting multiple arms of the immune system might improve protective efficacy. We compared SIV-specific humoral immunity induced in rhesus macaques by five vaccine regimens. Systemic regimens included ALVAC-SIVenv priming and Env boosting (ALVAC/Env); DNA immunization; and DNA plus Env co-immunization (DNA&Env). RepAd/Env combined mucosal replication-competent Ad-env priming with systemic Env boosting. A Peptide/Env regimen, given so...

  1. Systemic Therapy after Radiotherapy Significantly Reduces the Risk of Mortality of Patients with 1-3 Brain Metastases: A Retrospective Study of 250 Patients.

    Science.gov (United States)

    Li, Bo; Dai, Zhao-Xia; Chen, Yi-Dong; Liu, Yan-Wei; Liu, Shuai; Gu, Xue-Nan; Qiu, Xiao-Guang

    2017-12-20

    For patients with a brain metastasis (BM), systemic therapy is usually administered after the completion of radiotherapy, especially in cases of multiple BMs. However, the role of systemic therapy in patients with a limited number of BMs is not clear. Therefore, we conducted a retrospective study to explore this question. Consecutive patients with a pathologically confirmed malignancy and 1-3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China. A total of 250 patients were enrolled; of them, 135 received radiotherapy alone and 115 received radiotherapy plus systemic therapy. In patients receiving whole-brain radiation therapy (WBRT) as radiotherapy, 28 received WBRT alone and 35 patients received WBRT plus systemic therapy. Of the patients treated with stereotactic radiosurgery (SRS), 107 received SRS alone and 80 received SRS plus systemic therapy. Multivariate analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone (hazard ratio [HR] = 0.294, 95% confidence interval [CI] = 0.158-0.548). Further, when the analysis was conducted in subgroups of WBRT (HR = 0.230, 95% CI = 0.081-0.653) or SRS (HR = 0.305, 95% CI = 0.127-0.731), systemic therapy still showed the ability to reduce the risk of mortality in patients with BMs. Systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1-3 BMs.

  2. Prophylactic administration of porcine-derived lung surfactant is a significant factor in reducing the odds for peri-intraventricular haemorrhage in premature infants.

    Science.gov (United States)

    Walti, Hervé; Paris-Llado, Josefa; Egberts, Johannes; Brand, Roland; Bevilacqua, Giulio; Gardini, Fabrizio; Bréart, Gérard

    2002-01-01

    We hypothesized that prophylactic treatment with a porcine-modified lung surfactant (PLS) reduces the rate of peri-intraventricular haemorrhage (PIVH) more than rescue treatment. We performed a meta-analysis of three prophylactic versus rescue trials conducted with PLS in four countries using individual data. Overall (grades 1-4) or severe (grades 3 and 4) PIVH of 671 newborns was the outcome. A logistic regression analysis was performed. Prophylactic exposure to PLS was a significant independent factor in reducing the incidence of overall (OR 0.65; 95% CI 0.47-0.90) and severe (OR 0.56; 95% CI 0.35-0.89) PIVH. Moreover, for severe PIVH, the adjusted OR for outborn babies exposed to prophylactic treatment with PLS was highly significant (OR 0.11; 95% CI 0.02-to 0.49). The results we obtained show that prophylactic treatment with PLS reduces the rate of PIVH more than rescue treatment. Copyright 2002 S. Karger AG, Basel

  3. Functional Performance Evaluation of the Northwestern University Flexible Subischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral Amputation

    Science.gov (United States)

    2016-10-01

    Socket for Persons with Transfemoral Amputation PRINCIPAL INVESTIGATOR: Dr. Stefania Fatone, PhD CONTRACTING ORGANIZATION: Northwestern...University Flexible Subischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral Amputation 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...0708 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Stefania Fatone, PhD 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: s-fatone@northwestern.edu 5f. WORK

  4. The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

    Science.gov (United States)

    Geremia, N M; Hryciw, T; Bao, F; Streijger, F; Okon, E; Lee, J H T; Weaver, L C; Dekaban, G A; Kwon, B K; Brown, A

    2017-09-01

    We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  5. Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Christine M Fennessey

    2017-05-01

    Full Text Available HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes. In vitro infection of rhesus CD4+ T cells and in vivo infection of rhesus macaques revealed levels of viral replication of SIVmac239M comparable to parental SIVmac239. After intravenous inoculation of 2.2x105 infectious units of SIVmac239M, an average of 1,247 barcodes were identified during acute infection in 26 infected rhesus macaques. Of the barcodes identified in the stock, at least 85.6% actively replicated in at least one animal, and on average each barcode was found in 5 monkeys. Four infected animals were treated with combination antiretroviral therapy (cART for 82 days starting on day 6 post-infection (study 1. Plasma viremia was reduced from >106 to <15 vRNA copies/mL by the time treatment was interrupted. Virus rapidly rebounded following treatment interruption and between 87 and 136 distinct clonotypes were detected in plasma at peak rebound viremia. This study confirmed that SIVmac239M viremia could be successfully curtailed with cART, and that upon cART discontinuation, rebounding viral variants could be identified and quantified. An additional 6 animals infected with SIVmac239M were treated with cART beginning on day 4 post-infection for 305, 374, or 482 days (study 2. Upon treatment interruption, between 4 and 8 distinct viral clonotypes were detected in each animal at peak rebound

  6. Imaging lymphoid tissues in nonhuman primates to understand SIV pathogenesis and persistence.

    Science.gov (United States)

    Deleage, Claire; Turkbey, Baris; Estes, Jacob D

    2016-08-01

    CD4+ T cells are the primary HIV-1 target cell, with the vast majority of these cells residing within lymphoid tissue compartments throughout the body. Predictably, HIV-1 infection, replication, localization, reservoir establishment and persistence, as well as associated host immune and inflammatory responses and disease pathology principally take place within the tissues of the immune system. By virture of the fact that the virus-host struggle is played out within lymphoid and additional tissues compartments in HIV-1 infected individuals it is critical to understand HIV-1 infection and disease within these relevant tissue sites; however, there are obvious limitations to studying these dynamic processes in humans. Nonhuman primate (NHP) research has provided a vital bridge between basic and preclinical research and clinical studies, with experimental SIV infection of NHP models offering unique opportunities to understand key processes of HIV-1 infection and disease that are either not practically feasible or ethical in HIV-1 infected humans. In this review we will discuss current approaches to studying the tissue based immunopathogenesis of AIDS virus infection in NHPs, including both analyses of tissues obtained at biopsy or necropsy and complementary non-invasive imaging approaches that may have practical utility in monitoring HIV-1 disease in the clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Visualizing the Immune System: Providing Key Insights into HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    Jacob D. Estes

    2018-03-01

    Full Text Available Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens. Particularly in HIV/SIV disease, imaging technologies are of great importance in the investigation of the local interplay between the virus and host cells, with respect to understanding viral dynamics and persistence, immune responses (i.e., adaptive and innate inflammatory responses, tissue structure and pathologies, and changes to the surrounding milieu and function of immune cells. Merging imaging platforms with other cutting-edge technologies could lead to novel findings regarding the phenotype, function, and molecular signatures of particular immune cell targets, further promoting the development of new antiviral treatments and vaccination strategies.

  8. Oxygen-modifying treatment with ARCON reduces the prognostic significance of hemoglobin in squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Hoogsteen, Ilse J.; Pop, Lucas A.M.; Marres, Henri A.M.; Merkx, Matthijs A.W.; Hoogen, Franciscus J.A. van den; Kogel, Albert J. van der; Kaanders, Johannes H.A.M.

    2006-01-01

    Purpose: To evaluate the prognostic significance of hemoglobin (Hb) levels measured before and during treatment with accelerated radiotherapy with carbogen and nicotinamide (ARCON). Methods and Materials: Two hundred fifteen patients with locally advanced tumors of the head and neck were included in a phase II trial of ARCON. This treatment regimen combines accelerated radiotherapy for reduction of repopulation with carbogen breathing and nicotinamide to reduce hypoxia. In these patients, Hb levels were measured before, during, and after radiotherapy. Results: Preirradiation and postirradiation Hb levels were available for 206 and 195 patients respectively. Hb levels below normal were most frequently seen among patients with T4 (p < 0.001) and N2 (p < 0.01) disease. Patients with a larynx tumor had significantly higher Hb levels (p < 0.01) than other tumor sites. During radiotherapy, 69 patients experienced a decrease in Hb level. In a multivariate analysis there was no prognostic impact of Hb level on locoregional control, disease-free survival, and overall survival. Primary tumor site was independently prognostic for locoregional control (p = 0.018), and gender was the only prognostic factor for disease-free and overall survival (p < 0.05). High locoregional control rates were obtained for tumors of the larynx (77%) and oropharynx (72%). Conclusion: Hemoglobin level was not found to be of prognostic significance for outcome in patients with squamous cell carcinoma of the head and neck after oxygen-modifying treatment with ARCON

  9. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats.

    Science.gov (United States)

    Oguntibeju, Oluwafemi O; Meyer, Samantha; Aboua, Yapo G; Goboza, Mediline

    2016-01-01

    Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  10. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  11. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne

    2007-01-01

    Objective: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS) Research Design and Methods: Thirty PCOS patients were randomized to pioglitazone, 30 mg/day or placebo...... independent predictors of glucose, and lipid metabolism, whereas hsCRP and IL-6 showed no significant contribution. Following pioglitazone treatment, insulin sensitivity increased, whereas sCD36 (3.21(0.76 - 13.6) vs. 2.33 (0.84 - 6.46) relative units) and hsCRP decreased (p... measured in body composition. Conclusions: sCD36 and oxLDL correlated with measures of insulin sensitivity independent of central fat mass. Pioglitazone treatment reduced sCD36 while improving insulin-stimulated glucose metabolism, further supporting the association between sCD36 and insulin resistance...

  12. Cardiovascular risk in obese diabetic patients is significantly reduced one year after gastric bypass compared to one year of diabetes support and education.

    Science.gov (United States)

    Mor, Alessandro; Omotosho, Philip; Torquati, Alfonso

    2014-10-01

    Roux-en-Y gastric bypass (RYGB) reduces most of the obesity-related comorbidities known to increase the cardiovascular risk in obese subjects. The Framingham risk score (FRS) is designed to be independent of body weight and estimates the 10-year risk for coronary heart disease (CHD), myocardial infarction, stroke, cardiovascular disease (CVD), death from CHD, and death from CVD. Our aim was to evaluate the effectiveness of RYGB on improving the FRS when compared to a matched control group who underwent diabetes support and education program (DSE). In a prospective cohort study, we evaluated preoperatively and at 12 months, 61 morbidly obese subjects with diabetes. Thirty underwent laparoscopic RYGB, and 31 received 1 year of DSE, consisting of educational sessions on diet, nutrition, and exercise. Groups were matched for gender, age, weight, blood pressure, and cholesterol and triglyceride levels. Strict gender-specific FRS was used to assess the cardiovascular risk. Excess weight-loss percentages (%EWL) were 55.6 ± 15.1 in the RYGB group and 1.2 ± 10.8 in the DSE group (P RYGB patients experienced a significant decrease in all FRS, whereas control subjects did not show a significant decrease for the 10-year risk for CHD, CVD and death from CVD. The between-group differences for changes from baseline to 12 months in all FRS were significant. The 10-year risk reductions for CHD, MI, stroke, CVD, death from CHD, and death from CVD in the RYGB group relative to the DSE group were, respectively, 42, 48, 30, 39, 50, and 50%. No correlations between reduction in FRS and %EWL were found after RYGB. A significant improvement in the 10 year estimated cardiovascular risk is observed in patients undergoing RYGB, but not in those who were offered usual medical therapy plus DSE. However, the effects of RYGB on FRS are independent of weight loss.

  13. Fowlpoxvirus recombinants coding for the CIITA gene increase the expression of endogenous MHC-II and Fowlpox Gag/Pro and Env SIV transgenes.

    Science.gov (United States)

    Bissa, Massimiliano; Forlani, Greta; Zanotto, Carlo; Tosi, Giovanna; De Giuli Morghen, Carlo; Accolla, Roberto S; Radaelli, Antonia

    2018-01-01

    A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+ T cells. In this context, the class II transactivator (CIITA) has a pivotal role in triggering the adaptive immune response through induction of the expression of class-II major histocompatibility complex molecule (MHC-II), that can present antigens to CD4+ T helper cells. Here, we report on construction of novel FPgp and FPenv recombinants that express the highly immunogenic SIV Gag-pro and Env structural antigens. Several FP-based recombinants, with single or dual genes, were also developed that express CIITA, driven from H6 or SP promoters. These recombinants were used to infect CEF and Vero cells in vitro and determine transgene expression, which was evaluated by real-time PCR and Western blotting. Subcellular localisation of the different proteins was evaluated by confocal microscopy, whereas HLA-DR or MHC-II expression was measured by flow cytometry. Fowlpox recombinants were also used to infect syngeneic T/SA tumour cells, then injected into Balb/c mice to elicit MHC-II immune response and define the presentation of the SIV transgene products in the presence or absence of FPCIITA. Antibodies to Env were measured by ELISA. Our data show that the H6 promoter was more efficient than SP to drive CIITA expression and that CIITA can enhance the levels of the gag/pro and env gene products only when infection is performed by FP single recombinants. Also, CIITA expression is higher when carried by FP single recombinants than when combined with FPgp or FPenv constructs and can

  14. HIV vaccine research and discovery in the nonhuman primates model: a unified theory in acquisition prevention and control of SIV infection.

    Science.gov (United States)

    Lynch, Rebecca M; Yamamoto, Takuya; McDermott, Adrian B

    2013-07-01

    Here we highlight the latest advances in HIV vaccine concepts that will expand our knowledge on how to elicit effective acquisition-prevention and/or control of simian immunodeficiency virus (SIV) replication in the nonhuman primate (NHP) model. In the context of the promising analyses from the RV144 Thai Trial and the effective control of SIV replication exerted by rhCMV-(SIV) elicited EM CD8 T cells, the HIV field has recently shifted toward vaccine concepts that combine protection from acquisition with effective control of SIV replication. Current studies in the NHP model have demonstrated the efficacy of HIV-neutralizing antibodies via passive transfer, the potential importance of the CD4 Tfh subset, the ability to effectively model the RV144 vaccine trial and the capacity of an Ad26 prime and modified vaccinia Ankara virus boost to elicit Env-specific antibody and cellular responses that both limit acquisition and control heterologous SIVmac251 challenge. The latest work in the NHP model suggests that the next generation HIV-1 vaccines should aim to provoke a comprehensive adaptive immune response for both prevention of SIV acquisition as well as control of replication in breakthrough infection.

  15. Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Intractable Fatigue in Western Blot-Positive ‘Chronic Lyme Disease’ Patients: Preliminary Report

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2012-03-01

    Full Text Available Background: An open label 8-week preliminary study was conducted in a small number of patients to determine if a combination oral supplement containing a mixture of phosphoglycolipids, coenzyme Q10 and microencapsulated NADH and other nutrients could affect fatigue levels in long-term, Western blot-positive, multi-symptom ‘chronic Lyme disease’ patients (also called ‘post-treatment Lyme disease’ or ‘post Lyme syndrome’ with intractable fatigue. Methods: The subjects in this study were 6 males (mean age = 45.1 ± 12.4 years and 10 females (mean age = 54.6 ± 7.4 years with ‘chronic Lyme disease’ (determined by multiple symptoms and positive Western blot analysis that had been symptomatic with chronic fatigue for an average of 12.7 ± 6.6 years. They had been seen by multiple physicians (13.3 ± 7.6 and had used many other remedies, supplements and drugs (14.4 ± 7.4 without fatigue relief. Fatigue was monitored at 0, 7, 30 and 60 days using a validated instrument, the Piper Fatigue Scale.Results: Patients in this preliminary study responded to the combination test supplement, showing a 26% reduction in overall fatigue by the end of the 8-week trial (p< 0.0003. Analysis of subcategories of fatigue indicated that there were significant improvements in the ability to complete tasks and activities as well as significant improvements in mood and cognitive abilities. Regression analysis of the data indicated that reductions in fatigue were consistent and occurred with a high degree of confidence (R2= 0.998. Functional Foods in Health and Disease 2012, 2(3:35-47 Conclusions: The combination supplement was a safe and effective method to significantly reduce intractable fatigue in long-term patients with Western blot-positive ‘chronic Lyme disease.’

  16. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Taher, Ali T; Porter, John; Viprakasit, Vip; Kattamis, Antonis; Chuncharunee, Suporn; Sutcharitchan, Pranee; Siritanaratkul, Noppadol; Galanello, Renzo; Karakas, Zeynep; Lawniczek, Tomasz; Ros, Jacqueline; Zhang, Yiyun; Habr, Dany; Cappellini, Maria Domenica

    2012-08-02

    Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload and its associated complications despite receiving only occasional or no transfusions. The present 1-year, randomized, double-blind, placebo-controlled THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients. A total of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5 or 10 mg/kg/d of deferasirox or placebo. The means ± SD of the actual deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d starting dose cohorts were 5.7 ± 1.4 and 11.5 ± 2.9 mg/kg/d, respectively. At 1 year, the liver iron concentration (LIC) decreased significantly compared with placebo (least-squares mean [LSM] ± SEM, -2.33 ± 0.7 mg Fe/g dry weight [dw], P = .001, and -4.18 ± 0.69 mg Fe/g dw, P deferasirox groups, respectively (baseline values [means ± SD], 13.11 ± 7.29 and 14.56 ± 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased significantly compared with placebo by LSM -235 and -337 ng/mL for the deferasirox 5 and 10 mg/kg/d groups, respectively (P deferasirox significantly reduces iron overload in NTDT patients with a frequency of overall adverse events similar to placebo.

  17. A proper choice of route significantly reduces air pollution exposure--a study on bicycle and bus trips in urban streets.

    Science.gov (United States)

    Hertel, Ole; Hvidberg, Martin; Ketzel, Matthias; Storm, Lars; Stausgaard, Lizzi

    2008-01-15

    A proper selection of route through the urban area may significantly reduce the air pollution exposure. This is the main conclusion from the presented study. Air pollution exposure is determined for two selected cohorts along the route going from home to working place, and back from working place to home. Exposure is determined with a street pollution model for three scenarios: bicycling along the shortest possible route, bicycling along the low exposure route along less trafficked streets, and finally taking the shortest trip using public transport. Furthermore, calculations are performed for the cases the trip takes place inside as well as outside the traffic rush hours. The results show that the accumulated air pollution exposure for the low exposure route is between 10% and 30% lower for the primary pollutants (NO(x) and CO). However, the difference is insignificant and in some cases even negative for the secondary pollutants (NO(2) and PM(10)/PM(2.5)). Considering only the contribution from traffic in the travelled streets, the accumulated air pollution exposure is between 54% and 67% lower for the low exposure route. The bus is generally following highly trafficked streets, and the accumulated exposure along the bus route is therefore between 79% and 115% higher than the high exposure bicycle route (the short bicycle route). Travelling outside the rush hour time periods reduces the accumulated exposure between 10% and 30% for the primary pollutants, and between 5% and 20% for the secondary pollutants. The study indicates that a web based route planner for selecting the low exposure route through the city might be a good service for the public. In addition the public may be advised to travel outside rush hour time periods.

  18. Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal

    Directory of Open Access Journals (Sweden)

    Van Rompay Koen K A

    2012-07-01

    Full Text Available Abstract Background We reported previously that while prolonged tenofovir monotherapy of macaques infected with virulent simian immunodeficiency virus (SIV resulted invariably in the emergence of viral mutants with reduced in vitro drug susceptibility and a K65R mutation in reverse transcriptase, some animals controlled virus replication for years. Transient CD8+ cell depletion or short-term tenofovir interruption within 1 to 5 years of treatment demonstrated that a combination of CD8+ cell-mediated immune responses and continued tenofovir therapy was required for sustained suppression of viremia. We report here follow-up data on 5 such animals that received tenofovir for 8 to 14 years. Results Although one animal had a gradual increase in viremia from 3 years onwards, the other 4 tenofovir-treated animals maintained undetectable viremia with occasional viral blips (≤ 300 RNA copies/ml plasma. When tenofovir was withdrawn after 8 to 10 years from three animals with undetectable viremia, the pattern of occasional episodes of low viremia (≤ 3600 RNA/ml plasma continued throughout the 10-month follow-up period. These animals had low virus levels in lymphoid tissues, and evidence of multiple SIV-specific immune responses. Conclusion Under certain conditions (i.e., prolonged antiviral therapy initiated early after infection; viral mutants with reduced drug susceptibility a virus-host balance characterized by strong immunologic control of virus replication can be achieved. Although further research is needed to translate these findings into clinical applications, these observations provide hope for a functional cure of HIV infection via immunotherapeutic strategies that boost antiviral immunity and reduce the need for continuous antiretroviral therapy.

  19. A Rosa canina - Urtica dioica - Harpagophytum procumbens/zeyheri Combination Significantly Reduces Gonarthritis Symptoms in a Randomized, Placebo-Controlled Double-Blind Study.

    Science.gov (United States)

    Moré, Margret; Gruenwald, Joerg; Pohl, Ute; Uebelhack, Ralf

    2017-12-01

    The special formulation MA212 (Rosaxan) is composed of rosehip ( Rosa canina L.) puree/juice concentrate, nettle ( Urtica dioica L.) leaf extract, and devil's claw ( Harpagophytum procumbens DC. ex Meisn. or Harpagophytum zeyheri Decne.) root extract and also supplies vitamin D. It is a food for special medical purposes ([EU] No 609/2013) for the dietary management of pain in patients with gonarthritis.This 12-week randomized, placebo-controlled double-blind parallel-design study aimed to investigate the efficacy and safety of MA212 versus placebo in patients with gonarthritis.A 3D-HPLC-fingerprint (3-dimensional high pressure liquid chromatography fingerprint) of MA212 demonstrated the presence of its herbal ingredients. Ninety-two randomized patients consumed 40 mL of MA212 (n = 46) or placebo (n = 44) daily. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality-of-life scores at 0, 6, and 12 weeks, and analgesic consumption were documented. Statistically, the initial WOMAC subscores/scores did not differ between groups. During the study, their means significantly improved in both groups. The mean pre-post change of the WOMAC pain score (primary endpoint) was 29.87 in the MA212 group and 10.23 in the placebo group. The group difference demonstrated a significant superiority in favor of MA212 (p U  < 0.001; p t  < 0.001). Group comparisons of all WOMAC subscores/scores at 6 and 12 weeks reached same significances. Compared to placebo, both physical and mental quality of life significantly improved with MA212. There was a trend towards reduced analgesics consumption with MA212, compared to placebo. In the final efficacy evaluation, physicians (p Chi  < 0.001) and patients (p Chi  < 0.001) rated MA212 superior to placebo. MA212 was well tolerated.This study demonstrates excellent efficacy for MA212 in gonarthritis patients. Georg Thieme Verlag KG Stuttgart · New York.

  20. Use of a contact force-sensing ablation catheter with advanced catheter location significantly reduces fluoroscopy time and radiation dose in catheter ablation of atrial fibrillation.

    Science.gov (United States)

    Lee, Geoffrey; Hunter, Ross J; Lovell, Matthew J; Finlay, Malcom; Ullah, Waqas; Baker, Victoria; Dhinoja, Mehul B; Sporton, Simon; Earley, Mark J; Schilling, Richard J

    2016-02-01

    The aim of this study was to evaluate the 'real-world' impact of a novel contact force (CF)-sensing (SmartTouch™, Biosense Webster, Diamond Bar, CA, USA) catheter coupled with an advanced catheter location (ACL) system on fluoroscopy time and fluoroscopy dose during atrial fibrillation (AF) ablation. This was a retrospective observational cohort study of prospectively collected data of 1515 consecutive patients undergoing paroxysmal AF (PAF) and persistent AF (PerAF) ablation at a single institution between 2009 and 2014. Patients undergoing AF ablation with the SmartTouch catheter and the ACL system (SmartTouch group, n = 510) were compared with those undergoing AF ablation without this technology (control group, n = 1005). The primary outcomes were total fluoroscopy time (min) and fluoroscopy dose as measured by the dose-area product (mGy cm(2)). Secondary endpoints included total procedure time, total ablation time, and major cardiac complications (tamponade, pericardial effusion, and urgent cardiac surgery). The SmartTouch group had significantly lower fluoroscopy times (9.5 vs. 41 min, P fluoroscopy time of 3.5 min (interquartile range 6) for all AF ablations was achieved. There was no difference in the rate of cardiac complications (∼ 1.5%). SmartTouch™ CF-sensing catheter use with ACL™ during AF ablation significantly reduces fluoroscopy times by 77%, radiation dose by 71%, and procedural time by 19% but does not improve overall safety or the risk of cardiac complications. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  1. Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Venzon, David [Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Brocca-Cofano, Egidio; DiPasquale, Janet [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit [Advanced Bioscience Laboratories Inc., Rockville, MD 20850 (United States); Sui, Yongjun; Berzofsky, Jay A. [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Liu, Linda; Langermann, Solomon [Amplimmune Inc., Gaithersburg, MD 20878 (United States); Robert-Guroff, Marjorie, E-mail: guroffm@mail.nih.gov [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-15

    High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1{sup hi} expressing T cells and Tregs in PBMCs, and PD-1{sup hi} Tregs in lymph nodes. It transiently decreased expression of Ki67 and α{sub 4}β{sub 7} in PBMC CD4{sup +} and CD8{sup +} Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1{sup hi} cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1{sup hi} cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1{sup hi} cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire.

  2. Spatially controlled fabrication of a bright fluorescent nanodiamond-array with enhanced far-red Si-V luminescence

    International Nuclear Information System (INIS)

    Singh, Sonal; Thomas, Vinoy; Kharlampieva, Eugenia; Catledge, Shane A; Martyshkin, Dmitry; Kozlovskaya, Veronika

    2014-01-01

    We demonstrate a novel approach to precisely pattern fluorescent nanodiamond-arrays with enhanced far-red intense photostable luminescence from silicon-vacancy (Si-V) defect centers. The precision-patterned pre-growth seeding of nanodiamonds is achieved by a scanning probe ‘dip-pen’ nanolithography technique using electrostatically driven transfer of nanodiamonds from ‘inked’ cantilevers to a UV-treated hydrophilic SiO 2 substrate. The enhanced emission from nanodiamond dots in the far-red is achieved by incorporating Si-V defect centers in a subsequent chemical vapor deposition treatment. The development of a suitable nanodiamond ink and mechanism of ink transport, and the effect of humidity and dwell time on nanodiamond patterning are investigated. The precision patterning of as-printed (pre-CVD) arrays with dot diameter and dot height as small as 735 nm ± 27 nm and 61 nm ± 3 nm, respectively, and CVD-treated fluorescent ND-arrays with consistently patterned dots having diameter and height as small as 820 nm ± 20 nm and, 245 nm ± 23 nm, respectively, using 1 s dwell time and 30% RH is successfully achieved. We anticipate that the far-red intense photostable luminescence (∼738 nm) observed from Si-V defect centers integrated in spatially arranged nanodiamonds could be beneficial for the development of next generation fluorescence-based devices and applications. (paper)

  3. Symmetric dimeric bisbenzimidazoles DBP(n reduce methylation of RARB and PTEN while significantly increase methylation of rRNA genes in MCF-7 cancer cells.

    Directory of Open Access Journals (Sweden)

    Svetlana V Kostyuk

    Full Text Available Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n are able to block DNA methyltransferase activities. It was also found that DBP(n produces a moderate effect on the activation of total gene expression in HeLa-TI population containing epigenetically repressed avian sarcoma genome.It is shown that DBP(n are able to penetrate the cellular membranes and accumulate in breast carcinoma cell MCF-7, mainly in the mitochondria and in the nucleus, excluding the nucleolus. The DBP(n are non-toxic to the cells and have a weak overall demethylation effect on genomic DNA. DBP(n demethylate the promoter regions of the tumor suppressor genes PTEN and RARB. DBP(n promotes expression of the genes RARB, PTEN, CDKN2A, RUNX3, Apaf-1 and APC "silent" in the MCF-7 because of the hypermethylation of their promoter regions. Simultaneously with the demethylation of the DNA in the nucleus a significant increase in the methylation level of rRNA genes in the nucleolus was detected. Increased rDNA methylation correlated with a reduction of the rRNA amount in the cells by 20-30%. It is assumed that during DNA methyltransferase activity inhibition by the DBP(n in the nucleus, the enzyme is sequestered in the nucleolus and provides additional methylation of the rDNA that are not shielded by DBP(n.It is concluded that DBP (n are able to accumulate in the nucleus (excluding the nucleolus area and in the mitochondria of cancer cells, reducing mitochondrial potential. The DBP (n induce the demethylation of a cancer cell's genome, including the demethylation of the promoters of tumor suppressor genes. DBP (n significantly increase the methylation of ribosomal RNA genes in the nucleoli. Therefore the further study of these compounds is needed

  4. PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

    International Nuclear Information System (INIS)

    Ghorai, Atanu; Sarma, Asitikantha; Chowdhury, Priyanka; Ghosh, Utpal

    2016-01-01

    Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was

  5. Holstein-Friesian calves selected for divergence in residual feed intake during growth exhibited significant but reduced residual feed intake divergence in their first lactation.

    Science.gov (United States)

    Macdonald, K A; Pryce, J E; Spelman, R J; Davis, S R; Wales, W J; Waghorn, G C; Williams, Y J; Marett, L C; Hayes, B J

    2014-03-01

    Residual feed intake (RFI), as a measure of feed conversion during growth, was estimated for around 2,000 growing Holstein-Friesian heifer calves aged 6 to 9 mo in New Zealand and Australia, and individuals from the most and least efficient deciles (low and high RFI phenotypes) were retained. These animals (78 New Zealand cows, 105 Australian cows) were reevaluated during their first lactation to determine if divergence for RFI observed during growth was maintained during lactation. Mean daily body weight (BW) gain during assessment as calves had been 0.86 and 1.15 kg for the respective countries, and the divergence in RFI between most and least efficient deciles for growth was 21% (1.39 and 1.42 kg of dry matter, for New Zealand and Australia, respectively). At the commencement of evaluation during lactation, the cows were aged 26 to 29 mo. All were fed alfalfa and grass cubes; it was the sole diet in New Zealand, whereas 6 kg of crushed wheat/d was also fed in Australia. Measurements of RFI during lactation occurred for 34 to 37 d with measurements of milk production (daily), milk composition (2 to 3 times per week), BW and BW change (1 to 3 times per week), as well as body condition score (BCS). Daily milk production averaged 13.8 kg for New Zealand cows and 20.0 kg in Australia. No statistically significant differences were observed between calf RFI decile groups for dry matter intake, milk production, BW change, or BCS; however a significant difference was noted between groups for lactating RFI. Residual feed intake was about 3% lower for lactating cows identified as most efficient as growing calves, and no negative effects on production were observed. These results support the hypothesis that calves divergent for RFI during growth are also divergent for RFI when lactating. The causes for this reduced divergence need to be investigated to ensure that genetic selection programs based on low RFI (better efficiency) are robust. Copyright © 2014 American Dairy

  6. 830 nm light-emitting diode (led) phototherapy significantly reduced return-to-play in injured university athletes: a pilot study.

    Science.gov (United States)

    Foley, John; Vasily, David B; Bradle, Jeanna; Rudio, Catharine; Calderhead, R Glen

    2016-03-31

    For any committed athlete, getting back to conditioning and participation post-injury (return to play [RTP]) needs to be as swift as possible. The effects of near-infrared light-emitting diode (LED) therapy on pain control, blood flow enhancement and relaxation of muscle spasm (all aspects in the treatment of musculoskeletal injury) have attracted attention. The present pilot study was undertaken to assess the role of 830 nm LED phototherapy in safely accelerating RTP in injured university athletes. Over a 15-month period, a total of 395 injuries including sprains, strains, ligament damage, tendonitis and contusions were treated with 1,669 sessions of 830 nm LED phototherapy (mean of 4.3 treatments per injury, range 2 - 6). Efficacy was measured with pain attenuation on a visual analog scale (VAS) and the RTP period compared with historically-based anticipated RTP with conventional therapeutic intervention. A full set of treatment sessions and follow-up data was able to be recorded in 65 informed and consenting subjects who achieved pain relief on the VAS of up to 6 points in from 2-6 sessions. The average LED-mediated RTP in the 65 subjects was significantly shorter at 9.6 days, compared with the mean anticipated RTP of 19.23 days (p = 0.0066, paired two-tailed Student's t-test). A subjective satisfaction survey was carried out among the 112 students with injuries incurred from January to May, 2015. Eighty-eight (78.5%) were either very satisfied or satisfied, and only 8 (7.2%) were dissatisfied. For any motivated athlete, RTP may be the most important factor postinjury based on the resolution of pain and inflammation and repair to tissue trauma. 830 nm LED phototherapy significantly and safely reduced the RTP in dedicated university athletes over a wide range of injuries with no adverse events. One limitation of the present study was the subjective nature of the assessments, and the lack of any control groups. However, further controlled studies are warranted to

  7. Leukocyte-depletion of blood components does not significantly reduce the risk of infectious complications. Results of a double-blinded, randomized study

    DEFF Research Database (Denmark)

    Titlestad, I. L.; Ebbesen, L. S.; Ainsworth, A. P.

    2001-01-01

    Allogeneic blood transfusions are claimed to be an independent risk factor for postoperative infections in open colorectal surgery due to immunomodulation. Leukocyte-depletion of erythrocyte suspensions has been shown in some open randomized studies to reduce the rate of postoperative infection t...

  8. X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

    International Nuclear Information System (INIS)

    Feng, Youjun; Qi, Jianxun; Zhang, Huimin; Wang, Jinzi; Liu, Jinhua; Jiang, Fan; Gao, Feng

    2005-01-01

    X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β 2 m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides

  9. SIV-infected Chinese-origin rhesus macaques express specific MHC class I alleles in either elite controllers or normal progressors

    OpenAIRE

    Wambua, Daniel; Henderson, Ryan; Solomon, Christopher; Hunter, Meredith; Marx, Preston; Sette, Alessandro; Mothé, Bianca R.

    2011-01-01

    We characterized twelve SIV-infected Chinese-origin rhesus macaques for their entire MHC class I allele composition. Several MHC class I alleles were present in animals with varying outcomes of infections, either elite control or normal progression to AIDS disease. These MHC class I alleles may prove interesting targets for additional characterization.

  10. SIV-infected Chinese-origin rhesus macaques express specific MHC class I alleles in either elite controllers or normal progressors

    Science.gov (United States)

    Wambua, Daniel; Henderson, Ryan; Solomon, Christopher; Hunter, Meredith; Marx, Preston; Sette, Alessandro; Mothé, Bianca R.

    2011-01-01

    We characterized twelve SIV-infected Chinese-origin rhesus macaques for their entire MHC class I allele composition. Several MHC class I alleles were present in animals with varying outcomes of infections, either elite control or normal progression to AIDS disease. These MHC class I alleles may prove interesting targets for additional characterization. PMID:21781132

  11. Metaldyne: Plant-Wide Assessment at Royal Oak Finds Opportunities to Improve Manufacturing Efficiency, Reduce Energy Use, and Achieve Significant Cost Savings

    Energy Technology Data Exchange (ETDEWEB)

    2005-05-01

    This case study prepared for the U.S. Department of Energy's Industrial Technologies Program describes a plant-wide energy assessment conducted at the Metaldyne, Inc., forging plant in Royal Oak, Michigan. The assessment focused on reducing the plant's operating costs, inventory, and energy use. If the company were to implement all the recommendations that came out of the assessment, its total annual energy savings for electricity would be about 11.5 million kWh and annual cost savings would be $12.6 million.

  12. The co registration of initial PET on the CT-radiotherapy reduces significantly the variabilities of anatomo-clinical target volume in the child hodgkin disease

    International Nuclear Information System (INIS)

    Metwally, H.; Blouet, A.; David, I.; Rives, M.; Izar, F.; Courbon, F.; Filleron, T.; Laprie, A.; Plat, G.; Vial, J.

    2009-01-01

    It exists a great interobserver variability for the anatomo-clinical target volume (C.T.V.) definition in children suffering of Hodgkin disease. In this study, the co-registration of the PET with F.D.G. on the planning computed tomography has significantly lead to a greater coherence in the clinical target volume definition. (N.C.)

  13. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors

    DEFF Research Database (Denmark)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J

    2017-01-01

    in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e...... to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect...... of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague...

  14. Does Liposomal Bupivacaine (Exparel) Significantly Reduce Postoperative Pain/Numbness in Symptomatic Teeth with a Diagnosis of Necrosis? A Prospective, Randomized, Double-blind Trial.

    Science.gov (United States)

    Glenn, Brandon; Drum, Melissa; Reader, Al; Fowler, Sara; Nusstein, John; Beck, Mike

    2016-09-01

    Medical studies have shown some potential for infiltrations of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, San Diego, CA), a slow-release bupivacaine solution, to extend postoperative benefits of numbness/pain relief for up to several days. Because the Food and Drug Administration has approved Exparel only for infiltrations, we wanted to evaluate if it would be effective as an infiltration to control postoperative pain. The purpose of this study was to compare an infiltration of bupivacaine with liposomal bupivacaine for postoperative numbness and pain in symptomatic patients diagnosed with pulpal necrosis experiencing moderate to severe preoperative pain. One hundred patients randomly received a 4.0-mL buccal infiltration of either bupivacaine or liposomal bupivacaine after endodontic debridement. For postoperative pain, patients were given ibuprofen/acetaminophen, and they could receive narcotic pain medication as an escape. Patients recorded their level of numbness, pain, and medication use the night of the appointment and over the next 5 days. Success was defined as no or mild postoperative pain and no narcotic use. The success rate was 29% for the liposomal group and 22% for the bupivacaine group, with no significant difference (P = .4684) between the groups. Liposomal bupivacaine had some effect on soft tissue numbness, pain, and use of non-narcotic medications, but it was not clinically significant. There was no significant difference in the need for escape medication. For symptomatic patients diagnosed with pulpal necrosis experiencing moderate to severe preoperative pain, a 4.0-mL infiltration of liposomal bupivacaine did not result in a statistically significant increase in postoperative success compared with an infiltration of 4.0 mL bupivacaine. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  15. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Directory of Open Access Journals (Sweden)

    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  16. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection

    Science.gov (United States)

    Damouche, Abderaouf; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-01-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  17. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Science.gov (United States)

    Damouche, Abderaouf; Lazure, Thierry; Avettand-Fènoël, Véronique; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-09-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  18. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Jean Pierre Schatzmann Peron

    Full Text Available Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC, which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

  19. Peak medial (but not lateral) hamstring activity is significantly lower during stance phase of running. An EMG investigation using a reduced gravity treadmill.

    Science.gov (United States)

    Hansen, Clint; Einarson, Einar; Thomson, Athol; Whiteley, Rodney

    2017-09-01

    The hamstrings are seen to work during late swing phase (presumably to decelerate the extending shank) then during stance phase (presumably stabilizing the knee and contributing to horizontal force production during propulsion) of running. A better understanding of this hamstring activation during running may contribute to injury prevention and performance enhancement (targeting the specific role via specific contraction mode). Twenty active adult males underwent surface EMG recordings of their medial and lateral hamstrings while running on a reduced gravity treadmill. Participants underwent 36 different conditions for combinations of 50%-100% altering bodyweight (10% increments) & 6-16km/h (2km/h increments, i.e.: 36 conditions) for a minimum of 6 strides of each leg (maximum 32). EMG was normalized to the peak value seen for each individual during any stride in any trial to describe relative activation levels during gait. Increasing running speed effected greater increases in EMG for all muscles than did altering bodyweight. Peak EMG for the lateral hamstrings during running trials was similar for both swing and stance phase whereas the medial hamstrings showed an approximate 20% reduction during stance compared to swing phase. It is suggested that the lateral hamstrings work equally hard during swing and stance phase however the medial hamstrings are loaded slightly less every stance phase. Likely this helps explain the higher incidence of lateral hamstring injury. Hamstring injury prevention and rehabilitation programs incorporating running should consider running speed as more potent stimulus for increasing hamstring muscle activation than impact loading. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors.

    Science.gov (United States)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J; Holst, Jens Juul; Sorensen, Charlotte M

    2017-12-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague-Dawley rats and SHR received a 20 min intrarenal infusion of GLP-1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP-1 was assessed in isolated interlobar arteries from normo- and hypertensive rats. We found no expression of GLP-1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP-1 receptor. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  1. Young coconut juice significantly reduces histopathological changes in the brain that are induced by hormonal imbalance: a possible implication to postmenopausal women.

    Science.gov (United States)

    Radenahmad, N; Saleh, F; Sawangjaroen, K; Rundorn, W; Withyachumnarnkul, B; Connor, J R

    2009-06-01

    Some degenerative diseases of the nervous system have been linked to hormonal imbalance in postmenopausal women. It is argued that young coconut juice (YCJ) could have some estrogen-like characteristics, but this is still debatable. Our aim was to investigate this argument, and to examine whether YCJ has any neuroprotective effects. Four groups of female rats (10 in each group) were included in this study. These included sham-operated, overiectomized (ovx), ovx and receiving estradiol benzoate (EB) injections intraperitoneally, and ovx and receiving YCJ orally. At the end of the five-week study, the rats were sacrificed, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. Moreover, the rat brains were excised, and the cortical pyramidal neurons were examined using markers of neuronal cell death, namely anti-neurofilament (NF200) and anti-parvalbumin (PV) antibodies. Our results showed that the rat group which received YCJ had its serum E2 level significantly (Phormonal imbalance could induce some brain pathologies in females.

  2. The chemical digestion of Ti6Al7Nb scaffolds produced by Selective Laser Melting reduces significantly ability of Pseudomonas aeruginosa to form biofilm.

    Science.gov (United States)

    Junka, Adam F; Szymczyk, Patrycja; Secewicz, Anna; Pawlak, Andrzej; Smutnicka, Danuta; Ziółkowski, Grzegorz; Bartoszewicz, Marzenna; Chlebus, Edward

    2016-01-01

    In our previous work we reported the impact of hydrofluoric and nitric acid used for chemical polishing of Ti-6Al-7Nb scaffolds on decrease of the number of Staphylococcus aureus biofilm forming cells. Herein, we tested impact of the aforementioned substances on biofilm of Gram-negative microorganism, Pseudomonas aeruginosa, dangerous pathogen responsible for plethora of implant-related infections. The Ti-6Al-7Nb scaffolds were manufactured using Selective Laser Melting method. Scaffolds were subjected to chemical polishing using a mixture of nitric acid and fluoride or left intact (control group). Pseudomonal biofilm was allowed to form on scaffolds for 24 hours and was removed by mechanical vortex shaking. The number of pseudomonal cells was estimated by means of quantitative culture and Scanning Electron Microscopy. The presence of nitric acid and fluoride on scaffold surfaces was assessed by means of IR and rentgen spetorscopy. Quantitative data were analysed using the Mann-Whitney test (P ≤ 0.05). Our results indicate that application of chemical polishing correlates with significant drop of biofilm-forming pseudomonal cells on the manufactured Ti-6Al-7Nb scaffolds ( p = 0.0133, Mann-Whitney test) compared to the number of biofilm-forming cells on non-polished scaffolds. As X-ray photoelectron spectroscopy revealed the presence of fluoride and nitrogen on the surface of scaffold, we speculate that drop of biofilm forming cells may be caused by biofilm-supressing activity of these two elements.

  3. Full-length genome sequence of a simian immunodeficiency virus (SIV) infecting a captive agile mangabey (Cercocebus agilis) is closely related to SIVrcm infecting wild red-capped mangabeys (Cercocebus torquatus) in Cameroon.

    Science.gov (United States)

    Ahuka-Mundeke, Steve; Liegeois, Florian; Ayouba, Ahidjo; Foupouapouognini, Yacouba; Nerrienet, Eric; Delaporte, Eric; Peeters, Martine

    2010-12-01

    Simian immunodeficiency viruses (SIVs) are lentiviruses that infect an extensive number of wild African primate species. Here we describe for the first time SIV infection in a captive agile mangabey (Cercocebus agilis) from Cameroon. Phylogenetic analysis of the full-length genome sequence of SIVagi-00CM312 showed that this novel virus fell into the SIVrcm lineage and was most closely related to a newly characterized SIVrcm strain (SIVrcm-02CM8081) from a wild-caught red-capped mangabey (Cercocebus torquatus) from Cameroon. In contrast to red-capped mangabeys, no 24 bp deletion in CCR5 has been observed in the agile mangabey. Further studies on wild agile mangabeys are needed to determine whether agile and red-capped mangabeys are naturally infected with the same SIV lineage, or whether this agile mangabey became infected with an SIVrcm strain in captivity. However, our study shows that agile mangabeys are susceptible to SIV infection.

  4. "Eesti taluarhitektuur. Püsiv ja muutuv : Eesti Vabaõhumuuseumi näitus = Estonian farm architecture. Enduring and changing : an Estonian Open Air Museum exhibition / Heiki Pärdi

    Index Scriptorium Estoniae

    Pärdi, Heiki, 1951-

    2015-01-01

    Eesti Vabaõhumuuseumi näitus "Eesti taluarhitektuur. Püsiv ja muutuv". Näituse autor Heiki Pärdi, kuraator Elo Lutsepp, kujundaja Jan Skolimowski (KAMP Arhitektid). 2014. aasta Kultuurkapitali Arhitektuuripreemia kandidaat

  5. A peptide-loaded dendritic cell based cytotoxic T-lymphocyte (CTL vaccination strategy using peptides that span SIV Tat, Rev, and Env overlapping reading frames

    Directory of Open Access Journals (Sweden)

    Marx Preston A

    2006-01-01

    Full Text Available Abstract CTL based vaccine strategies in the macaque model of AIDS have shown promise in slowing the progression to disease. However, rapid CTL escape viruses can emerge rendering such vaccination useless. We hypothesized that such escape is made more difficult if the immunizing CTL epitope falls within a region of the virus that has a high density of overlapping reading frames which encode several viral proteins. To test this hypothesis, we immunized macaques using a peptide-loaded dendritic cell approach employing epitopes in the second coding exon of SIV Tat which spans reading frames for both Env and Rev. We report here that autologous dendritic cells, loaded with SIV peptides from Tat, Rev, and Env, induced a distinct cellular immune response measurable ex vivo. However, conclusive in vivo control of a challenge inoculation of SIVmac239 was not observed suggesting that CTL epitopes within densely overlapping reading frames are also subject to escape mutations.

  6. Quilting after mastectomy significantly reduces seroma formation

    African Journals Online (AJOL)

    surgical procedure that eliminates the anatomical dead space remaining after mastectomy (Fig. 1). It involves placing interrupted absorbable sutures between the mastectomy flap and pectoral muscle prior to wound closure. It has been described in several studies assessing the technique at donor sites of autologous breast.

  7. Nuclear energy significantly reduces carbon dioxide emissions

    International Nuclear Information System (INIS)

    Koprda, V.

    2006-01-01

    This article is devoted to nuclear energy, to its acceptability, compatibility and sustainability. Nuclear energy is non-dispensable part of energy sources with vast innovation potential. The safety of nuclear energy, radioactive waste deposition, and prevention of risk from misuse of nuclear material have to be very seriously adjudged and solved. Nuclear energy is one of the ways how to decrease the contamination of atmosphere with carbon dioxide and it solves partially also the problem of global increase of temperature and climate changes. Given are the main factors responsible for the renaissance of nuclear energy. (author)

  8. Impact of short-term HAART initiated during the chronic stage or shortly post-exposure on SIV infection of male genital organs.

    Directory of Open Access Journals (Sweden)

    Marina Moreau

    Full Text Available BACKGROUND: The male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART. The origin of this persistent shedding is currently unknown. Phylogenetic studies indicated that HIV in semen from untreated men arises from local sources and/or passive diffusion from the blood. We previously demonstrated in human and macaque low levels and localized infection of several semen-producing organs by HIV/SIV. Using a macaque model, this study investigates the impact of short term HAART (2-4 weeks initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs. METHODOLOGY/PRINCIPAL FINDINGS: Short term HAART during the chronic stage decreased blood viral load. No major impact of HAART was observed on SIV DNA levels in male genital organs using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells were detected in all male genital tract organs from untreated and treated animals with undetectable blood viral load following HAART. Infected CD68+ myeloid cells and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male genital tissues infection, although it failed to prevent systemic infection. In both cases, HAART tended to decrease the number of CD3+ T cells in the male organs. CONCLUSIONS: Our results indicate that the established infection of male genital organs is not greatly impacted by short term HAART, whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract. Further investigations are now needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART.

  9. Reactions of SIV species with organic compounds: formation mechanisms of organo-sulfur derivatives in atmospheric aerosols

    Science.gov (United States)

    Passananti, Monica; Shang, Jing; Dupart, Yoan; Perrier, Sébastien; George, Christian

    2015-04-01

    Secondary organic aerosol (SOA) have an important impact on climate, air quality and human health. However the chemical reactions involved in their formation and growth are not fully understood or well-constrained in climate models. It is well known that inorganic sulfur (mainly in oxidation states (+IV) and (+VI)) plays a key role in aerosol formation, for instance sulfuric acid is known to be a good nucleating gas. In addition, acid-catalyzed heterogeneous reactions of organic compounds has shown to produce new particles, with a clear enhancement in the presence of ozone (Iinuma 2013). Organosulfates have been detected in tropospheric particles and aqueous phases, which suggests they are products of secondary organic aerosol formation process (Tolocka 2012). Originally, the production of organosulfates was explained by the esterification reaction of alcohols, but this reaction in atmosphere is kinetically negligible. Other formation pathways have been suggested such as hydrolysis of peroxides and reaction of organic matter with sulfite and sulfate radical anions (SO3-, SO4-) (Nozière 2010), but it remains unclear if these can completely explain atmospheric organo-sulfur aerosol loading. To better understand the formation of organo-sulfur compounds, we started to investigate the reactivity of SIV species (SO2 and SO32-) with respect to specific functional groups (organic acids and double bonds) on atmospherically relevant carboxylic acids and alkenes. The experiments were carried out in the homogeneous aqueous phase and at the solid-gas interface. A custom built coated-wall flow tube reactor was developed to control relativity humidity, SO2 concentration, temperature and gas flow rate. Homogeneous and heterogeneous reaction kinetics were measured and resulting products were identified using liquid chromatography coupled with an orbitrap mass spectrometer (LC-HR-MS). The experiments were performed with and without the presence of ozone in order to evaluate any

  10. Complement-mediated virus infectivity neutralisation by HLA antibodies is associated with sterilising immunity to SIV challenge in the macaque model for HIV/AIDS.

    Science.gov (United States)

    Page, Mark; Quartey-Papafio, Ruby; Robinson, Mark; Hassall, Mark; Cranage, Martin; Stott, James; Almond, Neil

    2014-01-01

    Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed.

  11. Enhanced expression of HIV and SIV vaccine antigens in the structural gene region of live attenuated rubella viral vectors and their incorporation into virions.

    Science.gov (United States)

    Virnik, Konstantin; Ni, Yisheng; Berkower, Ira

    2013-04-19

    Despite the urgent need for an HIV vaccine, its development has been hindered by virus variability, weak immunogenicity of conserved epitopes, and limited durability of the immune response. For other viruses, difficulties with immunogenicity were overcome by developing live attenuated vaccine strains. However, there is no reliable method of attenuation for HIV, and an attenuated strain would risk reversion to wild type. We have developed rubella viral vectors, based on the live attenuated vaccine strain RA27/3, which are capable of expressing important HIV and SIV vaccine antigens. The rubella vaccine strain has demonstrated safety, immunogenicity, and long lasting protection in millions of children. Rubella vectors combine the growth and immunogenicity of live rubella vaccine with the antigenicity of HIV or SIV inserts. This is the first report showing that live attenuated rubella vectors can stably express HIV and SIV vaccine antigens at an insertion site located within the structural gene region. Unlike the Not I site described previously, the new site accommodates a broader range of vaccine antigens without interfering with essential viral functions. In addition, antigens expressed at the structural site were controlled by the strong subgenomic promoter, resulting in higher levels and longer duration of antigen expression. The inserts were expressed as part of the structural polyprotein, processed to free antigen, and incorporated into rubella virions. The rubella vaccine strain readily infects rhesus macaques, and these animals will be the model of choice for testing vector growth in vivo and immunogenicity. Published by Elsevier Ltd.

  12. Supplementary Material for: Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia

    2016-01-01

    Abstract Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  13. Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia A.

    2016-04-23

    Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  14. Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection

    Science.gov (United States)

    Folkvord, Joy M.; Levy, David N.; Rakasz, Eva G.; Connick, Elizabeth

    2016-01-01

    During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8 T cells are a regulatory subset differing from conventional CD8 T cells, and constitute the majority of CD8 T cells in the follicle. This subset, CD8 follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit enhanced expression of Tim-3 and IL-10, and express less perforin compared to conventional CD8 T cells. CD8 TFR modestly limit HIV replication in follicular helper T cells (TFH), impair TFH IL-21 production via Tim-3, and inhibit IgG production by B cells during ex vivo HIV infection. CD8 TFR induce TFH apoptosis through HLA-E, but induce less apoptosis than conventional CD8 T cells. These data demonstrate that a unique regulatory CD8 population exists in follicles that impairs GC function in HIV infection. PMID:27716848

  15. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ruy M [Los Alamos National Laboratory

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

  16. Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs.

    Science.gov (United States)

    Alaoui, Lamine; Palomino, Gustavo; Zurawski, Sandy; Zurawski, Gerard; Coindre, Sixtine; Dereuddre-Bosquet, Nathalie; Lecuroux, Camille; Goujard, Cecile; Vaslin, Bruno; Bourgeois, Christine; Roques, Pierre; Le Grand, Roger; Lambotte, Olivier; Favier, Benoit

    2017-11-13

    Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.

  17. Organic contaminants degradation from the S(IV) autoxidation process catalyzed by ferrous-manganous ions: A noticeable Mn(III) oxidation process.

    Science.gov (United States)

    Zhang, Jiaming; Ma, Jun; Song, Haoran; Sun, Shaofang; Zhang, Zhongxiang; Yang, Tao

    2018-04-15

    Remarkable atrazine degradation in the S(IV) autoxidation process catalyzed by Fe 2+ -Mn 2+ (Fe 2+ /Mn 2+ /sulfite) was demonstrated in this study. Competitive kinetic experiments, alcohol inhibiting methods and electron spin resonance (ESR) experiments proved that sulfur radicals were not the major oxidation species. Mn(III) was demonstrated to be the primary active species in the Fe 2+ /Mn 2+ /sulfite process based on the comparison of oxidation selectivity. Moreover, the inhibiting effect of the Mn(III) hydrolysis and the S(IV) autoxidation in the presence of organic contaminants indicated the existence of three Mn(III) consumption routes in the Fe 2+ /Mn 2+ /sulfite process. The absence of hydroxyl radical and sulfate radical was interpreted by the competitive dynamics method. The oxidation capacity of the Fe 2+ /Mn 2+ /sulfite was independent of the initial pH (4.0-6.0) because the fast decay of S(IV) decreased initial pH below 4.0 rapidly. The rate of ATZ degradation was independent of the dissolved oxygen (DO) because that the major DO consumption process was not the rate determining step during the production of SO 5 •- . Phosphate and bicarbonate were confirmed to have greater inhibitory effects than other environmental factors because of their strong pH buffering capacity and complexing capacity for Fe 3+ . The proposed acetylation degradation pathway of ATZ showed the application of the Fe 2+ /Mn 2+ /sulfite process in the research of contaminants degradation pathways. This work investigated the characteristics of the Fe 2+ /Mn 2+ /sulfite process in the presence of organic contaminants, which might promote the development of Mn(III) oxidation technology. Copyright © 2018. Published by Elsevier Ltd.

  18. Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

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    Maria S. Salvato

    2007-01-01

    Full Text Available Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203. Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

  19. Complex assembly, crystallization and preliminary X-ray crystallographic studies of rhesus macaque MHC Mamu-A*01 complexed with an immunodominant SIV-Gag nonapeptide

    International Nuclear Information System (INIS)

    Chu, Fuliang; Lou, Zhiyong; Gao, Bin; Bell, John I.; Rao, Zihe; Gao, George F.

    2005-01-01

    Crystallization of the first rhesus macaque MHC class I complex. Simian immunodeficiency virus (SIV) infection in rhesus macaques has been used as the best model for the study of human immunodeficiency virus (HIV) infection in humans, especially in the cytotoxic T-lymphocyte (CTL) response. However, the structure of rhesus macaque (or any other monkey model) major histocompatibility complex class I (MHC I) presenting a specific peptide (the ligand for CTL) has not yet been elucidated. Here, using in vitro refolding, the preparation of the complex of the rhesus macaque MHC I allele (Mamu-A*01) with human β 2 m and an immunodominant peptide, CTPYDINQM (Gag-CM9), derived from SIV Gag protein is reported. The complex (45 kDa) was crystallized; the crystal belongs to space group I422, with unit-cell parameters a = b = 183.8, c = 155.2 Å. The crystal contains two molecules in the asymmetric unit and diffracts X-rays to 2.8 Å resolution. The structure is being solved by molecular replacement and this is the first attempt to determined the crystal structure of a peptide–nonhuman primate MHC complex

  20. Combined single-cell quantitation of host and SIV genes and proteins ex vivo reveals host-pathogen interactions in individual cells.

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    Diane L Bolton

    2017-06-01

    Full Text Available CD4 T cells harboring HIV-1/SIV represent a formidable hurdle to eradicating infection, and yet their detailed phenotype remains unknown. Here we integrate two single-cell technologies, flow cytometry and highly multiplexed quantitative RT-PCR, to characterize SIV-infected CD4 T cells directly ex vivo. Within individual cells, we correlate the cellular phenotype, in terms of host protein and RNA expression, with stages of the viral life cycle defined by combinatorial expression of viral RNAs. Spliced RNA+ infected cells display multiple memory and activation phenotypes, indicating virus production by diverse CD4 T cell subsets. In most (but not all cells, progressive infection accompanies post-transcriptional downregulation of CD4 protein, while surface MHC class I is largely retained. Interferon-stimulated genes were also commonly upregulated. Thus, we demonstrate that combined quantitation of transcriptional and post-transcriptional regulation at the single-cell level informs in vivo mechanisms of viral replication and immune evasion.

  1. Treatment with a belly-board device significantly reduces the volume of small bowel irradiated and results in low acute toxicity in adjuvant radiotherapy for gynecologic cancer: results of a prospective study

    International Nuclear Information System (INIS)

    Martin, Joseph; Fitzpatrick, Kathryn; Horan, Gail; McCloy, Roisin; Buckney, Steve; O'Neill, Louise; Faul, Clare

    2005-01-01

    Background and purpose: To determine whether treatment prone on a belly-board significantly reduces the volume of small bowel irradiated in women receiving adjuvant radiotherapy for gynecologic cancer, and to prospectively study acute small bowel toxicity using an accepted recording instrument. Material and methods: Thirty-two gynecologic patients underwent simulation with CT scanning supine and prone. Small bowel was delineated on every CT slice, and treatment was prone on the belly-board using 3-5 fields-typically Anterior, Right and Left Lateral, plus or minus Lateral Boosts. Median prescribed dose was 50.4 Gy and all treatments were delivered in 1.8 Gy fractions. Concomitant Cisplatin was administered in 13 patients with cervical carcinoma. Comparison of small bowel dose-volumes was made between supine and prone, with each subject acting as their own matched pair. Acute small bowel toxicity was prospectively measured using the Common Toxicity Criteria: Version 2.0. Results: Treatment prone on the belly-board significantly reduced the volume of small bowel receiving ≥100; ≥95; ≥90; and ≥80% of the prescribed dose, but not ≥50%. This was found whether volume was defined in cubic centimeters or % of total small bowel volume. Of 29 evaluable subjects, 2 (7%) experienced 1 episode each of grade 3 diarrhoea. All other toxicity events were grade 2 or less and comprised diarrhoea (59%), abdominal pain or cramping (48%), nausea (38%), anorexia (17%), vomiting (10%). There were no Grade 4 events and no treatment days were lost due to toxicity. Conclusions: Treatment prone on a belly-board device results in significant small bowel sparing, during adjuvant radiotherapy for gynecologic cancer. The absence of Grade 4 events or Treatment Days Lost compares favorably with the published literature

  2. The Purification Method Using Iodixanol (Optiprep)-Based Density Gradient Significantly Reduces Cytokine/Chemokine Production from Human Islet Preparations, Leading to Prolong β-Cell Survival During Culture

    Science.gov (United States)

    Mita, Atsuyoshi; Ricordi, Camillo; Miki, Atsushi; Barker, Scott; Khan, Aisha; Alvarez, Alejandro; Hashikura, Yasuhiko; Miyagawa, Shin-ichi; Ichii, Hirohito

    2009-01-01

    Improved islet isolation has still been important to obtain adequate islet numbers for islet transplantation. Although Ficol-based density gradient is widely used for purification in most islet processing centers, OptiPrep-based density gradient is recently used in the limited centers and their clinical outcomes are excellent. Cytokine/chemokine production from islet preparations for transplantation widely varies. Some cytokines/chemokines have been reported to cause apoptosis in human islet preparations after isolation. Reducing cytokine/chemokine production is a key to improve islet numbers after isolation and islet transplantation outcome. The aim of current study is to investigate the variability of pro-inflammatory cytokine/chemokine production from islet preparations purified by different density gradient. After digestion of human pancreata, pre-purification digests were devided into two groups and purified using semi-automated cell processor with Ficoll-based and OptiPrep-based density gradient. Islet preparations were cultured for 2 days and assessed regarding islet cell viability (FDA/PI), fractional β-cell viability and β-cell content. Cytokine/chemokine production from islet preparations was also examined. After purification, purity, post-purification IEQ and islet recovery rate were comparable between two groups. Although FDA/PI and fractional β-cell viability showed no significant differences, β-cell survival during culture significantly increased in OptiPrep-based density gradient group when compared to Ficoll-based density gradient group. TNF-α, IL-1β, IFN-γ, IL-6 and MIP-1β production from OptiPrep-based density gradient group significantly decreased. OptiPrep-based density gradient can reduce cytokine-production when compared to Ficoll-based density gradient, resulting in improvement of quantity of β-cell mass. Cytokine profiling could spot new light on assessment of islet preparations before transplantation. PMID:19249543

  3. Design and methods of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen SignificantlY) study: An investigator-blinded randomized controlled trial of education and feedback intervention to reduce inappropriate echocardiograms.

    Science.gov (United States)

    Bhatia, R Sacha; Ivers, Noah; Yin, Cindy X; Myers, Dorothy; Nesbitt, Gillian; Edwards, Jeremy; Yared, Kibar; Wadhera, Rishi; Wu, Justina C; Wong, Brian; Hansen, Mark; Weinerman, Adina; Shadowitz, Steven; Johri, Amer; Farkouh, Michael; Thavendiranathan, Paaladinesh; Udell, Jacob A; Rambihar, Sherryn; Chow, Chi-Ming; Hall, Judith; Thorpe, Kevin E; Rakowski, Harry; Weiner, Rory B

    2015-08-01

    Appropriate use criteria (AUC) for transthoracic echocardiography (TTE) were developed to address concerns regarding inappropriate use of TTE. A previous pilot study suggests that an educational and feedback intervention can reduce inappropriate TTEs ordered by physicians in training. It is unknown if this type of intervention will be effective when targeted at attending level physicians in a variety of clinical settings. The aim of this international, multicenter study is to evaluate the hypothesis that an AUC-based educational and feedback intervention will reduce the proportion of inappropriate echocardiograms ordered by attending physicians in the ambulatory environment. In an ongoing multicentered, investigator-blinded, randomized controlled trial across Canada and the United States, cardiologists and primary care physicians practicing in the ambulatory setting will be enrolled. The intervention arm will receive (1) a lecture outlining the AUC and most recent available evidence highlighting appropriate use of TTE, (2) access to the American Society of Echocardiography mobile phone app, and (3) individualized feedback reports e-mailed monthly summarizing TTE ordering behavior including information on inappropriate TTEs and brief explanations of the inappropriate designation. The control group will receive no education on TTE appropriate use and order TTEs as usual practice. The Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly in an education RCT) study is the first multicenter randomized trial of an AUC-based educational intervention. The study will examine whether an education and feedback intervention will reduce the rate of outpatient inappropriate TTEs ordered by attending level cardiologists and primary care physicians (www.clinicaltrials.gov identifier NCT02038101). Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Immunogenicity of a reduced-dose whole killed rabies vaccine is significantly enhanced by ISCOMATRIX™ adjuvant, Merck amorphous aluminum hydroxylphosphate sulfate (MAA) or a synthetic TLR9 agonist in rhesus macaques.

    Science.gov (United States)

    DiStefano, Daniel; Antonello, Joseph M; Bett, Andrew J; Medi, Muneeswara B; Casimiro, Danilo R; ter Meulen, Jan

    2013-10-01

    There is a need for novel rabies vaccines suitable for short course, pre- and post-exposure prophylactic regimens which require reduced doses of antigen to address the current worldwide supply issue. We evaluated in rhesus macaques the immunogenicity of a quarter-dose of a standard rabies vaccine formulated with Merck's amorphous aluminum hydroxylphosphate sulfate adjuvant, the saponin-based ISCOMATRIX™ adjuvant, or a synthetic TLR9 agonist. All adjuvants significantly increased the magnitude and durability of the humoral immune response as measured by rapid fluorescent focus inhibition test (RFFIT). Several three-dose vaccine regimens resulted in adequate neutralizing antibody of ≥ 0.5 IU/ml earlier than the critical day seven post the first dose. Rabies vaccine with ISCOMATRIX™ adjuvant given at days 0 and 3 resulted in neutralizing antibody titers which developed faster and were up to one log10 higher compared to WHO-recommended intramuscular and intradermal regimens and furthermore, passive administration of human rabies immunoglobulin did not interfere with immunogenicity of this reduced dose, short course vaccine regimen. Adjuvantation of whole-killed rabies vaccine for intramuscular injection may therefore be a viable alternative to intradermal application of non-adjuvanted vaccine for both pre- and post-exposure regimens. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Multiconfiguration Pair-Density Functional Theory Predicts Spin-State Ordering in Iron Complexes with the Same Accuracy as Complete Active Space Second-Order Perturbation Theory at a Significantly Reduced Computational Cost.

    Science.gov (United States)

    Wilbraham, Liam; Verma, Pragya; Truhlar, Donald G; Gagliardi, Laura; Ciofini, Ilaria

    2017-05-04

    The spin-state orderings in nine Fe(II) and Fe(III) complexes with ligands of diverse ligand-field strength were investigated with multiconfiguration pair-density functional theory (MC-PDFT). The performance of this method was compared to that of complete active space second-order perturbation theory (CASPT2) and Kohn-Sham density functional theory. We also investigated the dependence of CASPT2 and MC-PDFT results on the size of the active-space. MC-PDFT reproduces the CASPT2 spin-state ordering, the dependence on the ligand field strength, and the dependence on active space at a computational cost that is significantly reduced as compared to CASPT2.

  6. Şemseddin Sivȃsȋ’nin Tasavvufȋ Tecrübesinde Rizȃ-yı Bȃrȋ Düşüncesi

    Directory of Open Access Journals (Sweden)

    Kadir Özköse

    2015-12-01

    Full Text Available Halvetiyyenin dört ana kolundan biri olan Şemsiyyenin pȋri konumundaki Şemseddin Sivȃsȋ’nin eserlerinden hareketle hazırladığımız bu makale Şemseddin Sivȃsȋ’nin sȗfȋ tecrübesini okumaya dönük bir çalışmadır. Mensur ve manzum eserlerinin herbirinde Şemseddin Sivȃsȋ ana tema olarak Allah’ın rızasını merkeze almıştır. İlahi rızanın her zaman gündemde olmasını, kulluğun ilahi rıza ekseninde gerçekleşmesini istemiştir. Lutfun da hoş kahrın da hoş anlayışına bağlı olan Şemseddin Sivȃsȋ ilahi takdire boyun eğmiş, ne varlığa sevinmeyi ne de yokluktan yerinmeyi öngörmüştür. Rıza halinin kemalini o, mücahede eğitimne, sabır ve sebat gayretine, tevazu duygusuna, ihlas hassasiyetine ve zikir diriliğine bağlamıştır. Makalemizde Şemseddin Sivȃsȋ’nin rızanın ehemmiyetine ve rıza makamına ulaşmayı sağlayan teel ölçütlere dikkat çekmeye çalıştık.

  7. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset

    Science.gov (United States)

    Ploquin, Mickaël J.; Casrouge, Armanda; Huot, Nicolas; Passaes, Caroline; Lécuroux, Camille; Essat, Asma; Boufassa, Faroudy; Jacquelin, Béatrice; Jochems, Simon P.; Petitjean, Gaël; Angin, Mathieu; Gärtner, Kathleen; Garcia-Tellez, Thalía; Booiman, Thijs; Boeser-Nunnink, Brigitte D.; Roques, Pierre; Saez-Cirion, Asier; Vaslin, Bruno; Dereudre-Bosquet, Nathalie; Barré-Sinoussi, Françoise; Ghislain, Mathilde; Rouzioux, Christine; Lambotte, Olivier; Albert, Matthew L.; Goujard, Cécile; Kootstra, Neeltje; Meyer, Laurence; Müller-Trutwin, Michaela C.

    2016-01-01

    Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort), as well as during controlled and uncontrolled viremia (ANRS cohorts). We also addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10. PMID:27509048

  8. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

    Directory of Open Access Journals (Sweden)

    Mickaël J Ploquin

    2016-08-01

    Full Text Available Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort, as well as during controlled and uncontrolled viremia (ANRS cohorts. We also addressed IP-10 expression levels with regards to lymphoid tissues (LT and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

  9. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells

    Directory of Open Access Journals (Sweden)

    John Zaunders

    2017-04-01

    Full Text Available BackgroundT follicular helper (Tfh cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4+ T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.MethodologyTfh and other CD4+ T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV+ subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay.ResultsPhylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV+ subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5+PD-1intermediate(int+ memory CD4+ T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1int cells survive, carry SIV provirus, and differentiate into PD-1hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5+ Tfh and pre-Tfh cells from human tonsils.ConclusionThe major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population

  10. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells.

    Science.gov (United States)

    Xu, Yin; Phetsouphanh, Chansavath; Suzuki, Kazuo; Aggrawal, Anu; Graff-Dubois, Stephanie; Roche, Michael; Bailey, Michelle; Alcantara, Sheilajen; Cashin, Kieran; Sivasubramaniam, Rahuram; Koelsch, Kersten K; Autran, Brigitte; Harvey, Richard; Gorry, Paul R; Moris, Arnaud; Cooper, David A; Turville, Stuart; Kent, Stephen J; Kelleher, Anthony D; Zaunders, John

    2017-01-01

    T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4 + T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells. Tfh and other CD4 + T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV + subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay. Phylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV + subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5 + PD-1 intermediate(int)+ memory CD4 + T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1 int cells survive, carry SIV provirus, and differentiate into PD-1 hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1 hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5 + Tfh and pre-Tfh cells from human tonsils. The major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population. As the generation of Tfh are important

  11. Left-colon water exchange preserves the benefits of whole colon water exchange at reduced cecal intubation time conferring significant advantage in diagnostic colonoscopy - a prospective, randomized controlled trial.

    Science.gov (United States)

    Wang, Xiangping; Luo, Hui; Xiang, Yi; Leung, Felix W; Wang, Limei; Zhang, Linhui; Liu, Zhiguo; Wu, Kaichun; Fan, Daiming; Pan, Yanglin; Guo, Xuegang

    2015-07-01

    Whole-colon water exchange (WWE) reduces insertion pain, increases cecal intubation success and adenoma detection rate, but requires longer insertion time, compared to air insufflation (AI) colonoscopy. We hypothesized that water exchange limited to the left colon (LWE) can speed up insertion with equivalent results. This prospective, randomized controlled study (NCT01735266) allocated patients (18-80 years) to WWE, LWE or AI group (1:1:1). The primary outcome was cecal intubation time. Three hundred subjects were randomized to the WWE (n = 100), LWE (n = 100) or AI group (n = 100). Ninety-four to ninety-five per cent of patients underwent diagnostic colonoscopy. Baseline characteristics were balanced. The median insertion time was shorter in LWE group (4.8 min (95%CI: 3.2-6.2)) than those in WWE (7.5 min (95%CI: 6.0-10.3)) and AI (6.4 min (95%CI: 4.2-9.8)) (both p rates in unsedated patients of the two water exchange methods (WWE 99%, LWE 99%) were significantly higher than that (89.8%) in AI group (p = 0.01). The final success rates were comparable among the three groups after sedation was given. Maximum pain scores and number of patients needing abdominal compression between WWE and LWE groups were comparable, both lower than those in AI group (p higher in WWE group. By preserving the benefits of WWE and reducing insertion time, LWE is appropriate for diagnostic colonoscopy, especially in settings with tight scheduling of patients. The higher PDR in the right colon in WWE group deserves to be further investigated.

  12. Reproducible deep-inspiration breath-hold irradiation with forward intensity-modulated radiotherapy for left-sided breast cancer significantly reduces cardiac radiation exposure compared to inverse intensity-modulated radiotherapy.

    Science.gov (United States)

    Bolukbasi, Yasemin; Saglam, Yucel; Selek, Ugur; Topkan, Erkan; Kataria, Anglina; Unal, Zeynep; Alpan, Vildan

    2014-01-01

    To investigate the objective utility of our clinical routine of reproducible deep-inspiration breath-hold irradiation for left-sided breast cancer patients on reducing cardiac exposure. Free-breathing and reproducible deep-inspiration breath-hold scans were evaluated for our 10 consecutive left-sided breast cancer patients treated with reproducible deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated radiotherapy plans were generated for each computed tomography dataset. Reproducible deep-inspiration breath-hold plans with forward intensity-modulated radiotherapy significantly spared the heart and left anterior descending artery compared to generated free-breathing plans based on mean doses - free-breathing vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy, P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66 cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P = 0.007) - whereas they revealed no additional burden on the ipsilateral lung. Reproducible deep-inspiration breath-hold and free-breathing plans with inverse intensity-modulated radiotherapy provided similar organ at risk sparing by reducing the mean doses to the left ventricle, left anterior descending artery, heart, V10-V20 of the heart and right ventricle. However, forward intensity-modulated radiotherapy showed significant reduction in doses to the left ventricle, left anterior descending artery, heart, right ventricle, and contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses for free-breathing vs reproducible deep-inspiration breath-hold of the proximal left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50 Gy

  13. Direct Targeting of Macrophages With Methylglyoxal-Bis-Guanylhydrazone Decreases SIV-Associated Cardiovascular Inflammation and Pathology.

    Science.gov (United States)

    Walker, Joshua A; Miller, Andrew D; Burdo, Tricia H; McGrath, Michael S; Williams, Kenneth C

    2017-04-15

    Despite effective combination antiretroviral therapy, HIV-infected individuals develop comorbidities, including cardiovascular disease, where activated macrophages play a key role. To date, few therapies target activated monocytes and macrophages. We evaluated a novel oral form of the polyamine biosynthesis inhibitor methylglyoxal-bis-guanylhydrazone (MGBG) on cardiovascular inflammation, carotid artery intima-media thickness (cIMT), and fibrosis in a simian immunodeficiency virus infection model of AIDS. Eleven simian immunodeficiency virus-infected animals received MGBG (30 mg/kg) once daily and 8 received a placebo control both beginning at 21 days postinfection (dpi). Animals were time sacrificed at 49 days post infection (dpi), when their matched placebo controls developed AIDS (63, 70, 77, 80), or at the study end-point (84 dpi). Aorta, carotid artery, and cardiac tissues were analyzed. Quantitative analyses of macrophage populations and T lymphocytes were done and correlated with cIMT and fibrosis. MGBG treatment resulted in 2.19-fold (CD163), 1.86-fold (CD68), 2.31-fold (CD206), and 2.12-fold (MAC387) decreases in macrophages in carotid arteries and significant 2.07-fold (CD163), 1.61-fold (CD68), 1.95-fold (MAC387), and 1.62-fold (CD206) decreases in macrophages in cardiac tissues. cIMT (1.49-fold) and fibrosis (2.05-fold) also were significantly decreased with MGBG treatment. Numbers of macrophage and the degree of fibrosis in treated animals were similar to uninfected animals. A positive correlation between decreased macrophage in the carotid artery and cIMT, and cardiac macrophages and fibrosis was found. These data demonstrate that directly targeting macrophages with MGBG can reduce cardiovascular inflammation, cIMT, and fibrosis. They suggest that therapies targeting macrophages with HIV could be used in conjunction with combination antiretroviral therapy.

  14. Immunogenicity in pig-tailed macaques of poliovirus replicons expressing HIV-1 and SIV antigens and protection against SHIV-89.6P disease

    International Nuclear Information System (INIS)

    Fultz, Patricia N.; Stallworth, Jackie; Porter, Donna; Novak, Miroslav; Anderson, Marie J.; Morrow, Casey D.

    2003-01-01

    In the search for an effective vaccine against the human immunodeficiency virus (HIV), novel ways to deliver viral antigens are being evaluated. One such approach is the use of nonreplicating viral vectors encoding HIV and/or SIV genes that are expressed after infection of host cells. Nonreplicating poliovirus vectors, termed replicons, that expressed HIV-1/HXB2 and SIVmac239 gag and various HIV-1 env genes from different clades were tested for immunogenicity and protective efficacy against intravenous challenge of pig-tailed macaques with SHIV-89.6P. To maximize both cellular and humoral immune responses, a prime-boost regimen was used. Initially, macaques were immunized four times over 35 weeks by either the intranasal and intrarectal or the intramuscular (im) route with mixtures of poliovirus replicons expressing HIV-1 gag and multiple env genes. Immunization with replicons alone induced both serum antibodies and lymphocyte proliferative responses. After boosting with purified Env protein, neutralizing antibodies to SHIV-89.6P were induced in four of five immunized animals. In a second experiment, four macaques were immunized im three times over 27 weeks with replicons expressing the SIVmac239 gag and HIV-1/HXB2 env genes. All immunized animals were then boosted twice with purified HIV-1-89.6 rgp140-Env and SIVmac239 p55-Gag proteins. Four control animals received only the two protein inoculations. Immunized and control animals were then challenged intravenously with the pathogenic SHIV-89.6P. After challenge the animals were monitored for virus isolation from peripheral blood mononuclear cells and plasma viremia and for changes in virus-specific antibody titers. Naieve pig-tailed macaques experienced rapid loss of CD4 + T cells and died between 38 and 62 weeks after infection. In contrast, macaques immunized with replicons and proteins rapidly cleared plasma virus and did not experience sustained loss of CD4 + lymphocytes. Furthermore, two of the four macaques

  15. Application of feces extracts and synthetic analogues of the host marking pheromone of Anastrepha ludens significantly reduces fruit infestation by A. obliqua in tropical plum and mango backyard orchards.

    Science.gov (United States)

    Aluja, Martín; Díaz-Fleischer, F; Boller, E F; Hurter, J; Edmunds, A J F; Hagmann, L; Patrian, B; Reyes, J

    2009-12-01

    We determined the efficacy of three potential oviposition deterrents in reducing fruit infestation by Anastrepha obliqua in tropical plum and mango orchards. These were: (1) Extracts of feces of Mexican fruit fly, Anastrepha ludens, known to contain the A. ludens host marking pheromone (HMP) and (2) two fully synthetic simplified analogues of the naturally occurring compound, which we have named desmethyl A. ludens HMP (DM-HMP) and Anastrephamide. Two applications of feces extracts 2 or 3 wk before fruit color break reduced A. obliqua infestation in plums by 94.1, 75.9, and 72% when measured 8, 14, and 25 d, respectively, after application. The natural A. ludens-HMP containing extract retained its effectiveness despite considerable rainfall (112.5 mm) and high A. obliqua populations. The synthetic desmethyl HMP derivative (DM-HMP) also reduced infestation in plums by 53.3 and 58.7% when measured, 18 and 26 d, respectively, after application. Finally, applications of Anastrephamide resulted in fruit loss cut by half and an 80% reduction in numbers of fly larvae per fruit. Our results confirm previous findings indicating that there is interspecific cross-recognition of the HMP in two of the most pestiferous Anastrepha species and open the door for the development of a highly selective, biorational Anastrepha management scheme.

  16. Kinetics and mechanism of the oxidation of S(IV) by ozone in aqueous solution with particular reference to SO2 conversion in nonurban tropospheric clouds

    Science.gov (United States)

    Maahs, H. G.

    1983-01-01

    Results are presented from a laboratory study of the kinetics of the S(IV)-O3 reaction in aqueous solution, including measurements of the effects of UV radiation, dissolved transition metals, and an antioxidant (hydroquinone) on the rate. On the basis of the results, relative rates of S(IV) conversion by O3 in tropospheric cloud water are compared with those predicted for H2O2 and for O2. The reaction mechanism is discussed, with an outline given of the elements of a possible reaction scheme. Application of the rate constants obtained to SO2 conversion in cloud water predicts conversion rates by ozone to be competitive with those by H2O2 at pH above about 4.5 and to dominate at pH above about 5.5. It is pointed out that since these pH's are typical for nonurban tropospheric cloud water, ozone is a potentially important contributor to the overall oxidative conversion of SO2 to sulfate in the nonurban troposphere.

  17. Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections.

    Science.gov (United States)

    Asmal, Mohammed; Lane, Sophie; Tian, Meijuan; Nickel, Gabrielle; Venner, Colin; Dirk, Brennan; Dikeakos, Jimmy; Luedemann, Corinne; Mach, Linh; Balachandran, Harikrishnan; Buzby, Adam; Rao, Srinivas; Letvin, Norman; Gao, Yong; Arts, Eric J

    2016-12-01

    For studies on vaccines and therapies for HIV disease, SIV-HIV chimeric viruses harboring the HIV-1 env gene (SHIVenv) remain the best virus in non-human primate models. However, there are still very few SHIVenv viruses that can cause AIDS in non-CD8-depleted animals. In the present study, a recently created CCR5-using SHIVenv_B3 virus with env gene derived from acute/early HIV-1 infections (AHI) successfully established pathogenic infection in macaques. Through a series of investigations on the evolution, mutational profile, and phenotype of the virus and the resultant humoral immune response in infected rhesus macaques, we found that the E32K mutation in the Env C1 domain was associated with macaque pathogenesis, and that the electrostatic interactions in Env may favor E32K at the gp120 N terminus and "lock" the binding to heptad repeat 1 of gp41 in the trimer and produce a SHIVenv with increased fitness and pathogenesis during macaque infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The V1 region of gp120 is preferentially selected during SIV/HIV transmission and is indispensable for envelope function and virus infection.

    Science.gov (United States)

    Li, Yanpeng; Dittmer, Ulf; Wang, Yan; Song, Jiping; Sun, Binlian; Yang, Rongge

    2016-06-01

    A transmission bottleneck occurs during each human immunodeficiency virus (HIV) transmission event, which allows only a few viruses to establish new infection. However, the genetic characteristics of the transmitted viruses that are preferentially selected have not been fully elucidated. Here, we analyzed amino acids changes in the envelope protein during simian immunodeficiency virus (SIV)/HIV deep transmission history and current HIV evolution within the last 15-20 years. Our results confirmed that the V1V2 region of gp120 protein, particularly V1, was preferentially selected. A shorter V1 region was preferred during transmission history, while during epidemic, HIV may evolve to an expanded V1 region gradually and thus escape immune recognition. We then constructed different HIV-1 V1 mutants using different HIV-1 subtypes to elucidate the role of the V1 region in envelope function. We found that the V1 region, although highly variable, was indispensable for virus entry and infection, probably because V1 deletion mutants exhibited impaired processing of gp160 into mature gp120 and gp41. Additionally, the V1 region affected Env incorporation. These results indicated that the V1 region played a critical role in HIV transmission and infection.

  19. Activation of the blood-brain barrier by SIV (simian immunodeficiency virus) requires cell-associated virus and is not restricted to endothelial cell activation.

    Science.gov (United States)

    MacLean, A G; Rasmussen, T A; Bieniemy, D; Lackner, A A

    2004-11-01

    The primary cell infected during acute HIV neuropathogenesis is the monocyte-derived macrophage. We have demonstrated that there is activation of the BBB (blood-brain barrier) during acute viral infection and at terminal AIDS. However, it has never been determined if there is a requirement for the virus to be carried through the BBB or how these Trojan horses would be induced to cross the BBB. We added SIVmac251-infected (SIV is simian immunodeficiency virus) mononuclear cells (and their supernatants) to the luminal or abluminal compartment of our BBB model. There was activation of both sides of the BBB model, only if viral-infected cells were added to the luminal compartment, as opposed to the addition of cell-free supernatants. This suggests that cell-associated virus is essential for the activation of the BBB. This, in turn, would be expected to lead to further infiltration of cells capable of viral infection. VCAM-1 (vascular cell adhesion molecule 1) staining revealed, for the first time, that there is an absolute requirement for virally infected cells, and not just the presence of virus for the activation of the BBB.

  20. The oxidation capacity of Mn3O4 nanoparticles is significantly enhanced by anchoring them onto reduced graphene oxide to facilitate regeneration of surface-associated Mn(III).

    Science.gov (United States)

    Duan, Lin; Wang, Zhongyuan; Hou, Yan; Wang, Zepeng; Gao, Guandao; Chen, Wei; Alvarez, Pedro J J

    2016-10-15

    Metal oxides are often anchored to graphene materials to achieve greater contaminant removal efficiency. To date, the enhanced performance has mainly been attributed to the role of graphene materials as a conductor for electron transfer. Herein, we report a new mechanism via which graphene materials enhance oxidation of organic contaminants by metal oxides. Specifically, Mn3O4-rGO nanocomposites (Mn3O4 nanoparticles anchored to reduced graphene oxide (rGO) nanosheets) enhanced oxidation of 1-naphthylamine (used here as a reaction probe) compared to bare Mn3O4. Spectroscopic analyses (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) show that the rGO component of Mn3O4-rGO was further reduced during the oxidation of 1-naphthylamine, although rGO reduction was not the result of direct interaction with 1-naphthylamine. We postulate that rGO improved the oxidation efficiency of anchored Mn3O4 by re-oxidizing Mn(II) formed from the reaction between Mn3O4 and 1-naphthylamine, thereby regenerating the surface-associated oxidant Mn(III). The proposed role of rGO was verified by separate experiments demonstrating its ability to oxidize dissolved Mn(II) to Mn(III), which subsequently can oxidize 1-naphthylamine. The role of dissolved oxygen in re-oxidizing Mn(II) was ruled out by anoxic (N2-purged) control experiments showing similar results as O2-sparged tests. Opposite pH effects on the oxidation efficiency of Mn3O4-rGO versus bare Mn3O4 were also observed, corroborating the proposed mechanism because higher pH facilitates oxidation of surface-associated Mn(II) even though it lowers the oxidation potential of Mn3O4. Overall, these findings may guide the development of novel metal oxide-graphene nanocomposites for contaminant removal. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Histomorphometric Assessment of Cancellous and Cortical Bone Material Distribution in the Proximal Humerus of Normal and Osteoporotic Individuals: Significantly Reduced Bone Stock in the Metaphyseal and Subcapital Regions of Osteoporotic Individuals.

    Science.gov (United States)

    Sprecher, Christoph M; Schmidutz, Florian; Helfen, Tobias; Richards, R Geoff; Blauth, Michael; Milz, Stefan

    2015-12-01

    Osteoporosis is a systemic disorder predominantly affecting postmenopausal women but also men at an advanced age. Both genders may suffer from low-energy fractures of, for example, the proximal humerus when reduction of the bone stock or/and quality has occurred.The aim of the current study was to compare the amount of bone in typical fracture zones of the proximal humerus in osteoporotic and non-osteoporotic individuals.The amount of bone in the proximal humerus was determined histomorphometrically in frontal plane sections. The donor bones were allocated to normal and osteoporotic groups using the T-score from distal radius DXA measurements of the same extremities. The T-score evaluation was done according to WHO criteria. Regional thickness of the subchondral plate and the metaphyseal cortical bone were measured using interactive image analysis.At all measured locations the amount of cancellous bone was significantly lower in individuals from the osteoporotic group compared to the non-osteoporotic one. The osteoporotic group showed more significant differences between regions of the same bone than the non-osteoporotic group. In both groups the subchondral cancellous bone and the subchondral plate were least affected by bone loss. In contrast, the medial metaphyseal region in the osteoporotic group exhibited higher bone loss in comparison to the lateral side.This observation may explain prevailing fracture patterns, which frequently involve compression fractures and certainly has an influence on the stability of implants placed in this medial region. It should be considered when planning the anchoring of osteosynthesis materials in osteoporotic patients with fractures of the proximal humerus.

  2. Deletions within the 3' Non-Translated Region of Alfalfa mosaic virus RNA4 Do Not Affect Replication but Significantly Reduce Long-Distance Movement of Chimeric Tobacco mosaic virus

    Directory of Open Access Journals (Sweden)

    Vidadi Yusibov

    2013-07-01

    Full Text Available Alfalfa mosaic virus (AlMV RNAs 1 and 2 with deletions in their 3' non‑translated regions (NTRs have been previously shown to be encapsidated into virions by coat protein (CP expressed from RNA3, indicating that the 3' NTRs of RNAs 1 and 2 are not required for virion assembly. Here, we constructed various mutants by deleting sequences within the 3' NTR of AlMV subgenomic (sg RNA4 (same as of RNA3 and examined the effect of these deletions on replication and translation of chimeric Tobacco mosaic virus (TMV expressing AlMV sgRNA4 from the TMV CP sg promoter (Av/A4 in tobacco protoplasts and Nicotiana benthamiana plants. While the Av/A4 mutants were as competent as the wild-type Av/A4 in RNA replication in protoplasts, their encapsidation, long-distance movement and virus accumulation varied significantly in N. benthamiana. These data suggest that the 3' NTR of AlMV sgRNA4 contains potential elements necessary for virus encapsidation.

  3. Reduced dosage of β-catenin provides significant rescue of cardiac outflow tract anomalies in a Tbx1 conditional null mouse model of 22q11.2 deletion syndrome.

    Directory of Open Access Journals (Sweden)

    Silvia E Racedo

    2017-03-01

    Full Text Available The 22q11.2 deletion syndrome (22q11.2DS; velo-cardio-facial syndrome; DiGeorge syndrome is a congenital anomaly disorder in which haploinsufficiency of TBX1, encoding a T-box transcription factor, is the major candidate for cardiac outflow tract (OFT malformations. Inactivation of Tbx1 in the anterior heart field (AHF mesoderm in the mouse results in premature expression of pro-differentiation genes and a persistent truncus arteriosus (PTA in which septation does not form between the aorta and pulmonary trunk. Canonical Wnt/β-catenin has major roles in cardiac OFT development that may act upstream of Tbx1. Consistent with an antagonistic relationship, we found the opposite gene expression changes occurred in the AHF in β-catenin loss of function embryos compared to Tbx1 loss of function embryos, providing an opportunity to test for genetic rescue. When both alleles of Tbx1 and one allele of β-catenin were inactivated in the Mef2c-AHF-Cre domain, 61% of them (n = 34 showed partial or complete rescue of the PTA defect. Upregulated genes that were oppositely changed in expression in individual mutant embryos were normalized in significantly rescued embryos. Further, β-catenin was increased in expression when Tbx1 was inactivated, suggesting that there may be a negative feedback loop between canonical Wnt and Tbx1 in the AHF to allow the formation of the OFT. We suggest that alteration of this balance may contribute to variable expressivity in 22q11.2DS.

  4. IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation

    Directory of Open Access Journals (Sweden)

    Mbofung Carl MF

    2009-03-01

    Full Text Available Abstract Background A recent in vitro study indicates that IGOB131, a novel seed extract of the traditional West African food plant Irvingia gabonensis, favorably impacts adipogenesis through a variety of critical metabolic pathways including PPAR gamma, leptin, adiponectin, and glycerol-3 phosphate dehydrogenase. This study was therefore aimed at evaluating the effects of IGOB131, an extract of Irvingia gabonensis, on body weight and associated metabolic parameters in overweight human volunteers. Methods The study participants comprised of 102 healthy, overweight and/or obese volunteers (defined as BMI > 25 kg/m2 randomly divided into two groups. The groups received on a daily basis, either 150 mg of IGOB131 or matching placebo in a double blinded fashion, 30–60 minutes before lunch and dinner. At baseline, 4, 8 and 10 weeks of the study, subjects were evaluated for changes in anthropometrics and metabolic parameters to include fasting lipids, blood glucose, C-reactive protein, adiponectin, and leptin. Results Significant improvements in body weight, body fat, and waist circumference as well as plasma total cholesterol, LDL cholesterol, blood glucose, C-reactive protein, adiponectin and leptin levels were observed in the IGOB131 group compared with the placebo group. Conclusion Irvingia gabonensis administered 150 mg twice daily before meals to overweight and/or obese human volunteers favorably impacts body weight and a variety of parameters characteristic of the metabolic syndrome. This is the first double blind randomized placebo controlled clinical trial regarding the anti-obesity and lipid profile modulating effects of an Irvingia gabonensis extract. The positive clinical results, together with our previously published mechanisms of gene expression modulation related to key metabolic pathways in lipid metabolism, provide impetus for much larger clinical studies. Irvingia gabonensis extract may prove to be a useful tool in dealing with the

  5. Corticothalamic and corticotectal somatosensory projections from the anterior ectosylvian sulcus (SIV cortex) in neonatal cats: an anatomical demonstration with HRP and /sup 3/H-leucine

    Energy Technology Data Exchange (ETDEWEB)

    McHaffie, J.G.; Kruger, L.; Clemo, H.R.; Stein, B.E.

    1988-08-01

    Corticothalamic and corticotectal projections from the anterior ectosylvian sulcus (AES) in neonatal cats were studied with anterograde and retrograde neuroanatomical techniques. When the injection site was relatively restricted to the sulcal walls and fundus of the rostral AES (i.e., the SIV cortex), heavy ipsilateral thalamic label was observed in the medial subdivision of the posterior group, in the suprageniculate nucleus, and in the external medullary lamina. No terminal label was seen in the contralateral thalamus although the contralateral homotopic cortex was heavily labeled. Within the ventrobasal complex (VB), dense axonal label was observed in fascicles that traversed VB, but only light terminal label was observed within VB itself. However, in cases where the tracer spread into adjacent SII, terminal label in VB was pronounced. Similarly, when the injection site extended into auditory cortex, terminal label was observed in the lateral and intermediate subdivisions of the posterior group. Rostral AES injections produced distinct, predominantly ipsilateral, terminal label in the superior colliculus that was distributed in two tiers: a discontinuous band in the stratum griseum intermedium and a more diffuse band in stratum griseum profundum. Caudally, dense terminal label was seen in the intercollicular zone and dorsolateral periaqueductal gray. When the injection site did not include rostral AES, no label was observed in the superior colliculus. Horseradish peroxidase injections into the superior colliculus of neonates produced retrogradely labeled neurons throughout the AES, but none was found on the crown of the gyrus where SII is located. Thus, the neonatal corticotectal somatosensory projection arises exclusively from AES and parallels that found in adults.

  6. Progression to AIDS in SIV-Infected Rhesus Macaques is Associated with Distinct KIR and MHC class I Polymorphisms and NK Cell Dysfunction

    Science.gov (United States)

    Albrecht, Christina; Malzahn, Dörthe; Brameier, Markus; Hermes, Meike; Ansari, Aftab A.; Walter, Lutz

    2014-01-01

    Killer cell immunoglobulin-like receptors (KIR) regulate the activity of natural killer (NK) cells and have been shown to be associated with susceptibility to a number of human infectious diseases. Here, we analyzed NK cell function and genetic associations in a cohort of 52 rhesus macaques experimentally infected with SIVmac and subsequently stratified into high viral load (HVL) and low viral load (LVL) plasma viral loads at set point. This stratification coincided with fast (HVL) and slow (LVL) disease progression indicated by the disease course and critical clinical parameters including CD4+ T cell counts. HVL animals revealed sustained proliferation of NK cells but distinct loss of peripheral blood NK cell numbers and lytic function. Genetic analyses revealed that KIR genes 3DL05, 3DS05, and 3DL10 as well as 3DSW08, 3DLW03, and 3DSW09 are correlated, most likely due to underlying haplotypes. SIV-infection outcome associated with presence of transcripts for two inhibitory KIR genes (KIR3DL02, KIR3DL10) and three activating KIR genes (KIR3DSW08, KIR3DS02, KIR3DS05). Presence of KIR3DL02 and KIR3DSW08 was associated with LVL outcome, whereas presence of KIR3DS02 was associated with HVL outcome. Furthermore, we identified epistasis between KIR and MHC class I alleles as the transcript presence of the correlated genes KIR3DL05, KIR3DS05, and KIR3DL10 increased HVL risk when Mamu-B*012 transcripts were also present or when Mamu-A1*001 transcripts were absent. These genetic associations were mirrored by changes in the numbers, the level of proliferation, and lytic capabilities of NK cells as well as overall survival time and gastro-intestinal tissue viral load. PMID:25506344

  7. Protective efficacy of a virus-vectored multi-component vaccine against porcine reproductive and respiratory syndrome virus, porcine circovirus type 2 and swine influenza virus.

    Science.gov (United States)

    Tian, Debin; Sooryanarain, Harini; Matzinger, Shannon R; Gauger, Phil C; Karuppannan, Anbu K; Elankumaran, Subbiah; Opriessnig, Tanja; Meng, Xiang-Jin

    2017-12-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2) and swine influenza virus (SIV) are three of the most economically important swine pathogens, causing immense economic losses to the global swine industry. Monovalent commercial vaccines against each of the three viruses are routinely used in pig farms worldwide. A trivalent vaccine against all three pathogens would greatly simplify the vaccination programme and reduce the financial burden to the swine industry. In this study, by using an attenuated strain of PRRSV (strain DS722) as a live virus vector, we generated a multi-component vaccine virus, DS722-SIV-PCV2, which expresses the protective antigens from SIV and PCV2. The DS722-SIV-PCV2 trivalent vaccine virus replicates well, and expresses PCV2 capsid and SIV HA proteins in vitro. A subsequent vaccination and challenge study in 48 pigs revealed that the DS722-SIV-PCV2-vaccinated pigs had significantly reduced lung lesions and viral RNA loads when challenged with PRRSV. Upon challenge with PCV2, the vaccinated pigs had partially reduced lymphoid lesions and viral DNA loads, and when challenged with SIV the vaccinated pigs had significantly reduced acute respiratory sign scores. The results from this study demonstrate the potential of DS722-SIV-PCV2 as a candidate trivalent vaccine, and also shed light on exploring PRRSV as a potential live virus vaccine vector.

  8. A big oil company's approach to significantly reduce fatal incidents

    NARCIS (Netherlands)

    Peuscher, W.; Groeneweg, J.

    2012-01-01

    Within the Shell Group of companies (Shell), keeping people safe at work is a deeply held value and the company actively pursues the goal of no harm to people. Shell actively works to build a culture where every employee and contractor takes responsibility for making this goal possible - it is

  9. RDX-based nanocomposite microparticles for significantly reduced shock sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Qiu Hongwei, E-mail: hqiu@stevens.edu [Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, Hoboken, NJ 07030 (United States); Stepanov, Victor; Di Stasio, Anthony R. [U.S. Army - Armament Research, Development, and Engineering Center, Picatinny, NJ 07806 (United States); Chou, Tsengming; Lee, Woo Y. [Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, Hoboken, NJ 07030 (United States)

    2011-01-15

    Cyclotrimethylenetrinitramine (RDX)-based nanocomposite microparticles were produced by a simple, yet novel spray drying method. The microparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and high performance liquid chromatography (HPLC), which shows that they consist of small RDX crystals ({approx}0.1-1 {mu}m) uniformly and discretely dispersed in a binder. The microparticles were subsequently pressed to produce dense energetic materials which exhibited a markedly lower shock sensitivity. The low sensitivity was attributed to small crystal size as well as small void size ({approx}250 nm). The method developed in this work may be suitable for the preparation of a wide range of insensitive explosive compositions.

  10. RDX-based nanocomposite microparticles for significantly reduced shock sensitivity

    International Nuclear Information System (INIS)

    Qiu Hongwei; Stepanov, Victor; Di Stasio, Anthony R.; Chou, Tsengming; Lee, Woo Y.

    2011-01-01

    Cyclotrimethylenetrinitramine (RDX)-based nanocomposite microparticles were produced by a simple, yet novel spray drying method. The microparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and high performance liquid chromatography (HPLC), which shows that they consist of small RDX crystals (∼0.1-1 μm) uniformly and discretely dispersed in a binder. The microparticles were subsequently pressed to produce dense energetic materials which exhibited a markedly lower shock sensitivity. The low sensitivity was attributed to small crystal size as well as small void size (∼250 nm). The method developed in this work may be suitable for the preparation of a wide range of insensitive explosive compositions.

  11. RDX-based nanocomposite microparticles for significantly reduced shock sensitivity.

    Science.gov (United States)

    Qiu, Hongwei; Stepanov, Victor; Di Stasio, Anthony R; Chou, Tsengming; Lee, Woo Y

    2011-01-15

    Cyclotrimethylenetrinitramine (RDX)-based nanocomposite microparticles were produced by a simple, yet novel spray drying method. The microparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and high performance liquid chromatography (HPLC), which shows that they consist of small RDX crystals (∼0.1-1 μm) uniformly and discretely dispersed in a binder. The microparticles were subsequently pressed to produce dense energetic materials which exhibited a markedly lower shock sensitivity. The low sensitivity was attributed to small crystal size as well as small void size (∼250 nm). The method developed in this work may be suitable for the preparation of a wide range of insensitive explosive compositions. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag.

    Science.gov (United States)

    Coleman, John W; Wright, Kevin J; Wallace, Olivia L; Sharma, Palka; Arendt, Heather; Martinez, Jennifer; DeStefano, Joanne; Zamb, Timothy P; Zhang, Xinsheng; Parks, Christopher L

    2015-03-01

    Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Detecting Novelty and Significance

    Science.gov (United States)

    Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

    2013-01-01

    Studies of cognition often use an “oddball” paradigm to study effects of stimulus novelty and significance on information processing. However, an oddball tends to be perceptually more novel than the standard, repeated stimulus as well as more relevant to the ongoing task, making it difficult to disentangle effects due to perceptual novelty and stimulus significance. In the current study, effects of perceptual novelty and significance on ERPs were assessed in a passive viewing context by presenting repeated and novel pictures (natural scenes) that either signaled significant information regarding the current context or not. A fronto-central N2 component was primarily affected by perceptual novelty, whereas a centro-parietal P3 component was modulated by both stimulus significance and novelty. The data support an interpretation that the N2 reflects perceptual fluency and is attenuated when a current stimulus matches an active memory representation and that the amplitude of the P3 reflects stimulus meaning and significance. PMID:19400680

  14. Significant NRC Enforcement Actions

    Data.gov (United States)

    Nuclear Regulatory Commission — This dataset provides a list of Nuclear Regulartory Commission (NRC) issued significant enforcement actions. These actions, referred to as "escalated", are issued by...

  15. Significant Tsunami Events

    Science.gov (United States)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  16. Significant engineering developments

    International Nuclear Information System (INIS)

    Pon, G.A.

    1987-01-01

    The CANDU nuclear power system is a successful product of creative intelligence combined with the tenacious pursuit of practical solutions to complex engineering challenges. Outstanding engineering developments have transformed a demanding technology into a safe, economic and reliable one. Among the noteworthy developments that have been made CANDU the world's best performing reactor system are those relating to fuel, pressure tubes, heavy water production and management, steam generators, live-load valve packing, pump seals, on-power refuelling and computer control. In addition to pragmatic engineering accomplishments, there has been significant engineering input to guide the direction and shaping of the unique form of safety design and regulation of the CANDU system

  17. Safety significance evaluation system

    International Nuclear Information System (INIS)

    Lew, B.S.; Yee, D.; Brewer, W.K.; Quattro, P.J.; Kirby, K.D.

    1991-01-01

    This paper reports that the Pacific Gas and Electric Company (PG and E), in cooperation with ABZ, Incorporated and Science Applications International Corporation (SAIC), investigated the use of artificial intelligence-based programming techniques to assist utility personnel in regulatory compliance problems. The result of this investigation is that artificial intelligence-based programming techniques can successfully be applied to this problem. To demonstrate this, a general methodology was developed and several prototype systems based on this methodology were developed. The prototypes address U.S. Nuclear Regulatory Commission (NRC) event reportability requirements, technical specification compliance based on plant equipment status, and quality assurance assistance. This collection of prototype modules is named the safety significance evaluation system

  18. Anthropological significance of phenylketonuria.

    Science.gov (United States)

    Saugstad, L F

    1975-01-01

    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations.

  19. Tumor significant dose

    International Nuclear Information System (INIS)

    Supe, S.J.; Nagalaxmi, K.V.; Meenakshi, L.

    1983-01-01

    In the practice of radiotherapy, various concepts like NSD, CRE, TDF, and BIR are being used to evaluate the biological effectiveness of the treatment schedules on the normal tissues. This has been accepted as the tolerance of the normal tissue is the limiting factor in the treatment of cancers. At present when various schedules are tried, attention is therefore paid to the biological damage of the normal tissues only and it is expected that the damage to the cancerous tissues would be extensive enough to control the cancer. Attempt is made in the present work to evaluate the concent of tumor significant dose (TSD) which will represent the damage to the cancerous tissue. Strandquist in the analysis of a large number of cases of squamous cell carcinoma found that for the 5 fraction/week treatment, the total dose required to bring about the same damage for the cancerous tissue is proportional to T/sup -0.22/, where T is the overall time over which the dose is delivered. Using this finding the TSD was defined as DxN/sup -p/xT/sup -q/, where D is the total dose, N the number of fractions, T the overall time p and q are the exponents to be suitably chosen. The values of p and q are adjusted such that p+q< or =0.24, and p varies from 0.0 to 0.24 and q varies from 0.0 to 0.22. Cases of cancer of cervix uteri treated between 1978 and 1980 in the V. N. Cancer Centre, Kuppuswamy Naidu Memorial Hospital, Coimbatore, India were analyzed on the basis of these formulations. These data, coupled with the clinical experience, were used for choice of a formula for the TSD. Further, the dose schedules used in the British Institute of Radiology fraction- ation studies were also used to propose that the tumor significant dose is represented by DxN/sup -0.18/xT/sup -0.06/

  20. Fungi producing significant mycotoxins.

    Science.gov (United States)

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

  1. REDUCING INDOOR HUMIDITY SIGNIFICANTLY REDUCES DUST MITES AND ALLERGEN IN HOMES. (R825250)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. New analytical methodology for analysing S(IV) species at low pH solutions by one stage titration method (bichromatometry) with a clear colour change. Could potentially replace the state-of-art-method iodometry at low pH analysis due higher accuracy.

    Science.gov (United States)

    Santasalo-Aarnio, Annukka; Galfi, Istvan; Virtanen, Jorma; Gasik, Michael M

    2017-01-01

    A new, faster and more reliable analytical methodology for S(IV) species analysis at low pH solutions by bichromatometry is proposed. For decades the state of the art methodology has been iodometry that is still well justified method for neutral solutions, thus at low pH media possess various side reactions increasing inaccuracy. In contrast, the new methodology has no side reactions at low pH media, requires only one titration step and provides a clear color change if S(IV) species are present in the solution. The method is validated using model solutions with known concentrations and applied to analyses of gaseous SO2 from purged solution in low pH media samples. The results indicate that bichromatometry can accurately analyze SO2 from liquid samples having pH even below 0 relevant to metallurgical industrial processes.

  3. Prenatal supplementation with Corn Soya Blend Plus reduces the risk of maternal anemia in late gestation and lowers the rate of preterm birth but does not significantly improve maternal weight gain and birth anthropometric measurements in rural Cambodian women: a randomized trial.

    Science.gov (United States)

    Janmohamed, Amynah; Karakochuk, Crystal D; Boungnasiri, Somchit; Chapman, Gwen E; Janssen, Patricia A; Brant, Rollin; Green, Timothy J; McLean, Judy

    2016-02-01

    Corn Soya Blend (CSB) Plus is a fortified dietary supplement used to help Cambodian women meet their nutritional requirements in pregnancy, although little is known about its ability to improve pregnancy outcomes. This study assessed the effect of prenatal CSB Plus supplementation on birth weight and secondary outcomes of low birth weight (birth length and head circumference, preterm birth (birth weight between the CSB Plus and control group (46 g; 95% CI: -31, 123 g; P = 0.24). Significant reductions were observed in preterm birth (OR = 0.33; 95% CI: 0.12, 0.89) and anemia at 36-38 wk (OR = 0.51; 95% CI: 0.34, 0.77). There were no significant differences in low birth weight, small for gestational age, birth length, head circumference, or maternal weight gain. A higher rate of fetal loss was observed in the treatment group (10.2% compared with 3.7%; P birth size but did reduce maternal anemia in late gestation and preterm birth in comparison with women consuming a normal diet. The unexpectedly higher rate of fetal loss in the treatment group is concerning and warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01413776. © 2016 American Society for Nutrition.

  4. Full-Length Genome Analyses of Two New Simian Immunodeficiency Virus (SIV Strains from Mustached Monkeys (C. Cephus in Gabon Illustrate a Complex Evolutionary History among the SIVmus/mon/gsn Lineage

    Directory of Open Access Journals (Sweden)

    Florian Liégeois

    2014-07-01

    Full Text Available The Simian Immunodeficiency Virus (SIV mus/mon/gsn lineage is a descendant of one of the precursor viruses to the HIV-1/SIVcpz/gor viral lineage. SIVmus and SIVgsn were sequenced from mustached and greater spot nosed monkeys in Cameroon and SIVmon from mona monkeys in Cameroon and Nigeria. In order to further document the genetic diversity of SIVmus, we analyzed two full-length genomes of new strains identified in Gabon. The whole genomes obtained showed the expected reading frames for gag, pol, vif, vpr, tat, rev, env, nef, and also for a vpu gene. Analyses showed that the Gabonese SIVmus strains were closely related and formed a monophyletic clade within the SIVmus/mon/gsn lineage. Nonetheless, within this lineage, the position of both new SIVmus differed according to the gene analyzed. In pol and nef gene, phylogenetic topologies suggested different evolutions for each of the two new SIVmus strains whereas in the other nucleic fragments studied, their positions fluctuated between SIVmon, SIVmus-1, and SIVgsn. In addition, in C1 domain of env, we identified an insertion of seven amino acids characteristic for the SIVmus/mon/gsn and HIV‑1/SIVcpz/SIVgor lineages. Our results show a high genetic diversity of SIVmus in mustached monkeys and suggest cross-species transmission events and recombination within SIVmus/mon/gsn lineage. Additionally, in Central Africa, hunters continue to be exposed to these simian viruses, and this represents a potential threat to humans.

  5. Reducing Resistance

    DEFF Research Database (Denmark)

    Lindell, Johanna

    care may influence decisions on antibiotic use. Based on video-and audio recordings of physician-patient consultations it is investigated how treatment recommendations are presented, can be changed, are forecast and explained, and finally, how they seemingly meet resistance and how this resistance......Antibiotic resistance is a growing public health problem both nationally and internationally, and efficient strategies are needed to reduce unnecessary use. This dissertation presents four research studies, which examine how communication between general practitioners and patients in Danish primary...... is responded to.The first study in the dissertation suggests that treatment recommendations on antibiotics are often done in a way that encourages patient acceptance. In extension of this, the second study of the dissertation examines a case, where acceptance of such a recommendation is changed into a shared...

  6. Reducing sedentarism

    DEFF Research Database (Denmark)

    Brown, Wendy; Andersen, Lars Bo; Sigmund, Anderssen

    being a health risk will be briefly considered. Second, a review of the evidence on the health effects of sitting will be presented. This will include results from observational cohort studies on the relationships between sitting and diabetes, cardiovascular diseases, cancers, depression, obesity...... include sitting during leisure time, at work, and during commuting. Sedentary behaviors such as TV viewing, using a computer or driving a car typically demands low levels of energy expenditure. Youth and adults spend most of their waking time sitting or doing light activities, and most of them do little......, type 2 diabetes, musculoskeletal diseases, and psychological disorders. In addition, low level of energy expenditure is one of the key determinants of the current epidemic of overweight and obesity in Europe. In order to both reduce sitting time and to increase the level of physical activity...

  7. Automated detection and recognition of diagnostically significant ...

    African Journals Online (AJOL)

    ... points and the use of automated means of searching for ECG lines. The system increases the reliability of decoding ECG by a doctor-cardiologist for the purpose of diagnosis and significantly reduces the time to perform this procedure. Keywords: ECG; ECG annotation; the state machine; state diagram; UML; LabVIEW ...

  8. Reducing costs by reducing size

    International Nuclear Information System (INIS)

    Hayns, M.R.; Shepherd, J.

    1991-01-01

    The present paper discusses briefly the many factors, including capital cost, which have to be taken into account in determining whether a series of power stations based on a small nuclear plant can be competitive with a series based on traditional large unit sizes giving the guaranteed level of supply. The 320 MWe UK/US Safe Integral Reactor is described as a good example of how the factors discussed can be beneficially incorporated into a design using proven technology. Finally it goes on to illustrate how the overall costs of a generating system can indeed by reduced by use of the 320 MWe Safe Integral Reactor rather than conventional units of around 1200 MWe. (author). 9 figs

  9. On statistical significance of signal

    International Nuclear Information System (INIS)

    Zhu Yongsheng

    2006-01-01

    A definition for the statistical significance of a signal in an experiment is proposed by establishing a correlation between the observed p-value and the normal distribution integral probability, which is suitable for both counting experiment and continuous test statistics. The explicit expressions to calculate the statistical significance for both cases are given. (author)

  10. Historical Significant Volcanic Eruption Locations

    Data.gov (United States)

    Department of Homeland Security — A significant eruption is classified as one that meets at least one of the following criteriacaused fatalities, caused moderate damage (approximately $1 million or...

  11. Significance of irradiation of blood

    International Nuclear Information System (INIS)

    Sekine, Hiroshi; Gotoh, Eisuke; Mochizuki, Sachio

    1992-01-01

    Many reports of fatal GVHD occurring in non-immunocompromised patients after blood transfusion have been published in Japan. One explantation is that transfused lymphocytes were simulated and attack the recipient organs recognized as HLA incompatible. That is so called 'one-way matching'. To reduce the risk of post-transfusion GVHD, one of the most convenient methods is to irradiate the donated blood at an appropriate dose for inactivation of lymphocytes. Because no one knows about the late effect of irradiated blood, it is necessary to make the prospective safety control. (author)

  12. Significance evaluation in factor graphs

    DEFF Research Database (Denmark)

    Madsen, Tobias; Hobolth, Asger; Jensen, Jens Ledet

    2017-01-01

    in genomics and the multiple-testing issues accompanying them, accurate significance evaluation is of great importance. We here address the problem of evaluating statistical significance of observations from factor graph models. Results Two novel numerical approximations for evaluation of statistical...... significance are presented. First a method using importance sampling. Second a saddlepoint approximation based method. We develop algorithms to efficiently compute the approximations and compare them to naive sampling and the normal approximation. The individual merits of the methods are analysed both from....... Conclusions The applicability of saddlepoint approximation and importance sampling is demonstrated on known models in the factor graph framework. Using the two methods we can substantially improve computational cost without compromising accuracy. This contribution allows analyses of large datasets...

  13. The historical significance of oak

    Science.gov (United States)

    J. V. Thirgood

    1971-01-01

    A brief history of the importance of oak in Europe, contrasting the methods used in France and Britain to propagate the species and manage the forests for continued productivity. The significance of oak as a strategic resource during the sailing-ship era is stressed, and mention is made of the early development of oak management in North America. The international...

  14. Factors Influencing Seasonal Influenza Vaccination Uptake in Emergency Medical Services Workers: A Concept Mapping Approach.

    Science.gov (United States)

    Subramaniam, Dipti P; Baker, Elizabeth A; Zelicoff, Alan P; Elliott, Michael B

    2016-08-01

    Seasonal influenza has serious impacts on morbidity and mortality and has a significant economic toll through lost workforce time and strains on the health system. Health workers, particularly emergency medical services (EMS) workers have the potential to transmit influenza to those in their care, yet little is known of the factors that influence EMS workers' decisions regarding seasonal influenza vaccination (SIV) uptake, a key factor in reducing potential for transmitting disease. This study utilizes a modified Theory of Planned Behavior (TPB) model as a guiding framework to explore the factors that influence SIV uptake in EMS workers. Concept mapping, which consists of six-stages (preparation, generation, structuring, representation, interpretation, and utilization) that use quantitative and qualitative approaches, was used to identify participants' perspectives towards SIV. This study identified nine EMS-conceptualized factors that influence EMS workers' vaccination intent and behavior. The EMS-conceptualized factors align with the modified TPB model and suggest the need to consider community-wide approaches that were not initially conceptualized in the model. Additionally, the expansion of non-pharmaceutical measures went above and beyond original conceptualization. Overall, this study demonstrates the need to develop customized interventions such as messages highlighting the importance of EMS workers receiving SIV as the optimum solution. EMS workers who do not intend to receive the SIV should be provided with accurate information on the SIV to dispel misconceptions. Finally, EMS workers should also receive interventions which promote voluntary vaccination, encouraging them to be proactive in the health decisions they make for themselves.

  15. In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts.

    Science.gov (United States)

    Seki, Sayuri; Nomura, Takushi; Nishizawa, Masako; Yamamoto, Hiroyuki; Ishii, Hiroshi; Matsuoka, Saori; Shiino, Teiichiro; Sato, Hironori; Mizuta, Kazuta; Sakawaki, Hiromi; Miura, Tomoyuki; Naruse, Taeko K; Kimura, Akinori; Matano, Tetsuro

    2017-09-01

    CD8+ T-cell responses exert strong suppressive pressure on HIV replication and select for viral escape mutations. Some of these major histocompatibility complex class I (MHC-I)-associated mutations result in reduction of in vitro viral replicative capacity. While these mutations can revert after viral transmission to MHC-I-disparate hosts, recent studies have suggested that these MHC-I-associated mutations accumulate in populations and make viruses less pathogenic in vitro. Here, we directly show an increase in the in vivo virulence of an MHC-I-adapted virus serially-passaged through MHC-I-mismatched hosts in a macaque AIDS model despite a reduction in in vitro viral fitness. The first passage simian immunodeficiency virus (1pSIV) obtained 1 year after SIVmac239 infection in a macaque possessing a protective MHC-I haplotype 90-120-Ia was transmitted into 90-120-Ia- macaques, whose plasma 1 year post-infection was transmitted into other 90-120-Ia- macaques to obtain the third passage SIV (3pSIV). Most of the 90-120-Ia-associated mutations selected in 1pSIV did not revert even in 3pSIV. 3pSIV showed lower in vitro viral fitness but induced persistent viremia in 90-120-Ia- macaques. Remarkably, 3pSIV infection in 90-120-Ia+ macaques resulted in significantly higher viral loads and reduced survival compared to wild-type SIVmac239. These results indicate that MHC-I-adapted SIVs serially-transmitted through MHC-I-mismatched hosts can have higher virulence in MHC-I-matched hosts despite their lower in vitro viral fitness. This study suggests that multiply-passaged HIVs could result in loss of HIV-specific CD8+ T cell responses in human populations and the in vivo pathogenic potential of these escaped viruses may be enhanced.

  16. In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts.

    Directory of Open Access Journals (Sweden)

    Sayuri Seki

    2017-09-01

    Full Text Available CD8+ T-cell responses exert strong suppressive pressure on HIV replication and select for viral escape mutations. Some of these major histocompatibility complex class I (MHC-I-associated mutations result in reduction of in vitro viral replicative capacity. While these mutations can revert after viral transmission to MHC-I-disparate hosts, recent studies have suggested that these MHC-I-associated mutations accumulate in populations and make viruses less pathogenic in vitro. Here, we directly show an increase in the in vivo virulence of an MHC-I-adapted virus serially-passaged through MHC-I-mismatched hosts in a macaque AIDS model despite a reduction in in vitro viral fitness. The first passage simian immunodeficiency virus (1pSIV obtained 1 year after SIVmac239 infection in a macaque possessing a protective MHC-I haplotype 90-120-Ia was transmitted into 90-120-Ia- macaques, whose plasma 1 year post-infection was transmitted into other 90-120-Ia- macaques to obtain the third passage SIV (3pSIV. Most of the 90-120-Ia-associated mutations selected in 1pSIV did not revert even in 3pSIV. 3pSIV showed lower in vitro viral fitness but induced persistent viremia in 90-120-Ia- macaques. Remarkably, 3pSIV infection in 90-120-Ia+ macaques resulted in significantly higher viral loads and reduced survival compared to wild-type SIVmac239. These results indicate that MHC-I-adapted SIVs serially-transmitted through MHC-I-mismatched hosts can have higher virulence in MHC-I-matched hosts despite their lower in vitro viral fitness. This study suggests that multiply-passaged HIVs could result in loss of HIV-specific CD8+ T cell responses in human populations and the in vivo pathogenic potential of these escaped viruses may be enhanced.

  17. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1994-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  18. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1992-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July - September 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  19. Ecological Significance of Marine Microzooplankton

    Digital Repository Service at National Institute of Oceanography (India)

    Godhantaraman, N.

    al., 1996). Extensive research have been conducted on the ecological significance of major plankton communities in marine coastal and aquatic ecosystems both tropical as well as temperate waters. Research on microzooplankton received less attention... by planktologists because of their important role in the aquatic ecosystems/pelagic food web by providing a link between pico- and nanoplankton and higher trophic levels of meso- and macrozooplankton and fish larvae. Researchers have identified that microzooplankton...

  20. Synthetic definition of biological significance

    International Nuclear Information System (INIS)

    Buffington, J.D.

    1975-01-01

    The central theme of the workshop is recounted and the views of the authors are summarized. Areas of broad agreement or disagreement, unifying principles, and research needs are identified. Authors' views are consolidated into concepts that have practical utility for the scientist making impact assessments. The need for decision-makers and managers to be cognizant of the recommendations made herein is discussed. Finally, bringing together the diverse views of the workshop participants, a conceptual definition of biological significance is synthesized

  1. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1993-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  2. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1991-02-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  3. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1992-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  4. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1992-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  5. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1991-07-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April-June 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  6. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1993-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  7. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1993-06-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  8. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1992-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  9. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1990-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  10. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1991-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  11. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1989-06-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  12. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1990-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  13. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1990-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  14. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1989-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  15. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1991-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  16. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1993-09-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  17. Moral significance of phenomenal consciousness.

    Science.gov (United States)

    Levy, Neil; Savulescu, Julian

    2009-01-01

    Recent work in neuroimaging suggests that some patients diagnosed as being in the persistent vegetative state are actually conscious. In this paper, we critically examine this new evidence. We argue that though it remains open to alternative interpretations, it strongly suggests the presence of consciousness in some patients. However, we argue that its ethical significance is less than many people seem to think. There are several different kinds of consciousness, and though all kinds of consciousness have some ethical significance, different kinds underwrite different kinds of moral value. Demonstrating that patients have phenomenal consciousness--conscious states with some kind of qualitative feel to them--shows that they are moral patients, whose welfare must be taken into consideration. But only if they are subjects of a sophisticated kind of access consciousness--where access consciousness entails global availability of information to cognitive systems--are they persons, in the technical sense of the word employed by philosophers. In this sense, being a person is having the full moral status of ordinary human beings. We call for further research which might settle whether patients who manifest signs of consciousness possess the sophisticated kind of access consciousness required for personhood.

  18. Clinical significance of the fabella

    International Nuclear Information System (INIS)

    Dodevski, A.; Lazarova-Tosovska, D.; Zhivadinovik, J.; Lazareska, M.

    2012-01-01

    Full text: Introduction: There is variable number of sesamoid bones in the human body; one of them is fabella, located in the tendon of the gastrocnemius muscle. Aim of this study was to investigate the frequency of occurrence of fabella in the Macedonian population and to discuss about clinical importance of this bone. Materials and methods: We retrospectively examined radiographs of 53 patients who had knee exams undertaken for a variety of clinical reasons, performed as a part of their medical treatment. Over a time span of six months, 53 patients (38 males and 15 females, age range 19-60 years, mean age of 36.7±12.3 years) were examined. Results: In seven (13.2%) patients of 53 analyzed reports, fabella was found in the lateral tendon of gastrocnemius muscle. We did not find a significant gender or side difference in the appearance of fabella. Conclusion: Although anatomic studies emphasized a lack of significance of the fabella, this bone has been associated with a spectrum of pathology affecting the knee as fabellar syndrome, perineal nerve injury and fracture. We should think of this sesamoid bone while performing diagnostic and surgical procedures

  19. Monoclonal gammopathies of renal significance.

    Science.gov (United States)

    Caravaca-Fontán, Fernando; Gutiérrez, Eduardo; Delgado Lillo, Ramón; Praga, Manuel

    The term monoclonal gammopathy of renal significance (MGRS) comprises a group of diseases pathogenetically characterised by proliferation of a B-cell or plasma cell clone that synthesises and secretes a monoclonal immunoglobulin or its components (light and/or heavy chains), that may deposit and cause glomerular, tubular, interstitial and/or vascular damage. The importance of differentiating the term MGRS from other monoclonal gammopathies lies in the fact that diagnostic and therapeutic procedures aimed at controlling monoclonal protein synthesis and secretion can be indicated, irrespective of the classic criteria based on malignant tumour expansion. Renal pathology associated with MGRS is highly heterogeneous, and therefore renal biopsy should be considered a key diagnostic tool. A precise diagnostic approach, however, must also identify the monoclonal protein in plasma and/or in urine, together with a complete haematological study in order to determine the nature and extension of cell clones. Recent advances in the understanding of these entities have resulted in significant improvements in clinical course and survival in several forms of MGRS, although more studies and clinical experience are needed in order to delineate more effective therapeutic strategies. In this review, we summarise the main clinical and pathological features of MGRS, highlighting the most appropriate diagnostic approach and current therapeutic options. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Pathological Significance of Mitochondrial Glycation

    Directory of Open Access Journals (Sweden)

    Pamela Boon Li Pun

    2012-01-01

    Full Text Available Glycation, the nonenzymatic glycosylation of biomolecules, is commonly observed in diabetes and ageing. Reactive dicarbonyl species such as methylglyoxal and glyoxal are thought to be major physiological precursors of glycation. Because these dicarbonyls tend to be formed intracellularly, the levels of advanced glycation end products on cellular proteins are higher than on extracellular ones. The formation of glycation adducts within cells can have severe functional consequences such as inhibition of protein activity and promotion of DNA mutations. Although several lines of evidence suggest that there are specific mitochondrial targets of glycation, and mitochondrial dysfunction itself has been implicated in disease and ageing, it is unclear if glycation of biomolecules specifically within mitochondria induces dysfunction and contributes to disease pathology. We discuss here the possibility that mitochondrial glycation contributes to disease, focussing on diabetes, ageing, cancer, and neurodegeneration, and highlight the current limitations in our understanding of the pathological significance of mitochondrial glycation.

  1. Statistical Significance for Hierarchical Clustering

    Science.gov (United States)

    Kimes, Patrick K.; Liu, Yufeng; Hayes, D. Neil; Marron, J. S.

    2017-01-01

    Summary Cluster analysis has proved to be an invaluable tool for the exploratory and unsupervised analysis of high dimensional datasets. Among methods for clustering, hierarchical approaches have enjoyed substantial popularity in genomics and other fields for their ability to simultaneously uncover multiple layers of clustering structure. A critical and challenging question in cluster analysis is whether the identified clusters represent important underlying structure or are artifacts of natural sampling variation. Few approaches have been proposed for addressing this problem in the context of hierarchical clustering, for which the problem is further complicated by the natural tree structure of the partition, and the multiplicity of tests required to parse the layers of nested clusters. In this paper, we propose a Monte Carlo based approach for testing statistical significance in hierarchical clustering which addresses these issues. The approach is implemented as a sequential testing procedure guaranteeing control of the family-wise error rate. Theoretical justification is provided for our approach, and its power to detect true clustering structure is illustrated through several simulation studies and applications to two cancer gene expression datasets. PMID:28099990

  2. Astrobiological significance of chemolithoautotrophic acidophiles

    Science.gov (United States)

    Pikuta, Elena V.; Hoover, Richard B.

    2004-02-01

    For more than a century (since Winogradsky discovered lithautotrophic bacteria) there has been a dilemma in microbiology about life that first inhabited the Earth. Which types of life forms first appeared in the primordial oceans during the earliest geological period on Earth as the primary ancestors of modern biological diversity? How did a metabolism of ancestors evolve: from lithoautotrophic to lithoheterotrophic and organoheterotrophic or from organoheterotrophic to organautotrophic and lithomixotrophic types? At the present time, it is known that chemolithoheterotrophic and chemolithoautotrophic metabolizing bacteria are wide spread in different ecosystems. On Earth the acidic ecosystems are associated with geysers, volcanic fumaroles, hot springs, deep sea hydrothermal vents, caves, acid mine drainage and other technogenic ecosystems. Bioleaching played a significant roel on a global geological scale during the Earth's formation. This important feature of bacteria has been successfully applied in industry. The lithoautotrophs include Bacteria and Archaea belonging to diverse genera containing thermophilic and mesophilic species. In this paper we discuss the lithotrophic microbial acidophiles and present some data with a description of new acidophilic iron- and sulfur-oxidizing bacterium isolated from the Chena Hot Springs in Alaska. We also consider the possible relevance of microbial acidophiles to Venus, Io, and acidic inclusions in glaciers and icy moons.

  3. Clinical significance of procoagulant microparticles.

    Science.gov (United States)

    Nomura, Shosaku; Shimizu, Michiomi

    2015-01-01

    Microparticles (MPs) are small membrane vesicles that are released from many different cell types by exocytic budding of the plasma membrane in response to cellular activation or apoptosis. MPs may also be involved in clinical diseases because they express phospholipids, which function as procoagulants. Although flow cytometry is the most widely used method for studying MPs, some novel assays, such as tissue factor-dependent procoagulant assay or the ELISA method, have been reported. However, the use of quantification of MP as a clinical tool is still controversial. Elevated platelet-derived MP, endothelial cell-derived MP, and monocyte-derived MP concentrations are documented in almost all thrombotic diseases occurring in venous and arterial beds. However, the significance of MPs in various clinical conditions remains controversial. An example of this controversy is that it is unknown if MPs found in peripheral blood vessels cause thrombosis or whether they are the result of thrombosis. Numerous studies have shown that not only the quantity, but also the cellular origin and composition of circulating MPs, are dependent on the type of disease, the disease state, and medical treatment. Additionally, many different functions have been attributed to MPs. Therefore, the number and type of clinical disorders associated with elevated MPs are currently increasing. However, MPs were initially thought to be small particles with procoagulant activity. Taken together, our review suggests that MPs may be a useful biomarker to identify thrombosis.

  4. Determining Semantically Related Significant Genes.

    Science.gov (United States)

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  5. Statistically significant relational data mining :

    Energy Technology Data Exchange (ETDEWEB)

    Berry, Jonathan W.; Leung, Vitus Joseph; Phillips, Cynthia Ann; Pinar, Ali; Robinson, David Gerald; Berger-Wolf, Tanya; Bhowmick, Sanjukta; Casleton, Emily; Kaiser, Mark; Nordman, Daniel J.; Wilson, Alyson G.

    2014-02-01

    This report summarizes the work performed under the project (3z(BStatitically significant relational data mining.(3y (BThe goal of the project was to add more statistical rigor to the fairly ad hoc area of data mining on graphs. Our goal was to develop better algorithms and better ways to evaluate algorithm quality. We concetrated on algorithms for community detection, approximate pattern matching, and graph similarity measures. Approximate pattern matching involves finding an instance of a relatively small pattern, expressed with tolerance, in a large graph of data observed with uncertainty. This report gathers the abstracts and references for the eight refereed publications that have appeared as part of this work. We then archive three pieces of research that have not yet been published. The first is theoretical and experimental evidence that a popular statistical measure for comparison of community assignments favors over-resolved communities over approximations to a ground truth. The second are statistically motivated methods for measuring the quality of an approximate match of a small pattern in a large graph. The third is a new probabilistic random graph model. Statisticians favor these models for graph analysis. The new local structure graph model overcomes some of the issues with popular models such as exponential random graph models and latent variable models.

  6. Detection of significant protein coevolution.

    Science.gov (United States)

    Ochoa, David; Juan, David; Valencia, Alfonso; Pazos, Florencio

    2015-07-01

    The evolution of proteins cannot be fully understood without taking into account the coevolutionary linkages entangling them. From a practical point of view, coevolution between protein families has been used as a way of detecting protein interactions and functional relationships from genomic information. The most common approach to inferring protein coevolution involves the quantification of phylogenetic tree similarity using a family of methodologies termed mirrortree. In spite of their success, a fundamental problem of these approaches is the lack of an adequate statistical framework to assess the significance of a given coevolutionary score (tree similarity). As a consequence, a number of ad hoc filters and arbitrary thresholds are required in an attempt to obtain a final set of confident coevolutionary signals. In this work, we developed a method for associating confidence estimators (P values) to the tree-similarity scores, using a null model specifically designed for the tree comparison problem. We show how this approach largely improves the quality and coverage (number of pairs that can be evaluated) of the detected coevolution in all the stages of the mirrortree workflow, independently of the starting genomic information. This not only leads to a better understanding of protein coevolution and its biological implications, but also to obtain a highly reliable and comprehensive network of predicted interactions, as well as information on the substructure of macromolecular complexes using only genomic information. The software and datasets used in this work are freely available at: http://csbg.cnb.csic.es/pMT/. pazos@cnb.csic.es Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Rationale and design of a randomized, double-blind, event-driven, multicentre study comparing the efficacy and safety of oral rivaroxaban with placebo for reducing the risk of death, myocardial infarction or stroke in subjects with heart failure and significant coronary artery disease following an exacerbation of heart failure: the COMMANDER HF trial.

    Science.gov (United States)

    Zannad, Faiez; Greenberg, Barry; Cleland, John G F; Gheorghiade, Mihai; van Veldhuisen, Dirk J; Mehra, Mandeep R; Anker, Stefan D; Byra, William M; Fu, Min; Mills, Roger M

    2015-07-01

    Thrombin is a critical element of crosstalk between pathways contributing to worsening of established heart failure (HF). The aim of this study is to explore the efficacy and safety of rivaroxaban 2.5 mg bid compared with placebo (with standard care) after an exacerbation of HF in patients with reduced ejection fraction (HF-rEF) and documented coronary artery disease. This is an international prospective, multicentre, randomized, double-blind, placebo-controlled, event-driven study of approximately 5000 patients for a targeted 984 events. Patients must have a recent symptomatic exacerbation of HF, increased plasma concentrations of natriuretic peptides (B-type natriuretic peptide ≥200 pg/mL or N-terminal pro-B-type natriuretic peptide ≥800 pg/mL), with left ventricular ejection fraction ≤40% and coronary artery disease. Patients requiring anticoagulation for atrial fibrillation or other conditions will be excluded. After an index event (overnight hospitalization, emergency department or observation unit admission, or unscheduled outpatient parenteral treatment for worsening HF), patients will be randomized 1:1 to rivaroxaban or placebo (with standard of care). The primary efficacy outcome event is a composite of all-cause mortality, myocardial infarction or stroke. The principal safety outcome events are the composite of fatal bleeding or bleeding into a critical space with potential permanent disability, bleeding events requiring hospitalization and major bleeding events according to International Society on Thrombosis and Haemostasis bleeding criteria. COMMANDER HF is the first prospective study of a target-specific oral antithrombotic agent in HF. It will provide important information regarding rivaroxaban use following an HF event in an HF-rEF patient population with coronary artery disease. © 2015 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

  8. Traditional Indian spices and their health significance.

    Science.gov (United States)

    Krishnaswamy, Kamala

    2008-01-01

    India has been recognized all over the world for spices and medicinal plants. Both exhibit a wide range of physiological and pharmacological properties. Current biomedical efforts are focused on their scientific merits, to provide science-based evidence for the traditional uses and to develop either functional foods or nutraceuticals. The Indian traditional medical systems use turmeric for wound healing, rheumatic disorders, gastrointestinal symptoms, deworming, rhinitis and as a cosmetic. Studies in India have explored its anti-inflammatory, cholekinetic and anti-oxidant potentials with the recent investigations focusing on its preventive effect on precarcinogenic, anti-inflammatory and anti atherosclerotic effects in biological systems both under in vitro and in vivo conditions in animals and humans. Both turmeric and curcumin were found to increase detoxifying enzymes, prevent DNA damage, improve DNA repair, decrease mutations and tumour formation and exhibit antioxidative potential in animals. Limited clinical studies suggest that turmeric can significantly impact excretion of mutagens in urine in smokers and regress precancerous palatal lesions. It reduces DNA adducts and micronuclei in oral epithelial cells. It prevents formation of nitroso compounds both in vivo and in vitro. It delays induced cataract in diabetes and reduces hyperlipidemia in obese rats. Recently several molecular targets have been identified for therapeutic / preventive effects of turmeric. Fenugreek seeds, a rich source of soluble fiber used in Indian cuisine reduces blood glucose and lipids and can be used as a food adjuvant in diabetes. Similarly garlic, onions, and ginger have been found to modulate favourably the process of carcinogenesis.

  9. Tolerance to Chronic Delta-9-Tetrahydrocannabinol (Δ9-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus

    Science.gov (United States)

    Winsauer, Peter J.; Molina, Patricia E.; Amedee, Angela M.; Filipeanu, Catalin M.; McGoey, Robin R.; Troxclair, Dana A.; Walker, Edith M.; Birke, Leslie L.; Stouwe, Curtis Vande; Howard, Jessica M.; Leonard, Stuart T.; Moerschbaecher, Joseph M.; Lewis, Peter B.

    2011-01-01

    Although Δ9-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ9-THC before and after inoculation with simian immunodeficiency virus(SIVmac251, 100 TCID50/ml, i.v.). Prior to chronic Δ9-THC and SIV inoculation, 0.032– 0.32 mg/kg of Δ9-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ9-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7–12 months irrespective of SIV infection (i.e., +THC/−SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ9-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ9-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection. PMID:21463073

  10. Minocycline reduces ethanol drinking.

    Science.gov (United States)

    Agrawal, R G; Hewetson, A; George, C M; Syapin, P J; Bergeson, S E

    2011-06-01

    Alcoholism is a disease characterized by continued alcohol consumption despite recurring negative consequences. Thus, medications that reduce the drive to consume alcohol can be beneficial in treating alcoholism. The neurobiological systems that regulate alcohol consumption are complex and not fully understood. Currently, medications are available to treat alcoholism that act either by causing accumulation of a toxic metabolite of ethanol, or by targeting specific transmitter receptors. The purpose of our study was to investigate a new potential therapeutic pathway, neuroimmune interactions, for effects on ethanol consumption. We hypothesized that neuroimmune activity of brain glia may have a role in drinking. We utilized minocycline, a second generation tetracycline antibiotic that has immune modulatory actions, to test our hypothesis because it is known to suppress microglia, and to a lesser extent astroglia, activity following many types of insults to the brain. Treatment with 50mg/kg minocycline significantly reduced ethanol intake in male and female C57Bl/6J mice using a free choice voluntary drinking model. Saline injections did not alter ethanol intake. Minocycline had little effect on water intake or body weight change. The underlying mechanism whereby minocycline reduced ethanol intake requires further study. The results suggest that drugs that alter neuroimmune pathways may represent a new approach to developing additional therapies to treat alcoholism. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Gradual extinction reduces Reinstatement

    Directory of Open Access Journals (Sweden)

    Youssef eShiban

    2015-09-01

    Full Text Available The current study investigated whether gradually reducing the frequency of aversive stimuli during extinction can prevent the return of fear. Thirty-one participants of a three-stage procedure (acquisition, extinction and a reinstatement test on day two were randomly assigned to a standard extinction (SE and gradual extinction (GE procedure. The two groups differed only in the extinction procedure. While the SE group ran through a regular extinction process without any negative events, the frequency of the aversive stimuli during the extinction phase was gradually reduced for the GE group. The unconditioned stimulus was an air blast (5 bar, 10 ms. A spider and a scorpion were used as conditioned stimuli. The outcome variables were contingency ratings and physiological measures (skin conductance response and startle response. There were no differences found between the two groups for the acquisition and extinction phases concerning contingency ratings, SCR, or startle response. Gradual extinction compared to standard extinction significantly reduced the return of fear in the reinstatement test for the startle response but not for skin conductance response or contingency ratings. This study was successful in translating the findings in rodent to humans. The results suggest that the gradual extinction process is suitable for increasing the efficacy of fear extinction.

  12. Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis

    DEFF Research Database (Denmark)

    Wichman, Johanna Eva Märta; Winther, Kristian Hillert; Bonnema, Steen Joop

    2016-01-01

    3366 records. Controlled trials in adults (≥18 years of age) with AIT, comparing selenium with or without levothyroxine (LT4), versus placebo and/or LT4, were eligible. Assessed outcomes were serum thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) autoantibody levels, and immunomodulatory effects...

  13. The estimation error of skeletal muscle capillary supply is significantly reduced by 3D Metod

    Czech Academy of Sciences Publication Activity Database

    Čebašek, V.; Eržen, I.; Vyhnal, Aleš; Janáček, Jiří; Ribarič, S.; Kubínová, Lucie

    2010-01-01

    Roč. 79, č. 1 (2010), s. 40-46 ISSN 0026-2862 R&D Projects: GA MŠk(CZ) MEB090910; GA MŠk(CZ) LC06063; GA ČR(CZ) GD204/09/H084 Institutional research plan: CEZ:AV0Z50110509 Keywords : confocal microscopy * capillaries * length measurement Subject RIV: EA - Cell Biology Impact factor: 2.390, year: 2010

  14. The Natural Surfactant Glycerol Monolaurate Significantly Reduces Development of Staphylococcus aureus and Enterococcus faecalis Biofilms

    Science.gov (United States)

    Hess, Donavon J.; Henry-Stanley, Michelle J.

    2015-01-01

    Abstract Background: Bacterial biofilms are involved in a large proportion of clinical infections, including device-related infections. Unfortunately, biofilm-associated bacteria are typically less susceptible to antibiotics, and infected devices must often be removed. On the basis of a recent observation that lipid-rich biofilm matrix material is present in early biofilm formation and may protect a population of bacteria from interacting with ordinarily diffusible small molecules, we hypothesized that surfactants may be useful in preventing biofilm development. Methods: Experimental Staphylococcus aureus or Enterococcus faecalis biofilms were cultivated on surgical suture suspended in a growth medium supplemented with the natural surfactant glycerol monolaurate (GML) or with a component molecule, lauric acid. After 16 h incubation, the numbers of viable biofilm-associated bacteria were measured by standard microbiologic techniques and biofilm biomass was measured using the colorimetric crystal violet assay. Results: Both GML and lauric acid were effective in inhibiting biofilm development as measured by decreased numbers of viable biofilm-associated bacteria as well as decreased biofilm biomass. Compared with lauric acid on a molar basis, GML represented a more effective inhibitor of biofilms formed by either S. aureus or E. faecalis. Conclusions: Because the natural surfactant GML inhibited biofilm development, resulting data were consistent with the hypothesis that lipids may play an important role in biofilm growth, implying that interfering with lipid formation may help control development of clinically relevant biofilms. PMID:26110557

  15. Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy

    NARCIS (Netherlands)

    G. Mulligan (George); D.I. Lichter (David); A.D. Bacco (Alessandra Di); S.J. Blakemore (Stephen); A. Berger (Allison); E. Koenig (Erik); H. Bernard (Hugues); W.L. Trepicchio (William); B. Li (Bin); R. Neuwirth (Rachel); N. Chattopadhyay (Nibedita); J.B. Bolen (Joseph); A.J. Dorner (Andrew); H. van de Velde (Helgi); D. Ricci (Deborah); S. Jagannath (Sundar); J.R. Berenson (James); P.G. Richardson (Paul Gerard); E.A. Stadtmauer (Edward); R.Z. Orlowski (Robert); S. Lonial (Sagar); K.C. Anderson (Kenneth); P. Sonneveld (Pieter); J.F. San Miguel (Jesús Fernando); D.-L. Esseltine (Dixie-Lee); M. Schu (Matthew)

    2014-01-01

    textabstractVarious translocations and mutations have been identified in myeloma, and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41

  16. Reducing Dysfunctional Beliefs about Sleep Does Not Significantly Improve Insomnia in Cognitive Behavioral Therapy

    OpenAIRE

    Okajima, Isa; Nakajima, Shun; Ochi, Moeko; Inoue, Yuichi

    2014-01-01

    The present study examined to examine whether improvement of insomnia is mediated by a reduction in sleep-related dysfunctional beliefs through cognitive behavioral therapy for insomnia. In total, 64 patients with chronic insomnia received cognitive behavioral therapy for insomnia consisting of 6 biweekly individual treatment sessions of 50 minutes in length. Participants were asked to complete the Athens Insomnia Scale and the Dysfunctional Beliefs and Attitudes about Sleep scale both at the...

  17. A Novel 5-Enolpyruvylshikimate-3-Phosphate Synthase from Rahnella aquatilis with Significantly Reduced Glyphosate Sensitivity

    Science.gov (United States)

    Xiong, Ai-Sheng; Zhao, Wei; Fu, Xiao-Yan; Han, Hong-Juan; Chen, Chen; Jin, Xiao-Fen; Yao, Quan-Hong

    2012-01-01

    The 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.19) is a key enzyme in the shikimate pathway for the production of aromatic amino acids and chorismate-derived secondary metabolites in plants, fungi, and microorganisms. It is also the target of the broad-spectrum herbicide glyphosate. Natural glyphosate resistance is generally thought to occur within microorganisms in a strong selective pressure condition. Rahnella aquatilis strain GR20, an antagonist against pathogenic agrobacterial strains of grape crown gall, was isolated from the rhizosphere of grape in glyphosate-contaminated vineyards. A novel gene encoding EPSPS was identified from the isolated bacterium by complementation of an Escherichia coli auxotrophic aroA mutant. The EPSPS, named AroAR.aquatilis, was expressed and purified from E. coli, and key kinetic values were determined. The full-length enzyme exhibited higher tolerance to glyphosate than the E. coli EPSPS (AroAE.coli), while retaining high affinity for the substrate phosphoenolpyruvate. Transgenic plants of AroAR.aquatilis were also observed to be more resistant to glyphosate at a concentration of 5 mM than that of AroAE.coli. To probe the sites contributing to increased tolerance to glyphosate, mutant R.aquatilis EPSPS enzymes were produced with the c-strand of subdomain 3 and the f-strand of subdomain 5 (Thr38Lys, Arg40Val, Arg222Gln, Ser224Val, Ile225Val, and Gln226Lys) substituted by the corresponding region of the E. coli EPSPS. The mutant enzyme exhibited greater sensitivity to glyphosate than the wild type R.aquatilis EPSPS with little change of affinity for its first substrate, shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP). The effect of the residues on subdomain 5 on glyphosate resistance was more obvious. PMID:22870190

  18. ITS technologies reduce delay, crashes and emissions, with significant returns on investment : research spotlight.

    Science.gov (United States)

    2015-07-01

    Intelligent transportation systems (ITS) technologies have gained popularity in recent years as a method for relieving road congestion and improving safety through better traf c and incident management. Since 2006, MDOT has invested more than $100 mi...

  19. Long-term agricultural management maximizing hay production can significantly reduce belowground C storage

    Czech Academy of Sciences Publication Activity Database

    Sochorová, Lenka; Jansa, Jan; Verbruggen, E.; Hejcman, M.; Schellberg, J.; Kiers, E. T.; Johnson, N. C.

    2016-01-01

    Roč. 220, March (2016), s. 104-114 ISSN 0167-8809 R&D Projects: GA MŠk(CZ) LK11224 Institutional support: RVO:61388971 Keywords : Arbuscular mycorrhiza * Nitrogen * Phosphorus Subject RIV: EH - Ecology, Behaviour Impact factor: 4.099, year: 2016

  20. Clinical significance of reduced cerebral metabolism in multiple sclerosis. A combined PET and MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xiayan; Tanaka, Makoto; Kondo, Susumu; Okamoto, Koichi [Gunma Univ., Maebashi (Japan). School of Medicine; Hirai, Shunsaku

    1998-04-01

    Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease`s natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO{sub 2}). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman`s rank correlation coefficients. A general reduction in rCBF and rCMRO{sub 2} in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO{sub 2}. A correlation between the decrease in rCMRO{sub 2} and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information. (author)

  1. Clinical significance of reduced cerebral metabolism in multiple sclerosis. A combined PET and MRI study

    International Nuclear Information System (INIS)

    Sun, Xiayan; Tanaka, Makoto; Kondo, Susumu; Okamoto, Koichi; Hirai, Shunsaku

    1998-01-01

    Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease's natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO 2 ). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman's rank correlation coefficients. A general reduction in rCBF and rCMRO 2 in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO 2 . A correlation between the decrease in rCMRO 2 and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information. (author)

  2. Significance of increased and reduced proteasome activity in the pathomechanism of selected disorders

    Directory of Open Access Journals (Sweden)

    Marzena Tylicka

    2016-05-01

    Full Text Available Proteasomes are structures responsible for the elimination of damaged and misfolded proteins. Thus, they also regulate the most important intracellular processes. Changes in their functions can lead to many molecular diseases. There are two possible disorders in the function of proteasomes. Their increasing activity causes excessive degradation of important cell proteins. On the other hand, their insufficiency can inhibit the degradation of pathological proteins and lead to their accumulation.The increase of proteasome activity and the degradation of important proteins are observed in many pathological disorders. Therefore the study of pharmacological methods using proteasome inhibitors has gained growing interest in the last years. This review summarizes recent findings regarding the role of proteasomes in pathogenesis of selected diseases and discusses the potential use of proteasomes in diagnosis of different disorders.

  3. A method for risk-informed safety significance categorization using the analytic hierarchy process and bayesian belief networks

    International Nuclear Information System (INIS)

    Ha, Jun Su; Seong, Poong Hyun

    2004-01-01

    A risk-informed safety significance categorization (RISSC) is to categorize structures, systems, or components (SSCs) of a nuclear power plant (NPP) into two or more groups, according to their safety significance using both probabilistic and deterministic insights. In the conventional methods for the RISSC, the SSCs are quantitatively categorized according to their importance measures for the initial categorization. The final decisions (categorizations) of SSCs, however, are qualitatively made by an expert panel through discussions and adjustments of opinions by using the probabilistic insights compiled in the initial categorization process and combining the probabilistic insights with the deterministic insights. Therefore, owing to the qualitative and linear decision-making process, the conventional methods have the demerits as follows: (1) they are very costly in terms of time and labor, (2) it is not easy to reach the final decision, when the opinions of the experts are in conflict and (3) they have an overlapping process due to the linear paradigm (the categorization is performed twice - first, by the engineers who propose the method, and second, by the expert panel). In this work, a method for RISSC using the analytic hierarchy process (AHP) and bayesian belief networks (BBN) is proposed to overcome the demerits of the conventional methods and to effectively arrive at a final decision (or categorization). By using the AHP and BBN, the expert panel takes part in the early stage of the categorization (that is, the quantification process) and the safety significance based on both probabilistic and deterministic insights is quantified. According to that safety significance, SSCs are quantitatively categorized into three categories such as high safety significant category (Hi), potentially safety significant category (Po), or low safety significant category (Lo). The proposed method was applied to the components such as CC-V073, CV-V530, and SI-V644 in Ulchin Unit

  4. Reduced Rank Regression

    DEFF Research Database (Denmark)

    Johansen, Søren

    2008-01-01

    The reduced rank regression model is a multivariate regression model with a coefficient matrix with reduced rank. The reduced rank regression algorithm is an estimation procedure, which estimates the reduced rank regression model. It is related to canonical correlations and involves calculating...

  5. Prognostic significance of erythropoietin in pancreatic adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Thilo Welsch

    Full Text Available BACKGROUND: Erythropoietin (Epo administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC. METHODOLOGY: The clinico-pathological relevance of hemoglobin (Hb, n = 150, serum Epo (sEpo, n = 87 and tissue expression of Epo/Epo receptor (EpoR, n = 104 was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. RESULTS: Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05 and PDAC (p<0.001, reaching anemic grade in one third of patients. While inversely correlating to Hb (r = -0.46, 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99 but not in PDAC (O/P = 0.85. Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01--although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥ 16 mU/ml were not significantly different in M0 (20% and M1 (30% groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05. The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. CONCLUSION/SIGNIFICANCE: Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold

  6. Reduced Multiplication Modules

    Indian Academy of Sciences (India)

    for some ideal of . As defined for a commutative ring , an -module is said to be reduced if the intersection of prime submodules of is zero. The prime spectrum and minimal prime submodules of the reduced module are studied.

  7. Reduced multiplication modules

    Indian Academy of Sciences (India)

    for some ideal of . As defined for a commutative ring , an -module is said to be reduced if the intersection of prime submodules of is zero. The prime spectrum and minimal prime submodules of the reduced module are studied.

  8. Structural mode significance using INCA. [Interactive Controls Analysis computer program

    Science.gov (United States)

    Bauer, Frank H.; Downing, John P.; Thorpe, Christopher J.

    1990-01-01

    Structural finite element models are often too large to be used in the design and analysis of control systems. Model reduction techniques must be applied to reduce the structural model to manageable size. In the past, engineers either performed the model order reduction by hand or used distinct computer programs to retrieve the data, to perform the significance analysis and to reduce the order of the model. To expedite this process, the latest version of INCA has been expanded to include an interactive graphical structural mode significance and model order reduction capability.

  9. Rackspace: Significance of Cloud Computing to CERN

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    The research collaboration between Rackspace and CERN is contributing to how OpenStack cloud computing will move science work around the world for CERN, and to reducing the barriers between clouds for Rackspace.

  10. 23 CFR 630.1010 - Significant projects.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Significant projects. 630.1010 Section 630.1010 Highways... PRECONSTRUCTION PROCEDURES Work Zone Safety and Mobility § 630.1010 Significant projects. (a) A significant project is one that, alone or in combination with other concurrent projects nearby is anticipated to cause...

  11. 48 CFR 2110.7003 - Significant events.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Significant events. 2110..., AND OTHER PURCHASE DESCRIPTIONS Contract Specifications 2110.7003 Significant events. The contractor is required to inform the contracting officer of all significant events. ...

  12. Role and significance of total phenols during rooting of Protea ...

    African Journals Online (AJOL)

    The high total phenol content was associated with significantly higher rooting percentage and increased the number of roots formed. Blanching reduced the time needed for the cuttings to root sufficiently to be transplanted to the field by 30 days. Analyses of different parts of cuttings throughout the entire rooting period ...

  13. Reduced caloric intake during endotoxemia reduces arginine availability and metabolism.

    Science.gov (United States)

    Poeze, Martijn; Bruins, Maaike J; Luiking, Yvette C; Deutz, Nicolaas E

    2010-04-01

    Inadequate caloric intake increases the risk of sepsis-induced complications. Metabolic changes during sepsis indicate that the availability of the amino acid l-arginine decreases. Availability of arginine may further decrease during reduced caloric intake, which thereby limits the adaptive response of arginine-nitric oxide metabolism during sepsis. We tested the hypothesis that reduced caloric intake during endotoxemia, as an experimental model for sepsis, further reduces arginine availability. In a randomized trial, a 7-d reduced caloric intake feed regimen (RE; n = 9) was compared with a normal control feed regimen (CE; n = 9), before 24 h of endotoxemia, as a model for sepsis. Whole-body arginine-nitric oxide metabolism and protein metabolism were measured by using a stable-isotope infusion of [(15)N(2)]arginine, [(13)C-(2)H(2)]citrulline, [(2)H(5)]phenylalanine, and [(2)H(2)]tyrosine. Plasma pyruvate and lactate concentrations were determined by fully automated HPLC. Pre-endotoxin arginine appearance was significantly lower in the RE group than in the CE group (P = 0.002). During endotoxemia, arginine appearance increased in the CE animals but not in the RE animals (P = 0.04). In addition, nitric oxide production was significantly lower in the RE animals (P endotoxemia in the RE group than in the CE group (P endotoxemia but increased significantly during endotoxemia in the RE group (P = 0.04). A well-nourished condition before prolonged endotoxemia results in a better ability to adapt to endotoxin-induced metabolic deterioration of arginine-nitric oxide metabolism than does reduced caloric intake before endotoxemia.

  14. Reducing the impact.

    Science.gov (United States)

    Mahathir, M

    1997-01-01

    In Asia, attempts to control HIV/AIDS through education have not achieved the necessary behavior changes. This is especially true for young women who are unable to apply their knowledge to their sex behavior because of inequalities in gender relations. Thus, the impact of AIDS on women is significantly greater in settings where the status of women is low. Women in developing countries are at greatest risk because the epidemic is fueled by poverty, lack of information, and lack of autonomy. Prosperity in a developing country, such as Malaysia, entails its own risks because it creates new social norms and values that exist in tandem with debilitating old norms, such as the patriarchy that disempowers women and a resurgence in polygamy and wife abandonment. Subservient gender roles not only increase women's chances of infection, they also target women as the primary caregivers for infected individuals. Young girls may have to abandon school to care for infected parents, and female health care providers are assigned to the lowest ranks of the profession. While most women have been infected by their husbands, they must also bear the stigma of being considered immoral infectors of their husbands. The futures of AIDS widows and orphans is jeopardized by the discrimination that attends the disease, and if the mother dies, her young children face a higher death rate. In settings new to the epidemic, it is difficult to convince men of the importance of addressing women's needs and of seeking the input of women in policy and program development. Only by empowering both sexes to work together to protect society will there be a reasonable chance of reducing the impact of HIV/AIDS.

  15. Regionally Significant Ecological Areas - MLCCS derived 2008

    Data.gov (United States)

    Minnesota Department of Natural Resources — This is an analysis of regionally significant Terrestrial and Wetland Ecological Areas in the seven county metropolitan area. Individual forest, grassland and...

  16. Central Region Regionally Ecological Significant Areas

    Data.gov (United States)

    Minnesota Department of Natural Resources — This is an analysis of regionally significant Terrestrial and Wetland Ecological Areas in the seven county metropolitan area. Individual forest, grassland and...

  17. How do we make sense of significance?

    DEFF Research Database (Denmark)

    Lyhne, Ivar; Kørnøv, Lone

    2013-01-01

    Determination of significance is widely recognised as an important step in environmental assessment (EA) processes. The prescriptive literature and guidance on significance determination is comprehensive within the field of EA, whereas descriptive and explorative studies of how we go about making...... sense, or construct meaning, of actions to determine significance are few. This article makes use of sense-making theory to explore how sense-making among EA researchers and practitioners influence significance determination. Focus is on the situation when persons have their first look at information...

  18. Hypoxia: Exposure Time Until Significant Performance Effects

    Science.gov (United States)

    2016-03-07

    1994). Acute hypoxia fails to influence two aspects of short-term memory : implications for the source of cognitive deficits. Aviation, Space...Naval Medical Research Unit Dayton HYPOXIA : EXPOSURE TIME UNTIL SIGNIFICANT PERFORMANCE EFFECTS PHILLIPS, J.P., DRUMMOND, L.A...Andrews, CAPT, MSC, USN Commanding Officer i 1 ARTICLE TYPE: Research Article TITLE: Hypoxia : Exposure Time Until Significant Performance

  19. The Vernier Caliper and Significant Figures.

    Science.gov (United States)

    Oberhofer, E. S.

    1985-01-01

    Misconceptions occur because the caliper is often read with the same significant figures as a meter stick; however, the precision of the vernier caliper is greater than the precision of a meter stick. Clarification of scale reading, precision of both tools, and significant figures are discussed. (JN)

  20. Evolution of the Significant Figure Rules

    Science.gov (United States)

    Carter, Ashley R.

    2013-01-01

    Today, almost all introductory physics textbooks include standardized "rules" on how to find the number of significant figures in a calculated value. And yet, 30 years ago these rules were almost nonexistent. Why have we increased the role of significant figures in introductory classes, and should we continue this trend? A look back at…

  1. Prevalence Of Asymptomatic Significant Bacteriuria In Schoolgirls ...

    African Journals Online (AJOL)

    Enterococcus faecalis was found to be the predominant bacteria cause instead of Escherichia coli as reported in some literature. Girls in the age group 11 – 12 years had the highest prevalence of asymptomatic significant bacteriuria. Prevention of asymptomatic significant bacteriuria in schoolgirls rely on strict and proper ...

  2. The thresholds for statistical and clinical significance

    DEFF Research Database (Denmark)

    Jakobsen, Janus Christian; Gluud, Christian; Winkel, Per

    2014-01-01

    , assessment of intervention effects in randomised clinical trials deserves more rigour in order to become more valid. METHODS: Several methodologies for assessing the statistical and clinical significance of intervention effects in randomised clinical trials were considered. Balancing simplicity......BACKGROUND: Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does...... not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore...

  3. Reducing Pesticide Drift

    Science.gov (United States)

    Provides information about pesticide spray drift, including problems associated with drift, managing risks from drift and the voluntary Drift Reduction Technology program that seeks to reduce spray drift through improved spray equipment design.

  4. Determining Reduced Order Models for Optimal Stochastic Reduced Order Models

    Energy Technology Data Exchange (ETDEWEB)

    Bonney, Matthew S. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Brake, Matthew R.W. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2015-08-01

    The use of parameterized reduced order models(PROMs) within the stochastic reduced order model (SROM) framework is a logical progression for both methods. In this report, five different parameterized reduced order models are selected and critiqued against the other models along with truth model for the example of the Brake-Reuss beam. The models are: a Taylor series using finite difference, a proper orthogonal decomposition of the the output, a Craig-Bampton representation of the model, a method that uses Hyper-Dual numbers to determine the sensitivities, and a Meta-Model method that uses the Hyper-Dual results and constructs a polynomial curve to better represent the output data. The methods are compared against a parameter sweep and a distribution propagation where the first four statistical moments are used as a comparison. Each method produces very accurate results with the Craig-Bampton reduction having the least accurate results. The models are also compared based on time requirements for the evaluation of each model where the Meta- Model requires the least amount of time for computation by a significant amount. Each of the five models provided accurate results in a reasonable time frame. The determination of which model to use is dependent on the availability of the high-fidelity model and how many evaluations can be performed. Analysis of the output distribution is examined by using a large Monte-Carlo simulation along with a reduced simulation using Latin Hypercube and the stochastic reduced order model sampling technique. Both techniques produced accurate results. The stochastic reduced order modeling technique produced less error when compared to an exhaustive sampling for the majority of methods.

  5. REDUCED PROTECTIVE CLOTHING DETERMINATIONS

    International Nuclear Information System (INIS)

    BROWN, R.L.

    2003-01-01

    This technical basis document defines conditions where reduced protective clothing can be allowed, defines reduced protective clothing, and documents the regulatory review that determines the process is compliant with the Tank Farm Radiological Control Manual (TFRCM) and Title 10, Part 835, of the Code of Federal Regulations (10CFR835). The criteria, standards, and requirements contained in this document apply only to Tank Farm Contractor (TFC) facilities

  6. Physiological significance of ECL-cell histamine.

    OpenAIRE

    Andersson, K.; Chen, D.; Mattsson, H.; Sundler, F.; Håkanson, R.

    1998-01-01

    In the oxyntic mucosa of the mammalian stomach, histamine is stored in ECL cells and in mucosal mast cells. In the rat, at least 80 percent of oxyntic mucosal histamine resides in the ECL cells. Histamine is a key factor in the regulation of gastric acid secretion. Following depletion of ECL-cell histamine by treatment with alpha-fluoromethylhistidine (alpha-FMH), basal acid secretion was reduced, and gastrin-stimulated acid secretion was abolished. Vagally-induced acid secretion (by insulin ...

  7. Mining significant semantic locations from GPS data

    DEFF Research Database (Denmark)

    Cao, Xin; Cong, Gao; Jensen, Christian S.

    2010-01-01

    With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

  8. Discovering the Significance of Scientific Design Practice

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Baskerville, Richard

    2016-01-01

    This paper discusses and defines the achievement of significance in design science research. We review the values and processes of old-science and how this mode of science attacks the complexity of scientific knowledge production through analysis. We then explain how new-science attacks...... the complexity of scientific knowledge production through synthesis. The work argues that significance of the new-science contribution in design science can be obfuscated when wrapped in old-science. This understanding helps reveal how new-science, such as design science research, constitutes its significance...

  9. Mining Significant Semantic Locations from GPS Data

    DEFF Research Database (Denmark)

    Cao, Xin; Cong, Gao; Jensen, Christian Søndergaard

    2010-01-01

    With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

  10. SRS Process Facility Significance Fire Frequency

    International Nuclear Information System (INIS)

    Sarrack, A.G.

    1995-10-01

    This report documents the method and assumptions of a study performed to determine a site generic process facility significant fire initiator frequency and explains the proper way this value should be used

  11. IMPORTANCE AND CLINICAL SIGNIFICANCE OF SERUM SIALIC ...

    African Journals Online (AJOL)

    Open Access DOWNLOAD FULL TEXT Subscription or Fee Access. IMPORTANCE AND CLINICAL SIGNIFICANCE OF SERUM SIALIC ACID AND LACTATE DEHYDROGENASE DETERMINATION IN CERVICAL CANCER PATIENTS. Farouk H. Saber, Essam F. Hammouda, Mohamed Khaled M, Essam A. Afifi. Abstract.

  12. SRS Process Facility Significance Fire Frequency

    Energy Technology Data Exchange (ETDEWEB)

    Sarrack, A.G. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1995-10-01

    This report documents the method and assumptions of a study performed to determine a site generic process facility significant fire initiator frequency and explains the proper way this value should be used.

  13. Economically Significant Sites - OSPR [ds356

    Data.gov (United States)

    California Natural Resource Agency — This point data set shows locations of Economically Significant Sites along the California coast from Del Norte to San Diego counties. Data for locating these points...

  14. SIGWX Charts - High Level Significant Weather

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — High level significant weather (SIGWX) forecasts are provided for the en-route portion of international flights. NOAA's National Weather Service Aviation Center...

  15. Understanding cultural significance, the edible mushrooms case

    OpenAIRE

    Garibay-Orijel, Roberto; Caballero, Javier; Estrada-Torres, Arturo; Cifuentes, Joaqu?n

    2007-01-01

    Abstract Background Cultural significance is a keystone in quantitative ethnobiology, which offers the possibility to make inferences about traditional nomenclature systems, use, appropriation and valuing of natural resources. In the present work, using as model the traditional mycological knowledge of Zapotecs from Oaxaca, Mexico, we analyze the cultural significance of wild edible resources. Methods In 2003 we applied 95 questionnaires to a random sample of informants. With this data we int...

  16. Building stones can be of geoheritage significance

    Science.gov (United States)

    Brocx, Margaret; Semeniuk, Vic

    2017-04-01

    Building stones have generally been assigned values according to their cultural, aesthetic, and rarity significance, amongst other criteria, but they also may have geoheritage significance. This is akin to the geoheritage significance ascribed to minerals and fossils housed as ex situ specimens in museums. We proffer the notion that building stones can be of geoheritage value particularly where they comprise permanent buildings, they illustrate significant windows into the history of the Earth, and they can be visited as an ex situ museum locality (e.g., the "Blue Granite" of Iceland) for education as part of building-stone tours. For some rocks the quarries that supplied the building stone are no longer in existence and hence the building stones provide the only record of that type of material; for other rocks, the building stone may illustrate features in the lithology no longer present in the quarry itself (e.g., rare and large xenoliths). Building stones are particularly significant as they are often polished and manifest structures, fabrics, and textures not evident in outcrop. We illustrate here examples of building stone of geoheritage significance using Australian and International examples. Australian designated stones could include the "Sydney Sandstone" or "Victorian Bluestone". For international examples, there is the famous "Carrara Marble" in Italy and the widely known "Portland Limestone" from southern England, the latter having been utilized for St Pauls Cathedral in London and the UN building in New York City.

  17. Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome.

    Science.gov (United States)

    Yoon, Sung-Jae; Rahman, Md Saidur; Kwon, Woo-Sung; Park, Yoo-Jin; Pang, Myung-Geol

    2016-01-01

    Although cryopreservation has been developed and optimized over the past decades, it causes various stresses, including cold shock, osmotic stress, and ice crystal formation, thereby reducing fertility. During cryopreservation, addition of cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause damage to spermatozoa. To identify the effects of CPA addition during cryopreservation, we assessed the motility (%), motion kinematics, capacitation status, and viability of epididymal spermatozoa using computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the effects of CPA addition were also demonstrated at the proteome level using two-dimensional electrophoresis. Our results demonstrated that CPA addition significantly reduced sperm motility (%), curvilinear velocity, viability (%), and non-capacitated spermatozoa, whereas straightness and acrosome-reacted spermatozoa increased significantly (p 3 fold, p sperm cryopreservation.

  18. Vaccination-challenge studies with a Port Chalmers/73 (H3N2)-based swine influenza virus vaccine: Reflections on vaccine strain updates and on the vaccine potency test.

    Science.gov (United States)

    De Vleeschauwer, Annebel; Qiu, Yu; Van Reeth, Kristien

    2015-05-11

    The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu(®) and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0-7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998-2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test

  19. Discovering the Significance of Scientific Design Practice

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Baskerville, Richard

    This paper aims at discussing and defining what it is that makes design science research significant. First it reviews the values and processes of old science and how this attacks complexity through analysis. It then shows how new science attacks complexity through synthesis. Then the paper argues...... that new science is burdened and limited in realizing its potential when cloaking itself in old science wrappers. This point is then demonstrated by two cases. The paper discusses how new science constitutes its significance. This discussion translates an old science framework of theory significance uses...... the same two cases to illustrate the framework. The paper ultimately aims to provide a better groundwork on which design science research can realize its fundamental potential as new science....

  20. Statistical significance of cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    Smith Andrew D

    2007-01-01

    Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

  1. Tank closure reducing grout

    Energy Technology Data Exchange (ETDEWEB)

    Caldwell, T.B.

    1997-04-18

    A reducing grout has been developed for closing high level waste tanks at the Savannah River Site in Aiken, South Carolina. The grout has a low redox potential, which minimizes the mobility of Sr{sup 90}, the radionuclide with the highest dose potential after closure. The grout also has a high pH which reduces the solubility of the plutonium isotopes. The grout has a high compressive strength and low permeability, which enhances its ability to limit the migration of contaminants after closure. The grout was designed and tested by Construction Technology Laboratories, Inc. Placement methods were developed by the Savannah River Site personnel.

  2. Tank closure reducing grout

    International Nuclear Information System (INIS)

    Caldwell, T.B.

    1997-01-01

    A reducing grout has been developed for closing high level waste tanks at the Savannah River Site in Aiken, South Carolina. The grout has a low redox potential, which minimizes the mobility of Sr 90 , the radionuclide with the highest dose potential after closure. The grout also has a high pH which reduces the solubility of the plutonium isotopes. The grout has a high compressive strength and low permeability, which enhances its ability to limit the migration of contaminants after closure. The grout was designed and tested by Construction Technology Laboratories, Inc. Placement methods were developed by the Savannah River Site personnel

  3. Formal conditions for the significance-effect

    DEFF Research Database (Denmark)

    Thellefsen, Torkild Leo; Sørensen, Bent; Thellefsen, Martin

    2006-01-01

    The significance-effect is the right effect of meaning caused upon an interpreting mind. The right effect is understood as the right interpretation of an intended meaning caused by a sign communicated by an utterer. In the article, which is inspired by Charles S. Peirce's doctrine of signs, his...

  4. Soil physicochemical properties and their significance for ...

    African Journals Online (AJOL)

    Soil physicochemical properties and their significance for sustainable sugarcane production in Kesem Allaideghe plains irrigation project area, Eastern Ethiopia. ... In order to improve soil structure and water availability, addition of gypsum, plant residues and organic matter are recommended. Keywords: Soil survey ...

  5. Chemical and Biological Significance of Naturally Occurring ...

    African Journals Online (AJOL)

    PROF HORSFALL

    Chemical and Biological Significance of Naturally Occurring Additives on. African Black Soap and its Performance. IKOTUN, A. ... attribute of the soap includes gentleness on the skin, rich lather, protection against skin disorders ... soap, the effects of its modifications with some commonly used natural products, as well as the ...

  6. Formal conditions for the significance-effect

    DEFF Research Database (Denmark)

    Thellefsen, Torkild Leo; Sørensen, Bent; Thellefsen, Martin

    2006-01-01

    The significance-effect is the right effect of meaning caused upon an interpreting mind. The right effect is understood as the right interpretation of an intended meaning caused by a sign communicated by an utterer. In the article, which is inspired by Charles S. Peirce's doctrine of signs, his s...

  7. Hemodynamic significance of internal carotid artery disease

    DEFF Research Database (Denmark)

    Schroeder, T

    1988-01-01

    a significant improvement in baseline flow occur. Flow reserve determined by cerebral vasodilation, however, will improve in most patients with hemodynamic failure. In addition, some patients in the low-pressure group develop marked, but temporary, hyperperfusion after reconstruction of very high grade carotid...

  8. The Historical Significance of the Universal Declaration.

    Science.gov (United States)

    Eide, Asbjorn

    1998-01-01

    Explains the historical significance of the Universal Declaration of Human Rights. Focuses on the initiative for the Declaration and its elaboration, the precursors to modern human rights, the foundation of the Declaration, the rights contained in the Universal Declaration, three modes of human rights analysis, and global governance and human…

  9. Petrochemistry and geotectonic significance of enderbite ...

    African Journals Online (AJOL)

    Petrochemistry and geotectonic significance of enderbite-charnockite association in the Pan-African Obudu plateau, southeastern Nigeria. VU Ukaegbu, FT Beka. Abstract. No Abstract. Journal of Mining and Geology Vol. 43 (1) 2007: pp. 1-14. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT ...

  10. Surface characterization based upon significant topographic features

    Energy Technology Data Exchange (ETDEWEB)

    Blanc, J; Grime, D; Blateyron, F, E-mail: fblateyron@digitalsurf.fr [Digital Surf, 16 rue Lavoisier, F-25000 Besancon (France)

    2011-08-19

    Watershed segmentation and Wolf pruning, as defined in ISO 25178-2, allow the detection of significant features on surfaces and their characterization in terms of dimension, area, volume, curvature, shape or morphology. These new tools provide a robust way to specify functional surfaces.

  11. Significant Bacteriuria in Pregnancy in Enugu, Nigeria ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence, demographic characteristics and microbiological assessment of the causative agents of significant bacteriuria in healthy pregnant women and its effect on pregnancy in women in Enugu, Eastern Nigeria. Materials and Methods: A prospective study based on data obtained from ...

  12. Bullying in Academe: Prevalent, Significant, and Incessant

    Science.gov (United States)

    Cassell, Macgorine A.

    2011-01-01

    This paper examines the top-down perspective of bullying and mobbing of professors by analyzing why it is prevalent, significant, and incessant and then proposes a framework to produce a caring, respectful, and safe environment for professors to engage in their teaching, scholarship, and service. The author suggests that the failure of…

  13. Surface characterization based upon significant topographic features

    International Nuclear Information System (INIS)

    Blanc, J; Grime, D; Blateyron, F

    2011-01-01

    Watershed segmentation and Wolf pruning, as defined in ISO 25178-2, allow the detection of significant features on surfaces and their characterization in terms of dimension, area, volume, curvature, shape or morphology. These new tools provide a robust way to specify functional surfaces.

  14. The Policy Significance of Inequality Decompositions

    OpenAIRE

    Kanbur, Ravi

    2003-01-01

    Economists are now familiar with “between” and “within” group inequality decompositions, for race, gender, spatial units, etc. But what exactly is the normative significance of the empirical results produced by these decompositions? This paper raises some basic questions about policy interpretations of decompositions that are found in the literature.

  15. 7 CFR 3015.93 - Significant developments.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER, DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE REGULATIONS Monitoring and Reporting Program Performance § 3015.93 Significant developments. Events may occur between the scheduled performance reporting dates...

  16. Significant improvement of electrochemical performance of Cu ...

    Indian Academy of Sciences (India)

    Significant improvement of electrochemical performance of Cu-coated LiVPO4F cathode material for lithium-ion batteries ... School of Mechanical Engineering and Automation, Northeastern University, Shenyang 110819, China; School of Mechanical Engineering, Shenyang University of Chemical Technology, Shenyang ...

  17. The Significance of the Nursery School

    Science.gov (United States)

    Gesell, Arnold

    2017-01-01

    From the standpoint of mental health and perhaps even from the standpoint of human culture, the complete realization of the educational possibilities of the preschool child is of foundational significance. Normative and comparative studies performed at a psychological clinic at Yale examining norms of development in children from one month to five…

  18. Cystic echinococcosis: prevalence and economic significance in ...

    African Journals Online (AJOL)

    A cross-sectional study was conducted from November 2015 to April 2016 at ELFORA export abattoir to determine the prevalence, cyst viability, organ distribution and economic significance of small ruminant cystic echinococcosis. A total of 850 small ruminants (400 sheep and 450 goats), were examined for the presence of ...

  19. 32 CFR 651.39 - Significance.

    Science.gov (United States)

    2010-07-01

    ... existing pollution standards; cause water, air, noise, soil, or underground pollution; impair visibility... Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) ENVIRONMENTAL QUALITY ENVIRONMENTAL ANALYSIS OF ARMY ACTIONS (AR 200-2) Environmental Assessment § 651.39 Significance. (a) If the...

  20. Significance of Assimilation and Fractional Crystallization (AFC ...

    Indian Academy of Sciences (India)

    57

    andesites of the Chhotaudepur area plot close to a consistent mixing trend between typical mantle composition ... Deccan tholeiites and alkaline felsic rocks also exhibit a significant trend of crustal contamination. .... Keeping the rate of assimilation to fractional crystallization (r) as 0.3, the binary plotting was carried out and.

  1. Changing relationships with significant others: Reflections of ...

    African Journals Online (AJOL)

    Symbolic interactionism provides the framework for analysing the building of relationships between elite athletes and their significant others. In-depth interviews were conducted with elite throwers and decathlon athletes. The sample included current (n=15) and retired (n=5) student-athletes, parents (n=5), coaches (n=2) ...

  2. Significant Workplace Change: Perspectives of Survivors

    Science.gov (United States)

    Kohut, Ann Marie

    2010-01-01

    The ever-increasing pace of workplace change is well documented in the literature, yet little is known about how an individual adapts to significant change in the workplace. Continuous learning is key to successful adaptation; however, are employees' adaptation to change influenced by their approaches to learning? The purpose of this study was to…

  3. Mycotoxins: significance to global economics and health

    Science.gov (United States)

    Mycotoxins are fungal metabolites produced my micro-fungi (molds and mildews) that have significant impacts on global economics and health. Some of these metabolites are beneficial, but most are harmful and have been associated with well-known epidemics dating back to medieval times. The terms ‘myco...

  4. Scope and Significance of Eating Disorders.

    Science.gov (United States)

    Mitchell, James E.; Eckert, Elke D.

    1987-01-01

    Describes the increasing prevalence of anorexia nervosa and bulimia in many industrialized societies, and their association with significant morbidity and mortality. Discusses the genetic risks for the development of anorexia nervosa, and treatment strategies. Of these, pharmacotherapy and psychotherapy, particularly those incorporating…

  5. Significance of Literature in Foreign Language Teaching

    Science.gov (United States)

    Babaee, Ruzbeh; Yahya, Wan Roselezam Bt Wan

    2014-01-01

    This research aims to consider literature as a significant tool for teaching fundamental language skills including speaking, listening, reading and writing. Reasons for the use of literature in language classrooms and major factors for choosing appropriate kinds of literary texts in such classes should be highlighted in order to make readers aware…

  6. Reduced multiplication modules

    Indian Academy of Sciences (India)

    if M is a von Neumann regular module (VNM); i.e., every principal submodule of M is a summand submodule. Also if M is an injective R-module, then M is a VNM. Keywords. Multiplication module; reduced module; minimal prime submodule;. Zariski topology; extremally disconnected. 1. Introduction. In this paper all rings are ...

  7. with glutathione reduced (GSH)

    Indian Academy of Sciences (India)

    Unknown

    try involving 4f–4f transitions on Nd(III) and glutathione reduced (GSH) in the absence and presence of. Zn(II) have been carried out in aquated ... transition spectra of Pr(III) with lysozyme by using energy interaction parameters to ... DMF and dioxane of A/R grade from Qualigens. The absorption spectra were recorded on a ...

  8. Reduced Braginskii equations

    Energy Technology Data Exchange (ETDEWEB)

    Yagi, M. [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment; Horton, W. [Texas Univ., Austin, TX (United States). Inst. for Fusion Studies

    1993-11-01

    A set of reduced Braginskii equations is derived without assuming flute ordering and the Boussinesq approximation. These model equations conserve the physical energy. It is crucial at finite {beta} that we solve the perpendicular component of Ohm`s law to conserve the physical energy while ensuring the relation {del} {center_dot} j = 0.

  9. Reduced Braginskii equations

    International Nuclear Information System (INIS)

    Yagi, M.; Horton, W.

    1993-11-01

    A set of reduced Braginskii equations is derived without assuming flute ordering and the Boussinesq approximation. These model equations conserve the physical energy. It is crucial at finite β that we solve the perpendicular component of Ohm's law to conserve the physical energy while ensuring the relation ∇ · j = 0

  10. Variational quantum algorithms with significantly fewer measurements

    Science.gov (United States)

    Babbush, Ryan; McClean, Jarrod; Ding, Nan; Wiebe, Nathan; Boixo, Sergio; Neven, Hartmut

    Variational quantum algorithms provide an approach for using near-term quantum hardware to model diverse physical systems. Systems of interacting fermions, e.g. most materials and chemical reactions, are natural targets due to classical intractability at small sizes and the scientific value of solutions. However, recent work has cast doubt on the viability of chemistry applications due to an extremely large number of measurements that may be required. We overcome this problem by developing strategies which reduce the required measurements by orders of magnitude. Our approach involves an adaptive Bayesian model, simultaneous operator measurement, careful selection of basis functions and insights from N-representability theory. Most improvements are obtained by upper-bounding the required resources and then transforming the problem representation in a fashion that minimizes those upper-bounds. Our results suggest that even for some classically intractable molecules, energies can be measured to chemical precision using existing technology.

  11. Significant growth in. LED use predicted.

    Science.gov (United States)

    Simpson, Mike

    2012-03-01

    Although LED lighting has its critics, a number of whom (see article 'LED--panacea or marketing hype', HEJ--February 2012) are concerned about what they claim are some manufacturers' 'exaggerated claims' about lighting efficiency and lamp lifetime, Philips Lighting believes that, such are the advances being made in this innovative lighting technology, that LED's overall share of the European lighting market will have risen from around 7% in 2008 to 25% by 2020 and that, a decade later, it will account for a remarkable 75% of lighting sales. In the UK, Philips' technical and design director for Lighting, Mike Simpson, told HEJ editor, Jonathan Baillie, healthcare estates and facilities managers are increasingly recognising the potential to save energy, reduce carbon emissions, and cut maintenance costs, using LED.

  12. Understanding cultural significance, the edible mushrooms case.

    Science.gov (United States)

    Garibay-Orijel, Roberto; Caballero, Javier; Estrada-Torres, Arturo; Cifuentes, Joaquín

    2007-01-11

    Cultural significance is a keystone in quantitative ethnobiology, which offers the possibility to make inferences about traditional nomenclature systems, use, appropriation and valuing of natural resources. In the present work, using as model the traditional mycological knowledge of Zapotecs from Oaxaca, Mexico, we analyze the cultural significance of wild edible resources. In 2003 we applied 95 questionnaires to a random sample of informants. With this data we integrated the Edible Mushroom Cultural Significance Index. This index included eight variables: frequency of mention, perceived abundance, use frequency, taste, multifunctional food use, knowledge transmission, health and economy. Data were analyzed in an inductive perspective using ordination and grouping techniques to reveal the behavior of species in a cultural multivariate dimension. In each variable the species had different conducts. Cantharellus cibarius s.l. was the species with most frequency of mention. Pleurotus sp. had the highest perceived abundance. C. cibarius s.l. was the most frequently consumed species. Gomphus clavatus was the most palatable species and also ranked highest in the multifunctional food index. Cortinarius secc. Malacii sp. had the highest traditional importance. Only Tricholoma magnivelare was identified as a health enhancer. It also had the most economic importance. According to the compound index, C. cibarius s.l., the Amanita caesarea complex, Ramaria spp. and Neolentinus lepideus were the mushrooms with highest cultural significance. Multivariate analysis showed that interviewees identify three main groups of mushrooms: species with high traditional values, frequent consumption and known by the majority; species that are less known, infrequently consumed and without salient characteristics; and species with low traditional values, with high economic value and health enhancers. The compound index divided the cultural significance into several cultural domains and showed

  13. Understanding cultural significance, the edible mushrooms case

    Directory of Open Access Journals (Sweden)

    Cifuentes Joaquín

    2007-01-01

    Full Text Available Abstract Background Cultural significance is a keystone in quantitative ethnobiology, which offers the possibility to make inferences about traditional nomenclature systems, use, appropriation and valuing of natural resources. In the present work, using as model the traditional mycological knowledge of Zapotecs from Oaxaca, Mexico, we analyze the cultural significance of wild edible resources. Methods In 2003 we applied 95 questionnaires to a random sample of informants. With this data we integrated the Edible Mushroom Cultural Significance Index. This index included eight variables: frequency of mention, perceived abundance, use frequency, taste, multifunctional food use, knowledge transmission, health and economy. Data were analyzed in an inductive perspective using ordination and grouping techniques to reveal the behavior of species in a cultural multivariate dimension. Results In each variable the species had different conducts. Cantharellus cibarius s.l. was the species with most frequency of mention. Pleurotus sp. had the highest perceived abundance. C. cibarius s.l. was the most frequently consumed species. Gomphus clavatus was the most palatable species and also ranked highest in the multifunctional food index. Cortinarius secc.Malacii sp. had the highest traditional importance. Only Tricholoma magnivelare was identified as a health enhancer. It also had the most economic importance. According to the compound index, C. cibarius s.l., the Amanita caesarea complex, Ramaria spp. and Neolentinus lepideus were the mushrooms with highest cultural significance. Multivariate analysis showed that interviewees identify three main groups of mushrooms: species with high traditional values, frequent consumption and known by the majority; species that are less known, infrequently consumed and without salient characteristics; and species with low traditional values, with high economic value and health enhancers. Conclusion The compound index divided

  14. Significant incidents in nuclear fuel cycle facilities

    International Nuclear Information System (INIS)

    1996-03-01

    In contrast to nuclear power plants, events in nuclear fuel cycle facilities are not well documented. The INES database covers all the nuclear fuel cycle facilities; however, it was developed in the early 1990s and does not contain information on events prior to that. The purpose of the present report is to collect significant events and analyze them in order to give a safety related overview of nuclear fuel cycle facilities. Significant incidents were selected using the following criteria: release of radioactive material or exposure to radiation; degradation of items important to safety; and deficiencies in design, quality assurance, etc. which include criticality incidents, fire, explosion, radioactive release and contamination. This report includes an explanation, where possible, of root causes, lessons learned and action taken. 4 refs, 4 tabs

  15. Cross wavelet analysis: significance testing and pitfalls

    Directory of Open Access Journals (Sweden)

    D. Maraun

    2004-01-01

    Full Text Available In this paper, we present a detailed evaluation of cross wavelet analysis of bivariate time series. We develop a statistical test for zero wavelet coherency based on Monte Carlo simulations. If at least one of the two processes considered is Gaussian white noise, an approximative formula for the critical value can be utilized. In a second part, typical pitfalls of wavelet cross spectra and wavelet coherency are discussed. The wavelet cross spectrum appears to be not suitable for significance testing the interrelation between two processes. Instead, one should rather apply wavelet coherency. Furthermore we investigate problems due to multiple testing. Based on these results, we show that coherency between ENSO and NAO is an artefact for most of the time from 1900 to 1995. However, during a distinct period from around 1920 to 1940, significant coherency between the two phenomena occurs.

  16. Early memories: Clinical relevance and significance.

    Science.gov (United States)

    van der Watt, Gillian; Coall, David; Sng, Adelln; Janca, Aleksandar

    2016-02-01

    The purpose of this research was to examine earliest memories in patients with a mental disorder and their clinical relevance to diagnosis and treatment. A semi-structured early memory questionnaire was developed and 50 patients with anxiety, depression or a psychotic disorder were interviewed. A thematic analysis was conducted to extract dominant themes from the qualitative data. Family events, play, and receiving attention were dominant themes of pleasant memories, while unpleasant memories consisted of fear-provoking situations, abuse/violence, and death-related themes. Participants were able to recall the feelings they had experienced at the time of their earliest memories and most participants stated that their first memories had significant impact in their lives. The findings of this exploratory study suggest that earliest memories may be of clinical significance for diagnostic and therapeutic interventions in psychiatry. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  17. Practical significance of the difference in means

    Directory of Open Access Journals (Sweden)

    H. S. Steyn (JR.

    2000-06-01

    Full Text Available It is shown how the standardised difference (the effect size between two population means can be used to establish significance when the populations are observed in totality. When dealing with two samples methods are given to determine the practical importance of a statistically significant difference. The usual effect size formula is adapted to deal with cases where populations have different standard deviations. Opsomming Dit word aangetoon hoe die gestandaardiseerde verskil (die effekgrootte tussen twee populasiegemiddeldes gebruik kan word om beduidenheid t.o.v. volledig waargenome populasies te bepaal. In die geval van twee steekproewe word metodes gegee om die praktiese belangrikheid van 'n statistiese beduidende verskil vas te stel. Die gewone effekgrootte formule word aangepas ten einde gevalle waar populasies verskillende standaardafwykings het te hanteer.

  18. Obesity and Onset of Significant Depressive symptoms

    Science.gov (United States)

    Vogelzangs, Nicole; Kritchevsky, Stephen B; Beekman, Aartjan TF; Brenes, Gretchen A; Newman, Anne B; Satterfield, Suzanne; Yaffe, Kristine; Harris, Tamara B; Penninx, Brenda WJH

    2012-01-01

    Objective Although several cross-sectional studies have linked obesity and depression, less is known about their longitudinal association and about the relative influence of obesity subtypes. We prospectively examined whether (abdominal) obesity increased the risk of onset of depression in a population-based sample of older persons. Method Participants were 2540 non-depressed well-functioning white and black persons, aged 70–79 years, enrolled in the Health ABC Study, an ongoing prospective community-based cohort study. Overall obesity was assessed by body mass index and percent body fat (measured by dual energy x-ray absorptiometry), whereas abdominal obesity measures included waist circumference, sagittal diameter, and visceral fat (measured by computer tomography). Onset of significant depressive symptoms was defined as a Center for Epidemiological Studies Depression 10-item score ≥ 10 at any annual follow-up over 5 years and/or new antidepressant medication use. Persistent depression was defined as depression at two consecutive follow-up visits. Results Over 5 years, significant depressive symptoms emerged in 23.7% of initially non-depressed persons. In men, both overall (BMI: HR per SD increase=1.20, 95%CI=1.03–1.40) and abdominal obesity (visceral fat: HR per SD increase=1.19, 95%CI=1.07–1.33) predicted onset of depressive symptoms after adjustment for sociodemographics. When BMI and visceral fat were adjusted for each other, only visceral fat was significantly associated with depression onset (HR=1.18, 95%CI=1.04–1.34). Stronger associations were found for persistent depressive symptoms. No associations were found in women. Conclusion This study shows that obesity, in particular visceral fat, increases the risk of onset of significant depressive symptoms in men. These results suggest that specific mechanisms might relate visceral fat to the onset of depression. PMID:20021992

  19. EXPLORE SIGNIFICANT FACTORS TO AFFECT CUSTOMER INVOLVEMENT

    OpenAIRE

    Yu-Jia Hu

    2012-01-01

    Although literature review supported the concept that customer loyalty, brand equity and perceived risk are significant factors to affect customer involvement, very limited studies have extensively examined the relationship among those variables. This research applied quantitative study to comprehensively explore the relationship between customer loyalty, brand equity, perceived risk and customer involvement for consumers. The population for this research was identified as consumers having th...

  20. Prevalence of significant bacteriuria among symptomatic and ...

    African Journals Online (AJOL)

    Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 16.0 (SPSS, Inc., Chicago, Ill). Results: A total of 100 consenting participants were recruited into the study. The mean age was: 23.42 ± 8.31 years and a range of 14‑50 years. Only 9% (9/100) had significant bacteriuria while 44.4% (4/9) ...

  1. Significance and radioimmunoassay of gastric inhibitory polypeptide

    International Nuclear Information System (INIS)

    Zheng Ping; Zeng Minde; Yuan Jimin

    1995-01-01

    We have established the GIP Radioimmunoassay which has high sensitivity and specificity by labelling with iodogen and purified with HPLC. Using this method, the plasma GIP level was measured in 64 cases of which there are 10 normal individuals, 25 cases of diabetes and 29 cases of liver cirrhosis . The results showed that the plasma GIP level was significantly increased in patients with liver cirrhosis and correlated to degree of glucose tolerance damage

  2. Significance of postoperative irradiation for breast cancer

    International Nuclear Information System (INIS)

    Murai, Nobuko; Ogami, Koji; Nishikawa, Kiyoshi; Koga, Kenji; Waki, Norio; Higashi, Hidefumi; Hayashi, Asami; Shibata, Koichiro; Watanabe, Katsuji

    1986-01-01

    From 1978 through 1983, 27 patients were treated with surgery followed by irradiation (irradiated group) and 29 with surery alone (non-irradiated group). In the irradiated group, 10 had stage II and 17 stage III; in the non-irradiated group, 25 had stage II and 4 stage III. The most common histology was medullary tubular carcinoma (MTC). There was no significant difference in survivals at 3 years and 5 years between the groups. Similarly, no significant difference was seen among stage II patients. Patients with MTC tended to have worse survivals in the irradiated group than in the non-irradiated group, with no statistically significant difference. Among stage II patients, no major differences in local recurrence were seen between the groups; the incidence of distant metastases tended to be high in the irradiated group. The incidence of both local recurrence and distant metastases for stage III patients showed a tendency to be higher in the irradiated group than in the non-irradiated group. The results indicated no apparent benifit of postoperative irradiation for breast cancer. A randomized clinical trial is needed for the evaluation of postoperative irradiation for breast cancer. (Namekawa, K.)

  3. Reducing teenage pregnancy.

    Science.gov (United States)

    Fallon, Debbie

    2011-03-01

    The Teenage Pregnancy Independent Advisory Group (TPIAG) was established in 2000 to advise the government about reducing teenage pregnancy rates and supporting teenage parents to continue with their education. The group reached the end of its tenure in December 2010. This short article highlights some of the key issues from the final report and provides some insights into past achievements and future directions from an interview with Gill Frances, TPIAG's chair.

  4. Reducing Employment Insecurity

    Directory of Open Access Journals (Sweden)

    Florence Lebert

    2016-10-01

    Full Text Available The perception of job insecurity is known to be a stressful condition for employees. Less is known about employment insecurity and the ways employees and their families deal with it. This study investigates whether participation in further training is a strategy that employees adopt to reduce perceived employment insecurity. As participation in further training is often costly and time-consuming, we assume that the family context is of importance for the decision to take part in further training. To take account of possible self-selection, we apply a propensity score matching procedure on longitudinal data from the Swiss Household Panel (2004-2013. Three main findings can be emphasized: first, participation in further training is not a strategy adopted particularly by employees who perceive high employment insecurity as they are less likely to train than their secure counterparts. Second, even though further training is not a strategy that is actively adopted, employees who train subsequently report lower levels of perceived employment insecurity. Third, the family context indeed influences the likelihood to train: partnered employees are more likely to train and preschool-aged children act as a constraint on women’s but enhance men’s participation in further training. Yet, in the context of high perceived employment insecurity, children generally reduce their parents’ likelihood to train as the parents may turn to other strategies that reduce perceived employment insecurity.

  5. Significance of wood extractives for wood bonding.

    Science.gov (United States)

    Roffael, Edmone

    2016-02-01

    Wood contains primary extractives, which are present in all woods, and secondary extractives, which are confined in certain wood species. Extractives in wood play a major role in wood-bonding processes, as they can contribute to or determine the bonding relevant properties of wood such as acidity and wettability. Therefore, extractives play an immanent role in bonding of wood chips and wood fibres with common synthetic adhesives such as urea-formaldehyde-resins (UF-resins) and phenol-formaldehyde-resins (PF-resins). Extractives of high acidity accelerate the curing of acid curing UF-resins and decelerate bonding with alkaline hardening PF-resins. Water-soluble extractives like free sugars are detrimental for bonding of wood with cement. Polyphenolic extractives (tannins) can be used as a binder in the wood-based industry. Additionally, extractives in wood can react with formaldehyde and reduce the formaldehyde emission of wood-based panels. Moreover, some wood extractives are volatile organic compounds (VOC) and insofar also relevant to the emission of VOC from wood and wood-based panels.

  6. [Significance and technique of autologous chondrocyte transplantation].

    Science.gov (United States)

    Fritz, J; Gaissmaier, C; Schewe, B; Weise, K

    2005-08-01

    The bad risk for an early onset of osteoarthritis in the knee increases with the size of a cartilage defect. A collateral meniscus- or ligament-tear will enforce this hazard in addition. In order to avoid such a development, relevant full-thickness cartilage defects should be reconstructed biologically and attendant meniscus- or ligament-tears as well as varus- or valgus deformities should be treated. A number of studies, including some prospective-randomized trials, have shown that autologous chondrocyte transplantation (ACT) is the most reliable procedure for a surgical treatment of full-thickness cartilage defects larger than 4 cm (2) in adults. One disadvantage of ACT is the extensive approach to the joint and often a hypertrophy of the repair tissue. To solve these problems, some different biomaterials for a matrix-assisted ACT have been developed. The scaffold we use has a covering membrane upside and a collagen-sponge carrying the chondrocytes. By means of special surgical instruments a minimally invasive implantation is possible, reducing the side-effects of an extensive approach. Animal studies showed the regeneration of a hyaline cartilage using our described system. However, results of current clinical studies with the different scaffolds must be awaited before an universal application of matrix-assisted ACT can be recommended.

  7. Medial fracture line significance in calcaneus fracture.

    Science.gov (United States)

    Ogut, Tahir; Ayhan, Egemen; Kantarci, Fatih; Unlu, Mehmet C; Salih, Muhammet

    2011-01-01

    In Sanders' classification of calcaneus fractures, the medial fracture line (subtype C) is close to the tarsal canal, which contains an artery for the talus and calcaneus. We hypothesized that because of this brittle vascular localization, patients with C line fracture patterns might describe radiologic subtalar arthritis more often and have more complaints. The purpose of the present study was to compare the results of C line fracture patterns with other types of calcaneus fractures. A total of 25 surgically treated feet were involved. Regarding Sanders' classification, group 1 included fractures involving the C line (11 feet), and group 2 included fractures not involving the C line (14 feet). Patient age at admission, trauma date, and interval until surgery were obtained from the patients' medical records. The Bohler angles were determined from the radiographs. At the last follow-up visit, the radiologist graded subtalar arthritis using computed tomography. For clinical follow-up, the American Orthopaedic Foot and Ankle Society and Maryland scores were assessed. No significant differences were found in mean age, follow-up period, delay to surgery, or postoperative Bohler angle between the 2 groups. The mean preoperative Bohler angle was significantly low for group 1. Although not significantly different, the mean American Orthopaedic Foot and Ankle Society and Maryland scores were lower for group 1 (81.9 and 84.3) than group 2 (87.8 and 92.0), and the median subtalar arthritis grade was greater for group 1 (score 2) than for group 2 (score 1.5). The worse results with C line fracture patterns despite satisfactory reduction might result from sinus tarsi artery damage. Angiographic investigations could clarify this theory in the future. Consequently, surgeons must inform and should hesitate to operate on patients with these highly comminuted C line calcaneus fractures. Copyright © 2011 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All

  8. Os odontoideum: a significant radiographic finding

    International Nuclear Information System (INIS)

    Choit, Rachel L.; Reilly, Christopher W.; Jamieson, Douglas H.

    2005-01-01

    Os odontoideum can lead to instability of the atlantoaxial joint and places the spinal cord at significant risk for acute catastrophic events after minor trauma or chronic neurological change. We present two cases of os odontoideum in pediatric patients that were not appreciated at earlier remote imaging but were, in retrospect, detectable. One patient presented with an acute spinal cord injury. Incorporating assessment of dens integrity into the evaluation algorithm for all pediatric cervical spine studies should lead to early detection of os odontoideum lesions and allow referral to appropriate clinical spinal services for evaluation, surveillance and possible surgery to prevent future complications. (orig.)

  9. Os odontoideum: a significant radiographic finding

    Energy Technology Data Exchange (ETDEWEB)

    Choit, Rachel L.; Reilly, Christopher W. [BC Children' s Hospital, Department of Orthopaedics, Vancouver, BC (Canada); Jamieson, Douglas H. [BC Children' s Hospital, Department of Radiology, Vancouver (Canada)

    2005-08-01

    Os odontoideum can lead to instability of the atlantoaxial joint and places the spinal cord at significant risk for acute catastrophic events after minor trauma or chronic neurological change. We present two cases of os odontoideum in pediatric patients that were not appreciated at earlier remote imaging but were, in retrospect, detectable. One patient presented with an acute spinal cord injury. Incorporating assessment of dens integrity into the evaluation algorithm for all pediatric cervical spine studies should lead to early detection of os odontoideum lesions and allow referral to appropriate clinical spinal services for evaluation, surveillance and possible surgery to prevent future complications. (orig.)

  10. Detecting significant changes in protein abundance

    Directory of Open Access Journals (Sweden)

    Kai Kammers

    2015-06-01

    Full Text Available We review and demonstrate how an empirical Bayes method, shrinking a protein's sample variance towards a pooled estimate, leads to far more powerful and stable inference to detect significant changes in protein abundance compared to ordinary t-tests. Using examples from isobaric mass labelled proteomic experiments we show how to analyze data from multiple experiments simultaneously, and discuss the effects of missing data on the inference. We also present easy to use open source software for normalization of mass spectrometry data and inference based on moderated test statistics.

  11. Non-destructive testing: significant facts

    International Nuclear Information System (INIS)

    Espejo, Hector; Ruch, Marta C.

    2006-01-01

    In the last fifty years different organisations, both public and private, have been assigned to the mission of introducing into the country the most relevant aspects of the modern technological discipline 'Non Destructive Testing' (NDT) through a manifold of activities, such as training and education, research, development, technical assistance and services, personnel qualification/certification and standardisation. A review is given of the significant facts in this process, in which the Argentine Atomic Energy Commission, CNEA, played a leading part, a balance of the accomplishments is made and a forecast of the future of the activity is sketched. (author) [es

  12. Class I Area Significant Impact Levels

    Science.gov (United States)

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  13. Assessing the significance of Heidegger's Black Notebooks

    Directory of Open Access Journals (Sweden)

    J. Malpas

    2018-03-01

    Full Text Available The publication of Heidegger's Black Notebooks (Schwarze Hefte has provoked a storm of controversy. Much of this has centred on the pro-Nazi and anti-Semitic comments the volumes contain. But these aspects of the Notebooks are perhaps the least surprising and important. This essay offers a summary overview of the issues to which the Notebooks give rise, at the same time as it also aims to provide a preliminary assessment of their overall significance, especially in relation to what they show about the nature and development of Heidegger's thinking from the early 1930s to the late 1940s.

  14. Significant exposures to isoeugenol derivatives in perfumes

    DEFF Research Database (Denmark)

    Rastogi, S.C.; Johansen, Jeanne Duus

    2008-01-01

    in perfumes/aftershaves. Materials and Methods: 29 international brand perfumes/aftershaves were analysed for the target fragrance ingredient by gas chromatography-mass spectrometery. All samples were analysed in duplicate at detection levels of 1-5 p.p.m. Results: 16 products (55%) contained isoeugenol...... was not detected in any of the investigated products. Conclusions: Isoeugenyl acetate is present in perfumes/aftershaves, in some products in significant amounts. This may lead to elicitation of contact allergy in isoeugenol-sensitized individuals and may contribute to unchanged levels of isoeugenol sensitization...

  15. Significance and popularity in music production.

    Science.gov (United States)

    Monechi, Bernardo; Gravino, Pietro; Servedio, Vito D P; Tria, Francesca; Loreto, Vittorio

    2017-07-01

    Creative industries constantly strive for fame and popularity. Though highly desirable, popularity is not the only achievement artistic creations might ever acquire. Leaving a longstanding mark in the global production and influencing future works is an even more important achievement, usually acknowledged by experts and scholars. 'Significant' or 'influential' works are not always well known to the public or have sometimes been long forgotten by the vast majority. In this paper, we focus on the duality between what is successful and what is significant in the musical context. To this end, we consider a user-generated set of tags collected through an online music platform, whose evolving co-occurrence network mirrors the growing conceptual space underlying music production. We define a set of general metrics aiming at characterizing music albums throughout history, and their relationships with the overall musical production. We show how these metrics allow to classify albums according to their current popularity or their belonging to expert-made lists of important albums. In this way, we provide the scientific community and the public at large with quantitative tools to tell apart popular albums from culturally or aesthetically relevant artworks. The generality of the methodology presented here lends itself to be used in all those fields where innovation and creativity are in play.

  16. Sonographic ally Detected Architectural Distortion: Clinical Significance

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Shin Kee; Seo, Bo Kyoung; Yi, Ann; Cha, Sang Hoon; Kim, Baek Hyun; Cho, Kyu Ran; Kim, Young Sik; Son, Gil Soo; Kim, Young Soo; Kim, Hee Young [Korea University Ansan Hospital, Ansan (Korea, Republic of)

    2008-12-15

    Architectural distortion is a suspicious abnormality for the diagnosis of breast cancer. The aim of this study was to investigate the clinical significance of sonographic ally detected architectural distortion. From January 2006 to June 2008, 20 patients were identified who had sonographic ally detected architectural distortions without a history of trauma or surgery and abnormal mammographic findings related to an architectural distortion. All of the lesions were pathologically verified. We evaluated the clinical and pathological findings and then assessed the clinical significance of the sonographic ally detected architectural distortions. Based on the clinical findings, one (5%) of the 20 patients had a palpable lump and the remaining 19 patients had no symptoms. No patient had a family history of breast cancer. Based on the pathological findings, three (15%) patients had malignancies. The malignant lesions included invasive ductal carcinomas (n = 2) and ductal carcinoma in situ (n = 1). Four (20%) patients had high-risk lesions: atypical ductal hyperplasia (n = 3) and lobular carcinoma in situ (n = 1). The remaining 13 (65%) patients had benign lesions, however, seven (35%) out of 13 patients had mild-risk lesions (three intraductal papillomas, three moderate or florid epithelial hyperplasia and one sclerosing adenosis). Of the sonographic ally detected architectural distortions, 35% were breast cancers or high-risk lesions and 35% were mild-risk lesions. Thus, a biopsy might be needed for an architectural distortion without an associated mass as depicted on breast ultrasound, even though the mammographic findings are normal

  17. Could patients' coughing have communicative significance?

    Science.gov (United States)

    Bailey, Julia V

    2008-01-01

    Medical discourse positions patients with coughs and colds negatively, so consulting health services with 'minor' respiratory illness is therefore more accountable than for other medical problems. Patients face dilemmas since they must persuade doctors of the doctorability of their illness without being seen as hypochondriacal, and they risk losing face if doctors decide that there is nothing much wrong. It is known that the placement of non-lexical features of talk such as laughing or crying can have interactional meaning. Using a data set of video-recorded doctor-patient cough and cold consultations, this study explores whether patients' coughing could have communicative significance. The study is a qualitative analysis of 33 consultations drawing on a constructionist, sociolinguistic analytic approach. Coughing is co-ordinated with talk rather than occurring randomly. Coughing helps patients to demonstrate the doctorability of their symptoms and to legitimize their claims for medical attention. Coughing is also associated with resistance to 'no problem' diagnoses, resulting in changes in the trajectory of talk (for example, soliciting more explanation from doctors and/or re-negotiation of doctors' investigation or treatment plans). Coughing is undoubtedly a manifestation of respiratory illness, but also has communicative significance in consultations for coughs and colds.

  18. Microscopic fungi as significant sesquiterpene emission sources

    Science.gov (United States)

    HorváTh, Eszter; Hoffer, AndráS.; SebőK, Flóra; Dobolyi, Csaba; Szoboszlay, SáNdor; Kriszt, BaláZs; GelencséR, AndráS.

    2011-08-01

    Among the volatile organic compounds emitted by vegetation, isoprene, monoterpenes, sesquiterpenes, and their derivatives are thought to contribute to secondary organic aerosol formation. Although it is well known that microscopic fungi globally turn over vast amount of carbon by decomposing the organic matter in the soil, vegetation is considered as the exclusive source of biogenic secondary organic aerosol precursors in various atmospheric models. Secondary fungal metabolites including sesquiterpenes have been recognized as characteristic volatile organic compounds emitted by fungi. In the present study, we investigated the rates of sesquiterpene emission of microscopic fungi to establish their potential significance compared to those from vegetation. To sample the headspace of the pure culture of some common fungi, we used an aseptic flow-through apparatus designed for solid phase microextraction in our laboratory. The identified sesquiterpenes in the headspace extracts were quantified for eight strains of microscopic fungi belonging to four different genera. Our results showed that microscopic fungi emit a considerable amount of sesquiterpenes. Based on our first estimations microscopic fungi may be considered as potentially significant sesquiterpene emission sources whose contribution to secondary organic aerosol formation may be comparable to that of vegetation.

  19. Significance and popularity in music production

    Science.gov (United States)

    Monechi, Bernardo; Gravino, Pietro; Servedio, Vito D. P.; Tria, Francesca; Loreto, Vittorio

    2017-07-01

    Creative industries constantly strive for fame and popularity. Though highly desirable, popularity is not the only achievement artistic creations might ever acquire. Leaving a longstanding mark in the global production and influencing future works is an even more important achievement, usually acknowledged by experts and scholars. `Significant' or `influential' works are not always well known to the public or have sometimes been long forgotten by the vast majority. In this paper, we focus on the duality between what is successful and what is significant in the musical context. To this end, we consider a user-generated set of tags collected through an online music platform, whose evolving co-occurrence network mirrors the growing conceptual space underlying music production. We define a set of general metrics aiming at characterizing music albums throughout history, and their relationships with the overall musical production. We show how these metrics allow to classify albums according to their current popularity or their belonging to expert-made lists of important albums. In this way, we provide the scientific community and the public at large with quantitative tools to tell apart popular albums from culturally or aesthetically relevant artworks. The generality of the methodology presented here lends itself to be used in all those fields where innovation and creativity are in play.

  20. Sonographic ally Detected Architectural Distortion: Clinical Significance

    International Nuclear Information System (INIS)

    Kim, Shin Kee; Seo, Bo Kyoung; Yi, Ann; Cha, Sang Hoon; Kim, Baek Hyun; Cho, Kyu Ran; Kim, Young Sik; Son, Gil Soo; Kim, Young Soo; Kim, Hee Young

    2008-01-01

    Architectural distortion is a suspicious abnormality for the diagnosis of breast cancer. The aim of this study was to investigate the clinical significance of sonographic ally detected architectural distortion. From January 2006 to June 2008, 20 patients were identified who had sonographic ally detected architectural distortions without a history of trauma or surgery and abnormal mammographic findings related to an architectural distortion. All of the lesions were pathologically verified. We evaluated the clinical and pathological findings and then assessed the clinical significance of the sonographic ally detected architectural distortions. Based on the clinical findings, one (5%) of the 20 patients had a palpable lump and the remaining 19 patients had no symptoms. No patient had a family history of breast cancer. Based on the pathological findings, three (15%) patients had malignancies. The malignant lesions included invasive ductal carcinomas (n = 2) and ductal carcinoma in situ (n = 1). Four (20%) patients had high-risk lesions: atypical ductal hyperplasia (n = 3) and lobular carcinoma in situ (n = 1). The remaining 13 (65%) patients had benign lesions, however, seven (35%) out of 13 patients had mild-risk lesions (three intraductal papillomas, three moderate or florid epithelial hyperplasia and one sclerosing adenosis). Of the sonographic ally detected architectural distortions, 35% were breast cancers or high-risk lesions and 35% were mild-risk lesions. Thus, a biopsy might be needed for an architectural distortion without an associated mass as depicted on breast ultrasound, even though the mammographic findings are normal

  1. Pharmacotherapy to reduce arrhythmic mortality

    Directory of Open Access Journals (Sweden)

    Amit Vora

    2014-01-01

    Full Text Available Fatal ventricular arrhythmias and heart failure are the common modes of death in patients with cardiovascular diseases. Intracardiac defibrillator (ICD implantation reduces arrhythmic mortality to a significant extent in the high risk patient. However, there continues to be a need for effective drug therapy to reduce the arrhythmic and overall mortality in patients with or without an ICD. Although anti-arrhythmic drugs (AAD appear inferior to ICD, the role of beta-blockers and to an extent amiodarone along with non AAD like angiotensin converting enzyme inhibitors (ACE-I, mineralocorticoid blockers (MRB and HMG-CoA reductase inhibitors (statins need to be emphasized. There have been many drug trials and meta-analysis to this effect and we review the role of drugs especially in their ability to reduce arrhythmic mortality and sudden cardiac death (SCD. The focus is on post myocardial infarction (MI and heart failure patients with a brief overview of role of drugs in channelopathies.

  2. Significant determinants of mouse pain behaviour.

    Directory of Open Access Journals (Sweden)

    Michael S Minett

    Full Text Available Transgenic mouse behavioural analysis has furthered our understanding of the molecular and cellular mechanisms underlying damage sensing and pain. However, it is not unusual for conflicting data on the pain phenotypes of knockout mice to be generated by reputable groups. Here we focus on some technical aspects of measuring mouse pain behaviour that are often overlooked, which may help explain discrepancies in the pain literature. We examined touch perception using von Frey hairs and mechanical pain thresholds using the Randall-Selitto test. Thermal pain thresholds were measured using the Hargreaves apparatus and a thermal place preference test. Sodium channel Nav1.7 knockout mice show a mechanical deficit in the hairy skin, but not the paw, whilst shaving the abdominal hair abolished this phenotype. Nav1.7, Nav1.8 and Nav1.9 knockout mice show deficits in noxious mechanosensation in the tail, but not the paw. TRPA1 knockout mice, however, have a loss of noxious mechanosensation in the paw but not the tail. Studies of heat and cold sensitivity also show variability depending on the intensity of the stimulus. Deleting Nav1.7, Nav1.8 or Nav1.9 in Nav1.8-positive sensory neurons attenuates responses to slow noxious heat ramps, whilst responses to fast noxious heat ramps are only reduced when Nav1.7 is lost in large diameter sensory neurons. Deleting Nav1.7 from all sensory neurons attenuates responses to noxious cooling but not extreme cold. Finally, circadian rhythms dramatically influence behavioural outcome measures such as von Frey responses, which change by 80% over the day. These observations demonstrate that fully characterising the phenotype of a transgenic mouse strain requires a range of behavioural pain models. Failure to conduct behavioural tests at different anatomical locations, stimulus intensities, and at different points in the circadian cycle may lead to a pain behavioural phenotype being misinterpreted, or missed altogether.

  3. Arcuate foramen and its clinical significance

    International Nuclear Information System (INIS)

    Cakmark, O.; Gurdal, E.; Cavdar, S.; Ekinci, G.; Yildiz, E.

    2005-01-01

    The present study determines the degree of ossification of the posterior atlanto-occipital membrane in dry bone, plane lateral cervical spine radiographs and computer tomography (CT). The average length, width and the area of the arcuate foramen were measured on dry bone and on cervical CT. Further, age, gender and complaints of the patients of shoulder and arm pain, neck pain, headache, vertigo, and lacrimation in relation to the presence of bony complete or incomplete arcuate foramen were evaluated. From February 2004 to January 2005 60 dry atlases were obtained from the Anatomy Department, University of Marmara, Istanbul, Turkey and 416 lateral cervical spine radiographs were obtained from the Radiology department for neurological and orthopedic evaluations. Each complete arcuate foramen was calculated with the aid of Clemex Vision PE demo version computer program. Among the 60 dry atlases examined 7 (11.7%) had complete and 2 (3.3 %) had incomplete bony bridge formation. Of the 416 plane lateral cervical spine radiographs examined, 30 (7.2%) had complete and 26 (6.25%) had incomplete bony bridge formation. Of the 30 complete arcuate foramen 24 (80%) were females and 6 (20%) were males. The frequency of having a complete arcuate foramen in females was 8.45%, and in males it was 4.55%. Further, of the 26 incomplete arcuate foramen 20 (76.9%) were females and 6 (23.1%) were males. The frequency of having an incomplete arcuate foramen in females was 7%, and in males was 4.55%. The statistical evaluations showed that patients with complete arcuate foramen had significant complaints of shoulder-arm pain (p=0.0072), neck pain (p=0.0072) and vertigo (p=0.0598) compared to patients with incomplete arcuate foramen. The patients with complete arcuate foramen had a headache ratio of 12:30 and this ratio was 2:26 in patients with incomplete arcuate foramen and the difference between complete and incomplete arcuate foramen was statistically significant (p=0.0062). Further

  4. Significance of high level test data in piping design

    International Nuclear Information System (INIS)

    McLean, J.L.; Bitner, J.L.

    1991-01-01

    During the 1980's the piping technical community in the U.S. initiated a series of research activities aimed at reducing the conservatism inherent in nuclear piping design. One of these activities was directed at the application of the ASME Code rules to the design of piping subjected to dynamic loads. This paper surveys the test data obtained from three groups in the U.S. and none in the U.K., and correlates the findings as they relate to the failure modes of piping subjected to seismic loads. The failure modes experienced as the result of testing at dynamic loads significantly in excess of anticipated loads specified for any of the ASME Code service levels are discussed. A recommendation is presented for modifying the Code piping rules to reduce the conservatism inherent in seismic design

  5. THRESHOLD OF SIGNIFICANCE IN STRESS MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Elena RUSE

    2015-12-01

    Full Text Available Stress management is the individual's ability to handle any situation, external conditions, to match the demands of the external environment. The researchers revealed several stages in the stress response. A first phase was called ‘‘alert reaction'' or ‘‘immediate reaction to stress‘‘, phase in which there are physiological modifications and manifestations that occur under psychological aspect. Adaptation phase is the phase in which the reactions from the first phase diminishes or disappears. Exhaustion phase is related to the diversity of stress factors and time and may exceed the resources of the human body to adapt. Influencing factors may be: limited, cognitive, perceptual, and a priori. But there is a threshold of significance in stress management. Once the reaction to external stimuli occurs, awareness is needed. The capability effect occurs, any side effect goes away and comes out the ''I AM'' effect.

  6. Significance and potential benefits of the CTBT

    International Nuclear Information System (INIS)

    Sato, M.

    1999-01-01

    This presentation is based on the Treaty stipulation on international cooperation: 'The States parties undertake to promote cooperation among themselves to facilitate and participate in the fullest possible exchange relating to technologies used in the verification of the Non-proliferation Treaty in order to enable States to strengthen national implementation of verification measures; and to enable States to benefit from the application of such technologies for peaceful purposes'. Political significance of the Treaty and the potential benefits of participating in the CTBT regime are exposed. It is concluded that international cooperation under the CTBT regime is an element in broadening Treaty support and participation, thereby contributing to an early establishment and the efficient operation of the Treaty verification regime. The PTS will assist the States Signatories to facilitate and promote cooperation among themselves in the fullest exchange of information relating to verification-related technologies so that they may benefit from participation in the Treaty regime

  7. Immune senescence: significance of the stromal microenvironment

    Science.gov (United States)

    Masters, A. R.; Haynes, L.; Su, D.‐M.

    2016-01-01

    Summary The immune system undergoes age‐associated changes known as immunosenescence, resulting in increased susceptibility to infections, cancers and autoimmunity in the aged. The basis of our understanding of immunosenescence has been derived primarily from studies examining intrinsic defects within many of the cells of the immune system. While these studies have provided insight into the mechanisms of immunosenescence, a picture is now emerging that the stromal microenvironment within lymphoid organs also contributes significantly to the age‐associated decline of immune function. These extrinsic defects appear to impact the functional activity of immune cells and may offer a potential target to recover immune activity. Indeed, rejuvenation studies which have targeted the stromal niche have restored immune function in aged successfully, highlighting the impact of the microenvironment towards the aetiology of immunosenescence. PMID:27529161

  8. The insignificance of statistical significance testing

    Science.gov (United States)

    Johnson, Douglas H.

    1999-01-01

    Despite their use in scientific journals such as The Journal of Wildlife Management, statistical hypothesis tests add very little value to the products of research. Indeed, they frequently confuse the interpretation of data. This paper describes how statistical hypothesis tests are often viewed, and then contrasts that interpretation with the correct one. I discuss the arbitrariness of P-values, conclusions that the null hypothesis is true, power analysis, and distinctions between statistical and biological significance. Statistical hypothesis testing, in which the null hypothesis about the properties of a population is almost always known a priori to be false, is contrasted with scientific hypothesis testing, which examines a credible null hypothesis about phenomena in nature. More meaningful alternatives are briefly outlined, including estimation and confidence intervals for determining the importance of factors, decision theory for guiding actions in the face of uncertainty, and Bayesian approaches to hypothesis testing and other statistical practices.

  9. Boiling significantly promotes photodegradation of perfluorooctane sulfonate.

    Science.gov (United States)

    Lyu, Xian-Jin; Li, Wen-Wei; Lam, Paul K S; Yu, Han-Qing

    2015-11-01

    The application of photochemical processes for perfluorooctane sulfonate (PFOS) degradation has been limited by a low treatment efficiency. This study reports a significant acceleration of PFOS photodegradation under boiling condition compared with the non-boiling control. The PFOS decomposition rate increased with the increasing boiling intensity, but declined at a higher hydronium level or under oxygenation. These results suggest that the boiling state of solution resulted in higher effective concentrations of reactants at the gas-liquid interface and enhanced the interfacial mass transfer, thereby accelerating the PFOS decomposition. This study broadens our knowledge of PFOS photodegradation process and may have implications for development of efficient photodegradation technologies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Swiss solar power statistics 2007 - Significant expansion

    International Nuclear Information System (INIS)

    Hostettler, T.

    2008-01-01

    This article presents and discusses the 2007 statistics for solar power in Switzerland. A significant number of new installations is noted as is the high production figures from newer installations. The basics behind the compilation of the Swiss solar power statistics are briefly reviewed and an overview for the period 1989 to 2007 is presented which includes figures on the number of photovoltaic plant in service and installed peak power. Typical production figures in kilowatt-hours (kWh) per installed kilowatt-peak power (kWp) are presented and discussed for installations of various sizes. Increased production after inverter replacement in older installations is noted. Finally, the general political situation in Switzerland as far as solar power is concerned are briefly discussed as are international developments.

  11. Urban building recognition during significant temporal variations

    DEFF Research Database (Denmark)

    Nguyen, Phuong Giang; Andersen, Hans Jørgen

    2008-01-01

    In literature, existing researches on building recognition mainly concentrate on scales, rotations, and viewpoints variance. In urban environment, large temporal variations of weather and lighting conditions should also be considered as major challenges for robust recognition. For instances......, there are differences between images captured during daytime and nighttime, especially significant changes in building appearances between seasons because of the differences in light setting. To date, these large temporal variation issues have not been fully investigated. In this paper, we therefore focus...... on constructing a system that deals with the temporal difference factors in recognizing urban buildings. In order to build such a system, two main criteria are raised, namely the efficiency of the recognition algorithm and the speed for interactive search purpose. For recognition purpose, we exploit the MOPS...

  12. Risk control and the minimum significant risk

    International Nuclear Information System (INIS)

    Seiler, F.A.; Alvarez, J.L.

    1996-01-01

    Risk management implies that the risk manager can, by his actions, exercise at least a modicum of control over the risk in question. In the terminology of control theory, a management action is a control signal imposed as feedback on the system to bring about a desired change in the state of the system. In the terminology of risk management, an action is taken to bring a predicted risk to lower values. Even if it is assumed that the management action taken is 100% effective and that the projected risk reduction is infinitely well known, there is a lower limit to the desired effects that can be achieved. It is based on the fact that all risks, such as the incidence of cancer, exhibit a degree of variability due to a number of extraneous factors such as age at exposure, sex, location, and some lifestyle parameters such as smoking or the consumption of alcohol. If the control signal is much smaller than the variability of the risk, the signal is lost in the noise and control is lost. This defines a minimum controllable risk based on the variability of the risk over the population considered. This quantity is the counterpart of the minimum significant risk which is defined by the uncertainties of the risk model. Both the minimum controllable risk and the minimum significant risk are evaluated for radiation carcinogenesis and are shown to be of the same order of magnitude. For a realistic management action, the assumptions of perfectly effective action and perfect model prediction made above have to be dropped, resulting in an effective minimum controllable risk which is determined by both risk limits. Any action below that effective limit is futile, but it is also unethical due to the ethical requirement of doing more good than harm. Finally, some implications of the effective minimum controllable risk on the use of the ALARA principle and on the evaluation of remedial action goals are presented

  13. Quantifying the clinical significance of cannabis withdrawal.

    Directory of Open Access Journals (Sweden)

    David J Allsop

    Full Text Available Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV. This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt.A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p=0.0001. Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p=0.03. Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p=0.001.Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.

  14. Quantifying the Clinical Significance of Cannabis Withdrawal

    Science.gov (United States)

    Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

    2012-01-01

    Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

  15. [Clinical significance of nausea in migraine].

    Science.gov (United States)

    Serousova, O V; Karpova, M I; Dolgushina, A I; Vasilenko, A F; Markova, V V; Altman, D S

    2017-01-01

    To study the prevalence and intensity of nausea in pain, prodromal and postdromal phases of migraine paroxysm, and in between the paroxysms in migraine patients, depending on the type of migraine paroxysm and frequency of pain days, and to evaluate an effect of nausea on the course of migraine. One hundred and four patients with migraine, aged from 18 to 60 years, were examined. The intensity of nausea was evaluated by a 5-point verbal analogue scale, and its intensity in between the paroxysms by the Gastrointestinal Symptom Rating Scale. All of the patients underwent a complex examination of the gastrointestinal tract. Paroxysms with accompanying nausea were found in 90% patients. Acute nausea was associated with older age, earlier onset and longer experience of migraine. In a group of patients with acute nausea, the frequency and intensity of migraine paroxysms, probability of reoccuring pain in the first day and the severity of social disability were higher. Development of nausea in between the paroxysms and its intensity was significantly higher in patients with high intensity of nausea in migraine paroxysms. Nausea in the prodrome was significantly associated with migraine without aura and chronicity of the disorder. Patients with nausea in the prodrome also had a longer painful phase and more severe social disability. No relationship between organic diseases of the digestive tract and nausea was found. Nausea can have its own pathological mechanisms not related to concomitant diseases of the digestive tract that should be taken into account in therapeutic interventions aimed at improving quality of life of the patients.

  16. Reducing natural disaster vulnerability

    Science.gov (United States)

    Zielinski, Sarah

    2006-04-01

    Because poor countries are vulnerable to the impact of natural disasters, the U.K. Department for International Development (DFID) launched on 30 March a new policy to better integrate natural disaster risk reduction into development and humanitarian activities. Gareth Thomas, U.K. development minister, said, ``There is nothing we can do to stop hurricanes, tsunamis, and earthquakes from striking. But what we can do is help put simple measures in place, such as better built houses, schools, and hospitals alongside more high-tech early warning systems to reduce the loss of life.''

  17. Advances in Significance Testing for Cluster Detection

    Science.gov (United States)

    Coleman, Deidra Andrea

    Over the past two decades, much attention has been given to data driven project goals such as the Human Genome Project and the development of syndromic surveillance systems. A major component of these types of projects is analyzing the abundance of data. Detecting clusters within the data can be beneficial as it can lead to the identification of specified sequences of DNA nucleotides that are related to important biological functions or the locations of epidemics such as disease outbreaks or bioterrorism attacks. Cluster detection techniques require efficient and accurate hypothesis testing procedures. In this dissertation, we improve upon the hypothesis testing procedures for cluster detection by enhancing distributional theory and providing an alternative method for spatial cluster detection using syndromic surveillance data. In Chapter 2, we provide an efficient method to compute the exact distribution of the number and coverage of h-clumps of a collection of words. This method involves defining a Markov chain using a minimal deterministic automaton to reduce the number of states needed for computation. We allow words of the collection to contain other words of the collection making the method more general. We use our method to compute the distributions of the number and coverage of h-clumps in the Chi motif of H. influenza.. In Chapter 3, we provide an efficient algorithm to compute the exact distribution of multiple window discrete scan statistics for higher-order, multi-state Markovian sequences. This algorithm involves defining a Markov chain to efficiently keep track of probabilities needed to compute p-values of the statistic. We use our algorithm to identify cases where the available approximation does not perform well. We also use our algorithm to detect unusual clusters of made free throw shots by National Basketball Association players during the 2009-2010 regular season. In Chapter 4, we give a procedure to detect outbreaks using syndromic

  18. The significance of protein intake and catabolism.

    Science.gov (United States)

    Flanigan, M J; Lim, V S; Redlin, J

    1995-10-01

    Diet and nutrition are integral to the management of individuals with renal disease. Uremia engenders anorexia, nausea, meat aversion, and emesis, disturbances that ultimately reduce appetite and cause weight loss and malnutrition. Protein restriction can alleviate these uremic symptoms and improve patient health and vigor, but overly zealous protein restriction may, itself, produce malnutrition. This is particularly likely when energy intake is restricted by either design or anorexia. End-stage renal disease patients require renal replacement therapy for survival, and although dialysis is life sustaining, it neither replaces normal kidney function nor obviates the need for dietary management. In this setting of controlled, persistent uremia, undernutrition can develop surreptitiously. Dialysis physicians have long regarded malnutrition as a sign of uncontrolled uremia and failing health. This supposition has now been validated by epidemiologic studies demonstrating that serum albumin and protein catabolic rate (PCR) discriminate between dialysis patients at high and low risk of death or illness. This correlation of undernutrition with health and survival persists across wide ranges of age, medical diagnoses, and dialysis prescriptions. Because PCR is readily measured using urea kinetic analyses, it has been promoted as a patient monitoring tool and under steady-state conditions it is a reliable method of determining protein intake. Although a single PCR measurement does not integrate day-to-day dietary and metabolic fluctuations and contains an inherent uncertainty of +/- 20%, sequential measurements can be used to assess changes in an individual's dietary protein intake. PCR defines nitrogen losses and, when normalized to a realistic index of metabolic activity (metabolically active body size), it can disclose subtle individual variances in nitrogen utilization. These normalized protein catabolic rates (NPCR) do not, however, measure or describe overall nutrition

  19. Clinically significant drug interactions with newer antidepressants.

    Science.gov (United States)

    Spina, Edoardo; Trifirò, Gianluca; Caraci, Filippo

    2012-01-01

    After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone. In general, by virtue of a more selective mechanism of action and receptor profile, newer antidepressants carry a relatively low risk for pharmacodynamic drug interactions, at least as compared with first-generation antidepressants, i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). On the other hand, they are susceptible to pharmacokinetic drug interactions. All new antidepressants are extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes, and therefore may be the target of metabolically based drug interactions. Concomitant administration of inhibitors or inducers of the CYP isoenzymes involved in the biotransformation of specific antidepressants may cause changes in their plasma concentrations. However, due to their relatively wide margin of safety, the consequences of such kinetic modifications are usually not clinically relevant. Conversely, some newer antidepressants may cause pharmacokinetic interactions through their ability to inhibit specific CYPs. With regard to this, duloxetine and bupropion are moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactions may occur when they are coadministered with substrates of these isoforms, especially compounds with a narrow therapeutic index. The other new antidepressants are only weak inhibitors or are not inhibitors of CYP isoforms at

  20. Assessing statistical significance in causal graphs.

    Science.gov (United States)

    Chindelevitch, Leonid; Loh, Po-Ru; Enayetallah, Ahmed; Berger, Bonnie; Ziemek, Daniel

    2012-02-20

    Causal graphs are an increasingly popular tool for the analysis of biological datasets. In particular, signed causal graphs--directed graphs whose edges additionally have a sign denoting upregulation or downregulation--can be used to model regulatory networks within a cell. Such models allow prediction of downstream effects of regulation of biological entities; conversely, they also enable inference of causative agents behind observed expression changes. However, due to their complex nature, signed causal graph models present special challenges with respect to assessing statistical significance. In this paper we frame and solve two fundamental computational problems that arise in practice when computing appropriate null distributions for hypothesis testing. First, we show how to compute a p-value for agreement between observed and model-predicted classifications of gene transcripts as upregulated, downregulated, or neither. Specifically, how likely are the classifications to agree to the same extent under the null distribution of the observed classification being randomized? This problem, which we call "Ternary Dot Product Distribution" owing to its mathematical form, can be viewed as a generalization of Fisher's exact test to ternary variables. We present two computationally efficient algorithms for computing the Ternary Dot Product Distribution and investigate its combinatorial structure analytically and numerically to establish computational complexity bounds.Second, we develop an algorithm for efficiently performing random sampling of causal graphs. This enables p-value computation under a different, equally important null distribution obtained by randomizing the graph topology but keeping fixed its basic structure: connectedness and the positive and negative in- and out-degrees of each vertex. We provide an algorithm for sampling a graph from this distribution uniformly at random. We also highlight theoretical challenges unique to signed causal graphs

  1. Significant exposures to isoeugenol derivatives in perfumes.

    Science.gov (United States)

    Rastogi, Suresh Chandra; Johansen, Jeanne Duus

    2008-05-01

    Isoeugenol, an important fragrance allergen in consumers, has been restricted to 200 p.p.m. since 1998 according to guidelines issued by the fragrance industry. However, no decline in contact allergy to isoeugnol has been detected. It has been speculated that isoeugenol derivatives, especially isoeugenyl acetate, are used instead. Isoeugenyl acetate is probably metabolized in the skin to isoeugenol and gives positive patch test reactions in 1/3 of isoeugenol-sensitized individuals. To investigate the content of isoeugenol, isoeugenyl acetate, and two isoeugenol ethers in perfumes/aftershaves. 29 international brand perfumes/aftershaves were analysed for the target fragrance ingredient by gas chromatography-mass spectrometry. All samples were analysed in duplicate at detection levels of 1-5 p.p.m. 16 products (55%) contained isoeugenol. The maximum concentration was 202 p.p.m. 10 products (34%) contained isoeugenyl acetate, which in 9 cases occurred together with isoeugenol. The concentrations of isoeugenyl acetate ranged from 20 to 4689 p.p.m. 13 products (44%) contained 64.9-1755.0 p.p.m. isoeugenyl methyl ether. Isoeugenyl benzyl ether was not detected in any of the investigated products. Isoeugenyl acetate is present in perfumes/aftershaves, in some products in significant amounts. This may lead to elicitation of contact allergy in isoeugenol-sensitized individuals and may contribute to unchanged levels of isoeugenol sensitization.

  2. The measure and significance of Bateman's principles.

    Science.gov (United States)

    Collet, Julie M; Dean, Rebecca F; Worley, Kirsty; Richardson, David S; Pizzari, Tommaso

    2014-05-07

    Bateman's principles explain sex roles and sexual dimorphism through sex-specific variance in mating success, reproductive success and their relationships within sexes (Bateman gradients). Empirical tests of these principles, however, have come under intense scrutiny. Here, we experimentally show that in replicate groups of red junglefowl, Gallus gallus, mating and reproductive successes were more variable in males than in females, resulting in a steeper male Bateman gradient, consistent with Bateman's principles. However, we use novel quantitative techniques to reveal that current methods typically overestimate Bateman's principles because they (i) infer mating success indirectly from offspring parentage, and thus miss matings that fail to result in fertilization, and (ii) measure Bateman gradients through the univariate regression of reproductive over mating success, without considering the substantial influence of other components of male reproductive success, namely female fecundity and paternity share. We also find a significant female Bateman gradient but show that this likely emerges as spurious consequences of male preference for fecund females, emphasizing the need for experimental approaches to establish the causal relationship between reproductive and mating success. While providing qualitative support for Bateman's principles, our study demonstrates how current approaches can generate a misleading view of sex differences and roles.

  3. CT diagnostic significance of tuboovarian abscess

    International Nuclear Information System (INIS)

    Du Tieqiao; Dong Jie; Xu Quanying; An Haiqin; Sang Chunyu

    2006-01-01

    Objective: To analyze computed tomographic (CT) imaging features of tuboovarian abscess as well as to discuss CT diagnostic significance. Methods: Ten patients with tuboovarian abscess were performed CT enhancing scans. Results: Ten patients manifested thick-walled, cystic-solid complex adnexal mass and indistinct margins on CT imaging. Internal thick septations and layered enhancement of the mass border on CT contrast images were common. Associated findings of CT included thickening of' the uterosacral ligaments in 9 of 10 patients, increased attenuation of the presacral and perirectal fat secondary to edema in 9 patients, serpiginous structure corresponding to a dilated, pus-filled fallopian tube in 6 patients and fluid-filled within uterine cavity in 4 patients. On CT scans, the inflammatory infiltration of adnexal abscesses involved pelvic structure included adhesion with borders of uterus in 9 patients, adhesion with rectal or sigmoid in 4 patients and pelvic wall or bowel loop in 3 patients. Two cases with peritoneal thicken showed ascites on CT images and right adnexal tuboovarian abscess in 2 patients were associated with appendicitis. Conclusion: CT can reveal pelvic adjacent organs involvement or adhesion and inflammatory infihration of pelvic floor soft-tissues or fascial planes except showing cystic solid complex mass of adnexal location so that indicating characteristics and the extent of the suspected pelvic inflammatory diseases. CT can be valuable in difficult cases of gynecologic infective diseases. (authors)

  4. Death, Catastrophe, and the Significance of Tragedy

    Directory of Open Access Journals (Sweden)

    Jennifer Ballengee

    2014-05-01

    Full Text Available This NANO note will examine the tension between representation, memorial, and the catastrophe of death that emerges in the space of tragedy, as the problem arises in two quite different works: Oedipus at Colonus, a fairly typical fifth-century Greek tragedy, and Falling Man, Don DeLillo’s novel that, in its attempt to address the events of 9/11, reflects in form and subject matter many of Aristotle’s terms of tragic representation. It is not the intent of this note to engage with the recent proliferation of work in “performance theory.” Rather than being concerned with an imagined exchange between audience and actor, this study examines how the supplementary relationship of gesture and speech in tragedy disrupts the public/private distinction, and how this articulation effects and enables the public memorialization of death. Thus, this paper will consider the representation of death as an event whose catastrophic, and somewhat mysterious, collision of the public and the private lends it its tragic significance.

  5. Significance of blood examination in radiation workers

    International Nuclear Information System (INIS)

    Mori, Hirofumi; Nakamura, Shinobu; Ando, Atsushi; Kojima, Kazuhiko; Kikuta, Yoko.

    1978-01-01

    Blood examination made for the past 3 years revealed that the influences of chronic exposure of extremely small amounts of radiation (an average of 5 mrem/day) on peripheral blood are not detected. However, the blood examination, which is prescribed at least twice a year by law, is for determining whether or not the results of blood examination are within a normal range. Therefore, even though influences of a large amount of radiation are detected, it has little significance as a monitoring of chronic exposure of extremely small amounts of radiation. If the blood examination is used as a monitoring method for detecting exposure, it is important to compare the results with the previous ones in the same individuals. It is also necessary to increase the number of examinations and to study the blood more in detail. However, before that, the standard of the evaluation should be more defined because of its obscurity. The present blood examination is useful in managing the health generally. However, it is not good as a monitoring for chronic exposure of the extremely small amounts of radiation. Therefore, a routine biological method to be able to monitor radiation more precisely, is required. (Namekawa, K.)

  6. Clinical significance of perceptible fetal motion.

    Science.gov (United States)

    Rayburn, W F

    1980-09-15

    The monitoring of fetal activity during the last trimester of pregnancy has been proposed to be useful in assessing fetal welfare. The maternal perception of fetal activity was tested among 82 patients using real-time ultrasonography. All perceived fetal movements were visualized on the scanner and involved motion of the lower limbs. Conversely, 82% of all visualized motions of fetal limbs were perceived by the patients. All combined motions of fetal trunk with limbs were preceived by the patients and described as strong movements, whereas clusters of isolated, weak motions of the fetal limbs were less accurately perceived (56% accuracy). The number of fetal movements perceived during the 15-minute test period was significantly (p fetal motion was present (44 of 45 cases) than when it was absent (five of 10 cases). These findings reveal that perceived fetal motion is: (1) reliable; (2) related to the strength of lower limb motion; (3) increased with ruptured amniotic membranes; and (4) reassuring if considered to be active.

  7. Significance of surgical management for cystic prolactinoma.

    Science.gov (United States)

    Ogiwara, Toshihiro; Horiuchi, Tetsuyoshi; Nagm, Alhusain; Goto, Tetsuya; Hongo, Kazuhiro

    2017-04-01

    It is generally accepted that dopamine agonists (DA) represent the first-line treatment for most patients with prolactinoma, and patients become candidates for surgical intervention when DA is contraindicated. Surgical indication for cystic prolactinoma remains controversial. This study was performed to investigate the significance of surgery for cystic prolactinoma. A total of 28 patients that underwent transsphenoidal resection of prolactinoma between February 2004 and May 2016 were reviewed. Five consecutive patients with cystic prolactinoma were included in this study. Our surgical strategy for cystic prolactinoma was categorized as follows: first, when the purpose of surgical resection was normalization of the prolactin level, aggressive resection was performed; second, when volume reduction was essential to relieve the visual symptoms and headache, internal decompression was performed followed by DA therapy. The clinical outcomes were analyzed accordingly. All cystic prolactinoma were resected via the transsphenoidal approach without any complications, and all symptoms including visual impairment and hypogonadal activity were finally relieved combined with medication. Surgery for cystic prolactinoma could be a better option. Transsphenoidal surgery is relatively safe to remove the cystic prolactinoma, additionally it can normalize the prolactine level and achieve adequate and rapid decompression of optic chiasm. The risk of transsphenoidal surgery is highly dependent on the skill of the surgeon and treatment decision for cystic prolactinoma needs to be individualized for each patient.

  8. Making lasting memories: Remembering the significant

    Science.gov (United States)

    McGaugh, James L.

    2013-01-01

    Although forgetting is the common fate of most of our experiences, much evidence indicates that emotional arousal enhances the storage of memories, thus serving to create, selectively, lasting memories of our more important experiences. The neurobiological systems mediating emotional arousal and memory are very closely linked. The adrenal stress hormones epinephrine and corticosterone released by emotional arousal regulate the consolidation of long-term memory. The amygdala plays a critical role in mediating these stress hormone influences. The release of norepinephrine in the amygdala and the activation of noradrenergic receptors are essential for stress hormone-induced memory enhancement. The findings of both animal and human studies provide compelling evidence that stress-induced activation of the amygdala and its interactions with other brain regions involved in processing memory play a critical role in ensuring that emotionally significant experiences are well-remembered. Recent research has determined that some human subjects have highly superior autobiographic memory of their daily experiences and that there are structural differences in the brains of these subjects compared with the brains of subjects who do not have such memory. Understanding of neurobiological bases of such exceptional memory may provide additional insights into the processes underlying the selectivity of memory. PMID:23754441

  9. PROMPT Ia SUPERNOVAE ARE SIGNIFICANTLY DELAYED

    International Nuclear Information System (INIS)

    Raskin, Cody; Scannapieco, Evan; Rhoads, James; Della Valle, Massimo

    2009-01-01

    The time delay between the formation of a population of stars and the onset of type Ia supernovae (SNe Ia) sets important limits on the masses and nature of SN Ia progenitors. Here, we use a new observational technique to measure this time delay by comparing the spatial distributions of SNe Ia to their local environments. Previous work attempted such analyses encompassing the entire host of each SN Ia, yielding inconclusive results. Our approach confines the analysis only to the relevant portions of the hosts, allowing us to show that even so-called prompt SNe Ia that trace star formation on cosmic timescales exhibit a significant delay time of 200-500 million years. This implies that either the majority of Ia companion stars have main-sequence masses less than 3 M sun , or that most SNe Ia arise from double white dwarf binaries. Our results are also consistent with a SNe Ia rate that traces the white dwarf formation rate, scaled by a fixed efficiency factor.

  10. Taxonomic significance of trichomes micromorphology in cucurbits

    Science.gov (United States)

    Ali, Mohammad Ajmal; Al-Hemaid, Fahad M.A.

    2010-01-01

    Studies on trichomes micromorphology using Scanning Electron Microscope (SEM) were undertaken in 23 species with one variety under 13 genera of the family Cucurbitaceae (viz., Benincasa hispida (Thunb.) Cogn., Citrullus lanatus (Thunb.) Matsum. & Nakai, Cucumis melo var. agrestis Naudin, Cucumis sativus L., Diplocyclos palmatus (L.) C. Jeffrey, Edgaria dargeelingensis C.B. Clarke, Gynostemma burmanicum King ex Chakr., Gynostemma pentaphyllum (Thunb.) Makino, Gynostemma pubescens (Gagnep.) C.Y. Wu, Hemsleya dipterygia Kuang & A.M. Lu, Lagenaria siceraria (Molina) Standl., Luffa acutangula (L.) Roxb., Luffa cylindrica M. Roem., Luffa echinata Roxb., Melothria heterophylla (Lour.) Cogn., Melothria leucocarpa (Blume) Cogn., Melothria maderspatana (L.) Cogn., Sechium edule (Jacq.) Sw., Thladiantha cordifolia (Blume) Cogn., Trichosanthes cucumerina L., T. cucumerina var. anguina (L.) Haines, Trichosanthes dioica Roxb., Trichosanthes lepiniana (Naudin) Cogn. and T. tricuspidata Lour.). The trichomes in the family Cucurbitaceae vary from unicellular to multicellular, conical to elongated, smooth to ridges, with or without flattened disk at base and cyctolithic appendages, thin to thick walled, curved at apices to blunt. Trichomes micromorphology in the family Cucurbitaceae was found significant taxonomically. PMID:23961108

  11. Taxonomic significance of trichomes micromorphology in cucurbits.

    Science.gov (United States)

    Ali, Mohammad Ajmal; Al-Hemaid, Fahad M A

    2011-01-01

    Studies on trichomes micromorphology using Scanning Electron Microscope (SEM) were undertaken in 23 species with one variety under 13 genera of the family Cucurbitaceae (viz., Benincasa hispida (Thunb.) Cogn., Citrullus lanatus (Thunb.) Matsum. & Nakai, Cucumis melo var. agrestis Naudin, Cucumis sativus L., Diplocyclos palmatus (L.) C. Jeffrey, Edgaria dargeelingensis C.B. Clarke, Gynostemma burmanicum King ex Chakr., Gynostemma pentaphyllum (Thunb.) Makino, Gynostemma pubescens (Gagnep.) C.Y. Wu, Hemsleya dipterygia Kuang & A.M. Lu, Lagenaria siceraria (Molina) Standl., Luffa acutangula (L.) Roxb., Luffa cylindrica M. Roem., Luffa echinata Roxb., Melothria heterophylla (Lour.) Cogn., Melothria leucocarpa (Blume) Cogn., Melothria maderspatana (L.) Cogn., Sechium edule (Jacq.) Sw., Thladiantha cordifolia (Blume) Cogn., Trichosanthes cucumerina L., T. cucumerina var. anguina (L.) Haines, Trichosanthes dioica Roxb., Trichosanthes lepiniana (Naudin) Cogn. and T. tricuspidata Lour.). The trichomes in the family Cucurbitaceae vary from unicellular to multicellular, conical to elongated, smooth to ridges, with or without flattened disk at base and cyctolithic appendages, thin to thick walled, curved at apices to blunt. Trichomes micromorphology in the family Cucurbitaceae was found significant taxonomically.

  12. Evolutionary significance of ageing in the wild.

    Science.gov (United States)

    Kowald, Axel; Kirkwood, Thomas B L

    2015-11-01

    Human lifespan has risen dramatically over the last 150 years, leading to a significant increase in the fraction of aged people in the population. Until recently it was believed that this contrasted strongly with the situation in wild populations of animals, where the likelihood of encountering demonstrably senescent individuals was believed to be negligible. Over the recent years, however, a series of field studies has appeared that shows ageing can also be observed for many species in the wild. We discuss here the relevance of this finding for the different evolutionary theories of ageing, since it has been claimed that ageing in the wild is incompatible with the so-called non-adaptive (non-programmed) theories, i.e. those in which ageing is presumed not to offer a direct selection benefit. We show that a certain proportion of aged individuals in the population is fully compatible with the antagonistic pleiotropy and the disposable soma theories, while it is difficult to reconcile with the mutation accumulation theory. We also quantify the costs of ageing using life history data from recent field studies and a range of possible metrics. We discuss the merits and problems of the different metrics and also introduce a new metric, yearly death toll, that aims directly at quantifying the deaths caused by the ageing process. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Significance of FISH in clinical cytogenetics

    Energy Technology Data Exchange (ETDEWEB)

    Gopal Rao, V.V.N.; Harris, S.; Roop, H. [H.A. Chapman Institute of Medical Genetics, Tulsa, OK (United States)] [and others

    1994-09-01

    Ever since its discovery, FISH technology has become an invaluable adjunct to conventional cytogenetics. FISH has been instrumental in resolving previously unresolved cytogenetic dilemmas. FISH has been used to elucidate complex as well as subtle chromosomal translocations, in detection of microdeletions, to confirm duplications and inversions and to identify marker chromosomes. We report a few selected cases where FISH proved to be invaluable in not only confirming the anomaly, but also in arriving at an accurate diagnosis and appropriate counseling of the patients. These include 3 cases of prenatal and 3 cases of postnatal diagnosis. The results clearly demonstrate the significance of FISH in identifying and interpreting the difficult karyotype in clinical cytogenetics. In addition, FISH has been used to rule out microdeletions in Prader-Willi (16), Angelman (3), Miller-Dieker (7), DiGeorge (4) and Smith-Magenis (1) syndrome patients. Without FISH in the majority of these cases, it would not have been possible to accurately identify the karyotype and interpret the results. Hence, we recommend that FISH be used as a powerful adjunct to conventional cytogenetics in order to arrive at an accurate interpretation of the results but not to replace routine cytogenetic studies.

  14. Significant and Basic Innovations in Urban Planning

    Science.gov (United States)

    Kolyasnikov, V. A.

    2017-11-01

    The article considers the development features of the innovative urban planning in the USSR and Russia in XVIII - XX centuries. Innovative urban planning is defined as an activity on innovations creation and their implementation to obtain a socio-economic, political, environmental or other effect. In the course of urban development history this activity represents a cyclic wave process in which there are phases of rise and fall. The study of cyclic waves in the development of innovative urban planning uses the concept of basic and epochal innovations selection. This concept was developed by scientists for the study of cyclic wave processes in economics. Its adaptation to the conditions of innovative urban planning development allows one to introduce the concept of “basic innovation” and “significant innovation” in the theory and practice of settlement formation and their systems as well as to identify opportunities to highlight these innovations in the history of Russian urban planning. From these positions, six innovation waves committed to the urban development over the past 300 years are being investigated. The observed basic innovations in the domestic urban area show that urban development is a vital area for ensuring the country’s geopolitical security. Basic innovations are translated in time and modernized under new conditions of urban planning development. In this regard, we can predict the development of four basic innovations in post-Soviet Russia.

  15. Significance and popularity in music production

    Science.gov (United States)

    Gravino, Pietro; Servedio, Vito D. P.; Tria, Francesca; Loreto, Vittorio

    2017-01-01

    Creative industries constantly strive for fame and popularity. Though highly desirable, popularity is not the only achievement artistic creations might ever acquire. Leaving a longstanding mark in the global production and influencing future works is an even more important achievement, usually acknowledged by experts and scholars. ‘Significant’ or ‘influential’ works are not always well known to the public or have sometimes been long forgotten by the vast majority. In this paper, we focus on the duality between what is successful and what is significant in the musical context. To this end, we consider a user-generated set of tags collected through an online music platform, whose evolving co-occurrence network mirrors the growing conceptual space underlying music production. We define a set of general metrics aiming at characterizing music albums throughout history, and their relationships with the overall musical production. We show how these metrics allow to classify albums according to their current popularity or their belonging to expert-made lists of important albums. In this way, we provide the scientific community and the public at large with quantitative tools to tell apart popular albums from culturally or aesthetically relevant artworks. The generality of the methodology presented here lends itself to be used in all those fields where innovation and creativity are in play. PMID:28791169

  16. Exploring the economic significance of small and medium enterprises

    Directory of Open Access Journals (Sweden)

    Ashenafi Beyene Fanta

    2015-01-01

    Full Text Available This paper aims at providing a detailed account of economic significance of small and medium enterprises by drawing on the extant body of empirical literature. It has been noted that studies on the link between SME development and economic growth are inconclusive. While modeling growth in the SME sector and its impact on economic development is a matter of ongoing scientific investigation, we emphasized on the most conspicuous economic benefits of SMEs that includes, among others, job creation, contribution to national output, reducing income inequality and poverty. We believe this may help researchers frame their future investigations in line with the benefits discussed in the paper.

  17. Improved survival in rhesus macaques immunized with modified vaccinia virus Ankara recombinants expressing simian immunodeficiency virus envelope correlates with reduction in memory CD4+ T-cell loss and higher titers of neutralizing antibody.

    Science.gov (United States)

    Ourmanov, Ilnour; Kuwata, Takeo; Goeken, Robert; Goldstein, Simoy; Iyengar, Ranjani; Buckler-White, Alicia; Lafont, Bernard; Hirsch, Vanessa M

    2009-06-01

    Previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high viremia and AIDS following challenge with a pathogenic strain of SIV. Although all animals became infected, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines compared with animals that received nonrecombinant MVA. Most importantly, the reduction in viremia resulted in a significant increase in median and cumulative survival. Continued analysis of these animals over the subsequent 9 years has shown that they maintain a survival advantage, although all but two of the macaques have progressed to AIDS. Importantly, improved survival correlated with preservation of memory CD4(+) T cells in the peripheral blood. The greatest survival advantage was observed in macaques immunized with regimens containing SIV Env, and the titer of neutralizing antibodies to the challenge virus prior to or shortly following challenge correlated with preservation of CD4(+) T cells. These data are consistent with a role for neutralizing antibodies in nonsterilizing protection from high viremia and associated memory CD4(+) T-cell loss.

  18. Psoriasis causes significant economic burden to patients.

    Science.gov (United States)

    Mustonen, A; Mattila, K; Leino, M; Koulu, L; Tuominen, R

    2014-06-01

    Psoriasis results in expenses to patients from many cost sources. Psoriasis treatments may result in considerable time and traveling costs, yet many studies fail to account for these costs. The objective of this study was to evaluate the multidimensional economic burden of psoriasis to patients. The study was based on 232 Finnish patients with psoriasis or psoriatic arthritis visiting a tertiary level dermatological clinic during a 1-year study period between October 1, 2009 and September 30, 2010. The data were based on a patient questionnaire, clinical data from the medical records and reimbursement data from the Finnish Social Insurance Institution. Item costs were based on true costs charged from the patients and all time cost estimates were based on the Human Capital Approach method. 199 patients with psoriasis and 33 with psoriatic arthritis were included in the study. Total costs were higher for patients receiving traditional systemic medications or phototherapy than those not receiving such treatment. Travel costs and travel time costs accounted for more than 60% of the costs of phototherapy. Skin care at home was time consuming and thus caused significant burden to patients. The majority of the visit costs arose from hospital visits and only a small proportion were attributed to visiting primary health care providers. Visit charges and other patient co-payments were estimated to play a minor role in the total cost of psoriasis incurred by patients, while travel costs and lost time comprised the majority of the costs, which should not be omitted in future studies regarding costs of treatments.

  19. Weight in Parkinson's Disease: Phenotypical Significance.

    Science.gov (United States)

    Sharma, Jagdish C; Lewis, Anna

    2017-01-01

    Body weight in Parkinson's disease (PD) is a significant nonmotor feature. Weight homeostasis is a complex physiological process and gets deranged in PD patients leading to changes in weight. While both the low and high body weight have been reported as risk factors for PD, the majority of PD patients have a lower weight and a subset of patients lose weight during the course of the disease, while a small proportion gain weight. A number of clinical parameters such as older age, impaired cognition, severity of disease, and an imbalance of food intake determined by satiety and hunger hormones have been reported to be associated with but not the cause of weight change. Low body weight and weight loss have a negative impact on disease severity, dyskinesia quality of life, and mortality indicative of disease progression. An early assessment of olfactory impairment seems to identify patients at risk of weight loss, the patients with more severe olfactory loss-anosmic group, lose weight as compared to the patients with some preservation of olfaction, the hyposmic group. Higher levodopa dose per kilogram body weight increases the risk of dyskinesia, higher body weight seems to be protective against this complication. The identification of PD patients according to the nonmotor phenotype of "Park-olfaction-weight-phenotype" and the "olfaction-weight-dyskinesia" triad should help to develop strategies to prevent weight reduction and improve general health and complications of PD patients. The phenotype seems to reflect a differential prodromal pathology and influence clinical disease. Higher body weight patients would benefit from life style changes to achieve a healthy profile. Weight monitoring and weight orientated approach to management of PD patients should help to improve their outcome. Body weight change might be a surrogate to disease progression and may be used to investigate neuroprotection strategies. © 2017 Elsevier Inc. All rights reserved.

  20. Significance of venous anastomosis in fingertip replantation.

    Science.gov (United States)

    Hattori, Yasunori; Doi, Kazuteru; Ikeda, Keisuke; Abe, Yukio; Dhawan, Vikas

    2003-03-01

    Adequate venous outflow is the most important factor for successful fingertip replantation. The authors have attempted venous anastomosis in all cases of fingertip replantation to overcome postoperative congestion. In this article, the significance of venous repair for fingertip replantation is described from the authors' results of 64 complete fingertip amputations in 55 consecutive patients, which were replanted from January of 1996 to June of 2001. The overall survival rate was 86 percent. Of the 44 replantations in zone I, 37 survived, and the success rate was 84 percent. Of the 20 replantations in zone II, 18 survived, and the success rate was 90 percent. Venous anastomosis was attempted in all cases, but it was possible in 39 zone I and in all zone II replantations. For arterial repair, vein grafts were necessary in 17 of the 44 zone I and in one of the 20 zone II replantations; for venous repair, they were necessary in six zone I replantations and one zone II replantation. Postoperative vascular complications occurred in 15 replantations. There were five cases of arterial thrombosis and 10 cases of venous congestion. Venous congestion occurred in nine zone I and one zone II replantations. In five of these 10 replantations, venous anastomosis was not possible. In another five replantations, venous outflow was established at the time of surgery, but occlusion occurred subsequently. Except for the five failures resulting from arterial thrombosis, successful venous repair was possible in 49 of 59 replantations (83 percent). Despite the demand for skillful microsurgical technique and longer operation time, the authors' results using venous anastomosis in successful fingertip replantations are encouraging. By performing venous anastomosis, external bleeding can be avoided and a higher survival rate can be achieved. Venous anastomosis for fingertip replantation is a reliable and worthwhile procedure.