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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. Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells

    Science.gov (United States)

    Milush, Jeffrey M.; Mir, Kiran D.; Sundaravaradan, Vasudha; Gordon, Shari N.; Engram, Jessica; Cano, Christopher A.; Reeves, Jacqueline D.; Anton, Elizabeth; O’Neill, Eduardo; Butler, Eboneé; Hancock, Kathy; Cole, Kelly S.; Brenchley, Jason M.; Else, James G.; Silvestri, Guido; Sodora, Donald L.

    2011-01-01

    SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4+ T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3+CD4–CD8– T cells (double-negative T cells) partially compensates for CD4+ T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4+ T cells to SIV-negative animals resulted in rapid loss of CD4+ T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4+ T cell–like helper functions upon SIV-induced CD4+ T cell depletion in this species. PMID:21317533

  3. Adipose Tissue: Sanctuary for HIV/SIV Persistence and Replication.

    Science.gov (United States)

    Pallikkuth, Suresh; Mohan, Mahesh

    2015-12-01

    This commentary highlights new findings from a recent study identifying adipose tissue as a potential HIV reservoir and a major site of inflammation during chronic human/simian immunodeficiency virus (HIV/SIV) infection. A concise discussion about upcoming challenges and new research avenues for reducing chronic adipose inflammation during HIV/SIV infection is presented. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Sucralfate significantly reduces ciprofloxacin concentrations in serum.

    OpenAIRE

    Garrelts, J C; Godley, P J; Peterie, J D; Gerlach, E H; Yakshe, C C

    1990-01-01

    The effect of sucralfate on the bioavailability of ciprofloxacin was evaluated in eight healthy subjects utilizing a randomized, crossover design. The area under the concentration-time curve from 0 to 12 h was reduced from 8.8 to 1.1 micrograms.h/ml by sucralfate (P less than 0.005). Similarly, the maximum concentration of ciprofloxacin in serum was reduced from 2.0 to 0.2 micrograms/ml (P less than 0.005). We conclude that concurrent ingestion of sucralfate significantly reduces the concentr...

  5. Enhanced cellular immune response against SIV Gag induced by immunization with DNA vaccines expressing assembly and release-defective SIV Gag proteins

    International Nuclear Information System (INIS)

    Bu Zhigao; Ye Ling; Compans, Richard W.; Yang Chinglai

    2003-01-01

    Codon-optimized genes were synthesized for the SIVmac239 Gag, a mutant Gag with mutations in the major homology region, and a chimeric Gag containing a protein destruction signal at the N-terminus of Gag. The mutant and chimeric Gag were expressed at levels comparable to that observed for the wild-type Gag protein but their stability and release into the medium were found to be significantly reduced. Immunization of mice with DNA vectors encoding the mutant or chimeric Gag induced fourfold higher levels of anti-SIV Gag CD4 T cell responses than the DNA vector encoding the wild-type SIV Gag. Moreover, anti-SIV Gag CD8 T cell responses induced by DNA vectors encoding the mutant or chimeric Gag were found to be 5- to 10-fold higher than those induced by the DNA construct for the wild-type Gag. These results indicate that mutations disrupting assembly and/or stability of the SIV Gag protein effectively enhance its immunogenicity when expressed from DNA vaccines

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

    Science.gov (United States)

    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.

  7. Quilting after mastectomy significantly reduces seroma formation

    African Journals Online (AJOL)

    reduce or prevent seroma formation among mastectomy patients ... of this prospective study is to evaluate the effect of surgical quilting ... Seroma was more common in smokers (p=0.003) and was not decreased by the .... explain its aetiology.

  8. Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

    Science.gov (United States)

    Malkevitch, Nina V; Patterson, L Jean; Aldrich, M Kristine; Wu, Yichen; Venzon, David; Florese, Ruth H; Kalyanaraman, V S; Pal, Ranajit; Lee, Eun Mi; Zhao, Jun; Cristillo, Anthony; Robert-Guroff, Marjorie

    2006-09-15

    Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained protection against re-challenge.

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

    Directory of Open Access Journals (Sweden)

    Strasak Alexander

    2009-06-01

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

  10. Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

    Science.gov (United States)

    Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S Munir; Fenizia, Claudio; Lifson, Jeffrey D; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David; Franchini, Genoveffa

    2013-02-01

    The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8(+) T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV(mac251) that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+) T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV(mac251) acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV(mac251)-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV(mac251) infectivity in cells that express high levels of α(4)β(7) integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.

  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. 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

  13. Control of viremia and prevention of AIDS following immunotherapy of SIV-infected macaques with peptide-pulsed blood.

    Directory of Open Access Journals (Sweden)

    Robert De Rose

    2008-05-01

    Full Text Available Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIV(mac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably approximately 10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans.

  14. Attenuation of Pathogenic Immune Responses during Infection with Human and Simian Immunodeficiency Virus (HIV/SIV) by the Tetracycline Derivative Minocycline

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    Drewes, Julia L.; Szeto, Gregory L.; Engle, Elizabeth L.; Liao, Zhaohao; Shearer, Gene M.; Zink, M. Christine; Graham, David R.

    2014-01-01

    HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo. PMID:24732038

  15. 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...

  16. 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

  17. 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.

  18. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. Next-generation nozzle check valve significantly reduces operating costs

    Energy Technology Data Exchange (ETDEWEB)

    Roorda, O. [SMX International, Toronto, ON (Canada)

    2009-01-15

    Check valves perform an important function in preventing reverse flow and protecting plant and mechanical equipment. However, the variety of different types of valves and extreme differences in performance even within one type can change maintenance requirements and life cycle costs, amounting to millions of dollars over the typical 15-year design life of piping components. A next-generation non-slam nozzle check valve which prevents return flow has greatly reduced operating costs by protecting the mechanical equipment in a piping system. This article described the check valve varieties such as the swing check valve, a dual-plate check valve, and nozzle check valves. Advancements in optimized design of a non-slam nozzle check valve were also discussed, with particular reference to computer flow modelling such as computational fluid dynamics; computer stress modelling such as finite element analysis; and flow testing (using rapid prototype development and flow loop testing), both to improve dynamic performance and reduce hydraulic losses. The benefits of maximized dynamic performance and minimized pressure loss from the new designed valve were also outlined. It was concluded that this latest non-slam nozzle check valve design has potential applications in natural gas, liquefied natural gas, and oil pipelines, including subsea applications, as well as refineries, and petrochemical plants among others, and is suitable for horizontal and vertical installation. The result of this next-generation nozzle check valve design is not only superior performance, and effective protection of mechanical equipment but also minimized life cycle costs. 1 fig.

  1. PA positioning significantly reduces testicular dose during sacroiliac joint radiography

    Energy Technology Data Exchange (ETDEWEB)

    Mekis, Nejc [Faculty of Health Sciences, University of Ljubljana (Slovenia); Mc Entee, Mark F., E-mail: mark.mcentee@ucd.i [School of Medicine and Medical Science, University College Dublin 4 (Ireland); Stegnar, Peter [Jozef Stefan International Postgraduate School, Ljubljana (Slovenia)

    2010-11-15

    Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p {<=} 0.009) with no statistically significant reduction in image quality (p {<=} 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p {<=} 0.020) and 94.9% lower with protection (p {<=} 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p {<=} 0.559); but was lowered by its use in the PA (p {<=} 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

  2. PA positioning significantly reduces testicular dose during sacroiliac joint radiography

    International Nuclear Information System (INIS)

    Mekis, Nejc; Mc Entee, Mark F.; Stegnar, Peter

    2010-01-01

    Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p ≤ 0.009) with no statistically significant reduction in image quality (p ≤ 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p ≤ 0.020) and 94.9% lower with protection (p ≤ 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p ≤ 0.559); but was lowered by its use in the PA (p ≤ 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

  3. Innate Lymphoid Cells in HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    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.

  4. Innate Lymphoid Cells in HIV/SIV Infections.

    Science.gov (United States)

    Shah, Spandan V; Manickam, Cordelia; Ram, Daniel R; Reeves, R Keith

    2017-01-01

    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.

  5. An "escape clock" for estimating the turnover of SIV DNA in resting CD4⁺ T cells.

    Directory of Open Access Journals (Sweden)

    Jeanette Reece

    Full Text Available Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies. Most studies suggest that cells with latently integrated HIV decay very slowly under therapy. However, it is much more difficult to study the turnover and persistence of HIV DNA during active infection. We have developed an "escape clock" approach for measuring the turnover of HIV DNA in resting CD4+ T cells. This approach studies the replacement of wild-type (WT SIV DNA present in early infection by CTL escape mutant (EM strains during later infection. Using a strain-specific real time PCR assay, we quantified the relative amounts of WT and EM strains in plasma SIV RNA and cellular SIV DNA. Thus we can track the formation and turnover of SIV DNA in sorted resting CD4+ T cells. We studied serial plasma and PBMC samples from 20 SIV-infected Mane-A*10 positive pigtail macaques that have a signature Gag CTL escape mutation. In animals with low viral load, WT virus laid down early in infection is extremely stable, and the decay of this WT species is very slow, consistent with findings in subjects on anti-retroviral medications. However, during active, high level infection, most SIV DNA in resting cells was turning over rapidly, suggesting a large pool of short-lived DNA produced by recent infection events. Our results suggest that, in order to reduce the formation of a stable population of SIV DNA, it will be important either to intervene very early or intervene during active replication.

  6. 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)

  7. '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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates.

    Science.gov (United States)

    Ault, Alida; Tennant, Sharon M; Gorres, J Patrick; Eckhaus, Michael; Sandler, Netanya G; Roque, Annelys; Livio, Sofie; Bao, Saran; Foulds, Kathryn E; Kao, Shing-Fen; Roederer, Mario; Schmidlein, Patrick; Boyd, Mary Adetinuke; Pasetti, Marcela F; Douek, Daniel C; Estes, Jacob D; Nabel, Gary J; Levine, Myron M; Rao, Srinivas S

    2013-12-02

    Nontyphoidal Salmonella (NTS) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. Vaccination against invasive NTS disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute one strategy to elicit protection. However, they must particularly be shown to be adequately attenuated for consideration of immunocompromised subjects. Accordingly, we examined the safety and tolerability of an oral live attenuated Salmonella typhimurium vaccine candidate, CVD 1921, in an established chronic simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated clinical parameters, histopathology, and measured differences in mucosal permeability to wild-type and vaccine strains. Compared to the wild-type S. typhimurium strain I77 in both SIV-infected and SIV-uninfected nonhuman primate hosts, this live-attenuated vaccine shows reduced shedding and systemic spread, exhibits limited pathological disease manifestations in the digestive tract, and induces low levels of cellular infiltration in tissues. Furthermore, wild-type S. typhimurium induces increased intestinal epithelial damage and permeability, with infiltration of neutrophils and macrophages in both SIV-infected and SIV-uninfected nonhuman primates compared to the vaccine strain. Based on shedding, systemic spread, and histopathology, the live-attenuated S. typhimurium strain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques. Copyright © 2013. Published by Elsevier Ltd.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    KAUST Repository

    Mai, Paul Martin; Schorlemmer, Danijel; Page, Morgan; Ampuero, Jean‐Paul; Asano, Kimiyuki; Causse, Mathieu; Custodio, Susana; Fan, Wenyuan; Festa, Gaetano; Galis, Martin; Gallovic, Frantisek; Imperatori, Walter; Kä ser, Martin; Malytskyy, Dmytro; Okuwaki, Ryo; Pollitz, Fred; Passone, Luca; Razafindrakoto, Hoby; Sekiguchi, Haruko; Song, Seok Goo; Somala, Surendra N.; Thingbaijam, Kiran Kumar; Twardzik, Cedric; van Driel, Martin; Vyas, Jagdish Chandra; Wang, Rongjiang; Yagi, Yuji; Zielke, Olaf

    2016-01-01

    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.

  13. 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.

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

    Science.gov (United States)

    Mai, P. Martin; Schorlemmer, Danijel; Page, Morgan T.; Ampuero, Jean-Paul; Asano, Kimiyuki; Causse, Mathieu; Custodio, Susana; Fan, Wenyuan; Festa, Gaetano; Galis, Martin; Gallovic, Frantisek; Imperatori, Walter; Käser, Martin; Malytskyy, Dmytro; Okuwaki, Ryo; Pollitz, Fred; Passone, Luca; Razafindrakoto, Hoby N. T.; Sekiguchi, Haruko; Song, Seok Goo; Somala, Surendra N.; Thingbaijam, Kiran K. S.; Twardzik, Cedric; van Driel, Martin; Vyas, Jagdish C.; Wang, Rongjiang; Yagi, Yuji; Zielke, Olaf

    2016-01-01

    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. Stochastic inequalities and applications to dynamics analysis of a novel SIVS epidemic model with jumps

    Directory of Open Access Journals (Sweden)

    Xiaona Leng

    2017-06-01

    Full Text Available Abstract This paper proposes a new nonlinear stochastic SIVS epidemic model with double epidemic hypothesis and Lévy jumps. The main purpose of this paper is to investigate the threshold dynamics of the stochastic SIVS epidemic model. By using the technique of a series of stochastic inequalities, we obtain sufficient conditions for the persistence in mean and extinction of the stochastic system and the threshold which governs the extinction and the spread of the epidemic diseases. Finally, this paper describes the results of numerical simulations investigating the dynamical effects of stochastic disturbance. Our results significantly improve and generalize the corresponding results in recent literatures. The developed theoretical methods and stochastic inequalities technique can be used to investigate the high-dimensional nonlinear stochastic differential systems.

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

    Directory of Open Access Journals (Sweden)

    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. The Earthquake Source Inversion Validation (SIV) - Project: Summary, Status, Outlook

    Science.gov (United States)

    Mai, P. M.

    2017-12-01

    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, this kinematic source inversion is ill-posed and returns non-unique solutions, as seen for instance in multiple source models for the same earthquake, obtained by different research teams, that often exhibit remarkable dissimilarities. To address the uncertainties in earthquake-source inversions and to understand strengths and weaknesses of various methods, the Source Inversion Validation (SIV) project developed a set of forward-modeling exercises and inversion benchmarks. Several research teams then use these validation exercises to test their codes and methods, but also to develop and benchmark new approaches. In this presentation I will summarize the SIV strategy, the existing benchmark exercises and corresponding results. Using various waveform-misfit criteria and newly developed statistical comparison tools to quantify source-model (dis)similarities, the SIV platforms is able to rank solutions and identify particularly promising source inversion approaches. Existing SIV exercises (with related data and descriptions) and all computational tools remain available via the open online collaboration platform; additional exercises and benchmark tests will be uploaded once they are fully developed. I encourage source modelers to use the SIV benchmarks for developing and testing new methods. The SIV efforts have already led to several promising new techniques for tackling the earthquake-source imaging problem. I expect that future SIV benchmarks will provide further innovations and insights into earthquake source kinematics that will ultimately help to better understand the dynamics of the rupture process.

  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. Altered immune responses in rhesus macaques co-infected with SIV and Plasmodium cynomolgi: an animal model for coincident AIDS and relapsing malaria.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Koehler

    2009-09-01

    Full Text Available Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens.Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naïve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response.These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions.

  1. Immunological alterations and associated diseases in mandrills (Mandrillus sphinx) naturally co-infected with SIV and STLV.

    Science.gov (United States)

    Souquière, Sandrine; Makuwa, Maria; Sallé, Bettina; Lepelletier, Yves; Mortreux, Franck; Hermine, Olivier; Kazanji, Mirdad

    2014-04-01

    Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+) T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS

    Science.gov (United States)

    Campbell, Jennifer H.; Burdo, Tricia H.; Autissier, Patrick; Bombardier, Jeffrey P.; Westmoreland, Susan V.; Soulas, Caroline; González, R. Gilberto; Ratai, Eva-Maria; Williams, Kenneth C.

    2011-01-01

    Background Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline's functions are not well defined. Methods Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy (1H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied. Results Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14loCD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/Cr (neuronal injury) and circulating CD14+CD16+ and CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation. Conclusion Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation. PMID:21494695

  6. 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.

  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

    2018-05-01

    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. Altered regional homogeneity of brain spontaneous signals in SIV infected rhesus macaque model.

    Science.gov (United States)

    Zhao, Jing; Jing, Bin; Chen, Feng; Liu, Jiaojiao; Wang, Yuanyuan; Li, Hongjun

    2017-04-01

    Regional homogeneity (ReHo), a measurement from resting-state functional magnetic imaging (rs-fMRI) to reflect local synchronization of brain activities, has been widely explored in previous studies of neurological diseases. SIV infected model for detecting the neurological changes with progression was studied. In the study, six rhesus macaques infected by simian immunodeficiency virus (SIV) were scanned by resting-state fMRI at the following time points: before SIV inoculation (baseline), 12weeks and 24weeks post inoculation (12wpi, 24wpi). Meanwhile, the immunological parameters including serum percentage of CD4+ T cell, CD4/CD8 ratio and absolute CD4+ T cell number were measured and analyzed. In comparison of baseline, significant decreased ReHo was found in the left superior frontal gyrus, left superior temporal gyrus, left hippocampus, right precuneus, left angular gyrus, and bilateral occipital gyrus; in contrast increased ReHo in putamen at 12wpi. Moreover, at the time of 24wpi, decreased ReHo was observed in the right postcentral gyrus, left precentral gyrus, posterior cingulated gyrus and thalamus, while ReHo was increased in the left putamen, hippocampus, left anterior cingulated cortex and precentral cortex. The correlation analysis revealed that ReHo in the superior frontal gyrus showed negative association with CD4/CD8 ratio and positive with absolute CD4+ T cell number. The correlation analysis showed that percentage of CD4+ was correlated with the ReHo values in right middle frontal gyrus, bilateral thalamus and amygdala positively; negative relationship with left putamen, left superior frontal gyrus, left superior and middle temporal gyrus. The study first indicates that hippocampus, putamen, frontal and occipital lobe were impaired by using rs-fMRI and correlated with immunological parameters. Thus, ReHo value can be utilized as a noninvasive biomarker of spontaneous brain activity changes caused by the progression of neurological impairments

  9. A pilot weight reduction program over one year significantly reduced DNA strand breaks in obese subjects

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Wagner

    2015-05-01

    Conclusion: A sustainable lifestyle change under supervision including physical activity and diet quality over a period of one year was not only responsible to reduce body weight and BMI but also led to significant reduction in all parameters of the comet assay. These results underline the importance of body weight reduction and highlight the positive changes in DNA stability.

  10. 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

  11. The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

    Science.gov (United States)

    Mordekar, S R; Guthrie, P; Bonham, J R; Olpin, S E; Hargreaves, I; Baxter, P S

    2006-03-01

    Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.

  12. 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.

  13. Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria.

    Science.gov (United States)

    Liu, Cindy M; Hungate, Bruce A; Tobian, Aaron A R; Serwadda, David; Ravel, Jacques; Lester, Richard; Kigozi, Godfrey; Aziz, Maliha; Galiwango, Ronald M; Nalugoda, Fred; Contente-Cuomo, Tania L; Wawer, Maria J; Keim, Paul; Gray, Ronald H; Price, Lance B

    2013-04-16

    Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable.

  14. 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.

  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

    BACKGROUND: Our objective was to reduce hands-off time during cardiopulmonary resuscitation as increased hands-off time leads to higher mortality. METHODS: The European Resuscitation Council (ERC) 2005 and ERC 2010 guidelines were compared with an alternative sequence (ALT). Pulseless ventricular...... physicians were included. All had prior experience in advanced life support. Chest compressions were shorter interrupted using ALT (mean, 6.7 vs 13.0 seconds). Analyzing data for ventricular tachycardia scenarios only, hands-off time was shorter using ALT (mean, 7.1 vs 18.2 seconds). In ERC 2010 vs ALT, 12...... physicians were included. Two physicians had not prior experience in advanced life support. Hands-off time was reduced using ALT (mean, 3.9 vs 5.6 seconds). Looking solely at ventricular tachycardia scenarios, hands-off time was shortened using ALT (mean, 4.5 vs 7.6 seconds). No significant reduction...

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  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. 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

  2. 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.

  3. 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.

  4. Implementation of standardized follow-up care significantly reduces peritonitis in children on chronic peritoneal dialysis.

    Science.gov (United States)

    Neu, Alicia M; Richardson, Troy; Lawlor, John; Stuart, Jayne; Newland, Jason; McAfee, Nancy; Warady, Bradley A

    2016-06-01

    The Standardizing Care to improve Outcomes in Pediatric End stage renal disease (SCOPE) Collaborative aims to reduce peritonitis rates in pediatric chronic peritoneal dialysis patients by increasing implementation of standardized care practices. To assess this, monthly care bundle compliance and annualized monthly peritonitis rates were evaluated from 24 SCOPE centers that were participating at collaborative launch and that provided peritonitis rates for the 13 months prior to launch. Changes in bundle compliance were assessed using either a logistic regression model or a generalized linear mixed model. Changes in average annualized peritonitis rates over time were illustrated using the latter model. In the first 36 months of the collaborative, 644 patients with 7977 follow-up encounters were included. The likelihood of compliance with follow-up care practices increased significantly (odds ratio 1.15, 95% confidence interval 1.10, 1.19). Mean monthly peritonitis rates significantly decreased from 0.63 episodes per patient year (95% confidence interval 0.43, 0.92) prelaunch to 0.42 (95% confidence interval 0.31, 0.57) at 36 months postlaunch. A sensitivity analysis confirmed that as mean follow-up compliance increased, peritonitis rates decreased, reaching statistical significance at 80% at which point the prelaunch rate was 42% higher than the rate in the months following achievement of 80% compliance. In its first 3 years, the SCOPE Collaborative has increased the implementation of standardized follow-up care and demonstrated a significant reduction in average monthly peritonitis rates. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  5. 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.

  6. DMPD: Monocyte/macrophage traffic in HIV and SIV encephalitis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960230 Monocyte/macrophage traffic in HIV and SIV encephalitis. Kim WK, Corey S, ...Alvarez X, Williams K. J Leukoc Biol. 2003 Nov;74(5):650-6. Epub 2003 Aug 11. (.png) (.svg) (.html) (.csml) Show Monocyte/macrophage... traffic in HIV and SIV encephalitis. PubmedID 12960230 Title Monocyte/macrophage tr

  7. 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

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

    KAUST Repository

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

    2018-01-01

    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.

  9. 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.

  10. 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.

  11. Using lytic bacteriophages to eliminate or significantly reduce contamination of food by foodborne bacterial pathogens.

    Science.gov (United States)

    Sulakvelidze, Alexander

    2013-10-01

    Bacteriophages (also called 'phages') are viruses that kill bacteria. They are arguably the oldest (3 billion years old, by some estimates) and most ubiquitous (total number estimated to be 10(30) -10(32) ) known organisms on Earth. Phages play a key role in maintaining microbial balance in every ecosystem where bacteria exist, and they are part of the normal microflora of all fresh, unprocessed foods. Interest in various practical applications of bacteriophages has been gaining momentum recently, with perhaps the most attention focused on using them to improve food safety. That approach, called 'phage biocontrol', typically includes three main types of applications: (i) using phages to treat domesticated livestock in order to reduce their intestinal colonization with, and shedding of, specific bacterial pathogens; (ii) treatments for decontaminating inanimate surfaces in food-processing facilities and other food establishments, so that foods processed on those surfaces are not cross-contaminated with the targeted pathogens; and (iii) post-harvest treatments involving direct applications of phages onto the harvested foods. This mini-review primarily focuses on the last type of intervention, which has been gaining the most momentum recently. Indeed, the results of recent studies dealing with improving food safety, and several recent regulatory approvals of various commercial phage preparations developed for post-harvest food safety applications, strongly support the idea that lytic phages may provide a safe, environmentally-friendly, and effective approach for significantly reducing contamination of various foods with foodborne bacterial pathogens. However, some important technical and nontechnical problems may need to be addressed before phage biocontrol protocols can become an integral part of routine food safety intervention strategies implemented by food industries in the USA. © 2013 Society of Chemical Industry.

  12. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    Science.gov (United States)

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time.

    Science.gov (United States)

    Fonoff, Erich Talamoni; Azevedo, Angelo; Angelos, Jairo Silva Dos; Martinez, Raquel Chacon Ruiz; Navarro, Jessie; Reis, Paul Rodrigo; Sepulveda, Miguel Ernesto San Martin; Cury, Rubens Gisbert; Ghilardi, Maria Gabriela Dos Santos; Teixeira, Manoel Jacobsen; Lopez, William Omar Contreras

    2016-07-01

    OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional

  18. Loading the Saturn I S-IV Stage into Pregnant Guppy

    Science.gov (United States)

    1965-01-01

    The photograph shows the loading operation of the Saturn I S-IV stage (second stage) into the Pregnant Guppy at the Redstone Airfield, Huntsville, Alabama. The Pregnant Guppy was a Boeing B-377 Stratocruiser modified to transport various stages of Saturn launch vehicles. The modification project called for lengthening the fuselage to accommodate the S-IV stage. After the flight test of that modification, phase two called for the enlargement of the plane's cabin section to approximately double its normal volume. The fuselage separated just aft of the wing's trailing edge to load and unload the S-IV and other cargoes.

  19. 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

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

    OpenAIRE

    Giles, M.; Morley, N.; Baggs, E.M.; Daniell, T.J.

    2012-01-01

    The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium\\ud (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for\\ud the loss of nitrate (NO−\\ud 3 ) and production of the potent greenhouse gas, nitrous oxide (N2O).\\ud A number of factors are known to control these processes, including O2 concentrations and\\ud moisture content, N, C, pH, and the size and community structure of nitrate reducing organisms\\ud responsible for the ...

  1. Pegasus project. DLC coating and low viscosity oil reduce energy losses significantly

    Energy Technology Data Exchange (ETDEWEB)

    Doerwald, Dave; Jacobs, Ruud [Hauzer Techno Coating (Netherlands). Tribological Coatings

    2012-03-15

    Pegasus, the flying horse from Greek mythology, is a suitable name for the research project initiated by a German automotive OEM with participation of Hauzer Techno Coating and several automotive suppliers. It will enable future automotive vehicles to reduce fuel consumption without losing power. The project described in this article focuses on the rear differential, because reducing friction here can contribute considerably to efficiency improvement of the whole vehicle. Surfaces, coating and oil viscosity have been investigated and interesting conclusions have been reached. (orig.)

  2. 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...

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Madeline Eleanore Giles

    2012-12-01

    Full Text Available 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 cm 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.

  5. 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 ([Formula: see text]) and production of the potent greenhouse gas, nitrous oxide (N(2)O). A number of factors are known to control these processes, including O(2) 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 N(2)O production from soils.

  6. Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

    2003-01-01

    To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

  7. 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.

  8. 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.

  9. Significantly reduced c-axis thermal diffusivity of graphene-based papers

    Science.gov (United States)

    Han, Meng; Xie, Yangsu; Liu, Jing; Zhang, Jingchao; Wang, Xinwei

    2018-06-01

    Owing to their very high thermal conductivity as well as large surface-to-volume ratio, graphene-based films/papers have been proposed as promising candidates of lightweight thermal interface materials and lateral heat spreaders. In this work, we study the cross-plane (c-axis) thermal conductivity (k c ) and diffusivity (α c ) of two typical graphene-based papers, which are partially reduced graphene paper (PRGP) and graphene oxide paper (GOP), and compare their thermal properties with highly-reduced graphene paper and graphite. The determined α c of PRGP varies from (1.02 ± 0.09) × 10‑7 m2 s‑1 at 295 K to (2.31 ± 0.18) × 10‑7 m2 s‑1 at 12 K. This low α c is mainly attributed to the strong phonon scattering at the grain boundaries and defect centers due to the small grain sizes and high-level defects. For GOP, α c varies from (1.52 ± 0.05) × 10‑7 m2 s‑1 at 295 K to (2.28 ± 0.08) × 10‑7 m2 s‑1 at 12.5 K. The cross-plane thermal transport of GOP is attributed to the high density of functional groups between carbon layers which provide weak thermal transport tunnels across the layers in the absence of direct energy coupling among layers. This work sheds light on the understanding and optimizing of nanostructure of graphene-based paper-like materials for desired thermal performance.

  10. Inefficient Nef-mediated downmodulation of CD3 and MHC-I correlates with loss of CD4+T cells in natural SIV infection.

    Directory of Open Access Journals (Sweden)

    Michael Schindler

    2008-07-01

    Full Text Available Recent data suggest that Nef-mediated downmodulation of TCR-CD3 may protect SIVsmm-infected sooty mangabeys (SMs against the loss of CD4+ T cells. However, the mechanisms underlying this protective effect remain unclear. To further assess the role of Nef in nonpathogenic SIV infection, we cloned nef alleles from 11 SIVsmm-infected SMs with high (>500 and 15 animals with low (<500 CD4+ T-cells/microl in bulk into proviral HIV-1 IRES/eGFP constructs and analyzed their effects on the phenotype, activation, and apoptosis of primary T cells. We found that not only efficient Nef-mediated downmodulation of TCR-CD3 but also of MHC-I correlated with preserved CD4+ T cell counts, as well as with high numbers of Ki67+CD4+ and CD8+CD28+ T cells and reduced CD95 expression by CD4+ T cells. Moreover, effective MHC-I downregulation correlated with low proportions of effector and high percentages of naïve and memory CD8+ T cells. We found that T cells infected with viruses expressing Nef alleles from the CD4low SM group expressed significantly higher levels of the CD69, interleukin (IL-2 and programmed death (PD-1 receptors than those expressing Nefs from the CD4high group. SIVsmm Nef alleles that were less active in downmodulating TCR-CD3 were also less potent in suppressing the activation of virally infected T cells and subsequent cell death. However, only nef alleles from a single animal with very low CD4+ T cell counts rendered T cells hyper-responsive to activation, similar to those of HIV-1. Our data suggest that Nef may protect the natural hosts of SIV against the loss of CD4+ T cells by at least two mechanisms: (i downmodulation of TCR-CD3 to prevent activation-induced cell death and to suppress the induction of PD-1 that may impair T cell function and survival, and (ii downmodulation of MHC-I to reduce CTL lysis of virally infected CD4+ T cells and/or bystander CD8+ T cell activation.

  11. 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.

  12. 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.

  13. Technological significances to reduce the material problems. Feasibility of heat flux reduction

    International Nuclear Information System (INIS)

    Yamazaki, Seiichiro; Shimada, Michiya.

    1994-01-01

    For a divertor plate in a fusion power reactor, a high temperature coolant must be used for heat removal to keep thermal efficiency high. It makes the temperature and thermal stress of wall materials higher than the design limits. Issues of the coolant itself, e.g. burnout of high temperature water, will also become a serious problem. Sputtering erosion of the surface material will be a great concern of its lifetime. Therefore, it is necessary to reduce the heat and particle loads to the divertor plate technologically. The feasibility of some technological methods of heat reduction, such as separatrix sweeping, is discussed. As one of the most promising ideas, the methods of radiative cooling of the divertor plasma are summarized based on the recent results of large tokamaks. The feasibility of remote radiative cooling and gas divertor is discussed. The ideas are considered in recent design studies of tokamak power reactors and experimental reactors. By way of example, conceptual designs of divertor plate for the steady state tokamak power reactor are described. (author)

  14. 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......-four patients fulfilled our criteria for thrombolysis, but only the last 35 patients included received thrombolytic therapy. As thrombolysis was not available in our Department at the start of the study, the first 39 patients included were conservatively treated (controls). No significant differences...... in baseline clinical characteristics were found between the two groups. In-hospital atrial fibrillation and digoxin therapy was more prevalent in controls (P less than 0.05). During exercise, thrombolysed patients reached a higher maximal work capacity compared with controls: 160 +/- 41 vs 139 +/- 34 W (P...

  15. 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

    BACKGROUND: Selenium supplementation may decrease circulating thyroid autoantibodies in patients with chronic autoimmune thyroiditis (AIT), but the available trials are heterogenous. This study expands and critically reappraises the knowledge on this topic. METHODS: A literature search identified...... 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...... and LT4-untreated. Heterogeneity was estimated using I(2), and quality of evidence was assessed per outcome, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: In LT4-treated populations, the selenium group had significantly lower TPOAb levels after...

  16. 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)

  17. Ad libitum Mediterranean and Low Fat Diets both Significantly Reduce Hepatic Steatosis: a Randomized Controlled Trial.

    Science.gov (United States)

    Properzi, Catherine; O'Sullivan, Therese A; Sherriff, Jill L; Ching, Helena L; Jeffrey, Garry P; Buckley, Rachel F; Tibballs, Jonathan; MacQuillan, Gerry C; Garas, George; Adams, Leon A

    2018-05-05

    Although diet induced weight loss is first-line treatment for patients with non-alcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for either improvement in NAFLD or associated cardio-metabolic risk factors regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets [Mediterranean (MD) or Low Fat (LF)] on hepatic steatosis and cardio-metabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs LF). Hepatic steatosis was determined via magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 subjects completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat but lower carbohydrate and sodium intakes compared to LF subjects (pfat reduction between the groups (p=0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups [-1.6 (±2.1)kg in LF vs -2.1 (±2.5)kg in MD, (p=0.52)]. Within-group improvements in the Framingham risk score, total cholesterol, serum triglyceride, and HbA1c were observed in the MD (all pvs. 64%, p=0.048). Ad libitum low fat and Mediterranean diets both improve hepatic steatosis to a similar degree. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  18. 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.

  19. Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.

    Science.gov (United States)

    Jiang, Bin; Suen, Rachel; Wertheim, Jason A; Ameer, Guillermo A

    2016-12-12

    Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.

  20. Thyroid function appears to be significantly reduced in Space-borne MDS mice

    Science.gov (United States)

    Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

    It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH

  1. A brief history of the discovery of natural simian immunodeficiency virus (SIV) infections in captive sooty mangabey monkeys.

    Science.gov (United States)

    Gormus, Bobby J; Martin, Louis N; Baskin, Gary B

    2004-01-01

    Experimental leprosy studies using Mycobacterium leprae inoculum isolated from a sooty mangabey monkey (SMM) resulted in the accidental discovery that SMM's asymptomatically carry simian immunodeficiency virus (SIV) that is pathogenic in macaques. We showed that the SMM virus, SIVDelta, was antigenically related to SIVmac, which had been identified in macaques, and to the human immunodeficiency virus (HIV). Similar asymptomatic natural SIV infections had been reported in African green monkeys (AGM). Our results together with observations of others led us to propose that both SIVmac and SIVDelta originated in SMM and that SIV emerged in humans as a result of early African nonhuman primate SIV trans-species infections in humans.

  2. Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

    Science.gov (United States)

    Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

    2012-11-26

    Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (Pnow hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. 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.

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

    Science.gov (United States)

    Adnan, Sama; Reeves, R Keith; Gillis, Jacqueline; Wong, Fay E; Yu, Yi; Camp, Jeremy V; Li, Qingsheng; Connole, Michelle; Li, Yuan; Piatak, Michael; Lifson, Jeffrey D; Li, Wenjun; Keele, Brandon F; Kozlowski, Pamela A; Desrosiers, Ronald C; Haase, Ashley T; Johnson, R Paul

    2016-12-01

    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.

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

    Science.gov (United States)

    McCarthy, Kevin R; Johnson, Welkin E; Kirmaier, Andrea

    2016-01-01

    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.

  6. 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.

  7. 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.

  8. A novel CD4-conjugated ultraviolet light-activated photocatalyst inactivates HIV-1 and SIV efficiently.

    Science.gov (United States)

    Yamaguchi, Koushi; Sugiyama, Takahiro; Kato, Shinji; Kondo, Yoichi; Ageyama, Naohide; Kanekiyo, Masaru; Iwata, Misao; Koyanagi, Yoshio; Yamamoto, Naoki; Honda, Mitsuo

    2008-08-01

    In this study, we found that the electric potential derived from the redox reaction of ultraviolet (UV)-illuminated CD4-conjugated titanium dioxide (TiO2) inactivated a wide range of high-titered primary HIV-1 isolates, regardless of virus co-receptor usage or genetic clade. In vitro incubation of HIV-1 isolates with CD4-conjugated TiO2 (CD4-TiO2) followed by UV illumination led to inhibition of viral infectivity in both H9 cells and peripheral blood mononuclear cells as well as to the complete inactivation of plasma virions from HIV-1-infected individuals. Treatment with a newly established extra-corporeal circulation system with the photocatalyst in rhesus macaques completely inactivated plasma virus in the system and effectively reduced the infectious plasma viral load. Furthermore, plasma viremia and infectious viral loads were controlled following a second therapeutic photocatalyst treatment during primary SIV(mac239) infection of macaques. Our findings suggest that this therapeutic immunophysical strategy may help control human immunodeficiency viral infection in vivo.

  9. ACVP-02: Plasma SIV/SHIV RNA Viral Load Measurements through the AIDS and Cancer Virus Program Quantitative Molecular Diagnostics Core | Frederick National Laboratory for Cancer Research

    Science.gov (United States)

    The SIV plasma viral load assay performed by the Quantitative Molecular Diagnostics Core (QMDC) utilizes reagents specifically designed to detect and accurately quantify the full range of SIV/SHIV viral variants and clones in common usage in the rese

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.

    Directory of Open Access Journals (Sweden)

    Natalia Guerra-Pérez

    Full Text Available Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques, while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.

  15. 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.

    , PPDj-specific IFN-γ responses or positive PPDa or PPDb skin tests developed in vaccinees. Antibodies and cell-mediated immune responses were developed against FET11 antigens, however. At necropsy 8 or 12 months of age, relative Map burden was determined in a number of gut tissues by quantitative IS900...... 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......-γ assay responses from 40 to 52 weeks compared to non-vaccinated calves. These results indicate the FET11 vaccine can be used to accelerate eradication of paratuberculosis while surveillance or test-and-manage control programs for tuberculosis and Johne’s disease remain in place. Funded by EMIDA ERA...

  16. 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

    nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys-low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells-suggesting closer similarities with nonpathogenetic mechanisms evolved...

  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. 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.

  19. Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition.

    Science.gov (United States)

    Villareal, Dennis T; Kotyk, John J; Armamento-Villareal, Reina C; Kenguva, Venkata; Seaman, Pamela; Shahar, Allon; Wald, Michael J; Kleerekoper, Michael; Fontana, Luigi

    2011-02-01

    Calorie restriction (CR) reduces bone quantity but not bone quality in rodents. Nothing is known regarding the long-term effects of CR with adequate intake of vitamin and minerals on bone quantity and quality in middle-aged lean individuals. In this study, we evaluated body composition, bone mineral density (BMD), and serum markers of bone turnover and inflammation in 32 volunteers who had been eating a CR diet (approximately 35% less calories than controls) for an average of 6.8 ± 5.2 years (mean age 52.7 ± 10.3 years) and 32 age- and sex-matched sedentary controls eating Western diets (WD). In a subgroup of 10 CR and 10 WD volunteers, we also measured trabecular bone (TB) microarchitecture of the distal radius using high-resolution magnetic resonance imaging. We found that the CR volunteers had significantly lower body mass index than the WD volunteers (18.9 ± 1.2 vs. 26.5 ± 2.2 kg m(-2) ; P = 0.0001). BMD of the lumbar spine (0.870 ± 0.11 vs. 1.138 ± 0.12 g cm(-2) , P = 0.0001) and hip (0.806 ± 0.12 vs. 1.047 ± 0.12 g cm(-2) , P = 0.0001) was also lower in the CR than in the WD group. Serum C-terminal telopeptide and bone-specific alkaline phosphatase concentration were similar between groups, while serum C-reactive protein (0.19 ± 0.26 vs. 1.46 ± 1.56 mg L(-1) , P = 0.0001) was lower in the CR group. Trabecular bone microarchitecture parameters such as the erosion index (0.916 ± 0.087 vs. 0.877 ± 0.088; P = 0.739) and surface-to-curve ratio (10.3 ± 1.4 vs. 12.1 ± 2.1, P = 0.440) were not significantly different between groups. These findings suggest that markedly reduced BMD is not associated with significantly reduced bone quality in middle-aged men and women practicing long-term calorie restriction with adequate nutrition.

  20. 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)

  1. 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.

  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. Significant Association between Sulfate-Reducing Bacteria and Uranium-Reducing Microbial Communities as Revealed by a Combined Massively Parallel Sequencing-Indicator Species Approach▿ †

    Science.gov (United States)

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K.; Jardine, Philip M.; Zhou, Jizhong; Criddle, Craig S.; Marsh, Terence L.; Tiedje, James M.

    2010-01-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared. PMID:20729318

  4. Significant association between sulfate-reducing bacteria and uranium-reducing microbial communities as revealed by a combined massively parallel sequencing-indicator species approach.

    Science.gov (United States)

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K; Jardine, Philip M; Zhou, Jizhong; Criddle, Craig S; Marsh, Terence L; Tiedje, James M

    2010-10-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared.

  5. 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

  6. 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).

  7. Potent corticosteroid cream (mometasone furoate) significantly reduces acute radiation dermatitis: results from a double-blind, randomized study

    International Nuclear Information System (INIS)

    Bostroem, Aasa; Lindman, Henrik; Swartling, Carl; Berne, Berit; Bergh, Jonas

    2001-01-01

    Purpose: Radiation-induced dermatitis is a very common side effect of radiation therapy, and may necessitate interruption of the therapy. There is a substantial lack of evidence-based treatments for this condition. The aim of this study was to investigate the effect of mometasone furoate cream (MMF) on radiation dermatitis in a prospective, double-blind, randomized study. Material and methods: The study comprised 49 patients with node-negative breast cancer. They were operated on with sector resection and scheduled for postoperative radiotherapy using photons with identical radiation qualities and dosage to the breast parenchyma. The patients were randomized to receive either MMF or emollient cream. The cream was applied on the irradiated skin twice a week from the start of radiotherapy until the 12th fraction (24 Gy) and thereafter once daily until 3 weeks after completion of radiation. Both groups additionally received non-blinded emollient cream daily. The intensity of the acute radiation dermatitis was evaluated on a weekly basis regarding erythema and pigmentation, using a reflectance spectrophotometer together with visual scoring of the skin reactions. Results: MMF in combination with emollient cream treatment significantly decreased acute radiation dermatitis (P=0.0033) compared with emollient cream alone. There was no significant difference in pigmentation between the two groups. Conclusions: Adding MMF, a potent topical corticosteroid, to an emollient cream is statistically significantly more effective than emollient cream alone in reducing acute radiation dermatitis

  8. 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)

  9. 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.

  10. Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: efficacy against repeated mucosal R5 clade C SHIV challenges.

    Science.gov (United States)

    Lakhashe, Samir K; Velu, Vijayakumar; Sciaranghella, Gaia; Siddappa, Nagadenahalli B; Dipasquale, Janet M; Hemashettar, Girish; Yoon, John K; Rasmussen, Robert A; Yang, Feng; Lee, Sandra J; Montefiori, David C; Novembre, Francis J; Villinger, François; Amara, Rama Rao; Kahn, Maria; Hu, Shiu-Lok; Li, Sufen; Li, Zhongxia; Frankel, Fred R; Robert-Guroff, Marjorie; Johnson, Welkin E; Lieberman, Judy; Ruprecht, Ruth M

    2011-08-05

    We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239 gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus > 90%; these RM also had strong SIV Gag-specific proliferation of CD8⁺ T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the α4β7-expressing CD4⁺ T cells; the latter have been implicated as preferential virus targets in vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Walking with a four wheeled walker (rollator) significantly reduces EMG lower-limb muscle activity in healthy subjects.

    Science.gov (United States)

    Suica, Zorica; Romkes, Jacqueline; Tal, Amir; Maguire, Clare

    2016-01-01

    To investigate the immediate effect of four-wheeled- walker(rollator)walking on lower-limb muscle activity and trunk-sway in healthy subjects. In this cross-sectional design electromyographic (EMG) data was collected in six lower-limb muscle groups and trunk-sway was measured as peak-to-peak angular displacement of the centre-of-mass (level L2/3) in the sagittal and frontal-planes using the SwayStar balance system. 19 subjects walked at self-selected speed firstly without a rollator then in randomised order 1. with rollator 2. with rollator with increased weight-bearing. Rollator-walking caused statistically significant reductions in EMG activity in lower-limb muscle groups and effect-sizes were medium to large. Increased weight-bearing increased the effect. Trunk-sway in the sagittal and frontal-planes showed no statistically significant difference between conditions. Rollator-walking reduces lower-limb muscle activity but trunk-sway remains unchanged as stability is likely gained through forces generated by the upper-limbs. Short-term stability is gained but the long-term effect is unclear and requires investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Cerebral Embolic Protection During Transcatheter Aortic Valve Replacement Significantly Reduces Death and Stroke Compared With Unprotected Procedures.

    Science.gov (United States)

    Seeger, Julia; Gonska, Birgid; Otto, Markus; Rottbauer, Wolfgang; Wöhrle, Jochen

    2017-11-27

    The aim of this study was to evaluate the impact of cerebral embolic protection on stroke-free survival in patients undergoing transcatheter aortic valve replacement (TAVR). Imaging data on cerebral embolic protection devices have demonstrated a significant reduction in number and volume of cerebral lesions. A total of 802 consecutive patients were enrolled. The Sentinel cerebral embolic protection device (Claret Medical Inc., Santa Rosa, California) was used in 34.9% (n = 280) of consecutive patients. In 65.1% (n = 522) of patients TAVR was performed in the identical setting except without cerebral embolic protection. Neurological follow-up was done within 7 days post-procedure. The primary endpoint was a composite of all-cause mortality or all-stroke according to Valve Academic Research Consortium-2 criteria within 7 days. Propensity score matching was performed to account for possible confounders. Both filters of the device were successfully positioned in 280 of 305 (91.8%) consecutive patients. With use of cerebral embolic protection rate of disabling and nondisabling stroke was significantly reduced from 4.6% to 1.4% (p = 0.03; odds ratio: 0.29, 95% confidence interval: 0.10 to 0.93) in the propensity-matched population (n = 560). The primary endpoint occurred significantly less frequently, with 2.1% (n = 6 of 280) in the protected group compared with 6.8% (n = 19 of 280) in the control group (p = 0.01; odds ratio: 0.30; 95% confidence interval: 0.12 to 0.77). In multivariable analysis Society of Thoracic Surgeons score for mortality (p = 0.02) and TAVR without protection (p = 0.02) were independent predictors for the primary endpoint. In patients undergoing TAVR use of a cerebral embolic protection device demonstrated a significant higher rate of stroke-free survival compared with unprotected TAVR. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans.

    Science.gov (United States)

    Opländer, Christian; Volkmar, Christine M; Paunel-Görgülü, Adnana; Fritsch, Thomas; van Faassen, Ernst E; Mürtz, Manfred; Grieb, Gerrit; Bozkurt, Ahmet; Hemmrich, Karsten; Windolf, Joachim; Suschek, Christoph V

    2012-02-15

    Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. 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.

  19. 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.

  20. 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.

  1. Intradermal immunization with inactivated swine influenza virus and adjuvant polydi(sodium carboxylatoethylphenoxy)phosphazene (PCEP) induced humoral and cell-mediated immunity and reduced lung viral titres in pigs.

    Science.gov (United States)

    Magiri, Royford; Lai, Ken; Chaffey, Alyssa; Zhou, Yan; Pyo, Hyun-Mi; Gerdts, Volker; Wilson, Heather L; Mutwiri, George

    2018-03-14

    Swine influenza virus is endemic worldwide and it is responsible for significant economic losses to the swine industry. A vaccine that stimulates a rapid and long-lasting protective immune response to prevent this infection is highly sought. Poly[di(sodium carboxylatoethylphenoxy)-phosphazene (PCEP) has demonstrated adjuvant activity when formulated as part of multiple vaccines in mice and pigs. In this study we examined the magnitude and type of immune response induced in pigs vaccinated via the intramuscular or intradermal routes with inactivated swine influenza virus (SIV) H1N1 vaccine formulated with PCEP. Intradermal administration of PCEP-adjuvanted inactivated SIV vaccine stimulated significant anti-SIV antibody titres, increased neutralizing antibodies, and significantly reduced lung virus load with limited reduction of gross lung lesions after challenge with virulent H1N1 relative to control animals. These results indicate that PCEP may be effective as a vaccine adjuvant against swine influenza viruses in pigs and should be considered a potential candidate adjuvant for future swine intradermal influenza vaccines. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. 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.

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

    Science.gov (United States)

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

    2013-06-01

    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, 550 mA (450-600) vs. 650 mA (500-711.25) (median (interquartile range)), respectively, P ASIR group compared with FBP group, 4.29 mSv (2.84-6.02) vs. 5.84 mSv (3.88-8.39) (median (interquartile range)), respectively, P ASIR was associated with increased image noise compared with FBP (39.93 ± 10.22 vs. 37.63 ± 18.79 (mean ± standard deviation), respectively, P ASIR reduces the radiation dose of CCTA without affecting the image quality. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

  4. Secukinumab Significantly Reduces Psoriasis-Related Work Impairment and Indirect Costs Compared With Ustekinumab and Etanercept in the United Kingdom.

    Science.gov (United States)

    Warren, R B; Halliday, A; Graham, C N; Gilloteau, I; Miles, L; McBride, D

    2018-05-30

    Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown. To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK). This was a post hoc analysis of work impairment data collected in the CLEAR study (secukinumab vs. ustekinumab) and applied to the FIXTURE study (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (1) overall work impairment derived from Work Productivity and Activity Impairment data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (2) weekly/annual work productivity loss by PASI response level; (3) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (4) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients in CLEAR at Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different timepoints and with patient cohorts, including FIXTURE. In CLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higher PASI: PASI hours; PASI 50-74: 13.3%/4.45 hours; PASI 75-89: 6.4%/2.14 hours; PASI ≥90: 4.9%/1.65 hours. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12; P=0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17; Ρreduced work impairment and associated indirect costs of psoriasis compared with ustekinumab and etanercept at Week 16 through 52 in the UK. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Epithelium-innate immune cell axis in mucosal responses to SIV.

    Science.gov (United States)

    Shang, L; Duan, L; Perkey, K E; Wietgrefe, S; Zupancic, M; Smith, A J; Southern, P J; Johnson, R P; Haase, A T

    2017-03-01

    In the SIV (simian immunodeficiency virus)-rhesus macaque model of HIV-1 (human immunodeficiency virus type I) transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T-cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T-cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T-cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment, and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Vaccination of pigs two weeks before infection significantly reduces transmission of foot-and-mouth disease virus

    NARCIS (Netherlands)

    Eble, P.L.; Bouma, A.; Bruin, de M.G.M.; Hemert-Kluitenberg, van F.; Oirschot, van J.T.; Dekker, A.

    2004-01-01

    The objective of this study was to investigate whether and at what time interval could vaccination reduce transmission of foot-and-Mouth disease virus (FMDV) among pigs. Reduction of virus transmission by vaccination was determined experimentally. Transmission of FMDV was studied in three groups of

  11. 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

    , 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...... significance of class separations downstream of dimensionality reduction algorithms. In addition, we demonstrate the design and utility of the ClusterSignificance package and utilize it to determine the importance of long non-coding RNA expression in the identity of multiple hematological malignancies....

  12. 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.

  13. The Source Inversion Validation (SIV) Initiative: A Collaborative Study on Uncertainty Quantification in Earthquake Source Inversions

    Science.gov (United States)

    Mai, P. M.; Schorlemmer, D.; Page, M.

    2012-04-01

    Earthquake source inversions image the spatio-temporal rupture evolution on one or more fault planes using seismic and/or geodetic data. Such studies are critically important for earthquake seismology in general, and for advancing seismic hazard analysis in particular, as they reveal earthquake source complexity and help (i) to investigate earthquake mechanics; (ii) to develop spontaneous dynamic rupture models; (iii) to build models for generating rupture realizations for ground-motion simulations. In applications (i - iii), the underlying finite-fault source models are regarded as "data" (input information), but their uncertainties are essentially unknown. After all, source models are obtained from solving an inherently ill-posed inverse problem to which many a priori assumptions and uncertain observations are applied. The Source Inversion Validation (SIV) project is a collaborative effort to better understand the variability between rupture models for a single earthquake (as manifested in the finite-source rupture model database) and to develop robust uncertainty quantification for earthquake source inversions. The SIV project highlights the need to develop a long-standing and rigorous testing platform to examine the current state-of-the-art in earthquake source inversion, and to develop and test novel source inversion approaches. We will review the current status of the SIV project, and report the findings and conclusions of the recent workshops. We will briefly discuss several source-inversion methods, how they treat uncertainties in data, and assess the posterior model uncertainty. Case studies include initial forward-modeling tests on Green's function calculations, and inversion results for synthetic data from spontaneous dynamic crack-like strike-slip earthquake on steeply dipping fault, embedded in a layered crustal velocity-density structure.

  14. 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...... characterized by a significant containment of bacterial burden in gut tissues compared to non-vaccinated animals. There was no cross-reaction with bovine tuberculosis in vaccinated animals. This novel multi-stage vaccine has the potential to become a marker vaccine for paratuberculosis....

  15. Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance.

    Science.gov (United States)

    Tian, Mengqian; Chen, Ruoyu; Li, Tianwen; Xiao, Bingxiu

    2018-03-01

    Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about circRNAs' diagnostic values for gastric cancer, one of the worldwide most common diseases of mortality. The hsa_circ_0003159 levels in 108 paired gastric cancer tissues and adjacent non-tumorous tissues from surgical patients with gastric cancer were first detected by real-time quantitative reverse transcription-polymerase chain reaction. Then, the relationships between hsa_circ_0003159 expression levels in gastric cancer tissues and the clinicopathological factors of patients with gastric cancer were analyzed. Finally, its diagnostic value was evaluated through the receiver operating characteristic curve. Compared with paired adjacent non-tumorous tissues, hsa_circ_0003159 expression was significantly down-regulated in gastric cancer tissues. What is more, we found that hsa_circ_0003159 expression levels were significantly negatively associated with gender, distal metastasis, and tumor-node-metastasis stage. All of the results suggest that hsa_circ_0003159 may be a potential cancer marker of patients with gastric cancer. © 2017 Wiley Periodicals, Inc.

  16. β-Hydroxy-β-methylbutyrate (HMB) supplementation and resistance exercise significantly reduce abdominal adiposity in healthy elderly men.

    Science.gov (United States)

    Stout, Jeffrey R; Fukuda, David H; Kendall, Kristina L; Smith-Ryan, Abbie E; Moon, Jordan R; Hoffman, Jay R

    2015-04-01

    The effects of 12-weeks of HMB ingestion and resistance training (RT) on abdominal adiposity were examined in 48 men (66-78 yrs). All participants were randomly assigned to 1 of 4 groups: no-training placebo (NT-PL), HMB only (NT-HMB), RT with PL (RT-PL), or HMB with RT (RT-HMB). DXA was used to estimate abdominal fat mass (AFM) by placing the region of interest over the L1-L4 region of the spine. Outcomes were assessed by ANCOVA, with Bonferroni-corrected pairwise comparisons. Baseline AFM values were used as the covariate. The ANCOVA indicated a significant difference (p = 0.013) between group means for the adjusted posttest AFM values (mean (kg) ± SE: NT-PL = 2.59 ± 0.06; NT-HMB = 2.59 ± 0.61; RT-PL = 2.59 ± 0.62; RT-HMB = 2.34 ± 0.61). The pairwise comparisons indicated that AFM following the intervention period in the RT-HMB group was significantly less than NT-PL (p = 0.013), NT-HMB (p = 0.011), and RT-PL (p = 0.010). These data suggested that HMB in combination with 12 weeks of RT decreased AFM in elderly men. Copyright © 2015. Published by Elsevier Inc.

  17. Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

    Science.gov (United States)

    Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

    2013-01-01

    The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

  18. 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.

  19. 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.

  20. Postoperative Stiffness Requiring Manipulation Under Anesthesia Is Significantly Reduced After Simultaneous Versus Staged Bilateral Total Knee Arthroplasty.

    Science.gov (United States)

    Meehan, John P; Monazzam, Shafagh; Miles, Troy; Danielsen, Beate; White, Richard H

    2017-12-20

    adjust for relevant risk factors, the 90-day odds ratio (OR) of undergoing manipulation after simultaneous bilateral TKA was significantly lower than that for unilateral TKA (OR = 0.70; 95% confidence interval [CI], 0.57 to 0.86) and staged bilateral TKA (OR = 0.71; 95% CI, 0.57 to 0.90). Similarly, at 180 days, the odds of undergoing manipulation were significantly lower after simultaneous bilateral TKA than after both unilateral TKA (OR = 0.71; 95% CI, 0.59 to 0.84) and staged bilateral TKA (OR = 0.76; 95% CI, 0.63 to 0.93). The frequency of manipulation was significantly associated with younger age, fewer comorbidities, black race, and the absence of obesity. Although the ORs were small (close to 1), simultaneous bilateral TKA had a significantly decreased rate of stiffness requiring manipulation under anesthesia at 90 days and 180 days after knee replacement compared with that after staged bilateral TKA and unilateral TKA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

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

    Energy Technology Data Exchange (ETDEWEB)

    Alex, Sruthi Ann; Rajiv, Sundaramoorthy [Centre for Nanobiotechnology, VIT University, Vellore (India); Chakravarty, Sujay [UGC-DAE CSR, Kalpakkam, Node, Kokilamedu (India); Chandrasekaran, N. [Centre for Nanobiotechnology, VIT University, Vellore (India); Mukherjee, Amitava, E-mail: amit.mookerjea@gmail.com [Centre for Nanobiotechnology, VIT University, Vellore (India)

    2017-02-01

    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.

  2. 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.

  3. [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

  4. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

    Directory of Open Access Journals (Sweden)

    Sandrine Peruchon

    Full Text Available BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART. Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.. We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-CD27(+ B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid

  5. Weight loss significantly reduces serum lipocalin-2 levels in overweight and obese women with polycystic ovary syndrome.

    Science.gov (United States)

    Koiou, Ekaterini; Tziomalos, Konstantinos; Katsikis, Ilias; Kandaraki, Eleni A; Kalaitzakis, Emmanuil; Delkos, Dimitrios; Vosnakis, Christos; Panidis, Dimitrios

    2012-01-01

    Serum lipocalin-2 levels are elevated in obese patients. We assessed serum lipocalin-2 levels in polycystic ovary syndrome (PCOS) and the effects of weight loss or metformin on these levels. Forty-seven overweight/obese patients with PCOS [body mass index (BMI) >27 kg/m(2)] were instructed to follow a low-calorie diet, to exercise and were given orlistat or sibutramine for 6 months. Twenty-five normal weight patients with PCOS (BMI weight and 25 overweight/obese healthy female volunteers comprised the control groups. Serum lipocalin-2 levels did not differ between overweight/obese patients with PCOS and overweight/obese controls (p = 0.258), or between normal weight patients with PCOS and normal weight controls (p = 0.878). Lipocalin-2 levels were higher in overweight/obese patients with PCOS than in normal weight patients with PCOS (p weight loss resulted in a fall in lipocalin-2 levels (p weight patients with PCOS, treatment with metformin did not affect lipocalin-2 levels (p = 0.484). In conclusion, PCOS per se is not associated with elevated lipocalin-2 levels. Weight loss induces a significant reduction in lipocalin-2 levels in overweight/obese patients with PCOS.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Influence of NO2 and metal ions on oxidation of aqueous-phase S(IV in atmospheric concentrations

    Directory of Open Access Journals (Sweden)

    Cláudia R. Martins

    2008-06-01

    Full Text Available An investigation was made of the influence of atmospheric concentrations (15 or 130 ppbv of NO2 on the aqueous-phase oxidation rate of S(IV in the presence and absence of Fe(III, Mn(II and Cr(VI metal ions under controlled experimental conditions (pH, T, concentration of reactants, etc.. The reaction rate in the presence of the NO2 flow was slower than the reaction rate using only clean air with an initial S(IV concentration of 10-4 mol/L. NO2 appears to react with S(IV, producing a kind of inhibitor that slows down the reaction. Conversely, tenfold lower concentrations of S(IV ([S(IV]º = 10-5 mol/L caused a faster reaction in the presence of NO2 than the reaction using purified air. Under these conditions, therefore, the equilibrium shifts to sulfate formation. With the addition of Fe(III, Mn(II or Cr(VI in the presence of a NO2 flow, the reaction occurred faster under all the conditions in which S(IV oxidation was investigated.A reação de oxidação de S(IV em fase aquosa foi estudada em laboratório em presença de NO2 dos íons metálicos Fe(III, Mn(II, e Cr(VI sob condições experimentais controladas (pH, T, concentração dos reagentes, etc.. Na presença de corrente de ar com NO2 (15 ou 130 ppbv a reação de oxidação de S(IV ocorreu mais lentamente do que na presença de ar purificado, para uma concentração inicial de S(IV de 10-4 mol/L. Ao contrário, para concentração inicial de S(IV dez vezes menor ([S(IV]° = 10-5 mol/L a reação ocorreu mais rapidamente na presença de NO2. A explicação está relacionada com o equilíbrio envolvendo a formação de espécies intermediárias de longa vida, que impedem o prosseguimento da reação, porém a depender das concentrações relativas de S(IV e NO2, essas espécies se decompõem deslocando o equilíbrio no sentido de formação de sulfato. A adição dos íons Fe(III, Mn(II ou Cr(VI em presença de corrente de ar com NO2 indicou atividade catalítica para esses íons, em todas

  8. Determining the Structure of an Unliganded and Fully Glycosylated SIV gp120 Envelope Glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Bing; Vogan, Erik M.; Gong, Haiyun; Skehel, John J.; Wiley, Don C.; Harrison, Stephen C. (Harvard-Med); (NIMR)

    2010-07-13

    HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 {angstrom} resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.

  9. 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.

  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. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

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

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    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

  17. Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA

    International Nuclear Information System (INIS)

    Buckley, Kathleen A.; Li Peilin; Khimani, Anis H.; Hofmann-Lehmann, Regina; Liska, Vladimir; Anderson, Daniel C.; McClure, Harold M.; Ruprecht, Ruth M.

    2003-01-01

    The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVΔ3 (the live attenuated vaccine strain derived from SIVmac239), or SIVΔ3+ (a pathogenic progeny virus that had evolved from SIVΔ3). All six monkeys developed immunodeficiency and progressed to fatal disease. Although many divergent mutations arose in env among the different hosts, three regions consistently mutated in all monkeys studied; these similar mutations developed independently even though the animals had received only a single infectious molecular clone rather than standard viral inocula that contain viral quasispecies. Together, these data indicate that the env genes of SIVmac239, SIVΔ3, and SIVΔ3+, in the context of different proviral backbones, evolve similarly in different hosts during disease progression

  18. 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.

  19. 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.

  20. Spatially Controlled Fabrication of Brightly Fluorescent Nanodiamond-Array with Enhanced Far-Red Si-V Luminescence

    Science.gov (United States)

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

    2014-01-01

    We demonstrate a novel approach to precise 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 scanning probe “Dip-Pen” nanolithography technique using electrostatically-driven transfer of nanodiamonds from “inked” cantilevers to a UV-treated hydrophilic SiO2 substrate. The enhanced emission from nanodiamond-dots in the far-red is achieved by incorporating Si-V defect centers in subsequent chemical vapor deposition treatment. The development of a suitable nanodiamond ink, mechanism of ink transport, and effect of humidity, 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, 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, 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 the next generation fluorescent based devices and applications. PMID:24394286

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

    Science.gov (United States)

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

    2014-01-31

    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 SiO2 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.

  2. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir

    2013-01-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during...... the perinatal period. Pregnant Wistar rats were administered a 200mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND...

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats.

    Science.gov (United States)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir; Bock, Elisabeth

    2013-07-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during the perinatal period. Pregnant Wistar rats were administered a 200 mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND40 but no effect of prenatal prochloraz exposure on social investigation or acquisition of social-olfactory memory. Copyright © 2012 Elsevier GmbH. All rights reserved.

  9. 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

  10. 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.

  11. 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.’

  12. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2016-02-01

    group (P=0.0123. There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596, 2-year (P=0.8620, 5-year (P=0.2737, or overall follow-up mortality after HTX (P=0.1049. Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786.Conclusion: Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with increased mortality after HTX. Keywords: amiodarone, atrial fibrillation, heart failure, heart transplantation, mortality

  13. 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.

  14. 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.

  15. Gene expression of Lactobacillus plantarum and the commensal microbiota in the ileum of healthy and early SIV-infected rhesus macaques

    Science.gov (United States)

    Golomb, Benjamin L.; Hirao, Lauren A.; Dandekar, Satya; Marco, Maria L.

    2016-01-01

    Chronic HIV infection results in impairment of gut-associated lymphoid tissue leading to systemic immune activation. We previously showed that in early SIV-infected rhesus macaques intestinal dysfunction is initiated with the induction of the IL-1β pathway in the small intestine and reversed by treatment with an exogenous Lactobacillus plantarum strain. Here, we provide evidence that the transcriptomes of L. plantarum and ileal microbiota are not altered shortly after SIV infection. L. plantarum adapts to the small intestine by expressing genes required for tolerating oxidative stress, modifying cell surface composition, and consumption of host glycans. The ileal microbiota of L. plantarum-containing healthy and SIV+ rhesus macaques also transcribed genes for host glycan metabolism as well as for cobalamin biosynthesis. Expression of these pathways by bacteria were proposed but not previously demonstrated in the mammalian small intestine. PMID:27102350

  16. 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)

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

    International Nuclear Information System (INIS)

    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine; Venzon, David; Brocca-Cofano, Egidio; DiPasquale, Janet; Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit; Sui, Yongjun; Berzofsky, Jay A.; Liu, Linda; Langermann, Solomon; Robert-Guroff, Marjorie

    2013-01-01

    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 hi expressing T cells and Tregs in PBMCs, and PD-1 hi Tregs in lymph nodes. It transiently decreased expression of Ki67 and α 4 β 7 in PBMC CD4 + and CD8 + Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1 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 hi cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1 hi cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire

  18. Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry.

    Directory of Open Access Journals (Sweden)

    Rachid Sougrat

    2007-05-01

    Full Text Available The envelope glycoproteins of primate lentiviruses, including human and simian immunodeficiency viruses (HIV and SIV, are heterodimers of a transmembrane glycoprotein (usually gp41, and a surface glycoprotein (gp120, which binds CD4 on target cells to initiate viral entry. We have used electron tomography to determine the three-dimensional architectures of purified SIV virions in isolation and in contact with CD4+ target cells. The trimeric viral envelope glycoprotein surface spikes are heterogeneous in appearance and typically approximately 120 A long and approximately 120 A wide at the distal end. Docking of SIV or HIV-1 on the T cell surface occurs via a neck-shaped contact region that is approximately 400 A wide and consistently consists of a closely spaced cluster of five to seven rod-shaped features, each approximately 100 A long and approximately 100 A wide. This distinctive structure is not observed when viruses are incubated with T lymphocytes in the presence of anti-CD4 antibodies, the CCR5 antagonist TAK779, or the peptide entry inhibitor SIVmac251 C34. For virions bound to cells, few trimers were observed away from this cluster at the virion-cell interface, even in cases where virus preparations showing as many as 70 envelope glycoprotein trimers per virus particle were used. This contact zone, which we term the "entry claw", provides a spatial context to understand the molecular mechanisms of viral entry. Determination of the molecular composition and structure of the entry claw may facilitate the identification of improved drugs for the inhibition of HIV-1 entry.

  19. 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.

  20. Myocardial fatty acid imaging with 123I-BMIPP in patients with chronic right ventricular pressure overload. Clinical significance of reduced uptake in interventricular septum

    International Nuclear Information System (INIS)

    Hori, Yoshiro; Ishida, Yoshio; Fukuchi, Kazuki; Hayashida, Kouhei; Takamiya, Makoto

    2002-01-01

    Regionally reduced 123 I-beta-methyliodophenyl pentadecanoic acid (123I-BMIPP) uptake in the interventricular septum (SEP) is observed in some patients with chronic right ventricular (RV) pressure overload. We studied the significance of this finding by comparing it with mean pulmonary arterial pressure (mPAP). 123 I-BMIPP SPECT imaging was carried out in 21 patients with pulmonary hypertension (PH; 51+-14 years; 11 men and 10 women; 7 with primary pulmonary hypertension, 11 with pulmonary thromboembolism, and 3 with atrial septal defect). mPAP ranged from 25 to 81 mmHg (49±16 mmHg). Using a midventricular horizontal long-axis plane, regional BMIPP distributions in the RV free wall and SEP were estimated by referring to those in the LV free wall. Count ratios of the RV free wall and SEP to the LV free wall (RV/LV, SEP/LV) were determined by ROI analysis. RV/LV showed a linear correlation with mPAP (r=0.42). However, SEP/LV was inversely correlated with mPAP (r=-0.49). When SEP/RV was compared among three regions of SEP in each patient, basal SEP/RV was most sensitively decreased in response to increased mPAP (r=-0.70). These results suggest that the assessment of septal tracer uptake in 123 I-BMIPP SPECT imaging is useful for evaluating the severity of RV pressure overload in patients with PH. (author)

  1. Oxidation of S(IV) in Seawater by Pulsed High Voltage Discharge Plasma with TiO2/Ti Electrode as Catalyst

    Science.gov (United States)

    Gong, Jianying; Zhang, Xingwang; Wang, Xiaoping; Lei, Lecheng

    2013-12-01

    Oxidation of S(IV) to S(VI) in the effluent of a flue gas desulfurization(FGD) system is very critical for industrial applications of seawater FGD. This paper reports a pulsed corona discharge oxidation process combined with a TiO2 photocatalyst to convert S(IV) to S(VI) in artificial seawater. Experimental results show that the oxidation of S(IV) in artificial seawater is enhanced in the pulsed discharge plasma process through the application of TiO2 coating electrodes. The oxidation rate of S(IV) using Ti metal as a ground electrode is about 2.0×10-4 mol · L-1 · min-1, the oxidation rate using TiO2/Ti electrode prepared by annealing at 500°C in air is 4.5×10-4 mol · L-1 · min-1, an increase with a factor 2.25. The annealing temperature for preparing TiO2/Ti electrode has a strong effect on the oxidation of S(IV) in artificial seawater. The results of in-situ emission spectroscopic analysis show that chemically active species (i.e. hydroxyl radicals and oxygen radicals) are produced in the pulsed discharge plasma process. Compared with the traditional air oxidation process and the sole plasma-induced oxidation process, the combined application of TiO2 photocatalysts and a pulsed high-voltage electrical discharge process is useful in enhancing the energy and conversion efficiency of S(IV) for the seawater FGD system.

  2. 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

  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. 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

  5. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Youjun [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Qi, Jianxun [Graduate School, Chinese Academy of Sciences, Beijing (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Zhang, Huimin; Wang, Jinzi [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Liu, Jinhua [College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Jiang, Fan [Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Gao, Feng, E-mail: gaofeng@im.ac.cn [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

    2006-01-01

    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{sub 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.

  7. Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors, similar to human DC-SIGN

    NARCIS (Netherlands)

    Geijtenbeek, T. B.; Koopman, G.; van Duijnhoven, G. C.; van Vliet, S. J.; van Schijndel, A. C.; Engering, A.; Heeney, J. L.; van Kooyk, Y.

    2001-01-01

    Dendritic cells (DC) have been implicated in the pathogenesis of both human and simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by DC. Abundant expression in lymphoid tissues also implies a

  8. The Secretion of IL-22 from Mucosal NKp44+ NK Cells Is Associated with Microbial Translocation and Virus Infection in SIV/SHIV-Infected Chinese Macaques

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2014-01-01

    Full Text Available Microbial translocation (MT causes systemic immune activation in chronic human immunodeficiency virus (HIV infection. The role of a novel subtype of innate lymphoid cells, the NKp44+ NK cells, in HIV/simian immunodeficiency virus- (SIV- induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV- infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44+ NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44+ NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44+ NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44+ NK cells and interleukin-22 (IL-22 secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44+ NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.

  9. 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.; Bustamante, Eduardo A.; Bortell, Nikki; Morsey, Brenda; Fox, Howard S.; Ravasi, Timothy; Marcondes, Maria Cecilia Garibaldi

    2016-01-01

    /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

  10. 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; Bustamante, Eduardo; Bortell, Nikki; Morsey, Brenda; Fox, Howard; Ravasi, Timothy; Marcondes, Maria

    2016-01-01

    /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

  11. 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...

  12. Viral CTL escape mutants are generated in lymph nodes and subsequently become fixed in plasma and rectal mucosa during acute SIV infection of macaques.

    Directory of Open Access Journals (Sweden)

    Thomas H Vanderford

    2011-05-01

    Full Text Available SIV(mac239 infection of rhesus macaques (RMs results in AIDS despite the generation of a strong antiviral cytotoxic T lymphocyte (CTL response, possibly due to the emergence of viral escape mutants that prevent recognition of infected cells by CTLs. To determine the anatomic origin of these SIV mutants, we longitudinally assessed the presence of CTL escape variants in two MamuA*01-restricted immunodominant epitopes (Tat-SL8 and Gag-CM9 in the plasma, PBMCs, lymph nodes (LN, and rectal biopsies (RB of fifteen SIV(mac239-infected RMs. As expected, Gag-CM9 did not exhibit signs of escape before day 84 post infection. In contrast, Tat-SL8 escape mutants were apparent in all tissues by day 14 post infection. Interestingly LNs and plasma exhibited the highest level of escape at day 14 and day 28 post infection, respectively, with the rate of escape in the RB remaining lower throughout the acute infection. The possibility that CTL escape occurs in LNs before RBs is confirmed by the observation that the specific mutants found at high frequency in LNs at day 14 post infection became dominant at day 28 post infection in plasma, PBMC, and RB. Finally, the frequency of escape mutants in plasma at day 28 post infection correlated strongly with the level Tat-SL8-specific CD8 T cells in the LN and PBMC at day 14 post infection. These results indicate that LNs represent the primary source of CTL escape mutants during the acute phase of SIV(mac239 infection, suggesting that LNs are the main anatomic sites of virus replication and/or the tissues in which CTL pressure is most effective in selecting SIV escape variants.

  13. Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.

    Science.gov (United States)

    Downey, Luke A; Sands, Helen; Jones, Lewis; Clow, Angela; Evans, Phil; Stalder, Tobias; Parrott, Andrew C

    2015-05-01

    The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users. Copyright © 2015 John Wiley & Sons, Ltd.

  14. 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.

  15. 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.)

  16. 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...... units), oxLDL (44.9 (26.9 - 75.1) vs. 36.1 (23.4 - 55.5) U/l), and hsCRP (0.26 (0.03 - 2.41) vs. 0.12 (0.02 - 0.81) mg/dl) were significantly increased in PCOS patients vs. controls (geometric mean (+/- 2SD)). In PCOS, positive correlations were found between central fat mass and sCD36 (r=0.43), hs......CRP (r=0.43), and IL-6 (r=0.42), all pPCOS patients and controls (n=44). sCD36 and oxLDL were significant...

  17. 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.

  18. 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

  19. Reduced estimated glomerular filtration rate (eGFR 73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

    Science.gov (United States)

    Blute, Michael L; Kucherov, Victor; Rushmer, Timothy J; Damodaran, Shivashankar; Shi, Fangfang; Abel, E Jason; Jarrard, David F; Richards, Kyle A; Messing, Edward M; Downs, Tracy M

    2017-09-01

    To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) 73 m 2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of 73 m 2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 27% for patients with an eGFR of 73 m 2 (P 73 m 2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 71% for patients with an eGFR of 73 m 2 (P = 0.01). Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  20. Intra-articular laser treatment plus Platelet Rich Plasma (PRP) significantly reduces pain in many patients who had failed prior PRP treatment

    Science.gov (United States)

    Prodromos, Chadwick C.; Finkle, Susan; Dawes, Alexander; Dizon, Angelo

    2018-02-01

    INTRODUCTION: In our practice Platelet Rich Plasma (PRP) injections effectively reduce pain in most but not all arthritic patients. However, for patients who fail PRP treatment, no good alternative currently exists except total joint replacement surgery. Low level laser therapy (LLLT) on the surface of the skin has not been helpful for arthritis patients in our experience. However, we hypothesized that intra-articular laser treatment would be an effective augmentation to PRP injection and would increase its efficacy in patients who had failed prior PRP injection alone. METHODS: We offered Intra-articular Low Level Laser Therapy (IAL) treatment in conjunction with repeat PRP injection to patients who had received no benefit from PRP injection alone at our center. They were the treatment group. They were not charged for PRP or IAL. They also served as a historical control group since they had all had failed PRP treatment alone. 28 patients (30 joints) accepted treatment after informed consent. 22 knees, 4 hips, 2 shoulder glenohumeral joints and 1 first carpo-metacarpal (1st CMC) joint were treated RESULTS: All patients were followed up at 1 month and no adverse events were seen from the treatment. At 6 months post treatment 46% of patients had good outcomes, and at 1 year 17% still showed improvement after treatment. 11 patients failed treatment and went on to joint replacement. DISCUSSION: A single treatment of IAL with PRP salvaged 46% of patients who had failed PRP treatment alone, allowing avoidance of surgery and good pain control.

  1. 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.

  2. 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.

  3. 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.

  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 Multiplex Microsphere-Based Immunoassay Increases the Sensitivity of SIV-Specific Antibody Detection in Serum Samples and Mucosal Specimens Collected from Rhesus Macaques Infected with SIVmac239.

    Science.gov (United States)

    Powell, Rebecca L R; Ouellette, Ian; Lindsay, Ross W; Parks, Christopher L; King, C Richter; McDermott, Adrian B; Morrow, Gavin

    2013-06-01

    Results from recent HIV-1 vaccine studies have indicated that high serum antibody (Ab) titers may not be necessary for Ab-mediated protection, and that Abs localized to mucosal sites might be critical for preventing infection. Enzyme-linked immunosorbent assay (ELISA) has been used for decades as the gold standard for Ab measurement, though recently, highly sensitive microsphere-based assays have become available, with potential utility for improved detection of Abs. In this study, we assessed the Bio-Plex(®) Suspension Array System for the detection of simian immunodeficiency virus (SIV)-specific Abs in rhesus macaques (RMs) chronically infected with SIV, whose serum or mucosal SIV-specific Ab titers were negative by ELISA. We developed a SIVmac239-specific 4-plex bead array for the simultaneous detection of Abs binding to Env, Gag, Pol, and Nef. The 4-plex assay was used to quantify SIV-specific serum IgG and rectal swab IgA titers from control (SIV-naive) and SIVmac239-infected RMs. The Bio-Plex assay specifically detected anti-SIV Abs in specimens from SIV-infected animals for all four analytes when compared to SIV-naive control samples (p≤0.04). Furthermore, in 70% of Env and 79% of Gag ELISA-negative serum samples, specific Ab was detected using the Bio-Plex assay. Similarly, 71% of Env and 48% of Gag ELISA-negative rectal swab samples were identified as positive using the Bio-Plex assay. Importantly, assay specificity (i.e., probability of true positives) was comparable to ELISA (94%-100%). The results reported here indicate that microsphere-based methods provide a substantial improvement over ELISA for the detection of Ab responses, aid in detecting specific Abs when analyzing samples containing low levels of Abs, such as during the early stages of a vaccine trial, and may be valuable in attempts to link protective efficacy of vaccines with induced Ab responses.

  6. 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.

  7. Identification of SIV Nef CD8(+) T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model.

    Science.gov (United States)

    Nomura, Takushi; Yamamoto, Hiroyuki; Takahashi, Naofumi; Naruse, Taeko K; Kimura, Akinori; Matano, Tetsuro

    2014-07-25

    Virus-specific CD8(+) T-cell responses are crucial for the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. Multiple studies on HIV-infected individuals and SIV-infected macaques have indicated association of several major histocompatibility complex class I (MHC-I) genotypes with lower viral loads and delayed AIDS progression. Understanding of the viral control mechanism associated with these MHC-I genotypes would contribute to the development of intervention strategy for HIV control. We have previously reported a rhesus MHC-I haplotype, 90-120-Ia, associated with lower viral loads after SIVmac239 infection. Gag206-216 and Gag241-249 epitope-specific CD8(+) T-cell responses have been shown to play a central role in the reduction of viral loads, whereas the effect of Nef-specific CD8(+) T-cell responses induced in all the 90-120-Ia(+) macaques on SIV replication remains unknown. Here, we identified three CD8(+) T-cell epitopes, Nef9-19, Nef89-97, and Nef193-203, associated with 90-120-Ia. Nef9-19 and Nef193-203 epitope-specific CD8(+) T-cell responses frequently selected for mutations resulting in viral escape from recognition by these CD8(+) T cells, indicating that these CD8(+) T cells exert strong suppressive pressure on SIV replication. Results would be useful for elucidation of the viral control mechanism associated with 90-120-Ia. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA on SIV-infected Chinese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Binhua Ling

    Full Text Available Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM treated with intensive combination antiretroviral therapy (cART and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA.SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations.Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters.The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

  9. 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)

  10. 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.

  11. 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.

  12. 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.

  13. Pre-Treatment Deep Curettage Can Significantly Reduce Tumour Thickness in Thick Basal Cell Carcinoma While Maintaining a Favourable Cosmetic Outcome When Used in Combination with Topical Photodynamic Therapy

    International Nuclear Information System (INIS)

    Christensen, E.; Mork, C.; Foss, O. A.

    2011-01-01

    Topical photodynamic therapy (PDT) has limitations in the treatment of thick skin tumours. The aim of the study was to evaluate the effect of pre-PDT deep curettage on tumour thickness in thick (≥2 mm) basal cell carcinoma (BCC). Additionally, 3-month treatment outcome and change of tumour thickness from diagnosis to treatment were investigated. At diagnosis, mean tumour thickness was 2.3 mm (range 2.0-4.0). Pre- and post-curettage biopsies were taken from each tumour prior to PDT. Of 32 verified BCCs, tumour thickness was reduced by 50% after deep curettage (ρ≤0.001) . Mean tumour thickness was also reduced from diagnosis to treatment. At 3-month followup, complete tumour response was found in 93% and the cosmetic outcome was rated excellent or good in 100% of cases. In conclusion, deep curettage significantly reduces BCC thickness and may with topical PDT provide a favourable clinical and cosmetic short-term outcome.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM.

    Science.gov (United States)

    Stagi, Stefano; Lapi, Elisabetta; Seminara, Salvatore; Pelosi, Paola; Del Greco, Paolo; Capirchio, Laura; Strano, Massimo; Giglio, Sabrina; Chiarelli, Francesco; de Martino, Maurizio

    2015-02-15

    Treatments for childhood obesity are critically needed because of the risk of developing co-morbidities, although the interventions are frequently time-consuming, frustrating, difficult, and expensive. We conducted a longitudinal, randomised, clinical study, based on a per protocol analysis, on 133 obese children and adolescents (n = 69 males and 64 females; median age, 11.3 years) with family history of obesity and type 2 diabetes mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53 patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard, only a LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic and disposition indexes were calculated at T0 and after 1 year (T1). At T1, the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p 1) in Arm A and from 2.23 to 1.99 (p 13.2% to 5.6%; p 1) and B (p 1) and B (p obese children and adolescents with family history of obesity and T2DM.

  4. On the scavenging of SO2 by large and small rain drops. 5. A wind tunnel and theoretical study of the desorption of SO2 from water drops containing S(IV)

    International Nuclear Information System (INIS)

    Mitra, S.K.; Hannemann, A.U.

    1993-01-01

    An experimental and theoretical study has been carried out to investigate the fate of desorption of SO 2 from water drops falling at terminal velocity in air. The experiments were carried out in the Mainz vertical wind tunnel in which water drops of various sizes containing S(IV) in various concentrations were freely suspended in the vertical airstream of the tunnel. The results were compared with the predictions of theoretical models, and with the experiments of Walcek et al. This comparison shows that the predictions of the diffusion model of Kronig and Brink in the formulation given by Walcek and Pruppacher agree well with the experimental results. In contrast, the predictions of the diffusion model which assumes complete internal mixing inside a drop agrees with the experimental results only if the concentration of S(IV) inside the drop is less than that equivalent of an equilibrium SO 2 concentration of 15 ppbv. At larger concentrations, the theoretical predictions of the model for complete internal mixing progressively deviate from the experimental results. It is further shown that Barrie's double film model can be used to interpret the resistance to diffusion inside a drop in terms of a diffusion boundary layer inside the drop which increases in thickness with decreasing concentration of S(IV). Applying our results to the desorption of SO 2 from small and large rain drops falling below an assumed cloud base, shows that for typical contents of S(IV) inside the drops substantial amounts of SO 2 will desorb from these drops unless H 2 O 2 is present in the surrounding air

  5. 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.

  6. 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

  7. Activation/proliferation and apoptosis of bystander goat lymphocytes induced by a macrophage-tropic chimeric caprine arthritis encephalitis virus expressing SIV Nef

    International Nuclear Information System (INIS)

    Bouzar, Baya Amel; Rea, Angela; Hoc-Villet, Stephanie; Garnier, Celine; Guiguen, Francois; Jin Yuhuai; Narayan, Opendra; Chebloune, Yahia

    2007-01-01

    Caprine arthritis encephalitis virus (CAEV) is the natural lentivirus of goats, well known for its tropism for macrophages and its inability to cause infection in lymphocytes. The viral genome lacks nef, tat, vpu and vpx coding sequences. To test the hypothesis that when nef is expressed by the viral genome, the virus became toxic for lymphocytes during replication in macrophages, we inserted the SIVsmm PBj14 nef coding sequences into the genome of CAEV thereby generating CAEV-nef. This recombinant virus is not infectious for lymphocytes but is fully replication competent in goat macrophages in which it constitutively expresses the SIV Nef. We found that goat lymphocytes cocultured with CAEV-nef-infected macrophages became activated, showing increased expression of the interleukin-2 receptor (IL-2R). Activation correlated with increased proliferation of the cells. Interestingly, a dual effect in terms of apoptosis regulation was observed in exposed goat lymphocytes. Nef was found first to induce a protection of lymphocytes from apoptosis during the first few days following exposure to infected macrophages, but later it induced increased apoptosis in the activated lymphocytes. This new recombinant virus provides a model to study the functions of Nef in the context of infection of macrophages, but in absence of infection of T lymphocytes and brings new insights into the biological effects of Nef on lymphocytes

  8. Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract.

    Science.gov (United States)

    Stieh, Daniel J; Maric, Danijela; Kelley, Z L; Anderson, Meegan R; Hattaway, Holly Z; Beilfuss, Beth A; Rothwangl, Katharina B; Veazey, Ronald S; Hope, Thomas J

    2014-10-01

    The majority of new HIV infections occur in women as a result of heterosexual intercourse, overcoming multiple innate barriers to infection within the mucosa. However, the avenues through which infection is established, and the nature of bottlenecks to transmission, have been the source of considerable investigation and contention. Using a high dose of a single round non-replicating SIV-based vector containing a novel dual reporter system, we determined the sites of infection by the inoculum using the rhesus macaque vaginal transmission model. Here we show that the entire female reproductive tract (FRT), including the vagina, ecto- and endocervix, along with ovaries and local draining lymph nodes can contain transduced cells only 48 hours after inoculation. The distribution of infection shows that virions quickly disseminate after exposure and can access target cells throughout the FRT, with an apparent preference for infection in squamous vaginal and ectocervical mucosa. JRFL enveloped virions infect diverse CD4 expressing cell types, with T cells resident throughout the FRT representing the primary target. These findings establish a new perspective that the entire FRT is susceptible and virus can reach as far as the ovary and local draining lymph nodes. Based on these findings, it is essential that protective mechanisms for prevention of HIV acquisition must be present at protective levels throughout the entire FRT to provide complete protection.

  9. Prostate health index significantly reduced unnecessary prostate biopsies in patients with PSA 2-10 ng/mL and PSA >10 ng/mL: Results from a Multicenter Study in China.

    Science.gov (United States)

    Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Helfand, Brian T; Brendler, Charles B; Conran, Carly A; Packiam, Vignesh; Gong, Jian; Wu, Yishuo; Zheng, Siqun L; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng

    2017-08-01

    The performance of prostate health index (phi) in predicting prostate biopsy outcomes has been well established for patients with prostate-specific antigen (PSA) values between 2 and 10 ng/mL. However, the performance of phi remains unknown in patients with PSA >10 ng/mL, the vast majority in Chinese biopsy patients. We aimed to assess the ability of phi to predict prostate cancer (PCa) and high-grade disease (Gleason Score ≥7) on biopsy in a Chinese population. This is a prospective, observational, multi-center study of consecutive patients who underwent a transrectal ultrasound guided prostate biopsy at four hospitals in Shanghai, China from August 2013 to December 2014. In the cohort of 1538 patients, the detection rate of PCa was 40.2%. phi had a significantly better predictive performance for PCa than total PSA (tPSA). The areas under the receiver operating characteristic curve (AUC) were 0.90 and 0.79 for phi and tPSA, respectively, P 10 ng/mL (N = 838, 54.5%). The detection rates of PCa were 35.9% and 57.7% in patients with tPSA 10.1-20 and 20.1-50 ng/mL, respectively. The AUCs of phi (0.79 and 0.89, for these two groups, respectively) were also significantly higher than tPSA (0.57 and 0.63, respectively), both P 10 ng/mL). © 2017 Wiley Periodicals, Inc.

  10. 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

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

    International Nuclear Information System (INIS)

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

    1988-01-01

    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

  12. 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

  13. 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

    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...... registration took 30 minutes. On an Nvidia Geforce 8800GTX GPU in the same machine this registration took 37 seconds, making the GPU version 48.7 times faster. The nine image series of different respiration phases were registered to the same reference image (full inhale). Accuracy was evaluated on landmark...

  14. 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.

  15. Detection of microbial translocation in HIV and SIV infection using the Limulus amebocyte lysate assay is masked by serum and plasma.

    Directory of Open Access Journals (Sweden)

    Ashwin Balagopal

    Full Text Available Microbial translocation (MT is thought to be a major contributor to the pathogenesis of HIV-related immune activation, and circulating lipopolysaccharide (LPS from gram-negative bacteria is the principle measurement of this process. However, related research has been impeded by inconsistent LPS test results.Specimens were obtained from HIV-infected adults enrolled in the PEARLS study (ACTG A5175 and HIV-HCV co-infected participants enrolled in a study of liver disease staging using MRI elastography. Pig-tailed macaque specimens were obtained from SIV-infected and -uninfected animals. Samples were tested for LPS using the LAL assay with diazo-coupling modifications to improve sensitive detection.When exogenous LPS was added to macaque plasma, >25% inhibition of LPS detection was found in 10/10 (100% samples at 20% plasma concentration compared to control; in contrast 5/10 (50% samples at 2% plasma concentration (p = 0.07 and 0/10 (0% at 0.1% plasma concentration (p = 0.004 showed >25% inhibition of LPS detection. Similarly, when LPS was added to human serum, >25% inhibition of LPS detection was found in 5/12 (42% of samples at 2% serum concentration compared to control, while 0/12 (0% of samples in 0.1% serum showed >25% inhibition of LPS detection (p = 0.07. Likewise, LPS detection in human sera without exogenous LPS was improved by dilution: LPS was detected in 2/12 (17% human samples in 2% serum, ranging from 3,436-4,736 pg/mL, compared to 9/12 (75% samples in 0.1% serum, ranging from 123 pg/mL -60,131 pg/mL (p = 0.016. In a separate validation cohort of HIV-HCV co-infected participants sampled at two different times on the same day, LPS measured in 0.2% plasma and with diazo-coupling was closely correlated between the first and second samples (R = 0.66, p<0.05.Undiluted serum and plasma mask LPS detection. The extent of MT may be substantially underestimated.

  16. 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

  17. 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...

  18. 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/

  19. Testing Significance Testing

    Directory of Open Access Journals (Sweden)

    Joachim I. Krueger

    2018-04-01

    Full Text Available The practice of Significance Testing (ST remains widespread in psychological science despite continual criticism of its flaws and abuses. Using simulation experiments, we address four concerns about ST and for two of these we compare ST’s performance with prominent alternatives. We find the following: First, the 'p' values delivered by ST predict the posterior probability of the tested hypothesis well under many research conditions. Second, low 'p' values support inductive inferences because they are most likely to occur when the tested hypothesis is false. Third, 'p' values track likelihood ratios without raising the uncertainties of relative inference. Fourth, 'p' values predict the replicability of research findings better than confidence intervals do. Given these results, we conclude that 'p' values may be used judiciously as a heuristic tool for inductive inference. Yet, 'p' values cannot bear the full burden of inference. We encourage researchers to be flexible in their selection and use of statistical methods.

  20. 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

  1. Predicting significant torso trauma.

    Science.gov (United States)

    Nirula, Ram; Talmor, Daniel; Brasel, Karen

    2005-07-01

    Identification of motor vehicle crash (MVC) characteristics associated with thoracoabdominal injury would advance the development of automatic crash notification systems (ACNS) by improving triage and response times. Our objective was to determine the relationships between MVC characteristics and thoracoabdominal trauma to develop a torso injury probability model. Drivers involved in crashes from 1993 to 2001 within the National Automotive Sampling System were reviewed. Relationships between torso injury and MVC characteristics were assessed using multivariate logistic regression. Receiver operating characteristic curves were used to compare the model to current ACNS models. There were a total of 56,466 drivers. Age, ejection, braking, avoidance, velocity, restraints, passenger-side impact, rollover, and vehicle weight and type were associated with injury (p < 0.05). The area under the receiver operating characteristic curve (83.9) was significantly greater than current ACNS models. We have developed a thoracoabdominal injury probability model that may improve patient triage when used with ACNS.

  2. Gas revenue increasingly significant

    International Nuclear Information System (INIS)

    Megill, R.E.

    1991-01-01

    This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

  3. 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/

  4. Uranium chemistry: significant advances

    International Nuclear Information System (INIS)

    Mazzanti, M.

    2011-01-01

    The author reviews recent progress in uranium chemistry achieved in CEA laboratories. Like its neighbors in the Mendeleev chart uranium undergoes hydrolysis, oxidation and disproportionation reactions which make the chemistry of these species in water highly complex. The study of the chemistry of uranium in an anhydrous medium has led to correlate the structural and electronic differences observed in the interaction of uranium(III) and the lanthanides(III) with nitrogen or sulfur molecules and the effectiveness of these molecules in An(III)/Ln(III) separation via liquid-liquid extraction. Recent work on the redox reactivity of trivalent uranium U(III) in an organic medium with molecules such as water or an azide ion (N 3 - ) in stoichiometric quantities, led to extremely interesting uranium aggregates particular those involved in actinide migration in the environment or in aggregation problems in the fuel processing cycle. Another significant advance was the discovery of a compound containing the uranyl ion with a degree of oxidation (V) UO 2 + , obtained by oxidation of uranium(III). Recently chemists have succeeded in blocking the disproportionation reaction of uranyl(V) and in stabilizing polymetallic complexes of uranyl(V), opening the way to to a systematic study of the reactivity and the electronic and magnetic properties of uranyl(V) compounds. (A.C.)

  5. Meaning and significance of

    Directory of Open Access Journals (Sweden)

    Ph D Student Roman Mihaela

    2011-05-01

    Full Text Available The concept of "public accountability" is a challenge for political science as a new concept in this area in full debate and developement ,both in theory and practice. This paper is a theoretical approach of displaying some definitions, relevant meanings and significance odf the concept in political science. The importance of this concept is that although originally it was used as a tool to improve effectiveness and eficiency of public governance, it has gradually become a purpose it itself. "Accountability" has become an image of good governance first in the United States of America then in the European Union.Nevertheless,the concept is vaguely defined and provides ambiguous images of good governance.This paper begins with the presentation of some general meanings of the concept as they emerge from specialized dictionaries and ancyclopaedies and continues with the meanings developed in political science. The concept of "public accontability" is rooted in economics and management literature,becoming increasingly relevant in today's political science both in theory and discourse as well as in practice in formulating and evaluating public policies. A first conclusin that emerges from, the analysis of the evolution of this term is that it requires a conceptual clarification in political science. A clear definition will then enable an appropriate model of proving the system of public accountability in formulating and assessing public policies, in order to implement a system of assessment and monitoring thereof.

  6. Significant Radionuclides Determination

    Energy Technology Data Exchange (ETDEWEB)

    Jo A. Ziegler

    2001-07-31

    The purpose of this calculation is to identify radionuclides that are significant to offsite doses from potential preclosure events for spent nuclear fuel (SNF) and high-level radioactive waste expected to be received at the potential Monitored Geologic Repository (MGR). In this calculation, high-level radioactive waste is included in references to DOE SNF. A previous document, ''DOE SNF DBE Offsite Dose Calculations'' (CRWMS M&O 1999b), calculated the source terms and offsite doses for Department of Energy (DOE) and Naval SNF for use in design basis event analyses. This calculation reproduces only DOE SNF work (i.e., no naval SNF work is included in this calculation) created in ''DOE SNF DBE Offsite Dose Calculations'' and expands the calculation to include DOE SNF expected to produce a high dose consequence (even though the quantity of the SNF is expected to be small) and SNF owned by commercial nuclear power producers. The calculation does not address any specific off-normal/DBE event scenarios for receiving, handling, or packaging of SNF. The results of this calculation are developed for comparative analysis to establish the important radionuclides and do not represent the final source terms to be used for license application. This calculation will be used as input to preclosure safety analyses and is performed in accordance with procedure AP-3.12Q, ''Calculations'', and is subject to the requirements of DOE/RW-0333P, ''Quality Assurance Requirements and Description'' (DOE 2000) as determined by the activity evaluation contained in ''Technical Work Plan for: Preclosure Safety Analysis, TWP-MGR-SE-000010'' (CRWMS M&O 2000b) in accordance with procedure AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities''.

  7. 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.

  8. The energetic significance of cooking.

    Science.gov (United States)

    Carmody, Rachel N; Wrangham, Richard W

    2009-10-01

    While cooking has long been argued to improve the diet, the nature of the improvement has not been well defined. As a result, the evolutionary significance of cooking has variously been proposed as being substantial or relatively trivial. In this paper, we evaluate the hypothesis that an important and consistent effect of cooking food is a rise in its net energy value. The pathways by which cooking influences net energy value differ for starch, protein, and lipid, and we therefore consider plant and animal foods separately. Evidence of compromised physiological performance among individuals on raw diets supports the hypothesis that cooked diets tend to provide energy. Mechanisms contributing to energy being gained from cooking include increased digestibility of starch and protein, reduced costs of digestion for cooked versus raw meat, and reduced energetic costs of detoxification and defence against pathogens. If cooking consistently improves the energetic value of foods through such mechanisms, its evolutionary impact depends partly on the relative energetic benefits of non-thermal processing methods used prior to cooking. We suggest that if non-thermal processing methods such as pounding were used by Lower Palaeolithic Homo, they likely provided an important increase in energy gain over unprocessed raw diets. However, cooking has critical effects not easily achievable by non-thermal processing, including the relatively complete gelatinisation of starch, efficient denaturing of proteins, and killing of food borne pathogens. This means that however sophisticated the non-thermal processing methods were, cooking would have conferred incremental energetic benefits. While much remains to be discovered, we conclude that the adoption of cooking would have led to an important rise in energy availability. For this reason, we predict that cooking had substantial evolutionary significance.

  9. 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...

  10. 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

  11. 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...

  12. 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)

  13. 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...

  14. Significant Lactic Acidosis from Albuterol

    Directory of Open Access Journals (Sweden)

    Deborah Diercks

    2018-03-01

    Full Text Available Lactic acidosis is a clinical entity that demands rapid assessment and treatment to prevent significant morbidity and mortality. With increased lactate use across many clinical scenarios, lactate values themselves cannot be interpreted apart from their appropriate clinical picture. The significance of Type B lactic acidosis is likely understated in the emergency department (ED. Given the mortality that sepsis confers, a serum lactate is an important screening study. That said, it is with extreme caution that we should interpret and react to the resultant elevated value. We report a patient with a significant lactic acidosis. Though he had a high lactate value, he did not require aggressive resuscitation. A different classification scheme for lactic acidosis that focuses on the bifurcation of the “dangerous” and “not dangerous” causes of lactic acidosis may be of benefit. In addition, this case is demonstrative of the potential overuse of lactates in the ED.

  15. 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...

  16. Shrinkage Reducing Admixture for Concrete

    OpenAIRE

    ECT Team, Purdue

    2007-01-01

    Concrete shrinkage cracking is a common problem in all types of concrete structures, especially for structures and environments where the cracks are prevalent and the repercussions are most severe. A liquid shrinkage reducing admixture for concrete, developed by GRACE Construction Products and ARCO Chemical Company, that reduces significantly the shrinkage during concrete drying and potentially reduces overall cracking over time.

  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. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1990-09-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 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

  8. Clinical significance of neonatal menstruation.

    Science.gov (United States)

    Brosens, Ivo; Benagiano, Giuseppe

    2016-01-01

    Past studies have clearly shown the existence of a spectrum of endometrial progesterone responses in neonatal endometrium, varying from proliferation to full decidualization with menstrual-like shedding. The bleedings represent, similar to what occurs in adult menstruation, a progesterone withdrawal bleeding. Today, the bleeding is completely neglected and considered an uneventful episode of no clinical significance. Yet clinical studies have linked the risk of bleeding to a series of events indicating fetal distress. The potential link between the progesterone response and major adolescent disorders requires to be investigated by prospective studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. The co registration of initial PET on the CT-radiotherapy reduces significantly the variabilities of anatomo-clinical target volume in the child hodgkin disease; La coregistration de la TEP initiale sur la scanographie de radiotherapie diminue significativement les variabilites de volume cible anatomoclinique dans la maladie de Hodgkin de l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Metwally, H.; Blouet, A.; David, I.; Rives, M.; Izar, F.; Courbon, F.; Filleron, T.; Laprie, A. [Institut Claudius-Regaud, 31 - Toulouse (France); Plat, G.; Vial, J. [CHU-hopital des Enfants, 31 - Toulouse (France)

    2009-10-15

    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.)

  19. 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.

  20. 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

  1. The significance of small streams

    Science.gov (United States)

    Wohl, Ellen

    2017-09-01

    Headwaters, defined here as first- and secondorder streams, make up 70%‒80% of the total channel length of river networks. These small streams exert a critical influence on downstream portions of the river network by: retaining or transmitting sediment and nutrients; providing habitat and refuge for diverse aquatic and riparian organisms; creating migration corridors; and governing connectivity at the watershed-scale. The upstream-most extent of the channel network and the longitudinal continuity and lateral extent of headwaters can be difficult to delineate, however, and people are less likely to recognize the importance of headwaters relative to other portions of a river network. Consequently, headwaters commonly lack the legal protections accorded to other portions of a river network and are more likely to be significantly altered or completely obliterated by land use.

  2. No significant fuel failures (NSFF)

    International Nuclear Information System (INIS)

    Domaratzki, Z.

    1979-01-01

    It has long been recognized that no emergency core cooling system (ECCS) could be absolutely guaranteed to prevent fuel failures. In 1976 the Atomic Energy Control Board decided that the objective for an ECCS should be to prevent fuel failures, but if the objective could not be met it should be shown that the consequences are acceptable for dual failures comprising any LOCA combined with an assumed impairment of containment. Out of the review of the Bruce A plant came the definition of 'no significant fuel failures': for any postulated LOCA combined with any one mode of containment impairment the resultant dose to a person at the edge of the exclusion zone is less than the reference dose limits for dual failures

  3. Ritual Significance in Mycenaean Hairstyles

    Directory of Open Access Journals (Sweden)

    Hsu, Florence Sheng-chieh

    2012-04-01

    Full Text Available Although the frescoes excavated from Bronze Age sites on the Greek mainland provide evidence for female figures in the Mycenaean society, the hairstyles of these figures have not been studied in detail. As in many other ancient cultures, hairstyles were not only an exhibition of beauty and fashion, but they also represented certain age groups or a person’s social status. The Mycenaeans inherited many of their hairstyles from their Minoan predecessors, although differences existed as well. It is also possible there may have been a shift in meaning for seemingly similar looking hairstyles from the Minoan to the Mycenaean periods. Female figures, which compose most of the Mycenaean figures in frescoes known to date, are fine examples for discussing the artistic representation and potential significance of Mycenaean hairstyles. By comparing with Minoan hairstyles, discussions of Mycenaean examples lead to conclusions in the relationship between hairstyles and ritual activities in the Mycenaean society.

  4. Reducing rotor weight

    Energy Technology Data Exchange (ETDEWEB)

    Cheney, M.C. [PS Enterprises, Inc., Glastonbury, CT (United States)

    1997-12-31

    The cost of energy for renewables has gained greater significance in recent years due to the drop in price in some competing energy sources, particularly natural gas. In pursuit of lower manufacturing costs for wind turbine systems, work was conducted to explore an innovative rotor designed to reduce weight and cost over conventional rotor systems. Trade-off studies were conducted to measure the influence of number of blades, stiffness, and manufacturing method on COE. The study showed that increasing number of blades at constant solidity significantly reduced rotor weight and that manufacturing the blades using pultrusion technology produced the lowest cost per pound. Under contracts with the National Renewable Energy Laboratory and the California Energy Commission, a 400 kW (33m diameter) turbine was designed employing this technology. The project included tests of an 80 kW (15.5m diameter) dynamically scaled rotor which demonstrated the viability of the design.

  5. Significant biases affecting abundance determinations

    Science.gov (United States)

    Wesson, Roger

    2015-08-01

    I have developed two highly efficient codes to automate analyses of emission line nebulae. The tools place particular emphasis on the propagation of uncertainties. The first tool, ALFA, uses a genetic algorithm to rapidly optimise the parameters of gaussian fits to line profiles. It can fit emission line spectra of arbitrary resolution, wavelength range and depth, with no user input at all. It is well suited to highly multiplexed spectroscopy such as that now being carried out with instruments such as MUSE at the VLT. The second tool, NEAT, carries out a full analysis of emission line fluxes, robustly propagating uncertainties using a Monte Carlo technique.Using these tools, I have found that considerable biases can be introduced into abundance determinations if the uncertainty distribution of emission lines is not well characterised. For weak lines, normally distributed uncertainties are generally assumed, though it is incorrect to do so, and significant biases can result. I discuss observational evidence of these biases. The two new codes contain routines to correctly characterise the probability distributions, giving more reliable results in analyses of emission line nebulae.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

    BACKGROUND: Oak moss absolute, an extract from the lichen Evernia prunastri, is a valued perfume ingredient but contains extreme allergens. OBJECTIVES: To compare the elicitation properties of two preparations of oak moss absolute: 'classic oak moss', the historically used preparation, and 'new o...

  13. 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.

  14. Reducing infant mortality.

    Science.gov (United States)

    Johnson, T R

    1994-01-01

    Public health and social policies at the population level (e.g., oral rehydration therapy and immunization) are responsible for the major reduction in infant mortality worldwide. The gap in infant mortality rates between developing and developed regions is much less than that in maternal mortality rates. This indicates that maternal and child health (MCH) programs and women's health care should be combined. Since 1950, 66% of infant deaths occur in the 1st 28 days, indicating adverse prenatal and intrapartum events (e.g., congenital malformation and birth injuries). Infection, especially pneumonia and diarrhea, and low birth weight are the major causes of infant mortality worldwide. An estimated US$25 billion are needed to secure the resources to control major childhood diseases, reduce malnutrition 50%, reduce child deaths by 4 million/year, provide potable water and sanitation to all communities, provide basic education, and make family planning available to all. This cost for saving children's lives is lower than current expenditures for cigarettes (US$50 billion in Europe/year). Vitamin A supplementation, breast feeding, and prenatal diagnosis of congenital malformations are low-cost strategies that can significantly affect infant well-being and reduce child mortality in many developing countries. The US has a higher infant mortality rate than have other developed countries. The American College of Obstetricians and Gynecologists and the US National Institutes of Health are focusing on prematurity, low birth weight, multiple pregnancy, violence, alcohol abuse, and poverty to reduce infant mortality. Obstetricians should be important members of MCH teams, which also include traditional birth attendants, community health workers, nurses, midwives, and medical officers. We have the financial resources to allocate resources to improve MCH care and to reduce infant mortality.

  15. A novel protective MHC-I haplotype not associated with dominant Gag-specific CD8+ T-cell responses in SIVmac239 infection of Burmese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Naofumi Takahashi

    Full Text Available Several major histocompatibility complex class I (MHC-I alleles are associated with lower viral loads and slower disease progression in human immunodeficiency virus (HIV and simian immunodeficiency virus (SIV infections. Immune-correlates analyses in these MHC-I-related HIV/SIV controllers would lead to elucidation of the mechanism for viral control. Viral control associated with some protective MHC-I alleles is attributed to CD8+ T-cell responses targeting Gag epitopes. We have been trying to know the mechanism of SIV control in multiple groups of Burmese rhesus macaques sharing MHC-I genotypes at the haplotype level. Here, we found a protective MHC-I haplotype, 90-010-Id (D, which is not associated with dominant Gag-specific CD8+ T-cell responses. Viral loads in five D+ animals became significantly lower than those in our previous cohorts after 6 months. Most D+ animals showed predominant Nef-specific but not Gag-specific CD8+ T-cell responses after SIV challenge. Further analyses suggested two Nef-epitope-specific CD8+ T-cell responses exerting strong suppressive pressure on SIV replication. Another set of five D+ animals that received a prophylactic vaccine using a Gag-expressing Sendai virus vector showed significantly reduced viral loads compared to unvaccinated D+ animals at 3 months, suggesting rapid SIV control by Gag-specific CD8+ T-cell responses in addition to Nef-specific ones. These results present a pattern of SIV control with involvement of non-Gag antigen-specific CD8+ T-cell responses.

  16. Regional and global significance of nuclear energy

    International Nuclear Information System (INIS)

    Schilling, H.D.

    1995-01-01

    Measures to combat poverty and improve the standard of living in countries of the Third World will inevitably boost global demand for energy, and energy conservation measures will not be able to offset this increase. Nuclear energy will regain significance in the framework of approaches adopted to resolve the energy problem, which primarily is an ecologic problem created by an extremely large flow of materials. The extraordinarily high energy density of nuclear fuels can contribute to markedly reduce the flow of materials; and at that, electric energy is an efficient substitute for primary energy forms. Thus nuclear electricity generation is of double benefit to the ecology. Engineering goals in nuclear technology thus gain a service aspect, with progress in power plant engineering and design aiming not only at enhanced engineered safety, but also at regaining public acceptance of and confidence in nuclear power plant technology. (orig./UA) [de

  17. 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...

  18. A novel 5-enolpyruvylshikimate-3-phosphate synthase from Rahnella aquatilis with significantly reduced glyphosate sensitivity.

    Directory of Open Access Journals (Sweden)

    Ri-He Peng

    Full Text Available 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 AroA(R. 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 (AroA(E. coli, while retaining high affinity for the substrate phosphoenolpyruvate. Transgenic plants of AroA(R. aquatilis were also observed to be more resistant to glyphosate at a concentration of 5 mM than that of AroA(E. 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.

  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

    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)

  1. 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.

    . Consideration of the oasis analogy for chemosyntheticcommunities at Gulf of Mexico hydrocarbon vents. Geo. Mar. Lett. 14,149-159 Douglas, A.E.,2004. Strategies in antagonistic and cooperative interactions. Microbial Evolution. Gene Establishment, survival... and fuels. Plenum, New York, pp 277?296. MacAvoy, S.A., Macko, S.A., Joye, S.B., 2002. Fatty acid carbon isotope signatures in chemosynthetic mussels and tube worms from Gulf of Mexico hydrocarbon seep communities. Chem.Geol. 185, 1 ? 8. Michaelis, W...

  2. Long-term agricultural management maximizing hay production can significantly reduce belowground C storage

    NARCIS (Netherlands)

    Sochorová, L.; Jansa, J.; Verbruggen, E.; Hejcman, M.; Schellberg, J.; Kiers, E.T.

    2016-01-01

    Liming and fertilization of grasslands have been used for centuries to sustain hay production. Besides improving hay yields, these practices induce compositional shifts in plant and soil microbial communities, including symbiotic arbuscular mycorrhizal (AM) fungi. However, in spite of increasing

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

    OpenAIRE

    An, Chongwei; Li, Hequn; Ye, Baoyun; Wang, Jingyu

    2017-01-01

    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 sph...

  4. 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

  5. Teenage Smoking: Higher Excise Tax Should Significantly Reduce the Number of Smokers

    Science.gov (United States)

    1989-06-30

    12 to 17, in the United States, about 3.5 million use tobacco products, almost 3 million smoke marijuana , 6 million drink alcohol, and 1 million use...particularly in indoor environments. As a result nonsmokers tend to face a greater risk of cancer and of becoming less healthy in general. (The details on

  6. Significant enhancement of the thermoelectric figure of merit of polycrystalline Si films by reducing grain size

    International Nuclear Information System (INIS)

    Valalaki, K; Nassiopoulou, A G; Vouroutzis, N

    2016-01-01

    The thermoelectric properties of p-type polycrystalline silicon thin films deposited by low pressure chemical vapour deposition (LPCVD) were accurately determined at room temperature and the thermoelectric figure of merit was deduced as a function of film thickness, ranging from 100 to 500 nm. The effect of film thickness on their thermoelectric performance is discussed. More than threefold increase in the thermoelectric figure of merit of the 100 nm thick polysilicon film was observed compared to the 500 nm thick film, reaching a value as high as 0.033. This enhancement is mainly the result of the smaller grain size in the thinner films. With the decrease in grain size the resistivity of the films is increased twofold and electrical conductivity decreased, however the Seebeck coefficient is increased by 30% and the thermal conductivity is decreased eightfold, being mainly at the origin of the increased figure of merit of the 100 nm film. Our experimental results were compared to known theoretical models and the possible mechanisms involved are presented and discussed. (paper)

  7. Microplastic contamination of river beds significantly reduced by catchment-wide flooding

    Science.gov (United States)

    Hurley, Rachel; Woodward, Jamie; Rothwell, James J.

    2018-04-01

    Microplastic contamination of the oceans is one of the world's most pressing environmental concerns. The terrestrial component of the global microplastic budget is not well understood because sources, stores and fluxes are poorly quantified. We report catchment-wide patterns of microplastic contamination, classified by type, size and density, in channel bed sediments at 40 sites across urban, suburban and rural river catchments in northwest England. Microplastic contamination was pervasive on all river channel beds. We found multiple urban contamination hotspots with a maximum microplastic concentration of approximately 517,000 particles m-2. After a period of severe flooding in winter 2015/16, all sites were resampled. Microplastic concentrations had fallen at 28 sites and 18 saw a decrease of one order of magnitude. The flooding exported approximately 70% of the microplastic load stored on these river beds (equivalent to 0.85 ± 0.27 tonnes or 43 ± 14 billion particles) and eradicated microbead contamination at 7 sites. We conclude that microplastic contamination is efficiently flushed from river catchments during flooding.

  8. 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

  9. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

    International Nuclear Information System (INIS)

    Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

    2008-01-01

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-γ enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus

  10. Radiological significance of thorium processing in manufacturing

    International Nuclear Information System (INIS)

    Davis, M.W.

    1985-01-01

    The study of thorium processing in manufacturing comprised monitoring programs at a plant where thorium dioxide was in use and another where the use of thorium nitrate had been discontinued. The measurements of the solubility in simulated lung fluid proved that both materials belonged in the Y Class with dissolution half-times greater than 500 days. Bioassay measurements of 20 subjects from both facilities proved that in vitro monitoring methods, urine, feces, hair and nails analysis were not sufficient indicators of thorium uptake. In vivo monitoring by phoswich and large sodium iodide detectors were proven to be good methods of determining thorium lung burdens. The thoron in breath technique was shown to have a lower limit of sensitivity than lung counting, however, due to lack of information regarding the thoron escape rate from the thorium particles in the lungs the method is not as accurate as lung counting. Two subjects at the thorium dioxide facility had lung burdens of 21+- 16 Bq and 29+- 24 Bq Th 232 and one at the thorium nitrate facility had a lung burden of 37+- 13 Bq. Improvements in the procedures and use of a glove box were among the recommendations to reduce the inhalation of thorium by workers at the thorium dioxide facility. Decontamination of several rooms at the thorium nitrate facility and sealing of the walls and floors were recommended in order to reduce the escape of thoron gas into the room air. The risk to non Atomic Radiation Workers was primarily due to thoron daughters in air while gamma radiation and thorium in air were less important. Conversely, at the thorium dioxide facility the inhalation of thorium in air was the most significant exposure pathway

  11. 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...

  12. Global warming: the significance of methane

    International Nuclear Information System (INIS)

    Dessus, B.; Le Treut, H.; Laponche, B.

    2008-01-01

    the concept of Global Warming Potential (GWP) indicates the relative contribution to global warming over a given period (for example 100 years) of a pulse emission at the start of the period of 1 kg of a specific greenhouse gas (GHG) in comparison to the contribution, over the same period, of an emission of 1 kg of CO 2 . The GWPs calculated for different time intervals take into account the differences in atmospheric lifetimes of the different GHGs. Using the '100-year GWP' to measure non CO 2 GHG emissions is not well suited to the case of permanent or long lifetime measures whose effectiveness is to be assessed at a given time horizon. In this context, it contributes to significantly playing down the importance of reducing emissions of GHGs with short atmospheric lifetimes. Thus, for example, methane which is not emitted over the period 2020- 2100 as a result of a landfill site being closed in 2020 will have an impact (as opposed to if the site remained in operation) that would be far greater towards 2100 compared to a CO 2 emission source that has also been stopped permanently and whose climate impact is measured in an equivalent manner. Using the GWP is only appropriate if applied year after year to time horizons considered to be of concern or decisive by climate studies, thus in particular 2050, 2100 and 2150. This is all the more significant as climate experts' current concerns lead them not only to advocate long-term stabilisation of GHG concentrations but also to avoid as far as possible intermediate excess of these concentrations over the coming century. Finally, it is noted that CH 4 prevention policies implemented in the short term may continue to have a long-term impact greater than merely taking into account the current GWP would imply. To more or less ignore the impact of CH 4 as it is unsuitable for accounting purposes affects the exclusive character of the link that may exist between the issue of GHGs and that of energy. Furthermore, if the

  13. 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

  14. Impact significance determination-Back to basics

    International Nuclear Information System (INIS)

    Lawrence, David P.

    2007-01-01

    Impact significance determination is widely recognized as a vital and critical EIA activity. But impact significance related concepts are poorly understood. And the quality of approaches for impact significance determination in EIA practice remains highly variable. This article seeks to help establish a sound and practical conceptual foundation for formulating and evaluating impact significance determination approaches. It addresses the nature (what is impact significance?), the core characteristics (what are the major properties of significance determination?), the rationale (why are impact significance determinations necessary?), the procedural and substantive objectives (what do impact significance determinations seek to achieve?), and the process for making impact significance judgments (how is impact significance determination conducted?). By identifying fundamental attributes and key distinctions associated with impact significance determinations, a basis is provided for designing and evaluating impact significance determination procedures at both the regulatory and applied levels

  15. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Matusali, G.; Dereuddre-Bosquet, N.; Le Tortorec, A.; Moreau, M.; Satie, A.-P.; Mahé, D.; Roumaud, P.; Bourry, O.; Sylla, N.; Bernard-Stoecklin, S.; Pruvost, A.; Le Grand, R.

    2015-01-01

    ABSTRACT A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCE A substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV

  16. Reduced abrasion drilling fluid

    NARCIS (Netherlands)

    2010-01-01

    A reduced abrasion drilling fluid system and method of drilling a borehole by circulating the reduced abrasion drilling fluid through the borehole is disclosed. The reduced abrasion drilling fluid comprises a drilling fluid, a first additive and a weighting agent, wherein the weighting agent has a

  17. Reduced abrasion drilling fluid

    NARCIS (Netherlands)

    2012-01-01

    A reduced abrasion drilling fluid system and method of drilling a borehole by circulating the reduced abrasion drilling fluid through the borehole is disclosed. The reduced abrasion drilling fluid comprises a drilling fluid, a first additive and a weighting agent, wherein the weighting agent has a

  18. 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.

  19. 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.

  20. Creating Significant Learning Experiences across Disciplines

    Science.gov (United States)

    Levine, Laura E.; Fallahi, Carolyn R.; Nicoll-Senft, Joan M.; Tessier, Jack T.; Watson, Cheryl L.; Wood, Rebecca M.

    2008-01-01

    The purpose of this study was to use Fink's (2003) taxonomy of significant learning to redesign courses and assess student learning. Significant improvements were found across the semester for students in the six courses, but there were differences in which taxa showed improvement in each course. The meta-analysis showed significant, positive…

  1. 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...

  2. 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 ...

  3. 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.

  4. Reducible oxide based catalysts

    Science.gov (United States)

    Thompson, Levi T.; Kim, Chang Hwan; Bej, Shyamal K.

    2010-04-06

    A catalyst is disclosed herein. The catalyst includes a reducible oxide support and at least one noble metal fixed on the reducible oxide support. The noble metal(s) is loaded on the support at a substantially constant temperature and pH.

  5. Direct oxide reducing method

    International Nuclear Information System (INIS)

    Tokiwai, Moriyasu.

    1995-01-01

    Calcium oxides and magnetic oxides as wastes generated upon direct reduction are subjected to molten salt electrolysis, and reduced metallic calcium and magnesium are separated and recovered. Then calcium and magnesium are used recyclically as the reducing agent upon conducting direct oxide reduction. Even calcium oxides and magnesium oxides, which have high melting points and difficult to be melted usually, can be melted in molten salts of mixed fluorides or chlorides by molten-salt electrolysis. Oxides are decomposed by electrolysis, and oxygen is removed in the form of carbon monoxide, while the reduced metallic calcium and magnesium rise above the molten salts on the side of a cathode, and then separated. Since only carbon monoxide is generated as radioactive wastes upon molten salt electrolysis, the amount of radioactive wastes can be greatly reduced, and the amount of the reducing agent used can also be decreased remarkably. (N.H.)

  6. Methodology, theoretical framework and scholarly significance: An ...

    African Journals Online (AJOL)

    Methodology, theoretical framework and scholarly significance: An overview ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... Keywords: Legal Research, Methodology, Theory, Pedagogy, Legal Training, Scholarship ...

  7. Impact significance determination-Pushing the boundaries

    International Nuclear Information System (INIS)

    Lawrence, David P.

    2007-01-01

    Impact significance determination practice tends to be highly variable. Too often insufficient consideration is given to good practice insights. Also, impact significance determinations are frequently narrowly defined addressing, for example, only individual, negative impacts, focusing on bio-physical impacts, and not seeking to integrate either the Precautionary Principle or sustainability. This article seeks to extend the boundaries of impact significance determination practice by providing an overview of good general impact significance practices, together with stakeholder roles and potential methods for addressing significance determination challenges. Relevant thresholds, criteria, contextual considerations and support methods are also highlighted. The analysis is then extended to address how impact significance determination practices change for positive as compared with negative impacts, for cumulative as compared with individual impacts, for socio-economic as compared with bio-physical impacts, when the Precautionary Principle is integrated into the process, and when sustainability contributions drive the EIA process and related impact significance determinations. These refinements can assist EIA practitioners in ensuring that the scope and nature of impact significance determinations reflect the broadened scope of emerging EIA requirements and practices. Suggestions are included for further refining and testing of the proposed changes to impact significance determination practice

  8. 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...

  9. 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...

  10. Pipeline Drag Reducers

    International Nuclear Information System (INIS)

    Marawan, H.

    2004-01-01

    Pipeline drag reducers have proven to be an extremely powerful tool in fluid transportation. High molecular weight polymers are used to reduce the frictional pressure loss ratio in crude oil pipelines, refined fuel and aqueous pipelines. Chemical structure of the main used pipeline drag reducers is one of the following polymers and copolymers classified according to the type of fluid to ; low density polyethylene, copolymer of I-hexane cross linked with divinyl benzene, polyacrylamide, polyalkylene oxide polymers and their copolymers, fluorocarbons, polyalkyl methacrylates and terpolymer of styrene, alkyl acrylate and acrylic acid. Drag reduction is the increase in pump ability of a fluid caused by the addition of small amounts of an additive to the fluid. The effectiveness of a drag reducer is normally expressed in terms of percent drag reduction. Frictional pressure loss in a pipeline system is a waste of energy and it costly. The drag reducing additive minimizes the flow turbulence, increases throughput and reduces the energy costs. The Flow can be increased by more than 80 % with existing assets. The effectiveness of the injected drag reducer in Mostorod to Tanta crude oil pipeline achieved 35.4 % drag reduction and 23.2 % flow increase of the actual performance The experimental application of DRA on Arab Petroleum Pipeline Company (Summed) achieved a flow increase ranging from 9-32 %

  11. The thresholds for statistical and clinical significance

    DEFF Research Database (Denmark)

    Jakobsen, Janus Christian; Gluud, Christian; Winkel, Per

    2014-01-01

    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...... of the probability that a given trial result is compatible with a 'null' effect (corresponding to the P-value) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation; (3) adjust the confidence intervals and the statistical significance...

  12. What if there were no significance tests?

    CERN Document Server

    Harlow, Lisa L; Steiger, James H

    2013-01-01

    This book is the result of a spirited debate stimulated by a recent meeting of the Society of Multivariate Experimental Psychology. Although the viewpoints span a range of perspectives, the overriding theme that emerges states that significance testing may still be useful if supplemented with some or all of the following -- Bayesian logic, caution, confidence intervals, effect sizes and power, other goodness of approximation measures, replication and meta-analysis, sound reasoning, and theory appraisal and corroboration. The book is organized into five general areas. The first presents an overview of significance testing issues that sythesizes the highlights of the remainder of the book. The next discusses the debate in which significance testing should be rejected or retained. The third outlines various methods that may supplement current significance testing procedures. The fourth discusses Bayesian approaches and methods and the use of confidence intervals versus significance tests. The last presents the p...

  13. 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.

  14. Reducing Childhood Obesity

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... Ga. were the first three We Can! cities. Obesity Research: A New Approach The percentage of children ...

  15. Transdermal drug delivery: approaches and significance

    OpenAIRE

    Murthy, SATHYANARAYANA

    2012-01-01

    S Narasimha MurthyDepartment of Pharmaceutics, The University of Mississippi, USATransdermal drug delivery systems deliver drugs through the skin as an alternative to oral, intravascular, subcutaneous, and transmucosal routes. Potential advantages of transdermal delivery include, but are not limited to, elimination of first-pass metabolism, steady delivery/blood levels, better patient compliance, reduced systemic drug interactions, possible dose intervention, avoidance of medically assisted d...

  16. Encouraging generic use can yield significant savings.

    Science.gov (United States)

    Zimmerman, Christina

    2012-11-01

    Key findings. (1) Zero copayment for generic drugs is the greatest influencer of generic statin utilization. (2) Both higher copayments for generic drugs and lower copayments for competing brands are associated with a decreased probability of using generic statins. (3) Prior authorization and step therapy requirements for brand-name statins are associated with an increased use of generic drugs. (4) Greater use of generic statins should reduce costs for patients, plans, and Medicare.

  17. Reducing The Nuclear Danger

    Science.gov (United States)

    1995-10-01

    off convention • Eliminate the civil use of HEU (includes RERTR ) • Reduce stockpiles of civil HEU and plutonium • Promote alternatives to the...these countries. ANL supports the Department’s Reduced Enrichment for Research and Test Reactor ( RERTR ) Program by providing the technical means to...scientists and engineers at 60 institutes in Russia, Ukraine, Kazakhstan and Belarus. The United States and Russia have agreed to pursue a joint RERTR

  18. Using reduce in supersymmetry

    International Nuclear Information System (INIS)

    Santos, R.P. dos.

    1987-01-01

    A procedure which allows one to do Supersymmetry calculus in REDUCE is described. Using the concept of an eight-dimensional 'superspace' (spanned by four space-time and four anticommuting coordinates) and of 'superfields' (which represent an entire supermultiplet of particles that transform among themselves), covariant derivatives with respect to supersymmetry are defined. Then, combining the vector facility and LET statement in REDUCE, spinors are simulated in a way to control the algebraic manipulation. (G.D.F.) [pt

  19. 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...

  20. 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...

  1. 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...

  2. 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

  3. 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.

  4. Can a significance test be genuinely Bayesian?

    OpenAIRE

    Pereira, Carlos A. de B.; Stern, Julio Michael; Wechsler, Sergio

    2008-01-01

    The Full Bayesian Significance Test, FBST, is extensively reviewed. Its test statistic, a genuine Bayesian measure of evidence, is discussed in detail. Its behavior in some problems of statistical inference like testing for independence in contingency tables is discussed.

  5. 40 CFR 1508.27 - Significantly.

    Science.gov (United States)

    2010-07-01

    ... Register of Historic Places or may cause loss or destruction of significant scientific, cultural, or... cultural resources, park lands, prime farmlands, wetlands, wild and scenic rivers, or ecologically critical...

  6. 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...

  7. Contribution of radiodiagnosis to genetically significant dose

    International Nuclear Information System (INIS)

    Pele, J.M.; Ouvrard, R.

    Surveys were carried out in France on 33,000 X-ray medical examinations. The genetically significant dose to the whole population from roentgenography and fluoroscopy, for typical examinations, should be about 65mrads [fr

  8. 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

  9. 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...

  10. Asymptomatic bacteriuria. Clinical significance and management.

    Science.gov (United States)

    Raz, Raul

    2003-10-01

    The clinical significance and management of asymptomatic bacteriuria (ASB) differs according to different groups of patients. ASB requires antibiotic treatment in pregnant women, children aged 5-6 years and prior to invasive genitourinary procedures. However, there is a consensus that ASB in the elderly, healthy school girls and young women, diabetic women and patients with indwelling catheters or intermittent catheterization has no clinical significance and antibiotic prescription is not indicated.

  11. 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...... semeiotics and his theory of communication, we account for the formal conditions that have to be present for the release of the significance-effect....

  12. Significance of Hemispheric Security for Mexico

    Science.gov (United States)

    2003-04-07

    La Seguridad Internacional, la Nueva Geopolitica Continental y Mexico ,” Seminario Internacional sobre Misiones de Paz, Seguridad y Defensa, Rio de...USAWC STRATEGY RESEARCH PROJECT SIGNIFICANCE OF HEMISPHERIC SECURITY FOR MEXICO by LTC Enrique Garcia Jaramillo Cavalry, Mexican Army COL Joseph R...xx-xx-2002 to xx-xx-2003 4. TITLE AND SUBTITLE Significance of Hemispheric Security for Mexico Unclassified 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

  13. 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.

  14. Significance of Lead Residues in Mallard Tissues

    Science.gov (United States)

    Longcore, J.R.; Locke, L.N.; Bagley, George E.; Andrews, R.

    1974-01-01

    Tissues of adult, lead-dosed mallards that either died or were sacrificed were analyzed for lead. Lead levels in brains, tibiae, and breast muscle of ducks that died and in tibiae of ducks that were sacrificed increased significantly from dosage until death. Lead in the heart, lung, and blood from sacrificed ducks decreased significantly from dosage until death. Lead concentrations in tissues from ducks in the two groups were not significantly different except for the liver, kidney, and lung. Average lead levels in the livers and kidneys of ducks that died were significantly higher than those in ducks that were sacrificed. The mean concentration of lead in the lungs of the ducks sacrificed was significantly higher than the mean level in the lungs of ducks that died. Measurements of the lead concentrations in this study, when compared with lead levels reported in the literature for avian and non-avian species, showed that arbitrary diagnostic levels indicating lead poisoning could be set. In mallard ducks, lead levels exceeding 3 ppm in the brain, 6 to 20 ppm in the kidney or liver, or 10 ppm in clotted blood from the heart indicated acute exposure to lead.

  15. Clinical significance of anismus in encopresis.

    Science.gov (United States)

    Catto-Smith, A G; Nolan, T M; Coffey, C M

    1998-09-01

    Treatments designed to relieve paradoxical contraction of the anal sphincters during defecation (anismus) have had limited success in children with encopresis. This has raised doubts as to the clinical relevance of this diagnosis in childhood as anorectal dysfunction. Our aim was to determine whether, in patients who had treatment-resistant encopresis, the presence of electromyographic anismus was associated with increased faecal retention. Sixty-eight children with soiling (mean age 8.7+/-2.06 years) were assessed by clinical examination, abdominal radiography and then with anorectal manometry. Patients with electromyographic anismus (n=32; 47%) had significantly increased radiographic rectal faecal retention and were significantly less likely to be able to defecate water-filled balloons. There were no significant differences in response to prior therapy, history of primary encopresis, behavioural adjustment or in sociodemographic data. Our results suggest that electromyographic anismus is associated with obstructed defecation and faecal retention.

  16. Innovative Phase Change Approach for Significant Energy Savings

    Science.gov (United States)

    2016-09-01

    related to the production, use, transmission , storage, control, or conservation of energy that will – (A) reduce the need for additional energy supplies...Conditions set for operation were: a. The computer with the broadband wireless card is to be used for data collection, transmission and...FINAL REPORT Innovative Phase Change Approach for Significant Energy Savings ESTCP Project EW-201138 SEPTEMBER 2016 Dr. Aly H Shaaban Applied

  17. Significant improvement in the thermal annealing process of optical resonators

    Science.gov (United States)

    Salzenstein, Patrice; Zarubin, Mikhail

    2017-05-01

    Thermal annealing performed during process improves the quality of the roughness of optical resonators reducing stresses at the periphery of their surface thus allowing higher Q-factors. After a preliminary realization, the design of the oven and the electronic method were significantly improved thanks to nichrome resistant alloy wires and chopped basalt fibers for thermal isolation during the annealing process. Q-factors can then be improved.

  18. 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.

  19. 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-making, including important differences in the way individuals screen and scope. These patterns concern what we notice, how fast we frame the choice, and when we are critical about the provided information. The indications provide a basis for reflections on practice and on how to organise EA...

  20. 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

  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. 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...

  3. Incidence and Significance of Haematemesis in Cirrhosis

    African Journals Online (AJOL)

    1974-06-08

    Jun 8, 1974 ... veloped encephalopathy and coma. It was found that more patients fell into the latter group (50 cases) than into the group with haematemesis (with or without encephalopathy). (45 cases), but there was no significant difference in the mortality rate of the groups. s. Afr. Med. l., 48, 1155 (1974). It has for some ...

  4. Encounter Probability of Significant Wave Height

    DEFF Research Database (Denmark)

    Liu, Z.; Burcharth, H. F.

    The determination of the design wave height (often given as the significant wave height) is usually based on statistical analysis of long-term extreme wave height measurement or hindcast. The result of such extreme wave height analysis is often given as the design wave height corresponding to a c...

  5. 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…

  6. 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…

  7. 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 ...

  8. 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 ...

  9. 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…

  10. 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…

  11. 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 ...

  12. 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…

  13. 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...

  14. [Current clinical significance of anaerobic bacteremia].

    Science.gov (United States)

    Jirsa, Roman; Marešová, Veronika; Brož, Zdeněk

    2010-10-01

    to estimate tje current clinical significance of anaerobic bacteremia in a group of Czech hospitals. this retrospective analysis comprised 8 444 anaerobic blood cultures in patients admitted to four Czech hospitals between 2004 and 2007. in 16 patients, blood cultures yielded significant anaerobic bacteria. Thus, anaerobic bacteremia accounted for less than 2 % of clinically significant bacteremia. Four patients (18 %) died but none of the deaths could be clearly attributable to anaerobic bacteria in the bloodstream. The most common comorbidities predisposing to anaerobic bacteremia and the most frequent sources of infection were similar to those reported by other authors. The majority of anaerobic bacteremia cases were due to gram-negative bacteria, followed by Clostridium perfringens and, surprisingly, Eubacterium spp. (particularly Eubacterium lentum). anaerobic bacteremia remains rare. The comparison of our data with those by other authors suggests that (despite the reported high mortality) the actual clinical significance of anaerobic bacteremia is rather controversial and that the anaerobic bacteremia might not correspond to more serious pathogenic role of the anaerobic bacteria as the source of infection.

  15. 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 argue...

  16. 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.

  17. 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

  18. Reuse, Reduce, Recycle.

    Science.gov (United States)

    Briscoe, Georgia

    1991-01-01

    Discussion of recycling paper in law libraries is also applicable to other types of libraries. Results of surveys of law libraries that investigated recycling practices in 1987 and again in 1990 are reported, and suggestions for reducing the amount of paper used and reusing as much as possible are offered. (LRW)

  19. 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 ...

  20. Reduced Braginskii equations

    International Nuclear Information System (INIS)

    Yagi, M.; Horton, W.

    1994-01-01

    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 the perpendicular component of Ohm's law be solved to ensure ∇·j=0 for energy conservation

  1. Rheological measurements in reduced gravity

    Science.gov (United States)

    Bakhtiyarov, Sayavur I.; Overfelt, Ruel A.

    1999-01-01

    Rheology of fluidized beds and settling suspensions were studied experimentally in a series of reduced gravity parabolic flights aboard NASA's KC-135 aircraft. Silica sands of two different size distributions were fluidized by air. The slurries were made using silica sand and Glycerol solution. The experimental set up incorporated instrumentation to measure the air flow rate, the pressure drop and the apparent viscosity of the fluidized sand and sand suspensions at a wide range of the shear rates. The fluidization chamber and container had transparent walls to allow visualization of the structure changes involved in fluidization and in Couette flow in reduced gravity. Experiments were performed over a broad range of gravitational accelerations including microgravity and double gravity conditions. The results of the flight and ground experiments reveal significant differences in overall void fraction and hence in the apparent viscosity of fluidized sand and sand suspensions under microgravity as compared to one-g conditions.

  2. Physiological significance of polyploidization in mammalian cells.

    Science.gov (United States)

    Pandit, Shusil K; Westendorp, Bart; de Bruin, Alain

    2013-11-01

    Programmed polyploidization occurs in all mammalian species during development and aging in selected tissues, but the biological properties of polyploid cells remain obscure. Spontaneous polyploidization arises during stress and has been observed in a variety of pathological conditions, such as cancer and degenerative diseases. A major challenge in the field is to test the predicted functions of polyploidization in vivo. However, recent genetic mouse models with diminished polyploidization phenotypes represent novel, powerful tools to unravel the biological function of polyploidization. Contrary to a longstanding hypothesis, polyploidization appears to not be required for differentiation and has no obvious impact on proliferation. Instead, polyploidization leads to increased cell size and genetic diversity, which could promote better adaptation to chronic injury or stress. We discuss here the consequences of reducing polyploidization in mice and review which stress responses and molecular signals trigger polyploidization during development and disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Significance of stepwise excretion pattern in renogram

    International Nuclear Information System (INIS)

    Tamaki, Nagara; Ishihara, Takashi; Mori, Toru; Bito, Sanae; Ito, Hidetomi

    1981-01-01

    In 204 routine renogram examinations using 131 I-iodohippurate, stepwise excretion curves were observed in 22 cases (14 with chronic thyroiditis, 4 with idiopathic edema, 3 with lower urinary tract disorders, and 1 with Bartter's syndrome). Such a phenomenon was observed in 74% of euthyroid edematous patients with chronic thyroiditis and 57% of patients with idiopathic edema. The stepwise pattern was considered to have certain correlations with spasm or increased peristalsis of the urinary tract through the studies of excretory urogram, butylscopolamine treated renogram, and regional renogram. In one of these edematous patients with chronic thyroiditis, this renogram pattern could not be reproduced after bed rest corresponding with the clinical evidence that physical rest reduce the edema. Thus, the stepwise excretory pattern in renogram seemed to be a useful indicator of the fluctuating edema in patients with chronic thyroiditis and idiopathic edema. (author)

  4. Hypothermia reduces sulphur mustard toxicity

    International Nuclear Information System (INIS)

    Mi Lei; Gong Wenrong; Nelson, Peggy; Martin, Leanne; Sawyer, Thomas W.

    2003-01-01

    The effect of temperature on the development of sulphur mustard (HD)-induced toxicity was investigated in first passage cultures of human skin keratinocytes and on hairless guinea pig skin. When cells exposed to HD were incubated at 37 deg. C, a concentration-dependent decline in viability was observed that was maximal by 2 days. In contrast, no significant HD-induced toxicity was evident up to 4 days posttreatment when the cells were incubated at 25 deg. C. However, these protective effects were lost by 24 h when the cells were switched back to 37 deg. C. The protective effects of hypothermia were also demonstrated when apoptotic endpoints were examined. The HD concentration-dependent induction of fragmented DNA (as quantitated using soluble DNA and the TUNEL reaction), morphology, and p53 expression were all significantly depressed when cell cultures were incubated at 25 deg. C compared to 37 deg. C. When animals were exposed to HD vapour for 2, 4, and 6 min and left at room temperature, lesions were produced whose severity was dependent on exposure time and that were maximal by 72 h posttreatment. Moderate cooling (5-10 deg. C) of HD exposure sites posttreatment (4-6 h) significantly reduced the severity of the resultant lesions. However, in contrast to the in vitro results, these effects were permanent. It appears that the early and noninvasive act of cooling HD-exposed skin may provide a facile means of reducing the severity of HD-induced cutaneous lesions

  5. Significant incidents in nuclear fuel cycle facilities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  6. 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

  7. Respiratory neuroplasticity - Overview, significance and future directions.

    Science.gov (United States)

    Fuller, David D; Mitchell, Gordon S

    2017-01-01

    Neuroplasticity is an important property of the neural system controlling breathing. However, our appreciation for its importance is still relatively new, and we have much to learn concerning different forms of plasticity, their underlying mechanisms, and their biological and clinical significance. In this brief review, we discuss several well-studied models of respiratory plasticity, including plasticity initiated by inactivity in the respiratory system, intermittent and sustained hypoxia, and traumatic injury to the spinal cord. Other aspects of respiratory plasticity are considered in other contributions to this special edition of Experimental Neurology on respiratory plasticity. Finally, we conclude with discussions concerning the biological and clinical significance of respiratory motor plasticity, and areas in need of future research effort. Copyright © 2016. Published by Elsevier Inc.

  8. Dual purpose or not? The significant factors

    International Nuclear Information System (INIS)

    Bak, W.; Roland, V.

    1999-01-01

    The development of spent fuel storage systems requires consideration of many factors in making design decisions. A significant issue affecting the design is the need to incorporate transportability of the canister or cask system design, which results in major changes to the storage system design. This paper presents a review of the significant factors affecting storage system design to incorporate transportation requirements and looks at the trends in both the United States and Europe where Transnucleaire and its US affiliated companies Transnuclear Inc., Transnuclear West and PacTec are active. A discussion is also presented relative to the pros and cons of whether the spent fuel storage system vendor should anticipate these transportation needs in the design of their systems. (author)

  9. 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.

  10. 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

  11. 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) ...

  12. Impact significance determination-Designing an approach

    International Nuclear Information System (INIS)

    Lawrence, David P.

    2007-01-01

    The question of how best to go about determining the significance of impacts has, to date, only been addressed in a partial and preliminary way. The assumption tends to be made that it is either only necessary to provide explicit, justified reasons for a judgment about significance and/or to explicitly apply a prescribed procedure-a procedure usually involving the staged application of thresholds and/or criteria. The detailed attributes, strengths and limitations of such approaches and possible alternative approaches have yet to be explored systematically. This article addresses these deficiencies by analyzing the characteristics, specific methods and positive and negative tendencies of three general impact significance determination approaches-the technical approach, the collaborative approach and the reasoned argumentation approach. A range of potential composite approaches are also described. With an enhanced understanding of these approaches, together with potential combinations, EIA practitioners and other EIA participants can be in a better position to select an approach appropriate to their needs, to reinforce the positive tendencies and offset the negative tendencies of the selected approach and to combine the best qualities of more than one approach

  13. 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.)

  14. Clinical significance of dental root canal microflora.

    Science.gov (United States)

    Gomes, B P; Lilley, J D; Drucker, D B

    1996-01-01

    Previous work by this group has shown that a significant association exists between pain and the presence of either Prevotella or Peptostreptococcus spp. in dental root canals. The aim of this study was to examine a more extensive series of canals microbiologically, to determine whether any other particular endodontic symptoms or clinical signs showed specific associations with individual bacterial species. Seventy root canals were examined microbiologically and clinical data collected to investigate in detail such associations. Of the canals studied, 37 were associated with pain, 49 with tenderness to percussion, 23 with swelling, six with purulent exudate and 57 presented with wet root canals. Anaerobes were isolated from 70.3% of painful canals and from 29.7% of pain-free canals. Significant associations were found between (a) pain and either Prevotella spp. or peptostreptococci, both with P spp. (P Eubacterium spp. (P spp. or Pstr. micros, both with P spp. (each P Eubacterium, Peptostreptococcus, Prevotella or Propionibacterium (each P < 0.05). It was concluded that several different endodontic clinical signs and symptoms are significantly associated with specific bacterial species.

  15. Why reduce health inequalities?

    Science.gov (United States)

    Woodward, A; Kawachi, I

    2000-12-01

    It is well known that social, cultural and economic factors cause substantial inequalities in health. Should we strive to achieve a more even share of good health, beyond improving the average health status of the population? We examine four arguments for the reduction of health inequalities.1 Inequalities are unfair. Inequalities in health are undesirable to the extent that they are unfair, or unjust. Distinguishing between health inequalities and health inequities can be contentious. Our view is that inequalities become "unfair" when poor health is itself the consequence of an unjust distribution of the underlying social determinants of health (for example, unequal opportunities in education or employment).2 Inequalities affect everyone. Conditions that lead to marked health disparities are detrimental to all members of society. Some types of health inequalities have obvious spillover effects on the rest of society, for example, the spread of infectious diseases, the consequences of alcohol and drug misuse, or the occurrence of violence and crime.3 Inequalities are avoidable. Disparities in health are avoidable to the extent that they stem from identifiable policy options exercised by governments, such as tax policy, regulation of business and labour, welfare benefits and health care funding. It follows that health inequalities are, in principle, amenable to policy interventions. A government that cares about improving the health of the population ought therefore to incorporate considerations of the health impact of alternative options in its policy setting process.3 Interventions to reduce health inequalities are cost effective. Public health programmes that reduce health inequalities can also be cost effective. The case can be made to give priority to such programmes (for example, improving access to cervical cancer screening in low income women) on efficiency grounds. On the other hand, few programmes designed to reduce health inequalities have been formally

  16. Dietary Polyphenols and Their Biological Significance

    Directory of Open Access Journals (Sweden)

    Hongxiang Lou

    2007-09-01

    Full Text Available Dietary polyphenols represent a wide variety of compounds that occur in fruits,vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They aremostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins andphenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis,anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascularprotection, improvement of the endothelial function, as well as inhibition of angiogenesisand cell proliferation activity. Most of these biological actions have been attributed to theirintrinsic reducing capabilities. They may also offer indirect protection by activatingendogenous defense systems and by modulating cellular signaling processes such asnuclear factor-kappa B (NF-кB activation, activator protein-1(AP-1 DNA binding,glutathione biosynthesis, phosphoinositide 3 (PI3-kinase/protein kinase B (Akt pathway,mitogen-activated protein kinase (MAPK proteins [extracellular signal-regulated proteinkinase (ERK, c-jun N-terminal kinase (JNK and P38 ] activation, and the translocationinto the nucleus of nuclear factor erythroid 2 related factor 2 (Nrf2. This paper covers themost recent literature on the subject, and describes the biological mechanisms of action andprotective effects of dietary polyphenols.

  17. 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.

  18. 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.

  19. 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.)

  20. 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.

  1. Perspectives on Gandhi’s Significance Today

    Directory of Open Access Journals (Sweden)

    Michael Simpson

    2016-12-01

    Full Text Available Gandhi’s example has inspired countless political struggles worldwide over the past century. We might then ask how his thought has been transferred and translated when taken out of the particular historical and geographic context in which he lived. How have Gandhi’s ideas been changed or altered when adopted in different contexts? Which aspects of Gandhi’s thinking remain most relevant to struggles for social and environmental justice today? These are just a few of the questions that were discussed at the “Perspectives on Gandhi’s Significance Workshop” hosted by Reed College in Portland Oregon (USA, on April 16th, 2016.

  2. Significant events caused by extraneous acts

    International Nuclear Information System (INIS)

    Verlaeken, J.

    1987-01-01

    The operating experience feedback system of VINCOTTE, called ARIANE, consists, among others, of preparing synthesis reports on specific safety concerns. A recent report deals with significant events caused by extranous acts. Events attributable to human error are numerous. Confusion errors have already been analysed in several publications (NES IRS 664 etc.). However, are described here some ten incidents where extranous acts occurred: ZION 2 (September 76), OYSTER CREEK (May 79), PALISADES (January 81), CATAWBA (August 85), etc. The contributing factors for these unfortunate initiatives are explained; several resort to psychological influences. Corrective actions are discussed, and some general lessons are drawn. (author)

  3. Medical significance of the essential biological metals

    International Nuclear Information System (INIS)

    Davies, I.J.T.

    1977-01-01

    The medical significance of the essential biological metals such as zinc, copper and molybdenum as well as their nutritional and biochemical importance are reviewed. The following topics are treated: biochemical actions of the essential biological metals; the concept of essentiality; the development of knowledge about the essential biological metals. Data are given on zinc deficiency and hypogonadismi in humans, zinc and acrodermatitis enterophatica, zinc and the skin, zinc in diabetes mellitus, zinc and insulin, zinc and the liver; copper functions, copper deficiency - ''sway back'' in sheep, copper and haemopoiesis, copper and the function of blood vessels; molybdenum and dental caries in humans, oesophageal carcinoma and molybdenum deficiency in humans. (T.G.)

  4. 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

  5. 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.)

  6. Significant exposures to isoeugenol derivaties in perfumes

    DEFF Research Database (Denmark)

    Rastogi, Suresh Chandra; 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 spectrometry. 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....

  7. pancreatic steatosis: diagnosis and clinical significance

    Directory of Open Access Journals (Sweden)

    Murat Daðdeviren

    2017-03-01

    Full Text Available Pancreatic steatosis (PS, with increased use of abdominal imaging in recent years generally appears as incidental. But it is a condition that is often overlooked. The reason for this is not yet fully demonstrated the clinical significance of PS while. However, in recent years, there are some studies conducted on the relationship with ps and other disease such as diabetes, metabolic syndrome, acute and chronic pancreatitis and pancreatic cancer. In this review, the etiology, diagnosis, treatment and clinical characteristics of ps were evaluated in the light of recent literature and current approaches. [J Contemp Med 2017; 7(1.000: 107-112

  8. Significance of abolishing British National Oil Corporation

    Energy Technology Data Exchange (ETDEWEB)

    Mabro, R

    1985-04-01

    The decision to abolish British National Oil Corporation has greater significance than any commentator, so far, has cared to admit. Mr. Mabro says the Government has done much more than get rid of an institution it had previously weakened and emasculated; in effect, it had abdicated its responsibilities for the pricing of North Sea oil. He further observes that these moves may be consistent with the tenets of a simplistic free-market ideology: they betray, however, a lack of understanding of the economics of oil, and of the UK economic interest in oil.

  9. 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.

  10. 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

  11. Adaptive significance of root grafting in trees

    Energy Technology Data Exchange (ETDEWEB)

    Loehle, C.; Jones, R.

    1988-12-31

    Root grafting has long been observed in forest trees but the adaptive significance of this trait has not been fully explained. Various authors have proposed that root grafting between trees contributes to mechanical support by linking adjacent root systems. Keeley proposes that this trait would be of greatest advantage in swamps where soils provide poor mechanical support. He provides as evidence a greenhouse study of Nyssa sylvatica Marsh in which seedlings of swamp provenance formed between-individual root grafts more frequently than upland provenance seedlings. In agreement with this within-species study, Keeley observed that arid zone species rarely exhibit grafts. Keeley also demonstrated that vines graft less commonly than trees, and herbs never do. Since the need for mechanical support coincides with this trend, these data seem to support his model. In this paper, the authors explore the mechanisms and ecological significance of root grafting, leading to predictions of root grafting incidence. Some observations support and some contradict the mechanical support hypothesis.

  12. 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.

  13. 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.

  14. 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

  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. Origin and significance of defects in welds

    International Nuclear Information System (INIS)

    Lundin, C.D.

    1984-01-01

    In the past 10 to 15 years significant advances have taken place in the understanding of the origin and nature of weld discontinuities. The furthering of the knowledge of hot cracking, cold cracking, lamellar tearing and porosity formation is due to the development and utilization of sophisticated techniques for microscopy and microanalysis and the concerted efforts of many researchers in the U.S. and abroad. Concurrent with the progress toward better definition of the metallurgical mechanisms for discontinuity formation, the development of the fracture mechanics approach for the assessment of the significance of the discontinuities was brought into focus. It is the marriage of the metallurgical understanding of formation and the mechanics assessment of relevance that permits discontinuities to be treated with a new degree of sophistication. The many types of cracking and porosity formation were the subjects of numerous studies in the intervening years. This presentation will treat the various types of weld discontinuities which have their origin closely related to a metallurgical mechanism. Emphasis will be placed on hot cracking, and porosity formation with information presented on cold cracking, reheat cracking and lamellar tearing. The employment of the newer metallurgical tools will be discussed in terms of their utilization in determining the cause of discontinuity formation

  17. Biased lineups: sequential presentation reduces the problem.

    Science.gov (United States)

    Lindsay, R C; Lea, J A; Nosworthy, G J; Fulford, J A; Hector, J; LeVan, V; Seabrook, C

    1991-12-01

    Biased lineups have been shown to increase significantly false, but not correct, identification rates (Lindsay, Wallbridge, & Drennan, 1987; Lindsay & Wells, 1980; Malpass & Devine, 1981). Lindsay and Wells (1985) found that sequential lineup presentation reduced false identification rates, presumably by reducing reliance on relative judgment processes. Five staged-crime experiments were conducted to examine the effect of lineup biases and sequential presentation on eyewitness recognition accuracy. Sequential lineup presentation significantly reduced false identification rates from fair lineups as well as from lineups biased with regard to foil similarity, instructions, or witness attire, and from lineups biased in all of these ways. The results support recommendations that police present lineups sequentially.

  18. 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

  19. Why the CDM can reduce carbon leakage

    International Nuclear Information System (INIS)

    Kallbekken, S.

    2006-04-01

    Carbon leakage is an important concern because it can reduce the environmental effectiveness of the Kyoto Protocol. The Clean Development Mechanism, one of the flexibility mechanisms allowed under the protocol, has the potential to reduce carbon leakage significantly because it reduces the relative competitive disadvantage to Annex B countries of restricting greenhouse gas emissions. The economic intuition behind this mechanism is explored in a theoretical analysis. It is then analyzed numerically using a CGE model. The results indicate that, assuming appropriate accounting for leakage and under realistic assumptions on CDM activity, the CDM has the potential to reduce the magnitude of carbon leakage by around three fifths

  20. Response to a spill of national significance

    International Nuclear Information System (INIS)

    Jensen, D.S.; Pond, R.; Johnson, M.H.

    1993-01-01

    Responding to a spill of national significance (SONS), such as the 1989 Exxon Valdez spill, requires an augmenting organization to support the local response organization. The US Coast Guard has developed SONS protocol to be better prepared to respond to these infrequent catastrophic spills. A flag-level Coast Guard officer assumes the role of national incident commander (NIC) and federal on-scene coordinator (OSC), and is supported by a national incident task force (NITF). The major role of the NITF is to develop a national response strategy, acquire response resources and allocate them efficiently, and effectively deal with many peripheral national issues. Unified command concepts have been incorporated into the NITF and its primary organizational elements. In addition, frequent training and exercising is essential to keep the SONS protocol's preparedness at an acceptable level

  1. The significance of vector magnetic field measurements

    Science.gov (United States)

    Hagyard, M. J.

    1990-01-01

    Observations of four flaring solar active regions, obtained during 1980-1986 with the NASA Marshall vector magnetograph (Hagyard et al., 1982 and 1985), are presented graphically and characterized in detail, with reference to nearly simultaneous Big Bear Solar Observatory and USAF ASW H-alpha images. It is shown that the flares occurred where local photospheric magnetic fields differed most from the potential field, with initial brightening on either side of a magnetic-neutral line near the point of maximum angular shear (rather than that of maximum magnetic-field strength, typically 1 kG or greater). Particular emphasis is placed on the fact that these significant nonpotential features were detected only by measuring all three components of the vector magnetic field.

  2. Bayesian approaches for detecting significant deterioration

    International Nuclear Information System (INIS)

    Roed, Willy; Aven, Terje

    2009-01-01

    Risk indicators can provide useful input to risk management processes and are given increased attention in the Norwegian petroleum industry. Examples include indicators expressing the proportion of test failures of safety and barrier systems. Such indicators give valuable information about the performance of the systems and provide a basis for trend evaluations. Early warning of a possible deterioration is essential due to the importance of the systems in focus, but what should be the basis for the warning criterion? This paper presents and discusses several Bayesian approaches for the establishment of a warning criterion to disclose significant deterioration. The Norwegian petroleum industry is the starting point for this paper, but the study is relevant for other application areas as well

  3. 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.

  4. 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.

  5. 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.

  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. 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

  8. 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

  9. Prognostic significance of serum bilirubin in stroke

    International Nuclear Information System (INIS)

    Arslan, A.; Ismail, M.; Khan, F.; Khan, A.; Khattak, M.B.; Anwar, M.J.

    2011-01-01

    Background: Oxidative injury is an important cause of the neurologic lesion in stroke. Serum bilirubin is considered a natural antioxidant that may affect the prognosis of stroke. The purpose of this study was to evaluate the prognostic significance of bilirubin in stroke patients. Methods: A prospective cross-sectional study was conducted in Medical Units of Khyber Teaching Hospital, Peshawar. Inpatients admitted with acute attack of stroke were included in this study. Data regarding serum bilirubin and concurrent cerebrovascular risk factors were collected. National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were used to analyse stroke's severity and functional outcomes, respectively. Results: Hypertension, diabetes mellitus and heart diseases were the most common risk factors. Patients were divided into 3 groups on the basis of serum bilirubin, i.e., =0.6 mg/dl (Group-1), 0.7-0.9 mg/dl (Group-2), and =1.0 mg/dl (Group-3). The mean pre-hospitalisation NIHSS score for Groups 1, 2 and 3 was 5.62, 11.66 and 25.33, respectively; and post-hospitalisation score was 0.875, 3.76 and 16.26, respectively. The pre-hospitalisation mRS score was 4 for Group-1, 4.52 for Group-2 and 4.93 for Group-3; while post-hospitalisation Mrs Score was 1.50, 2.38 and 4.26, respectively. Average serum bilirubin level was significantly higher in patients with poor outcomes as compared with good outcomes (p<0.01). Conclusions: This study suggests that higher serum bilirubin levels were associated with increased stroke severity, longer hospitalisation and poor prognosis. (author)

  10. 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.

  11. Immunophenotyping in leukemia and its diagnostic significance

    Directory of Open Access Journals (Sweden)

    S. B. Kresno

    2004-09-01

    Full Text Available The identification of cell surface markers, defined as clusters of differentiation antigens (CD’s could be used to classify and sub-classify leukemia. Although the same antigens are expressed on normal cells, the phenotype on malignant cells are aberrantly and frequently asynchronously expressed and may be present in combinations not observed in normal blood or bone marrow. Aberrant expression of surface antigens corresponds with poor therapeutic response and short survival. Additional surface marker analysis complementary to morphologic evaluation and cytochemical staining has greatly improved our ability to characterize hematologic malignancies. A review and illustration on the diagnostic significance of immunophenotyping in leukemia will be presented. Data from 225 patients having complete assessments including morphology, cytochemistry and immunophenotyping in the period of 1994-2001 were collected and analyzed. Based on morphologic evaluation and cytochemistry, the diagnosis of acute myeloid leukemia and acute lymphoblastic leukemia were established in 51.1% and 48.9% of cases, respectively. Based on immunophenotyping AML was found in 49.0% of the cases. ALL could be classified into 4.9% pre-B-ALL, 18.7% B-ALL, and 14.7% T-ALL. Cases expressing cross-lineage antigens were found in 12.7%. The prognostic significance of these aberrant expression of antigens for those cases has yet to be established but some of the cases responded poorly to therapy. Immunophenotyping provides the tool to: 1 distinguish normal from clonal populations of leukemic cells; 2 define lineage and reveal the stage of maturation; 3 identify inappropriate expression of lineage associated antigens; 4 provides more informations to establish diagnosis and prognosis compared to standard methods. (Med J Indones 2004; 13: 195-202 Keywords: Immunophenotyping, clusters of differentiation antigens, lineage associated antigens

  12. Real significance of skin contamination is

    International Nuclear Information System (INIS)

    Sudmann, R.H.

    1983-01-01

    For five decades, health physicists have discussed the thickness, area, significance of radioactive contamination and the exposures to various portions of the skin. Concern about instances of skin contamination extend beyond the resultant organ dose simply because it is a recognizable and quantifiable event. As such, there is a tendency for management and regulatory agencies to use it as a trend indicator. The final result is a score card similar to the list of OSHA reportable accidents. In fact, the skin contamination incidence rate has a somewhat different meaning to the health physicist, to the manager, and to the regulator. The question must then be asked, What is the true significance of skin contamination, Is it the resultant skin dose, Is it an indicator of loss of control, Is it both or neither. In order to answer these questions, Rockwell Hanford Operations began analysis of the previous five years records of skin contamination cases. Since by policy each incidence of skin contamination is documented, a large percentage of the 425 records analyzed were of low level activity (less than 100 dpm/cm 2 ) on the extremeties, primarily hands and fingers. Most of these cases were readily decontaminated with soap and water. Individual elements studied included: detection/monitoring methods and limits; impact of type of operation on the incidence rate; causes of and methods for reduction of the incidence rate; reporting and documentation; and dose assessment. Results of the study indicate that skin contamination rarely presents a beta dose problem because it is normally highly localized on the extremeties. Only in unusual cases does it represent a potential for internal deposition. Thus, the real importance of skin contamination incidence is as an indicator of deteriorating conditions and should be reviewed by health physicists, managers and regulators as such

  13. 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.

  14. 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

  15. Reduced cost of ownership

    International Nuclear Information System (INIS)

    Wyse, W.H.; Newton, J.C.

    1995-01-01

    There is common drive throughout industry towards reduced costs of ownership of plant and equipment. Rolls-Royce and Associates Ltd. has developed the systems and expertise necessary to achieve these objectives. This Paper outlines the methods being used on existing facilities, and describes a new all embracing process called Planned Lifetime Management. This process, based on the military standard Integrated Logistic Support, ensures that all aspects of support are clearly identified at the design stage and that support is monitored to allow through-life support costs to be optimized. (author)

  16. The significance of Campylobacter jejuni infection in poultry: a review.

    Science.gov (United States)

    Shane, S M

    1992-01-01

    Campylobacter is a significant cause of enterocolitis in consumers of undercooked poultry meat. Campylobacter jejuni is the most significant of the three thermophilic Campylobacter species, and is responsible for intestinal colonization in poultry and food-borne enteritis in humans. Generally, C. jejuni is apathogenic in poultry, although newly hatched chicks and turkeys may develop a transient diarrhoea following infection. Modern intensive poultry production favours the introduction of infection into commercial growing units, resulting in intestinal colonization during the second to fourth weeks inclusive. Routes of infection include contaminated fomites, infected water supply, rodents, insects, and free-living birds. Vertical transmission is considered unlikely. Contamination of poultry meat is enhanced by deficiencies in transport and processing of broilers and turkeys. Scalding, defeathering and evisceration represent the significant points of cross-contamination during processing. Epidemiological correlation has been established between consumption of contaminated chicken and outbreaks of human campylobacteriosis. Amelioration of infection by application of improved standards of hygiene and decontamination is possible in the context of commercial poultry production. Improvement in washing of carcasses, and the application of chemical disinfectants and gamma irradiation have the potential to reduce the prevalence of C. jejuni contamination in poultry meat. These innovations, together with improved storage and handling of meat products, will reduce the risk of campylobacteriosis to consumers.

  17. Carotid endarterectomy significantly improves postoperative laryngeal sensitivity.

    Science.gov (United States)

    Hammer, Georg Philipp; Tomazic, Peter Valentin; Vasicek, Sarah; Graupp, Matthias; Gugatschka, Markus; Baumann, Anneliese; Konstantiniuk, Peter; Koter, Stephan Herwig

    2016-11-01

    Iatrogenic injury of the vagus nerve or its branches during carotid endarterectomy (CEA) can result in globus sensation, dysphagia, and even vocal fold immobility. Knowledge of morphologic and functional laryngopharyngeal outcomes after CEA is poor. The present study was performed to determine potential iatrogenic damage to the laryngeal innervation after CEA. An area of particular interest was the supraglottic sensory threshold, which was examined by Fiberoptic Endoscopic Evaluation of Swallowing With Sensory Testing (FEESST; Pentax Medical Company, Montvale, NJ), a validated and safe method for the determination of the motor and sensory components of swallowing. FEESST was used preoperatively in 32 patients scheduled to undergo CEA and twice postoperatively to examine the motor and sensory components of swallowing. In this endolaryngeal examination, laryngopharyngeal sensory thresholds (in mm Hg) were defined as normal at 6.0 mm Hg APP, with a value >10.0 mm Hg APP indicating abolished laryngeal adductor reflex. Acoustic voice parameters were also analyzed for further functional changes of the larynx. The mean ± standard deviation preoperative FEESST measures showed no significant differences (P = .065) between the operated-on side (6.73 ± 1.73 mm Hg) and the opposite side (5.83 ± 1.68 mm Hg). At 2 days postoperatively, the threshold increased (P = .001) to 7.62 ± 1.98 mm Hg on the operated-on side. A laryngopharyngeal mucosal hematoma on the operated side was endoscopically detectable in eight patients (30.8%); in these patients, we found a markedly elevated (P = .021) measure of 9.50 ± 0.93 mm Hg. On the opposite (nonoperated-on) side of the laryngopharynx, the thresholds remained at the same level as preoperatively over all assessments (P >.05), whereas the differences between the operated and nonoperated-on sides and the hematoma and nonhematoma groups were highly significant (P = .004 and P = .001, respectively). Surprisingly, the

  18. 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.)

  19. 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

  20. 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.

  1. Clinical significance of anaplasia in childhood rhabdomyosarcoma.

    Science.gov (United States)

    Sidhom, Iman; El Nadi, Enas; Taha, Hala; Elkinaai, Naglaa; Zaghloul, Mohamed S; Younes, Alaa; Labib, Rania; Sabry, Mohamed

    2015-06-01

    The presence of anaplastic features has been known to correlate with poor clinical outcome in various pediatric malignancies, including Wilms tumor and medulloblastoma but not in rhabdomyosarcoma. Aim was to study the frequency of anaplasia at presentation in childhood rhabdomyosarcoma and its relationship to clinical and pathological characteristics as well as to outcome. Anaplasia was retrospectively assessed in 105 consecutive pediatric rhabdomyosarcoma patients who were registered at the Children's Cancer Hospital in Egypt (CCHE) during the period from July 2007 till the end of May 2010. Anaplasia was diagnosed in 18 patients (17.1%), focal in 10 (9.5%) and diffuse in 8 (7.6%). The distribution of anaplasia was found to be more common in older patients having age⩾10 years. Also it was more likely to occur in the high risk group and in tumors with unfavorable histology (alveolar subtype), and stage IV. The 3-year failure free survival rates for patients with and without anaplasia were 27.8±10.6% and 53.4±5.8%, respectively (p=0.014) and the 3-year overall survival rates were 35.3±11.6% and 61±6%, respectively (p=0.019). The frequency of anaplasia in pediatric patients with rhabdomyosarcoma in our study was 17.1%. The presence of anaplasia had statistically significant worse clinical outcome. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  2. Clinical significance of anaplasia in childhood rhabdomyosarcoma

    International Nuclear Information System (INIS)

    Sidhom, I.; El Nadi, E.; Taha, H.; Elkinaai, N.; Zaghloul, M.S.; Younes, A.; Labib, R.; Sabry, M.

    2015-01-01

    Background: The presence of anaplastic features has been known to correlate with poor clinical outcome in various pediatric malignancies, including Wilms tumor and medulloblastoma but not in rhabdomyosarcoma. Aim: Aim was to study the frequency of anaplasia at presentation in childhood rhabdomyosarcoma and its relationship to clinical and pathological characteristics as well as to outcome. Patients and Methods: Anaplasia was retrospectively assessed in 105 consecutive pediatric rhabdomyosarcoma patients who were registered at the Children’s Cancer Hospital in Egypt (CCHE) during the period from July 2007 till the end of May 2010. Results: Anaplasia was diagnosed in 18 patients (17.1%), focal in 10 (9.5%) and diffuse in 8 (7.6%). The distribution of anaplasia was found to be more common in older patients having age P 10 years. Also it was more likely to occur in the high risk group and in tumors with unfavorable histology (alveolar subtype), and stage IV. The 3-year failure free survival rates for patients with and without anaplasia were 27.8 ± 10.6% and 53.4 ± 5.8%, respectively (p = 0.014) and the 3-year overall survival rates were 35.3 ± 11.6% and 61 ± 6%, respectively (p = 0.019). Conclusions: The frequency of anaplasia in pediatric patients with rhabdomyosarcoma in our study was 17.1%. The presence of anaplasia had statistically significant worse clinical outcome

  3. 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.

  4. 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

  5. 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)

  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. 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.

  8. 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.

  9. 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.

  10. Medical Significance of Microorganisms in Spacecraft Environment

    Science.gov (United States)

    Pierson, Duane L.; Ott, C. Mark

    2007-01-01

    Microorganisms can spoil food supplies, contaminate drinking water, release noxious volatile compounds, initiate allergic responses, contaminate the environment, and cause infectious diseases. International acceptability limits have been established for bacterial and fungal contaminants in air and on surfaces, and environmental monitoring is conducted to ensure compliance. Allowable levels of microorganism in water and food have also been established. Environmental monitoring of the space shuttle, the Mir, and the ISS have allowed for some general conclusions. Generally, the bacteria found in air and on interior surfaces are largely of human origin such as Staphylococcus spp., Micrococcus spp. Common environmental genera such as Bacillus spp. are the most commonly isolated bacteria from all spacecraft. Yeast species associated with humans such as Candida spp. are commonly found. Aspergillus spp., Penicillium spp., and Cladosporium spp. are the most commonly isolated filamentous fungi. Microbial levels in the environment differ significantly depending upon humidity levels, condensate accumulation, and availability of carbon sources. However, human "normal flora" of bacteria and fungi can result in serious, life-threatening diseases if human immunity is compromised. Disease incidence is expected to increase as mission duration increases.

  11. [The significance of meat quality in marketing].

    Science.gov (United States)

    Kallweit, E

    1994-07-01

    Food quality in general and meat quality in particular are not only evaluated by means of objective quality traits but the entire production process is gaining more attention by the modern consumer. Due to this development quality programs were developed to define the majority of the processes in all production and marketing steps which are again linked by contracts. Not all of these items are quality relevant, but are concessions to ethic principles (animal welfare etc.). This is demonstrated by the example of Scharrel-pork production. The price differentiation at the pork market is still influenced predominantly by quantitative carcass traits. On the European market quality programs still are of minor significance. Premiums which are paid for high quality standards are more or less compensated by higher production costs and lower lean meat percentages, which must be expected in stress susceptible strains. The high efforts to establish quality programs, however, help to improve the quality level in general, and secure the market shares for local producers.

  12. Bedtime Blood Pressure Chronotherapy Significantly Improves Hypertension Management.

    Science.gov (United States)

    Hermida, Ramón C; Ayala, Diana E; Fernández, José R; Mojón, Artemio; Crespo, Juan J; Ríos, María T; Smolensky, Michael H

    2017-10-01

    Consistent evidence of numerous studies substantiates the asleep blood pressure (BP) mean derived from ambulatory BP monitoring (ABPM) is both an independent and a stronger predictor of cardiovascular disease (CVD) risk than are daytime clinic BP measurements or the ABPM-determined awake or 24-hour BP means. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of 6 different classes and their combinations significantly improves BP control, particularly sleep-time BP, and reduces adverse effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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.

  14. 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.

  15. 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.

  16. Clinical significance of autoantibodies in autoimmune hepatitis.

    Science.gov (United States)

    Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

    2013-10-01

    The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. The significance of routines in nursing practice.

    Science.gov (United States)

    Rytterström, Patrik; Unosson, Mitra; Arman, Maria

    2011-12-01

    The aim of this study was to illuminate the significance of routines in nursing practice. Clinical nursing is performed under the guidance of routines to varying degrees. In the nursing literature, routine is described as having both negative and positive aspects, but use of the term is inconsistent, and empirical evidence is sparse. In the research on organisational routines, a distinction is made between routine as a rule and routine as action. A qualitative design using a phenomenological-hermeneutic approach. Data collection from three focus groups focused on nurses' experience of routines. Seventeen individual interviews from a previous study focusing on caring culture were also analysed in a secondary qualitative analysis. All participants were employed as 'qualified nursing pool' nurses. Routines are experienced as pragmatic, obstructive and meaningful. The aim of the pragmatic routine was to ensure that daily working life works; this routine is practised more on the basis of rational arguments and obvious intentions. The obstructive routine had negative consequences for nursing practice and was described as nursing losing its humanity and violating the patient's integrity. The meaningful routine involved becoming one with the routine and for the nurses, it felt right and meaningful to adapt to it. Routines become meaningful when the individual action is in harmony with the cultural pattern on which the nursing work is based. Instead of letting contemporary practice passively become routine, routines can be assessed and developed using research and theoretical underpinnings as a starting point for nursing practice. Leaders have a special responsibility to develop and support meaningful routines. One approach could be to let wards examine their routines from a patient perspective on the basis of the themes of pragmatic, meaningful and obstructive routine. © 2010 Blackwell Publishing Ltd.

  18. Identification of sequence motifs significantly associated with antisense activity

    Directory of Open Access Journals (Sweden)

    Peek Andrew S

    2007-06-01

    mediators to speed the process along like the RNA Induced Silencing Complex (RISC in RNAi. The independence of motif position and antisense activity also allows us to bypass consideration of this feature in the modelling process, promoting model efficiency and reducing the chance of overfitting when predicting antisense activity. The increase in SVR correlation with significant features compared to nearest-neighbour features indicates that thermodynamics alone is likely not the only factor in determining antisense efficiency.

  19. Reducing Outdoor Advertising

    Directory of Open Access Journals (Sweden)

    Patrice de Rendinger

    2006-05-01

    Full Text Available The fundamental concept is that public space is not a private property. So, a facade (the outer skin, the last millimeter belongs to the town, not to the owner of the building. Changing the rendering, a window, adding or removing anything from a facade requires a permission delivered by the town's authority.In places like Paris, Bordeaux, Marseilles, Lyon, Strasbourg… everywhere one can find a registrated building such as a cathedral, a castle, or a group of ancient buildings, a national administration is controlling this permission. This administration is called «historical monuments administration» and is locally lead by a specialized architect.In the late seventies, French government decided to reduce advertising on the roads and on the city walls. Advertising on the road was leading to a confusion reducing the efficacy of the roadsigns and direction signs, which is dangerous. The reduction was under control of a national administration: the ministry of equipment in charge of the roads design. Advertising on the walls with publicity boards was under control of the cities. Every city has a townplanning regulation. Many cities included forbidding advertisement boards on the walls in this regulation.A couple of firms, but mainly once (Decaux found clever to give a hand to the cities to control advertising. Decaux developed a line of bus stop shelters including advertisements and advertising panels and paid the cities the right to put rather smaller publicities on the public domain.Now Decaux is no more alone on this market and the cities are comparing offers.Marseille turned to a foreign advertising firm who pays three times the price Decaux paid… for half of the advertising surface. Freiburg erased totally the public domain advertisements, selling the tramways and bus coachwork as advertising spaces. Paris is reopening the advertising market before the end of Deacaux's contract and will pay Deacaux a huge amount

  20. Reduced NOX combustion method

    International Nuclear Information System (INIS)

    Delano, M.A.

    1991-01-01

    This patent describes a method for combusting fuel and oxidant to achieve reduced formation of nitrogen oxides. It comprises: It comprises: heating a combustion zone to a temperature at least equal to 1500 degrees F.; injecting into the heated combustion zone a stream of oxidant at a velocity within the range of from 200 to 1070 feet per second; injecting into the combustion zone, spaced from the oxidant stream, a fuel stream at a velocity such that the ratio of oxidant stream velocity to fuel stream velocity does not exceed 20; aspirating combustion gases into the oxidant stream and thereafter intermixing the aspirated oxidant stream and fuel stream to form a combustible mixture; combusting the combustible mixture to produce combustion gases for the aspiration; and maintaining the fuel stream substantially free from contact with oxidant prior to the intermixture with aspirated oxidant

  1. Method of reducing zirconium

    International Nuclear Information System (INIS)

    Megy, J.A.

    1980-01-01

    A method was developed for making nuclear-grade zirconium from a zirconium compound, which ismore economical than previous methods since it uses aluminum as the reductant metal rather than the more expensive magnesium. A fused salt phase containing the zirconium compound to be reduced is first prepared. The fused salt phase is then contacted with a molten metal phase which contains aluminum and zinc. The reduction is effected by mutual displacment. Aluminum is transported from the molten metal phase to the fused salt phase, replacing zirconium in the salt. Zirconium is transported from the fused salt phase to the molten metal phase. The fused salt phase and the molten metal phase are then separated, and the solvent metal and zirconium are separated by distillation or other means. (DN)

  2. Prognostic Significance of Signet Ring Gastric Cancer

    Science.gov (United States)

    Taghavi, Sharven; Jayarajan, Senthil N.; Davey, Adam; Willis, Alliric I.

    2012-01-01

    Purpose Studies in Asia have questioned the dictum that signet ring cell carcinoma (SRC) has a worse prognosis than other forms of gastric cancer. Our study determined differences in presentation and outcomes between SRC and gastric adenocarcinoma (AC) in the United States. Patients and Methods The National Cancer Institute Surveillance, Epidemiology, and End Results database was reviewed for SRC and AC from 2004 to 2007. Results We reviewed 10,246 cases of patients with gastric cancer, including 2,666 of SRC and 7,580 of AC. SRC presented in younger patients (61.9 v 68.7 years; P < .001) and less often in men (52.7% v 68.7%; P < .001). SRC patients were more frequently black (11.3% v 10.9%), Asian (16.4% v 13.2%), American Indian/Alaska Native (0.9% v 0.8%), or Hispanic (23.3% v 14.0%; P < .001). SRC was more likely to be stage T3-4 (45.8% v 33.3%), have lymph node spread (59.7% v 51.8%), and distant metastases (40.2% v 37.6%; P < .001). SRC was more likely to be found in the lower (30.7% v 24.2%) and middle stomach (30.6% v 20.7%; P < .001). Median survival was not different between the two (AC, 14.0 months v SRC, 13.0 months; P = .073). Multivariable analyses demonstrated SRC was not associated with mortality (hazard ratio [HR], 1.05; 95% CI, 0.96 to 1.11; P = .150). Mortality was associated with age (HR, 1.01; 95% CI, 1.01 to 1.02; P < .001), black race (HR, 1.10; 95% CI, 1.01 to 1.20; P = .026), and tumor grade. Variables associated with lower mortality risk included Asian race (HR, 0.83; 95% CI, 0.77 to 0.91; P < .001) and surgery (HR, 0.37; 95% CI, 0.34 to 0.39; P < .001). Conclusion In the United States, SRC significantly differs from AC in extent of disease at presentation. However, when adjusted for stage, SRC does not portend a worse prognosis. PMID:22927530

  3. Biological significance of soluble IL-2 receptor

    Directory of Open Access Journals (Sweden)

    Calogero Caruso

    1993-01-01

    Full Text Available A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC activation and interleukin-2 receptor (IL-2R expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting

  4. Increasing the statistical significance of entanglement detection in experiments.

    Science.gov (United States)

    Jungnitsch, Bastian; Niekamp, Sönke; Kleinmann, Matthias; Gühne, Otfried; Lu, He; Gao, Wei-Bo; Chen, Yu-Ao; Chen, Zeng-Bing; Pan, Jian-Wei

    2010-05-28

    Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. Experimentally, we observe this phenomenon in a four-photon experiment, testing the Mermin and Ardehali inequality for different levels of noise. Furthermore, we provide a way to develop entanglement tests with high statistical significance.

  5. IMAGE STEGANOGRAPHY DENGAN METODE LEAST SIGNIFICANT BIT (LSB

    Directory of Open Access Journals (Sweden)

    M. Miftakul Amin

    2014-02-01

    Full Text Available Security in delivering a secret message is an important factor in the spread of information in cyberspace. Protecting that message to be delivered to the party entitled to, should be made a message concealment mechanism. The purpose of this study was to hide a secret text message into digital images in true color 24 bit RGB format. The method used to insert a secret message using the LSB (Least Significant Bit by replacing the last bit or 8th bit in each RGB color component. RGB image file types option considering that messages can be inserted capacity greater than if use a grayscale image, this is because in one pixel can be inserted 3 bits message. Tests provide results that are hidden messages into a digital image does not reduce significantly the quality of the digital image, and the message has been hidden can be extracted again, so that messages can be delivered to the recipient safely.

  6. Significance of NTM infections in Croatia

    Directory of Open Access Journals (Sweden)

    V Katalinic-Jankovic

    2015-01-01

    laboratory are sent to the National Reference Laboratory for identification. NTM strains have been systematically recorded and reported since 1982. In the last decade, two retrospective analyses were done to assess the clinical relevance of different NTM species and the burden of pulmonary NTM disease. Over the past decade, a 30-fold increase in overall NTM isolation rates and a 4-fold increase in PNTM incidence were observed. Mycobacterium xenopi was the most frequently seen causative agent of pulmonary NTM disease, but the degree of clinical relevance (i.e., percentage of patients meeting the diagnosis criteria, per species was higher for isolates of MAC (66.5% and M. kansasii (57.2%. Only about 30% of the M. xenopi isolates represented true disease. Further, interesting regional differences were observed. Clinically relevant NTM isolates were significantly more often found in the coastal region of Croatia, and the average annual incidence of the PNTM was twice as high in coastal compared with the continental region. The overall burden of PNTM in Croatia is still low compared with tuberculosis. This can, in part, explain the observed lack of knowledge of NTM infections among respiratory specialists. Since these pathogens are increasingly common worldwide, especially in countries where the incidence of tuberculosis is declining, a constant rising of awareness and knowledge is necessary.

  7. Significance testing in ridge regression for genetic data

    Directory of Open Access Journals (Sweden)

    De Iorio Maria

    2011-09-01

    Full Text Available Abstract Background Technological developments have increased the feasibility of large scale genetic association studies. Densely typed genetic markers are obtained using SNP arrays, next-generation sequencing technologies and imputation. However, SNPs typed using these methods can be highly correlated due to linkage disequilibrium among them, and standard multiple regression techniques fail with these data sets due to their high dimensionality and correlation structure. There has been increasing interest in using penalised regression in the analysis of high dimensional data. Ridge regression is one such penalised regression technique which does not perform variable selection, instead estimating a regression coefficient for each predictor variable. It is therefore desirable to obtain an estimate of the significance of each ridge regression coefficient. Results We develop and evaluate a test of significance for ridge regression coefficients. Using simulation studies, we demonstrate that the performance of the test is comparable to that of a permutation test, with the advantage of a much-reduced computational cost. We introduce the p-value trace, a plot of the negative logarithm of the p-values of ridge regression coefficients with increasing shrinkage parameter, which enables the visualisation of the change in p-value of the regression coefficients with increasing penalisation. We apply the proposed method to a lung cancer case-control data set from EPIC, the European Prospective Investigation into Cancer and Nutrition. Conclusions The proposed test is a useful alternative to a permutation test for the estimation of the significance of ridge regression coefficients, at a much-reduced computational cost. The p-value trace is an informative graphical tool for evaluating the results of a test of significance of ridge regression coefficients as the shrinkage parameter increases, and the proposed test makes its production computationally feasible.

  8. Significant Association between Sulfate-Reducing Bacteria and Uranium-Reducing Microbial Communities as Revealed by a Combined Massively Parallel Sequencing-Indicator Species Approach▿ †

    OpenAIRE

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K.; Jardine, Philip M.; Zhou, Jizhong; Criddle, Craig S.; Marsh, Terence L.

    2010-01-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remedi...

  9. Generalized reduced magnetohydrodynamic equations

    International Nuclear Information System (INIS)

    Kruger, S.E.

    1999-01-01

    A new derivation of reduced magnetohydrodynamic (MHD) equations is presented. A multiple-time-scale expansion is employed. It has the advantage of clearly separating the three time scales of the problem associated with (1) MHD equilibrium, (2) fluctuations whose wave vector is aligned perpendicular to the magnetic field, and (3) those aligned parallel to the magnetic field. The derivation is carried out without relying on a large aspect ratio assumption; therefore this model can be applied to any general configuration. By accounting for the MHD equilibrium and constraints to eliminate the fast perpendicular waves, equations are derived to evolve scalar potential quantities on a time scale associated with the parallel wave vector (shear-Alfven wave time scale), which is the time scale of interest for MHD instability studies. Careful attention is given in the derivation to satisfy energy conservation and to have manifestly divergence-free magnetic fields to all orders in the expansion parameter. Additionally, neoclassical closures and equilibrium shear flow effects are easily accounted for in this model. Equations for the inner resistive layer are derived which reproduce the linear ideal and resistive stability criterion of Glasser, Greene, and Johnson. The equations have been programmed into a spectral initial value code and run with shear flow that is consistent with the equilibrium input into the code. Linear results of tearing modes with shear flow are presented which differentiate the effects of shear flow gradients in the layer with the effects of the shear flow decoupling multiple harmonics

  10. Reducing maintenance costs

    International Nuclear Information System (INIS)

    Zaiss, W.; Reuschle, K.; Baier, B.

    2002-01-01

    The increasingly more expensive maintenance measures, cuts in the cost budget, and the loss of know-how on the part of vendors all require a change of policy with respect to maintenance concepts of the part of operators. This also applies to the existing valve concepts, the drives included. Under these aspects, the current drive, which is self-actuated and actuated by outside media, for a parallel-plate valve of a nomial width of 700 was reconsidered. The effort served to reduce maintenance costs and, at the same time, simplify the drive concept as well as cut back on the number of in-service inspections. Moreover, the number of active components were to be minimized and installation conditions in the plant were to be improved. When the boundary conditions to be observed with respect to process technology had been laid down, the competent technical department developed a concept of modification of the drive. A major constituent part was the demonstration of the functioning capability of the new drive under accident conditions. It was achieved mainly by an analytical approach. In the resultant drive concept, the same control valves are employed to actuate a driving cylinder by means of self-actuation or by an outside medium as a function of pressure. (orig.) [de

  11. Generalized reduced MHD equations

    International Nuclear Information System (INIS)

    Kruger, S.E.; Hegna, C.C.; Callen, J.D.

    1998-07-01

    A new derivation of reduced magnetohydrodynamic (MHD) equations is presented. A multiple-time-scale expansion is employed. It has the advantage of clearly separating the three time scales of the problem associated with (1) MHD equilibrium, (2) fluctuations whose wave vector is aligned perpendicular to the magnetic field, and (3) those aligned parallel to the magnetic field. The derivation is carried out without relying on a large aspect ratio assumption; therefore this model can be applied to any general toroidal configuration. By accounting for the MHD equilibrium and constraints to eliminate the fast perpendicular waves, equations are derived to evolve scalar potential quantities on a time scale associated with the parallel wave vector (shear-alfven wave time scale), which is the time scale of interest for MHD instability studies. Careful attention is given in the derivation to satisfy energy conservation and to have manifestly divergence-free magnetic fields to all orders in the expansion parameter. Additionally, neoclassical closures and equilibrium shear flow effects are easily accounted for in this model. Equations for the inner resistive layer are derived which reproduce the linear ideal and resistive stability criterion of Glasser, Greene, and Johnson

  12. Post-exposure vaccination with multi-stage vaccine significantly reduce map level in tissues without interference in diagnostics

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, Claus; Melvang, Heidi Mikkelsen

    A new (Fet11) vaccine against paratuberculosis based on recombinant antigens from acute and latent stages of Map infection was developed to be used without interference with diagnostic tests for bovine TB and Johne’s disease. Calves were orally inoculated with 2x10E10 live Map in their third week...... of life and randomly assigned to four groups of seven calves each. One group was left unvaccinated, while other calves were post-exposure vaccinated with either a whole-cell vaccine at 16 weeks, or Fet11 vaccine at 3 and 7, or 16 and 20 weeks of age, respectively. Antibody responses were measured by ID...... Screen® ELISA and individual vaccine protein ELISAs along with FACS and IFN-γ responses to PPDj and to individual vaccine proteins. At termination 8 or 12 months of age, Map burden in a number of gut tissues was determined by quantitative IS900 PCR and histopathology. Fet11 vaccination of calves at 16...

  13. 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

    ... plans maintained by commercial airlines. See section 402 of PPA '06 for a special rule that applies to certain plans maintained by an employer that is a commercial passenger airline or the principal business of which is providing catering services to a commercial passenger airline. Under this special rule...

  14. Crossing the Telemedicine Chasm: Have the U.S. Barriers to Widespread Adoption of Telemedicine Been Significantly Reduced?

    Directory of Open Access Journals (Sweden)

    Cynthia LeRouge

    2013-11-01

    Full Text Available Barriers have challenged widespread telemedicine adoption by health care organizations for 40 years. These barriers have been technological, financial, and legal and have also involved business strategy and human resources. The article canvasses recent trends—events and activities in each of these areas as well as US health reform activities that might help to break down these barriers. The key to telemedicine success in the future is to view it as an integral part of health care services and not as a stand-alone project. Telemedicine must move from experimental and separate to integrated and equivalent to other health services within health care organizations. Furthermore, telemedicine serves as vital connective tissue for expanding health care organization networks.

  15. Cone-morse implant connection system significantly reduces bacterial leakage between implant and abutment: an in vitro study.

    Science.gov (United States)

    Baj, A; Bolzoni, A; Russillo, A; Lauritano, D; Palmieri, A; Cura, F; Silvestre, F J; Giannì, A B

    2017-01-01

    Osseointegrated implants are very popular dental treatments today in the world. In osseointegrated implants, the occlusal forces are transmitted from prosthesis through an abutment to a dental implant. The abutment is connected to the implant by mean of a screw. A screw is the most used mean for connecting an implant to an abutment. Frequently the screws break and are lost. There is an alternative to screw retained abutment systems: the cone-morse connection (CMC). The CMC, thanks to the absence of the abutment screw, guarantees no micro-gaps, no micro-movements, and a reduction of bacterial leakage between implant and abutment. As P. gingivalis and T. forsythia penetration might have clinical relevance, it was the purpose of this investigation to evaluate molecular leakage of these two bacteria in a new CMC implants systems (Leone Spa®, Florence, Italy). To identify the capability of the implant to protect the internal space from the external environment, the passage of genetically modified Escherichia coli across implant-abutment interface was evaluated. Four cone-morse Leone implants (Leone® Spa, Florence, Italy) were immerged in a bacterial culture for 24 h and bacteria amount was then measured inside implant-abutment interface with Real-time PCR. Bacteria were detected inside all studied implants, with a median percentage of 3% for P. gingivalis and 4% for T. forsythia. Cone-morse connection implant system has very low bacterial leakage percentage and is similar to one-piece implants.

  16. Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly reduces the risk of PSA progression in early prostate cancer

    DEFF Research Database (Denmark)

    See, W; Iversen, P; Wirth, M

    2003-01-01

    To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer.......To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer....

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

    Science.gov (United States)

    The 2015 Global Burden of Disease (GBD) study has listed air pollution as the fourth-ranking global mortality risk factor. Few studies have attempted to understand how these burdens change through time, especially in the United States (US). Here we aim to estimate air pollution-r...

  18. Significantly reduced health burden from ambient air pollution in the United States under emission reductions from 1990 to 2010

    Science.gov (United States)

    The 2015 Global Burden of Disease (GBD) study has listed air pollution as the fourth-ranking global mortality risk factor. Many studies have estimated the global or national burden of disease attributed to air pollution. However, little effort has been focused on understanding ho...

  19. American ginseng significantly reduced the progression of high-fat-diet-enhanced colon carcinogenesis in ApcMin/+mice

    Directory of Open Access Journals (Sweden)

    Chunhao Yu

    2015-07-01

    Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

  20. Is Systemic Operation Design Capable of Reducing Significantly Bias in Operational Level Planning Caused by Military Organizational Culture?

    Science.gov (United States)

    2006-05-25

    drape shallow ‘rival’ ideas across them. At best this constitutes a waste of time and at worse a new source of poor judgments. Nor is such...quoted in 1 (UK) Armoured Division Draft Future Divisional Headquarters Structure Review ref G3/3800 dated 19 Jul 05. APPENDIX II – Structuring...and divisional level (HQ 1 UK Armoured Division) through to the operational and strategic interface (Project ROBERTS 2).64 Functions in a Deployed