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Sample records for high levels nef

  1. Effector kinase coupling enables high-throughput screens for direct HIV-1 Nef antagonists with antiretroviral activity.

    PubMed

    Emert-Sedlak, Lori A; Narute, Purushottam; Shu, Sherry T; Poe, Jerrod A; Shi, Haibin; Yanamala, Naveena; Alvarado, John Jeff; Lazo, John S; Yeh, Joanne I; Johnston, Paul A; Smithgall, Thomas E

    2013-01-24

    HIV-1 Nef, a critical AIDS progression factor, represents an important target protein for antiretroviral drug discovery. Because Nef lacks intrinsic enzymatic activity, we developed an assay that couples Nef to the activation of Hck, a Src family member and Nef effector protein. Using this assay, we screened a large, diverse chemical library and identified small molecules that block Nef-dependent Hck activity with low micromolar potency. Of these, a diphenylpyrazolo compound demonstrated submicromolar potency in HIV-1 replication assays against a broad range of primary Nef variants. This compound binds directly to Nef via a pocket formed by the Nef dimerization interface and disrupts Nef dimerization in cells. Coupling of nonenzymatic viral accessory factors to host cell effector proteins amenable to high-throughput screening may represent a general strategy for the discovery of new antimicrobial agents. PMID:23352142

  2. Nef Stimulates Human Immunodeficiency Virus Type 1 Replication in Primary T Cells by Enhancing Virion-Associated gp120 Levels: Coreceptor-Dependent Requirement for Nef in Viral Replication†

    PubMed Central

    Lundquist, Christopher A.; Zhou, Jing; Aiken, Christopher

    2004-01-01

    The Nef protein enhances human immunodeficiency virus type 1 (HIV-1) replication through an unknown mechanism. We and others have previously reported that efficient HIV-1 replication in activated primary CD4+ T cells depends on the ability of Nef to downregulate CD4 from the cell surface. Here we demonstrate that Nef greatly enhances the infectivity of HIV-1 particles produced in primary T cells. Nef-defective HIV-1 particles contained significantly reduced quantities of gp120 on their surface; however, Nef did not affect the levels of virion-associated gp41, indicating that Nef indirectly stabilizes the association of gp120 with gp41. Surprisingly, Nef was not required for efficient replication of viruses that use CCR5 for entry, nor did Nef influence the infectivity or gp120 content of these virions. Nef also inhibited the incorporation of CD4 into HIV-1 particles released from primary T cells. We propose that Nef, by downregulating cell surface CD4, enhances HIV-1 replication by inhibiting CD4-induced dissociation of gp120 from gp41. The preferential requirement for Nef in the replication of X4-tropic HIV-1 suggests that the ability of Nef to downregulate CD4 may be most important at later stages of disease when X4-tropic viruses emerge. PMID:15163722

  3. A single amino acid in the SH3 domain of Hck determines its high affinity and specificity in binding to HIV-1 Nef protein.

    PubMed Central

    Lee, C H; Leung, B; Lemmon, M A; Zheng, J; Cowburn, D; Kuriyan, J; Saksela, K

    1995-01-01

    We have examined the differential binding of Hck and Fyn to HIV-1 Nef to elucidate the structural basis of SH3 binding affinity and specificity. Full-length Nef bound to Hck SH3 with the highest affinity reported for an SH3-mediated interaction (KD 250 nM). In contrast to Hck, affinity of the highly homologous Fyn SH3 for Nef was too weak (KD > 20 microM) to be accurately determined. We show that this distinct specificity lies in a variable loop, the 'RT loop', positioned close to conserved SH3 residues implicated in the binding of proline-rich (PxxP) motifs. A mutant Fyn SH3 with a single amino acid substitution (R96I) in its RT loop had an affinity (KD 380 nM) for Nef comparable with that of Hck SH3. Based on additional mutagenesis studies we propose that the selective recognition of Nef by Hck SH3 is determined by hydrophobic interactions involving an isoleucine residue in its RT loop. Although Nef contains a PxxP motif which is necessary for the interaction with Hck SH3, high affinity binding was only observed for intact Nef protein. The binding of a peptide containing the Nef PxxP motif showed > 300-fold weaker affinity for Hck SH3 than full-length Nef. Images PMID:7588629

  4. HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis.

    PubMed

    Cui, Huanhuan L; Ditiatkovski, Michael; Kesani, Rajitha; Bobryshev, Yuri V; Liu, Yingying; Geyer, Matthias; Mukhamedova, Nigora; Bukrinsky, Michael; Sviridov, Dmitri

    2014-07-01

    Patients with HIV are at an increased risk of cardiovascular disease. In this study we investigated the effect of Nef, a secreted HIV protein responsible for the impairment of cholesterol efflux, on the development of atherosclerosis in two animal models. ApoE(-/-) mice fed a high-fat diet and C57BL/6 mice fed a high-fat, high-cholesterol diet were injected with recombinant Nef (40 ng/injection) or vehicle, and the effects of Nef on development of atherosclerosis, inflammation, and dyslipidemia were assessed. In apoE(-/-) mice, Nef significantly increased the size of atherosclerotic lesions and caused vessel remodeling. Nef caused elevation of total cholesterol and triglyceride levels in the plasma while reducing high-density lipoprotein cholesterol levels. These changes were accompanied by a reduction of ABCA1 abundance in the liver, but not in the vessels. In C57BL/6 mice, Nef caused a significant number of lipid-laden macrophages presented in adventitia of the vessels; these cells were absent from the vessels of control mice. Nef caused sharp elevations of plasma triglyceride levels and body weight. Taken together, our findings suggest that Nef causes dyslipidemia and accumulation of cholesterol in macrophages within the vessel wall, supporting the role of Nef in pathogenesis of atherosclerosis in HIV-infected patients.-Cui, H. L., Ditiatkovski, M., Kesani, R., Bobryshev, Y. V., Liu, Y., Geyer, M., Mukhamedova, N., Bukrinsky, M., Sviridov, D. HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis. PMID:24642731

  5. HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis

    PubMed Central

    Cui, Huanhuan L.; Ditiatkovski, Michael; Kesani, Rajitha; Bobryshev, Yuri V.; Liu, Yingying; Geyer, Matthias; Mukhamedova, Nigora; Bukrinsky, Michael; Sviridov, Dmitri

    2014-01-01

    Patients with HIV are at an increased risk of cardiovascular disease. In this study we investigated the effect of Nef, a secreted HIV protein responsible for the impairment of cholesterol efflux, on the development of atherosclerosis in two animal models. ApoE−/− mice fed a high-fat diet and C57BL/6 mice fed a high-fat, high-cholesterol diet were injected with recombinant Nef (40 ng/injection) or vehicle, and the effects of Nef on development of atherosclerosis, inflammation, and dyslipidemia were assessed. In apoE−/− mice, Nef significantly increased the size of atherosclerotic lesions and caused vessel remodeling. Nef caused elevation of total cholesterol and triglyceride levels in the plasma while reducing high-density lipoprotein cholesterol levels. These changes were accompanied by a reduction of ABCA1 abundance in the liver, but not in the vessels. In C57BL/6 mice, Nef caused a significant number of lipid-laden macrophages presented in adventitia of the vessels; these cells were absent from the vessels of control mice. Nef caused sharp elevations of plasma triglyceride levels and body weight. Taken together, our findings suggest that Nef causes dyslipidemia and accumulation of cholesterol in macrophages within the vessel wall, supporting the role of Nef in pathogenesis of atherosclerosis in HIV-infected patients.—Cui, H. L., Ditiatkovski, M., Kesani, R., Bobryshev, Y. V., Liu, Y., Geyer, M., Mukhamedova, N., Bukrinsky, M., Sviridov, D. HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis. PMID:24642731

  6. Requirements for the production of high-titre C3 nephritic factor (NEF) antibody in vitro.

    PubMed Central

    Marín, M A; Fontán, G; López-Trascasa, M

    1992-01-01

    C3 nephritic factor (NEF) is an IgG autoantibody directed against neoantigenic determinants of the alternative C3 convertase (C3b.Bb). Structural and functional studies require important amounts of this antibody, which are difficult to obtain from patients' sera. We have developed a method for increasing NEF production in vitro. Epstein-Barr virus is a herpes virus which transforms B lymphocytes. Some authors were able to induce the production of NEF in vitro after infection with Epstein-Barr virus (EBV). These works were preformed without any previous cellular selection of B cells. We have performed a method of preselecting antigen-binding cells prior to EBV transformation. Non-preselected cells yielded 0.16 U/million cells in culture (U/M) of NEF antibody, whereas enriched cells for NEF antibody in eliminated 8 U/M (sheep erythrocytes coated with anti-IgG, A, M). Specific NEF synthesis can be increased, in peripheral blood mononuclear cells (PBMC) from patients by in vitro stimulation with the antigens recognized by NEF [C3b.Bb, 21,000 MW protein from patients' E membranes and 26,000 MW protein from sheep E membranes (ShE)]. The highest stimulation is induced by the C3b.Bb and by 26,000 MW protein, 21,000 MW protein had lowest stimulatory effect. In this work also we have shown that patients having NEF antibody in sera have an increase of the CD5-CD19 subset, when compared with the controls. Images Figure 2 PMID:1321794

  7. Replication of HIV-1 deleted Nef mutants in chronically immune activated human T cells.

    PubMed

    Shapira-Nahor, Orit; Maayan, Shlomo; Peden, Keith W C; Rabinowitz, Ruth; Schlesinger, Michael; Alian, Akram; Panet, Amos

    2002-11-10

    Lymphocytes (PBMC) obtained from blood of HIV-sera negative Ethiopian immigrants (ETH) were highly susceptible to HIV-1 infection in vitro with no need for stimulation by mitogens. As the HIV nef gene product has been shown to enhance viral replication in stimulated primary lymphocytes, we investigated in this work the role of Nef in viral replication in the ETH cells. Lymphocytes obtained from ETH individuals supported high replication of wild-type HIV-1 and low but significant replication level of the two deleted Nef mutants (encode truncated Nef proteins consisting only of either the first 35 or the first 86 amino acids of Nef). In contrast, no replication was observed in nonactivated cells obtained from non-ETH individuals. After activation of the PBMC from ETH individuals with PHA, replication of both wild-type strains and the two deleted Nef mutant viruses further increased. The CD4(+) T cells of ETH individuals exhibited elevated levels of the surface activation markers CD45RO and HLA-DR, compared with T cells derived from non-ETH group. Likewise, expression of the chemokine receptors CCR5 and CXCR4 on these cells was higher in the ETH group than in the non-ETH group. Replication of HIV-1 wild-type and the isogenic-deleted Nef mutants was significantly correlated with the proportion of ETH cells expressing CD45RO and the chemokine receptors. This study suggests that HIV-1 may respond differently to several activation states characteristic of T cells. One activation state, defined by chronically activated lymphocytes from ETH individuals, is permissive to the wild-type HIV-1 and, to a lesser degree, to the Nef mutants. Further activation of these cells by exogenous stimuli enhances replication of the virus. Our results support the notion that Nef enhances the basal level of T cell activation and consequently, viral replication. PMID:12482665

  8. Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

    PubMed Central

    Brügger, Britta; Krautkrämer, Ellen; Tibroni, Nadine; Munte, Claudia E; Rauch, Susanne; Leibrecht, Iris; Glass, Bärbel; Breuer, Sebastian; Geyer, Matthias; Kräusslich, Hans-Georg; Kalbitzer, Hans Robert; Wieland, Felix T; Fackler, Oliver T

    2007-01-01

    Background The Nef protein of Human Immunodeficiency Viruses optimizes viral spread in the infected host by manipulating cellular transport and signal transduction machineries. Nef also boosts the infectivity of HIV particles by an unknown mechanism. Recent studies suggested a correlation between the association of Nef with lipid raft microdomains and its positive effects on virion infectivity. Furthermore, the lipidome analysis of HIV-1 particles revealed a marked enrichment of classical raft lipids and thus identified HIV-1 virions as an example for naturally occurring membrane microdomains. Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition. Results Quantitative mass spectrometric lipidome analysis of highly purified HIV-1 particles revealed that the presence of Nef during virus production from T lymphocytes enforced their raft character via a significant reduction of polyunsaturated phosphatidylcholine species and a specific enrichment of sphingomyelin. In contrast, Nef did not significantly affect virion levels of phosphoglycerolipids or cholesterol. The observed alterations in virion lipid composition were insufficient to mediate Nef's effect on particle infectivity and Nef augmented virion infectivity independently of whether virus entry was targeted to or excluded from membrane microdomains. However, altered lipid compositions similar to those observed in virions were also detected in detergent-resistant membrane preparations of virus producing cells. Conclusion Nef alters not only the proteome but also the lipid composition of host cell microdomains. This novel activity represents a previously unrecognized mechanism by which Nef could manipulate HIV-1 target cells to facilitate virus propagation in vivo. PMID:17908312

  9. Secretion Modification Region-Derived Peptide Disrupts HIV-1 Nef's Interaction with Mortalin and Blocks Virus and Nef Exosome Release

    PubMed Central

    Shelton, Martin N.; Huang, Ming-Bo; Ali, Syed A.; Powell, Michael D.

    2012-01-01

    Nef is secreted from infected cells in exosomes and is found in abundance in the sera of HIV-infected individuals. Secreted exosomal Nef (exNef) induces apoptosis in uninfected CD4+ T cells and may be a key component of HIV pathogenesis. The exosomal pathway has been implicated in HIV-1 virus release, suggesting a possible link between these two viral processes. However, the underlying mechanisms and cellular components of exNef secretion have not been elucidated. We have previously described a Nef motif, the secretion modification region (SMR; amino acids 66 to 70), that is required for exNef secretion. In silico modeling data suggest that this motif can form a putative binding pocket. We hypothesized that the Nef SMR binds a cellular protein involved in protein trafficking and that inhibition of this interaction would abrogate exNef secretion. By using tandem mass spectrometry and coimmunoprecipitation with a novel SMR-based peptide (SMRwt) that blocks exNef secretion and HIV-1 virus release, we identified mortalin as an SMR-specific cellular protein. A second set of coimmunoprecipitation experiments with full-length Nef confirmed that mortalin interacts with Nef via Nef's SMR motif and that this interaction is disrupted by the SMRwt peptide. Overexpression and microRNA knockdown of mortalin revealed a positive correlation between exNef secretion levels and mortalin protein expression. Using antibody inhibition we demonstrated that the Nef/mortalin interaction is necessary for exNef secretion. Taken together, this work constitutes a significant step in understanding the underlying mechanism of exNef secretion, identifies a novel host-pathogen interaction, and introduces an HIV-derived peptide with antiviral properties. PMID:22013042

  10. Structural basis for the inhibition of HIV-1 Nef by a high-affinity binding single-domain antibody

    PubMed Central

    2014-01-01

    Background The HIV-1 Nef protein is essential for AIDS pathogenesis by its interaction with host cell surface receptors and signaling factors. Despite its critical role as a virulence factor Nef is not targeted by current antiviral strategies. Results We have determined the crystal structure of the complex formed by a camelid single-domain antibody fragment, termed sdAb19, bound to HIV-1 Nef together with a stabilizing SH3 domain. sdAb19 forms a stoichiometric 1:1 complex with Nef and binds to a conformationally conserved surface at the C-terminus of Nef that overlaps with functionally important interaction sites involved in Nef-induced perturbations of signaling and trafficking pathways. The antibody fragment binds Nef with low nanomolar affinity, which could be attenuated to micromolar affinity range by site-directed mutagenesis of key interaction residues in sdAb19. Fusion of the SH3 domain to sdAb19, termed Neffin, leads to a significantly increased affinity for Nef and formation of a stoichiometric 2:2 Nef–Neffin complex. The 19 kDa Neffin protein inhibits all functions of Nef as CD4 and MHC-I downregulation, association with Pak2, and the increase in virus infectivity and replication. Conclusions Together, sdAb19 and Neffin thus represent efficient tools for the rational development of antiviral strategies against HIV-1 Nef. PMID:24620746

  11. HIV-1 Nef: Taking Control of Protein Trafficking.

    PubMed

    Pereira, Estela A; daSilva, Luis L P

    2016-09-01

    The Nef protein of the human immunodeficiency virus is a crucial determinant of viral pathogenesis and disease progression. Nef is abundantly expressed early in infection and is thought to optimize the cellular environment for viral replication. Nef controls expression levels of various cell surface molecules that play important roles in immunity and virus life cycle, by directly interfering with the itinerary of these proteins within the endocytic and late secretory pathways. To exert these functions, Nef physically interacts with host proteins that regulate protein trafficking. In recent years, considerable progress was made in identifying host-cell-interacting partners for Nef, and the molecular machinery used by Nef to interfere with protein trafficking has started to be unraveled. Here, we briefly review the knowledge gained and discuss new findings regarding the mechanisms by which Nef modifies the intracellular trafficking pathways to prevent antigen presentation, facilitate viral particle release and enhance the infectivity of HIV-1 virions. PMID:27161574

  12. Translation of HLA-HIV associations to the cellular level: HIV adapts to inflate CD8 T cell responses against Nef and HLA-adapted variant epitopes.

    PubMed

    Almeida, Coral-Ann M; Bronke, Corine; Roberts, Steven G; McKinnon, Elizabeth; Keane, Niamh M; Chopra, Abha; Kadie, Carl; Carlson, Jonathan; Haas, David W; Riddler, Sharon A; Haubrich, Richard; Heckerman, David; Mallal, Simon; John, Mina

    2011-09-01

    Strong statistical associations between polymorphisms in HIV-1 population sequences and carriage of HLA class I alleles have been widely used to identify possible sites of CD8 T cell immune selection in vivo. However, there have been few attempts to prospectively and systematically test these genetic hypotheses arising from population-based studies at a cellular, functional level. We assayed CD8 T cell epitope-specific IFN-γ responses in 290 individuals from the same cohort, which gave rise to 874 HLA-HIV associations in genetic analyses, taking into account autologous viral sequences and individual HLA genotypes. We found immunological evidence for 58% of 374 associations tested as sites of primary immune selection and identified up to 50 novel HIV-1 epitopes using this reverse-genomics approach. Many HLA-adapted epitopes elicited equivalent or higher-magnitude IFN-γ responses than did the nonadapted epitopes, particularly in Nef. At a population level, inclusion of all of the immunoreactive variant CD8 T cell epitopes in Gag, Pol, Nef, and Env suggested that HIV adaptation leads to an inflation of Nef-directed immune responses relative to other proteins. We concluded that HLA-HIV associations mark viral epitopes subject to CD8 T cell selection. These results can be used to guide functional studies of specific epitopes and escape mutations, as well as to test, train, and evaluate analytical models of viral escape and fitness. The inflation of Nef and HLA-adapted variant responses may have negative effects on natural and vaccine immunity against HIV and, therefore, has implications for diversity coverage approaches in HIV vaccine design. PMID:21821798

  13. Analysis of human immunodeficiency virus type 1 nef gene sequences present in vivo.

    PubMed Central

    Shugars, D C; Smith, M S; Glueck, D H; Nantermet, P V; Seillier-Moiseiwitsch, F; Swanstrom, R

    1993-01-01

    The nef genes of the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) and the related simian immunodeficiency viruses (SIVs) encode a protein (Nef) whose role in virus replication and cytopathicity remains uncertain. As an attempt to elucidate the function of nef, we characterized the nucleotide and corresponding protein sequences of naturally occurring nef genes obtained from several HIV-1-infected individuals. A consensus Nef sequence was derived and used to identify several features that were highly conserved among the Nef sequences. These features included a nearly invariant myristylation signal, regions of sequence polymorphism and variable duplication, a region with an acidic charge, a (Pxx)4 repeat sequence, and a potential protein kinase C phosphorylation site. Clustering of premature stop codons at position 124 was noted in 6 of the 54 Nef sequences. Further analysis revealed four stretches of residues that were highly conserved not only among the patient-derived HIV-1 Nef sequences, but also among the Nef sequences of HIV-2 and the SIVs, suggesting that Nef proteins expressed by these retroviruses are functionally equivalent. The "Nef-defining" sequences were used to evaluate the sequence alignments of known proteins reported to share sequence similarity with Nef sequences and to conduct additional computer-based searches for similar protein sequences. A gene encoding the consensus Nef sequence was also generated. This gene encodes a full-length Nef protein that should be a valuable tool in further studies of Nef function. Images PMID:8043040

  14. A Truncated Nef Peptide from SIVcpz Inhibits the Production of HIV-1 Infectious Progeny.

    PubMed

    Sabino Cunha, Marcela; Lima Sampaio, Thatiane; Peterlin, B Matija; Jesus da Costa, Luciana

    2016-01-01

    Nef proteins from all primate Lentiviruses, including the simian immunodeficiency virus of chimpanzees (SIVcpz), increase viral progeny infectivity. However, the function of Nef involved with the increase in viral infectivity is still not completely understood. Nonetheless, until now, studies investigating the functions of Nef from SIVcpz have been conducted in the context of the HIV-1 proviruses. In an attempt to investigate the role played by Nef during the replication cycle of an SIVcpz, a Nef-defective derivative was obtained from the SIVcpzWTGab2 clone by introducing a frame shift mutation at a unique restriction site within the nef sequence. This nef-deleted clone expresses an N-terminal 74-amino acid truncated peptide of Nef and was named SIVcpz-tNef. We found that the SIVcpz-tNef does not behave as a classic nef-deleted HIV-1 or simian immunodeficiency virus of macaques SIVmac. Markedly, SIVcpz-tNef progeny from both Hek-293T and Molt producer cells were completely non-infectious. Moreover, the loss in infectivity of SIVcpz-tNef correlated with the inhibition of Gag and GagPol processing. A marked accumulation of Gag and very low levels of reverse transcriptase were detected in viral lysates. Furthermore, these observations were reproduced once the tNef peptide was expressed in trans both in SIVcpzΔNef and HIV-1WT expressing cells, demonstrating that the truncated peptide is a dominant negative for viral processing and infectivity for both SIVcpz and HIV-1. We demonstrated that the truncated Nef peptide binds to GagPol outside the protease region and by doing so probably blocks processing of both GagPol and Gag precursors at a very early stage. This study demonstrates for the first time that naturally-occurring Nef peptides can potently block lentiviral processing and infectivity. PMID:27399760

  15. A Truncated Nef Peptide from SIVcpz Inhibits the Production of HIV-1 Infectious Progeny

    PubMed Central

    Sabino Cunha, Marcela; Lima Sampaio, Thatiane; Peterlin, B. Matija; Jesus da Costa, Luciana

    2016-01-01

    Nef proteins from all primate Lentiviruses, including the simian immunodeficiency virus of chimpanzees (SIVcpz), increase viral progeny infectivity. However, the function of Nef involved with the increase in viral infectivity is still not completely understood. Nonetheless, until now, studies investigating the functions of Nef from SIVcpz have been conducted in the context of the HIV-1 proviruses. In an attempt to investigate the role played by Nef during the replication cycle of an SIVcpz, a Nef-defective derivative was obtained from the SIVcpzWTGab2 clone by introducing a frame shift mutation at a unique restriction site within the nef sequence. This nef-deleted clone expresses an N-terminal 74-amino acid truncated peptide of Nef and was named SIVcpz-tNef. We found that the SIVcpz-tNef does not behave as a classic nef-deleted HIV-1 or simian immunodeficiency virus of macaques SIVmac. Markedly, SIVcpz-tNef progeny from both Hek-293T and Molt producer cells were completely non-infectious. Moreover, the loss in infectivity of SIVcpz-tNef correlated with the inhibition of Gag and GagPol processing. A marked accumulation of Gag and very low levels of reverse transcriptase were detected in viral lysates. Furthermore, these observations were reproduced once the tNef peptide was expressed in trans both in SIVcpzΔNef and HIV-1WT expressing cells, demonstrating that the truncated peptide is a dominant negative for viral processing and infectivity for both SIVcpz and HIV-1. We demonstrated that the truncated Nef peptide binds to GagPol outside the protease region and by doing so probably blocks processing of both GagPol and Gag precursors at a very early stage. This study demonstrates for the first time that naturally-occurring Nef peptides can potently block lentiviral processing and infectivity. PMID:27399760

  16. One hundred years and still counting: the story of NEF--yesterday, today, and tomorrow.

    PubMed

    Bowar-Ferres, Susan L; Fitzpatrick, M Louise; McClure, Margaret L

    2014-01-01

    Nurses Educational Funds, Inc (NEF) is the oldest and largest professionally endorsed source of funds for advanced study in nursing, which celebrated its Centennial in 2012. This philanthropic nonprofit organization is notable for its roots; NEF was organized by nurses specifically for nurses. Its history dates back to 1912, when it began in memory of Isabel Hampton Robb at Teacher's College, where the first graduate nursing education programs began. The initial Robb Memorial Fund was incorporated as a nonprofit organization in 1941 and officially became Nursing Educational Funds, Inc, in 1954. The NEF's sole mission is to raise money and give it for graduate-level scholarships in nursing education, service, practice, and research. Since its origin, more than 1000 doctoral and master's students from a broad array of schools across the nation have been recipients of awards. The NEF Board is a totally volunteer, highly dedicated group of nursing, business, and other professional leaders, who are steadfastly committed to this critical effort. Scholarships for graduate nursing education are imperative to meet the need to grow the pipeline of faculty. As charged by the 2010 Institute of Medicine report, the goal to increase the number of baccalaureate nurses to 80% of the workforce and to double the number of nurses with doctoral degrees both by 2020 speak to the heart of NEF. Funds raised currently are largely from Board members, individual donors, modest foundational support, and a number of bequests. As the nursing population grows older, the potential for bequests or planned giving becomes a realistic goal. Former NEF scholars have not unfortunately been a financial source, although pay back is an expectation. Nurses are the best ones to tell this compelling story to corporations and foundations as NEF continues to persist in the commitment to support graduate nursing education. PMID:25208153

  17. Protein–protein interaction inhibition (2P2I) combining high throughput and virtual screening: Application to the HIV-1 Nef protein

    PubMed Central

    Betzi, Stéphane; Restouin, Audrey; Opi, Sandrine; Arold, Stefan T.; Parrot, Isabelle; Guerlesquin, Françoise; Morelli, Xavier; Collette, Yves

    2007-01-01

    Protein–protein recognition is the cornerstone of multiple cellular and pathological functions. Therefore, protein–protein interaction inhibition (2P2I) is endowed with great therapeutic potential despite the initial belief that 2P2I was refractory to small-molecule intervention. Improved knowledge of complex molecular binding surfaces has recently stimulated renewed interest for 2P2I, especially after identification of “hot spots” and first inhibitory compounds. However, the combination of target complexity and lack of starting compound has thwarted experimental results and created intellectual barriers. Here we combined virtual and experimental screening when no previously known inhibitors can be used as starting point in a structure-based research program that targets an SH3 binding surface of the HIV type I Nef protein. High-throughput docking and application of a pharmacophoric filter on one hand and search for analogy on the other hand identified drug-like compounds that were further confirmed to bind Nef in the micromolar range (isothermal titration calorimetry), to target the Nef SH3 binding surface (NMR experiments), and to efficiently compete for Nef–SH3 interactions (cell-based assay, GST pull-down). Initial identification of these compounds by virtual screening was validated by screening of the very same library of compounds in the cell-based assay, demonstrating that a significant enrichment factor was attained by the in silico screening. To our knowledge, our results identify the first set of drug-like compounds that functionally target the HIV-1 Nef SH3 binding surface and provide the basis for a powerful discovery process that should help to speed up 2P2I strategies and open avenues for new class of antiviral molecules. PMID:18042718

  18. Association of Nef with the Human Immunodeficiency Virus Type 1 Core

    PubMed Central

    Kotov, Alexander; Zhou, Jing; Flicker, Paula; Aiken, Christopher

    1999-01-01

    Highly conserved among primate lentiviruses, the human immunodeficiency virus type 1 (HIV-1) Nef protein enhances viral infectivity by an unknown mechanism. Nef-defective virions are blocked at a stage of the HIV-1 life cycle between entry and reverse transcription, possibly virus uncoating. Nef is present in purified HIV-1 particles; however, it has not been determined whether Nef is specifically recruited into HIV-1 particles or whether virion-associated Nef plays a functional role in HIV-1 replication. To address the specificity and potential functionality of virion-associated Nef, we determined the subviral localization of Nef. HIV-1 cores were isolated by detergent treatment of concentrated virions followed by equilibrium density gradient sedimentation. Relative to HIV-1 virions, HIV-1 cores contained equivalent amounts of reverse transcriptase and integrase, decreased amounts of the viral matrix protein, and trace quantities of the viral transmembrane glycoprotein gp41. Examination of the particles by electron microscopy revealed cone-shaped structures characteristic of lentiviral cores. Similar quantities of proteolytically processed Nef protein were detected in gradient fractions of HIV-1 cores and intact virions. In addition, detergent-resistant subviral complexes isolated from immature HIV-1 particles contained similar quantities of Nef as untreated virions. These results demonstrate that Nef stably associates with the HIV-1 core and suggest that virion-associated Nef plays a functional role in accelerating HIV-1 replication. PMID:10482638

  19. HIV-1 Nef Breaches Placental Barrier in Rat Model

    PubMed Central

    Singh, Poonam; Agnihotri, Saurabh Kumar; Tewari, Mahesh Chandra; Kumar, Sadan; Sachdev, Monika; Tripathi, Raj Kamal

    2012-01-01

    The vertical transmission of HIV-1 from the mother to fetus is known, but the molecular mechanism regulating this transmission is not fully characterized. The fetus is highly protected by the placenta, which does not permit microbial pathogens to cross the placental barrier. In the present study, a rat model was established to observe the effect of HIV-1 protein Nef on placental barrier. Evans blue dye was used to assay permeability of placental barrier and fourteen day pregnant Sprague Dawley rats were injected intravenously with 2% Evans blue dye along with various concentrations of recombinant Nef. After an hour, animals were sacrificed and dye migration was observed through the assimilation of peripheral blood into fetus. Interestingly, traces of recombinant Nef protein were detected in the embryo as well as amniotic fluid and amniotic membrane along with placenta and uterus. Our study indicates that recombinant HIV-1-Nef protein breaches the placental barrier and allows the migration of Evans blue dye to the growing fetus. Further the concentration of Nef protein in blood is directly proportional to the intensity of dye migration and to the amount of Nef protein detected in uterus, placenta, amniotic membrane, amniotic fluid and embryo. Based on this study, it can be concluded that the HIV-1 Nef protein has a direct effect on breaching of the placental barrier in the model we have established in this study. Our observations will be helpful to understand the molecular mechanisms related to this breach of placental barrier by Nef in humans and may be helpful to identify specific Nef inhibitors. PMID:23240037

  20. HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice

    SciTech Connect

    Hanna, Zaher . E-mail: Zaher.Hanna@ircm.qc.ca; Priceputu, Elena; Hu, Chunyan; Vincent, Patrick; Jolicoeur, Paul

    2006-03-01

    HIV-1 Nef has the ability to downmodulate CD4 cell surface expression. Several studies have shown that CD4 downregulation is required for efficient virus replication and high infectivity. However, the pathophysiological relevance of this phenomenon in vivo, independently of its role in sustaining high virus loads, remains unclear. We studied the impact of the CD4 downregulation function of Nef on its pathogenesis in vivo, in the absence of viral replication, in the CD4C/HIV transgenic (Tg) mouse model. Two independent Nef mutants (RD35/36AA and D174K), known to abrogate CD4 downregulation, were tested in Tg mice. Flow cytometry analysis showed that downregulation of murine CD4 was severely decreased or abrogated on Tg T cells expressing respectively Nef{sup RD35/36AA} and Nef{sup D174K}. Similarly, the severe depletion of double-positive CD4{sup +}CD8{sup +} and of single-positive CD4{sup +}CD8{sup -} thymocytes, usually observed with Nef{sup Wt}, was not detected in Nef{sup RD35/36AA} and Nef{sup D174K} Tg mice. However, both mutant Tg mice showed a partial depletion of peripheral CD4{sup +} T cells. This was accompanied, as previously reported for Net{sup Wt} Tg mice, by the presence of an activated/memory-like phenotype (CD69{sup +}, CD25{sup +}, CD44{sup +}, CD45RB{sup Low}, CD62{sup Low}) of CD4{sup +} T cells expressing Nef{sup RD35/36AA} and to a lesser extent Nef{sup D174K}. In addition, both mutants retained the ability to block CD4{sup +} T cell proliferation in vitro after anti-CD3 stimulation, but not to enhance apoptosis/death of CD4{sup +} T cells. Therefore, it appears that Nef-mediated CD4 downregulation is associated with thymic defects, but segregates independently of the activated/memory-like phenotype, of the partial depletion and of the impaired in vitro proliferation of peripheral CD4{sup +} T cells. Histopathological assessment revealed the total absence of or decrease severity and frequency of organ AIDS-like diseases (lung, heart and kidney

  1. HIV-1 Nef Induces CCL5 production in astrocytes through p38-MAPK and PI3K/Akt pathway and utilizes NF-kB, CEBP and AP-1 transcription factors

    NASA Astrophysics Data System (ADS)

    Liu, Xun; Shah, Ankit; Gangwani, Mohitkumar R.; Silverstein, Peter S.; Fu, Mingui; Kumar, Anil

    2014-03-01

    The prevalence of HIV-associated neurocognitive disorders (HAND) remains high in patients infected with HIV-1. The production of pro-inflammatory cytokines by astrocytes/microglia exposed to viral proteins is thought to be one of the mechanisms leading to HIV-1- mediated neurotoxicity. In the present study we examined the effects of Nef on CCL5 induction in astrocytes. The results demonstrate that CCL5 is significantly induced in Nef-transfected SVGA astrocytes. To determine the mechanisms responsible for the increased CCL5 caused by Nef, we employed siRNA and chemical antagonists. Antagonists of NF-κB, PI3K, and p38 significantly reduced the expression levels of CCL5 induced by Nef transfection. Furthermore, specific siRNAs demonstrated that the Akt, p38MAPK, NF-κB, CEBP, and AP-1 pathways play a role in Nef-mediated CCL5 expression. The results demonstrated that the PI3K/Akt and p38 MAPK pathways, along with the transcription factors NF-κB, CEBP, and AP-1, are involved in Nef-induced CCL5 production in astrocytes.

  2. HIV-1 Nef Induces CCL5 production in astrocytes through p38-MAPK and PI3K/Akt pathway and utilizes NF-kB, CEBP and AP-1 transcription factors

    PubMed Central

    Liu, Xun; Shah, Ankit; Gangwani, Mohitkumar R.; Silverstein, Peter S.; Fu, Mingui; Kumar, Anil

    2014-01-01

    The prevalence of HIV-associated neurocognitive disorders (HAND) remains high in patients infected with HIV-1. The production of pro-inflammatory cytokines by astrocytes/microglia exposed to viral proteins is thought to be one of the mechanisms leading to HIV-1- mediated neurotoxicity. In the present study we examined the effects of Nef on CCL5 induction in astrocytes. The results demonstrate that CCL5 is significantly induced in Nef-transfected SVGA astrocytes. To determine the mechanisms responsible for the increased CCL5 caused by Nef, we employed siRNA and chemical antagonists. Antagonists of NF-κB, PI3K, and p38 significantly reduced the expression levels of CCL5 induced by Nef transfection. Furthermore, specific siRNAs demonstrated that the Akt, p38MAPK, NF-κB, CEBP, and AP-1 pathways play a role in Nef-mediated CCL5 expression. The results demonstrated that the PI3K/Akt and p38 MAPK pathways, along with the transcription factors NF-κB, CEBP, and AP-1, are involved in Nef-induced CCL5 production in astrocytes. PMID:24658403

  3. Genetic and Functional Diversity of Human Immunodeficiency Virus Type 1 Subtype B Nef Primary Isolates

    PubMed Central

    Foster, John L.; Molina, Rene P.; Luo, Tianci; Arora, Vivek K.; Huang, Yaoxing; Ho, David D.; Garcia, J. Victor

    2001-01-01

    We have characterized the functional integrity of seven primary Nef isolates: five from a long-term nonprogressing human immunodeficiency virus (HIV)-infected individual and one each from two patients with AIDS. One of the seven Nefs was defective for CD4 downregulation, two others were defective for PAK-2 activation, and one Nef was defective for PAK-2 activation and major histocompatibility complex (MHC) class I downregulation. Five of the Nefs were tested and found to be functional for the enhancement of virus particle infectivity. The structural basis for each of the functional defects has been analyzed by constructing a consensus nef, followed by mutational analysis of the variant amino acid residues. Mutations A29V and F193I were deleterious to CD4 downregulation and PAK-2 activation, respectively, while S189R rendered Nef defective for both MHC class I downregulation and PAK-2 activation. A search of the literature identified HIVs from five patients with Nefs predominantly mutated at F193 and from one patient with Nefs predominantly mutated at A29. A29 is highly conserved in all HIV subtypes except for subtype E. F193 is conserved in subtype B (and possibly in the closely related subtype D), but none of the other HIV group M subtypes. Our results suggest that functional distinctions may exist between HIV subtypes. PMID:11160665

  4. Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells

    PubMed Central

    Weiler, Andrea M.; Das, Arpita; Akinyosoye, Oluwasayo; Cui, Sherry; O'Connor, Shelby L.; Scheef, Elizabeth A.; Reed, Jason S.; Panganiban, Antonito T.; Sacha, Jonah B.; Rakasz, Eva G.; Friedrich, Thomas C.

    2015-01-01

    Nef-specific CD8+ T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165–173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef's major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication. PMID:26637459

  5. Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells.

    PubMed

    Weiler, Andrea M; Das, Arpita; Akinyosoye, Oluwasayo; Cui, Sherry; O'Connor, Shelby L; Scheef, Elizabeth A; Reed, Jason S; Panganiban, Antonito T; Sacha, Jonah B; Rakasz, Eva G; Friedrich, Thomas C; Maness, Nicholas J

    2016-02-01

    Nef-specific CD8(+) T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165-173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef's major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication. PMID:26637459

  6. Primate lentiviral Nef proteins deregulate T-cell development by multiple mechanisms

    PubMed Central

    2013-01-01

    Background A nef gene is present in all primate lentiviral genomes and is important for high viral loads and progression to AIDS in human or experimental macaque hosts of HIV or SIV, respectively. In these hosts, infection of the thymus results in a decreased output of naive T cells that may contribute to the development of immunodeficiency. We have previously shown that HIV-1 subtype B Nef proteins can block human T-cell development. However, the underlying mechanism(s) and the conservation of this Nef function between different groups of HIV and SIV remained to be determined. Results We investigated whether reduction of thymic output is a conserved function of highly divergent lentiviral Nef proteins including those from both types of human immunodeficiency viruses (HIV-1 and HIV-2), their direct simian counterparts (SIVcpz, SIVgor and SIVsmm, respectively), and some additional SIV strains. We found that expression of most of these nef alleles in thymocyte progenitors impaired T-cell development and reduced thymic output. For HIV-1 Nef, binding to active p21 protein (Cdc42/Rac)-activated kinase (PAK2) was a major determinant of this function. In contrast, selective disruption of PAK2 binding did not eliminate the effect on T-cell development of SIVmac239 Nef, as was shown by expressing mutants in a newly discovered PAK2 activating structural motif (PASM) constituted by residues I117, H121, T218 and Y221, as well as previously described mutants. Rather, down-modulation of cell surface CD3 was sufficient for reduced thymic output by SIVmac Nef, while other functions of SIV Nefs contributed. Conclusions Our results indicate that primate lentiviral Nef proteins impair development of thymocyte precursors into T cells in multiple ways. The interaction of HIV-1 Nef with active PAK2 by HIV-1 seem to be most detrimental, and downregulation of CD3 by HIV-2 and most SIV Nef proteins sufficient for reduced thymic output. Since the reduction of thymic output by Nef is a

  7. HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

    PubMed Central

    Stolp, Bettina; Imle, Andrea; Coelho, Fernanda Matos; Hons, Miroslav; Gorina, Roser; Lyck, Ruth; Stein, Jens V.; Fackler, Oliver T.

    2012-01-01

    HIV-1 negative factor (Nef) elevates virus replication and contributes to immune evasion in vivo. As one of its established in vitro activities, Nef interferes with T-lymphocyte chemotaxis by reducing host cell actin dynamics. To explore Nef’s influence on in vivo recirculation of T lymphocytes, we assessed lymph-node homing of Nef-expressing primary murine lymphocytes and found a drastic impairment in homing to peripheral lymph nodes. Intravital imaging and 3D immunofluorescence reconstruction of lymph nodes revealed that Nef potently impaired T-lymphocyte extravasation through high endothelial venules and reduced subsequent parenchymal motility. Ex vivo analyses of transendothelial migration revealed that Nef disrupted T-lymphocyte polarization and interfered with diapedesis and migration in the narrow subendothelial space. Consistently, Nef specifically affected T-lymphocyte motility modes used in dense environments that pose high physical barriers to migration. Mechanistically, inhibition of lymph node homing, subendothelial migration and cell polarization, but not diapedesis, depended on Nef’s ability to inhibit host cell actin remodeling. Nef-mediated interference with in vivo recirculation of T lymphocytes may compromise T-cell help and thus represents an important mechanism for its function as a HIV pathogenicity factor. PMID:23093676

  8. A truncated form of Nef selected during pathogenic reversion of simian immunodeficiency virus SIVmac239Deltanef increases viral replication.

    PubMed

    Chakrabarti, Lisa A; Metzner, Karin J; Ivanovic, Tijana; Cheng, Hua; Louis-Virelizier, Jean; Connor, Ruth I; Cheng-Mayer, Cecilia

    2003-01-01

    The live, attenuated vaccine simian immunodeficiency virus SIVmac239Deltanef efficiently protects rhesus macaques against infection with wild-type SIVmac but occasionally causes CD4(+) T-cell depletion and progression to simian AIDS (SAIDS). Virus recovered from a vaccinated macaque (Rh1490) that progressed to SAIDS had acquired an additional deletion in the nef gene, resulting in a frameshift that restored the original nef open reading frame (R. I. Connor, D. C. Montefiori, J. M. Binley, J. P. Moore, S. Bonhoeffer, A. Gettie, E. A. Fenamore, K. E. Sheridan, D. D. Ho, P. J. Dailey, and P. A. Marx, J. Virol. 72:7501-7509, 1998). Intravenous inoculation of the Rh1490 viral isolate into four naive rhesus macaques induced CD4(+) T-cell depletion and disease in three out of four animals within 2 years, indicating a restoration of virulence. A DNA fragment encompassing the truncated nef gene amplified from the Rh1490 isolate was inserted into the genetic backbone of SIVmac239. The resulting clone, SIVmac239-Delta2nef, expressed a Nef protein of approximately 23 kDa, while the original SIVmac239Deltanef clone expressed a shorter protein of 8 kDa. The revertant form of Nef did not cause downregulation of CD4, CD3, or major histocompatibility complex class I. The infectivity of SIVmac239-Delta2nef was similar to that of SIVmac239Deltanef in single-cycle assays using indicator cell lines. In contrast, SIVmac239-Delta2nef replicated more efficiently than SIVmac239Deltanef in peripheral blood mononuclear cell (PBMC) cultures infected under unstimulated conditions. The p27 Gag antigen levels in SIVmac239-Delta2nef-infected cultures were still lower than those obtained with wild-type SIVmac239, consistent with a partial recovery of Nef function. The transcriptional activity of long terminal repeat (LTR)-luciferase constructs containing the nef deletions did not differ markedly from that of wild-type LTR. Introduction of a premature stop codon within Nef-Delta2 abolished the

  9. HIV-1 Nef and Vpu Are Functionally Redundant Broad-Spectrum Modulators of Cell Surface Receptors, Including Tetraspanins

    PubMed Central

    Haller, Claudia; Müller, Birthe; Fritz, Joëlle V.; Lamas-Murua, Miguel; Stolp, Bettina; Pujol, François M.; Keppler, Oliver T.

    2014-01-01

    ABSTRACT HIV-1 Nef and Vpu are thought to optimize virus replication in the infected host, at least in part via their ability to interfere with vesicular host cell trafficking. Despite the use of distinct molecular mechanisms, Nef and Vpu share specificity for some molecules such as CD4 and major histocompatibility complex class I (MHC-I), while disruption of intracellular transport of the host cell restriction factor CD317/tetherin represents a specialized activity of Vpu not exerted by HIV-1 Nef. To establish a profile of host cell receptors whose intracellular transport is affected by Nef, Vpu, or both, we comprehensively analyzed the effect of these accessory viral proteins on cell surface receptor levels on A3.01 T lymphocytes. Thirty-six out of 105 detectable receptors were significantly downregulated by HIV-1 Nef, revealing a previously unappreciated scope with which HIV-1 Nef remodels the cell surface of infected cells. Remarkably, the effects of HIV-1 Vpu on host cell receptor exposure largely matched those of HIV-1 Nef in breadth and specificity (32 of 105, all also targeted by Nef), even though the magnitude was generally less pronounced. Of particular note, cell surface exposure of all members of the tetraspanin (TSPAN) protein family analyzed was reduced by both Nef and Vpu, and the viral proteins triggered the enrichment of TSPANs in a perinuclear area of the cell. While Vpu displayed significant colocalization and physical association with TSPANs, interactions of Nef with TSPANs were less robust. TSPANs thus emerge as a major target of deregulation in host cell vesicular transport by HIV-1 Nef and Vpu. The conservation of this activity in two independent accessory proteins suggests its importance for the spread of HIV-1 in the infected host. IMPORTANCE In this paper, we define that HIV-1 Nef and Vpu display a surprising functional overlap and affect the cell surface exposure of a previously unexpected breadth of cellular receptors. Our analyses

  10. SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef.

    PubMed

    Usami, Yoshiko; Wu, Yuanfei; Göttlinger, Heinrich G

    2015-10-01

    HIV-1 Nef and the unrelated mouse leukaemia virus glycosylated Gag (glycoGag) strongly enhance the infectivity of HIV-1 virions produced in certain cell types in a clathrin-dependent manner. Here we show that Nef and glycoGag prevent the incorporation of the multipass transmembrane proteins serine incorporator 3 (SERINC3) and SERINC5 into HIV-1 virions to an extent that correlates with infectivity enhancement. Silencing of both SERINC3 and SERINC5 precisely phenocopied the effects of Nef and glycoGag on HIV-1 infectivity. The infectivity of nef-deficient virions increased more than 100-fold when produced in double-knockout human CD4(+) T cells that lack both SERINC3 and SERINC5, and re-expression experiments confirmed that the absence of SERINC3 and SERINC5 accounted for the infectivity enhancement. Furthermore, SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef. SERINC3 and SERINC5 are highly expressed in primary human HIV-1 target cells, and inhibiting their downregulation by Nef is a potential strategy to combat HIV/AIDS. PMID:26416733

  11. SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef

    PubMed Central

    Usami, Yoshiko; Wu, Yuanfei; Göttlinger, Heinrich G.

    2015-01-01

    HIV-1 Nef and the unrelated murine leukemia virus glycoGag strongly enhance the infectivity of HIV-1 virions produced in certain cell types in a clathrin-dependent manner. Here we show that Nef and glycoGag prevent the incorporation of the multipass transmembrane proteins SERINC3 and SERINC5 into HIV-1 virions to an extent that correlates with infectivity enhancement. Silencing of SERINC3 together with SERINC5 precisely phenocopied the effects of Nef and glycoGag on HIV-1 infectivities. The infectivity of nef-deficient virions increased more than 100-fold when produced in double-knockout human CD4+ T cells that lack both SERINC3 and SERINC5, and re-expression experiments confirmed that the absence of SERINC3 and SERINC5 accounted for the infectivity enhancement. Furthermore, SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef. SERINC3 and SERINC5 are highly expressed in primary human HIV-1 target cells, and inhibiting their downregulation by Nef is a potential strategy to combat HIV/AIDS. PMID:26416733

  12. Expression of Nef Downregulates CXCR4, the Major Coreceptor of Human Immunodeficiency Virus, from the Surfaces of Target Cells and Thereby Enhances Resistance to Superinfection▿

    PubMed Central

    Venzke, Stephanie; Michel, Nico; Allespach, Ina; Fackler, Oliver T.; Keppler, Oliver T.

    2006-01-01

    Lentiviral Nef proteins are key factors for pathogenesis and are known to downregulate functionally important molecules, including CD4 and major histocompatibility complex class I (MHC-I), from the surfaces of infected cells. Recently, we demonstrated that Nef reduces cell surface levels of the human immunodeficiency virus type 1 (HIV-1) entry coreceptor CCR5 (N. Michel, I. Allespach, S. Venzke, O. T. Fackler, and O. T. Keppler, Curr. Biol. 15:714-723, 2005). Here, we report that Nef downregulates the second major HIV-1 coreceptor, CXCR4, from the surfaces of HIV-infected primary CD4 T lymphocytes with efficiencies comparable to those of the natural CXCR4 ligand, stromal cell-derived factor-1 alpha. Analysis of a panel of mutants of HIV-1SF2 Nef revealed that the viral protein utilized the same signature motifs for downmodulation of CXCR4 and MHC-I, including the proline-rich motif P73P76P79P82 and the acidic cluster motif E66E67E68E69. Expression of wild-type Nef, but not of specific Nef mutants, resulted in a perinuclear accumulation of the coreceptor. Remarkably, the carboxy terminus of CXCR4, which harbors the classical motifs critical for basal and ligand-induced receptor endocytosis, was dispensable for the Nef-mediated reduction of surface exposure. Functionally, the ability of Nef to simultaneously downmodulate CXCR4 and CD4 correlated with maximum-level protection of Nef-expressing target cells from fusion with cells exposing X4 HIV-1 envelopes. Furthermore, the Nef-mediated downregulation of CXCR4 alone on target T lymphocytes was sufficient to diminish cells' susceptibility to X4 HIV-1 virions at the entry step. The downregulation of chemokine coreceptors is a conserved activity of Nef to modulate infected cells, an important functional consequence of which is an enhanced resistance to HIV superinfection. PMID:16928758

  13. Nef Neutralizes the Ability of Exosomes from CD4+ T Cells to Act as Decoys during HIV-1 Infection

    PubMed Central

    da Silva, Elaine Z. M.; Silveira, Paola P.; da Silva-Januário, Mara E.; Arruda, Eurico; Jamur, Maria C.; Oliver, Constance; Aguiar, Renato S.; daSilva, Luis L. P.

    2014-01-01

    Nef is an HIV-1 accessory protein that promotes viral replication and pathogenesis. A key function of Nef is to ensure sustained depletion of CD4 and MHC-I molecules in infected cells by inducing targeting of these proteins to multivesicular bodies (MVBs), and ultimately to lysosomes for degradation. Nef also affects cellular secretory routes promoting its own secretion via exosomes. To better understand the effects of Nef on the exocytic pathway, we investigated whether this viral factor modifies the composition of exosomes released by T lymphocytes. We showed that both CD4 and MHC-I molecules are secreted in exosomes from T cells and that the expression of Nef reduces the amount of these proteins in exosomes. To investigate the functional role for this novel activity of Nef, we performed in vitro HIV-1 infection assays in the presence of distinct populations of exosomes. We demonstrated that exosomes released by CD4+ T cells, but not CD4− T cells, efficiently inhibit HIV-1 infection in vitro. Because CD4 is the main receptor for HIV-1 infection, these results suggest that CD4 molecules displayed on the surface of exosomes can bind to envelope proteins of HIV-1 hindering virus interaction with target cells and infection. Importantly, CD4-depleted exosomes released by CD4+ T cells expressing Nef have a reduced capacity to inhibit HIV-1 infection in vitro. These results provide evidence that Nef promotes HIV-1 infection by reducing the expression of CD4 in exosomes from infected cells, besides the original role of Nef in reducing the CD4 levels at the cell surface. PMID:25423108

  14. HIV-1 Protein Nef Inhibits Activity of ATP-binding Cassette Transporter A1 by Targeting Endoplasmic Reticulum Chaperone Calnexin*

    PubMed Central

    Jennelle, Lucas; Hunegnaw, Ruth; Dubrovsky, Larisa; Pushkarsky, Tatiana; Fitzgerald, Michael L.; Sviridov, Dmitri; Popratiloff, Anastas; Brichacek, Beda; Bukrinsky, Michael

    2014-01-01

    HIV-infected patients are at increased risk of developing atherosclerosis, in part due to an altered high density lipoprotein profile exacerbated by down-modulation and impairment of ATP-binding cassette transporter A1 (ABCA1) activity by the HIV-1 protein Nef. However, the mechanisms of this Nef effect remain unknown. Here, we show that Nef interacts with an endoplasmic reticulum chaperone calnexin, which regulates folding and maturation of glycosylated proteins. Nef disrupted interaction between calnexin and ABCA1 but increased affinity and enhanced interaction of calnexin with HIV-1 gp160. The Nef mutant that did not bind to calnexin did not affect the calnexin-ABCA1 interaction. Interaction with calnexin was essential for functionality of ABCA1, as knockdown of calnexin blocked the ABCA1 exit from the endoplasmic reticulum, reduced ABCA1 abundance, and inhibited cholesterol efflux; the same effects were observed after Nef overexpression. However, the effects of calnexin knockdown and Nef on cholesterol efflux were not additive; in fact, the combined effect of these two factors together did not differ significantly from the effect of calnexin knockdown alone. Interestingly, gp160 and ABCA1 interacted with calnexin differently; although gp160 binding to calnexin was dependent on glycosylation, glycosylation was of little importance for the interaction between ABCA1 and calnexin. Thus, Nef regulates the activity of calnexin to stimulate its interaction with gp160 at the expense of ABCA1. This study identifies a mechanism for Nef-dependent inactivation of ABCA1 and dysregulation of cholesterol metabolism. PMID:25170080

  15. Human immunodeficiency virus type 1 Nef binds directly to Lck and mitogen-activated protein kinase, inhibiting kinase activity.

    PubMed Central

    Greenway, A; Azad, A; Mills, J; McPhee, D

    1996-01-01

    It is now well established that human immunodeficiency virus type I (HIV-1) Nef contributes substantially to disease pathogenesis by augmenting virus replication and markedly perturbing T-cell function. The effect of Nef on host cell activation could be explained in part by its interaction with specific cellular proteins involved in signal transduction, including at least a member of the src family kinase, Lck, and the serine/threonine kinase, mitogen-activated protein kinase (MAPK). Recombinant Nef directly interacted with purified Lck and MAPK in coprecipitation experiments and binding assays. A proline-rich repeat sequence [(Pxx)4] in Nef occurring between amino acid residues 69 to 78 is highly conserved and bears strong resemblance to a defined consensus sequence identified as an SH3 binding domain present in several proteins which can interact with the SH3 domain of various signalling and cytoskeletal proteins. Binding and coprecipitation assays with short synthetic peptides corresponding to the proline-rich repeat sequence [(Pxx)4] of Nef and the SH2, SH3, or SH2 and SH3 domains of Lck revealed that the interaction between these two proteins is at least in part mediated by the proline repeat sequence of Nef and the SH3 domain of Lck. In addition to direct binding to full-length Nef, MAPK was also shown to bind the same proline repeat motif. Nef protein significantly decreased the in vitro kinase activity of Lck and MAPK. Inhibition of key members of signalling cascades, including those emanating from the T-cell receptor, by the HIV-1 Nef protein undoubtedly alters the ability of the infected T cell to respond to antigens or cytokines, facilitating HIV-1 replication and contributing to HIV-1-induced disease pathogenesis. PMID:8794306

  16. Pathogenesis of HIV-associated pulmonary hypertension: potential role of HIV-1 Nef.

    PubMed

    Almodovar, Sharilyn; Hsue, Priscilla Y; Morelli, Julie; Huang, Laurence; Flores, Sonia C

    2011-06-01

    Infection with HIV increases the risk for lung diseases, including noninfectious pulmonary hypertension (PH). HIV-associated PH (HIV-PH) is an important lung disease in HIV-infected persons who live longer with antiretrovirals. The early stages of HIV-PH may be overlooked by healthcare providers due to nonspecific symptoms, including progressive dyspnea and nonproductive cough. HIV-PH may be detected via chest radiographs, CT scans, or electrocardiograms, but Doppler echocardiography is the most useful screening test to identify candidates for right heart catheterization. HIV-PH has a poor prognosis with high mortality; improved biomarkers to identify earlier stages of PH would benefit clinical care. The HIV-PH mechanism remains unknown, but HIV proteins such as Tat and Nef may play a role. HIV-1 Nef is a broad-spectrum adaptor protein that may affect HIV-infected and uninfected pulmonary vascular cells. Studies in macaques suggest that Nef is important in HIV-PH pathogenesis because monkeys infected with a chimeric simian immunodeficiency virus (SIV) expressing HIV-nef (SHIVnef) alleles, but not monkeys infected with the native SIV, develop pulmonary vascular remodeling. Four consistent amino acid mutations arose spontaneously in Nef passaged in the monkeys. To translate these findings to humans, one research endeavor of the Lung HIV Study focuses on the identification of HIV nef mutations in HIV-infected individuals with PH compared with HIV-infected normotensive patients. We present some of the preliminary evidence. Ongoing longitudinal studies will establish the connection between Nef mutations and the propensity for HIV-PH. PMID:21653533

  17. CD8+ T cell epitope-flanking mutations disrupt proteasomal processing of HIV-1 Nef.

    PubMed

    Milicic, Anita; Price, David A; Zimbwa, Peter; Booth, Bruce L; Brown, Helen L; Easterbrook, Philippa J; Olsen, Kara; Robinson, Nicola; Gileadi, Uzi; Sewell, Andrew K; Cerundolo, Vincenzo; Phillips, Rodney E

    2005-10-01

    CTL play a critical role in the control of HIV and SIV. However, intrinsic genetic instability enables these immunodeficiency viruses to evade detection by CTL through mutation of targeted antigenic sites. These mutations can impair binding of viral epitopes to the presenting MHC class I molecule or disrupt TCR-mediated recognition. In certain regions of the virus, functional constraints are likely to limit the capacity for variation within epitopes. Mutations elsewhere in the protein, however, might still enable immune escape through effects on Ag processing. In this study, we describe the coincident emergence of three mutations in a highly conserved region of Nef during primary HIV-1 infection. These mutations (R69K, A81G, and H87R) flank the HLA B*35-restricted VY8 epitope and persisted to fixation as the early CTL response to this Ag waned. The variant form of Nef showed a reduced capacity to activate VY8-specific CTL, although protein stability and expression levels were unchanged. This effect was associated with altered processing by the proteasome that caused partial destruction of the VY8 epitope. Our data demonstrate that a variant HIV genotype can significantly impair proteasomal epitope processing and substantiate the concept of immune evasion through diminished Ag generation. These observations also indicate that the scale of viral escape may be significantly underestimated if only intraepitope variation is evaluated. PMID:16177107

  18. The accessory factor Nef links HIV-1 to Tec/Btk kinases in an Src homology 3 domain-dependent manner.

    PubMed

    Tarafdar, Sreya; Poe, Jerrod A; Smithgall, Thomas E

    2014-05-30

    The HIV-1 Nef virulence factor interacts with multiple host cell-signaling proteins. Nef binds to the Src homology 3 domains of Src family kinases, resulting in kinase activation important for viral infectivity, replication, and MHC-I down-regulation. Itk and other Tec family kinases are also present in HIV target cells, and Itk has been linked to HIV-1 infectivity and replication. However, the molecular mechanism linking Itk to HIV-1 is unknown. In this study, we explored the interaction of Nef with Tec family kinases using a cell-based bimolecular fluorescence complementation assay. In this approach, interaction of Nef with a partner kinase juxtaposes nonfluorescent YFP fragments fused to the C terminus of each protein, resulting in YFP complementation and a bright fluorescent signal. Using bimolecular fluorescence complementation, we observed that Nef interacts with the Tec family members Bmx, Btk, and Itk but not Tec or Txk. Interaction with Nef occurs through the kinase Src homology 3 domains and localizes to the plasma membrane. Allelic variants of Nef from all major HIV-1 subtypes interacted strongly with Itk in this assay, demonstrating the highly conserved nature of this interaction. A selective small molecule inhibitor of Itk kinase activity (BMS-509744) potently blocked wild-type HIV-1 infectivity and replication, but not that of a Nef-defective mutant. Nef induced constitutive Itk activation in transfected cells that was sensitive to inhibitor treatment. Taken together, these results provide the first evidence that Nef interacts with cytoplasmic tyrosine kinases of the Tec family and suggest that Nef provides a mechanistic link between HIV-1 and Itk signaling in the viral life cycle. PMID:24722985

  19. Small molecule inhibition of HIV-1-induced MHC-I down-regulation identifies a temporally regulated switch in Nef action.

    PubMed

    Dikeakos, Jimmy D; Atkins, Katelyn M; Thomas, Laurel; Emert-Sedlak, Lori; Byeon, In-Ja L; Jung, Jinwon; Ahn, Jinwoo; Wortman, Matthew D; Kukull, Ben; Saito, Masumichi; Koizumi, Hirokazu; Williamson, Danielle M; Hiyoshi, Masateru; Barklis, Eric; Takiguchi, Masafumi; Suzu, Shinya; Gronenborn, Angela M; Smithgall, Thomas E; Thomas, Gary

    2010-10-01

    HIV-1 Nef triggers down-regulation of cell-surface MHC-I by assembling a Src family kinase (SFK)-ZAP-70/Syk-PI3K cascade. Here, we report that chemical disruption of the Nef-SFK interaction with the small molecule inhibitor 2c blocks assembly of the multi-kinase complex and represses HIV-1-mediated MHC-I down-regulation in primary CD4(+) T-cells. 2c did not interfere with the PACS-2-dependent trafficking of Nef required for the Nef-SFK interaction or the AP-1 and PACS-1-dependent sequestering of internalized MHC-I, suggesting the inhibitor specifically interfered with the Nef-SFK interaction required for triggering MHC-I down-regulation. Transport studies revealed Nef directs a highly regulated program to down-regulate MHC-I in primary CD4(+) T-cells. During the first two days after infection, Nef assembles the 2c-sensitive multi-kinase complex to trigger down-regulation of cell-surface MHC-I. By three days postinfection Nef switches to a stoichiometric mode that prevents surface delivery of newly synthesized MHC-I. Pharmacologic inhibition of the multi-kinase cascade prevents the Nef-dependent block in MHC-I transport, suggesting the signaling and stoichiometric modes are causally linked. Together, these studies resolve the seemingly controversial models that describe Nef-induced MHC-I down-regulation and provide new insights into the mechanism of Nef action. PMID:20702582

  20. Mutation of a diacidic motif in SIV-PBj Nef impairs T-cell activation and enteropathic disease

    PubMed Central

    2011-01-01

    Background The non-pathogenic course of SIV infection in its natural host is characterized by robust viral replication in the absence of chronic immune activation and T cell proliferation. In contrast, acutely lethal enteropathic SIVsmm strain PBj induces a strong immune activation and causes a severe acute and lethal disease in pig-tailed macaques after cross-species transmission. One important pathogenicity factor of the PBj virus is the PBj-Nef protein, which contains a conserved diacidic motif and, unusually, an immunoreceptor tyrosine-based activation motif (ITAM). Results Mutation of the diacidic motif in the Nef protein of the SIVsmmPBj abolishes the acute phenotype of this virus. In vitro, wild-type and mutant PBj (PBj-Nef202/203GG) viruses replicated to similar levels in macaque PBMCs, but PBj-Nef202/203GG no longer triggers ERK mitogen-activated protein (MAP) kinase pathway including an alteration of a Nef-associated Raf-1/ERK-2 multiprotein signaling complex. Moreover, stimulation of IL-2 and down-modulation of CD4 and CD28 were impaired in the mutant virus. Pig-tailed macaques infected with PBj-Nef202/203GG did not show enteropathic complications and lethality as observed with wild-type PBj virus, despite efficient replication of both viruses in vivo. Furthermore, PBj-Nef202/203GG infected animals revealed reduced T-cell activation in periphery lymphoid organs and no detectable induction of IL-2 and IL-6. Conclusions In sum, we report here that mutation of the diacidic motif in the PBj-Nef protein abolishes disease progression in pig-tailed macaques despite efficient replication. These data suggest that alterations in the ability of a lentivirus to promote T cell activation and proliferation can have a dramatic impact on its pathogenic potential. PMID:21366921

  1. Membrane-Associated Conformation of HIV-1 Nef Investigated with Hydrogen Exchange Mass Spectrometry at a Langmuir Monolayer.

    PubMed

    Pirrone, Gregory F; Emert-Sedlak, Lori A; Wales, Thomas E; Smithgall, Thomas E; Kent, Michael S; Engen, John R

    2015-07-21

    In the companion paper to this work, we described development of a new type of hydrogen exchange (HX) mass spectrometry (MS) measurement that integrates Langmuir monolayers. With Langmuir monolayers, the lipid packing density can be reproducibly controlled and changed as desired. Analysis of HX in proteins that may undergo conformational changes as a function of lipid packing (for example, conformational rearrangements after insertion into a lipid layer) are then possible. We previously used neutron reflection to characterize just such a conformational change in the myristoylated HIV-1 Nef protein (myrNef): at high lipid packing density, myrNef could not insert into the lipids and maintained a compact conformation adjacent to the monolayer, whereas at lower lipid packing density, myrNef was able to insert N-terminal arm residues, causing displacement of the core domain away from the monolayer. In order to locate where conformation may have been altered by lipid association, we applied the HX MS Langmuir monolayer method to myrNef associated with monolayers of packing densities identical to those used for the prior neutron reflection measurements. The results show that the N-terminal region and the C-terminal unstructured loop undergo conformational changes when associated with a low density lipid monolayer. The results are not consistent with the hypothesis of myrNef dimerization upon membrane association in the absence of other myrNef binding partners. The HX MS Langmuir monolayer method provides new and meaningful information for myrNef that helps explain necessary conformational changes required for function at the membrane. PMID:26133569

  2. The HIV-1 Nef Protein Binds Argonaute-2 and Functions as a Viral Suppressor of RNA Interference

    PubMed Central

    Aqil, Madeeha; Naqvi, Afsar Raza; Bano, Aalia Shahr; Jameel, Shahid

    2013-01-01

    The HIV-1 accessory protein Nef is an important virulence factor. It associates with cellular membranes and modulates the endocytic machinery and signaling pathways. Nef also increases the proliferation of multivesicular bodies (MVBs), which are sites for virus assembly and budding in macrophages. The RNA interference (RNAi) pathway proteins Ago2 and GW182 localize to MVBs, suggesting these to be sites for assembly and turnover of the miRNA-induced silencing complex (miRISC). While RNAi affects HIV replication, it is not clear if the virus encodes a suppressor activity to overcome this innate host response. Here we show that Nef colocalizes with MVBs and binds Ago2 through two highly conserved Glycine-Tryptophan (GW) motifs, mutations in which abolish Nef binding to Ago2 and reduce virus yield and infectivity. Nef also inhibits the slicing activity of Ago2 and disturbs the sorting of GW182 into exosomes resulting in the suppression of miRNA-induced silencing. Thus, besides its other activities, the HIV-1 Nef protein is also proposed to function as a viral suppressor of RNAi (VSR). PMID:24023945

  3. Human immunodeficiency virus type 1 Nef recruits the guanine exchange factor Vav1 via an unexpected interface into plasma membrane microdomains for association with p21-activated kinase 2 activity.

    PubMed

    Rauch, Susanne; Pulkkinen, Kati; Saksela, Kalle; Fackler, Oliver T

    2008-03-01

    Alterations of T-cell receptor signaling by human immunodeficiency virus type 1 (HIV-1) Nef involve its association with a highly active subpopulation of p21-activated kinase 2 (PAK2) within a dynamic signalosome assembled in detergent-insoluble membrane microdomains. Nef-PAK2 complexes contain the GTPases Rac and Cdc42 as well as a factor providing guanine nucleotide exchange factor (GEF) activity for Rac/Cdc42. However, the identity of this GEF has remained controversial. Previous studies suggested the association of Nef with at least three independent GEFs, Vav, DOCK2/ELMO1, and betaPix. Here we used a broad panel of approaches to address which of these GEFs is involved in the functional interaction of Nef with PAK2 activity. Biochemical fractionation and confocal microscopy revealed that Nef recruits Vav1, but not DOCK2/ELMO1 or betaPix, to membrane microdomains. Transient RNAi knockdown, analysis of cell lines defective for expression of Vav1 or DOCK2 as well as use of a betaPix binding-deficient PAK2 variant confirmed a role for Vav1 but not DOCK2 or betaPix in Nef's association with PAK2 activity. Nef-mediated microdomain recruitment of Vav1 occurred independently of the Src homology 3 domain binding PxxP motif, which is known to connect Nef to many cellular signaling processes. Instead, a recently described protein interaction surface surrounding Nef residue F195 was identified as critical for Nef-mediated raft recruitment of Vav1. These results identify Vav1 as a relevant component of the Nef-PAK2 signalosome and provide a molecular basis for the role of F195 in formation of a catalytically active Nef-PAK2 complex. PMID:18094167

  4. Optimized Replicating Renilla Luciferase Reporter HIV-1 Utilizing Novel Internal Ribosome Entry Site Elements for Native Nef Expression and Function.

    PubMed

    Alberti, Michael O; Jones, Jennifer J; Miglietta, Riccardo; Ding, Haitao; Bakshi, Rakesh K; Edmonds, Tara G; Kappes, John C; Ochsenbauer, Christina

    2015-12-01

    We previously developed replication-competent reporter HIV-1 (referred to herein as LucR.T2A reporter viruses), utilizing a "ribosome skipping" T2A peptide strategy to link Renilla luciferase (LucR) with Nef expression. The demonstrated utility for HIV-1 vaccine and transmission study applications included measurement of neutralizing antibody (NAb) activity in vaccine sera, improved cell-mediated virus inhibition assays, such as T cell-mediated virus inhibition and antibody-dependent cell-mediated cytotoxicity (ADCC) assays, and humanized mouse models. Herein, we extend our prior work and introduce reporter virus technology for applications that require fully functional Nef. We demonstrate that in CD4(+) T cells productively infected with LucR.T2A reporter viruses, T2A peptide-driven Nef expression and function, such as down-regulation of surface CD4 and MHC-I, were impaired. We overcame this limitation of LucR.T2A reporter viruses and achieved physiological Nef expression and function by engineering novel LucR reporter HIV-1 comprising 11 different internal ribosome entry site (IRES) elements chosen for size and relative activity. A range of Nef expression was observed in 293T cells transfected with the different LucR.IRES reporter virus constructs. Iteratively, we identified IRES reporter genomes that expressed Nef closest to physiological levels and produced virus with infectivity, titers, and replication kinetics similar to nonreporter viruses. Our results demonstrated that LucR reporter activity was stable over multiple replication cycles in peripheral blood mononuclear cells (PBMCs). Furthermore, we analyzed Nef functionality, i.e., down-modulation of MHC-I and CD4, following infection of T cell lines and PBMCs. Unlike LucR.T2A reporter virus, one of the redesigned LucR.IRES reporter viruses [containing the modified encephalomyocarditis virus (EMCV) 6ATR IRES element, "6ATRi"] demonstrated Nef expression and function similar to parental "nonreporter" virus

  5. Molecular characterization of HIV-1 Nef and ACOT8 interaction: insights from in silico structural predictions and in vitro functional assays

    PubMed Central

    Serena, Michela; Giorgetti, Alejandro; Busato, Mirko; Gasparini, Francesca; Diani, Erica; Romanelli, Maria Grazia; Zipeto, Donato

    2016-01-01

    HIV-1 Nef interacts with several cellular proteins, among which the human peroxisomal thioesterase 8 (ACOT8). This interaction may be involved in the endocytosis regulation of membrane proteins and might modulate lipid composition in membrane rafts. Nef regions involved in the interaction have been experimentally characterized, whereas structural details of the ACOT8 protein are unknown. The lack of structural information hampers the comprehension of the functional consequences of the complex formation during HIV-1 infection. We modelled, through in silico predictions, the ACOT8 structure and we observed a high charge complementarity between Nef and ACOT8 surfaces, which allowed the identification of the ACOT8 putative contact points involved in the interaction. The predictions were validated by in vitro assays through the development of ACOT8 deletion mutants. Coimmunoprecipitation and immunofluorescence analyses showed that ACOT8 Arg45-Phe55 and Arg86-Pro93 regions are involved in Nef association. In addition, K91S mutation abrogated the interaction with Nef, indicating that Lys91 plays a key role in the interaction. Finally, when associated with ACOT8, Nef may be preserved from degradation. These findings improve the comprehension of the association between HIV-1 Nef and ACOT8, helping elucidating the biological effect of their interaction. PMID:26927806

  6. Molecular characterization of HIV-1 Nef and ACOT8 interaction: insights from in silico structural predictions and in vitro functional assays

    NASA Astrophysics Data System (ADS)

    Serena, Michela; Giorgetti, Alejandro; Busato, Mirko; Gasparini, Francesca; Diani, Erica; Romanelli, Maria Grazia; Zipeto, Donato

    2016-03-01

    HIV-1 Nef interacts with several cellular proteins, among which the human peroxisomal thioesterase 8 (ACOT8). This interaction may be involved in the endocytosis regulation of membrane proteins and might modulate lipid composition in membrane rafts. Nef regions involved in the interaction have been experimentally characterized, whereas structural details of the ACOT8 protein are unknown. The lack of structural information hampers the comprehension of the functional consequences of the complex formation during HIV-1 infection. We modelled, through in silico predictions, the ACOT8 structure and we observed a high charge complementarity between Nef and ACOT8 surfaces, which allowed the identification of the ACOT8 putative contact points involved in the interaction. The predictions were validated by in vitro assays through the development of ACOT8 deletion mutants. Coimmunoprecipitation and immunofluorescence analyses showed that ACOT8 Arg45-Phe55 and Arg86-Pro93 regions are involved in Nef association. In addition, K91S mutation abrogated the interaction with Nef, indicating that Lys91 plays a key role in the interaction. Finally, when associated with ACOT8, Nef may be preserved from degradation. These findings improve the comprehension of the association between HIV-1 Nef and ACOT8, helping elucidating the biological effect of their interaction.

  7. Downregulation of the T-Cell Receptor by Human Immunodeficiency Virus Type 2 Nef Does Not Protect against Disease Progression▿

    PubMed Central

    Feldmann, Jérôme; Leligdowicz, Aleksandra; Jaye, Assan; Dong, Tao; Whittle, Hilton; Rowland-Jones, Sarah L.

    2009-01-01

    Chronic immune activation is thought to play a major role in human immunodeficiency virus (HIV) pathogenesis, but the relative contributions of multiple factors to immune activation are not known. One proposed mechanism to protect against immune activation is the ability of Nef proteins from some HIV and simian immunodeficiency virus strains to downregulate the T-cell receptor (TCR)-CD3 complex of the infected cell, thereby reducing the potential for deleterious activation. HIV type 1 (HIV-1) Nef has lost this property. In contrast to HIV-1, HIV-2 infection is characterized by a marked disparity in the disease course, with most individuals maintaining a normal life span. In this study, we examined the relationship between the ability of HIV-2 Nef proteins to downregulate the TCR and immune activation, comparing progressors and nonprogressors. Representative Nef variants were isolated from 28 HIV-2-infected individuals. We assessed their abilities to downregulate the TCR from the surfaces of CD4 T cells. In the same individuals, the activation of peripheral lymphocytes was evaluated by measurement of the expression levels of HLA-DR and CD38. We observed a striking correlation of the TCR downregulation efficiency of HIV-2 Nef variants with immune activation in individuals with a low viral load. This strongly suggests that Nef expression can influence the activation state of the immune systems of infected individuals. However, the efficiency of TCR downregulation by Nef was not reduced in progressing individuals, showing that TCR downregulation does not protect against progression in HIV-2 infection. PMID:19812166

  8. Dynamic features of apo and bound HIV-Nef protein reveal the anti-HIV dimerization inhibition mechanism.

    PubMed

    Moonsamy, Suri; Bhakat, Soumendranath; Soliman, Mahmoud E S

    2015-01-01

    The first account on the dynamic features of Nef or negative factor, a small myristoylated protein located in the cytoplasm believes to increase HIV-1 viral titer level, is reported herein. Due to its major role in HIV-1 pathogenicity, Nef protein is considered an emerging target in anti-HIV drug design and discovery process. In this study, comparative long-range all-atom molecular dynamics simulations were employed for apo and bound protein to unveil molecular mechanism of HIV-Nef dimerization and inhibition. Results clearly revealed that B9, a newly discovered Nef inhibitor, binds at the dimeric interface of Nef protein and caused significant separation between orthogonally opposed residues, namely Asp108, Leu112 and Gln104. Large differences in magnitudes were observed in the radius of gyration (∼1.5 Å), per-residue fluctuation (∼2 Å), C-alpha deviations (∼2 Å) which confirm a comparatively more flexible nature of apo conformation due to rapid dimeric association. Compared to the bound conformer, a more globally correlated motion in case of apo structure of HIV-Nef confirms the process of dimeric association. This clearly highlights the process of inhibition as a result of ligand binding. The difference in principal component analysis (PCA) scatter plot and per-residue mobility plot across first two normal modes further justifies the same findings. The in-depth dynamic analyses of Nef protein presented in this report would serve crucial in understanding its function and inhibition mechanisms. Information on inhibitor binding mode would also assist in designing of potential inhibitors against this important HIV target. PMID:26355431

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

    PubMed Central

    Veglia, Filippo; Goode, Diana; Truong, Rosaline; Derby, Nina; Blanchard, James; Grasperge, Brooke; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

    2016-01-01

    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. PMID:26886938

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

    PubMed

    Guerra-Pérez, Natalia; Aravantinou, Meropi; Veglia, Filippo; Goode, Diana; Truong, Rosaline; Derby, Nina; Blanchard, James; Grasperge, Brooke; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

    2016-01-01

    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. PMID:26886938

  11. Structural constraints on human immunodeficiency virus type 1 Nef function

    SciTech Connect

    Raney, Alexa; Shaw, Alice Y.; Foster, John L.; Garcia, J. Victor

    2007-11-10

    HIV-1 Nef is a multifunctional protein that exerts its activities through interactions with multiple cellular partners. Nef uses different domains and mechanisms to exert its functions including cell surface down-modulation of CD4 and MHC-I receptors and activation of the serine/threonine kinase PAK-2. We inserted tags at the C-terminus and proximal to the N-terminus of Nef and the effects on Nef's structure/function relationships were examined. We discovered significant defects in MHC-I down-modulation with the insertion of HA/FLAG tags at either region. We also found impaired PAK-2 activation with a C-terminal fusion with GFP. Interestingly, Nef-GFP and Nef-GH{sub 7} induced MHC-I down-modulation, suggesting that the negative charge of the HA/FLAG tag could contribute to the observed defect. Together, these observations highlight elements of Nef's functional complexity and demonstrate previously unsuspected structural requirements for PAK-2 activation and MHC-1 down-modulation in Nef's flexible N- and C-terminal regions.

  12. High potassium level

    MedlinePlus

    High potassium level is a problem in which the amount of potassium in the blood is higher than normal. The medical ... There are often no symptoms with a high level of potassium. When symptoms do occur, they may ...

  13. CD8 T Cell Response Maturation Defined by Anentropic Specificity and Repertoire Depth Correlates with SIVΔnef-induced Protection

    PubMed Central

    Adnan, Sama; Colantonio, Arnaud D.; Yu, Yi; Gillis, Jacqueline; Wong, Fay E.; Becker, Ericka A.; Reeves, R. Keith; Lifson, Jeffrey D.; O’Connor, Shelby L.; Johnson, R. Paul

    2015-01-01

    The live attenuated simian immunodeficiency virus (LASIV) vaccine SIVΔnef is one of the most effective vaccines in inducing protection against wild-type lentiviral challenge, yet little is known about the mechanisms underlying its remarkable protective efficacy. Here, we exploit deep sequencing technology and comprehensive CD8 T cell epitope mapping to deconstruct the CD8 T cell response, to identify the regions of immune pressure and viral escape, and to delineate the effect of epitope escape on the evolution of the CD8 T cell response in SIVΔnef-vaccinated animals. We demonstrate that the initial CD8 T cell response in the acute phase of SIVΔnef infection is mounted predominantly against more variable epitopes, followed by widespread sequence evolution and viral escape. Furthermore, we show that epitope escape expands the CD8 T cell repertoire that targets highly conserved epitopes, defined as anentropic specificity, and generates de novo responses to the escaped epitope variants during the vaccination period. These results correlate SIVΔnef-induced protection with expanded anentropic specificity and increased response depth. Importantly, these findings render SIVΔnef, long the gold standard in HIV/SIV vaccine research, as a proof-of-concept vaccine that highlights the significance of the twin principles of anentropic specificity and repertoire depth in successful vaccine design. PMID:25688559

  14. High blood cholesterol levels

    MedlinePlus

    ... gov/ency/article/000403.htm High blood cholesterol levels To use the sharing features on this page, ... called "bad" cholesterol For many people, abnormal cholesterol levels are partly due to an unhealthy lifestyle. This ...

  15. Activation pathways and human immunodeficiency virus type 1 replication are not altered in CD4+ T cells expressing the nef protein.

    PubMed

    Schwartz, O; Arenzana-Seisdedos, F; Heard, J M; Danos, O

    1992-05-01

    While recent studies in Rhesus monkeys have pointed out the importance of an intact nef gene for the development of acquired immunodeficiency syndrome (AIDS), no biological function has been so far unambiguously attributed to its product. Since Nef has been described to possess GTP-binding properties and to down-regulate CD4 cell surface expression, we looked for evidences of Nef interfering with the transduction of activating signals in human CD4+ T cells. We used a murine leukemia retroviral vector to express the HIV-1BRU nef gene in two permanent tumoral T-cell lines (CEM and Jurkat) and in two nonimmortalized, interleukin-2 (IL2)-dependent, T-cell clones. The single copy recombinant provirus integrated in the genome of these cells directed the synthesis of a 27-kD protein with a half-life greater than 5 h. The levels of expression of cell surface molecules involved in T-cell functions (CD4, CD3, CD28, CD29, IL-2 receptor) were not modified in cell populations expressing Nef. In immunocompetent T-cell clones, cell proliferation and lymphokine production in response to activating stimuli (IL-2, alloantigens, phorbol esters, or antibodies directed against CD2, CD3, CD4, CD28) remained unmodified. Moreover, the presence of Nef did not change the kinetics of human immunodeficiency virus (HIV) infection. PMID:1355346

  16. The human immunodeficiency virus antigen Nef forms protein bodies in leaves of transgenic tobacco when fused to zeolin.

    PubMed

    de Virgilio, Maddalena; De Marchis, Francesca; Bellucci, Michele; Mainieri, Davide; Rossi, Marika; Benvenuto, Eugenio; Arcioni, Sergio; Vitale, Alessandro

    2008-01-01

    Protein bodies (PB) are stable polymers naturally formed by certain seed storage proteins within the endoplasmic reticulum (ER). The human immunodeficiency virus negative factor (Nef) protein, a potential antigen for the development of an anti-viral vaccine, is highly unstable when introduced into the plant secretory pathway, probably because of folding defects in the ER environment. The aim of this study was to promote the formation of Nef-containing PB in tobacco (Nicotiana tabacum) leaves by fusing the Nef sequence to the N-terminal domains of the maize storage protein gamma-zein or to the chimeric protein zeolin (which efficiently forms PB and is composed of the vacuolar storage protein phaseolin fused to the N-terminal domains of gamma-zein). Protein blots and pulse-chase indicate that fusions between Nef and the same gamma-zein domains present in zeolin are degraded by ER quality control. Consistently, a mutated zeolin, in which wild-type phaseolin was substituted with a defective version known to be degraded by ER quality control, is unstable in plant cells. Fusion of Nef to the entire zeolin sequence instead allows the formation of PB detectable by electron microscopy and subcellular fractionation, leading to zeolin-Nef accumulation higher than 1% of total soluble protein, consistently reproduced in independent transgenic plants. It is concluded that zeolin, but not its gamma-zein portion, has a positive dominant effect over ER quality control degradation. These results provide insights into the requirements for PB formation and avoidance of quality-control degradation, and indicate a strategy for enhancing foreign protein accumulation in plants. PMID:18540021

  17. The human immunodeficiency virus antigen Nef forms protein bodies in leaves of transgenic tobacco when fused to zeolin

    PubMed Central

    de Virgilio, Maddalena; Bellucci, Michele; Mainieri, Davide; Rossi, Marika; Benvenuto, Eugenio; Arcioni, Sergio; Vitale, Alessandro

    2008-01-01

    Protein bodies (PB) are stable polymers naturally formed by certain seed storage proteins within the endoplasmic reticulum (ER). The human immunodeficiency virus negative factor (Nef) protein, a potential antigen for the development of an anti-viral vaccine, is highly unstable when introduced into the plant secretory pathway, probably because of folding defects in the ER environment. The aim of this study was to promote the formation of Nef-containing PB in tobacco (Nicotiana tabacum) leaves by fusing the Nef sequence to the N-terminal domains of the maize storage protein γ-zein or to the chimeric protein zeolin (which efficiently forms PB and is composed of the vacuolar storage protein phaseolin fused to the N-terminal domains of γ-zein). Protein blots and pulse–chase indicate that fusions between Nef and the same γ-zein domains present in zeolin are degraded by ER quality control. Consistently, a mutated zeolin, in which wild-type phaseolin was substituted with a defective version known to be degraded by ER quality control, is unstable in plant cells. Fusion of Nef to the entire zeolin sequence instead allows the formation of PB detectable by electron microscopy and subcellular fractionation, leading to zeolin–Nef accumulation higher than 1% of total soluble protein, consistently reproduced in independent transgenic plants. It is concluded that zeolin, but not its γ-zein portion, has a positive dominant effect over ER quality control degradation. These results provide insights into the requirements for PB formation and avoidance of quality-control degradation, and indicate a strategy for enhancing foreign protein accumulation in plants. PMID:18540021

  18. Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins

    DOEpatents

    Korber, Bette T.; Perkins, Simon; Bhattacharya, Tanmoy; Fischer, William M.; Theiler, James; Letvin, Norman; Haynes, Barton F.; Hahn, Beatrice H.; Yusim, Karina; Kuiken, Carla

    2012-02-21

    The present invention relates to mosaic clade M HIV-1 Nef polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  19. Human Immunodeficiency Virus Type 1 Nef Inhibits Autophagy through Transcription Factor EB Sequestration.

    PubMed

    Campbell, Grant R; Rawat, Pratima; Bruckman, Rachel S; Spector, Stephen A

    2015-06-01

    HIV Nef acts as an anti-autophagic maturation factor through interaction with beclin-1 (BECN1). We report that exposure of macrophages to infectious or non-infectious purified HIV induces toll-like receptor 8 (TLR8) and BECN1 dependent dephosphorylation and nuclear translocation of TFEB and that this correlates with an increase in autophagy markers. RNA interference for ATG13, TFEB, TLR8, or BECN1 inhibits this HIV-induced autophagy. However, once HIV establishes a productive infection, TFEB phosphorylation and cytoplasmic sequestration are increased resulting in decreased autophagy markers. Moreover, by 7 d post-infection, autophagy levels are similar to mock infected controls. Conversely, although Nef deleted HIV similarly induces TFEB dephosphorylation and nuclear localization, and increases autophagy, these levels remain elevated during continued productive infection. Thus, the interaction between HIV and TLR8 serves as a signal for autophagy induction that is dependent upon the dephosphorylation and nuclear translocation of TFEB. During permissive infection, Nef binds BECN1 resulting in mammalian target of rapamycin (MTOR) activation, TFEB phosphorylation and cytosolic sequestration, and the inhibition of autophagy. To our knowledge, this is the first report of a virus modulating TFEB localization and helps to explain how HIV modulates autophagy to promote its own replication and cell survival. PMID:26115100

  20. Human Immunodeficiency Virus Type 1 Nef Inhibits Autophagy through Transcription Factor EB Sequestration

    PubMed Central

    Campbell, Grant R.; Rawat, Pratima; Bruckman, Rachel S.; Spector, Stephen A.

    2015-01-01

    HIV Nef acts as an anti-autophagic maturation factor through interaction with beclin-1 (BECN1). We report that exposure of macrophages to infectious or non-infectious purified HIV induces toll-like receptor 8 (TLR8) and BECN1 dependent dephosphorylation and nuclear translocation of TFEB and that this correlates with an increase in autophagy markers. RNA interference for ATG13, TFEB, TLR8, or BECN1 inhibits this HIV-induced autophagy. However, once HIV establishes a productive infection, TFEB phosphorylation and cytoplasmic sequestration are increased resulting in decreased autophagy markers. Moreover, by 7 d post-infection, autophagy levels are similar to mock infected controls. Conversely, although Nef deleted HIV similarly induces TFEB dephosphorylation and nuclear localization, and increases autophagy, these levels remain elevated during continued productive infection. Thus, the interaction between HIV and TLR8 serves as a signal for autophagy induction that is dependent upon the dephosphorylation and nuclear translocation of TFEB. During permissive infection, Nef binds BECN1 resulting in mammalian target of rapamycin (MTOR) activation, TFEB phosphorylation and cytosolic sequestration, and the inhibition of autophagy. To our knowledge, this is the first report of a virus modulating TFEB localization and helps to explain how HIV modulates autophagy to promote its own replication and cell survival. PMID:26115100

  1. High level nuclear waste

    SciTech Connect

    Crandall, J L

    1980-01-01

    The DOE Division of Waste Products through a lead office at Savannah River is developing a program to immobilize all US high-level nuclear waste for terminal disposal. DOE high-level wastes include those at the Hanford Plant, the Idaho Chemical Processing Plant, and the Savannah River Plant. Commercial high-level wastes, for which DOE is also developing immobilization technology, include those at the Nuclear Fuel Services Plant and any future commercial fuels reprocessing plants. The first immobilization plant is to be the Defense Waste Processing Facility at Savannah River, scheduled for 1983 project submission to Congress and 1989 operation. Waste forms are still being selected for this plant. Borosilicate glass is currently the reference form, but alternate candidates include concretes, calcines, other glasses, ceramics, and matrix forms.

  2. Epitopes of human immunodeficiency virus regulatory proteins tat, nef, and rev are expressed in normal human tissue.

    PubMed Central

    Parmentier, H. K.; van Wichen, D. F.; Meyling, F. H.; Goudsmit, J.; Schuurman, H. J.

    1992-01-01

    The expression of regulatory proteins tat, rev, and nef of human immunodeficiency virus type-1 (HIV-1) and tat of HIV-2 was studied in frozen sections of lymph nodes from HIV-1-infected individuals, and various tissues from uninfected persons. In HIV-1-positive lymph nodes, monoclonal antibodies to HIV-1-tat stained solitary cells in the germinal centers and interfollicular zones, and vascular endothelium. Staining by an anti-nef monoclonal antibody was restricted to follicular dendritic cells, whereas anti-rev antibody bound to fibriohistiocytes and high endothelial venules. The antibodies used labeled several cell types in tissues from uninfected individuals. Anti-HIV-1-tat antibodies labeled blood vessels and Hassall's corpuscles in skin and thymus; goblet cells in intestinal tissue and trachea; neural cells in brain and spinal cord; and zymogen-producing cells in pancreas. Anti-rev antibody stained high endothelial venules, Hassall's corpuscles and histiocytes. One anti-nef antibody solely stained follicular dendritic cells in spleen, tonsil, lymph node and Peyer's patches, whereas two other anti-nef antibodies bound to astrocytes, solitary cells in the interfollicular zones of lymph nodes, and skin cells. The current results hamper the immunohistochemical study for pathogenetic and diagnostic use of HIV regulatory protein expression in infected tissue specimens or cells. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1279980

  3. Association with PAK2 Enables Functional Interactions of Lentiviral Nef Proteins with the Exocyst Complex

    PubMed Central

    Imle, Andrea; Abraham, Libin; Tsopoulidis, Nikolaos; Hoflack, Bernard; Saksela, Kalle

    2015-01-01

    ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication and contributes to immune evasion in vivo, but the underlying molecular mechanisms remain incompletely defined. Nef interferes with host cell actin dynamics to restrict T lymphocyte responses to chemokine stimulation and T cell receptor engagement. This relies on the assembly of a labile multiprotein complex including the host kinase PAK2 that Nef usurps to phosphorylate and inactivate the actin-severing factor cofilin. Components of the exocyst complex (EXOC), an octameric protein complex involved in vesicular transport and actin remodeling, were recently reported to interact with Nef via the same molecular surface that mediates PAK2 association. Exploring the functional relevance of EXOC in Nef-PAK2 complex assembly/function, we found Nef-EXOC interactions to be specifically mediated by the PAK2 interface of Nef, to occur in infected human T lymphocytes, and to be conserved among lentiviral Nef proteins. In turn, EXOC was dispensable for direct downstream effector functions of Nef-associated PAK2. Surprisingly, PAK2 was essential for Nef-EXOC association, which required a functional Rac1/Cdc42 binding site but not the catalytic activity of PAK2. EXOC was dispensable for Nef functions in vesicular transport but critical for inhibition of actin remodeling and proximal signaling upon T cell receptor engagement. Thus, Nef exploits PAK2 in a stepwise mechanism in which its kinase activity cooperates with an adaptor function for EXOC to inhibit host cell actin dynamics. PMID:26350970

  4. Formation of a Unique Cluster of G-Quadruplex Structures in the HIV-1 nef Coding Region: Implications for Antiviral Activity

    PubMed Central

    Perrone, Rosalba; Nadai, Matteo; Poe, Jerrod A.; Frasson, Ilaria; Palumbo, Manlio; Palù, Giorgio; Smithgall, Thomas E.; Richter, Sara N.

    2013-01-01

    G-quadruplexes are tetraplex structures of nucleic acids that can form in G-rich sequences. Their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they have been proposed to be directly involved in gene regulation at the level of transcription. Because the HIV-1 Nef protein is a fundamental factor for efficient viral replication, infectivity and pathogenesis invitro and invivo, we investigated G-quadruplex formation in the HIV-1 nef gene to assess the potential for viral inhibition through G-quadruplex stabilization. A comprehensive computational analysis of the nef coding region of available strains showed the presence of three conserved sequences that were uniquely clustered. Biophysical testing proved that G-quadruplex conformations were efficiently stabilized or induced by G-quadruplex ligands in all three sequences. Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was significantly repressed in an antiviral assay. These data constitute the first evidence of the possibility to regulate HIV-1 gene expression and infectivity through G-quadruplex targeting and therefore open a new avenue for viral treatment. PMID:24015290

  5. Formation of a unique cluster of G-quadruplex structures in the HIV-1 Nef coding region: implications for antiviral activity.

    PubMed

    Perrone, Rosalba; Nadai, Matteo; Poe, Jerrod A; Frasson, Ilaria; Palumbo, Manlio; Palù, Giorgio; Smithgall, Thomas E; Richter, Sara N

    2013-01-01

    G-quadruplexes are tetraplex structures of nucleic acids that can form in G-rich sequences. Their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they have been proposed to be directly involved in gene regulation at the level of transcription. Because the HIV-1 Nef protein is a fundamental factor for efficient viral replication, infectivity and pathogenesis in vitro and in vivo, we investigated G-quadruplex formation in the HIV-1 nef gene to assess the potential for viral inhibition through G-quadruplex stabilization. A comprehensive computational analysis of the nef coding region of available strains showed the presence of three conserved sequences that were uniquely clustered. Biophysical testing proved that G-quadruplex conformations were efficiently stabilized or induced by G-quadruplex ligands in all three sequences. Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was significantly repressed in an antiviral assay. These data constitute the first evidence of the possibility to regulate HIV-1 gene expression and infectivity through G-quadruplex targeting and therefore open a new avenue for viral treatment. PMID:24015290

  6. A Genome-Wide Screen for Machinery Involved in Downregulation of MHC Class I by HIV-1 Nef

    PubMed Central

    Choma, Maja K.; Lumb, Jennifer; Kozik, Patrycja; Robinson, Margaret S.

    2015-01-01

    The HIV-1-encoded protein, Nef, plays a key role in the development of AIDS. One of Nef’s functions is to keep MHC class I off the surface of infected cells, a process that requires the host proteins clathrin and AP-1. To identify other proteins involved in this pathway, we carried out a genome-wide siRNA library screen on HeLa cells co-expressing HLA-A2 and an inducible form of Nef. Out of 21,121 siRNA pools, 100 were selected for further analysis, based on their ability to either inhibit or enhance downregulation of MHC-I by Nef. When cells were treated with the same siRNA pools as those used in the screen, 79% produced a similar phenotype. However, when the cells were treated with different siRNA reagents targeting the same genes, only 16% produced a similar phenotype. This indicates that most of the hits found in the original screen are likely to have been off-target, an important concern that is often not taken into account in siRNA screening studies. Nevertheless, we identified novel host factors involved in Nef-induced downregulation of MHC-I, including four genes, MIIP, CAMSAP3, SLC6A3, and KCTD19, where multiple reagents produced a strong inhibitory effect on Nef activity. Other hits slightly below our very high stringency cutoff point may also deserve further study. Thus, our dataset is a valuable resource for scientists investigating the pathogenesis of HIV. PMID:26466362

  7. Tracking the Emergence of Host-Specific Simian Immunodeficiency Virus env and nef Populations Reveals nef Early Adaptation and Convergent Evolution in Brain of Naturally Progressing Rhesus Macaques

    PubMed Central

    Lamers, Susanna L.; Nolan, David J.; Rife, Brittany D.; Fogel, Gary B.; McGrath, Michael S.; Burdo, Tricia H.; Autissier, Patrick; Williams, Kenneth C.; Goodenow, Maureen M.

    2015-01-01

    ABSTRACT While a clear understanding of the events leading to successful establishment of host-specific viral populations and productive infection in the central nervous system (CNS) has not yet been reached, the simian immunodeficiency virus (SIV)-infected rhesus macaque provides a powerful model for the study of human immunodeficiency virus (HIV) intrahost evolution and neuropathogenesis. The evolution of the gp120 and nef genes, which encode two key proteins required for the establishment and maintenance of infection, was assessed in macaques that were intravenously inoculated with the same viral swarm and allowed to naturally progress to simian AIDS and potential SIV-associated encephalitis (SIVE). Longitudinal plasma samples and immune markers were monitored until terminal illness. Single-genome sequencing was employed to amplify full-length env through nef transcripts from plasma over time and from brain tissues at necropsy. nef sequences diverged from the founder virus faster than gp120 diverged. Host-specific sequence populations were detected in nef (∼92 days) before they were detected in gp120 (∼182 days). At necropsy, similar brain nef sequences were found in different macaques, indicating convergent evolution, while gp120 brain sequences remained largely host specific. Molecular clock and selection analyses showed weaker clock-like behavior and stronger selection pressure in nef than in gp120, with the strongest nef selection in the macaque with SIVE. Rapid nef diversification, occurring prior to gp120 diversification, indicates that early adaptation of nef in the new host is essential for successful infection. Moreover, the convergent evolution of nef sequences in the CNS suggests a significant role for nef in establishing neurotropic strains. IMPORTANCE The SIV-infected rhesus macaque model closely resembles HIV-1 immunopathogenesis, neuropathogenesis, and disease progression in humans. Macaques were intravenously infected with identical viral

  8. Live Attenuated Rev-Independent Nef¯SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques

    PubMed Central

    Byrareddy, Siddappa N.; Ayash-Rashkovsky, Mila; Kramer, Victor G.; Lee, Sandra J.; Correll, Mick; Novembre, Francis J.; Villinger, Francois; Johnson, Welkin E.; von Gegerfelt, Agneta; Felber, Barbara K.; Ruprecht, Ruth M.

    2013-01-01

    Background Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef¯ simian immunodeficiency virus (Rev-Ind Nef¯SIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges. Methodology/Principal Findings Three groups of four RM were inoculated with Rev-Ind Nef¯SIV and compared. Group 1 was inoculated 8 years prior and again 15 months before low dose intrarectal challenges with SIVsmE660. Group 2 animals were inoculated with Rev-Ind Nef¯SIV at 15 months and Group 3 at 2 weeks prior to the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls. All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660. Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became superinfected with the challenge virus, in contrast to the two other vaccine groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene expression analysis showed significant upregulation of innate immune response-related chemokines and their receptors, most notably CCR5 in Group 3 animals during acute infection with Rev-Ind Nef¯SIV. Conclusions/Significance We conclude that although Rev-Ind Nef¯SIV remained apathogenic, acute replication of the vaccine strain was not protective but associated with increased acquisition of heterologous mucosal SIVsmE660 challenges. PMID:24098702

  9. Characterization of CD8+ T Cell Differentiation following SIVΔnef Vaccination by Transcription Factor Expression Profiling

    PubMed Central

    Billingsley, James M.; Rajakumar, Premeela A.; Connole, Michelle A.; Salisch, Nadine C.; Adnan, Sama; Kuzmichev, Yury V.; Hong, Henoch S.; Reeves, R. Keith; Kang, Hyung-joo; Li, Wenjun; Li, Qingsheng; Haase, Ashley T.; Johnson, R. Paul

    2015-01-01

    The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8+ T cell responses induced by SIVΔnef. As a novel approach to characterize cell differentiation following vaccination, we used multi-target qPCR to measure transcription factor expression in naïve and memory subsets of CD8++ T cells, and in SIV-specific CD8+ T cells obtained from SIVΔnef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised clustering of expression profiles organized naïve and memory CD8+ T cells into groups concordant with cell surface phenotype. Transcription factor expression patterns in SIV-specific CD8+ T cells in SIVΔnef-vaccinated animals were distinct from those observed in purified CD8+ T cell subsets obtained from naïve animals, and were intermediate to expression profiles of purified central memory and effector memory T cells. Expression of transcription factors elicited by SIVΔnef vaccination also varied over time: cells obtained at later time points, temporally associated with greater protection, appeared more central-memory like than cells obtained at earlier time points, which appeared more effector memory-like. Expression of transcription factors associated with effector differentiation, such as ID2 and RUNX3, were decreased over time, while expression of transcription factors associated with quiescence or memory differentiation, such as TCF7, BCOR and EOMES, increased. CD8+ T cells specific for a more conserved epitope expressed higher levels of TBX21 and BATF, and appeared more effector-like than cells specific for an escaped epitope, consistent with continued activation by replicating vaccine virus. These data suggest transcription factor expression profiling is a novel method that can provide additional data complementary to the analysis of memory cell differentiation based on classical phenotypic markers. Additionally, these data

  10. Nef gene evolution from a single transmitted strain in acute SIV infection

    PubMed Central

    Bimber, Benjamin N; Chugh, Pauline; Giorgi, Elena E; Kim, Baek; Almudevar, Anthony L; Dewhurst, Stephen; O'Connor, David H; Lee, Ha Youn

    2009-01-01

    Background The acute phase of immunodeficiency virus infection plays a crucial role in determining steady-state virus load and subsequent progression of disease in both humans and nonhuman primates. The acute period is also the time when vaccine-mediated effects on host immunity are likely to exert their major effects on virus infection. Recently we developed a Monte-Carlo (MC) simulation with mathematical analysis of viral evolution during primary HIV-1 infection that enables classification of new HIV-1 infections originating from multiple versus single transmitted viral strains and the estimation of time elapsed following infection. Results A total of 322 SIV nef SIV sequences, collected during the first 3 weeks following experimental infection of two rhesus macaques with the SIVmac239 clone, were analyzed and found to display a comparable level of genetic diversity, 0.015% to 0.052%, with that of env sequences from acute HIV-1 infection, 0.005% to 0.127%. We confirmed that the acute HIV-1 infection model correctly identified the experimental SIV infections in rhesus macaques as "homogenous" infections, initiated by a single founder strain. The consensus sequence of the sampled strains corresponded to the transmitted sequence as the model predicted. However, measured sequential decrease in diversity at day 7, 11, and 18 post infection violated the model assumption, neutral evolution without any selection. Conclusion While nef gene evolution over the first 3 weeks of SIV infection originating from a single transmitted strain showed a comparable rate of sequence evolution to that observed during acute HIV-1 infection, a purifying selection for the founder nef gene was observed during the early phase of experimental infection of a nonhuman primate. PMID:19505314

  11. Nef enhances HIV-1 infectivity via association with the virus assembly complex

    SciTech Connect

    Qi Mingli; Aiken, Christopher

    2008-04-10

    The HIV-1 accessory protein Nef enhances virus infectivity by facilitating an early post-entry step of infection. Nef acts in the virus producer cell, leading to a beneficial modification to HIV-1 particles. Nef itself is incorporated into HIV-1 particles, where it is cleaved by the viral protease during virion maturation. To probe the role of virion-associated Nef in HIV-1 infection, we generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle assembly. Pharmacologic or genetic inhibition of CypA-Nef binding to Gag prevented incorporation of CypA-Nef into virions and inhibited infectivity enhancement. Our results indicate that infectivity enhancement by Nef requires its association with a component of the assembling HIV-1 particle.

  12. Nef Enhances HIV-1 Infectivity via Association with the Virus Assembly Complex

    PubMed Central

    Qi, Mingli; Aiken, Christopher

    2008-01-01

    The HIV-1 accessory protein Nef enhances virus infectivity by facilitating an early post-entry step of infection. Nef acts in the virus producer cell, leading to a beneficial modification to HIV-1 particles. Nef itself is incorporated into HIV-1 particles, where it is cleaved by the viral protease during virion maturation. To probe the role of virion-associated Nef in HIV-1 infection, we generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle assembly. Pharmacologic or genetic inhibition of CypA-Nef binding to Gag prevented incorporation of CypA-Nef into virions and inhibited infectivity enhancement. Our results indicate that infectivity enhancement by Nef requires its association with a component of the assembling HIV-1 particle. PMID:18191978

  13. High blood cholesterol levels

    MedlinePlus

    Steps you can take to improve their cholesterol levels, and help prevent heart disease and a heart attack include: Quit smoking. This is the single biggest change you can make to reduce your risk of heart attack and stroke. Eat foods ...

  14. Hydrogen Exchange Mass Spectrometry of Related Proteins with Divergent Sequences: A Comparative Study of HIV-1 Nef Allelic Variants

    NASA Astrophysics Data System (ADS)

    Wales, Thomas E.; Poe, Jerrod A.; Emert-Sedlak, Lori; Morgan, Christopher R.; Smithgall, Thomas E.; Engen, John R.

    2016-03-01

    Hydrogen exchange mass spectrometry can be used to compare the conformation and dynamics of proteins that are similar in tertiary structure. If relative deuterium levels are measured, differences in sequence, deuterium forward- and back-exchange, peptide retention time, and protease digestion patterns all complicate the data analysis. We illustrate what can be learned from such data sets by analyzing five variants (Consensus G2E, SF2, NL4-3, ELI, and LTNP4) of the HIV-1 Nef protein, both alone and when bound to the human Hck SH3 domain. Regions with similar sequence could be compared between variants. Although much of the hydrogen exchange features were preserved across the five proteins, the kinetics of Nef binding to Hck SH3 were not the same. These observations may be related to biological function, particularly for ELI Nef where we also observed an impaired ability to downregulate CD4 surface presentation. The data illustrate some of the caveats that must be considered for comparison experiments and provide a framework for investigations of other protein relatives, families, and superfamilies with HX MS.

  15. Hydrogen Exchange Mass Spectrometry of Related Proteins with Divergent Sequences: A Comparative Study of HIV-1 Nef Allelic Variants.

    PubMed

    Wales, Thomas E; Poe, Jerrod A; Emert-Sedlak, Lori; Morgan, Christopher R; Smithgall, Thomas E; Engen, John R

    2016-06-01

    Hydrogen exchange mass spectrometry can be used to compare the conformation and dynamics of proteins that are similar in tertiary structure. If relative deuterium levels are measured, differences in sequence, deuterium forward- and back-exchange, peptide retention time, and protease digestion patterns all complicate the data analysis. We illustrate what can be learned from such data sets by analyzing five variants (Consensus G2E, SF2, NL4-3, ELI, and LTNP4) of the HIV-1 Nef protein, both alone and when bound to the human Hck SH3 domain. Regions with similar sequence could be compared between variants. Although much of the hydrogen exchange features were preserved across the five proteins, the kinetics of Nef binding to Hck SH3 were not the same. These observations may be related to biological function, particularly for ELI Nef where we also observed an impaired ability to downregulate CD4 surface presentation. The data illustrate some of the caveats that must be considered for comparison experiments and provide a framework for investigations of other protein relatives, families, and superfamilies with HX MS. Graphical Abstract ᅟ. PMID:27032648

  16. Hydrogen Exchange Mass Spectrometry of Related Proteins with Divergent Sequences: A Comparative Study of HIV-1 Nef Allelic Variants

    NASA Astrophysics Data System (ADS)

    Wales, Thomas E.; Poe, Jerrod A.; Emert-Sedlak, Lori; Morgan, Christopher R.; Smithgall, Thomas E.; Engen, John R.

    2016-06-01

    Hydrogen exchange mass spectrometry can be used to compare the conformation and dynamics of proteins that are similar in tertiary structure. If relative deuterium levels are measured, differences in sequence, deuterium forward- and back-exchange, peptide retention time, and protease digestion patterns all complicate the data analysis. We illustrate what can be learned from such data sets by analyzing five variants (Consensus G2E, SF2, NL4-3, ELI, and LTNP4) of the HIV-1 Nef protein, both alone and when bound to the human Hck SH3 domain. Regions with similar sequence could be compared between variants. Although much of the hydrogen exchange features were preserved across the five proteins, the kinetics of Nef binding to Hck SH3 were not the same. These observations may be related to biological function, particularly for ELI Nef where we also observed an impaired ability to downregulate CD4 surface presentation. The data illustrate some of the caveats that must be considered for comparison experiments and provide a framework for investigations of other protein relatives, families, and superfamilies with HX MS.

  17. Relative Resistance of HLA-B to Downregulation by Naturally Occurring HIV-1 Nef Sequences

    PubMed Central

    Mahiti, Macdonald; Toyoda, Mako; Jia, Xiaofei; Kuang, Xiaomei T.; Mwimanzi, Francis; Mwimanzi, Philip; Walker, Bruce D.; Xiong, Yong; Brumme, Zabrina L.; Brockman, Mark A.

    2016-01-01

    ABSTRACT HIV-1 Nef binds to the cytoplasmic region of HLA-A and HLA-B and downregulates these molecules from the surface of virus-infected cells, thus evading immune detection by CD8+ T cells. Polymorphic residues within the HLA cytoplasmic region may affect Nef’s downregulation activity. However, the effects of HLA polymorphisms on recognition by primary Nef isolates remain elusive, as do the specific Nef regions responsible for downregulation of HLA-A versus HLA-B. Here, we examined 46 Nef clones isolated from chronically HIV-1 subtype B-infected subjects for their ability to downregulate various HLA-A, HLA-B, and HLA-C molecules on the surface of virus-infected cells. Overall, HLA-B exhibited greater resistance to Nef-mediated downregulation than HLA-A, regardless of the cell type examined. As expected, no Nef clone downregulated HLA-C. Importantly, the differential abilities of patient-derived Nef clones to downregulate HLA-A and HLA-B correlated inversely with the sensitivities of HIV-infected target cells to recognition by effector cells expressing an HIV-1 Gag-specific T cell receptor. Nef codon function analysis implicated amino acid variation at position 202 (Nef-202) in differentially affecting the ability to downregulate HLA-A and HLA-B, an observation that was subsequently confirmed by experiments using Nef mutants constructed by site-directed mutagenesis. The in silico and mutagenesis analyses further suggested that Nef-202 may interact with the C-terminal Cys-Lys-Val residues of HLA-A, which are absent in HLA-B. Taken together, the results show that natural polymorphisms within Nef modulate its interaction with natural polymorphisms in the HLA cytoplasmic tails, thereby affecting the efficiency of HLA downregulation and consequent recognition by HIV-specific T cells. These results thus extend our understanding of this complex pathway of retroviral immune evasion. PMID:26787826

  18. Gene expression profiling reveals Nef induced deregulation of lipid metabolism in HIV-1 infected T cells.

    PubMed

    Shrivastava, Surya; Trivedi, Jay; Mitra, Debashis

    2016-03-25

    Human Immunodeficiency Virus-1 (HIV-1) encodes a 27 kDa Negative Factor or Nef protein, which is increasingly proving to be a misnomer. Nef seems to be crucial for AIDS progression as individuals infected with nef-deleted strain of HIV were reported to become Long Term Non Progressors (LTNP). These findings necessitate tracing of Nef's footprint on landscape of cellular transcriptome favoring HIV-1 pathogenesis. We have tried to explore effect of Nef on cellular gene expression profile in conjunction with rest of HIV-1 proteins. Our results show that 237 genes are differentially regulated due to the presence of Nef during infection, which belong to several broad categories like "signaling", "apoptosis", "transcription" and "lipid metabolism" in gene ontology analysis. Furthermore, our results show that Nef causes disruption of lipid content in HIV-1 infected T cells. Molecular inhibitors of lipid metabolism like Atorvastatin and Ranolazine were found to have profound effect on wild type virus as compared to nef-deleted HIV-1. Thus our results suggest that interference in lipid metabolism is a potential mechanism through which Nef contributes in enhancing HIV-1 pathogenesis. PMID:26915805

  19. HIV-1 Nef binds with human GCC185 protein and regulates mannose 6 phosphate receptor recycling.

    PubMed

    Kumar, Manjeet; Kaur, Supinder; Nazir, Aamir; Tripathi, Raj Kamal

    2016-05-20

    HIV-1 Nef modulates cellular function that enhances viral replication in vivo which culminate into AIDS pathogenesis. With no enzymatic activity, Nef regulates cellular function through host protein interaction. Interestingly, trans-cellular introduction of recombinant Nef protein in Caenorhabditis elegans results in AIDS like pathogenesis which might share common pathophysiology because the gene sequence of C. elegans and humans share considerable homology. Therefore employing C. elegans based initial screen complemented with sequence based homology search we identified GCC185 as novel host protein interacting with HIV-1 Nef. The detailed molecular characterization revealed N-terminal EEEE65 acidic domain of Nef as key region for interaction. GCC185 is a tethering protein that binds with Rab9 transport vesicles. Our results show that Nef-GCC185 interaction disrupts Rab9 interaction resulting in delocalization of CI-MPR (cation independent Mannose 6 phosphate receptor) resulting in elevated secretion of hexosaminidase. In agreement with this, our studies identified novel host GCC185 protein that interacts with Nef EEEE65 acidic domain interfering GCC185-Rab9 vesicle membrane fusion responsible for retrograde vesicular transport of CI-MPR from late endosomes to TGN. In light of existing report suggesting critical role of Nef-GCC185 interaction reveals valuable mechanistic insights affecting specific protein transport pathway in docking of late endosome derived Rab9 bearing transport vesicle at TGN elucidating role of Nef during viral pathogenesis. PMID:27105913

  20. Mechanistic Independence of Nef and Cyclophilin A Enhancement of Human Immunodeficiency Virus Type 1 Infectivity

    PubMed Central

    Aiken, Christopher

    2013-01-01

    Optimal HIV-1 infectivity requires the presence of both the viral factor Nef and the cellular protein cyclophilin A (CyPA) during virion assembly. These two proteins are integral components of HIV-1 particles. Both CyPA and Nef facilitate a step in the viral life cycle occurring between penetration and reverse transcription, suggesting a common mechanism of action. Experiments were performed to test the potential interplay of Nef- and CyPA-mediated enhancement of HIV-1 infectivity. In single-cycle infection assays, nef-defective virions were partially resistant to cyclosporin A (CsA), a drug which inhibits the binding of CyPA to the HIV-1 Gag precursor and CyPA incorporation into virions. Genetic dissection of the relative contributions of Nef and the cyclophilin A-Gag interaction to HIV-1 infectivity demonstrated the independence of these two effects. Nef was not required for incorporation of CyPA into HIV-1 virions, and vice-versa. Surprisingly, CyPA-deficient virions remained sensitive to inhibition by CsA, in a manner that depended strongly on the presence of a functional nef gene. These results demonstrate that Nef and CyPA act independently to render HIV-1 particles fully infectious. They further suggest that in addition to blocking the CyPA-Gag interaction, CsA can also inhibit HIV-1 replication through a novel mechanism involving suppression of Nef-directed enhancement of virus infectivity. PMID:9705263

  1. Neutron Reflectometry Study of the Conformation of HIV Nef Bound to Lipid Membranes

    PubMed Central

    Kent, Michael S.; Murton, Jaclyn K.; Sasaki, Darryl Y.; Satija, Sushil; Akgun, Bulent; Nanda, Hirsh; Curtis, Joseph E.; Majewski, Jaroslaw; Morgan, Christopher R.; Engen, John R.

    2010-01-01

    Nef is an HIV-1 accessory protein that directly contributes to AIDS progression. Nef is myristoylated on the N-terminus, associates with membranes, and may undergo a transition from a solution conformation to a membrane-associated conformation. It has been hypothesized that conformational rearrangement enables membrane-associated Nef to interact with cellular proteins. Despite its medical relevance, to our knowledge there is no direct information about the conformation of membrane-bound Nef. In this work, we used neutron reflection to reveal what we believe are the first details of the conformation of membrane-bound Nef. The conformation of Nef was probed upon binding to Langmuir monolayers through the interaction of an N-terminal His tag with a synthetic metal-chelating lipid, which models one of the possible limiting cases for myr-Nef. The data indicate that residues are inserted into the lipid headgroups during interaction, and that the core domain lies directly against the lipid headgroups, with a thickness of ∼40 Å. Binding of Nef through the N-terminal His tag apparently facilitates insertion of residues, as no insertion occurred upon binding of Nef through weak electrostatic interactions in the absence of the specific interaction through the His tag. PMID:20858440

  2. Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef

    SciTech Connect

    Jia, Xiaofei; Singh, Rajendra; Homann, Stefanie; Yang, Haitao; Guatelli, John; Xiong, Yong

    2012-10-24

    The HIV-1 protein Nef inhibits antigen presentation by class I major histocompatibility complex (MHC-I). We determined the mechanism of this activity by solving the crystal structure of a protein complex comprising Nef, the MHC-I cytoplasmic domain (MHC-I CD) and the {mu}1 subunit of the clathrin adaptor protein complex 1. A ternary, cooperative interaction clamps the MHC-I CD into a narrow binding groove at the Nef-{mu}1 interface, which encompasses the cargo-recognition site of {mu}1 and the proline-rich strand of Nef. The Nef C terminus induces a previously unobserved conformational change in {mu}1, whereas the N terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on {mu}1 recognize acidic clusters in Nef and MHC-I. The structure shows how Nef functions as a clathrin-associated sorting protein to alter the specificity of host membrane trafficking and enable viral evasion of adaptive immunity.

  3. Structural Basis of Evasion of Cellular Adaptive Immunity by HIV-1 Nef

    PubMed Central

    Jia, Xiaofei; Singh, Rajendra; Homann, Stefanie; Yang, Haitao; Guatelli, John; Xiong, Yong

    2012-01-01

    The HIV-1 protein Nef inhibits antigen presentation by class I MHC (MHC-I). Here the mechanism of this activity is revealed by the crystal structure of a protein complex consisting of Nef, the MHC-I cytoplasmic domain (MHC-I CD), and the μ1 subunit of the clathrin adaptor protein complex 1. A ternary, cooperative interaction clamps the MHC-I CD into a narrow binding groove at the Nef-μ1 interface encompassing the cargo-recognition site of μ1 and the proline rich strand of Nef. The Nef C-terminus induces a novel conformational change in μ1, while the N-terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on μ1 recognize acidic clusters in Nef and MHC-I. The structure shows how Nef functions as a clathrin-associated sorting protein to alter the specificity of host membrane trafficking and enable viral evasion of adaptive immunity. PMID:22705789

  4. Nef Does Not Affect the Efficiency of Human Immunodeficiency Virus Type 1 Fusion with Target Cells

    PubMed Central

    Tobiume, Minoru; Lineberger, Janet E.; Lundquist, Christopher A.; Miller, Michael D.; Aiken, Christopher

    2003-01-01

    The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef stimulates viral infectivity by an unknown mechanism. Recent studies have suggested that Nef may act by regulating the efficiency of virus entry into cells. Here we provide evidence to the contrary. Using a quantitative assay of HIV-1 virus-cell fusion, we observed equivalent rates and extents of fusion of wild-type and Nef-defective HIV-1 particles with MT-4 cells and CD4-expressing HeLa cells. In studies using soluble CD4 (sCD4) to inhibit infection, wild-type and Nef-defective HIV-1 escaped the sCD4 block with similar kinetics. We conclude that Nef acts at a postentry step in infection, probably by facilitating intracellular transport of the HIV-1 ribonucleoprotein complex. PMID:12970449

  5. High-level-waste immobilization

    SciTech Connect

    Crandall, J L

    1982-01-01

    Analysis of risks, environmental effects, process feasibility, and costs for disposal of immobilized high-level wastes in geologic repositories indicates that the disposal system safety has a low sensitivity to the choice of the waste disposal form.

  6. Construction of Nef-positive doxycycline-dependent HIV-1 variants using bicistronic expression elements.

    PubMed

    van der Velden, Yme U; Kleibeuker, Wendy; Harwig, Alex; Klaver, Bep; Siteur-van Rijnstra, Esther; Frankin, Esmay; Berkhout, Ben; Das, Atze T

    2016-01-15

    Conditionally replicating HIV-1 variants that can be switched on and off at will are attractive tools for HIV research. We previously developed a genetically modified HIV-1 variant that replicates exclusively when doxycycline (dox) is administered. The nef gene in this HIV-rtTA variant was replaced with the gene encoding the dox-dependent rtTA transcriptional activator. Because loss of Nef expression compromises virus replication in primary cells and precludes studies on Nef function, we tested different approaches to restore Nef production in HIV-rtTA. Strategies that involved translation via an EMCV or synthetic internal ribosome entry site (IRES) failed because these elements were incompatible with efficient virus replication. Fusion protein approaches with the FMDV 2A peptide and human ubiquitin were successful and resulted in genetically-stable Nef-expressing HIV-rtTA strains that replicate more efficiently in primary T-cells and human immune system (HIS) mice than Nef-deficient variants, thus confirming the positive effect of Nef on in vivo virus replication. PMID:26615334

  7. HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes▿

    PubMed Central

    Nobile, Cinzia; Rudnicka, Dominika; Hasan, Milena; Aulner, Nathalie; Porrot, Françoise; Machu, Christophe; Renaud, Olivier; Prévost, Marie-Christine; Hivroz, Claire; Schwartz, Olivier; Sol-Foulon, Nathalie

    2010-01-01

    The HIV-1 Nef protein is a pathogenic factor modulating the behavior of infected cells. Nef induces actin cytoskeleton changes and impairs cell migration toward chemokines. We further characterized the morphology, cytoskeleton dynamics, and motility of HIV-1-infected lymphocytes. By using scanning electron microscopy, confocal immunofluorescence microscopy, and ImageStream technology, which combines flow cytometry and automated imaging, we report that HIV-1 induces a characteristic remodeling of the actin cytoskeleton. In infected lymphocytes, ruffle formation is inhibited, whereas long, thin filopodium-like protrusions are induced. Cells infected with HIV with nef deleted display a normal phenotype, and Nef expression alone, in the absence of other viral proteins, induces morphological changes. We also used an innovative imaging system to immobilize and visualize living individual cells in suspension. When combined with confocal “axial tomography,” this technique greatly enhances three-dimensional optical resolution. With this technique, we confirmed the induction of long filopodium-like structures in unfixed Nef-expressing lymphocytes. The cytoskeleton reorganization induced by Nef is associated with an important impairment of cell movements. The adhesion and spreading of infected cells to fibronectin, their spontaneous motility, and their migration toward chemokines (CXCL12, CCL3, and CCL19) were all significantly decreased. Therefore, Nef induces complex effects on the lymphocyte actin cytoskeleton and cellular morphology, which likely impacts the capacity of infected cells to circulate and to encounter and communicate with bystander cells. PMID:20015995

  8. Mutational analysis of the human immunodeficiency virus type 1 Eli Nef function.

    PubMed Central

    Zazopoulos, E; Haseltine, W A

    1992-01-01

    The studies presented here define an internally consistent experimental system that permits systematic analysis of the effect of nef on the rate of the human immunodeficiency virus type 1 (HIV-1) replication in a CD4+ tumor T-cell line and in primary peripheral blood mononuclear cells. The parental full-length Nef protein, derived from the Eli strain of HIV-1, accelerates virus replication in both cell types. Mutations that destabilize or alter the intracellular location of the protein affect the ability of the Nef protein to accelerate virus replication. A set of mutants was made in amino acids proposed to be required for Nef function, including threonine and serine residues proposed to be targets for phosphorylation, and in sequences thought to resemble the G-1, G-3, and G-4 sites of the family of G proteins. In most cases alterations of the critical amino acids yield stable Nef proteins of parental phenotype. These results challenge the existing theories for the mechanism of Nef function. The results also identify two residues in the carboxyl half of the protein that are important for Nef function. Images PMID:1631166

  9. High pressure liquid level monitor

    DOEpatents

    Bean, Vern E.; Long, Frederick G.

    1984-01-01

    A liquid level monitor for tracking the level of a coal slurry in a high-pressure vessel including a toroidal-shaped float with magnetically permeable bands thereon disposed within the vessel, two pairs of magnetic field generators and detectors disposed outside the vessel adjacent the top and bottom thereof and magnetically coupled to the magnetically permeable bands on the float, and signal processing circuitry for combining signals from the top and bottom detectors for generating a monotonically increasing analog control signal which is a function of liquid level. The control signal may be utilized to operate high-pressure control valves associated with processes in which the high-pressure vessel is used.

  10. Nef Enhances Human Immunodeficiency Virus Type 1 Infectivity Resulting from Intervirion Fusion: Evidence Supporting a Role for Nef at the Virion Envelope

    PubMed Central

    Zhou, Jing; Aiken, Christopher

    2001-01-01

    The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef stimulates viral infectivity by facilitating an early event in the HIV-1 life cycle. Although no structural or biochemical defects in Nef-defective HIV-1 particles have been demonstrated, the Nef protein is incorporated into HIV-1 particles. To localize the function of Nef within the virus particle, we developed a novel technology involving fusion of enveloped donor HIV-1 particles bearing core defects with envelope-defective target virions bearing HIV-1 receptors. Although neither virus alone was capable of infecting CD4+ target cells, the incubation of donor and target virions prior to addition to target cells resulted in infection. This effect, termed “virion transcomplementation,” required a functional Env protein on the donor virus and CD4 and an appropriate coreceptor on target virions. To provide evidence for intervirion fusion as the mechanism of complementation, experiments were performed using dual-enveloped HIV-1 particles bearing both HIV-1 and ecotropic murine leukemia virus (E-MLV) Env proteins as donor virions. Infection of CD4-negative target cells bearing E-MLV receptors was prevented by HIV-1 entry inhibitors when added before, but not after, incubation of donor and target virions prior to the addition to cells. When we used Nef+ and Nef− donor and target virions, Nef enhanced infection when present in donor virions. In contrast, no effect of Nef was detected when present in the target virus. These results reveal a potential mechanism for enhancing HIV-1 diversity in vivo through the rescue of defective viral genomes and provide a novel genetic system for the functional analysis of virion-associated proteins in HIV-1 infection. PMID:11390586

  11. Vaccine-Induced Simian Immunodeficiency Virus-Specific CD8+ T-Cell Responses Focused on a Single Nef Epitope Select for Escape Variants Shortly after Infection

    PubMed Central

    Tully, Damien C.; Cruz, Michael A.; Power, Karen A.; Veloso de Santana, Marlon G.; Bean, David J.; Ogilvie, Colin B.; Gadgil, Rujuta; Lima, Noemia S.; Magnani, Diogo M.; Ejima, Keisuke; Allison, David B.; Piatak, Michael; Altman, John D.; Parks, Christopher L.; Rakasz, Eva G.; Capuano, Saverio; Galler, Ricardo; Bonaldo, Myrna C.; Lifson, Jeffrey D.; Allen, Todd M.; Watkins, David I.

    2015-01-01

    ABSTRACT Certain major histocompatibility complex class I (MHC-I) alleles (e.g., HLA-B*27) are enriched among human immunodeficiency virus type 1 (HIV-1)-infected individuals who suppress viremia without treatment (termed “elite controllers” [ECs]). Likewise, Mamu-B*08 expression also predisposes rhesus macaques to control simian immunodeficiency virus (SIV) replication. Given the similarities between Mamu-B*08 and HLA-B*27, SIV-infected Mamu-B*08+ animals provide a model to investigate HLA-B*27-mediated elite control. We have recently shown that vaccination with three immunodominant Mamu-B*08-restricted epitopes (Vif RL8, Vif RL9, and Nef RL10) increased the incidence of elite control in Mamu-B*08+ macaques after challenge with the pathogenic SIVmac239 clone. Furthermore, a correlate analysis revealed that CD8+ T cells targeting Nef RL10 was correlated with improved outcome. Interestingly, this epitope is conserved between SIV and HIV-1 and exhibits a delayed and atypical escape pattern. These features led us to postulate that a monotypic vaccine-induced Nef RL10-specific CD8+ T-cell response would facilitate the development of elite control in Mamu-B*08+ animals following repeated intrarectal challenges with SIVmac239. To test this, we vaccinated Mamu-B*08+ animals with nef inserts in which Nef RL10 was either left intact (group 1) or disrupted by mutations (group 2). Although monkeys in both groups mounted Nef-specific cellular responses, only those in group 1 developed Nef RL10-specific CD8+ T cells. These vaccine-induced effector memory CD8+ T cells did not prevent infection. Escape variants emerged rapidly in the group 1 vaccinees, and ultimately, the numbers of ECs were similar in groups 1 and 2. High-frequency vaccine-induced CD8+ T cells focused on a single conserved epitope and therefore did not prevent infection or increase the incidence of elite control in Mamu-B*08+ macaques. IMPORTANCE Since elite control of chronic-phase viremia is a classic

  12. High-Level Radioactive Waste.

    ERIC Educational Resources Information Center

    Hayden, Howard C.

    1995-01-01

    Presents a method to calculate the amount of high-level radioactive waste by taking into consideration the following factors: the fission process that yields the waste, identification of the waste, the energy required to run a 1-GWe plant for one year, and the uranium mass required to produce that energy. Briefly discusses waste disposal and…

  13. The CMS high level trigger

    NASA Astrophysics Data System (ADS)

    Gori, Valentina

    2014-05-01

    The CMS experiment has been designed with a 2-level trigger system: the Level 1 Trigger, implemented on custom-designed electronics, and the High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a tradeoff between the complexity of the algorithms running on the available computing power, the sustainable output rate, and the selection efficiency. Here we will present the performance of the main triggers used during the 2012 data taking, ranging from simpler single-object selections to more complex algorithms combining different objects, and applying analysis-level reconstruction and selection. We will discuss the optimisation of the triggers and the specific techniques to cope with the increasing LHC pile-up, reducing its impact on the physics performance.

  14. The CMS High Level Trigger

    NASA Astrophysics Data System (ADS)

    Trocino, Daniele

    2014-06-01

    The CMS experiment has been designed with a two-level trigger system: the Level-1 Trigger, implemented in custom-designed electronics, and the High-Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a tradeoff between the complexity of the algorithms running with the available computing power, the sustainable output rate, and the selection efficiency. We present the performance of the main triggers used during the 2012 data taking, ranging from simple single-object selections to more complex algorithms combining different objects, and applying analysis-level reconstruction and selection. We discuss the optimisation of the trigger and the specific techniques to cope with the increasing LHC pile-up, reducing its impact on the physics performance.

  15. Disassembly of Human Immunodeficiency Virus Type 1 Cores In Vitro Reveals Association of Nef with the Subviral Ribonucleoprotein Complex

    PubMed Central

    Forshey, Brett M.; Aiken, Christopher

    2003-01-01

    The human immunodeficiency virus type 1 (HIV-1) virulence factor Nef enhances viral infectivity in single-cycle infection assays and accelerates HIV-1 replication in vitro. It has been reported that the effects of Nef are mediated early after viral entry and before the completion of reverse transcription, as viral DNA synthesis is strongly attenuated during infection by Nef-defective virions. Our previous work has demonstrated that Nef is associated with mature HIV-1 cores, implicating Nef in the regulation of HIV-1 core stability. Here we report a comparative analysis of HIV-1 cores isolated from wild-type and Nef-defective particles. We observed no effect of Nef on HIV-1 core structure or stability; however, Nef cosedimented with a subviral ribonucleoprotein complex following dissociation of CA. These results indicate that Nef interacts tightly with an internal component of the HIV-1 core. They further suggest that virion-associated Nef may facilitate an early step in HIV-1 infection following dissociation of the viral capsid in the target cell. PMID:12634398

  16. Human immunodeficiency virus (HIV) nef-specific cytotoxic T lymphocytes in noninfected heterosexual contact of HIV-infected patients.

    PubMed Central

    Langlade-Demoyen, P; Ngo-Giang-Huong, N; Ferchal, F; Oksenhendler, E

    1994-01-01

    We report on the detection of HIV-specific cytotoxic T lymphocytes (CTL) among 23 regular partners of HIV-infected individuals. 15 of the 46 individuals enrolled in the study were positive for HLA-A2.1 typing. Among the 23 contacts studied, 7 were seropositive and 16 were seronegative on repeated tests. None of the 16 seronegative contacts were positive for p24 antigenemia nor were they positive by the lymphocytes coculture assay, although, in two instances HIV-1 DNA could be detected by PCR (in one case using a gag SK 38/39 primer, and in the other using a primer for the pol P3/P4 primer). These two individuals remained seronegative for 18 and 36 mo, respectively. HIV-specific cytotoxicity was performed in the 15 HLA-A2.1 subjects (7 indexes, 2 seropositive contacts, and 6 seronegative contacts) and in 4 HLA-matched HIV negative donors. CTL specific for env, gag, or nef proteins could not be detected in unstimulated bulk cultures of peripheral blood lymphocytes in any of the six seronegative contacts. However, using a limiting dilution assay we found an usually high frequency of HIV nef-specific CTL precursors (CTLp) for HIV env and gag was very similar to that observed in seronegative HLA-matched healthy donors. Because no presence of HIV could be demonstrated in these individuals, these findings argue against the possibility of a silent HIV infection and suggest that a CTL response against nef may be involved in a rapid and effective clearance of the virus after sexual exposure. PMID:8132769

  17. Conformational transition of membrane-associated terminally-acylated HIV-1 Nef

    PubMed Central

    Akgun, Bulent; Satija, Sushil; Nanda, Hirsh; Pirrone, Gregory F.; Shi, Xiaomeng; Engen, John R.; Kent, Michael S.

    2013-01-01

    Many proteins are post-translationally modified by acylation targetting them to lipid membranes. While methods such as X-ray crystallography and NMR are available to determine the structure of folded proteins in solution, the precise position of folded domains relative to a membrane remains largely unknown. We used neutron and X-ray reflection methods to measure the displacement of the core domain of HIV Nef from lipid membranes upon insertion of the N-terminal myristate group. Nef is one of several HIV-1 accessory proteins and an essential factor in AIDS progression. Upon insertion of the myristate and residues from the N-terminal arm, Nef transitions from a closed to open conformation that positions the core domain 70 Å from the lipid headgroups. This work rules out speculation that the Nef core remains closely associated with the membrane to optimize interactions with the cytoplasmic domain of MHC-1. PMID:24035710

  18. p21-Activated Kinase 1 Plays a Critical Role in Cellular Activation by Nef

    PubMed Central

    Fackler, Oliver T.; Lu, Xiaobin; Frost, Jeffrey A.; Geyer, Matthias; Jiang, Bing; Luo, Wen; Abo, Arie; Alberts, Arthur S.; Peterlin, B. Matija

    2000-01-01

    The activation of Nef-associated kinase (NAK) by Nef from human and simian immunodeficiency viruses is critical for efficient viral replication and pathogenesis. This induction occurs via the guanine nucleotide exchange factor Vav and the small GTPases Rac1 and Cdc42. In this study, we identified NAK as p21-activated kinase 1 (PAK1). PAK1 bound to Nef in vitro and in vivo. Moreover, the induction of cytoskeletal rearrangements such as the formation of trichopodia, the activation of Jun N-terminal kinase, and the increase of viral production were blocked by an inhibitory peptide that targets the kinase activity of PAK1 (PAK1 83-149). These results identify NAK as PAK1 and emphasize the central role its kinase activity plays in cytoskeletal rearrangements and cellular signaling by Nef. PMID:10713183

  19. HIV-Nef and ADAM17-Containing Plasma Extracellular Vesicles Induce and Correlate with Immune Pathogenesis in Chronic HIV Infection

    PubMed Central

    Lee, Jung-Hyun; Schierer, Stephan; Blume, Katja; Dindorf, Jochen; Wittki, Sebastian; Xiang, Wei; Ostalecki, Christian; Koliha, Nina; Wild, Stefan; Schuler, Gerold; Fackler, Oliver T.; Saksela, Kalle; Harrer, Thomas; Baur, Andreas S.

    2016-01-01

    Antiretroviral therapy (ART) efficiently suppresses HIV replication but immune activation and low CD4 T cell counts often persist. The underlying mechanism of this ART-resistant pathogenesis is not clear. We observed that levels of plasma extracellular vesicles (pEV) are strongly elevated in HIV infection and do not decline during ART. Surprisingly, these vesicles contained the viral accessory proteins Nef and Vpu, which are assumed to be not expressed under efficient ART, as well as pro-inflammatory effectors, including activated ADAM17. HIV pEV were characterized by the presence of activated αvβ3 and absence of CD81 and Tsg101. Correlating with immune activation, peripheral monocytes ingested large amounts of pEV, giving rise to an increased population of CD1c+ CD14+ cells that secreted inflammatory cytokines. Importantly, the pro-inflammatory content, particularly ADAM17 activity, correlated with low T cell counts. Preliminary evidence suggested that HIV pEV derived from peripheral mononuclear cells and from an unknown myeloid cell population. In summary we propose an important role of pro-inflammatory pEV in chronic HIV infection due to ongoing viral Nef activity. PMID:27211553

  20. Human immunodeficiency virus type 1 Nef associates with a member of the p21-activated kinase family.

    PubMed Central

    Nunn, M F; Marsh, J W

    1996-01-01

    Although human immunodeficiency virus (HIV) Nef is essential for the induction of AIDS, its biochemical function has remained an enigma. In this study, HIV Nef protein is shown to associate with a serine-threonine kinase that recognizes histone H4 as a substrate, is serologically related to rat p21-activated kinase (PAK), and is specifically activated by Rac and Cdc42. These characteristics define the Nef-associated kinase as belonging to the PAK family. PAKs initiate kinase cascades in response to environmental stimuli, and their identification as a target of Nef implicates these signaling molecules in HIV pathogenesis and provides a novel target for clinical intervention. PMID:8709241

  1. Selective Restriction of Nef-Defective Human Immunodeficiency Virus Type 1 by a Proteasome-Dependent Mechanism▿

    PubMed Central

    Qi, Mingli; Aiken, Christopher

    2007-01-01

    The Nef protein enhances human immunodeficiency virus type 1 (HIV-1) infectivity by facilitating an early postentry step in the virus life cycle. We report here that the addition of MG132 or lactacystin, each a specific inhibitor of cellular proteasome activity, preferentially enhances cellular permissiveness to infection by Nef-defective versus wild-type HIV-1. Pseudotyping by the glycoprotein of vesicular stomatitis virus rendered Nef-defective HIV-1 particles minimally responsive to the enhancing effects of proteasome inhibitors. These results suggest that Nef enhances the infectivity of HIV-1 particles by reducing their susceptibility to proteasomal degradation in target cells. PMID:17108041

  2. A Bidirectional SF2/ASF- and SRp40-Dependent Splicing Enhancer Regulates Human Immunodeficiency Virus Type 1 rev, env, vpu, and nef Gene Expression

    PubMed Central

    Caputi, Massimo; Freund, Marcel; Kammler, Susanne; Asang, Corinna; Schaal, Heiner

    2004-01-01

    The integrated human immunodeficiency virus type 1 (HIV-1) genome is transcribed in a single pre-mRNA that is alternatively spliced into more than 40 mRNAs. We characterized a novel bidirectional exonic splicing enhancer (ESE) that regulates the expression of the HIV-1 env, vpu, rev, and nef mRNAs. The ESE is localized downstream of the vpu-, env-, and nef-specific 3′ splice site no. 5. SF2/ASF and SRp40 activate the ESE and are required for efficient 3′ splice site usage and binding of the U1 snRNP to the downstream 5′ splice site no. 4. U1 snRNP binding to the 5′ splice site no. 4 is required for splicing of the rev and nef mRNAs and to increase expression of the partially spliced env mRNA. Finally, our results indicate that this ESE is necessary for the recruitment of the U1 snRNP to the 5′ splice site no. 4, even when the 5′ splice site and the U1 snRNA have been mutated to obtain a perfect complementary match. The ESE characterized here is highly conserved in most viral subtypes. PMID:15163745

  3. Proteomic Profiling of SupT1 Cells Reveal Modulation of Host Proteins by HIV-1 Nef Variants

    PubMed Central

    Saxena, Reshu; Gupta, Sudipti; Singh, Kavita; Mitra, Kalyan; Tripathi, Anil Kumar; Tripathi, Raj Kamal

    2015-01-01

    Nef is an accessory viral protein that promotes HIV-1 replication, facilitating alterations in cellular pathways via multiple protein-protein interactions. The advent of proteomics has expanded the focus on better identification of novel molecular pathways regulating disease progression. In this study, nef was sequenced from randomly selected patients, however, sequence variability identified did not elicited any specific mutation that could have segregated HIV-1 patients in different stages of disease progression. To explore the difference in Nef functionality based on sequence variability we used proteomics approach. Proteomic profiling was done to compare the effect of Nef variants in host cell protein expression. 2DGE in control and Nef transfected SupT1 cells demonstrated several differentially expressed proteins. Fourteen protein spots were detected with more than 1.5 fold difference. Significant down regulation was seen in six unique protein spots in the Nef treated cells. Proteins were identified as Cyclophilin A, EIF5A-1 isoform B, Rho GDI 1 isoform a, VDAC1, OTUB1 and α-enolase isoform 1 (ENO1) through LC-MS/MS. The differential expression of the 6 proteins was analyzed by Real time PCR, Western blotting and Immunofluorescence studies with two Nef variants (RP14 and RP01) in SupT1 cells. There was contrasting difference between the effect of these Nef variants upon the expression of these six proteins. Downregulation of α-enolase (ENO1), VDAC1 and OTUB1 was more significant by Nef RP01 whereas Cyclophilin A and RhoGDI were found to be more downregulated by Nef RP14. This difference in Nef variants upon host protein expression was also studied through a site directed mutant of Nef RP01 (55AAAAAAA61) and the effect was found to be reversed. Deciphering the role of these proteins mediated by Nef variants will open a new avenue of research in understanding Nef mediated pathogenesis. Overall study determines modulation of cellular protein expression in T

  4. High level white noise generator

    DOEpatents

    Borkowski, Casimer J.; Blalock, Theron V.

    1979-01-01

    A wide band, stable, random noise source with a high and well-defined output power spectral density is provided which may be used for accurate calibration of Johnson Noise Power Thermometers (JNPT) and other applications requiring a stable, wide band, well-defined noise power spectral density. The noise source is based on the fact that the open-circuit thermal noise voltage of a feedback resistor, connecting the output to the input of a special inverting amplifier, is available at the amplifier output from an equivalent low output impedance caused by the feedback mechanism. The noise power spectral density level at the noise source output is equivalent to the density of the open-circuit thermal noise or a 100 ohm resistor at a temperature of approximately 64,000 Kelvins. The noise source has an output power spectral density that is flat to within 0.1% (0.0043 db) in the frequency range of from 1 KHz to 100 KHz which brackets typical passbands of the signal-processing channels of JNPT's. Two embodiments, one of higher accuracy that is suitable for use as a standards instrument and another that is particularly adapted for ambient temperature operation, are illustrated in this application.

  5. HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation

    PubMed Central

    Rosa, Annachiara; Chande, Ajit; Ziglio, Serena; Sanctis, Veronica De; Bertorelli, Roberto; Goh, Shih Lin; McCauley, Sean M.; Nowosielska, Anetta; Antonarakis, Stylianos E.; Luban, Jeremy; Santoni, Federico Andrea; Pizzato, Massimo

    2016-01-01

    HIV-1 Nef, a protein important for the development of AIDS, has well-characterized effects on host membrane trafficking and receptor downregulation. By an unidentified mechanism, Nef increases the intrinsic infectivity of HIV-1 virions in a host-cell-dependent manner. Here we identify the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as a potent inhibitor of HIV-1 particle infectivity that is counteracted by Nef. SERINC5 localizes to the plasma membrane, where it is efficiently incorporated into budding HIV-1 virions and impairs subsequent virion penetration of susceptible target cells. Nef redirects SERINC5 to a Rab7-positive endosomal compartment and thereby excludes it from HIV-1 particles. The ability to counteract SERINC5 was conserved in Nef encoded by diverse primate immunodeficiency viruses, as well as in the structurally unrelated glycosylated Gag from murine leukaemia virus. These examples of functional conservation and convergent evolution emphasize the fundamental importance of SERINC5 as a potent anti-retroviral factor. PMID:26416734

  6. Optimizing High Level Waste Disposal

    SciTech Connect

    Dirk Gombert

    2005-09-01

    If society is ever to reap the potential benefits of nuclear energy, technologists must close the fuel-cycle completely. A closed cycle equates to a continued supply of fuel and safe reactors, but also reliable and comprehensive closure of waste issues. High level waste (HLW) disposal in borosilicate glass (BSG) is based on 1970s era evaluations. This host matrix is very adaptable to sequestering a wide variety of radionuclides found in raffinates from spent fuel reprocessing. However, it is now known that the current system is far from optimal for disposal of the diverse HLW streams, and proven alternatives are available to reduce costs by billions of dollars. The basis for HLW disposal should be reassessed to consider extensive waste form and process technology research and development efforts, which have been conducted by the United States Department of Energy (USDOE), international agencies and the private sector. Matching the waste form to the waste chemistry and using currently available technology could increase the waste content in waste forms to 50% or more and double processing rates. Optimization of the HLW disposal system would accelerate HLW disposition and increase repository capacity. This does not necessarily require developing new waste forms, the emphasis should be on qualifying existing matrices to demonstrate protection equal to or better than the baseline glass performance. Also, this proposed effort does not necessarily require developing new technology concepts. The emphasis is on demonstrating existing technology that is clearly better (reliability, productivity, cost) than current technology, and justifying its use in future facilities or retrofitted facilities. Higher waste processing and disposal efficiency can be realized by performing the engineering analyses and trade-studies necessary to select the most efficient methods for processing the full spectrum of wastes across the nuclear complex. This paper will describe technologies being

  7. Nef-Mediated Downregulation of CD4 Enhances Human Immunodeficiency Virus Type 1 Replication in Primary T Lymphocytes

    PubMed Central

    Lundquist, Christopher A.; Tobiume, Minoru; Zhou, Jing; Unutmaz, Derya; Aiken, Christopher

    2002-01-01

    The accessory protein Nef plays a crucial role in primate lentivirus pathogenesis. Nef enhances human immunodeficiency virus type 1 (HIV-1) infectivity in culture and stimulates viral replication in primary T cells. In this study, we investigated the relationship between HIV-1 replication efficiency in CD4+ T cells purified from human blood and two various known activities of Nef, CD4 downregulation and single-cycle infectivity enhancement. Using a battery of reporter viruses containing point mutations in nef, we observed a strong genetic correlation between CD4 downregulation by Nef during acute HIV-1 infection of activated T cells and HIV-1 replication efficiency in T cells. In contrast, HIV-1 replication ability was not significantly correlated with the ability of Nef to enhance single-cycle virion infectivity, as determined by using viruses produced in cells lacking CD4. These results demonstrate that CD4 downregulation by Nef plays a crucial role in HIV-1 replication in activated T cells and underscore the potential for the development of therapies targeting this conserved activity of Nef. PMID:11932428

  8. Potential impact of viral load and genetic makeup of HIV type 1 on mother-to-child transmission: characterization of env-C2V3C3 and nef sequences.

    PubMed

    Pádua, Elizabeth; Parreira, Ricardo; Tendeiro, Rita; Nunes, Baltazar; Castela, João; Soares, Isabel; Mouzinho, Ana; Reis, Eduarda; Paixão, Maria Teresa

    2009-11-01

    HIV-1 mother-to-child transmission (MTCT) was evaluated in terms of the molecular characterization of the env and nef genomic regions and quantification of maternal RNA viral loads. Assignment of viral subtype was achieved by direct sequencing of PCR 1172 products amplified from proviral DNA in 45 HIV-1-nontransmitting mothers (NTM), along with 13 pairs of HIV-1-transmitting mothers (TM) and their infected children (C). Analysis of the env C2V3C3 and nef sequences revealed that subtypes G and B, and their genetic combinations (AG, BG), accounted for over 84.5% of all viruses identified. The genetic structure form envA-nefG was the most commonly observed, with a lower frequency in the NTM (13.3%) compared to the TM (23.1%) group. A greater number of genetic forms was observed among NTM, namely the presence of sequences assigned to subtypes D and F, as well as the intergenetic A/J, and C/U, recombinant forms, along with a mosaic provirus with a complex putative envA-nefEGE genetic structure. No significant differences were found when RNA viral loads were evaluated as a function of the viral subtypes. Nevertheless, a relatively high quantification of HIV-1 RNA was obtained in the NTM group, emphasizing the importance of the compliance and effectiveness of therapeutic schemes to control viral replication and reduce the risk of HIV vertical transmission. V3 sequences displaying features associated with the R5 phenotype dominated in both groups. Both C2V3C3 and Nef's functional domains were conserved during HIV-1 vertical transmission. PMID:19886833

  9. High temperature liquid level sensor

    DOEpatents

    Tokarz, Richard D.

    1983-01-01

    A length of metal sheathed metal oxide cable is perforated to permit liquid access to the insulation about a pair of conductors spaced close to one another. Changes in resistance across the conductors will be a function of liquid level, since the wetted insulation will have greater electrical conductivity than that of the dry insulation above the liquid elevation.

  10. HIV-1 Nef Is Transferred from Expressing T Cells to Hepatocytic Cells through Conduits and Enhances HCV Replication

    PubMed Central

    Park, In-Woo; Fan, Yan; Luo, Xiaoyu; Ryou, Myoung-Gwi; Liu, Jinfeng; Green, Linden; He, Johnny J.

    2014-01-01

    HIV-1 infection enhances HCV replication and as a consequence accelerates HCV-mediated hepatocellular carcinoma (HCC). However, the precise molecular mechanism by which this takes place is currently unknown. Our data showed that infectious HIV-1 failed to replicate in human hepatocytic cell lines. No discernible virus replication was observed, even when the cell lines transfected with HIV-1 proviral DNA were co-cultured with Jurkat T cells, indicating that the problem of liver deterioration in the co-infected patient is not due to the replication of HIV-1 in the hepatocytes of the HCV infected host. Instead, HIV-1 Nef protein was transferred from nef-expressing T cells to hepatocytic cells through conduits, wherein up to 16% (average 10%) of the cells harbored the transferred Nef, when the hepatocytic cells were co-cultured with nef-expressing Jurkat cells for 24 h. Further, Nef altered the size and numbers of lipid droplets (LD), and consistently up-regulated HCV replication by 1.5∼2.5 fold in the target subgenomic replicon cells, which is remarkable in relation to the initially indolent viral replication. Nef also dramatically augmented reactive oxygen species (ROS) production and enhanced ethanol-mediated up-regulation of HCV replication so as to accelerate HCC. Taken together, these data indicate that HIV-1 Nef is a critical element in accelerating progression of liver pathogenesis via enhancing HCV replication and coordinating modulation of key intra- and extra-cellular molecules for liver decay. PMID:24911518

  11. High-Level Data Races

    NASA Technical Reports Server (NTRS)

    Artho, Cyrille; Havelund, Klaus; Biere, Armin; Koga, Dennis (Technical Monitor)

    2003-01-01

    Data races are a common problem in concurrent and multi-threaded programming. They are hard to detect without proper tool support. Despite the successful application of these tools, experience shows that the notion of data race is not powerful enough to capture certain types of inconsistencies occurring in practice. In this paper we investigate data races on a higher abstraction layer. This enables us to detect inconsistent uses of shared variables, even if no classical race condition occurs. For example, a data structure representing a coordinate pair may have to be treated atomically. By lifting the meaning of a data race to a higher level, such problems can now be covered. The paper defines the concepts view and view consistency to give a notation for this novel kind of property. It describes what kinds of errors can be detected with this new definition, and where its limitations are. It also gives a formal guideline for using data structures in a multi-threading environment.

  12. HIV-1 Nef promotes the localization of Gag to the cell membrane and facilitates viral cell-to-cell transfer

    PubMed Central

    2013-01-01

    Background Newly synthesized HIV-1 particles assemble at the plasma membrane of infected cells, before being released as free virions or being transferred through direct cell-to-cell contacts to neighboring cells. Localization of HIV-1 Gag precursor at the cell membrane is necessary and sufficient to trigger viral assembly, whereas the GagPol precursor is additionally required to generate a fully matured virion. HIV-1 Nef is an accessory protein that optimizes viral replication through partly defined mechanisms. Whether Nef modulates Gag and/or GagPol localization and assembly at the membrane and facilitates viral cell-to-cell transfer has not been extensively characterized so far. Results We report that Nef increases the total amount of Gag proteins present in infected cells, and promotes Gag localization at the cell membrane. Moreover, the processing of p55 into p24 is improved in the presence of Nef. We also examined the effect of Nef during HIV-1 cell-to-cell transfer. We show that without Nef, viral transfer through direct contacts between infected cells and target cells is impaired. With a nef-deleted virus, the number of HIV-1 positive target cells after a short 2h co-culture is reduced, and viral material transferred to uninfected cells is less matured. At later time points, this defect is associated with a reduction in the productive infection of new target cells. Conclusions Our results highlight a previously unappreciated role of Nef during the viral replication cycle. Nef promotes HIV-1 Gag membrane localization and processing, and facilitates viral cell-to-cell transfer. PMID:23899341

  13. High fertility level in Tibet.

    PubMed

    Zhang, T

    1997-08-01

    This article presents a profile of fertility patterns in Tibet Autonomous Region for 1989. Data were obtained from the 1982 and 1990 China Censuses and from a 1988 fertility and contraception survey. Findings indicate that the total fertility rate (TFR) was 4.36 children/woman in 1989. TFR in Tibet is higher than in other provinces with a Tibetan population. Tibetan TFR was 4.07 among Tibetan women in Qinghai, 3.30 in Sichuan, 3.0 in Yunnan, and 2.8 in Gansu. TFR was 2.16 in Tibet's towns and 1.82 in Lhasa city, compared to 4.57 in counties. In Tibet, the birth rate rose from 31.05/1000 in 1981, to 31.14 in 1989. Ngari prefecture had an even higher birth rate of 35.67 in 1989. Other Tibetan prefectures had lower birth rates. During 1982-89, the birth rate declined to 26.19 in Lhasa City, to 29.36 in Shannan prefecture, and to 27.09 in Nagqu prefecture. Tibet's TFR fluctuated during 1950-57 between 3.20 and 3.80. It rose after 1958, from 4.0 to over 5.0, and remained high at 4.22 in 1989. TFR increased from older to younger women. The average number of live births also increased from older to younger women. This unusual feature is linked with high infertility and the number of women remaining celibate. Infertility was 17.7% among women aged 60-64 years, 14.8% among women aged 55-59, and 12.2% among women aged 50-54. 45.29% of women had parities of 1-2 children, ranging from 85.21% in the city, 77.92% in towns, and 42.20% in rural areas. The percentage of Tibetan women having 4 or more children was 5.82% in the city, 10.14% in towns, and 42.91% in rural areas. TFR was reversely correlated with educational status. TFR was highest among illiterates and semiliterates (4.59) and lowest for college educated women (1.28). Illiterate and semi-literate women comprised 13% of women with 4 children. PMID:12321529

  14. Spotlight on HIV-1 Nef: SERINC3 and SERINC5 Identified as Restriction Factors Antagonized by the Pathogenesis Factor

    PubMed Central

    Fackler, Oliver T.

    2015-01-01

    The Nef protein is an accessory gene product encoded by human immunodeficiency virus types 1 and 2 (HIV-1/-2) and simian immunodeficiency virus (SIV) that boosts virus replication in the infected host and accelerates disease progression. Unlike the HIV-1 accessory proteins Vif, Vpr and Vpu, Nef was, until recently, not known to antagonize the antiviral activity of a host cell restriction factor. Two recent reports now describe the host cell proteins serine incorporator 3 and 5 (SERINC3 and SERINC5) as potent inhibitors of HIV-1 particle infectivity and demonstrate that Nef counteracts these effects. These findings establish SERINC3/5 as restrictions to HIV replication in human cells and define a novel activity for the HIV pathogenesis factor Nef. PMID:26703715

  15. HIV-1 Nef sequence and functional compartmentalization in the gut is not due to differential cytotoxic T lymphocyte selective pressure.

    PubMed

    Lewis, Martha J; Frohnen, Patricia; Ibarrondo, F Javier; Reed, Diane; Iyer, Varun; Ng, Hwee L; Elliott, Julie; Yang, Otto O; Anton, Peter

    2013-01-01

    The gut is the largest lymphoid organ in the body and a site of active HIV-1 replication and immune surveillance. The gut is a reservoir of persistent infection in some individuals with fully suppressed plasma viremia on combination antiretroviral therapy (cART) although the cause of this persistence is unknown. The HIV-1 accessory protein Nef contributes to persistence through multiple functions including immune evasion and increasing infectivity. Previous studies showed that Nef's function is shaped by cytotoxic T lymphocyte (CTL) responses and that there are distinct populations of Nef within tissue compartments. We asked whether Nef's sequence and/or function are compartmentalized in the gut and how compartmentalization relates to local CTL immune responses. Primary nef quasispecies from paired plasma and sigmoid colon biopsies from chronically infected subjects not on therapy were sequenced and cloned into Env(-) Vpu(-) pseudotyped reporter viruses. CTL responses were mapped by IFN-γ ELISpot using expanded CD8+ cells from blood and gut with pools of overlapping peptides covering the entire HIV proteome. CD4 and MHC Class I Nef-mediated downregulation was measured by flow cytometry. Multiple tests indicated compartmentalization of nef sequences in 5 of 8 subjects. There was also compartmentalization of function with MHC Class I downregulation relatively well preserved, but significant loss of CD4 downregulation specifically by gut quasispecies in 5 of 7 subjects. There was no compartmentalization of CTL responses in 6 of 8 subjects, and the selective pressure on quasispecies correlated with the magnitude CTL response regardless of location. These results demonstrate that Nef adapts via diverse pathways to local selective pressures within gut mucosa, which may be predominated by factors other than CTL responses such as target cell availability. The finding of a functionally distinct population within gut mucosa offers some insight into how HIV-1 may persist in

  16. Specific cleavage sites of Nef proteins from human immunodeficiency virus types 1 and 2 for the viral proteases.

    PubMed Central

    Schorr, J; Kellner, R; Fackler, O; Freund, J; Konvalinka, J; Kienzle, N; Kräusslich, H G; Mueller-Lantzsch, N; Kalbitzer, H R

    1996-01-01

    Human immunodeficiency virus type 2 (HIV-2) Nef is proteolytically cleaved by the HIV-2-encoded protease. The proteolysis is not influenced by the absence or presence of the N-terminal myristoylation. The main cleavage site is located between residues 39 and 40, suggesting a protease recognition sequence, GGEY-SQFQ. As observed previously for Nef protein from HIV-1, a large, stable core domain with an apparent molecular mass of 30 kDa is produced by the proteolytic activity. Cleavage of Nef from HIV-1 in two domains by its own protease or the protease from HIV-2 is also independent of Nef myristoylation. However, processing of HIV-1 Nef by the HIV-2 protease is less selective than that by the HIV-1 protease: the obtained core fragment is heterogeneous at its N terminus and has an additional cleavage site between amino acids 99 and 100. Preliminary experiments suggest that the full-length Nef of HIV-2 and the core domain are part of the HIV-2 particles, analogous to the situation reported recently for HIV-1. PMID:8971042

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

    SciTech Connect

    Bouzar, Baya Amel; Rea, Angela; Hoc-Villet, Stephanie; Garnier, Celine; Guiguen, Francois; Jin Yuhuai; Narayan, Opendra; Chebloune, Yahia . E-mail: ychebloune@kumc.edu

    2007-08-01

    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.

  18. Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence.

    PubMed

    Sugden, Scott M; Bego, Mariana G; Pham, Tram N Q; Cohen, Éric A

    2016-03-01

    The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection. PMID:26950141

  19. Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence

    PubMed Central

    Sugden, Scott M.; Bego, Mariana G.; Pham, Tram N.Q.; Cohen, Éric A.

    2016-01-01

    The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection. PMID:26950141

  20. Parallel Processing at the High School Level.

    ERIC Educational Resources Information Center

    Sheary, Kathryn Anne

    This study investigated the ability of high school students to cognitively understand and implement parallel processing. Data indicates that most parallel processing is being taught at the university level. Instructional modules on C, Linux, and the parallel processing language, P4, were designed to show that high school students are highly…

  1. High-Level Application Framework for LCLS

    SciTech Connect

    Chu, P; Chevtsov, S.; Fairley, D.; Larrieu, C.; Rock, J.; Rogind, D.; White, G.; Zalazny, M.; /SLAC

    2008-04-22

    A framework for high level accelerator application software is being developed for the Linac Coherent Light Source (LCLS). The framework is based on plug-in technology developed by an open source project, Eclipse. Many existing functionalities provided by Eclipse are available to high-level applications written within this framework. The framework also contains static data storage configuration and dynamic data connectivity. Because the framework is Eclipse-based, it is highly compatible with any other Eclipse plug-ins. The entire infrastructure of the software framework will be presented. Planned applications and plug-ins based on the framework are also presented.

  2. Future high sea levels in south Sweden

    SciTech Connect

    Blomgren, S.H.; Hanson, H.

    1997-12-31

    An estimation of future mean high water levels in Oeresund and the southwest Baltic Sea is presented together with a discussion of probable consequences for Falsterbo Peninsula, a trumpet-shaped sandy formation of some 25 km{sup 2} size situated in the very southwest corner of Sweden. A literature review coupled with sea-level measurements and observations made in the area every four hours since October 1945 are given and comprise the base for the present analysis.

  3. A Software Architecture for High Level Applications

    SciTech Connect

    Shen,G.

    2009-05-04

    A modular software platform for high level applications is under development at the National Synchrotron Light Source II project. This platform is based on client-server architecture, and the components of high level applications on this platform will be modular and distributed, and therefore reusable. An online model server is indispensable for model based control. Different accelerator facilities have different requirements for the online simulation. To supply various accelerator simulators, a set of narrow and general application programming interfaces is developed based on Tracy-3 and Elegant. This paper describes the system architecture for the modular high level applications, the design of narrow and general application programming interface for an online model server, and the prototype of online model server.

  4. High-level waste processing and disposal

    NASA Astrophysics Data System (ADS)

    Crandall, J. L.; Drause, H.; Sombret, C.; Uematsu, K.

    The national high level waste disposal plans for France, the Federal Republic of Germany, Japan, and the United States are covered. Three conclusions are reached. The first conclusion is that an excellent technology already exists for high level waste disposal. With appropriate packaging, spent fuel seems to be an acceptable waste form. Borosilicate glass reprocessing waste forms are well understood, in production in France, and scheduled for production in the next few years in a number of other countries. For final disposal, a number of candidate geological repository sites have been identified and several demonstration sites opened. The second conclusion is that adequate financing and a legal basis for waste disposal are in place in most countries. Costs of high level waste disposal will probably and about 5 to 10% to the costs of nuclear electric power. Third conclusion is less optimistic.

  5. High-level radioactive wastes. Supplement 1

    SciTech Connect

    McLaren, L.H.

    1984-09-01

    This bibliography contains information on high-level radioactive wastes included in the Department of Energy's Energy Data Base from August 1982 through December 1983. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes, each preceded by a brief description, are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number. 1452 citations.

  6. PAIRWISE BLENDING OF HIGH LEVEL WASTE (HLW)

    SciTech Connect

    CERTA, P.J.

    2006-02-22

    The primary objective of this study is to demonstrate a mission scenario that uses pairwise and incidental blending of high level waste (HLW) to reduce the total mass of HLW glass. Secondary objectives include understanding how recent refinements to the tank waste inventory and solubility assumptions affect the mass of HLW glass and how logistical constraints may affect the efficacy of HLW blending.

  7. Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef.

    PubMed

    Matheson, Nicholas J; Sumner, Jonathan; Wals, Kim; Rapiteanu, Radu; Weekes, Michael P; Vigan, Raphael; Weinelt, Julia; Schindler, Michael; Antrobus, Robin; Costa, Ana S H; Frezza, Christian; Clish, Clary B; Neil, Stuart J D; Lehner, Paul J

    2015-10-14

    Critical cell surface immunoreceptors downregulated during HIV infection have previously been identified using non-systematic, candidate approaches. To gain a comprehensive, unbiased overview of how HIV infection remodels the T cell surface, we took a distinct, systems-level, quantitative proteomic approach. >100 plasma membrane proteins, many without characterized immune functions, were downregulated during HIV infection. Host factors targeted by the viral accessory proteins Vpu or Nef included the amino acid transporter SNAT1 and the serine carriers SERINC3/5. We focused on SNAT1, a β-TrCP-dependent Vpu substrate. SNAT1 antagonism was acquired by Vpu variants from the lineage of SIVcpz/HIV-1 viruses responsible for pandemic AIDS. We found marked SNAT1 induction in activated primary human CD4+ T cells, and used Consumption and Release (CoRe) metabolomics to identify alanine as an endogenous SNAT1 substrate required for T cell mitogenesis. Downregulation of SNAT1 therefore defines a unique paradigm of HIV interference with immunometabolism. PMID:26439863

  8. Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef

    PubMed Central

    Matheson, Nicholas J.; Sumner, Jonathan; Wals, Kim; Rapiteanu, Radu; Weekes, Michael P.; Vigan, Raphael; Weinelt, Julia; Schindler, Michael; Antrobus, Robin; Costa, Ana S.H.; Frezza, Christian; Clish, Clary B.; Neil, Stuart J.D.; Lehner, Paul J.

    2015-01-01

    Summary Critical cell surface immunoreceptors downregulated during HIV infection have previously been identified using non-systematic, candidate approaches. To gain a comprehensive, unbiased overview of how HIV infection remodels the T cell surface, we took a distinct, systems-level, quantitative proteomic approach. >100 plasma membrane proteins, many without characterized immune functions, were downregulated during HIV infection. Host factors targeted by the viral accessory proteins Vpu or Nef included the amino acid transporter SNAT1 and the serine carriers SERINC3/5. We focused on SNAT1, a β-TrCP-dependent Vpu substrate. SNAT1 antagonism was acquired by Vpu variants from the lineage of SIVcpz/HIV-1 viruses responsible for pandemic AIDS. We found marked SNAT1 induction in activated primary human CD4+ T cells, and used Consumption and Release (CoRe) metabolomics to identify alanine as an endogenous SNAT1 substrate required for T cell mitogenesis. Downregulation of SNAT1 therefore defines a unique paradigm of HIV interference with immunometabolism. PMID:26439863

  9. The CMS High-Level Trigger

    SciTech Connect

    Covarelli, R.

    2009-12-17

    At the startup of the LHC, the CMS data acquisition is expected to be able to sustain an event readout rate of up to 100 kHz from the Level-1 trigger. These events will be read into a large processor farm which will run the 'High-Level Trigger'(HLT) selection algorithms and will output a rate of about 150 Hz for permanent data storage. In this report HLT performances are shown for selections based on muons, electrons, photons, jets, missing transverse energy, {tau} leptons and b quarks: expected efficiencies, background rates and CPU time consumption are reported as well as relaxation criteria foreseen for a LHC startup instantaneous luminosity.

  10. Plants tolerant of high boron levels.

    PubMed

    Miwa, Kyoko; Takano, Junpei; Omori, Hiroyuki; Seki, Motoaki; Shinozaki, Kazuo; Fujiwara, Toru

    2007-11-30

    Reduced crop productivity due to soils containing toxic levels of boron (B) is a worldwide problem in food production. It is estimated that up to 17% of the barley yield losses in southern Australia are caused by B toxicity. We found that the expression of AtBOR4, an Arabidopsis paralog of BOR1, the first identified boron transporter gene, generates plants that are tolerant of high B levels. BOR4 is a polarly localized borate exporter that enhances B efflux from roots. The present study is a foundation for the improvement of crop productivity in soils containing excess B, which are distributed in arid areas of the world. PMID:18048682

  11. High-Level Waste Melter Study Report

    SciTech Connect

    Perez Jr, Joseph M; Bickford, Dennis F; Day, Delbert E; Kim, Dong-Sang; Lambert, Steven L; Marra, Sharon L; Peeler, David K; Strachan, Denis M; Triplett, Mark B; Vienna, John D; Wittman, Richard S

    2001-07-13

    At the Hanford Site in Richland, Washington, the path to site cleanup involves vitrification of the majority of the wastes that currently reside in large underground tanks. A Joule-heated glass melter is the equipment of choice for vitrifying the high-level fraction of these wastes. Even though this technology has general national and international acceptance, opportunities may exist to improve or change the technology to reduce the enormous cost of accomplishing the mission of site cleanup. Consequently, the U.S. Department of Energy requested the staff of the Tanks Focus Area to review immobilization technologies, waste forms, and modifications to requirements for solidification of the high-level waste fraction at Hanford to determine what aspects could affect cost reductions with reasonable long-term risk. The results of this study are summarized in this report.

  12. High level intelligent control of telerobotics systems

    NASA Technical Reports Server (NTRS)

    Mckee, James

    1988-01-01

    A high level robot command language is proposed for the autonomous mode of an advanced telerobotics system and a predictive display mechanism for the teleoperational model. It is believed that any such system will involve some mixture of these two modes, since, although artificial intelligence can facilitate significant autonomy, a system that can resort to teleoperation will always have the advantage. The high level command language will allow humans to give the robot instructions in a very natural manner. The robot will then analyze these instructions to infer meaning so that is can translate the task into lower level executable primitives. If, however, the robot is unable to perform the task autonomously, it will switch to the teleoperational mode. The time delay between control movement and actual robot movement has always been a problem in teleoperations. The remote operator may not actually see (via a monitor) the results of high actions for several seconds. A computer generated predictive display system is proposed whereby the operator can see a real-time model of the robot's environment and the delayed video picture on the monitor at the same time.

  13. Performance of the CMS High Level Trigger

    NASA Astrophysics Data System (ADS)

    Perrotta, Andrea

    2015-12-01

    The CMS experiment has been designed with a 2-level trigger system. The first level is implemented using custom-designed electronics. The second level is the so-called High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. For Run II of the Large Hadron Collider, the increases in center-of-mass energy and luminosity will raise the event rate to a level challenging for the HLT algorithms. The increase in the number of interactions per bunch crossing, on average 25 in 2012, and expected to be around 40 in Run II, will be an additional complication. We present here the expected performance of the main triggers that will be used during the 2015 data taking campaign, paying particular attention to the new approaches that have been developed to cope with the challenges of the new run. This includes improvements in HLT electron and photon reconstruction as well as better performing muon triggers. We will also present the performance of the improved tracking and vertexing algorithms, discussing their impact on the b-tagging performance as well as on the jet and missing energy reconstruction.

  14. Highly Pathogenic Simian Immunodeficiency Virus mne Variants That Emerge during the Course of Infection Evolve Enhanced Infectivity and the Ability To Downregulate CD4 but Not Class I Major Histocompatibility Complex Antigens

    PubMed Central

    Patel, Parul G.; Yu Kimata, Monica T.; Biggins, Julia E.; Wilson, Joelle M.; Kimata, Jason T.

    2002-01-01

    The replicative, cytopathic, and antigenic properties of simian immunodeficiency virus (SIV) variants influence its replication efficiency in vivo. To further define the viral properties and determinants that may be important for high-level replication in vivo and progression to AIDS, we compared a minimally pathogenic SIVmne molecular clone with two highly pathogenic variants cloned from late stages of infection. Both variants had evolved greater infectivity than the parental clone due to mutations in nef. Interestingly, a pol determinant in one of the highly pathogenic variants also contributed to its increased infectivity. Furthermore, because replication in vivo may also be influenced by the ability of a virus to evade the cellular immune response of the host, we examined whether the variants were more capable of downregulating surface expression of class I major histocompatibility complex (MHC). Decreased MHC class I expression was not observed in cells infected with any of the viruses. Furthermore, the Nef proteins of the highly pathogenic variants only slightly reduced surface MHC class I expression in transfected cells, although they efficiently downregulated CD4. Together, these data demonstrate that mutations which can enhance viral infectivity, as well as CD4 downregulation, may be important for efficient replication of SIV in the host. However, Nef-mediated reduction of MHC class I expression does not appear to be critical for the increased in vivo replicative ability of highly pathogenic late variants. PMID:12050354

  15. EAP high-level product architecture

    NASA Astrophysics Data System (ADS)

    Gudlaugsson, T. V.; Mortensen, N. H.; Sarban, R.

    2013-04-01

    EAP technology has the potential to be used in a wide range of applications. This poses the challenge to the EAP component manufacturers to develop components for a wide variety of products. Danfoss Polypower A/S is developing an EAP technology platform, which can form the basis for a variety of EAP technology products while keeping complexity under control. High level product architecture has been developed for the mechanical part of EAP transducers, as the foundation for platform development. A generic description of an EAP transducer forms the core of the high level product architecture. This description breaks down the EAP transducer into organs that perform the functions that may be present in an EAP transducer. A physical instance of an EAP transducer contains a combination of the organs needed to fulfill the task of actuator, sensor, and generation. Alternative principles for each organ allow the function of the EAP transducers to be changed, by basing the EAP transducers on a different combination of organ alternatives. A model providing an overview of the high level product architecture has been developed to support daily development and cooperation across development teams. The platform approach has resulted in the first version of an EAP technology platform, on which multiple EAP products can be based. The contents of the platform have been the result of multi-disciplinary development work at Danfoss PolyPower, as well as collaboration with potential customers and research institutions. Initial results from applying the platform on demonstrator design for potential applications are promising. The scope of the article does not include technical details.

  16. The high-level trigger of ALICE

    NASA Astrophysics Data System (ADS)

    Tilsner, H.; Alt, T.; Aurbakken, K.; Grastveit, G.; Helstrup, H.; Lindenstruth, V.; Loizides, C.; Nystrand, J.; Roehrich, D.; Skaali, B.; Steinbeck, T.; Ullaland, K.; Vestbo, A.; Vik, T.

    One of the main tracking detectors of the forthcoming ALICE Experiment at the LHC is a cylindrical Time Projection Chamber (TPC) with an expected data volume of about 75 MByte per event. This data volume, in combination with the presumed maximum bandwidth of 1.2 GByte/s to the mass storage system, would limit the maximum event rate to 20 Hz. In order to achieve higher event rates, online data processing has to be applied. This implies either the detection and read-out of only those events which contain interesting physical signatures or an efficient compression of the data by modeling techniques. In order to cope with the anticipated data rate, massive parallel computing power is required. It will be provided in form of a clustered farm of SMP-nodes, based on off-the-shelf PCs, which are connected with a high bandwidth low overhead network. This High-Level Trigger (HLT) will be able to process a data rate of 25 GByte/s online. The front-end electronics of the individual sub-detectors is connected to the HLT via an optical link and a custom PCI card which is mounted in the clustered PCs. The PCI card is equipped with an FPGA necessary for the implementation of the PCI-bus protocol. Therefore, this FPGA can also be used to assist the host processor with first-level processing. The first-level processing done on the FPGA includes conventional cluster-finding for low multiplicity events and local track finding based on the Hough Transformation of the raw data for high multiplicity events. PACS: 07.05.-t Computers in experimental physics - 07.05.Hd Data acquisition: hardware and software - 29.85.+c Computer data analysis

  17. Regulation of high density lipoprotein levels

    SciTech Connect

    Krauss, R.M.

    1982-03-01

    An increasing awareness of the physiologic and pathologic importance of serum high density lipoproteins (HDL) has led to a large number of observations regarding factors which influence their concentrations. HDL consists of a heterogeneous collection of macromolecules with diverse physical properties and chemical constituents. While laboratory techniques have made it possible to measure HDL and their individual components, there are as yet large gaps in our knowledge of the biochemical mechanisms and clinical significance of changes in these laboratory parameters. In this review, current concepts of the structure and metabolism of HDL will be briefly summarized, and the factors influencing their levels in humans will be surveyed. 313 references.

  18. The effects of high level infrasound

    SciTech Connect

    Johnson, D.L.

    1980-02-01

    This paper will attempt to survey the current knowledge on the effects of relative high levels of infrasound on humans. While this conference is concerned mainly about hearing, some discussion of other physiological effects is appropriate. Such discussion also serves to highlight a basic question, 'Is hearing the main concern of infrasound and low frequency exposure, or is there a more sensitive mechanism'. It would be comforting to know that the focal point of this conference is indeed the most important concern. Therefore, besides hearing loss and auditory threshold of infrasonic and low frequency exposure, four other effects will be provided. These are performance, respiration, annoyance, and vibration.

  19. High-level waste qualification: Managing uncertainty

    SciTech Connect

    Pulsipher, B.A.

    1993-09-01

    A vitrification facility is being developed by the U.S. Department of Energy (DOE) at the West Valley Demonstration Plant (WVDP) near Buffalo, New York, where approximately 300 canisters of high-level nuclear waste glass will be produced. To assure that the produced waste form is acceptable, uncertainty must be managed. Statistical issues arise due to sampling, waste variations, processing uncertainties, and analytical variations. This paper presents elements of a strategy to characterize and manage the uncertainties associated with demonstrating that an acceptable waste form product is achieved. Specific examples are provided within the context of statistical work performed by Pacific Northwest Laboratory (PNL).

  20. Service Oriented Architecture for High Level Applications

    SciTech Connect

    Chu, Chungming; Chevtsov, Sergei; Wu, Juhao; Shen, Guobao; /Brookhaven

    2012-06-28

    Standalone high level applications often suffer from poor performance and reliability due to lengthy initialization, heavy computation and rapid graphical update. Service-oriented architecture (SOA) is trying to separate the initialization and computation from applications and to distribute such work to various service providers. Heavy computation such as beam tracking will be done periodically on a dedicated server and data will be available to client applications at all time. Industrial standard service architecture can help to improve the performance, reliability and maintainability of the service. Robustness will also be improved by reducing the complexity of individual client applications.

  1. The High Level Data Reduction Library

    NASA Astrophysics Data System (ADS)

    Ballester, P.; Gabasch, A.; Jung, Y.; Modigliani, A.; Taylor, J.; Coccato, L.; Freudling, W.; Neeser, M.; Marchetti, E.

    2015-09-01

    The European Southern Observatory (ESO) provides pipelines to reduce data for most of the instruments at its Very Large telescope (VLT). These pipelines are written as part of the development of VLT instruments, and are used both in the ESO's operational environment and by science users who receive VLT data. All the pipelines are highly specific geared toward instruments. However, experience showed that the independently developed pipelines include significant overlap, duplication and slight variations of similar algorithms. In order to reduce the cost of development, verification and maintenance of ESO pipelines, and at the same time improve the scientific quality of pipelines data products, ESO decided to develop a limited set of versatile high-level scientific functions that are to be used in all future pipelines. The routines are provided by the High-level Data Reduction Library (HDRL). To reach this goal, we first compare several candidate algorithms and verify them during a prototype phase using data sets from several instruments. Once the best algorithm and error model have been chosen, we start a design and implementation phase. The coding of HDRL is done in plain C and using the Common Pipeline Library (CPL) functionality. HDRL adopts consistent function naming conventions and a well defined API to minimise future maintenance costs, implements error propagation, uses pixel quality information, employs OpenMP to take advantage of multi-core processors, and is verified with extensive unit and regression tests. This poster describes the status of the project and the lesson learned during the development of reusable code implementing algorithms of high scientific quality.

  2. Analysis of T cell responses to chimpanzee adenovirus vectors encoding HIV gag–pol–nef antigen

    PubMed Central

    Herath, S.; Le Heron, A.; Colloca, S.; Bergin, P.; Patterson, S.; Weber, J.; Tatoud, R.; Dickson, G.

    2015-01-01

    Adenoviruses have been shown to be both immunogenic and efficient at presenting HIV proteins but recent trials have suggested that they may play a role in increasing the risk of HIV acquisition. This risk may be associated with the presence of pre-existing immunity to the viral vectors. Chimpanzee adenoviruses (chAd) have low seroprevalence in human populations and so reduce this risk. ChAd3 and chAd63 were used to deliver an HIV gag, pol and nef transgene. ELISpot analysis of T cell responses in mice showed that both chAd vectors were able to induce an immune response to Gag and Pol peptides but that only the chAd3 vector induced responses to Nef peptides. Although the route of injection did not influence the magnitude of immune responses to either chAd vector, the dose of vector did. Taken together these results demonstrate that chimpanzee adenoviruses are suitable vector candidates for the delivery of HIV proteins and could be used for an HIV vaccine and furthermore the chAd3 vector produces a broader response to the HIV transgene. PMID:26546736

  3. Analysis of T cell responses to chimpanzee adenovirus vectors encoding HIV gag-pol-nef antigen.

    PubMed

    Herath, S; Le Heron, A; Colloca, S; Bergin, P; Patterson, S; Weber, J; Tatoud, R; Dickson, G

    2015-12-16

    Adenoviruses have been shown to be both immunogenic and efficient at presenting HIV proteins but recent trials have suggested that they may play a role in increasing the risk of HIV acquisition. This risk may be associated with the presence of pre-existing immunity to the viral vectors. Chimpanzee adenoviruses (chAd) have low seroprevalence in human populations and so reduce this risk. ChAd3 and chAd63 were used to deliver an HIV gag, pol and nef transgene. ELISpot analysis of T cell responses in mice showed that both chAd vectors were able to induce an immune response to Gag and Pol peptides but that only the chAd3 vector induced responses to Nef peptides. Although the route of injection did not influence the magnitude of immune responses to either chAd vector, the dose of vector did. Taken together these results demonstrate that chimpanzee adenoviruses are suitable vector candidates for the delivery of HIV proteins and could be used for an HIV vaccine and furthermore the chAd3 vector produces a broader response to the HIV transgene. PMID:26546736

  4. HIV-1 infection of T cells and macrophages are differentially modulated by virion-associated Hck: a Nef-dependent phenomenon.

    PubMed

    Cornall, Alyssa; Mak, Johnson; Greenway, Alison; Tachedjian, Gilda

    2013-09-01

    The proline repeat motif (PxxP) of Nef is required for interaction with the SH3 domains of macrophage-specific Src kinase Hck. However, the implication of this interaction for viral replication and infectivity in macrophages and T lymphocytes remains unclear. Experiments in HIV-1 infected macrophages confirmed the presence of a Nef:Hck complex which was dependent on the Nef proline repeat motif. The proline repeat motif of Nef also enhanced both HIV-1 infection and replication in macrophages, and was required for incorporation of Hck into viral particles. Unexpectedly, wild-type Hck inhibited infection of macrophages, but Hck was shown to enhance infection of primary T lymphocytes. These results indicate that the interaction between Nef and Hck is important for Nef-dependent modulation of viral infectivity. Hck-dependent enhancement of HIV-1 infection of T cells suggests that Nef-Hck interaction may contribute to the spread of HIV-1 infection from macrophages to T cells by modulating events in the producer cell, virion and target cell. PMID:24051604

  5. HIV-1 Nef and KSHV oncogene K1 synergistically promote angiogenesis by inducing cellular miR-718 to regulate the PTEN/AKT/mTOR signaling pathway

    PubMed Central

    Xue, Min; Yao, Shuihong; Hu, Minmin; Li, Wan; Hao, Tingting; Zhou, Feng; Zhu, Xiaofei; Lu, Hongmei; Qin, Di; Yan, Qin; Zhu, Jianzhong; Gao, Shou-Jiang; Lu, Chun

    2014-01-01

    Kaposi's sarcoma (KS) is an AIDS-defining cancer with aberrant neovascularization caused by KS-associated herpesvirus (KSHV). Although the interaction between HIV-1 and KSHV plays a pivotal role in promoting the aggressive manifestations of KS, the pathogenesis underlying AIDS-KS remains largely unknown. Here we examined HIV-1 Nef protein promotion of KSHV oncoprotein K1-induced angiogenesis. We showed that both internalized and ectopic expression of Nef in endothelial cells synergized with K1 to facilitate vascular tube formation and cell proliferation, and enhance angiogenesis in a chicken CAM model. In vivo experiments further indicated that Nef accelerated K1-induced angiogenesis and tumorigenesis in athymic nu/nu mice. Mechanistic studies revealed that Nef and K1 synergistically activated PI3K/AKT/mTOR signaling by downregulating PTEN. Furthermore, Nef and K1 induced cellular miR-718, which inhibited PTEN expression by directly targeting a seed sequence in the 3′ UTR of its mRNA. Inhibition of miR-718 expression increased PTEN synthesis and suppressed the synergistic effect of Nef- and K1-induced angiogenesis and tumorigenesis. These results indicate that, by targeting PTEN, miR-718 mediates Nef- and K1-induced angiogenesis via activation of AKT/mTOR signaling. Our results demonstrate an essential role of miR-718/AKT/mTOR axis in AIDS-KS and thus may represent an attractive therapeutic target. PMID:25104021

  6. Oral immunization with recombinant Mycobacterium bovis BCG simian immunodeficiency virus nef induces local and systemic cytotoxic T-lymphocyte responses in mice.

    PubMed Central

    Lagranderie, M; Balazuc, A M; Gicquel, B; Gheorghiu, M

    1997-01-01

    Recombinant live Mycobacterium bovis BCG vectors (rBCG) induce strong cellular and humoral immune responses against various antigens after either systemic or oral immunization of mice. Cytotoxic T-lymphocyte (CTL) responses may contribute to the control of human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infections whose portal of entry is the gastrointestinal or genital mucosa. In this study, we immunized BALB/c mice with a recombinant BCG SIV nef and observed its behavior in oropharyngeal and target organ lymphoid tissues. The cellular immune responses, particularly the intestinal intraepithelial and systemic CTL responses, were investigated. The results showed that rBCG SIV nef translocated the oropharyngeal mucosa and intestinal epithelium. It diffused to and persisted in target lymphoid organs. Specific SIV Nef peptide proliferative responses and cytokine production were observed. Strong systemic and mucosal CTL responses were induced. In particular, we demonstrated direct specific anti-Nef CTL in intestinal intraepithelial CD8beta+ T cells. These findings provide evidence that orally administered rBCG SIV nef may contribute to local defenses against viral invasion. Therefore, rBCG SIV nef could be a candidate vaccine to protect against SIV infection and may be used to develop an oral rBCG HIV nef vaccine. PMID:9032366

  7. CMS High Level Trigger Timing Measurements

    NASA Astrophysics Data System (ADS)

    Richardson, Clint

    2015-12-01

    The two-level trigger system employed by CMS consists of the Level 1 (L1) Trigger, which is implemented using custom-built electronics, and the High Level Trigger (HLT), a farm of commercial CPUs running a streamlined version of the offline CMS reconstruction software. The operational L1 output rate of 100 kHz, together with the number of CPUs in the HLT farm, imposes a fundamental constraint on the amount of time available for the HLT to process events. Exceeding this limit impacts the experiment's ability to collect data efficiently. Hence, there is a critical need to characterize the performance of the HLT farm as well as the algorithms run prior to start up in order to ensure optimal data taking. Additional complications arise from the fact that the HLT farm consists of multiple generations of hardware and there can be subtleties in machine performance. We present our methods of measuring the timing performance of the CMS HLT, including the challenges of making such measurements. Results for the performance of various Intel Xeon architectures from 2009-2014 and different data taking scenarios are also presented.

  8. High accuracy electronic material level sensor

    DOEpatents

    McEwan, Thomas E.

    1997-01-01

    The High Accuracy Electronic Material Level Sensor (electronic dipstick) is a sensor based on time domain reflectometry (TDR) of very short electrical pulses. Pulses are propagated along a transmission line or guide wire that is partially immersed in the material being measured; a launcher plate is positioned at the beginning of the guide wire. Reflected pulses are produced at the material interface due to the change in dielectric constant. The time difference of the reflections at the launcher plate and at the material interface are used to determine the material level. Improved performance is obtained by the incorporation of: 1) a high accuracy time base that is referenced to a quartz crystal, 2) an ultrawideband directional sampler to allow operation without an interconnect cable between the electronics module and the guide wire, 3) constant fraction discriminators (CFDs) that allow accurate measurements regardless of material dielectric constants, and reduce or eliminate errors induced by triple-transit or "ghost" reflections on the interconnect cable. These improvements make the dipstick accurate to better than 0.1%.

  9. High accuracy electronic material level sensor

    DOEpatents

    McEwan, T.E.

    1997-03-11

    The High Accuracy Electronic Material Level Sensor (electronic dipstick) is a sensor based on time domain reflectometry (TDR) of very short electrical pulses. Pulses are propagated along a transmission line or guide wire that is partially immersed in the material being measured; a launcher plate is positioned at the beginning of the guide wire. Reflected pulses are produced at the material interface due to the change in dielectric constant. The time difference of the reflections at the launcher plate and at the material interface are used to determine the material level. Improved performance is obtained by the incorporation of: (1) a high accuracy time base that is referenced to a quartz crystal, (2) an ultrawideband directional sampler to allow operation without an interconnect cable between the electronics module and the guide wire, (3) constant fraction discriminators (CFDs) that allow accurate measurements regardless of material dielectric constants, and reduce or eliminate errors induced by triple-transit or ``ghost`` reflections on the interconnect cable. These improvements make the dipstick accurate to better than 0.1%. 4 figs.

  10. Technetium Chemistry in High-Level Waste

    SciTech Connect

    Hess, Nancy J.

    2006-06-01

    Tc contamination is found within the DOE complex at those sites whose mission involved extraction of plutonium from irradiated uranium fuel or isotopic enrichment of uranium. At the Hanford Site, chemical separations and extraction processes generated large amounts of high level and transuranic wastes that are currently stored in underground tanks. The waste from these extraction processes is currently stored in underground High Level Waste (HLW) tanks. However, the chemistry of the HLW in any given tank is greatly complicated by repeated efforts to reduce volume and recover isotopes. These processes ultimately resulted in mixing of waste streams from different processes. As a result, the chemistry and the fate of Tc in HLW tanks are not well understood. This lack of understanding has been made evident in the failed efforts to leach Tc from sludge and to remove Tc from supernatants prior to immobilization. Although recent interest in Tc chemistry has shifted from pretreatment chemistry to waste residuals, both needs are served by a fundamental understanding of Tc chemistry.

  11. Genetic drift can dominate short-term human immunodeficiency virus type 1 nef quasispecies evolution in vivo.

    PubMed Central

    Plikat, U; Nieselt-Struwe, K; Meyerhans, A

    1997-01-01

    The evolution of human immunodeficiency virus (HIV) type 1 nef quasispecies in a patient clonally infected with a contaminated batch of blood clotting factor IX was monitored. nef sequences were derived at 11, 25, and 41 months postinfection from infected peripheral blood mononuclear cells after molecular cloning of PCR-amplified proviral DNA. The phylogenetic relationships among a total of 41 informative sequences were established by split decomposition analysis and used as a basis to establish a substitution matrix and to score synonymous (s) and nonsynonymous (ns) substitutions. The number of observed in-phase stop codons within the nef sequences was comparable to that expected on a random basis. Similarly, the numbers of observed s and ns substitutions did not differ significantly from expected values. No codon position was preferentially mutated. The maximum sequence divergence increased in a linear manner, with approximately 4.4 nucleotide and approximately 3.2 amino acid changes per year. It appears that stochastic processes strongly influence short-term HIV nef quasispecies evolution in vivo. PMID:9151810

  12. Intra-host competition between nef-defective escape mutants and wild-type human immunodeficiency virus type 1.

    PubMed Central

    Altes, H K; Jansen, V A

    2000-01-01

    Various forms of nef genes with deletions at conserved positions along the sequence have been reported to persist in human immunodeficiency virus type 1 infected patients. We investigate the forces maintaining such variants in the proviral population. The main selection pressures are preservation of function and host immune response. The crippled Nef protein might have fewer epitopes, and as such be less visible to the specific immune response, but it will lose some function. Does a trade-off between avoidance of the immune response and loss of function explain the dynamics of the crippled virus found in the patients? To answer this question, we formulated a deterministic model of the virus-host interactions. We found that when the crippled protein presents few epitopes and suffers little loss of function, the two viral types can coexist. Otherwise, the wild-type comes to prevail. The mutant form might initially dominate, but as the selective pressure by the CD84+ T cells decreases over the course of infection, the advantage for the crippled form of losing epitopes disappears. Hence, we go from a situation of coexistence of wild-type and mutant, to a situation of only full-length nef. The results are discussed in the context of the suggested use of live attenuated vaccines having deletions in nef. PMID:10687825

  13. Visual high-level regions respond to high-level stimulus content in the absence of low-level confounds.

    PubMed

    Schindler, Andreas; Bartels, Andreas

    2016-05-15

    High-level regions of the ventral stream exhibit strong category selectivity to stimuli such as faces, houses, or objects. However, recent studies suggest that at least part of this selectivity stems from low-level differences inherent to images of the different categories. For example, visual outdoor and indoor scenes as well as houses differ in spatial frequency, rectilinearity and obliqueness when compared to face or object images. Correspondingly, scene responsive para-hippocampal place area (PPA) showed strong preference to low-level properties of visual scenes also in the absence of high-level scene content. This raises the question whether all high-level responses in PPA, the fusiform face area (FFA), or the object-responsive lateral occipital compex (LOC) may actually be explained by systematic differences in low-level features. In the present study we contrasted two classes of simple stimuli consisting of ten rectangles each. While both were matched in visual low-level features only one class of rectangle arrangements gave rise to a percept compatible with a high-level 3D layout such as a scene or an object. We found that areas PPA, transverse occipital sulcus (TOS, also referred to as occipital place area, OPA), as well as FFA and LOC showed robust responses to the visual scene class compared to the low-level matched control. Our results suggest that visual category responsive regions are not purely driven by low-level visual features but also by the high-level perceptual stimulus interpretation. PMID:26975552

  14. Beam size measurement at high radiation levels

    SciTech Connect

    Decker, F.J.

    1991-05-01

    At the end of the Stanford Linear Accelerator the high energy electron and positron beams are quite small. Beam sizes below 100 {mu}m ({sigma}) as well as the transverse distribution, especially tails, have to be determined. Fluorescent screens observed by TV cameras provide a quick two-dimensional picture, which can be analyzed by digitization. For running the SLAC Linear Collider (SLC) with low backgrounds at the interaction point, collimators are installed at the end of the linac. This causes a high radiation level so that the nearby cameras die within two weeks and so-called radiation hard'' cameras within two months. Therefore an optical system has been built, which guides a 5 mm wide picture with a resolution of about 30 {mu}m over a distance of 12 m to an accessible region. The overall resolution is limited by the screen thickness, optical diffraction and the line resolution of the camera. Vibration, chromatic effects or air fluctuations play a much less important role. The pictures are colored to get fast information about the beam current, size and tails. Beside the emittance, more information about the tail size and betatron phase is obtained by using four screens. This will help to develop tail compensation schemes to decrease the emittance growth in the linac at high currents. 4 refs., 2 figs.

  15. Reusable and Extensible High Level Data Distributions

    NASA Technical Reports Server (NTRS)

    Diaconescu, Roxana E.; Chamberlain, Bradford; James, Mark L.; Zima, Hans P.

    2005-01-01

    This paper presents a reusable design of a data distribution framework for data parallel high performance applications. We are implementing the design in the context of the Chapel high productivity programming language. Distributions in Chapel are a means to express locality in systems composed of large numbers of processor and memory components connected by a network. Since distributions have a great effect on,the performance of applications, it is important that the distribution strategy can be chosen by a user. At the same time, high productivity concerns require that the user is shielded from error-prone, tedious details such as communication and synchronization. We propose an approach to distributions that enables the user to refine a language-provided distribution type and adjust it to optimize the performance of the application. Additionally, we conceal from the user low-level communication and synchronization details to increase productivity. To emphasize the generality of our distribution machinery, we present its abstract design in the form of a design pattern, which is independent of a concrete implementation. To illustrate the applicability of our distribution framework design, we outline the implementation of data distributions in terms of the Chapel language.

  16. High-level connectionist models. Semiannual report

    SciTech Connect

    Pollack, J.B.

    1989-08-01

    The major achievement of this semiannum was the significant revision and extension of the Recursive Auto-Associative Memory (RAAM) work for publication in the journal Artificial Intelligence. Included as an appendix to this report, the article includes several new elements: (1) Background - The work was more clearly set into the area of recursive distributed representations, machine learning, and the adequacy of the connectionist approach for high-level cognitive modeling; (2) New Experiment - RAAM was applied to finding compact representations for sequences of letters; (3) Analysis - The developed representations were analyzed as features which range from categorical to distinctive. Categorical features distinguish between conceptual categories while distinctive features vary within categories and discriminate or label the members. The representations were also analyzed geometrically; and (4) Applications - Feasibility studies were performed and described on inference by association, and on using RAAM-generated patterns along with cascaded networks for natural language parsing. Both of these remain long-term goals of the project.

  17. Umbra's High Level Architecture (HLA) Interface

    SciTech Connect

    GOTTLIEB, ERIC JOSEPH; MCDONALD, MICHAEL J.; OPPEL III, FRED J.

    2002-04-01

    This report describes Umbra's High Level Architecture HLA library. This library serves as an interface to the Defense Simulation and Modeling Office's (DMSO) Run Time Infrastructure Next Generation Version 1.3 (RTI NG1.3) software library and enables Umbra-based models to be federated into HLA environments. The Umbra library was built to enable the modeling of robots for military and security system concept evaluation. A first application provides component technologies that ideally fit the US Army JPSD's Joint Virtual Battlespace (JVB) simulation framework for Objective Force concept analysis. In addition to describing the Umbra HLA library, the report describes general issues of integrating Umbra with RTI code and outlines ways of building models to support particular HLA simulation frameworks like the JVB.

  18. Airway injury during high-level exercise.

    PubMed

    Kippelen, Pascale; Anderson, Sandra D

    2012-05-01

    Airway epithelial cells act as a physical barrier against environmental toxins and injury, and modulate inflammation and the immune response. As such, maintenance of their integrity is critical. Evidence is accumulating to suggest that exercise can cause injury to the airway epithelium. This seems the case particularly for competitive athletes performing high-level exercise, or when exercise takes place in extreme environmental conditions such as in cold dry air or in polluted air. Dehydration of the small airways and increased forces exerted on to the airway surface during severe hyperpnoea are thought to be key factors in determining the occurrence of injury of the airway epithelium. The injury-repair process of the airway epithelium may contribute to the development of the bronchial hyper-responsiveness that is documented in many elite athletes. PMID:22247295

  19. HIGH LEVEL RF FOR THE SNS RING.

    SciTech Connect

    ZALTSMAN,A.; BLASKIEWICZ,M.; BRENNAN,J.; BRODOWSKI,J.; METH,M.; SPITZ,R.; SEVERINO,F.

    2002-06-03

    A high level RF system (HLRF) consisting of power amplifiers (PA's) and ferrite loaded cavities is being designed and built by Brookhaven National Laboratory (BNL) for the Spallation Neutron Source (SNS) project. It is a fixed frequency, two harmonic system whose main function is to maintain a gap for the kicker rise time. Three cavities running at the fundamental harmonic (h=l) will provide 40 kV and one cavity at the second harmonic (h=2) will provide 20 kV. Each cavity has two gaps with a design voltage of 10 kV per gap and will be driven by a power amplifier (PA) directly adjacent to it. The PA uses a 600kW tetrode to provide the necessary drive current. The anode of the tetrode is magnetically coupled to the downstream cell of the cavity. Drive to the PA will be provided by a wide band, solid state amplifier located remotely. A dynamic tuning scheme will be implemented to help compensate for the effect of beam loading.

  20. Decontamination of high-level waste canisters

    SciTech Connect

    Nesbitt, J.F.; Slate, S.C.; Fetrow, L.K.

    1980-12-01

    This report presents evaluations of several methods for the in-process decontamination of metallic canisters containing any one of a number of solidified high-level waste (HLW) forms. The use of steam-water, steam, abrasive blasting, electropolishing, liquid honing, vibratory finishing and soaking have been tested or evaluated as potential techniques to decontaminate the outer surfaces of HLW canisters. Either these techniques have been tested or available literature has been examined to assess their applicability to the decontamination of HLW canisters. Electropolishing has been found to be the most thorough method to remove radionuclides and other foreign material that may be deposited on or in the outer surface of a canister during any of the HLW processes. Steam or steam-water spraying techniques may be adequate for some applications but fail to remove all contaminated forms that could be present in some of the HLW processes. Liquid honing and abrasive blasting remove contamination and foreign material very quickly and effectively from small areas and components although these blasting techniques tend to disperse the material removed from the cleaned surfaces. Vibratory finishing is very capable of removing the bulk of contamination and foreign matter from a variety of materials. However, special vibratory finishing equipment would have to be designed and adapted for a remote process. Soaking techniques take long periods of time and may not remove all of the smearable contamination. If soaking involves pickling baths that use corrosive agents, these agents may cause erosion of grain boundaries that results in rough surfaces.

  1. One Protein to Rule them All: Modulation of Cell Surface Receptors and Molecules by HIV Nef

    PubMed Central

    Landi, Alessia; Iannucci, Veronica; Nuffel, Anouk Van; Meuwissen, Pieter; Verhasselt, Bruno

    2011-01-01

    The HIV-1, HIV-2 and SIV Nef protein are known to modulate the expression of several cell surface receptors and molecules to escape the immune system, to alter T cell activation, to enhance viral replication, infectivity and transmission and overall to ensure the optimal environment for infection outcome. Consistent and continuous efforts have been made over the years to characterize the modulation of expression of each of these molecules, in the hope that a better understanding of these processes essential for HIV infection and/or pathogenesis will eventually highlight new therapeutic targets. In this article we provide an extensive review of the knowledge gained so far on this important and evolving topic. PMID:22103833

  2. HIV-1 Nef Induces Proinflammatory State in Macrophages through Its Acidic Cluster Domain: Involvement of TNF Alpha Receptor Associated Factor 2

    PubMed Central

    Fiorucci, Gianna; Vaccari, Gabriele; Acconcia, Filippo; Chiarabelli, Cristiano; Leone, Stefano; Noto, Alessia; Horenkamp, Florian A.; Manrique, Santiago; Romeo, Giovanna; Polticelli, Fabio; Geyer, Matthias; Affabris, Elisabetta

    2011-01-01

    Background HIV-1 Nef is a virulence factor that plays multiple roles during HIV replication. Recently, it has been described that Nef intersects the CD40 signalling in macrophages, leading to modification in the pattern of secreted factors that appear able to recruit, activate and render T lymphocytes susceptible to HIV infection. The engagement of CD40 by CD40L induces the activation of different signalling cascades that require the recruitment of specific tumor necrosis factor receptor-associated factors (i.e. TRAFs). We hypothesized that TRAFs might be involved in the rapid activation of NF-κB, MAPKs and IRF-3 that were previously described in Nef-treated macrophages to induce the synthesis and secretion of proinflammatory cytokines, chemokines and IFNβ to activate STAT1, -2 and -3. Methodology/Principal Findings Searching for possible TRAF binding sites on Nef, we found a TRAF2 consensus binding site in the AQEEEE sequence encompassing the conserved four-glutamate acidic cluster. Here we show that all the signalling effects we observed in Nef treated macrophages depend on the integrity of the acidic cluster. In addition, Nef was able to interact in vitro with TRAF2, but not TRAF6, and this interaction involved the acidic cluster. Finally silencing experiments in THP-1 monocytic cells indicate that both TRAF2 and, surprisingly, TRAF6 are required for the Nef-induced tyrosine phosphorylation of STAT1 and STAT2. Conclusions Results reported here revealed TRAF2 as a new possible cellular interactor of Nef and highlighted that in monocytes/macrophages this viral protein is able to manipulate both the TRAF/NF-κB and TRAF/IRF-3 signalling axes, thereby inducing the synthesis of proinflammatory cytokines and chemokines as well as IFNβ. PMID:21886773

  3. DEFENSE HIGH LEVEL WASTE GLASS DEGRADATION

    SciTech Connect

    W. Ebert

    2001-09-20

    The purpose of this Analysis/Model Report (AMR) is to document the analyses that were done to develop models for radionuclide release from high-level waste (HLW) glass dissolution that can be integrated into performance assessment (PA) calculations conducted to support site recommendation and license application for the Yucca Mountain site. This report was developed in accordance with the ''Technical Work Plan for Waste Form Degradation Process Model Report for SR'' (CRWMS M&O 2000a). It specifically addresses the item, ''Defense High Level Waste Glass Degradation'', of the product technical work plan. The AP-3.15Q Attachment 1 screening criteria determines the importance for its intended use of the HLW glass model derived herein to be in the category ''Other Factors for the Postclosure Safety Case-Waste Form Performance'', and thus indicates that this factor does not contribute significantly to the postclosure safety strategy. Because the release of radionuclides from the glass will depend on the prior dissolution of the glass, the dissolution rate of the glass imposes an upper bound on the radionuclide release rate. The approach taken to provide a bound for the radionuclide release is to develop models that can be used to calculate the dissolution rate of waste glass when contacted by water in the disposal site. The release rate of a particular radionuclide can then be calculated by multiplying the glass dissolution rate by the mass fraction of that radionuclide in the glass and by the surface area of glass contacted by water. The scope includes consideration of the three modes by which water may contact waste glass in the disposal system: contact by humid air, dripping water, and immersion. The models for glass dissolution under these contact modes are all based on the rate expression for aqueous dissolution of borosilicate glasses. The mechanism and rate expression for aqueous dissolution are adequately understood; the analyses in this AMR were conducted to

  4. Fermilab tevatron high level RF accelerating systems

    SciTech Connect

    Kerns, Q.; Kerns, C.; Miller, H.; Reid, J.; Tawzer, S.; Webber, R.; Wildman, D.

    1985-10-01

    Eight tuned rf cavities have been installed and operated in the F0 straight section of the Tevatron. Their mechanical placement along the beam line enables them to be operated for colliding beams as two independent groups of four cavities, group 1-4 accelerating antiprotons and group 5-8 accelerating protons. The only difference is that the spacing between cavities 4 and 5 was increased to stay clear of the F0 colliding point. The cavities can easily be rephased by switching cables in a low-level distribution system (fan-out) so that the full accelerating capability of all eight cavities can be used during fixed target operations. Likewise, the cables from capacitive probes on each cavity gap can be switched to proper lengths and summed in a fan-back system to give an rf signal representing the amplitude and phase as ''seen by the beam,'' separately for protons and antiprotons. Such signals have been used to phase lock the Tevatron to the Main Ring for synchronous transfer. A cavity consists of two quarter-wave resonators placed back to back with a coaxial drift tube separating the two accelerating gaps by ..pi.. radians. The cavities are very similar to the prototype which has been previously described/sup 3/ and is operating as Station 8 in the Tevatron. Only additional water cooling around the high current region of the drift tube supports and a double loop used to monitor the unbalance current through the Hipernom mode damping resistor have been added. Each cavity has a Q of about7100, a shunt impedance of 1.2 M..cap omega.., and is capable of running cw with a peak accelerating voltage of 360

  5. Human Immunodeficiency Virus Type 1 Particles Pseudotyped with Envelope Proteins That Fuse at Low pH No Longer Require Nef for Optimal Infectivity

    PubMed Central

    Chazal, Nathalie; Singer, Gregory; Aiken, Christopher; Hammarskjöld, Marie-Louise; Rekosh, David

    2001-01-01

    We have investigated the effects of Nef on infectivity in the context of various viral envelope proteins. These experiments were performed with a minimal vector system where Nef is the only accessory protein present. Our results support the hypothesis that the route of entry influences the ability of Nef to enhance human immunodeficiency virus (HIV) infectivity. We show that HIV particles pseudotyped with Ebola virus glycoprotein or vesicular stomatitis virus glycoprotein (VSV-G), which fuse at low pH, do not require Nef for optimal infectivity. In contrast, Nef significantly enhances the infectivity of virus particles that contain envelope proteins that fuse at neutral pH (CCR5-dependent HIV Env, CXCR4-dependent HIV Env, or amphotropic murine leukemia virus Env). In addition, our results demonstrate that virus particles containing mixed CXCR4-dependent HIV and VSV-G envelope proteins show a conditional requirement for Nef for optimal infectivity, depending on which protein is allowed to facilitate entry. PMID:11264394

  6. High bicarbonate levels in narcoleptic children.

    PubMed

    Franco, Patricia; Junqua, Aurelie; Guignard-Perret, Anne; Raoux, Aude; Perier, Magali; Raverot, Veronique; Claustrat, Bruno; Gustin, Marie-Paule; Inocente, Clara Odilia; Lin, Jian-Sheng

    2016-04-01

    The objective of this study was to evaluate the levels of plasma bicarbonate levels in narcoleptic children. Clinical, electrophysiological data and bicarbonate levels were evaluated retrospectively in children seen in our paediatric national reference centre for hypersomnia. The cohort included 23 control subjects (11.5 ± 4 years, 43% boys) and 51 patients presenting de-novo narcolepsy (N) (12.7 ± 3.7 years, 47% boys). In narcoleptic children, cataplexy was present in 78% and DQB1*0602 was positive in 96%. The control children were less obese (2 versus 47%, P = 0.001). Compared with control subjects, narcoleptic children had higher bicarbonate levels (P = 0.02) as well as higher PCO2 (P < 0.01) and lower venous pH gas (P < 0.01). Bicarbonate levels higher than 27 mmol L(-1) were found in 41.2% of the narcoleptic children and 4.2% of the controls (P = 0.001). Bicarbonate levels were correlated with the Adapted Epworth Sleepiness Scale (P = 0.01). Narcoleptic patients without obesity often had bicarbonate levels higher than 27 mmol L (-1) (55 versus 25%, P = 0.025). No differences were found between children with and without cataplexy. In conclusion, narcoleptic patients had higher bicarbonate plasma levels compared to control children. This result could be a marker of hypoventilation in this pathology, provoking an increase in PCO2 and therefore a respiratory acidosis, compensated by an increase in plasma bicarbonates. This simple screening tool could be useful for prioritizing children for sleep laboratory evaluation in practice. PMID:26574184

  7. Statistics of high-level scene context

    PubMed Central

    Greene, Michelle R.

    2013-01-01

    Context is critical for recognizing environments and for searching for objects within them: contextual associations have been shown to modulate reaction time and object recognition accuracy, as well as influence the distribution of eye movements and patterns of brain activations. However, we have not yet systematically quantified the relationships between objects and their scene environments. Here I seek to fill this gap by providing descriptive statistics of object-scene relationships. A total of 48, 167 objects were hand-labeled in 3499 scenes using the LabelMe tool (Russell et al., 2008). From these data, I computed a variety of descriptive statistics at three different levels of analysis: the ensemble statistics that describe the density and spatial distribution of unnamed “things” in the scene; the bag of words level where scenes are described by the list of objects contained within them; and the structural level where the spatial distribution and relationships between the objects are measured. The utility of each level of description for scene categorization was assessed through the use of linear classifiers, and the plausibility of each level for modeling human scene categorization is discussed. Of the three levels, ensemble statistics were found to be the most informative (per feature), and also best explained human patterns of categorization errors. Although a bag of words classifier had similar performance to human observers, it had a markedly different pattern of errors. However, certain objects are more useful than others, and ceiling classification performance could be achieved using only the 64 most informative objects. As object location tends not to vary as a function of category, structural information provided little additional information. Additionally, these data provide valuable information on natural scene redundancy that can be exploited for machine vision, and can help the visual cognition community to design experiments guided by

  8. High School Accounting at Two Instructional Levels.

    ERIC Educational Resources Information Center

    Helme, Rebecca E.

    1980-01-01

    Offering two levels of accounting results in a broader base of student enrollment. Reiterating theory, giving practical examples, and stressing "why" as well as "how" enable the instructor to foster the environment the students need. The teacher must also instill self-confidence in the students. (JOW)

  9. Period analysis at high noise level

    NASA Astrophysics Data System (ADS)

    Kovacs, G.

    1980-05-01

    Analytical expressions are derived for the variances of three types of periodograms due to normal-distributed noise present in the data: the conventional Fourier spectrum, the method of Warner and Robinson (1972), and Jurkevich's method (1971). The equivalence of the Jurkevich method and that of Warner and Robinson is proved. The optimum phase cell number of the Warner-Robinson method is given; this number depends on the data length, signal form, and noise level. Results are illustrated by the analysis of two typical forms of light curves: an eclipsing type light curve and an RRa curve.

  10. High Power Amplifier Harmonic Output Level Measurement

    NASA Technical Reports Server (NTRS)

    Perez, R. M.; Hoppe, D. J.; Khan, A. R.

    1995-01-01

    A method is presented for the measurement of the harmonic output power of high power klystron amplifiers, involving coherent hemispherical radiation pattern measurements of the radiated klystron output. Results are discussed for the operation in saturated and unsaturated conditions, and with a waveguide harmonic filter included.

  11. How High Glucose Levels Affect Tendon Homeostasis.

    PubMed

    Snedeker, Jess G

    2016-01-01

    Among the many factors playing a role in tendon disease, unregulated biochemical reactions between glucose and the collagen extracellular matrix are coming increasingly into focus. We have shown that formation of advanced glycation end-products that cross-link the collagen extracellular matrix can drastically affect cellular level mechanical properties of the matrix, and in turn affect cell-level biomechanical stimuli during physiological loading of the tissue. We suggest that these may adversely affect tendon cell response to matrix damage, as well as the quality of the consequent repair. If such mechanical feedback loops are altered, the ability of tendon cells to maintain tissue in a functional, healthy state may be compromised. Although key foundational elements of biochemical, biomechanical, and biological understanding are now in place, the full extent of how these aspects interact, including the precise mechanisms by which advanced glycation end-products pathologically disrupt connective tissue homeostasis and damage repair, are only beginning to be adequately appreciated. PMID:27535261

  12. 46 CFR 182.530 - Bilge high level alarms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Bilge high level alarms. 182.530 Section 182.530... TONS) MACHINERY INSTALLATION Bilge and Ballast Systems § 182.530 Bilge high level alarms. (a) On a... operating station to indicate a high water level in each of the following normally unmanned spaces: (1)...

  13. 46 CFR 182.530 - Bilge high level alarms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Bilge high level alarms. 182.530 Section 182.530... TONS) MACHINERY INSTALLATION Bilge and Ballast Systems § 182.530 Bilge high level alarms. (a) On a... operating station to indicate a high water level in each of the following normally unmanned spaces: (1)...

  14. 46 CFR 119.530 - Bilge high level alarms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Bilge high level alarms. 119.530 Section 119.530... Bilge and Ballast Systems § 119.530 Bilge high level alarms. (a) Each vessel must be provided with a visual and audible alarm at the operating station to indicate a high water level in each of the...

  15. 46 CFR 119.530 - Bilge high level alarms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Bilge high level alarms. 119.530 Section 119.530... Bilge and Ballast Systems § 119.530 Bilge high level alarms. (a) Each vessel must be provided with a visual and audible alarm at the operating station to indicate a high water level in each of the...

  16. 46 CFR 182.530 - Bilge high level alarms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Bilge high level alarms. 182.530 Section 182.530... TONS) MACHINERY INSTALLATION Bilge and Ballast Systems § 182.530 Bilge high level alarms. (a) On a... operating station to indicate a high water level in each of the following normally unmanned spaces: (1)...

  17. 46 CFR 182.530 - Bilge high level alarms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Bilge high level alarms. 182.530 Section 182.530... TONS) MACHINERY INSTALLATION Bilge and Ballast Systems § 182.530 Bilge high level alarms. (a) On a... operating station to indicate a high water level in each of the following normally unmanned spaces: (1)...

  18. 46 CFR 119.530 - Bilge high level alarms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Bilge high level alarms. 119.530 Section 119.530... Bilge and Ballast Systems § 119.530 Bilge high level alarms. (a) Each vessel must be provided with a visual and audible alarm at the operating station to indicate a high water level in each of the...

  19. 46 CFR 119.530 - Bilge high level alarms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Bilge high level alarms. 119.530 Section 119.530... Bilge and Ballast Systems § 119.530 Bilge high level alarms. (a) Each vessel must be provided with a visual and audible alarm at the operating station to indicate a high water level in each of the...

  20. 46 CFR 119.530 - Bilge high level alarms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Bilge high level alarms. 119.530 Section 119.530... Bilge and Ballast Systems § 119.530 Bilge high level alarms. (a) Each vessel must be provided with a visual and audible alarm at the operating station to indicate a high water level in each of the...

  1. Fermilab Tevatron high level rf accelerating systems

    SciTech Connect

    Kerns, Q.; Kerns, C.; Miller, H.; Tawser, S.; Reid, J.; Webber, R.; Wildman, D.

    1985-06-01

    Eight tuned rf cavities have been installed and operated in the F0 straight section of the Tevatron. Their mechanical placement along the beam line enables them to be operated for colliding beams as two independent groups of four cavities, group 1-4 accelerating antiprotons and group 5-8 accelerating protons. The only difference is that the spacing between cavities 4 and 5 was increased to stay clear of the F0 colliding point. The cavities can easily be rephased by switching cables in a low-level distribution system (fan-out) so that the full accelerating capability of all eight cavities can be used during fixed target operations. Likewise, the cables from capacitive probes on each cavity gap can be switched to proper lengths and summed in a fan-back system to give an rf signal representing the amplitude and phase as ''seen by the beam,'' separately for protons and antiprotons. Such signals have been used to phase lock the Tevatron to the Main Ring for synchronous transfer.

  2. Bumblebee Pupae Contain High Levels of Aluminium

    PubMed Central

    Exley, Christopher; Rotheray, Ellen; Goulson, David

    2015-01-01

    The causes of declines in bees and other pollinators remains an on-going debate. While recent attention has focussed upon pesticides, other environmental pollutants have largely been ignored. Aluminium is the most significant environmental contaminant of recent times and we speculated that it could be a factor in pollinator decline. Herein we have measured the content of aluminium in bumblebee pupae taken from naturally foraging colonies in the UK. Individual pupae were acid-digested in a microwave oven and their aluminium content determined using transversely heated graphite furnace atomic absorption spectrometry. Pupae were heavily contaminated with aluminium giving values between 13.4 and 193.4 μg/g dry wt. and a mean (SD) value of 51.0 (33.0) μg/g dry wt. for the 72 pupae tested. Mean aluminium content was shown to be a significant negative predictor of average pupal weight in colonies. While no other statistically significant relationships were found relating aluminium to bee or colony health, the actual content of aluminium in pupae are extremely high and demonstrate significant exposure to aluminium. Bees rely heavily on cognitive function and aluminium is a known neurotoxin with links, for example, to Alzheimer’s disease in humans. The significant contamination of bumblebee pupae by aluminium raises the intriguing spectre of cognitive dysfunction playing a role in their population decline. PMID:26042788

  3. Tuning of AKT-pathway by Nef and its blockade by protease inhibitors results in limited recovery in latently HIV infected T-cell line

    PubMed Central

    Kumar, Amit; Abbas, Wasim; Colin, Laurence; Khan, Kashif Aziz; Bouchat, Sophie; Varin, Audrey; Larbi, Anis; Gatot, Jean-Stéphane; Kabeya, Kabamba; Vanhulle, Caroline; Delacourt, Nadège; Pasquereau, Sébastien; Coquard, Laurie; Borch, Alexandra; König, Renate; Clumeck, Nathan; De Wit, Stephane; Rohr, Olivier; Rouzioux, Christine; Fulop, Tamas; Van Lint, Carine; Herbein, Georges

    2016-01-01

    Akt signaling plays a central role in many biological processes, which are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. We found that Akt interacts with HIV-1 Nef protein. In primary T cells treated with exogenous Nef or acutely infected with Nef-expressing HIV-1 in vitro, Akt became phosphorylated on serine473 and threonine308. In vitro, Akt activation mediated by Nef in T-cells was blocked by HIV protease inhibitors (PI), but not by reverse transcriptase inhibitors (RTI). Ex vivo, we found that the Akt pathway is hyperactivated in peripheral blood lymphocytes (PBLs) from cART naïve HIV-1-infected patients. PBLs isolated from PI-treated patients, but not from RTI-treated patients, exhibited decreased Akt activation, T-cell proliferation and IL-2 production. We found that PI but not RTI can block HIV-1 reactivation in latently infected J-Lat lymphoid cells stimulated with various stimuli. Using luciferase measurement, we further confirmed that Nef-mediated reactivation of HIV-1 from latency in 1G5 cells was blocked by PI parallel to decreased Akt activation. Our results indicate that PI-mediated blockade of Akt activation could impact the HIV-1 reservoir and support the need to further assess the therapeutic use of HIV-1 PI in order to curtail latently infected cells in HIV-1-infected patients. PMID:27076174

  4. Tuning of AKT-pathway by Nef and its blockade by protease inhibitors results in limited recovery in latently HIV infected T-cell line.

    PubMed

    Kumar, Amit; Abbas, Wasim; Colin, Laurence; Khan, Kashif Aziz; Bouchat, Sophie; Varin, Audrey; Larbi, Anis; Gatot, Jean-Stéphane; Kabeya, Kabamba; Vanhulle, Caroline; Delacourt, Nadège; Pasquereau, Sébastien; Coquard, Laurie; Borch, Alexandra; König, Renate; Clumeck, Nathan; De Wit, Stephane; Rohr, Olivier; Rouzioux, Christine; Fulop, Tamas; Van Lint, Carine; Herbein, Georges

    2016-01-01

    Akt signaling plays a central role in many biological processes, which are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. We found that Akt interacts with HIV-1 Nef protein. In primary T cells treated with exogenous Nef or acutely infected with Nef-expressing HIV-1 in vitro, Akt became phosphorylated on serine(473) and threonine(308). In vitro, Akt activation mediated by Nef in T-cells was blocked by HIV protease inhibitors (PI), but not by reverse transcriptase inhibitors (RTI). Ex vivo, we found that the Akt pathway is hyperactivated in peripheral blood lymphocytes (PBLs) from cART naïve HIV-1-infected patients. PBLs isolated from PI-treated patients, but not from RTI-treated patients, exhibited decreased Akt activation, T-cell proliferation and IL-2 production. We found that PI but not RTI can block HIV-1 reactivation in latently infected J-Lat lymphoid cells stimulated with various stimuli. Using luciferase measurement, we further confirmed that Nef-mediated reactivation of HIV-1 from latency in 1G5 cells was blocked by PI parallel to decreased Akt activation. Our results indicate that PI-mediated blockade of Akt activation could impact the HIV-1 reservoir and support the need to further assess the therapeutic use of HIV-1 PI in order to curtail latently infected cells in HIV-1-infected patients. PMID:27076174

  5. 40 CFR 227.30 - High-level radioactive waste.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false High-level radioactive waste. 227.30 Section 227.30 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from...

  6. 40 CFR 227.30 - High-level radioactive waste.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false High-level radioactive waste. 227.30 Section 227.30 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from...

  7. 40 CFR 227.30 - High-level radioactive waste.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true High-level radioactive waste. 227.30 Section 227.30 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from...

  8. 40 CFR 227.30 - High-level radioactive waste.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false High-level radioactive waste. 227.30 Section 227.30 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from...

  9. Analysis of Cyberbullying Sensitivity Levels of High School Students and Their Perceived Social Support Levels

    ERIC Educational Resources Information Center

    Akturk, Ahmet Oguz

    2015-01-01

    Purpose: The purpose of this paper is to determine the cyberbullying sensitivity levels of high school students and their perceived social supports levels, and analyze the variables that predict cyberbullying sensitivity. In addition, whether cyberbullying sensitivity levels and social support levels differed according to gender was also…

  10. A Framework for Translating a High Level Security Policy into Low Level Security Mechanisms

    NASA Astrophysics Data System (ADS)

    Hassan, Ahmed A.; Bahgat, Waleed M.

    2010-01-01

    Security policies have different components; firewall, active directory, and IDS are some examples of these components. Enforcement of network security policies to low level security mechanisms faces some essential difficulties. Consistency, verification, and maintenance are the major ones of these difficulties. One approach to overcome these difficulties is to automate the process of translation of high level security policy into low level security mechanisms. This paper introduces a framework of an automation process that translates a high level security policy into low level security mechanisms. The framework is described in terms of three phases; in the first phase all network assets are categorized according to their roles in the network security and relations between them are identified to constitute the network security model. This proposed model is based on organization based access control (OrBAC). However, the proposed model extend the OrBAC model to include not only access control policy but also some other administrative security policies like auditing policy. Besides, the proposed model enables matching of each rule of the high level security policy with the corresponding ones of the low level security policy. Through the second phase of the proposed framework, the high level security policy is mapped into the network security model. The second phase could be considered as a translation of the high level security policy into an intermediate model level. Finally, the intermediate model level is translated automatically into low level security mechanism. The paper illustrates the applicability of proposed approach through an application example.

  11. Mucosal Humoral Immune Response to SIVmac239∆nef Vaccination and Vaginal Challenge.

    PubMed

    Zeng, Ming; Smith, Anthony J; Shang, Liang; Wietgrefe, Stephen W; Voss, James E; Carlis, John V; Li, Qingsheng; Piatak, Michael; Lifson, Jeffrey D; Johnson, R Paul; Haase, Ashley T

    2016-03-15

    Live attenuated vaccines such as SIV with a deleted nef gene have provided the most robust protection against subsequent vaginal challenge with wild-type (WT) SIV in the SIV-rhesus macaque model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV-1 vaccine. One such prechallenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG Abs reacting with the viral envelope glycoprotein trimeric gp41; 2) produced by plasma cells in the submucosa and ectopic tertiary lymphoid follicles in the ectocervix and vagina; and 3) concentrated on the path of virus entry by the neonatal FcR in the overlying epithelium. We now examine the mucosal production of the Ab component of this system after vaginal challenge. We show that vaginal challenge immediately elicits striking increases in plasma cells not only in the female reproductive tract but also at other mucosal sites, and that these increases correlate with low but persistent replication at mucosal sites. We describe vaginal ectopic follicles that are structurally and functionally organized similar to follicles in secondary lymphoid organs, and we provide inferential evidence for a key role of the female reproductive tract epithelium in facilitating Ab production, affinity maturation, and class switch recombination. Vaccination thus accesses an epithelial-immune system axis in the female reproductive tract to respond to exposure to mucosal pathogens. Designing strategies to mimic this system could advance development of an effective HIV-1 vaccine. PMID:26864031

  12. Low-level awareness accompanies "unconscious" high-level processing during continuous flash suppression.

    PubMed

    Gelbard-Sagiv, Hagar; Faivre, Nathan; Mudrik, Liad; Koch, Christof

    2016-01-01

    The scope and limits of unconscious processing are a matter of ongoing debate. Lately, continuous flash suppression (CFS), a technique for suppressing visual stimuli, has been widely used to demonstrate surprisingly high-level processing of invisible stimuli. Yet, recent studies showed that CFS might actually allow low-level features of the stimulus to escape suppression and be consciously perceived. The influence of such low-level awareness on high-level processing might easily go unnoticed, as studies usually only probe the visibility of the feature of interest, and not that of lower-level features. For instance, face identity is held to be processed unconsciously since subjects who fail to judge the identity of suppressed faces still show identity priming effects. Here we challenge these results, showing that such high-level priming effects are indeed induced by faces whose identity is invisible, but critically, only when a lower-level feature, such as color or location, is visible. No evidence for identity processing was found when subjects had no conscious access to any feature of the suppressed face. These results suggest that high-level processing of an image might be enabled by-or co-occur with-conscious access to some of its low-level features, even when these features are not relevant to the processed dimension. Accordingly, they call for further investigation of lower-level awareness during CFS, and reevaluation of other unconscious high-level processing findings. PMID:26756173

  13. Process for solidifying high-level nuclear waste

    DOEpatents

    Ross, Wayne A.

    1978-01-01

    The addition of a small amount of reducing agent to a mixture of a high-level radioactive waste calcine and glass frit before the mixture is melted will produce a more homogeneous glass which is leach-resistant and suitable for long-term storage of high-level radioactive waste products.

  14. 46 CFR 153.409 - High level alarms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false High level alarms. 153.409 Section 153.409 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Gauging Systems § 153.409 High level alarms. When Table...

  15. Physical Activity Levels in Portuguese High School Physical Education

    ERIC Educational Resources Information Center

    Marmeleira, Jose Francisco Filipe; Aldeias, Nuno Micael Carrasqueira; da Graca, Pedro Miguel dos Santos Medeira

    2012-01-01

    The main aim of this study was to evaluate the physical activity (PA) levels of high school Portuguese students during physical education (PE) and investigate the association of PA levels with students' goal orientation and intrinsic motivation. Forty-six students from three high schools participated. Heart rate telemetry and pedometry were used…

  16. Predictors of Placement in Lower Level versus Higher Level High School Mathematics

    ERIC Educational Resources Information Center

    Archbald, Doug; Farley-Ripple, Elizabeth N.

    2012-01-01

    Educators and researchers have long been interested in determinants of access to honors level and college prep courses in high school. Factors influencing access to upper level mathematics courses are particularly important because of the hierarchical and sequential nature of this subject and because students who finish high school with only lower…

  17. Stable superconducting magnet. [high current levels below critical temperature

    NASA Technical Reports Server (NTRS)

    Boom, R. W. (Inventor)

    1967-01-01

    Operation of a superconducting magnet is considered. A method is described for; (1) obtaining a relatively high current in a superconducting magnet positioned in a bath of a gas refrigerant; (2) operating a superconducting magnet at a relatively high current level without training; and (3) operating a superconducting magnet containing a plurality of turns of a niobium zirconium wire at a relatively high current level without training.

  18. Reference commercial high-level waste glass and canister definition.

    SciTech Connect

    Slate, S.C.; Ross, W.A.; Partain, W.L.

    1981-09-01

    This report presents technical data and performance characteristics of a high-level waste glass and canister intended for use in the design of a complete waste encapsulation package suitable for disposal in a geologic repository. The borosilicate glass contained in the stainless steel canister represents the probable type of high-level waste product that will be produced in a commercial nuclear-fuel reprocessing plant. Development history is summarized for high-level liquid waste compositions, waste glass composition and characteristics, and canister design. The decay histories of the fission products and actinides (plus daughters) calculated by the ORIGEN-II code are presented.

  19. Human immunodeficiency virus type 1 Nef does not alter T-cell sensitivity to antigen-specific stimulation.

    PubMed Central

    Page, K A; van Schooten, W C; Feinberg, M B

    1997-01-01

    We have developed an in vitro model to study the influence that human immunodeficiency virus type 1 (HIV-1) may have on the ability of T cells to respond to antigenic challenge. We have examined consequences of HIV-1 gene expression on T-cell activation in antigen-dependent T cells that have stably integrated copies of replication-defective proviral HIV-1. Virus production by HIV-infected, antigen-dependent T cells was induced in response to antigenic stimulation and then decreased as infected cells returned to a state of quiescence. Contrary to the predictions of models proposing that Nef alters signal transduction pathways in T lymphocytes and thereby alters cellular activation, Nef expression in antigen-dependent T-cell clones did not influence their proliferative responses to low or intermediate concentrations of antigen and did not affect other measures of T-cell activation, such as induction of interleukin 2 receptor alpha-chain expression and cytokine production. In addition, we found no evidence for alteration of T-cell responsiveness to antigen by the gag, pol, vif, tat, or rev gene of HIV-1. PMID:9094653

  20. Production of recombinant HIV-1 nef protein using different expression host systems: a techno-economical comparison.

    PubMed

    Vermasvuori, Raisa; Koskinen, Jani; Salonen, Katri; Sirén, Noora; Weegar, Jan; Dahlbacka, John; Kalkkinen, Nisse; von Weymarn, Niklas

    2009-01-01

    Three popular expression host systems Escherichia coli, Pichia pastoris and Drosophila S2 were analyzed techno-economically using HIV-1 Nef protein as the model product. On scale of 100 mg protein, the labor costs corresponded to 52-83% of the manufacturing costs. When analyzing the cost impact of the different phases (strain/cell line construction, bioreactor production, and primary purification), we found that with the microbial host systems the strain construction phase was most significant generating 56% (E. coli) and 72% (P. pastoris) of the manufacturing costs, whereas with the Drosophila S2 system the cell line construction and bioreactor production phases were equally significant (46 and 47% of the total costs, respectively). With different titers and production goal of 100 mg of Nef protein, the costs of P. pastoris and Drosophila S2 systems were about two and four times higher than the respective costs of the E. coli system. When equal titers and bioreactor working volumes (10 L) were assumed for all three systems, the manufacturing costs of the bioreactor production of the P. pastoris and Drosophila S2 systems were about two and 2.5 times higher than the respective costs of the E. coli system. PMID:19224559

  1. Neptunium estimation in dissolver and high-level-waste solutions

    SciTech Connect

    Pathak, P.N.; Prabhu, D.R.; Kanekar, A.S.; Manchanda, V.K.

    2008-07-01

    This papers deals with the optimization of the experimental conditions for the estimation of {sup 237}Np in spent-fuel dissolver/high-level waste solutions using thenoyltrifluoroacetone as the extractant. (authors)

  2. HIGH-LEVEL OZONE DISINFECTION OF MUNICIPAL WASTEWATER EFFLUENTS

    EPA Science Inventory

    A 20 month operating experimental program was conducted at Marlborough, Massachusetts to evaluate the feasibility, engineering, and economic aspects of achieving high levels of effluent disinfection with ozone. The ozone research pilot facility was designed to operate at a consta...

  3. Field Trips as Cognitive Motivators for High Level Science Learning

    ERIC Educational Resources Information Center

    Hurley, Marlene M.

    2006-01-01

    Using a composite example of field trips from several years of traveling to Yellowstone with high school biology students, the author illustrates how to raise the cognitive level of science instruction and student learning through science field trips. The author examines what teachers can do to raise the level of both teaching and learning in all…

  4. Decision Document for Heat Removal from High Level Waste Tanks

    SciTech Connect

    WILLIS, W.L.

    2000-07-31

    This document establishes the combination of design and operational configurations that will be used to provide heat removal from high-level waste tanks during Phase 1 waste feed delivery to prevent the waste temperature from exceeding tank safety requirement limits. The chosen method--to use the primary and annulus ventilation systems to remove heat from the high-level waste tanks--is documented herein.

  5. 46 CFR 182.530 - Bilge high level alarms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Bilge high level alarms. 182.530 Section 182.530 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) MACHINERY INSTALLATION Bilge and Ballast Systems § 182.530 Bilge high level alarms. (a) On a vessel of at least 7.9 meters (26 feet) in...

  6. High-Level Waste System Process Interface Description

    SciTech Connect

    d'Entremont, P.D.

    1999-01-14

    The High-Level Waste System is a set of six different processes interconnected by pipelines. These processes function as one large treatment plant that receives, stores, and treats high-level wastes from various generators at SRS and converts them into forms suitable for final disposal. The three major forms are borosilicate glass, which will be eventually disposed of in a Federal Repository, Saltstone to be buried on site, and treated water effluent that is released to the environment.

  7. Effect of high fluoride and high fat on serum lipid levels and oxidative stress in rabbits.

    PubMed

    Sun, Liyan; Gao, Yanhui; Zhang, Wei; Liu, Hui; Sun, Dianjun

    2014-11-01

    The purpose of this study was to explore the effects of high fluoride and high fat on triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total antioxidant capacity (T-AOC), lipid peroxide (LPO) and malondialdehyde (MDA) in rabbits. A factorial experimental design was used, with two factors (fluoride and fat) and three levels. Seventy-two male rabbits were randomly assigned into nine groups according to initial weight and serum lipid levels. The rabbits were fed with basic feed, moderate fat feed or high fat feed and drank tap water, fluoridated water at levels of 50 and 100mgfluorion/L freely. Biological materials were collected after 5 months, and serum lipid, T-AOC, LPO, and MDA levels were then measured. Using these data, the separate and interactive effects of high fluoride and high fat were analyzed. High fluoride and high fat both increased serum levels of TC, HDL-C and LDL-C significantly (P<0.05), and there was also a synergistic effect between high fluoride and high fat (P<0.05). High fluoride and high fat had different effects on TG levels: high fat significantly increased TG levels (P<0.01) whereas high fluoride had nothing to do with TG levels (P>0.05). High fat significantly elevated LPO and MDA levels and lowered T-AOC levels in serum (P<0.05). Similarly, high fluoride significantly increased LPO and MDA levels in serum (P<0.05). However, there was no interactive effect between high fat and high fluoride on these indexes. In summary, high fluoride and high fat increased serum TC and LDL-C levels individually and synergistically, and this would cause and aggravate hypercholesterolemia in rabbits. At the same time, high fluoride and high fat both made the accumulation of product of oxidative stress in experimental animals. PMID:25461561

  8. Comparison of HIV-1 nef and gag Variations and Host HLA Characteristics as Determinants of Disease Progression among HIV-1 Vertically Infected Kenyan Children

    PubMed Central

    Saina, Matilda Chelimo; Bi, Xiuqiong; Lihana, Raphael; Lwembe, Raphael; Ishizaki, Azumi; Panikulam, Annie; Palakudy, Tresa; Musoke, Rachel; Owens, Mary; Songok, Elijah Maritim; Ichimura, Hiroshi

    2015-01-01

    Objectives Disease progression varies among HIV-1-infected individuals. The present study aimed to explore possible viral and host factors affecting disease progression in HIV-1-infected children. Methods Since 2000, 102 HIV-1 vertically-infected children have been followed-up in Kenya. Here we studied 29 children (15 male/14 female) who started antiretroviral treatment at <5 years of age (rapid progressors; RP), and 32 (17 male/15 female) who started at >10 years of age (slow progressors; SP). Sequence variations in the HIV-1 gag and nef genes and the HLA class I-related epitopes were compared between the two groups. Results Based on nef sequences, HIV-1 subtypes A1/D were detected in 62.5%/12.5% of RP and 66.7%/20% of SP, with no significant difference in subtype distribution between groups (p = 0.8). In the ten Nef functional domains, only the PxxP3 region showed significantly greater variation in RP (33.3%) than SP (7.7%, p = 0.048). Gag sequences did not significantly differ between groups. The reportedly protective HLA-A alleles, A*74:01, A*32:01 and A*26, were more commonly observed in SP (50.0%) than RP (11.1%, p = 0.010), whereas the reportedly disease-susceptible HLA-B*45:01 was more common in RP (33.3%) than SP (7.4%, p = 0.045). Compared to RP, SP showed a significantly higher median number of predicted HLA-B-related 12-mer epitopes in Nef (3 vs. 2, p = 0.037), HLA-B-related 11-mer epitopes in Gag (2 vs. 1, p = 0.029), and HLA-A-related 9-mer epitopes in Gag (4 vs. 1, p = 0.051). SP also had fewer HLA-C-related epitopes in Nef (median 4 vs. 5, p = 0.046) and HLA-C-related 11-mer epitopes in Gag (median 1 vs. 1.5, p = 0.044) than RP. Conclusions Compared to rapid progressors, slow progressors had more protective HLA-A alleles and more HLA-B-related epitopes in both the Nef and Gag proteins. These results suggest that the host factor HLA plays a stronger role in disease progression than the Nef and Gag sequence variations in HIV-1-infected Kenyan children

  9. The effect of high altitude on nasal nitric oxide levels.

    PubMed

    Altundag, Aytug; Salihoglu, Murat; Cayonu, Melih; Cingi, Cemal; Tekeli, Hakan; Hummel, Thomas

    2014-09-01

    The aim of the present study was to investigate whether nasal nitric oxide (nNO) levels change in relation to high altitude in a natural setting where the weather conditions were favorable. The present study included 41 healthy volunteers without a history of acute rhinosinusitis within 3 weeks and nasal polyposis. The study group consisted of 31 males (76 %) and 10 females (24 %) and the mean age of the study population was 38 ± 10 years. The volunteers encamped for 2 days in a mountain village at an altitude of 1,500 m above sea level (masl) and proceeded to highlands at an altitude of 2,200 masl throughout the day. The measurements of nNO were done randomly, either first at the mountain village or at sea level. Each participant had nNO values both at sea level and at high altitude at the end of the study. The nNO values of sea level and high altitude were compared to investigate the effect of high altitude on nNO levels. The mean of average nNO measurements at the high altitude was 74.2 ± 41 parts-per-billion (ppb) and the mean of the measurements at sea level was 93.4 ± 45 ppb. The change in nNO depending on the altitude level was statistically significant (p < 0.001). The current investigation showed that nNO levels were decreased at high altitude even if the weather conditions were favorable, such as temperature, humidity, and wind. PMID:24972544

  10. Does high serum uric acid level cause aspirin resistance?

    PubMed

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage. PMID:26656902

  11. An overview of very high level software design methods

    NASA Technical Reports Server (NTRS)

    Asdjodi, Maryam; Hooper, James W.

    1988-01-01

    Very High Level design methods emphasize automatic transfer of requirements to formal design specifications, and/or may concentrate on automatic transformation of formal design specifications that include some semantic information of the system into machine executable form. Very high level design methods range from general domain independent methods to approaches implementable for specific applications or domains. Applying AI techniques, abstract programming methods, domain heuristics, software engineering tools, library-based programming and other methods different approaches for higher level software design are being developed. Though one finds that a given approach does not always fall exactly in any specific class, this paper provides a classification for very high level design methods including examples for each class. These methods are analyzed and compared based on their basic approaches, strengths and feasibility for future expansion toward automatic development of software systems.

  12. Student Achievement Levels Raised at Chandler High School.

    ERIC Educational Resources Information Center

    Profiles, Programs & Products, 1983

    1983-01-01

    Chandler (Arizona) High School has reported a dramatic increase in student achievement levels since implementing a number of management, curriculum, and discipline policy changes. Among the program changes that contributed to these gains are: (1) creation of a positive school environment, with high expectations for teachers, emphasis on high…

  13. A Testing Instrument for High School Arabic, Level III.

    ERIC Educational Resources Information Center

    Wolowelsky, Joel B.

    The Arabic language examination was designed for Jewish immigrants from Syria wishing to satisfy New York State language requirements for high school graduation by indicating their proficiency in Arabic. The test is essentially a translation of a state test of Hebrew, and is intended to test Arabic at the third-year high school level. The…

  14. Determination of the nuclear level density at high excitation energy

    SciTech Connect

    Chbihi, A.; Sobotka, L.G.; Nicolis, N.G.; Sarantites, D.G.; Stracener, D.W.; Majka, Z. ); Hensley, D.C.; Beene, J.R.; Halbert, M.L. )

    1991-02-01

    Evaporation simulations are presented to illustrate the problems associated with the determination of the nuclear level density constant at high excitation energy from evaporation spectra. The methods of using either the total (whole chain) spectra or the difference (from two different initial excitation energies) spectra are discussed. Data from the study of the reaction 701 MeV {sup 28}Si+{sup 100}Mo are presented and both methods are used to extract the level density constant. We find that in order to reproduce the slopes of the light particle spectra the level density constant must have a value near 1/10{ital A}-- 1 / 11 {ital A} for excited nuclei with statistical temperatures in the range of 3.5 to 5.5 MeV. This presumes that the only parameter adjustment required to treat the decay of highly exited nuclei is the level density constant. If this is so, the shapes of the evaporation spectra imply a reduction in the level density constant from the value required to explain the decay of less highly excited nuclei, a conclusion reached by others. However, the reduced level density constant leads to an overproduction of deuterons and tritons. This suggests that a more complicated set of parameter adjustments may be required to treat the decay of highly excited nuclei.

  15. An Investigation of Source and Receiver Apprehension at the Junior High, Senior High and College Levels.

    ERIC Educational Resources Information Center

    McDowell, Earl E.; McDowell, Carlene E.

    1978-01-01

    The Personal Report of Communication Apprehension and the Receiver Apprehension Test are used to determine the relationship between speech and listening apprehension at each educational level (junior high, senior high, and college); differences among educational levels and between sexes; and the interaction effect of educational level and sex. (JF)

  16. Oxidative Stress Levels in Aqueous Humor from High Myopic Patients

    PubMed Central

    Kim, Eun Bi; Kim, Ha Kyoung; Hyon, Joon Young; Wee, Won Ryang

    2016-01-01

    Purpose To compare oxidative stress status in the aqueous humor of highly myopic eyes and control eyes. Methods Aqueous humor samples were collected from 15 highly myopic eyes (high myopia group) and 23 cataractous eyes (control group) during cataract surgery. Central corneal thickness, corneal endothelial cell density, hexagonality of corneal endothelial cells, and cell area of corneal endothelial cells were measured using specular microscopy. Axial length was measured using ultrasound biometry. 8-Hydroxydeoxyguanosine (8-OHdG) and malondialdehyde levels were measured using enzyme-linked immunosorbent assay. Results 8-OHdG level was lower in the aqueous humor of myopic patients than in that of control group (p = 0.014) and was positively correlated with central corneal thickness and negatively correlated with axial length (r = 0.511, p = 0.02; r = -0.382, p < 0.001). There was no correlation between 8-OHdG level and corneal endothelial cell density, hexagonality, or cell area. Malondialdehyde level did not show any correlation with any parameters evaluated. Conclusions 8-OHdG might be a sensitive biomarker for evaluating oxidative stress status in the eye. Oxidative stress level was lower in the aqueous humor of highly myopic eyes compared to that in control eyes, which indicates lower metabolic activity in these eyes. PMID:27247516

  17. High Level Waste (HLW) Feed Process Control Strategy

    SciTech Connect

    STAEHR, T.W.

    2000-06-14

    The primary purpose of this document is to describe the overall process control strategy for monitoring and controlling the functions associated with the Phase 1B high-level waste feed delivery. This document provides the basis for process monitoring and control functions and requirements needed throughput the double-shell tank system during Phase 1 high-level waste feed delivery. This document is intended to be used by (1) the developers of the future Process Control Plan and (2) the developers of the monitoring and control system.

  18. Photovoltaic (PV) Impact Assessment for Very High Penetration Levels

    SciTech Connect

    Cheng, Danling; Mather, Barry A.; Seguin, Richard; Hambrick, Joshua; Broadwater, Robert P.

    2016-01-01

    This paper describes a granular approach for investigating the impacts of very high photovoltaic (PV) generation penetration. Studies on two real-world distribution feeders connected to PV plants are presented. The studies include both steady-state and time-series power flow analyses, which include the effects of solar variability. The goal of the study is to predict the effects of increasing levels of PV generation as it reaches very high penetration levels. The loss and return of generation with and without regulation is simulated to capture short-term problems such as voltage fluctuations. Impact results from the analyses are described along with potential mitigations.

  19. Disposal of high-level nuclear waste in space

    NASA Astrophysics Data System (ADS)

    Coopersmith, Jonathan

    1992-08-01

    A solution of launching high-level nuclear waste into space is suggested. Disposal in space includes solidifying the wastes, embedding them in an explosion-proof vehicle, and launching it into earth orbit, and then into a solar orbit. The benefits of such a system include not only the safe disposal of high-level waste but also the establishment of an infrastructure for large-scale space exploration and development. Particular attention is given to the wide range of technical choices along with the societal, economic, and political factors needed for success.

  20. Sterilization, high-level disinfection, and environmental cleaning.

    PubMed

    Rutala, William A; Weber, David J

    2011-03-01

    Failure to perform proper disinfection and sterilization of medical devices may lead to introduction of pathogens, resulting in infection. New techniques have been developed for achieving high-level disinfection and adequate environmental cleanliness. This article examines new technologies for sterilization and high-level disinfection of critical and semicritical items, respectively, and because semicritical items carry the greatest risk of infection, the authors discuss reprocessing semicritical items such as endoscopes and automated endoscope reprocessors, endocavitary probes, prostate biopsy probes, tonometers, laryngoscopes, and infrared coagulation devices. In addition, current issues and practices associated with environmental cleaning are reviewed. PMID:21315994

  1. High level radioactive waste management facility design criteria

    SciTech Connect

    Sheikh, N.A.; Salaymeh, S.R.

    1993-10-01

    This paper discusses the engineering systems for the structural design of the Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS). At the DWPF, high level radioactive liquids will be mixed with glass particles and heated in a melter. This molten glass will then be poured into stainless steel canisters where it will harden. This process will transform the high level waste into a more stable, manageable substance. This paper discuss the structural design requirements for this unique one of a kind facility. A special emphasis will be concentrated on the design criteria pertaining to earthquake, wind and tornado, and flooding.

  2. The Use of ARTEMIS with High-Level Applications

    SciTech Connect

    B. A. Bowling; H. Shoaee; S. Witherspoon

    1995-10-01

    ARTEMIS is an online accelerator modeling server developed at CEBAF. One of the design goals of ARTEMIS was to provide an integrated modeling environment for high- level accelerator diagnostic and control applications such as automated beam steering, Linac Energy management (LEM) and the fast feedback system. This report illustrates the use of ARTEMIS in these applications as well as the application interface using the EPICS cdev device support API. Concentration is placed on the design and implementation aspects of high- level applications which utilize the ARTEMIS server for information on beam dynamics. Performance benchmarks for various model operations provided by ARTEMIS are also discussed.

  3. Final report on cermet high-level waste forms

    SciTech Connect

    Kobisk, E.H.; Quinby, T.C.; Aaron, W.S.

    1981-08-01

    Cermets are being developed as an alternate method for the fixation of defense and commercial high level radioactive waste in a terminal disposal form. Following initial feasibility assessments of this waste form, consisting of ceramic particles dispersed in an iron-nickel base alloy, significantly improved processing methods were developed. The characterization of cermets has continued through property determinations on samples prepared by various methods from a variety of simulated and actual high-level wastes. This report describes the status of development of the cermet waste form as it has evolved since 1977. 6 tables, 18 figures.

  4. MMP for moduli of sheaves on K3s via wall-crossing: nef and movable cones, Lagrangian fibrations

    NASA Astrophysics Data System (ADS)

    Bayer, Arend; Macrì, Emanuele

    2014-12-01

    We use wall-crossing with respect to Bridgeland stability conditions to systematically study the birational geometry of a moduli space M of stable sheaves on a K3 surface X: 1. We describe the nef cone, the movable cone, and the effective cone of M in terms of the Mukai lattice of X. 2. We establish a long-standing conjecture that predicts the existence of a birational Lagrangian fibration on M whenever M admits an integral divisor class D of square zero (with respect to the Beauville-Bogomolov form). These results are proved using a natural map from the space of Bridgeland stability conditions Stab(X) to the cone Mov(X) of movable divisors on M; this map relates wall-crossing in Stab(X) to birational transformations of M. In particular, every minimal model of M appears as a moduli space of Bridgeland-stable objects on X.

  5. Low voltage to high voltage level shifter and related methods

    NASA Technical Reports Server (NTRS)

    Mentze, Erik J. (Inventor); Hess, Herbert L. (Inventor); Buck, Kevin M. (Inventor); Cox, David F. (Inventor)

    2006-01-01

    A shifter circuit comprises a high and low voltage buffer stages and an output buffer stage. The high voltage buffer stage comprises multiple transistors arranged in a transistor stack having a plurality of intermediate nodes connecting individual transistors along the stack. The transistor stack is connected between a voltage level being shifted to and an input voltage. An inverter of this stage comprises multiple inputs and an output. Inverter inputs are connected to a respective intermediate node of the transistor stack. The low voltage buffer stage has an input connected to the input voltage and an output, and is operably connected to the high voltage buffer stage. The low voltage buffer stage is connected between a voltage level being shifted away from and a lower voltage. The output buffer stage is driven by the outputs of the high voltage buffer stage inverter and the low voltage buffer stage.

  6. Modeling future high-resolution dynamic sea level change

    NASA Astrophysics Data System (ADS)

    Brunnabend, Sandra-Esther; Dijkstra, Henk A.; Kliphuis, Michael A.; van Werkhoven, Ben; Bal, Henri E.; van Meersbergen, Maarten; Seinstra, Frank; Maassen, Jason

    2015-04-01

    Different studies have shown that resolving ocean eddies and representing boundary currents are of major importance when simulating changes in dynamic sea level on regional scale. Therefore, we use the strongly eddying global model version of the Parallel Ocean Program to simulate high-resolution future (up to the year 2100) sea surface height variations (SSH) under the SRES-A1B atmospheric forcing scenario. Results show dynamic sea level changes in the Southern Ocean that are caused by the southward shift in the westerly winds. The warming ocean (global mean sea surface temperature rises by about 2°C over the period 2000-2100) leads to a strong reduction of the Atlantic Meridional Overturning Circulation (AMOC). The magnitude of this reduction is affected by a feedback involving the heat transport to the sub-polar gyre region and evaporation over the North Atlantic region. The ocean circulation changes cause regional deviations from global mean sea level change in the North Atlantic. At coastal regions of eastern North America, dynamic sea level change leads to a positive deviation from global mean sea level change in the order of several decimeters. In the sub-polar gyre region a negative deviation from global mean sea level occurs. In the western North Atlantic, not only mean regional sea level is changed but also its variability, caused by shifted eddy pathways. This leads to a change in the frequency distribution of SSH anomalies, which has important consequences for regional sea level extremes.

  7. The tracking of high level waste shipments-TRANSCOM system

    SciTech Connect

    Johnson, P.E.; Joy, D.S.; Pope, R.B.

    1995-12-31

    The TRANSCOM (transportation tracking and communication) system is the U.S. Department of Energy`s (DOE`s) real-time system for tracking shipments of spent fuel, high-level wastes, and other high-visibility shipments of radioactive material. The TRANSCOM system has been operational since 1988. The system was used during FY1993 to track almost 100 shipments within the US.DOE complex, and it is accessed weekly by 10 to 20 users.

  8. Satellites to Delta n = 1 transitions between high-lying levels of multiply ionized atoms

    NASA Astrophysics Data System (ADS)

    Koenig, R.; Kolk, K.-H.; Koshelev, K. N.; Kunze, H.-J.

    1989-04-01

    In a theta pinch discharge satellites to Delta n = 1 transitions between high-lying levels are observed for the ions Si IX, Si X, and Si XI, but not for Si XII. They are identified as Delta n = 1 transitions between the corresponding levels of doubly excited systems. At high densities, the series of Rydberg levels above their respective thermal limit are collisionally coupled to their ionization limit. The intensity ratio of a transition to that of its satellite thus offers the unique possibility of measuring the ratio of the population density in the ground energy level of the next ionization stage to that in the lowest excited levels of this ion.

  9. The ATLAS Data Acquisition and High Level Trigger system

    NASA Astrophysics Data System (ADS)

    The ATLAS TDAQ Collaboration

    2016-06-01

    This paper describes the data acquisition and high level trigger system of the ATLAS experiment at the Large Hadron Collider at CERN, as deployed during Run 1. Data flow as well as control, configuration and monitoring aspects are addressed. An overview of the functionality of the system and of its performance is presented and design choices are discussed.

  10. Student Achievement Levels Climb at Ribault Senior High School.

    ERIC Educational Resources Information Center

    Profiles, Programs & Products, 1983

    1983-01-01

    Ribault (Florida) Senior High School has reported a dramatic increase in student achievement levels since implementing a comprehensive college preparation curriculum. Among the program changes that contributed to those gains are: (1) the establishment and consistent enforcement of a strong discipline program, including rules for student conduct, a…

  11. A comparison of high-level waste form characteristics

    SciTech Connect

    Salmon, R.; Notz, K.J.

    1991-01-01

    There are currently about 1055 million curies of high-level waste with a thermal output of about 2950 kilowatts (KW) at four sites in the United States: West Valley Demonstration Project (WVDP), Savannah River Site (SRS), Hanford Site (HANF), and Idaho National Engineering Laboratory (INEL). These quantities are expected to increase to about 1200 million curies and 3570 kw by the end of year 2020. Under the Nuclear Waste Policy Act, this high-level waste must ultimately be disposed of in a geologic repository. Accordingly, canisters of high-level waste immobilized in borosilicate glass or glass-ceramic mixtures are to be produced at the four sites and stored there until a repository becomes available. Data on the estimated production schedules and on the physical, chemical, and radiological characteristics of the canisters of immobilized high-level waste have been collected in OCRWM's Waste Characteristics Data Base, including recent updates an revisions. Comparisons of some of these data for the four sites are presented in this report. 14 refs., 3 tabs.

  12. 40 CFR 227.30 - High-level radioactive waste.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false High-level radioactive waste. 227.30 Section 227.30 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Definitions § 227.30...

  13. A Preview of High School Level Economic Software.

    ERIC Educational Resources Information Center

    Kincade, Jeannine H.

    The purpose of this study was to locate and evaluate high-school-level economic software compatible with an Apple II or IIe computer. To identify software, computer searches were run, bibliographies were scanned, and reviews were collected. Only software that was recommended by some outside source was included in the evaluation. The following…

  14. High level cognitive information processing in neural networks

    NASA Technical Reports Server (NTRS)

    Barnden, John A.; Fields, Christopher A.

    1992-01-01

    Two related research efforts were addressed: (1) high-level connectionist cognitive modeling; and (2) local neural circuit modeling. The goals of the first effort were to develop connectionist models of high-level cognitive processes such as problem solving or natural language understanding, and to understand the computational requirements of such models. The goals of the second effort were to develop biologically-realistic model of local neural circuits, and to understand the computational behavior of such models. In keeping with the nature of NASA's Innovative Research Program, all the work conducted under the grant was highly innovative. For instance, the following ideas, all summarized, are contributions to the study of connectionist/neural networks: (1) the temporal-winner-take-all, relative-position encoding, and pattern-similarity association techniques; (2) the importation of logical combinators into connection; (3) the use of analogy-based reasoning as a bridge across the gap between the traditional symbolic paradigm and the connectionist paradigm; and (4) the application of connectionism to the domain of belief representation/reasoning. The work on local neural circuit modeling also departs significantly from the work of related researchers. In particular, its concentration on low-level neural phenomena that could support high-level cognitive processing is unusual within the area of biological local circuit modeling, and also serves to expand the horizons of the artificial neural net field.

  15. MIXING PROCESSES IN HIGH-LEVEL WASTE TANKS

    EPA Science Inventory

    Flammable gases can be generated in DOE high-level waste tanks, including radiolytic hydrogen, and during cesium precipitation from salt solutions, benzene. Under normal operating conditions the potential for deflagration or detonation from these gases is precluded by purging and...

  16. THE XAL INFRASTRUCTURE FOR HIGH LEVEL CONTROL ROOM APPLICATIONS

    SciTech Connect

    Shishlo, Andrei P; Allen, Christopher K; Chu, Paul; Galambos, John D; Pelaia II, Tom

    2009-01-01

    XAL is a Java programming framework for building high-level control applications related to accelerator physics. The structure, details of implementation, and interaction between components, auxiliary XAL packages, and the latest modifications are discussed. A general overview of XAL applications created for the SNS project is presented.

  17. High-Level waste process and product data annotated bibliography

    SciTech Connect

    Stegen, G.E.

    1996-02-13

    The objective of this document is to provide information on available issued documents that will assist interested parties in finding available data on high-level waste and transuranic waste feed compositions, properties, behavior in candidate processing operations, and behavior on candidate product glasses made from those wastes. This initial compilation is only a partial list of available references.

  18. Rice lines with high leaf mineral nutrient levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phosphorus (P) and Potassium (K), and sometimes other mineral nutrients are often applied as fertilizer, in addition to Nitrogen, to help achieve high yields in Texas rice production. For some mineral nutrients, total levels in soil would be sufficient to support the desired rice crop growth, but th...

  19. Typewriter Modifications for Persons Who Are High-Level Quadriplegics.

    ERIC Educational Resources Information Center

    O'Reagan, James R.; And Others

    Standard, common electric typewriters are not completely suited to the needs of a high-level quadriplegic typing with a mouthstick. Experiences show that for complete control of a typewriter a mouthstick user needs the combined features of one-button correction, electric forward and reverse indexing, and easy character viewing. To modify a…

  20. The Estuary Guide. Level 3: High School. Draft.

    ERIC Educational Resources Information Center

    Alexander, Glen; And Others

    Estuaries are marine systems that serve as nurseries for animals, links in the migratory pathways, and habitat for a complex community of organisms. This curriculum guide intended for use at the high school level seeks to teach what estuaries are; provide opportunities to practice decision-making that affects estuaries; and encourage students to…

  1. The Politics of High-Level Manpower Supply in Tanzania

    ERIC Educational Resources Information Center

    Brooke-Smith, Robin

    1978-01-01

    In its policies related to high-level manpower, the Tanzanian Government attaches great importance to the university, viewing it as a key institution in its policies for national development. Describes the difficulties the administration of President Nyerere has had in using the university as a political tool and analyzes various instances of…

  2. Effective Communication: High-Level Management Receptive to Low-Level Management Ideas.

    ERIC Educational Resources Information Center

    Chressanthis, June D.; Janousek, Kelly

    Based on the premise that senior staff or high-level managers have the knowledge and experience required to make daily decisions and also have a degree of power and respect, this document proposes that these managers are in a position to be effective leaders who can and should foster an atmosphere of receptiveness for innovation and positive…

  3. High levels of plasma protein C in nephrotic syndrome.

    PubMed

    Pabinger-Fasching, I; Lechner, K; Niessner, H; Schmidt, P; Balzar, E; Mannhalter, C

    1985-02-18

    In patients with severe nephrotic syndrome determinations of plasma protein C: Ag levels (8 patients: 5 adults, 3 children) and protein C activity (3 out of 8 patients) revealed significantly elevated plasma protein C concentrations. Furthermore we observed a significant inverse correlation of protein C: Ag to AT III: Ag levels. No protein C: Ag could be detected in the urine of two patients studied. We conclude from our data, that changes of plasma protein C do not contribute to the high thrombotic tendency in nephrotic syndrome. PMID:3838827

  4. Overview of high-level waste management accomplishments

    SciTech Connect

    Lawroski, H; Berreth, J R; Freeby, W A

    1980-01-01

    Storage of power reactor spent fuel is necessary at present because of the lack of reprocessing operations particularly in the U.S. By considering the above solidification and storage scenario, there is more than reasonable assurance that acceptable, stable, low heat generation rate, solidified waste can be produced, and safely disposed. The public perception of no waste disposal solutions is being exploited by detractors of nuclear power application. The inability to even point to one overall system demonstration lends credibility to the negative assertions. By delaying the gathering of on-line information to qualify repository sites, and to implement a demonstration, the actions of the nuclear power detractors are self serving in that they can continue to point out there is no demonstration of satisfactory high-level waste disposal. By maintaining the liquid and solidified high-level waste in secure above ground storage until acceptable decay heat generation rates are achieved, by producing a compatible, high integrity, solid waste form, by providing a second or even third barrier as a compound container and by inserting the enclosed waste form in a qualified repository with spacing to assure moderately low temperature disposal conditions, there appears to be no technical reason for not progressing further with the disposal of high-level wastes and needed implementation of the complete nuclear power fuel cycle.

  5. High levels of molecular chlorine in the Arctic atmosphere

    NASA Astrophysics Data System (ADS)

    Liao, Jin; Huey, L. Gregory; Liu, Zhen; Tanner, David J.; Cantrell, Chris A.; Orlando, John J.; Flocke, Frank M.; Shepson, Paul B.; Weinheimer, Andrew J.; Hall, Samuel R.; Ullmann, Kirk; Beine, Harry J.; Wang, Yuhang; Ingall, Ellery D.; Stephens, Chelsea R.; Hornbrook, Rebecca S.; Apel, Eric C.; Riemer, Daniel; Fried, Alan; Mauldin, Roy L.; Smith, James N.; Staebler, Ralf M.; Neuman, J. Andrew; Nowak, John B.

    2014-02-01

    Chlorine radicals can function as a strong atmospheric oxidant, particularly in polar regions, where levels of hydroxyl radicals are low. In the atmosphere, chlorine radicals expedite the degradation of methane and tropospheric ozone, and the oxidation of mercury to more toxic forms. Here we present direct measurements of molecular chlorine levels in the Arctic marine boundary layer in Barrow, Alaska, collected in the spring of 2009 over a six-week period using chemical ionization mass spectrometry. We report high levels of molecular chlorine, of up to 400 pptv. Concentrations peaked in the early morning and late afternoon, and fell to near-zero levels at night. Average daytime molecular chlorine levels were correlated with ozone concentrations, suggesting that sunlight and ozone are required for molecular chlorine formation. Using a time-dependent box model, we estimate that the chlorine radicals produced from the photolysis of molecular chlorine oxidized more methane than hydroxyl radicals, on average, and enhanced the abundance of short-lived peroxy radicals. Elevated hydroperoxyl radical levels, in turn, promoted the formation of hypobromous acid, which catalyses mercury oxidation and the breakdown of tropospheric ozone. We therefore suggest that molecular chlorine exerts a significant effect on the atmospheric chemistry of the Arctic.

  6. Measuring the effects of high CO₂ levels in Caenorhabditis elegans.

    PubMed

    Zuela, Noam; Friedman, Nurit; Zaslaver, Alon; Gruenbaum, Yosef

    2014-08-01

    Carbon dioxide (CO2) is an important molecule in cell metabolism. It is also a byproduct of many physiological processes. In humans, impaired lung function and lung diseases disrupt the body's ability to dispose of CO2 and elevate its levels in the body (hypercapnia). Animal models allow further understanding of how CO2 is sensed in the body and what are the physiological responses to high CO2 levels. This information can provide new strategies in the battle against the detrimental effects of CO2 accumulation in lung diseases. The nematode Caenorhabditis elegans provides us with such a model animal due to its natural ability to sense and navigate through varying concentrations of CO2, as well as the fact that it can be genetically manipulated with ease. Here we describe the different methods used to measure the effects elevated levels of CO2 have on the molecular sensing mechanism and physiology of C. elegans. PMID:24650565

  7. A high resolution water level forecast for the German Bight

    NASA Astrophysics Data System (ADS)

    Niehüser, Sebastian; Dangendorf, Sönke; Arns, Arne; Jensen, Jürgen

    2016-04-01

    Many coastal regions worldwide are potentially endangered by storm surges which can cause disastrous damages and loss of life. Due to climate change induced sea level rise, an accumulation of such events is expected by the end of the 21th century. Therefore, advanced storm surge warnings are needed to be prepared when another storm surge hits the coast. In the shallow southeastern North Sea these storm surge warnings are nowadays routinely provided for selected tide gauge locations along a coastline through state-of-the-art forecast systems, which are based on a coupled system of empirical tidal predictions and numerical storm surge forecasts. Along the German North Sea coastline, the Federal Maritime and Hydrographic Agency in cooperation with the German Weather Service is responsible for the storm surge warnings. They provide accurate, high frequency and real-time water level forecasts for up to six days ahead at selected tide gauge sites via internet, telephone and broadcast. Since water levels along the German North Sea coastline are dominated by shallow water effects and a very complex bathymetric structure of the seabed, the pointwise forecast is not necessarily transferable to un-gauged areas between the tide gauges. Here we aim to close this existing gap and develop water level forecasts with a high spatial (continuously with a resolution of at least 1 kilometer) as well as a high temporal (at least 15-minute values) resolution along the entire German North Sea coastline. We introduce a new methodology for water level forecasts which combines empirical or statistical and numerical models. While the tidal forecast is performed by non-parametric interpolation techniques between un-gauged and gauged sites, storm surges are estimated on the basis of statistical/empirical storm surge formulas taken from a numerical model hindcast. The procedure will be implemented in the operational mode forced with numerical weather forecasts.

  8. High-level waste management technology program plan

    SciTech Connect

    Harmon, H.D.

    1995-01-01

    The purpose of this plan is to document the integrated technology program plan for the Savannah River Site (SRS) High-Level Waste (HLW) Management System. The mission of the SRS HLW System is to receive and store SRS high-level wastes in a see and environmentally sound, and to convert these wastes into forms suitable for final disposal. These final disposal forms are borosilicate glass to be sent to the Federal Repository, Saltstone grout to be disposed of on site, and treated waste water to be released to the environment via a permitted outfall. Thus, the technology development activities described herein are those activities required to enable successful accomplishment of this mission. The technology program is based on specific needs of the SRS HLW System and organized following the systems engineering level 3 functions. Technology needs for each level 3 function are listed as reference, enhancements, and alternatives. Finally, FY-95 funding, deliverables, and schedules are s in Chapter IV with details on the specific tasks that are funded in FY-95 provided in Appendix A. The information in this report represents the vision of activities as defined at the beginning of the fiscal year. Depending on emergent issues, funding changes, and other factors, programs and milestones may be adjusted during the fiscal year. The FY-95 SRS HLW technology program strongly emphasizes startup support for the Defense Waste Processing Facility and In-Tank Precipitation. Closure of technical issues associated with these operations has been given highest priority. Consequently, efforts on longer term enhancements and alternatives are receiving minimal funding. However, High-Level Waste Management is committed to participation in the national Radioactive Waste Tank Remediation Technology Focus Area. 4 refs., 5 figs., 9 tabs.

  9. TE-domestication and horizontal transfer in a putative Nef-AP1mu mimic of HLA-A cytoplasmic domain re-trafficking.

    PubMed

    Murray, Joseph S; Murray, Elaina H

    2016-01-01

    Genes of the major histocompatibility complex (MHC; also called HLA in human) are polymorphic elements in the genomes of sharks to humans. Class-I and class-II MHC loci appear responsible for much of the genetic linkage to myriad disease states via the capacity to bind short (~8-15 a.a.) peptides of a given pathogen's proteome, or in some cases, the altered proteomes of cancerous cells, and even (in autoimmunity) certain nominal 'self' peptides (Janeway, 2004).(1) Unfortunately, little is known about how the canonical structure of the MHC-I/-II peptide-presenting gene evolved, particularly since beyond ~500 Mya (sharks) no paralogs exist.(2,3) We previously reported that HLA-A isotype alleles with the α1-helix, R65 motif, are wide-spread in phylogeny, but that the α 2-helix, H151R motif, has apparently segregated out of most species. Surprisingly, an uncharacterized orf in T. syrichta (Loc-103275158) encoded R151, but within a truncated A-23 like gene containing 5'- and 3'- footprints of the transposon (TE), tigger-1; the extant tarsier A-23 allele is totally missing exon-3 and part-of exon-4; together, suggesting TE-mediated inactivation of an intact/ancestral A-23 allele (Murray, 2015a).(4) The unique Loc-103275158 orf encodes a putative 15-exon transcript with no apparent paralogs throughout phylogeny. However, an HLA-A11 like gene in M. leucophaeus with a shortened C-terminal domain, and an HLA-A like orf in C. atys with two linked α1/α2/α3 domains, both contain a second transmembrane segment, which is conserved in Loc-103275158. Thus, we could model the putative protein with its Nef-like tail domain docked to its MHC-I like α3 domain (i.e., on the same side of a membrane). This modeled tertiary structure is strikingly similar to the solved structure of the Nef:MHC-I CD:AP1mu transporter (Jia, 2012).(5) Nef:AP1mu binds the CD of MHC-I in trafficking MHC-I away from the trans-golgi and into the endocytic pathway in HIV-1 infected cells. The CD loop of the

  10. Management of data quality of high level waste characterization

    SciTech Connect

    Winters, W.I., Westinghouse Hanford

    1996-06-12

    Over the past 10 years, the Hanford Site has been transitioning from nuclear materials production to Site cleanup operations. High-level waste characterization at the Hanford Site provides data to support present waste processing operations, tank safety programs, and future waste disposal programs. Quality elements in the high-level waste characterization program will be presented by following a sample through the data quality objective, sampling, laboratory analysis and data review process. Transition from production to cleanup has resulted in changes in quality systems and program; the changes, as well as other issues in these quality programs, will be described. Laboratory assessment through quality control and performance evaluation programs will be described, and data assessments in the laboratory and final reporting in the tank characterization reports will be discussed.

  11. Evaluation and selection of candidate high-level waste forms

    SciTech Connect

    Bernadzikowski, T. A.; Allender, J. S.; Butler, J. L.; Gordon, D. E.; Gould, Jr., T. H.; Stone, J. A.

    1982-03-01

    Seven candidate waste forms being developed under the direction of the Department of Energy's National High-Level Waste (HLW) Technology Program, were evaluated as potential media for the immobilization and geologic disposal of high-level nuclear wastes. The evaluation combined preliminary waste form evaluations conducted at DOE defense waste-sites and independent laboratories, peer review assessments, a product performance evaluation, and a processability analysis. Based on the combined results of these four inputs, two of the seven forms, borosilicate glass and a titanate based ceramic, SYNROC, were selected as the reference and alternative forms for continued development and evaluation in the National HLW Program. Both the glass and ceramic forms are viable candidates for use at each of the DOE defense waste-sites; they are also potential candidates for immobilization of commercial reprocessing wastes. This report describes the waste form screening process, and discusses each of the four major inputs considered in the selection of the two forms.

  12. Multipurpose optimization models for high level waste vitrification

    SciTech Connect

    Hoza, M.

    1994-08-01

    Optimal Waste Loading (OWL) models have been developed as multipurpose tools for high-level waste studies for the Tank Waste Remediation Program at Hanford. Using nonlinear programming techniques, these models maximize the waste loading of the vitrified waste and optimize the glass formers composition such that the glass produced has the appropriate properties within the melter, and the resultant vitrified waste form meets the requirements for disposal. The OWL model can be used for a single waste stream or for blended streams. The models can determine optimal continuous blends or optimal discrete blends of a number of different wastes. The OWL models have been used to identify the most restrictive constraints, to evaluate prospective waste pretreatment methods, to formulate and evaluate blending strategies, and to determine the impacts of variability in the wastes. The OWL models will be used to aid in the design of frits and the maximize the waste in the glass for High-Level Waste (HLW) vitrification.

  13. Radioactive high level waste insight modelling for geological disposal facilities

    NASA Astrophysics Data System (ADS)

    Carter, Alexander; Kelly, Martin; Bailey, Lucy

    Within this paper we present a simplified analytical model to provide insight into the key performance measures of a generic disposal system for high level waste within a geological disposal facility. The model assumes a low solubility waste matrix within a corrosion resistant disposal container surrounded by a low permeability buffer. Radionuclides migrate from the disposal area through a porous geosphere to the biosphere and give a radiological dose to a receptor. The system of equations describing the migration is transformed into Laplace space and an approximation used to determine peak values for the radionuclide mass transfer rate entering the biosphere. Results from the model are compared with those from more detailed numerical models for key radionuclides in the UK high level waste inventory. Such an insight model can provide a valuable second line of argument to assist in confirming the results of more detailed models and build confidence in the safety case for a geological disposal facility.

  14. Review of High Level Waste Tanks Ultrasonic Inspection Data

    SciTech Connect

    Wiersma, B

    2006-03-09

    A review of the data collected during ultrasonic inspection of the Type I high level waste tanks has been completed. The data was analyzed for relevance to the possibility of vapor space corrosion and liquid/air interface corrosion. The review of the Type I tank UT inspection data has confirmed that the vapor space general corrosion is not an unusually aggressive phenomena and correlates well with predicted corrosion rates for steel exposed to bulk solution. The corrosion rates are seen to decrease with time as expected. The review of the temperature data did not reveal any obvious correlations between high temperatures and the occurrences of leaks. The complex nature of temperature-humidity interaction, particularly with respect to vapor corrosion requires further understanding to infer any correlation. The review of the waste level data also did not reveal any obvious correlations.

  15. RETENTION OF SULFATE IN HIGH LEVEL RADIOACTIVE WASTE GLASS

    SciTech Connect

    Fox, K.

    2010-09-07

    High level radioactive wastes are being vitrified at the Savannah River Site for long term disposal. Many of the wastes contain sulfate at concentrations that can be difficult to retain in borosilicate glass. This study involves efforts to optimize the composition of a glass frit for combination with the waste to improve sulfate retention while meeting other process and product performance constraints. The fabrication and characterization of several series of simulated waste glasses are described. The experiments are detailed chronologically, to provide insight into part of the engineering studies used in developing frit compositions for an operating high level waste vitrification facility. The results lead to the recommendation of a specific frit composition and a concentration limit for sulfate in the glass for the next batch of sludge to be processed at Savannah River.

  16. High Level Information Fusion (HLIF) with nested fusion loops

    NASA Astrophysics Data System (ADS)

    Woodley, Robert; Gosnell, Michael; Fischer, Amber

    2013-05-01

    Situation modeling and threat prediction require higher levels of data fusion in order to provide actionable information. Beyond the sensor data and sources the analyst has access to, the use of out-sourced and re-sourced data is becoming common. Through the years, some common frameworks have emerged for dealing with information fusion—perhaps the most ubiquitous being the JDL Data Fusion Group and their initial 4-level data fusion model. Since these initial developments, numerous models of information fusion have emerged, hoping to better capture the human-centric process of data analyses within a machine-centric framework. 21st Century Systems, Inc. has developed Fusion with Uncertainty Reasoning using Nested Assessment Characterizer Elements (FURNACE) to address challenges of high level information fusion and handle bias, ambiguity, and uncertainty (BAU) for Situation Modeling, Threat Modeling, and Threat Prediction. It combines JDL fusion levels with nested fusion loops and state-of-the-art data reasoning. Initial research has shown that FURNACE is able to reduce BAU and improve the fusion process by allowing high level information fusion (HLIF) to affect lower levels without the double counting of information or other biasing issues. The initial FURNACE project was focused on the underlying algorithms to produce a fusion system able to handle BAU and repurposed data in a cohesive manner. FURNACE supports analyst's efforts to develop situation models, threat models, and threat predictions to increase situational awareness of the battlespace. FURNACE will not only revolutionize the military intelligence realm, but also benefit the larger homeland defense, law enforcement, and business intelligence markets.

  17. Ionization chamber for measurements of high-level tritium gas

    SciTech Connect

    Carstens, D.H.W.; David, W.R.

    1980-01-01

    The construction and calibration of a simple ionization-chamber apparatus for measurement of high level tritium gas is described. The apparatus uses an easily constructed but rugged chamber containing the unknown gas and an inexpensive digital multimeter for measuring the ion current. The equipment after calibration is suitable for measuring 0.01 to 100% tritium gas in hydrogen-helium mixes with an accuracy of a few percent. At both the high and low limits of measurements deviations from the predicted theoretical current are observed. These are briefly discussed.

  18. FLUIDIZED BED STEAM REFORMING ENABLING ORGANIC HIGH LEVEL WASTE DISPOSAL

    SciTech Connect

    Williams, M

    2008-05-09

    Waste streams planned for generation by the Global Nuclear Energy Partnership (GNEP) and existing radioactive High Level Waste (HLW) streams containing organic compounds such as the Tank 48H waste stream at Savannah River Site have completed simulant and radioactive testing, respectfully, by Savannah River National Laboratory (SRNL). GNEP waste streams will include up to 53 wt% organic compounds and nitrates up to 56 wt%. Decomposition of high nitrate streams requires reducing conditions, e.g. provided by organic additives such as sugar or coal, to reduce NOX in the off-gas to N2 to meet Clean Air Act (CAA) standards during processing. Thus, organics will be present during the waste form stabilization process regardless of the GNEP processes utilized and exists in some of the high level radioactive waste tanks at Savannah River Site and Hanford Tank Farms, e.g. organics in the feed or organics used for nitrate destruction. Waste streams containing high organic concentrations cannot be stabilized with the existing HLW Best Developed Available Technology (BDAT) which is HLW vitrification (HLVIT) unless the organics are removed by pretreatment. The alternative waste stabilization pretreatment process of Fluidized Bed Steam Reforming (FBSR) operates at moderate temperatures (650-750 C) compared to vitrification (1150-1300 C). The FBSR process has been demonstrated on GNEP simulated waste and radioactive waste containing high organics from Tank 48H to convert organics to CAA compliant gases, create no secondary liquid waste streams and create a stable mineral waste form.

  19. Automatic rule generation for high-level vision

    NASA Technical Reports Server (NTRS)

    Rhee, Frank Chung-Hoon; Krishnapuram, Raghu

    1992-01-01

    Many high-level vision systems use rule-based approaches to solving problems such as autonomous navigation and image understanding. The rules are usually elaborated by experts. However, this procedure may be rather tedious. In this paper, we propose a method to generate such rules automatically from training data. The proposed method is also capable of filtering out irrelevant features and criteria from the rules.

  20. Case for retrievable high-level nuclear waste disposal

    USGS Publications Warehouse

    Roseboom, Eugene H., Jr.

    1994-01-01

    Plans for the nation's first high-level nuclear waste repository have called for permanently closing and sealing the repository soon after it is filled. However, the hydrologic environment of the proposed site at Yucca Mountain, Nevada, should allow the repository to be kept open and the waste retrievable indefinitely. This would allow direct monitoring of the repository and maintain the options for future generations to improve upon the disposal methods or use the uranium in the spent fuel as an energy resource.

  1. Mixing Processes in High-Level Waste Tanks - Final Report

    SciTech Connect

    Peterson, P.F.

    1999-05-24

    The mixing processes in large, complex enclosures using one-dimensional differential equations, with transport in free and wall jets is modeled using standard integral techniques. With this goal in mind, we have constructed a simple, computationally efficient numerical tool, the Berkeley Mechanistic Mixing Model, which can be used to predict the transient evolution of fuel and oxygen concentrations in DOE high-level waste tanks following loss of ventilation, and validate the model against a series of experiments.

  2. [Corrosion testing of high level radioactive waste. Final report

    SciTech Connect

    1996-06-01

    Alloys under consideration as candidates for the high level nuclear waste containers at Yucca Mountain were exposed to a range of corrosion conditions and their performance measured. The alloys tested were Incoloy 825, 70/30 Copper-Nickel, Monel 400, Hastelloy C- 22, and low carbon steel. The test conditions varied were: temperature, concentration, agitation, and crevice simulation. Only in the case of carbon steel was significant attack noted. This attack appeared to be transport limited.

  3. Executive functions in kindergarteners with high levels of disruptive behaviours.

    PubMed

    Monette, Sébastien; Bigras, Marc; Guay, Marie-Claude

    2015-11-01

    Executive function (EF) deficits have yet to be demonstrated convincingly in children with disruptive behaviour disorders (DBD), as only a few studies have reported these. The presence of EF weaknesses in children with DBD has often been contested on account of the high comorbidity between DBD and attention-deficit/hyperactivity disorder (ADHD) and of methodological shortcomings regarding EF measures. Against this background, the link between EF and disruptive behaviours in kindergarteners was investigated using a carefully selected battery of EF measures. Three groups of kindergarteners were compared: (1) a group combining high levels of disruptive behaviours and ADHD symptoms (COMB); (2) a group presenting high levels of disruptive/aggressive behaviours and low levels of ADHD symptoms (AGG); and (3) a normative group (NOR). Children in the COMB and AGG groups presented weaker inhibition capacities compared with normative peers. Also, only the COMB group showed weaker working memory capacities compared with the NOR group. Results support the idea that preschool children with DBD have weaker inhibition capacities and that this weakness could be common to both ADHD and DBD. PMID:26198079

  4. Handbook of high-level radioactive waste transportation

    SciTech Connect

    Sattler, L.R.

    1992-10-01

    The High-Level Radioactive Waste Transportation Handbook serves as a reference to which state officials and members of the general public may turn for information on radioactive waste transportation and on the federal government`s system for transporting this waste under the Civilian Radioactive Waste Management Program. The Handbook condenses and updates information contained in the Midwestern High-Level Radioactive Waste Transportation Primer. It is intended primarily to assist legislators who, in the future, may be called upon to enact legislation pertaining to the transportation of radioactive waste through their jurisdictions. The Handbook is divided into two sections. The first section places the federal government`s program for transporting radioactive waste in context. It provides background information on nuclear waste production in the United States and traces the emergence of federal policy for disposing of radioactive waste. The second section covers the history of radioactive waste transportation; summarizes major pieces of legislation pertaining to the transportation of radioactive waste; and provides an overview of the radioactive waste transportation program developed by the US Department of Energy (DOE). To supplement this information, a summary of pertinent federal and state legislation and a glossary of terms are included as appendices, as is a list of publications produced by the Midwestern Office of The Council of State Governments (CSG-MW) as part of the Midwestern High-Level Radioactive Waste Transportation Project.

  5. Materials Science of High-Level Nuclear Waste Immobilization

    SciTech Connect

    Weber, William J.; Navrotsky, Alexandra; Stefanovsky, S. V.; Vance, E. R.; Vernaz, Etienne Y.

    2009-01-09

    With the increasing demand for the development of more nuclear power comes the responsibility to address the technical challenges of immobilizing high-level nuclear wastes in stable solid forms for interim storage or disposition in geologic repositories. The immobilization of high-level nuclear wastes has been an active area of research and development for over 50 years. Borosilicate glasses and complex ceramic composites have been developed to meet many technical challenges and current needs, although regulatory issues, which vary widely from country to country, have yet to be resolved. Cooperative international programs to develop advanced proliferation-resistant nuclear technologies to close the nuclear fuel cycle and increase the efficiency of nuclear energy production might create new separation waste streams that could demand new concepts and materials for nuclear waste immobilization. This article reviews the current state-of-the-art understanding regarding the materials science of glasses and ceramics for the immobilization of high-level nuclear waste and excess nuclear materials and discusses approaches to address new waste streams.

  6. Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages.

    PubMed Central

    Murphy, K M; Sweet, M J; Ross, I L; Hume, D A

    1993-01-01

    The RAW264 murine macrophage cell line was used as a model to examine the role of the tat and nef gene products in the transcription regulation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in macrophages. Contrary to claims that the activity of the HIV-1 LTR responds poorly in rodent cells to trans activation by the viral tat gene product, cotransfection of RAW264 cells with a tat expression plasmid in transient transfection assays caused a > 20-fold increase in reporter gene expression that was inhibited by mutations in the TAR region. RAW264 cells stably transfected with the tat plasmid displayed similarly elevated HIV-1 LTR-driven reporter gene activity. By contrast to previous reports indicating a negative role for nef in HIV transcription, cotransfection of RAW264 cells with a nef expression plasmid trans activated the HIV-1 LTR driving either a chloramphenicol acetyltransferase or a luciferase reporter gene. The action of nef was specific to the LTR, as expression of nef had no effect on the activity of the simian virus 40, c-fms, urokinase plasminogen activator, or type 5 acid phosphatase promoter. trans-activating activity was also manifested by a frameshift mutant expressing only the first 35 amino acids of the protein. The effects of nef were multiplicative with those of tat gene product and occurred even in the presence of bacterial lipopolysaccharide, which itself activated LTR-directed transcription. Examination of the effects of selected mutations in the LTR revealed that neither the kappa B sites in the direct repeat enhancer nor the TAR region was required as a cis-acting element in nef action. The action of nef was not species restricted; it was able to trans activate in the human monocyte-like cell line Mono Mac 6. The presence of a nef expression cassette in a neomycin phosphotransferase gene expression plasmid greatly reduced the number of G418-resistant colonies generated in stable transfection of RAW264 cells

  7. High Levels of Molecular Chlorine found in the Arctic Atmosphere

    NASA Astrophysics Data System (ADS)

    Liao, J.; Huey, L. G.; Liu, Z.; Tanner, D.; Cantrell, C. A.; Orlando, J. J.; Flocke, F. M.; Shepson, P. B.; Weinheimer, A. J.; Hall, S. R.; Beine, H.; Wang, Y.; Ingall, E. D.; Thompson, C. R.; Hornbrook, R. S.; Apel, E. C.; Fried, A.; Mauldin, L.; Smith, J. N.; Staebler, R. M.; Neuman, J. A.; Nowak, J. B.

    2014-12-01

    Chlorine radicals are a strong atmospheric oxidant, particularly in polar regions where levels of hydroxyl radicals can be quite low. In the atmosphere, chlorine radicals expedite the degradation of methane and tropospheric ozone and the oxidation of mercury to more toxic forms. Here, we present direct measurements of molecular chlorine levels in the Arctic marine boundary layer in Barrow, Alaska, collected in the spring of 2009 over a six-week period using chemical ionization mass spectrometry. We detected high levels of molecular chlorine of up to 400 pptv. Concentrations peaked in the early morning and late afternoon and fell to near-zero levels at night. Average daytime molecular chlorine levels were correlated with ozone concentrations, suggesting that sunlight and ozone are required for molecular chlorine formation. Using a time-dependent box model, we estimated that the chlorine radicals produced from the photolysis of molecular chlorine on average oxidized more methane than hydroxyl radicals and enhanced the abundance of short-lived peroxy radicals. Elevated hydroperoxyl radical levels, in turn, promoted the formation of hypobromous acid, which catalyzed mercury oxidation and the breakdown of tropospheric ozone. Therefore, we propose that molecular chlorine exerts a significant effect on the atmospheric chemistry in the Arctic. While the formation mechanisms of molecular chlorine are not yet understood, the main potential sources of chlorine include snowpack, sea salt, and sea ice. There is recent evidence of molecular halogen (Br2 and Cl2) formation in the Arctic snowpack. The coverage and composition of the snow may control halogen chemistry in the Arctic. Changes of sea ice and snow cover in the changing climate may affect air-snow-ice interaction and have a significant impact on the levels of radicals, ozone, mercury and methane in the Arctic troposphere.

  8. Radiative Lifetimes for High Levels of Neutral Fe

    NASA Astrophysics Data System (ADS)

    Lawler, James E.; Den Hartog, E.; Guzman, A.

    2013-01-01

    New radiative lifetime measurements for ~ 50 high lying levels of Fe I are reported. Laboratory astrophysics faces a challenge to provide basic spectroscopic data, especially reliable atomic transition probabilities, in the IR region for abundance studies. The availability of HgCdTe (HAWAII) detector arrays has opened IR spectral regions for extensive new spectroscopic studies. The SDSS III APOGEE project in the H-Band is an important example which will penetrate the dust obscuring the Galactic bulge. APOGEE will survey elemental abundances of 100,000 red giant stars in the bulge, bar, disk, and halo of the Milky Way. Many stellar spectra in the H-Band are, as expected, dominated by transitions of Fe I. Most of these IR transitions connect high levels of Fe. Our program has started an effort to meet this challenge with new radiative lifetime measurements on high lying levels of Fe I using time resolved laser induced fluorescence (TRLIF). The TRLIF method is typically accurate to 5% and is efficient. Our goal is to combine these accurate, absolute radiative lifetimes with emission branching fractions [1] to determine log(gf) values of the highest quality for Fe I lines in the UV, visible, and IR. This method was used very successfully by O’Brian et al. [2] on lower levels of Fe I. This method is still the best available for all but very simple spectra for which ab-initio theory is more accurate. Supported by NSF grant AST-0907732. [1] Branching fractions are being measured by M. Ruffoni and J. C. Pickering at Imperial College London. [2] O'Brian, T. R., Wickliffe, M. E., Lawler, J. E., Whaling, W., & Brault, J. W. 1991, J. Opt. Soc. Am. B 8, 1185

  9. Exceptionally high levels of multiple mating in an army ant

    NASA Astrophysics Data System (ADS)

    Denny, A. Jay; Franks, Nigel R.; Powell, Scott; Edwards, Keith J.

    Most species of social insects have singly mated queens, although there are notable exceptions. Competing hypotheses have been proposed to explain the evolution of high levels of multiple mating, but this issue is far from resolved. Here we use microsatellites to investigate mating frequency in the army ant Eciton burchellii and show that queens mate with an exceptionally large number of males, eclipsing all but one other social insect species for which data are available. In addition we present evidence that suggests that mating is serial, continuing throughout the lifetime of the queen. This is the first demonstration of serial mating among social hymenoptera. We propose that high paternity within colonies is most likely to have evolved to increase genetic diversity and to counter high pathogen and parasite loads.

  10. ALICE: Project Overview and High Level Science Products

    NASA Astrophysics Data System (ADS)

    Soummer, Remi; Choquet, Elodie; Pueyo, Laurent; Brendan Hagan, J.; Gofas-Salas, Elena; Rajan, Abhijith; Perrin, Marshall D.; Chen, Christine; Debes, John H.; Golimowski, David A.; Hines, Dean C.; Schneider, Glenn; N'Diaye, Mamadou; Mawet, Dimitri; Marois, Christian; Barman, Travis

    2015-01-01

    We report on the status of the ALICE project (Archival Legacy Investigation of Circumstellar Environments), which consists in a consistent reanalysis of the entire HST-NICMOS coronagraphic archive. Over the last two years, we have developed a sophisticated pipeline able to handle the data of the 400 stars of the archive. This pipeline builds on the Karhunen-Loeve Image Projection (KLIP) algorithm, and was completed in the fall of 2014. We discuss the first processing and analysis results of the overall reduction campaign. As we will deliver high-level science products to the STScI MAST archive, we are defining a new standard format for high-contrast science products, which will be compatible with every new high-contrast imaging instrument (GPI, SPHERE, P1640, CHARIS, etc.) and used by the JWST coronagraphs. We present here the specifications of this standard.

  11. High-level power analysis and optimization techniques

    NASA Astrophysics Data System (ADS)

    Raghunathan, Anand

    1997-12-01

    This thesis combines two ubiquitous trends in the VLSI design world--the move towards designing at higher levels of design abstraction, and the increasing importance of power consumption as a design metric. Power estimation and optimization tools are becoming an increasingly important part of design flows, driven by a variety of requirements such as prolonging battery life in portable computing and communication devices, thermal considerations and system cooling and packaging costs, reliability issues (e.g. electromigration, ground bounce, and I-R drops in the power network), and environmental concerns. This thesis presents a suite of techniques to automatically perform power analysis and optimization for designs at the architecture or register-transfer, and behavior or algorithm levels of the design hierarchy. High-level synthesis refers to the process of synthesizing, from an abstract behavioral description, a register-transfer implementation that satisfies the desired constraints. High-level synthesis tools typically perform one or more of the following tasks: transformations, module selection, clock selection, scheduling, and resource allocation and assignment (also called resource sharing or hardware sharing). High-level synthesis techniques for minimizing the area, maximizing the performance, and enhancing the testability of the synthesized designs have been investigated. This thesis presents high-level synthesis techniques that minimize power consumption in the synthesized data paths. This thesis investigates the effects of resource sharing on the power consumption in the data path, provides techniques to efficiently estimate power consumption during resource sharing, and resource sharing algorithms to minimize power consumption. The RTL circuit that is obtained from the high-level synthesis process can be further optimized for power by applying power-reducing RTL transformations. This thesis presents macro-modeling and estimation techniques for switching

  12. Characterization of Transducers and Resonators under High Drive Levels

    NASA Technical Reports Server (NTRS)

    Sherrit, Stewart; Bao, X.; Sigel, D. A.; Gradziel, M. J.; Askins, S. A.; Dolgin, B. P.; Bar-Cohen, Y.

    2001-01-01

    In many applications, piezoelectric transducers are driven at AC voltage levels well beyond the level for which the material was nominally characterized. In this paper we describe an experimental setup that allows for the determination of the main transducer or resonator properties under large AC drive. A sinusoidal voltage from a waveform generator is amplified and applied across the transducer/resonator in series with a known high power resistor. The amplitude of applied voltage and the amplitude and the relative phase of the current through the resistor are monitored on a digital scope. The frequency of the applied signal is swept through resonance and the voltage/current signals are recorded. After corrections for the series resistance and parasitic elements the technique allows for the determination of the complex impedance spectra of the sample as a function of frequency. In addition, access to the current signal allows for the direct investigation of non-linear effects through the application of Fourier transform techniques on the current signal. Our results indicate that care is required when interpreting impedance data at high drive level due to the frequency dependence of the dissipated power. Although the transducer/resonator at a single frequency and after many cycles may reach thermal equilibrium, the spectra as a whole cannot be considered an isothermal measurement due to the temperature change with frequency. Methods to correct for this effect will be discussed. Results determined from resonators of both soft and hard PZT and a ultrasonic horn transducer are presented.

  13. Ultrasonic level sensors for liquids under high pressure

    NASA Technical Reports Server (NTRS)

    Zuckerwar, A. J.; Mazel, D. S.; Hodges, D. Y.

    1986-01-01

    An ultrasonic level sensor of novel design continuously measures the level of a liquid subjected to a high pressure (up to about 40 MPa), as is sometimes required for the effective transfer of the liquid. The sensor operates as a composite resonator fabricated from a standard high-pressure plug. A flat-bottom hole is machined into the plug along its center line. An ultrasonic transducer is bonded rigidly to the interior surface of the bottom wall, while the exterior surface is in contact with the liquid. Although the bottom wall is designed to satisfy the pressure code, it is still sufficiently thin to permit ready excitation of the axisymmetric plate modes of vibration. The liquid level is measured by a conventional pulse-echo technique. A prototype sensor was tested successfully in a 2300-l water vessel at pressures up to about 37 MPa. A spectral analysis of the transmitted pulse reveals that the flexural, extensional, thickness-shear, and radial plate modes are excited into vibration, but none of these appears to be significantly affected by the pressurization of the liquid.

  14. Space augmentation of military high-level waste disposal

    NASA Technical Reports Server (NTRS)

    English, T.; Lees, L.; Divita, E.

    1979-01-01

    Space disposal of selected components of military high-level waste (HLW) is considered. This disposal option offers the promise of eliminating the long-lived radionuclides in military HLW from the earth. A space mission which meets the dual requirements of long-term orbital stability and a maximum of one space shuttle launch per week over a period of 20-40 years, is a heliocentric orbit about halfway between the orbits of earth and Venus. Space disposal of high-level radioactive waste is characterized by long-term predictability and short-term uncertainties which must be reduced to acceptably low levels. For example, failure of either the Orbit Transfer Vehicle after leaving low earth orbit, or the storable propellant stage failure at perihelion would leave the nuclear waste package in an unplanned and potentially unstable orbit. Since potential earth reencounter and subsequent burn-up in the earth's atmosphere is unacceptable, a deep space rendezvous, docking, and retrieval capability must be developed.

  15. Ultrasonic level sensors for liquids under high pressure

    NASA Astrophysics Data System (ADS)

    Zuckerwar, A. J.; Mazel, D. S.; Hodges, D. Y.

    1986-09-01

    An ultrasonic level sensor of novel design continuously measures the level of a liquid subjected to a high pressure (up to about 40 MPa), as is sometimes required for the effective transfer of the liquid. The sensor operates as a composite resonator fabricated from a standard high-pressure plug. A flat-bottom hole is machined into the plug along its center line. An ultrasonic transducer is bonded rigidly to the interior surface of the bottom wall, while the exterior surface is in contact with the liquid. Although the bottom wall is designed to satisfy the pressure code, it is still sufficiently thin to permit ready excitation of the axisymmetric plate modes of vibration. The liquid level is measured by a conventional pulse-echo technique. A prototype sensor was tested successfully in a 2300-l water vessel at pressures up to about 37 MPa. A spectral analysis of the transmitted pulse reveals that the flexural, extensional, thickness-shear, and radial plate modes are excited into vibration, but none of these appears to be significantly affected by the pressurization of the liquid.

  16. High level language-based robotic control system

    NASA Technical Reports Server (NTRS)

    Rodriguez, Guillermo (Inventor); Kruetz, Kenneth K. (Inventor); Jain, Abhinandan (Inventor)

    1994-01-01

    This invention is a robot control system based on a high level language implementing a spatial operator algebra. There are two high level languages included within the system. At the highest level, applications programs can be written in a robot-oriented applications language including broad operators such as MOVE and GRASP. The robot-oriented applications language statements are translated into statements in the spatial operator algebra language. Programming can also take place using the spatial operator algebra language. The statements in the spatial operator algebra language from either source are then translated into machine language statements for execution by a digital control computer. The system also includes the capability of executing the control code sequences in a simulation mode before actual execution to assure proper action at execution time. The robot's environment is checked as part of the process and dynamic reconfiguration is also possible. The languages and system allow the programming and control of multiple arms and the use of inward/outward spatial recursions in which every computational step can be related to a transformation from one point in the mechanical robot to another point to name two major advantages.

  17. High level language-based robotic control system

    NASA Technical Reports Server (NTRS)

    Rodriguez, Guillermo (Inventor); Kreutz, Kenneth K. (Inventor); Jain, Abhinandan (Inventor)

    1996-01-01

    This invention is a robot control system based on a high level language implementing a spatial operator algebra. There are two high level languages included within the system. At the highest level, applications programs can be written in a robot-oriented applications language including broad operators such as MOVE and GRASP. The robot-oriented applications language statements are translated into statements in the spatial operator algebra language. Programming can also take place using the spatial operator algebra language. The statements in the spatial operator algebra language from either source are then translated into machine language statements for execution by a digital control computer. The system also includes the capability of executing the control code sequences in a simulation mode before actual execution to assure proper action at execution time. The robot's environment is checked as part of the process and dynamic reconfiguration is also possible. The languages and system allow the programming and control of multiple arms and the use of inward/outward spatial recursions in which every computational step can be related to a transformation from one point in the mechanical robot to another point to name two major advantages.

  18. Permitting plan for the high-level waste interim storage

    SciTech Connect

    Deffenbaugh, M.L.

    1997-04-23

    This document addresses the environmental permitting requirements for the transportation and interim storage of solidified high-level waste (HLW) produced during Phase 1 of the Hanford Site privatization effort. Solidified HLW consists of canisters containing vitrified HLW (glass) and containers that hold cesium separated during low-level waste pretreatment. The glass canisters and cesium containers will be transported to the Canister Storage Building (CSB) in a U.S. Department of Energy (DOE)-provided transportation cask via diesel-powered tractor trailer. Tri-Party Agreement (TPA) Milestone M-90 establishes a new major milestone, and associated interim milestones and target dates, governing acquisition and/or modification of facilities necessary for: (1) interim storage of Tank Waste Remediation Systems (TWRS) immobilized HLW (IHLW) and other canistered high-level waste forms; and (2) interim storage and disposal of TWRS immobilized low-activity tank waste (ILAW). An environmental requirements checklist and narrative was developed to identify the permitting path forward for the HLW interim storage (HLWIS) project (See Appendix B). This permitting plan will follow the permitting logic developed in that checklist.

  19. Elevated glucose levels in early puerperium, and association with high cortisol levels during parturition.

    PubMed

    Risberg, Anitha; Sjöquist, Mats; Wedenberg, Kaj; Larsson, Anders

    2016-07-01

    Background Gestational diabetes is one of the commonest metabolic problems associated with pregnancy and an accurate diagnosis is critical for the care. Research has shown that pregnant women have high levels of cortisol during the last stage of parturition. As cortisol is a diabetogenic hormone causing increased glucose levels, we wanted to study the association between cortisol and glucose levels during parturition. Materials and methods Glucose and cortisol were analyzed during parturition in 50 females divided according to slow (n = 11) and normal labors (n = 39). Blood samples were analyzed three times during the parturition and four times in the first day after delivery. Glucose levels were also measured once in each trimester. Results In the normal group, the glucose concentration increased from 6.2 (IQR 5.6-8.0) mmol/L in the latency phase to 11.6 (10.0-13.3) mmol/L at aftercare (p < 0.05). After parturition the glucose concentrations decreased gradually. There were significant Spearman rank correlations between glucose and cortisol values. Conclusions The changes associated with birth cause significant elevations of cortisol and glucose around parturition. PMID:26985979

  20. Alternate methods for high level pyrotechnic shock simulation

    NASA Astrophysics Data System (ADS)

    Gray, Phillip J., Sr.

    Two effective methods to recreate a realistic pyrotechnic shock are presented. The first method employs a resonant beam and is used for SRS levels of 12,000 G or more. The test unit is at one end of the beam and a hammer strikes the opposite end causing a shock to be transmitted to the other end of the fixture. The second method is based on a standard shaker system with a resonant beam to amplify the input signal. The engineer defines the duration of the shock signal induced to the vibration amplifier using the GenRad 2514 controller. The shock signal is then input via the shaker to the resonant beam, which amplifies the signal to produce the desired response at the end of the fixture. The shock response spectrum stays within a +/-6 dB tolerance with levels as high as 3000 G peak. These methods are repeatable, reliable, cost-effective, and consistent with a real pyroevent.

  1. University-Level Research Projects for High School Students

    NASA Technical Reports Server (NTRS)

    McConnell, Mark L.

    2000-01-01

    The goal of this project was to provide an opportunity for high school students to participate in university-level research projects. In this case, students from Pinkerton Academy (Derry, New Hampshire) were invited to participate in efforts to catalog data from the COMPTEL experiment on NASA's Compton Gamma-Ray Observatory (CGRO). These activities were part of a senior level honors course at Pinkerton. Although the success of this particular program was rather limited, we feel that the general concept is a sound one. In principle, the concept of partnerships between local schools and university researchers is one that could be especially attractive to soft money researchers. Programs can be carefully designed to benefit both the students and the research program.

  2. Effects of high vs low-level radiation exposure

    SciTech Connect

    Bond, V.P.

    1983-01-01

    In order to appreciate adequately the various possible effects of radiation, particularly from high-level vs low-level radiation exposure (HLRE, vs LLRE), it is necessary to understand the substantial differences between (a) exposure as used in exposure-incidence curves, which are always initially linear and without threshold, and (b) dose as used in dose-response curves, which always have a threshold, above which the function is curvilinear with increasing slope. The differences are discussed first in terms of generally familiar nonradiation situations involving dose vs exposure, and then specifically in terms of exposure to radiation, vs a dose of radiation. Examples are given of relevant biomedical findings illustrating that, while dose can be used with HLRE, it is inappropriate and misleading the LLRE where exposure is the conceptually correct measure of the amount of radiation involved.

  3. Engineering Escherichia coli for high-level production of propionate.

    PubMed

    Akawi, Lamees; Srirangan, Kajan; Liu, Xuejia; Moo-Young, Murray; Perry Chou, C

    2015-07-01

    Mounting environmental concerns associated with the use of petroleum-based chemical manufacturing practices has generated significant interest in the development of biological alternatives for the production of propionate. However, biological platforms for propionate production have been limited to strict anaerobes, such as Propionibacteria and select Clostridia. In this work, we demonstrated high-level heterologous production of propionate under microaerobic conditions in engineered Escherichia coli. Activation of the native Sleeping beauty mutase (Sbm) operon not only transformed E. coli to be propionogenic (i.e., propionate-producing) but also introduced an intracellular "flux competition" between the traditional C2-fermentative pathway and the novel C3-fermentative pathway. Dissimilation of the major carbon source of glycerol was identified to critically affect such "flux competition" and, therefore, propionate synthesis. As a result, the propionogenic E. coli was further engineered by inactivation or overexpression of various genes involved in the glycerol dissimilation pathways and their individual genetic effects on propionate production were investigated. Generally, knocking out genes involved in glycerol dissimilation (except glpA) can minimize levels of solventogenesis and shift more dissimilated carbon flux toward the C3-fermentative pathway. For optimal propionate production with high C3:C2-fermentative product ratios, glycerol dissimilation should be channeled through the respiratory pathway and, upon suppressed solventogenesis with minimal production of highly reduced alcohols, the alternative NADH-consuming route associated with propionate synthesis can be critical for more flexible redox balancing. With the implementation of various biochemical and genetic strategies, high propionate titers of more than 11 g/L with high yields up to 0.4 g-propionate/g-glycerol (accounting for ~50 % of dissimilated glycerol) were achieved, demonstrating the

  4. CEMENTITIOUS GROUT FOR CLOSING SRS HIGH LEVEL WASTE TANKS - #12315

    SciTech Connect

    Langton, C.; Burns, H.; Stefanko, D.

    2012-01-10

    In 1997, the first two United States Department of Energy (US DOE) high level waste tanks (Tanks 17-F and 20-F: Type IV, single shell tanks) were taken out of service (permanently closed) at the Savannah River Site (SRS). In 2012, the DOE plans to remove from service two additional Savannah River Site (SRS) Type IV high-level waste tanks, Tanks 18-F and 19-F. These tanks were constructed in the late 1950's and received low-heat waste and do not contain cooling coils. Operational closure of Tanks 18-F and 19-F is intended to be consistent with the applicable requirements of the Resource Conservation and Recovery Act (RCRA) and the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and will be performed in accordance with South Carolina Department of Health and Environmental Control (SCDHEC). The closure will physically stabilize two 4.92E+04 cubic meter (1.3 E+06 gallon) carbon steel tanks and isolate and stabilize any residual contaminants left in the tanks. The closure will also fill, physically stabilize and isolate ancillary equipment abandoned in the tanks. A Performance Assessment (PA) has been developed to assess the long-term fate and transport of residual contamination in the environment resulting from the operational closure of the F-Area Tank Farm (FTF) waste tanks. Next generation flowable, zero-bleed cementitious grouts were designed, tested, and specified for closing Tanks 18-F and 19-F and for filling the abandoned equipment. Fill requirements were developed for both the tank and equipment grouts. All grout formulations were required to be alkaline with a pH of 12.4 and chemically reduction potential (Eh) of -200 to -400 to stabilize selected potential contaminants of concern. This was achieved by including Portland cement and Grade 100 slag in the mixes, respectively. Ingredients and proportions of cementitious reagents were selected and adjusted, respectively, to support the mass placement strategy developed by closure

  5. Development of a High Level Waste Tank Inspection System

    SciTech Connect

    Appel, D.K.; Loibl, M.W.; Meese, D.C.

    1995-03-21

    The Westinghouse Savannah River Technology Center was requested by it`s sister site, West Valley Nuclear Service (WVNS), to develop a remote inspection system to gather wall thickness readings of their High Level Waste Tanks. WVNS management chose to take a proactive approach to gain current information on two tanks t hat had been in service since the early 70`s. The tanks contain high level waste, are buried underground, and have only two access ports to an annular space between the tank and the secondary concrete vault. A specialized remote system was proposed to provide both a visual surveillance and ultrasonic thickness measurements of the tank walls. A magnetic wheeled crawler was the basis for the remote delivery system integrated with an off-the-shelf Ultrasonic Data Acquisition System. A development program was initiated for Savannah River Technology Center (SRTC) to design, fabricate, and test a remote system based on the Crawler. The system was completed and involved three crawlers to perform the needed tasks, an Ultrasonic Crawler, a Camera Crawler, and a Surface Prep Crawler. The crawlers were computer controlled so that their operation could be done remotely and their position on the wall could be tracked. The Ultrasonic Crawler controls were interfaced with ABB Amdata`s I-PC, Ultrasonic Data Acquisition System so that thickness mapping of the wall could be obtained. A second system was requested by Westinghouse Savannah River Company (WSRC), to perform just ultrasonic mapping on their similar Waste Storage Tanks; however, the system needed to be interfaced with the P-scan Ultrasonic Data Acquisition System. Both remote inspection systems were completed 9/94. Qualifications tests were conducted by WVNS prior to implementation on the actual tank and tank development was achieved 10/94. The second inspection system was deployed at WSRC 11/94 with success, and the system is now in continuous service inspecting the remaining high level waste tanks at WSRC.

  6. Defense High Level Waste Disposal Container System Description Document

    SciTech Connect

    N. E. Pettit

    2001-07-13

    The Defense High Level Waste Disposal Container System supports the confinement and isolation of waste within the Engineered Barrier System of the Monitored Geologic Repository (MGR). Disposal containers are loaded and sealed in the surface waste handling facilities, transferred to the underground through the accesses using a rail mounted transporter, and emplaced in emplacement drifts. The defense high level waste (HLW) disposal container provides long-term confinement of the commercial HLW and defense HLW (including immobilized plutonium waste forms [IPWF]) placed within disposable canisters, and withstands the loading, transfer, emplacement, and retrieval loads and environments. US Department of Energy (DOE)-owned spent nuclear fuel (SNF) in disposable canisters may also be placed in a defense HLW disposal container along with commercial HLW waste forms, which is known as co-disposal. The Defense High Level Waste Disposal Container System provides containment of waste for a designated period of time, and limits radionuclide release. The disposal container/waste package maintains the waste in a designated configuration, withstands maximum handling and rockfall loads, limits the individual canister temperatures after emplacement, resists corrosion in the expected handling and repository environments, and provides containment of waste in the event of an accident. Defense HLW disposal containers for HLW disposal will hold up to five HLW canisters. Defense HLW disposal containers for co-disposal will hold up to five HLW canisters arranged in a ring and one DOE SNF canister inserted in the center and/or one or more DOE SNF canisters displacing a HLW canister in the ring. Defense HLW disposal containers also will hold two Multi-Canister Overpacks (MCOs) and two HLW canisters in one disposal container. The disposal container will include outer and inner cylinders, outer and inner cylinder lids, and may include a canister guide. An exterior label will provide a means by

  7. Stagnation Region Heat Transfer Augmentation at Very High Turbulence Levels

    SciTech Connect

    Ames, Forrest; Kingery, Joseph E.

    2015-06-17

    A database for stagnation region heat transfer has been extended to include heat transfer measurements acquired downstream from a new high intensity turbulence generator. This work was motivated by gas turbine industry heat transfer designers who deal with heat transfer environments with increasing Reynolds numbers and very high turbulence levels. The new mock aero-combustor turbulence generator produces turbulence levels which average 17.4%, which is 37% higher than the older turbulence generator. The increased level of turbulence is caused by the reduced contraction ratio from the liner to the exit. Heat transfer measurements were acquired on two large cylindrical leading edge test surfaces having a four to one range in leading edge diameter (40.64 cm and 10.16 cm). Gandvarapu and Ames [1] previously acquired heat transfer measurements for six turbulence conditions including three grid conditions, two lower turbulence aero-combustor conditions, and a low turbulence condition. The data are documented and tabulated for an eight to one range in Reynolds numbers for each test surface with Reynolds numbers ranging from 62,500 to 500,000 for the large leading edge and 15,625 to 125,000 for the smaller leading edge. The data show augmentation levels of up to 136% in the stagnation region for the large leading edge. This heat transfer rate is an increase over the previous aero-combustor turbulence generator which had augmentation levels up to 110%. Note, the rate of increase in heat transfer augmentation decreases for the large cylindrical leading edge inferring only a limited level of turbulence intensification in the stagnation region. The smaller cylindrical leading edge shows more consistency with earlier stagnation region heat transfer results correlated on the TRL (Turbulence, Reynolds number, Length scale) parameter. The downstream regions of both test surfaces continue to accelerate the flow but at a much lower rate than the leading edge. Bypass transition occurs

  8. HIGH LEVELS OF URANIUM IN GROUNDWATER OF ULAANBAATAR, MONGOLIA

    PubMed Central

    Nriagu, Jerome; Nam, Dong-Ha; Ayanwola, Titilayo A.; Dinh, Hau; Erdenechimeg, Erdenebayar; Ochir, Chimedsuren; Bolormaa, Tsend-Ayush

    2011-01-01

    Water samples collected from 129 wells in seven of the nine sub-divisions of Ulaanbaatar were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) using Clean Lab methods. The levels of many trace elements were found to be very low with the average concentrations (ranges in brackets) being 0.9 (<0.1-7.9) μg/L for As; 7.7 (0.12-177) μg/L for Mn; 0.2 (<0.05-1.9) μg/L for Co; 16 (<0.1-686) μg/L for Zn; 0.7 (<0.1-1.8) μg/L for Se; <0.1 (<0.02-0.69) μg/L for Cd; and 1.3 (<0.02-32) μg/L for Pb. The levels of uranium were surprisingly elevated (mean, 4.6 μg/L; range <0.01-57 μg/L, with the values for many samples exceeding the World Health Organization's guideline of 15 μg/L for uranium in drinking water. Local rocks and soils appear to be the natural source of the uranium. The levels of uranium in Ulaanbaatar's groundwater are in the range that has been associated with nephrotoxicity, high blood pressure, bone dysfunction and likely reproductive impairment in human populations. We consider the risk associated with drinking the groundwater with elevated levels of uranium in Ulaanbaatar to be a matter for some public health concern and conclude that the paucity of data on chronic effects of low level exposure is a risk factor for continuing the injury to many people in this city. PMID:22142646

  9. Modern Alchemy: Solidifying high-level nuclear waste

    SciTech Connect

    Newton, C.C.

    1997-07-01

    The U.S. Department of Energy is putting a modern version of alchemy to work to produce an answer to a decades-old problem. It is taking place at the Savannah River Site (SRS) in Aiken, South Carolina and at the West Valley Demonstration Project (WVDP) near Buffalo, New York. At both locations, contractor Westinghouse Electric Corporation is applying technology that is turning liquid high-level radioactive waste (HLW) into a stabilized, durable glass for safer and easier management. The process is called vitrification. SRS and WVDP are now operating the nation`s first full-scale HLW vitrification plants.

  10. Corrosion and failure processes in high-level waste tanks

    SciTech Connect

    Mahidhara, R.K.; Elleman, T.S.; Murty, K.L.

    1992-11-01

    A large amount of radioactive waste has been stored safely at the Savannah River and Hanford sites over the past 46 years. The aim of this report is to review the experimental corrosion studies at Savannah River and Hanford with the intention of identifying the types and rates of corrosion encountered and indicate how these data contribute to tank failure predictions. The compositions of the High-Level Wastes, mild steels used in the construction of the waste tanks and degradation-modes particularly stress corrosion cracking and pitting are discussed. Current concerns at the Hanford Site are highlighted.

  11. CLASSIFICATION OF THE MGR DEFENSE HIGH LEVEL WASTE DISPOSAL CONTIANER

    SciTech Connect

    J.A. Ziegler

    1999-08-31

    The purpose of this analysis is to document the Quality Assurance (QA) classification of the Monitored Geologic Repository (MGR) defense high-level waste disposal container system structures, systems and components (SSCs) performed by the MGR Safety Assurance Department. This analysis also provides the basis for revision of YMP/90-55Q, Q-List (YMP 1998). The Q-List identifies those MGR SSCs subject to the requirements of DOE/RW-0333PY ''Quality Assurance Requirements and Description'' (QARD) (DOE 1998).

  12. THE AMERICAN HIGH SCHOOL GRADUATION RATE: TRENDS AND LEVELS*

    PubMed Central

    Heckman, James J.; LaFontaine, Paul A.

    2009-01-01

    This paper applies a unified methodology to multiple data sets to estimate both the levels and trends in U.S. high school graduation rates. We establish that (a) the true rate is substantially lower than widely used measures; (b) it peaked in the early 1970s; (c) majority/minority differentials are substantial and have not converged for 35 years; (d) lower post-1970 rates are not solely due to increasing immigrant and minority populations; (e) our findings explain part of the slowdown in college attendance and rising college wage premiums; and (f) widening graduation differentials by gender help explain increasing male-female college attendance gaps. PMID:20625528

  13. Solidification of Savannah River Plant high-level waste

    SciTech Connect

    Maher, R; Shafranek, L F; Stevens, III, W R

    1983-01-01

    The Department of Energy, in accord with recommendations from the Du Pont Company, has started construction of a Defense Waste Processing Facility (DWPF) at the Savannah River Plant. The facility should be completed by the end of 1988, and full-scale operation should begin in 1990. This facility will immobilize in borosilicate glass the large quantity of high-level radioactive waste now stored at the plant plus the waste to be generated from continued chemical reprocessing operations. The existing wastes at the Savannah River Plant will be completely converted by about 2010. 21 figures.

  14. High-level neutron coincidence counter maintenance manual

    SciTech Connect

    Swansen, J.; Collinsworth, P.

    1983-05-01

    High-level neutron coincidence counter operational (field) calibration and usage is well known. This manual makes explicit basic (shop) check-out, calibration, and testing of new units and is a guide for repair of failed in-service units. Operational criteria for the major electronic functions are detailed, as are adjustments and calibration procedures, and recurrent mechanical/electromechanical problems are addressed. Some system tests are included for quality assurance. Data on nonstandard large-scale integrated (circuit) components and a schematic set are also included.

  15. Market Designs for High Levels of Variable Generation: Preprint

    SciTech Connect

    Milligan, M.; Holttinen, H.; Kiviluoma, J.; Orths, A.; Lynch, M.; Soder, L.

    2014-10-01

    Variable renewable generation is increasing in penetration in modern power systems, leading to higher variability in the supply and price of electricity as well as lower average spot prices. This raises new challenges, particularly in ensuring sufficient capacity and flexibility from conventional technologies. Because the fixed costs and lifetimes of electricity generation investments are significant, designing markets and regulations that ensure the efficient integration of renewable generation is a significant challenge. This papers reviews the state of play of market designs for high levels of variable generation in the United States and Europe and considers new developments in both regions.

  16. Linearization of the Fermilab recycler high level RF

    SciTech Connect

    Joseph E Dey; Tom Kubicki; John Reid

    2003-05-28

    In studying the Recycler high level RF, it was found that at 89 kHz, the lowest frequency required by the system, some nonlinearities in magnitude and phase were discovered. The visible evidence of this was that beam injected in a barrier bucket had a definite slope at the top. Using a network analyzer, the S-parameter S{sub 21} was realized for the overall system and from mathematical modeling a second order numerator and denominator transfer function was found. The inverse of this transfer function gives their linearization transfer function. The linearization transfer function was realized in hardware by summing a high pass, band pass and low pass filter together. The resulting magnitude and phase plots, along with actual beam response will be shown.

  17. Wind resource quality affected by high levels of renewables

    DOE PAGESBeta

    Diakov, Victor

    2015-06-17

    For solar photovoltaic (PV) and wind resources, the capacity factor is an important parameter describing the quality of the resource. As the share of variable renewable resources (such as PV and wind) on the electric system is increasing, so does curtailment (and the fraction of time when it cannot be avoided). At high levels of renewable generation, curtailments effectively change the practical measure of resource quality from capacity factor to the incremental capacity factor. The latter accounts only for generation during hours of no curtailment and is directly connected with the marginal capital cost of renewable generators for a givenmore » level of renewable generation during the year. The Western U.S. wind generation is analyzed hourly for a system with 75% of annual generation from wind, and it is found that the value for the system of resources with equal capacity factors can vary by a factor of 2, which highlights the importance of using the incremental capacity factor instead. Finally, the effect is expected to be more pronounced in smaller geographic areas (or when transmission limitations imposed) and less pronounced at lower levels of renewable energy in the system with less curtailment.« less

  18. Wind resource quality affected by high levels of renewables

    SciTech Connect

    Diakov, Victor

    2015-06-17

    For solar photovoltaic (PV) and wind resources, the capacity factor is an important parameter describing the quality of the resource. As the share of variable renewable resources (such as PV and wind) on the electric system is increasing, so does curtailment (and the fraction of time when it cannot be avoided). At high levels of renewable generation, curtailments effectively change the practical measure of resource quality from capacity factor to the incremental capacity factor. The latter accounts only for generation during hours of no curtailment and is directly connected with the marginal capital cost of renewable generators for a given level of renewable generation during the year. The Western U.S. wind generation is analyzed hourly for a system with 75% of annual generation from wind, and it is found that the value for the system of resources with equal capacity factors can vary by a factor of 2, which highlights the importance of using the incremental capacity factor instead. Finally, the effect is expected to be more pronounced in smaller geographic areas (or when transmission limitations imposed) and less pronounced at lower levels of renewable energy in the system with less curtailment.

  19. Attenuation of high-level impulses by earmuffs.

    PubMed

    Zera, Jan; Mlynski, Rafal

    2007-10-01

    Attenuation of high-level acoustic impulses (noise reduction) by various types of earmuffs was measured using a laboratory source of type A impulses and an artificial test fixture compatible with the ISO 4869-3 standard. The measurements were made for impulses of peak sound-pressure levels (SPLs) from 150 to 170 dB. The rise time and A duration of the impulses depended on their SPL and were within a range of 12-400 mus (rise time) and 0.4-1.1 ms (A duration). The results showed that earmuff peak level attenuation increases by about 10 dB when the impulse's rise time and the A duration are reduced. The results also demonstrated that the signals under the earmuff cup have a longer rise and A duration than the original impulses recorded outside the earmuff. Results of the measurements were used to check the validity of various hearing damage risk criteria that specify the maximum permissible exposure to impulse noise. The present data lead to the conclusion that procedures in which hearing damage risk is assessed only from signal attenuation, without taking into consideration changes in the signal waveform under the earmuff, tend to underestimate the risk of hearing damage. PMID:17902846

  20. The CMS High Level Trigger System: Experience and Future Development

    NASA Astrophysics Data System (ADS)

    Bauer, G.; Behrens, U.; Bowen, M.; Branson, J.; Bukowiec, S.; Cittolin, S.; Coarasa, J. A.; Deldicque, C.; Dobson, M.; Dupont, A.; Erhan, S.; Flossdorf, A.; Gigi, D.; Glege, F.; Gomez-Reino, R.; Hartl, C.; Hegeman, J.; Holzner, A.; Hwong, Y. L.; Masetti, L.; Meijers, F.; Meschi, E.; Mommsen, R. K.; O'Dell, V.; Orsini, L.; Paus, C.; Petrucci, A.; Pieri, M.; Polese, G.; Racz, A.; Raginel, O.; Sakulin, H.; Sani, M.; Schwick, C.; Shpakov, D.; Simon, S.; Spataru, A. C.; Sumorok, K.

    2012-12-01

    The CMS experiment at the LHC features a two-level trigger system. Events accepted by the first level trigger, at a maximum rate of 100 kHz, are read out by the Data Acquisition system (DAQ), and subsequently assembled in memory in a farm of computers running a software high-level trigger (HLT), which selects interesting events for offline storage and analysis at a rate of order few hundred Hz. The HLT algorithms consist of sequences of offline-style reconstruction and filtering modules, executed on a farm of 0(10000) CPU cores built from commodity hardware. Experience from the operation of the HLT system in the collider run 2010/2011 is reported. The current architecture of the CMS HLT, its integration with the CMS reconstruction framework and the CMS DAQ, are discussed in the light of future development. The possible short- and medium-term evolution of the HLT software infrastructure to support extensions of the HLT computing power, and to address remaining performance and maintenance issues, are discussed.

  1. Historical high-resolution dynamic sea level variations

    NASA Astrophysics Data System (ADS)

    Brunnabend, Sandra-Esther; Dijkstra, Henk A.; Kliphuis, Michael; van Werkhoven, Ben; Bal, Henri E.; Maassen, Jason; van Meersbergen, Maarten; Seinstra, Frank

    2014-05-01

    To investigate future changes in the dynamics of the ocean and therefore in dynamic sea level, ocean models need to be able to adequately represent oceanic dynamical processes. Therefore, resolving ocean eddies and representing boundary currents is of major importance. In this study, we investigate historical variations in dynamical sea surface height using the strongly eddying global version of the Parallel Ocean Program (POP). First, differences in high and low-resolution ocean model results (0.1 vs. 1.0 degree) were analyzed using a climatological atmospheric forcing dataset. Second, we forced the high-resolution model by atmospheric conditions over the period from 1950 to 2000 that are derived from a simulation using the ECHAM5-OM1 model (within the ESSENCE project, see www.knmi.nl/~sterl/Essence/). In general, the large-scale ocean fields of the POP model simulation agree well with those of the low-resolution ocean model (MPI-OM) results. Variations occur due to the different models used and, especially, due to the capability of the high-resolution POP model to resolve eddies. A comparison of high-resolution ocean model results with in-situ measurements, such as dynamic topography provided by altimetry, and salinity and temperature provided by the WOA2013, also show good agreement.

  2. Spent fuel and high-level radioactive waste transportation report

    SciTech Connect

    Not Available

    1989-11-01

    This publication is intended to provide its readers with an introduction to the issues surrounding the subject of transportation of spent nuclear fuel and high-level radioactive waste, especially as those issues impact the southern region of the United States. It was originally issued by the Southern States Energy Board (SSEB) in July 1987 as the Spent Nuclear Fuel and High-Level Radioactive Waste Transportation Primer, a document patterned on work performed by the Western Interstate Energy Board and designed as a ``comprehensive overview of the issues.`` This work differs from that earlier effort in that it is designed for the educated layman with little or no background in nuclear waste issues. In addition, this document is not a comprehensive examination of nuclear waste issues but should instead serve as a general introduction to the subject. Owing to changes in the nuclear waste management system, program activities by the US Department of Energy and other federal agencies and developing technologies, much of this information is dated quickly. While this report uses the most recent data available, readers should keep in mind that some of the material is subject to rapid change. SSEB plans periodic updates in the future to account for changes in the program. Replacement pages sew be supplied to all parties in receipt of this publication provided they remain on the SSEB mailing list.

  3. ATW system impact on high-level waste

    SciTech Connect

    Arthur, E.D.

    1992-12-01

    This report discusses the Accelerator Transmutation of Waste (ATW) concept which aims at destruction of key long-lived radionuclides in high-level nuclear waste (HLW), both fission products and actinides. This focus makes it different from most other transmutation concepts which concentrate primarily on actinide burning. The ATW system uses an accelerator-driven, sub-critical assembly to create an intense thermal neutron environment for radionuclide transmutation. This feature allows rapid transmutation under low-inventory system conditions, which in turn, has a direct impact on the size of chemical separations and materials handling components of the system. Inventories in ATW are factors of eight to thirty times smaller than reactor systems of equivalent thermal power. Chemical separations systems are relatively small in scale and can be optimized to achieve high decontamination factors and minimized waste streams. The low-inventory feature also directly impacts material amounts remaining in the system at its end of life. In addition to its low-inventory operation, the accelerator-driven neutron source features of ATW are key to providing a sufficient level of neutrons to allow transmutation of long-lived fission products.

  4. High level radioactive waste glass production and product description

    SciTech Connect

    Sproull, J.F.; Marra, S.L.; Jantzen, C.M.

    1993-12-01

    This report examines borosilicate glass as a means of immobilizing high-level radioactive wastes. Borosilicate glass will encapsulate most of the defense and some of the commercial HLW in the US. The resulting waste forms must meet the requirements of the WA-SRD and the WAPS, which include a short term PCT durability test. The waste form producer must report the composition(s) of the borosilicate waste glass(es) produced but can choose the composition(s) to meet site-specific requirements. Although the waste form composition is the primary determinant of durability, the redox state of the glass; the existence, content, and composition of crystals; and the presence of glass-in-glass phase separation can affect durability. The waste glass should be formulated to avoid phase separation regions. The ultimate result of this effort will be a waste form which is much more stable and potentially less mobile than the liquid high level radioactive waste is currently.

  5. Unexpectedly high mercury level in pelleted commercial fish feed

    SciTech Connect

    Choi, M.H.; Cech, J.J. Jr.

    1998-10-01

    An unexpectedly high mercury (Hg) level was found in a pelleted commercial fish feed used to feed fish in laboratory and fish farm settings. Mean total Hg (T-Hg) concentration in the commercial fish pellets was 66 ppb. Mean total selenium (T-Se) concentration in the pellets was 1,120 ppb (ranging from 790 to 1,360 ppb). Total Hg and Se in the whole blood of Sacramento blackfish and in the fish feed were determined by inductively coupled plasma-mass spectrometry (ICP-MS). During a 10-week sampling period T-Hg in blood fluctuated between 35 and 56 ppb. A highly significant, positive correlation was found between T-Hg in the fish blood and in the fish feed through the sampling period. On the other hand, no correlation was found between T-Se in the fish feed and T-Hg or T-Se blood level. Researchers working with fish in Hg studies need to know that fish pellets may contain Hg and to consider the influence of these pellets in their results.

  6. How to achieve high-level expression of microbial enzymes

    PubMed Central

    Liu, Long; Yang, Haiquan; Shin, Hyun-dong; Chen, Rachel R.; Li, Jianghua; Du, Guocheng; Chen, Jian

    2013-01-01

    Microbial enzymes have been used in a large number of fields, such as chemical, agricultural and biopharmaceutical industries. The enzyme production rate and yield are the main factors to consider when choosing the appropriate expression system for the production of recombinant proteins. Recombinant enzymes have been expressed in bacteria (e.g., Escherichia coli, Bacillus and lactic acid bacteria), filamentous fungi (e.g., Aspergillus) and yeasts (e.g., Pichia pastoris). The favorable and very advantageous characteristics of these species have resulted in an increasing number of biotechnological applications. Bacterial hosts (e.g., E. coli) can be used to quickly and easily overexpress recombinant enzymes; however, bacterial systems cannot express very large proteins and proteins that require post-translational modifications. The main bacterial expression hosts, with the exception of lactic acid bacteria and filamentous fungi, can produce several toxins which are not compatible with the expression of recombinant enzymes in food and drugs. However, due to the multiplicity of the physiological impacts arising from high-level expression of genes encoding the enzymes and expression hosts, the goal of overproduction can hardly be achieved, and therefore, the yield of recombinant enzymes is limited. In this review, the recent strategies used for the high-level expression of microbial enzymes in the hosts mentioned above are summarized and the prospects are also discussed. We hope this review will contribute to the development of the enzyme-related research field. PMID:23686280

  7. Spent fuel and high-level radioactive waste transportation report

    SciTech Connect

    Not Available

    1990-11-01

    This publication is intended to provide its readers with an introduction to the issues surrounding the subject of transportation of spent nuclear fuel and high-level radioactive waste, especially as those issues impact the southern region of the United States. It was originally issued by the Southern States Energy Board (SSEB) in July 1987 as the Spent Nuclear Fuel and High-Level Radioactive Waste Transportation Primer, a document patterned on work performed by the Western Interstate Energy Board and designed as a ``comprehensive overview of the issues.`` This work differs from that earlier effort in that it is designed for the educated layman with little or no background in nuclear waste issues. In addition, this document is not a comprehensive examination of nuclear waste issues but should instead serve as a general introduction to the subject. Owing to changes in the nuclear waste management system, program activities by the US Department of Energy and other federal agencies and developing technologies, much of this information is dated quickly. While this report uses the most recent data available, readers should keep in mind that some of the material is subject to rapid change. SSEB plans periodic updates in the future to account for changes in the program. Replacement pages will be supplied to all parties in receipt of this publication provided they remain on the SSEB mailing list.

  8. Spent Fuel and High-Level Radioactive Waste Transportation Report

    SciTech Connect

    Not Available

    1992-03-01

    This publication is intended to provide its readers with an introduction to the issues surrounding the subject of transportation of spent nuclear fuel and high-level radioactive waste, especially as those issues impact the southern region of the United States. It was originally issued by SSEB in July 1987 as the Spent Nuclear Fuel and High-Level Radioactive Waste Transportation Primer, a document patterned on work performed by the Western Interstate Energy Board and designed as a ``comprehensive overview of the issues.`` This work differs from that earlier effort in that it is designed for the educated layman with little or no background in nuclear waste Issues. In addition. this document is not a comprehensive examination of nuclear waste issues but should instead serve as a general introduction to the subject. Owing to changes in the nuclear waste management system, program activities by the US Department of Energy and other federal agencies and developing technologies, much of this information is dated quickly. While this report uses the most recent data available, readers should keep in mind that some of the material is subject to rapid change. SSEB plans periodic updates in the future to account for changes in the program. Replacement pages will be supplied to all parties in receipt of this publication provided they remain on the SSEB mailing list.

  9. Multi-Level High School Classes: Astronomy Diagnostic Test Results

    NASA Astrophysics Data System (ADS)

    Hubbard, R.; Hufnagel, B.

    2001-12-01

    A content survey, the Astronomy Diagnostic Test (ADT) designed for undergraduate non-science astronomy courses, was administered as a post-course survey to five senior high classes in a Maryland high school. In 2001, the five classes chosen included all three levels of physics and an astronomy class. Each class had an even distribution of male and female students, with a total of 115 girls and 104 boys as subjects. Results of the survey include: (1) The Advanced Placement (AP) physics class scored highest and general physics lowest. (2) The AP class, most of whom will major in engineering or computer sciences, had a mean ADT score similar to post-course undergraduate non-science astronomy classes. (3) For all five classes, the girls had lower mean scores than the boys. (4) In two classes the girls' self-reported mean confidence was 40% lower than the boys' confidence; in the other three classes the confidence levels were the same. Additional detailed research was done on the three cosmology and ten physics questions in the ADT; girls outperformed the boys in only two of these thirteen questions.

  10. VITRIFICATION OF HIGH LEVEL WASTE AT THE SAVANNAH RIVER SITE

    SciTech Connect

    Fox, K.; Peeler, D.

    2009-06-17

    The objective of this study was to experimentally measure the properties and performance of a series of glasses with compositions that could represent high level waste Sludge Batch 5 (SB5) as vitrified at the Savannah River Site Defense Waste Processing Facility. These data were used to guide frit optimization efforts as the SB5 composition was finalized. Glass compositions for this study were developed by combining a series of SB5 composition projections with a group of candidate frits. The study glasses were fabricated using depleted uranium and their chemical compositions, crystalline contents and chemical durabilities were characterized. Trevorite was the only crystalline phase that was identified in a few of the study glasses after slow cooling, and is not of concern as spinels have been shown to have little impact on the durability of high level waste glasses. Chemical durability was quantified using the Product Consistency Test (PCT). All of the glasses had very acceptable durability performance. The results of this study indicate that a frit composition can be identified that will provide a processable and durable glass when combined with SB5.

  11. High-level hepatitis B virus replication in transgenic mice.

    PubMed Central

    Guidotti, L G; Matzke, B; Schaller, H; Chisari, F V

    1995-01-01

    Hepatitis B virus (HBV) transgenic mice whose hepatocytes replicate the virus at levels comparable to that in the infected livers of patients with chronic hepatitis have been produced, without any evidence of cytopathology. High-level viral gene expression was obtained in the liver and kidney tissues in three independent lineages. These animals were produced with a terminally redundant viral DNA construct (HBV 1.3) that starts just upstream of HBV enhancer I, extends completely around the circular viral genome, and ends just downstream of the unique polyadenylation site in HBV. In these animals, the viral mRNA is more abundant in centrilobular hepatocytes than elsewhere in the hepatic lobule. High-level viral DNA replication occurs inside viral nucleocapsid particles that preferentially form in the cytoplasm of these centrilobular hepatocytes, suggesting that an expression threshold must be reached for nucleocapsid assembly and viral replication to occur. Despite the restricted distribution of the viral replication machinery in centrilobular cytoplasmic nucleocapsids, nucleocapsid particles are detectable in the vast majority of hepatocyte nuclei throughout the hepatic lobule. The intranuclear nucleocapsid particles are empty, however, suggesting that viral nucleocapsid particle assembly occurs independently in the nucleus and the cytoplasm of the hepatocyte and implying that cytoplasmic nucleocapsid particles do not transport the viral genome across the nuclear membrane into the nucleus during the viral life cycle. This model creates the opportunity to examine the influence of viral and host factors on HBV pathogenesis and replication and to assess the antiviral potential of pharmacological agents and physiological processes, including the immune response. PMID:7666518

  12. Department of Energy pretreatment of high-level and low-level wastes

    SciTech Connect

    McGinnis, C.P.; Hunt, R.D.

    1995-12-31

    The remediation of the 1 {times} 10{sup 8} gal of highly radioactive waste in the underground storage tanks (USTs) at five US Department of Energy (DOE) sites is one of DOE`s greatest challenges. Therefore, the DOE Office of Environmental Management has created the Tank Focus Area (TFA) to manage an integrated technology development program that results in the safe and efficient remediation of UST waste. The TFA has divided its efforts into five areas, which are safety, characterization, retrieval/closure, pretreatment, and immobilization. All DOE pretreatment activities are integrated by the Pretreatment Technical Integration Manager of the TFA. For FY 1996, the 14 pretreatment tasks are divided into 3 systems: supernate separations, sludge treatment, and solid/liquid separation. The plans and recent results of these TFA tasks, which include two 25,000-gal demonstrations and two former TFA tasks on Cs removal, are presented. The pretreatment goals are to minimize the volume of high-level waste and the radioactivity in low-level waste.

  13. Confidence Level and Sensitivity Limits in High Contrast Imaging

    SciTech Connect

    Marois, C

    2007-11-07

    In long adaptive optics corrected exposures, exoplanet detections are currently limited by speckle noise originating from the telescope and instrument optics, and it is expected that such noise will also limit future high-contrast imaging instruments for both ground and space-based telescopes. Previous theoretical analysis have shown that the time intensity variations of a single speckle follows a modified Rician. It is first demonstrated here that for a circular pupil this temporal intensity distribution also represents the speckle spatial intensity distribution at a fix separation from the point spread function center; this fact is demonstrated using numerical simulations for coronagraphic and non-coronagraphic data. The real statistical distribution of the noise needs to be taken into account explicitly when selecting a detection threshold appropriate for some desired confidence level. In this paper, a technique is described to obtain the pixel intensity distribution of an image and its corresponding confidence level as a function of the detection threshold. Using numerical simulations, it is shown that in the presence of speckles noise, a detection threshold up to three times higher is required to obtain a confidence level equivalent to that at 5{sigma} for Gaussian noise. The technique is then tested using TRIDENT CFHT and angular differential imaging NIRI Gemini adaptive optics data. It is found that the angular differential imaging technique produces quasi-Gaussian residuals, a remarkable result compared to classical adaptive optic imaging. A power-law is finally derived to predict the 1-3 x 10{sup -7} confidence level detection threshold when averaging a partially correlated non-Gaussian noise.

  14. Confidence Level and Sensitivity Limits in High Contrast Imaging

    SciTech Connect

    Marois, C; LaFreniere, D; Macintosh, B; Doyon, R

    2008-06-02

    In long adaptive optics corrected exposures, exoplanet detections are currently limited by speckle noise originating from the telescope and instrument optics, and it is expected that such noise will also limit future high-contrast imaging instruments for both ground and space-based telescopes. Previous theoretical analysis have shown that the time intensity variations of a single speckle follows a modified Rician. It is first demonstrated here that for a circular pupil this temporal intensity distribution also represents the speckle spatial intensity distribution at a fix separation from the point spread function center; this fact is demonstrated using numerical simulations for coronagraphic and non-coronagraphic data. The real statistical distribution of the noise needs to be taken into account explicitly when selecting a detection threshold appropriate for some desired confidence level. In this paper, a technique is described to obtain the pixel intensity distribution of an image and its corresponding confidence level as a function of the detection threshold. Using numerical simulations, it is shown that in the presence of speckles noise, a detection threshold up to three times higher is required to obtain a confidence level equivalent to that at 5{sigma} for Gaussian noise. The technique is then tested using TRIDENT CFHT and angular differential imaging NIRI Gemini adaptive optics data. It is found that the angular differential imaging technique produces quasi-Gaussian residuals, a remarkable result compared to classical adaptive optic imaging. A power-law is finally derived to predict the 1-3 x 10{sup -7} confidence level detection threshold when averaging a partially correlated non-Gaussian noise.

  15. Engineering neural systems for high-level problem solving.

    PubMed

    Sylvester, Jared; Reggia, James

    2016-07-01

    There is a long-standing, sometimes contentious debate in AI concerning the relative merits of a symbolic, top-down approach vs. a neural, bottom-up approach to engineering intelligent machine behaviors. While neurocomputational methods excel at lower-level cognitive tasks (incremental learning for pattern classification, low-level sensorimotor control, fault tolerance and processing of noisy data, etc.), they are largely non-competitive with top-down symbolic methods for tasks involving high-level cognitive problem solving (goal-directed reasoning, metacognition, planning, etc.). Here we take a step towards addressing this limitation by developing a purely neural framework named galis. Our goal in this work is to integrate top-down (non-symbolic) control of a neural network system with more traditional bottom-up neural computations. galis is based on attractor networks that can be "programmed" with temporal sequences of hand-crafted instructions that control problem solving by gating the activity retention of, communication between, and learning done by other neural networks. We demonstrate the effectiveness of this approach by showing that it can be applied successfully to solve sequential card matching problems, using both human performance and a top-down symbolic algorithm as experimental controls. Solving this kind of problem makes use of top-down attention control and the binding together of visual features in ways that are easy for symbolic AI systems but not for neural networks to achieve. Our model can not only be instructed on how to solve card matching problems successfully, but its performance also qualitatively (and sometimes quantitatively) matches the performance of both human subjects that we had perform the same task and the top-down symbolic algorithm that we used as an experimental control. We conclude that the core principles underlying the galis framework provide a promising approach to engineering purely neurocomputational systems for problem

  16. High-Voltage-Input Level Translator Using Standard CMOS

    NASA Technical Reports Server (NTRS)

    Yager, Jeremy A.; Mojarradi, Mohammad M.; Vo, Tuan A.; Blalock, Benjamin J.

    2011-01-01

    proposed integrated circuit would translate (1) a pair of input signals having a low differential potential and a possibly high common-mode potential into (2) a pair of output signals having the same low differential potential and a low common-mode potential. As used here, "low" and "high" refer to potentials that are, respectively, below or above the nominal supply potential (3.3 V) at which standard complementary metal oxide/semiconductor (CMOS) integrated circuits are designed to operate. The input common-mode potential could lie between 0 and 10 V; the output common-mode potential would be 2 V. This translation would make it possible to process the pair of signals by use of standard 3.3-V CMOS analog and/or mixed-signal (analog and digital) circuitry on the same integrated-circuit chip. A schematic of the circuit is shown in the figure. Standard 3.3-V CMOS circuitry cannot withstand input potentials greater than about 4 V. However, there are many applications that involve low-differential-potential, high-common-mode-potential input signal pairs and in which standard 3.3-V CMOS circuitry, which is relatively inexpensive, would be the most appropriate circuitry for performing other functions on the integrated-circuit chip that handles the high-potential input signals. Thus, there is a need to combine high-voltage input circuitry with standard low-voltage CMOS circuitry on the same integrated-circuit chip. The proposed circuit would satisfy this need. In the proposed circuit, the input signals would be coupled into both a level-shifting pair and a common-mode-sensing pair of CMOS transistors. The output of the level-shifting pair would be fed as input to a differential pair of transistors. The resulting differential current output would pass through six standoff transistors to be mirrored into an output branch by four heterojunction bipolar transistors. The mirrored differential current would be converted back to potential by a pair of diode-connected transistors

  17. LIQUIDUS TEMPERATURE AND PRIMARY CRYSTALLIZATION PHASES IN HIGH-ZIRCONIA HIGH-LEVEL WASTE BOROSILICATE GLASSES

    EPA Science Inventory

    Liquidus temperature (TL) studies of high-Zr high-level waste (HLW) borosilicate glasseshave identified three primary phases: baddelyite (ZrO2), zircon (ZrSiO4), and alkali-zirconiumsilicates, such as parakeldyshite (Na2ZrSi2O7). Using published TL data for HLW glasses withthe...

  18. Do Highly Effective Principals Also Have High Levels of Cultural Intelligence?

    ERIC Educational Resources Information Center

    Naughton, Whitney Michelle

    2010-01-01

    Purpose: The purpose of this study was to determine if elementary school principals who exhibit characteristics of highly effective principals also possess high levels of cultural intelligence. Methodology: Three instruments were used in this study, combining both qualitative and quantitative approaches to the collection of data. The first…

  19. High-Level Fluorescence Labeling of Gram-Positive Pathogens

    PubMed Central

    Aymanns, Simone; Mauerer, Stefanie; van Zandbergen, Ger; Wolz, Christiane; Spellerberg, Barbara

    2011-01-01

    Fluorescence labeling of bacterial pathogens has a broad range of interesting applications including the observation of living bacteria within host cells. We constructed a novel vector based on the E. coli streptococcal shuttle plasmid pAT28 that can propagate in numerous bacterial species from different genera. The plasmid harbors a promoterless copy of the green fluorescent variant gene egfp under the control of the CAMP-factor gene (cfb) promoter of Streptococcus agalactiae and was designated pBSU101. Upon transfer of the plasmid into streptococci, the bacteria show a distinct and easily detectable fluorescence using a standard fluorescence microscope and quantification by FACS-analysis demonstrated values that were 10–50 times increased over the respective controls. To assess the suitability of the construct for high efficiency fluorescence labeling in different gram-positive pathogens, numerous species were transformed. We successfully labeled Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. equisimilis, Enterococcus faecalis, Enterococcus faecium, Streptococcus mutans, Streptococcus anginosus and Staphylococcus aureus strains utilizing the EGFP reporter plasmid pBSU101. In all of these species the presence of the cfb promoter construct resulted in high-level EGFP expression that could be further increased by growing the streptococcal and enterococcal cultures under high oxygen conditions through continuous aeration. PMID:21731607

  20. Modeling and optimization of defense high level waste removal sequencing

    NASA Astrophysics Data System (ADS)

    Paul, Pran Krishna

    A novel methodology has been developed which makes possible a very fast running computational tool, capable of performing 30 to 50 years of simulation of the entire Savannah River Site (SRS) high level waste complex in less than 2 minutes on a work station. The methodology has been implemented in the Production Planning Model (ProdMod) simulation code which uses Aspen Technology's dynamic simulation software development package SPEEDUP. ProdMod is a pseudo-dynamic simulation code solely based on algebraic equations, using no differential equations. The dynamic nature of the plant process is captured using linear constructs in which the time dependence is implicit. Another innovative approach implemented in ProdMod development is the mapping of event-space on to time-space and vice versa, which accelerates the computation without sacrificing the necessary details in the event-space. ProdMod uses this approach in coupling the time-space continuous simulation with the event-space batch simulation, avoiding the discontinuities inherent in dynamic simulation batch processing. In addition, a general purpose optimization scheme has been devised based on the pseudo-dynamic constructs and the event- and time-space algorithms of ProdMod. The optimization scheme couples a FORTRAN based stand-alone optimization driver with the SPEEDUP based ProdMod simulator to perform dynamic optimization. The scheme is capable of generating single or multiple optimal input conditions for different types of objective functions over single or multiple years of operations depending on the nature of the objective function and operating constraints. The resultant optimal inputs are then interfaced with ProdMod to simulate the dynamic behavior of the waste processing operations. At the conclusion on an optimized advancement step, the simulation parameters are then passed to the optimization driver to generate the next set of optimized parameters. An optimization algorithm using linear programming

  1. High-level waste tank farm set point document

    SciTech Connect

    Anthony, J.A. III

    1995-01-15

    Setpoints for nuclear safety-related instrumentation are required for actions determined by the design authorization basis. Minimum requirements need to be established for assuring that setpoints are established and held within specified limits. This document establishes the controlling methodology for changing setpoints of all classifications. The instrumentation under consideration involve the transfer, storage, and volume reduction of radioactive liquid waste in the F- and H-Area High-Level Radioactive Waste Tank Farms. The setpoint document will encompass the PROCESS AREA listed in the Safety Analysis Report (SAR) (DPSTSA-200-10 Sup 18) which includes the diversion box HDB-8 facility. In addition to the PROCESS AREAS listed in the SAR, Building 299-H and the Effluent Transfer Facility (ETF) are also included in the scope.

  2. High Level Waste System Impacts from Acid Dissolution of Sludge

    SciTech Connect

    KETUSKY, EDWARD

    2006-04-20

    This research evaluates the ability of OLI{copyright} equilibrium based software to forecast Savannah River Site High Level Waste system impacts from oxalic acid dissolution of Tank 1-15 sludge heels. Without further laboratory and field testing, only the use of oxalic acid can be considered plausible to support sludge heel dissolution on multiple tanks. Using OLI{copyright} and available test results, a dissolution model is constructed and validated. Material and energy balances, coupled with the model, identify potential safety concerns. Overpressurization and overheating are shown to be unlikely. Corrosion induced hydrogen could, however, overwhelm the tank ventilation. While pH adjustment can restore the minimal hydrogen generation, resultant precipitates will notably increase the sludge volume. OLI{copyright} is used to develop a flowsheet such that additional sludge vitrification canisters and other negative system impacts are minimized. Sensitivity analyses are used to assess the processability impacts from variations in the sludge/quantities of acids.

  3. Using the CMS High Level Trigger as a Cloud Resource

    NASA Astrophysics Data System (ADS)

    Colling, David; Huffman, Adam; McCrae, Alison; Lahiff, Andrew; Grandi, Claudio; Cinquilli, Mattia; Gowdy, Stephen; Coarasa, Jose Antonio; Tiradani, Anthony; Ozga, Wojciech; Chaze, Olivier; Sgaravatto, Massimo; Bauer, Daniela

    2014-06-01

    The CMS High Level Trigger is a compute farm of more than 10,000 cores. During data taking this resource is heavily used and is an integral part of the experiment's triggering system. However, outside of data taking periods this resource is largely unused. We describe why CMS wants to use the HLT as a cloud resource (outside of data taking periods) and how this has been achieved. In doing this we have turned a single-use cluster into an agile resource for CMS production computing. While we are able to use the HLT as a production cloud resource, there is still considerable further work that CMS needs to carry out before this resource can be used with the desired agility. This report, therefore, represents a snapshot of this activity at the time of CHEP 2013.

  4. Socioeconomic studies of high-level nuclear waste disposal.

    PubMed

    White, G F; Bronzini, M S; Colglazier, E W; Dohrenwend, B; Erikson, K; Hansen, R; Kneese, A V; Moore, R; Page, E B; Rappaport, R A

    1994-11-01

    The socioeconomic investigations of possible impacts of the proposed repository for high-level nuclear waste at Yucca Mountain, Nevada, have been unprecedented in several respects. They bear on the public decision that sooner or later will be made as to where and how to dispose permanently of the waste presently at military weapons installations and that continues to accumulate at nuclear power stations. No final decision has yet been made. There is no clear precedent from other countries. The organization of state and federal studies is unique. The state studies involve more disciplines than any previous efforts. They have been carried out in parallel to federal studies and have pioneered in defining some problems and appropriate research methods. A recent annotated bibliography provides interested scientists with a compact guide to the 178 published reports, as well as to relevant journal articles and related documents. PMID:7971963

  5. Socioeconomic studies of high-level nuclear waste disposal.

    PubMed Central

    White, G F; Bronzini, M S; Colglazier, E W; Dohrenwend, B; Erikson, K; Hansen, R; Kneese, A V; Moore, R; Page, E B; Rappaport, R A

    1994-01-01

    The socioeconomic investigations of possible impacts of the proposed repository for high-level nuclear waste at Yucca Mountain, Nevada, have been unprecedented in several respects. They bear on the public decision that sooner or later will be made as to where and how to dispose permanently of the waste presently at military weapons installations and that continues to accumulate at nuclear power stations. No final decision has yet been made. There is no clear precedent from other countries. The organization of state and federal studies is unique. The state studies involve more disciplines than any previous efforts. They have been carried out in parallel to federal studies and have pioneered in defining some problems and appropriate research methods. A recent annotated bibliography provides interested scientists with a compact guide to the 178 published reports, as well as to relevant journal articles and related documents. PMID:7971963

  6. A High-Level Language for Rule-Based Modelling

    PubMed Central

    Pedersen, Michael; Phillips, Andrew; Plotkin, Gordon D.

    2015-01-01

    Rule-based languages such as Kappa excel in their support for handling the combinatorial complexities prevalent in many biological systems, including signalling pathways. But Kappa provides little structure for organising rules, and large models can therefore be hard to read and maintain. This paper introduces a high-level, modular extension of Kappa called LBS-κ. We demonstrate the constructs of the language through examples and three case studies: a chemotaxis switch ring, a MAPK cascade, and an insulin signalling pathway. We then provide a formal definition of LBS-κ through an abstract syntax and a translation to plain Kappa. The translation is implemented in a compiler tool which is available as a web application. We finally demonstrate how to increase the expressivity of LBS-κ through embedded scripts in a general-purpose programming language, a technique which we view as generally applicable to other domain specific languages. PMID:26043208

  7. SIMULANT DEVELOPMENT FOR SAVANNAH RIVER SITE HIGH LEVEL WASTE

    SciTech Connect

    Stone, M; Russell Eibling, R; David Koopman, D; Dan Lambert, D; Paul Burket, P

    2007-09-04

    The Defense Waste Processing Facility (DWPF) at the Savannah River Site vitrifies High Level Waste (HLW) for repository internment. The process consists of three major steps: waste pretreatment, vitrification, and canister decontamination/sealing. The HLW consists of insoluble metal hydroxides (primarily iron, aluminum, magnesium, manganese, and uranium) and soluble sodium salts (carbonate, hydroxide, nitrite, nitrate, and sulfate). The HLW is processed in large batches through DWPF; DWPF has recently completed processing Sludge Batch 3 (SB3) and is currently processing Sludge Batch 4 (SB4). The composition of metal species in SB4 is shown in Table 1 as a function of the ratio of a metal to iron. Simulants remove radioactive species and renormalize the remaining species. Supernate composition is shown in Table 2.

  8. High-spin level scheme of {sup 183}Au

    SciTech Connect

    Song, L.T.; Zhou, X.H.; Zhang, Y. H.; Guo, Y. X.; Lei, X.G.; Zheng, Y.; Liu, M.L.; De Angelis, G.; Marginean, N.; Gadea, A.; Napoli, D.R.; Axiotis, M.; Rusu, C.; Martinez, T.

    2005-01-01

    High-spin states in {sup 183}Au have been studied experimentally using the {sup 159}Tb({sup 29}Si,5n){sup 183}Au reaction at a beam energy of 140 MeV. Three- or higherfold {gamma}-ray coincidences have been measured using the detector array of GASP. The level scheme of {sup 183}Au was revised and extended. A rotational band proposed as the unfavored signature branch of the {pi}i{sub 13/2} band has been observed for {sup 183}Au. Interaction properties between the two negative-signature bands of the {pi}h{sub 9/2}-{pi}f{sub 7/2} system have been discussed for the light odd-A Au nuclei.

  9. Blending resources to teach high school level astronomy

    NASA Astrophysics Data System (ADS)

    Rudiger, Lance

    This presentation will assist educators in incorporating various resources into a High School Level Astronomy course. I will use information and materials (slides, videos and handouts). I will share information I have gained as a mentor teacher in programs for NASA (JPL Solar System Ambassador), NRAO (National Radio Astronomy Observatory), AAS (American Astronomical Society Teacher Resource Agent and Leader workshop) and NYSUT State Science Comm. I will also present materials and information from workshops I have given at the SUNY@Potsdam Planetarium for educators, community members and students. I will also share a space science summer program I developed for Upward Bound at St. Lawrence University. This was mostly for Native Americans or economically disadvantaged.

  10. High level radioactive waste vitrification process equipment component testing

    SciTech Connect

    Siemens, D.H.; Heath, W.O.; Larson, D.E.; Craig, S.N.; Berger, D.N.; Goles, R.W.

    1985-04-01

    Remote operability and maintainability of vitrification equipment were assessed under shielded-cell conditions. The equipment tested will be applied to immobilize high-level and transuranic liquid waste slurries that resulted from plutonium production for defense weapons. Equipment tested included: a turntable for handling waste canisters under the melter; a removable discharge cone in the melter overflow section; a thermocouple jumper that extends into a shielded cell; remote instrument and electrical connectors; remote, mechanical, and heat transfer aspects of the melter glass overflow section; a reamer to clean out plugged nozzles in the melter top; a closed circuit camera to view the melter interior; and a device to retrieve samples of the glass product. A test was also conducted to evaluate liquid metals for use in a liquid metal sealing system.

  11. High-Level Language Production in Parkinson's Disease: A Review

    PubMed Central

    Altmann, Lori J. P.; Troche, Michelle S.

    2011-01-01

    This paper discusses impairments of high-level, complex language production in Parkinson's disease (PD), defined as sentence and discourse production, and situates these impairments within the framework of current psycholinguistic theories of language production. The paper comprises three major sections, an overview of the effects of PD on the brain and cognition, a review of the literature on language production in PD, and a discussion of the stages of the language production process that are impaired in PD. Overall, the literature converges on a few common characteristics of language production in PD: reduced information content, impaired grammaticality, disrupted fluency, and reduced syntactic complexity. Many studies also document the strong impact of differences in cognitive ability on language production. Based on the data, PD affects all stages of language production including conceptualization and functional and positional processing. Furthermore, impairments at all stages appear to be exacerbated by impairments in cognitive abilities. PMID:21860777

  12. 4.5 Meter high level waste canister study

    SciTech Connect

    Calmus, R. B.

    1997-10-01

    The Tank Waste Remediation System (TWRS) Storage and Disposal Project has established the Immobilized High-Level Waste (IBLW) Storage Sub-Project to provide the capability to store Phase I and II BLW products generated by private vendors. A design/construction project, Project W-464, was established under the Sub-Project to provide the Phase I capability. Project W-464 will retrofit the Hanford Site Canister Storage Building (CSB) to accommodate the Phase I I-ILW products. Project W-464 conceptual design is currently being performed to interim store 3.0 m-long BLW stainless steel canisters with a 0.61 in diameter, DOE is considering using a 4.5 in canister of the same diameter to reduce permanent disposal costs. This study was performed to assess the impact of replacing the 3.0 in canister with the 4.5 in canister. The summary cost and schedule impacts are described.

  13. Midwestern High-Level Radioactive Waste Transportation Project

    SciTech Connect

    Dantoin, T.S.

    1990-12-01

    For more than half a century, the Council of State Governments has served as a common ground for the states of the nation. The Council is a nonprofit, state-supported and -directed service organization that provides research and resources, identifies trends, supplies answers and creates a network for legislative, executive and judicial branch representatives. This List of Available Resources was prepared with the support of the US Department of Energy, Cooperative Agreement No. DE-FC02-89CH10402. However, any opinions, findings, conclusions, or recommendations expressed herein are those of the author(s) and do not necessarily reflect the views of DOE. The purpose of the agreement, and reports issued pursuant to it, is to identify and analyze regional issues pertaining to the transportation of high-level radioactive waste and to inform Midwestern state officials with respect to technical issues and regulatory concerns related to waste transportation.

  14. Calculates Neutron Production in Canisters of High-level Waste

    Energy Science and Technology Software Center (ESTSC)

    1993-01-15

    ALPHN calculates the (alpha,n) neutron production rate of a canister of vitrified high-level waste. The user supplies the chemical composition of the glass or glass-ceramic and the curies of the alpha-emitting actinides present. The output of the program gives the (alpha,n) neutron production of each actinide in neutrons per second and the total for the canister. The (alpha,n) neutron production rates are source terms only; that is, they are production rates within the glass andmore » do not take into account the shielding effect of the glass. For a given glass composition, the user can calculate up to eight cases simultaneously; these cases are based on the same glass composition but contain different quantities of actinides per canister.« less

  15. A high-level language for rule-based modelling.

    PubMed

    Pedersen, Michael; Phillips, Andrew; Plotkin, Gordon D

    2015-01-01

    Rule-based languages such as Kappa excel in their support for handling the combinatorial complexities prevalent in many biological systems, including signalling pathways. But Kappa provides little structure for organising rules, and large models can therefore be hard to read and maintain. This paper introduces a high-level, modular extension of Kappa called LBS-κ. We demonstrate the constructs of the language through examples and three case studies: a chemotaxis switch ring, a MAPK cascade, and an insulin signalling pathway. We then provide a formal definition of LBS-κ through an abstract syntax and a translation to plain Kappa. The translation is implemented in a compiler tool which is available as a web application. We finally demonstrate how to increase the expressivity of LBS-κ through embedded scripts in a general-purpose programming language, a technique which we view as generally applicable to other domain specific languages. PMID:26043208

  16. PLUTONIUM/HIGH-LEVEL VITRIFIED WASTE BDBE DOSE CALCULATION

    SciTech Connect

    J.A. Ziegler

    2000-11-20

    The purpose of this calculation is to provide a dose consequence analysis of high-level waste (HLW) consisting of plutonium immobilized in vitrified HLW to be handled at the proposed Monitored Geologic Repository at Yucca Mountain for a beyond design basis event (BDBE) under expected conditions using best estimate values for each calculation parameter. In addition to the dose calculation, a plutonium respirable particle size for dose calculation use is derived. The current concept for this waste form is plutonium disks enclosed in cans immobilized in canisters of vitrified HLW (i.e., glass). The plutonium inventory at risk used for this calculation is selected from Plutonium Immobilization Project Input for Yucca Mountain Total Systems Performance Assessment (Shaw 1999). The BDBE examined in this calculation is a nonmechanistic initiating event and the sequence of events that follow to cause a radiological release. This analysis will provide the radiological releases and dose consequences for a postulated BDBE. Results may be considered in other analyses to determine or modify the safety classification and quality assurance level of repository structures, systems, and components. This calculation uses best available technical information because the BDBE frequency is very low (i.e., less than 1.0E-6 events/year) and is not required for License Application for the Monitored Geologic Repository. The results of this calculation will not be used as part of a licensing or design basis.

  17. Experimental oscillator strengths of highly excited levels of Mo II

    NASA Astrophysics Data System (ADS)

    Aragón, C.; Aguilera, J. A.; Ortiz, M.; Mayo-García, R.

    2016-05-01

    Measurements of 161 oscillator strengths arising from highly excited levels of Mo II are presented, 148 of which are obtained for the first time. These results extend the previous ones already published on lower excited levels of Mo II. A laser-induced plasma generated from a fused glass sample prepared from molybdenum oxide with a Mo atomic concentration of 0.1% was used to obtain the presented radiative parameters via laser-induced breakdown spectroscopy. Measurements were carried out with an electron density of (2.5 ± 0.1) · 1017 cm‑3 and an electron temperature of 14 400 ± 200 K as the plasma evolved in air at atmospheric pressure. As a consequence, an optically thin plasma and a local thermodynamic equilibrium environment were then present in the measurements. In order to put on an absolute scale the relative intensities, both the combination of branching fractions with measured lifetimes and the comparison of well-known lines using the plasma temperature were carried out. Also, the new results are compared with previously theoretical and obtained experimental values wherever possible.

  18. A High School Project Seminar on Sea Level Rise

    NASA Astrophysics Data System (ADS)

    Seitz, M.; Bosch, W.

    2012-04-01

    In Bavaria the curriculum of the upper grade of high school includes a so called project seminar, running over one and a half year. The aims of the seminar are to let the pupils learn to work on a specific topic, to organize themselves in a team, to improve their soft skills and become familiar with the working life. The topic of the project seminar, jointly organized by the Bertold-Brecht-Gymnasium in Munich and the Deutsche Geodätische Forschungsinstitut (DGFI) was on the "Global sea level rise". A team of 13 pupils computed the mean sea level rise by using on the one hand altimetry data of TOPEX, Jason-1 and Jason2 and on the other hand data of globally distributed tide gauges, corrected for vertical crustal movements derived from GPS products. The results of the two independent approaches were compared with each other and discussed considering also statements and discussions found in press, TV, and the web. Finally, a presentation was prepared and presented at school.

  19. The LHCb Data Acquisition and High Level Trigger Processing Architecture

    NASA Astrophysics Data System (ADS)

    Frank, M.; Gaspar, C.; Jost, B.; Neufeld, N.

    2015-12-01

    The LHCb experiment at the LHC accelerator at CERN collects collisions of particle bunches at 40 MHz. After a first level of hardware trigger with an output rate of 1 MHz, the physically interesting collisions are selected by running dedicated trigger algorithms in the High Level Trigger (HLT) computing farm. This farm consists of up to roughly 25000 CPU cores in roughly 1750 physical nodes each equipped with up to 4 TB local storage space. This work describes the LHCb online system with an emphasis on the developments implemented during the current long shutdown (LS1). We will elaborate the architecture to treble the available CPU power of the HLT farm and the technicalities to determine and verify precise calibration and alignment constants which are fed to the HLT event selection procedure. We will describe how the constants are fed into a two stage HLT event selection facility using extensively the local disk buffering capabilities on the worker nodes. With the installed disk buffers, the CPU resources can be used during periods of up to ten days without beams. These periods in the past accounted to more than 70% of the total time.

  20. Hemipelvectomy: high-level amputation surgery and prosthetic rehabilitation.

    PubMed

    Houdek, Matthew T; Kralovec, Michael E; Andrews, Karen L

    2014-07-01

    The hemipelvectomy, most commonly performed for pelvic tumor resection, is one of the most technically demanding and invasive surgical procedures performed today. Adequate soft tissue coverage and wound complications after hemipelvectomy are important considerations. Rehabilitation after hemipelvectomy is optimally managed by a multidisciplinary integrated team. Understanding the functional outcomes for this population assists the rehabilitation team to counsel patients, plan goals, and determine discharge needs. The most important rehabilitation goal is the optimal restoration of the patient's functional independence. Factors such as age, sex, etiology, level of amputation, and general health play important roles in determining prosthetic use. The three main criteria for successful prosthetic rehabilitation of patients with high-level amputation are comfort, function, and cosmesis. Recent advances in hip and knee joints have contributed to increased function. Prosthetic use after hemipelvectomy improves balance and decreases the need for a gait aid. Using a prosthesis helps maintain muscle strength and tone, cardiovascular health, and functional mobility. With new advances in prosthetic components, patients are choosing to use their prostheses for primary mobility. PMID:24508940

  1. Adaptation, high-level vision, and the phenomenology of perception

    NASA Astrophysics Data System (ADS)

    Webster, Michael A.

    2002-06-01

    To what extent do we have shared or unique visual experiences? This paper examines how the answer to this question is constrained by known processes of visual adaptation. Adaptation constantly recalibrates visual sensitivity so that our vision is matched to the stimuli that we are currently exposed to. These processes normalize perception not only to low-level features in the image, but to high-level, biologically relevant properties of the visual world. They can therefore strongly impact many natural perceptual judgments. To the extent that observers are exposed to and thus adapted by a different environment, their vision will be normalized in different ways and their subjective visual experience will differ. These differences are illustrated by considering how adaptation can influence human face perception. To the extent that observers are exposed and adapted to common properties in the environment, their vision will be adjusted toward common states, and in this respect they will have a common visual experience. This is illustrated by reviewing the effects of adaptation on the perception of image blur. In either case, it is the similarities or differences in the stimuli - and not the intrinsic similarities or differences in the observers - which determine the relative states of adaptation. Thus at least some aspects of our private internal experience are controlled by external factors that are accessible to objective measurement.

  2. High-level waste program integration within the DOE complex

    SciTech Connect

    Valentine, J.H.; Davis, N.R.; Malone, K.; Schaus, P.S.

    1998-03-01

    Eleven major Department of Energy (DOE) site contractors were chartered by the Assistant Secretary to use a systems engineering approach to develop and evaluate technically defensible cost savings opportunities across the complex. Known as the complex-wide Environmental Management Integration (EMI), this process evaluated all the major DOE waste streams including high level waste (HLW). Across the DOE complex, this waste stream has the highest life cycle cost and is scheduled to take until at least 2035 before all HLW is processed for disposal. Technical contract experts from the four DOE sites that manage high level waste participated in the integration analysis: Hanford, Savannah River Site (SRS), Idaho National Engineering and Environmental Laboratory (INEEL), and West Valley Demonstration Project (WVDP). In addition, subject matter experts from the Yucca Mountain Project and the Tanks Focus Area participated in the analysis. Also, departmental representatives from the US Department of Energy Headquarters (DOE-HQ) monitored the analysis and results. Workouts were held throughout the year to develop recommendations to achieve a complex-wide integrated program. From this effort, the HLW Environmental Management (EM) Team identified a set of programmatic and technical opportunities that could result in potential cost savings and avoidance in excess of $18 billion and an accelerated completion of the HLW mission by seven years. The cost savings, schedule improvements, and volume reduction are attributed to a multifaceted HLW treatment disposal strategy which involves waste pretreatment, standardized waste matrices, risk-based retrieval, early development and deployment of a shipping system for glass canisters, and reasonable, low cost tank closure.

  3. THE HIGH-ENERGY IMPULSIVE GROUND-LEVEL ENHANCEMENT

    SciTech Connect

    McCracken, K. G.; Moraal, H.; Shea, M. A.

    2012-12-20

    We have studied short-lived (21 minute average duration), highly anisotropic pulses of cosmic rays that constitute the first phase of 10 large ground-level enhancements (GLEs), and which extend to rigidities in the range 5-20 GV. We provide a set of constraints that must be met by any putative acceleration mechanism for this type of solar-energetic-particle (SEP) event. The pulses usually have very short rise-times (three to five minutes) at all rigidities, and exhibit the remarkable feature that the intensity drops precipitously by 50% to 70% from the maximum within another three to five minutes. Both the rising and falling phases exhibit velocity dispersion, which indicates that there are particles with rigidities in the range 1 < P (GV) < 3 in the beam, and the evidence is that there is little scattering en route from the Sun. We name these events the high-energy impulsive ground-level enhancement (HEI GLE). We argue that the time-dependence observed at Earth at {approx}5 GV is a close approximation to that of the SEP pulse injected into the open heliospheric magnetic field in the vicinity of the Sun. We conclude that the temporal characteristics of the HEI GLE impose nine constraints on any putative acceleration process. Two of the HEI GLEs are preceded by short-lived, fast-rising neutron and >90 MeV gamma-ray bursts, indicating that freshly accelerated SEPs had impinged on higher-density matter in the chromosphere prior to the departure of the SEP pulse for Earth. This study was based on an updated archive of the 71 GLEs in the historic record, which is now available for public use.

  4. High level waste characterization in support of low level waste certification. I. HLW supernate radionuclide characterization

    SciTech Connect

    Jamison, M.E.; d`Entremont, P.D.; Clemmons, J.S.; Bess, C.E.; Brown, D.F.

    1994-07-08

    High Level Waste Programs has radioactive waste storage, treatment and processing facilities that are located in the F and H Areas at the Savannah River Site. These facilities include the Effluent Treatment Facility (ETF), F and H Area Tank Farms, Extended Sludge Processing (ESP), and In-Tank Precipitation (ITP). Job wastes are generated from operation, maintenance, and construction activities inside radiological areas. These items may have been contaminated with radioactive supernate, salt, and sludge material. Most of these wastes will be disposed of in the E-area Vaults. Therefore, an isotopic and hazardous characterization must be performed. The characterization of HLW supernate radionuclides is discussed in Chapter I. The characterization for salt and sludge phases, which can also contaminate LLW, will be included in other Chapters.

  5. Ultrafilter Conditions for High Level Waste Sludge Processing

    SciTech Connect

    Geeting, John GH; Hallen, Richard T.; Peterson, Reid A.

    2006-08-28

    An evaluation of the optimal filtration conditions was performed based on test data obtained from filtration of a High Level Waste Sludge sample from the Hanford tank farms. This evaluation was performed using the anticipated configuration for the Waste Treatment Plant at the Hanford site. Testing was performed to identify the optimal pressure drop and cross flow velocity for filtration at both high and low solids loading. However, this analysis indicates that the actual filtration rate achieved is relatively insensitive to these conditions under anticipated operating conditions. The maximum filter flux was obtained by adjusting the system control valve pressure from 400 to 650 kPa while the filter feed concentration increased from 5 to 20 wt%. However, operating the system with a constant control valve pressure drop of 500 kPa resulted in a less than 1% reduction in the average filter flux. Also note that allowing the control valve pressure to swing as much as +/- 20% resulted in less than a 5% decrease in filter flux.

  6. Bubble growth by rectified diffusion at high gas supersaturation levels.

    PubMed

    Ilinskii, Yurii A; Wilson, Preston S; Hamilton, Mark F

    2008-10-01

    For high gas supersaturation levels in liquids, on the order of 300% as predicted in capillaries of marine mammals following a series of dives [D. S. Houser, R. Howard, and S. Ridgway, J. Theor. Biol. 213, 183-195 (2001)], standard mathematical models of both static and rectified diffusion are found to underestimate the rate of bubble growth by 10%-20%. The discrepancy is demonstrated by comparing predictions based on existing mathematical models with direct numerical solutions of the differential equations for gas diffusion in the liquid and thermal conditions in the bubble. Underestimation of bubble growth by existing mathematical models is due to the underlying assumption that the gas concentration in the liquid is given by its value for a bubble of constant equilibrium radius. This assumption is violated when high supersaturation causes the bubble to grow too fast in relation to the time scale associated with diffusion. Rapid bubble growth results in an increased gas concentration gradient at the bubble wall and therefore a growth rate in excess of predictions based on constant equilibrium bubble radius. PMID:19062834

  7. High estradiol levels improve false memory rates and meta-memory in highly schizotypal women.

    PubMed

    Hodgetts, Sophie; Hausmann, Markus; Weis, Susanne

    2015-10-30

    Overconfidence in false memories is often found in patients with schizophrenia and healthy participants with high levels of schizotypy, indicating an impairment of meta-cognition within the memory domain. In general, cognitive control is suggested to be modulated by natural fluctuations in oestrogen. However, whether oestrogen exerts beneficial effects on meta-memory has not yet been investigated. The present study sought to provide evidence that high levels of schizotypy are associated with increased false memory rates and overconfidence in false memories, and that these processes may be modulated by natural differences in estradiol levels. Using the Deese-Roediger-McDermott paradigm, it was found that highly schizotypal participants with high estradiol produced significantly fewer false memories than those with low estradiol. No such difference was found within the low schizotypy participants. Highly schizotypal participants with high estradiol were also less confident in their false memories than those with low estradiol; low schizotypy participants with high estradiol were more confident. However, these differences only approached significance. These findings suggest that the beneficial effect of estradiol on memory and meta-memory observed in healthy participants is specific to highly schizotypal individuals and might be related to individual differences in baseline dopaminergic activity. PMID:26292620

  8. Defense High Level Waste Disposal Container System Description

    SciTech Connect

    2000-10-12

    The Defense High Level Waste Disposal Container System supports the confinement and isolation of waste within the Engineered Barrier System of the Monitored Geologic Repository (MGR). Disposal containers are loaded and sealed in the surface waste handling facilities, transferred to the underground through the accesses using a rail mounted transporter, and emplaced in emplacement drifts. The defense high level waste (HLW) disposal container provides long-term confinement of the commercial HLW and defense HLW (including immobilized plutonium waste forms (IPWF)) placed within disposable canisters, and withstands the loading, transfer, emplacement, and retrieval loads and environments. U.S. Department of Energy (DOE)-owned spent nuclear fuel (SNF) in disposable canisters may also be placed in a defense HLW disposal container along with commercial HLW waste forms, which is known as 'co-disposal'. The Defense High Level Waste Disposal Container System provides containment of waste for a designated period of time, and limits radionuclide release. The disposal container/waste package maintains the waste in a designated configuration, withstands maximum handling and rockfall loads, limits the individual canister temperatures after emplacement, resists corrosion in the expected handling and repository environments, and provides containment of waste in the event of an accident. Defense HLW disposal containers for HLW disposal will hold up to five HLW canisters. Defense HLW disposal containers for co-disposal will hold up to five HLW canisters arranged in a ring and one DOE SNF canister in the ring. Defense HLW disposal containers also will hold two Multi-Canister Overpacks (MCOs) and two HLW canisters in one disposal container. The disposal container will include outer and inner cylinders, outer and inner cylinder lids, and may include a canister guide. An exterior label will provide a means by which to identify the disposal container and its contents. Different materials

  9. Review of high-level waste form properties. [146 bibliographies

    SciTech Connect

    Rusin, J.M.

    1980-12-01

    This report is a review of waste form options for the immobilization of high-level-liquid wastes from the nuclear fuel cycle. This review covers the status of international research and development on waste forms as of May 1979. Although the emphasis in this report is on waste form properties, process parameters are discussed where they may affect final waste form properties. A summary table is provided listing properties of various nuclear waste form options. It is concluded that proposed waste forms have properties falling within a relatively narrow range. In regard to crystalline versus glass waste forms, the conclusion is that either glass of crystalline materials can be shown to have some advantage when a single property is considered; however, at this date no single waste form offers optimum properties over the entire range of characteristics investigated. A long-term effort has been applied to the development of glass and calcine waste forms. Several additional waste forms have enough promise to warrant continued research and development to bring their state of development up to that of glass and calcine. Synthetic minerals, the multibarrier approach with coated particles in a metal matrix, and high pressure-high temperature ceramics offer potential advantages and need further study. Although this report discusses waste form properties, the total waste management system should be considered in the final selection of a waste form option. Canister design, canister materials, overpacks, engineered barriers, and repository characteristics, as well as the waste form, affect the overall performance of a waste management system. These parameters were not considered in this comparison.

  10. Activity profile of high-level Australian lacrosse players.

    PubMed

    Polley, Chris S; Cormack, Stuart J; Gabbett, Tim J; Polglaze, Ted

    2015-01-01

    Despite lacrosse being one of the fastest growing team sports in the world, there is a paucity of information detailing the activity profile of high-level players. Microtechnology systems (global positioning systems and accelerometers) provide the opportunity to obtain detailed information on the activity profile in lacrosse. Therefore, this study aimed to analyze the activity profile of lacrosse match-play using microtechnology. Activity profile variables assessed relative to minutes of playing time included relative distance (meter per minute), distance spent standing (0-0.1 m·min), walking (0.2-1.7 m·min), jogging (1.8-3.2 m·min), running (3.3-5.6 m·min), sprinting (≥5.7 m·min), number of high, moderate, low accelerations and decelerations, and player load (PL per minute), calculated as the square root of the sum of the squared instantaneous rate of change in acceleration in 3 vectors (medio-lateral, anterior-posterior, and vertical). Activity was recorded from 14 lacrosse players over 4 matches during a national tournament. Players were separated into positions of attack, midfield, or defense. Differences (effect size [ES] ± 90% confidence interval) between positions and periods of play were considered likely positive when there was ≥75% likelihood of the difference exceeding an ES threshold of 0.2. Midfielders had likely covered higher (mean ± SD) meters per minute (100 ± 11) compared with attackers (87 ± 14; ES = 0.89 ± 1.04) and defenders (79 ± 14; ES = 1.54 ± 0.94) and more moderate and high accelerations and decelerations. Almost all variables across positions were reduced in quarter 4 compared with quarter 1. Coaches should accommodate for positional differences when preparing lacrosse players for competition. PMID:25264672

  11. Interleukin-1- and Type I Interferon-Dependent Enhanced Immunogenicity of an NYVAC-HIV-1 Env-Gag-Pol-Nef Vaccine Vector with Dual Deletions of Type I and Type II Interferon-Binding Proteins

    PubMed Central

    Delaloye, Julie; Filali-Mouhim, Abdelali; Cameron, Mark J.; Haddad, Elias K.; Harari, Alexandre; Goulet, Jean-Pierre; Gomez, Carmen E.; Perdiguero, Beatriz; Esteban, Mariano; Pantaleo, Giuseppe; Roger, Thierry; Sékaly, Rafick-Pierre

    2015-01-01

    ABSTRACT NYVAC, a highly attenuated, replication-restricted poxvirus, is a safe and immunogenic vaccine vector. Deletion of immune evasion genes from the poxvirus genome is an attractive strategy for improving the immunogenic properties of poxviruses. Using systems biology approaches, we describe herein the enhanced immunological profile of NYVAC vectors expressing the HIV-1 clade C env, gag, pol, and nef genes (NYVAC-C) with single or double deletions of genes encoding type I (ΔB19R) or type II (ΔB8R) interferon (IFN)-binding proteins. Transcriptomic analyses of human monocytes infected with NYVAC-C, NYVAC-C with the B19R deletion (NYVAC-C-ΔB19R), or NYVAC-C with B8R and B19R deletions (NYVAC-C-ΔB8RB19R) revealed a concerted upregulation of innate immune pathways (IFN-stimulated genes [ISGs]) of increasing magnitude with NYVAC-C-ΔB19R and NYVAC-C-ΔB8RB19R than with NYVAC-C. Deletion of B8R and B19R resulted in an enhanced activation of IRF3, IRF7, and STAT1 and the robust production of type I IFNs and of ISGs, whose expression was inhibited by anti-type I IFN antibodies. Interestingly, NYVAC-C-ΔB8RB19R induced the production of much higher levels of proinflammatory cytokines (tumor necrosis factor [TNF], interleukin-6 [IL-6], and IL-8) than NYVAC-C or NYVAC-C-ΔB19R as well as a strong inflammasome response (caspase-1 and IL-1β) in infected monocytes. Top network analyses showed that this broad response mediated by the deletion of B8R and B19R was organized around two upregulated gene expression nodes (TNF and IRF7). Consistent with these findings, monocytes infected with NYVAC-C-ΔB8RB19R induced a stronger type I IFN-dependent and IL-1-dependent allogeneic CD4+ T cell response than monocytes infected with NYVAC-C or NYVAC-C-ΔB19R. Dual deletion of type I and type II IFN immune evasion genes in NYVAC markedly enhanced its immunogenic properties via its induction of the increased expression of type I IFNs and IL-1β and make it an attractive candidate HIV

  12. [Identification of high-lying odd energy levels of uranium by resonant ionization mass spectrometry].

    PubMed

    Du, H; Shi, G; Huang, M; Jin, C

    2000-06-01

    Single-colour and two-colour multiphoton resonant ionization spectra of uranium atom were studied extensively with a Nd:YAG laser-pumped dye laser atomic beam apparatus time-of-flight mass spectrometer in our laboratory. The energy locations of high-lying odd-parity levels in the region 33,003-34,264 cm-1, measured by a two-colour three-step ionization technique, were reported here. The angular momentum quantum number J was uniquely assigned for these levels by using angular momentum selection rules. PMID:12958925

  13. High levels of untreated distress and fatigue in cancer patients.

    PubMed

    Carlson, L E; Angen, M; Cullum, J; Goodey, E; Koopmans, J; Lamont, L; MacRae, J H; Martin, M; Pelletier, G; Robinson, J; Simpson, J S A; Speca, M; Tillotson, L; Bultz, B D

    2004-06-14

    The purpose of the study was to assess a large representative sample of cancer patients on distress levels, common psychosocial problems, and awareness and use of psychosocial support services. A total of 3095 patients were assessed over a 4-week period with the Brief Symptom Inventory-18 (BSI-18), a common problems checklist, and on awareness and use of psychosocial resources. Full data was available on 2776 patients. On average, patients were 60 years old, Caucasian (78.3%), and middle class. Approximately, half were attending for follow-up care. Types of cancer varied, with the largest groups being breast (23.5%), prostate (16.9%), colorectal (7.5%), and lung (5.8%) cancer patients. Overall, 37.8% of all patients met criteria for general distress in the clinical range. A higher proportion of men met case criteria for somatisation, and more women for depression. There were no gender differences in anxiety or overall distress severity. Minority patients were more likely to be distressed, as were those with lower income, cancers other than prostate, and those currently on active treatment. Lung, pancreatic, head and neck, Hodgkin's disease, and brain cancer patients were the most distressed. Almost half of all patients who met distress criteria had not sought professional psychosocial support nor did they intend to in the future. In conclusion, distress is very common in cancer patients across diagnoses and across the disease trajectory. Many patients who report high levels of distress are not taking advantage of available supportive resources. Barriers to such use, and factors predicting distress and use of psychosocial care, require further exploration. PMID:15162149

  14. Cementitious Grout for Closing SRS High Level Waste Tanks - 12315

    SciTech Connect

    Langton, C.A.; Stefanko, D.B.; Burns, H.H.; Waymer, J.; Mhyre, W.B.; Herbert, J.E.; Jolly, J.C. Jr.

    2012-07-01

    In 1997, the first two United States Department of Energy (US DOE) high level waste tanks (Tanks 17-F and 20-F: Type IV, single shell tanks) were taken out of service (permanently closed) at the Savannah River Site (SRS). In 2012, the DOE plans to remove from service two additional Savannah River Site (SRS) Type IV high-level waste tanks, Tanks 18-F and 19-F. These tanks were constructed in the late 1950's and received low-heat waste and do not contain cooling coils. Operational closure of Tanks 18-F and 19-F is intended to be consistent with the applicable requirements of the Resource Conservation and Recovery Act (RCRA) and the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and will be performed in accordance with South Carolina Department of Health and Environmental Control (SCDHEC). The closure will physically stabilize two 4.92E+04 cubic meter (1.3 E+06 gallon) carbon steel tanks and isolate and stabilize any residual contaminants left in the tanks. Ancillary equipment abandoned in the tanks will also be filled to the extent practical. A Performance Assessment (PA) has been developed to assess the long-term fate and transport of residual contamination in the environment resulting from the operational closure of the F-Area Tank Farm (FTF) waste tanks. Next generation flowable, zero-bleed cementitious grouts were designed, tested, and specified for closing Tanks 18-F and 19-F and for filling the abandoned equipment. Fill requirements were developed for both the tank and equipment grouts. All grout formulations were required to be alkaline with a pH of 12.4 and to be chemically reducing with a reduction potential (Eh) of -200 to -400. Grouts with this chemistry stabilize potential contaminants of concern. This was achieved by including Portland cement and Grade 100 slag in the mixes, respectively. Ingredients and proportions of cementitious reagents were selected and adjusted to support the mass placement strategy developed by

  15. Spent nuclear fuel project high-level information management plan

    SciTech Connect

    Main, G.C.

    1996-09-13

    This document presents the results of the Spent Nuclear Fuel Project (SNFP) Information Management Planning Project (IMPP), a short-term project that identified information management (IM) issues and opportunities within the SNFP and outlined a high-level plan to address them. This high-level plan for the SNMFP IM focuses on specific examples from within the SNFP. The plan`s recommendations can be characterized in several ways. Some recommendations address specific challenges that the SNFP faces. Others form the basis for making smooth transitions in several important IM areas. Still others identify areas where further study and planning are indicated. The team`s knowledge of developments in the IM industry and at the Hanford Site were crucial in deciding where to recommend that the SNFP act and where they should wait for Site plans to be made. Because of the fast pace of the SNFP and demands on SNFP staff, input and interaction were primarily between the IMPP team and members of the SNFP Information Management Steering Committee (IMSC). Key input to the IMPP came from a workshop where IMSC members and their delegates developed a set of draft IM principles. These principles, described in Section 2, became the foundation for the recommendations found in the transition plan outlined in Section 5. Availability of SNFP staff was limited, so project documents were used as a basis for much of the work. The team, realizing that the status of the project and the environment are continually changing, tried to keep abreast of major developments since those documents were generated. To the extent possible, the information contained in this document is current as of the end of fiscal year (FY) 1995. Programs and organizations on the Hanford Site as a whole are trying to maximize their return on IM investments. They are coordinating IM activities and trying to leverage existing capabilities. However, the SNFP cannot just rely on Sitewide activities to meet its IM requirements

  16. Crystalline plutonium hosts derived from high-level waste formulations.

    SciTech Connect

    O'Holleran, T. P.

    1998-04-24

    The Department of Energy has selected immobilization for disposal in a repository as one approach for disposing of excess plutonium (1). Materials for immobilizing weapons-grade plutonium for repository disposal must meet the ''spent fuel standard'' by providing a radiation field similar to spent fuel (2). Such a radiation field can be provided by incorporating fission products from high-level waste into the waste form. Experiments were performed to evaluate the feasibility of incorporating high-level waste (HLW) stored at the Idaho Chemical Processing Plant (ICPP) into plutonium dispositioning materials to meet the spent fuel standard. A variety of materials and preparation techniques were evaluated based on prior experience developing waste forms for immobilizing HLW. These included crystalline ceramic compositions prepared by conventional sintering and hot isostatic pressing (HIP), and glass formulations prepared by conventional melting. Because plutonium solubility in silicate melts is limited, glass formulations were intentionally devitrified to partition plutonium into crystalline host phases, thereby allowing increased overall plutonium loading. Samarium, added as a representative rare earth neutron absorber, also tended to partition into the plutonium host phases. Because the crystalline plutonium host phases are chemically more inert, the plutonium is more effectively isolated from the environment, and its attractiveness for proliferation is reduced. In the initial phase of evaluating each material and preparation method, cerium was used as a surrogate for plutonium. For promising materials, additional preparation experiments were performed using plutonium to verify the behavior of cerium as a surrogate. These experiments demonstrated that cerium performed well as a surrogate for plutonium. For the most part, cerium and plutonium partitioned onto the same crystalline phases, and no anomalous changes in oxidation state were observed. The only observed

  17. Interventions for Individuals With High Levels of Needle Fear

    PubMed Central

    Noel, Melanie; Taddio, Anna; Antony, Martin M.; Asmundson, Gordon J.G.; Riddell, Rebecca Pillai; Chambers, Christine T.; Shah, Vibhuti

    2015-01-01

    Background: This systematic review evaluated the effectiveness of exposure-based psychological and physical interventions for the management of high levels of needle fear and/or phobia and fainting in children and adults. Design/Methods: A systematic review identified relevant randomized and quasi-randomized controlled trials of children, adults, or both with high levels of needle fear, including phobia (if not available, then populations with other specific phobias were included). Critically important outcomes were self-reported fear specific to the feared situation and stimulus (psychological interventions) or fainting (applied muscle tension). Data were pooled using standardized mean difference (SMD) or relative risk with 95% confidence intervals. Results: The systematic review included 11 trials. In vivo exposure-based therapy for children 7 years and above showed benefit on specific fear (n=234; SMD: −1.71 [95% CI: −2.72, −0.7]). In vivo exposure-based therapy with adults reduced fear of needles posttreatment (n=20; SMD: −1.09 [−2.04, −0.14]) but not at 1-year follow-up (n=20; SMD: −0.28 [−1.16, 0.6]). Compared with single session, a benefit was observed for multiple sessions of exposure-based therapy posttreatment (n=93; SMD: −0.66 [−1.08, −0.24]) but not after 1 year (n=83; SMD: −0.37 [−0.87, 0.13]). Non in vivo e.g., imaginal exposure-based therapy in children reduced specific fear posttreatment (n=41; SMD: −0.88 [−1.7, −0.05]) and at 3 months (n=24; SMD: −0.89 [−1.73, −0.04]). Non in vivo exposure-based therapy for adults showed benefit on specific fear (n=68; SMD: −0.62 [−1.11, −0.14]) but not procedural fear (n=17; SMD: 0.18 [−0.87, 1.23]). Applied tension showed benefit on fainting posttreatment (n=20; SMD: −1.16 [−2.12, −0.19]) and after 1 year (n=20; SMD: −0.97 [−1.91, −0.03]) compared with exposure alone. Conclusions: Exposure-based psychological interventions and applied muscle tension show

  18. High resolution geodetic techniques for monitoring fluid levels over time

    NASA Astrophysics Data System (ADS)

    Hare, Jennifer Thompson

    1998-11-01

    In the first study, a novel surveillance technique is developed in which surface gravity observations are used to monitor the progress of a gas cap waterflood in the 8200 ft (2500 m) deep Prudhoe Bay reservoir, Alaska. This cost-effective method requires that high-precision gravity surveys be repeated every 3 to 5 years. Differences in the gravity field with time reflect changes in the reservoir fluid density distribution. A preliminary field test at Prudhoe Bay indicates survey accuracy of 5 to 10 mu Gal can be achieved for gravity data using a modified Lacoste & Romberg "G" type meter or Scintrex CG-3M combined with Global Positioning System (GPS) positioning. Forward gravity modeling of a suite of reservoir simulations of the proposed waterflood predicts variation in surface measurements of 100 mu Gal after 5 years of injection, and 180 to 250 mu Gal after 15 years. A constrained, least-squares method is used to invert synthetic gravity data for subsurface density distributions. The modeling procedure has been formulated to allow testing of the models for sensitivity to gravity sampling patterns, noise characteristics, and various constraints on model parameters such as density range, total mass, and model moment of inertia. Horizontal feature resolution of the waterflood is about 5000 ft (1520 m) for constrained inverse models from synthetic gravity with 5 mu Gal standard deviation noise. Results of the modeling indicate that inversion of time-lapse gravity data is a viable and promising technique for monitoring reservoir gas cap waterfloods. In the second study, the problem of how to estimate ancient lake levels from the geomorphology of remnant shoreline terraces is investigated. High resolution, GPS controlled, topographic data from around the highstand shoreline of Pleistocene Lake Lahontan in western Nevada provide the means for isolating coherent terrace features which are related to the paleoshoreline level. Determination of an unambiguous point or

  19. High-level disinfection of gastrointestinal endoscope reprocessing

    PubMed Central

    Chiu, King-Wah; Lu, Lung-Sheng; Chiou, Shue-Shian

    2015-01-01

    High level disinfection (HLD) of the gastrointestinal (GI) endoscope is not simply a slogan, but rather is a form of experimental monitoring-based medicine. By definition, GI endoscopy is a semicritical medical device. Hence, such medical devices require major quality assurance for disinfection. And because many of these items are temperature sensitive, low-temperature chemical methods, such as liquid chemical germicide, must be used rather than steam sterilization. In summarizing guidelines for infection prevention and control for GI endoscopy, there are three important steps that must be highlighted: manual washing, HLD with automated endoscope reprocessor, and drying. Strict adherence to current guidelines is required because compared to any other medical device, the GI endoscope is associated with more outbreaks linked to inadequate cleaning or disinfecting during HLD. Both experimental evaluation on the surveillance bacterial cultures and in-use clinical results have shown that, the monitoring of the stringent processes to prevent and control infection is an essential component of the broader strategy to ensure the delivery of safe endoscopy services, because endoscope reprocessing is a multistep procedure involving numerous factors that can interfere with its efficacy. Based on our years of experience in the surveillance of culture monitoring of endoscopic reprocessing, we aim in this study to carefully describe what details require attention in the GI endoscopy disinfection and to share our experience so that patients can be provided with high quality and safe medical practices. Quality management encompasses all aspects of pre- and post-procedural care including the efficiency of the endoscopy unit and reprocessing area, as well as the endoscopic procedure itself. PMID:25699232

  20. Deep borehole disposal of high-level radioactive waste.

    SciTech Connect

    Stein, Joshua S.; Freeze, Geoffrey A.; Brady, Patrick Vane; Swift, Peter N.; Rechard, Robert Paul; Arnold, Bill Walter; Kanney, Joseph F.; Bauer, Stephen J.

    2009-07-01

    Preliminary evaluation of deep borehole disposal of high-level radioactive waste and spent nuclear fuel indicates the potential for excellent long-term safety performance at costs competitive with mined repositories. Significant fluid flow through basement rock is prevented, in part, by low permeabilities, poorly connected transport pathways, and overburden self-sealing. Deep fluids also resist vertical movement because they are density stratified. Thermal hydrologic calculations estimate the thermal pulse from emplaced waste to be small (less than 20 C at 10 meters from the borehole, for less than a few hundred years), and to result in maximum total vertical fluid movement of {approx}100 m. Reducing conditions will sharply limit solubilities of most dose-critical radionuclides at depth, and high ionic strengths of deep fluids will prevent colloidal transport. For the bounding analysis of this report, waste is envisioned to be emplaced as fuel assemblies stacked inside drill casing that are lowered, and emplaced using off-the-shelf oilfield and geothermal drilling techniques, into the lower 1-2 km portion of a vertical borehole {approx}45 cm in diameter and 3-5 km deep, followed by borehole sealing. Deep borehole disposal of radioactive waste in the United States would require modifications to the Nuclear Waste Policy Act and to applicable regulatory standards for long-term performance set by the US Environmental Protection Agency (40 CFR part 191) and US Nuclear Regulatory Commission (10 CFR part 60). The performance analysis described here is based on the assumption that long-term standards for deep borehole disposal would be identical in the key regards to those prescribed for existing repositories (40 CFR part 197 and 10 CFR part 63).

  1. High-level disinfection of gastrointestinal endoscope reprocessing.

    PubMed

    Chiu, King-Wah; Lu, Lung-Sheng; Chiou, Shue-Shian

    2015-02-20

    High level disinfection (HLD) of the gastrointestinal (GI) endoscope is not simply a slogan, but rather is a form of experimental monitoring-based medicine. By definition, GI endoscopy is a semicritical medical device. Hence, such medical devices require major quality assurance for disinfection. And because many of these items are temperature sensitive, low-temperature chemical methods, such as liquid chemical germicide, must be used rather than steam sterilization. In summarizing guidelines for infection prevention and control for GI endoscopy, there are three important steps that must be highlighted: manual washing, HLD with automated endoscope reprocessor, and drying. Strict adherence to current guidelines is required because compared to any other medical device, the GI endoscope is associated with more outbreaks linked to inadequate cleaning or disinfecting during HLD. Both experimental evaluation on the surveillance bacterial cultures and in-use clinical results have shown that, the monitoring of the stringent processes to prevent and control infection is an essential component of the broader strategy to ensure the delivery of safe endoscopy services, because endoscope reprocessing is a multistep procedure involving numerous factors that can interfere with its efficacy. Based on our years of experience in the surveillance of culture monitoring of endoscopic reprocessing, we aim in this study to carefully describe what details require attention in the GI endoscopy disinfection and to share our experience so that patients can be provided with high quality and safe medical practices. Quality management encompasses all aspects of pre- and post-procedural care including the efficiency of the endoscopy unit and reprocessing area, as well as the endoscopic procedure itself. PMID:25699232

  2. High-Level Performance Modeling of SAR Systems

    NASA Technical Reports Server (NTRS)

    Chen, Curtis

    2006-01-01

    SAUSAGE (Still Another Utility for SAR Analysis that s General and Extensible) is a computer program for modeling (see figure) the performance of synthetic- aperture radar (SAR) or interferometric synthetic-aperture radar (InSAR or IFSAR) systems. The user is assumed to be familiar with the basic principles of SAR imaging and interferometry. Given design parameters (e.g., altitude, power, and bandwidth) that characterize a radar system, the software predicts various performance metrics (e.g., signal-to-noise ratio and resolution). SAUSAGE is intended to be a general software tool for quick, high-level evaluation of radar designs; it is not meant to capture all the subtleties, nuances, and particulars of specific systems. SAUSAGE was written to facilitate the exploration of engineering tradeoffs within the multidimensional space of design parameters. Typically, this space is examined through an iterative process of adjusting the values of the design parameters and examining the effects of the adjustments on the overall performance of the system at each iteration. The software is designed to be modular and extensible to enable consideration of a variety of operating modes and antenna beam patterns, including, for example, strip-map and spotlight SAR acquisitions, polarimetry, burst modes, and squinted geometries.

  3. THERMAL ANALYSIS OF GEOLOGIC HIGH-LEVEL RADIOACTIVE WASTE PACKAGES

    SciTech Connect

    Hensel, S.; Lee, S.

    2010-04-20

    The engineering design of disposal of the high level waste (HLW) packages in a geologic repository requires a thermal analysis to provide the temperature history of the packages. Calculated temperatures are used to demonstrate compliance with criteria for waste acceptance into the geologic disposal gallery system and as input to assess the transient thermal characteristics of the vitrified HLW Package. The objective of the work was to evaluate the thermal performance of the supercontainer containing the vitrified HLW in a non-backfilled and unventilated underground disposal gallery. In order to achieve the objective, transient computational models for a geologic vitrified HLW package were developed by using a computational fluid dynamics method, and calculations for the HLW disposal gallery of the current Belgian geological repository reference design were performed. An initial two-dimensional model was used to conduct some parametric sensitivity studies to better understand the geologic system's thermal response. The effect of heat decay, number of co-disposed supercontainers, domain size, humidity, thermal conductivity and thermal emissivity were studied. Later, a more accurate three-dimensional model was developed by considering the conduction-convection cooling mechanism coupled with radiation, and the effect of the number of supercontainers (3, 4 and 8) was studied in more detail, as well as a bounding case with zero heat flux at both ends. The modeling methodology and results of the sensitivity studies will be presented.

  4. High Level Waste Feed Certification in Hanford Double Shell Tanks

    SciTech Connect

    Thien, Micheal G.; Wells, Beric E.; Adamson, Duane J.

    2010-03-01

    The ability to effectively mix, sample, certify, and deliver consistent batches of High Level Waste (HLW) feed from the Hanford Double Shell Tanks (DST) to the Waste Treatment and Immobilization Plant (WTP) presents a significant mission risk with potential to impact mission length and the quantity of HLW glass produced. DOE’s River Protection Project (RPP) mission modeling and WTP facility modeling assume that individual 3785 cubic meter (1 million gallon) HLW feed tanks are homogenously mixed, representatively sampled, and consistently delivered to the WTP. It has been demonstrated that homogenous mixing of HLW sludge in Hanford DSTs is not likely achievable with the baseline design thereby causing representative sampling and consistent feed delivery to be more difficult. Inconsistent feed to the WTP could cause additional batch to batch operational adjustments that reduces operating efficiency and has the potential to increase the overall mission length. The Hanford mixing and sampling demonstration program will identify DST mixing performance capability, will evaluate representative sampling techniques, and will estimate feed batch consistency. An evaluation of demonstration program results will identify potential mission improvement considerations that will help ensure successful mission completion. This paper will discuss the history, progress, and future activities that will define and mitigate the mission risk.

  5. High Level Rule Modeling Language for Airline Crew Pairing

    NASA Astrophysics Data System (ADS)

    Mutlu, Erdal; Birbil, Ş. Ilker; Bülbül, Kerem; Yenigün, Hüsnü

    2011-09-01

    The crew pairing problem is an airline optimization problem where a set of least costly pairings (consecutive flights to be flown by a single crew) that covers every flight in a given flight network is sought. A pairing is defined by using a very complex set of feasibility rules imposed by international and national regulatory agencies, and also by the airline itself. The cost of a pairing is also defined by using complicated rules. When an optimization engine generates a sequence of flights from a given flight network, it has to check all these feasibility rules to ensure whether the sequence forms a valid pairing. Likewise, the engine needs to calculate the cost of the pairing by using certain rules. However, the rules used for checking the feasibility and calculating the costs are usually not static. Furthermore, the airline companies carry out what-if-type analyses through testing several alternate scenarios in each planning period. Therefore, embedding the implementation of feasibility checking and cost calculation rules into the source code of the optimization engine is not a practical approach. In this work, a high level language called ARUS is introduced for describing the feasibility and cost calculation rules. A compiler for ARUS is also implemented in this work to generate a dynamic link library to be used by crew pairing optimization engines.

  6. The GRAVITY instrument software/high-level software

    NASA Astrophysics Data System (ADS)

    Burtscher, Leonard; Wieprecht, Ekkehard; Ott, Thomas; Kok, Yitping; Yazici, Senol; Anugu, Narsireddy; Dembet, Roderick; Fedou, Pierre; Lacour, Sylvestre; Ott, Jürgen; Paumard, Thibaut; Lapeyrere, Vincent; Kervella, Pierre; Abuter, Roberto; Pozna, Eszter; Eisenhauer, Frank; Blind, Nicolas; Genzel, Reinhard; Gillessen, Stefan; Hans, Oliver; Haug, Marcus; Haussmann, Frank; Kellner, Stefan; Lippa, Magdalena; Pfuhl, Oliver; Sturm, Eckhard; Weber, Johannes; Amorim, Antonio; Brandner, Wolfgang; Rousselet-Perraut, Karine; Perrin, Guy S.; Straubmeier, Christian; Schöller, Markus

    2014-07-01

    GRAVITY is the four-beam, near-infrared, AO-assisted, fringe tracking, astrometric and imaging instrument for the Very Large Telescope Interferometer (VLTI). It is requiring the development of one of the most complex instrument software systems ever built for an ESO instrument. Apart from its many interfaces and interdependencies, one of the most challenging aspects is the overall performance and stability of this complex system. The three infrared detectors and the fast reflective memory network (RMN) recorder contribute a total data rate of up to 20 MiB/s accumulating to a maximum of 250 GiB of data per night. The detectors, the two instrument Local Control Units (LCUs) as well as the five LCUs running applications under TAC (Tools for Advanced Control) architecture, are interconnected with fast Ethernet, RMN fibers and dedicated fiber connections as well as signals for the time synchronization. Here we give a simplified overview of all subsystems of GRAVITY and their interfaces and discuss two examples of high-level applications during observations: the acquisition procedure and the gathering and merging of data to the final FITS file.

  7. Anthropometric characteristics of high level European junior basketball players.

    PubMed

    Jelicić, M; Sekulić, D; Marinović, M

    2002-12-01

    The purpose of the research was to assess anthropometric status of European high-level junior basketball players and to determine anthropometric differences between the players playing in different game positions (guards, forwards, centers). The sample consisted of 132 young basketball players, participants of the European Junior Basketball Championship, Zadar, 2000. Participants were measured with 31 measures (anthropometric variables), on the basis of which two body composition measures (BMI and relative body fat) and somatotype were calculated. The basic statistical parameters were computed. The analysis of variance and discriminant canonical analysis were employed to determine the differences between positions in play. Results indicate that prominent longitudinal and transversal skeletal dimensions as well as circumference measures characterize players on the position of centers, but they do not have significantly larger skinfold measures in relation to forwards. Centers are also predominantly ectomorphic compared with other players. Guards achieved significantly lower values in all spaces and they are predominantly mesomorphic. Further investigations are necessary in order to assess potential changes in status of these parameters when the participants will reach the age of senior players and afterwards, as well as to determine relations between anthropometric status and skill related variables. PMID:12674837

  8. The ALICE High Level Trigger: status and plans

    NASA Astrophysics Data System (ADS)

    Krzewicki, Mikolaj; Rohr, David; Gorbunov, Sergey; Breitner, Timo; Lehrbach, Johannes; Lindenstruth, Volker; Berzano, Dario

    2015-12-01

    The ALICE High Level Trigger (HLT) is an online reconstruction, triggering and data compression system used in the ALICE experiment at CERN. Unique among the LHC experiments, it extensively uses modern coprocessor technologies like general purpose graphic processing units (GPGPU) and field programmable gate arrays (FPGA) in the data flow. Realtime data compression is performed using a cluster finder algorithm implemented on FPGA boards. These data, instead of raw clusters, are used in the subsequent processing and storage, resulting in a compression factor of around 4. Track finding is performed using a cellular automaton and a Kalman filter algorithm on GPGPU hardware, where both CUDA and OpenCL technologies can be used interchangeably. The ALICE upgrade requires further development of online concepts to include detector calibration and stronger data compression. The current HLT farm will be used as a test bed for online calibration and both synchronous and asynchronous processing frameworks already before the upgrade, during Run 2. For opportunistic use as a Grid computing site during periods of inactivity of the experiment a virtualisation based setup is deployed.

  9. Defense High-Level Waste Leaching Mechanisms Program. Final report

    SciTech Connect

    Mendel, J.E.

    1984-08-01

    The Defense High-Level Waste Leaching Mechanisms Program brought six major US laboratories together for three years of cooperative research. The participants reached a consensus that solubility of the leached glass species, particularly solubility in the altered surface layer, is the dominant factor controlling the leaching behavior of defense waste glass in a system in which the flow of leachant is constrained, as it will be in a deep geologic repository. Also, once the surface of waste glass is contacted by ground water, the kinetics of establishing solubility control are relatively rapid. The concentrations of leached species reach saturation, or steady-state concentrations, within a few months to a year at 70 to 90/sup 0/C. Thus, reaction kinetics, which were the main subject of earlier leaching mechanisms studies, are now shown to assume much less importance. The dominance of solubility means that the leach rate is, in fact, directly proportional to ground water flow rate. Doubling the flow rate doubles the effective leach rate. This relationship is expected to obtain in most, if not all, repository situations.

  10. Application of SYNROC to high-level defense wastes

    SciTech Connect

    Tewhey, J.D.; Hoenig, C.L.; Newkirk, H.W.; Rozsa, R.B.; Coles, D.G.; Ryerson, F.J.

    1981-01-01

    The SYNROC method for immobilization of high-level nuclear reactor wastes is currently being applied to US defense wastes in tank storage at Savannah River, South Carolina. The minerals zirconolite, perovskite, and hollandite are used in SYNROC D formulations to immobilize fission products and actinides that comprise up to 10% of defense waste sludges and coexisting solutions. Additional phases in SYNROC D are nepheline, the host phase for sodium; and spinel, the host for excess aluminum and iron. Up to 70 wt % of calcined sludge can be incorporated with 30 wt % of SYNROC additives to produce a waste form consisting of 10% nepheline, 30% spinel, and approximately 20% each of the radioactive waste-bearing phases. Urea coprecipitation and spray drying/calcining methods have been used in the laboratory to produce homogeneous, reactive ceramic powders. Hot pressing and sintering at temperatures from 1000 to 1100/sup 0/C result in waste form products with greater than 97% of theoretical density. Hot isostatic pressing has recently been implemented as a processing alternative. Characterization of waste-form mineralogy has been done by means of XRD, SEM, and electron microprobe. Leaching of SYNROC D samples is currently being carried out. Assessment of radiation damage effects and physical properties of SYNROC D will commence in FY 81.

  11. Why consider subseabed disposal of high-level nuclear waste

    SciTech Connect

    Heath, G. R.; Hollister, C. D.; Anderson, D. R.; Leinen, M.

    1980-01-01

    Large areas of the deep seabed warrant assessment as potential disposal sites for high-level radioactive waste because: (1) they are far from seismically and tectonically active lithospheric plate boundaries; (2) they are far from active or young volcanos; (3) they contain thick layers of very uniform fine-grained clays; (4) they are devoid of natural resources likely to be exploited in the forseeable future; (5) the geologic and oceanographic processes governing the deposition of sediments in such areas are well understood, and are remarkably insensitive to past oceanographic and climatic changes; and (6) sedmentary records of tens of millions of years of slow, uninterrupted deposition of fine grained clay support predictions of the future stability of such sites. Data accumulated to date on the permeability, ion-retardation properties, and mechanical strength of pelagic clay sediments indicate that they can act as a primary barrier to the escape of buried nuclides. Work in progress should determine within the current decade whether subseabed disposal is environmentally acceptable and technically feasible, as well as address the legal, political and social issues raised by this new concept.

  12. Process Design Concepts for Stabilization of High Level Waste Calcine

    SciTech Connect

    T. R. Thomas; A. K. Herbst

    2005-06-01

    The current baseline assumption is that packaging ¡§as is¡¨ and direct disposal of high level waste (HLW) calcine in a Monitored Geologic Repository will be allowed. The fall back position is to develop a stabilized waste form for the HLW calcine, that will meet repository waste acceptance criteria currently in place, in case regulatory initiatives are unsuccessful. A decision between direct disposal or a stabilization alternative is anticipated by June 2006. The purposes of this Engineering Design File (EDF) are to provide a pre-conceptual design on three low temperature processes under development for stabilization of high level waste calcine (i.e., the grout, hydroceramic grout, and iron phosphate ceramic processes) and to support a down selection among the three candidates. The key assumptions for the pre-conceptual design assessment are that a) a waste treatment plant would operate over eight years for 200 days a year, b) a design processing rate of 3.67 m3/day or 4670 kg/day of HLW calcine would be needed, and c) the performance of waste form would remove the HLW calcine from the hazardous waste category, and d) the waste form loadings would range from about 21-25 wt% calcine. The conclusions of this EDF study are that: (a) To date, the grout formulation appears to be the best candidate stabilizer among the three being tested for HLW calcine and appears to be the easiest to mix, pour, and cure. (b) Only minor differences would exist between the process steps of the grout and hydroceramic grout stabilization processes. If temperature control of the mixer at about 80„aC is required, it would add a major level of complexity to the iron phosphate stabilization process. (c) It is too early in the development program to determine which stabilizer will produce the minimum amount of stabilized waste form for the entire HLW inventory, but the volume is assumed to be within the range of 12,250 to 14,470 m3. (d) The stacked vessel height of the hot process vessels

  13. Millimeter-Wave Measurements of High Level and Low Level Activity Glass Melts

    SciTech Connect

    Woskov, Paul P.; Sundaram, S.K.; Daniel, William E., Jr.

    2006-06-01

    The primary objectives of the current research is to develop on-line sensors for characterizing molten glass in high-level and low-activity waste glass melters using millimeter-wave (MMW) technology and to use this technology to do novel research of melt dynamics. Existing and planned waste glass melters lack sophisticated diagnostics due to the hot, corrosive, and radioactive melter environments. Without process control diagnostics, the Defense Waste Processing Facility (DWPF) and the Waste Treatment Plant (WTP) under construction at Hanford operate by a feed forward process control scheme that relies on predictive models with large uncertainties. This scheme severely limits production throughput and waste loading. Also operations at DWPF have shown susceptibility to anomalies such as pouring, foaming, and combustion gas build up, which can seriously disrupt operations. Future waste chemistries will be even more challenging. The scientific goals of this project are to develop new reliable on-line monitoring capability for important glass process parameters such as temperature profiles, emissivity, density, viscosity, and other characteristics using the unique advantages of millimeter wave electromagnetic radiation that can be eventually implemented in the operating melters. Once successfully developed and implemented, significant cost savings would be realized in melter operations by increasing production through put, reduced storage volumes (through higher waste loading), and reduced risks (prevention or mitigation of anomalies).

  14. Burning experiments and late Paleozoic high O2 levels

    NASA Astrophysics Data System (ADS)

    Wildman, R.; Essenhigh, R.; Berner, R.; Hickey, L.; Wildman, C.

    2003-04-01

    The Paleozoic rise of land plants brought about increased burial of organic matter and a resulting increase in atmospheric oxygen concentrations. Levels as high as 30-35% O2 may have been reached during the Permo-Carboniferous (Berner and Canfield, 1989; Berner, 2001). However, burning experiments based solely on paper (Watson, 1978) have challenged these results, the claim being that if the oxygen made up more than 25% of the atmosphere, the frequency and intensity of forest fires would increase sufficiently to prevent the continued existence of plant life. Thus, since plants have persisted, it is possible that fires served as a negative feedback against excessive oxygen levels. An initial study of Paleozoic wildfire behavior via thermogravimetric analysis (TGA) was conducted under ambient and enriched oxygen conditions to simulate present and ancient atmospheres. The tests focused on natural fuels, specifically tree leaves and wood, tree fern fibers, and sphagnum peat-moss, simulating Permo-Carboniferous upland and swampland ecosystems, respectively. Three conclusions are: (1) enriched oxygen increases the rate of mass loss during burning; (2) fuel chemistry (cellulose vs. lignin) influences burning patterns; and (3) in geometrically heterogeneous fuels, geometry affects burning rate significantly. Both geometrically and chemically, paper resists fire poorly; thus, we found that it loses its mass at lower temperatures than forest materials and is therefore a poor proxy for Paleozoic ecosystems. Further study of Paleozoic wildfire spread behavior is currently being conducted. Fires are lit using pine dowels, which allow for reproducible fuel density. Steady-state, one-dimensional flame-spread is measured with thermocouples anchored two inches above the fuel bed. Both oxygen concentration of the air supply to the fire and moisture content of the fuels are varied, as we suspect that these are two main controls of wildfire spread. Burning fuels of varying moisture

  15. JET MIXING ANALYSIS FOR SRS HIGH-LEVEL WASTE RECOVERY

    SciTech Connect

    Lee, S.

    2011-07-05

    The process of recovering the waste in storage tanks at the Savannah River Site (SRS) typically requires mixing the contents of the tank to ensure uniformity of the discharge stream. Mixing is accomplished with one to four slurry pumps located within the tank liquid. The slurry pump may be fixed in position or they may rotate depending on the specific mixing requirements. The high-level waste in Tank 48 contains insoluble solids in the form of potassium tetraphenyl borate compounds (KTPB), monosodium titanate (MST), and sludge. Tank 48 is equipped with 4 slurry pumps, which are intended to suspend the insoluble solids prior to transfer of the waste to the Fluidized Bed Steam Reformer (FBSR) process. The FBSR process is being designed for a normal feed of 3.05 wt% insoluble solids. A chemical characterization study has shown the insoluble solids concentration is approximately 3.05 wt% when well-mixed. The project is requesting a Computational Fluid Dynamics (CFD) mixing study from SRNL to determine the solids behavior with 2, 3, and 4 slurry pumps in operation and an estimate of the insoluble solids concentration at the suction of the transfer pump to the FBSR process. The impact of cooling coils is not considered in the current work. The work consists of two principal objectives by taking a CFD approach: (1) To estimate insoluble solids concentration transferred from Tank 48 to the Waste Feed Tank in the FBSR process and (2) To assess the impact of different combinations of four slurry pumps on insoluble solids suspension and mixing in Tank 48. For this work, several different combinations of a maximum of four pumps are considered to determine the resulting flow patterns and local flow velocities which are thought to be associated with sludge particle mixing. Two different elevations of pump nozzles are used for an assessment of the flow patterns on the tank mixing. Pump design and operating parameters used for the analysis are summarized in Table 1. The baseline

  16. Reusable, Extensible High-Level Data-Distribution Concept

    NASA Technical Reports Server (NTRS)

    James, Mark; Zima, Hans; Diaconescua, Roxana

    2007-01-01

    A framework for high-level specification of data distributions in data-parallel application programs has been conceived. [As used here, distributions signifies means to express locality (more specifically, locations of specified pieces of data) in a computing system composed of many processor and memory components connected by a network.] Inasmuch as distributions exert a great effect on the performances of application programs, it is important that a distribution strategy be flexible, so that distributions can be adapted to the requirements of those programs. At the same time, for the sake of productivity in programming and execution, it is desirable that users be shielded from such error-prone, tedious details as those of communication and synchronization. As desired, the present framework enables a user to refine a distribution type and adjust it to optimize the performance of an application program and conceals, from the user, the low-level details of communication and synchronization. The framework provides for a reusable, extensible, data-distribution design, denoted the design pattern, that is independent of a concrete implementation. The design pattern abstracts over coding patterns that have been found to be commonly encountered in both manually and automatically generated distributed parallel programs. The following description of the present framework is necessarily oversimplified to fit within the space available for this article. Distributions are among the elements of a conceptual data-distribution machinery, some of the other elements being denoted domains, index sets, and data collections (see figure). Associated with each domain is one index set and one distribution. A distribution class interface (where "class" is used in the object-oriented-programming sense) includes operations that enable specification of the mapping of an index to a unit of locality. Thus, "Map(Index)" specifies a unit, while "LocalLayout(Index)" specifies the local address

  17. Oasis: A high-level/high-performance open source Navier-Stokes solver

    NASA Astrophysics Data System (ADS)

    Mortensen, Mikael; Valen-Sendstad, Kristian

    2015-03-01

    Oasis is a high-level/high-performance finite element Navier-Stokes solver written from scratch in Python using building blocks from the FEniCS project (fenicsproject.org). The solver is unstructured and targets large-scale applications in complex geometries on massively parallel clusters. Oasis utilizes MPI and interfaces, through FEniCS, to the linear algebra backend PETSc. Oasis advocates a high-level, programmable user interface through the creation of highly flexible Python modules for new problems. Through the high-level Python interface the user is placed in complete control of every aspect of the solver. A version of the solver, that is using piecewise linear elements for both velocity and pressure, is shown to reproduce very well the classical, spectral, turbulent channel simulations of Moser et al. (1999). The computational speed is strongly dominated by the iterative solvers provided by the linear algebra backend, which is arguably the best performance any similar implicit solver using PETSc may hope for. Higher order accuracy is also demonstrated and new solvers may be easily added within the same framework.

  18. Removal of cesium from a high-level calcined waste by high temperature volatilization

    SciTech Connect

    Del Debbio, J.A.

    1994-11-01

    Pyrochemical methods are being evaluated for the separation of actinides and fission products from inert material in high-level waste calcine. Separation processes have the potential of reducing waste disposal costs by reducing the volume of high-level waste requiring final disposal in a repository. Tests were conducted to evaluate high temperature volatilization for removing {sup 137}Cs from four types of calcines. The results for pilot plant calcines indicate greater than 99% cesium removal for alumina and fluorinel/sodium calcines heated at 1000{degree}C and 99% removal for zirconia calcine heated at 1100{degree}C. Tests with actual calcine generated at the New Waste Calcining Facility (NWCF) from a blend of aluminium, sodium and zirconium/fluorinel wastes resulted in 96% cesium removal at 1000{degree}C and greater than 99% removal at 1170{degree}C.

  19. An integrated framework for high level design of high performance signal processing circuits on FPGAs

    NASA Astrophysics Data System (ADS)

    Benkrid, K.; Belkacemi, S.; Sukhsawas, S.

    2005-06-01

    This paper proposes an integrated framework for the high level design of high performance signal processing algorithms' implementations on FPGAs. The framework emerged from a constant need to rapidly implement increasingly complicated algorithms on FPGAs while maintaining the high performance needed in many real time digital signal processing applications. This is particularly important for application developers who often rely on iterative and interactive development methodologies. The central idea behind the proposed framework is to dynamically integrate high performance structural hardware description languages with higher level hardware languages in other to help satisfy the dual requirement of high level design and high performance implementation. The paper illustrates this by integrating two environments: Celoxica's Handel-C language, and HIDE, a structural hardware environment developed at the Queen's University of Belfast. On the one hand, Handel-C has been proven to be very useful in the rapid design and prototyping of FPGA circuits, especially control intensive ones. On the other hand, HIDE, has been used extensively, and successfully, in the generation of highly optimised parameterisable FPGA cores. In this paper, this is illustrated in the construction of a scalable and fully parameterisable core for image algebra's five core neighbourhood operations, where fully floorplanned efficient FPGA configurations, in the form of EDIF netlists, are generated automatically for instances of the core. In the proposed combined framework, highly optimised data paths are invoked dynamically from within Handel-C, and are synthesized using HIDE. Although the idea might seem simple prima facie, it could have serious implications on the design of future generations of hardware description languages.

  20. Level 1 Tornado PRA for the High Flux Beam Reactor

    SciTech Connect

    Bozoki, G.E.; Conrad, C.S.

    1994-05-01

    This report describes a risk analysis primarily directed at providing an estimate for the frequency of tornado induced damage to the core of the High Flux Beam Reactor (HFBR), and thus it constitutes a Level 1 Probabilistic Risk Assessment (PRA) covering tornado induced accident sequences. The basic methodology of the risk analysis was to develop a ``tornado specific`` plant logic model that integrates the internal random hardware failures with failures caused externally by the tornado strike and includes operator errors worsened by the tornado modified environment. The tornado hazard frequency, as well as earlier prepared structural and equipment fragility data, were used as input data to the model. To keep modeling/calculational complexity as simple as reasonable a ``bounding`` type, slightly conservative, approach was applied. By a thorough screening process a single dominant initiating event was selected as a representative initiator, defined as: ``Tornado Induced Loss of Offsite Power.`` The frequency of this initiator was determined to be 6.37E-5/year. The safety response of the HFBR facility resulted in a total Conditional Core Damage Probability of .621. Thus, the point estimate of the HFBR`s Tornado Induced Core Damage Frequency (CDF) was found to be: (CDF){sub Tornado} = 3.96E-5/year. This value represents only 7.8% of the internal CDF and thus is considered to be a small contribution to the overall facility risk expressed in terms of total Core Damage Frequency. In addition to providing the estimate of (CDF){sub Tornado}, the report documents, the relative importance of various tornado induced system, component, and operator failures that contribute most to (CDF){sub Tornado}.

  1. Stability of High-Level Radioactive Waste Forms

    SciTech Connect

    Besmann, T.M.

    2001-06-22

    High-level waste (HLW) glass compositions, processing schemes, limits on waste content, and corrosion/dissolution release models are dependent on an accurate knowledge of melting temperatures and thermochemical values. Unfortunately, existing models for predicting these temperatures are empirically-based, depending on extrapolations of experimental information. In addition, present models of leaching behavior of glass waste forms use simplistic assumptions or experimentally measured values obtained under non-realistic conditions. There is thus a critical need for both more accurate and more widely applicable models for HLW glass behavior, which this project addressed. Significant progress was made in this project on modeling HLW glass. Borosilicate glass was accurately represented along with the additional important components that contain iron, lithium, potassium, magnesium, and calcium. The formation of crystalline inclusions in the glass, an issue in Hanford HLW formulations, was modeled and shown to be predictive. Thus the results of this work have already demonstrated practical benefits with the ability to map compositional regions where crystalline material forms, and therefore avoid that detrimental effect. With regard to a fundamental understanding, added insights on the behavior of the components of glass have been obtained, including the potential formation of molecular clusters. The EMSP project had very significant effects beyond the confines of Environmental Management. The models developed for glass have been used to solve a very costly problem in the corrosion of refractories for glass production. The effort resulted in another laboratory, Sandia National Laboratories-Livermore, to become conversant in the techniques and to apply those through a DOE Office of Industrial Technologies project joint with PPG Industries. The glass industry as a whole is now cognizant of these capabilities, and there is a Glass Manufacturer's Research Institute proposal

  2. PLUTONIUM/HIGH-LEVEL VITRIFIED WASTE BDBE DOSE CALCULATION

    SciTech Connect

    D.C. Richardson

    2003-03-19

    In accordance with the Nuclear Waste Policy Amendments Act of 1987, Yucca Mountain was designated as the site to be investigated as a potential repository for the disposal of high-level radioactive waste. The Yucca Mountain site is an undeveloped area located on the southwestern edge of the Nevada Test Site (NTS), about 100 miles northwest of Las Vegas. The site currently lacks rail service or an existing right-of-way. If the Yucca Mountain site is found suitable for the repository, rail service is desirable to the Office of Civilian Waste Management (OCRWM) Program because of the potential of rail transportation to reduce costs and to reduce the number of shipments relative to highway transportation. A Preliminary Rail Access Study evaluated 13 potential rail spur options. Alternative routes within the major options were also developed. Each of these options was then evaluated for potential land use conflicts and access to regional rail carriers. Three potential routes having few land use conflicts and having access to regional carriers were recommended for further investigation. Figure 1-1 shows these three routes. The Jean route is estimated to be about 120 miles long, the Carlin route to be about 365 miles long, and Caliente route to be about 365 miles long. The remaining ten routes continue to be monitored and should any of the present conflicts change, a re-evaluation of that route will be made. Complete details of the evaluation of the 13 routes can be found in the previous study. The DOE has not identified any preferred route and recognizes that the transportation issues need a full and open treatment under the National Environmental Policy Act. The issue of transportation will be included in public hearings to support development of the Environmental Impact Statement (EIS) proceedings for either the Monitored Retrievable Storage Facility or the Yucca Mountain Project or both.

  3. High-Level Waste Systems Plan. Revision 7

    SciTech Connect

    Brooke, J.N.; Gregory, M.V.; Paul, P.; Taylor, G.; Wise, F.E.; Davis, N.R.; Wells, M.N.

    1996-10-01

    This revision of the High-Level Waste (HLW) System Plan aligns SRS HLW program planning with the DOE Savannah River (DOE-SR) Ten Year Plan (QC-96-0005, Draft 8/6), which was issued in July 1996. The objective of the Ten Year Plan is to complete cleanup at most nuclear sites within the next ten years. The two key principles of the Ten Year Plan are to accelerate the reduction of the most urgent risks to human health and the environment and to reduce mortgage costs. Accordingly, this System Plan describes the HLW program that will remove HLW from all 24 old-style tanks, and close 20 of those tanks, by 2006 with vitrification of all HLW by 2018. To achieve these goals, the DWPF canister production rate is projected to climb to 300 canisters per year starting in FY06, and remain at that rate through the end of the program in FY18, (Compare that to past System Plans, in which DWPF production peaked at 200 canisters per year, and the program did not complete until 2026.) An additional $247M (FY98 dollars) must be made available as requested over the ten year planning period, including a one-time $10M to enhance Late Wash attainment. If appropriate resources are made available, facility attainment issues are resolved and regulatory support is sufficient, then completion of the HLW program in 2018 would achieve a $3.3 billion cost savings to DOE, versus the cost of completing the program in 2026. Facility status information is current as of October 31, 1996.

  4. Concerns--High Sea Levels and Temperatures Seen Next Century.

    ERIC Educational Resources Information Center

    Ryan, Paul R.

    1984-01-01

    A National Research Council committee recently concluded that atmospheric carbon dioxide levels will "most likely" double by late in the next century, causing an increase in the earth's average temperature. Effects of the increase on sea levels, global climate, and other parameters are discussed. (JN)

  5. Persisting High Levels of Synovial Fluid Markers after Cartilage Repair

    PubMed Central

    Konttinen, Yrjö T.; Peterson, Lars; Lindahl, Anders; Kiviranta, Ilkka

    2008-01-01

    Local attempts to repair a cartilage lesion could cause increased levels of anabolic and catabolic factors in the synovial fluid. After repair with regenerated cartilage, the homeostasis of the cartilage ideally would return to normal. In this pilot study, we first hypothesized levels of synovial fluid markers would be higher in patients with cartilage lesions than in patients with no cartilage lesions, and then we hypothesized the levels of synovial fluid markers would decrease after cartilage repair. We collected synovial fluid samples from 10 patients before autologous chondrocyte transplantation of the knee. One year later, a second set of samples was collected and arthroscopic evaluation of the repair site was performed. Fifteen patients undergoing knee arthroscopy for various symptoms but with no apparent cartilage lesions served as control subjects. We measured synovial fluid matrix metalloproteinase-3 (MMP-3) and insulinlike growth factor-I (IGF-I) concentrations with specific activity and enzyme-linked immunosorbent assays, respectively. The levels of MMP-3 and IGF-I were higher in patients having cartilage lesions than in control subjects with no cartilage lesions. One year after cartilage repair, the lesions were filled with repair tissue, but the levels of MMP-3 and IGF-I remained elevated, indicating either graft remodeling or early degeneration. Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18709427

  6. High-efficiency sample preparation approach to determine acrylamide levels in high-fat foods.

    PubMed

    Li, Xiaodan; Li, Jinwei; Cao, Peirang; Liu, Yuanfa

    2016-08-01

    An improved sample preparation method was developed to enhance acrylamide recovery in high-fat foods. Prior to concentration, distilled deionized water was added to protect acrylamide from degradation, resulting in a higher acrylamide recovery rate from fried potato chips. A Chrome-Matrix C18 column (2.6 μm, 2.1 × 100 mm) was used for the first time to analyze acrylamide levels using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry, displaying good separation of acrylamide from interference. A solid-phase extraction procedure was avoided, and an average recovery of >89.00% was achieved from different food matrices for three different acrylamide spiking levels. Good reproducibility was observed, with an intraday relative standard deviation of 0.04-2.38%, and an interday relative standard deviation of 2.34-3.26%. Thus, combining the improved sample preparation method for acrylamide analysis with the separation on a Chrome-Matrix C18 column (2.6 μm, 2.1 × 100 mm) using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry is highly useful for analyzing acrylamide levels in complex food matrices. PMID:27279364

  7. High level waste interim storge architecture selection - decision report

    SciTech Connect

    Calmus, R.B.

    1996-09-27

    The U.S. Department of Energy (DOE) has embarked upon a course to acquire Hanford Site tank waste treatment and immobilization services using privatized facilities (RL 1996a). This plan contains a two-phased approach. Phase I is a proof-of-principle/connnercial demonstration- scale effort and Phase II is a fiill-scale production effort. In accordance with the planned approach, interim storage and disposal of various products from privatized facilities are to be DOE fumished. The high-level waste (BLW) interim storage options, or alternative architectures, were identified and evaluated to provide the framework from which to select the most viable method of Phase I BLW interim storage (Calmus 1996). This evaluation, hereafter referred to as the Alternative Architecture Evaluation, was performed to established performance and risk criteria (technical merit, cost, schedule, etc.). Based on evaluation results, preliminary architectures and path forward reconunendations were provided for consideration in the architecture decision- maldng process. The decision-making process used for selection of a Phase I solidified BLW interim storage architecture was conducted in accordance with an approved Decision Plan (see the attachment). This decision process was based on TSEP-07,Decision Management Procedure (WHC 1995). The established decision process entailed a Decision Board, consisting of Westinghouse Hanford Company (VY`HC) management staff, and included appointment of a VTHC Decision Maker. The Alternative Architecture Evaluation results and preliminary recommendations were presented to the Decision Board members for their consideration in the decision-making process. The Alternative Architecture Evaluation was prepared and issued before issuance of @C-IP- 123 1, Alternatives Generation and Analysis Procedure (WI-IC 1996a), but was deemed by the Board to fully meet the intent of WHC-IP-1231. The Decision Board members concurred with the bulk of the Alternative Architecture

  8. Impact testing of simulated high-level waste glass canisters

    SciTech Connect

    Peterson, M.E.; Alzheimer, J.M.; Slate, S.C.

    1985-01-01

    Three Savannah River Laboratory reference high-level waste canisters were subjected to impact tests at the Pacific Northwest Laboratory in Richland, Washington, in June 1983. The purpose of the test was to determine the integrity of the canister, nozzle, and final closure weld and to assess the effects of impacts on the glass. Two of the canisters were fabricated from 304L stainless steel and the third canister from titanium. The titanium canister was subjected to two drops. The first drop was vertical from 9.14 m onto an unyielding surface with the bottom corner of the canister receiving the impact. No failure occurred during this drop. The second drop was vertical from 9.14 m onto an unyielding surface with the corner of the fill nozzle receiving the impact. A large breach in the canister occurred in the region where the fill nozzle joins the dished head. The first stainless steel canister was dropped with the corner of the fill nozzle receiving the impact. The canister showed significant strain with no rupturing in the region where the fill nozzle joins the dished head. The second canister was dropped with the bottom corner receiving the impact and also, dropped horizontally onto an unyielding vertical solid steel cylinder in a puncture test. The bottom drop did not damage the weld and the puncture test did not rupture the canister body. The glass particles in the damaged zone of these canisters were sampled and analyzed for particle size. A comparison was made with control canister in which no impact had occurred. The particle size distribution for the control canisters and the zones of damaged glass were determined down to 1.5 ..mu..m. The quantity of glass fines, smaller than 10 ..mu..m, which must be determined for transportation safety studies, was found to be the largest in the bottom-damaged zone. The total amount of fines smaller than 10 ..mu..m after impact was less than 0.01 wt % of the total amount of glass in the canister.

  9. Confidence Level and Sensitivity Limits in High-Contrast Imaging

    NASA Astrophysics Data System (ADS)

    Marois, Christian; Lafrenière, David; Macintosh, Bruce; Doyon, René

    2008-01-01

    In long adaptive optics corrected exposures, exoplanet detections are currently limited by speckle noise originating from the telescope and instrument optics, and it is expected that such noise will also limit future high-contrast imaging instruments for both ground- and space-based telescopes. Previous theoretical analyses have shown that the time intensity variations of a single speckle follow a modified Rician. It is first demonstrated here that for a circular pupil, this temporal intensity distribution also represents the speckle spatial intensity distribution at a fixed separation from the point-spread function center; this fact is demonstrated using numerical simulations for coronagraphic and noncoronagraphic data. The real statistical distribution of the noise needs to be taken into account explicitly when selecting a detection threshold appropriate for some desired confidence level (CL). In this paper, a technique is described to obtain the pixel intensity distribution of an image and its corresponding CL as a function of the detection threshold. Using numerical simulations, it is shown that in the presence of speckle noise, a detection threshold up to 3 times higher is required to obtain a CL equivalent to that at 5 σ for Gaussian noise. The technique is then tested on data acquired by simultaneous spectral differential imaging with TRIDENT and by angular differential imaging with NIRI. It is found that the angular differential imaging technique produces quasi-Gaussian residuals, a remarkable result compared to classical adaptive optic imaging. Finally, a power law is derived to predict the 1 - 3 × 10-7 CL detection threshold when averaging a partially correlated non-Gaussian noise. Based on observations obtained at the Canada-France-Hawaii Telescope (CFHT), which is operated by the National Research Council of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France, and the University of

  10. High Technology Internship at the Secondary Level. Final Report.

    ERIC Educational Resources Information Center

    Noll, Clifford J.

    A program was conducted during the Spring semester, 1985, in the San Antonio area to place high school juniors and seniors from three high schools in the Edgewood Independent School District in three-month interships in high-technology industries. Students traveled to their training locations on school-provided transportation on Mondays through…

  11. Avoided level crossings in very highly charged ions

    NASA Astrophysics Data System (ADS)

    Beiersdorfer, P.; Scofield, J. H.; Brown, G. V.; Chen, M. H.; Hell, N.; Osterheld, A. L.; Vogel, D. A.; Wong, K. L.

    2016-05-01

    We report a systematic measurement of the (2p1/2 -13 d3/2) J =1 and (2s1/2 -13 p1/2) J =1 levels in 14 neonlike ions between Ba46 + and Pb72 + and document the effects of their avoided crossing near Z =68 . Strong mixing affects the oscillator strengths over a surprisingly wide range of atomic numbers and leads to the vanishing of one transition two atomic numbers below the crossing. The crossing voids the otherwise correct expectation that the (2p1/2 -13 d3/2) J =1 level energy is only weakly affected by quantum electrodynamics (QED). For about 10 atomic numbers surrounding the crossing, its QED contributions are anomalously large, attaining almost equality to those affecting the (2s1/2 -13 p1/2) J =1 level. As a result, the accuracy of energy level calculations appears compromised near the crossing.

  12. Low copper and high manganese levels in prion protein plaques

    USGS Publications Warehouse

    Johnson, Christopher J.; Gilbert, P.U.P.A.; Abrecth, Mike; Baldwin, Katherine L.; Russell, Robin E.; Pedersen, Joel A.; McKenzie, Debbie

    2013-01-01

    Accumulation of aggregates rich in an abnormally folded form of the prion protein characterize the neurodegeneration caused by transmissible spongiform encephalopathies (TSEs). The molecular triggers of plaque formation and neurodegeneration remain unknown, but analyses of TSE-infected brain homogenates and preparations enriched for abnormal prion protein suggest that reduced levels of copper and increased levels of manganese are associated with disease. The objectives of this study were to: (1) assess copper and manganese levels in healthy and TSE-infected Syrian hamster brain homogenates; (2) determine if the distribution of these metals can be mapped in TSE-infected brain tissue using X-ray photoelectron emission microscopy (X-PEEM) with synchrotron radiation; and (3) use X-PEEM to assess the relative amounts of copper and manganese in prion plaques in situ. In agreement with studies of other TSEs and species, we found reduced brain levels of copper and increased levels of manganese associated with disease in our hamster model. We also found that the in situ levels of these metals in brainstem were sufficient to image by X-PEEM. Using immunolabeled prion plaques in directly adjacent tissue sections to identify regions to image by X-PEEM, we found a statistically significant relationship of copper-manganese dysregulation in prion plaques: copper was depleted whereas manganese was enriched. These data provide evidence for prion plaques altering local transition metal distribution in the TSE-infected central nervous system.

  13. Novel Adenovirus type 5 vaccine platform induces cellular immunity against HIV-1 Gag, Pol, Nef despite the presence of Ad5 immunity.

    PubMed

    Gabitzsch, Elizabeth S; Xu, Younong; Yoshida, Lois H; Balint, Joseph; Amalfitano, Andrea; Jones, Frank R

    2009-10-30

    Recombinant Adenovirus serotype 5 (Ad5) vectors have been used as vaccine platforms in numerous animal and human clinical studies. The immune response induced by Ad5 vaccines can be mitigated due to pre-existing Ad5 immunity. We previously reported the use of a novel Ad5 platform to induce cellular immune responses (CMI) against HIV-1 Gag in Ad5 hyper immune mice. Here, the effectiveness of the Ad5 [E1-, E2b-] vaccine platform was evaluated using a triad mixture of HIV-1 Gag, Pol, and Nef as antigenic transgenes. Broad CMI was induced following vaccination with the HIV-1 expressing vectors in Ad5 naïve and Ad5 immunized mice. A mixture of the three vaccines induced CMI against each transgene product even in the presence of hyper Ad5 immunity. These studies revealed that CMI responses to immunization with Ad5 [E1-, E2b-]-gag, Ad5 [E1-, E2b-]-pol or Ad5 [E1-, E2b-]-nef vectors were transgene specific and did not induce CMI responses against irrelevant antigens such as carcinoembryonic antigen (CEA), herpes simplex virus glycoprotein B (HSV), cytomegalovirus (CMV) or influenza virus antigens. We are evaluating this recombinant triad viral vector as an HIV-1 vaccine in a non-human primate model and the data indicate that the vaccine is worthy of clinical evaluation. PMID:19559110

  14. Functional assessment of high level ice-dancing.

    PubMed

    Roi, G S; Mevio, M; Occhi, G; Gemma, S; Facchini, R

    1989-06-01

    In these studies the anthropometric characteristics and some functional characteristics of ice-dancers are analysed. It has been shown that the maximum oxygen uptake is similar to that of classical ballet dancers. Tests effected on the ice revealed a high production of lactate, the involvement of the anaerobic metabolism, and high heart rates. It is concluded that the high production of lactate during the free dance on ice is due to the isometric muscular contraction, necessary to maintain certain positions. PMID:2593659

  15. Advanced High-Level Waste Glass Research and Development Plan

    SciTech Connect

    Peeler, David K.; Vienna, John D.; Schweiger, Michael J.; Fox, Kevin M.

    2015-07-01

    The U.S. Department of Energy Office of River Protection (ORP) has implemented an integrated program to increase the loading of Hanford tank wastes in glass while meeting melter lifetime expectancies and process, regulatory, and product quality requirements. The integrated ORP program is focused on providing a technical, science-based foundation from which key decisions can be made regarding the successful operation of the Hanford Tank Waste Treatment and Immobilization Plant (WTP) facilities. The fundamental data stemming from this program will support development of advanced glass formulations, key process control models, and tactical processing strategies to ensure safe and successful operations for both the low-activity waste (LAW) and high-level waste (HLW) vitrification facilities with an appreciation toward reducing overall mission life. The purpose of this advanced HLW glass research and development plan is to identify the near-, mid-, and longer-term research and development activities required to develop and validate advanced HLW glasses and their associated models to support facility operations at WTP, including both direct feed and full pretreatment flowsheets. This plan also integrates technical support of facility operations and waste qualification activities to show the interdependence of these activities with the advanced waste glass (AWG) program to support the full WTP mission. Figure ES-1 shows these key ORP programmatic activities and their interfaces with both WTP facility operations and qualification needs. The plan is a living document that will be updated to reflect key advancements and mission strategy changes. The research outlined here is motivated by the potential for substantial economic benefits (e.g., significant increases in waste throughput and reductions in glass volumes) that will be realized when advancements in glass formulation continue and models supporting facility operations are implemented. Developing and applying advanced

  16. Development of Crystal-Tolerant High-Level Waste Glasses

    SciTech Connect

    Matyas, Josef; Vienna, John D.; Schaible, Micah J.; Rodriguez, Carmen P.; Crum, Jarrod V.; Arrigoni, Alyssa L.; Tate, Rachel M.

    2010-12-17

    Twenty five glasses were formulated. They were batched from HLW AZ-101 simulant or raw chemicals and melted and tested with a series of tests to elucidate the effect of spinel-forming components (Ni, Fe, Cr, Mn, and Zn), Al, and noble metals (Rh2O3 and RuO2) on the accumulation rate of spinel crystals in the glass discharge riser of the high-level waste (HLW) melter. In addition, the processing properties of glasses, such as the viscosity and TL, were measured as a function of temperature and composition. Furthermore, the settling of spinel crystals in transparent low-viscosity fluids was studied at room temperature to access the shape factor and hindered settling coefficient of spinel crystals in the Stokes equation. The experimental results suggest that Ni is the most troublesome component of all the studied spinel-forming components producing settling layers of up to 10.5 mm in just 20 days in Ni-rich glasses if noble metals or a higher concentration of Fe was not introduced in the glass. The layer of this thickness can potentially plug the bottom of the riser, preventing glass from being discharged from the melter. The noble metals, Fe, and Al were the components that significantly slowed down or stopped the accumulation of spinel at the bottom. Particles of Rh2O3 and RuO2, hematite and nepheline, acted as nucleation sites significantly increasing the number of crystals and therefore decreasing the average crystal size. The settling rate of ≤10-μm crystal size around the settling velocity of crystals was too low to produce thick layers. The experimental data for the thickness of settled layers in the glasses prepared from AZ-101 simulant were used to build a linear empirical model that can predict crystal accumulation in the riser of the melter as a function of concentration of spinel-forming components in glass. The developed model predicts the thicknesses of accumulated layers quite well, R2 = 0.985, and can be become an efficient tool for the formulation

  17. High-performance gamma spectroscopy for equipment retrieval from Hanford high-level nuclear waste tanks

    NASA Astrophysics Data System (ADS)

    Troyer, Gary L.; Hillesand, K. E.; Goodwin, S. G.; Kessler, S. F.; Killian, E. W.; Legare, D.; Nelson, Joseph V., Jr.; Richard, R. F.; Nordquist, E. M.

    1999-01-01

    The cleanup of high level defense nuclear waste at the Hanford site presents several progressive challenges. Among these is the removal and disposal of various components from buried active waste tanks to allow new equipment insertion or hazards mitigation. A unique automated retrieval system at the tank provides for retrieval, high pressure washing, inventory measurement, and containment for disposal. Key to the inventory measurement is a three detector HPGe high performance gamma spectroscopy system capable of recovering data at up to ninety per cent saturation (200,000 counts per second). Data recovery is based on a unique embedded electronic pulser and specialized software to report the inventory. Each of the detectors have different shielding specified through Monte Carlo simulation with the MCNP program. This shielding provides performance over a dynamic range of eight orders of magnitude. System description, calibration issues and operational experiences are discussed.

  18. The Outdoor School Inspires Potentially Highly Qualified Middle Level Teachers

    ERIC Educational Resources Information Center

    Watson, Patricia A.; Doue, Walter

    2007-01-01

    Take 50 university education students who may not be quite sure they want to be teachers. Pour them all into a charter bus, and drive them five hours to a remote Texas Hill Country location. Mix in equal parts of enthusiasm and dedication, well-planned interdisciplinary curriculum, and face-to-face interaction with middle level students. Let…

  19. Levels of Meaning in Reading Comprehension of High School Students.

    ERIC Educational Resources Information Center

    Ehrenreich, Zachary; Knafle, June D.

    Working on the hypothesis that if readers had several alternative correct meanings of a given text set before them they would select the one in accordance with their abstract abilities and intellectual maturity, a study investigated the measurement of levels of meaning as illustrated in taxonomies and focused on the applicability of the taxonomies…

  20. High Smog Levels Seen in Mecca During the Annual Pilgrimage

    NASA Astrophysics Data System (ADS)

    Urton, James

    2014-12-01

    In 2012, the Hajj drew 3.5 million Muslims to Mecca for 5 days of prayer and spiritual enlightenment. The annual pilgrimage, one of the largest annual gatherings of people in the world, also brings dangerous levels of air pollution to Islam's holiest city.

  1. New Generation Nuclear Plant -- High Level Functions and Requirements

    SciTech Connect

    J. M. Ryskamp; E. J. Gorski; E. A. Harvego; S. T. Khericha; G. A. Beitel

    2003-09-01

    This functions and requirements (F&R) document was prepared for the Next Generation Nuclear Plant (NGNP) Project. The highest-level functions and requirements for the NGNP preconceptual design are identified in this document, which establishes performance definitions for what the NGNP will achieve. NGNP designs will be developed based on these requirements by commercial vendor(s).

  2. Wafer level reliability for high-performance VLSI design

    NASA Technical Reports Server (NTRS)

    Root, Bryan J.; Seefeldt, James D.

    1987-01-01

    As very large scale integration architecture requires higher package density, reliability of these devices has approached a critical level. Previous processing techniques allowed a large window for varying reliability. However, as scaling and higher current densities push reliability to its limit, tighter control and instant feedback becomes critical. Several test structures developed to monitor reliability at the wafer level are described. For example, a test structure was developed to monitor metal integrity in seconds as opposed to weeks or months for conventional testing. Another structure monitors mobile ion contamination at critical steps in the process. Thus the reliability jeopardy can be assessed during fabrication preventing defective devices from ever being placed in the field. Most importantly, the reliability can be assessed on each wafer as opposed to an occasional sample.

  3. Low-level waste disposal in highly populated areas

    SciTech Connect

    Kowalski, E.; McCombie, C.; Issler, H.

    1989-11-01

    Nuclear-generated electricity supplies almost 40% of the demand in Switzerland (the rest being hydro-power). Allowing for a certain reserve and assuming an operational life-time of 40 years for each reactor, and taking into account wastes from decommissioning and from medicine, industry and research, the total amount of low-level radioactive waste to be disposed of is about 175,000 m{sup 3}. Since there are no unpopulated areas in Switzerland, and since Swiss Federal Law specifies that the safety of disposal may not depend upon supervision of the repository, no shallow-land burial has been foreseen, even for short-lived low-level waste. Instead, geological disposal in a mined cavern system with access through a horizontal tunnel was selected as the best way of meeting the requirements and ensuring the necessary public acceptance.

  4. Exploiting Aura OMI Level 2 Data with High Resolution Visualization

    NASA Astrophysics Data System (ADS)

    Wei, J. C.; Yang, W.; Johnson, J. E.; Zhao, P.; Gerasimov, I. V.; Pham, L.; Vicente, G. A.; Shen, S.

    2014-12-01

    Satellite data products are important for a wide variety of applications that can bring far-reaching benefits to the science community and the broader society. These benefits can best be achieved if the satellite data are well utilized and interpreted, such as model inputs from satellite, or extreme event (such as volcano eruption, dust storm, …etc) interpretation from satellite. Unfortunately, this is not always the case, despite the abundance and relative maturity of numerous satellite data products provided by NASA and other organizations. One way to help users better understand the satellite data is to provide data along with 'Images', including accurate pixel-level (Level 2) information, pixel coverage area delineation, and science team recommended quality screening for individual geophysical parameters. Goddard Earth Sciences Data and Information Services Center (GES DISC) always strives to best support (i.e., Software-as-a-service, SaaS) the user-community for NASA Earth Science Data. In this case, we will present a new visualization tool that helps users exploiting Aura Ozone Monitoring Instrument (OMI) Level 2 data. This new visualization service utilizes Open Geospatial Consortium (OGC) standard-compliant Web Mapping Service (WMS) and Web Coverage Service (WCS) calls in the backend infrastructure. The functionality of the service allows users to select data sources (e.g., multiple parameters under the same measurement, like NO2 and SO2 from OMI Level 2 or same parameter with different methods of aggregation, like NO2 in OMNO2G and OMNO2D products), defining area-of-interest and temporal extents, zooming, panning, overlaying, sliding, and data subsetting and reformatting. The interface will also be able to connect to other OGC WMS and WCS servers, which will greatly enhance its expandability to integrate additional outside data/map sources (such as Global Imagery Browse Services (GIBS)).

  5. High Efficiency Gradient Echo Memory with 3-Level Atoms

    NASA Astrophysics Data System (ADS)

    Buchler, B. C.; Hosseini, M.; Hétet, G.; Sparkes, B. M.; Longdell, J. J.; Sellars, M. J.; Lam, P. K.

    2011-10-01

    We present experimental results demonstrating 87% efficiency for single pulse recall, and storage of up to 20 pulses using a three level gradient echo memory with hot rubidium vapour as the storage medium. We also present results showing pulse resequencing, as well as pulse splitting and spectral manipulation. The decoherence mechanisms affecting the system, in particular scattering due to the control field and how it can be minimised by turning the control field off during storage, are also discussed.

  6. Corrosion issues in high-level nuclear waste containers

    NASA Astrophysics Data System (ADS)

    Asl, Samin Sharifi

    In this dissertation different aspects of corrosion and electrochemistry of copper, candidate canister material in Scandinavian high-level nuclear waste disposal program, including the thermodynamics and kinetics of the reactions that are predicted to occur in the practical system have been studied. A comprehensive thermodynamic study of copper in contact with granitic groundwater of the type and composition that is expected in the Forsmark repository in Sweden has been performed. Our primary objective was to ascertain whether copper would exist in the thermodynamically immune state in the repository, in which case corrosion could not occur and the issue of corrosion in the assessment of the storage technology would be moot. In spite of the fact that metallic copper has been found to exist for geological times in granitic geological formations, copper is well-known to be activated from the immune state to corrode by specific species that may exist in the environment. The principal activator of copper is known to be sulfur in its various forms, including sulfide (H2S, HS-, S2-), polysulfide (H2Sx, HSx -, Sx 2-), poly sulfur thiosulfate ( SxO3 2-), and polythionates (SxO6 2-). A comprehensive study of this aspect of copper chemistry has never been reported, and yet an understanding of this issue is vital for assessing whether copper is a suitable material for fabricating canisters for the disposal of HLNW. Our study identifies and explores those species that activate copper; these species include sulfur-containing entities as well as other, non-sulfur species that may be present in the repository. The effects of temperature, solution pH, and hydrogen pressure on the kinetics of the hydrogen electrode reaction (HER) on copper in borate buffer solution have been studied by means of steady-state polarization measurements, including electrochemical impedance spectroscopy (EIS). In order to obtain electrokinetic parameters, such as the exchange current density and the

  7. SCATHA survey of high-level spacecraft charging in sunlight

    NASA Technical Reports Server (NTRS)

    Mullen, E. G.; Gussenhoven, M. S.; Hardy, D. A.; Aggson, T. A.; Ledley, B. G.

    1986-01-01

    The statistical occurrence of spacecraft charging at near-geosynchronous orbit in daylight is studied with reference to results of an experiment conducted on the SCATHA satellite. In particular, it is found that: (1) the external current that creates high negative satellite frame potentials is the high-energy electron current from the electron population with energies greater than about 30 keV; (2) the electron current to the satellite from particles with energies less than about 30 keV neither drives the frame potential nor provides the current to balance the high-energy populations; and (3) the ion current provided from the entire range of measured ions is also not the primary source of the balancing current.

  8. HIGH ALUMINUM HLW (HIGH LEVEL WASTE ) GLASSES FOR HANFORDS WTP (WASTE TREATMENT PROJECT)

    SciTech Connect

    KRUGER AA; BOWAN BW; JOSEPH I; GAN H; KOT WK; MATLACK KS; PEGG IL

    2010-01-04

    This paper presents the results of glass formulation development and melter testing to identify high waste loading glasses to treat high-Al high level waste (HLW) at Hanford. Previous glass formulations developed for this HLW had high waste loadings but their processing rates were lower that desired. The present work was aimed at improving the glass processing rate while maintaining high waste loadings. Glass formulations were designed, prepared at crucible-scale and characterized to determine their properties relevant to processing and product quality. Glass formulations that met these requirements were screened for melt rates using small-scale tests. The small-scale melt rate screening included vertical gradient furnace (VGF) and direct feed consumption (DFC) melter tests. Based on the results of these tests, modified glass formulations were developed and selected for larger scale melter tests to determine their processing rate. Melter tests were conducted on the DuraMelter 100 (DMIOO) with a melt surface area of 0.11 m{sup 2} and the DuraMelter 1200 (DMI200) HLW Pilot Melter with a melt surface area of 1.2 m{sup 2}. The newly developed glass formulations had waste loadings as high as 50 wt%, with corresponding Al{sub 2}O{sub 3} concentration in the glass of 26.63 wt%. The new glass formulations showed glass production rates as high as 1900 kg/(m{sup 2}.day) under nominal melter operating conditions. The demonstrated glass production rates are much higher than the current requirement of 800 kg/(m{sup 2}.day) and anticipated future enhanced Hanford Tank Waste Treatment and Immobilization Plant (WTP) requirement of 1000 kg/(m{sup 2}.day).

  9. High-level waste program progress report, April 1, 1980-June 30, 1980

    SciTech Connect

    1980-08-01

    The highlights of this report are on: waste management analysis for nuclear fuel cycles; fixation of waste in concrete; study of ceramic and cermet waste forms; alternative high-level waste forms development; and high-level waste container development.

  10. Liquidus Temperature and Primary Crystallization Phases in High-Zirconia High-Level Waste Borosilicate Glasses

    SciTech Connect

    Plaisted, Trevor J.; Hrma, Pavel R.; Vienna, John D.; Jiricka, Antonin

    1999-12-09

    Liquidus temperature (TL) studies of high-Zr high-level waste (HLW) borosilicate glasses have identified three primary phases: baddelyite (ZrO2), zircon (ZrSiO4), and alkali-zirconium silicates, such as parakeldyshite (Na2ZrSi2O7). Using published TL data for HLW glasses with these primary phases, we have computed partial specific TLs for major glass components. On the Na2O-SiO2-ZrO2 submixture, we have determined approximate positions of the boundaries between the baddelyite, zircon, and parakeldyshite primary phase fields. The maximum that can dissolve at 1150?C in a borosilicate HLW glass subjected to common processability and acceptability constraints appears to be 16.5 mass% ZrO2.

  11. Project Water Science. General Science High School Level.

    ERIC Educational Resources Information Center

    Water Education Foundation, Sacramento, CA.

    This teacher's guide presents 12 hands-on laboratory activities for high school science classes that cover the environmental issue of water resources in California. The activities are separated into three sections. Five activities in the section on water quality address the topics of groundwater, water hardness, bottled water, water purity, and…

  12. Threat Level High (School): Curriculum Reform with Violence in Mind

    ERIC Educational Resources Information Center

    Hawkes, T. Elijah; Twemlow, Stuart W.

    2015-01-01

    When school communities are troubled by violence, or threats of violence, at the hands of young people, educators have an opportunity to learn about aggression and adolescent identity development. A disturbing threat incident provides the point of departure for this principal's reflection on how high school curriculum can better meet the identity…

  13. Work Exploration At The Junior-High Level

    ERIC Educational Resources Information Center

    Devin, Paul

    1969-01-01

    The New Horizons Project provides 300 Des Moines inter-city junior high school students, who possess skills but are not making satisfactory academic progress, with work-study, extra guidance, and individual attention in an effort to increase their chance of vocational, social, civic and academic success. (Author/JG)

  14. Teaching World Literature at the High School Level.

    ERIC Educational Resources Information Center

    Piechowski, Marjorie

    Selections from world literature can increase high school students' interest in reading, their familiarity with age-old literary themes, their understanding of literary genres, their awareness of varying cultures, and their skill in analyzing and writing about literature. A world literature course with those aims introduced in a small Wisconsin…

  15. Risk Factors and Levels of Risk for High School Dropouts

    ERIC Educational Resources Information Center

    Suh, Suhyun; Suh, Jingyo

    2007-01-01

    The study in this article identifies three major risk categories of high school dropouts and evaluates the impact of possible prevention strategies. As students accumulate these risks, they became more likely to drop out and prevention programs become less effective. Additionally, it was found that factors influencing the decision to drop out vary…

  16. Professional Staffing Levels and Fourth-Grade Student Research in Rural Schools with High-Poverty Levels

    ERIC Educational Resources Information Center

    Krueger, Karla Steege; Donham, Jean

    2013-01-01

    Rural schools in high-poverty areas are often understaffed. This descriptive phenomenological study examined fourth-grade state research projects in high-poverty rural Iowa schools to reveal the influence of school librarians' staffing levels on student learning of research skills. To determine evidence of students' critical literacy, ethical use…

  17. 21 CFR 880.6885 - Liquid chemical sterilants/high level disinfectants.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Liquid chemical sterilants/high level... and Personal Use Miscellaneous Devices § 880.6885 Liquid chemical sterilants/high level disinfectants. (a) Identification. A liquid chemical sterilant/high level disinfectant is a germicide that...

  18. 21 CFR 880.6885 - Liquid chemical sterilants/high level disinfectants.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Liquid chemical sterilants/high level... and Personal Use Miscellaneous Devices § 880.6885 Liquid chemical sterilants/high level disinfectants. (a) Identification. A liquid chemical sterilant/high level disinfectant is a germicide that...

  19. 21 CFR 880.6885 - Liquid chemical sterilants/high level disinfectants.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Liquid chemical sterilants/high level... and Personal Use Miscellaneous Devices § 880.6885 Liquid chemical sterilants/high level disinfectants. (a) Identification. A liquid chemical sterilant/high level disinfectant is a germicide that...

  20. 21 CFR 880.6885 - Liquid chemical sterilants/high level disinfectants.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Liquid chemical sterilants/high level... and Personal Use Miscellaneous Devices § 880.6885 Liquid chemical sterilants/high level disinfectants. (a) Identification. A liquid chemical sterilant/high level disinfectant is a germicide that...

  1. 21 CFR 880.6885 - Liquid chemical sterilants/high level disinfectants.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Liquid chemical sterilants/high level... and Personal Use Miscellaneous Devices § 880.6885 Liquid chemical sterilants/high level disinfectants. (a) Identification. A liquid chemical sterilant/high level disinfectant is a germicide that...

  2. High Level Architecture (HLA) federation with Umbra and OPNET federates.

    SciTech Connect

    Oppel, Fred John III; Hart, Brian; Van Leeuwen, Brian P.

    2004-03-01

    Network-centric systems that depend on mobile wireless ad hoc networks for their information exchange require detailed analysis to support their development. In many cases, this critical analysis is best provided with high-fidelity system simulations that include the effects of network architectures and protocols. In this research, we developed a high-fidelity system simulation capability using an HLA federation. The HLA federation, consisting of the Umbra system simulator and OPNET Modeler network simulator, provides a means for the system simulator to both affect, and be affected by, events in the network simulator. Advances are also made in increasing the fidelity of the wireless communication channel and reducing simulation run-time with a dead reckoning capability. A simulation experiment is included to demonstrate the developed modeling and simulation capability.

  3. Nova laser system at ultra high fluence levels

    SciTech Connect

    Hunt, J.T.

    1985-01-01

    The Nova experimental facility consists of a ten arm laser system and five experimental stations and was completed in December 1984. Two of these stations are used for inertial confinement fusion (ICF) experiments and the other three are dedicated to doing large aperture (30 to 74 cm) laser experiments. The laser system is deployed in a master oscillator-power amplifier architecture and uses Nd: phosphate glass for the active medium. The fundamental wavelength of the system is 1.05 microns. Frequency converters constructed from potassium dihydrogen phosphate (KDP) crystals are located at the end of each of the ten arms and are used to produce high power frequency doubled (0.53 microns) and tripled (0.35 microns) beams for either ICF or laser experiments. Thus, the Nova laser system can produce high power beams with wavelengths ranging from the infrared to the ultraviolet.

  4. Effects of high doping levels on silicon solar cell performance

    NASA Technical Reports Server (NTRS)

    Godlewski, M. P.; Brandhorst, H. W., Jr.; Baraona, C. R.

    1975-01-01

    Open-circuit voltages measured in silicon solar cells made from 0.01 ohm-cm material are 150 mV lower than voltages calculated from simple diffusion theory and cannot be explained by poor diffusion lengths or surface leakage currents. An analytical study was made to determine whether high doping effects, which increase the intrinsic carrier concentration, could account for the low observed voltages and to determine the limits on voltage and efficiency imposed by high doping effects. The results indicate that the observed variation of voltage with base resistivity is predicted by these effects. A maximum efficiency of 19% (AMO) and a voltage of 0.7 volts were calculated for 0.1 ohm-cm cells assuming an optimum diffused layer impurity profile.

  5. High levels of melatonin generated during the brewing process.

    PubMed

    Garcia-Moreno, H; Calvo, J R; Maldonado, M D

    2013-08-01

    Beer is a beverage consumed worldwide. It is produced from cereals (barley or wheat) and contains a wide array of bioactive phytochemicals and nutraceutical compounds. Specifically, high melatonin concentrations have been found in beer. Beers with high alcohol content are those that present the greatest concentrations of melatonin and vice versa. In this study, gel filtration chromatography and ELISA were combined for melatonin determination. We brewed beer to determine, for the first time, the beer production steps in which melatonin appears. We conclude that the barley, which is malted and ground in the early process, and the yeast, during the second fermentation, are the largest contributors to the enrichment of the beer with melatonin. PMID:23607887

  6. Stagnation region heat transfer augmentation at very high turbulence levels

    DOE PAGESBeta

    Kingery, Joseph E.; Ames, Forrest E.

    2016-08-01

    Current land-based gas turbines are growing in size producing higher approach flow Reynolds numbers at the leading edge of turbine nozzles. These vanes are subjected to high intensity large scale turbulence. This present paper reports on the research which significantly expands the parameter range for stagnation region heat transfer augmenta-tion due to high intensity turbulence. Heat transfer measurements were acquired over two constant heat flux test surfaces with large diameter leading edges (10.16 cm and 40.64 cm). The test surfaces were placed downstream from a new high intensity (17.4%) mock combustor and tested over an eight to one range inmore » approach flow Reynolds number for each test surface. Stagnation region heat transfer augmentation for the smaller (ReD = 15,625–125,000) and larger (ReD = 62,500–500,000) leading edge regions ranged from 45% to 81% and 80% to 136%, respectively. Furthermore, these data also include heat transfer distributions over the full test surface compared with the earlier data acquired at six additional inlet turbulence conditions. These surfaces exhibit continued but more moderate acceleration downstream from the stagnation regions and these data are expected to be useful in testing bypass transition predictive approaches. This database will be useful to gas turbine heat transfer design engineers. [DOI: 10.1115/1.4032677]« less

  7. High Voltage Breakdown Levels in Various EPC Potting Materials

    NASA Technical Reports Server (NTRS)

    Komm, David S.

    2006-01-01

    This viewgraph presentation reviews exploration activities at JPL into various potting materials. Since high power space-borne microwave transmitters invariably use a vacuum tube as a final power amplifier, and this tube requires high electrode voltages for operation. The associated high voltage insulation typically represents a significant fraction of the mass of the transmitter. Since mass is always a premium resource on board spacecraft, we have been investigating materials with the potential to reduce the mass required for our applications here at JPL. This paper describes electrical breakdown results obtained with various potting materials. Conathane EN-11 (polyurethane) is the traditional HVPS encapsulant at JPL, but due to temperature limitations and durability issues it was deemed inappropriate for the particular application (i.e., CloudSat radar). The choices for the best available materials were epoxies, or silicones. Epoxies are too rigid, and were deemed inadvisable. Two silicones were further investigated (i.e.,ASTM E595- 93e2: GE RTV566(R) and Dow Corning 93-500X(R), another compound was considered (i.e., DC material, Sylgard 184(R)). "Loading" (adding filler materials) the potting compound will frequently alter the final material properties. Powdered alumina and borosilicate glass known as "microballoons" were investigated as possible loading materials. The testing of the materials is described. Each of the two loading materials offers advantages and disadvantages. The advantages and disadvantages are described.

  8. Project MAGNET High-level Vector Survey Data Reduction

    NASA Technical Reports Server (NTRS)

    Coleman, Rachel J.

    1992-01-01

    Since 1951, the U.S. Navy, under its Project MAGNET program, has been continuously collecting vector aeromagnetic survey data to support the U.S. Defense Mapping Agency's world magnetic and charting program. During this forty-year period, a variety of survey platforms and instrumentation configurations have been used. The current Project MAGNET survey platform is a Navy Orion RP-3D aircraft which has been specially modified and specially equipped with a redundant suite of navigational positioning, attitude, and magnetic sensors. A review of the survey data collection procedures and calibration and editing techniques applied to the data generated by this suite of instrumentation will be presented. Among the topics covered will be the determination of its parameters from the low-level calibration maneuvers flown over geomagnetic observatories.

  9. Copper uptake by Eichhornia crassipes exposed at high level concentrations.

    PubMed

    Melignani, Eliana; de Cabo, Laura Isabel; Faggi, Ana María

    2015-06-01

    The objective of this study was to assess the growth of water hyacinth (Eichhornia crassipes) and its ability to accumulate Cu from polluted water with high Cu concentrations and a mixture of other contaminants under short-term exposure, in order to use this species for the remediation of highly contaminated sites. Two hydroponic experiments were performed under greenhouse conditions for 7 days. One of them consisted of growing water hyacinth in Hoagland solution supplemented with 15 or 25 mg Cu/L and a control. The other one contained water hyacinth growing in polluted river water supplemented with 15 mg Cu/L and a control. Cu was accumulated principally in roots. The maximum Cu concentration was 23,387.2 mg/kg dw in the treatment of 25 mg Cu/L in Hoagland solution. Cu translocation from roots to leaves was low. The mixture of 15 mg Cu/L with polluted water did not appear to have toxic effects on the water hyacinth. This plant showed a remarkable uptake capacity under elevated Cu concentrations in a mixture of pollutants similar to pure industrial effluents in a short time of exposure. This result has not been reported before, to our knowledge. This species is suitable for phytoremediation of waters subject to discharge of mixed industrial effluents containing elevated Cu concentrations (≥15 mg Cu/L), as well as nutrient-rich domestic wastewaters. PMID:25529492

  10. PLUTONIUM/HIGH LEVEL VITRIFIED WASTE - DBE OFFSITE DOSE CALCULATION

    SciTech Connect

    S. O. Bader

    1999-09-20

    The purpose of this calculation is to provide a bounding dose consequence analysis of the immobilized plutonium (can-in-canister) waste form to be handled at the Monitored Geologic Repository (MGR) at Yucca Mountain. The current concept for the Plutonium Can-in-Canister waste form is provided in Attachment III. A typical design basis event (DBE) defines a scenario that generally includes an initiating event and the sequences of events that follow. This analysis will provide (1) radiological releases and dose consequences for a postulated, bounding DBE and (2) design-related assumptions on which the calculated dose consequences are based. This analysis is part of the safety design basis for the repository. Results will be used in other analyses to determine or modify the safety classification and quality assurance level of repository structures, systems, and components (SSCs). The Quality Assurance (QA) program applies to this calculation. The work reported in this document is part of the analysis of MGR DBEs and is performed using AP-3.12Q, Calculations. The work done for this analysis was evaluated according to QAP-2-0, Control of Activities. This evaluation determined that such activities are subject to DOE/RW/0333PY Quality Assurance Requirements and Description (DOE 1998), requirements. This calculation is quality affecting because the results may be used to support analyses of repository SSCs per QAP-2-3, Classification of Permanent Items.

  11. High levels of lipid peroxidation in semen of diabetic patients.

    PubMed

    La Vignera, S; Condorelli, R A; Vicari, E; D'Agata, R; Salemi, M; Calogero, A E

    2012-05-01

    The aim of this study was to evaluate the level of malondialdehyde (MDA) (one of the final products of lipid peroxidation and well-known marker of oxidative stress) in semen of infertile men with type 2 diabetes and to investigate its relationship with their glycaemic control. Forty infertile men with type 2 diabetes were evaluated. The mean ages were 36.5 ± 8.0. Men with diabetes were divided into two groups. Group A (n = 20) with glycated haemoglobin >10% and group B (n = 20) with glycated haemoglobin <7%. A single sample was examined according to the criteria of the World Health Organization (WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction, 1999, Cambridge University Press). MDA was assessed using the thiobarbituric acid method. MDA concentration in semen of group A patients (0.95 ± 0.35 nmol ml(-1)) was significantly higher than in group B patients (0.43 ± 0.13 nmol ml(-1)) (P value < 0.05) and had negative relationship with sperm density (r = -.717; P value < 0.05), total sperm count (r = -.625; P value < 0.05), progressive motility (r = -.489; P value < 0.05) and normal forms (r = -.545; P value < 0.05). Based on these results, it could be concluded that increase in lipid peroxidation in men with diabetes with poor metabolic control was associated with low sperm quality. PMID:21919944

  12. High levels of confusion for cholesterol awareness campaigns.

    PubMed

    Hall, Danika V

    2008-09-15

    Earlier this year, two industry-sponsored advertising campaigns for cholesterol awareness that target the general public were launched in Australia. These campaigns aimed to alert the public to the risks associated with having high cholesterol and encouraged cholesterol testing for wider groups than those specified by the National Heart Foundation. General practitioners should be aware of the potential for the two campaigns to confuse the general public as to who should be tested, and where. The campaign sponsors (Unilever Australasia and Pfizer) each have the potential to benefit by increased market share for their products, and increased profits. These disease awareness campaigns are examples of what is increasingly being termed "condition branding" by pharmaceutical marketing experts. PMID:18803537

  13. High level triggers for explosive mafic volcanism: Albano Maar, Italy

    NASA Astrophysics Data System (ADS)

    Cross, J. K.; Tomlinson, E. L.; Giordano, G.; Smith, V. C.; De Benedetti, A. A.; Roberge, J.; Manning, C. J.; Wulf, S.; Menzies, M. A.

    2014-03-01

    Colli Albani is a quiescent caldera complex located within the Roman Magmatic Province (RMP), Italy. The recent Via dei Laghi phreatomagmatic eruptions led to the formation of nested maars. Albano Maar is the largest and has erupted seven times between ca 69-33 ka. The highly explosive nature of the Albano Maar eruptions is at odds with the predominant relatively mafic (SiO2 = 48-52 wt.%) foiditic (K2O = 9 wt.%) composition of the magma. The deposits have been previously interpreted as phreatomagmatic, however they contain large amounts (up to 30%vol) of deep seated xenoliths, skarns and all pre-volcanic subsurface units. All of the xenoliths have been excavated from depths of up to 6 km, rather than being limited to the depth at which magma and water interaction is likely to have occurred, suggesting an alternative trigger for eruption. High precision geochemical glass and mineral data of fresh juvenile (magmatic) clasts from the small volume explosive deposits indicate that the magmas have evolved along one of two evolutionary paths towards foidite or phonolite. The foiditic melts record ca. 50% mixing between the most primitive magma and Ca-rich melt, late stage prior to eruption. A major result of our study is finding that the generation of Ca-rich melts via assimilation of limestone, may provide storage for significant amounts of CO2 that can be released during a mixing event with silicate magma. Differences in melt evolution are inferred as having been controlled by variations in storage conditions: residence time and magma volume.

  14. Developmental and cognitive characteristics of "high-level potentialities" (highly gifted) children.

    PubMed

    Vaivre-Douret, Laurence

    2011-01-01

    This study covers the interesting field of the development in gifted children which is often neglected in pediatrics because psychomotor development data are still rare, since "gifted" children are generally noticed towards the end of their primary schooling by IQ measurement. Developmental studies have shown the evidence from several fields that children identified as "high-level potentialities" or "intellectually gifted" develop sensory, locomotor, neuropsychological, and language skills earlier than typically expected. The hypothesis is offered that the earlier development originates from biological processes affecting the physical development of the brain and in turn even intellectual abilities are developed earlier, potentially allowing for advanced development. Further it is discussed how these developmental advances interact with the social environment and in certain circumstances may entail increased risk for developing socioemotional difficulties and learning disabilities that often go unaddressed due to the masking by the advance intellectual abilities. PMID:21977044

  15. Developmental and Cognitive Characteristics of “High-Level Potentialities” (Highly Gifted) Children

    PubMed Central

    Vaivre-Douret, Laurence

    2011-01-01

    This study covers the interesting field of the development in gifted children which is often neglected in pediatrics because psychomotor development data are still rare, since “gifted” children are generally noticed towards the end of their primary schooling by IQ measurement. Developmental studies have shown the evidence from several fields that children identified as “high-level potentialities” or “intellectually gifted” develop sensory, locomotor, neuropsychological, and language skills earlier than typically expected. The hypothesis is offered that the earlier development originates from biological processes affecting the physical development of the brain and in turn even intellectual abilities are developed earlier, potentially allowing for advanced development. Further it is discussed how these developmental advances interact with the social environment and in certain circumstances may entail increased risk for developing socioemotional difficulties and learning disabilities that often go unaddressed due to the masking by the advance intellectual abilities. PMID:21977044

  16. Assembly of highly standardized gene fragments for high-level production of porphyrins in E. coli.

    PubMed

    Nielsen, Morten T; Madsen, Karina M; Seppälä, Susanna; Christensen, Ulla; Riisberg, Lone; Harrison, Scott J; Møller, Birger Lindberg; Nørholm, Morten H H

    2015-03-20

    Standardization of molecular cloning greatly facilitates advanced DNA engineering, parts sharing, and collaborative efforts such as the iGEM competition. All of these attributes facilitate exploitation of the wealth of genetic information made available by genome and RNA sequencing. Standardization also comes at the cost of reduced flexibility. We addressed this paradox by formulating a set of design principles aimed at maximizing standardization while maintaining high flexibility in choice of cloning technique and minimizing the impact of standard sequences. The design principles were applied to formulate a molecular cloning pipeline and iteratively assemble and optimize a six-gene pathway for protoporphyrin IX synthesis in Escherichia coli. State of the art production levels were achieved through two simple cycles of engineering and screening. The principles defined here are generally applicable and simplifies the experimental design of projects aimed at biosynthetic pathway construction or engineering. PMID:24905856

  17. PLUTONIUM SOLUBILITY IN HIGH-LEVEL WASTE ALKALI BOROSILICATE GLASS

    SciTech Connect

    Marra, J.; Crawford, C.; Fox, K.; Bibler, N.

    2011-01-04

    The solubility of plutonium in a Sludge Batch 6 (SB6) reference glass and the effect of incorporation of Pu in the glass on specific glass properties were evaluated. A Pu loading of 1 wt % in glass was studied. Prior to actual plutonium glass testing, surrogate testing (using Hf as a surrogate for Pu) was conducted to evaluate the homogeneity of significant quantities of Hf (Pu) in the glass, determine the most appropriate methods to evaluate homogeneity for Pu glass testing, and to evaluate the impact of Hf loading in the glass on select glass properties. Surrogate testing was conducted using Hf to represent between 0 and 1 wt % Pu in glass on an equivalent molar basis. A Pu loading of 1 wt % in glass translated to {approx}18 kg Pu per Defense Waste Processing Facility (DWPF) canister, or about 10X the current allowed limit per the Waste Acceptance Product Specifications (2500 g/m{sup 3} of glass or about 1700 g/canister) and about 30X the current allowable concentration based on the fissile material concentration limit referenced in the Yucca Mountain Project License Application (897 g/m{sup 3}3 of glass or about 600 g Pu/canister). Based on historical process throughput data, this level was considered to represent a reasonable upper bound for Pu loading based on the ability to provide Pu containing feed to the DWPF. The task elements included evaluating the distribution of Pu in the glass (e.g. homogeneity), evaluating crystallization within the glass, evaluating select glass properties (with surrogates), and evaluating durability using the Product Consistency Test -- Method A (PCT-A). The behavior of Pu in the melter was evaluated using paper studies and corresponding analyses of DWPF melter pour samples.The results of the testing indicated that at 1 wt % Pu in the glass, the Pu was homogeneously distributed and did not result in any formation of plutonium-containing crystalline phases as long as the glass was prepared under 'well-mixed' conditions. The

  18. Operational experience with the ALICE High Level Trigger

    NASA Astrophysics Data System (ADS)

    Szostak, Artur

    2012-12-01

    The ALICE HLT is a dedicated real-time system for online event reconstruction and triggering. Its main goal is to reduce the raw data volume read from the detectors by an order of magnitude, to fit within the available data acquisition bandwidth. This is accomplished by a combination of data compression and triggering. When HLT is enabled, data is recorded only for events selected by HLT. The combination of both approaches allows for flexible data reduction strategies. Event reconstruction places a high computational load on HLT. Thus, a large dedicated computing cluster is required, comprising 248 machines, all interconnected with InfiniBand. Running a large system like HLT in production mode proves to be a challenge. During the 2010 pp and Pb-Pb data-taking period, many problems were experienced that led to a sub-optimal operational efficiency. Lessons were learned and certain crucial changes were made to the architecture and software in preparation for the 2011 Pb-Pb run, in which HLT had a vital role performing data compression for ALICE's largest detector, the TPC. An overview of the status of the HLT and experience from the 2010/2011 production runs are presented. Emphasis is given to the overall performance, showing an improved efficiency and stability in 2011 compared to 2010, attributed to the significant improvements made to the system. Further opportunities for improvement are identified and discussed.

  19. HYPERFINE STRUCTURE CONSTANTS OF ENERGETICALLY HIGH-LYING LEVELS OF ODD PARITY OF ATOMIC VANADIUM

    SciTech Connect

    Güzelçimen, F.; Yapıcı, B.; Demir, G.; Er, A.; Öztürk, I. K.; Başar, Gö.; Kröger, S.; Tamanis, M.; Ferber, R.; Docenko, D.; Başar, Gü. E-mail: sophie.kroeger@htw-berlin.de

    2014-09-01

    High-resolution Fourier transform spectra of a vanadium-argon plasma have been recorded in the wavelength range of 365-670 nm (15,000-27,400 cm{sup –1}). Optical bandpass filters were used in the experimental setup to enhance the sensitivity of the Fourier transform spectrometer. In total, 138 atomic vanadium spectral lines showing resolved or partially resolved hyperfine structure have been analyzed to determine the magnetic dipole hyperfine structure constants A of the involved energy levels. One of the investigated lines has not been previously classified. As a result, the magnetic dipole hyperfine structure constants A for 90 energy levels are presented: 35 of them belong to the configuration 3d {sup 3}4s4p and 55 to the configuration 3d {sup 4}4p. Of these 90 constants, 67 have been determined for the first time, with 23 corresponding to the configuration 3d {sup 3}4s4p and 44 to 3d {sup 4}4p.

  20. Variational study on the vibrational level structure and vibrational level mixing of highly vibrationally excited S₀ D₂CO.

    PubMed

    Rashev, Svetoslav; Moule, David C; Rashev, Vladimir

    2012-11-01

    We perform converged high precision variational calculations to determine the frequencies of a large number of vibrational levels in S(0) D(2)CO, extending from low to very high excess vibrational energies. For the calculations we use our specific vibrational method (recently employed for studies on H(2)CO), consisting of a combination of a search/selection algorithm and a Lanczos iteration procedure. Using the same method we perform large scale converged calculations on the vibrational level spectral structure and fragmentation at selected highly excited overtone states, up to excess vibrational energies of ∼17,000 cm(-1), in order to study the characteristics of intramolecular vibrational redistribution (IVR), vibrational level density and mode selectivity. PMID:22750345

  1. 3-D MAPPING TECHNOLOGIES FOR HIGH LEVEL WASTE TANKS

    SciTech Connect

    Marzolf, A.; Folsom, M.

    2010-08-31

    time-of-flight data (3D image) collected with a single laser pulse, high frame rates, direct calculation of range, blur-free images without motion distortion, no need for precision scanning mechanisms, ability to combine 3D flash LIDAR with 2D cameras for 2D texture over 3D depth, and no moving parts. The major disadvantage of the 3D flash LIDAR camera is the cost of approximately $150,000, not including the software development time and repackaging of the camera for deployment in the waste tanks.

  2. Flooding in Myanmar: joint occurrence of high discharges and high sea water levels?

    NASA Astrophysics Data System (ADS)

    Bouaziz, Laurène; Sperna Weiland, Frederiek; Vatvani, Deepak; Diermanse, Ferdinand

    2016-04-01

    In the summer of 2015 serious flooding occurred in Myanmar when cyclone Komen made landfall in Bangladesh, bringing strong winds and heavy rains to Myanmar. The cyclone struck the country during the monsoon season and resulted in widespread flooding, temporarily displacing over 1.6 million people. It was hypothesized that there could be a relation between occurrences of storm surges and extreme discharges in Myanmar. Comparable studies have shown that dependence between storm surge at Hoek van Holland in the Netherlands and high river discharges of the Rhine at Lobith exist with a lag of 6 days (Klerk et. al, 2015). The processes generating high discharges in the Ayeyarwady river and storm surges along the Myanmar coast were analyzed using global precipitation data (EU FP7 eartH2Observe), a distributed wflow-sbm hydrological model of the Ayeyarwady and a global storm surge model. About 15 historical tropical storms and hurricanes affecting Myanmar since 1992 were analyzed in terms of rainfall distribution over the country, discharged river flow volumes and storm surge extent and magnitude. All storms except for Komen in 2015 occurred between October and May, which does not coincide with the monsoon season (mainly June, July and August). The intensities and the paths of the 15 studied cyclones varied considerably and largely affected the spatial extent and the magnitude of storm surges. The study showed that high Ayeyarwady river flows and high surges generally do not coincide for the following reasons: the large scale of the river basin, the estimated one week travel time of water from the upstream catchment to the mouth, the occurrence of the majority of historical storms outside the monsoon season and the (relatively) limited spatial extent of a storm surge (at the scale of Myanmar). While the applied method is deemed successful for the identification of joint probabilities of surges and river discharges, this study indicates that such analyses are more relevant

  3. High Plasticizer Levels In Males Linked to Delayed Pregnancy for Female Partners

    MedlinePlus

    ... News Release Wednesday, March 5, 2014 High plasticizer levels in males linked to delayed pregnancy for female ... particular aspects of reproductive health, such as hormone levels. “Our study shows that exposure to certain phthalates ...

  4. An Investigation of High School Seniors' Assertiveness Levels Based on Their Demographic Characteristics

    ERIC Educational Resources Information Center

    Çam, Ibrahim

    2015-01-01

    High school students who are in the development age or in the last class and have chance to win the university exams or disposal stage of the business life must also have a high level of assertiveness. In this context, the purpose of this research is to compare the assertiveness levels of high school seniors. The study group consists of 312 high…

  5. Percentage of Adults with High Cholesterol Whose LDL Cholesterol Levels Are Adequately Controlled

    MedlinePlus

    ... of Adults with High Cholesterol Whose LDL Cholesterol Levels are Adequately Controlled High cholesterol can double a ... with High Cholesterol that is Controlled by Education Level 8k4c-k22f Download these data » Click on legends ...

  6. Extraction of high-quality RNA from germinating barley (Hordeum vulgare L.) seeds containing high levels of starch.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Comparative evaluation of gene expression levels can lead to improved understanding of the gene networks underlying traits of economic importance. Extraction of high-quality RNA from germinating barley seeds that contain high levels of starch is of vital importance for analysing the expression of ca...

  7. The sleep of elite athletes at sea level and high altitude: a comparison of sea-level natives and high-altitude natives (ISA3600)

    PubMed Central

    Roach, Gregory D; Schmidt, Walter F; Aughey, Robert J; Bourdon, Pitre C; Soria, Rudy; Claros, Jesus C Jimenez; Garvican-Lewis, Laura A; Buchheit, Martin; Simpson, Ben M; Hammond, Kristal; Kley, Marlen; Wachsmuth, Nadine; Gore, Christopher J; Sargent, Charli

    2013-01-01

    Background Altitude exposure causes acute sleep disruption in non-athletes, but little is known about its effects in elite athletes. The aim of this study was to examine the effects of altitude on two groups of elite athletes, that is, sea-level natives and high-altitude natives. Methods Sea-level natives were members of the Australian under-17 soccer team (n=14). High-altitude natives were members of a Bolivian under-20 club team (n=12). Teams participated in an 18-day (19 nights) training camp in Bolivia, with 6 nights at near sea level in Santa Cruz (430 m) and 13 nights at high altitude in La Paz (3600 m). Sleep was assessed on every day/night using activity monitors. Results The Australians’ sleep was shorter, and of poorer quality, on the first night at altitude compared with sea level. Sleep quality returned to normal by the end of the first week at altitude, but sleep quantity had still not stabilised at its normal level after 2 weeks. The quantity and quality of sleep obtained by the Bolivians was similar, or greater, on all nights at altitude compared with sea level. The Australians tended to obtain more sleep than the Bolivians at sea level and altitude, but the quality of the Bolivians’ sleep tended to be better than that of the Australians at altitude. Conclusions Exposure to high altitude causes acute and chronic disruption to the sleep of elite athletes who are sea-level natives, but it does not affect the sleep of elite athletes who are high-altitude natives. PMID:24282197

  8. High rates of phasing errors in highly polymorphic species with low levels of linkage disequilibrium.

    PubMed

    Bukowicki, Marek; Franssen, Susanne U; Schlötterer, Christian

    2016-07-01

    Short read sequencing of diploid individuals does not permit the direct inference of the sequence on each of the two homologous chromosomes. Although various phasing software packages exist, they were primarily tailored for and tested on human data, which differ from other species in factors that influence phasing, such as SNP density, amounts of linkage disequilibrium (LD) and sample sizes. Despite becoming increasingly popular for other species, the reliability of phasing in non-human data has not been evaluated to a sufficient extent. We scrutinized the phasing accuracy for Drosophila melanogaster, a species with high polymorphism levels and reduced LD relative to humans. We phased two D. melanogaster populations and compared the results to the known haplotypes. The performance increased with size of the reference panel and was highest when the reference panel and phased individuals were from the same population. Full genomic SNP data and inclusion of sequence read information also improved phasing. Despite humans and Drosophila having similar switch error rates between polymorphic sites, the distances between switch errors were much shorter in Drosophila with only fragments <300-1500 bp being correctly phased with ≥95% confidence. This suggests that the higher SNP density cannot compensate for the higher recombination rate in D. melanogaster. Furthermore, we show that populations that have gone through demographic events such as bottlenecks can be phased with higher accuracy. Our results highlight that statistically phased data are particularly error prone in species with large population sizes or populations lacking suitable reference panels. PMID:26929272

  9. High illumination resolution test of low-light-level image intensifier

    NASA Astrophysics Data System (ADS)

    Bai, Xiaofeng; Yin, Lei; Zhu, Yufeng; He, Yingping; Miao, Zhuang; Hu, Wen; Hou, Zhipeng; Shi, Hongli

    2013-08-01

    High illumination resolution, which directly determines the applied characteristic of night vision system in flashlight or high light level condition, is an important performance parameter for evaluating the characteristic of low light level image intensifier used in high light level condition. In this article, according to the limited resolution test technique, the test principle, test condition and test method to high illumination resolution are described in detail associated with operation mode and protective way of low light level image intensifier. Test system for measuring the high illumination resolution has been founded based on the limited resolution test system. The value of high illumination for measuring the high illumination resolution has been calculated in theory and measured by illuminometer. High illumination resolution of low light level image intensifiers have been measured in test system, results show that high illumination resolution test system is satisfied the need for measuring high illumination resolution of low light level image intensifier, and test system output light illumination must be greater than 1×103 lux. Light of high illumination, which can be correctly measured by illuminometer, is transferred legitimately. That is worthwhile to evaluate the operational characteristic of low light level image intensifier.

  10. Decadal-scale variations of trophic levels at high trophic levels in the Yellow Sea and the Bohai Sea ecosystem

    NASA Astrophysics Data System (ADS)

    Zhang, B.; Tang, Q.; Jin, X.

    2007-09-01

    A total of 2759 stomachs collected from a bottom trawl survey carried out by R/V "Bei Dou" in the Yellow Sea between 32°00 and 36°30N in autumn 2000 and spring 2001 were examined. The trophic levels (TL) of eight dominant fish species were calculated based on stomach contents, and trophic levels of 17 dominant species in the Yellow Sea and the Bohai Sea reported in later 1950s and mid-1980s were estimated so as to be comparable. The results indicated that the mean trophic level at high trophic levels declined from 4.06 in 1959-1960 to 3.41 in 1998-1999, or 0.16-0.19·decade - 1 (mean 0.17·decade - 1 ) in the Bohai Sea, and from 3.61 in 1985-1986 to 3.40 in 2000-2001, or 0.14·decade - 1 in the Yellow Sea; all higher than global trend. The dominant species composition in the Yellow Sea and the Bohai Sea changed, with the percentage of planktivorous species increases and piscivorous or omnivorous species decreases, and this was one of the main reasons for the decline in mean trophic level at high tropic levels. Another main reason was intraspecific changes in TL. Similarly, many factors caused decline of trophic levels in the dominant fish species in the Yellow Sea and the Bohai Sea. Firstly, TL of the same prey got lower, and anchovy ( Engraulis japonicus) as prey was most representative. Secondly, TLs of diet composition getting lower resulted in not only decline of trophic levels but also changed feeding habits of some species, such as spotted velvetfish ( Erisphex pottii) and Trichiurus muticus in the Yellow Sea. Thirdly, species size getting smaller also resulted in not only decline of trophic levels but also changed feeding habits of some species, such as Bambay duck ( Harpodon nehereus) and largehead hairtail ( Trichiurus haumela). Furthermore, fishing pressure and climate change may be interfering to cause fishing down the food web in the China coastal ocean.

  11. Immunization of HIV-1-Infected Persons With Autologous Dendritic Cells Transfected With mRNA Encoding HIV-1 Gag and Nef: Results of a Randomized, Placebo-Controlled Clinical Trial

    PubMed Central

    Kwon, Douglas S.; Macklin, Eric A.; Shopis, Janet R.; McLean, Anna P.; McBrine, Nicole; Flynn, Theresa; Peter, Lauren; Sbrolla, Amy; Kaufmann, Daniel E.; Porichis, Filippos; Walker, Bruce D.; Bhardwaj, Nina; Barouch, Dan H.; Kavanagh, Daniel G.

    2016-01-01

    Background: HIV-1 eradication may require reactivation of latent virus along with stimulation of HIV-1-specific immune responses to clear infected cells. Immunization with autologous dendritic cells (DCs) transfected with viral mRNA is a promising strategy for eliciting HIV-1-specific immune responses. We performed a randomized controlled clinical trial to evaluate the immunogenicity of this approach in HIV-1-infected persons on antiretroviral therapy. Methods: Fifteen participants were randomized 2:1 to receive intradermal immunization with HIV-1 Gag- and Nef-transfected DCs (vaccine) or mock-transfected DCs (placebo) at weeks 0, 2, 6, and 10. All participants also received DCs pulsed with keyhole limpet hemocyanin (KLH) to assess whether responses to a neo-antigen could be induced. Results: After immunization, there were no differences in interferon-gamma enzyme-linked immunospot responses to HIV-1 Gag or Nef in the vaccine or placebo group. CD4 proliferative responses to KLH increased 2.4-fold (P = 0.026) and CD8 proliferative responses to KLH increased 2.5-fold (P = 0.053) after vaccination. There were increases in CD4 proliferative responses to HIV-1 Gag (2.5-fold vs. baseline, 3.4-fold vs. placebo, P = 0.054) and HIV-1 Nef (2.3-fold vs. baseline, 6.3-fold vs. placebo, P = 0.009) among vaccine recipients, but these responses were short-lived. Conclusion: Immunization with DCs transfected with mRNA encoding HIV-1 Gag and Nef did not induce significant interferon-gamma enzyme-linked immunospot responses. There were increases in proliferative responses to HIV-1 antigens and to a neo-antigen, KLH, but the effects were transient. Dendritic cell vaccination should be optimized to elicit stronger and long-lasting immune responses for this strategy to be effective as an HIV-1 therapeutic vaccine. PMID:26379068

  12. Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A.

    PubMed Central

    Aiken, C

    1997-01-01

    Human immunodeficiency virus type 1 (HIV-1) normally enters cells by direct fusion with the plasma membrane. In this report, HIV-1 particles capable of infecting cells through an endocytic pathway are described. Chimeric viruses composed of the HIV-1 core and the envelope glycoprotein of vesicular stomatitis virus (VSV-G) were constructed and are herein termed HIV-1(VSV) pseudotypes. HIV-1(VSV) pseudotypes were 20- to 130-fold more infectious than nonpseudotyped HIV-1. Infection by HIV-1(VSV) pseudotypes was markedly diminished by ammonium chloride and concanamycin A, a selective inhibitor of vacuolar H+ ATPases, demonstrating that these viruses require endosomal acidification to achieve productive infection. HIV-1 is thus capable of performing all of the viral functions necessary for infection when entry is targeted to an endocytic route. Maximal HIV-1 infectivity requires the presence of the viral Nef protein and the cellular protein cyclophilin A (CyPA) during virus assembly. Pseudotyping by VSV-G markedly suppressed the requirement for Nef. HIV-1(VSV) particles were also resistant to inhibition by cyclosporin A; however, the deleterious effect of a gag mutation inhibiting CyPA incorporation was not relieved by VSV-G. These results suggest that Nef acts at a step of the HIV-1 life cycle that is either circumvented or facilitated by targeting virus entry to an endocytic pathway. The findings also support the hypothesis that Nef and CyPA enhance HIV-1 infectivity through independent processes and demonstrate a mechanistic difference between reduction of HIV-1 infectivity by cyclosporin A and gag mutations that decrease HIV-1 incorporation of CyPA. PMID:9223476

  13. Oblique Orientation Discrimination Thresholds Are Superior in Those with a High Level of Autistic Traits

    ERIC Educational Resources Information Center

    Dickinson, Abigail; Jones, Myles; Milne, Elizabeth

    2014-01-01

    Enhanced low-level perception, although present in individuals with autism, is not seen in individuals with high, but non-clinical, levels of autistic traits (Brock et al.in "Percept Lond" 40(6):739. doi:10.1068/p6953, 2011). This is surprising, as many of the higher-level visual differences found in autism have been shown to correlate…

  14. Comprehension of College-Level Text with High School Students Underperforming in Literacy

    ERIC Educational Resources Information Center

    Newton, Stephen Vincent

    2012-01-01

    The ability to comprehend sophisticated text is a requisite skill for success at the collegiate level. Unfortunately, there is a large disparity between the complexity of texts used in high schools and those used at the collegiate level. Students may be underprepared if they have never been exposed to texts with the level of rigor that college…

  15. Changes in Badminton Game Play across Developmental Skill Levels among High School Students

    ERIC Educational Resources Information Center

    Wang, Jianyu; Liu, Wenhao

    2012-01-01

    The study examined changes in badminton game play across developmental skill levels among high school students in a physical education setting. Videotapes of badminton game play of 80 students (40 boys and 40 girls) in the four developmental skill levels (each skill level had 10 boys and 10 girls) were randomly selected from a database associated…

  16. High level language for measurement complex control based on the computer E-100I

    NASA Technical Reports Server (NTRS)

    Zubkov, B. V.

    1980-01-01

    A high level language was designed to control the process of conducting an experiment using the computer "Elektrinika-1001". Program examples are given to control the measuring and actuating devices. The procedure of including these programs in the suggested high level language is described.

  17. Alternatives Generation and Analysis for Heat Removal from High Level Waste Tanks

    SciTech Connect

    WILLIS, W.L.

    2000-06-15

    This document addresses the preferred combination of design and operational configurations to provide heat removal from high-level waste tanks during Phase 1 waste feed delivery to prevent the waste temperature from exceeding tank safety requirement limits. An interim decision for the preferred method to remove the heat from the high-level waste tanks during waste feed delivery operations is presented herein.

  18. Teaching a High-Level Contextualized Mathematics Curriculum to Adult Basic Learners

    ERIC Educational Resources Information Center

    Showalter, Daniel A.; Wollett, Chelsie; Reynolds, Sharon

    2014-01-01

    This paper reports on the implementation of a high level contextualized mathematics curriculum by 12 adult basic instructors in a midwestern state. The 10-week pilot curriculum embedded high level mathematics in contexts that were familiar to adult learners. Instructors' weekly online posts were coded, and the following themes emerged: (a)…

  19. 40 CFR 1065.725 - High-level ethanol-gasoline blends.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ethanol used for blending must be either denatured ethanol meeting the specifications in 40 CFR 80.1610... 40 Protection of Environment 33 2014-07-01 2014-07-01 false High-level ethanol-gasoline blends... Calibration Standards § 1065.725 High-level ethanol-gasoline blends. For testing vehicles capable of...

  20. Hi-LAB: A New Measure of Aptitude for High-Level Language Proficiency

    ERIC Educational Resources Information Center

    Linck, Jared A.; Hughes, Meredith M.; Campbell, Susan G.; Silbert, Noah H.; Tare, Medha; Jackson, Scott R.; Smith, Benjamin K.; Bunting, Michael F.; Doughty, Catherine J.

    2013-01-01

    Few adult second language (L2) learners successfully attain high-level proficiency. Although decades of research on beginning to intermediate stages of L2 learning have identified a number of predictors of the rate of acquisition, little research has examined factors relevant to predicting very high levels of L2 proficiency. The current study,…

  1. Inspection and evaluation of Nuclear Fuel Services high-level waste storage system, program plan

    NASA Astrophysics Data System (ADS)

    1980-01-01

    Information concerning the condition of the high-level waste tanks at the Western New York State Nuclear Service center near West Valley, New York is presented. This information is to be used in evaluating the safety of continued storage and in the development of alternatives for final disposition of the high-level waste.

  2. Characteristics Data Base: Programmer's guide to the High-Level Waste Data Base

    SciTech Connect

    Jones, K.E. ); Salmon, R. )

    1990-08-01

    The High-Level Waste Data Base is a menu-driven PC data base developed as part of OCRWM's technical data base on the characteristics of potential repository wastes, which also includes spent fuel and other materials. This programmer's guide completes the documentation for the High-Level Waste Data Base, the user's guide having been published previously. 3 figs.

  3. Investigation of High School Students' Reading Compherension Levels According to Various Variables

    ERIC Educational Resources Information Center

    Ceran, Dilek

    2015-01-01

    The purpose of this study is to investigate the level of reading comprehension of high school students in their fields of study and learning strategies to explain the relationship between the level of reading comprehension. This working group is composed of 11th grade high school students. In this study, relational model was used. In the study…

  4. Fe I Oscillator Strengths for Transitions from High-lying Even-parity Levels

    NASA Astrophysics Data System (ADS)

    Den Hartog, E. A.; Ruffoni, M. P.; Lawler, J. E.; Pickering, J. C.; Lind, K.; Brewer, N. R.

    2014-12-01

    New radiative lifetimes, measured to ±5% accuracy, are reported for 31 even-parity levels of Fe I ranging from 45061 cm-1 to 56842 cm-1. These lifetimes have been measured using single-step and two-step time-resolved laser-induced fluorescence on a slow atomic beam of iron atoms. Branching fractions have been attempted for all of these levels, and completed for 20 levels. This set of levels represents an extension of the collaborative work reported in Ruffoni et al. The radiative lifetimes combined with the branching fractions yields new oscillator strengths for 203 lines of Fe I. Utilizing a 1D-LTE model of the solar photosphere, spectral syntheses for a subset of these lines which are unblended in the solar spectrum yields a mean iron abundance of langlog[ɛ(Fe)]rang = 7.45 ± 0.06.

  5. Fe I OSCILLATOR STRENGTHS FOR TRANSITIONS FROM HIGH-LYING EVEN-PARITY LEVELS

    SciTech Connect

    Den Hartog, E. A.; Lawler, J. E.; Brewer, N. R.; Ruffoni, M. P.; Pickering, J. C.; Lind, K.

    2015-01-01

    New radiative lifetimes, measured to ±5% accuracy, are reported for 31 even-parity levels of Fe I ranging from 45061 cm{sup –1} to 56842 cm{sup –1}. These lifetimes have been measured using single-step and two-step time-resolved laser-induced fluorescence on a slow atomic beam of iron atoms. Branching fractions have been attempted for all of these levels, and completed for 20 levels. This set of levels represents an extension of the collaborative work reported in Ruffoni et al. The radiative lifetimes combined with the branching fractions yields new oscillator strengths for 203 lines of Fe I. Utilizing a 1D-LTE model of the solar photosphere, spectral syntheses for a subset of these lines which are unblended in the solar spectrum yields a mean iron abundance of (log[ε(Fe)]) = 7.45 ± 0.06.

  6. Low-level and high-level modulations of fixational saccades and high frequency oscillatory brain activity in a visual object classification task

    PubMed Central

    Kosilo, Maciej; Wuerger, Sophie M.; Craddock, Matt; Jennings, Ben J.; Hunt, Amelia R.; Martinovic, Jasna

    2013-01-01

    Until recently induced gamma-band activity (GBA) was considered a neural marker of cortical object representation. However, induced GBA in the electroencephalogram (EEG) is susceptible to artifacts caused by miniature fixational saccades. Recent studies have demonstrated that fixational saccades also reflect high-level representational processes. Do high-level as opposed to low-level factors influence fixational saccades? What is the effect of these factors on artifact-free GBA? To investigate this, we conducted separate eye tracking and EEG experiments using identical designs. Participants classified line drawings as objects or non-objects. To introduce low-level differences, contours were defined along different directions in cardinal color space: S-cone-isolating, intermediate isoluminant, or a full-color stimulus, the latter containing an additional achromatic component. Prior to the classification task, object discrimination thresholds were measured and stimuli were scaled to matching suprathreshold levels for each participant. In both experiments, behavioral performance was best for full-color stimuli and worst for S-cone isolating stimuli. Saccade rates 200–700 ms after stimulus onset were modulated independently by low and high-level factors, being higher for full-color stimuli than for S-cone isolating stimuli and higher for objects. Low-amplitude evoked GBA and total GBA were observed in very few conditions, showing that paradigms with isoluminant stimuli may not be ideal for eliciting such responses. We conclude that cortical loops involved in the processing of objects are preferentially excited by stimuli that contain achromatic information. Their activation can lead to relatively early exploratory eye movements even for foveally-presented stimuli. PMID:24391611

  7. Low-level and high-level modulations of fixational saccades and high frequency oscillatory brain activity in a visual object classification task.

    PubMed

    Kosilo, Maciej; Wuerger, Sophie M; Craddock, Matt; Jennings, Ben J; Hunt, Amelia R; Martinovic, Jasna

    2013-01-01

    Until recently induced gamma-band activity (GBA) was considered a neural marker of cortical object representation. However, induced GBA in the electroencephalogram (EEG) is susceptible to artifacts caused by miniature fixational saccades. Recent studies have demonstrated that fixational saccades also reflect high-level representational processes. Do high-level as opposed to low-level factors influence fixational saccades? What is the effect of these factors on artifact-free GBA? To investigate this, we conducted separate eye tracking and EEG experiments using identical designs. Participants classified line drawings as objects or non-objects. To introduce low-level differences, contours were defined along different directions in cardinal color space: S-cone-isolating, intermediate isoluminant, or a full-color stimulus, the latter containing an additional achromatic component. Prior to the classification task, object discrimination thresholds were measured and stimuli were scaled to matching suprathreshold levels for each participant. In both experiments, behavioral performance was best for full-color stimuli and worst for S-cone isolating stimuli. Saccade rates 200-700 ms after stimulus onset were modulated independently by low and high-level factors, being higher for full-color stimuli than for S-cone isolating stimuli and higher for objects. Low-amplitude evoked GBA and total GBA were observed in very few conditions, showing that paradigms with isoluminant stimuli may not be ideal for eliciting such responses. We conclude that cortical loops involved in the processing of objects are preferentially excited by stimuli that contain achromatic information. Their activation can lead to relatively early exploratory eye movements even for foveally-presented stimuli. PMID:24391611

  8. Systemic High School Reform in Two States: The Serendipity of State-Level Action

    ERIC Educational Resources Information Center

    Hamann, Edmund T.

    2005-01-01

    Maine and Vermont have been national leaders in state-level coordination of high school reform. Both recently developed almost interchangeable, new, voluntary, statewide frameworks that describe multiple ways high schools should change. Both frameworks--Promising Futures (Maine Commission on Secondary Education 1998) and High Schools on the Move…

  9. Investigation of High School Students' Attitude and Anxiety Levels towards Mathematics in Terms of Some Variables

    ERIC Educational Resources Information Center

    Dursun, Semsettin

    2015-01-01

    The purpose of this study was to investigate Turkish high school students' attitude and anxiety levels towards mathematics. For this purpose, the methodology employed in this study was a descriptive study. The participants of the study consisted of 361 high school students from three different high school types from a province in Turkey during…

  10. L1Track: A fast Level 1 track trigger for the ATLAS high luminosity upgrade

    NASA Astrophysics Data System (ADS)

    Cerri, Alessandro

    2016-07-01

    With the planned high-luminosity upgrade of the LHC (HL-LHC), the ATLAS detector will see its collision rate increase by approximately a factor of 5 with respect to the current LHC operation. The earliest hardware-based ATLAS trigger stage ("Level 1") will have to provide a higher rejection factor in a more difficult environment: a new improved Level 1 trigger architecture is under study, which includes the possibility of extracting with low latency and high accuracy tracking information in time for the decision taking process. In this context, the feasibility of potential approaches aimed at providing low-latency high-quality tracking at Level 1 is discussed.

  11. Demonstration of Caustic-Side Solvent Extraction with Savannah River Site High Level Waste

    SciTech Connect

    Walker, D.D.

    2001-08-27

    Researchers successfully demonstrated the chemistry and process equipment of the Caustic-Side Solvent Extraction (CSSX) flowsheet for the decontamination of high level waste using a 33-stage, 2-cm centrifugal contactor apparatus at the Savannah River Technology Center. This represents the first CSSX process demonstration using Savannah River Site (SRS) high level waste. Three tests lasting 6, 12, and 48 hours processed simulated average SRS waste, simulated Tank 37H/44F composite waste, and Tank 37H/44F high level waste, respectively.

  12. Preliminary estimates of cost savings for defense high level waste vitrification options

    SciTech Connect

    Merrill, R.A.; Chapman, C.C.

    1993-09-01

    The potential for realizing cost savings in the disposal of defense high-level waste through process and design modificatins has been considered. Proposed modifications range from simple changes in the canister design to development of an advanced melter capable of processing glass with a higher waste loading. Preliminary calculations estimate the total disposal cost (not including capital or operating costs) for defense high-level waste to be about $7.9 billion dollars for the reference conditions described in this paper, while projected savings resulting from the proposed process and design changes could reduce the disposal cost of defense high-level waste by up to $5.2 billion.

  13. Ontological Problem-Solving Framework for Assigning Sensor Systems and Algorithms to High-Level Missions

    PubMed Central

    Qualls, Joseph; Russomanno, David J.

    2011-01-01

    The lack of knowledge models to represent sensor systems, algorithms, and missions makes opportunistically discovering a synthesis of systems and algorithms that can satisfy high-level mission specifications impractical. A novel ontological problem-solving framework has been designed that leverages knowledge models describing sensors, algorithms, and high-level missions to facilitate automated inference of assigning systems to subtasks that may satisfy a given mission specification. To demonstrate the efficacy of the ontological problem-solving architecture, a family of persistence surveillance sensor systems and algorithms has been instantiated in a prototype environment to demonstrate the assignment of systems to subtasks of high-level missions. PMID:22164081

  14. Evaluation of high-level clouds in cloud resolving model simulations with ARM and KWAJEX observations

    SciTech Connect

    Liu, Zheng; Muhlbauer, Andreas; Ackerman, Thomas

    2015-11-05

    In this paper, we evaluate high-level clouds in a cloud resolving model during two convective cases, ARM9707 and KWAJEX. The simulated joint histograms of cloud occurrence and radar reflectivity compare well with cloud radar and satellite observations when using a two-moment microphysics scheme. However, simulations performed with a single moment microphysical scheme exhibit low biases of approximately 20 dB. During convective events, two-moment microphysical overestimate the amount of high-level cloud and one-moment microphysics precipitate too readily and underestimate the amount and height of high-level cloud. For ARM9707, persistent large positive biases in high-level cloud are found, which are not sensitive to changes in ice particle fall velocity and ice nuclei number concentration in the two-moment microphysics. These biases are caused by biases in large-scale forcing and maintained by the periodic lateral boundary conditions. The combined effects include significant biases in high-level cloud amount, radiation, and high sensitivity of cloud amount to nudging time scale in both convective cases. The high sensitivity of high-level cloud amount to the thermodynamic nudging time scale suggests that thermodynamic nudging can be a powerful ‘‘tuning’’ parameter for the simulated cloud and radiation but should be applied with caution. The role of the periodic lateral boundary conditions in reinforcing the biases in cloud and radiation suggests that reducing the uncertainty in the large-scale forcing in high levels is important for similar convective cases and has far reaching implications for simulating high-level clouds in super-parameterized global climate models such as the multiscale modeling framework.

  15. Evaluation of high-level clouds in cloud resolving model simulations with ARM and KWAJEX observations

    DOE PAGESBeta

    Liu, Zheng; Muhlbauer, Andreas; Ackerman, Thomas

    2015-11-05

    In this paper, we evaluate high-level clouds in a cloud resolving model during two convective cases, ARM9707 and KWAJEX. The simulated joint histograms of cloud occurrence and radar reflectivity compare well with cloud radar and satellite observations when using a two-moment microphysics scheme. However, simulations performed with a single moment microphysical scheme exhibit low biases of approximately 20 dB. During convective events, two-moment microphysical overestimate the amount of high-level cloud and one-moment microphysics precipitate too readily and underestimate the amount and height of high-level cloud. For ARM9707, persistent large positive biases in high-level cloud are found, which are not sensitivemore » to changes in ice particle fall velocity and ice nuclei number concentration in the two-moment microphysics. These biases are caused by biases in large-scale forcing and maintained by the periodic lateral boundary conditions. The combined effects include significant biases in high-level cloud amount, radiation, and high sensitivity of cloud amount to nudging time scale in both convective cases. The high sensitivity of high-level cloud amount to the thermodynamic nudging time scale suggests that thermodynamic nudging can be a powerful ‘‘tuning’’ parameter for the simulated cloud and radiation but should be applied with caution. The role of the periodic lateral boundary conditions in reinforcing the biases in cloud and radiation suggests that reducing the uncertainty in the large-scale forcing in high levels is important for similar convective cases and has far reaching implications for simulating high-level clouds in super-parameterized global climate models such as the multiscale modeling framework.« less

  16. Evaluation of high-level clouds in cloud resolving model simulations with ARM and KWAJEX observations

    NASA Astrophysics Data System (ADS)

    Liu, Zheng; Muhlbauer, Andreas; Ackerman, Thomas

    2015-12-01

    In this study, we evaluate high-level clouds in a cloud resolving model during two convective cases, ARM9707 and KWAJEX. The simulated joint histograms of cloud occurrence and radar reflectivity compare well with cloud radar and satellite observations when using a two-moment microphysics scheme. However, simulations performed with a single moment microphysical scheme exhibit low biases of approximately 20 dB. During convective events, two-moment microphysical overestimate the amount of high-level cloud and one-moment microphysics precipitate too readily and underestimate the amount and height of high-level cloud. For ARM9707, persistent large positive biases in high-level cloud are found, which are not sensitive to changes in ice particle fall velocity and ice nuclei number concentration in the two-moment microphysics. These biases are caused by biases in large-scale forcing and maintained by the periodic lateral boundary conditions. The combined effects include significant biases in high-level cloud amount, radiation, and high sensitivity of cloud amount to nudging time scale in both convective cases. The high sensitivity of high-level cloud amount to the thermodynamic nudging time scale suggests that thermodynamic nudging can be a powerful "tuning" parameter for the simulated cloud and radiation but should be applied with caution. The role of the periodic lateral boundary conditions in reinforcing the biases in cloud and radiation suggests that reducing the uncertainty in the large-scale forcing in high levels is important for similar convective cases and has far reaching implications for simulating high-level clouds in super-parameterized global climate models such as the multiscale modeling framework.

  17. A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults

    PubMed Central

    Omosa-Manyonyi, Gloria; Mpendo, Juliet; Ruzagira, Eugene; Kilembe, William; Chomba, Elwyn; Roman, François; Bourguignon, Patricia; Koutsoukos, Marguerite; Collard, Alix; Voss, Gerald; Laufer, Dagna; Stevens, Gwynn; Hayes, Peter; Clark, Lorna; Cormier, Emmanuel; Dally, Len; Barin, Burc; Ackland, Jim; Syvertsen, Kristen; Zachariah, Devika; Anas, Kamaal; Sayeed, Eddy; Lombardo, Angela; Gilmour, Jill; Cox, Josephine; Fast, Patricia; Priddy, Frances

    2015-01-01

    Background Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses. Methods In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured. Results The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration. Conclusion Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses. Trial Registration ClinicalTrials.gov NCT01264445 PMID:25961283

  18. Estimation of Failure Frequency for Type I and II High Level Waste Tanks

    SciTech Connect

    Subramanian, K.H.

    2001-05-15

    The failure frequency of Type I and Type II High Level Waste tanks was calculated. The degradation mechanism that could lead to large break failure and the credits taken for steps taken to prevent large break failure were considered.

  19. A Multi-Level Self-Paced High School Chemistry Project

    ERIC Educational Resources Information Center

    Burr, Cec

    1976-01-01

    Described is a three-level self paced high school chemistry course developed for Queensland, Australia schools. The design involves a modification of the Keller Method. A sample unit test is included. (SL)

  20. Assessment of high-level waste form conformance with proposed regulatory and repository criteria

    SciTech Connect

    Gordon, D E; Gray, P L; Jennings, A S; Permar, P H

    1982-04-01

    Federal regulatory criteria for geologic disposal of high-level waste are under development. Also, interim performance specifications for high-level waste forms in geologic isolation are being developed within the Federal program responsible for repository selection and operation. Two high-level waste forms, borosilicate glass and crystalline ceramic, have been selected as candidate immobilization forms for the Defense Waste Processing Facility (DWPF) which is to immobilize high-level wastes at the Savannah River Plant (SRP). An assessment of how these two waste forms conform with the proposed regulatory criteria and repository specifications was performed. Both forms were determined to be in conformance with postulated rules for radionuclide releases and radiation exposures throughout the entire waste disposal system, as well as with proposed repository operation requirements.

  1. Demonstration of Small Tank Tetraphenylborate Precipitation Process Using Savannah River Site High Level Waste

    SciTech Connect

    Peters, T.B.

    2001-09-10

    This report details the experimental effort to demonstrate the continuous precipitation of cesium from Savannah River Site High Level Waste using sodium tetraphenylborate. In addition, the experiments examined the removal of strontium and various actinides through addition of monosodium titanate.

  2. OCCURRENCE OF HIGH-LEVEL AMINOGLYCOSIDE RESISTANCE IN ENVIRONMENTAL ISOLATES OF ENTEROCOCCI

    EPA Science Inventory

    High-level resistance fo aminoglycosides was observed in environmental isolates of enterococci. Various aquatic habitats, including agricultural runoff, creeks, rivers, wastewater, and wells, were analyzed. Strains of Enterococcus faecalis, e.faecium, E. gallinarum, and other Ent...

  3. Anomalously high noise levels in a fibre Bragg grating semiconductor laser

    SciTech Connect

    Kurnosov, V D; Kurnosov, K V

    2015-01-31

    Taking into account gain nonlinearity allows one to obtain anomalously high noise levels in a fibre Bragg grating laser diode. This paper examines the effect of the gain nonlinearity due to spectral hole burning on noise characteristics. (lasers)

  4. Energy levels and the de Broglie relationship for high school students

    NASA Astrophysics Data System (ADS)

    Gianino, Concetto

    2008-07-01

    In this article, four examples of possible lessons on energy levels for high school are described: a particle in a box, a finite square well, the hydrogen atom and a harmonic oscillator. The energy levels are deduced through the use of the steady-state condition and the de Broglie relationship. In particular, the harmonic oscillator energy levels are deduced using correspondence with circular uniform motion.

  5. Water-level records for the northern High Plains of Colorado, 1979-83

    USGS Publications Warehouse

    Blattner, Joe L.; Rasmuson, Bruce D.

    1983-01-01

    Water-level measurements were made in 638 wells in the winter of 1982-83, in the northern High Plains of Colorado. The water-level measurements for the winter of 1982-83 and for four preceding winters are given in a table, which also contains the location, depth, land-surface elevation and the aquifer for each well. (USGS)

  6. Energy Levels and the de Broglie Relationship for High School Students

    ERIC Educational Resources Information Center

    Gianino, Concetto

    2008-01-01

    In this article, four examples of possible lessons on energy levels for high school are described: a particle in a box, a finite square well, the hydrogen atom and a harmonic oscillator. The energy levels are deduced through the use of the steady-state condition and the de Broglie relationship. In particular, the harmonic oscillator energy levels…

  7. Teachers' Ratings of Social Competence of Children with High Versus Low Levels of Depressive Symptoms.

    ERIC Educational Resources Information Center

    Shah, Farhana; Morgan, Sam B.

    1996-01-01

    Examined the relationship between children's self-ratings of depressive symptoms and teachers' ratings of the children's situational social competence. Results show that teachers rated those children who reported high levels of depressive symptoms as having more problems in social competence when compared to children who reported low levels of…

  8. High D-dimer levels increase the likelihood of pulmonary embolism.

    PubMed

    Tick, L W; Nijkeuter, M; Kramer, M H H; Hovens, M M C; Büller, H R; Leebeek, F W G; Huisman, M V

    2008-08-01

    Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied. PMID:18452520

  9. High Level Manpower and Technological Change in the Steel Industry: Implications for Corporate Manpower Planning.

    ERIC Educational Resources Information Center

    Hiestand, Dale L.

    The purpose of this study was to examine the role that high level manpower plays in the establishment of new technologies at the plant and industry level. The steel industry was selected as an appropriate industry to approach these questions due to: its considerable technological changes; its straightforward, easier-to-understand technology; its…

  10. High-Stakes Testing and Its Relationship to Stress Levels of Secondary Teachers

    ERIC Educational Resources Information Center

    Christian, Sonya Colman

    2010-01-01

    This study investigated the relationship between high-stakes testing and the stress levels of secondary teachers in Jackson's Jackson Public School District. The independent variables of age, gender, subject taught, teaching experience, degree and school level were used to determine the differences of the various groups. A survey was piloted and…

  11. Measuring the Outliers: An Introduction to Out-of-Level Testing with High-Achieving Students

    ERIC Educational Resources Information Center

    Rambo-Hernandez, Karen E.; Warne, Russell T.

    2015-01-01

    Out-of-level testing is an underused strategy for addressing the needs of students who score in the extremes, and when used wisely, it could provide educators with a much more accurate picture of what students know. Out-of-level testing has been shown to be an effective assessment strategy with high-achieving students; however, out-of-level…

  12. Alkaline Earth Core Level Photoemission Spectroscopy of High-Temperature Superconductors

    NASA Technical Reports Server (NTRS)

    Vasquez, R.

    1993-01-01

    This paper examines photoemission measurements of the alkaline Earth core levels of high-temperature superconductors and related materials, models that seek to explain the large negative shifts observed relative to the corresponding alkaline Earth metals, and the effect of lattice site disorder on the core level spectra and the presence or absence of intrinsic surface peaks.

  13. THE OCCURRENCE OF HIGH LEVELS OF LIPIDS IN FUNDULUS HETERCLITUS FROM A HIGHLY PCB CONTAIMINATED SITE

    EPA Science Inventory

    A population model constructed by Munns et al. (1997) for Fundulus heteroclitus predicts that populations in severely impacted ecosystems such as New Bedford Harbor, a highly PCB contaminated Superfund site, should be under severe stress. However, cursory assessment of the fish p...

  14. Immobilized high-level waste interim storage alternatives generation and analysis and decision report

    SciTech Connect

    CALMUS, R.B.

    1999-05-18

    This report presents a study of alternative system architectures to provide onsite interim storage for the immobilized high-level waste produced by the Tank Waste Remediation System (TWRS) privatization vendor. It examines the contract and program changes that have occurred and evaluates their impacts on the baseline immobilized high-level waste (IHLW) interim storage strategy. In addition, this report documents the recommended initial interim storage architecture and implementation path forward.

  15. Sustained high levels of neuroprotective, high molecular weight, phosphorylated tau in the longest-lived rodent

    PubMed Central

    Orr, Miranda E.; Garbarino, Valentina R.; Salinas, Angelica; Buffenstein, Rochelle

    2016-01-01

    Tau protein is primarily expressed in neuronal axons and modulates microtubule stability. Tau phosphorylation, aggregation and subcellular mislocalization coincide with neurodegeneration in numerous diseases, including Alzheimer's disease [AD]. During AD pathogenesis, tau misprocessing accompanies Aß accumulation; however, AD animal models, despite elevated Aß, fail to develop tauopathy. To assess whether lack of tau pathology is linked to short lifespan common to most AD models, we examined tau processing in extraordinarily long-lived, mouse-sized naked mole-rats (NMR; ~32 years), which express appreciable levels of Aß throughout life. NMRs, like other mammals, displayed highest tau phosphorylation during brain development. While tau phosphorylation decreased with aging, unexpectedly adult NMRs had higher levels than transgenic mice overexpressing mutant human tau. However, in sharp contrast with the somatodendritic accumulation of misprocessed tau in the transgenic mice, NMRs maintain axonal tau localization. Intriguingly, the adult NMR tau protein is 88kDa, much larger than 45-68kDa tau expressed in other mammals. We propose that this 88kDa tau protein may offer exceptional microtubule stability and neuroprotection against lifelong elevated Aß. PMID:25576082

  16. Changes in Water Levels and Storage in the High Plains Aquifer, Predevelopment to 2007

    USGS Publications Warehouse

    McGuire, V.L.

    2009-01-01

    The High Plains aquifer underlies 111.6 million acres (174,000 square miles) in parts of eight States - Colorado, Kansas, Nebraska, New Mexico, Oklahoma, South Dakota, Texas, and Wyoming. The area overlying the High Plains aquifer is one of the primary agricultural regions in the Nation. Water-level declines began in parts of the High Plains aquifer soon after the beginning of substantial irrigation with ground water in the aquifer area. By 1980, water levels in the High Plains aquifer in parts of Texas, Oklahoma, and southwestern Kansas had declined more than 100 feet (Luckey and others, 1981). In response to these water-level declines, the U.S. Geological Survey (USGS), in collaboration with numerous Federal, State, and local water-resources agencies, began monitoring more than 7,000 wells in 1988 to assess annual water-level changes in the aquifer. This fact sheet summarizes changes in water levels and drainable water in storage in the High Plains aquifer from predevelopment (before about 1950) to 2007 and serves as a companion product to a USGS report that presents more detailed and technical information about water-level and storage changes in the High Plains aquifer during this period (McGuire, 2009).

  17. Host Genetic Determinants of T Cell Responses to the MRKAd5 HIV-1 gag/pol/nef Vaccine in the Step Trial

    PubMed Central

    Fellay, Jacques; Frahm, Nicole; Shianna, Kevin V.; Cirulli, Elizabeth T.; Casimiro, Danilo R.; Robertson, Michael N.; Haynes, Barton F.; Geraghty, Daniel E.; McElrath, M. Juliana

    2011-01-01

    Understanding how human genetic variation impacts individual response to immunogens is fundamental for rational vaccine development. To explore host mechanisms involved in cellular immune responses to the MRKAd5 human immunodeficiency virus type 1 (HIV-1) gag/pol/nef vaccine tested in the Step trial, we performed a genome-wide association study of determinants of HIV-specific T cell responses, measured by interferon γ enzyme-linked immunospot assays. No human genetic variant reached genome-wide significance, but polymorphisms located in the major histocompatibility complex (MHC) region showed the strongest association with response to the HIV-1 Gag protein: HLA-B alleles known to be associated with differences in HIV-1 control were responsible for these associations. The implication of the same HLA alleles in vaccine-induced cellular immunity and in natural immune control is of relevance for vaccine design. Furthermore, our results demonstrate the importance of considering the host immunogenetic background in the analysis of immune responses to T cell vaccines. PMID:21278214

  18. Delta-Doping at Wafer Level for High Throughput, High Yield Fabrication of Silicon Imaging Arrays

    NASA Technical Reports Server (NTRS)

    Hoenk, Michael E. (Inventor); Nikzad, Shoulch (Inventor); Jones, Todd J. (Inventor); Greer, Frank (Inventor); Carver, Alexander G. (Inventor)

    2014-01-01

    Systems and methods for producing high quantum efficiency silicon devices. A silicon MBE has a preparation chamber that provides for cleaning silicon surfaces using an oxygen plasma to remove impurities and a gaseous (dry) NH3 + NF3 room temperature oxide removal process that leaves the silicon surface hydrogen terminated. Silicon wafers up to 8 inches in diameter have devices that can be fabricated using the cleaning procedures and MBE processing, including delta doping.

  19. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

    PubMed

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

    2013-07-15

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. PMID:23673156

  20. Effects of high CO2 levels on dynamic photosynthesis: carbon gain, mechanisms, and environmental interactions.

    PubMed

    Tomimatsu, Hajime; Tang, Yanhong

    2016-05-01

    Understanding the photosynthetic responses of terrestrial plants to environments with high levels of CO2 is essential to address the ecological effects of elevated atmospheric CO2. Most photosynthetic models used for global carbon issues are based on steady-state photosynthesis, whereby photosynthesis is measured under constant environmental conditions; however, terrestrial plant photosynthesis under natural conditions is highly dynamic, and photosynthetic rates change in response to rapid changes in environmental factors. To predict future contributions of photosynthesis to the global carbon cycle, it is necessary to understand the dynamic nature of photosynthesis in relation to high CO2 levels. In this review, we summarize the current body of knowledge on the photosynthetic response to changes in light intensity under experimentally elevated CO2 conditions. We found that short-term exposure to high CO2 enhances photosynthetic rate, reduces photosynthetic induction time, and reduces post-illumination CO2 burst, resulting in increased leaf carbon gain during dynamic photosynthesis. However, long-term exposure to high CO2 during plant growth has varying effects on dynamic photosynthesis. High levels of CO2 increase the carbon gain in photosynthetic induction in some species, but have no significant effects in other species. Some studies have shown that high CO2 levels reduce the biochemical limitation on RuBP regeneration and Rubisco activation during photosynthetic induction, whereas the effects of high levels of CO2 on stomatal conductance differ among species. Few studies have examined the influence of environmental factors on effects of high levels of CO2 on dynamic photosynthesis. We identified several knowledge gaps that should be addressed to aid future predictions of photosynthesis in high-CO2 environments. PMID:27094437