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  1. High levels of anti-Nef antibodies may prevent AIDS disease progression in vertically HIV-1-infected infants

    PubMed Central

    Corró, Guillermo; Crudeli, Cintia Milena; Rocco, Carlos Alberto; Marino, Silvia Alejandra; Sen, Luisa

    2014-01-01

    Introduction HIV-1-associated CD4+ T-cell depletion is a consequence of uninfected cell death. Nef is one of the viral factors that trigger apoptosis on bystander cells, though the plasma Nef levels do not correlate with Th lymphocytes counts. The aim of our study was to evaluate whether anti-Nef antibodies were involved in paediatric AIDS development and whether they can prevent the CD4+ T-cell depletion in vertically infected children. Methods Two hundred and seventy three HIV-1 vertically infected children seen at Garrahan Paediatric Hospital were randomly included in the study, adding 13 selected cases: seven LTNP (long-term non-progressors) and six RP (rapid progressors) children (n total=286). Specific anti-HIV-1-Nef antibodies were titrated by indirect ELISA and compared between groups. The plasma blocking effect on Nef-dependent cytotoxicity was evaluated in Jurkat cells using recombinant Nef as apoptotic stimulus and patient plasmas as blockers, measuring the apoptotic levels using Annexin-V stain and flow cytometry. Results Only 63.4% of the patients had specific anti-Nef antibodies, and the levels of anti-Nef antibodies found in the selected LTNPs plasmas were always significantly higher (p=1.55×10−4) than those in RPs or general HIV-1+ paediatric populations. The LTNPs’ plasma had a strong inhibitory effect on Nef-dependent cytotoxicity even at high dilutions, while RP plasmas had little or no effect on Nef-induced apoptosis. Discussion and conclusions High anti-Nef antibody levels are associated and predict slow or non-progression to AIDS in vertically HIV-1-infected children. They could be an efficient tool in preventing Nef-associated bystander effect, preserving CD4+ T-cells and the immune function in the context of paediatric HIV-1 infection. PMID:24560340

  2. High-level HIV-1 Nef transient expression in Nicotiana benthamiana using the P19 gene silencing suppressor protein of Artichoke Mottled Crinckle Virus

    PubMed Central

    2009-01-01

    Background In recent years, different HIV antigens have been successfully expressed in plants by either stable transformation or transient expression systems. Among HIV proteins, Nef is considered a promising target for the formulation of a multi-component vaccine due to its implication in the first steps of viral infection. Attempts to express Nef as a single protein product (not fused to a stabilizing protein) in transgenic plants resulted in disappointingly low yields (about 0.5% of total soluble protein). In this work we describe a transient expression system based on co-agroinfiltration of plant virus gene silencing suppressor proteins in Nicotiana benthamiana, followed by a two-step affinity purification protocol of plant-derived Nef. Results The effect of three gene silencing viral suppressor proteins (P25 of Potato Virus X, P19 of either Artichoke Mottled Crinckle virus and Tomato Bushy Stunt virus) on Nef transient expression yield was evaluated. The P19 protein of Artichoke Mottled Crinckle virus (AMCV-P19) gave the highest expression yield in vacuum co-agroinfiltration experiments reaching 1.3% of total soluble protein, a level almost three times higher than that previously reported in stable transgenic plants. The high yield observed in the co-agroinfiltrated plants was correlated to a remarkable decrease of Nef-specific small interfering RNAs (siRNAs) indicating an effective modulation of RNA silencing mechanisms by AMCV-P19. Interestingly, we also showed that expression levels in top leaves of vacuum co-agroinfiltrated plants were noticeably reduced compared to bottom leaves. Moreover, purification of Nef from agroinfiltrated tissue was achieved by a two-step immobilized metal ion affinity chromatography protocol with yields of 250 ng/g of fresh tissue. Conclusion We demonstrated that expression level of HIV-1 Nef in plant can be improved using a transient expression system enhanced by the AMCV-P19 gene silencing suppressor protein. Moreover, plant

  3. Plant-based strategies aimed at expressing HIV antigens and neutralizing antibodies at high levels. Nef as a case study.

    PubMed

    Marusic, Carla; Vitale, Alessandro; Pedrazzini, Emanuela; Donini, Marcello; Frigerio, Lorenzo; Bock, Ralph; Dix, Philip J; McCabe, Matthew S; Bellucci, Michele; Benvenuto, Eugenio

    2009-08-01

    The first evidence that plants represent a valid, safe and cost-effective alternative to traditional expression systems for large-scale production of antigens and antibodies was described more than 10 years ago. Since then, considerable improvements have been made to increase the yield of plant-produced proteins. These include the use of signal sequences to target proteins to different cellular compartments, plastid transformation to achieve high transgene dosage, codon usage optimization to boost gene expression, and protein fusions to improve recombinant protein stability and accumulation. Thus, several HIV/SIV antigens and neutralizing anti-HIV antibodies have recently been successfully expressed in plants by stable nuclear or plastid transformation, and by transient expression systems based on plant virus vectors or Agrobacterium-mediated infection. The current article gives an overview of plant expressed HIV antigens and antibodies and provides an account of the use of different strategies aimed at increasing the expression of the accessory multifunctional HIV-1 Nef protein in transgenic plants.

  4. A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression

    PubMed Central

    Johnson, Aaron L.; Dirk, Brennan S.; Coutu, Mathieu; Haeryfar, S. M. Mansour; Arts, Eric J.; Finzi, Andrés

    2016-01-01

    ABSTRACT Extensive genetic diversity is a defining characteristic of human immunodeficiency virus type 1 (HIV-1) and poses a significant barrier to the development of an effective vaccine. To better understand the impact of this genetic diversity on the HIV-1 pathogenic factor Nef, we compiled a panel of reference strains from the NIH Los Alamos HIV Database. Initial sequence analysis identified point mutations at Nef residues 13, 84, and 92 in subtype C reference strain C.BR92025 from Brazil. Functional analysis revealed impaired major histocompatibility complex class I and CD4 downregulation of strain C.BR92025 Nef, which corresponded to decreased protein expression. Metabolic labeling demonstrated that strain C.BR92025 Nef has a greater rate of protein turnover than subtype B reference strain B.JRFL that, on the basis of mutational analysis, is related to Nef residue A84. An alanine-to-valine substitution at position 84, located in alpha helix 2 of Nef, was sufficient to alter the rate of turnover of an otherwise highly expressed Nef protein. In conclusion, these findings highlight HIV-1 Nef residue A84 as a major determinant of protein expression that may offer an additional avenue to disrupt or mediate the effects of this key HIV-1 pathogenic factor. IMPORTANCE The HIV-1 Nef protein has been established as a key pathogenic determinant of HIV/AIDS, but there is little knowledge of how the extensive genetic diversity of HIV-1 affects Nef function. Upon compiling a set of subtype-specific reference strains, we identified a subtype C reference strain, C.BR92025, that contained natural polymorphisms at otherwise highly conserved residues 13, 84, and 92. Interestingly, strain C.BR92025 Nef displayed impaired Nef function and had decreased protein expression. We have demonstrated that strain C.BR92025 Nef has a higher rate of protein turnover than highly expressed Nef proteins and that this higher rate of protein turnover is due to an alanine-to-valine substitution

  5. The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages

    PubMed Central

    1994-01-01

    Considerable controversy and uncertainty have surrounded the biological function of the Human Immunodeficiency Virus (HIV)-1 nef gene product. Initial studies suggested that this early, nonstructural viral protein functioned as a negative regulatory factor; thus, it was proposed to play a role in establishing or maintaining viral latency. In contrast, studies in Simian Immunodeficiency Virus (SIV)mac-infected rhesus monkeys have suggested that Nef is not a negative factor but rather plays a central role in promoting high-level viral replication and is required for viral pathogenesis in vivo. We sought to define a tissue culture system that would approximate the in vivo setting for virus infection in order to assess the role of HIV-1 Nef in viral replication. We show that infection of mitogen-activated peripheral blood mononuclear cells (PBMC) with Nef+ HIV results in enhanced replication as evidenced by earlier gag p24 expression when compared with infections performed with nef mutant viruses. Moreover, when unstimulated freshly isolated PBMC are infected with Nef+ and Nef- viruses and then subsequently activated with mitogen, the Nef-induced difference in viral replication kinetics is even more pronounced, with the Nef- viruses requiring much more time in culture for appreciable growth. A positive effect of Nef on viral replication was also observed in primary macrophages infected with a recombinant of YU-2, a patient- derived molecular clone with macrophage tropism. These positive effects of Nef on viral replication are dependent on the initial multiplicity of infection (MOI), in that infections of unstimulated PBMC at low MOI are most dependent upon intact nef for subsequent viral growth. We now provide evidence that the Nef+ HIV is more infectious than Nef- HIV from both a tissue culture infectious dose analysis, and a single-cell HIV infection assay. In the latter case, we demonstrate that infection with equivalent doses of HIV based on virion-associated gag p

  6. Efficient Nef-mediated downmodulation of TCR-CD3 and CD28 is associated with high CD4+ T cell counts in viremic HIV-2 infection.

    PubMed

    Khalid, Mohammad; Yu, Hangxing; Sauter, Daniel; Usmani, Shariq M; Schmokel, Jan; Feldman, Jerome; Gruters, Rob A; van der Ende, Marchina E; Geyer, Matthias; Rowland-Jones, Sarah; Osterhaus, Albert D; Kirchhoff, Frank

    2012-05-01

    The role of the multifunctional accessory Nef protein in the immunopathogenesis of HIV-2 infection is currently poorly understood. Here, we performed comprehensive functional analyses of 50 nef genes from 21 viremic (plasma viral load, >500 copies/ml) and 16 nonviremic (<500) HIV-2-infected individuals. On average, nef alleles from both groups were equally active in modulating CD4, TCR-CD3, CD28, MHC-I, and Ii cell surface expression and in enhancing virion infectivity. Thus, many HIV-2-infected individuals efficiently control the virus in spite of efficient Nef function. However, the potency of nef alleles in downmodulating TCR-CD3 and CD28 to suppress the activation and apoptosis of T cells correlated with high numbers of CD4(+) T cells in viremic patients. No such correlations were observed in HIV-2-infected individuals with undetectable viral load. Further functional analyses showed that the Nef-mediated downmodulation of TCR-CD3 suppressed the induction of Fas, Fas-L, PD-1, and CTLA-4 cell surface expression as well as the secretion of gamma interferon (IFN-γ) by primary CD4(+) T cells. Moreover, we identified a single naturally occurring amino acid variation (I132T) in the core domain of HIV-2 Nef that selectively disrupts its ability to downmodulate TCR-CD3 and results in functional properties highly reminiscent of HIV-1 Nef proteins. Taken together, our data suggest that the efficient Nef-mediated downmodulation of TCR-CD3 and CD28 help viremic HIV-2-infected individuals to maintain normal CD4(+) T cell homeostasis by preventing T cell activation and by suppressing the induction of death receptors that may affect the functionality and survival of both virally infected and uninfected bystander cells.

  7. 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

  8. A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities.

    PubMed

    Martínez-Bonet, Marta; Palladino, Claudia; Briz, Veronica; Rudolph, Jochen M; Fackler, Oliver T; Relloso, Miguel; Muñoz-Fernandez, Maria Angeles; Madrid, Ricardo

    2015-01-01

    To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121-137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection.

  9. A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities

    PubMed Central

    Martínez-Bonet, Marta; Palladino, Claudia; Briz, Veronica; Rudolph, Jochen M.; Fackler, Oliver T.; Relloso, Miguel; Muñoz-Fernandez, Maria Angeles; Madrid, Ricardo

    2015-01-01

    To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121–137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection. PMID:26700863

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

    PubMed Central

    Gillis, Jacqueline; Wong, Fay E.; Yu, Yi; Camp, Jeremy V.; Li, Qingsheng; Connole, Michelle; Li, Yuan; Lifson, Jeffrey D.; Li, Wenjun; Keele, Brandon F.; Kozlowski, Pamela A.; Desrosiers, Ronald C.; Haase, Ashley T.

    2016-01-01

    Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination. PMID:27959961

  11. Secretion modification region-derived peptide disrupts HIV-1 Nef's interaction with mortalin and blocks virus and Nef exosome release.

    PubMed

    Shelton, Martin N; Huang, Ming-Bo; Ali, Syed A; Powell, Michael D; Bond, Vincent C

    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.

  12. 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

  13. HIV-1 Nef Impairs Key Functional Activities in Human Macrophages through CD36 Downregulation

    PubMed Central

    Olivetta, Eleonora; Tirelli, Valentina; Chiozzini, Chiara; Scazzocchio, Beatrice; Romano, Ignazio; Arenaccio, Claudia; Sanchez, Massimo

    2014-01-01

    Monocytes and macrophages utilize the class A and B scavenger receptors to recognize and perform phagocytosis of invading microbes before a pathogen-specific immune response is generated. HIV-1 Nef protein affects the innate immune system impairing oxidative burst response and phagocytic capacity of macrophages. Our data show that exogenous recombinant myristoylated Nef protein induces a marked CD36 downregulation in monocytes from Peripheral Blood Mononuclear Cells, in Monocyte-Derived Macrophages (MDMs) differentiated by cytokines and in MDMs contained in a mixed culture obtained expanding PBMCs under Human Erythroid Massive Amplification condition. Under the latter culture condition we identify three main populations after 6 days of expansion: lymphocytes (37.8±14.7%), erythroblasts (46.7±6.1%) and MDMs (15.7±7.5%). The Nef addition to the cell culture significantly downregulates CD36 expression in MDMs, but not in erythroid cells. Furthermore, CD36 inhibition is highly specific since it does not modify the expression levels of other MDM markers such as CD14, CD11c, CD86, CD68, CD206, Toll-like Receptor 2 and Toll-like Receptor 4. Similar results were obtained in MDMs infected with VSV-G pseudotyped HIV-1-expressing Nef. The reduced CD36 membrane expression is associated with decrease of correspondent CD36 mRNA transcript. Furthermore, Nef-induced CD36 downregulation is linked to both impaired scavenger activity with reduced capability to take up oxidized lipoproteins and to significant decreased phagocytosis of fluorescent beads and GFP-expressing Salmonella tiphymurium. In addition we observed that Nef induces TNF-α release in MDMs. Although these data suggest a possible involvement of TNF-α in mediating Nef activity, our results exclude a possible relationship between Nef-induced TNF-α release and Nef-mediated CD36 downregulation. The present work shows that HIV-1 Nef protein may have a role in the strategies elaborated by HIV-1 to alter pathogen

  14. 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

  15. Development and validation of a high-content bimolecular fluorescence complementation assay for small-molecule inhibitors of HIV-1 Nef dimerization.

    PubMed

    Poe, Jerrod A; Vollmer, Laura; Vogt, Andreas; Smithgall, Thomas E

    2014-04-01

    Nef is a human immunodeficiency virus 1 (HIV-1) accessory factor essential for viral pathogenesis and AIDS progression. Many Nef functions require dimerization, and small molecules that block Nef dimerization may represent antiretroviral drug leads. Here we describe a cell-based assay for Nef dimerization inhibitors based on bimolecular fluorescence complementation (BiFC). Nef was fused to nonfluorescent, complementary fragments of yellow fluorescent protein (YFP) and coexpressed in the same cell population. Dimerization of Nef resulted in juxtaposition of the YFP fragments and reconstitution of the fluorophore. For automation, the Nef-YFP fusion proteins plus a monomeric red fluorescent protein (mRFP) reporter were expressed from a single vector, separated by picornavirus "2A" linker peptides to permit equivalent translation of all three proteins. Validation studies revealed a critical role for gating on the mRFP-positive subpopulation of transfected cells, as well as use of the mRFP signal to normalize the Nef-BiFC signal. Nef-BiFC/mRFP ratios resulting from cells expressing wild-type versus dimerization-defective Nef were very clearly separated, with Z factors consistently in the 0.6 to 0.7 range. A fully automated pilot screen of the National Cancer Institute Diversity Set III identified several hit compounds that reproducibly blocked Nef dimerization in the low micromolar range. This BiFC-based assay has the potential to identify cell-active small molecules that directly interfere with Nef dimerization and function.

  16. Suppression of HIV-1 Nef translation by Sam68 mutant-induced stress granules and nef mRNA sequestration

    PubMed Central

    Henao-Mejia, Jorge; Liu, Ying; Park, In-Woo; Zhang, Jizhong; Sanford, Jeremy; He, Johnny J.

    2009-01-01

    SUMMARY HIV-1 Nef plays important roles in HIV-1 replication and pathogenesis. It is translated from completely spliced HIV-1 RNA, its expression is inherently regulated at the levels of viral DNA transcription and RNA splicing. Here we show that Sam68 cytoplasmic mutants potently suppress Nef expression. The suppression requires Sam68 domain aa269-321 and is correlated with its ability to induce stress granules. In addition, the suppression is specific to Nef, and direct binding to nef mRNA 3′UTR confers the suppression specificity. Furthermore, nef mRNA is targeted to and enriched in these induced stress granules. Importantly, Nef suppression occurs in the context of HIV-1 infection of CD4+ T lymphocytes with little MHC I and CD4 down-regulation. Taken together, these results demonstrate that stress granule induction and nef mRNA sequestration account for this translational suppression of Nef expression and offers a new strategy for development of anti-HIV therapeutics to buttress our fight against HIV/AIDS. PMID:19150430

  17. Effects of HIV-1 Nef on retrograde transport from the plasma membrane to the endoplasmic reticulum.

    PubMed

    Johannes, Ludger; Pezo, Valérie; Mallard, Frédéric; Tenza, Danièle; Wiltz, Aimée; Saint-Pol, Agnès; Helft, Julie; Antony, Claude; Benaroch, Philippe

    2003-05-01

    HIV-1 Nef protein down-regulates several important immunoreceptors through interactions with components of the intracellular sorting machinery. Nef expression is also known to induce modifications of the endocytic pathway. Here, we analyzed the effects of Nef on retrograde transport, from the plasma membrane to the endoplasmic reticulum using Shiga toxin B-subunit (STxB). Nef expression inhibited access of STxB to the endoplasmic reticulum, but did not modify the surface expression level of STxB receptor, Gb3, nor its internalization rate as measured with a newly developed assay. Mutation of the myristoylation site or of a di-leucine motif of Nef involved in the interaction with the clathrin adaptor complexes AP1 and AP2 abolished the inhibition of retrograde transport. In contrast, mutations of Nef motifs known to interact with PACS-1, beta COP or a subunit of the v-ATPase did not modify the inhibitory activity of Nef on retrograde transport. Ultrastructural analysis revealed that Nef was present in clusters located on endosomal or Golgi membranes together with internalized STxB. Furthermore, in strongly Nef-expressing cells, STxB accumulated in endosomal structures that labeled with AP1. Our observations show that Nef perturbs retrograde transport between the early endosome and the endoplasmic reticulum. The potential transport steps targeted by Nef are discussed.

  18. HIV-1 Nef breaches placental barrier in rat model.

    PubMed

    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.

  19. Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS

    PubMed Central

    Carl, Silke; Greenough, Thomas C.; Krumbiegel, Mandy; Greenberg, Michael; Skowronski, Jacek; Sullivan, John L.; Kirchhoff, Frank

    2001-01-01

    The human immunodeficiency virus type 1 (HIV-1) Nef protein has several independent functions that might contribute to efficient viral replication in vivo. Since HIV-1 adapts rapidly to its host environment, we investigated if different Nef properties are associated with disease progression. Functional analysis revealed that nef alleles obtained during late stages of infection did not efficiently downmodulate class I major histocompatibility complex but were highly active in the stimulation of viral replication. In comparison, functional activity in downregulation of CD4 and enhancement of HIV-1 infectivity were maintained or enhanced after AIDS progression. Our results demonstrate that various Nef activities are modulated during the course of HIV-1 infection to maintain high viral loads at different stages of disease progression. These findings suggest that all in vitro Nef functions investigated contribute to AIDS pathogenesis and indicate that nef variants with increased pathogenicity emerge in a significant number of HIV-1-infected individuals. PMID:11264355

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

    PubMed

    Hanna, Zaher; 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(RD35/36AA) and Nef(D174K). Similarly, the severe depletion of double-positive CD4+CD8+ and of single-positive CD4+CD8- thymocytes, usually observed with Nef(Wt), was not detected in Nef(RD35/36AA) and Nef(D174K) Tg mice. However, both mutant Tg mice showed a partial depletion of peripheral CD4+ T cells. This was accompanied, as previously reported for Net(Wt) Tg mice, by the presence of an activated/memory-like phenotype (CD69+, CD25+, CD44+, CD45RB(Low), CD62(Low)) of CD4+ T cells expressing Nef(RD35/36AA) and to a lesser extent Nef(D174K). In addition, both mutants retained the ability to block CD4+ T cell proliferation in vitro after anti-CD3 stimulation, but not to enhance apoptosis/death of CD4+ 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+ T cells. Histopathological assessment revealed the total absence of or decrease severity and frequency of organ AIDS-like diseases (lung, heart and kidney pathologies) in respectively Nef(RD35/36AA) and Nef(D174K) Tg mice, relative to those developing in Nef(Wt) Tg

  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

    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.

  3. Nef induces apoptosis by activating JNK signaling pathway and inhibits NF-kappaB-dependent immune responses in Drosophila.

    PubMed

    Lee, Sung Bae; Park, Jeehye; Jung, Jae U; Chung, Jongkyeong

    2005-05-01

    The human immunodeficiency virus type 1 (HIV-1) nef gene encodes a 27-kDa protein that plays a crucial role during AIDS pathogenesis, but its exact functional mechanism has not been fully elucidated and remains controversial. The present study illuminated the in vivo functions of Nef using Drosophila, in which genetic analyses can be conveniently conducted. Using Drosophila transgenic lines for wild-type Nef, we demonstrated that Nef is not involved in the regulation of cell proliferation but rather specifically induces caspase-dependent apoptosis in wings in a cell-autonomous manner. Interestingly, myristoylation-defective Nef completely failed to induce the apoptotic wing phenotypes, consistent with previous reports demonstrating a crucial role for membrane localization of Nef in vivo. Further genetic and immunohistochemical studies revealed that Nef-dependent JNK activation is responsible for apoptosis. Furthermore, we found that ectopic expression of Nef inhibits Drosophila innate immune responses including Relish NF-kappaB activation with subsequent induction of an antimicrobial peptide, diptericin. The in vivo functions of Nef in Drosophila are highly consistent with those found in mammals and so we propose that Nef regulates evolutionarily highly conserved signaling molecules of the JNK and NF-kappaB signaling pathways at the plasma membrane, and consequently modulates apoptosis and immune responses in HIV target cells.

  4. HIV-1 Nef regulates the release of superoxide anions from human macrophages

    PubMed Central

    2005-01-01

    The NADPH oxidase enzymatic complex participates in the oxidative burst by producing ROS (reactive oxygen species). Altered levels of ROS production may have pathogenetic implications due to the loss of some innate immune functions such as oxidative burst and phagocytosis. Considering that HIV-1 Nef protein plays a primary role in AIDS pathogenesis, by affecting the immune system, we sought to dissect possible effects of Nef on the release of superoxide anions. We show here that the inducible expression of Nef in human phagocytic cells modulates the superoxide release in a biphasic manner. In particular, an early Nef-induced increase of the superoxide release was followed by a dramatic decrease starting from 10 h after the Nef induction. This was observed whatever the presence of cell activators such as GM-CSF (granulocyte/macrophage colony-stimulating factor) or fMLP (N-formyl-L-methionyl-L-leucyl-L-phenylalanine). Whereas the early increase in superoxide release is probably the result of the already described Nef-dependent activation of PAK-2 (p21-activated kinase 2)–Rac2, we were interested in investigating the mechanisms underlying the late inhibition of superoxide release observed originally. In this regard, we individuated at least three independent requirements for the Nef-induced blockade of superoxide release: (i) the active protein synthesis; (ii) both the membrane localization and the interaction with endocytotic machinery of Nef; and (iii) the release of soluble factor(s). Moreover, we observed that IL-10 (interleukin-10) inhibits superoxide release, whereas its depletion restored NADPH oxidase activity. We propose that the cell membrane-to-lysosome Nef transit leads to the synthesis and release of soluble factor(s) and, among them, IL-10 might significantly contribute to the inhibition of NAPDH oxidase activity. PMID:15847608

  5. Synthesis and Structure-activity Analysis of Diphenylpyrazolodiazene Inhibitors of the HIV-1 Nef Virulence Factor

    PubMed Central

    Iyer, Prema C.; Zhao, Jielu; Emert-Sedlak, Lori A.; Moore, Kerry; Smithgall, Thomas E.; Day, Billy W.

    2014-01-01

    HIV-1 Nef is a critical AIDS progression factor yet underexplored target for antiretroviral drug discovery. A recent high-throughput screen for pharmacological inhibitors of Nef-dependent Src-family kinase activation identified a diphenylpyrazolodiazene hit compound with submicromolar potency in HIV-1 replication assays against a broad range of primary Nef variants. This compound, known as ‘B9’, binds directly to Nef and inhibits is dimerization in cells as a possible mechanism of action. Here were synthesized a diverse set of B9 analogs and identified structural features essential to antiretroviral activity. Chemical modifications to each of the three rings present in the parent compound were identified that did not compromise antiviral action. These analogs will guide the development of next-generation compounds with appropriate pharmacological profiles for assessment of antiretroviral activity in vivo. PMID:24650642

  6. CD4 and MHC class I down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates

    PubMed Central

    Gray, Lachlan R.; Gabuzda, Dana; Cowley, Daniel; Ellett, Anne; Chiavaroli, Lisa; Wesselingh, Steven L.; Churchill, Melissa J.; Gorry, Paul R.

    2015-01-01

    HIV-1 nef undergoes adaptive evolution in the CNS, reflecting altered requirements for HIV-1 replication in macrophages/microglia and brain-specific immune selection pressures. The role of Nef in HIV-1 neurotropism and the pathogenesis of HIV-associated dementia (HAD) is unclear. In this study, we characterized 82 nef alleles cloned from brain, CSF, spinal cord and blood/lymphoid tissue-derived HIV-1 isolates from 7 subjects with HAD. CNS isolate-derived nef alleles were genetically compartmentalized and had reduced sequence diversity compared to those from lymphoid tissue isolates. Defective nef alleles predominated in a brain-derived isolate from one of the 7 subjects (MACS2-br). The ability of Nef to down-modulate CD4 and MHC class 1 (MHC-1) was generally conserved among nef alleles from both CNS and lymphoid tissues. However, the potency of CD4 and MHC-1 down-modulation was variable, which was associated with sequence alterations known to influence these Nef functions. These results suggest that CD4 and MHC-1 down-modulation are highly conserved functions among nef alleles from CNS- and lymphoid tissue-derived HIV-1 isolates that may contribute to viral replication and escape from immune surveillance in the CNS. PMID:21165790

  7. CD4 cell surface downregulation in HIV-1 Nef transgenic mice is a consequence of intracellular sequestration.

    PubMed Central

    Brady, H J; Pennington, D J; Miles, C G; Dzierzak, E A

    1993-01-01

    The Nef gene product is a regulatory protein of HIV whose biological function is poorly understood. Nef has been thought to have a negative effect on viral replication in vitro but has been shown in studies with SIV to be necessary in the establishment of viraemia in vivo. In vitro studies in various human cell lines have shown that Nef downregulates the expression of cell surface CD4 and thus could have effects on the immune response. We have generated four transgenic mouse lines, with constructs containing two different Nef alleles under the control of CD2 regulatory elements to examine the interaction of Nef with the host immune system in vivo. In adult transgenic mice we have found marked downregulation in the level of CD4 on the surface of double positive thymocytes and a decrease in the number of CD4+ T cells in the thymus. Functional analyses have revealed a decrease in the total activation of transgenic thymocytes by anti-CD3 epsilon antibody. By specific intracellular staining of T cells in such mice we have found CD4 colocalizing with a Golgi-specific marker. These results strongly suggest a Nef mediated effect on developing CD4 thymocytes resulting from interference of Nef in the intracellular trafficking or post-translational modification of CD4. Images PMID:8262036

  8. HIV-1 Nef responsiveness is determined by Env variable regions involved in trimer association and correlates with neutralization sensitivity.

    PubMed

    Usami, Yoshiko; Göttlinger, Heinrich

    2013-11-14

    HIV-1 Nef and the unrelated murine leukemia virus glycoGag similarly enhance the infectivity of HIV-1 virions. We now show that the effects of Nef and glycoGag are similarly determined by variable regions of HIV-1 gp120 that control Env trimer association and neutralization sensitivity. Whereas neutralization-sensitive X4-tropic Env proteins conferred high responsiveness to Nef and glycoGag, particles bearing neutralization-resistant R5-tropic Envs were considerably less affected. The profoundly different Nef/glycoGag responsiveness of a neutralization-resistant and a neutralization-sensitive R5-tropic Env could be switched by exchanging their gp120 V1/V2 regions, which also switches their neutralization sensitivity. Within V1/V2, the same determinants governed Nef/glycoGag responsiveness and neutralization sensitivity, indicating that these phenotypes are mechanistically linked. The V1/V2 and V3 regions, which form an apical trimer-association domain, together determined the Nef and glycoGag responsiveness of an X4-tropic Env. Our results suggest that Nef and glycoGag counteract the inactivation of Env spikes with relatively unstable apical trimer-association domains.

  9. Changes in the Plasticity of HIV-1 Nef RNA during the Evolution of the North American Epidemic

    PubMed Central

    Manzourolajdad, Amirhossein; Gonzalez, Mileidy; Spouge, John L.

    2016-01-01

    Because of a high mutation rate, HIV exists as a viral swarm of many sequence variants evolving under various selective pressures from the human immune system. Although the Nef gene codes for the most immunogenic of HIV accessory proteins, which alone makes it of great interest to HIV research, it also encodes an RNA structure, whose contribution to HIV virulence has been largely unexplored. Nef RNA helps HIV escape RNA interference (RNAi) through nucleotide changes and alternative folding. This study examines Historic and Modern Datasets of patient HIV-1 Nef sequences during the evolution of the North American epidemic for local changes in RNA plasticity. By definition, RNA plasticity refers to an RNA molecule’s ability to take alternative folds (i.e., alternative conformations). Our most important finding is that an evolutionarily conserved region of the HIV-1 Nef gene, which we denote by R2, recently underwent a statistically significant increase in its RNA plasticity. Thus, our results indicate that Modern Nef R2 typically accommodates an alternative fold more readily than Historic Nef R2. Moreover, the increase in RNA plasticity resides mostly in synonymous nucleotide changes, which cannot be a response to selective pressures on the Nef protein. R2 may therefore be of interest in the development of antiviral RNAi therapies. PMID:27685447

  10. 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

  11. Reduced cell surface expression of processed human immunodeficiency virus type 1 envelope glycoprotein in the presence of Nef.

    PubMed Central

    Schwartz, O; Rivière, Y; Heard, J M; Danos, O

    1993-01-01

    nef genes from two laboratory grown human immunodeficiency virus type 1 (HIV-1) strains and from two proviruses that had not been propagated in vitro were introduced into CD4+ lymphoblastoid CEM cells. The stable expression of all four Nef proteins was associated with an almost complete abrogation of CD4 cell surface localization. The consequences of the presence of Nef on gp160 cleavage, gp120 surface localization, and envelope-induced cytopathic effect were examined in CEM cells in which the HIV-1 env gene was expressed from a vaccinia virus vector. The presence of Nef did not modify the processing of gp160 into its subunits but resulted in a significant decrease of cell surface levels of gp120, associated with a dramatic reduction of the fusion-mediated cell death. Surface levels of mutant envelope glycoproteins unable to bind CD4 were not altered in Nef-expressing cells, suggesting that the phenomenon was CD4 dependent. The intracellular accumulation of fully processed envelope glycoproteins could significantly delay the cytopathic effect associated with envelope surface expression in HIV-infected cells and may be relevant to the selective advantage associated with Nef during the in vivo infectious process. Images PMID:8497051

  12. The membrane-associated conformation of HIV-1 Nef investigated with hydrogen exchange mass spectrometry at a Langmuir monolayer

    PubMed Central

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

    2015-01-01

    In the companion paper to this work, we have 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 lipid 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

  13. Human immunodeficiency virus type 1 Nef-induced down-modulation of CD4 is due to rapid internalization and degradation of surface CD4.

    PubMed Central

    Rhee, S S; Marsh, J W

    1994-01-01

    Human immunodeficiency virus type 1 (HIV-1) Nef is a myristylated protein with a relative molecular mass of 27 kDa, is localized to the cytoplasmic surfaces of cellular membranes, and has been reported to down-modulate CD4 in human T cells. To understand the mechanism of HIV-1 Nef-mediated down-modulation of cell surface CD4, we expressed Nef protein in human T-cell line VB. Expression of HIV-1 Nef protein down-modulated surface CD4 molecules. In pulse-chase experiments, CD4 molecules in Nef-expressing cells were synthesized at normal levels. However, the bulk of newly synthesized CD4 protein was degraded with a half-life of approximately 6 h, compared with the 24-h half-life in control cells. This Nef-induced acceleration of CD4 turnover was inhibited by lysosomotropic agents NH4Cl and chloroquine as well as by the protease inhibitor leupeptin. Surface CD4 biotinylation experiments demonstrated that CD4 molecules in Nef-expressing T cells are transported to the plasma membrane with normal kinetics but are then rapidly internalized. Therefore, HIV-1 Nef-induced down-modulation of CD4 is due to rapid internalization of surface CD4 and subsequent degradation by an acid-dependent process, potentially lysosomal. Additionally, in a Nef-expressing cell, we find accelerated dissociation of the T-cell tyrosine kinase p56lck and CD4 but only after the complex reaches the plasma membrane. This implies that HIV-1 Nef protein might play a role in triggering a series of T-cell activation-like events, which contribute to p56lck dissociation and internalization of surface CD4 molecules. Images PMID:8035515

  14. Nef proteins from simian immunodeficiency viruses are tetherin antagonists

    PubMed Central

    Zhang, Fengwen; Wilson, Sam J.; Langford, Wilmina; Virgen, Beatriz; Gregory, Devon; Johnson, Marc; Munch, Jan; Kirchhoff, Frank; Bieniasz, Paul D.; Hatziioannou, Theodora

    2010-01-01

    The tetherin/BST2/CD317 protein blocks the release of HIV-1 and other enveloped viruses by inducing tethering of nascent particles to infected cell surfaces. The HIV-1 Vpu protein antagonizes the antiviral activity of human but not monkey tetherins and many simian immunodeficiency viruses (SIVs) do not encode Vpu. Here, we show that the apparently ‘missing’ anti-tetherin activity in SIVs has been acquired by several SIV Nef proteins. Specifically, SIVMAC/SIVSMM, SIVAGM and SIVBLU Nef proteins can suppress tetherin activity. Notably, tetherin antagonism by SIV Nef proteins is species-specific, is genetically separable from other Nef activities and is most evident with simian rather than human tetherin proteins. Accordingly, a critical determinant of sensitivity to SIVMAC Nef in the tetherin cytoplasmic tail is variable in nonhuman primate tetherins and deleted in human tetherin, likely due to selective pressures imposed by viral antagonists, perhaps including Nef proteins. PMID:19501037

  15. 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

  16. 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.

  17. Repair and evolution of nef in vivo modulates simian immunodeficiency virus virulence.

    PubMed Central

    Whatmore, A M; Cook, N; Hall, G A; Sharpe, S; Rud, E W; Cranage, M P

    1995-01-01

    Experimental evidence from the simian immunodeficiency virus (SIV) model of AIDS has shown that the nef gene is critical in the pathogenesis of AIDS. Consequently, nef is of considerable interest in both antiviral drug and vaccine development. Preliminary findings in two rhesus macaques indicated that a deletion of only 12 bp found in the overlapping nef/3' long terminal repeat (LTR) region (9501 to 9512) of the SIVmacC8 molecular clone was associated with reduced virus isolation frequency. We show that this deletion can be repaired in vivo by a sequence duplication event and that sequence evolution continues until the predicted amino acid sequence of the repair is virtually indistinguishable from that of the virulent wild type. These changes occurred concomitantly with reversion to virulence, evidenced by a high virus isolation frequency and load, decline in anti-p27 antibody, substantial reduction in the CD4/CD8 ratio, and development of opportunistic infections associated with AIDS. These findings clearly illustrate the capacity for repair of small attenuating deletions in primate lentiviruses and also strongly suggest that the region from 9501 to 9512 in the SIV nef/3' LTR region is of biological relevance. In addition, the ability of attenuated virus to revert to virulence raises fundamental questions regarding the nature of superinfection immunity. PMID:7609080

  18. 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.

  19. Human immunodeficiency virus type 1 nef quasispecies in pathological tissue.

    PubMed Central

    Blumberg, B M; Epstein, L G; Saito, Y; Chen, D; Sharer, L R; Anand, R

    1992-01-01

    The role of the nef gene in human immunodeficiency virus type 1 (HIV-1) infection is poorly understood. To provide a basis for studies on the role of nef in AIDS, we used targeted polymerase chain reaction amplification and DNA sequencing to determine the structure of nef genes in pathologic tissue from HIV-1-infected children and adults. We find that the nef reading frame is open in 92% of clones derived from both brain and lymphocytic tissue of children, suggesting that nef is expressed in these tissues. One HIV-1 clone, BRVA, obtained by coculture from the brain of an adult AIDS patient with progressive dementia, was previously shown to contain a duplicated region in nef. We show here that similar duplications are widespread in both adults and children with AIDS. However, coculture strongly selects against the broad spectrum of nef quasispecies found in tissue. These findings suggest functional selection for nef quasispecies in pathologic tissues during HIV-1 infection of the human host. Images PMID:1501274

  20. Mechanisms of HIV-1 Nef Function and Intracellular Signaling

    PubMed Central

    Foster, John L.; Denial, Sarah J.; Temple, Brenda R. S.; Garcia, J. Victor

    2013-01-01

    Advances in the last several years have enhanced mechanistic understanding of Nef induced CD4 and MHCI downregulation and have suggested a new paradigm for analyzing Nef function. In both of these cases, Nef acts by forming ternary complexes with significant contributions to stability imparted by non-canonical interactions. The mutational analyses and binding assays that have led to these conclusions are discussed. The recent progress has been dependent on conservative mutations and multi-protein binding assays. The poorly understood Nef functions of p21 activated protein kinase (PAK2) activation, enhancement of virion infectivity, and inhibition of immunoglobulin class switching are also likely to involve ternary complexes and non-canonical interactions. Hence, investigation of these latter Nef functions should benefit from a similar approach. Six historically used alanine substitutions for determining structure-function relationships of Nef are discussed. These are M20A, E62A/E63A/E64A/E65A (AAAA), P72A/P75A (AXXA), R106A, L164A/L165A, and D174A/D175A. Investigations of less disruptive mutations in place of AAAA and AXXA have led to different interpretations of mechanism. Two recent examples of this alternate approach applied to PAK2 activation F191 and critical residue D123 are presented. The implications of the new findings and the resulting new paradigm for Nef structure-function are discussed with respect to creating a map of Nef functions on the protein surface. We report the results of a PPI-Pred analysis for protein-protein interfaces. There are three predicted patches produced by the analysis which describe regions consistent with the currently known mutational analyses of Nef function. PMID:21336563

  1. The cytoplasmic domain of CD4 is sufficient for its down-regulation from the cell surface by human immunodeficiency virus type 1 Nef.

    PubMed Central

    Anderson, S J; Lenburg, M; Landau, N R; Garcia, J V

    1994-01-01

    Human immunodeficiency virus type 1 Nef down-regulates surface expression of murine and human CD4 but not human CD8. We recently reported that the cytoplasmic domain of CD4 is required for its down-regulation by Nef. Using a chimeric molecule composed of the extracellular and transmembrane domains of human CD8 fused to the cytoplasmic domain of human CD4, we show here that the cytoplasmic domain of CD4 is sufficient for down-regulation by Nef. Since the cytoplasmic domain of CD4 is also the site of its association with p56lck, we used a series of CD4 mutants to determine whether the regions of the cytoplasmic domain of CD4 required for down-regulation by Nef are the same as those required for p56lck binding. Our results indicate that the portion of the cytoplasmic domain required for the down-regulation of CD4 by Nef overlaps with the binding site of p56lck, but the cysteine residues which are essential for the association of CD4 with p56lck are not required. This observation raised the possibility that Nef competes with p56lck for binding to CD4. However, under conditions which are considerably milder than those permissive for coimmunoprecipitation of CD4 and p56lck, we found no evidence for an association between Nef and CD4. While a decrease in total CD4 was observed in lysates of cells expressing Nef, the levels of p56lck were not significantly affected. Pulse-chase experiments further revealed a decrease in the half-life of CD4 in Nef-expressing cells. These results show that the decrease in surface CD4 expression induced by Nef is mediated at least in part by a decrease in the half-life of CD4 protein. These results also indicate that a large portion of p56lck is free of CD4 in T cells expressing Nef, which could have a significant effect on T-cell function. Images PMID:8151774

  2. High blood cholesterol levels

    MedlinePlus

    ... Outlook (Prognosis) High cholesterol levels can lead to hardening of the arteries , also called atherosclerosis. This occurs ... and safe drinking Coronary heart disease Cushing syndrome Hardening of the arteries Hypothyroidism Overweight Stroke Triglyceride level ...

  3. 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

  4. 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.

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

    DOEpatents

    Korber, Bette T [Los Alamos, NM; Perkins, Simon [Los Alamos, NM; Bhattacharya, Tanmoy [Los Alamos, NM; Fischer, William M [Los Alamos, NM; Theiler, James [Los Alamos, NM; Letvin, Norman [Boston, MA; Haynes, Barton F [Durham, NC; Hahn, Beatrice H [Birmingham, AL; Yusim, Karina [Los Alamos, NM; Kuiken, Carla [Los Alamos, NM

    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.

  6. Association between a naturally arising polymorphism within a functional region of HIV-1 Nef and disease progression in chronic HIV-1 infection.

    PubMed

    Meribe, Stanley C; Hasan, Zafrul; Mahiti, Macdonald; Mwimanzi, Francis; Toyoda, Mako; Mori, Masahiko; Gatanaga, Hiroyuki; Kikuchi, Tadashi; Miura, Toshiyuki; Kawana-Tachikawa, Ai; Iwamoto, Aikichi; Oka, Shinichi; Ueno, Takamasa

    2015-08-01

    HIV-1 Nef mediates downregulation of HLA class I (HLA-I) through a number of highly conserved sequence motifs. We investigated the in vivo implication(s) of naturally arising polymorphisms in functional motifs in HIV-1 Nef that are associated with HLA-I downregulation, including the acidic cluster, polyproline, di-arginine and Met-20 regions. Plasma samples from treatment-naive, chronically HIV-1 infected subjects were collected after obtaining informed consent, and viral RNA was extracted and amplified by nested RT-PCR. The resultant nef amplicons were sequenced directly, and subtype-B sequences with an intact open reading frame (n = 406) were included in our analyses. There was over-representation of isoleucine at position 20 (Ile-20) in our dataset when compared to sequences in the Los Alamos sequence database (17.7 vs. 6.9 %, p = 0.0309). The presence of having Ile-20 in Nef was found to be associated with higher median plasma viral load (p = 0.013), independent of associated codons or viral lineage effects, whereas no clinical association was found with polymorphisms in the other functional motifs. Moreover, introduction of a Met-20-to-Ile mutation in a laboratory strain SF2 Nef resulted in a modest, albeit not statistically significant, increase in HLA class I downregulation activity (p = 0.06). Taken together, we have identified a naturally arising polymorphism, Ile-20, within HIV-1 subtype B Nef that is associated with poorer disease outcome.

  7. 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

  8. Chimeric human/murine monoclonal IgM antibodies to HIV-1 Nef antigen expressed on chronically infected cells.

    PubMed

    Kawai, Masahiro; He, Lianying; Kawamura, Takeshi; Omoto, Shinya; Fujii, Yoichi R; Okada, Noriko

    2003-01-01

    Human IgM antibody (Ab) to gangliosides induced cytolysis of HIV-1-infected cells by homologous human complement. We expected that any human IgM Ab reactive with HIV-1 infected cells could cause complement-mediated cytolysis. The trans-chromosome mouse (TC mouse) contains human chromosomes harboring genes responsible for immunoglobulin production. Spleen cells from TC mice immunized with recombinant Nef were fused with mouse myeloma cells to generate hybridomas, and we selected those that produced human mu-chain-positive Abs reactive with Nef fixed on an ELISA plate. However, the L-chain of the monoclonal Abs (mAbs) were murine lambda in type and were chimeric, and we could not succeed in obtaining mAb with human mu- and human kappa-chains. The chimeric mAbs reacted with the HIV-1 infected cells as seen with flow cytometric analysis, and the surface expression of Nef was also detectable on chronically infected OM10.1 cells which had no detectable gp120. However, although the reaction of the chimeric IgM mAb with HIV-1-infected MOLT4 cells induced C3 deposition on cell surfaces on incubation with fresh human serum, the cells remained unlysed, as determined by 51Cr release assay. The amount of Nef antigen on the cells might not have been high enough to overcome the function of HRF20 (CD59) that restricts formation of membrane attack complexes of homologous complement. However, combination of anti-Nef IgM mAb with other IgM mAbs reactive with the surface of HIV-1-infected cells may induce a synergistic effect in complement mediated cytolysis.

  9. Fusogenic activity of amino-terminal region of HIV type 1 Nef protein.

    PubMed

    Curtain, C C; Separovic, F; Rivett, D; Kirkpatrick, A; Waring, A J; Gordon, L M; Azad, A A

    1994-10-01

    We have studied two isoforms of Nef, Nef-27 and Nef-25, which were produced in E. coli. Nef-25 lacked the first 18 N-terminal residues of Nef-27 and both were nonmyristylated. Nef-27 fuses small unilamellar dipalmitoyl phosphatidylcholine vesicles (SUVs), as indicated by enhanced light scattering of SUVs and lipid mixing using concentration-dependent fluorescence dequenching. Nef-27 also causes the appearance of a shifted isotropic peak in the 31P NMR spectra of these vesicles, suggesting that protein interactions induce nonlamellar lipid structures. Recombinant Nef-25, which lacks only the 18 N-terminal residues of Nef-27, does not fuse vesicles and has little effect on the 31P NMR spectra. On the other hand, synthetic peptides consisting of 18 or 21 of the N-terminal residues of Nef-27 are strongly membrane perturbing, causing vesicle fusion and inducing isotropic peaks in the 31P NMR spectrum. Endogenous fluorescence spectra of the N-terminal peptide (21 residues) with SUVs show that the N-terminal sequence of Nef may achieve these perturbing effects by inserting its hydrophobic side into the lipid bilayer. Theoretical calculations using hydrophobic moment plot analysis indicate that short-length stretches (i.e., six amino acid residues) of the N-terminal sequence may insert into the lipid bilayer as multimeric alpha helices or beta sheets. The above-described membrane activities of Nef-27, which principally reside in its N-terminal domain, may play critical role(s) in certain functional properties of the full-length protein. For example, the fusogenic activity of the N-terminal sequence may be involved in the extracellular release of Nef-27, much of which appears to be associated with small membrane vesicles. The fusion activity may also be relevant to the ability of Nef-27 to downregulate CD4 and IL-2 receptors when this protein is electroporated into cultured lymphocytes, an activity not possessed by Nef-25.

  10. A strategy of antigen incorporation into exosomes: comparing cross-presentation levels of antigens delivered by engineered exosomes and by lentiviral virus-like particles.

    PubMed

    Lattanzi, Laura; Federico, Maurizio

    2012-11-26

    Among strategies aimed at developing new nanoparticle-based vaccines, exosomes hold much promise. They are nanovesicles released by basically all eukaryotic cell types originating from intraluminal vesicles which accumulate in multivesicular bodies. Exosomes have immunogenic properties whose strength correlates with the amounts of associated antigens. Engineering antigens to target them in exosomes represents the last frontier in terms of nanoparticle-based vaccines. Here we report a new method to incorporate protein antigens in exosomes relying on the unique properties of a mutant of the HIV-1 Nef protein, Nef(mut). This is a biologically inactive mutant we found incorporating into exosomes at high levels also when fused at its C-terminus with foreign proteins. We compared both biochemical and antigenic properties of Nef(mut) exosomes with those of previously characterized Nef(mut) -based lentiviral virus-like particles (VLPs). We found that exosomes incorporate Nef(mut) and fusion protein derivatives with similar efficiency of VLPs. When an envelope fusion protein was associated with both exosomes and VLPs to favor cross-presentation of associated antigens, Nef(mut) and its derivatives incorporated in exosomes were cross-presented at levels at least similar to what observed when the antigens were delivered by engineered VLPs. This occurred despite exosomes entered target cells with an apparent lower efficiency than VLPs. The unique properties of HIV-1 Nef(mut) in terms of exosome incorporation efficiency, carrier of foreign antigens, and lack of anti-cellular effects open the way toward the development of a flexible, safe, cost-effective exosome-based CD8(+) T cell vaccine platform.

  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. Inhibition of Nef- and phorbol ester-induced CD4 degradation by macrolide antibiotics.

    PubMed Central

    Luo, T; Anderson, S J; Garcia, J V

    1996-01-01

    Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS. The simian immunodeficiency virus (SIV) causes a similar syndrome in macaques. The product of the nef gene of SIV has been shown to be important for virus replication and disease progression in vivo. In vitro, both SIV and HIV Nef downregulate surface expression of CD4 and accelerate total CD4 turnover. The mechanism by which Nef downregulates CD4 has not been established. A current model suggests that Nef enhances cell surface CD4 endocytosis and degradation in lysosomes. However, this was recently challenged when CD4 was found to accumulate in early endosomes of cells expressing Nef. Because inhibition of Nef function might halt virus replication and disease progression, we tested two macrolide antibiotics for their ability to inhibit Nef function. Concanamycin B (ConB) and bafilomycin A1 (BFLA1) are specific inhibitors of acidification of cell endosomes and lysosomes and, unlike other inhibitors, do not affect transport. Although ConB (25 nM) and BFLA1 (100 nM) blocked phorbol myristate acetate- and Nef-induced CD4 degradation in human monocyte U937 cells, CD4 surface expression was not recovered. Instead, CD4 accumulated in lysosomes. To determine if Nef is directly responsible for CD4 degradation or if they bind to each other in a manner similar to Vpu, transcripts of human CD4 and HIV-1 nef were cotranslated in vitro. Our results indicate that under our experimental conditions, Nef does not affect CD4 stability and does not associate with CD4 in this in vitro system. Our data suggest that (i) CD4 downregulation by Nef results in degradation of CD4 in lysosomes, (ii) inhibition of CD4 degradation by macrolide antibiotics does not restore surface expression, and (iii) the inhibition of CD4 expression by Nef appears to be indirect and is likely to involve cellular factors. PMID:8627671

  13. Cytolytic T lymphocytes (CTLs) from HIV-1 subtype C-infected Indian patients recognize CTL epitopes from a conserved immunodominant region of HIV-1 Gag and Nef.

    PubMed

    Thakar, Madhuri R; Bhonge, Leena S; Lakhashe, Samir K; Shankarkumar, U; Sane, Suvarna S; Kulkarni, Smita S; Mahajan, Bharati A; Paranjape, Ramesh S

    2005-09-01

    Analysis of the human immunodeficiency virus type 1 (HIV-1) cytolytic T lymphocyte (CTL) epitopes recognized by the targeted population is critical for HIV-1 vaccine design. Peripheral blood mononuclear cells from 47 Indian subjects at different stages of HIV-1 infection were tested for HIV-1 Gag-, Nef-, and Env-specific T cell responses by interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay, using pools of overlapping peptides. The Gag and Nef antigens were targeted by 83% and 36% of responders. Five immunodominant regions, 4 in Gag and 1 in Nef, were identified in the study; these regions are conserved across clades, including the African subtype C clade. Three antigenic regions were also found to be recognized by CTLs of the study participants. These regions were not identified as immunodominant regions in studies performed in Africa, which highlights the importance of differential clustering of responses within HIV-1 subtype C. Twenty-six putative epitopes--15 Gag (10 in p24 and 5 in p17), 10 Nef, and 1 Env (gp 41)--were predicted using a combination of peptide matrix ELISPOT assay and CTL epitope-prediction software. Ninety percent of the predicted epitopes were clustered in the conserved immunodominant regions of the Gag and Nef antigens. Of 26 predicted epitopes, 8 were promiscuous, 3 of which were highly conserved across clades. Three Gag and 4 Nef epitopes were novel. The identification of conserved epitopes will be important in the planning of an HIV-1 vaccine strategy for subtype C-affected regions.

  14. High potassium level

    MedlinePlus

    ... symptoms. Tests that may be ordered include: Electrocardiogram (ECG) Potassium level Your provider will likely check your ... have danger signs, such as changes in an ECG . Emergency treatment may include: Calcium given into your ...

  15. Virological and Immunological Characterization of Novel NYVAC-Based HIV/AIDS Vaccine Candidates Expressing Clade C Trimeric Soluble gp140(ZM96) and Gag(ZM96)-Pol-Nef(CN54) as Virus-Like Particles

    PubMed Central

    Perdiguero, Beatriz; Gómez, Carmen Elena; Cepeda, Victoria; Sánchez-Sampedro, Lucas; García-Arriaza, Juan; Mejías-Pérez, Ernesto; Jiménez, Victoria; Sánchez, Cristina; Sorzano, Carlos Óscar S.; Oliveros, Juan Carlos; Delaloye, Julie; Roger, Thierry; Calandra, Thierry; Asbach, Benedikt; Wagner, Ralf; Kibler, Karen V.; Jacobs, Bertram L.; Pantaleo, Giuseppe

    2014-01-01

    (CN54) as VLPs. These vectors are stable and express high levels of both HIV-1 antigens. Gag-induced VLPs do not interfere with NYVAC morphogenesis, are highly attenuated in immunocompromised and newborn mice after intracranial inoculation, trigger specific innate immune responses in human cells, and activate T (Env-specific CD4 and Gag-specific CD8) and B cell immune responses to the HIV antigens, leading to high antibody titers against gp140. For these reasons, these vectors can be considered vaccine candidates against HIV/AIDS and currently are being tested in macaques and humans. PMID:25355891

  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. Expression and biochemical characterization of human immunodeficiency virus type 1 nef gene product.

    PubMed Central

    Kaminchik, J; Bashan, N; Pinchasi, D; Amit, B; Sarver, N; Johnston, M I; Fischer, M; Yavin, Z; Gorecki, M; Panet, A

    1990-01-01

    nef genes from human immunodeficiency virus type 1 isolates BH10 and LAV1 (lymphadenopathy-associated virus type 1) were expressed in Escherichia coli under the deo operon promoter. The two proteins found in the soluble compartment of the bacterial lysate were purified by ion-exchange column chromatography to apparent homogeneity. Determination of the amino-terminal sequence revealed glycine as the first amino acid in the Nef protein, indicating removal of the initiator methionine during expression in E. coli. Under native conditions, the recombinant Nef protein is a monomer of 23 kilodaltons. In denaturing polyacrylamide gels, however, BH10 and LAV1 Nef proteins migrate as 28 and 26 kilodaltons, respectively. GTP binding and GTPase activity were monitored during Nef protein purification. These activities did not copurify with the recombinant Nef protein from either the BH10 or the LAV1 isolate. Purified recombinant BH10 Nef protein was used as an immunogen to elicit mouse monoclonal antibodies. A series of monoclonal antibodies were obtained which reacted with sequences at either the amino or carboxy terminus of Nef. In addition, a conformational epitope reacting with native BH10, but not LAV1, Nef was isolated. Images PMID:2191151

  18. Interactions between Nef and AIP1 proliferate multivesicular bodies and facilitate egress of HIV-1

    PubMed Central

    Costa, Luciana J; Chen, Nan; Lopes, Adriana; Aguiar, Renato S; Tanuri, Amilcar; Plemenitas, Ana; Peterlin, B Matija

    2006-01-01

    Background Nef is an accessory protein of primate lentiviruses, HIV-1, HIV-2 and SIV. Besides removing CD4 and MHC class I from the surface and activating cellular signaling cascades, Nef also binds GagPol during late stages of the viral replicative cycle. In this report, we investigated further the ability of Nef to facilitate the replication of HIV-1. Results To this end, first the release of new viral particles was much lower in the absence of Nef in a T cell line. Since the same results were obtained in the absence of the viral envelope using pseudo-typed viruses, this phenomenon was independent of CD4 and enhanced infectivity. Next, we found that Nef not only possesses a consensus motif for but also binds AIP1 in vitro and in vivo. AIP1 is the critical intermediate in the formation of multivesicular bodies (MVBs), which play an important role in the budding and release of viruses from infected cells. Indeed, Nef proliferated MVBs in cells, but only when its AIP1-binding site was intact. Finally, these functions of Nef were reproduced in primary macrophages, where the wild type but not mutant Nef proteins led to increased release of new viral particles from infected cells. Conclusion We conclude that by binding GagPol and AIP1, Nef not only proliferates MVBs but also contributes to the egress of viral particles from infected cells. PMID:16764724

  19. The human immunodeficiency virus (HIV) Rev-binding protein (HRB) is a co-factor for HIV-1 Nef-mediated CD4 downregulation.

    PubMed

    Landi, Alessia; Timermans, Cristina Garcia; Naessens, Evelien; Vanderstraeten, Hanne; Stove, Veronique; Verhasselt, Bruno

    2016-03-01

    Human immunodeficiency virus type 1 (HIV-1)-mediated CD4 downregulation is an important determinant of viral replication in vivo. Research on cellular co-factors involved in this process could lead to the identification of potential therapeutic targets. We found that CD4 surface levels were significantly higher in HIV-1-infected cells knocked-down for the HIV Rev-binding protein (HRB) compared with control cells. HRB knock-down affected CD4 downregulation induced by Nef but not by HIV-1 Vpu. Interestingly, the knock-down of the related protein HRBL (HRB-like), but not of the HRB interaction partner EPS15 (epidermal growth factor receptor pathway substrate 15), increased CD4 levels in Vpu-expressing cells significantly. Both of these proteins are known to be involved in HIV-1-mediated CD4 downregulation as co-factors of HIV-1 Nef. These results identify HRB as a previously unknown co-factor for HIV-1 Nef-mediated CD4 downregulation and highlight differences with the related protein HRBL, which affects the CD4 downregulation in a dual role as co-factor of both HIV-1 Nef and Vpu.

  20. Activation of NFAT-Dependent Gene Expression by Nef: Conservation among Divergent Nef Alleles, Dependence on SH3 Binding and Membrane Association, and Cooperation with Protein Kinase C-θ

    PubMed Central

    Manninen, Aki; Huotari, Päivi; Hiipakka, Marita; Renkema, G. Herma; Saksela, Kalle

    2001-01-01

    Here we show that the potential to regulate NFAT is a conserved property of different Nef alleles and that Nef residues involved in membrane targeting and SH3 binding are critical for this function. Cotransfection of an activated protein kinase C-θ (PKC-θ) with Nef implicated PKC-θ as a possible physiological cofactor of Nef in promoting NFAT-dependent gene expression and T-cell activation. PMID:11222731

  1. Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists.

    PubMed

    Emert-Sedlak, Lori A; Loughran, H Marie; Shi, Haibin; Kulp, John L; Shu, Sherry T; Zhao, Jielu; Day, Billy W; Wrobel, Jay E; Reitz, Allen B; Smithgall, Thomas E

    2016-03-01

    The HIV-1 Nef accessory factor enhances viral replication and promotes immune system evasion of HIV-infected cells, making it an attractive target for drug discovery. Recently we described a novel class of diphenylpyrazolodiazene compounds that bind directly to Nef in vitro and inhibit Nef-dependent HIV-1 infectivity and replication in cell culture. However, these first-generation Nef antagonists have several structural liabilities, including an azo linkage that led to poor oral bioavailability. The azo group was therefore replaced with either a one- or two-carbon linker. The resulting set of non-azo analogs retained nanomolar binding affinity for Nef by surface plasmon resonance, while inhibiting HIV-1 replication with micromolar potency in cell-based assays without cytotoxicity. Computational docking studies show that these non-azo analogs occupy the same predicted binding site within the HIV-1 Nef dimer interface as the original azo compound. Computational methods also identified a hot spot for inhibitor binding within this site that is defined by conserved HIV-1 Nef residues Asp108, Leu112, and Pro122. Pharmacokinetic evaluation of the non-azo B9 analogs in mice showed that replacement of the azo linkage dramatically enhanced oral bioavailability without substantially affecting plasma half-life or clearance. The improved oral bioavailability of non-azo diphenylpyrazolo Nef antagonists provides a starting point for further drug lead optimization in support of future efficacy testing in animal models of HIV/AIDS.

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

    SciTech Connect

    Velden, Yme U. van der; 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. - Highlights: • Different approaches to encode additional proteins in the HIV-1 genome were tested. • IRES translation elements are incompatible with efficient HIV-1 replication. • Ubiquitin and 2A fusion protein approaches allow efficient HIV-1 replication. • Doxycycline-controlled HIV-1 variants that encode all viral proteins were developed. • Nef stimulates HIV-rtTA replication in primary cells and human immune system mice.

  4. How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4.

    PubMed

    Ren, Xuefeng; Park, Sang Yoon; Bonifacino, Juan S; Hurley, James H

    2014-01-01

    The Nef protein of HIV-1 downregulates the cell surface co-receptor CD4 by hijacking the clathrin adaptor complex AP-2. The structural basis for the hijacking of AP-2 by Nef is revealed by a 2.9 Å crystal structure of Nef bound to the α and σ2 subunits of AP-2. Nef binds to AP-2 via its central loop (residues 149-179) and its core. The determinants for Nef binding include residues that directly contact AP-2 and others that stabilize the binding-competent conformation of the central loop. Residues involved in both direct and indirect interactions are required for the binding of Nef to AP-2 and for downregulation of CD4. These results lead to a model for the docking of the full AP-2 tetramer to membranes as bound to Nef, such that the cytosolic tail of CD4 is situated to interact with its binding site on Nef. DOI: http://dx.doi.org/10.7554/eLife.01754.001.

  5. Is the high virulence of HIV-1 an unfortunate coincidence of primate lentiviral evolution?

    PubMed

    Kirchhoff, Frank

    2009-06-01

    In the subset of primate lentiviruses that contain a vpu gene - HIV-1 and its simian precursors - the Nef protein has lost the ability to down-modulate CD3, block T cell activation and suppress programmed death. Vpu counteracts a host restriction factor induced by the inflammatory cytokine interferon-alpha. I propose that the acquisition of vpu may have allowed the viral lineage that gave rise to HIV-1 to evolve towards greater pathogenicity by removing the selective pressure for a protective Nef function that prevents damagingly high levels of immune activation.

  6. HIV-1 Nef associates with p22-phox, a component of the NADPH oxidase protein complex.

    PubMed

    Salmen, Siham; Colmenares, Melisa; Peterson, Darrel L; Reyes, Elbert; Rosales, Jose D; Berrueta, Lisbeth

    2010-01-01

    Altered neutrophil function may contribute to the development of AIDS during the course of HIV infection. It has been described that Nef, a regulatory protein from HIV, can modulate superoxide production in other cells, therefore altered superoxide production in neutrophils from HIV infected patients, could be secondary to a direct effect of Nef on components of the NADPH oxidase complex. In this work, we describe that Nef, was capable of increasing superoxide production in human neutrophils. Furthermore, a specific association between Nef and p22-phox, a membrane component of the NADPH oxidase complex, was found. We propose that this association may reflect a capability of Nef to modulate by direct association, the enzymatic complex responsible for one of the most efficient innate defense mechanisms in phagocytes, contributing to the pathogenesis of the disease.

  7. Extracellular Nef Protein Targets CD4+ T Cells for Apoptosis by Interacting with CXCR4 Surface Receptors

    PubMed Central

    James, Cleve O.; Huang, Ming-Bo; Khan, Mafuz; Garcia-Barrio, Minerva; Powell, Michael D.; Bond, Vincent C.

    2004-01-01

    The effects of soluble Nef protein on CD4+ T cells were examined. CD4+-T-cell cultures exposed to soluble Nef were analyzed for apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and hallmarks of apoptosis including cytoplasmic shrinkage, nuclear fragmentation, DNA laddering, and caspase activation. We observed dose- and time-dependent inductions of apoptosis. DNA laddering and activated caspase 3 were also evident. Cells treated with Nef/protein kinase inhibitor complexes were protected from Nef-induced apoptosis, suggesting possible roles for protein kinases in the apoptosis pathway. Similarly, cells treated with Nef/anti-Nef antibody complexes were protected from Nef-induced apoptosis. The cellular receptor responsible for Nef-induced apoptosis was identified through antibody- and ligand-blocking experiments as a receptor commonly involved in viral entry. CXCR4 antibodies, as well as the endogenous ligand SDF-1α, were effective in blocking Nef-induced apoptosis, while CCR5 and CD4 antibodies were ineffective. Moreover, a CXCR4-deficient cell line, MDA-MB-468, which was resistant to Nef-induced apoptosis, became sensitive upon transfection with a CXCR4-expressing vector. This study suggests that extracellular Nef protein could contribute to the decline of CD4 counts prior to and during the onset of AIDS in patients with human immunodeficiency virus type 1 infections. PMID:14990729

  8. Characterization of Three nef-Defective Human Immunodeficiency Virus Type 1 Strains Associated with Long-Term Nonprogression

    PubMed Central

    Rhodes, David I.; Ashton, Lesley; Solomon, Ajantha; Carr, Andrew; Cooper, David; Kaldor, John; Deacon, Nicholas

    2000-01-01

    Long-term survivors (LTS) of human immunodeficiency virus type 1 (HIV-1) infection provide an opportunity to investigate both viral and host factors that influence the rate of disease progression. We have identified three HIV-1-infected individuals in Australia who have been infected for over 11 years with viruses that contain deletions in the nef and nef-long terminal repeat (nef/LTR) overlap regions. These viruses differ from each other and from other nef-defective strains of HIV-1 previously identified in Australia. One individual, LTS 3, is infected with a virus containing a nef gene with a deletion of 29 bp from the nef/LTR overlap region, resulting in a truncated Nef open reading frame. In addition to the Nef defect, only viruses containing truncated Vif open reading frames of 37 or 69 amino acids could be detected in peripheral blood mononuclear cells isolated from this patient. LTS 3 had a viral load of less than 20 copies of RNA/ml of plasma. The other two long-term survivors, LTS 9 and LTS 11, had loads of less than 200 copies of RNA/ml of plasma and are infected with viruses with larger deletions in both the nef alone and nef/LTR overlap regions. These viruses contain wild-type vif, vpu, and vpr accessory genes. All three strains of virus had envelope sequences characteristic of macrophagetropic viruses. These findings further indicate the reduced pathogenic potential of nef-defective viruses. PMID:11044102

  9. HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling

    PubMed Central

    Dirk, Brennan S.; Pawlak, Emily N.; Johnson, Aaron L.; Van Nynatten, Logan R.; Jacob, Rajesh A.; Heit, Bryan; Dikeakos, Jimmy D.

    2016-01-01

    A defining characteristic of HIV-1 infection is the ability of the virus to persist within the host. Specifically, MHC-I downregulation by the HIV-1 accessory protein Nef is of critical importance in preventing infected cells from cytotoxic T-cell mediated killing. Nef downregulates MHC-I by modulating the host membrane trafficking machinery, resulting in the endocytosis and eventual sequestration of MHC-I within the cell. In the current report, we utilized the intracellular protein-protein interaction reporter system, bimolecular fluorescence complementation (BiFC), in combination with super-resolution microscopy, to track the Nef/MHC-I interaction and determine its subcellular localization in cells. We demonstrate that this interaction occurs upon Nef binding the MHC-I cytoplasmic tail early during endocytosis in a Rab5-positive endosome. Disruption of early endosome regulation inhibited Nef-dependent MHC-I downregulation, demonstrating that Nef hijacks the early endosome to sequester MHC-I within the cell. Furthermore, super-resolution imaging identified that the Nef:MHC-I BiFC complex transits through both early and late endosomes before ultimately residing at the trans-Golgi network. Together we demonstrate the importance of the early stages of the endocytic network in the removal of MHC-I from the cell surface and its re-localization within the cell, which allows HIV-1 to optimally evade host immune responses. PMID:27841315

  10. 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

  11. Mouse Models for Studies of In Vivo Functions of HIV-1 Nef.

    PubMed

    Zou, Wei; Zhang, Lunli

    2016-01-01

    In vitro studies have demonstrated that HIV-1 Nef has several important activities, promoting viral replication and pathogenesis. These activities include downregulation of cell surface molecules CD4 and major histocompatibility complex class I, enhancement of viral infectivity, activation of p21-activated kinase 2, and inhibition of immunoglobulin class switching. But how important each in vitro activity is to in vivo Nef function remains elusive. To address this question, several small animal models have been developed in the past two decades, such as Nef transgenic mice, SCID-hu mice, and humanized mice. Each of those models has its own pros and cons. Easy access and relative inexpensiveness have made small animal models the favorite models for HIV research. This review will be focused on the recent progress in the understanding of the in vivo functions of HIV-1 Nef obtained from studies using these small animal models.

  12. Evidence for Adaptive Evolution at the Divergence Between Lymphoid and Brain HIV-1 nef Genes

    PubMed Central

    Olivieri, Kevin C.; Agopian, Kristin A.; Mukerji, Joya

    2010-01-01

    Abstract Human immunodeficiency virus type 1 (HIV) infection of the central nervous system frequently causes HIV-associated neurocognitive disorders (HAND). The role of HIV Nef and other accessory proteins in HAND pathogenesis is unclear. To determine whether HIV nef undergoes adaptive selection in brain, we cloned 100 nef sequences (n = 30 brain and n = 70 lymphoid) from four patients with AIDS and HIV-associated dementia (HAD). Normalized nonsynonymous substitutions were more frequent at the divergence of lymphoid and brain sequences, indicating stronger adaptive selection in brain compared to lymphoid tissue. Brain-specific nonsynonymous substitutions were found within an NH3-terminal CTL epitope, the PACS1 binding motif, or positions predicted to be important for activation of the myeloid-restricted Src family tyrosine kinase Hck. These results suggest that adaptive selection of HIV nef in brain may reflect altered requirements for efficient replication in macrophages and brain-specific immune selection pressures. PMID:20377428

  13. 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…

  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. Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension.

    PubMed

    Almodovar, Sharilyn; Knight, Rob; Allshouse, Amanda A; Roemer, Sarah; Lozupone, Catherine; McDonald, Daniel; Widmann, Jeremy; Voelkel, Norbert F; Shelton, Robert J; Suarez, Edu B; Hammer, Kenneth W; Goujard, Cecile; Petrosillo, Nicola; Simonneau, Gerald; Hsue, Priscilla Y; Humbert, Marc; Flores, Sonia C

    2012-06-01

    Severe pulmonary hypertension (PH) associated with vascular remodeling is a long-term complication of HIV infection (HIV-PH) affecting 1/200 infected individuals vs. 1/200,000 frequency in the uninfected population. Factors accounting for increased PH susceptibility in HIV-infected individuals are unknown. Rhesus macaques infected with chimeric SHIVnef virions but not with SIV display PH-like pulmonary vascular remodeling suggesting that HIV-Nef is associated with PH; these monkeys showed changes in nef sequences that correlated with pathogenesis after passage in vivo. We further examined whether HIV-nef alleles in HIV-PH subjects have signature sequences associated with the disease phenotype. We evaluated specimens from participants with and without HIV-PH from European Registries and validated results with samples collected as part of the Lung-HIV Studies in San Francisco. We found that 10 polymorphisms in nef were overrepresented in blood cells or lung tissue specimens from European HIV-PH individuals but significantly less frequent in HIV-infected individuals without PH. These polymorphisms mapped to known functional domains in Nef. In the validation cohort, 7/10 polymorphisms in the HIV-nef gene were confirmed; these polymorphisms arose independently from viral load, CD4(+) T cell counts, length of infection, and antiretroviral therapy status. Two out of 10 polymorphisms were previously reported in macaques with PH-like pulmonary vascular remodeling. Cloned recombinant Nef proteins from clinical samples down-regulated CD4, suggesting that these primary isolates are functional. This study offers new insights into the association between Nef polymorphisms in functional domains and the HIV-PH phenotype. The utility of these polymorphisms as predictors of PH should be examined in a larger population.

  16. RPython high-level synthesis

    NASA Astrophysics Data System (ADS)

    Cieszewski, Radoslaw; Linczuk, Maciej

    2016-09-01

    The development of FPGA technology and the increasing complexity of applications in recent decades have forced compilers to move to higher abstraction levels. Compilers interprets an algorithmic description of a desired behavior written in High-Level Languages (HLLs) and translate it to Hardware Description Languages (HDLs). This paper presents a RPython based High-Level synthesis (HLS) compiler. The compiler get the configuration parameters and map RPython program to VHDL. Then, VHDL code can be used to program FPGA chips. In comparison of other technologies usage, FPGAs have the potential to achieve far greater performance than software as a result of omitting the fetch-decode-execute operations of General Purpose Processors (GPUs), and introduce more parallel computation. This can be exploited by utilizing many resources at the same time. Creating parallel algorithms computed with FPGAs in pure HDL is difficult and time consuming. Implementation time can be greatly reduced with High-Level Synthesis compiler. This article describes design methodologies and tools, implementation and first results of created VHDL backend for RPython compiler.

  17. Human Immunodeficiency Virus Type 1 Nef-Induced CD4 Cell Surface Downregulation Is Inhibited by Ikarugamycin

    PubMed Central

    Luo, Tianci; Fredericksen, Brenda L.; Hasumi, Keiji; Endo, Akira; Garcia, J. Victor

    2001-01-01

    One well-characterized in vitro function of Nef is its ability to remove CD4, the human immunodeficiency virus (HIV) receptor, from the cell surface. Nef accomplishes this by accelerating the internalization and degradation of CD4. Current models propose that Nef promotes CD4 internalization via an increased association of CD4 with clathrin-coated pits (CCP). Here, we investigated the effect of a naturally occurring antiprotozoan antibiotic, ikarugamycin (IKA), on CD4 cell surface expression in human monocytic cells stably expressing HIV type 1 SF2 Nef. IKA was able to efficiently restore CD4 cell surface expression in Nef-expressing cells without affecting either CD4 synthesis or Nef expression. In addition, we demonstrate that IKA is also capable of efficiently blocking CD4 down-modulation in response to phorbol myristate acetate. Our data suggest that IKA may be an efficient and useful inhibitor of CCP-dependent endocytosis. PMID:11160755

  18. Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling

    PubMed Central

    Campbell, Patrick E.; Isayev, Olexandr; Ali, Syed A.; Roth, William W.; Huang, Ming-Bo; Powell, Michael D.; Leszczynski, Jerzy

    2012-01-01

    The HIV-1 accessory protein Nef plays an active role in the pathogenesis of AIDS by its numerous cellular interactions that facilitate the release of virus particles. This 27 kDa protein is required for maintenance of the viral replication in HIV, and is also known to contribute to immune evasion, blocking of apoptosis in virus-infected cells and enhancement of virus infectivity. Nef has been shown to be secreted and is present on the surface of virus-infected cells. Recent studies from our laboratory have shown that the Nef protein is secreted from nef-transfected and HIV-1-infected cells in small exosome-like vesicles (40–100 nm diam.) that do not contain virions. We have identified three amino-terminal domains of Nef as necessary for secretion: (i) the four arginine residues (17,19,21, 22) comprising the basic region; (ii) the phosphofurin acidic cluster sequence (PACS) composed of four glutamic acid residues (61–64); (iii) a previously unknown motif spanning amino acid residues 65–69 (VGFPV) which we named the secretion modification region (SMR). In this study, we have used population-based phylogeny data and sequence analysis to characterize the conservation of the Nef SMR domain that regulates vesicle secretion. We have performed in silico computational chemistry analysis involving molecular dynamic structure modeling of mutations in the SMR motif. Sequence analysis of Nef from HIV-1-infected patients, including slow progressors (SP), long term progressors (LTP) and long term non-progressors (LTNP) demonstrated 99 % conservation of the Nef SMR motif. Computational analysis including modeling of wild-type HIV-1 Nef and V66A Nef SMR mutant using structural homology and molecular dynamics of ligand-associated interactions indicated significant structural changes in the Nef mutant, thus supporting the importance of the SMR domain for mediating Nef vesicle secretion. PMID:22643973

  19. Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen

    PubMed Central

    2013-01-01

    Background HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoting viral infectivity, replication and downregulation of cell-surface MHC-I molecules. In this study, we developed a yeast-based phenotypic screen to identify small molecules that inhibit the Nef-Hck complex. Results Nef-Hck interaction was faithfully reconstituted in yeast cells, resulting in kinase activation and growth arrest. Yeast cells expressing the Nef-Hck complex were used to screen a library of small heterocyclic compounds for their ability to rescue growth inhibition. The screen identified a dihydrobenzo-1,4-dioxin-substituted analog of 2-quinoxalinyl-3-aminobenzene-sulfonamide (DQBS) as a potent inhibitor of Nef-dependent HIV-1 replication and MHC-I downregulation in T-cells. Docking studies predicted direct binding of DQBS to Nef which was confirmed in differential scanning fluorimetry assays with recombinant purified Nef protein. DQBS also potently inhibited the replication of HIV-1 NL4-3 chimeras expressing Nef alleles representative of all M-group HIV-1 clades. Conclusions Our findings demonstrate the utility of a yeast-based growth reversion assay for the identification of small molecule Nef antagonists. Inhibitors of Nef function discovered with this assay, such as DQBS, may complement the activity of current antiretroviral therapies by enabling immune recognition of HIV-infected cells through the rescue of cell surface MHC-I. PMID:24229420

  20. CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef.

    PubMed Central

    Chen, B K; Gandhi, R T; Baltimore, D

    1996-01-01

    The human immunodeficiency virus type 1 (HIV-1) genes vpu, env, and nef have all been implicated in modulating the levels of cell surface CD4 on infected cells. To quantitatively assess the relative contribution of each gene product to the regulation of CD4 during HIV infection of Jurkat T cells and peripheral blood mononuclear cells, we have developed an infectious HIV reporter system which expresses different combinations of these genes. To distinguish infected cells in the early or late stages of infection from uninfected cells, these viruses were designed to express human placental alkaline phosphatase with the kinetics of either early or late viral genes. Flow cytometry to detect placental alkaline phosphatase and CD4 in infected cells showed that vpu, env, and nef are independently capable of down-modulation of CD4. As predicted by their respective expression patterns, nef down-modulated CD4 rapidly during the early phase of virus infection whereas vpu and env functioned late in the infection. In both Jurkat cells and peripheral blood mononuclear cells, a combination of the three genes was more efficient than any one or two genes, demonstrating that all three genes are required to achieve maximal CD4 down-modulation. In primary cells, down-modulation of CD4 was less efficient than in Jurkat cells and there was a stronger dependence on nef function for reducing cell surface CD4. HIV therefore has three genes that are able to independently down-modulate CD4; together, they can eliminate the bulk of cell surface CD4. PMID:8709227

  1. 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

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

    PubMed

    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

    2016-04-01

    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.

  3. 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.

  4. IL-12 and GM-CSF in DNA/MVA Immunizations against HIV-1 CRF12_BF Nef Induced T-Cell Responses With an Enhanced Magnitude, Breadth and Quality

    PubMed Central

    Rodríguez, Ana María; Falivene, Juliana; Holgado, María Pía; Turk, Gabriela; Gherardi, María Magdalena

    2012-01-01

    In Argentina, the HIV epidemic is characterized by the co-circulation of subtype B and BF recombinant viral variants. Nef is an HIV protein highly variable among subtypes, making it a good tool to study the impact of HIV variability in the vaccine design setting. We have previously reported a specific cellular response against NefBF with low cross-reactivity to NefB in mice. The aim of this work was to analyze whether the co-administration of IL-12 and GM-CSF, using DNA and MVA vaccine vectors, could improve the final cellular response induced. Mice received three DNA priming doses of a plasmid that express NefBF plus DNAs expressing IL-12 and/or GM-CSF. Afterwards, all the groups were boosted with a MVAnefBF dose. The highest increase in the magnitude of the NefBF response, compared to that induced in the control was found in the IL-12 group. Importantly, a response with higher breadth was detected in groups which received IL-12 or GM-CSF, evidenced as an increased frequency of recognition of homologous (BF) and heterologous (B) Nef peptides, as well as a higher number of other Nef peptide pools representing different viral subtypes. However, these improvements were lost when both DNA cytokines were simultaneously administered, as the response was focused against the immunodominant peptide with a detrimental response towards subdominant epitopes. The pattern of cytokines secreted and the specific-T-cell proliferative capacity were improved in IL-12 and IL-12+GM-CSF groups. Importantly IL-12 generated a significant higher T-cell avidity against a B heterologous peptide. This study indicates that the incorporation of DNA expressing IL-12 in DNA/MVA schemes produced the best results in terms of improvements of T-cell-response key properties such as breadth, cross-reactivity and quality (avidity and pattern of cytokines secreted). These relevant results contribute to the design of strategies aimed to induce T-cell responses against HIV antigens with higher quality

  5. 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

  6. Species-Specific Activity of SIV Nef and HIV-1 Vpu in Overcoming Restriction by Tetherin/BST2

    PubMed Central

    Neidermyer, William; Rahmberg, Andrew; Mackey, John; Fofana, Ismael Ben; Johnson, Welkin E.; Westmoreland, Susan; Evans, David T.

    2009-01-01

    Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host–cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the SIVsmm/mac/HIV-2 lineage do not have a vpu gene, this activity has likely been assumed by other viral gene products. We found that deletion of the SIVmac239 nef gene significantly impaired virus release in cells expressing rhesus macaque tetherin. Virus release could be restored by expressing Nef in trans. However, Nef was unable to facilitate virus release in the presence of human tetherin. Conversely, Vpu enhanced virus release in the presence of human tetherin, but not in the presence of rhesus tetherin. In accordance with the species-specificity of Nef in mediating virus release, SIV Nef downregulated cell-surface expression of rhesus tetherin, but did not downregulate human tetherin. The specificity of SIV Nef for rhesus tetherin mapped to four amino acids in the cytoplasmic domain of the molecule that are missing from human tetherin, whereas the specificity of Vpu for human tetherin mapped to amino acid differences in the transmembrane domain. Nef alleles of SIVsmm, HIV-2 and HIV-1 were also able to rescue virus release in the presence of both rhesus macaque and sooty mangabey tetherin, but were generally ineffective against human tetherin. Thus, the ability of Nef to antagonize tetherin from these Old World primates appears to be conserved among the primate lentiviruses. These results identify Nef as the viral gene product of SIV that opposes restriction by tetherin in rhesus macaques and sooty mangabeys, and reveal species-specificity in the activities of both Nef and Vpu in overcoming tetherin in their respective hosts. PMID:19436700

  7. 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.

  8. SIVsm Tat, Rev, and Nef1: functional characteristics of r-GV internalization on isotypes, cytokines, and intracellular degradation

    PubMed Central

    2010-01-01

    Background Recombinant gas vesicles (r-GV) from Halobacterium sp. strain SD109 expressing cassettes with different SIVsm inserts, have potential utility as an effective antigen display system for immunogen testing in vivo and for initial epitope assessments in vitro. Previous mouse model studies demonstrated immunization with r-GV expressing selected exogenous sequences elicited a prolonged immune response. Here we tested segments from three SIVsm genes (tat, rev, and nef) each surface displayed by r-GV. As with HIV, for SIVsm the proteins encoded by tat, rev and nef respectively serve critical and diverse functions: effects on efficient viral RNA polymerase II transcription, regulation of viral gene expression and effects on specific signaling functions through the assembly of multiprotein complexes. Humoral responses to r-GVTat, Rev or Nef1 elicited in vivo, associated changes in selected cell cytokine production following r-GV internalization, and the capacity of J774A.1 macrophage cells to degrade these internalized display/delivery particles in vitro were examined. Results The in vivo studies involving r-GV immunizations and in vitro studies of r-GV uptake by J774A.1 macrophages demonstrated: (i) tests for antibody isotypes in immunized mice sera showed activation and re-stimulation of memory B cells, (ii) during long term immune response to the epitopes, primarily the IgG1 isotype was produced, (iii) in vitro, macrophage degradation of r-GV containing different SIVsm inserts occurred over a period of days resulting in an inherent slow breakdown and degradation of the SIVsm peptide inserts, (iv) vesicle specific GvpC, a larger protein, degraded more slowly than the recombinant peptide inserts and (v) in vitro uptake and degradation of the r-GV populations tested was associated with SIVsm insert specific patterns for cytokines IL-10, IL-12 and IL-18. Conclusions Together these findings provide new information underscoring r-GV potential. They can clearly

  9. High-Level Connectionist Models

    DTIC Science & Technology

    1990-04-01

    Freeman, 1987) and on the mathematical level ( Derrida & Meir, 1988; Huberman & Hogg, 1987; Kurten, 1987). It is time that this link be further...Wesley. Derrida B. & Meir, R. (198sL80moac behavior of a layered neural network. Phys. Rev. A, 38. Elman, J. L. (1988). Findi4 Structure in Time. Report...and Huberman, 1983; Kurten and Clark. 1986; Babcock and Westervelt, 1987; Derrida and Meir, 1988; Riedal et al., 1988; Sompolin- sky et al., 1988

  10. Differential signaling mechanism for HIV-1 Nef-mediated production of IL-6 and IL-8 in human astrocytes.

    PubMed

    Liu, Xun; Kumar, Anil

    2015-06-15

    Variety of HIV-1 viral proteins including HIV-1 Nef are known to activate astrocytes and microglia in the brain and cause the release of pro-inflammatory cytokines, which is thought to be one of the mechanisms leading to HIV-1- mediated neurotoxicity. IL-6 and IL-8 have been found in the CSF of patients with HIV-1 associated dementia (HAD), suggesting that they might play important roles in HIV-1 neuropathology. In the present study we examined the effects of HIV-1 Nef on IL-6 and IL-8 induction in astrocytes. The results demonstrate that both IL-6 and IL-8 are significantly induced in HIV-1 Nef-transfected SVGA astrocytes and HIV-1 Nef-treated primary fetal astrocytes. We also determined the molecular mechanisms responsible for the HIV-1 Nef-induced increased IL-6 and IL-8 by using chemical inhibitors and siRNAs against PI3K/Akt/PKC, p38 MAPK, NF-κB, CEBP and AP-1. Our results clearly demonstrate that the PI3K/PKC, p38 MAPK, NF-κB and AP-1 pathways are involved in HIV-1 Nef-induced IL-6 production in astrocytes, while PI3K/PKC and NF-κB pathways are involved in HIV-1 Nef-induced IL-8 production. These results offer new potential targets to develop therapeutic strategy for treatment of HIV-1 associated neurological disorders, prevalent in > 40% of individuals infected with HIV-1.

  11. 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

  12. Nef from primary isolates of human immunodeficiency virus type 1 suppresses surface CD4 expression in human and mouse T cells.

    PubMed Central

    Anderson, S; Shugars, D C; Swanstrom, R; Garcia, J V

    1993-01-01

    The human immunodeficiency virus type 1 (HIV-1) nef gene was originally described as a negative regulator of transcription from the viral long terminal repeat promoter. This observation has been disputed, and the function of Nef remains unclear. In vivo experiments have indicated that an intact nef gene is required for disease progression in macaques infected with simian immunodeficiency virus, suggesting a role for Nef in the pathogenesis of AIDS. We and others have previously shown that expression of Nef in cells bearing surface CD4 results in a sustained decrease in surface CD4 expression. This was demonstrated for Nef from two laboratory strains of HIV-1, Bru and SF2. Because both of these isolates were passaged in vitro prior to molecular cloning and in vitro passage can result in mutations which might alter nef gene function, we have analyzed two primary isolates of Nef for their ability to suppress cell surface CD4 expression. The nef genes of HIV-1 isolates from two patients with fewer than 200 CD4+ T cells per mm3 of blood were introduced into human and mouse T-cell lines by retrovirus-mediated gene transfer. Expression of Nef from both isolates correlated with a decrease in surface expression of both human and mouse CD4. To determine whether the ability to suppress surface CD4 expression is a general function of Nef, we also tested an artificially generated consensus nef gene derived from analysis of 54 patient isolates of HIV-1. Expression of the consensus Nef protein also correlated with decreased cell surface CD4 expression in both mouse and human T-cell lines. These results suggest that the ability to suppress cell surface CD4 expression is an intrinsic feature of HIV-1 Nef. Images PMID:8331733

  13. Cell-based Fluorescence Complementation Reveals a Role for HIV-1 Nef Protein Dimerization in AP-2 Adaptor Recruitment and CD4 Co-receptor Down-regulation.

    PubMed

    Shu, Sherry T; Emert-Sedlak, Lori A; Smithgall, Thomas E

    2017-02-17

    The HIV-1 Nef accessory factor enhances viral infectivity, immune evasion, and AIDS progression. Nef triggers rapid down-regulation of CD4 via the endocytic adaptor protein 2 (AP-2) complex, a process linked to enhanced viral infectivity and immune escape. Here, we describe a bimolecular fluorescence complementation (BiFC) assay to visualize the interaction of Nef with AP-2 and CD4 in living cells. Interacting protein pairs were fused to complementary non-fluorescent fragments of YFP and co-expressed in 293T cells. Nef interactions with both CD4 and AP-2 resulted in complementation of YFP and a bright fluorescent signal by confocal microcopy that localized to the cell periphery. Co-expression of the AP-2 α subunit enhanced the Nef·AP-2 σ2 subunit BiFC signal and vice versa, suggesting that the AP-2 α-σ2 hemicomplex interacts cooperatively with Nef. Mutagenesis of Nef amino acids Arg-134, Glu-174, and Asp-175, which stabilize Nef for AP-2 α-σ2 binding in a recent co-crystal structure, substantially reduced AP-2 interaction without affecting CD4 binding. A dimerization-defective mutant of Nef failed to interact with either CD4 or AP-2 in the BiFC assay, indicating that Nef quaternary structure is required for CD4 and AP-2 recruitment as well as CD4 down-regulation. A small molecule previously shown to bind the Nef dimerization interface also reduced Nef interactions with AP-2 and CD4 and restored CD4 expression to the surface of HIV-infected cells. Our findings provide a mechanistic explanation for previous observations that dimerization-defective Nef mutants fail to down-regulate CD4 and validate the Nef dimerization interface as a target site for antiretroviral drug development.

  14. HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.

    PubMed

    Shen, Qing-Tao; Ren, Xuefeng; Zhang, Rui; Lee, Il-Hyung; Hurley, James H

    2015-10-23

    The lentiviruses HIV and simian immunodeficiency virus (SIV) subvert intracellular membrane traffic as part of their replication cycle. The lentiviral Nef protein helps viruses evade innate and adaptive immune defenses by hijacking the adaptor protein 1 (AP-1) and AP-2 clathrin adaptors. We found that HIV-1 Nef and the guanosine triphosphatase Arf1 induced trimerization and activation of AP-1. Here we report the cryo-electron microscopy structures of the Nef- and Arf1-bound AP-1 trimer in the active and inactive states. A central nucleus of three Arf1 molecules organizes the trimers. We combined the open trimer with a known dimer structure and thus predicted a hexagonal assembly with inner and outer faces that bind the membranes and clathrin, respectively. Hexagons were directly visualized and the model validated by reconstituting clathrin cage assembly. Arf1 and Nef thus play interconnected roles in allosteric activation, cargo recruitment, and coat assembly, revealing an unexpectedly intricate organization of the inner AP-1 layer of the clathrin coat.

  15. The HIV proteins Tat and Nef promote human bone marrow mesenchymal stem cell senescence and alter osteoblastic differentiation.

    PubMed

    Beaupere, Carine; Garcia, Marie; Larghero, Jerome; Fève, Bruno; Capeau, Jacqueline; Lagathu, Claire

    2015-08-01

    To maintain bone mass turnover and bone mineral density (BMD), bone marrow (BM) mesenchymal stem cells (MSCs) are constantly recruited and subsequently differentiated into osteoblasts. HIV-infected patients present lower BMD than non-HIV infected individuals and a higher prevalence of osteopenia/osteoporosis. In antiretroviral treatment (ART)-naive patients, encoded HIV proteins represent pathogenic candidates. They are released by infected cells within BM and can impact on neighbouring cells. In this study, we tested whether HIV proteins Tat and/or Nef could induce senescence of human BM-MSCs and reduce their capacity to differentiate into osteoblasts. When compared to nontreated cells, MSCs chronically treated with Tat and/or Nef up to 30 days reduced their proliferative activity and underwent early senescence, associated with increased oxidative stress and mitochondrial dysfunction. The antioxidant molecule N-acetyl- cysteine had no or minimal effects on Tat- or Nef-induced senescence. Tat but not Nef induced an early increase in NF-κB activity and cytokine/chemokine secretion. Tat-induced effects were prevented by the NF-κB inhibitor parthenolide, indicating that Tat triggered senescence via NF-κB activation leading to oxidative stress. Otherwise, Nef- but not Tat-treated cells displayed early inhibition of autophagy. Rapamycin, an autophagy inducer, reversed Nef-induced senescence and oxidative stress. Moreover, Tat+Nef had cumulative effects. Finally, Tat and/or Nef decreased the MSC potential of osteoblastic differentiation. In conclusion, our in vitro data show that Tat and Nef could reduce the number of available precursors by inducing MSC senescence, through either enhanced inflammation or reduced autophagy. These results offer new insights into the pathophysiological mechanisms of decreased BMD in HIV-infected patients.

  16. The HIV proteins Tat and Nef promote human bone marrow mesenchymal stem cell senescence and alter osteoblastic differentiation

    PubMed Central

    Beaupere, Carine; Garcia, Marie; Larghero, Jerome; Fève, Bruno; Capeau, Jacqueline; Lagathu, Claire

    2015-01-01

    To maintain bone mass turnover and bone mineral density (BMD), bone marrow (BM) mesenchymal stem cells (MSCs) are constantly recruited and subsequently differentiated into osteoblasts. HIV-infected patients present lower BMD than non-HIV infected individuals and a higher prevalence of osteopenia/osteoporosis. In antiretroviral treatment (ART)-naive patients, encoded HIV proteins represent pathogenic candidates. They are released by infected cells within BM and can impact on neighbouring cells. In this study, we tested whether HIV proteins Tat and/or Nef could induce senescence of human BM-MSCs and reduce their capacity to differentiate into osteoblasts. When compared to nontreated cells, MSCs chronically treated with Tat and/or Nef up to 30 days reduced their proliferative activity and underwent early senescence, associated with increased oxidative stress and mitochondrial dysfunction. The antioxidant molecule N-acetyl- cysteine had no or minimal effects on Tat- or Nef-induced senescence. Tat but not Nef induced an early increase in NF-κB activity and cytokine/chemokine secretion. Tat-induced effects were prevented by the NF-κB inhibitor parthenolide, indicating that Tat triggered senescence via NF-κB activation leading to oxidative stress. Otherwise, Nef- but not Tat-treated cells displayed early inhibition of autophagy. Rapamycin, an autophagy inducer, reversed Nef-induced senescence and oxidative stress. Moreover, Tat+Nef had cumulative effects. Finally, Tat and/or Nef decreased the MSC potential of osteoblastic differentiation. In conclusion, our in vitro data show that Tat and Nef could reduce the number of available precursors by inducing MSC senescence, through either enhanced inflammation or reduced autophagy. These results offer new insights into the pathophysiological mechanisms of decreased BMD in HIV-infected patients. PMID:25847297

  17. 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.

  18. HIV’s Nef Interacts with β-Catenin of the Wnt Signaling Pathway in HEK293 Cells

    PubMed Central

    Weiser, Keren; Barton, Meredith; Gershoony, Dafna; DasGupta, Ramanuj; Cardozo, Timothy

    2013-01-01

    The Wnt signaling pathway is implicated in major physiologic cellular functions, such as proliferation, migration, cell fate specification, maintenance of pluripotency and induction of tumorigenicity. Proliferation and migration are important responses of T-cells, which are major cellular targets of HIV infection. Using an informatics screen, we identified a previously unsuspected interaction between HIV’s Nef protein and β-catenin, a key component of the Wnt pathway. A segment in Nef contains identical amino acids at key positions and structurally mimics the β-catenin binding sites on endogenous β-catenin ligands. The interaction between Nef and β-catenin was confirmed in vitro and in a co-immunoprecipitation from HEK293 cells. Moreover, the introduction of Nef into HEK293 cells specifically inhibited a Wnt pathway reporter. PMID:24130899

  19. Dissociation of the CD4 downregulation and viral infectivity enhancement functions of human immunodeficiency virus type 1 Nef.

    PubMed Central

    Goldsmith, M A; Warmerdam, M T; Atchison, R E; Miller, M D; Greene, W C

    1995-01-01

    Recent evidence indicates that the nef gene of human immunodeficiency virus type 1 augments rather than inhibits viral replication in both cell culture and in vivo models. In addition, nef alters various normal cellular processes, including the display of CD4 on the cell surface. However, it remains unknown whether the enhancement of infectivity and the downregulation of CD4 represent linked or independent biologic properties of this single protein. In the present studies, mutational analyses were performed to define structure-function relationships within the Nef protein that mediate these effects. To assess the functional consequences of these mutations, sensitive and reliable assays were developed to quantitate the viral infectivity enhancement and CD4 downregulation functions of Nef. The results indicate that membrane-targeting sequences at the N terminus of Nef are important for both functions of Nef, while certain other conserved regions are dispensable for both functions. A conserved proline-X-X repeat segment in the central core of the protein, which is reminiscent of an SH3-binding domain, is critical for the enhancement of infectivity function but is dispensable for CD4 downregulation. However, the downregulation of CD4 by Nef appears to involve a two-step process requiring the initial dissociation of p56lck from CD4 to permit engagement of the endocytic apparatus by CD4. Together, these findings demonstrate that the infectivity enhancement and CD4 downregulation activities of human immunodeficiency virus type 1 Nef can be dissociated. Thus, these processes may be independent of one another in the viral replication cycle. PMID:7769669

  20. Brain transcriptome-wide screen for HIV-1 Nef protein interaction partners reveals various membrane-associated proteins.

    PubMed

    Kammula, Ellen C; Mötter, Jessica; Gorgels, Alexandra; Jonas, Esther; Hoffmann, Silke; Willbold, Dieter

    2012-01-01

    HIV-1 Nef protein contributes essentially to the pathology of AIDS by a variety of protein-protein-interactions within the host cell. The versatile functionality of Nef is partially attributed to different conformational states and posttranslational modifications, such as myristoylation. Up to now, many interaction partners of Nef have been identified using classical yeast two-hybrid screens. Such screens rely on transcriptional activation of reporter genes in the nucleus to detect interactions. Thus, the identification of Nef interaction partners that are integral membrane proteins, membrane-associated proteins or other proteins that do not translocate into the nucleus is hampered. In the present study, a split-ubiquitin based yeast two-hybrid screen was used to identify novel membrane-localized interaction partners of Nef. More than 80% of the hereby identified interaction partners of Nef are transmembrane proteins. The identified hits are GPM6B, GPM6A, BAP31, TSPAN7, CYB5B, CD320/TCblR, VSIG4, PMEPA1, OCIAD1, ITGB1, CHN1, PH4, CLDN10, HSPA9, APR-3, PEBP1 and B3GNT, which are involved in diverse cellular processes like signaling, apoptosis, neurogenesis, cell adhesion and protein trafficking or quality control. For a subfraction of the hereby identified proteins we present data supporting their direct interaction with HIV-1 Nef. We discuss the results with respect to many phenotypes observed in HIV infected cells and patients. The identified Nef interaction partners may help to further elucidate the molecular basis of HIV-related diseases.

  1. Nef-M1, a peptide antagonist of CXCR4, inhibits tumor angiogenesis and epithelial‑to‑mesenchymal transition in colon and breast cancers.

    PubMed

    Katkoori, Venkat R; Basson, Marc D; Bond, Vincent C; Manne, Upender; Bumpers, Harvey L

    2015-09-29

    The Nef-M1 peptide competes effectively with the natural ligand of CXC chemokine receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and inhibit growth in colon cancer (CRC) and breast cancer (BC). Its role in tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT) regulation, key steps involved in tumor growth and metastasis, are unknown. We evaluated the angioinhibitory effect of Nef-M1 peptide and examined its role in the inhibition of EMT in these cancers. Colon (HT29) and breast (MDA-MB231) cancer cells expressing CXCR4 were studied in vitro and in xenograft tumors propagated in severe combined immunodeficient mice. The mice were treated intraperitoneally with Nef-M1 or scrambled amino acid sequence of Nef-M1 (sNef-M1) peptide, a negative control, starting at the time of tumor implantation. Sections from tumors were evaluated for tumor angiogenesis, as measured by microvessel density (MVD) based on immunostaining of endothelial markers. In vitro tumor angiogenesis was assessed by treating human umbilical vein endothelial cells with conditioned media from the tumor cell lines. A BC cell line (MDA-MB 468) which does not express CXCR4 was used to study the actions of Nef-M1 peptide. Western blot and immunofluorescence analyses assessed the effect of Nef-M1 on tumor angiogenesis and EMT in both tumors and cancer cells. Metastatic lesions of CRC and BC expressed more CXCR4 than primary lesions. It was also found that tumors from mice treated with sNef-M1 had well established vascularity, while Nef-M1 treated tumors had very poor vascularization. Indeed, the mean MVD was lower in tumors from Nef-M1 treated mice than in sNef-M1 treated tumors. Nef-M1 treated tumor has poor morphology and loss of endothelial integrity. Although conditioned medium from CRC or BC cells supported HUVEC tube formation, the conditioned medium from Nef-M1 treated CRC or BC cells did not support tube formation. Western blot analyses revealed that Nef-M1

  2. Association of the dopamine receptor interacting protein gene, NEF3, with early response to antipsychotic medication.

    PubMed

    Strous, Rael D; Greenbaum, Lior; Kanyas, Kyra; Merbl, Yifat; Horowitz, Anat; Karni, Osnat; Viglin, Dina; Olender, Tsviya; Deshpande, Smita N; Lancet, Doron; Ben-Asher, Edna; Lerer, Bernard

    2007-06-01

    Genetic variation in antipsychotic drug targets could underlie variability among patients in the time required for antipsychotic effects to be elicited. In a clinical, pharmacogenetic study we focused on the dopamine receptor interacting protein (DRIP) gene family. DRIPs are pivotally involved in regulating dopamine receptor signal transduction. Consecutively hospitalized, acutely psychotic patients with DSM-IV schizophrenia (n=121) were included in the study if they received treatment with typical antipsychotic medication (TYP, n=72) or TYP plus risperidone (TYP-R, n=49) for at least 2 wk. Clinical state and adverse effects were rated at baseline and after 2 wk. Patients improved significantly on both TYP and TYP-R with no significant difference between them. Early responders were defined as patients whose PANSS change scores were greater than the median. Twenty-two single nucleotide polymorphisms (SNPs) were analysed in five DRIP-encoding genes. Two SNPs in NEF3, which encodes the DRIP, neurofilament-medium (NF-M), were associated with early response (rs1457266, p=0.01; rs1379357, p=0.006). A 5 SNP haplotype spanning NEF3 was over-represented in early responders (p=0.015), in the combined patient group and in the TYP group alone. These findings suggest that variation in NEF3, most likely functional variants that are in linkage disequilibrium with the SNPs that we studied, influences rate of response to TYP. Since NEF3 is primarily associated with dopamine D1 receptor function, the evidence for a complementary role of dopamine D1 receptors in antipsychotic effects is considered. The findings reported here open an interesting research avenue in the pharmacogenetics of antipsychotic effects but require replication in larger samples treated in a controlled context.

  3. 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.

  4. 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

  5. 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

    2016-03-03

    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.

  6. 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…

  7. 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.

  8. Mutations in the nef and vif genes associated with progression to AIDS in elite controller and slow-progressor patients.

    PubMed

    Cruz, Nadia V G; Amorim, Raquel; Oliveira, Fátima E; Speranza, Francisco A C; Costa, Luciana J

    2013-04-01

    Progression towards AIDS can vary from 5 to 10 years from the establishment of the primary infection by HIV-1 to more than 10 years in the complete absence of antiretroviral therapy. Several factors can contribute to the outcome of HIV infection, including host genetic and viral replicating characteristics. Historically, nef-deleted viral genomes have been associated with disease progression. Therefore, the lentiviral Nef protein is regarded as a progression factor. The objective of this work was to characterize the nef gene from a group of treatment naive patients infected with HIV-1 for more than 10 years. These patients were classified as long-term non-progressors, elite controller, and slow-progressors according to clinical and laboratorial data. A premature stop codon within the nef gene leading to the expression of a truncated peptide was observed on samples from the elite controller patient. For the slow-progressor patients, several degrees of deletions at the C-terminal of Nef were observed predicting a loss of function of this protein. The vif gene was characterized for these patients and a rare mutation that predicts a miss localization of the Vif protein to the nucleus of infected cells that could prevent its function as an APOBEC neutralization factor was also observed. These data indicate the importance of the HIV accessory proteins as factors that contribute to the outcome of AIDS.

  9. Case hardenability at high carbon levels

    SciTech Connect

    Walton, H.W.

    1995-02-01

    Loss of hardenability in the case was thought to be responsible for a lower than specified hardness found on a large carburized bushing. Pseudo Jominy testing on several high hardenability carburizing grades confirmed that hardenability fade was present at carbon levels above 0.65% and particularly for those steels containing molybdenum. Analysis of previous work provided a formula for calculating Jominy hardenability at various carbon levels. Again the results confirmed that the loss of hardenability was more severe in steels containing molybdenum.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Antibodies to gp41 and nef in otherwise HIV-negative homosexual man with Kaposi's sarcoma.

    PubMed

    Bowden, F J; McPhee, D A; Deacon, N J; Cumming, S A; Doherty, R R; Sonza, S; Lucas, C R; Crowe, S M

    1991-06-01

    A homosexual man with histologically confirmed Kaposi's sarcoma remained seronegative for HIV-1, HIV-2, and HTLV-1 on conventional tests over a 4-year period. HIV cultures were also negative on thirteen separate occasions. However, serum antibodies to synthetic peptide analogues of the gp41 and nef regions of HIV-1 were consistently detected on an enzyme immunoassay. Tests with the polymerase chain reaction with primers directed to the gag and env regions were negative. The antigens to which the antibodies were produced might have come from a defective HIV mutant, another retrovirus, or a hitherto unknown "agent of Kaposi's sarcoma" with similar antigenic epitopes.

  16. Python based high-level synthesis compiler

    NASA Astrophysics Data System (ADS)

    Cieszewski, Radosław; Pozniak, Krzysztof; Romaniuk, Ryszard

    2014-11-01

    This paper presents a python based High-Level synthesis (HLS) compiler. The compiler interprets an algorithmic description of a desired behavior written in Python and map it to VHDL. FPGA combines many benefits of both software and ASIC implementations. Like software, the mapped circuit is flexible, and can be reconfigured over the lifetime of the system. FPGAs therefore have the potential to achieve far greater performance than software as a result of bypassing the fetch-decode-execute operations of traditional processors, and possibly exploiting a greater level of parallelism. Creating parallel programs implemented in FPGAs is not trivial. This article describes design, implementation and first results of created Python based compiler.

  17. 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.

  18. Commissioning of the CMS High Level Trigger

    SciTech Connect

    Agostino, Lorenzo; et al.

    2009-08-01

    The CMS experiment will collect data from the proton-proton collisions delivered by the Large Hadron Collider (LHC) at a centre-of-mass energy up to 14 TeV. The CMS trigger system is designed to cope with unprecedented luminosities and LHC bunch-crossing rates up to 40 MHz. The unique CMS trigger architecture only employs two trigger levels. The Level-1 trigger is implemented using custom electronics, while the High Level Trigger (HLT) is based on software algorithms running on a large cluster of commercial processors, the Event Filter Farm. We present the major functionalities of the CMS High Level Trigger system as of the starting of LHC beams operations in September 2008. The validation of the HLT system in the online environment with Monte Carlo simulated data and its commissioning during cosmic rays data taking campaigns are discussed in detail. We conclude with the description of the HLT operations with the first circulating LHC beams before the incident occurred the 19th September 2008.

  19. 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.

  20. Liquid level measurement in high level nuclear waste slurries

    SciTech Connect

    Weeks, G.E.; Heckendorn, F.M.; Postles, R.L.

    1990-01-01

    Accurate liquid level measurement has been a difficult problem to solve for the Defense Waste Processing Facility (DWPF). The nuclear waste sludge tends to plug or degrade most commercially available liquid-level measurement sensors. A liquid-level measurement system that meets demanding accuracy requirements for the DWPF has been developed. The system uses a pneumatic 1:1 pressure repeater as a sensor and a computerized error correction system. 2 figs.

  1. 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

  2. Proton Affinity Calculations with High Level Methods.

    PubMed

    Kolboe, Stein

    2014-08-12

    Proton affinities, stretching from small reference compounds, up to the methylbenzenes and naphthalene and anthracene, have been calculated with high accuracy computational methods, viz. W1BD, G4, G3B3, CBS-QB3, and M06-2X. Computed and the currently accepted reference proton affinities are generally in excellent accord, but there are deviations. The literature value for propene appears to be 6-7 kJ/mol too high. Reported proton affinities for the methylbenzenes seem 4-5 kJ/mol too high. G4 and G3 computations generally give results in good accord with the high level W1BD. Proton affinity values computed with the CBS-QB3 scheme are too low, and the error increases with increasing molecule size, reaching nearly 10 kJ/mol for the xylenes. The functional M06-2X fails markedly for some of the small reference compounds, in particular, for CO and ketene, but calculates methylbenzene proton affinities with high accuracy.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Exposure to unusually high indoor radon levels

    SciTech Connect

    Rasheed, F.N. )

    1993-03-27

    Unusually high indoor radon concentrations were reported in a small village in western Tyrol, Austria. The authors have measured the seasonal course of indoor radon concentrations in 390 houses of this village. 71% of houses in winter and 33% in summer, showed radon values on the ground floor above the Austrian action level of 400 Bq/cm[sup 3]. This proportion results in an unusually high indoor radon exposure of the population. The radon source was an 8,700-year-old rock slide of granite gneiss, the largest of the alpine crystalline rocks. It has a strong emanating power because its rocks are heavily fractured and show a slightly increased uranium content. Previous reports show increased lung cancer mortality, myeloid leukemia, kidney cancer, melanoma, and prostate cancer resulting from indoor radon exposure. However, many studies fail to provide accurate information on indoor radon concentrations, classifying them merely as low, intermediate, and high, or they record only minor increases in indoor radon concentrations. Mortality data for 1970-91 were used to calculate age and sex standardized mortality rates (SMR) for 51 sites of carcinoma. The total population of Tyrol were controls. A significantly higher risk was recorded for lung cancer. The high SMR for lung cancer in female subjects is especially striking. Because the numbers were low for the other cancer sites, these were combined in one group to calculate the SMR. No significant increase in SMR was found for this group.

  8. 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.

  9. 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%.

  10. High Level Waste Disposal System Optimization

    SciTech Connect

    Dirk Gombert; M. Connolly; J. Roach; W. Holtzscheiter

    2005-02-01

    The high level waste (HLW) disposal system consists of the Yucca Mountain Facility (YMF) and waste product (e.g. glass) generation facilities. Responsibility for management is shared between the U. S. Department of Energy (DOE) Offices of Civilian Radioactive Waste Management (DOE-RW) and Environmental Management (DOE-EM). The DOE-RW license application and the Waste Acceptance System Requirements Document (WASRD), as well as the DOE-EM Waste Acceptance Product Specification for Vitrified High Level Waste Forms (WAPS) govern the overall performance of the system. This basis for HLW disposal should be reassessed to consider waste form and process technology research and development (R&D), which have been conducted by DOE-EM, international agencies (i.e. ANSTO, CEA), and the private sector; as well as the technical bases for including additional waste forms in the final license application. This will yield a more optimized HLW disposal system to accelerate HLW disposition, more efficient utilization of the YMF, and overall system cost reduction.

  11. 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.

  12. Comparative genetic variability in HIV-1 subtype C nef gene in early age groups of infants.

    PubMed

    Husain, Mohammad; Sharma, Uma; Gupta, Poonam; Singhal, Megha; Singh, Supriya; Gupta, Sunil; Venkatesh, S; Rai, Arvind

    2017-03-31

    Targeting properties of vertically transmitted viruses in early infancy is important to understand disease progression. To investigate genotypic characteristics of transmitted viruses, blood samples were obtained from infants aged 6 weeks-18 months, categorized in two age groups, acute (≤6 months) and early (>6-18 months). Nef having an important role in pathogenesis was selected to explore the viral characteristics. A total of 57 PCR positive samples, amplified by nef gene were sequenced. Analysis showed that 50 sequences belonged to subtype C. In one sequence of acute age group, a long insertion of 10 residues (AAERMRRAEP) in variable region and a 13 residues deletion (ATNNADCAWLEAQ) around proteolytic cleavage region of gene in another sequence was observed. Insertions were also observed in sequences of early age group, however, they ranged from 2-8 residues only. In one sequence of early age group, 3/4 Arginines at positions 19,21,22 of Arginine cluster were mutated to Glutamine, Alanine and Glutamine respectively. Entropy analysis of two age groups revealed presence of several residues with statistically significant differences in their variability. Among these, 15 (R18,R23,R24; A66,L68,Q71; E74,E77,E78; V87,M92; R119, P144, E167 and C176) belonged to functional motifs, out of which, 12 were in acute age group, suggesting that variability was greater in this group. Prediction of HLA binding peptide motif revealed that epitope LTFGWCFKL was present in >80% study sequences. This epitope was also present in maximum number of HLA types circulating in India and vaccine candidate sequences, suggesting that it may be helpful in designing an epitope-based vaccine. This article is protected by copyright. All rights reserved.

  13. Mucosal humoral immune response to SIVmac239Δnef vaccination and vaginal challenge

    PubMed Central

    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.

    2016-01-01

    Live attenuated vaccines such as SIV with a deleted nef gene (SIVmac239Δnef) have provided the most robust protection against subsequent vaginal challenge with wild type (WT) SIV in the SIV-rhesus macaque (RM) model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV-1 vaccine. One such pre-challenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG antibodies reacting with the viral envelope glycoprotein, trimeric gp41 (gp41t); 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 Fc receptor in the overlying epithelium. We now examine the mucosal production of antibody component of this system post-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 like follicles in secondary lymphoid organs, and provide inferential evidence for a key role of the female reproductive tract epithelium in facilitating antibody 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

  14. 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.

  15. 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.

  16. HIV-1 Nef Binds a Subpopulation of MHC-I throughout Its Trafficking Itinerary and Down-regulates MHC-I by Perturbing Both Anterograde and Retrograde Trafficking*

    PubMed Central

    Yi, Ling; Rosales, Tilman; Rose, Jeremy J.; Chaudhury, Bhabhadeb; Knutson, Jay R.; Venkatesan, Sundararajan

    2010-01-01

    The HIV protein Nef is thought to mediate immune evasion and promote viral persistence in part by down-regulating major histocompatibility complex class I protein (MHC-I or HLA-I) from the cell surface. Two different models have been proposed to explain this phenomenon as follows: 1) stimulation of MHC-I retrograde trafficking from and aberrant recycling to the plasma membrane, and 2) inhibition of anterograde trafficking of newly synthesized HLA-I from the endoplasmic reticulum to the plasma membrane. We show here that Nef simultaneously uses both mechanisms to down-regulate HLA-I in peripheral blood mononuclear cells or HeLa cells. Consistent with this, we found by using fluorescence correlation spectroscopy that a third of diffusing HLA-I at the endoplasmic reticulum, Golgi/trans-Golgi network, and the plasma membrane (PM) was associated with Nef. The binding of Nef was similarly avid for native HLA-I and recombinant HLA-I A2 at the PM. Nef binding to HLA-I at the PM was sensitive to specific inhibition of endocytosis. It was also attenuated by cyclodextrin disruption of PM lipid micro-domain architecture, a change that also retarded lateral diffusion and induced large clusters of HLA-I. In all, our data support a model for Nef down-regulation of HLA-I that involves both major trafficking itineraries and persistent protein-protein interactions throughout the cell. PMID:20622010

  17. 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

  18. 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

  19. Choledocholithiasis presenting with very high transaminase level

    PubMed Central

    Agahi, Amy; McNair, Alistair

    2012-01-01

    We present three cases of choledocholithiasis presenting with a rise in transaminase to levels normally associated with acute hepatitis (alanine aminotransferase in excess of 1000 IU/l). All three cases had repeated investigation for liver disease before identification of common bile duct stones with magnetic resonance cholangiopancreatogram, and removal at endoscopic retrograde cholangiopancreatogram. We discuss the existing literature and the potential mechanisms of hepatocyte injury in extrahepatic obstruction. PMID:23188856

  20. 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.

  1. 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...

  2. 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... 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)...

  3. Infrared Thermography in High Level Waste

    SciTech Connect

    GLEATON, DAVIDT.

    2004-08-24

    The Savannah River Site is a Department of Energy, government-owned, company-operated industrial complex built in the 1950s to produce materials used in nuclear weapons. Five reactors were built to support the production of nuclear weapons material. Irradiated materials were moved from the reactors to one of the two chemical separation plants. In these facilities, known as ''canyons,'' the irradiated fuel and target assemblies were chemically processed to separate useful products from waste. Unfortunately, the by-product waste of nuclear material production was a highly radioactive liquid that had to be stored and maintained. In 1993 a strategy was developed to implement predictive maintenance technologies in the Liquid Waste Disposition Project Division responsible for processing the liquid waste. Responsibilities include the processing and treatment of 51 underground tanks designed to hold 750,000 to1,300,000 gallons of liquid waste and operation of a facility that vitrifies highly radioactive liquid waste into glass logs. Electrical and mechanical equipment monitored at these facilities is very similar to that found in non-nuclear industrial plants. Annual inspections are performed on electrical components, roof systems, and mechanical equipment. Troubleshooting and post installation and post-maintenance infrared inspections are performed as needed. In conclusion, regardless of the industry, the use of infrared thermography has proven to be an efficient and effective method of inspection to help improve plant safety and reliability through early detection of equipment problems.

  4. Fermilab Tevatron high level RF accelerating systems

    NASA Astrophysics Data System (ADS)

    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 a 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.

  5. 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

  6. Bumblebee pupae contain high levels of aluminium.

    PubMed

    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.

  7. 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...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from the operation of the first cycle solvent extraction system, or equivalent, and the concentrated waste...

  8. 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...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from the operation of the first cycle solvent extraction system, or equivalent, and the concentrated waste...

  9. 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...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from the operation of the first cycle solvent extraction system, or equivalent, and the concentrated waste...

  10. 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...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from the operation of the first cycle solvent extraction system, or equivalent, and the concentrated waste...

  11. 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...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from the operation of the first cycle solvent extraction system, or equivalent, and the concentrated waste...

  12. Study of the HIV-2 Env Cytoplasmic Tail Variability and Its Impact on Tat, Rev and Nef

    PubMed Central

    Bakouche, Nordine; Vandenbroucke, Anne-Thérèse; Goubau, Patrick; Ruelle, Jean

    2013-01-01

    Background The HIV-2 env’s 3’ end encodes the cytoplasmic tail (CT) of the Env protein. This genomic region also encodes the rev, Tat and Nef protein in overlapping reading frames. We studied the variability in the CT coding region in 46 clinical specimens and in 2 reference strains by sequencing and by culturing. The aims were to analyse the variability of Env CT and the evolution of proteins expressed from overlapping coding sequences. Results A 70% reduction of the length of the CT region affected the HIV-2 ROD and EHO strains in vitro due to a premature stop codon in the env gene. In clinical samples this wasn’t observed, but the CT length varied due to insertions and deletions. We noted 3 conserved and 3 variable regions in the CT. The conserved regions were those containing residues involved in Env endocytosis, the potential HIV-2 CT region implicated in the NF-kB activation and the potential end of the lentiviral lytic peptide one. The variable regions were the potential HIV-2 Kennedy region, the potential lentiviral lytic peptide two and the beginning of the potential lentiviral lytic peptide one. A very hydrophobic region was coded downstream of the premature stop codon observed in vitro, suggesting a membrane spanning region. Interestingly, the nucleotides that are responsible for the variability of the CT don’t impact rev and Nef. However, in the Kennedy-like coding region variability resulted only from nucleotide changes that impacted Env and Tat together. Conclusion The HIV-2 Env, Tat and Rev C-terminal part are subject to major length variations in both clinical samples and cultured strains. The HIV-2 Env CT contains variable and conserved regions. These regions don’t affect the rev and Nef amino acids composition which evolves independently. In contrast, Tat co-evolves with the Env CT. PMID:24223892

  13. Overlapping cis sites used for splicing of HIV-1 env/nef and rev mRNAs.

    PubMed

    Swanson, A K; Stoltzfus, C M

    1998-12-18

    Alternative splicing is used to generate more than 30 human immunodeficiency virus type 1 (HIV-1) spliced and unspliced mRNAs from a single primary transcript. The abundance of HIV-1 mRNAs is determined by the efficiencies with which its different 5' and 3' splice sites are used. Three splice sites (A4c, A4a, and A4b) are upstream of the rev initiator AUG. RNAs spliced at A4c, A4a, and A4b are used as mRNAs for Rev. Another 3' splice site (A5) is immediately downstream of the rev initiator. RNAs spliced at A5 are used as mRNAs for Env and Nef. In this report, primer extension analysis of splicing intermediates was used to show that there are eight branch points in this region, all of which map to adenosine residues. In addition, cis elements recognized by the cellular splicing machinery overlap; the two most 3' branch points overlap with the AG dinucleotides at rev 3' splice sites A4a and A4b. Competition of the overlapping cis sites for different splicing factors may play a role in maintaining the appropriate balance of mRNAs in HIV-1-infected cells. In support of this possibility, mutations at rev 3' splice site A4b AG dinucleotide dramatically increased splicing of the env/nef 3' splice site A5. This correlated with increased usage of the four most 3' branch points, which include those within the rev 3' splice site AG dinucleotides. Consistent with these results, analysis of a mutant in which three of the four env/nef branch points were inactivated indicated that use of splice site A5 was inhibited and splicing was shifted predominantly to the most 5' rev 3' splice site A4c with preferential use of the two most 5' branch points. Our results suggest that spliceosomes formed at rev A4a-4b, rev A4c, and env/nef A5 3' splice sites each recognize different subsets of the eight branch point sequences.

  14. 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…

  15. Potent, Persistent Induction and Modulation of Cellular Immune Responses in Rhesus Macaques Primed with Ad5hr-Simian Immunodeficiency Virus (SIV) env/rev, gag, and/or nef Vaccines and Boosted with SIV gp120

    PubMed Central

    Patterson, L. Jean; Malkevitch, Nina; Pinczewski, Joel; Venzon, David; Lou, Yuanmei; Peng, Bo; Munch, Cindy; Leonard, Melissa; Richardson, Ersell; Aldrich, Kristine; Kalyanaraman, V. S.; Pavlakis, George N.; Robert-Guroff, Marjorie

    2003-01-01

    Immunity elicited by multicomponent vaccines delivered by replication-competent Ad5hr-simian immunodeficiency virus (SIV) recombinants was systematically investigated. Rhesus macaques were immunized mucosally at weeks 0 and 12 with Ad5hr-SIVsmH4 env/rev, with or without Ad5hr-SIVmac239 gag or Ad5hr-SIVmac239 nef, or with all three recombinants. The total Ad5hr dosage was comparably adjusted among all animals with empty Ad5hr-ΔE3 vector. The macaques were boosted with SIV gp120 in monophosphoryl A-stable emulsion adjuvant at 24 and 36 weeks. Controls received Ad5hr-ΔE3 vector or adjuvant only. By ELISPOT analysis, all four SIV gene products elicited potent cellular immune responses that persisted 42 weeks post-initial immunization. Unexpectedly, modulation of this cellular immune response was observed among macaques receiving one, two, or three Ad5hr-SIV recombinants. Env responses were significantly enhanced throughout the immunization period in macaques immunized with Ad5hr-SIV env/rev plus Ad5hr-SIV gag and tended to be higher in macaques that also received Ad5hr-SIV nef. Macaques primed with all three recombinants displayed significant down-modulation in numbers of gamma interferon (IFN-γ)-secreting cells specific for SIV Nef, and the Env- and Gag-specific responses were also diminished. Modulation of antibody responses was not observed. Down-modulation was seen only during the period of Ad5hr-recombinant priming, not during subunit boosting, although SIV-specific IFN-γ-secreting cells persisted. The effect was not attributable to Ad5hr replication differences among immunization groups. Vaccine delivery via replication-competent live vectors, which can persistently infect new cells and continuously present low-level antigen, may be advantageous in overcoming competition among complex immunogens for immune recognition. Effects of current multicomponent vaccines on individual immune responses should be evaluated with regard to future vaccine design. PMID

  16. 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…

  17. 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.

  18. Tech Prep Implementation. Self-Assessment Inventory. Middle/High School Level. Postsecondary Level.

    ERIC Educational Resources Information Center

    Partnership for Academic and Career Education, Pendleton, SC.

    These two self-assessment inventories are designed to be used for evaluation of tech prep implementation at the middle/high school and postsecondary levels. The middle/high school version is intended to be completed by the district/school, the postsecondary form by the technical college. The form provides for rating the level of implementation as…

  19. 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.

  20. Distinct transcriptome profiles of Gag-specific CD8+ T cells temporally correlated with the protection elicited by SIVΔnef live attenuated vaccine

    PubMed Central

    Lu, Wuxun; Wan, Yanmin; Ma, Fangrui; Johnson, R. Paul; Li, Qingsheng

    2017-01-01

    The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: macaques are not protected at 3–5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIVΔnef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A*01+ rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in TCR signaling, differentiation and maturation toward central memory cells, with increased expression of CCR7, TCRα, TCRβ, CD28 and decreased expression of CTLA-4, IFN-γ, RANTES, granzyme A and B. Our study suggests that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time contributes to the maturation of time-dependent protection. PMID:28333940

  1. 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.

  2. Pseudo-merohedral Twinning and Noncrystallographic Symmetry in Orthorhombic Crystals of SIVmac239 Nef Core Domain Bound to Different-length TCR Fragments

    SciTech Connect

    Kim, W.; Sigalov, A; Stern, L

    2010-01-01

    HIV/SIV Nef mediates many cellular processes through interactions with various cytoplasmic and membrane-associated host proteins, including the signalling subunit of the T-cell receptor (TCR{zeta}). Here, the crystallization strategy, methods and refinement procedures used to solve the structures of the core domain of the SIVmac239 isolate of Nef (Nef{sub core}) in complex with two different TCR{zeta} fragments are described. The structure of SIVmac239 Nef{sub core} bound to the longer TCR{zeta} polypeptide (Leu51-Asp93) was determined to 3.7 {angstrom} resolution (R{sub work} = 28.7%) in the tetragonal space group P4{sub 3}2{sub 1}2. The structure of SIVmac239 Nef{sub core} in complex with the shorter TCR{zeta} polypeptide (Ala63-Arg80) was determined to 2.05 {angstrom} resolution (R{sub work} = 17.0%), but only after the detection of nearly perfect pseudo-merohedral crystal twinning and proper assignment of the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}. The reduction in crystal space-group symmetry induced by the truncated TCR{zeta} polypeptide appears to be caused by the rearrangement of crystal-contact hydrogen-bonding networks and the substitution of crystallographic symmetry operations by similar noncrystallographic symmetry (NCS) operations. The combination of NCS rotations that were nearly parallel to the twin operation (k, h, -l) and a and b unit-cell parameters that were nearly identical predisposed the P2{sub 1}2{sub 1}2{sub 1} crystal form to pseudo-merohedral twinning.

  3. 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)

  4. Holism and High Level Wellness in the Treatment of Alcoholism.

    ERIC Educational Resources Information Center

    Bartha, Robert; Davis, Tom

    1982-01-01

    Discusses how a holistic and wellness philosophy is a viable alternative in the treatment of alcoholism. Describes five major dimensions of high-level wellness: nutritional awareness, physical fitness, stress management, environmental sensitivity, and self-responsibility. (RC)

  5. 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…

  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. Glucose level regulation via integral high-order sliding modes.

    PubMed

    Dorel, Lela

    2011-04-01

    Diabetes is a condition in which the body either does not produce enough insulin, or does not properly respond to it. This causes the glucose level in blood to increase. An algorithm based on Integral High-Order Sliding Mode technique is proposed, which keeps the normal blood glucose level automatically releasing insulin into the blood. The system is highly insensitive to inevitable parametric and model uncertainties, measurement noises and small delays.

  8. 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.

  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.

  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.

  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. 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…

  13. High Frequency Acoustic Propagation using Level Set Methods

    DTIC Science & Technology

    2007-01-01

    solution of the high frequency approximation to the wave equation. Traditional solutions to the Eikonal equation in high frequency acoustics are...curvature can be extracted at any point of the front from the level set function (provided the normal and curvature are well-defined at that point ), and... points per wavelength to resolve the wave). Ray tracing is therefore the current standard for high frequency propagation modeling. LSM may provide

  14. Mercury levels in high-end consumers of fish.

    PubMed

    Hightower, Jane M; Moore, Dan

    2003-04-01

    Consumption of food containing mercury has been identified as a health risk. The U.S. Environmental Protection Agency (U.S. EPA) and the National Academy of Sciences recommend keeping the whole blood mercury level < 5.0 microg/L or the hair level < 1.0 microg/g. This corresponds to a reference dose (RfD) of 0.1 microg/kg body weight per day. All patients in a 1-year period (n = 720) who came for an office visit in a private internal medicine practice in San Francisco, California, were evaluated for mercury excess using the current RfD. One hundred twenty-three patients were tested (93 females, 30 males). Of these, data were statistically analyzed for 89 subjects. Mercury levels ranged from 2.0 to 89.5 microg/L for the 89 subjects. The mean for 66 women was 15 microg/L [standard deviation (SD) = 15], and for 23 men was 13 microg/L (SD = 5); 89% had levels exceeding the RfD. Subjects consumed 30 different forms or types of fish. Swordfish had the highest correlation with mercury level. Sixty-seven patients with serial blood levels over time after stopping fish showed a decline in mercury levels; reduction was significant (p < 0.0001). A substantial fraction of patients had diets high in fish consumption; of these, a high proportion had blood mercury levels exceeding the maximum level recommended by the U.S. EPA and National Academy of Sciences. The mean level for women in this survey was 10 times that of mercury levels found in a recent population survey by the U.S. Centers for Disease Control and Prevention. Some children were > 40 times the national mean.

  15. High Frequency Monitoring System of Groundwater Level in Sheliao

    NASA Astrophysics Data System (ADS)

    Lee, C.; Chia, Y.; Chuang, P.

    2012-12-01

    Long-term groundwater monitoring had been executed since 1950s in Taiwan. In 1980s, with improving technology, various types of automatic reorders of groundwater level had become the most widely used equipment in groundwater monitoring. Among these devices, submersible pressure transducer is frequently selected to monitor groundwater level for its high frequency and high resolution. In this study, it is chosen to monitor groundwater level change in Sheliao well. On the other hand, factors which might influence the performance of recorded data were excluded in the early stage of establishment as well. And the final approach is to achieve a comprehensive understanding of the minor groundwater level change of Sheliao well, and specify its connection between precipitation, atmosphere, earth tide and earthquake. The Shelia well is located in central Taiwan, constructed in an unconfined aquifer, recorded hourly groundwater level change since 1997. We tried to establish a 1 Hz sampling rate pressure-sensing system in 2011 June. The groundwater level was monitored in a resolution of 2-mm. According to the records, several small-scale of fluctuations were observed and were all correlate well to the earthquakes. However, during the time that no earthquake occurred, some short-term fluctuations were still occurred, performed in a different pattern to those induced by earthquakes. After further investigation, those anomalous fluctuations of groundwater level were found corresponded to precipitation quite well. The fluctuations were observed under some specific condition, which involving different range of accumulated precipitation, rainfall intensity, and rainfall duration. The result implied groundwater level in Sheliao well changes with loading effect result from runoff on the ground surface and infiltration. And the earth tide lead to regularly change was also observed. We conclude that Sheliao can be characterized as a partial-confined aquifer with high frequency and high

  16. Trustworthy System Development Through High-Level Synthesis

    DTIC Science & Technology

    2014-09-01

    processor manufacturers have embraced the high-level synthesis ( HLS ) design philosophy. HLS offers the potential to explore the design space of electronic...circuits and systems more efficiently than traditional methods. In this thesis, we investigate the ap- plication of HLS to hardware-oriented security and...level synthesis ( HLS ) design phi- losophy. HLS offers the potential to explore the design space of electronic circuits and systems more efficiently than

  17. High-level aminoglycoside resistant enterococci isolated from swine.

    PubMed Central

    Jackson, C. R.; Fedorka-Cray, P. J.; Barrett, J. B.; Ladely, S. R.

    2005-01-01

    Approximately 42% (187/444) of swine enterococci collected between the years 1999 and 2000 exhibited high-level resistance to gentamicin (MIC > or =500 microg/ml), kanamycin (MIC > or =500 microg/ml), or streptomycin (MIC > or =1000 microg/ml). Eight aminoglycoside resistance genes were detected using PCR, most frequently ant(6)-Ia and aac(6')-Ii from Enterococcus faecium. Twenty-four per cent (45/187) of total high-level aminoglycoside-resistant isolates and 26% (4/15) of isolates resistant to high levels of all three antimicrobials were negative for all genes tested. These data suggest that enterococci isolated from swine contain diverse and possibly unidentified aminoglycoside resistance genes. PMID:15816164

  18. High-level aminoglycoside resistant enterococci isolated from swine.

    PubMed

    Jackson, C R; Fedorka-Cray, P J; Barrett, J B; Ladely, S R

    2005-04-01

    Approximately 42% (187/444) of swine enterococci collected between the years 1999 and 2000 exhibited high-level resistance to gentamicin (MIC > or =500 microg/ml), kanamycin (MIC > or =500 microg/ml), or streptomycin (MIC > or =1000 microg/ml). Eight aminoglycoside resistance genes were detected using PCR, most frequently ant(6)-Ia and aac(6')-Ii from Enterococcus faecium. Twenty-four per cent (45/187) of total high-level aminoglycoside-resistant isolates and 26% (4/15) of isolates resistant to high levels of all three antimicrobials were negative for all genes tested. These data suggest that enterococci isolated from swine contain diverse and possibly unidentified aminoglycoside resistance genes.

  19. 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.

  20. 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.

  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. 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.

  3. High-Level Event Recognition in Unconstrained Videos

    DTIC Science & Technology

    2013-01-01

    for polyphonic music. J Acoust Soc Am 122( 2 ):881–891 6. Aytar Y, ShahM, Luo J (2008) Utilizing semantic word similarity measures for video retrieval...Int J Multimed Info Retr (2013) 2 :73–101 DOI 10.1007/s13735-012-0024- 2 TRENDS AND SURVEYS High-level event recognition in unconstrained videos Yu...mob”). Techniques for recognizing such high-level events are essential for many practical applications such as Web video search, consumer video

  4. 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.

  5. Transmission Level High Temperature Superconducting Fault Current Limiter

    SciTech Connect

    Stewart, Gary

    2016-10-05

    The primary objective of this project was to demonstrate the feasibility and reliability of utilizing high-temperature superconducting (HTS) materials in a Transmission Level Superconducting Fault Current Limiter (SFCL) application. During the project, the type of high-temperature superconducting material used evolved from 1st generation (1G) BSCCO-2212 melt cast bulk high-temperature superconductors to 2nd generation (2G) YBCO-based high-temperature superconducting tape. The SFCL employed SuperPower's “Matrix” technology, that offers modular features to enable scale up to transmission voltage levels. The SFCL consists of individual modules that contain elements and parallel inductors that assist in carrying the current during the fault. A number of these modules are arranged in an m x n array to form the current-limiting matrix.

  6. 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.

  7. High-Level Overview of Data Needs for RE Analysis

    SciTech Connect

    Lopez, Anthony

    2016-12-22

    This presentation provides a high level overview of analysis topics and associated data needs. Types of renewable energy analysis are grouped into two buckets: First, analysis for renewable energy potential, and second, analysis for other goals. Data requirements are similar but and they build upon one another.

  8. 46 CFR 182.530 - Bilge high level alarms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... operating station to indicate a high water level in each of the following normally unmanned spaces: (1) A... space bilge, bilge well, shaft alley bilge, or other spaces subject to flooding from sea water piping... must be provided at the operating station to indicate when any automatic bilge pump is operating....

  9. 46 CFR 119.530 - Bilge high level alarms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... visual and audible alarm at the operating station to indicate a high water level in each of the following... flooding from sea water piping within the space; and (3) A space with a non-watertight closure , such as a... operating station to indicate when any automatic bilge pump is operating....

  10. 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…

  11. High-level manpower movement and Japan's foreign aid.

    PubMed

    Furuya, K

    1992-01-01

    "Japan's technical assistance programs to Asian countries are summarized. Movements of high-level manpower accompanying direct foreign investments by private enterprise are also reviewed. Proposals for increased human resources development include education and training of foreigners in Japan as well as the training of Japanese aid experts and the development of networks for information exchange."

  12. 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…

  13. 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...

  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. Structuring Peer Interaction To Promote High-Level Cognitive Processing.

    ERIC Educational Resources Information Center

    King, Alison

    2002-01-01

    Examines the kind of peer learning that demands high-level cognitive processing, discussing how peer interaction influences cognitive processes (structuring peer interaction and using guided reciprocal peer questioning); how to promote cognitive processing (knowledge construction and integration and socio- cognitive conflict); metacognition; and…

  16. Equity-Focused Schools Carry All Students to High Levels

    ERIC Educational Resources Information Center

    WestEd, 2014

    2014-01-01

    Despite decades of experience supporting efforts from local to state levels to improve learning for underserved students, Sonia Caus Gleason and WestEd's Nancy Gerzon could not point to examples of entire schools accomplishing what they believed was possible: high-poverty public schools personalizing learning for all students to consistently reach…

  17. 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.

  18. 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.

  19. On Programming Models for Service-Level High Availability

    SciTech Connect

    Engelmann, Christian; Scott, Stephen L; Leangsuksun, Chokchai; He, X.

    2007-01-01

    This paper provides an overview of existing programming models for service-level high availability and investigates their differences, similarities, advantages, and disadvantages. Its goal is to help to improve reuse of code and to allow adaptation to quality of service requirements by using a uniform programming model description. It further aims at encouraging a discussion about these programming models and their provided quality of service, such as availability, performance, serviceability, usability, and applicability. Within this context, the presented research focuses on providing high availability for services running on head and service nodes of high-performance computing systems.

  20. 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

  1. High-Level Waste Vitrification Facility Feasibility Study

    SciTech Connect

    D. A. Lopez

    1999-08-01

    A ''Settlement Agreement'' between the Department of Energy and the State of Idaho mandates that all radioactive high-level waste now stored at the Idaho Nuclear Technology and Engineering Center will be treated so that it is ready to be moved out of Idaho for disposal by a compliance date of 2035. This report investigates vitrification treatment of the high-level waste in a High-Level Waste Vitrification Facility based on the assumption that no more New Waste Calcining Facility campaigns will be conducted after June 2000. Under this option, the sodium-bearing waste remaining in the Idaho Nuclear Technology and Engineering Center Tank Farm, and newly generated liquid waste produced between now and the start of 2013, will be processed using a different option, such as a Cesium Ion Exchange Facility. The cesium-saturated waste from this other option will be sent to the Calcine Solids Storage Facilities to be mixed with existing calcine. The calcine and cesium-saturated waste will be processed in the High-Level Waste Vitrification Facility by the end of calendar year 2035. In addition, the High-Level Waste Vitrification Facility will process all newly-generated liquid waste produced between 2013 and the end of 2035. Vitrification of this waste is an acceptable treatment method for complying with the Settlement Agreement. This method involves vitrifying the waste and pouring it into stainless-steel canisters that will be ready for shipment out of Idaho to a disposal facility by 2035. These canisters will be stored at the Idaho National Engineering and Environmental Laboratory until they are sent to a national geologic repository. The operating period for vitrification treatment will be from the end of 2015 through 2035.

  2. Long-term high-level waste technology

    NASA Astrophysics Data System (ADS)

    Cornman, W. R.

    1980-07-01

    This series of reports summarizes research and development studies on the immobilization of high level wastes from the chemical reprocessing of nuclear reactor fuels. Immobilization of the wastes (defense and commercial) consists of placing them in a high integrity form with a very low potential for radionuclide release. Immobilization of commercial wastes is being considered on a contingency basis in the event that reprocessing is resumed. The basic plan for meeting the goal of immobilization of the DOE high level wastes is: (1) to develop technology to support a realistic choice of waste form alternatives for each of the three DOE sites; (2) to develop product and processing technology with sufficient scaleup to provide design data for full scale facilities; and (3) to construct and operate the facilities.

  3. [Medical image retrieval by high level semantic features and low level content features of image].

    PubMed

    Xie, Tianwen; Tang, Weijun; Zhao, Qiufeng; Zhao, Jiaao

    2009-12-01

    Content-based image retrieval aims at searching the similar images using low level features,and medical image retrieval needs it for the retrieval of similar images. Medical images contain not only a lot of content data, but also a lot of semantic information. This paper presents an approach by combining digital imaging and communications in medicine (DICOM) features and low level features to perform retrieval on medical image databases. At the first step, the semantic information is extracted from DICOM header for the pre-filtering of the images, and then dual-tree complex wavelet transfrom(DT-CWT) features of pre-filtered images and example images are extracted to retrieve similar images. Experimental results show that by combining the high level semantics (DICOM features) and low level content features (texture) the retrieval time is reduced and the performance of medical image retrieval is increased.

  4. Evolution of human immunodeficiency virus type 1 nef and long terminal repeat sequences over 4 years in vivo and in vitro.

    PubMed Central

    Delassus, S; Cheynier, R; Wain-Hobson, S

    1991-01-01

    The evolution of an 851-bp segment of the human immunodeficiency virus type 1 (HIV-1) genome encoding the nef open reading frame and U3/R elements of the long terminal repeat has been followed over a 4-year period in vivo and in vitro. The population of viral sequences at any given time was established by sequencing cloned polymerase chain reaction products. The samples studied were derived from the same man for whom a detailed analysis of the tat gene was previously described (A. Meyerhans, R. Cheynier, J. Albert, M. Seth, S. Kwok, J. Sninsky, L. Morfeldt-Manson, B. Asjö, and S. Wain-Hobson, Cell 58:901-910, 1989). Once again in vitro culture resulted in the selection of minor forms. Over a 4-year period in vivo, there was no obvious selection for, or outgrowth of, any particular nef or U3/R sequence. Few defective nef protein sequences were observed, which argues against nef acting as a negative regulatory factor. Although no functionally defective promoter/trans-activation-responsive elements were identified, the transactivation efficiencies varied between 0.2 and 2 times that of the control. The sequence encoding the most efficient trans-activation-responsive region did not outgrow others. The extreme genetic heterogeneity of the different samples of the locus, either in vivo or in vitro, indicates that there is no such thing as a single, distinct HIV sequence. It is suggested that different HIV-1 loci evolve independently, recombination being responsible for their uncoupling. PMID:1985198

  5. Landau-Level Splitting in Graphene in High Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Jiang, Z.; Small, J. P.; Purewal, M. S.; Tan, Y.-W.; Fazlollahi, M.; Chudow, J. D.; Jaszczak, J. A.; Stormer, H. L.; Kim, P.

    2006-04-01

    The quantum Hall (QH) effect in two-dimensional electrons and holes in high quality graphene samples is studied in strong magnetic fields up to 45 T. QH plateaus at filling factors ν=0,±1,±4 are discovered at magnetic fields B>20T, indicating the lifting of the fourfold degeneracy of the previously observed QH states at ν=±4(|n|+1/2), where n is the Landau-level index. In particular, the presence of the ν=0,±1 QH plateaus indicates that the Landau level at the charge neutral Dirac point splits into four sublevels, lifting sublattice and spin degeneracy. The QH effect at ν=±4 is investigated in a tilted magnetic field and can be attributed to lifting of the spin degeneracy of the n=1 Landau level.

  6. 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.

  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. 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.

  9. 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.

  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. 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.

  12. Life Extension of Aging High Level Waste (HLW) Tanks

    SciTech Connect

    BRYSON, D.

    2002-02-04

    The Double Shell Tanks (DSTs) play a critical role in the Hanford High-Level Waste Treatment Complex, and therefore activities are underway to protect and better understand these tanks. The DST Life Extension Program is focused on both tank life extension and on evaluation of tank integrity. Tank life extension activities focus on understanding tank failure modes and have produced key chemistry and operations controls to minimize tank corrosion and extend useful tank life. Tank integrity program activities have developed and applied key technologies to evaluate the condition of the tank structure and predict useful tank life. Program results to date indicate that DST useful life can be extended well beyond the original design life and allow the existing tanks to fill a critical function within the Hanford High-Level Waste Treatment Complex. In addition the tank life may now be more reliably predicted, facilitating improved planning for the use and possible future replacement of these tanks.

  13. 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.

  14. 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.

  15. Learning high-level features for chord recognition using Autoencoder

    NASA Astrophysics Data System (ADS)

    Phongthongloa, Vilailukkana; Kamonsantiroj, Suwatchai; Pipanmaekaporn, Luepol

    2016-07-01

    Chord transcription is valuable to do by itself. It is known that the manual transcription of chords is very tiresome, time-consuming. It requires, moreover, musical knowledge. Automatic chord recognition has recently attracted a number of researches in the Music Information Retrieval field. It has known that a pitch class profile (PCP) is the commonly signal representation of musical harmonic analysis. However, the PCP may contain additional non-harmonic noise such as harmonic overtones and transient noise. The problem of non-harmonic might be generating the sound energy in term of frequency more than the actual notes of the respective chord. Autoencoder neural network may be trained to learn a mapping from low level feature to one or more higher-level representation. These high-level representations can explain dependencies of the inputs and reduce the effect of non-harmonic noise. Then these improve features are fed into neural network classifier. The proposed high-level musical features show 80.90% of accuracy. The experimental results have shown that the proposed approach can achieve better performance in comparison with other based method.

  16. Local acceptance of a high-level nuclear waste repository.

    PubMed

    Sjöberg, Lennart

    2004-06-01

    The siting of nuclear waste facilities has been very difficult in all countries. Recent experience in Sweden indicates, however, that it may be possible, under certain circumstances, to gain local support for the siting of a high-level nuclear waste (HLNW) repository. The article reports on a study of attitudes and risk perceptions of people living in four municipalities in Sweden where HLNW siting was being intensely discussed at the political level, in media, and among the public. Data showed a relatively high level of consensus on acceptability of at least further investigation of the issue; in two cases local councils have since voted in favor of a go-ahead, and in one case only a very small majority defeated the issue. Models of policy attitudes showed that these were related to attitude to nuclear power, attributes of the perceived HLNW risk, and trust. Factors responsible for acceptance are discussed at several levels. One is the attitude to nuclear power, which is becoming more positive, probably because no viable alternatives are in sight. Other factors have to do with the extensive information programs conducted in these municipalities, and with the logical nature of the conclusion that they would be good candidates for hosting the national HLNW repository.

  17. 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.

  18. Hierarchical High Level Information Fusion (H2LIFT)

    DTIC Science & Technology

    2008-09-15

    National Strategy for Maritime Security‖, 2005. 11. J. Morgan and B. Wimmer, ― Enhancing Awareness in the Maritime Domain‖, CHIPS Magazine, 14-15, 2005...Intelligence, vol. 18, no. 3, pp. 475–496, 2004. 30. K. Sambhoos, et al., ― Enhancements to high level data fusion using graph matching and state space search...range and bearing calculations over long distances. Loran -C and GPS navigation receivers use ellipsoidal earth models to compute position and waypoint

  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.

    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. 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.

  2. 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.

  3. Adaptive user interfaces for relating high-level concepts to low-level photographic parameters

    NASA Astrophysics Data System (ADS)

    Scott, Edward; Madhawa Silva, Pubudu; Pardo, Bryan; Pappas, Thrasyvoulos N.

    2011-03-01

    Common controls for photographic editing can be difficult to use and have a significant learning curve. Often, a user does not know a direct mapping from a high-level concept (such as "soft") to the available parameters or controls. In addition, many concepts are subjective in nature, and the appropriate mapping may vary from user to user. To overcome these problems, we propose a system that can quickly learn a mapping from a high-level subjective concept onto low- level image controls using machine learning techniques. To learn such a concept, the system shows the user a series of training images that are generated by modifying a seed image along different dimensions (e.g., color, sharpness), and collects the user ratings of how well each training image matches the concept. Since it is known precisely how each modified example is different from the original, the system can determine the correlation between the user ratings and the image parameters to generate a controller tailored to the concept for the given user. The end result - a personalized image controller - is applicable to a variety of concepts. We have demonstrated the utility of this approach to relate low-level parameters, such as color balance and sharpness, to simple concepts, such as "lightness" and "crispness," as well as more complex and subjective concepts, such as "pleasantness." We have also applied the proposed approach to relate subband statistics (variance) to perceived roughness of visual textures (from the CUReT database).

  4. 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.

  5. Association between high cystatin C levels and carotid atherosclerosis

    PubMed Central

    Kobayashi, Toshiyuki; Yokokawa, Hirohide; Fujibayashi, Kazutoshi; Haniu, Tomomi; Hisaoka, Teruhiko; Fukuda, Hiroshi; Naito, Toshio

    2017-01-01

    AIM To investigate the association between carotid atherosclerosis and cystatin C (CysC) and to determine the optimal CysC cut-off value. METHODS One hundred twenty-eight subjects were included in this study. Atherosclerosis was defined as a maximum carotid plaque thickness (MCPT) of greater than 2 mm. A receiver operating characteristic curve analysis was used to determine the diagnostic value of serum CysC for atherosclerosis. The subjects were divided into two groups according to the CysC cut-off value. We screened for diabetes, hypertension, dyslipidemia, smoking status, alcohol consumption, and exercise behavior. The association between atherosclerosis and CysC levels was assessed using multivariate analysis. RESULTS The subjects were then divided into two groups according to the CysC cut-off value (0.73 mg/L). The median age of the high CysC group was 72 years (85% males), whereas that of the low CysC group was 61 years (63% males). The CysC levels were significantly correlated with Cr and estimated glomerular filtration rate (eGFR) values. Body-mass index, visceral fat area, hypertension, diabetes mellitus, and MCPT were significantly higher in the high CysC group than in the low CysC group. Furthermore, the eGFR was significantly lower in the high CysC group. Regarding lifestyle habits, only the exercise level was lower in the high CysC group than in the low CysC group. Multivariate analysis, adjusted for age and sex, revealed that high CysC levels were significantly associated with an MCPT of ≥ 2 mm (odds ratio: 2.92; 95%CI: 1.13-7.99). CONCLUSION Higher CysC levels were associated with an MCPT of ≥ 2 mm. The CysC cut-off value of 0.73 mg/L appears to aid in the diagnosis of atherosclerosis. PMID:28289532

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Prostate Cancer, High Cortisol Levels and Complex Hormonal Interaction.

    PubMed

    Fabre, Bibiana; Grosman, Halina; Gonzalez, Diego; Machulsky, Nahuel Fernandez; Repetto, Esteban M; Mesch, Viviana; Lopez, Miguel Angel; Mazza, Osvaldo; Berg, Gabriela

    2016-01-01

    Prostate cancer (PCa) is one of the most common diseases in men. It is important to assess prognostic factors and whether high cortisol levels and complex hormonal interactions could be responsible for PCa development. We evaluated the relationship between cortisol, leptin and estrogens in 141 men, 71 with PCa and the remaining 70 constituting a low risk group (LRG). They were recruited for this study from a total of 2906 middleaged men (ages 4570 years) who completed an evaluation for prostatic diseases at the Urology Division, Hospital de Clinicas "Jose de San Martin", University of Buenos Aires, in May 2009. In this cross sectional study, cortisol, PSA, totaltestosterone, freetestosterone, bioavailable testosterone, LH and estradiol were measured in serum. We observed increased cortisol levels in PCa patients as compared to LRG cases (p=0.004,). Leptin and estradiol levels were also higher in PCa patients (p=0.048; p<0.0001, respectively). Logistic regression analysis indicated that serum cortisol (OR: 1.110 (95% CI 1.0161.213), p=0.022), estradiol (OR: 1.044 (95% CI 1.0081.081), p=0.016) and leptin (OR: 1.248 (95% CI 1.0481.487), p=0.013) explained 27% of the variance of dependent variables, even after adjusting for age, smoking, BMI and waist circumference. We found increased cortisol levels in PCa patients as compared to LRG, as well as an altered circulating hormonal profile.

  15. 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.

  16. Quasimonomorphic mononucleotide repeats for high-level microsatellite instability analysis.

    PubMed

    Buhard, Olivier; Suraweera, Nirosha; Lectard, Aude; Duval, Alex; Hamelin, Richard

    2004-01-01

    Microsatellite instability (MSI) analysis is becoming more and more important to detect sporadic primary tumors of the MSI phenotype as well as in helping to determine Hereditary Non-Polyposis Colorectal Cancer (HNPCC) cases. After some years of conflicting data due to the absence of consensus markers for the MSI phenotype, a meeting held in Bethesda to clarify the situation proposed a set of 5 microsatellites (2 mononucleotide repeats and 3 dinucleotide repeats) to determine MSI tumors. A second Bethesda consensus meeting was held at the end of 2002. It was discussed here that the 1998 microsatellite panel could underestimate high-level MSI tumors and overestimate low-level MSI tumors. Amongst the suggested changes was the exclusive use of mononucleotide repeats in place of dinucleotide repeats. We have already proposed a pentaplex MSI screening test comprising 5 quasimonomorphic mononucleotide repeats. This article compares the advantages of mono or dinucleotide repeats in determining microsatellite instability.

  17. Quasimonomorphic Mononucleotide Repeats for High-Level Microsatellite Instability Analysis

    PubMed Central

    Buhard, Olivier; Suraweera, Nirosha; Lectard, Aude; Duval, Alex; Hamelin, Richard

    2004-01-01

    Microsatellite instability (MSI) analysis is becoming more and more important to detect sporadic primary tumors of the MSI phenotype as well as in helping to determine Hereditary Non-Polyposis Colorectal Cancer (HNPCC) cases. After some years of conflicting data due to the absence of consensus markers for the MSI phenotype, a meeting held in Bethesda to clarify the situation proposed a set of 5 microsatellites (2 mononucleotide repeats and 3 dinucleotide repeats) to determine MSI tumors. A second Bethesda consensus meeting was held at the end of 2002. It was discussed here that the 1998 microsatellite panel could underestimate high-level MSI tumors and overestimate low-level MSI tumors. Amongst the suggested changes was the exclusive use of mononucleotide repeats in place of dinucleotide repeats. We have already proposed a pentaplex MSI screening test comprising 5 quasimonomorphic mononucleotide repeats. This article compares the advantages of mono or dinucleotide repeats in determining microsatellite instability. PMID:15528790

  18. 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.

  19. Multiply spliced env and nef transcripts of simian immunodeficiency virus from West African green monkey (SIVagm-sab).

    PubMed

    Bibollet-Ruche, F; Cuny, G; Pourrut, X; Brengues, C; Galat-Luong, A; Galat, G; Delaporte, E

    1998-04-10

    We have characterized the spliced transcripts of nef and envelope genes of SIVagm from African green monkey of the sabaeus subspecies. Most of the transcripts we have studied, representing the most abundant mRNA species in our assay, have undergone a specific splicing event that removes a part of the trans-activation response (TAR) element. This region is predicted to form a stable secondary structure (four stem-loop elements in SIVagm-sab) that affects the trans-activation of viral gene expression by Tat and the translation of the viral transcripts. Contrary to what is observed in other viruses, in which this R-region splicing has also been described (e.g., HIV-2), the LTR splicing in SIVagm-sab removes part of the first stem-loop and the following ones, nearly completely disrupting the TAR element secondary structure. Because LTR splicing seems to be a conserved feature among the strains we have characterized, these results suggest that this phenomenon could have important consequences for virus replication, pathogenicity, and latency.

  20. Identification of new and unusual rev and nef transcripts expressed by an HIV type 1 primary isolate.

    PubMed

    Vega, Yolanda; Delgado, Elena; Carrera, Cristina; Nebreda, Paloma; Fernández-García, Aurora; Cuevas, María Teresa; Pérez-Álvarez, Lucía; Thomson, Michael M

    2013-07-01

    We analyzed RNA splice site usage in three HIV-1 subtype B primary isolates through reverse transcriptase polymerase chain reaction (RT-PCR) amplification of spliced RNAs using a fluorescently labeled primer, with computerized size determination and quantification of PCR products, which were also identified by clone sequencing. In one isolate, P2149-3, unusual and unreported spliced transcripts were detected. This isolate preferentially used for rev RNA generation a 3' splice site (3'ss) located five nucleotides upstream of A4a, previously identified only in a T cell line-adapted virus and in a group O isolate, and designated A4d. P2149-3 also used an unreported 3'ss for rev RNA generation, designated A4h, located 20 nucleotides upstream of 3'ss A4c. Additionally, unusual nef RNAs using 3'ss A5a and A7a and with exon composition 1.3.7 were identified. The identification of several unusual and unreported spliced transcripts in an HIV-1 primary isolate suggests a greater diversity of splice site usage in HIV-1 than previously appreciated.

  1. Identification of New and Unusual rev and nef Transcripts Expressed by an HIV Type 1 Primary Isolate

    PubMed Central

    Vega, Yolanda; Delgado, Elena; Carrera, Cristina; Nebreda, Paloma; Fernández-García, Aurora; Cuevas, María Teresa; Pérez-Álvarez, Lucía

    2013-01-01

    Abstract We analyzed RNA splice site usage in three HIV-1 subtype B primary isolates through reverse transcriptase polymerase chain reaction (RT-PCR) amplification of spliced RNAs using a fluorescently labeled primer, with computerized size determination and quantification of PCR products, which were also identified by clone sequencing. In one isolate, P2149-3, unusual and unreported spliced transcripts were detected. This isolate preferentially used for rev RNA generation a 3′ splice site (3′ss) located five nucleotides upstream of A4a, previously identified only in a T cell line-adapted virus and in a group O isolate, and designated A4d. P2149-3 also used an unreported 3′ss for rev RNA generation, designated A4h, located 20 nucleotides upstream of 3′ss A4c. Additionally, unusual nef RNAs using 3′ss A5a and A7a and with exon composition 1.3.7 were identified. The identification of several unusual and unreported spliced transcripts in an HIV-1 primary isolate suggests a greater diversity of splice site usage in HIV-1 than previously appreciated. PMID:23540799

  2. In this issue: Nef, a lingering problem; are there better immunoglobulins for human use; and Takayasu arteritis, still a mystery.

    PubMed

    Bot, Adrian

    2012-12-01

    The current issue of the International Reviews of Immunology brings the latest in three different areas of basic and clinical immunology. First, there is the lingering question of residual HIV-related pathology in patients on chronic antiretroviral therapy. The specific role of Nef in the macrophage-mediated disease manifested through lymphoma, metabolic disease and neurological disorder, is extensively discussed. A second topic is a clinical immunology one, a critical perspective on the efficacy and safety profile of various preparations of immunoglobulin products currently prescribed for a range of immunodeficiencies. Surprisingly, the authors showed that while the available preparations are equivalent from efficacy standpoint, they differ from the standpoint of toxicity. The third subject is again, in the arena of clinical immunology and deals with a relatively rare yet extremely puzzling disease -Takayasu arteritis -with a pathogenesis that needs elucidation and a dire need for better treatments. The authors provide a state of the art in terms of genetic association, other factors possibly involved in the onset and progression of this unusual inflammatory disease of large arteries, and provide a perspective on current standard of care and potential usefulness of TNF-α blockade as therapy for Takayasu arteritis.

  3. Salivary fluoride levels after use of high-fluoride dentifrice.

    PubMed

    Vale, Glauber Campos; Cruz, Priscila Figueiredo; Bohn, Ana Clarissa Cavalcante Elvas; de Moura, Marcoeli Silva

    2015-01-01

    The aim of the study was to evaluate salivary fluoride (F) availability after toothbrushing with a high-F dentifrice. Twelve adult volunteers took part in this crossover and blind study. F concentration in saliva was determined after brushing with a high-F dentifrice (5000 µg F/g) or with a conventional F concentration dentifrice (1100 µg F/g) followed by a 15 mL distilled water rinse. Samples of nonstimulated saliva were collected on the following times: before (baseline), and immediately after spit (time = 0) and after 1, 2, 3, 4, 5, 10, 15, 20, 30, 45, 60, 90, and 120 min. F analysis was performed with a fluoride-sensitive electrode and the area under curve of F salivary concentration × time (µg F/mL × min(-1)) was calculated. At baseline, no significant difference was found among dentifrices (P > 0.05). After brushing, both dentifrices caused an elevated fluoride level in saliva; however salivary F concentration was significantly higher at all times, when high-F dentifrice was used (P < 0.01). Even after 120 min, salivary F concentration was still higher than the baseline values for both dentifrices (P < 0.001). High-F dentifrice enhanced the bioavailability of salivary F, being an option for caries management in patients with high caries risk.

  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-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.

  9. 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.

  10. 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.

  11. High resolution measurement of water levels in optical components

    NASA Astrophysics Data System (ADS)

    Murrieta-Rico, Fabian N.; Petranovskii, Vitalii; Sergiyenko, Oleg; Hernandez-Balbuena, Daniel; Raymond-Herrera, Oscar

    2016-09-01

    Systems for optical analysis use vacuum chambers, where low pressures are reached. Remaining water molecules are the prevalent contaminant in high vacuum chambers. For this reason measurement of water levels is an important task that allows correct equipment operation. In this work, a different approach is presented for detecting and quantifying the water molecules inside a the vacuum chamber used in optical systems. A zeolite coated quartz crystal microbalance is used for detecting the water molecules, and the change in the resonance frequency is measured using a novel technique known as the principle of rational approximations. Theoretical results show how nanograms of adsorbed molecules are measured, and the number of molecules are quantified.

  12. Smoking as a determinant of high organochlorine levels in Greenland.

    PubMed

    Deutch, Bente; Pedersen, Henning Sloth; Jørgensen, Eva C Bonefeld; Hansen, Jens C

    2003-01-01

    The authors investigated the accumulation of organochlorines among smoking and nonsmoking Inuit hunters (n = 48) in Uummanaq, Greenland, a population with high dietary exposure to persistent organic pollutants (POPs). Human plasma organochlorine levels were positively correlated with age, marine diet, and smoking or plasma cotinine in multiple linear-regression models (p < 0.001). Body mass index was inversely correlated with organochlorine accumulation, independent of smoking status. These findings confirm that the source of POPs among the Inuit in Greenland is diet, but smoking is an important determinant of POP bioaccumulation. Smoking cessation may provide a means to lower the body burden of POPs.

  13. 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.

  14. High-level wastes: DOE names three sites for characterization

    SciTech Connect

    1986-07-01

    DOE announced in May 1986 that there will be there site characterization studies made to determine suitability for a high-level radioactive waste repository. The studies will include several test drillings to the proposed disposal depths. Yucca Mountain, Nevada; Deaf Smith Country, Texas, and Hanford, Washington were identified as the study sites, and further studies for a second repository site in the East were postponed. The affected states all filed suits in federal circuit courts because they were given no advance warning of the announcement of their selection or the decision to suspend work on a second repository. Criticisms of the selection process include the narrowing or DOE options.

  15. Psilocybin impairs high-level but not low-level motion perception.

    PubMed

    Carter, Olivia L; Pettigrew, John D; Burr, David C; Alais, David; Hasler, Felix; Vollenweider, Franz X

    2004-08-26

    The hallucinogenic serotonin(1A&2A) agonist psilocybin is known for its ability to induce illusions of motion in otherwise stationary objects or textured surfaces. This study investigated the effect of psilocybin on local and global motion processing in nine human volunteers. Using a forced choice direction of motion discrimination task we show that psilocybin selectively impairs coherence sensitivity for random dot patterns, likely mediated by high-level global motion detectors, but not contrast sensitivity for drifting gratings, believed to be mediated by low-level detectors. These results are in line with those observed within schizophrenic populations and are discussed in respect to the proposition that psilocybin may provide a model to investigate clinical psychosis and the pharmacological underpinnings of visual perception in normal populations.

  16. Abnormally high serum ferritin levels among professional road cyclists

    PubMed Central

    Zotter, H; Robinson, N; Zorzoli, M; Schattenberg, L; Saugy, M; Mangin, P

    2004-01-01

    Background: An international, longitudinal medical follow up examination of male professional road cyclists revealed excessively elevated serum ferritin levels. Objective: To evaluate the importance of elevated ferritin values among professional cyclists, their relationship with age and nationality, and their evolution over 3 years. Methods: Over 1000 serum ferritin values were collected. Other parameters were included in order to exclude conditions which might have increased ferritin levels without changing body iron stores. Results: In 1999, over 45% of riders displayed ferritin values above 300 ng/ml and one fourth levels over 500 ng/ml. These percentages had decreased to 27% and 9%, respectively, 3 years later, while the overall average, which was above the normal limits in 1999, had decreased by 33% in 3 years. Older cyclists had higher ferritin values than younger cyclists. There was also a relationship between ferritin levels and the nationality of the cyclists. Analysis of 714 riders in 2000 and 2002 showed only a slight and insignificant decrease in the mean ferritin value although those with initially elevated iron stores had a much greater decrease. Conclusion: Professional road cyclists used excessive iron supplementation leading to high serum ferritin levels correlating with increased body iron stores. Although the situation progressively improved over 3 years, it remains worrying as increased body iron stores are related to health complications. Therefore, prevention in addition to the fight against doping should be a main goal of the UCI. Aggressive therapy for athletes with excessive ferritin values should be carried out at or before the end of their careers. PMID:15562163

  17. High-level waste melter alternatives assessment report

    SciTech Connect

    Calmus, R.B.

    1995-02-01

    This document describes the Tank Waste Remediation System (TWRS) High-Level Waste (HLW) Program`s (hereafter referred to as HLW Program) Melter Candidate Assessment Activity performed in fiscal year (FY) 1994. The mission of the TWRS Program is to store, treat, and immobilize highly radioactive Hanford Site waste (current and future tank waste and encapsulated strontium and cesium isotopic sources) in an environmentally sound, safe, and cost-effective manner. The goal of the HLW Program is to immobilize the HLW fraction of pretreated tank waste into a vitrified product suitable for interim onsite storage and eventual offsite disposal at a geologic repository. Preparation of the encapsulated strontium and cesium isotopic sources for final disposal is also included in the HLW Program. As a result of trade studies performed in 1992 and 1993, processes planned for pretreatment of tank wastes were modified substantially because of increasing estimates of the quantity of high-level and transuranic tank waste remaining after pretreatment. This resulted in substantial increases in needed vitrification plant capacity compared to the capacity of original Hanford Waste Vitrification Plant (HWVP). The required capacity has not been finalized, but is expected to be four to eight times that of the HWVP design. The increased capacity requirements for the HLW vitrification plant`s melter prompted the assessment of candidate high-capacity HLW melter technologies to determine the most viable candidates and the required development and testing (D and T) focus required to select the Hanford Site HLW vitrification plant melter system. An assessment process was developed in early 1994. This document describes the assessment team, roles of team members, the phased assessment process and results, resulting recommendations, and the implementation strategy.

  18. Wind resource quality affected by high levels of renewables

    DOE PAGES

    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

  19. 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.

  20. High-spin level scheme of doubly odd 128I

    NASA Astrophysics Data System (ADS)

    Ding, B.; Wang, H. X.; Jiang, H.; Zhang, Y. H.; Zhou, X. H.; Zhao, Y. M.; Wang, S. T.; Liu, M. L.; Li, G. S.; Zheng, Y.; Zhang, N. T.; Zhou, H. B.; Ma, Y. J.; Sasakiz, Y.; Yamada, K.; Ohshima, H.; Yokose, S.; Ishizuka, M.; Komatsubara, T.; Furuno, K.

    2012-09-01

    High-spin states in the odd-odd 128I have been studied experimentally using the 124Sn(7Li, 3nγ)128I reaction at beam energies of 28 and 32 MeV. A level scheme built on the known T1/2=175 ns, (6-) isomer has been established. The low-lying states in the level scheme have been proposed to be associated with the πd5/2⊗νh11/2 and πg7/2⊗νh11/2 two-quasiparticle excitations. The strongly populated negative-parity states, forming a bandlike structure, have been assigned to be based on the πg7/2⊗νh11/2 configuration. The πh11/2⊗νh11/2 multiplet 9+, 10+, and 11+ members have been identified according to the systematics of the corresponding level structures observed in the lighter odd-odd iodine isotopes. The two-quasiparticle configuration assignments are supported by the nucleon pair approximation and empirical shell-model calculations.

  1. Pupil responses to high-level image content.

    PubMed

    Naber, Marnix; Nakayama, Ken

    2013-05-17

    The link between arousal and pupil dilation is well studied, but it is less known that other cognitive processes can trigger pupil responses. Here we present evidence that pupil responses can be induced by high-level scene processing, independent of changes in low-level features or arousal. In Experiment 1, we recorded changes in pupil diameter of observers while they viewed a variety of natural scenes with or without a sun that were presented either upright or inverted. Image inversion had the strongest effect on the pupil responses. The pupil constricted more to the onset of upright images as compared to inverted images. Furthermore, the amplitudes of pupil constrictions to viewing images containing a sun were larger relative to control images. In Experiment 2, we presented cartoon versions of upright and inverted pictures that included either a sun or a moon. The image backgrounds were kept identical across conditions. Similar to Experiment 1, upright images triggered pupil constrictions with larger amplitudes than inverted images and images of the sun evoked greater pupil contraction than images of the moon. We suggest that the modulations of pupil responses were due to higher-level interpretations of image content.

  2. Burning high-level TRU waste in fusion fission reactors

    NASA Astrophysics Data System (ADS)

    Shen, Yaosong

    2016-09-01

    Recently, the concept of actinide burning instead of a once-through fuel cycle for disposing spent nuclear fuel seems to get much more attention. A new method of burning high-level transuranic (TRU) waste combined with Thorium-Uranium (Th-U) fuel in the subcritical reactors driven by external fusion neutron sources is proposed in this paper. The thorium-based TRU fuel burns all of the long-lived actinides via a hard neutron spectrum while outputting power. A one-dimensional model of the reactor concept was built by means of the ONESN_BURN code with new data libraries. The numerical results included actinide radioactivity, biological hazard potential, and much higher burnup rate of high-level transuranic waste. The comparison of the fusion-fission reactor with the thermal reactor shows that the harder neutron spectrum is more efficient than the soft. The Th-U cycle produces less TRU, less radiotoxicity and fewer long-lived actinides. The Th-U cycle provides breeding of 233U with a long operation time (>20 years), hence significantly reducing the reactivity swing while improving safety and burnup.

  3. 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.

  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. 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.

  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. 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.

  8. 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.

  9. Status of high-level waste processing at West Valley

    SciTech Connect

    Howell, A.J.; Baker, M.N. )

    1991-11-01

    The US Department of Energy is charged with the solidification of high-level liquid waste remaining from nuclear fuel reprocessing activities that were conducted at West Valley, New York, between 1966 and 1972. The 2.27 million liters (600,000 gal) of waste in an underground storage tank has separated into a sludge layer, {approximately}10% of the original volume, and a liquid layer. Prior to the high-level waste (HLW) vitrification, volume reduction of the waste is necessary. Sine May 1988, West Valley has successfully processed >1.59 million liters (420,000 gal) of HLW. Processing to date has involved the removal of {sup 139}Cs from the HLW effluent by ion exchange, evaporation to concentrate the effluent to a predetermined salt concentration, and finally cementation. This process has removed {approximately}80% of the {sup 137}Cs from the HLW liquid phase. Modifications are currently being made to begin the second phase of the HLW processing at West Valley. The second phase of HLW processing will include the removal of plutonium as well as cesium from the HLW sludge. This paper describes the progress made to date and the modifications being made to the process and to the feed stream to begin the second phase of HLW processing.

  10. 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.

  11. 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

  12. 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.

  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. 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.

  15. 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

  16. High-level fluorescence labeling of gram-positive pathogens.

    PubMed

    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.

  17. 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

  18. 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.

  19. 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.

  20. The SEISMED High Level Security Policy for Health Care.

    PubMed

    Katsikas, S K

    1996-01-01

    The proliferation of the use of automated Health Information Systems in the everyday practice of health professionals has brought a number of issues related to the security of health information to a critical point. The preservation of security of health-related information can only be achieved through a concerted approach, comprising legal, organisational, technical and educational actions. These classes of actions constitute a complete "security framework", a key aspect of which is the set of rules, laws and regulations that govern the usage of information within a Health Care Establishment. This set is commonly referred to as "Security Policy". In this paper, the SEISMED High Level Security Policy for Health Care Establishments is presented.

  1. 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.

  2. High-level theoretical rovibrational spectroscopy of HCS+ isotopologues

    NASA Astrophysics Data System (ADS)

    Schröder, B.; Sebald, P.

    2016-12-01

    In this work the rovibrational spectrum of the HCS+ molecular cation is revisited through high-level electronic structure and variational rovibrational calculations. A local potential energy function is built from explicitly correlated coupled-cluster results, incorporating corrections for core-valence, scalar relativistic and higher-order excitation effects. The computed spectroscopic parameters, based on variational calculations with Watson's isomorphic Hamiltonian for linear molecules lead to a nearly perfect agreement with experimentally reported values (Rosenbaum et al., 1989). Furthermore, the documented Fermi resonance within the (0,00, 1) / (0,20, 0) and (1,00, 1) / (1,20, 0) pairs of states is clarified. Based on a newly developed electric dipole moment function transition dipole moments of fundamental transitions are predicted for the most important isotopologues.

  3. High-level tetracycline resistant Neisseria gonorrhoeae isolated in Portugal.

    PubMed

    Ferreira, E; Louro, D; Gomes, J P; Catry, M A; Pato, M V

    1997-05-01

    The first high-level tetracycline resistance (MIC > or = 16 mg/l) isolates of Neisseria gonorrhoeae (TRNG) were reported in 1990 from patients attending a Sexual Transmitted Disease (STD) Center in Lisbon. The TRNG prevalence was 4% in 1991, 5.3% in 1992 and 10,8% in 1994, exploding to 52.2% in 1995. The tet M determinant was evaluated by PCR. The digests of PCRP using HpaII produced the restriction pattern 2 for all the strains, except one (pattern 3). 78.3% of the TRNG strains were beta-lactamase producers and the 4.5 MDa penicillinase plasmid was the dominant (83%), 90% and 93.3% of the TRNG strains belonged to the auxotype NR and to the serogroup IA, respectively. The IA-8/NR class represented 58.3% of the TRNG isolates, suggesting a clonal spreading.

  4. 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.

  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. High level security policies for health care establishments.

    PubMed

    Katsikas, Sokratis; Kokolakis, Spyros

    2004-01-01

    Health Care Establishments (HCE) are today highly dependent upon Information and Communications Technologies (ICT). This increasing reliance upon ICT has stressed the need to foster security in Healthcare Information Systems (HIS). Security policies may have a significant contribution to this effort, but they could become the cause of portability and interoperability problems. Moreover, policies that fail to take into account all the aspects of HIS security, the legal and regulatory requirements, and the existence of several stakeholders may lead to ineffective or inefficient security measures. Policies of a special category, named Generic Security Policies (GSP), should be developed to provide policy-level harmonisation and guidance to policy-makers within HCE. Six such policies are comparatively reviewed herein.

  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 194}Pb

    SciTech Connect

    Kutsarova, T.; Stefanova, E. A.; Minkova, A.; Lalkovski, S.; Korichi, A.; Lopez-Martens, A.; Hannachi, F.; Huebel, H.; Goergen, A.; Jansen, A.; Schoenwasser, G.; Khoo, T. L.; Herskind, B.; Bergstroem, M.; Bazzacco, D.; Podolyak, Z.

    2009-01-15

    High-spin states in {sup 194}Pb have been populated in the {sup 168}Er({sup 30}Si,4n) reaction at 142 MeV. The emitted {gamma} rays were detected by the EUROBALL III multidetector array. The level scheme was considerably extended and many previously observed {gamma}-ray transitions were reordered. Four new magnetic rotational bands were observed. The energies and spins of the bandheads of all previously observed magnetic rotational bands were corrected based on the observation of new transitions. From nine observed bands, only one could not be connected to the lower lying states. Based on comparison systematics with neighboring Pb isotopes and tilted-axis cranking model calculations previously reported, configuration assignments to the observed bands have been made.

  9. Sandia National Laboratories' new high level acoustic test facility

    SciTech Connect

    Rogers, J. D.; Hendrick, D. M.

    1989-01-01

    A high intensity acoustic test facility has been designed and is under construction at Sandia National Laboratories in Albuquerque, NM. The chamber is designed to provide an acoustic environment of 154dB (re 20 {mu}Pa) overall sound pressure level over the bandwidth of 50 Hz to 10,000 Hz. The chamber has a volume of 16,000 cubic feet with interior dimensions of 21.6 ft {times} 24.6 ft {times} 30 ft. The construction of the chamber should be complete by the summer of 1990. This paper discusses the design goals and constraints of the facility. The construction characteristics are discussed in detail, as are the acoustic performance design characteristics. The authors hope that this work will help others in designing acoustic chambers. 12 refs., 6 figs.

  10. Respiratory physiology: adaptations to high-level exercise.

    PubMed

    McKenzie, Donald C

    2012-05-01

    Most exercise scientists would agree that the physiological determinants of peak endurance performance include the capacity to transport oxygen to the working muscle, diffusion from the muscle to the mitochondria, energy production and force generation, all influenced by signals from the central nervous system. In general, the capacity of the pulmonary system far exceeds the demands required for ventilation and gas exchange during exercise. Endurance training induces large and significant adaptations within the cardiovascular, musculoskeletal and haematological systems. However, the structural and functional properties of the lung and airways do not change in response to repetitive physical activity and, in elite athletes, the pulmonary system may become a limiting factor to exercise at sea level and altitude. As a consequence to this respiratory paradox, highly trained athletes may develop intrathoracic and extrathoracic obstruction, expiratory flow limitation, respiratory muscle fatigue and exercise-induced hypoxaemia. All of these maladaptations may influence performance.

  11. High level security policies for Healthcare Information Systems.

    PubMed

    Katsikas, Sokratis; Kokolakis, Spyros

    2003-01-01

    Healthcare Establishments (HCE) have are today highly dependent upon Information and Communications Technologies (ICT). This increasing reliance upon ICT has stressed the need to foster security in Healthcare Information Systems (HIS). Security policies may have a significant contribution to this effort, but they could become the cause of portability and interoperability problems. Moreover, policies that fail to take into account all the aspects of HIS security, the legal and regulatory requirements, and the existence of several stakeholders may lead to ineffective or inefficient security measures. Policies of a special category, named Generic Security Policies (GSPs), should be developed to provide policy-level harmonisation and guidance to policy-makers within HCEs. Five such policies are comparatively reviewed herein.

  12. High-level iodination of monoclonal antibody fragments for radiotherapy

    SciTech Connect

    Ferens, J.M.; Krohn, K.A.; Beaumier, P.L.; Brown, J.P.; Hellstroem, I.; Hellstroem, K.E.; Carrasquillo, J.A.; Larson, S.M.

    1984-03-01

    Two different murine monoclonal antibody Fab fragments specific for p97, a melanoma-associated antigen, were labeled with I-131 at high activity levels without excessive chemical damage. Up to 20 mg of Fab were labeled with up to 300 mCi of I-131 using the chloramine-T method and large working volumes at room temperature. As much as 90% of the initial activity was recovered as labeled product. The labeled Fabs varied in their sensitivity to radioiodination damage, as measured by an in vitro cell-binding assay. Radioiodination was performed safely using a remote iodination apparatus. The final product was of radiopharmaceutical quality suitable for clinical diagnosis and experimental radiotherapy in humans.

  13. Reinforcement learning for high-level fuzzy Petri nets.

    PubMed

    Shen, V L

    2003-01-01

    The author has developed a reinforcement learning algorithm for the high-level fuzzy Petri net (HLFPN) models in order to perform structure and parameter learning simultaneously. In addition to the HLFPN itself, the difference and similarity among a variety of subclasses concerning Petri nets are also discussed. As compared with the fuzzy adaptive learning control network (FALCON), the HLFPN model preserves the advantages that: 1) it offers more flexible learning capability because it is able to model both IF-THEN and IF-THEN-ELSE rules; 2) it allows multiple heterogeneous outputs to be drawn if they exist; 3) it offers a more compact data structure for fuzzy production rules so as to save information storage; and 4) it is able to learn faster due to its structural reduction. Finally, main results are presented in the form of seven propositions and supported by some experiments.

  14. 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.

  15. Vestibular contributions to high-level sensorimotor functions.

    PubMed

    Medendorp, W Pieter; Selen, Luc J P

    2017-02-02

    The vestibular system, which detects motion and orientation of the head in space, is known to be important in controlling gaze to stabilize vision, to ensure postural stability and to provide our sense of self-motion. While the brain's computations underlying these functions are extensively studied, the role of the vestibular system in higher level sensorimotor functions is less clear. This review covers new research on the vestibular influence on perceptual judgments, motor decisions, and the ability to learn multiple motor actions. Guided by concepts such as optimization, inference, estimation and control, we focus on how the brain determines causal relationships between memorized and visual representations in the updating of visual space, and how vestibular, visual and efferent motor information are integrated in the estimation of body motion. We also discuss evidence that these computations involve multiple coordinate representations, some of which can be probed in parietal cortex using neuronal oscillations derived from EEG. In addition, we describe work on decision making during self-motion, showing a clear modulation of bottom-up acceleration signals on decisions in the saccadic system. Finally, we consider the importance of vestibular signals as contextual cues in motor learning and recall. Taken together, these results emphasize the impact of vestibular information on high-level sensorimotor functions, and identify future directions for theoretical, behavioral, and neurophysiological investigations.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Sea level rise Contribution from High Mountain Asia by 20150

    NASA Astrophysics Data System (ADS)

    Zhao, Liyun; Moore, John; Ding, Ran

    2015-04-01

    We estimate individual area and volume change by 2050 of all 83,460 glaciers of high mountain Asia (HMA), with a total area of 118,263 km2, delineated in the Randolph Glacier Inventory version 4.0 which separates glacier complexes in its previous version into individual glaciers. We used the 25 km resolution regional climate model RegCM 3.0 temperature and precipitation change projections forced by the IPCC A1B scenario. Glacier simulations were based on a novel surface mass balance-altitude parameterization fitted to observational data, and various volume-area scaling approaches using Shuttle Radar Topography Mission surface topography of each individual glacier. We generate mass balance-altitude relations for all the glaciers by region using nearest available glacier measurements. Two method are used to model the Equilibrium line altitude (ELA) variation. One is to use ELA sensitivities to temperature and precipitation change vary by region based on the relative importance of sublimation and melting processes. The other is solved ELA implicitly for every year using the temperature at ELA and Degree Day model. We project total glacier area loss in high mountain Asia in 2050 to be 22% of their extent in 2000, and they will contribute 5-8 mm to global sea level rise.

  3. Control of high level radioactive waste-glass melters

    SciTech Connect

    Bickford, D.F.; Choi, A.S.

    1991-01-01

    Slurry Fed Melters (SFM) are being developed in the United States, Europe and Japan for the conversion of high-level radioactive waste to borosilicate glass for permanent disposal. The high transition metal, noble metal, nitrate, organic, and sulfate contents of these wastes lead to unique melter redox control requirements. Pilot waste-glass melter operations have indicated the possibility of nickel sulfide or noble-metal fission-product accumulation on melter floors, which can lead to distortion of electric heating patterns, and decrease melter life. Sulfide formation is prevented by control of the redox chemistry of the melter feed. The redox state of waste-glass melters is determined by balance between the reducing potential of organic compounds in the feed, and the oxidizing potential of gases above the melt, and nitrates and polyvalent elements in the waste. Semiquantitative models predicting limitations of organic content have been developed based on crucible testing. Computerized thermodynamic computations are being developed to predict the sequence and products of redox reactions and is assessing process variations. Continuous melter test results have been compared to improved computer staged-thermodynamic-models of redox behavior. Feed chemistry control to prevent sulfide and moderate noble metal accumulations are discussed. 17 refs., 3 figs.

  4. Seeking explanations for high levels of infant mortality in Pakistan.

    PubMed

    Sathar, Z A

    1987-01-01

    Data from the Fertility Module of the 1979 Population, Labour Force and Migration (PLM) Survey of Pakistan were analyzed to determine which of 4 factors were primarily responsible for the high infant mortality rate. The factors examined were poverty, childbearing and childrearing practices, distribution of health care and lack of individual attention given to children due to ignorance. These items were presented in a discussion format. Infant mortality in Pakistan is high at about 125-140/1000, for a country with mid-level per capita income. Income was not a good indicator of child mortality, primarily because it was difficult to determine, particularly in rural areas where non-cash income predominates. Wealth and status were good indicators of child survival. Child-rearing practices were somewhat important, as judged by birth order, breastfeeding duration and gender. Childbearing practices as shown by spacing were important determinants of survival. Health care facilities were somewhat important, indicated by higher mortality in rural areas. Rural neonates die from tetanus due to lack of immunization, or later from diarrheal disease due to lack of potable water or poor weaning practices. Maternal education was a strong indicator of survival, much more so than paternal education. Similarly, female heads of households increased survival, probably because they control financial allocations. The study suggested that rather than attempting to eliminate poverty overall, improvements in maternal education, nutrition, health care facilities and their use, and childbearing and child-rearing methods would do more to improve child survival in Pakistan.

  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. 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

  7. 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.

  8. 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.

  9. 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

  10. Transient - Photoresistance Spectroscopy of Deep Levels in High Resistivity Semiconductors

    NASA Astrophysics Data System (ADS)

    Seabaugh, Alan Carter

    A new photoinduced transient-resistance technique is proposed and examined for use in characterizing high -resistivity, short-lifetime semiconductors. In this technique, termed photoresistance deep-level transient spectroscopy (PR-DLTS), an optical pulse is used to generate excess carriers which are trapped by deep levels in the material. The ac resistance of the specimen is monitored, and the resistance transient which occurs after the illumination ends is signal processed in the same way as the capacitance transient in DLTS. A phenomenological model of the phototransient is used to derive an expression for the decay transient. Two limiting forms for the transient are predicted depending upon whether the emitted carriers are collected at the device contacts, or recombine in the bulk before being collected. In order to test this model, several methods for distinguishing between the predicted decays of the form exp(-(lamda)t) and (lamda)exp(-(lamda)t) were developed ((lamda) is the reciprocal time constant for the decay). The measured results are consistent with the predictions of the model, but an 'ideal' sample has not been found to fully test the predictions. On Au-doped Si, excellent agreement between published emission rates for the Au-acceptor and the apparent emission rates measured by PR-DLTS is found. In addition, PR-DLTS data for the Cr-related deep level in semi-insulating GaAs is consistent with published DLTS results on conducting GaAs. Comparison of the PR-DLTS technique with the dc current-transient technique, photoinduced transient spectroscopy (PITS), shows that the two techniques are sensitive to the same trapping/detrapping phenomena. Finally, the results of a comparative study of commercial semi-insulating GaAs are reported. Nineteen specimens from ten suppliers were examined using the PR -DLTS technique, including material grown by the horizontal Bridgman (HB) and liquid-encapsulated Czochralski (LEC) technique, both with and without Cr

  11. 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

  12. 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

  13. 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.

  14. 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).

  15. 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.

  16. 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.

  17. Potential for erosion corrosion of SRS high level waste tanks

    SciTech Connect

    Zapp, P.E.

    1994-01-01

    SRS high-level radioactive waste tanks will not experience erosion corrosion to any significant degree during slurry pump operations. Erosion corrosion in carbon steel structures at reported pump discharge velocities is dominated by electrochemical (corrosion) processes. Interruption of those processes, as by the addition of corrosion inhibitors, sharply reduces the rate of metal loss from erosion corrosion. The well-inhibited SRS waste tanks have a near-zero general corrosion rate, and therefore will be essentially immune to erosion corrosion. The experimental data on carbon steel erosion corrosion most relevant to SRS operations was obtained at the Hanford Site on simulated Purex waste. A metal loss rate of 2.4 mils per year was measured at a temperature of 102 C and a slurry velocity comparable to calculated SRS slurry velocities on ground specimens of the same carbon steel used in SRS waste tanks. Based on these data and the much lower expected temperatures, the metal loss rate of SRS tanks under waste removal and processing conditions should be insignificant, i.e. less than 1 mil per year.

  18. Metrics associated with NIH funding: a high-level view

    PubMed Central

    Jordan, Paul

    2011-01-01

    Objective To introduce the availability of grant-to-article linkage data associated with National Institutes of Health (NIH) grants and to perform a high-level analysis of the publication outputs and impacts associated with those grants. Design Articles were linked to the grants they acknowledge using the grant acknowledgment strings in PubMed using a parsing and matching process as embodied in the NIH Scientific Publication Information Retrieval & Evaluation System system. Additional data from PubMed and citation counts from Scopus were added to the linkage data. The data comprise 2 572 576 records from 1980 to 2009. Results The data show that synergies between NIH institutes are increasing over time; 29% of current articles acknowledge grants from multiple institutes. The median time lag to publication for a new grant is 3 years. Each grant contributes to approximately 1.7 articles per year, averaged over all grant types. Articles acknowledging US Public Health Service (PHS, which includes NIH) funding are cited twice as much as US-authored articles acknowledging no funding source. Articles acknowledging both PHS funding and a non-US government funding source receive on average 40% more citations that those acknowledging PHS funding sources alone. Conclusion The US PHS is effective at funding research with a higher-than-average impact. The data are amenable to further and much more detailed analysis. PMID:21527408

  19. 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.

  20. Identification of areas with high levels of untreated dental caries.

    PubMed

    Ellwood, R P; O'Mullane, D M

    1996-02-01

    In order to examine the geographical variation of dental health within 10 county districts in North Wales, 3538 children were examined. The associations between three demographic indicators, based on the 1981 OPCS census, and dental health outcomes were assessed for electoral wards within the county districts. The Townsend and Jarman indices were the first two indicators employed and the third was based on a mathematical model representing the variation in the mean number of untreated decayed surfaces per person for the wards. This model was developed using the children examined in the five most westerly county districts. Using the data derived from the five most easterly county districts, the three indicators were assessed. All three showed strong correlations (r > or = 0.88) with dental health. These results indicate that measures of dental health based on large administrative units may obscure variation within them. It is concluded that geographical methods of this type may be useful for targeting dental resources at small areas with high levels of need.

  1. 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.

  2. A high rate clarifier for load levelling in sewerage systems.

    PubMed

    Jago, R A; Davey, A; Li, H

    2003-01-01

    The combining of chemically assisted clarification with a proprietary physical separation technology has led to a high rate process for clarifying flocculated sewage and other waste streams. This hybrid physico-chemical system, known as the CDS Fine Solids Separation (FSS) System, was developed over a two year period within a sewage treatment plant environment. This paper summarises the results of a recent field trial of the system with a Victorian water authority which experiences heavy loading of sewers in a coastal town during holiday periods. The trial sought to evaluate the FSS as a tool for smoothing the load on the 11 km long sewer to the sewage treatment plant (STP). The FSS system could possibly enable the costly augmentation of the sewer to be deferred, particularly as the capacity of the existing sewer pipe is satisfactory for most of the year. Water quality parameters were determined for a range of flowrates and operational conditions over a two month period. Large reductions were achieved in TSS, TP, FC, turbidity and BOD5, with only minimal reductions in NH3 and TON. These results showed that the FSS could meet the authority's objectives for load levelling and would provide a 20-25% increase in effective sewer capacity. The data are also discussed in terms of possible use of the effluent from the FSS for water reuse applications.

  3. High-level simulation of JWST event-driven operations

    NASA Astrophysics Data System (ADS)

    Henry, R.; Kinzel, W.

    2012-09-01

    The James Webb Space Telescope (JWST) has an event-driven architecture: an onboard Observation Plan Executive (OPE) executes an Observation Plan (OP) consisting of a sequence of observing units (visits). During normal operations, ground action to update the OP is only expected to be necessary about once a week. This architecture is designed to tolerate uncertainty in visit duration, and occasional visit failures due to inability to acquire guide stars, without creating gaps in the observing timeline. The operations concept is complicated by the need for occasional scheduling of timecritical science and engineering visits that cannot tolerate much slippage without inducing gaps, and also by onboard momentum management. A prototype Python tool called the JWST Observation Plan Execution Simulator (JOPES) has recently been developed to simulate OP execution at a high level and analyze the response of the Observatory and OPE to both nominal and contingency scenarios. Incorporating both deterministic and stochastic behavior, JOPES has potential to be a powerful tool for several purposes: requirements analysis, system verification, systems engineering studies, and test data generation. It has already been successfully applied to a study of overhead estimation bias: whether to use conservative or average-case estimates for timing components that are inherently uncertain, such as those involving guide-star acquisition. JOPES is being enhanced to support interfaces to the operational Proposal Planning Subsystem (PPS) now being developed, with the objective of "closing the loop" between testing and simulation by feeding simulated event logs back into the PPS.

  4. EUVE GO Survey: High Levels of User Satisfaction

    NASA Astrophysics Data System (ADS)

    Stroozas, B. A.

    2000-12-01

    This paper describes the results of a detailed customer survey of Guest Observers (GOs) for NASA's Extreme Ultraviolet Explorer (EUVE) astronomy satellite observatory. The purpose of the research survey was to (1) measure the levels of GO customer satisfaction with respect to EUVE observing services, and (2) compare the observing experiences of EUVE GOs with their experiences using other satellite observatories. This survey was conducted as a business research project -- part of the author's graduate work as an MBA candidate. A total sample of 38 respondents, from a working population of 101 "active" EUVE GOs, participated in this survey. The results, which provided a profile of the "typical" EUVE GO, showed in a statistically significant fashion that these GOs were more than satisfied with the available EUVE observing services. In fact, the sample GOs generally rated their EUVE observing experiences to be better than average as compared to their experiences as GOs on other missions. These relatively high satisfaction results are particularly pleasing to the EUVE Project which, given its significantly reduced staffing environment at U.C. Berkeley, has continued to do more with less. This paper outlines the overall survey process: the relevant background and previous research, the survey design and methodology, and the final results and their interpretation. The paper also points out some general limitations and weaknesses of the study, along with some recommended actions for the EUVE Project and for NASA in general. This work was funded by NASA/UCB Cooperative Agreement NCC5-138.

  5. 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.

  6. 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

  7. 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).

  8. 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

  9. 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.

  10. Qualification of Innovative High Level Waste Pipeline Unplugging Technologies

    SciTech Connect

    McDaniel, D.; Gokaltun, S.; Varona, J.; Awwad, A.; Roelant, D.; Srivastava, R.

    2008-07-01

    In the past, some of the pipelines have plugged during high level waste (HLW) transfers resulting in schedule delays and increased costs. Furthermore, pipeline plugging has been cited by the 'best and brightest' technical review as one of the major issues that can result in unplanned outages at the Waste Treatment Plant causing inconsistent operation. As the DOE moves toward a more active high level waste retrieval, the site engineers will be faced with increasing cross-site pipeline waste slurry transfers that will result in increased probability of a pipeline getting plugged. Hence, availability of a pipeline unplugging tool/technology is crucial to ensure smooth operation of the waste transfers and in ensuring tank farm cleanup milestones are met. FIU had earlier tested and evaluated various unplugging technologies through an industry call. Based on mockup testing, two technologies were identified that could withstand the rigors of operation in a radioactive environment and with the ability to handle sharp 90 elbows. We present results of the second phase of detailed testing and evaluation of pipeline unplugging technologies and the objective is to qualify these pipeline unplugging technologies for subsequent deployment at a DOE facility. The current phase of testing and qualification comprises of a heavily instrumented 3-inch diameter (full-scale) pipeline facilitating extensive data acquisition for design optimization and performance evaluation, as it applies to three types of plugs atypical of the DOE HLW waste. Furthermore, the data from testing at three different lengths of pipe in conjunction with the physics of the process will assist in modeling the unplugging phenomenon that will then be used to scale-up process parameters and system variables for longer and site typical pipe lengths, which can extend as much as up to 19,000 ft. Detailed information resulting from the testing will provide the DOE end-user with sufficient data and understanding of the

  11. Electric Grid Expansion Planning with High Levels of Variable Generation

    SciTech Connect

    Hadley, Stanton W.; You, Shutang; Shankar, Mallikarjun; Liu, Yilu

    2016-02-01

    Renewables are taking a large proportion of generation capacity in U.S. power grids. As their randomness has increasing influence on power system operation, it is necessary to consider their impact on system expansion planning. To this end, this project studies the generation and transmission expansion co-optimization problem of the US Eastern Interconnection (EI) power grid with a high wind power penetration rate. In this project, the generation and transmission expansion problem for the EI system is modeled as a mixed-integer programming (MIP) problem. This study analyzed a time series creation method to capture the diversity of load and wind power across balancing regions in the EI system. The obtained time series can be easily introduced into the MIP co-optimization problem and then solved robustly through available MIP solvers. Simulation results show that the proposed time series generation method and the expansion co-optimization model and can improve the expansion result significantly after considering the diversity of wind and load across EI regions. The improved expansion plan that combines generation and transmission will aid system planners and policy makers to maximize the social welfare. This study shows that modelling load and wind variations and diversities across balancing regions will produce significantly different expansion result compared with former studies. For example, if wind is modeled in more details (by increasing the number of wind output levels) so that more wind blocks are considered in expansion planning, transmission expansion will be larger and the expansion timing will be earlier. Regarding generation expansion, more wind scenarios will slightly reduce wind generation expansion in the EI system and increase the expansion of other generation such as gas. Also, adopting detailed wind scenarios will reveal that it may be uneconomic to expand transmission networks for transmitting a large amount of wind power through a long distance

  12. 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}.

  13. High-level waste issues and resolutions document

    SciTech Connect

    Not Available

    1994-05-01

    The High-Level Waste (HLW) Issues and Resolutions Document recognizes US Department of Energy (DOE) complex-wide HLW issues and offers potential corrective actions for resolving these issues. Westinghouse Management and Operations (M&O) Contractors are effectively managing HLW for the Department of Energy at four sites: Idaho National Engineering Laboratory (INEL), Savannah River Site (SRS), West Valley Demonstration Project (WVDP), and Hanford Reservation. Each site is at varying stages of processing HLW into a more manageable form. This HLW Issues and Resolutions Document identifies five primary issues that must be resolved in order to reach the long-term objective of HLW repository disposal. As the current M&O contractor at DOE`s most difficult waste problem sites, Westinghouse recognizes that they have the responsibility to help solve some of the complexes` HLW problems in a cost effective manner by encouraging the M&Os to work together by sharing expertise, eliminating duplicate efforts, and sharing best practices. Pending an action plan, Westinghouse M&Os will take the initiative on those corrective actions identified as the responsibility of an M&O. This document captures issues important to the management of HLW. The proposed resolutions contained within this document set the framework for the M&Os and DOE work cooperatively to develop an action plan to solve some of the major complex-wide problems. Dialogue will continue between the M&Os, DOE, and other regulatory agencies to work jointly toward the goal of storing, treating, and immobilizing HLW for disposal in an environmentally sound, safe, and cost effective manner.

  14. 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

  15. 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.

  16. Compensatory Changes in the Cytoplasmic Tail of gp41 Confer Resistance to Tetherin/BST-2 in a Pathogenic Nef-deleted SIV

    PubMed Central

    Serra-Moreno, Ruth; Jia, Bin; Breed, Matthew; Alvarez, Xavier; Evans, David T.

    2011-01-01

    SUMMARY Tetherin (BST-2 or CD317) is an interferon-inducible transmembrane protein that inhibits virus release from infected cells. Whereas HIV-1 Vpu and HIV-2 Env counteract human tetherin, most SIVs use Nef to antagonize the tetherin proteins of their non-human primate hosts. Here we show that compensatory changes in the cytoplasmic domain of SIV gp41, acquired by a nef-deleted virus that regained a pathogenic phenotype in infected rhesus macaques, restore resistance to tetherin. These changes facilitate virus release in the presence of rhesus tetherin, but not human tetherin, and enhance virus replication in interferon-treated primary lymphocytes. The substitutions in gp41 result in a selective physical association with rhesus tetherin, and the internalization and sequestration of rhesus tetherin by a mechanism that depends on a conserved endocytosis motif in gp41. These results are consistent with HIV-2 Env antagonism of human tetherin, and suggest that the ability to oppose tetherin is important for lentiviral pathogenesis. PMID:21238946

  17. 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)

  18. A high-speed DAQ framework for future high-level trigger and event building clusters

    NASA Astrophysics Data System (ADS)

    Caselle, M.; Ardila Perez, L. E.; Balzer, M.; Dritschler, T.; Kopmann, A.; Mohr, H.; Rota, L.; Vogelgesang, M.; Weber, M.

    2017-03-01

    Modern data acquisition and trigger systems require a throughput of several GB/s and latencies of the order of microseconds. To satisfy such requirements, a heterogeneous readout system based on FPGA readout cards and GPU-based computing nodes coupled by InfiniBand has been developed. The incoming data from the back-end electronics is delivered directly into the internal memory of GPUs through a dedicated peer-to-peer PCIe communication. High performance DMA engines have been developed for direct communication between FPGAs and GPUs using "DirectGMA (AMD)" and "GPUDirect (NVIDIA)" technologies. The proposed infrastructure is a candidate for future generations of event building clusters, high-level trigger filter farms and low-level trigger system. In this paper the heterogeneous FPGA-GPU architecture will be presented and its performance be discussed.

  19. High-Dimensional Topological Insulators with Quaternionic Analytic Landau Levels

    NASA Astrophysics Data System (ADS)

    Li, Yi; Wu, Congjun

    2013-05-01

    We study the three-dimensional topological insulators in the continuum by coupling spin-1/2 fermions to the Aharonov-Casher SU(2) gauge field. They exhibit flat Landau levels in which orbital angular momentum and spin are coupled with a fixed helicity. The three-dimensional lowest Landau level wave functions exhibit the quaternionic analyticity as a generalization of the complex analyticity of the two-dimensional case. Each Landau level contributes one branch of gapless helical Dirac modes to the surface spectra, whose topological properties belong to the Z2 class. The flat Landau levels can be generalized to an arbitrary dimension. Interaction effects and experimental realizations are also studied.

  20. 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.

  1. High glucose levels boost the aggressiveness of highly metastatic cholangiocarcinoma cells via O-GlcNAcylation

    PubMed Central

    Phoomak, Chatchai; Vaeteewoottacharn, Kulthida; Silsirivanit, Atit; Saengboonmee, Charupong; Seubwai, Wunchana; Sawanyawisuth, Kanlayanee; Wongkham, Chaisiri; Wongkham, Sopit

    2017-01-01

    Increased glucose utilization is a feature of cancer cells to support cell survival, proliferation, and metastasis. An association between diabetes mellitus and cancer progression was previously demonstrated in cancers including cholangiocarcinoma (CCA). This study was aimed to determine the effects of high glucose on protein O-GlcNAcylation and metastatic potentials of CCA cells. Two pairs each of the parental low metastatic and highly metastatic CCA sublines were cultured in normal (5.6 mM) or high (25 mM) glucose media. The migration and invasion abilities were determined and underlying mechanisms were explored. Results revealed that high glucose promoted migration and invasion of CCA cells that were more pronounced in the highly metastatic sublines. Concomitantly, high glucose increased global O-GlcNAcylated proteins, the expressions of vimentin, hexokinase, glucosamine-fructose-6-phosphate amidotransferase (GFAT) and O-GlcNAc transferase of CCA cells. The glucose level that promoted migration/invasion was shown to be potentiated by the induction of GFAT, O-GlcNAcylation and an increase of O-GlcNAcylated vimentin and vimentin expression. Treatment with a GFAT inhibitor reduced global O-GlcNAcylated proteins, vimentin expression, and alleviated cell migration. Altogether, these results suggested the role of high glucose enhanced CCA metastasis via modulation of O-GlcNAcylation, through the expressions of GFAT and vimentin. PMID:28262738

  2. 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

  3. 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

  4. High density multi-level recording for archival data preservation

    NASA Astrophysics Data System (ADS)

    Holzner, F.; Paul, Ph.; Drechsler, U.; Despont, M.; Knoll, A. W.; Duerig, U.

    2011-07-01

    Archival data storage is predominantly based on magnetic tape technology. An alternative probe based multi-level recording scheme is proposed which specifically addresses the issue of long term data preservation. In a first step, the data are written as topographic relief in an organic resist. To achieve long term preservation, the relief structure is transferred in a Si based inorganic carrier by means of reactive ion etching. Thereby, the data are preserved as written in stone. Using 3-level logic, a storage density of 99 Gb/in2 is demonstrated and read-back of the data is accomplished with an error rate of 10-3 based on threshold detection. Exploiting etch anisotropy in layered substrates, logic levels can be physically separated from one another in different layers which enhances tamper resistance and also provides a means for heterogeneous storage concepts.

  5. 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.

  6. State-Level High School Improvement Systems Checklist

    ERIC Educational Resources Information Center

    National High School Center, 2007

    2007-01-01

    This checklist is designed to help states at various stages develop their system of support to reach struggling high schools. The checklist can be used to assess where your state is in terms of the elements of using existing support and guidance mechanisms, and reconfiguring and/or creating new structures to leverage system change for high school…

  7. 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).

  8. 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.

  9. [Potential of using inertial sensors in high level sports].

    PubMed

    Ruzova, T K; Andreev, D A; Shchukin, A I

    2013-01-01

    The article thoroughly covers development of wireless inertial sensors technology in medicine. The authors describe main criteria of diagnostic value of inertial sensors, advantages and prospects of using these systems in sports medicine, in comparison with other conventional methods of biomechanical examination in sports medicine. The results obtained necessitate further development of this approach, specifically creation of algorithms and methods of biomechanic examination of highly qualified athletes in high achievements sports.

  10. Correlation between High Density Lipoprotein Cholesterol (HDL) Level and Aerobic Activity Level.

    DTIC Science & Technology

    1987-04-01

    over a 40 day period for HDtJICholesteroll and Total Choleis- added with the "reverse" technique, This technique is only poai- tarot . The results are...Stand- tarot and Total Cholestero levels, it is beat that eet laoatr ard and a control Serum were each analyzed 10 times giving the * determinle its

  11. 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.

  12. High-level aftereffects to global scene properties.

    PubMed

    Greene, Michelle R; Oliva, Aude

    2010-12-01

    Adaptation is ubiquitous in the human visual system, allowing recalibration to the statistical regularities of its input. Previous work has shown that global scene properties such as openness and mean depth are informative dimensions of natural scene variation useful for human and machine scene categorization (Greene & Oliva, 2009b; Oliva & Torralba, 2001). A visual system that rapidly categorizes scenes using such statistical regularities should be continuously updated, and therefore is prone to adaptation along these dimensions. Using a rapid serial visual presentation paradigm, we show aftereffects to several global scene properties (magnitude 8-21%). In addition, aftereffects were preserved when the test image was presented 10 degrees away from the adapted location, suggesting that the origin of these aftereffects is not solely due to low-level adaptation. We show systematic modulation of observers' basic-level scene categorization performances after adapting to a global property, suggesting a strong representational role of global properties in rapid scene categorization.

  13. Connectionist Models and Parallelism in High Level Vision.

    DTIC Science & Technology

    1985-01-01

    another by spike frequency. This means that the conventional computer mechanism of passing complex symbolic structures cannot be used directly and that...many levels. Figure 2.2: The Necker Cube The stable coalition mechanism also has implications for the "grandmother cell" issue. Even the 3-unit loop...consistenc requirements. In general, we would like to view uniform dynamic links as a mechanism roughly equivalent to modifiable or I %. 9 conjunctive

  14. Factors Affecting Noise Levels of High-Speed Handpieces

    DTIC Science & Technology

    2012-06-01

    office communication and increase patient anxiety. Purpose: To determine if three noise-reducing techniques utilized in larger scale , non- dental...hearing loss may cause confusion, fear, and loneliness , and that sometimes hearing loss is accompanied by dizziness, which would be a handicap in the...employee noise exposures equal or exceed an 8- hour time-weighted average sound level (TWA) of 85 decibels measured on the A scale (slow response) or

  15. 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)).

  16. 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

  17. High antibody levels to P. gingivalis in cardiovascular disease.

    PubMed

    Bohnstedt, S; Cullinan, M P; Ford, P J; Palmer, J E; Leishman, S J; Westerman, B; Marshall, R I; West, M J; Seymour, G J

    2010-09-01

    Recent evidence suggests that strain variation in the serum IgG response to Porphyromonas gingivalis occurs in periodontal disease and cardiovascular disease (CVD). This study aimed to test the hypothesis that different P. gingivalis strains would elicit different levels of IgG, depending on a patient's cardiovascular (CV) and periodontal health. For CVD patients, serum antibody levels increased significantly with increasing numbers of deep pockets for all strains of P. gingivalis, except W50 (p < 0.001). We used a two-way analysis of variance to examine differences in antibody responses across several CV and periodontal groups simultaneously. There was a significant interaction effect (p < 0.05) between periodontal status and CV status for antibody levels to ATCC33277, UQD605, and Su63. This study shows variation in strain type with respect to serum IgG response in several CV and periodontal categories, providing further support for the role of the immune response to P. gingivalis in the relationship between periodontal disease and CVD.

  18. 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).

  19. A High School Level Course On Robot Design And Construction

    NASA Astrophysics Data System (ADS)

    Sadler, Paul M.; Crandall, Jack L.

    1984-02-01

    The Robotics Design and Construction Class at Sehome High School was developed to offer gifted and/or highly motivated students an in-depth introduction to a modern engineering topic. The course includes instruction in basic electronics, digital and radio electronics, construction skills, robotics literacy, construction of the HERO 1 Heathkit Robot, computer/ robot programming, and voice synthesis. A key element which leads to the success of the course is the involvement of various community assets including manpower and financial assistance. The instructors included a physics/electronics teacher, a computer science teacher, two retired engineers, and an electronics technician.

  20. 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…

  1. Plugging into Pop at the Junior High Level.

    ERIC Educational Resources Information Center

    Thompson, Dick

    1979-01-01

    Describes a junior high music program in Ridgewood, New Jersey, which capitalizes on student interest in popular music through courses in rock music history, pop music choral concerts, and facilities offering modern music production and performance equipment. This article is part of a theme issue on popular music. (SJL)

  2. Characterizations in High-Interest/Low-Vocabulary Level Fiction.

    ERIC Educational Resources Information Center

    Williams, Helen E.

    1987-01-01

    Analyzes 25 high-interest low-vocabulary fiction books and compares them to representative young adult literature in terms of 10 characteristics: youthful protagonist; adolescent's interpretation; direct exposition, dialogue, and confrontation; structural conventions; independent protagonist; consequential events; authoritative portrayals;…

  3. Making the Transition from Middle Level to High School.

    ERIC Educational Resources Information Center

    Hertzog, C. Jay; Morgan, P. Lena

    1999-01-01

    A survey of 97 Florida and Georgia middle schools and their receiving high schools revealed that schools with two or fewer transition practices had significantly higher attrition and dropout rates than schools implementing three or more practices. Sample programs include the ninth-grade house, parent nights, advisory/mentoring programs, and…

  4. 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…

  5. 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)

  6. 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…

  7. ZERO-VALENT IRON FOR HIGH-LEVEL ARSENITE REMOVAL

    EPA Science Inventory

    This study conducted by flow through column systems was aimed at investigating the feasibility of using zero-valent iron for arsenic remediation in groundwater. A high concentration arsenic solution (50 mg l-1) was prepared by using sodium arsenite (arsenic (III)) to simulate gr...

  8. Cost evaluation of a DSN high level real-time language

    NASA Technical Reports Server (NTRS)

    Mckenzie, M.

    1977-01-01

    The hypothesis that the implementation of a DSN High Level Real Time Language will reduce real time software expenditures is explored. The High Level Real Time Language is found to be both affordable and cost-effective.

  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. Perceptual learning of parametric face categories leads to the integration of high-level class-based information but not to high-level pop-out.

    PubMed

    Kietzmann, Tim C; König, Peter

    2010-11-24

    To date, the relative contribution of the different levels of the visual hierarchy during perceptual decisions remains unclear. Typical models of visual processing, with the reverse hierarchy theory (RHT) as a prominent example, strongly emphasize the role of higher levels and interpret lower levels as sequence of simple feature detectors. Here, we investigate this issue based on two analyses. Using a novel combination of perceptual learning based on two classes of parametric faces and a subsequent odd-one-out paradigm, we first test a vital prediction of RHT: high-level pop-out. With this experimental approach, we overcome the low-level confounds of previous studies while still introducing distinct high-level representations. Contrary to previous findings, our analyses show that there is no high-level pop-out, despite very early, near-perfect classification accuracy and extensive training of our subjects. Second, we explore the underlying form of category representation during subsequent stages of perceptual training. This is accomplished by including class-external and class-internal target-distractor combinations. Whereas the subjects' responses during the first sessions are best explained instance-based and dependent on low-level metric differences, later patterns exhibit the inclusion of high-level, class-based information that is independent of target-stimulus similarity. Finally, we show that the utilized level of information is highly task-dependent.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Game-theoretic High-Level Distributed Fusion

    DTIC Science & Technology

    2008-12-31

    theory quite an excitement and even daring hope among some mathematicians that it would do to the field of economics what Newtonian calculus did for...extended Neumann’s theory to N-person non -cooperative games and established the notion of what is now famously known as Nash-equilibrium that eventually...this area, we know an equilibrium solution exists for such N-person games, though actually finding an equilibrium is a highly non -trivial task (we

  16. High-Level Vision and Planning Workshop Proceedings

    DTIC Science & Technology

    1989-08-01

    in Reports. IDA Papers ame reviWed to ensure that they meet the high standards expected of rd papers in professional pournals orformal ency repots...based on local image attributes) • Physical and geometrical modeling (study of constraints imposed by physical world and imaging process) * Global...examine reasoning about other agents from two different perspectives, * the "prescriptive/descriptive" approach and the "jointly prescriptive" ap - proach

  17. High serum lactate level may predict death within 24 hours

    PubMed Central

    Zoubi, Abd Almajid; Kuria, Shiran; Blum, Nava

    2015-01-01

    Background Unexpected death within 24 hours of admission is a real challenge for the clinician in the emergency room. How to diagnose these patients and the right approach to prevent sudden death with 24 hours is still an enigma. The aims of our study were to find the independent factors that may affect the clinical outcome in the first 24 hours of admission to the hospital. Methods We performed a retrospective study defining unexpected death within 24 hours of admission in our Department of Medicine in the last 6 years. We found 43 patients who died within 24 hours of admission, and compared their clinical and biochemical characteristics to 6055 consecutive patients who were admitted in that period of time and did not die within the first 24 hours of admission. The parameters that were used include gender, age, temperature, clinical and laboratory criteria for SIRS, arterial blood lactate, and arterial blood pH. Results Most of the patients who died within 24 hours had sepsis with SIRS. These patients were older (78.6±14.7 vs. 65.2±20.2 years [p<.0001]), had higher lactate levels (8.0±4.8 vs. 2.1±1.8mmol/L [p<.0001]), and lower pH (7.2±0.2 vs. 7.4±0.1 [p<.0001]). Logistic regression analysis found that lactate was the strongest independent parameter to predict death within 24 hours of admission (OR 1.366 [95% CI 1.235–1.512]), followed by old age (OR 1.048 [95% CI 1.048–1.075] and low arterial blood pH (OR 0.007 [CI <0.001–0.147]). When gender was analyzed, pH was not an independent variable in females (only in males). Conclusions The significant independent variable that predicted death within 24 hours of admission was arterial blood lactate level on admission. Older age was also an independent variable; low pH affected only males, but was a less dominant variable. We suggest use of arterial blood lactate level on admission as a bio-marker in patients with suspected sepsis admitted to the hospital for risk assessment and prediction of death within 24

  18. High level fructan accumulation in a transgenic sugar beet.

    PubMed

    Sévenier, R; Hall, R D; van der Meer, I M; Hakkert, H J; van Tunen, A J; Koops, A J

    1998-09-01

    We have transformed sugar beet into a crop that produces fructans. The gene encoding 1-sucrose:sucrose fructosyl transferase (1-SST), which was isolated from Helianthus tuberosus, was introduced into sugar beet. In H. tuberosus, 1-SST mediates the first steps in fructan synthesis through the conversion of sucrose (GF) into low molecular weight fructans GF2, GF3, and GF4. In the taproot of sugar beet transformed with the 1-sst gene, the stored sucrose is almost totally converted into low molecular weight fructans. In contrast, 1-sst expression in the leaves resulted in only low levels of fructans. Despite the storage carbohydrate having been altered, the expression of the 1-sst gene did not have any visible effect on phenotype and did not affect the growth rate of the taproot as observed under greenhouse conditions.

  19. 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.

  20. Chern-Simons theory for electrons in high Landau levels

    NASA Astrophysics Data System (ADS)

    Rosenow, Bernd; Scheidl, Stefan

    2000-03-01

    The state of a two dimensional electron gas in a magnetic field and in the presence of Coulomb interactions is of fundamental interest. Particular attention has been devoted to a partially filled lowest Landau level (LLL), where the correlation-induced fractional quantum Hall effect and composite fermions were studied. The physics of these phenomena is well described by Chern-Simons (CS) theories. In this contribution we focus on intermediate fields, where a higher Landau level is partially filled. We suggest to use the power of the CS approach to tackle also electron correlations in intermediate LLs. For an interacting electron gas the possibility of an inhomogeneous, charge density wave (CDW) like state has been predicted theoretically [1]. Recent experiments [2] have provided evidence for a large anisotropy in the electrical resistivity, which would be consistent with the formation of a CDW sate. It turns out that a CDW ground state arises naturally in the framework of a CS theory and shows many similarities with the intermediate state of superconductors. To carry through our program, we first map particles in a partially filled higher LL onto an effective LLL system and solve this new problem with the help of statistical transmutation. [1] A.A. Koulakov, M.M. Fogler, and B.I. Shklovskii, Phys. Rev. Lett. 76, 499 (1996); R. Moessner and J. T. Chalker, Phys. Rev. B 54, 5006 (1996). [2] M.P. Lilly et al., Phys. Rev. Lett. 82, 394 (1999); R. R. Du et al., cond-mat/9812925; W. Pan et al., cond-mat/9903160; M. P. Lilly et al., cond-mat/9903196.

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 40 CFR 1065.725 - High-level ethanol-gasoline blends.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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 operating on a high-level ethanol-gasoline blend, create a test fuel as follows: (a) Add ethanol to an E10...

  7. 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.

  8. The Absence of the FQHE at High Landau Levels

    NASA Astrophysics Data System (ADS)

    Koulakov, A. A.; Fogler, M. M.

    1996-03-01

    In our earlier paper (A. A. Koulakov, M. M. Fogler, and B. I. Shklovskii, preprint cond-mat/9508017) we have studied the ground state of a two-dimensional electron liquid in a weak magnetic field using the Hartree-Fock approximation (HFA). We have found that the electron cluster in large ``bubbles'', which form a regular lattice with the period of the order of the cyclotron radius. In this work we numerically compare the energies of the ``bubble'' phase and the Laughlin liquids at Landau level (LL) with indices up to N = 10. In calculations, we take into account the screening of the Coulomb interactions at the upper partially occupied LL by electrons of the lower fully occupied LLs. Using the iterational HFA for the ``bubble'' phase, and ansatz wave-function for FQHE states at N > 0 (A. H. MacDonald and S. M. Girvin, Phys. Rev. B 33), 4009 (1986), we show that 1/3 and 1/5 FQHE states do not withstand the competition with the ``bubble'' phase at N > 1.

  9. Noninvasive respiratory management of high level spinal cord injury

    PubMed Central

    Bach, John R.

    2012-01-01

    This article describes noninvasive acute and long-term management of the respiratory muscle paralysis of high spinal cord injury (SCI). This includes full-setting, continuous ventilatory support by noninvasive intermittent positive pressure ventilation (NIV) to support inspiratory muscles and mechanically assisted coughing (MAC) to support inspiratory and expiratory muscles. The NIV and MAC can also be used to extubate or decannulate ‘unweanable’ patients with SCI, to prevent intercurrent respiratory tract infections from developing into pneumonia and acute respiratory failure (ARF), and to eliminate tracheostomy and resort to costly electrophrenic/diaphragm pacing (EPP/DP) for most ventilator users, while permitting glossopharyngeal breathing (GPB) for security in the event of ventilator failure. PMID:22525322

  10. Organization of high-level visual cortex in human infants

    PubMed Central

    Deen, Ben; Richardson, Hilary; Dilks, Daniel D.; Takahashi, Atsushi; Keil, Boris; Wald, Lawrence L.; Kanwisher, Nancy; Saxe, Rebecca

    2017-01-01

    How much of the structure of the human mind and brain is already specified at birth, and how much arises from experience? In this article, we consider the test case of extrastriate visual cortex, where a highly systematic functional organization is present in virtually every normal adult, including regions preferring behaviourally significant stimulus categories, such as faces, bodies, and scenes. Novel methods were developed to scan awake infants with fMRI, while they viewed multiple categories of visual stimuli. Here we report that the visual cortex of 4–6-month-old infants contains regions that respond preferentially to abstract categories (faces and scenes), with a spatial organization similar to adults. However, precise response profiles and patterns of activity across multiple visual categories differ between infants and adults. These results demonstrate that the large-scale organization of category preferences in visual cortex is adult-like within a few months after birth, but is subsequently refined through development. PMID:28072399

  11. High Level Ab Initio Kinetics as a Tool for Astrochemistry

    NASA Astrophysics Data System (ADS)

    Klippenstein, Stephen

    2015-05-01

    We will survey the application of ab initio theoretical kinetics to reactions of importance to astrochemistry. Illustrative examples will be taken from our calculations for (i) interstellar chemistry, (ii) Titan's atmospheric chemistry, and (iii) the chemistry of extrasolar giant planets. The accuracy of various aspects of the calculations will be summarized including (i) the underlying ab initio electronic structure calculations, (ii) the treatment of the high pressure recombination process, and (iii) the treatment of the pressure dependence of the kinetics. The applications will consider the chemistry of phosphorous on giant planets, the kinetics of water dimerization, the chemistry of nitrogen on Titan's atmosphere, as well as various reactions of interstellar chemistry interest such as the recombination of OH with H, and O(3P) reacting with C2H5, CH2, and CCS. Chemical Sciences and Engineering Division.

  12. Noninvasive respiratory management of high level spinal cord injury.

    PubMed

    Bach, John R

    2012-03-01

    This article describes noninvasive acute and long-term management of the respiratory muscle paralysis of high spinal cord injury (SCI). This includes full-setting, continuous ventilatory support by noninvasive intermittent positive pressure ventilation (NIV) to support inspiratory muscles and mechanically assisted coughing (MAC) to support inspiratory and expiratory muscles. The NIV and MAC can also be used to extubate or decannulate 'unweanable' patients with SCI, to prevent intercurrent respiratory tract infections from developing into pneumonia and acute respiratory failure (ARF), and to eliminate tracheostomy and resort to costly electrophrenic/diaphragm pacing (EPP/DP) for most ventilator users, while permitting glossopharyngeal breathing (GPB) for security in the event of ventilator failure.

  13. 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

  14. 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.

  15. Low-level interfaces for high-level parallel I/O

    NASA Technical Reports Server (NTRS)

    Nieuwejaar, Nils; Kotz, David

    1995-01-01

    As the I/O needs of parallel scientific applications increase, file systems for multiprocessors are being designed to provide applications with parallel access to multiple disks. Many parallel file systems present applications with a conventional Unix-like interface that allows the application to access multiple disks transparently. By tracing all the activity of a parallel file system in a production, scientific computing environment, we show that many applications exhibit highly regular, but nonconsecutive I/O access patterns. Since the conventional interface does not provide an efficient method of describing these patterns, we present three extensions to the interface that support strided, nested-strided, and nested-batched I/O requests. We show how these extensions can be used to express common access patterns.

  16. 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

  17. Cosmological hydrogen recombination: populations of the high-level substates

    NASA Astrophysics Data System (ADS)

    Chluba, J.; Rubiño-Martín, J. A.; Sunyaev, R. A.

    2007-02-01

    We present results for the spectral distortions of the cosmic microwave background (CMB) arising due to bound-bound transitions during the epoch of cosmological hydrogen recombination at frequencies down to ν ~100MHz. We extend our previous treatment of the recombination problem now including the main collisional processes and following the evolution of all the hydrogen angular momentum substates for up to 100 shells. We show that, due to the low baryon density of the Universe, even within the highest considered shell full statistical equilibrium (SE) is not reached and that at low frequencies the recombination spectrum is significantly different when assuming full SE for n > 2. We also directly compare our results for the ionization history to the output of the RECFAST code, showing that especially at low redshifts rather big differences arise. In the vicinity of the Thomson visibility function the electron fraction differs by roughly -0.6 per cent which affects the temperature and polarization power spectra by <~ 1 per cent. Furthermore, we shortly discuss the influence of free-free absorption and line broadening due to electron scattering on the bound-bound recombination spectrum and the generation of CMB angular fluctuations due to scattering of photons within the high shells.

  18. Influence of dietary lipids on hepatic mRNA levels of proteins regulating plasma lipoproteins in baboons with high and low levels of large high density lipoproteins.

    PubMed

    Kushwaha, R S; McMahan, C A; Mott, G E; Carey, K D; Reardon, C A; Getz, G S; McGill, H C

    1991-12-01

    Selective breeding of baboons has produced families with increased plasma levels of large high density lipoproteins (HDL1) and very low (VLDL) and low (LDL) density lipoproteins when the animals consume a diet enriched in cholesterol and saturated fat. High HDL1 baboons have a slower cholesteryl ester transfer, which may account for the accumulation of HDL1, but not of VLDL and LDL. To investigate the mechanism of accumulation of VLDL + LDL in plasma of the high HDL1 phenotype, we selected eight half-sib pairs of baboons, one member of each pair with high HDL1, the other member with little or no HDL1 on the same high cholesterol, saturated fat diet. Baboons were fed a chow diet and four experimental diets consisting of high and low cholesterol with corn oil, and high and low cholesterol with lard, each for 6 weeks, in a crossover design. Plasma lipids and lipoproteins and hepatic mRNA levels were measured on each diet. HDL1 phenotype, type of dietary fat, and dietary cholesterol affected plasma cholesterol and apolipoprotein (apo) B concentrations, whereas dietary fat alone affected plasma triglyceride and apoA-I concentrations. HDL1 phenotype and dietary cholesterol alone did not influence hepatic mRNA levels, whereas dietary lard, compared to corn oil, significantly increased hepatic apoE mRNA levels and decreased hepatic LDL receptor and HMG-CoA synthase mRNA levels. Hepatic apoA-I message was associated with cholesterol concentration in HDL fractions as well as with apoA-I concentrations in the plasma or HDL. However, hepatic apoB message level was not associated with plasma or LDL apoB levels. Total plasma cholesterol, including HDL, was negatively associated with hepatic LDL receptor and HMG-CoA synthase mRNA levels. However, compared with low HDL1 baboons, high HDL1 baboons had higher concentrations of LDL and HDL cholesterol at the same hepatic mRNA levels. These studies suggest that neither overproduction of apoB from the liver nor decreased hepatic LDL

  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. In Vitro Treatment of Human Monocytes/Macrophages with Myristoylated Recombinant Nef of Human Immunodeficiency Virus Type 1 Leads to the Activation of Mitogen-Activated Protein Kinases, IκB Kinases, and Interferon Regulatory Factor 3 and to the Release of Beta Interferon▿

    PubMed Central

    Mangino, Giorgio; Percario, Zulema A.; Fiorucci, Gianna; Vaccari, Gabriele; Manrique, Santiago; Romeo, Giovanna; Federico, Maurizio; Geyer, Matthias; Affabris, Elisabetta

    2007-01-01

    The viral protein Nef is a virulence factor that plays multiple roles during the early and late phases of human immunodeficiency virus (HIV) replication. Nef regulates the cell surface expression of critical proteins (including down-regulation of CD4 and major histocompatibility complex class I), T-cell receptor signaling, and apoptosis, inducing proapoptotic effects in uninfected bystander cells and antiapoptotic effects in infected cells. It has been proposed that Nef intersects the CD40 ligand signaling pathway in macrophages, leading to modification in the pattern of secreted factors that appear able to recruit and activate T lymphocytes, rendering them susceptible to HIV infection. There is also increasing evidence that in vitro cell treatment with Nef induces signaling effects. Exogenous Nef treatment is able to induce apoptosis in uninfected T cells, maturation in dendritic cells, and suppression of CD40-dependent immunoglobulin class switching in B cells. Previously, we reported that Nef treatment of primary human monocyte-derived macrophages (MDMs) induces a cycloheximide-independent activation of NF-κB and the synthesis and secretion of a set of chemokines/cytokines that activate STAT1 and STAT3. Here, we show that Nef treatment is capable of hijacking cellular signaling pathways, inducing a very rapid regulatory response in MDMs that is characterized by the rapid and transient phosphorylation of the α and β subunits of the IκB kinase complex and of JNK, ERK1/2, and p38 mitogen-activated protein kinase family members. In addition, we have observed the activation of interferon regulatory factor 3, leading to the synthesis of beta interferon mRNA and protein, which in turn induces STAT2 phosphorylation. All of these effects require Nef myristoylation. PMID:17182689

  1. High-Level Portuguese Visit to Paranal Observatory

    NASA Astrophysics Data System (ADS)

    1998-07-01

    Just some weeks after the successful First Light Event of the first 8.2-m VLT Unit Telescope, cf. ESO PR 06/98 , the Paranal Observatory will today receive the visit of a high-ranking delegation from Portugal. It is lead by the Portuguese Minister of Science and Technology, Professor Mariano Gago , accompanied by the Ambassador of Portugal to the Republic of Chile, Mr. Rui Félix-Alves . In 1990, an Agreement was signed that associates Portugal with the European Southern Observatory and accords this country observer status on the ESO Council and Committees. An additional, important provision is the declared intention that Portugal becomes a full member of the Organisation within a decade. The present visit takes place at a time that discussions about the actual implementation of this long-term goal have begun. The Minister and his advisers will have the opportunity to acquaint themselves with the recent progress of the Very Large Telescope project, now on track to provide astronomers in the ESO member states with the world's most powerful optical astronomical telescope within a few years. During the past years, a rapid build-up of Astronomy and Astrophysics has taken place in Portugal. At the same time and guided by the provisions of the Agreement, a closer and mutually profitable relationship has evolved between ESO and Portuguese scientists, many of whom have become involved in joint research with colleagues in the ESO member states. A large fraction of the related projects is based on data obtained at the ESO telescopes. More information In Portuguese: Webpage of Ministério da Ciência e da Tecnologia Information about the Portugal-ESO collaboration. See also the photos from the visit - ESO PR Photos 23a-c/98. How to obtain ESO Press Information ESO Press Information is made available on the World-Wide Web (URL: http://www.eso.org../). ESO Press Photos may be reproduced, if credit is given to the European Southern Observatory.

  2. 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.

  3. Correlation of low levels of nitrite and high levels of fetal hemoglobin in patients with sickle cell disease at baseline

    PubMed Central

    Elias, Darcielle Bruna Dias; Rocha, Lilianne Brito da Silva; Cavalcante, Maritza Barbosa; Pedrosa, Alano Martins; Justino, Izabel Cristina Bandeira; Gonçalves, Romélia Pinheiro

    2012-01-01

    Background Sickle cell disease is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and recurrent vaso-occlusive crises that reduces the quality of life of sufferers. Objective To evaluate the correlation of the levels of lactate dehydrogenase, malonaldehyde and nitrite to fetal hemoglobin in patients with sickle cell disease not under treatment with hydroxyurea in outpatients at a university hospital in Fortaleza, Ceará, Brazil. Methods Forty-four patients diagnosed with sickle cell disease were enrolled at baseline. Diagnosis was confirmed by evaluating the beta globin gene using polymerase chain reaction-restriction fragment length polymorphism. The concentration of fetal hemoglobin was obtained by high-performance liquid chromatography. Serum levels of nitrite, malonaldehyde and lactate dehydrogenase were measured by biochemical methods. Results Significantly higher levels of lactate dehydrogenase, nitrite and malonaldehyde were observed in patients with sickle cell disease compared to a control group. The study of the correlation between fetal hemoglobin levels and these variables showed a negative correlation with nitrite levels. No correlation was found between fetal hemoglobin and malonaldehyde or lactate dehydrogenase. When the study population was stratified according to fetal hemoglobin levels, a decrease in the levels of nitrite was observed with higher levels of fetal hemoglobin (p-value = 0.0415). Conclusion The results show that, similar to fetal hemoglobin levels, the concentration of nitrite can predict the clinical course of the disease, but should not be used alone as a modulator of prognosis in patients with sickle cell disease. PMID:23049438

  4. Leveling

    USGS Publications Warehouse

    1966-01-01

    Geodetic leveling by the U.S. Geological Survey provides a framework of accurate elevations for topographic mapping. Elevations are referred to the Sea Level Datum of 1929. Lines of leveling may be run either with automatic or with precise spirit levels, by either the center-wire or the three-wire method. For future use, the surveys are monumented with bench marks, using standard metal tablets or other marking devices. The elevations are adjusted by least squares or other suitable method and are published in lists of control.

  5. 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

  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. 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…

  8. Geographical distribution of drinking-water with high iodine level and association between high iodine level in drinking-water and goitre: a Chinese national investigation.

    PubMed

    Shen, Hongmei; Liu, Shoujun; Sun, Dianjun; Zhang, Shubin; Su, Xiaohui; Shen, Yanfeng; Han, Hepeng

    2011-07-01

    Excessive iodine intake can cause thyroid function disorders as can be caused by iodine deficiency. There are many people residing in areas with high iodine levels in drinking-water in China. The main aim of the present study was to map the geographical distribution of drinking-water with high iodine level in China and to determine the relationship between high iodine level in drinking-water and goitre prevalence. Iodine in drinking-water was measured in 1978 towns of eleven provinces in China, with a total of 28,857 water samples. We randomly selected children of 8-10 years old, examined the presence of goitre and measured their urinary iodine in 299 towns of nine provinces. Of the 1978 towns studied, 488 had iodine levels between 150 and 300 μg/l in drinking-water, and in 246 towns, the iodine level was >300 μg/l. These towns are mainly distributed along the original Yellow River flood areas, the second largest river in China. Of the 56 751 children examined, goitre prevalence was 6.3 % in the areas with drinking-water iodine levels of 150-300 μg/l and 11.0 % in the areas with drinking-water iodine >300 μg/l. Goitre prevalence increased with water and urinary iodine levels. For children with urinary iodine >1500 μg/l, goitre prevalence was 3.69 times higher than that for those with urinary iodine levels of 100-199 μg/l. The present study suggests that drinking-water with high iodine levels is distributed in eleven provinces of China. Goitre becomes more prevalent with the increase in iodine level in drinking-water. Therefore, it becomes important to prevent goitre through stopping the provision of iodised salt and providing normal drinking-water iodine through pipelines in these areas in China.

  9. 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

  10. Low zinc serum levels and high blood lead levels among school-age children in coastal area

    NASA Astrophysics Data System (ADS)

    Pramono, Adriyan; Panunggal, Binar; Rahfiludin, M. Zen; Swastawati, Fronthea

    2017-02-01

    The coverage of environmental lead toxicant was quiet wide. Lead exposure recently has been expected to be associated with zinc deficiency and blood indices disturbance. Emphasizing on children, which could absorb more than 50 % of lead that enters the body. Lead became the issue on the coastal area due to it has polluted the environment and waters as the source of fisheries products. This was a cross sectional study to determined nutritional status, blood lead levels, zinc serum levels, blood indices levels, fish intake among school children in coastal region of Semarang. This study was carried out on the school children aged between 8 and 12 years old in coastal region of Semarang. Nutritional status was figured out using anthropometry measurement. Blood lead and zinc serum levels were analyzed using the Atomic Absorbent Spectrophotometry (AAS) at a wavelength of 213.9 nm for zinc serum and 283.3 nm for blood lead. Blood indices was measured using auto blood hematology analyzer. Fish intake was assessed using 3-non consecutive days 24-hours food recall. The children had high lead levels (median 34.86 μg/dl, range 11.46 - 58.86 μg/dl) compared to WHO cut off. Zinc serum levels was low (median 18.10 μg/dl, range 10.25 – 41.39 μg/dl) compared to the Joint WHO/UNICEF/IAEA/IZiNCG cut off. Approximately 26.4% of children were anemic. This study concluded that all school children had high blood lead levels, low zinc serum, and presented microcytic hypochromic anemia. This phenomenon should be considered as public health concern.

  11. Hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2) are involved in the down-regulation of CD1a lipid antigen presentation by HIV-1 Nef in dendritic cells.

    PubMed

    Shinya, Eiji; Shimizu, Masumi; Owaki, Atsuko; Paoletti, Samantha; Mori, Lucia; De Libero, Gennaro; Takahashi, Hidemi

    2016-01-01

    Dendritic cells (DCs) play a major role in in vivo pathogenesis of HIV-1 infection. Therefore, DCs may provide a promising strategy to control and eventually overcome the fatal infection. Especially, immature DCs express all CD1s, the non-MHC lipid antigen -presenting molecules, and HIV-1 Nef down-regulates CD1 expression besides MHC. Moreover, CD1d-restricted CD4(+) NKT cells are infected by HIV-1, reducing the number of these cells in HIV-1-infected individuals. To understand the exact role of DCs and CD1-mediated immune response during HIV-1 infection, Nef down-regulation of CD1a-restricted lipid/glycolipid Ag presentation in iDCs was analyzed. We demonstrated the involvement of the association of Nef with hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2), and that Hck, which is expressed strongly in iDCs, augmented this mutual interaction. Hck might be another therapeutic target to preserve the function of HIV-1 infected DCs, which are potential reservoirs of HIV-1 even after antiretroviral therapy.

  12. HIGH D-DIMER LEVELS PREDICT A POOR OUTCOME IN PATIENTS WITH SEVERE TRAUMA, EVEN WITH HIGH FIBRINOGEN LEVELS ON ARRIVAL: A MULTICENTER RETROSPECTIVE STUDY.

    PubMed

    Hayakawa, Mineji; Maekawa, Kunihiko; Kushimoto, Shigeki; Kato, Hiroshi; Sasaki, Junichi; Ogura, Hiroshi; Matauoka, Tetsuya; Uejima, Toshifumi; Morimura, Naoto; Ishikura, Hiroyasu; Hagiwara, Akiyoshi; Takeda, Munekazu; Kaneko, Naoyuki; Saitoh, Daizoh; Kudo, Daisuke; Kanemura, Takashi; Shibusawa, Takayuki; Furugori, Shintaro; Nakamura, Yoshihiko; Shiraishi, Atsushi; Murata, Kiyoshi; Mayama, Gou; Yaguchi, Arino; Kim, Shiei; Takasu, Osamu; Nishiyama, Kazutaka

    2016-03-01

    Elevated D-dimer level in trauma patients is associated with tissue damage severity and is an indicator of hyperfibrinolysis during the early phase of trauma. To investigate the interacting effects of fibrinogen and D-dimer levels on arrival at the emergency department for massive transfusion and mortality in severe trauma patients in a multicenter retrospective study. This study included 519 adult trauma patients with an injury severity score ≥16. Patients with ≥10 units of red cell concentrate transfusion and/or death during the first 24 h were classified as having a poor outcome. Receiver operating characteristic curve analysis for predicting poor outcome showed the optimal cut-off fibrinogen and D-dimer values to be 190 mg/dL and 38 mg/L, respectively. On the basis of these values, patients were divided into four groups: low D-dimer (<38 mg/L)/high fibrinogen (>190 mg/dL), low D-dimer (<38 mg/L)/low fibrinogen (≤190 mg/dL), high D-dimer (≥38 mg/L)/high fibrinogen (>190 mg/dL), and high D-dimer (≥38 mg/L)/low fibrinogen (≤190 mg/dL). The survival rate was lower in the high D-dimer/low fibrinogen group than in the other groups. Moreover, the survival rate was lower in the high D-dimer/high fibrinogen group than in the low D-dimer/high fibrinogen and low D-dimer/low fibrinogen groups. High D-dimer level on arrival is a strong predictor of early death or requirement for massive transfusion in severe trauma patients, even with high fibrinogen levels.

  13. The Yo-Yo intermittent recovery test level 1 is reliable in young high-level soccer players.

    PubMed

    Deprez, D; Fransen, J; Lenoir, M; Philippaerts, Rm; Vaeyens, R

    2015-03-01

    The aim of the study was to investigate test reliability of the Yo-Yo intermittent recovery test level 1 (YYIR1) in 36 high-level youth soccer players, aged between 13 and 18 years. Players were divided into three age groups (U15, U17 and U19) and completed three YYIR1 in three consecutive weeks. Pairwise comparisons were used to investigate test reliability (for distances and heart rate responses) using technical error (TE), coefficient of variation (CV), intra-class correlation (ICC) and limits of agreement (LOA) with Bland-Altman plots. The mean YYIR1 distances for the U15, U17 and U19 groups were 2024 ± 470 m, 2404 ± 347 m and 2547 ± 337 m, respectively. The results revealed that the TEs varied between 74 and 172 m, CVs between 3.0 and 7.5%, and ICCs between 0.87 and 0.95 across all age groups for the YYIR1 distance. For heart rate responses, the TEs varied between 1 and 6 bpm, CVs between 0.7 and 4.8%, and ICCs between 0.73 and 0.97. The small ratio LOA revealed that any two YYIR1 performances in one week will not differ by more than 9 to 28% due to measurement error. In summary, the YYIR1 performance and the physiological responses have proven to be highly reliable in a sample of Belgian high-level youth soccer players, aged between 13 and 18 years. The demonstrated high level of intermittent endurance capacity in all age groups may be used for comparison of other prospective young soccer players.

  14. GEMS: Gifted Education Module System. Higher Level Thinking in the Junior High.

    ERIC Educational Resources Information Center

    Davis, Hilarie; And Others

    The curriculum, designed for use with gifted students at the junior high level, presents units of instruction which emphasize the higher level thinking skills of analysis, synthesis, and evaluation. An introductory section explains each of the three higher level skills and presents tasks illustrating each one. Four units are presented, complete…

  15. 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…

  16. Level of Voice Among Female and Male High School Students: Relational Context, Support, and Gender Orientation.

    ERIC Educational Resources Information Center

    Harter, Susan; Waters, Patricia L.; Whitesell, Nancy R.; Kastelic, Diana

    1998-01-01

    Examined levels of self-reported "voice" (authentic self expression) with various persons among high school students. Found no gender differences nor evidence that voice declines in female adolescents. Perceived support for voice predicted level of voice. Feminine girls reported lower levels of voice than androgynous girls in public relational…

  17. 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…

  18. 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.

  19. 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.

  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. 78 FR 14840 - U.S.-EU High Level Regulatory Cooperation Forum-Stakeholder Session

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-07

    ... BUDGET U.S.-EU High Level Regulatory Cooperation Forum--Stakeholder Session AGENCY: Office of Management... will hold a public meeting of the U.S.-EU High Level Regulatory Cooperation Forum (the ``Forum'') in...-cooperation-forum . Oral Presentations: Any persons wishing to present an oral statement at the public...

  3. 78 FR 70281 - United States-Mexico High Level Economic Dialogue

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-25

    ... United States-Mexico High Level Economic Dialogue AGENCY: International Trade Administration, Commerce... Register notice on the United States-Mexico High Level Economic Dialogue. DATES: The agency must receive... largest export market and third largest overall trading partner. The United States, in turn, is...

  4. 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.

  5. 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.

  6. 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…

  7. High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial

    PubMed Central

    Babina, Irina S.; Herrera-Abreu, Maria Teresa; Tarazona, Noelia; Peckitt, Clare; Kilgour, Elaine; Smith, Neil R.; Geh, Catherine; Rooney, Claire; Cutts, Ros; Campbell, James; Ning, Jian; Fenwick, Kerry; Swain, Amanda; Brown, Gina; Chua, Sue; Thomas, Anne; Johnston, Stephen R.D.; Ajaz, Mazhar; Sumpter, Katherine; Gillbanks, Angela; Watkins, David; Chau, Ian; Popat, Sanjay; Cunningham, David; Turner, Nicholas C.

    2017-01-01

    FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond. Using cell lines and patient-derived xenograft models, we show that high-level FGFR2 amplification initiates a distinct oncogene addiction phenotype, characterized by FGFR2-mediated transactivation of alternative receptor kinases, bringing PI3K/mTOR signaling under FGFR control. Signaling in low-level FGFR1-amplified cancers is more restricted to MAPK signaling, limiting sensitivity to FGFR inhibition. Finally, we show that circulating tumor DNA screening can identify high-level clonally amplified cancers. Our data provide a mechanistic understanding of the distinct pattern of oncogene addiction seen in highly amplified cancers and demonstrate the importance of clonality in predicting response to targeted therapy. Significance Robust single-agent response to FGFR inhibition is seen only in high-level FGFR-amplified cancers, with copy-number level dictating response to FGFR inhibition in vitro, in vivo, and in the clinic. High-level amplification of FGFR2 is relatively rare in gastric and breast cancers, and we show that screening for amplification in circulating tumor DNA may present a viable strategy to screen patients. PMID:27179038

  8. 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

  9. Low-level versus high-level placement of gold plates in the upper eyelid in patients with facial palsy

    PubMed Central

    Amer, Tarek A; El-Minawi, Hisham M; El-Shazly, Malak I

    2011-01-01

    Background: Lagophthalmos is a condition that results from facial paralysis causing functional as well as esthetic problems. This condition can be treated by a range of techniques, including tarsorrhaphy, facial slings, and canthopexies. Gold plates provide a solution for temporary or permanent lagophthalmos resulting from facial paralysis. This study discusses the use of gold plates in the treatment of lagophthalmos but with the introduction of gold plates in two different positions in the upper lids. Methods: Group 1 (38 eyes) had a low level of placement (2 mm from the lid margin) of gold plates, while Group 2 (23 eyes) had a high level of placement (5 mm from the lid margin). Results: Noticeable bulge was seen in 18.4% of Group 1 eyes compared with 13% in Group 2, and migration of the plate occurred in 2.6% and 0% of eyes in Group 1 and Group 2, respectively, as well as ptosis (7.8% and 4.3%) and conjunctival perforation (0% and 4.3%). The degree of improvement of eyelid closure, keratopathy, and visual acuity were the same for both techniques. Conclusion: Placement of gold plates at a higher level could avoid some of the drawbacks of lower level placement of these plates, such as upper eyelid bulge and ptosis, especially given the thinning of the eyelids and orbicularis muscles that occurs in facial palsy. PMID:21760718

  10. Engineering and Validation of a Vector for Concomitant Expression of Rare Transfer RNA (tRNA) and HIV-1 nef Genes in Escherichia coli.

    PubMed

    Mualif, Siti Aisyah; Teow, Sin-Yeang; Omar, Tasyriq Che; Chew, Yik Wei; Yusoff, Narazah Mohd; Ali, Syed A

    2015-01-01

    Relative ease in handling and manipulation of Escherichia coli strains make them primary candidate to express proteins heterologously. Overexpression of heterologous genes that contain codons infrequently used by E. coli is related with difficulties such as mRNA instability, early termination of transcription and/or translation, deletions and/or misincorporation, and cell growth inhibition. These codon bias -associated problems are addressed by co-expressing ColE1-compatible, rare tRNA expressing helper plasmids. However, this approach has inadequacies, which we have addressed by engineering an expression vector that concomitantly expresses the heterologous protein of interest, and rare tRNA genes in E. coli. The expression vector contains three (argU, ileY, leuW) rare tRNA genes and a useful multiple cloning site for easy in-frame cloning. To maintain the overall size of the parental plasmid vector, the rare tRNA genes replaced the non-essential DNA segments in the vector. The cloned gene is expressed under the control of T7 promoter and resulting recombinant protein has a C-terminal 6His tag for IMAC-mediated purification. We have evaluated the usefulness of this expression vector by expressing three HIV-1 genes namely HIV-1 p27 (nef), HIV-1 p24 (ca), and HIV-1 vif in NiCo21(DE3) E.coli and demonstrated the advantages of using expression vector that concomitantly expresses rare tRNA and heterologous genes.

  11. 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

  12. The Relationship between High School Teacher Perceived Principal Leadership Practices and Teacher Morale Levels

    ERIC Educational Resources Information Center

    Moore, Nora F.

    2012-01-01

    This quantitative study examined the relationship between five teacher perceived leadership practices of high school principals and the morale levels of the teachers in their schools. Two high schools (grades 10-12) in the upstate of South Carolina participated in the study. One hundred twelve high school teachers were surveyed using the…

  13. 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…

  14. 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…

  15. 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.

  16. 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

  17. 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.

  18. Radioactivity levels in the mostly local foodstuff consumed by residents of the high level natural radiation areas of Ramsar, Iran.

    PubMed

    Fathabadi, Nasrin; Salehi, Ali Akbar; Naddafi, Kazem; Kardan, Mohammad Reza; Yunesian, Masud; Nodehi, Ramin Nabizadeh; Deevband, Mohammad Reza; Shooshtari, Molood Gooniband; Hosseini, Saeedeh Sadat; Karimi, Mahtab

    2017-04-01

    Among High Level Natural Radiation Areas (HLNRAs) all over the world, the northern coastal city of Ramsar has been considered enormously important. Many studies have measured environmental radioactivity in Ramsar, however, no survey has been undertaken to measure concentrations in the diets of residents. This study determined the (226)Ra activity concentration in the daily diet of people of Ramsar. The samples were chosen from both normal and high level natural radiation areas and based on the daily consumption patterns of residents. About 150 different samples, which all are local and have the highest consumption, were collected during the four seasons. In these samples, after washing and drying and pretreatment, the radionuclide was determined by α-spectrometry. The mean radioactivity concentration of (226)Ra ranged between 5 ± 1 mBq kg(-1) wet weight (chino and meat) to 725 ± 480 mBq kg(-1) for tea dry leaves. The (226)Ra activity concentrations compared with the reference values of UNSCEAR appear to be higher in leafy vegetables, milk and meat product. Of the total daily dietary (226)Ra exposure for adults in Ramsar, the largest percentage was from eggs. The residents consuming eggs from household chickens may receive an elevated dose in the diet.

  19. 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...

  20. 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)

  1. 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...

  2. Retrieved waste properties and high-level waste critical component ratios for privatization waste feed delivery

    SciTech Connect

    Peters, B.B.

    1998-03-04

    The purpose for this document is to provide the basis for the retrieved waste properties and high-level waste critical component ratios specified in the System Specification for the Double-Shell Tank System.

  3. High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study

    PubMed Central

    2014-01-01

    Background The potentially detrimental role of progesterone during the follicular phase has been a matter of controversy for several years; however, few studies have analyzed the effects of combined raised estradiol and progesterone levels on pregnancy outcomes. The aim of the present study was to determine the influence of high progesterone levels on clinical outcomes in the context of high ovarian response. Methods We performed a retrospective cohort study that included 2850 women classified as high responders. The women were subdivided into six groups depending on their progesterone concentration on the day of human chorionic gonadotropin (hCG) administration: <0.5 ng/ml (1.81 ng/ml (>p90). Ovarian response was classified as high when > =20 oocytes were retrieved or when estradiol was > =3000 pg/ml. Clinical outcomes of each subgroup were analyzed. We also examined data from frozen-thawed embryo transfers. Results were analyzed with Student’s t- test to compare continuous variables and chi-squared test to compare proportions. A p-value of < =0.05 was considered statistically significant. Results The progesterone concentration increased with ovarian response, and elevated progesterone did not show a significant clinical impact on implantation rate and pregnancy rates. These data provide evidence that progesterone levels higher than 1.8 ng/ml do not have detrimental effect on oocyte quality or endometrial receptivity. Conclusions These data allow us to conclude that high progesterone levels correlate significantly with high estradiol levels and that in high responder women; progesterone levels do not show a significant clinical impact on results. PMID:25064138

  4. 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.

  5. 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…

  6. 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.

  7. 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…

  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.

  9. 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…

  10. Development of high-level streptomycin resistance affected by a plasmid in lactic streptococci.

    PubMed

    Sinha, R P

    1986-08-01

    Some lactose-negative (Lac-) mutants of Streptococcus lactis C2 and ML3 exhibited development of very high level streptomycin resistance after incubation with subinhibitory concentrations of the drug for 18 to 22 h. These drug-resistant mutants showed no loss of resistance even after 6 months of subculturing in broth without any drug. The parental Lac+ strains did not show mutation to high-level streptomycin resistance. The Lac+ characteristic of the parental strain was conjugally transferred to Lac- derivatives of C2 and ML3, showing the ability to mutate to high-level resistance. When transconjugants were analyzed for this characteristic, they showed both mutable and nonmutable Lac+ types. The results suggested that genetic information for mutation to high-level streptomycin resistance in lactic streptococci resides on the chromosome, and its expression is affected by a plasmid. The plasmid profiles of strains C2, ML3, C2 Lac-, ML3 Lac-, and two kinds of transconjugants confirmed the presence of a plasmid of approximately 5.5 megadaltons in strains showing no mutation to high-level streptomycin resistance, while strains missing such a plasmid exhibited high-level streptomycin resistance after incubation with subinhibitory concentrations of the drug.

  11. 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).

  12. Water-Level Changes in the High Plains Aquifer, 1980 to 1995

    USGS Publications Warehouse

    McGuire, Virginia L.; Sharpe, Jennifer B.

    1997-01-01

    The High Plains aquifer underlies one of the major agricultural areas in the world, including parts of Colorado, Kansas, Nebraska, New Mexico, Oklahoma, South Dakota, Texas, and Wyoming. Ground-water irrigation expanded rapidly after 1940 in the area underlain by the High Plains aquifer (called the 'High Plains region' in this report): 1949--2.1 million acres; 1959--6.1 million acres; 1969--9.0 million acres; 1978--12.9 million acres; and 1980--13.7 million acres (Gutentag and others, 1984; Thelin and Heimes, 1987). In 1990, 95 percent of the water withdrawn from the High Plains aquifer, 15.7 million acre-feet, was used for irrigation (Marilee Horn, U.S. Geological Survey, written commun., 1996). Water-level declines appeared in the High Plains aquifer soon after extensive ground-water irrigation development began. By 1980, water levels in the High Plains aquifer in parts of Texas, Oklahoma, and southwestern Kansas had declined more than 100 feet. In response to these declines, the U.S. Geological Survey, in cooperation with numerous Federal, State, and local water-resource agencies, began a ground-water monitoring program in 1988 to assess water-level change in the aquifer annually, using water-level measurements in more than 7,000 wells. The water-level measurements are made in winter or early spring, when water levels generally represent nonpumping conditions.

  13. 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.

  14. Comparative genome analysis of high-level penicillin resistance in Streptococcus pneumoniae.

    PubMed

    Tait-Kamradt, Amelia G; Cronan, Melissa; Dougherty, Thomas J

    2009-06-01

    Streptococcus pneumoniae strains with very high levels of penicillin resistance (minimum inhibitory concentration [MIC] >or=8 microg/ml) emerged in the 1990 s. Previous studies have traced the changes in penicillin binding proteins (PBP) that result in decreased penicillin susceptibility, and the role of several PBP genes in high-level resistance. In the present study, we investigated the changes that occurred at the two highest levels of penicillin resistance using NimbleGen's Comparative Genome Sequencing (CGS) technology. DNA from a highly resistant (Pen MIC 16 microg/ml) pneumococcus was used to serially transform the R6 strain to high-level resistance. Four distinct levels of penicillin resistance above the susceptible R6 strain (MIC 0.016 microg/ml) were identified. Using CGS technology, the entire genome sequences of the two highest levels of resistant transformants were examined for changes associated with the resistance phenotypes. At the third level of resistance, changes in PBPs 1a, 2b, and 2x were found, very similar to previous reports. At the fourth resistance level, two additional changes were observed in the R6 transformants. More changes were observed in PBP2x, as well as in peptidoglycan GlcNAc deacetylase (pdgA), which had a missense mutation in the coding region. Genetic transformation with polymerase chain reaction (PCR) products generated from the high-level resistant parent containing either the additional PBP2x or mutant pdgA gene did not increase the MIC of the third-level transformant. Only when both PCR products were simultaneously transformed into the third-level transformant did colonies emerge that were at the highest level of resistance (16-32 microg/ml), equivalent to the highly resistant parent strain. This is the first instance of the involvement of a variant pdgA gene in penicillin resistance. It is also clear from these experiments and the literature that there are multiple paths to the pneumococcus achieving high-level

  15. Assessment of thermal comfort level at pedestrian level in high-density urban area of Hong Kong

    NASA Astrophysics Data System (ADS)

    Ma, J.; Ng, E.; Yuan, C.; Lai, A.

    2015-12-01

    Hong Kong is a subtropical city which is very hot and humid in the summer. Pedestrians commonly experience thermal discomfort. Various studies have shown that the tall bulky buildings intensify the urban heat island effect and reduce urban air ventilation. However, relatively few studies have focused on modeling the thermal load at pedestrian level (~ 2 m). This study assesses the thermal comfort level, quantified by PET (Physiological Equivalent Temperature), using a GIS - based simulation approach. A thermal comfort level map shows the PET value of a typical summer afternoon in the high building density area. For example, the averaged PET in Sheung Wan is about 41 degree Celsius in a clear day and 38 degree Celsius in a cloudy day. This map shows where the walkways, colonnades, and greening is most needed. In addition, given a start point, a end point, and weather data, we generate the most comfort walking routes weighted by the PET. In the simulation, shortwave irradiance is calculated using the topographic radiation model (Fu and Rich, 1999) under various cloud cover scenarios; longwave irradiance is calculated based the radiative transfer equation (Swinbank, 1963). Combining these two factors, Tmrt (mean radiant temperature) is solved. And in some cases, the Tmrt differ more than 40 degree Celsius between areas under the sun and under the shades. Considering thermal load and wind information, we found that shading from buildings has stronger effect on PET than poor air ventilation resulted from dense buildings. We predict that pedestrians would feel more comfortable (lower PET) in a hot summer afternoon when walking in the higher building density area.

  16. Comparison of quality of facial scars after single low-level laser therapy and combined low-level with high-level (PDL 595 nm) laser therapy.

    PubMed

    Vranova, Jana; Remlova, Eva; Jelinkova, Helena; Rosina, Jozef; Dostalova, Tatjana

    2015-01-01

    The main goal of our study was to compare the quality of resulting facials scar 12 weeks after single and combined laser therapy. Forty-one children from age 1.5 to 5 years with facial scars after injury participated in the study. Thirty-one underwent laser therapy, 14 were treated using single low-level laser therapy (670 nm, fluence 3-5 J/cm(-2) ), and 17 underwent combined high-level laser therapy with non-ablative pulsed dye laser (PDL; 595 nm, spot size 7 mm, delay 0.45 ms or 1.5 ms, fluence 9-11 J/cm(-2) , cryogen spray/delay 20/30 ms) and low-level laser therapy. The control group consisted of 10 untreated children. Before treatment and at week 4, 8, and, 12 the scars were evaluated using the POSAS questionnaire. A statistically significant improvement in scars (between ratings before treatment and 4 weeks after therapy, before treatment and 8 weeks after therapy and before treatment and 12 weeks after therapy) was observed in all parameters in both treatment groups (p < 0.0001). For the HLLT+LLLT group the most significant enhancement in the quality of scars was found for all items and at all evaluations, except pigmentation and pliability. There was no improvement observed in quality of facial scars in the control group.

  17. Plastid-expressed 5-enolpyruvylshikimate-3-phosphate synthase genes provide high level glyphosate tolerance in tobacco.

    PubMed

    Ye, G N; Hajdukiewicz, P T; Broyles, D; Rodriguez, D; Xu, C W; Nehra, N; Staub, J M

    2001-02-01

    Plastid transformation (transplastomic) technology has several potential advantages for biotechnological applications including the use of unmodified prokaryotic genes for engineering, potential high-level gene expression and gene containment due to maternal inheritance in most crop plants. However, the efficacy of a plastid-encoded trait may change depending on plastid number and tissue type. We report a feasibility study in tobacco plastids to achieve high-level herbicide resistance in both vegetative tissues and reproductive organs. We chose to test glyphosate resistance via over-expression in plastids of tolerant forms of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Immunological, enzymatic and whole-plant assays were used to prove the efficacy of three different prokaryotic (Achromobacter, Agrobacterium and Bacillus) EPSPS genes. Using the Agrobacterium strain CP4 EPSPS as a model we identified translational control sequences that direct a 10,000-fold range of protein accumulation (to >10% total soluble protein in leaves). Plastid-expressed EPSPS could provide very high levels of glyphosate resistance, although levels of resistance in vegetative and reproductive tissues differed depending on EPSPS accumulation levels, and correlated to the plastid abundance in these tissues. Paradoxically, higher levels of plastid-expressed EPSPS protein accumulation were apparently required for efficacy than from a similar nuclear-encoded gene. Nevertheless, the demonstration of high-level glyphosate tolerance in vegetative and reproductive organs using transplastomic technology provides a necessary step for transfer of this technology to other crop species.

  18. Coastal barrier stratigraphy for Holocene high-resolution sea-level reconstruction

    PubMed Central

    Costas, Susana; Ferreira, Óscar; Plomaritis, Theocharis A.; Leorri, Eduardo

    2016-01-01

    The uncertainties surrounding present and future sea-level rise have revived the debate around sea-level changes through the deglaciation and mid- to late Holocene, from which arises a need for high-quality reconstructions of regional sea level. Here, we explore the stratigraphy of a sandy barrier to identify the best sea-level indicators and provide a new sea-level reconstruction for the central Portuguese coast over the past 6.5 ka. The selected indicators represent morphological features extracted from coastal barrier stratigraphy, beach berm and dune-beach contact. These features were mapped from high-resolution ground penetrating radar images of the subsurface and transformed into sea-level indicators through comparison with modern analogs and a chronology based on optically stimulated luminescence ages. Our reconstructions document a continuous but slow sea-level rise after 6.5 ka with an accumulated change in elevation of about 2 m. In the context of SW Europe, our results show good agreement with previous studies, including the Tagus isostatic model, with minor discrepancies that demand further improvement of regional models. This work reinforces the potential of barrier indicators to accurately reconstruct high-resolution mid- to late Holocene sea-level changes through simple approaches. PMID:27929122

  19. Coastal barrier stratigraphy for Holocene high-resolution sea-level reconstruction

    NASA Astrophysics Data System (ADS)

    Costas, Susana; Ferreira, Óscar; Plomaritis, Theocharis A.; Leorri, Eduardo

    2016-12-01

    The uncertainties surrounding present and future sea-level rise have revived the debate around sea-level changes through the deglaciation and mid- to late Holocene, from which arises a need for high-quality reconstructions of regional sea level. Here, we explore the stratigraphy of a sandy barrier to identify the best sea-level indicators and provide a new sea-level reconstruction for the central Portuguese coast over the past 6.5 ka. The selected indicators represent morphological features extracted from coastal barrier stratigraphy, beach berm and dune-beach contact. These features were mapped from high-resolution ground penetrating radar images of the subsurface and transformed into sea-level indicators through comparison with modern analogs and a chronology based on optically stimulated luminescence ages. Our reconstructions document a continuous but slow sea-level rise after 6.5 ka with an accumulated change in elevation of about 2 m. In the context of SW Europe, our results show good agreement with previous studies, including the Tagus isostatic model, with minor discrepancies that demand further improvement of regional models. This work reinforces the potential of barrier indicators to accurately reconstruct high-resolution mid- to late Holocene sea-level changes through simple approaches.

  20. Coastal barrier stratigraphy for Holocene high-resolution sea-level reconstruction.

    PubMed

    Costas, Susana; Ferreira, Óscar; Plomaritis, Theocharis A; Leorri, Eduardo

    2016-12-08

    The uncertainties surrounding present and future sea-level rise have revived the debate around sea-level changes through the deglaciation and mid- to late Holocene, from which arises a need for high-quality reconstructions of regional sea level. Here, we explore the stratigraphy of a sandy barrier to identify the best sea-level indicators and provide a new sea-level reconstruction for the central Portuguese coast over the past 6.5 ka. The selected indicators represent morphological features extracted from coastal barrier stratigraphy, beach berm and dune-beach contact. These features were mapped from high-resolution ground penetrating radar images of the subsurface and transformed into sea-level indicators through comparison with modern analogs and a chronology based on optically stimulated luminescence ages. Our reconstructions document a continuous but slow sea-level rise after 6.5 ka with an accumulated change in elevation of about 2 m. In the context of SW Europe, our results show good agreement with previous studies, including the Tagus isostatic model, with minor discrepancies that demand further improvement of regional models. This work reinforces the potential of barrier indicators to accurately reconstruct high-resolution mid- to late Holocene sea-level changes through simple approaches.

  1. Extending Automatic Parallelization to Optimize High-Level Abstractions for Multicore

    SciTech Connect

    Liao, C; Quinlan, D J; Willcock, J J; Panas, T

    2008-12-12

    Automatic introduction of OpenMP for sequential applications has attracted significant attention recently because of the proliferation of multicore processors and the simplicity of using OpenMP to express parallelism for shared-memory systems. However, most previous research has only focused on C and Fortran applications operating on primitive data types. C++ applications using high-level abstractions, such as STL containers and complex user-defined types, are largely ignored due to the lack of research compilers that are readily able to recognize high-level object-oriented abstractions and leverage their associated semantics. In this paper, we automatically parallelize C++ applications using ROSE, a multiple-language source-to-source compiler infrastructure which preserves the high-level abstractions and gives us access to their semantics. Several representative parallelization candidate kernels are used to explore semantic-aware parallelization strategies for high-level abstractions, combined with extended compiler analyses. Those kernels include an array-base computation loop, a loop with task-level parallelism, and a domain-specific tree traversal. Our work extends the applicability of automatic parallelization to modern applications using high-level abstractions and exposes more opportunities to take advantage of multicore processors.

  2. A Study of the Environmental Risk Perceptions and Environmental Awareness Levels of High School Students

    ERIC Educational Resources Information Center

    Anilan, Burcu

    2014-01-01

    This descriptive research was conducted to determine the levels of environmental risk perceptions and environmental awareness of high school students in Eskisehir. High school students in the towns Tepebasi and Odunpazari in the 2010-2011 school years constitute the universe of the research. The sample of the research is composed of 413 high…

  3. High School Students' Levels of Thinking in Regard to Statistical Study Design

    ERIC Educational Resources Information Center

    Groth, Randall

    2003-01-01

    The study describes levels of thinking in regard to the design of statistical studies. Clinical interviews were conducted with 15 students who were enrolled in high school or were recent high school graduates, and who represented a range of mathematical backgrounds. During the clinical interview sessions students were asked how they would go about…

  4. Is It Really Possible to Test All Educationally Significant Achievements with High Levels of Reliability?

    ERIC Educational Resources Information Center

    Davis, Andrew

    2015-01-01

    PISA claims that it can extend its reach from its current core subjects of Reading, Science, Maths and problem-solving. Yet given the requirement for high levels of reliability for PISA, especially in the light of its current high stakes character, proposed widening of its subject coverage cannot embrace some important aspects of the social and…

  5. High School Students' Career Decision-Making Pattern across Parenting Styles and Parental Attachment Levels

    ERIC Educational Resources Information Center

    Cenkseven-Onder, Fulya; Kirdok, Oguzhan; Isik, Erkan

    2010-01-01

    Introduction: The purpose of this research was to investigate career decision among high school students regarding to their parenting styles (authoritative, authoritarian, indulgent, and neglectful) and parental attachment levels. Method: With this purpose, 382 (200 females; 182 males) Turkish high school students aged 14-18 completed Career…

  6. Ethnic and Socioeconomic Comparisons of Fitness, Activity Levels, and Barriers to Exercise in High School Females

    ERIC Educational Resources Information Center

    Fahlman, Mariane M.; Hall, Heather L.; Lock, Robyn

    2006-01-01

    The purpose of this study was to determine if high school females differed in individual measures of health-related physical fitness, barriers to exercise, or activity level based on ethnicity or socioeconomic status. A cross-sectional sample consisting of African American (28%), Hispanic (23%), and white (49%) female high school students, 46%…

  7. Aligning High School and College Instruction: Preparing Students for Success in College Level Mathematics

    ERIC Educational Resources Information Center

    Alexander, Julie

    2013-01-01

    Across the United States, students are entering college with a need for improvement in basic mathematics and communication skills. In 2008, the Florida Legislature passed Senate Bill 1908 which changed the expectations for the senior year of high school for many students. Students who score within certain levels on the mandatory high school…

  8. The Role of High Level Play as a Predictor Social Functioning in Autism

    ERIC Educational Resources Information Center

    Manning, Margaret M.; Wainwright, Laurel D.

    2010-01-01

    Play and social abilities of a group of children diagnosed with high functioning autism were compared to a second group diagnosed with a variety of developmental language disorders (DLD). The children with autism engaged in fewer acts of high level play. The children with autism also had significantly lower social functioning than the DLD group…

  9. Effects of High School Students' Perceptions of School Life Quality on Their Academic Motivation Levels

    ERIC Educational Resources Information Center

    Akin Kösterelioglu, Meltem; Kösterelioglu, Ilker

    2015-01-01

    This study aims to identify the effects of high school students' perceptions of school life quality on their academic motivation levels. The study was conducted on a sample of high school students (n = 2371) in Amasya Province in the fall semester of 2013-2014 academic year. Study sample was selected with the help of cluster sampling method. Data…

  10. The Relationship between Internet and Computer Game Addiction Level and Shyness among High School Students

    ERIC Educational Resources Information Center

    Ayas, Tuncay

    2012-01-01

    This study is conducted to determine the relationship between the internet and computer games addiction level and the shyness among high school students. The participants of the study consist of 365 students attending high schools in Giresun city centre during 2009-2010 academic year. As a result of the study a positive, meaningful, and high…

  11. Comparative Functional Literacy of Adult Performance Level Graduates and Wichita East High School Graduating Seniors.

    ERIC Educational Resources Information Center

    Goodman, Deborah; Peppers, Jimmy

    1978-01-01

    Study compared fifty adult performance level (APL) graduates' scores to fifty high school graduates' scores for four APL knowledge areas. APL graduates scored significantly higher than high school graduates in consumer economics and occupational knowledge. No significant differences were recorded between groups in areas of community resources and…

  12. Students' College Preparation Level Based on Quality Factors of the High School Attended

    ERIC Educational Resources Information Center

    Richmond, Lori M.

    2011-01-01

    The present qualitative study examined the views and perspectives of five Executive Directors of Admissions of Midwestern colleges and universities to seek data on high school students' college preparation level based on the quality factors of the high school they attended. Interviews were conducted using multiple open-ended questions on various…

  13. Characterization of high fluence neutron induced defect levels in high resistivity silicon detectors using a laser deep level transient spectroscopy (L-DLTS)

    NASA Astrophysics Data System (ADS)

    Chengji, Li; Li, Zheng

    1994-03-01

    Neutron irradiated high resistivity (4-6 kΩ-cm) silicon detectors in the neutron fluence ( Φn) range of 5 × 10 11 n/cm 2 to 1 × 10 14 n/cm 2 have been studied using a laser deep level transient spectroscopy (L-DLTS). It has been found that the A-center (oxygen-vacancy, Ec = 0.17 eV) concentration increases with neutron fluence, reaching a maximum at Φn ≈ 5×10 12 n/cm 2 before decreasing with Φn. A broad peak has been found between 200 K and 300 K, which is the result of the overlap of three single levels: the V-V - ( Ec = 0.38 eV), the E-center (P-v, Ec = 0.44 eV), and a level at Ec = 0.56 eV that is probably V-V 0. At low neutron fluences ( Φn < 5 × 10 12 n/cm 2), this broad peak is dominated by V-V - and the E-centers. However, as the fluence increases ( Φn ≥ 5 × 10 12 n/cm 2), the peak becomes dominated by the level of Ec = 0.56 eV.

  14. THE RETRIEVAL KNOWLEDGE CENTER EVALUATION OF LOW TANK LEVEL MIXING TECHNOLOGIES FOR DOE HIGH LEVEL WASTE TANK RETRIEVAL 10516

    SciTech Connect

    Fellinger, A.

    2009-12-08

    The Department of Energy (DOE) Complex has over two-hundred underground storage tanks containing over 80-million gallons of legacy waste from the production of nuclear weapons. The majority of the waste is located at four major sites across the nation and is planned for treatment over a period of almost forty years. The DOE Office of Technology Innovation & Development within the Office of Environmental Management (DOE-EM) sponsors technology research and development programs to support processing advancements and technology maturation designed to improve the costs and schedule for disposal of the waste and closure of the tanks. Within the waste processing focus area are numerous technical initiatives which included the development of a suite of waste removal technologies to address the need for proven equipment and techniques to remove high level radioactive wastes from the waste tanks that are now over fifty years old. In an effort to enhance the efficiency of waste retrieval operations, the DOE-EM Office of Technology Innovation & Development funded an effort to improve communications and information sharing between the DOE's major waste tank locations as it relates to retrieval. The task, dubbed the Retrieval Knowledge Center (RKC) was co-lead by the Savannah River National Laboratory (SRNL) and the Pacific Northwest National Laboratory (PNNL) with core team members representing the Oak Ridge and Idaho sites, as well as, site contractors responsible for waste tank operations. One of the greatest challenges to the processing and closure of many of the tanks is complete removal of all tank contents. Sizeable challenges exist for retrieving waste from High Level Waste (HLW) tanks; with complications that are not normally found with tank retrieval in commercial applications. Technologies currently in use for waste retrieval are generally adequate for bulk removal; however, removal of tank heels, the materials settled in the bottom of the tank, using the same

  15. Intelligibility of speech in noise at high presentation levels: effects of hearing loss and frequency region.

    PubMed

    Summers, Van; Cord, Mary T

    2007-08-01

    These experiments examined how high presentation levels influence speech recognition for high- and low-frequency stimuli in noise. Normally hearing (NH) and hearing-impaired (HI) listeners were tested. In Experiment 1, high- and low-frequency bandwidths yielding 70%-correct word recognition in quiet were determined at levels associated with broadband speech at 75 dB SPL. In Experiment 2, broadband and band-limited sentences (based on passbands measured in Experiment 1) were presented at this level in speech-shaped noise filtered to the same frequency bandwidths as targets. Noise levels were adjusted to produce approximately 30%-correct word recognition. Frequency bandwidths and signal-to-noise ratios supporting criterion performance in Experiment 2 were tested at 75, 87.5, and 100 dB SPL in Experiment 3. Performance tended to decrease as levels increased. For NH listeners, this "rollover" effect was greater for high-frequency and broadband materials than for low-frequency stimuli. For HI listeners, the 75- to 87.5-dB increase improved signal audibility for high-frequency stimuli and rollover was not observed. However, the 87.5- to 100-dB increase produced qualitatively similar results for both groups: scores decreased most for high-frequency stimuli and least for low-frequency materials. Predictions of speech intelligibility by quantitative methods such as the Speech Intelligibility Index may be improved if rollover effects are modeled as frequency dependent.

  16. High Pressure Germination of Bacillus subtilis Spores with Alterations in Levels and Types of Germination Proteins

    DTIC Science & Technology

    2014-01-01

    1ITLE AND SUBTITLE 5a CONTRACTNUMBER High pressure germination of Bacillus subtilis spores with W911NF-09-l-0286 alterations in levels and types of...A moderate high pressure (mHP) of 150 megaPascals (MPa) triggers germination of Bacillus subtilis spores via germinant receptors (GRs), while...germination by a very high pressure (vHP) of550 MPa is GR-independent. The mHP and vHP germination of Bacillus subtilis spores with different levels ofGRs

  17. Association between Serum Interleukin-17A Level and High-Altitude Deacclimatization Syndrome

    PubMed Central

    He, Binfeng; Li, Hongli; Hu, Mingdong; Dong, Weijie; Wei, Zhenghua; Li, Jin; Yao, Wei; Guo, Xiaolan

    2016-01-01

    High-altitude deacclimatization syndrome (HADAS) is emerging as a severe public health issue that threatens the quality of life of individuals who return to lower altitude from high altitude. In this study, we measured serum levels of SOD, MDA, IL-17A, IL-10, TNF-α, and HADAS score in HADAS subjects at baseline and 50th and 100th days and to evaluate the relationship between interleukins, including IL-17A, and HADAS. Our data showed that and the serum IL-17A levels and HADAS score decreased over time in the HADAS group, and serum IL-17A levels were significantly higher in the HADAS group at baseline and 50th day compared with controls (p < 0.05). Furthermore, baseline serum levels of MDA and TNF-α were significantly higher, while SOD and IL-10 levels were lower in HADAS subjects compared with controls (p < 0.05). It is interesting that serum levels of IL-17A were clearly interrelated with HADAS incidence and severity (p < 0.05). ROC curve analysis showed that combined serum IL-17A and IL-10 levels were a better predictor of HADAS incidence than serum levels of IL-17A or IL-10 alone. These data suggest that serum levels of IL-17A are a novel predictive index of HADAS. PMID:27190491

  18. Determination of total cyanide in Hanford Site high-level wastes

    SciTech Connect

    Winters, W.I.; Pool, K.H.

    1994-05-01

    Nickel ferrocyanide compounds (Na{sub 2-x}Cs{sub x}NiFe (CN){sub 6}) were produced in a scavenging process to remove {sup 137}Cs from Hanford Site single-shell tank waste supernates. Methods for determining total cyanide in Hanford Site high-level wastes are needed for the evaluation of potential exothermic reactions between cyanide and oxidizers such as nitrate and for safe storage, processing, and management of the wastes in compliance with regulatory requirements. Hanford Site laboratory experience in determining cyanide in high-level wastes is summarized. Modifications were made to standard cyanide methods to permit improved handling of high-level waste samples and to eliminate interferences found in Hanford Site waste matrices. Interferences and associated procedure modifications caused by high nitrates/nitrite concentrations, insoluble nickel ferrocyanides, and organic complexants are described.

  19. Reproduction of European eel jeopardised by high levels of dioxins and dioxin-like PCBs?

    PubMed

    Geeraerts, C; Focant, J-F; Eppe, G; De Pauw, E; Belpaire, C

    2011-09-01

    Dioxins, furans and dioxin-like polychlorinated biphenyls (PCBs) were analysed in muscle tissue from yellow phased European eel (Anguilla anguilla) from 38 sites in Belgium. Dioxin concentrations in eel vary considerably between sampling locations, indicating that yellow eel is a good indicator of local pollution levels. Measured levels of dioxin-like PCBs are much higher than those of the dioxins and furans. In the majority of the sites, eel has levels considered to be detrimental for their reproduction. Field levels of dioxin and dioxin-like PCBs are therefore suggested as an additional causal factor contributing to the decline of the European eel. 42% of the sampling sites show especially dioxin-like PCB levels exceeding the European consumption level (with a factor 3 on average). Human consumption of eel, especially in these highly contaminated sites, seems unjustified.

  20. HIV-1 Nef-associated Factor 1 Enhances Viral Production by Interacting with CRM1 to Promote Nuclear Export of Unspliced HIV-1 gag mRNA.

    PubMed

    Ren, Xiao-Xin; Wang, Hai-Bo; Li, Chuan; Jiang, Jin-Feng; Xiong, Si-Dong; Jin, Xia; Wu, Li; Wang, Jian-Hua

    2016-02-26

    HIV-1 depends on host-cell-encoded factors to complete its life cycle. A comprehensive understanding of how HIV-1 manipulates host machineries during viral infection can facilitate the identification of host targets for antiviral drugs or gene therapy. The cellular protein Naf1 (HIV-1 Nef-associated factor 1) is a CRM1-dependent nucleo-cytoplasmic shuttling protein, and has been identified to regulate multiple receptor-mediated signal pathways in inflammation. The cytoplasm-located Naf1 can inhibit NF-κB activation through binding to A20, and the loss of Naf1 controlled NF-κB activation is associated with multiple autoimmune diseases. However, the effect of Naf1 on HIV-1 mRNA expression has not been characterized. In this study we found that the nucleus-located Naf1 could promote nuclear export of unspliced HIV-1 gag mRNA. We demonstrated that the association between Naf1 and CRM1 was required for this function as the inhibition or knockdown of CRM1 expression significantly impaired Naf1-promoted HIV-1 production. The mutation of Naf1 nuclear export signals (NESs) that account for CRM1 recruitment for nuclear export decreased Naf1 function. Additionally, the mutation of the nuclear localization signal (NLS) of Naf1 diminished its ability to promote HIV-1 production, demonstrating that the shuttling property of Naf1 is required for this function. Our results reveal a novel role of Naf1 in enhancing HIV-1 production, and provide a potential therapeutic target for controlling HIV-1 infection.

  1. Location and dynamics of the immunodominant CD8 T cell response to SIVΔnef immunization and SIVmac251 vaginal challenge.

    PubMed

    Sasikala-Appukuttan, Arun K; Kim, Hyeon O; Kinzel, Nikilyn J; Hong, Jung Joo; Smith, Anthony J; Wagstaff, Reece; Reilly, Cavan; Piatak, Michael; Lifson, Jeffrey D; Reeves, R Keith; Johnson, R Paul; Haase, Ashley T; Skinner, Pamela J

    2013-01-01

    Live-attenuated SIV vaccines (LAVs) have been the most effective to date in preventing or partially controlling infection by wild-type SIV in non-human primate models of HIV-1 transmission to women acting by mechanisms of protection that are not well understood. To gain insights into mechanisms of protection by LAVs that could aid development of effective vaccines to prevent HIV-1 transmission to women, we used in situ tetramer staining to determine whether increased densities or changes in the local distribution of SIV-specific CD8 T cells correlated with the maturation of SIVΔnef vaccine-induced protection prior to and after intra-vaginal challenge with wild-type SIVmac251. We evaluated the immunodominant Mamu-A1*001:01/Gag (CM9) and Mamu-A1*001:01/Tat (SL8) epitope response in genital and lymphoid tissues, and found that tetramer+ cells were present at all time points examined. In the cervical vaginal tissues, most tetramer+ cells were distributed diffusely throughout the lamina propria or co-localized with other CD8 T cells within lymphoid aggregates. The distribution and densities of the tetramer+ cells at the portal of entry did not correlate with the maturation of protection or change after challenge. Given these findings, we discuss the possibility that changes in other aspects of the immune system, including the quality of the resident population of virus-specific effector CD8 T cells could contribute to maturation of protection, as well as the potential for vaccine strategies that further increase the size and quality of this effector population to prevent HIV-1 transmission.

  2. Analysis of Groundwater-Level Changes in High-Frequency Monitoring Wells

    NASA Astrophysics Data System (ADS)

    LIU, C.; Lee, C.; Lin, C.; Chia, Y.; Kuo, K.

    2013-12-01

    Earthquake-related groundwater level changes have often been observed in many places in Taiwan. The monitoring well stations that reflected coseismic groundwater-level changes were often recorded in 1-hour interval, and installed in the coastal plain or hillsides. Hourly groundwater-level data have been recorded by a dense monitoring network since 1980s, but high-frequency data, in second interval, record instrument were installed in only a few monitoring wells starting from the mid-2000s. Two types of earthquake-related groundwater-level changes, oscillatory and sustained, can be observed from high-frequency monitoring data. In this study, we analyzed groundwater-level data from seven wells (Chishan, Donher, Hualien, Liujar, Naba, Sheliao, Tunwei) to investigate the characteristic of groundwater level to earthquakes and different background factors, such as rainfall, barometric pressure and earth tides. Five earthquake cases were studied, four occurred in Taiwan island, the 2010 ML6.4 Kaohsiung earthquake, the 2012 ML6.4 Pingtung earthquake, the 2013 ML6.2 and ML6.5 Nantou earthquake, and one happened distance away, the 2011 MW 9.0 Japan Tohoku earthquake. Oscillatory groundwater-level changes were observed from all earthquake events, but sustained changes differed in each well. The duration of sustained groundwater-level changes ranged from a few minutes to an hour, which may reflect the hydrogeological condition or the redistribution of crustal stress and strain. High-frequency and high-resolution data can reflect the process of coseismic groundwater-level change, and is an indicator for studying the response to earthquakes or fault movement.

  3. Pores and ridges: high-resolution fingerprint matching using level 3 features.

    PubMed

    Jain, Anil K; Chen, Yi; Demirkus, Meltem

    2007-01-01

    Fingerprint friction ridge details are generally described in a hierarchical order at three different levels, namely, Level 1 (pattern), Level 2 (minutia points), and Level 3 (pores and ridge contours). Although latent print examiners frequently take advantage of Level 3 features to assist in identification, Automated Fingerprint Identification Systems (AFIS) currently rely only on Level 1 and Level 2 features. In fact, the Federal Bureau of Investigation's (FBI) standard of fingerprint resolution for AFIS is 500 pixels per inch (ppi), which is inadequate for capturing Level 3 features, such as pores. With the advances in fingerprint sensing technology, many sensors are now equipped with dual resolution (500 ppi/1,000 ppi) scanning capability. However, increasing the scan resolution alone does not necessarily provide any performance improvement in fingerprint matching, unless an extended feature set is utilized. As a result, a systematic study to determine how much performance gain one can achieve by introducing Level 3 features in AFIS is highly desired. We propose a hierarchical matching system that utilizes features at all the three levels extracted from 1,000 ppi fingerprint scans. Level 3 features, including pores and ridge contours, are automatically extracted using Gabor filters and wavelet transform and are locally matched using the Iterative Closest Point (ICP) algorithm. Our experiments show that Level 3 features carry significant discriminatory information. There is a relative reduction of 20 percent in the equal error rate (EER) of the matching system when Level 3 features are employed in combination with Level 1 and 2 features. This significant performance gain is consistently observed across various quality fingerprint images.

  4. The audit of the Replacement High Level Waste Evaporator at the Savannah River Site

    SciTech Connect

    1995-06-26

    The Savannah River Site (Site), owned by the Departmen Energy (Department) and managed by Westinghouse Savannah River Company (Westinghouse), recently changed its primary mission from producing nuclear materials to environmental restoration and waste management. A major focus in the Site`s mission is the storage, treatment, stabilization, and disposal of high level radioactive waste materials. To accomplish this mission, the Site will integrate its high level waste treatment facilities into a High Level Waste System (System), which will process the radioactive waste material in six distinct batches. An integral part of the System is the Replacement High Level Waste Evaporator (Replacement Evaporator) which will evaporate water added to the high level waste during processing, thereby minimizing the volume of the waste stream. Currently, the System has the evaporator and tank farm capacity to accommodate the processing of the first batch of radioactive waste, which is scheduled to begin in March 1996. However, the system will need the Replacement Evaporator to accommodate the volume of water and solvent added during processing of the second batch of radioactive waste scheduled to begin processing in 2004.

  5. Factors related to high-level mobility in male servicemembers with traumatic lower-limb loss.

    PubMed

    Gaunaurd, Ignacio A; Roach, Kathryn E; Raya, Michele A; Hooper, Rebecca; Linberg, Alison A; Laferrier, Justin Z; Campbell, Stuart M; Scoville, Charles; Gailey, Robert S

    2013-01-01

    The purpose of this study was to examine the possible relationship between factors modifiable by rehabilitation interventions (rehabilitation factors), other factors related to lower-limb loss (other factors), and high-level mobility as measured by the Comprehensive High-Level Activity Mobility Predictor (CHAMP) in servicemembers (SMs) with traumatic lower-limb loss. One-hundred eighteen male SMs with either unilateral transtibial amputation (TTA), unilateral transfemoral amputation (TFA), or bilateral lower-limb amputation (BLLA) participated. Stepwise regression analysis was used to develop separate regression models of factors predicting CHAMP score. Regression models containing both rehabilitation factors and other factors explained 81% (TTA), 36% (TFA), and 91% (BLLA) of the variance in CHAMP score. Rehabilitation factors such as lower-limb strength and dynamic balance were found to be significantly related to CHAMP score and can be enhanced with the appropriate intervention. Further, the findings support the importance of salvaging the knee joint and its effect on high-level mobility capabilities. Lastly, the J-shaped energy storage and return feet were found to improve high-level mobility for SMs with TTA. These results could help guide rehabilitation and aid in developing appropriate interventions to assist in maximizing high-level mobility capabilities for SMs with traumatic lower-limb loss.

  6. [Plasma concentration of C-reactive protein in patients with high estrogen levels].

    PubMed

    Ricoux, R; Pontet, M; Tresca, J P; Engler, R

    1994-01-01

    The monitoring of inflammatory activity in patients with a high level of estrogen is controversial because the significance of a raised estradiol level on C-reactive protein (CRP) concentrations is a debated question. This prompted us to assay CRP by a sensitive Elisa in a sample of 30 patients with ovarian stimulation for in vitro fertilization, thus with high levels of estradiol. For 15 of these women, six to nine plasma samples were analyzed allowing a kinetic study of plasma levels of CRP, estradiol and sex steroid-binding plasma protein (SBP). No significant correlation was found between the concentrations of estradiol and CRP for the 30 patients. In the kinetic study, as mean estradiol levels rose exponentially from 50 to 1400 ng/l between day 5 and 14, the CRP level tended to vary markedly from one patient to another and sometimes from day to day, but there was never any relation with estradiol level. Furthermore, CRP did not significantly modify the slope of the regression line between estradiol concentration and the day of the menstrual cycle. In contrast, the effect of estradiol on SBP was clear, which supports the absence of estradiol effect on CRP level.

  7. Testing the high turbulence level breakdown of low-frequency gyrokinetics against high-frequency cyclokinetic simulations

    SciTech Connect

    Deng, Zhao; Waltz, R. E.

    2015-05-15

    This paper presents numerical simulations of the nonlinear cyclokinetic equations in the cyclotron harmonic representation [R. E. Waltz and Zhao Deng, Phys. Plasmas 20, 012507 (2013)]. Simulations are done with a local flux-tube geometry and with the parallel motion and variation suppressed using a newly developed rCYCLO code. Cyclokinetic simulations dynamically follow the high-frequency ion gyro-phase motion which is nonlinearly coupled into the low-frequency drift-waves possibly interrupting and suppressing gyro-averaging and increasing the transport over gyrokinetic levels. By comparing the more fundamental cyclokinetic simulations with the corresponding gyrokinetic simulations, the breakdown of gyrokinetics at high turbulence levels is quantitatively tested over a range of relative ion cyclotron frequency 10 < Ω*{sup  }< 100 where Ω*{sup  }= 1/ρ*, and ρ* is the relative ion gyroradius. The gyrokinetic linear mode rates closely match the cyclokinetic low-frequency rates for Ω*{sup  }> 5. Gyrokinetic transport recovers cyclokinetic transport at high relative ion cyclotron frequency (Ω*{sup  }≥ 50) and low turbulence level as required. Cyclokinetic transport is found to be lower than gyrokinetic transport at high turbulence levels and low-Ω* values with stable ion cyclotron (IC) modes. The gyrokinetic approximation is found to break down when the density perturbations exceed 20%. For cyclokinetic simulations with sufficiently unstable IC modes and sufficiently low Ω*{sup  }∼ 10, the high-frequency component of cyclokinetic transport level can exceed the gyrokinetic transport level. However, the low-frequency component of the cyclokinetic transport and turbulence level does not exceed that of gyrokinetics. At higher and more physically relevant Ω*{sup  }≥ 50 values and physically realistic IC driving rates, the low-frequency component of the cyclokinetic transport and turbulence level is still smaller than that of

  8. InGaAs communication photodiodes: from low to high power level designs

    NASA Astrophysics Data System (ADS)

    Achouche, M.

    2009-01-01

    While InGaAs absorption material has been used for various applications up to 1.6μm wavelength, specific designs for low level detection have become of main interest using high responsivity and low dark current detectors. By adding an avalanche multiplication layer to form an avalanche photodiode (APD) using the Separated Absorption and Multiplication (SAM) structure, one can take advantage of the very low noise properties of multiplication process in large bandgap Al(Ga)(In)As material to improve receiver sensitivity by >10dB. Under high power level injection, specific PIN structures have been developed to improve space charge effects as needed for power applications such as microwave analog photonic links. Specific designs to achieve simultaneously broad bandwidth, high responsivity, very high power saturation and high linearity will be discussed.

  9. 324 Building radiochemical engineering cells, high-level vault, low-level vault, and associated areas closure plan

    SciTech Connect

    Barnett, J.M.

    1998-03-25

    The Hanford Site, located adjacent to and north of Richland, Washington, is operated by the US Department of Energy, Richland Operations Office (RL). The 324 Building is located in the 300 Area of the Hanford Site. The 324 Building was constructed in the 1960s to support materials and chemical process research and development activities ranging from laboratory/bench-scale studies to full engineering-scale pilot plant demonstrations. In the mid-1990s, it was determined that dangerous waste and waste residues were being stored for greater than 90 days in the 324 Building Radiochemical Engineering Cells (REC) and in the High-Level Vault/Low-Level Vault (HLV/LLV) tanks. [These areas are not Resource Conservation and Recovery Act of 1976 (RCRA) permitted portions of the 324 Building.] Through the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) Milestone M-89, agreement was reached to close the nonpermitted RCRA unit in the 324 Building. This closure plan, managed under TPA Milestone M-20-55, addresses the identified building areas targeted by the Tri-Party Agreement and provides commitments to achieve the highest degree of compliance practicable, given the special technical difficulties of managing mixed waste that contains high-activity radioactive materials, and the physical limitations of working remotely in the areas within the subject closure unit. This closure plan is divided into nine chapters. Chapter 1.0 provides the introduction, historical perspective, 324 Building history and current mission, and the regulatory basis and strategy for managing the closure unit. Chapters 2.0, 3.0, 4.0, and 5.0 discuss the detailed facility description, process information, waste characteristics, and groundwater monitoring respectively. Chapter 6.0 deals with the closure strategy and performance standard, including the closure activities for the B-Cell, D-Cell, HLV, LLV; piping and miscellaneous associated building areas. Chapter 7.0 addresses the

  10. Spatiotemporal models for predicting high pollen concentration level of Corylus, Alnus, and Betula

    NASA Astrophysics Data System (ADS)

    Nowosad, Jakub

    2016-06-01

    Corylus, Alnus, and Betula trees are among the most important sources of allergic pollen in the temperate zone of the Northern Hemisphere and have a large impact on the quality of life and productivity of allergy sufferers. Therefore, it is important to predict high pollen concentrations, both in time and space. The aim of this study was to create and evaluate spatiotemporal models for predicting high Corylus, Alnus, and Betula pollen concentration levels, based on gridded meteorological data. Aerobiological monitoring was carried out in 11 cities in Poland and gathered, depending on the site, between 2 and 16 years of measurements. According to the first allergy symptoms during exposure, a high pollen count level was established for each taxon. An optimizing probability threshold technique was used for mitigation of the problem of imbalance in the pollen concentration levels. For each taxon, the model was built using a random forest method. The study revealed the possibility of moderately reliable prediction of Corylus and highly reliable prediction of Alnus and Betula high pollen concentration levels, using preprocessed gridded meteorological data. Cumulative growing degree days and potential evaporation proved to be two of the most important predictor variables in the models. The final models predicted not only for single locations but also for continuous areas. Furthermore, the proposed modeling framework could be used to predict high pollen concentrations of Corylus, Alnus, Betula, and other taxa, and in other countries.

  11. Spatiotemporal models for predicting high pollen concentration level of Corylus, Alnus, and Betula.

    PubMed

    Nowosad, Jakub

    2016-06-01

    Corylus, Alnus, and Betula trees are among the most important sources of allergic pollen in the temperate zone of the Northern Hemisphere and have a large impact on the quality of life and productivity of allergy sufferers. Therefore, it is important to predict high pollen concentrations, both in time and space. The aim of this study was to create and evaluate spatiotemporal models for predicting high Corylus, Alnus, and Betula pollen concentration levels, based on gridded meteorological data. Aerobiological monitoring was carried out in 11 cities in Poland and gathered, depending on the site, between 2 and 16 years of measurements. According to the first allergy symptoms during exposure, a high pollen count level was established for each taxon. An optimizing probability threshold technique was used for mitigation of the problem of imbalance in the pollen concentration levels. For each taxon, the model was built using a random forest method. The study revealed the possibility of moderately reliable prediction of Corylus and highly reliable prediction of Alnus and Betula high pollen concentration levels, using preprocessed gridded meteorological data. Cumulative growing degree days and potential evaporation proved to be two of the most important predictor variables in the models. The final models predicted not only for single locations but also for continuous areas. Furthermore, the proposed modeling framework could be used to predict high pollen concentrations of Corylus, Alnus, Betula, and other taxa, and in other countries.

  12. Back-Analyses of Landfill Instability Induced by High Water Level: Case Study of Shenzhen Landfill.

    PubMed

    Peng, Ren; Hou, Yujing; Zhan, Liangtong; Yao, Yangping

    2016-01-12

    In June 2008, the Shenzhen landfill slope failed. This case is used as an example to study the deformation characteristics and failure mode of a slope induced by high water levels. An integrated monitoring system, including water level gauges, electronic total stations, and inclinometers, was used to monitor the slope failure process. The field measurements suggest that the landfill landslide was caused by a deep slip along the weak interface of the composite liner system at the base of the landfill. The high water level is considered to be the main factor that caused this failure. To calculate the relative interface shear displacements in the geosynthetic multilayer liner system, a series of numerical direct shear tests were carried out. Based on the numerical results, the composite lining system simplified and the centrifuge modeling technique was used to quantitatively evaluate the effect of water levels on landfill instability.

  13. Back-Analyses of Landfill Instability Induced by High Water Level: Case Study of Shenzhen Landfill

    PubMed Central

    Peng, Ren; Hou, Yujing; Zhan, Liangtong; Yao, Yangping

    2016-01-01

    In June 2008, the Shenzhen landfill slope failed. This case is used as an example to study the deformation characteristics and failure mode of a slope induced by high water levels. An integrated monitoring system, including water level gauges, electronic total stations, and inclinometers, was used to monitor the slope failure process. The field measurements suggest that the landfill landslide was caused by a deep slip along the weak interface of the composite liner system at the base of the landfill. The high water level is considered to be the main factor that caused this failure. To calculate the relative interface shear displacements in the geosynthetic multilayer liner system, a series of numerical direct shear tests were carried out. Based on the numerical results, the composite lining system simplified and the centrifuge modeling technique was used to quantitatively evaluate the effect of water levels on landfill instability. PMID:26771627

  14. An improved retinal vessel segmentation method based on high level features for pathological images.

    PubMed

    Ganjee, Razieh; Azmi, Reza; Gholizadeh, Behrouz

    2014-09-01

    Most of the retinal blood vessel segmentation approaches use low level features, resulting in segmenting non-vessel structures together with vessel structures in pathological retinal images. In this paper, a new segmentation method based on high level features is proposed which can process the structure of vessel and non-vessel independently. In this method, segmentation is done in two steps. First, using low level features segmentation is accomplished. Second, using high level features, the non-vessel components are removed. For evaluation, STARE database is used which is publicly available in this field. The results show that the proposed method has 0.9536 accuracy and 0.0191 false positive average on all images of the database and 0.9542 accuracy and 0.0236 false positive average on pathological images. Therefore, the proposed approach shows acceptable accuracy on all images compared to other state of the art methods, and the least false positive average on pathological images.

  15. PBP 4 Mediates High-Level Resistance to New-Generation Cephalosporins in Staphylococcus aureus

    PubMed Central

    Chan, Liana C.; Gilbert, Aubre; Basuino, Li; da Costa, Thaina M.; Hamilton, Stephanie M.; dos Santos, Katia R.; Chambers, Henry F.

    2016-01-01

    Staphylococcus aureus is an important cause of both hospital- and community-associated methicillin-resistant S. aureus (MRSA) infections worldwide. β-Lactam antibiotics are the drugs of choice to treat S. aureus infections, but resistance to these and other antibiotics make treatment problematic. High-level β-lactam resistance of S. aureus has always been attributed to the horizontally acquired penicillin binding protein 2a (PBP 2a) encoded by the mecA gene. Here, we show that S. aureus can also express high-level resistance to β-lactams, including new-generation broad-spectrum cephalosporins that are active against methicillin-resistant strains, through an uncanonical core genome-encoded penicillin binding protein, PBP 4, a nonessential enzyme previously considered not to be important for staphylococcal β-lactam resistance. Our results show that PBP 4 can mediate high-level resistance to β-lactams. PMID:27067335

  16. Heat transfer analysis of the geologic disposal of spent fuel and high level waste storage canisters

    NASA Astrophysics Data System (ADS)

    Allen, G. K.

    1980-08-01

    Near-field temperatures resulting from the storage of high-level waste canisters and spent unreprocessed fuel assembly canisters in geologic formations were determined. Preliminary design of the repository was modeled for a heat transfer computer code, HEATING5, which used the finite difference method to evaluate transient heat transfer. The heat transfer system was evaluated with several two and three dimensional models which transfer heat by a combination of conduction, natural convention, and radiation. Physical properties of the materials in the model were based upon experimental values for the various geologic formations. The effects of canister spacing, fuel age, and use of an overpack were studied for the analysis of the spent fuel canisters; salt, granite, and basalt were considered as the storage media. The effects of canister diameter and use of an overpack were studied for the analysis of the high-level waste canisters; salt was considered as the only storage media for high-level waste canisters.

  17. High-level waste processing at the Savannah River Site: An update

    SciTech Connect

    Marra, J.E.; Bennett, W.M.; Elder, H.H.; Lee, E.D.; Marra, S.L.; Rutland, P.L.

    1997-09-01

    The Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS) in Aiken, SC mg began immobilizing high-level radioactive waste in borosilicate glass in 1996. Currently, the radioactive glass is being produced as a ``sludge-only`` composition by combining washed high-level waste sludge with glass frit. The glass is poured in stainless steel canisters which will eventually be disposed of in a permanent, geological repository. To date, DWPF has produced about 100 canisters of vitrified waste. Future processing operations will, be based on a ``coupled`` feed of washed high-level waste sludge, precipitated cesium, and glass frit. This paper provides an update of the processing activities completed to date, operational/flowsheet problems encountered, and programs underway to increase production rates.

  18. Predictors of High Level of Hostility among Homeless Men on Parole.

    PubMed

    Nyamathi, Adeline; Salem, Benissa; Farabee, David; Hall, Elizabeth; Zhang, Sheldon; Khalilifard, Farinaz; Faucette, Mark; Leake, Barbara

    2014-02-01

    High levels of hostility present a formidable challenge among homeless ex-offenders. This cross-sectional study assessed correlates of high levels of hostility using baseline data collected on recently-released male parolees (N=472; age 18-60) participating in a randomized trial focused on prevention of illicit drug use and recidivism. Predictors of high levels of hostility included greater depressive symptomatology, lower self-esteem, having a mother who was treated for alcohol/drugs, belonging to a gang, more tangible support, having used methamphetamine and having a history of cognitive difficulties. These findings highlight the need to understand predictors of hostility among recently released homeless men and how these predictors may relate to recidivism. Research implications are discussed as these findings will shape future nurse-led harm reduction and community-based interventions.

  19. High source levels and small active space of high-pitched song in bowhead whales (Balaena mysticetus).

    PubMed

    Tervo, Outi M; Christoffersen, Mads F; Simon, Malene; Miller, Lee A; Jensen, Frants H; Parks, Susan E; Madsen, Peter T

    2012-01-01

    The low-frequency, powerful vocalizations of blue and fin whales may potentially be detected by conspecifics across entire ocean basins. In contrast, humpback and bowhead whales produce equally powerful, but more complex broadband vocalizations composed of higher frequencies that suffer from higher attenuation. Here we evaluate the active space of high frequency song notes of bowhead whales (Balaena mysticetus) in Western Greenland using measurements of song source levels and ambient noise. Four independent, GPS-synchronized hydrophones were deployed through holes in the ice to localize vocalizing bowhead whales, estimate source levels and measure ambient noise. The song had a mean apparent source level of 185±2 dB rms re 1 µPa @ 1 m and a high mean centroid frequency of 444±48 Hz. Using measured ambient noise levels in the area and Arctic sound spreading models, the estimated active space of these song notes is between 40 and 130 km, an order of magnitude smaller than the estimated active space of low frequency blue and fin whale songs produced at similar source levels and for similar noise conditions. We propose that bowhead whales spatially compensate for their smaller communication range through mating aggregations that co-evolved with broadband song to form a complex and dynamic acoustically mediated sexual display.

  20. High Source Levels and Small Active Space of High-Pitched Song in Bowhead Whales (Balaena mysticetus)

    PubMed Central

    Tervo, Outi M.; Christoffersen, Mads F.; Simon, Malene; Miller, Lee A.; Jensen, Frants H.; Parks, Susan E.; Madsen, Peter T.

    2012-01-01

    The low-frequency, powerful vocalizations of blue and fin whales may potentially be detected by conspecifics across entire ocean basins. In contrast, humpback and bowhead whales produce equally powerful, but more complex broadband vocalizations composed of higher frequencies that suffer from higher attenuation. Here we evaluate the active space of high frequency song notes of bowhead whales (Balaena mysticetus) in Western Greenland using measurements of song source levels and ambient noise. Four independent, GPS-synchronized hydrophones were deployed through holes in the ice to localize vocalizing bowhead whales, estimate source levels and measure ambient noise. The song had a mean apparent source level of 185±2 dB rms re 1 µPa @ 1 m and a high mean centroid frequency of 444±48 Hz. Using measured ambient noise levels in the area and Arctic sound spreading models, the estimated active space of these song notes is between 40 and 130 km, an order of magnitude smaller than the estimated active space of low frequency blue and fin whale songs produced at similar source levels and for similar noise conditions. We propose that bowhead whales spatially compensate for their smaller communication range through mating aggregations that co-evolved with broadband song to form a complex and dynamic acoustically mediated sexual display. PMID:23300591