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Sample records for brucei paraflagellar rod

  1. A protein-protein interaction map of the Trypanosoma brucei paraflagellar rod.

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    Sylvain Lacomble

    Full Text Available We have conducted a protein interaction study of components within a specific sub-compartment of a eukaryotic flagellum. The trypanosome flagellum contains a para-crystalline extra-axonemal structure termed the paraflagellar rod (PFR with around forty identified components. We have used a Gateway cloning approach coupled with yeast two-hybrid, RNAi and 2D DiGE to define a protein-protein interaction network taking place in this structure. We define two clusters of interactions; the first being characterised by two proteins with a shared domain which is not sufficient for maintaining the interaction. The other cohort is populated by eight proteins, a number of which possess a PFR domain and sub-populations of this network exhibit dependency relationships. Finally, we provide clues as to the structural organisation of the PFR at the molecular level. This multi-strand approach shows that protein interactome data can be generated for insoluble protein complexes.

  2. Pure paraflagellar rod protein protects mice against Trypanosoma cruzi infection.

    OpenAIRE

    1995-01-01

    The paraflagellar rod proteins (PAR) purified from Trypanosoma cruzi epimastigotes were shown to protect mice against an otherwise lethal challenge inoculum of 10(3) bloodstream-form trypomastigotes. The injection route used for immunization was shown to have a marked impact on the development of protective immunity. Mice receiving subcutaneous (s.c.) injections of PAR proteins had reduced bloodstream parasitemias and showed 100% survival following challenge. In contrast, mice immunized via t...

  3. Cryptic Paraflagellar Rod in Endosymbiont-Containing Kinetoplastid Protozoa

    OpenAIRE

    2005-01-01

    Cilia and flagella are central to many biological processes in a diverse range of organisms. The kinetoplastid protozoa are very appealing models for the study of flagellar function, particularly in the light of the availability of extensive trypanosomatid genome information. In addition to the highly conserved 9 + 2 axoneme, the kinetoplastid flagellum contains a characteristic paraflagellar rod structure (PFR). The PFR is necessary for full motility and provides support for metabolic regula...

  4. Pure paraflagellar rod protein protects mice against Trypanosoma cruzi infection.

    Science.gov (United States)

    Wrightsman, R A; Miller, M J; Saborio, J L; Manning, J E

    1995-01-01

    The paraflagellar rod proteins (PAR) purified from Trypanosoma cruzi epimastigotes were shown to protect mice against an otherwise lethal challenge inoculum of 10(3) bloodstream-form trypomastigotes. The injection route used for immunization was shown to have a marked impact on the development of protective immunity. Mice receiving subcutaneous (s.c.) injections of PAR proteins had reduced bloodstream parasitemias and showed 100% survival following challenge. In contrast, mice immunized via the intraperitoneal (i.p.) route developed parasitemia levels equivalent to those of unimmunized controls and did not survive infection. Western blotting (immunoblotting) demonstrated that sera from both i.p. and s.c. immunized mice reacted specifically with PAR proteins; however, the antibody titer of the i.p. immunized mice was approximately 64-fold greater than that of the s.c. immunized mice, suggesting that the protective response in the s.c. immunized mice is cell mediated rather than humoral.

  5. Three-dimensional structure of the Trypanosome flagellum suggests that the paraflagellar rod functions as a biomechanical spring.

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    Louise C Hughes

    Full Text Available Flagellum motility is critical for normal human development and for transmission of pathogenic protozoa that cause tremendous human suffering worldwide. Biophysical principles underlying motility of eukaryotic flagella are conserved from protists to vertebrates. However, individual cells exhibit diverse waveforms that depend on cell-specific elaborations on basic flagellum architecture. Trypanosoma brucei is a uniflagellated protozoan parasite that causes African sleeping sickness. The T. brucei flagellum is comprised of a 9+2 axoneme and an extra-axonemal paraflagellar rod (PFR, but the three-dimensional (3D arrangement of the underlying structural units is poorly defined. Here, we use dual-axis electron tomography to determine the 3D architecture of the T. brucei flagellum. We define the T. brucei axonemal repeating unit. We observe direct connections between the PFR and axonemal dyneins, suggesting a mechanism by which mechanochemical signals may be transmitted from the PFR to axonemal dyneins. We find that the PFR itself is comprised of overlapping laths organized into distinct zones that are connected through twisting elements at the zonal interfaces. The overall structure has an underlying 57 nm repeating unit. Biomechanical properties inferred from PFR structure lead us to propose that the PFR functions as a biomechanical spring that may store and transmit energy derived from axonemal beating. These findings provide insight into the structural foundations that underlie the distinctive flagellar waveform that is a hallmark of T. brucei cell motility.

  6. Generation of a nanobody targeting the paraflagellar rod protein of trypanosomes.

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    Emmanuel Obishakin

    Full Text Available Trypanosomes are protozoan parasites that cause diseases in humans and livestock for which no vaccines are available. Disease eradication requires sensitive diagnostic tools and efficient treatment strategies. Immunodiagnostics based on antigen detection are preferable to antibody detection because the latter cannot differentiate between active infection and cure. Classical monoclonal antibodies are inaccessible to cryptic epitopes (based on their size-150 kDa, costly to produce and require cold chain maintenance, a condition that is difficult to achieve in trypanosomiasis endemic regions, which are mostly rural. Nanobodies are recombinant, heat-stable, small-sized (15 kDa, antigen-specific, single-domain, variable fragments derived from heavy chain-only antibodies in camelids. Because of numerous advantages over classical antibodies, we investigated the use of nanobodies for the targeting of trypanosome-specific antigens and diagnostic potential. An alpaca was immunized using lysates of Trypanosoma evansi. Using phage display and bio-panning techniques, a cross-reactive nanobody (Nb392 targeting all trypanosome species and isolates tested was selected. Imunoblotting, immunofluorescence microscopy, immunoprecipitation and mass spectrometry assays were combined to identify the target recognized. Nb392 targets paraflagellar rod protein (PFR1 of T. evansi, T. brucei, T. congolense and T. vivax. Two different RNAi mutants with defective PFR assembly (PFR2RNAi and KIF9BRNAi were used to confirm its specificity. In conclusion, using a complex protein mixture for alpaca immunization, we generated a highly specific nanobody (Nb392 that targets a conserved trypanosome protein, i.e., PFR1 in the flagella of trypanosomes. Nb392 is an excellent marker for the PFR and can be useful in the diagnosis of trypanosomiasis. In addition, as demonstrated, Nb392 can be a useful research or PFR protein isolation tool.

  7. Evidence for four distinct major protein components in the paraflagellar rod of Trypanosoma cruzi.

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    Fouts, D L; Stryker, G A; Gorski, K S; Miller, M J; Nguyen, T V; Wrightsman, R A; Manning, J E

    1998-08-21

    The major structural proteins present in the paraflagellar rod of Trypanosoma cruzi migrate on SDS-polyacrylamide gels as two distinct electrophoretic bands. The gene encoding a protein present in the faster migrating band, designated PAR 2, has been identified previously. Here we report the isolation and partial characterization of three genes, designated par 1, par 3, and par 4, that encode proteins present in the two paraflagellar rod protein bands. Peptide-specific polyclonal antibodies and monoclonal antibodies against the four proteins encoded by these genes shows that PAR 1 and PAR 3 are present only in the slower migrating paraflagellar rod band, and that PAR 2 and PAR 4 are present only in the faster migrating band. Analysis of the nucleotide sequence of these genes and the amino acid sequence of the conceptual proteins encoded by them indicates that par 2 shares high sequence similarity with par 3 and both are members of a common gene family, of which par 1 may be a distant member. Analysis of gene copy number and steady-state RNA levels suggest that the close stoichiometric ratio of the four PAR proteins is likely maintained by homeostatic regulation of RNA levels rather than gene dosage.

  8. Stage-specific expression of the Leishmania mexicana paraflagellar rod protein PFR-2.

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    Moore, L L; Santrich, C; LeBowitz, J H

    1996-10-01

    A screen for Leishmania mexicana genes encoding promastigote-specific flagellar proteins resulted in isolation of genes encoding the major components of the paraflagellar rod. One of these, PFR-2, was characterized extensively. PFR-2 genes are present in the genome as a tandem array of three genes designated PFR-2A, PFR-2B, PFR-2C. PFR-2A and PFR-2B are encoded by a 3.1 transcript while PFR-2C is encoded by a 3.8-kb transcript that has a 3' UTR different from that of the 3.1-kb transcript. Both of these mRNAs were 15-fold more abundant in promastigotes than in amastigotes. Two transcripts immediately upstream of the locus were constitutively expressed while two downstream transcripts were fourfold more abundant in promastigotes than in amastigotes. The PFR genes will provide a good model system for analysis of stage-specific gene regulation in Leishmania as well as assist in the characterization of the function and organization of the paraflagellar rod.

  9. A motility function for the paraflagellar rod of Leishmania parasites revealed by PFR-2 gene knockouts.

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    Santrich, C; Moore, L; Sherwin, T; Bastin, P; Brokaw, C; Gull, K; LeBowitz, J H

    1997-12-01

    We demonstrate a functional role for the paraflagellar rod (PFR) in motility of Leishmania mexicana. The PFR is a complex cytoskeletal structure running parallel to the axoneme in the flagella of kinetoplastid protozoa. The PFR is composed of a latticework of protein filaments whose major constituents are two related proteins (PFR-1 and PFR-2 in Leishmania). The molecular details of their assembly into PFR filaments are unknown as is the biological function of the PFR. As an approach to understanding the structure and function of the PFR in Leishmania, we made L. mexicana null mutants of PFR-2. PFR-2 minus parasites grow and divide normally in culture and still express the PFR-1 protein. They lack most of the PFR structure demonstrating that the PFR-2 protein is an essential constituent of the PFR. Detailed ultrastructural analysis of the PFR-2 null mutant reveals the presence of a residual inner substructure of the PFR which contains PFR-1 protein, indicating that PFR-1 can polymerize in the absence of PFR-2. The PFR-2 null mutant displays pronounced changes in flagellar beat waveform and forward swimming velocity, compared to wild type parasites consistent with decreased internal elastic bending resistance in PFR-lacking flagella, and indicating a functional role for the PFR in the motility of Leishmania.

  10. Structural changes of the paraflagellar rod during flagellar beating in Trypanosoma cruzi.

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    Gustavo Miranda Rocha

    Full Text Available BACKGROUND: Trypanosoma cruzi, the agent of Chagas disease, is a protozoan member of the Kinetoplastidae family characterized for the presence of specific and unique structures that are involved in different cell activities. One of them is the paraflagellar rod (PFR, a complex array of filaments connected to the flagellar axoneme. Although the function played by the PFR is not well established, it has been shown that silencing of the synthesis of its major proteins by either knockout of RNAi impairs and/or modifies the flagellar motility. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present results obtained by atomic force microscopy (AFM and transmission electron microscopy (TEM of replicas of quick-frozen, freeze-fractured, deep-etched and rotary-replicated cells to obtain detailed information of the PFR structures in regions of the flagellum in straight and in bent state. The images obtained show that the PFR is not a fixed and static structure. The pattern of organization of the PFR filament network differs between regions of the flagellum in a straight state and those in a bent state. Measurements of the distances between the PFR filaments and the filaments that connect the PFR to the axoneme as well as of the angles between the intercrossed filaments supported this idea. CONCLUSIONS/SIGNIFICANCE: Graphic computation based on the information obtained allowed the proposal of an animated model for the PFR structure during flagellar beating and provided a new way of observing PFR filaments during flagellar beating.

  11. A Negative Regulatory Element Controls mRNA Abundance of the Leishmania mexicana Paraflagellar Rod Gene PFR2†

    OpenAIRE

    2003-01-01

    The Leishmania mexicana PFR2 locus encodes a component of the paraflagellar rod (PFR), a flagellar structure found only in the insect stage of the life cycle. PFR2 mRNA levels are 10-fold lower in the mammalian stage than in the insect stage. Nuclear run-on experiments indicate that the change in PFR2 mRNA abundance is achieved posttranscriptionally. Deletion and block substitution analysis of the entire 1,400-nucleotide 3′ untranslated region (UTR) of PFR2C led to the identification of a reg...

  12. Paraflagellar rod proteins administered with alum and IL-12 or recombinant adenovirus expressing IL-12 generates antigen-specific responses and protective immunity in mice against Trypanosoma cruzi.

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    Wrightsman, R A; Manning, J E

    2000-01-31

    Successful vaccination of mice against an otherwise lethal challenge with the Peru strain of Trypanosoma cruzi necessitates the induction of a strong cell mediated immune response. Previously, immunization of mice with the paraflagellar rod proteins from Trypanosoma cruzi90% reduction in parasitemia in immunized mice challenged with the bloodstream stage of Trypanosoma cruzi.

  13. Paraflagellar rod protein-specific CD8+ cytotoxic T lymphocytes target Trypanosoma cruzi-infected host cells.

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    Wrightsman, Ruth A; Luhrs, Keith A; Fouts, David; Manning, Jerry E

    2002-08-01

    Our previous studies show that in mice immunized with the paraflagellar rod (PFR) proteins of Trypanosoma cruzi protective immunity against this protozoan parasite requires MHC class I-restricted T cell function. To determine whether PFR-specific CD8+ T cell subsets are generated during T. cruzi infection, potential CTL targets in the PFR proteins were identified by scanning the amino acid sequences of the four PFR proteins for regions of 8-10 amino acids that conform to predicted MHC class I H-2b binding motifs. A subset of the peptide sequences identified were synthesized and tested as target antigen in 51Cr-release assays with effector cells from chronically infected T. cruzi mice. Short-term cytotoxic T lymphocyte (CTL) lines specific for two of the peptides, PFR-1(164-171) and PFR-3(123-130), showed high levels of lytic activity against peptide-pulsed target cells, secreted interferon (IFN)-gamma in response to parasite-infected target cells, and were found to be CD8+, CD4-, CD3+, TCRalphabeta+ cells of the Tc1 subset. Challenge of PFR immunized CD8-/- and perforin-deficient (PKO) mice confirmed that while CD8+ cells are required for survival of T. cruzi challenge infection, perforin activity is not required. Furthermore, while lytic activity of PFR-specific CD8+ T cell lines derived from PKO mice was severely impaired, the IFN-gamma levels secreted by CTLs from PKO mice were equivalent to that of normal mice, suggesting that the critical role played by CD8+ T cells in immunity to the parasite may be secretion of type 1 cytokines rather than lysis of parasite infected host cells.

  14. Protection of mice against Trypanosoma cruzi by immunization with paraflagellar rod proteins requires T cell, but not B cell, function.

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    Miller, M J; Wrightsman, R A; Stryker, G A; Manning, J E

    1997-06-01

    Previous studies have shown that immunization of mice with the paraflagellar rod proteins (PAR) of Trypanosoma cruzi induces an immune response capable of protecting mice against an otherwise lethal challenge with this parasite. Herein, we define immunologic responses that do or do not play a critical role in PAR-mediated protection. Firstly, PAR-immunized Ab-deficient (muMT) strain mice survived an otherwise lethal T. cruzi challenge, indicating that a B cell response is not required for PAR-induced immunity. However, beta2m -/- mice, which are severely deficient in MHC class I and TCR alphabeta+ CD8+ CD4- T cells, did not survive challenge infection following PAR immunization, indicating that MHC class I/CD8+ T cell function is necessary for protection induced by PAR immunization. Surprisingly, PAR-immunized mice depleted of CD4+ T cells survived a T. cruzi challenge for >84 days postinfection while maintaining a parasitemia that is generally thought to be lethal (i.e., >10(6) trypomastigotes/ml), thus associating CD4+ T cell function with the process of parasite clearance. Consistent with this association, CD4+ T cells from PAR-immunized mice released INF-gamma and stimulated T. cruzi-infected macrophages to release nitric oxide. The importance of IFN-gamma in PAR-induced protective immunity is further indicated by the observation that PAR-immunized INF-gamma knockout mice developed an extremely high parasitemia and did not survive a challenge infection. Thus, while Ab-mediated immune mechanisms are not required for protection induced by PAR immunization, T cell responses are necessary for both elimination of bloodstream parasites and survival.

  15. Trypanosoma cruzi: protective immunity in mice immunized with paraflagellar rod proteins is associated with a T-helper type 1 response.

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    Miller, M J; Wrightsman, R A; Manning, J E

    1996-11-01

    We have examined the ability of mice to survive a lethal challenge with the parasitic hemoflagellate, Trypanosoma cruzi, following immunization with paraflagellar rod proteins (PAR) 1 and 2 either alone or in combination with the following adjuvants: Freund's, alum, QS-21, Ribi-700, or IL-12. PAR administered subcutaneously (sc) in combination with Freund's or alum provided significant protection, 100 and 83%, respectively, against a T. cruzi challenge. In contrast, PAR in combination with QS-21, Ribi-700, IL-12, or Freund's administered intraperitoneally (ip) or PAR alone provide no protection against a challenge. PAR-specific serum antibody titers and isotype profiles for several of the immunization regimens were determined, and no positive correlation could be seen between a protective immune response and either antibody titer or the subclass of antibody induced. We also examined the ability of PAR to stimulate T cells from the spleen and lymph nodes of mice immunized with PAR in combination with Freund's (sc), Freund's (ip), alum, or Ribi-700. Each of the adjuvants strongly enhanced the ability of enriched T cells to proliferate in a PAR-specific fashion, suggesting no obvious correlation between PAR-specific T cell activation and protection. However, examination of the cytokine profiles of the stimulated T cell groups showed that the protective groups differed from the nonprotective groups. While all four groups showed low levels of IL-10, the Freund's (sc) and alum groups had higher levels of IFN-gamma and IL-2 than Freund's (ip) and Ribi-700 groups, and most strikingly, no IL-4 could be detected in either the Freund's (sc) or the alum group, in contrast to significant levels of IL-4 in both the Freund's (ip) and the Ribi-700 group. These findings indicate that protective immunity in mice immunized with PAR is associated with a Th1-type response.

  16. Isolation and characterization of paraflagellar proteins from Trypanosoma cruzi.

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    Saborio, J L; Manuel Hernandez, J; Narayanswami, S; Wrightsman, R; Palmer, E; Manning, J

    1989-03-05

    Two different Trypanosoma cruzi polypeptides, with masses of 70 and 68 kDa were purified and characterized in this work. These two polypeptides designated PAR 1 and PAR 2, respectively, co-purified during each step of the isolation procedure and were found to be located exclusively in T. cruzi flagella by indirect immunofluorescence. A pre-embedding immunoelectron microscopy procedure, with a gold-tagged secondary antibody, permitted direct identification of PAR 2 as a component of the T. cruzi paraflagellar rod. PAR 1 and PAR 2 were found to be immunologically distinct and showed no cross-reactivity with actin, tubulin, intermediate filament proteins, or other proteins present in mammalian cells. The results presented indicate that PAR 1 and PAR 2 are the major components of T. cruzi paraflagellar filaments, and that these filaments have no counterpart in mammalian cells.

  17. A search for Trypanosoma brucei rhodesiense diagnostic antigens by proteomic screening and targeted cloning.

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    Theresa Manful

    Full Text Available BACKGROUND: The only available diagnostic method for East African trypanosomiasis is light microscopy of blood samples. A simple immunodiagnostic would greatly aid trypanosomiasis control. METHODOLOGY AND PRINCIPAL FINDINGS: To find trypanosome proteins that are specifically recognised by sera from human sleeping sickness patients, we have screened the Trypanosoma brucei brucei proteome by Western blotting. Using cytosolic, cytoskeletal and glycosomal fractions, we found that the vast majority of abundant trypanosome proteins is not specifically recognised by patient sera. We identified phosphoglycerate kinase (PGKC, heat shock protein (HSP70, and histones H2B and H3 as possible candidate diagnostic antigens. These proteins, plus paraflagellar rod protein 1, rhodesain (a cysteine protease, and an extracellular fragment of the Trypanosoma brucei nucleoside transporter TbNT10, were expressed in E. coli and tested for reactivity with patient and control sera. Only TbHSP70 was preferentially recognized by patient sera, but the sensitivity and specificity were insufficient for use of TbHSP70 alone as a diagnostic. Immunoprecipitation using a native protein extract revealed no specifically reacting proteins. CONCLUSIONS: No abundant T. brucei soluble, glycosomal or cytoskeletal protein is likely to be useful in diagnosis. To find useful diagnostic antigens it will therefore be necessary to use more sophisticated proteomic methods, or to test a very large panel of candidate proteins.

  18. Taxonomy Icon Data: Trypanosoma brucei [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Trypanosoma brucei Trypanosoma brucei Trypanosoma_brucei_L.png Trypanosoma_brucei_NL.png Trypanosoma_bruce...i_S.png Trypanosoma_brucei_NS.png http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Trypanosoma+bruce...i&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Trypanosoma+brucei&t=NL http://bioscie...ncedbc.jp/taxonomy_icon/icon.cgi?i=Trypanosoma+brucei&t=S http://biosciencedbc.jp.../taxonomy_icon/icon.cgi?i=Trypanosoma+brucei&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=121 ...

  19. Localization of serum resistance-associated protein in Trypanosoma brucei rhodesiense and transgenic Trypanosoma brucei brucei.

    Science.gov (United States)

    Bart, Jean-Mathieu; Cordon-Obras, Carlos; Vidal, Isabel; Reed, Jennifer; Perez-Pastrana, Esperanza; Cuevas, Laureano; Field, Mark C; Carrington, Mark; Navarro, Miguel

    2015-10-01

    African trypanosomes infect a broad range of mammals, but humans and some higher primates are protected by serum trypanosome lytic factors that contain apolipoprotein L1 (ApoL1). In the human-infective subspecies of Trypanosoma brucei, Trypanosoma brucei rhodesiense, a gene product derived from the variant surface glycoprotein gene family member, serum resistance-associated protein (SRA protein), protects against ApoL1-mediated lysis. Protection against trypanosome lytic factor requires the direct interaction between SRA protein and ApoL1 within the endocytic apparatus of the trypanosome, but some uncertainty remains as to the precise mechanism and location of this interaction. In order to provide more insight into the mechanism of SRA-mediated resistance to trypanosome lytic factor, we assessed the localization of SRA in T. b. rhodesiense EATRO3 using a novel monoclonal antibody raised against SRA together with a set of well-characterized endosomal markers. By three-dimensional deconvolved immunofluorescence single-cell analysis, combined with double-labelling immunoelectron microscopy, we found that ≈ 50% of SRA protein localized to the lysosome, with the remaining population being distributed through the endocytic pathway, but apparently absent from the flagellar pocket membrane. These data suggest that the SRA/trypanolytic factor interaction is intracellular, with the concentration within the endosomes potentially crucial for ensuring a high efficiency.

  20. Anti-trypanosomal effect of Peristrophe bicalyculata extract on Trypanosoma brucei brucei-infected rats

    Institute of Scientific and Technical Information of China (English)

    Abdulazeez Mansurah Abimbola; Ibrahim Abdulrazak Baba; Edibo Zakari Yenusa; Sidali Joseph Omanibe; Idris Habeeb Oladimeji

    2013-01-01

    Objective: To investigate the in vitro and in vivo effect of whole plant extracts of Peristrophe bicalyculata on Trypanosoma brucei brucei-infected rats. Methods: The experiment was divided into two phases: In the first phase, the anti-trypanosomal activity of the hot water, cold water, methanol and butanol extracts of the whole plant were determined by incubating with Trypanosoma brucei brucei. The cold water extract was partially-purified and the anti-trypanosomal activity of the fractions determined. In the second phase, Trypanosoma brucei brucei-infected rats were treated with fraction 2c for nine days. Packed cell volume (PCV), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol (TC), triacylglycerol (TAG), aspartate aminotransferase, alanine aminotransferases (ALT), alkaline phosphatase (ALP), total and direct bilirubin levels were determined at the end of the experiment. Results:Cold water extract immobilized 90%of the parasites after 60 min of incubation, and fraction 2c completely immobilized the parasites after 35 min. It significantly increased PCV in Trypanosoma brucei brucei-infected rats. Decreased TC, TAG, HDL and LDL levels of infected rats increased significantly when rats were treated with the fraction, while elevated levels of total bilirubin and ALT also decreased. The difference in urea, direct bilirubin and ALP was not significant when infected rats were compared to rats in other groups. Conclusions:The ability of the plant to ameliorate the infection-induced biochemical changes calls for detailed investigation of the potentials of the plant for antitrypanosomiasis drug delivery.

  1. Structural and Functional Highlights of Vacuolar Soluble Protein 1 from Pathogen Trypanosoma brucei brucei.

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    Jamwal, Abhishek; Round, Adam R; Bannwarth, Ludovic; Venien-Bryan, Catherine; Belrhali, Hassan; Yogavel, Manickam; Sharma, Amit

    2015-12-18

    Trypanosoma brucei (T. brucei) is responsible for the fatal human disease called African trypanosomiasis, or sleeping sickness. The causative parasite, Trypanosoma, encodes soluble versions of inorganic pyrophosphatases (PPase), also called vacuolar soluble proteins (VSPs), which are localized to its acidocalcisomes. The latter are acidic membrane-enclosed organelles rich in polyphosphate chains and divalent cations whose significance in these parasites remains unclear. We here report the crystal structure of T. brucei brucei acidocalcisomal PPases in a ternary complex with Mg(2+) and imidodiphosphate. The crystal structure reveals a novel structural architecture distinct from known class I PPases in its tetrameric oligomeric state in which a fused EF hand domain arranges around the catalytic PPase domain. This unprecedented assembly evident from TbbVSP1 crystal structure is further confirmed by SAXS and TEM data. SAXS data suggest structural flexibility in EF hand domains indicative of conformational plasticity within TbbVSP1.

  2. Structural and Functional Highlights of Vacuolar Soluble Protein 1 from Pathogen Trypanosoma brucei brucei*

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    Jamwal, Abhishek; Round, Adam R.; Bannwarth, Ludovic; Venien-Bryan, Catherine; Belrhali, Hassan; Yogavel, Manickam; Sharma, Amit

    2015-01-01

    Trypanosoma brucei (T. brucei) is responsible for the fatal human disease called African trypanosomiasis, or sleeping sickness. The causative parasite, Trypanosoma, encodes soluble versions of inorganic pyrophosphatases (PPase), also called vacuolar soluble proteins (VSPs), which are localized to its acidocalcisomes. The latter are acidic membrane-enclosed organelles rich in polyphosphate chains and divalent cations whose significance in these parasites remains unclear. We here report the crystal structure of T. brucei brucei acidocalcisomal PPases in a ternary complex with Mg2+ and imidodiphosphate. The crystal structure reveals a novel structural architecture distinct from known class I PPases in its tetrameric oligomeric state in which a fused EF hand domain arranges around the catalytic PPase domain. This unprecedented assembly evident from TbbVSP1 crystal structure is further confirmed by SAXS and TEM data. SAXS data suggest structural flexibility in EF hand domains indicative of conformational plasticity within TbbVSP1. PMID:26494625

  3. Trypanosoma brucei brucei: effects of ferrous iron and heme on ecto-nucleoside triphosphate diphosphohydrolase activity.

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    Leite, Milane S; Thomaz, Rachel; Oliveira, José Henrique M; Oliveira, Pedro L; Meyer-Fernandes, José Roberto

    2009-02-01

    Trypanosoma brucei brucei is the causative agent of animal African trypanosomiasis, also called nagana. Procyclic vector form resides in the midgut of the tsetse fly, which feeds exclusively on blood. Hemoglobin digestion occurs in the midgut resulting in an intense release of free heme. In the present study we show that the magnesium-dependent ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity of procyclic T. brucei brucei is inhibited by ferrous iron and heme. The inhibition of E-NTPDase activity by ferrous iron, but not by heme, was prevented by pre-incubation of cells with catalase. However, antioxidants that permeate cells, such as PEG-catalase and N-acetyl-cysteine prevented the inhibition of E-NTPDase by heme. Ferrous iron was able to induce an increase in lipid peroxidation, while heme did not. Therefore, both ferrous iron and heme can inhibit E-NTPDase activity of T. brucei brucei by means of formation of reactive oxygen species, but apparently acting through distinct mechanisms.

  4. Morphoelastic rods

    CERN Document Server

    Tiero, Alessandro

    2014-01-01

    We propose a mechanical theory describing elastic rods which, like plant organs, can grow and can change their intrinsic curvature and torsion. The equations ruling accretion and remodeling are obtained by combining balance laws involving non-standard forces with constitutive prescriptions filtered by a dissipation principle that takes into account both standard and non-standard working.

  5. Wild chimpanzees are infected by Trypanosoma brucei

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    Milan Jirků

    2015-12-01

    Finally, we demonstrated that the mandrill serum was able to efficiently lyse T. b. brucei and T. b. rhodesiense, and to some extent T. b. gambiense, while the chimpanzee serum failed to lyse any of these subspecies.

  6. A Protein Complex Map of Trypanosoma brucei.

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    Vahid H Gazestani

    2016-03-01

    Full Text Available The functions of the majority of trypanosomatid-specific proteins are unknown, hindering our understanding of the biology and pathogenesis of Trypanosomatida. While protein-protein interactions are highly informative about protein function, a global map of protein interactions and complexes is still lacking for these important human parasites. Here, benefiting from in-depth biochemical fractionation, we systematically interrogated the co-complex interactions of more than 3354 protein groups in procyclic life stage of Trypanosoma brucei, the protozoan parasite responsible for human African trypanosomiasis. Using a rigorous methodology, our analysis led to identification of 128 high-confidence complexes encompassing 716 protein groups, including 635 protein groups that lacked experimental annotation. These complexes correlate well with known pathways as well as for proteins co-expressed across the T. brucei life cycle, and provide potential functions for a large number of previously uncharacterized proteins. We validated the functions of several novel proteins associated with the RNA-editing machinery, identifying a candidate potentially involved in the mitochondrial post-transcriptional regulation of T. brucei. Our data provide an unprecedented view of the protein complex map of T. brucei, and serve as a reliable resource for further characterization of trypanosomatid proteins. The presented results in this study are available at: www.TrypsNetDB.org.

  7. Genetic control of resistance to Trypanosoma brucei brucei infection in mice.

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    Matyáš Síma

    2011-06-01

    Full Text Available BACKGROUND: Trypanosoma brucei brucei infects livestock, with severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to this parasite. However, no genes controlling these differences were mapped. METHODS: We studied the genetic control of survival after T. b. brucei infection using recombinant congenic (RC strains, which have a high mapping power. Each RC strain of BALB/c-c-STS/A (CcS/Dem series contains a different random subset of 12.5% genes from the parental "donor" strain STS/A and 87.5% genes from the "background" strain BALB/c. Although BALB/c and STS/A mice are similarly susceptible to T. b. brucei, the RC strain CcS-11 is more susceptible than either of them. We analyzed genetics of survival in T. b. brucei-infected F(2 hybrids between BALB/c and CcS-11. CcS-11 strain carries STS-derived segments on eight chromosomes. They were genotyped in the F(2 hybrid mice and their linkage with survival was tested by analysis of variance. RESULTS: We mapped four Tbbr (Trypanosoma brucei brucei response loci that influence survival after T. b. brucei infection. Tbbr1 (chromosome 3 and Tbbr2 (chromosome 12 have effects on survival independent of inter-genic interactions (main effects. Tbbr3 (chromosome 7 influences survival in interaction with Tbbr4 (chromosome 19. Tbbr2 is located on a segment 2.15 Mb short that contains only 26 genes. CONCLUSION: This study presents the first identification of chromosomal loci controlling susceptibility to T. b. brucei infection. While mapping in F(2 hybrids of inbred strains usually has a precision of 40-80 Mb, in RC strains we mapped Tbbr2 to a 2.15 Mb segment containing only 26 genes, which will enable an effective search for the candidate gene. Definition of susceptibility genes will improve the understanding of pathways and genetic diversity underlying the disease and may result in new strategies to overcome the active subversion of the immune system by T. b. brucei.

  8. CONTROL ROD

    Science.gov (United States)

    Zinn, W.H.; Ross, H.V.

    1958-11-18

    A control rod is described for a nuclear reactor. In certaln reactor designs it becomes desirable to use a control rod having great width but relatively llttle thickness. This patent is addressed to such a need. The neutron absorbing material is inserted in a triangular tube, leaving volds between the circular insert and the corners of the triangular tube. The material is positioned within the tube by the use of dummy spacers to achleve the desired absorption pattern, then the ends of the tubes are sealed with suitable plugs. The tubes may be welded or soldered together to form two flat surfaces of any desired width, and covered with sheetmetal to protect the tubes from damage. This design provides a control member that will not distort under the action of outside forces or be ruptured by gases generated within the jacketed control member.

  9. Motility modes of the parasite Trypanosoma brucei

    Science.gov (United States)

    Temel, Fatma Zeynep; Qu, Zijie; McAllaster, Michael; de Graffenried, Christopher; Breuer, Kenneth

    2015-11-01

    The parasitic single-celled protozoan Trypanosoma brucei causes African Sleeping Sickness, which is a fatal disease in humans and animals that threatens more than 60 million people in 36 African countries. Cell motility plays a critical role in the developmental phases and dissemination of the parasite. Unlike many other motile cells such as bacteria Escherichia coli or Caulobacter crescentus, the flagellum of T. brucei is attached along the length of its awl-like body, producing a unique mode of motility that is not fully understood or characterized. Here, we report on the motility of T. brucei, which swims using its single flagellum employing both rotating and undulating propulsion modes. We tracked cells in real-time in three dimensions using fluorescent microscopy. Data obtained from experiments using both short-term tracking within the field of view and long-term tracking using a tracking microscope were analyzed. Motility modes and swimming speed were analyzed as functions of cell size, rotation rate and undulation pattern. Research supported by NSF.

  10. Trypanosoma evansi is alike to Trypanosoma brucei brucei in the subcellular localisation of glycolytic enzymes

    Directory of Open Access Journals (Sweden)

    S Andrea Moreno

    2015-06-01

    Full Text Available Trypanosoma evansi, which causes surra, is descended from Trypanosoma brucei brucei, which causes nagana. Although both parasites are presumed to be metabolically similar, insufficient knowledge of T. evansi precludes a full comparison. Herein, we provide the first report on the subcellular localisation of the glycolytic enzymes in T. evansi, which is a alike to that of the bloodstream form (BSF of T. b. brucei: (i fructose-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, hexokinase, phosphofructokinase, glucose-6-phosphate isomerase, phosphoglycerate kinase, triosephosphate isomerase (glycolytic enzymes and glycerol-3-phosphate dehydrogenase (a glycolysis-auxiliary enzyme in glycosomes, (ii enolase, phosphoglycerate mutase, pyruvate kinase (glycolytic enzymes and a GAPDH isoenzyme in the cytosol, (iii malate dehydrogenase in cytosol and (iv glucose-6-phosphate dehydrogenase in both glycosomes and the cytosol. Specific enzymatic activities also suggest that T. evansi is alike to the BSF of T. b. brucei in glycolytic flux, which is much faster than the pentose phosphate pathway flux, and in the involvement of cytosolic GAPDH in the NAD+/NADH balance. These similarities were expected based on the close phylogenetic relationship of both parasites.

  11. Trypanosoma evansi is alike to Trypanosoma brucei brucei in the subcellular localisation of glycolytic enzymes.

    Science.gov (United States)

    Moreno, S Andrea; Nava, Mayerly

    2015-06-01

    Trypanosoma evansi, which causes surra, is descended from Trypanosoma brucei brucei, which causes nagana. Although both parasites are presumed to be metabolically similar, insufficient knowledge of T. evansi precludes a full comparison. Herein, we provide the first report on the subcellular localisation of the glycolytic enzymes in T. evansi, which is a alike to that of the bloodstream form (BSF) of T. b. brucei: (i) fructose-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hexokinase, phosphofructokinase, glucose-6-phosphate isomerase, phosphoglycerate kinase, triosephosphate isomerase (glycolytic enzymes) and glycerol-3-phosphate dehydrogenase (a glycolysis-auxiliary enzyme) in glycosomes, (ii) enolase, phosphoglycerate mutase, pyruvate kinase (glycolytic enzymes) and a GAPDH isoenzyme in the cytosol, (iii) malate dehydrogenase in cytosol and (iv) glucose-6-phosphate dehydrogenase in both glycosomes and the cytosol. Specific enzymatic activities also suggest that T. evansi is alike to the BSF of T. b. brucei in glycolytic flux, which is much faster than the pentose phosphate pathway flux, and in the involvement of cytosolic GAPDH in the NAD+/NADH balance. These similarities were expected based on the close phylogenetic relationship of both parasites.

  12. Cell-penetrating peptide TP10 shows broad-spectrum activity against both Plasmodium falciparum and Trypanosoma brucei brucei.

    Science.gov (United States)

    Arrighi, Romanico B G; Ebikeme, Charles; Jiang, Yang; Ranford-Cartwright, Lisa; Barrett, Michael P; Langel, Ulo; Faye, Ingrid

    2008-09-01

    Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both blood and mosquito stages, and against blood-stage Trypanosoma brucei brucei.

  13. CHARACTERIZATION AND ANTIPARASITIC ACTIVITY OF BENZOPHENONE THIOSEMICARBAZONES ON Trypanosoma brucei brucei

    Directory of Open Access Journals (Sweden)

    Georges C. Accrombessi

    2011-02-01

    Full Text Available The structure of four synthesized thiosemicarbazones, substituted or not, of benzophenone has been confirmed by spectrometrical analysis IR, NMR 1H and 13C. Their anti-trypanosomal activities were evaluated on Trypanosoma brucei brucei. Among these compounds, benzophenone 4 phenyl-3-thiosemicarbazone 4 has the highest activity with the half-inhibitory concentration (IC50 = 8.48 micromolar (µM. Benzophenone 4-methyl-3-thiosemicarbazone 3 and benzophenone thiosemicarbazone 1 showed moderate anti-trypanosomal activity with IC50 values equal to 23.27 µM and 67.17 µM respectively. Benzophenone 2 methyl-3-thiosemicarbazone 2 showed no activity up to IC50 = 371.74 µM.

  14. Proline Metabolism is Essential for Trypanosoma brucei brucei Survival in the Tsetse Vector

    Science.gov (United States)

    Mantilla, Brian S.; Dyer, Naomi A.; Biran, Marc; Bringaud, Frédéric; Lehane, Michael J.; Acosta-Serrano, Alvaro

    2017-01-01

    Adaptation to different nutritional environments is essential for life cycle completion by all Trypanosoma brucei sub-species. In the tsetse fly vector, L-proline is among the most abundant amino acids and is mainly used by the fly for lactation and to fuel flight muscle. The procyclic (insect) stage of T. b. brucei uses L-proline as its main carbon source, relying on an efficient catabolic pathway to convert it to glutamate, and then to succinate, acetate and alanine as the main secreted end products. Here we investigated the essentiality of an undisrupted proline catabolic pathway in T. b. brucei by studying mitochondrial Δ1-pyrroline-5-carboxylate dehydrogenase (TbP5CDH), which catalyzes the irreversible conversion of gamma-glutamate semialdehyde (γGS) into L-glutamate and NADH. In addition, we provided evidence for the absence of a functional proline biosynthetic pathway. TbP5CDH expression is developmentally regulated in the insect stages of the parasite, but absent in bloodstream forms grown in vitro. RNAi down-regulation of TbP5CDH severely affected the growth of procyclic trypanosomes in vitro in the absence of glucose, and altered the metabolic flux when proline was the sole carbon source. Furthermore, TbP5CDH knocked-down cells exhibited alterations in the mitochondrial inner membrane potential (ΔΨm), respiratory control ratio and ATP production. Also, changes in the proline-glutamate oxidative capacity slightly affected the surface expression of the major surface glycoprotein EP-procyclin. In the tsetse, TbP5CDH knocked-down cells were impaired and thus unable to colonize the fly’s midgut, probably due to the lack of glucose between bloodmeals. Altogether, our data show that the regulated expression of the proline metabolism pathway in T. b. brucei allows this parasite to adapt to the nutritional environment of the tsetse midgut. PMID:28114403

  15. Classical clinical signs in rats experimemtally infected with Trypanosoma brucei

    Institute of Scientific and Technical Information of China (English)

    Nwoha Rosemary Ijeoma Ogechi; Omamegbe Joseph Omolathebu

    2015-01-01

    Objective:To investigate clinical signs in Trypanosoma brucei infection in albino rats. Methods:Fourteen rats grouped into 2 with 7 rats in each group were used to determine classical clinical manifestation of Trypanosoma brucei infection in rats. Group A rats were uninfected control and Group B rats were infected with Trypanosoma brucei. Results:Parasitaemia was recorded in Group B by (3.86±0.34) d and the peak of parasitaemia was observed at Day 5 post infection. Classical signs observed included squint eyes, raised whiskers, lethargy, no weight loss, pyrexia, isolation from the other rats, and starry hair coat. Conclusions:These signs could be diagnostic or aid in diagnosis of Trypanosoma brucei infection in rats.

  16. Tie rod insertion test

    CERN Multimedia

    B. LEVESY

    2002-01-01

    The superconducting coil is inserted in the outer vaccum tank and supported by a set of tie rods. These tie rods are made of titanium alloy. This test reproduce the final insertion of the tie rods inside the outer vacuum tank.

  17. Phenolic Constituents of Medicinal Plants with Activity against Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Ya Nan Sun

    2016-04-01

    Full Text Available Neglected tropical diseases (NTDs affect over one billion people all over the world. These diseases are classified as neglected because they impact populations in areas with poor financial conditions and hence do not attract sufficient research investment. Human African Trypanosomiasis (HAT or sleeping sickness, caused by the parasite Trypanosoma brucei, is one of the NTDs. The current therapeutic interventions for T. brucei infections often have toxic side effects or require hospitalization so that they are not available in the rural environments where HAT occurs. Furthermore, parasite resistance is increasing, so that there is an urgent need to identify novel lead compounds against this infection. Recognizing the wide structural diversity of natural products, we desired to explore and identify novel antitrypanosomal chemotypes from a collection of natural products obtained from plants. In this study, 440 pure compounds from various medicinal plants were tested against T. brucei by in a screening using whole cell in vitro assays. As the result, twenty-two phenolic compounds exhibited potent activity against cultures of T. brucei. Among them, eight compounds—4, 7, 11, 14, 15, 18, 20, and 21—showed inhibitory activity against T. brucei, with IC50 values below 5 µM, ranging from 0.52 to 4.70 μM. Based on these results, we attempt to establish some general trends with respect to structure-activity relationships, which indicate that further investigation and optimization of these derivatives might enable the preparation of potentially useful compounds for treating HAT.

  18. Regulation and spatial organization of PCNA in Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Kaufmann, Doris; Gassen, Alwine [University of Munich (LMU), Department Biology I, Genetics, Grosshaderner Str. 2-4, 82152 Martinsried (Germany); Maiser, Andreas; Leonhardt, Heinrich [University of Munich (LMU), Department Biology II, Grosshaderner Str. 2-4, 82152 Martinsried (Germany); Janzen, Christian J., E-mail: christian.janzen@uni-wuerzburg.de [University of Munich (LMU), Department Biology I, Genetics, Grosshaderner Str. 2-4, 82152 Martinsried (Germany)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Characterization of the proliferating cell nuclear antigen in Trypanosoma brucei (TbPCNA). Black-Right-Pointing-Pointer TbPCNA is a suitable marker to detect replication in T. brucei. Black-Right-Pointing-Pointer TbPCNA distribution and regulation is different compared to closely related parasites T. cruzi and Leishmania donovani. -- Abstract: As in most eukaryotic cells, replication is regulated by a conserved group of proteins in the early-diverged parasite Trypanosoma brucei. Only a few components of the replication machinery have been described in this parasite and regulation, sub-nuclear localization and timing of replication are not well understood. We characterized the proliferating cell nuclear antigen in T. brucei (TbPCNA) to establish a spatial and temporal marker for replication. Interestingly, PCNA distribution and regulation is different compared to the closely related parasites Trypanosoma cruzi and Leishmania donovani. TbPCNA foci are clearly detectable during S phase of the cell cycle but in contrast to T. cruzi they are not preferentially located at the nuclear periphery. Furthermore, PCNA seems to be degraded when cells enter G2 phase in T. brucei suggesting different modes of replication regulation or functions of PCNA in these closely related eukaryotes.

  19. Effect of ivermectin on Trypanosoma brucei brucei in experimentally infected mice

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    Udensi K. Udensi & A.F. Fagbenro-Beyioku

    2012-09-01

    Full Text Available Background & objectives: Human and livestock African trypanosomiasis, otherwise known as sleeping sickness,is a neglected tropical disease of public health importance in west and central Africa. In view of the adverse sideeffects of the antitrypanosomal drugs, the relatively few side effects observed in ivermectin use, and becauseboth onchocerciasis and typanosomiasis occur in overlapping foci in Africa, it would be desirable if the ivermectinthat has been used successfully on onchocerciasis management could also be used in the control and treatmentof trypanosomiasis.Method: In this study, prophylactic and therapeutic effects of ivermectin (Mectizan were investigated in albinomice infected with a Nigerian strain of Trypanosoma brucei brucei.Results: A 300 μg/ml/kg dose had the most effective impact because it showed the highest mean survival time of12 days in both the treatment and prophylactic groups of mice. This dose also enhanced the defence capacity ofthe treated groups. It also had positive influence on the packed cell volume (PCV and the state of anaemia inthe trypanosome infected mice, hence, improving their survivability.Interpretation & conclusions: Our report indicates that using the 300 μg/ml/kg dose of ivermectin increases themean survival period from 5 to 12 days. This suggests that ivermectin could be possibly used in the treatment oftrypanosomiasis. Further studies will be required to show whether proper treatment may entail a single dose, asused in this study; an increased number of doses, or combinations with other drugs.

  20. Evaluation of In Vitro Activity of Essential Oils against Trypanosoma brucei brucei and Trypanosoma evansi

    Directory of Open Access Journals (Sweden)

    Nathan Habila

    2010-01-01

    Full Text Available Essential oils (EOs from Cymbopogon citratus (CC, Eucalyptus citriodora (EC, Eucalyptus camaldulensis (ED, and Citrus sinensis (CS were obtained by hydrodistillation process. The EOs were evaluated in vitro for activity against Trypanosoma brucei brucei (Tbb and Trypanosoma evansi (T. evansi. The EOs were found to possess antitrypanosomal activity in vitro in a dose-dependent pattern in a short period of time. The drop in number of parasite over time was achieved doses of 0.4 g/ml, 0.2 g/mL, and 0.1 g/mL for all the EOs. The concentration of 0.4 g/mL CC was more potent at 3 minutes and 2 minutes for Tbb and T. evansi, respectively. The GC-MS analysis of the EOs revealed presence of Cyclobutane (96.09% in CS, 6-octenal (77.11% in EC, Eucalyptol (75% in ED, and Citral (38.32% in CC among several other organic compounds. The results are discussed in relation to trypanosome chemotherapy.

  1. Nanomolar Inhibitors of Trypanosoma brucei RNA Triphosphatase

    Directory of Open Access Journals (Sweden)

    Paul Smith

    2016-02-01

    Full Text Available Eukaryal taxa differ with respect to the structure and mechanism of the RNA triphosphatase (RTPase component of the mRNA capping apparatus. Protozoa, fungi, and certain DNA viruses have a metal-dependent RTPase that belongs to the triphosphate tunnel metalloenzyme (TTM superfamily. Because the structures, active sites, and chemical mechanisms of the TTM-type RTPases differ from those of mammalian RTPases, the TTM RTPases are potential targets for antiprotozoal, antifungal, and antiviral drug discovery. Here, we employed RNA interference (RNAi knockdown methods to show that Trypanosoma brucei RTPase Cet1 (TbCet1 is necessary for proliferation of procyclic cells in culture. We then conducted a high-throughput biochemical screen for small-molecule inhibitors of the phosphohydrolase activity of TbCet1. We identified several classes of chemicals—including chlorogenic acids, phenolic glycopyranosides, flavonoids, and other phenolics—that inhibit TbCet1 with nanomolar to low-micromolar 50% inhibitory concentrations (IC50s. We confirmed the activity of these compounds, and tested various analogs thereof, by direct manual assays of TbCet1 phosphohydrolase activity. The most potent nanomolar inhibitors included tetracaffeoylquinic acid, 5-galloylgalloylquinic acid, pentagalloylglucose, rosmarinic acid, and miquelianin. TbCet1 inhibitors were less active (or inactive against the orthologous TTM-type RTPases of mimivirus, baculovirus, and budding yeast (Saccharomyces cerevisiae. Our results affirm that a TTM RTPase is subject to potent inhibition by small molecules, with the caveat that parallel screens against TTM RTPases from multiple different pathogens may be required to fully probe the chemical space of TTM inhibition.

  2. A tropical tale: how Naja nigricollis venom beats Trypanosoma brucei

    DEFF Research Database (Denmark)

    Martos Esteban, Andrea; Laustsen, Andreas Hougaard; Carrington, Mark

    Trypanosoma brucei is a parasitic protozoan species capable to infecting insect vectors whose bite further produces African sleeping sickness inhuman beings [1]. During the parasite’s extracellular life in the mammalian host,its outer coat, mainly composed of Variable Surface Glycoproteins (VSGs...

  3. In vitro antitrypanosomal activity of plant terpenes against Trypanosoma brucei.

    Science.gov (United States)

    Otoguro, Kazuhiko; Iwatsuki, Masato; Ishiyama, Aki; Namatame, Miyuki; Nishihara-Tukashima, Aki; Kiyohara, Hiroaki; Hashimoto, Toshihiro; Asakawa, Yoshinori; Omura, Satoshi; Yamada, Haruki

    2011-11-01

    During the course of screening to discover antitrypanosomal compounds, 24 known plant terpenes (6 sesquiterpenes, 14 sesquiterpene lactones and 4 diterpenes) were evaluated for in vitro antitrypanosomal activity against Trypanosoma brucei brucei. Among them, 22 terpenes exhibited antitrypanosomal activity. In particular, α-eudesmol, hinesol, nardosinone and 4-peroxy-1,2,4,5-tetrahydro-α-santonin all exhibited selective and potent antitrypanosomal activities in vitro. Detailed here in an in vitro antitrypanosomal properties and cytotoxicities of the 24 terpenes compared with two therapeutic antitrypanosomal drugs (eflornithine and suramin). This finding represents the first report of promising trypanocidal activity of these terpenes. Present results also provide some valuable insight with regard to structure-activity relationships and the possible mode of action of the compounds.

  4. Single molecule analysis of Trypanosoma brucei DNA replication dynamics.

    Science.gov (United States)

    Calderano, Simone Guedes; Drosopoulos, William C; Quaresma, Marina Mônaco; Marques, Catarina A; Kosiyatrakul, Settapong; McCulloch, Richard; Schildkraut, Carl L; Elias, Maria Carolina

    2015-03-11

    Eukaryotic genome duplication relies on origins of replication, distributed over multiple chromosomes, to initiate DNA replication. A recent genome-wide analysis of Trypanosoma brucei, the etiological agent of sleeping sickness, localized its replication origins to the boundaries of multigenic transcription units. To better understand genomic replication in this organism, we examined replication by single molecule analysis of replicated DNA. We determined the average speed of replication forks of procyclic and bloodstream form cells and we found that T. brucei DNA replication rate is similar to rates seen in other eukaryotes. We also analyzed the replication dynamics of a central region of chromosome 1 in procyclic forms. We present evidence for replication terminating within the central part of the chromosome and thus emanating from both sides, suggesting a previously unmapped origin toward the 5' extremity of chromosome 1. Also, termination is not at a fixed location in chromosome 1, but is rather variable. Importantly, we found a replication origin located near an ORC1/CDC6 binding site that is detected after replicative stress induced by hydroxyurea treatment, suggesting it may be a dormant origin activated in response to replicative stress. Collectively, our findings support the existence of more replication origins in T. brucei than previously appreciated.

  5. Trypanosoma brucei mitochondrial respiratome: Composition and organization in procyclic form

    KAUST Repository

    Acestor, Nathalie

    2011-05-24

    The mitochondrial respiratory chain is comprised of four different protein complexes (I-IV), which are responsible for electron transport and generation of proton gradient in the mitochondrial intermembrane space. This proton gradient is then used by F oF 1-ATP synthase (complex V) to produce ATP by oxidative phosphorylation. In this study, the respiratory complexes I, II, and III were affinity purified from Trypanosoma brucei procyclic form cells and their composition was determined by mass spectrometry. The results along with those that we previously reported for complexes IV and V showed that the respiratome of Trypanosoma is divergent because many of its proteins are unique to this group of organisms. The studies also identified two mitochondrial subunit proteins of respiratory complex IV that are encoded by edited RNAs. Proteomics data from analyses of complexes purified using numerous tagged component proteins in each of the five complexes were used to generate the first predicted protein-protein interaction network of the Trypanosoma brucei respiratory chain. These results provide the first comprehensive insight into the unique composition of the respiratory complexes in Trypanosoma brucei, an early diverged eukaryotic pathogen. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Intraclonal mating occurs during tsetse transmission of Trypanosoma brucei

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    Ferris Vanessa

    2009-09-01

    Full Text Available Abstract Background Mating in Trypanosoma brucei is a non-obligatory event, triggered by the co-occurrence of different strains in the salivary glands of the vector. Recombinants that result from intra- rather than interclonal mating have been detected, but only in crosses of two different trypanosome strains. This has led to the hypothesis that when trypanosomes recognize a different strain, they release a diffusible factor or pheromone that triggers mating in any cell in the vicinity whether it is of the same or a different strain. This idea assumes that the trypanosome can recognize self and non-self, although there is as yet no evidence for the existence of mating types in T. brucei. Results We investigated intraclonal mating in T. b. brucei by crossing red and green fluorescent lines of a single strain, so that recombinant progeny can be detected in the fly by yellow fluorescence. For strain 1738, seven flies had both red and green trypanosomes in the salivary glands and, in three, yellow trypanosomes were also observed, although they could not be recovered for subsequent analysis. Nonetheless, both red and non-fluorescent clones from these flies had recombinant genotypes as judged by microsatellite and karyotype analyses, and some also had raised DNA contents, suggesting recombination or genome duplication. Strain J10 produced similar results indicative of intraclonal mating. In contrast, trypanosome clones recovered from other flies showed that genotypes can be transmitted with fidelity. When a yellow hybrid clone expressing both red and green fluorescent protein genes was transmitted, the salivary glands contained a mixture of fluorescent-coloured trypanosomes, but only yellow and red clones were recovered. While loss of the GFP gene in the red clones could have resulted from gene conversion, some of these clones showed loss of heterozygosity and raised DNA contents as in the other single strain transmissions. Our observations suggest

  7. In Vitro Trypanocidal Activity of Antibodies to Bacterially Ex­pressed Trypanosoma brucei Tubulin

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    GW Lubega

    2012-09-01

    Full Text Available Background: There are only four drugs for treating African trypanosomiasis, a devastating disease in sub-Saharan Africa. With slow discovery of better drugs, vaccination is viewed as the best method of control. We previously showed that antibodies to native Trypanosoma brucei brucei tubulin inhibit the growth of trypanosomes in culture. Here, we aimed to determine the effect of antibodies to bacte­rially expressed trypanosome tubulin on T. brucei brucei growth. Methods: T. brucei brucei alpha and beta tubulin genes were individually expressed in Escherichia coli under the tryptophan promoter. Monoclonal tubulin antibodies reacted specifically with the ex­pressed tubulins with no cross-reaction with the opposite tubulin. Rabbits were immunized with 450μg each of the concentrated recombinant tubulin, and production of antibodies assessed by ELISA and Western blotting. The effect of polyclonal antibodies on trypanosome growth was deter­mined by culturing bloodstream T. brucei brucei in up to 25% of antisera. Results: Low antisera dilutions (25% from the immunized rabbits inhibited trypanosome growth. The most cytotoxic antisera were from one rabbit immunized with a mixture of both alpha and beta tubulins. However, the result was not reproduced in other rabbits and there was no apparent effect on growth at higher antisera dilutions. Conclusion: Antibodies to bacterially expressed trypanosome tubulin are not effective at killing cul­tured bloodstream trypanosomes.

  8. Biosynthesis and uptake of thiamine (vitamin B1) in bloodstream form Trypanosoma brucei brucei and interference of the vitamin with melarsen oxide activity.

    Science.gov (United States)

    Stoffel, Sabine A; Rodenko, Boris; Schweingruber, Anne-Marie; Mäser, Pascal; de Koning, Harry P; Schweingruber, M Ernst

    2006-02-01

    Bloodstream forms of Trypanosoma brucei brucei were cultivated in the presence and absence of thiamine (vitamin B1) and pyridoxine (vitamin B6). The vitamins do not change growth behaviour, indicating that Trypanosoma brucei is prototrophic for the two vitamins even though in silico no bona-fide thiamine-biosynthetic genes could be identified in the T. brucei genome. Intracellularly, thiamine is mainly present in its diphosphate form. We were unable to detect significant uptake of [3H]thiamine and structural thiamine analogues such as pyrithiamine, oxithiamine and amprolium were not toxic for the bloodstream forms of T. brucei, indicating that the organism does not have an efficient uptake system for thiamine and its analogues. We have previously shown that, in the fission yeast Saccharomyces pombe, the toxicity of melarsen oxide, the pharmacologically active derivative of the frontline sleeping sickness drug melarsoprol, is abolished by thiamine and the drug is taken up by a thiamine-regulated membrane protein which is responsible for the utilization of thiamine. We show here that thiamine also has weak effects on melarsen oxide-induced growth inhibition and lysis in T. brucei. These effects were consistent with a low affinity of thiamine for the P2 adenosine transporter that is responsible for uptake of melaminophenyl arsenicals in African trypanosomes.

  9. Morphoelastic rods. Part I: A single growing elastic rod

    KAUST Repository

    Moulton, D.E.

    2013-02-01

    A theory for the dynamics and statics of growing elastic rods is presented. First, a single growing rod is considered and the formalism of three-dimensional multiplicative decomposition of morphoelasticity is used to describe the bulk growth of Kirchhoff elastic rods. Possible constitutive laws for growth are discussed and analysed. Second, a rod constrained or glued to a rigid substrate is considered, with the mismatch between the attachment site and the growing rod inducing stress. This stress can eventually lead to instability, bifurcation, and buckling. © 2012 Elsevier Ltd. All rights reserved.

  10. Learning with Rods: One Account.

    Science.gov (United States)

    Cherry, Donald Esha

    This paper discusses one English as a Second Language (ESL) teacher's attempts to use cuisenaire rods as a language learning tool. Cuisenaire rods (sometimes called algebricks) vary in size from 1 x 1 x 10 centimeter sticks to 1 x 1 x 1 centimeter cubes, with each of the 10 sizes a different color. Although such rods have been used to teach…

  11. Rab23 is a flagellar protein in Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Field Mark C

    2011-06-01

    Full Text Available Abstract Background Rab small GTPases are important mediators of membrane transport, and orthologues frequently retain similar locations and functions, even between highly divergent taxa. In metazoan organisms Rab23 is an important negative regulator of Sonic hedgehog signaling and is crucial for correct development and differentiation of cellular lineages by virtue of an involvement in ciliary recycling. Previously, we reported that Trypanosoma brucei Rab23 localized to the nuclear envelope 1, which is clearly inconsistent with the mammalian location and function. As T. brucei is unicellular the potential that Rab23 has no role in cell signaling was possible. Here we sought to further investigate the role(s of Rab23 in T. brucei to determine if Rab23 was an example of a Rab protein with divergent function in distinct taxa. Methods/major findings The taxonomic distribution of Rab23 was examined and compared with the presence of flagella/cilia in representative taxa. Despite evidence for considerable secondary loss, we found a clear correlation between a conventional flagellar structure and the presence of a Rab23 orthologue in the genome. By epitope-tagging, Rab23 was localized and found to be present at the flagellum throughout the cell cycle. However, RNAi knockdown did not result in a flagellar defect, suggesting that Rab23 is not required for construction or maintenance of the flagellum. Conclusions The location of Rab23 at the flagellum is conserved between mammals and trypanosomes and the Rab23 gene is restricted to flagellated organisms. These data may suggest the presence of a Rab23-mediated signaling mechanism in trypanosomes.

  12. Selective inhibition of 6-phosphogluconate dehydrogenase from Trypanosoma brucei

    Science.gov (United States)

    Bertelli, Massimo; El-Bastawissy, Eman; Knaggs, Michael H.; Barrett, Michael P.; Hanau, Stefania; Gilbert, Ian H.

    2001-05-01

    A number of triphenylmethane derivatives have been screened against 6-phosphogluconate dehydrogenase from Trypanosoma brucei and sheep liver. Some of these compounds show good inhibition of the enzymes and also selectivity towards the parasite enzyme. Modelling was undertaken to dock the compounds into the active sites of both enzymes. Using a combination of DOCK 3.5 and FLEXIDOCK a correlation was obtained between docking score and both activity for the enzymes and selectivity. Visualisation of the docked structures of the inhibitors in the active sites of the enzymes yielded a possible explanation of the selectivity for the parasite enzyme.

  13. Minimum Information Loss Based Multi-kernel Learning for Flagellar Protein Recognition in Trypanosoma Brucei

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-12-01

    Trypanosma brucei (T. Brucei) is an important pathogen agent of African trypanosomiasis. The flagellum is an essential and multifunctional organelle of T. Brucei, thus it is very important to recognize the flagellar proteins from T. Brucei proteins for the purposes of both biological research and drug design. In this paper, we investigate computationally recognizing flagellar proteins in T. Brucei by pattern recognition methods. It is argued that an optimal decision function can be obtained as the difference of probability functions of flagella protein and the non-flagellar protein for the purpose of flagella protein recognition. We propose to learn a multi-kernel classification function to approximate this optimal decision function, by minimizing the information loss of such approximation which is measured by the Kull back-Leibler (KL) divergence. An iterative multi-kernel classifier learning algorithm is developed to minimize the KL divergence for the problem of T. Brucei flagella protein recognition, experiments show its advantage over other T. Brucei flagellar protein recognition and multi-kernel learning methods. © 2014 IEEE.

  14. Safety rod latch inspection

    Energy Technology Data Exchange (ETDEWEB)

    Leader, D.R.

    1992-02-01

    During an attempt to raise control rods from the 100 K reactor in December, one rod could not be withdrawn. Subsequent investigation revealed that a small button'' in the latch mechanism had broken off of the lock plunger'' and was wedged in a position that prevented rod withdrawal. Concern that this failure may have resulted from corrosion or some other metallurgical problem resulted in a request that SRL examine six typical latch mechanisms from the 100 L reactor by use of radiography and metallography. During the examination of the L-Area latches, a failed latch mechanism from the 100 K reactor was added to the investigation. Fourteen latches that had a history of problems were removed from K-Area and sent to SRL for inclusion in this study the week after the original seven assemblies were examined, bringing the total of latch assemblies discussed in this report to twenty one. Results of the examination of the K-Area latch that initiated this study is not included in this report.

  15. Safety rod latch inspection

    Energy Technology Data Exchange (ETDEWEB)

    Leader, D.R.

    1992-02-01

    During an attempt to raise control rods from the 100 K reactor in December, one rod could not be withdrawn. Subsequent investigation revealed that a small ``button`` in the latch mechanism had broken off of the ``lock plunger`` and was wedged in a position that prevented rod withdrawal. Concern that this failure may have resulted from corrosion or some other metallurgical problem resulted in a request that SRL examine six typical latch mechanisms from the 100 L reactor by use of radiography and metallography. During the examination of the L-Area latches, a failed latch mechanism from the 100 K reactor was added to the investigation. Fourteen latches that had a history of problems were removed from K-Area and sent to SRL for inclusion in this study the week after the original seven assemblies were examined, bringing the total of latch assemblies discussed in this report to twenty one. Results of the examination of the K-Area latch that initiated this study is not included in this report.

  16. Telomeric expression sites are highly conserved in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Christiane Hertz-Fowler

    Full Text Available Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs. The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.

  17. Combinations of alkaloids affecting different molecular targets with the saponin digitonin can synergistically enhance trypanocidal activity against Trypanosoma brucei brucei.

    Science.gov (United States)

    Krstin, Sonja; Peixoto, Herbenya Silva; Wink, Michael

    2015-11-01

    The flagellate Trypanosoma brucei causes sleeping sickness in humans and nagana in animals. Only a few drugs are registered to treat trypanosomiasis, but those drugs show severe side effects. Also, because some pathogen strains have become resistant, new strategies are urgently needed to combat this parasitic disease. An underexplored possibility is the application of combinations of several trypanocidal agents, which may potentiate their trypanocidal activity in a synergistic fashion. In this study, the potential synergism of mutual combinations of bioactive alkaloids and alkaloids with a membrane-active steroidal saponin, digitonin, was explored with regard to their effect on T. b. brucei. Alkaloids were selected that affect different molecular targets: berberine and chelerythrine (intercalation of DNA), piperine (induction of apoptosis), vinblastine (inhibition of microtubule assembly), emetine (intercalation of DNA, inhibition of protein biosynthesis), homoharringtonine (inhibition of protein biosynthesis), and digitonin (membrane permeabilization and uptake facilitation of polar compounds). Most combinations resulted in an enhanced trypanocidal effect. The addition of digitonin significantly stimulated the activity of almost all alkaloids against trypanosomes. The strongest effect was measured in a combination of digitonin with vinblastine. The highest dose reduction indexes (DRI) were measured in the two-drug combination of digitonin or piperine with vinblastine, where the dose of vinblastine could be reduced 9.07-fold or 7.05-fold, respectively. The synergistic effects of mutual combinations of alkaloids and of alkaloids with digitonin present a new avenue to treat trypanosomiasis but one which needs to be corroborated in future animal experiments.

  18. Antitrypanosomal effect of methanolic extract of Zingiber officinale (ginger on Trypanosoma brucei brucei-infected Wistar mice

    Directory of Open Access Journals (Sweden)

    P. I. Kobo

    2014-10-01

    Full Text Available Aim: The study was carried out to determine the in vivo antitrypanosomal effect of methanolic extract of Zingiber officinale (ginger in Trypanosoma brucei brucei-infected mice. Materials and Methods: Twenty-five mice were randomly allocated into five groups of five animals each. Group I and II were given Tween 80 (1 ml/kg and diminazene aceturate (3.5 mg/kg to serve as untreated and treated controls, respectively. Groups III-V received the extract at 200, 400 and 800 mg/kg body weight, respectively. All treatments were given for 6 consecutive days and through the oral route. The mean body weight, mean survival period and daily level of parasitaemia were evaluated. Results: Acute toxicity showed the extract to be relatively safe. There was an insignificant increase in body weight and survival rate of mice treated with the extract. The level of parasitaemia in the extract treated groups was decreased. Conclusion: This study shows the in vivo potential of methanolic extract of Z. officinale in the treatment of trypanosomiasis.

  19. Cone rod dystrophies

    Directory of Open Access Journals (Sweden)

    Hamel Christian P

    2007-02-01

    Full Text Available Abstract Cone rod dystrophies (CRDs (prevalence 1/40,000 are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP, also called the rod cone dystrophies (RCDs resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7. Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far. The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs, CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs, and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs. It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is

  20. Cofactor-independent phosphoglycerate mutase is an essential gene in procyclic form Trypanosoma brucei.

    Science.gov (United States)

    Djikeng, Appolinaire; Raverdy, Sylvine; Foster, Jeremy; Bartholomeu, Daniella; Zhang, Yinhua; El-Sayed, Najib M; Carlow, Clotilde

    2007-03-01

    Glycolysis and gluconeogenesis are, in part, driven by the interconversion of 3- and 2-phosphoglycerate (3-PG and 2-PG) which is performed by phosphoglycerate mutases (PGAMs) which can be cofactor dependant (dPGAM) or cofactor independent (iPGAM). The African trypanosome, Trypanosoma brucei, possesses the iPGAM form which is thought to play an important role in glycolysis. Here, we report on the use of RNA interference to down-regulate the T. brucei iPGAM in procyclic form T. brucei and evaluation of the resulting phenotype. We first demonstrated biochemically that depletion of the steady state levels of iPGM mRNA correlates with a marked reduction of enzyme activity. We further show that iPGAM is required for cell growth in procyclic T. brucei.

  1. Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation.

    Directory of Open Access Journals (Sweden)

    James P J Hall

    Full Text Available A main determinant of prolonged Trypanosoma brucei infection and transmission and success of the parasite is the interplay between host acquired immunity and antigenic variation of the parasite variant surface glycoprotein (VSG coat. About 0.1% of trypanosome divisions produce a switch to a different VSG through differential expression of an archive of hundreds of silent VSG genes and pseudogenes, but the patterns and extent of the trypanosome diversity phenotype, particularly in chronic infection, are unclear. We applied longitudinal VSG cDNA sequencing to estimate variant richness and test whether pseudogenes contribute to antigenic variation. We show that individual growth peaks can contain at least 15 distinct variants, are estimated computationally to comprise many more, and that antigenically distinct 'mosaic' VSGs arise from segmental gene conversion between donor VSG genes or pseudogenes. The potential for trypanosome antigenic variation is probably much greater than VSG archive size; mosaic VSGs are core to antigenic variation and chronic infection.

  2. Pathogenesis of anemia in Trypanosoma brucei-infected mice.

    Science.gov (United States)

    Amole, B O; Clarkson, A B; Shear, H L

    1982-01-01

    The pathogenesis of anemia was studied in trypanosome-infected mice. A strain of Trypanosoma brucei, TREU 667, was used which first produces an acute phase marked by waves of parasitemia. Erythrocytes from infected animals were coated with immunoglobulin M during or just before the waves of anemia and parasitological crises. Erythrocytes from normal animals could be sensitized with "precrisis" sera presumably containing antigen and antibody. These data suggest that anemia during the acute phase is due to sensitization of erythrocytes with immunoglobulin M-antigen complexes. The anemia is partially compensated by a strong erythropoietic response. The acute phase is followed by a chronic phase marked by a constant high parasitemia and immunosuppression. The less marked anemia occurring during this latter phase is due to hemodilution and perhaps a low but significant immune response to the parasites, which causes continuing erythrocyte sensitization by immunoglobulin M-antigen complexes. PMID:7201455

  3. Trypanosoma brucei: a putative RNA polymerase II promoter.

    Science.gov (United States)

    Bayele, Henry K

    2009-12-01

    RNA polymerase II (pol II) promoters are rare in the African trypanosome Trypanosoma brucei because gene regulation in the parasite is complex and polycistronic. Here, we describe a putative pol II promoter and its structure-function relationship. The promoter has features of an archetypal eukaryotic pol II promoter including putative canonical CCAAT and TATA boxes, and an initiator element. However, the spatial arrangement of these elements is only similar to yeast pol II promoters. Deletion mapping and transcription assays enabled delineation of a minimal promoter that could drive orientation-independent reporter gene expression suggesting that it may be a bidirectional promoter. In vitro transcription in a heterologous nuclear extract revealed that the promoter can be recognized by the basal eukaryotic transcription complex. This suggests that the transcription machinery in the parasite may be very similar to those of other eukaryotes.

  4. Cuisenaire Rods Go to College.

    Science.gov (United States)

    Chinn, Phyllis; And Others

    1992-01-01

    Presents examples of questions and answers arising from a hands-on and exploratory approach to discrete mathematics using cuisenaire rods. Combinatorial questions about trains formed of cuisenaire rods provide the setting for discovering numerical patterns by experimentation and organizing the results using induction and successive differences.…

  5. A luciferase based viability assay for ATP detection in 384-well format for high throughput whole cell screening of Trypanosoma brucei brucei bloodstream form strain 427

    Directory of Open Access Journals (Sweden)

    Avery Vicky M

    2009-11-01

    Full Text Available Abstract Background Human African Trypanosomiasis (HAT is caused by two trypanosome species, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Current drugs available for the treatment of HAT have significant issues related to toxicity, administration regimes with limited effectiveness across species and disease stages, thus there is a considerable need to find alternative drugs. A well recognised approach to identify new drug candidates is high throughput screening (HTS of large compound library collections. Results We describe here the development of a luciferase based viability assay in 384-well plate format suitable for HTS of T.b.brucei. The parameters that were explored to determine the final HTS assay conditions are described in detail and include DMSO tolerability, Z', diluents and cell inoculum density. Reference compound activities were determined for diminazene, staurosporine and pentamidine and compared to previously published IC50 data obtained. The assay has a comparable sensitivity to reference drugs and is more cost effective than the 96-well format currently reported for T.b.brucei. Conclusion Due to the reproducibility and sensitivity of this assay it is recommended for potential HTS application. As it is commercially available this assay can also be utilised in many laboratories for both large and small scale screening.

  6. Eulerian formulation of elastic rods

    Science.gov (United States)

    Huynen, Alexandre; Detournay, Emmanuel; Denoël, Vincent

    2016-06-01

    In numerous biological, medical and engineering applications, elastic rods are constrained to deform inside or around tube-like surfaces. To solve efficiently this class of problems, the equations governing the deflection of elastic rods are reformulated within the Eulerian framework of this generic tubular constraint defined as a perfectly stiff normal ringed surface. This reformulation hinges on describing the rod-deformed configuration by means of its relative position with respect to a reference curve, defined as the axis or spine curve of the constraint, and on restating the rod local equilibrium in terms of the curvilinear coordinate parametrizing this curve. Associated with a segmentation strategy, which partitions the global problem into a sequence of rod segments either in continuous contact with the constraint or free of contact (except for their extremities), this re-parametrization not only trivializes the detection of new contacts but also transforms these free boundary problems into classic two-points boundary-value problems and suppresses the isoperimetric constraints resulting from the imposition of the rod position at the extremities of each rod segment.

  7. Trypanosoma brucei CYP51: Essentiality and Targeting Therapy in an Experimental Model

    Science.gov (United States)

    Dauchy, Frédéric-Antoine; Bonhivers, Mélanie; Landrein, Nicolas; Dacheux, Denis; Courtois, Pierrette; Lauruol, Florian; Daulouède, Sylvie

    2016-01-01

    Trypanosoma brucei gambiense is the main causative agent of Human African Trypanosomiasis (HAT), also known as sleeping sickness. Because of limited alternatives and treatment toxicities, new therapeutic options are urgently needed for patients with HAT. Sterol 14alpha-demethylase (CYP51) is a potential drug target but its essentiality has not been determined in T. brucei. We used a tetracycline-inducible RNAi system to assess the essentiality of CYP51 in T. brucei bloodstream form (BSF) cells and we evaluated the effect of posaconazole, a well-tolerated triazole drug, within a panel of virulent strains in vitro and in a murine model. Expression of CYP51 in several T. brucei cell lines was demonstrated by western blot and its essentiality was demonstrated by RNA interference (CYP51RNAi) in vitro. Following reduction of TbCYP51 expression by RNAi, cell growth was reduced and eventually stopped compared to WT or non-induced cells, showing the requirement of CYP51 in T. brucei. These phenotypes were rescued by addition of ergosterol. Additionally, CYP51RNAi induction caused morphological defects with multiflagellated cells (ptrypanosomiasis. PMID:27855164

  8. Topological mixing with ghost rods

    Science.gov (United States)

    Gouillart, Emmanuelle; Thiffeault, Jean-Luc; Finn, Matthew D.

    2006-03-01

    Topological chaos relies on the periodic motion of obstacles in a two-dimensional flow in order to form nontrivial braids. This motion generates exponential stretching of material lines, and hence efficient mixing. Boyland, Aref, and Stremler [J. Fluid Mech. 403, 277 (2000)] have studied a specific periodic motion of rods that exhibits topological chaos in a viscous fluid. We show that it is possible to extend their work to cases where the motion of the stirring rods is topologically trivial by considering the dynamics of special periodic points that we call “ghost rods”, because they play a similar role to stirring rods. The ghost rods framework provides a new technique for quantifying chaos and gives insight into the mechanisms that produce chaos and mixing. Numerical simulations for Stokes flow support our results.

  9. MIF Contributes to Trypanosoma brucei Associated Immunopathogenicity Development

    Science.gov (United States)

    Stijlemans, Benoît; Leng, Lin; Brys, Lea; Sparkes, Amanda; Vansintjan, Liese; Caljon, Guy; Raes, Geert; Van Den Abbeele, Jan; Van Ginderachter, Jo A.; Beschin, Alain

    2014-01-01

    African trypanosomiasis is a chronic debilitating disease affecting the health and economic well-being of many people in developing countries. The pathogenicity associated with this disease involves a persistent inflammatory response, whereby M1-type myeloid cells, including Ly6Chigh inflammatory monocytes, are centrally implicated. A comparative gene analysis between trypanosusceptible and trypanotolerant animals identified MIF (macrophage migrating inhibitory factor) as an important pathogenic candidate molecule. Using MIF-deficient mice and anti-MIF antibody treated mice, we show that MIF mediates the pathogenic inflammatory immune response and increases the recruitment of inflammatory monocytes and neutrophils to contribute to liver injury in Trypanosoma brucei infected mice. Moreover, neutrophil-derived MIF contributed more significantly than monocyte-derived MIF to increased pathogenic liver TNF production and liver injury during trypanosome infection. MIF deficient animals also featured limited anemia, coinciding with increased iron bio-availability, improved erythropoiesis and reduced RBC clearance during the chronic phase of infection. Our data suggest that MIF promotes the most prominent pathological features of experimental trypanosome infections (i.e. anemia and liver injury), and prompt considering MIF as a novel target for treatment of trypanosomiasis-associated immunopathogenicity. PMID:25255103

  10. MIF contributes to Trypanosoma brucei associated immunopathogenicity development.

    Directory of Open Access Journals (Sweden)

    Benoît Stijlemans

    2014-09-01

    Full Text Available African trypanosomiasis is a chronic debilitating disease affecting the health and economic well-being of many people in developing countries. The pathogenicity associated with this disease involves a persistent inflammatory response, whereby M1-type myeloid cells, including Ly6C(high inflammatory monocytes, are centrally implicated. A comparative gene analysis between trypanosusceptible and trypanotolerant animals identified MIF (macrophage migrating inhibitory factor as an important pathogenic candidate molecule. Using MIF-deficient mice and anti-MIF antibody treated mice, we show that MIF mediates the pathogenic inflammatory immune response and increases the recruitment of inflammatory monocytes and neutrophils to contribute to liver injury in Trypanosoma brucei infected mice. Moreover, neutrophil-derived MIF contributed more significantly than monocyte-derived MIF to increased pathogenic liver TNF production and liver injury during trypanosome infection. MIF deficient animals also featured limited anemia, coinciding with increased iron bio-availability, improved erythropoiesis and reduced RBC clearance during the chronic phase of infection. Our data suggest that MIF promotes the most prominent pathological features of experimental trypanosome infections (i.e. anemia and liver injury, and prompt considering MIF as a novel target for treatment of trypanosomiasis-associated immunopathogenicity.

  11. Exosome secretion affects social motility in Trypanosoma brucei

    Science.gov (United States)

    Shaked, Hadassa; Arvatz, Gil; Tkacz, Itai Dov; Binder, Lior; Waldman Ben-Asher, Hiba; Okalang, Uthman; Chikne, Vaibhav; Cohen-Chalamish, Smadar; Michaeli, Shulamit

    2017-01-01

    Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo). This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites. PMID:28257521

  12. Proteins associated with SF3a60 in T. brucei.

    Directory of Open Access Journals (Sweden)

    Benson Nyambega

    Full Text Available Trypanosoma brucei relies on Spliced leader trans splicing to generate functional messenger RNAs. Trans splicing joins the specialized SL exon from the SL RNA to pre-mRNAs and is mediated by the trans-spliceosome, which is made up of small nuclear ribonucleoprotein particles and non-snRNP factors. Although the trans spliceosome is essential for trypanosomatid gene expression, not all spliceosomal protein factors are known and of these, only a few are completely characterized. In this study, we have characterized the trypanosome Splicing Factor, SF3a60, the only currently annotated SF3a component. As expected, epitope-tagged SF3a60 localizes in the trypanosome nucleus. SF3a60 is essential for cell viability but its depletion seem to have no detectable effect on trans-splicing. In addition, we used SF3a60 as bait in a Yeast-2-hybrid system screen and identified its interacting protein factors. The interactions with SF3a120, SF3a66 and SAP130 were confirmed by tandem affinity purification and mass spectrometry.

  13. Proteomics and the Trypanosoma brucei cytoskeleton: advances and opportunities.

    Science.gov (United States)

    Portman, Neil; Gull, Keith

    2012-08-01

    Trypanosoma brucei is the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan Africa. The pathogenicity and growth of the parasite are intimately linked to its shape and form. This is in turn derived from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage directly beneath the pellicular membrane and numerous other cytoskeletal structures such as the flagellum. The parasite undergoes extreme changes in cellular morphology during its life cycle and cell cycles which require a high level of integration and coordination of cytoskeletal processes. In this review we will discuss the role that proteomics techniques have had in advancing our understanding of the molecular composition of the cytoskeleton and its functions. We then consider future opportunities for the application of these techniques in terms of addressing some of the unanswered questions of trypanosome cytoskeletal cell biology with particular focus on the differences in the composition and organisation of the cytoskeleton through the trypanosome life-cycle.

  14. Protective effect of humus extract against Trypanosoma brucei infection in mice.

    Science.gov (United States)

    Kodama, Hiroshi; Denso; Okazaki, Fumi; Ishida, Saeko

    2008-11-01

    Humic substances are formed during the decomposition of organic matter in humus, and are found in many natural environments in which organic materials and microorganisms are present. Oral administration of humus extract to mice successfully induced effective protection against experimental challenge by the two subspecies, Trypanosoma brucei brucei and T. brucei gambiense. Mortality was most reduced among mice who received a 3% humus extract for 21 days in drinking water ad libitum. Spleen cells from humus-administered mice exhibited significant non-specific cytotoxic activity against L1210 mouse leukemia target cells. Also, spleen cells produced significantly higher amounts of Interferon-gamma when stimulated in vitro with Concanavalin A than cells from normal controls. These results clearly show that administration to mice of humus extract induced effective resistance against Trypanosoma infection. Enhancement of the innate immune system may be involved in host defense against trypanosomiasis.

  15. A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei

    Institute of Scientific and Technical Information of China (English)

    Ranjodh Sandhu; Samantha Sanford; Shrabani Basu; MinA Park; Unnati M Pandya; Bibo Li; Kausik Chakrabarti

    2013-01-01

    Telomerase is a ribonucleoprotein enzyme typically required for sustained cell proliferation.Although both telomerase activity and the telomerase catalytic protein component,TbTERT,have been identified in the eukaryotic pathogen Trypanosoma brucei,the RNA molecule that dictates telomere synthesis remains unknown.Here,we identify the RNA component of Trypanosoma brucei telomerase,TbTR,and provide phylogenetic and in vivo evidence for TbTR's native folding and activity.We show that TbTR is processed through trans-splicing,and is a capped transcript that interacts and copurifies with TbTERT in vivo.Deletion of TbTR caused progressive shortening of telomeres at a rate of 3-5 bp/population doubling (PD),which can be rescued by ectopic expression of a wild-type allele of TbTR in an apparent dose-dependent manner.Remarkably,introduction of mutations in the TbTR template domain resulted in corresponding mutant telomere sequences,demonstrating that telomere synthesis in T.brucei is dependent on TbTR.We also propose a secondary structure model for TbTR based on phylogenetic analysis and chemical probing experiments,thus defining TbTR domains that may have important functional implications in telomere synthesis.Identification and characterization of TbTR not only provide important insights into T.brucei telomere functions,which have been shown to play important roles in T.brucei pathogenesis,but also offer T.brucei as an attractive model system for studying telomerase biology in pathogenic protozoa and for comparative analysis of telomerase function with higher eukaryotes.

  16. Stearoyl-CoA desaturase is an essential enzyme for the parasitic protist Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Alloatti, Andres [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina); Gupta, Shreedhara; Gualdron-Lopez, Melisa; Nguewa, Paul A. [Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Universite Catholique de Louvain, Brussels (Belgium); Altabe, Silvia G. [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina); Deumer, Gladys; Wallemacq, Pierre [Department of Clinical Chemistry, Cliniques Universitaires Saint-Luc, LTAP, Universite Catholique de Louvain, Brussels (Belgium); Michels, Paul A.M. [Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Universite Catholique de Louvain, Brussels (Belgium); Uttaro, Antonio D., E-mail: toniuttaro@yahoo.com.ar [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina)

    2011-08-26

    Highlights: {yields} Inhibiting {Delta}9 desaturase drastically changes T. brucei's fatty-acid composition. {yields} Isoxyl specifically inhibits the {Delta}9 desaturase causing a growth arrest. {yields} RNA interference of desaturase expression causes a similar effect. {yields} Feeding T. brucei-infected mice with Isoxyl decreases the parasitemia. {yields} 70% of Isoxyl-treated mice survived the trypanosome infection. -- Abstract: Trypanosoma brucei, the etiologic agent of sleeping sickness, is exposed to important changes in nutrients and temperature during its life cycle. To adapt to these changes, the fluidity of its membranes plays a crucial role. This fluidity, mediated by the fatty-acid composition, is regulated by enzymes named desaturases. We have previously shown that the oleoyl desaturase is essential for Trypanosoma cruzi and T. brucei. In this work, we present experimental support for the relevance of stearoyl-CoA desaturase (SCD) for T. brucei's survival, in both its insect or procyclic-form (PCF) and bloodstream-form (BSF) stages. We evaluated this essentiality in two different ways: by generating a SCD knocked-down parasite line using RNA interference, and by chemical inhibition of the enzyme with two compounds, Isoxyl and a thiastearate with the sulfur atom at position 10 (10-TS). The effective concentration for 50% growth inhibition (EC{sub 50}) of PCF was 1.0 {+-} 0.2 {mu}M for Isoxyl and 5 {+-} 2 {mu}M for 10-TS, whereas BSF appeared more susceptible with EC{sub 50} values 0.10 {+-} 0.03 {mu}M (Isoxyl) and 1.0 {+-} 0.6 {mu}M (10-TS). RNA interference showed to be deleterious for both stages of the parasite. In addition, T. brucei-infected mice were fed with Isoxyl, causing a reduction of the parasitemia and an increase of the rodents' survival.

  17. The Third ATLAS ROD Workshop

    CERN Multimedia

    Poggioli, L.

    A new-style Workshop After two successful ATLAS ROD Workshops dedicated to the ROD hardware and held at the Geneva University in 1998 and in 2000, a new style Workshop took place at LAPP in Annecy on November 14-15, 2002. This time the Workshop was fully dedicated to the ROD-TDAQ integration and software in view of the near future integration activities of the final RODs for the detector assembly and commissioning. More precisely, the aim of this workshop was to get from the sub-detectors the parameters needed for T-DAQ, as well as status and plans from ROD builders. On the other hand, what was decided and assumed had to be stated (like EB decisions and URDs), and also support plans. The Workshop gathered about 70 participants from all ATLAS sub-detectors and the T-DAQ community. The quite dense agenda allowed nevertheless for many lively discussions, and for a dinner in the old town of Annecy. The Sessions The Workshop was organized in five main sessions: Assumptions and recommendations Sub-de...

  18. The cell cycle regulated transcriptome of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Stuart K Archer

    Full Text Available Progression of the eukaryotic cell cycle requires the regulation of hundreds of genes to ensure that they are expressed at the required times. Integral to cell cycle progression in yeast and animal cells are temporally controlled, progressive waves of transcription mediated by cell cycle-regulated transcription factors. However, in the kinetoplastids, a group of early-branching eukaryotes including many important pathogens, transcriptional regulation is almost completely absent, raising questions about the extent of cell-cycle regulation in these organisms and the mechanisms whereby regulation is achieved. Here, we analyse gene expression over the Trypanosoma brucei cell cycle, measuring changes in mRNA abundance on a transcriptome-wide scale. We developed a "double-cut" elutriation procedure to select unperturbed, highly synchronous cell populations from log-phase cultures, and compared this to synchronization by starvation. Transcriptome profiling over the cell cycle revealed the regulation of at least 430 genes. While only a minority were homologous to known cell cycle regulated transcripts in yeast or human, their functions correlated with the cellular processes occurring at the time of peak expression. We searched for potential target sites of RNA-binding proteins in these transcripts, which might earmark them for selective degradation or stabilization. Over-represented sequence motifs were found in several co-regulated transcript groups and were conserved in other kinetoplastids. Furthermore, we found evidence for cell-cycle regulation of a flagellar protein regulon with a highly conserved sequence motif, bearing similarity to consensus PUF-protein binding motifs. RNA sequence motifs that are functional in cell-cycle regulation were more widespread than previously expected and conserved within kinetoplastids. These findings highlight the central importance of post-transcriptional regulation in the proliferation of parasitic kinetoplastids.

  19. Topological Optimization of Rod Mixers

    Science.gov (United States)

    Finn, Matthew D.; Thiffeault, Jean-Luc

    2006-11-01

    Stirring of fluid with moving rods is necessary in many practical applications to achieve homogeneity. These rods are topological obstacles that force stretching of fluid elements. The resulting stretching and folding is commonly observed as filaments and striations, and is a precursor to mixing. In a space-time diagram, the trajectories of the rods form a braid [1], and the properties of this braid impose a minimal complexity in the flow. We discuss how optimal mixing protocols can be obtained by a judicious choice of braid, and how these protocols can be implemented using simple gearing [2].[12pt] [1] P. L. Boyland, H. Aref, and M. A. Stremler, JFM 403, 277 (2000).[8pt] [2] J.-L. Thiffeault and M. D. Finn, http://arxiv.org/nlin/0603003

  20. Isolation and characterization of kinetoplast DNA from the bloodstream form of Trypanosoma brucei.

    NARCIS (Netherlands)

    A.H. Fairlamb; P.O. Weislogel; J.H.J. Hoeijmakers (Jan); P. Borst (Piet)

    1978-01-01

    textabstractWe have used restriction endonucleases PstI, EcoRI, HapII, HhaI, and S1 nuclease to demonstrate the presence of a large complex component, the maxi-circle, in addition to the major mini-circle component in kinetoplast DNA (kDNA) networks of Trypanosoma brucei (East African Trypanosomiasi

  1. Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation

    NARCIS (Netherlands)

    Weelden, van S.W.H.; Fast, B.; Vogt, A.; Meer, van der P.; Saas, J.; Hellemond, van J.J.; Tielens, A.G.M.; Boshart, M.

    2003-01-01

    The importance of a functional Krebs cycle for energy generation in the procyclic stage of Trypanosoma brucei was investigated under physiological conditions during logarithmic phase growth of a pleomorphic parasite strain. Wild type procyclic cells and mutants with targeted deletion of the gene cod

  2. Dynamic Modelling under Uncertainty : The Case of Trypanosoma brucei Energy Metabolism

    NARCIS (Netherlands)

    Achcar, Fiona; Kerkhoven, Eduard J.; Bakker, Barbara M.; Barrett, Michael P.; Breitling, Rainer; Papin, Jason A.

    2012-01-01

    Kinetic models of metabolism require detailed knowledge of kinetic parameters. However, due to measurement errors or lack of data this knowledge is often uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei is a particularly well analysed example of a quantitative metabol

  3. Handling Uncertainty in Dynamic Models : The Pentose Phosphate Pathway in Trypanosoma brucei

    NARCIS (Netherlands)

    Kerkhoven, Eduard J.; Achcar, Fiona; Alibu, Vincent P.; Burchmore, Richard J.; Gilbert, Ian H.; Trybilo, Maciej; Driessen, Nicole N.; Gilbert, David; Breitling, Rainer; Bakker, Barbara M.; Barrett, Michael P.

    2013-01-01

    Dynamic models of metabolism can be useful in identifying potential drug targets, especially in unicellular organisms. A model of glycolysis in the causative agent of human African trypanosomiasis, Trypanosoma brucei, has already shown the utility of this approach. Here we add the pentose phosphate

  4. Involvement of lysosomes in the uptake of macromolecular material by bloodstream forms of Trypanosoma brucei.

    Science.gov (United States)

    Opperdoes, F R; Van Roy, J

    1982-09-01

    To investigate whether the lysosomes of Trypanosoma brucei are capable of uptake of macromolecules after internalization by the cell, we used Triton WR-1339, a non-digestible macromolecular compound, which is known to cause a marked decrease in the density of hepatic lysosomes due to massive intralysosomal storage. Intraperitoneal administration of 0.4 g/kg Triton WR-1339 to rats infected with T. brucei led to the development of a large vacuole in the trypanosomes between nucleus and kinetoplast within 22 h. Higher doses (2 g/kg) led to the disappearance of the trypanosomes from the blood and resulted in permanent cures (greater than 100 days). Lysosomes isolated from the trypanosomes of animals treated with a sub-curative dose showed a decrease in equilibrium density of 0.03 g/cm3 in sucrose gradients. These lysosomes were partly damaged as evidenced by a reduction in latency and an increase in the non-sedimentable part of lysosomal enzymes. We conclude that acid proteinase and alpha-mannosidase-containing organelles of T. brucei take up exogenous macromolecules and must therefore be considered as true lysosomes and that Triton WR-1339 acts in T. brucei as a true lysosomotropic drug. Its trypanocidal action probably results from an interference with lysosomal function.

  5. Novel molecular mechanism for targeting the parasite Trypanosoma brucei with snake venom toxins

    DEFF Research Database (Denmark)

    Martos Esteban, Andrea; Laustsen, Andreas Hougaard; Carrington, Mark

    Trypanosoma brucei is a parasitic protozoan species capable to infecting insect vectors whose bite further produces African sleeping sickness inhuman beings. During parasites’extracellular lives in the mammalian host, its outer coat, mainly composedof Variable surface glycoproteins (VSGs)[2], und...

  6. Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Galadriel A Hovel-Miner

    Full Text Available Trypanosoma brucei is a master of antigenic variation and immune response evasion. Utilizing a genomic repertoire of more than 1000 Variant Surface Glycoprotein-encoding genes (VSGs, T. brucei can change its protein coat by "switching" from the expression of one VSG to another. Each active VSG is monoallelically expressed from only one of approximately 15 subtelomeric sites. Switching VSG expression occurs by three predominant mechanisms, arguably the most significant of which is the non-reciprocal exchange of VSG containing DNA by duplicative gene conversion (GC. How T. brucei orchestrates its complex switching mechanisms remains to be elucidated. Recent work has demonstrated that an exogenous DNA break in the active site could initiate a GC based switch, yet the source of the switch-initiating DNA lesion under natural conditions is still unknown. Here we investigated the hypothesis that telomere length directly affects VSG switching. We demonstrate that telomerase deficient strains with short telomeres switch more frequently than genetically identical strains with long telomeres and that, when the telomere is short, switching preferentially occurs by GC. Our data supports the hypothesis that a short telomere at the active VSG expression site results in an increase in subtelomeric DNA breaks, which can initiate GC based switching. In addition to their significance for T. brucei and telomere biology, the findings presented here have implications for the many diverse pathogens that organize their antigenic genes in subtelomeric regions.

  7. Nucleic acid sequence-based amplification with oligochromatography for detection of Trypanosoma brucei in clinical samples

    NARCIS (Netherlands)

    C.M. Mugasa; T. Laurent; G.J. Schoone; P.A. Kager; G.W. Lubega; H.D.F.H. Schallig

    2009-01-01

    Molecular tools, such as real-time nucleic acid sequence-based amplification (NASBA) and PCR, have been developed to detect Trypanosoma brucei parasites in blood for the diagnosis of human African trypanosomiasis (HAT). Despite good sensitivity, these techniques are not implemented in HAT control pr

  8. Ribose 5-phosphate isomerase B knockdown compromises Trypanosoma brucei bloodstream form infectivity.

    Science.gov (United States)

    Loureiro, Inês; Faria, Joana; Clayton, Christine; Macedo-Ribeiro, Sandra; Santarém, Nuno; Roy, Nilanjan; Cordeiro-da-Siva, Anabela; Tavares, Joana

    2015-01-01

    Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of African sleeping sickness namely Trypanosoma brucei, have a type B ribose-5-phosphate isomerase. This enzyme is absent from humans, which have a structurally unrelated ribose 5-phosphate isomerase type A, and therefore has been proposed as an attractive drug target waiting further characterization. In this study, Trypanosoma brucei ribose 5-phosphate isomerase B showed in vitro isomerase activity. RNAi against this enzyme reduced parasites' in vitro growth, and more importantly, bloodstream forms infectivity. Mice infected with induced RNAi clones exhibited lower parasitaemia and a prolonged survival compared to control mice. Phenotypic reversion was achieved by complementing induced RNAi clones with an ectopic copy of Trypanosoma cruzi gene. Our results present the first functional characterization of Trypanosoma brucei ribose 5-phosphate isomerase B, and show the relevance of an enzyme belonging to the non-oxidative branch of the pentose phosphate pathway in the context of Trypanosoma brucei infection.

  9. The major transcripts of the kinetoplast Trypanosoma brucei are very small ribosomal RNA's.

    NARCIS (Netherlands)

    I.C. Eperon; J.W.G. Janssen; J.H.J. Hoeijmakers (Jan); P. Borst (Piet)

    1983-01-01

    textabstractThe nucleotide sequence has been determined of a 2.2 kb segment of kinetoplast DNA, which encodes the major mitochondrial transcripts (12S and 9S) of Trypanosoma brucei. The sequence shows that the 12S RNA is a large subunit rRNA, although sufficiently unusual for resistance to chloramph

  10. Biosynthesis of SUMOylated Proteins in Bacteria Using the Trypanosoma brucei Enzymatic System

    Science.gov (United States)

    Iribarren, Paula Ana; Berazategui, María Agustina; Cazzulo, Juan José; Alvarez, Vanina Eder

    2015-01-01

    Post-translational modification with the Small Ubiquitin-like Modifier (SUMO) is conserved in eukaryotic organisms and plays important regulatory roles in proteins affecting diverse cellular processes. In Trypanosoma brucei, member of one of the earliest branches in eukaryotic evolution, SUMO is essential for normal cell cycle progression and is likely to be involved in the epigenetic control of genes crucial for parasite survival, such as those encoding the variant surface glycoproteins. Molecular pathways modulated by SUMO have started to be discovered by proteomic studies; however, characterization of functional consequences is limited to a reduced number of targets. Here we present a bacterial strain engineered to produce SUMOylated proteins, by transferring SUMO from T. brucei together with the enzymes essential for its activation and conjugation. Due to the lack of background in E. coli, this system is useful to express and identify SUMOylated proteins directly in cell lysates by immunoblotting, and SUMOylated targets can be eventually purified for biochemical or structural studies. We applied this strategy to describe the ability of TbSUMO to form chains in vitro and to detect SUMOylation of a model substrate, PCNA both from Saccharomyces cerevisiae and from T. brucei. To further validate targets, we applied an in vitro deconjugation assay using the T. brucei SUMO-specific protease capable to revert the pattern of modification. This system represents a valuable tool for target validation, mutant generation and functional studies of SUMOylated proteins in trypanosomatids. PMID:26258470

  11. Mitochondrial outer membrane proteome of Trypanosoma brucei reveals novel factors required to maintain mitochondrial morphology.

    Science.gov (United States)

    Niemann, Moritz; Wiese, Sebastian; Mani, Jan; Chanfon, Astrid; Jackson, Christopher; Meisinger, Chris; Warscheid, Bettina; Schneider, André

    2013-02-01

    Trypanosoma brucei is a unicellular parasite that causes devastating diseases in humans and animals. It diverged from most other eukaryotes very early in evolution and, as a consequence, has an unusual mitochondrial biology. Moreover, mitochondrial functions and morphology are highly regulated throughout the life cycle of the parasite. The outer mitochondrial membrane defines the boundary of the organelle. Its properties are therefore key for understanding how the cytosol and mitochondria communicate and how the organelle is integrated into the metabolism of the whole cell. We have purified the mitochondrial outer membrane of T. brucei and characterized its proteome using label-free quantitative mass spectrometry for protein abundance profiling in combination with statistical analysis. Our results show that the trypanosomal outer membrane proteome consists of 82 proteins, two-thirds of which have never been associated with mitochondria before. 40 proteins share homology with proteins of known functions. The function of 42 proteins, 33 of which are specific to trypanosomatids, remains unknown. 11 proteins are essential for the disease-causing bloodstream form of T. brucei and therefore may be exploited as novel drug targets. A comparison with the outer membrane proteome of yeast defines a set of 17 common proteins that are likely present in the mitochondrial outer membrane of all eukaryotes. Known factors involved in the regulation of mitochondrial morphology are virtually absent in T. brucei. Interestingly, RNAi-mediated ablation of three outer membrane proteins of unknown function resulted in a collapse of the network-like mitochondrion of procyclic cells and for the first time identified factors that control mitochondrial shape in T. brucei.

  12. Mutational analysis of Trypanosoma brucei RNA editing ligase reveals regions critical for interaction with KREPA2.

    Directory of Open Access Journals (Sweden)

    Vaibhav Mehta

    Full Text Available The Trypanosoma brucei parasite causes the vector-borne disease African sleeping sickness. Mitochondrial mRNAs of T. brucei undergo posttranscriptional RNA editing to make mature, functional mRNAs. The final step of this process is catalyzed by the essential ligase, T. brucei RNA Editing Ligase 1 (TbREL1 and the closely related T. brucei RNA Editing Ligase 2 (TbREL2. While other ligases such as T7 DNA ligase have both a catalytic and an oligonucleotide/oligosaccharide-binding (OB-fold domain, T. brucei RNA editing ligases contain only the catalytic domain. The OB-fold domain, which is required for interaction with the substrate RNA, is provided in trans by KREPA2 (for TbREL1 and KREPA1 (for TbREL2. KREPA2 enhancement of TbREL1 ligase activity is presumed to occur via an OB-fold-mediated increase in substrate specificity and catalysis. We characterized the interaction between TbREL1 and KREPA2 in vitro using full-length, truncated, and point-mutated ligases. As previously shown, our data indicate strong, specific stimulation of TbREL1 catalytic activity by KREPA2. We narrowed the region of contact to the final 59 C-terminal residues of TbREL1. Specifically, the TbREL1 C-terminal KWKE (441-444 sequence appear to coordinate the KREPA2-mediated enhancement of TbREL1 activities. N-terminal residues F206, T264 and Y275 are crucial for the overall activity of TbREL1, particularly for F206, a mutation of this residue also disrupts KREPA2 interaction. Thus, we have identified the critical TbREL1 regions and amino acids that mediate the KREPA2 interaction.

  13. Control rods in LMFBRs: a physics assessment

    Energy Technology Data Exchange (ETDEWEB)

    McFarlane, H.F.; Collins, P.J.

    1982-08-01

    This physics assessment is based on roughly 300 control rod worth measurements in ZPPR from 1972 to 1981. All ZPPR assemblies simulated mixed-oxide LMFBRs, representing sizes of 350, 700, and 900 MWe. Control rod worth measurements included single rods, various combinations of rods, and Ta and Eu rods. Additional measurements studied variations in B/sub 4/C enrichment, rod interaction effects, variations in rod geometry, neutron streaming in sodium-filled channels, and axial worth profiles. Analyses were done with design-equivalent methods, using ENDF/B Version IV data. Some computations for the sensitivities to approximations in the methods have been included. Comparisons of these analyses with the experiments have allowed the status of control rod physics in the US to be clearly defined.

  14. Solid-state-laser-rod holder

    Science.gov (United States)

    Gettemy, D.J.; Barnes, N.P.; Griggs, J.E.

    1981-08-11

    The disclosure relates to a solid state laser rod holder comprising Invar, copper tubing, and epoxy joints. Materials and coefficients of expansion of the components of the holder combine with the rod to produce a joint which will give before the rod itself will. The rod may be lased at about 70 to 80/sup 0/K and returned from such a temperature to room temperature repeatedly without its or the holder's destruction.

  15. Solitary waves on nonlinear elastic rods. II

    DEFF Research Database (Denmark)

    Sørensen, Mads Peter; Christiansen, Peter Leth; Lomdahl, P. S.;

    1987-01-01

    In continuation of an earlier study of propagation of solitary waves on nonlinear elastic rods, numerical investigations of blowup, reflection, and fission at continuous and discontinuous variation of the cross section for the rod and reflection at the end of the rod are presented. The results...

  16. 21 CFR 876.4270 - Colostomy rod.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Colostomy rod. 876.4270 Section 876.4270 Food and... GASTROENTEROLOGY-UROLOGY DEVICES Surgical Devices § 876.4270 Colostomy rod. (a) Identification. A colostomy rod is a device used during the loop colostomy procedure. A loop of colon is surgically brought out...

  17. Phase behavior of colloidal silica rods

    NARCIS (Netherlands)

    Kuijk, A.; Byelov, D.; Petukhov, A.V.; van Blaaderen, A.; Imhof, A.

    2012-01-01

    Recently, a novel colloidal hard-rod-like model system was developed which consists of silica rods [Kuijk et al., JACS, 2011, 133, 2346]. Here, we present a study of the phase behavior of these rods, for aspect ratios ranging from 3.7 to 8.0. By combining real-space confocal laser scanning microscop

  18. T rypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo

    OpenAIRE

    Pena, Ana C.; Pimentel, Mafalda R; Manso, Helena; Vaz-Drago, Rita; Pinto-Neves, Daniel; Aresta-Branco, Francisco; Rijo-Ferreira, Filipa; Guegan, Fabien; Pedro Coelho, Luis; Carmo-Fonseca, Maria; Barbosa-Morais, Nuno L.; Figueiredo, Luisa M.

    2014-01-01

    T rypanosoma brucei is a unicellular parasite that causes sleeping sickness in humans. Most of its transcription is constitutive and driven by RNA polymerase II. RNA polymerase I (Pol I) transcribes not only ribosomal RNA genes, but also protein-encoding genes, including variant surface glycoproteins (VSGs) and procyclins. In T . brucei, histone H1 (H1) is required for VSG silencing and chromatin condensation. However, whether H1 has a genome-wide role in transcription is unknown. Here, using...

  19. Exploiting rod technology. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1990-06-01

    ROD development was proceeding apace until recent budgetary decisions caused funding support for ROD development to be drastically reduced. The funding which was originally provided by DARPA and the Balanced Technology Initiative (BTI) Office has been cut back to zero from $800K. To determine the aeroballistic coefficients of a candidate dart, ARDEC is currently supporting development out of its own 6.2 funds at about $100K. ARDEC has made slow progress toward achieving this end because of failures in the original dart during testing. It appears that the next dart design to be tested will diverge from the original concept visualized by DARPA and Science and Technology Associates (STA). STA, the design engineer, takes exception to these changes on the basis of inappropriate test conditions and insufficient testing. At this time, the full resolution of this issue will be difficult because of the current management structure, which separates the developer (ARDEC) from the designer (STA).

  20. ELECTROMAGNETIC APPARATUS FOR MOVING A ROD

    Science.gov (United States)

    Young, J.N.

    1958-04-22

    An electromagnetic apparatus for moving a rod-like member in small steps in either direction is described. The invention has particular application in the reactor field where the reactor control rods must be moved only a small distance and where the use of mechanical couplings is impractical due to the high- pressure seals required. A neutron-absorbing rod is mounted in a housing with gripping uaits that engage the rod, and coils for magnetizing the gripping units to make them grip, shift, and release the rod are located outside the housing.

  1. Clinical and hematological study of Trypanosoma brucei and Trypanosoma congolense in cattle in Mosul City, Iraq

    Directory of Open Access Journals (Sweden)

    Al-Badrani, B. A

    2012-03-01

    Full Text Available An out-break of trypanosomosis was reported and subsequently investigated in Mosul city, Iraq. Twenty seven blood samples were received at the Clinical pathology Laboratory of Veterinary Teaching Hospital, University of Mosul, from fifteen cows (2-5 years old and twelve calves (10-12 months old of different farms located around Mosul city. Clinical signs of the infected animals revealed fever, progressive weight loss, anemia, and frequent recumbent position. Identification of trypanosome species were based on their motility using morphological differentiation on Giemsa or Leishman stained that showed trypomastigot which can be classified according to the biometrical data into T. brucei and T. congolense. A decreased was also observed in some blood parameters. To our knowledge, this is the first record of T. brucei and T. congolense infection in cattle. This study also suggested that trypanosomosis is associated with introduction of exotic breeds of cattle into Mosul, Iraq.

  2. Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei

    Directory of Open Access Journals (Sweden)

    Michael Wink

    2008-10-01

    Full Text Available The potential induction of a programmed cell death (PCD in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine and veratridine induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC50 below 10 µM was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation.

  3. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Juan P de Macêdo

    2015-05-01

    Full Text Available Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug

  4. An essential signal peptide peptidase identified in an RNAi screen of serine peptidases of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Catherine X Moss

    Full Text Available The serine peptidases of Trypanosoma brucei have been viewed as potential drug targets. In particular, the S9 prolyl oligopeptidase subfamily is thought to be a good avenue for drug discovery. This is based on the finding that some S9 peptidases are secreted and active in the mammalian bloodstream, and that they are a class of enzyme against which drugs have successfully been developed. We collated a list of all serine peptidases in T. brucei, identifying 20 serine peptidase genes, of which nine are S9 peptidases. We screened all 20 serine peptidases by RNAi to determine which, if any, are essential for bloodstream form T. brucei survival. All S9 serine peptidases were dispensable for parasite survival in vitro, even when pairs of similar genes, coding for oligopeptidase B or prolyl oligopeptidase, were targeted simultaneously. We also found no effect on parasite survival in an animal host when the S9 peptidases oligopeptidase B, prolyl oligopeptidase or dipeptidyl peptidase 8 were targeted. The only serine peptidase to emerge from the RNAi screen as essential was a putative type-I signal peptide peptidase (SPP1. This gene was essential for parasite survival both in vitro and in vivo. The growth defect conferred by RNAi depletion of SPP1 was rescued by expression of a functional peptidase from an RNAi resistant SPP1 gene. However, expression of catalytically inactive SPP1 was unable to rescue cells from the SPP1 depleted phenotype, demonstrating that SPP1 serine peptidase activity is necessary for T. brucei survival.

  5. A transcription-independent epigenetic mechanism is associated with antigenic switching in Trypanosoma brucei

    OpenAIRE

    Aresta-Branco, Francisco; Pimenta, Silvia; Figueiredo, Luisa M.

    2015-01-01

    Antigenic variation in Trypanosoma brucei relies on periodic switching of variant surface glycoproteins (VSGs), which are transcribed monoallelically by RNA polymerase I from one of about 15 bloodstream expression sites (BES). Chromatin of the actively transcribed BES is depleted of nucleosomes, but it is unclear if this open conformation is a mere consequence of a high rate of transcription, or whether it is maintained by a transcription-independent mechanism. Using an inducible BES-silencin...

  6. Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi

    OpenAIRE

    Parsons, Marilyn; Worthey, Elizabeth A.; Ward, Pauline N; Mottram, Jeremy C.

    2005-01-01

    Background The trypanosomatids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, African sleeping sickness, and Chagas disease. These protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. However, the ways in which the parasites respond to their environment and coordinate intr...

  7. Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation.

    Science.gov (United States)

    van Weelden, Susanne W H; Fast, Beate; Vogt, Achim; van der Meer, Pieter; Saas, Joachim; van Hellemond, Jaap J; Tielens, Aloysius G M; Boshart, Michael

    2003-04-11

    The importance of a functional Krebs cycle for energy generation in the procyclic stage of Trypanosoma brucei was investigated under physiological conditions during logarithmic phase growth of a pleomorphic parasite strain. Wild type procyclic cells and mutants with targeted deletion of the gene coding for aconitase were derived by synchronous in vitro differentiation from wild type and mutant (Delta aco::NEO/Delta aco::HYG) bloodstream stage parasites, respectively, where aconitase is not expressed and is dispensable. No differences in intracellular levels of glycolytic and Krebs cycle intermediates were found in procyclic wild type and mutant cells, except for citrate that accumulated up to 90-fold in the mutants, confirming the absence of aconitase activity. Surprisingly, deletion of aconitase did not change differentiation nor the growth rate or the intracellular ATP/ADP ratio in those cells. Metabolic studies using radioactively labeled substrates and NMR analysis demonstrated that glucose and proline were not degraded via the Krebs cycle to CO(2). Instead, glucose was degraded to acetate, succinate, and alanine, whereas proline was degraded to succinate. Importantly, there was absolutely no difference in the metabolic products released by wild type and aconitase knockout parasites, and both were for survival strictly dependent on respiration via the mitochondrial electron transport chain. Hence, although the Krebs cycle enzymes are present, procyclic T. brucei do not use Krebs cycle activity for energy generation, but the mitochondrial respiratory chain is essential for survival and growth. We therefore propose a revised model of the energy metabolism of procyclic T. brucei.

  8. The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei.

    Science.gov (United States)

    van Hellemond, J J; Opperdoes, F R; Tielens, A G M

    2005-11-01

    African trypanosomes are parasitic protozoa that cause sleeping sickness and nagana. Trypanosomes are not only of scientific interest because of their clinical importance, but also because these protozoa contain several very unusual biological features, such as their specially adapted mitochondrion and the compartmentalization of glycolytic enzymes in glycosomes. The energy metabolism of Trypanosoma brucei differs significantly from that of their hosts and changes drastically during the life cycle. Despite the presence of all citric acid cycle enzymes in procyclic insect-stage T. brucei, citric acid cycle activity is not used for energy generation. Recent investigations on the influence of substrate availability on the type of energy metabolism showed that absence of glycolytic substrates did not induce a shift from a fermentative metabolism to complete oxidation of substrates. Apparently, insect-stage T. brucei use parts of the citric acid cycle for other purposes than for complete degradation of mitochondrial substrates. Parts of the cycle are suggested to be used for (i) transport of acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, (ii) degradation of proline and glutamate to succinate, (iii) generation of malate, which can then be used for gluconeogenesis. Therefore the citric acid cycle in trypanosomes does not function as a cycle.

  9. Experimental Trypanosoma brucei infection at immediate post partum period:effects on dam and the offspring

    Institute of Scientific and Technical Information of China (English)

    Izuchukwu S Ochiogu; Chukwuka N Uchendu; John I Ihedioha

    2010-01-01

    Objective:To investigate the effects of immediate post-partum infection with Trypanosoma brucei (T. brucei) on dam and offspring. Methods:Sixty female Albino rats (Rattus norvegicus) weighing between 130-170 g were used as animal model. The animals were divided as follows:25 infected between 1-5 days post partum; 10 infected unbred as positive controls; and 25 uninfected as negative controls. The following parameters were evaluated:packed cell volume (PCV), level of parasitaemia, survival time, litter size and litter weight at birth and on days 7, 14 and 21 post delivery, using conventional methods. Possible trans-mammary transmission of infection to litter through milk was also assessed. Results:The results showed a comparatively (P<0.05) higher mean PCV value for the uninfected negative control on the 8th day post infection compared with the infected groups which corresponded with the increasing level of parasitaemia in the two infected groups. Mean litter size and litter weights were higher (P< 0.05) in the uninfected controls on the 21st day. Survival time in the infected groups were similar. No evidence of trans-mammary transfer of infection was recorded. Conclusion:T. brucei infection during immediate post partum period is detrimental to the dam and impairs growth of the offspring.

  10. Advancing Trypanosoma brucei genome annotation through ribosome profiling and spliced leader mapping.

    Science.gov (United States)

    Parsons, Marilyn; Ramasamy, Gowthaman; Vasconcelos, Elton J R; Jensen, Bryan C; Myler, Peter J

    2015-08-01

    Since the initial publication of the trypanosomatid genomes, curation has been ongoing. Here we make use of existing Trypanosoma brucei ribosome profiling data to provide evidence of ribosome occupancy (and likely translation) of mRNAs from 225 currently unannotated coding sequences (CDSs). A small number of these putative genes correspond to extra copies of previously annotated genes, but 85% are novel. The median size of these novels CDSs is small (81 aa), indicating that past annotation work has excelled at detecting large CDSs. Of the unique CDSs confirmed here, over half have candidate orthologues in other trypanosomatid genomes, most of which were not yet annotated as protein-coding genes. Nonetheless, approximately one-third of the new CDSs were found only in T. brucei subspecies. Using ribosome footprints, RNA-Seq and spliced leader mapping data, we updated previous work to definitively revise the start sites for 414 CDSs as compared to the current gene models. The data pointed to several regions of the genome that had sequence errors that altered coding region boundaries. Finally, we consolidated this data with our previous work to propose elimination of 683 putative genes as protein-coding and arrive at a view of the translatome of slender bloodstream and procyclic culture form T. brucei.

  11. Discovery of Inhibitors of Trypanosoma brucei by Phenotypic Screening of a Focused Protein Kinase Library.

    Science.gov (United States)

    Woodland, Andrew; Thompson, Stephen; Cleghorn, Laura A T; Norcross, Neil; De Rycker, Manu; Grimaldi, Raffaella; Hallyburton, Irene; Rao, Bhavya; Norval, Suzanne; Stojanovski, Laste; Brun, Reto; Kaiser, Marcel; Frearson, Julie A; Gray, David W; Wyatt, Paul G; Read, Kevin D; Gilbert, Ian H

    2015-11-01

    A screen of a focused kinase inhibitor library against Trypanosoma brucei rhodesiense led to the identification of seven series, totaling 121 compounds, which showed >50 % inhibition at 5 μm. Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H-imidazo[4,5-b]pyrazin-2(3H)-one scaffold that showed sub-micromolar activity and excellent selectivity against the MRC5 cell line. Subsequent rounds of optimisation led to the identification of compounds that exhibited good in vitro drug metabolism and pharmacokinetics (DMPK) properties, although in general this series suffered from poor solubility. A scaffold-hopping exercise led to the identification of a 1H-pyrazolo[3,4-b]pyridine scaffold, which retained potency. A number of examples were assessed in a T. b. brucei growth assay, which could differentiate static and cidal action. Compounds from the 1H-imidazo[4,5-b]pyrazin-2(3H)-one series were found to be either static or growth-slowing and not cidal. Compounds with the 1H-pyrazolo[3,4-b]pyridine scaffold were found to be cidal and showed an unusual biphasic nature in this assay, suggesting they act by at least two mechanisms.

  12. NLP is a novel transcription regulator involved in VSG expression site control in Trypanosoma brucei.

    Science.gov (United States)

    Narayanan, Mani Shankar; Kushwaha, Manish; Ersfeld, Klaus; Fullbrook, Alexander; Stanne, Tara M; Rudenko, Gloria

    2011-03-01

    Trypanosoma brucei mono-allelically expresses one of approximately 1500 variant surface glycoprotein (VSG) genes while multiplying in the mammalian bloodstream. The active VSG is transcribed by RNA polymerase I in one of approximately 15 telomeric VSG expression sites (ESs). T. brucei is unusual in controlling gene expression predominantly post-transcriptionally, and how ESs are mono-allelically controlled remains a mystery. Here we identify a novel transcription regulator, which resembles a nucleoplasmin-like protein (NLP) with an AT-hook motif. NLP is key for ES control in bloodstream form T. brucei, as NLP knockdown results in 45- to 65-fold derepression of the silent VSG221 ES. NLP is also involved in repression of transcription in the inactive VSG Basic Copy arrays, minichromosomes and procyclin loci. NLP is shown to be enriched on the 177- and 50-bp simple sequence repeats, the non-transcribed regions around rDNA and procyclin, and both active and silent ESs. Blocking NLP synthesis leads to downregulation of the active ES, indicating that NLP plays a role in regulating appropriate levels of transcription of ESs in both their active and silent state. Discovery of the unusual transcription regulator NLP provides new insight into the factors that are critical for ES control.

  13. High temperature control rod assembly

    Energy Technology Data Exchange (ETDEWEB)

    Vollman, Russell E. (Solana Beach, CA)

    1991-01-01

    A high temperature nuclear control rod assembly comprises a plurality of substantially cylindrical segments flexibly joined together in succession by ball joints. The segments are made of a high temperature graphite or carbon-carbon composite. The segment includes a hollow cylindrical sleeve which has an opening for receiving neutron-absorbing material in the form of pellets or compacted rings. The sleeve has a threaded sleeve bore and outer threaded surface. A cylindrical support post has a threaded shaft at one end which is threadably engaged with the sleeve bore to rigidly couple the support post to the sleeve. The other end of the post is formed with a ball portion. A hollow cylindrical collar has an inner threaded surface engageable with the outer threaded surface of the sleeve to rigidly couple the collar to the sleeve. the collar also has a socket portion which cooperates with the ball portion to flexibly connect segments together to form a ball and socket-type joint. In another embodiment, the segment comprises a support member which has a threaded shaft portion and a ball surface portion. The threaded shaft portion is engageable with an inner threaded surface of a ring for rigidly coupling the support member to the ring. The ring in turn has an outer surface at one end which is threadably engageably with a hollow cylindrical sleeve. The other end of the sleeve is formed with a socket portion for engagement with a ball portion of the support member. In yet another embodiment, a secondary rod is slidably inserted in a hollow channel through the center of the segment to provide additional strength. A method for controlling a nuclear reactor utilizing the control rod assembly is also included.

  14. Topological Mixing with Ghost Rods

    OpenAIRE

    2005-01-01

    Topological chaos relies on the periodic motion of obstacles in a two-dimensional flow in order to form nontrivial braids. This motion generates exponential stretching of material lines, and hence efficient mixing. Boyland et al. [P. L. Boyland, H. Aref, and M. A. Stremler, J. Fluid Mech. 403, 277 (2000)] have studied a specific periodic motion of rods that exhibits topological chaos in a viscous fluid. We show that it is possible to extend their work to cases where the motion of the stirring...

  15. Reactor control rod timing system. [LMFBR

    Science.gov (United States)

    Wu, P.T.K.

    1980-03-18

    A fluid driven jet-edge whistle timing system is described for control rods of a nuclear reactor for producing real-time detection of the timing of each control rod in its scram operation. An important parameter in reactor safety, particularly for liquid metal fast breeder reactors (LMFBR), is the time deviation between the time the control rod is released and the time the rod actually reaches the down position. The whistle has a nearly pure tone signal with center frequency (above 100 kHz) far above the frequency band in which the energy of the background noise is concentrated. Each control rod can be fitted with a whistle with a different frequency so that there is no ambiguity in differentiating the signal from each control rod.

  16. Automatic safety rod for reactors. [LMFBR

    Science.gov (United States)

    Germer, J.H.

    1982-03-23

    An automatic safety rod for a nuclear reactor containing neutron absorbing material and designed to be inserted into a reactor core after a loss-of-flow. Actuation is based upon either a sudden decrease in core pressure drop or the pressure drop decreases below a predetermined minimum value. The automatic control rod includes a pressure regulating device whereby a controlled decrease in operating pressure due to reduced coolant flow does not cause the rod to drop into the core.

  17. Acoustic loading effects on oscillating rod bundles

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W.H.

    1980-01-01

    An analytical study of the interaction between an infinite acoustic medium and a cluster of circular rods is described. The acoustic field due to oscillating rods and the acoustic loading on the rods are first solved in a closed form. The acoustic loading is then used as a forcing function for rod responses, and the acousto-elastic couplings are solved simultaneously. Numerical examples are presented for several cases to illustrate the effects of various system parameters on the acoustic reaction force coefficients. The effect of the acoustic loading on the coupled eigenfrequencies are discussed.

  18. Identification of potent inhibitors of the Trypanosoma brucei methionyl-tRNA synthetase via high-throughput orthogonal screening.

    Science.gov (United States)

    Pedró-Rosa, Laura; Buckner, Frederick S; Ranade, Ranae M; Eberhart, Christina; Madoux, Franck; Gillespie, J Robert; Koh, Cho Yeow; Brown, Steven; Lohse, Jacqueline; Verlinde, Christophe L M; Fan, Erkang; Bannister, Thomas; Scampavia, Louis; Hol, Wim G J; Spicer, Timothy; Hodder, Peter

    2015-01-01

    Improved therapies for the treatment of Trypanosoma brucei, the etiological agent of the neglected tropical disease human African trypanosomiasis, are urgently needed. We targeted T. brucei methionyl-tRNA synthetase (MetRS), an aminoacyl-tRNA synthase (aaRS), which is considered an important drug target due to its role in protein synthesis, cell survival, and its significant differences in structure from its mammalian ortholog. Previous work using RNA interference of MetRS demonstrated growth inhibition of T. brucei, further validating it as an attractive target. We report the development and implementation of two orthogonal high-throughput screening assays to identify inhibitors of T. brucei MetRS. First, a chemiluminescence assay was implemented in a 1536-well plate format and used to monitor adenosine triphosphate depletion during the aminoacylation reaction. Hit confirmation then used a counterscreen in which adenosine monophosphate production was assessed using fluorescence polarization technology. In addition, a miniaturized cell viability assay was used to triage cytotoxic compounds. Finally, lower throughput assays involving whole parasite growth inhibition of both human and parasite MetRS were used to analyze compound selectivity and efficacy. The outcome of this high-throughput screening campaign has led to the discovery of 19 potent and selective T. brucei MetRS inhibitors.

  19. The Centriole Cartwheel Protein SAS-6 in Trypanosoma brucei Is Required for Probasal Body Biogenesis and Flagellum Assembly.

    Science.gov (United States)

    Hu, Huiqing; Liu, Yi; Zhou, Qing; Siegel, Sara; Li, Ziyin

    2015-09-01

    The centriole in eukaryotes functions as the cell's microtubule-organizing center (MTOC) to nucleate spindle assembly, and its biogenesis requires an evolutionarily conserved protein, SAS-6, which assembles the centriole cartwheel. Trypanosoma brucei, an early branching protozoan, possesses the basal body as its MTOC to nucleate flagellum biogenesis. However, little is known about the components of the basal body and their roles in basal body biogenesis and flagellum assembly. Here, we report that the T. brucei SAS-6 homolog, TbSAS-6, is localized to the mature basal body and the probasal body throughout the cell cycle. RNA interference (RNAi) of TbSAS-6 inhibited probasal body biogenesis, compromised flagellum assembly, and caused cytokinesis arrest. Surprisingly, overexpression of TbSAS-6 in T. brucei also impaired probasal body duplication and flagellum assembly, contrary to SAS-6 overexpression in humans, which produces supernumerary centrioles. Furthermore, we showed that depletion of T. brucei Polo-like kinase, TbPLK, or inhibition of TbPLK activity did not abolish TbSAS-6 localization to the basal body, in contrast to the essential role of Polo-like kinase in recruiting SAS-6 to centrioles in animals. Altogether, these results identified the essential role of TbSAS-6 in probasal body biogenesis and flagellum assembly and suggest the presence of a TbPLK-independent pathway governing basal body duplication in T. brucei.

  20. Study of the rod style SFRFQ structure

    CERN Document Server

    Yan Xue Qing; Chen J

    2002-01-01

    There is a problem about upper limit of energy in the RFQ structure, although it is a wonderful low-energy-suited high current accelerating structure. After proposing an improved rod style SFRFQ structure without reversed field, the author studies its energy gain and transverse motion. The rod style SFRFQ structure is roughly compared with diaphragm SFRFQ structure

  1. Viscoelasticity of suspensions of long, rigid rods

    NARCIS (Netherlands)

    Dhont, Jan K.G.; Briels, W.J.

    2003-01-01

    A microscopic theory for the viscoelastic behaviour of suspensions of rigid rods with excluded volume interactions is presented, which is valid in the asymptotic limit of very long and thin rods. Stresses arising from translational and rotational Brownian motion and direct interactions are calculate

  2. The phosphoarginine energy-buffering system of trypanosoma brucei involves multiple arginine kinase isoforms with different subcellular locations.

    Directory of Open Access Journals (Sweden)

    Frank Voncken

    Full Text Available Phosphagen energy-buffering systems play an essential role in regulating the cellular energy homeostasis in periods of high-energy demand or energy supply fluctuations. Here we describe the phosphoarginine/arginine kinase system of the kinetoplastid parasite Trypanosoma brucei, consisting of three highly similar arginine kinase isoforms (TbAK1-3. Immunofluorescence microscopy using myc-tagged protein versions revealed that each isoform is located in a specific subcellular compartment: TbAK1 is exclusively found in the flagellum, TbAK2 in the glycosome, and TbAK3 in the cytosol of T. brucei. The flagellar location of TbAK1 is dependent on a 22 amino acid long N-terminal sequence, which is sufficient for targeting a GFP-fusion protein to the trypanosome flagellum. The glycosomal location of TbAK2 is in agreement with the presence of a conserved peroxisomal targeting signal, the C-terminal tripeptide 'SNL'. TbAK3 lacks any apparent targeting sequences and is accordingly located in the cytosol of the parasite. Northern blot analysis indicated that each TbAK isoform is differentially expressed in bloodstream and procyclic forms of T. brucei, while the total cellular arginine kinase activity was 3-fold higher in bloodstream form trypanosomes. These results suggest a substantial change in the temporal and spatial energy requirements during parasite differentiation. Increased arginine kinase activity improved growth of procyclic form T. brucei during oxidative challenges with hydrogen peroxide. Elimination of the total cellular arginine kinase activity by RNA interference significantly decreased growth (>90% of procyclic form T. brucei under standard culture conditions and was lethal for this life cycle stage in the presence of hydrogen peroxide. The putative physiological roles of the different TbAK isoforms in T. brucei are further discussed.

  3. Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

    Science.gov (United States)

    Carnes, Jason; Anupama, Atashi; Balmer, Oliver; Jackson, Andrew; Lewis, Michael; Brown, Rob; Cestari, Igor; Desquesnes, Marc; Gendrin, Claire; Hertz-Fowler, Christiane; Imamura, Hideo; Ivens, Alasdair; Kořený, Luděk; Lai, De-Hua; MacLeod, Annette; McDermott, Suzanne M; Merritt, Chris; Monnerat, Severine; Moon, Wonjong; Myler, Peter; Phan, Isabelle; Ramasamy, Gowthaman; Sivam, Dhileep; Lun, Zhao-Rong; Lukeš, Julius; Stuart, Ken; Schnaufer, Achim

    2015-01-01

    Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

  4. Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice.

    Science.gov (United States)

    Rodgers, Jean; Bradley, Barbara; Kennedy, Peter G E; Sternberg, Jeremy M

    2015-01-01

    Invasion of the central nervous system (CNS) by African trypanosomes represents a critical step in the development of human African trypanosomiasis. In both clinical cases and experimental mouse infections it has been demonstrated that predisposition to CNS invasion is associated with a type 1 systemic inflammatory response. Using the Trypanosoma brucei brucei GVR35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine IL-10 lowers plasma IFN-γ and TNF-α concentrations, CNS parasitosis and ameliorates neuro-inflammatory pathology and clinical symptoms of disease. The results provide evidence that CNS invasion may be susceptible to immunological attenuation.

  5. The transcriptome of the human pathogen Trypanosoma brucei at single-nucleotide resolution.

    Directory of Open Access Journals (Sweden)

    Nikolay G Kolev

    Full Text Available The genome of Trypanosoma brucei, the causative agent of African trypanosomiasis, was published five years ago, yet identification of all genes and their transcripts remains to be accomplished. Annotation is challenged by the organization of genes transcribed by RNA polymerase II (Pol II into long unidirectional gene clusters with no knowledge of how transcription is initiated. Here we report a single-nucleotide resolution genomic map of the T. brucei transcriptome, adding 1,114 new transcripts, including 103 non-coding RNAs, confirming and correcting many of the annotated features and revealing an extensive heterogeneity of 5' and 3' ends. Some of the new transcripts encode polypeptides that are either conserved in T. cruzi and Leishmania major or were previously detected in mass spectrometry analyses. High-throughput RNA sequencing (RNA-Seq was sensitive enough to detect transcripts at putative Pol II transcription initiation sites. Our results, as well as recent data from the literature, indicate that transcription initiation is not solely restricted to regions at the beginning of gene clusters, but may occur at internal sites. We also provide evidence that transcription at all putative initiation sites in T. brucei is bidirectional, a recently recognized fundamental property of eukaryotic promoters. Our results have implications for gene expression patterns in other important human pathogens with similar genome organization (Trypanosoma cruzi, Leishmania sp. and revealed heterogeneity in pre-mRNA processing that could potentially contribute to the survival and success of the parasite population in the insect vector and the mammalian host.

  6. Eulerian Formulation of Spatially Constrained Elastic Rods

    Science.gov (United States)

    Huynen, Alexandre

    Slender elastic rods are ubiquitous in nature and technology. For a vast majority of applications, the rod deflection is restricted by an external constraint and a significant part of the elastic body is in contact with a stiff constraining surface. The research work presented in this doctoral dissertation formulates a computational model for the solution of elastic rods constrained inside or around frictionless tube-like surfaces. The segmentation strategy adopted to cope with this complex class of problems consists in sequencing the global problem into, comparatively simpler, elementary problems either in continuous contact with the constraint or contact-free between their extremities. Within the conventional Lagrangian formulation of elastic rods, this approach is however associated with two major drawbacks. First, the boundary conditions specifying the locations of the rod centerline at both extremities of each elementary problem lead to the establishment of isoperimetric constraints, i.e., integral constraints on the unknown length of the rod. Second, the assessment of the unilateral contact condition requires, in principle, the comparison of two curves parametrized by distinct curvilinear coordinates, viz. the rod centerline and the constraint axis. Both conspire to burden the computations associated with the method. To streamline the solution along the elementary problems and rationalize the assessment of the unilateral contact condition, the rod governing equations are reformulated within the Eulerian framework of the constraint. The methodical exploration of both types of elementary problems leads to specific formulations of the rod governing equations that stress the profound connection between the mechanics of the rod and the geometry of the constraint surface. The proposed Eulerian reformulation, which restates the rod local equilibrium in terms of the curvilinear coordinate associated with the constraint axis, describes the rod deformed configuration

  7. Trypanocidal activity of organotin chlorides on Trypanosoma brucei-infected mice

    Directory of Open Access Journals (Sweden)

    Shuaibu M.N.

    2000-03-01

    Full Text Available The organotin compounds dibulyltin (DBTC and diphenyltin dichlorides (DPTC were tested for trypanocidal activity on a Trypanosoma brucei-infected mice model. At a dose of 10 mg DBTC and 15 mg DPTC/kg/day for five consecutive days, they cleared the parasites from the peripheral blood of the infected mice. Subinoculation of some healthy mice with the homogenates of liver, spleen, kidney, cerebrospinal fluid and blood from the mice considered cured, showed a few cases of relapse. The LD50 of DBTC and DPTC are 90 mg/kg and 75 mg/kg respectively.

  8. A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans

    DEFF Research Database (Denmark)

    Vanhollebeke, Benoit; De Muylder, Géraldine; Nielsen, Marianne J;

    2008-01-01

    The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which...... receptor also recognized the complex between hemoglobin and haptoglobin-related protein, which explains its ability to capture trypanolytic HDLs. Thus, in humans the presence of haptoglobin-related protein has diverted the function of the trypanosome haptoglobin-hemoglobin receptor to elicit innate host...

  9. Zinc finger nuclease technology: A stable tool for high efficiency transformation in bloodstream form T. brucei.

    Science.gov (United States)

    Schumann, Gabriela; Kangussu-Marcolino, Monica M; Doiron, Nicholas; Käser, Sandro; de Assis Burle-Caldas, Gabriela; DaRocha, Wanderson D; Teixeira, Santuza M; Roditi, Isabel

    2017-02-20

    In Trypanosoma brucei, the generation of knockout mutants is relatively easy compared to other organisms as transfection methods are well established. These methods have their limitations, however, when it comes to the generation of genome-wide libraries that require a minimum of several hundred thousand transformants. Double-strand breaks with the meganuclease ISce-I dramatically increase transformation efficiency, but are not widely in use as cell lines need to be generated de novo before each transfection. Here we show that zinc finger nucleases are a robust and stable tool that can enhance transformation in bloodstream forms by more than an order of magnitude.

  10. Structures of aspartate aminotransferases from Trypanosoma brucei, Leishmania major and Giardia lamblia.

    Science.gov (United States)

    Abendroth, Jan; Choi, Ryan; Wall, Abigail; Clifton, Matthew C; Lukacs, Christine M; Staker, Bart L; Van Voorhis, Wesley; Myler, Peter; Lorimer, Don D; Edwards, Thomas E

    2015-05-01

    The structures of three aspartate aminotransferases (AATs) from eukaryotic pathogens were solved within the Seattle Structural Genomics Center for Infectious Disease (SSGCID). Both the open and closed conformations of AAT were observed. Pyridoxal phosphate was bound to the active site via a Schiff base to a conserved lysine. An active-site mutant showed that Trypanosoma brucei AAT still binds pyridoxal phosphate even in the absence of the tethering lysine. The structures highlight the challenges for the structure-based design of inhibitors targeting the active site, while showing options for inhibitor design targeting the N-terminal arm.

  11. Granular materials interacting with thin flexible rods

    Science.gov (United States)

    Neto, Alfredo Gay; Campello, Eduardo M. B.

    2016-01-01

    In this work, we develop a computational model for the simulation of problems wherein granular materials interact with thin flexible rods. We treat granular materials as a collection of spherical particles following a discrete element method (DEM) approach, while flexible rods are described by a large deformation finite element (FEM) rod formulation. Grain-to-grain, grain-to-rod, and rod-to-rod contacts are fully permitted and resolved. A simple and efficient strategy is proposed for coupling the motion of the two types (discrete and continuum) of materials within an iterative time-stepping solution scheme. Implementation details are shown and discussed. Validity and applicability of the model are assessed by means of a few numerical examples. We believe that robust, efficiently coupled DEM-FEM schemes can be a useful tool to the simulation of problems wherein granular materials interact with thin flexible rods, such as (but not limited to) bombardment of grains on beam structures, flow of granular materials over surfaces covered by threads of hair in many biological processes, flow of grains through filters and strainers in various industrial segregation processes, and many others.

  12. Control Rod Malfunction at the NRAD Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Thomas L. Maddock

    2010-05-01

    The neutron Radiography Reactor (NRAD) is a training, research, and isotope (TRIGA) reactor located at the INL. The reactor is normally shut down by the insertion of three control rods that drop into the core when power is removed from electromagnets. During a routine shutdown, indicator lights on the console showed that one of the control rods was not inserted. It was initially thought that the indicator lights were in error because of a limit switch that was out of adjustment. Through further testing, it was determined that the control rod did not drop when the scram switch was initially pressed. The control rod anomaly led to a six month shutdown of the reactor and an in depth investigation of the reactor protective system. The investigation looked into: scram switch operation, console modifications, and control rod drive mechanisms. A number of latent issues were discovered and corrected during the investigation. The cause of the control rod malfunction was found to be a buildup of corrosion in the control rod drive mechanism. The investigation resulted in modifications to equipment, changes to both operation and maintenance procedures, and additional training. No reoccurrences of the problem have been observed since corrective actions were implemented.

  13. Morphoelastic rods Part II: Growing birods

    Science.gov (United States)

    Lessinnes, Thomas; Moulton, Derek E.; Goriely, Alain

    2017-03-01

    The general problem of determining the shape and response of two attached growing elastic Kirchhoff rods is considered. A description of the kinematics of the individual interacting rods is introduced. Each rod has a given intrinsic shape and constitutive laws, and a map associating points on the two rods is defined. The resulting filamentary structure, a growing birod, can be seen as a new filamentary structure. This kinematic description is used to derive the general equilibrium equations for the shape of the rods under loads, or equivalently, for the new birod. It is shown that, in general, the birod is not simply a Kirchhoff rod but rather, due to the internal constraints, new effects can appear. The two-dimensional restriction is then considered explicitly and the limit for small deformation is shown to be equivalent to the classic Timsohenko bi-metallic strip problem. A number of examples and applications are presented. In particular, the problem of two attached rods with intrinsic helical shape and uniform growth is computed in detail and a host of new interesting solutions and bifurcations are observed.

  14. Tipping time of a quantum rod

    Energy Technology Data Exchange (ETDEWEB)

    Parrikar, Onkar [Birla Institute of Technology and Science-Pilani, Goa campus, Zuarinagar, Goa 4032726 (India)], E-mail: onkarsp@gmail.com

    2010-03-15

    The behaviour of a quantum rod, pivoted at its lower end on an impenetrable floor and restricted to moving in the vertical plane under the gravitational potential, is studied analytically under the approximation that the rod is initially localized to a 'small-enough' neighbourhood around the point of classical unstable equilibrium. It is shown that the rod evolves out of this neighbourhood. The time required for this to happen, i.e. the tipping time, is calculated using the semi-classical path integral. It is shown that equilibrium is recovered in the classical limit, and that our calculations are consistent with the uncertainty principle.

  15. High temperature control rod assembly

    Energy Technology Data Exchange (ETDEWEB)

    Vollman, R.E.

    1991-12-24

    This patent describes a control rod assembly for use in nuclear reactor control. It comprises segments, each the segment being made of a graphite composite material, each the segment having a chamber for containing neutron-absorbing material, wherein the chamber compromises a hollow cylindrical sleeve having a first end formed with an opening for receiving the neutron-absorbing material, and having a second end formed with a sleeve bore and an outer sleeve surface; a cylindrical weight-bearing support post positioned substantially centrally of the sleeve, the support post having a first end formed as a ball surface portion and a second end formed as a ball surface portion and a second end formed as a shaft, the shaft being engageable with the sleeve bore for rigidly coupling the support post axially within the hollow sleeve, a hollow cylindrical collar having a socket lip portion correspondingly shaped to receive the ball surface portion of an adjacent support post, and having an inner surface for engaging the outer sleeve surface on the second end of the sleeve to rigidly couple the collar to the sleeve.

  16. Trypanosoma brucei gambiense Type 1 populations from human patients are clonal and display geographical genetic differentiation.

    Science.gov (United States)

    Morrison, Liam J; Tait, Andy; McCormack, Gillian; Sweeney, Lindsay; Black, Alana; Truc, Philippe; Likeufack, Anne C L; Turner, C Michael; MacLeod, Annette

    2008-12-01

    We have rigorously tested the hypothesis that Trypanosoma brucei gambiense Type 1 is composed of genetically homogenous populations by examining the parasite population present in Human African Trypanosomiasis (HAT) patients from the Democratic Republic of Congo (DRC) and Cameroon (CAM). We amplified eight microsatellite markers by PCR directly from blood spots on FTA filters, thereby avoiding the significant parasite selection inherent in the traditional isolation techniques of rodent inoculation or in vitro culture. All microsatellite markers were polymorphic, although for four markers there was only polymorphism between the DRC and CAM populations, not within populations, suggesting very limited genetic exchange. Within the largest population from the DRC, Hardy-Weinberg equilibrium is not evident at any loci. This evidence suggests a clonal population. However, there was significant sub-structuring between the DRC and CAM samples (F(ST) = 0.32), indicating that Trypanosoma brucei gambiense Type 1 has genetically distinct clades. The data combine to indicate that genetic exchange plays a very limited role. The finding of distinct clades in different places suggests the possibility that samples from humans with clinical signs represent clonal expansions from an underlying population that requires identifying and characterising.

  17. KREX2 is not essential for either procyclic or bloodstream form Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Jason Carnes

    Full Text Available BACKGROUND: Most mitochondrial mRNAs in Trypanosoma brucei require RNA editing for maturation and translation. The edited RNAs primarily encode proteins of the oxidative phosphorylation system. These parasites undergo extensive changes in energy metabolism between the insect and bloodstream stages which are mirrored by alterations in RNA editing. Two U-specific exonucleases, KREX1 and KREX2, are both present in protein complexes (editosomes that catalyze RNA editing but the relative roles of each protein are not known. METHODOLOGY/PRINCIPAL FINDINGS: The requirement for KREX2 for RNA editing in vivo was assessed in both procyclic (insect and bloodstream form parasites by methods that use homologous recombination for gene elimination. These studies resulted in null mutant cells in which both alleles were eliminated. The viability of these cells demonstrates that KREX2 is not essential in either life cycle stage, despite certain defects in RNA editing in vivo. Furthermore, editosomes isolated from KREX2 null cells require KREX1 for in vitro U-specific exonuclease activity. CONCLUSIONS: KREX2 is a U-specific exonuclease that is dispensable for RNA editing in vivo in T. brucei BFs and PFs. This result suggests that the U deletion activity, which is required for RNA editing, is primarily mediated in vivo by KREX1 which is normally found associated with only one type of editosome. The retention of the KREX2 gene implies a non-essential role or a role that is essential in other life cycle stages or conditions.

  18. An Overview of Trypanosoma brucei Infections: An Intense Host–Parasite Interaction

    Science.gov (United States)

    Ponte-Sucre, Alicia

    2016-01-01

    Trypanosoma brucei rhodesiense and T. brucei gambiense, the causative agents of Human African Trypanosomiasis, are transmitted by tsetse flies. Within the vector, the parasite undergoes through transformations that prepares it to infect the human host. Sequentially these developmental stages are the replicative procyclic (in which the parasite surface is covered by procyclins) and trypo-epimastigote forms, as well as the non-replicative, infective, metacyclic form that develops in the vector salivary glands. As a pre-adaptation to their life in humans, metacyclic parasites begin to express and be densely covered by the Variant Surface Glycoprotein (VSG). Once the metacyclic form invades the human host the parasite develops into the bloodstream form. Herein the VSG triggers a humoral immune response. To avoid this humoral response, and essential for survival while in the bloodstream, the parasite changes its cover periodically and sheds into the surroundings the expressed VSG, thus evading the consequences of the immune system activation. Additionally, tools comparable to quorum sensing are used by the parasite for the successful parasite transmission from human to insect. On the other hand, the human host promotes clearance of the parasite triggering innate and adaptive immune responses and stimulating cytokine and chemokine secretion. All in all, the host–parasite interaction is extremely active and leads to responses that need multiple control sites to develop appropriately. PMID:28082973

  19. Analysis of the Trypanosoma brucei cell cycle by quantitative DAPI imaging.

    Science.gov (United States)

    Siegel, T Nicolai; Hekstra, Doeke R; Cross, George A M

    2008-08-01

    Trypanosoma brucei has two DNA compartments: the nucleus and the kinetoplast. DNA replication of these two compartments only partially coincides. Woodward and Gull [Woodward R, Gull K. Timing of nuclear and kinetoplast DNA replication and early morphological events in the cell cycle of Trypanosoma brucei. J Cell Sci 1990;95:49-57] comprehensively studied the relative timing of the replication and segregation of nuclear DNA (nDNA) and kinetoplast DNA (kDNA). Others have since assumed the consistency of morphological indicators of cell-cycle stage among strains and conditions. We report the use of quantitative DAPI imaging to determine the cell-cycle stage of individual procyclic cells. Using this approach, we found that kinetoplast elongation occurs mainly during nuclear S phase and not during G2, as previously assumed. We confirmed this finding by sorting cells by DNA content, followed by fluorescence microscopy. In addition, simultaneous quantitative imaging at two wavelengths can be used to determine the abundance of cell-cycle-regulated proteins during the cell cycle. We demonstrate this technique by co-staining for the non-acetylated state of lysine 4 of histone H4 (H4K4), which is enriched during nuclear S phase.

  20. Investigating the Chaperone Properties of a Novel Heat Shock Protein, Hsp70.c, from Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Adélle Burger

    2014-01-01

    Full Text Available The neglected tropical disease, African Trypanosomiasis, is fatal and has a crippling impact on economic development. Heat shock protein 70 (Hsp70 is an important molecular chaperone that is expressed in response to stress and Hsp40 acts as its co-chaperone. These proteins play a wide range of roles in the cell and they are required to assist the parasite as it moves from a cold blooded insect vector to a warm blooded mammalian host. A novel cytosolic Hsp70, from Trypanosoma brucei, TbHsp70.c, contains an acidic substrate binding domain and lacks the C-terminal EEVD motif. The ability of a cytosolic Hsp40 from Trypanosoma brucei J protein 2, Tbj2, to function as a co-chaperone of TbHsp70.c was investigated. The main objective was to functionally characterize TbHsp70.c to further expand our knowledge of parasite biology. TbHsp70.c and Tbj2 were heterologously expressed and purified and both proteins displayed the ability to suppress aggregation of thermolabile MDH and chemically denatured rhodanese. ATPase assays revealed a 2.8-fold stimulation of the ATPase activity of TbHsp70.c by Tbj2. TbHsp70.c and Tbj2 both demonstrated chaperone activity and Tbj2 functions as a co-chaperone of TbHsp70.c. In vivo heat stress experiments indicated upregulation of the expression levels of TbHsp70.c.

  1. Diversity and spation distribution of vectors and hosts of T. brucei gambiense in forest zones of Southern Cameroon: Epidemiological implications

    NARCIS (Netherlands)

    Massussi, J.A.; Mbida Mbida, J.A.; Djieto-Lordon, C.; Njiokou, F.; Laveissière, C.; Ploeg, van der J.D.

    2010-01-01

    Host and vector distribution of Trypanosoma brucei gambiense was studied in relation to habitat types and seasons. Six (19.35%) of the 31 mammal species recorded in Bipindi were reservoir hosts. Cercopithecus nictitans was confined to the undisturbed forest and the low intensive shifting cultivation

  2. Trypanosoma Brucei Aquaglyceroporins Facilitate the Uptake of Arsenite and Antimonite in a pH Dependent Way

    Directory of Open Access Journals (Sweden)

    Néstor L. Uzcátegui

    2013-09-01

    Full Text Available Background: Trypanosoma brucei is a primitive parasitic protozoan that thrives in diverse environments such as the midgut of the tsetse fly and the blood of a mammalian host. For an adequate adaptation to these environments, the parasite´s aquaglyceroporins play an important role. Methods and Results: In order to test their ability to transport trivalent arsenic and antimony, we expressed the three known Trypanosoma brucei aquaglyceroporins (TbAQPs in the heterologous systems of yeast null aquaporin mutant and Xenopus laevis oocytes. For both expression systems, we found a pH dependent intracellular accumulation of As(III or Sb(III mediated by all of the three TbAQPs, with the exception of TbAQP1-As(III uptake. Additionally, we observed that Trypanosoma brucei aquaglyceroporins allow the passage of As(III in both directions. Conclusion: Taken together, these results demonstrated that T. brucei aquaglyceroporins can serve as entry routes for As(III and Sb(III into the parasitic cell, and that this uptake is pH sensitive. Therefore, aquaporins of protozoan parasites may be considered useful as a vehicle for drug delivery.

  3. Immunospecific immunoglobulins and IL-10 as markers for Trypanosoma brucei rhodesiense late stage disease in experimentally infected vervet monkeys

    DEFF Research Database (Denmark)

    Ngotho, Maina; Kagira, J.M.; Jensen, Henrik Michael Elvang

    2009-01-01

    OBJECTIVE: To determine the usefulness of IL-10 and immunoglobulin M (IgM) as biomarkers for staging HAT in vervet monkeys, a useful pathogenesis model for humans. METHODS: Vervet monkeys were infected with Trypanosoma brucei rhodesiense and subsequently given sub-curative and curative treatment 28...

  4. Screening North American plant extracts in vitro against Trypanosoma brucei, the causative agent for Human African Trypanosomiasis

    Science.gov (United States)

    Natural products extracts from 522 plants collected from different parts of the North America were screened in vitro against trypamastigote forms of Trypanosoma brucei. The active extracts(150)with >90% inhibition at 20ug/mL concentrations from the plants namely, Alnus rubra, Hoita macrostachya, S...

  5. Computer simulation of rod-sphere mixtures

    CERN Document Server

    Antypov, D

    2003-01-01

    Results are presented from a series of simulations undertaken to investigate the effect of adding small spherical particles to a fluid of rods which would otherwise represent a liquid crystalline (LC) substance. Firstly, a bulk mixture of Hard Gaussian Overlap particles with an aspect ratio of 3:1 and hard spheres with diameters equal to the breadth of the rods is simulated at various sphere concentrations. Both mixing-demixing and isotropic-nematic transition are studied using Monte Carlo techniques. Secondly, the effect of adding Lennard-Jones particles to an LC system modelled using the well established Gay-Berne potential is investigated. These rod-sphere mixtures are simulated using both the original set of interaction parameters and a modified version of the rod-sphere potential proposed in this work. The subject of interest is the internal structure of the binary mixture and its dependence on density, temperature, concentration and various parameters characterising the intermolecular interactions. Both...

  6. Impact of AD995 alumina rods

    Energy Technology Data Exchange (ETDEWEB)

    Chhabildas, L.C.; Furnish, M.D.; Reinhart, W.D. [Sandia National Labs., Albuquerque, NM (United States); Grady, D.E. [Applied Research Associates, Inc., Albuquerque, NM (United States)

    1997-10-01

    Gas guns and velocity interferometric techniques have been used to determine the loading behavior of an AD995 alumina rod 19 mm in diameter by 75 mm and 150 mm long, respectively. Graded-density materials were used to impact both bare and sleeved alumina rods while the velocity interferometer was used to monitor the axial-velocity of the free end of the rods. Results of these experiments demonstrate that (1) a time-dependent stress pulse generated during impact allows an efficient transition from the initial uniaxial strain loading to a uniaxial stress state as the stress pulse propagates through the rod, and (2) the intermediate loading rates obtained in this configuration lie between split Hopkinson bar and shock-loading techniques.

  7. High Power Performance of Rod Fiber Amplifiers

    DEFF Research Database (Denmark)

    Johansen, Mette Marie; Michieletto, Mattia; Kristensen, Torben;

    2015-01-01

    An improved version of the DMF rod fiber is tested in a high power setup delivering 360W of stable signal power. Multiple testing degrades the fiber and transverse modal instability threshold from >360W to ~290W.......An improved version of the DMF rod fiber is tested in a high power setup delivering 360W of stable signal power. Multiple testing degrades the fiber and transverse modal instability threshold from >360W to ~290W....

  8. IMPACT CONICAL ROD ON HARD LIMITER

    Directory of Open Access Journals (Sweden)

    Ulitin G.

    2014-12-01

    Full Text Available The problem is considered of longitudinal impact conical rod in article. A recommendation on the use of the approximate method of calculation is based on an analysis of the influence of design parameters on the value of the main oscillation frequency. There was obtained an equation of the displacement and stress of the rod. Engineering dependence has been proposed to determine the maximum force in the impact section.

  9. Self-diagnosing braided composite rod

    OpenAIRE

    Fangueiro, Raúl; Zdraveva, E.; Pereira, Cristiana Gonilho; Ferreira, A; Lanceros-Méndez, S.

    2010-01-01

    This paper presents the development of a braided reinforced composite rod (BCR) able to both reinforce and monitor the stress state of concrete structures. Carbon fibers have been used as sensing and reinforcing materials along with glass fiber. Various composites rods have been produced using an author patented technique based on a modified conventional braiding machine. The materials investigated were prepared with different carbon fiber content as follows: BCR2 (77% glass/23...

  10. Microelectrophoresis of Silica Rods Using Confocal Microscopy.

    Science.gov (United States)

    Bakker, Henriëtte E; Besseling, Thijs H; Wijnhoven, Judith E G J; Helfferich, Peter H; van Blaaderen, Alfons; Imhof, Arnout

    2017-01-31

    The electrophoretic mobility and the zeta potential (ζ) of fluorescently labeled colloidal silica rods, with an aspect ratio of 3.8 and 6.1, were determined with microelectrophoresis measurements using confocal microscopy. In the case where the colloidal particles all move at the same speed parallel to the direction of the electric field, we record a xyz-stack over the whole depth of the capillary. This method is faster and more robust compared to taking xyt-series at different depths inside the capillary to obtain the parabolic flow profile, as was done in previous work from our group. In some cases, rodlike particles do not move all at the same speed in the electric field, but exhibit a velocity that depends on the angle between the long axis of the rod and the electric field. We measured the orientation-dependent velocity of individual silica rods during electrophoresis as a function of κa, where κ(-1) is the double layer thickness and a is the radius of the rod associated with the diameter. Thus, we determined the anisotropic electrophoretic mobility of the silica rods with different sized double layers. The size of the double layer was tuned by suspending silica rods in different solvents at different electrolyte concentrations. We compared these results with theoretical predictions. We show that even at already relatively high κa when the Smoluchowski limiting law is assumed to be valid (κa > 10), an orientation dependent velocity was measured. Furthermore, we observed that at decreasing values of κa the anisotropy in the electrophoretic mobility of the rods increases. However, in low polar solvents with κa < 1, this trend was reversed: the anisotropy in the electrophoretic mobility of the rods decreased. We argue that this decrease is due to end effects, which was already predicted theoretically. When end effects are not taken into account, this will lead to strong underestimation of the experimentally determined zeta potential.

  11. High-throughput rod-induced electrospinning

    Science.gov (United States)

    Wu, Dezhi; Xiao, Zhiming; Teh, Kwok Siong; Han, Zhibin; Luo, Guoxi; Shi, Chuan; Sun, Daoheng; Zhao, Jinbao; Lin, Liwei

    2016-09-01

    A high throughput electrospinning process, directly from flat polymer solution surfaces induced by a moving insulating rod, has been proposed and demonstrated. Different rods made of either phenolic resin or paper with a diameter of 1-3 cm and a resistance of about 100-500 MΩ, has been successfully utilized in the process. The rod is placed approximately 10 mm above the flat polymer solution surface with a moving speed of 0.005-0.4 m s-1 this causes the solution to generate multiple liquid jets under an applied voltage of 15-60 kV for the tip-less electrospinning process. The local electric field induced by the rod can boost electrohydrodynamic instability in order to generate Taylor cones and liquid jets. Experimentally, it is found that a large rod diameter and a small solution-to-rod distance can enhance the local electrical field to reduce the magnitude of the applied voltage. In the prototype setup with poly (ethylene oxide) polymer solution, an area of 5 cm  ×  10 cm and under an applied voltage of 60 kV, the maximum throughput of nanofibers is recorded to be approximately144 g m-2 h-1.

  12. Rigid rod anchored to infinite membrane.

    Science.gov (United States)

    Guo, Kunkun; Qiu, Feng; Zhang, Hongdong; Yang, Yuliang

    2005-08-15

    We investigate the shape deformation of an infinite membrane anchored by a rigid rod. The density profile of the rod is calculated by the self-consistent-field theory and the shape of the membrane is predicted by the Helfrich membrane elasticity theory [W. Helfrich, Z. Naturforsch. 28c, 693 (1973)]. It is found that the membrane bends away from the rigid rod when the interaction between the rod and the membrane is repulsive or weakly attractive (adsorption). However, the pulled height of the membrane at first increases and then decreases with the increase of the adsorption strength. Compared to a Gaussian chain with the same length, the rigid rod covers much larger area of the membrane, whereas exerts less local entropic pressure on the membrane. An evident gap is found between the membrane and the rigid rod because the membrane's curvature has to be continuous. These behaviors are compared with that of the flexible-polymer-anchored membranes studied by previous Monte Carlo simulations and theoretical analysis. It is straightforward to extend this method to more complicated and real biological systems, such as infinite membrane/multiple chains, protein inclusion, or systems with phase separation.

  13. Topological optimisation of rod-stirring devices

    CERN Document Server

    Finn, Matthew D

    2011-01-01

    There are many industrial situations where rods are used to stir a fluid, or where rods repeatedly stretch a material such as bread dough or taffy. The goal in these applications is to stretch either material lines (in a fluid) or the material itself (for dough or taffy) as rapidly as possible. The growth rate of material lines is conveniently given by the topological entropy of the rod motion. We discuss the problem of optimising such rod devices from a topological viewpoint. We express rod motions in terms of generators of the braid group, and assign a cost based on the minimum number of generators needed to write the braid. We show that for one cost function -- the topological entropy per generator -- the optimal growth rate is the logarithm of the golden ratio. For a more realistic cost function,involving the topological entropy per operation where rods are allowed to move together, the optimal growth rate is the logarithm of the silver ratio, $1+\\sqrt{2}$. We show how to construct devices that realise th...

  14. International symposium on fuel rod simulators: development and application

    Energy Technology Data Exchange (ETDEWEB)

    McCulloch, R.W. (comp.)

    1981-05-01

    Separate abstracts are included for each of the papers presented concerning fuel rod simulator operation and performance; simulator design and evaluation; clad heated fuel rod simulators and fuel rod simulators for cladding investigations; fuel rod simulator components and inspection; and simulator analytical modeling. Ten papers have previously been input to the Energy Data Base.

  15. Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates

    Directory of Open Access Journals (Sweden)

    Fabrice E. Graf

    2015-08-01

    Full Text Available Aquaglyceroporin-2 is a known determinant of melarsoprol–pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2–AQP3 tandem locus was described from melarsoprol–pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2–aqp3 null T. b. brucei does not. This proves that AQP2–AQP3 chimerization is the cause of melarsoprol–pentamidine cross-resistance in the T. b. gambiense isolates.

  16. Chimerization at the AQP2-AQP3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates.

    Science.gov (United States)

    Graf, Fabrice E; Baker, Nicola; Munday, Jane C; de Koning, Harry P; Horn, David; Mäser, Pascal

    2015-08-01

    Aquaglyceroporin-2 is a known determinant of melarsoprol-pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2-AQP3 tandem locus was described from melarsoprol-pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2-aqp3 null T. b. brucei does not. This proves that AQP2-AQP3 chimerization is the cause of melarsoprol-pentamidine cross-resistance in the T. b. gambiense isolates.

  17. Local Fuel Rod Crud Prediction Tool Applications

    Energy Technology Data Exchange (ETDEWEB)

    Krammen, Michael A.; Karoutas, Zeses E.; Wang, Guoqiang; Young, Michael Y

    2009-06-15

    A code system with attendant methods has been developed for modeling local fuel rod crud. This tool is used to perform the Crud Induced Localized Corrosion (CILC) risk assessment recommended by the EPRI crud and corrosion guidelines, which were developed in response to the INPO zero fuel failures by 2010 initiatives. The methodology is in production use. This paper will describe the range of problems the methodology has already been applied to and the especial pertinence to low duty fuel applications. The methodology begins with Computational Fluid Dynamics (CFD) computations over a fuel assembly grid span. The CFD results provide detailed relative variations in local heat transfer coefficient over the grid span. These very local relative variations are used to determine very local thermal hydraulic conditions over the entire axial length of every fuel rod in a reactor core over the life of the rod in reactor. The expansion using the local relative variations is currently accomplished with the HIDUTYDRV code. The very local thermal hydraulic conditions are combined with reactor coolant crud concentrations derived from EPRI BOA analysis as input to models for predicting very local fuel rod crud deposition. The reactor coolant crud concentrations are determined over each reactor cycle by reactor system wide crud mass balance calculations. The reactor coolant crud concentrations are used to calculate local crud thickness using mass transfer models which are a function of the local thermal conditions. The advanced crud deposition models also include models for calculating local crud dryout. Local crud deposition and crud dryout are strongly dependent on very local boiling or steaming, which are predicted through the translation of the CFD results. The local crud thickness and degree of local crud dryout are key factors in determining the margin or risk for local fuel rod cladding crud induced fuel failure. The development and first application of these methods was in

  18. Regulatory perspective on incomplete control rod insertions

    Energy Technology Data Exchange (ETDEWEB)

    Chatterton, M.

    1997-01-01

    The incomplete control rod insertions experienced at South Texas Unit 1 and Wolf Creek are of safety concern to the NRC staff because they represent potential precursors to loss of shutdown margin. Even before it was determined if these events were caused by the control rods or by the fuel there was an apparent correlation of the problem with high burnup fuel. It was determined that there was also a correlation between high burnup and high drag forces as well as with rod drop time histories and lack of rod recoil. The NRC staff initial actions were aimed at getting a perspective on the magnitude of the problem as far as the number of plants and the amount of fuel that could be involved, as well as the safety significance in terms of shutdown margin. As tests have been performed and data has been analyzed the focus has shifted more toward understanding the problem and the ways to eliminate it. At this time the staff`s understanding of the phenomena is that it was a combination of factors including burnup, power history and temperature. The problem appears to be very sensitive to these factors, the interaction of which is not clearly understood. The model developed by Westinghouse provides a possible explanation but there is not sufficient data to establish confidence levels and sensitivity studies involving the key parameters have not been done. While several fixes to the problem have been discussed, no definitive fixes have been proposed. Without complete understanding of the phenomena, or fixes that clearly eliminate the problem the safety concern remains. The safety significance depends on the amount of shutdown margin lost due to incomplete insertion of the control rods. Were the control rods to stick high in the core, the reactor could not be shutdown by the control rods and other means such as emergency boration would be required.

  19. Phylogeny of Trypanosoma brucei and Trypanosoma evansi in naturally infected cattle in Nigeria by analysis of repetitive and ribosomal DNA sequences.

    Science.gov (United States)

    Takeet, Michael I; Peters, Sunday O; Fagbemi, Benjamin O; De Donato, Marcos; Takeet, Vivian O; Wheto, Mathew; Imumorin, Ikhide G

    2016-08-01

    In continuing efforts to better understand the genetics of bovine trypanosomosis, we assessed genetic diversity of Trypanosoma brucei and Trypanosoma evansi in naturally infected Nigerian cattle using repetitive DNA and internal transcribed spacer 1 of rDNA sequences and compared these sequences to species from other countries. The length of repetitive DNA sequences in both species ranged from 161 to 244 bp and 239 to 240 bp for T. brucei and T. evansi, respectively, while the ITS1 rDNA sequences length range from 299 to 364 bp. The mean GC content of ITS1 rDNA sequences was 33.57 %, and that of repetitive sequences were 39.9 and 31.1 % for T. brucei and T. evansi, respectively. Result from sequence alignment revealed both T. brucei and T. evansi repetitive DNA sequences to be more polymorphic than ITS1 rDNA sequences, with moderate points of deletion and insertions. T. brucei separated into two clades when subjected to phylogenetic analysis. T. evansi repetitive DNA sequences clustered tightly within the T. brucei clade while the ITS1 rDNA sequences of T. brucei were clearly separated from T. theileri and T. vivax individually used as outgroups. This study suggest that ITS1 rDNA sequences may not be suitable for phylogenetic differentiation of the Trypanozoon group and also suggest that T. evansi may be a phenotypic variant of T. brucei which may have potential implications in designing prevention and therapeutic strategies.

  20. The contribution of chromosomal translocations to antigenic variation in Trypanosoma brucei.

    Science.gov (United States)

    Van der Ploeg, L H; Cornelissen, A W

    1984-11-13

    Genomic rearrangements influencing gene expression occur throughout nature. Several of these rearrangements disrupt normal gene expression, as exemplified by the genetic alterations caused by the mobile genetic elements of maize or Drosophila (see Shapiro 1983). Other rearrangements are part of the normal developmental programme of an organism. An understanding of the control of genomic rearrangements and their effects on gene expression should contribute to our insight into the mechanism of genetic programming and cellular development. The protozoan parasite Trypanosoma brucei exhibits a variety of genomic rearrangements that influence the expression of genes that code for versions of the variant surface glycoprotein (v.s.g.), which makes up the cell surface coat. V.s.g. genes are expressed in a mutually exclusive manner. Several v.s.g. genes are activated by duplicative transposition of the gene to a telomeric expression site where they are transcribed, while others can be activated without detectable genomic rearrangements. Recently we have been able to fractionate the chromosomes of T. brucei in agarose gels (Van der Ploeg et al. 1984 a). This led to the observations that duplicative transpositions occur inter-chromosomally and that the chromosomes of T. brucei are subject to frequent recombinations that displace hundreds of kilobase pairs. At least two and possibly more telomeric expression sites can be used for v.s.g. gene transcription. How these sites are activated and inactivated is still unsolved, but this does not depend on recombinations in the vicinity of the gene. Gross genomic rearrangements occur sometimes in correlation with antigenic switching and this suggests that such rearrangements have a function in regulating the mutually exclusive transcription of the different expression sites. V.s.g. genes consist of two exons. No physical linkage of the 35 nucleotide (n.t.) mini-exon to the v.s.g. gene main exon occurred within 15 kilobase pairs in

  1. Axial Vibration Confinement in Nonhomogenous Rods

    Directory of Open Access Journals (Sweden)

    S. Choura

    2005-01-01

    Full Text Available A design methodology for the vibration confinement of axial vibrations in nonhomogenous rods is proposed. This is achieved by a proper selection of a set of spatially dependent functions characterizing the rod material and geometric properties. Conditions for selecting such properties are established by constructing positive Lyapunov functions whose derivative with respect to the space variable is negative. It is shown that varying the shape of the rod alone is sufficient to confine the vibratory motion. In such a case, the vibration confinement requires that the eigenfunctions be exponentially decaying functions of space, where the notion of spatial domain stability is introduced as a concept dual to that of the time domain stability. It is also shown that vibration confinement can be produced if the rod density and/or stiffness are varied with respect to the space variable while the cross-section area is kept constant. Several case studies, supporting the developed conditions imposed on the spatially dependent functions for vibration confinement in vibrating rods, are discussed. Because variation in the geometric and material properties might decrease the critical buckling loads, we also discuss the buckling problem.

  2. Single Rod Vibration in Axial Flow

    Science.gov (United States)

    Weichselbaum, Noah; Wang, Shengfu; Bardet, Philippe

    2013-11-01

    Fluid structure interaction of a single rod in axial flow is a coupled dynamical system present in many application including nuclear reactors, steam generators, and towed antenna arrays. Fluid-structure response can be quantified thanks to detailed experimental data where both structure and fluid responses are recorded. Such datum deepen understanding of the physics inherent to the system and provide high-dimensionality quantitative measurements to validate coupled structural and CFD codes with various level of complexity. In this work, single rods fixed on both ends in a concentric pipe, are subjected to an axial flow with Reynolds number based on hydraulic diameter of Re =4000. Rods of varying material stiffness and diameter are utilized in the experiment resulting in a range of dimensionless U between 0.5 and 1, where U = (ρA/EI)1/2uL. Experimental measurements of the velocity field around the rod are taken with PIV from time-resolved Nd:YLF laser and a high speed CMOS camera. Three-dimensional and temporal vibration and deflection of the rod is recorded with shadowgraphy utilizing two sets of pulsed high power LED and dedicated CMOS camera. Through integration of these two diagnostics, it is possible to reconstruct the full FSI domain providing unique validation data.

  3. Dielectric rod feed for compact range reflector

    CERN Document Server

    Balabukha, Nikolay P; Shapkina, Natalia E

    2014-01-01

    A dielectric rod feed with a special radiation pattern of a tabletop form used for the compact range reflector is developed and analyzed. Application of this feed increases the size of the compact range quiet zone generated by the reflector. The feed consists of the dielectric rod made of polystyren, the rod is inserted into the circular waveguide with a corrugated flange. The waveguide is excited by the H11-mode. The rod is covered by the textolite biconical bushing and has a fluoroplastic insert in the vicinity of the bushing. Mathematical modeling was used to obtain the parameters of the feed for the optimal tabletop form of the radiation pattern. The problem of the electromagnetic radiation was solved for metal-dielectric bodies of rotation by method of integral equations with further solving of the problem of the synthesis for feed parameters. The dielectric rod feed was fabricated for the X-frequency range. Feed amplitude and phase patterns were measured in the frequency range 8.2-12.5 GHz. Presented re...

  4. Wetting of a partially immersed compliant rod

    Science.gov (United States)

    Hui, Chung-Yuen; Jagota, Anand

    2016-11-01

    The force on a solid rod partially immersed in a liquid is commonly used to determine the liquid-vapor surface tension by equating the measured force required to remove the rod from the liquid to the vertical component of the liquid-vapor surface tension. Here, we study how this process is affected when the rod is compliant. For equilibrium, we enforce force and configurational energy balance, including contributions from elastic energy. We show that, in general, the contact angle does not equal that given by Young's equation. If surface stresses are tensile, the strain in the immersed part of the rod is found to be compressive and to depend only on the solid-liquid surface stress. The strain in the dry part of the rod can be either tensile or compressive, depending on a combination of parameters that we identify. We also provide results for compliant plates partially immersed in a liquid under plane strain and plane stress. Our results can be used to extract solid surface stresses from such experiments.

  5. Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation.

    Science.gov (United States)

    Devlin, Rebecca; Marques, Catarina A; Paape, Daniel; Prorocic, Marko; Zurita-Leal, Andrea C; Campbell, Samantha J; Lapsley, Craig; Dickens, Nicholas; McCulloch, Richard

    2016-05-26

    Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating - a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility.

  6. Sec16 determines the size and functioning of the Golgi in the protist parasite, Trypanosoma brucei.

    Science.gov (United States)

    Sealey-Cardona, Marco; Schmidt, Katy; Demmel, Lars; Hirschmugl, Tatjana; Gesell, Tanja; Dong, Gang; Warren, Graham

    2014-06-01

    The Sec16 homologue in Trypanosoma brucei has been identified and characterized. TbSec16 colocalizes with COPII components at the single endoplasmic reticulum exit site (ERES), which is next to the single Golgi stack in the insect (procyclic) form of this organism. Depletion of TbSec16 reduces the size of the ERES and the Golgi, and slows growth and transport of a secretory marker to the cell surface; conversely, overexpression of TbSec16 increases the size of the ERES and Golgi but has no effect on growth or secretion. Together these data suggest that TbSec16 regulates the size of the ERES and Golgi and this size is set for optimal growth of the organism.

  7. Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice

    OpenAIRE

    Trindade, Sandra; Rijo-Ferreira, Filipa; Carvalho, Tânia; Pinto-Neves, Daniel; Guegan, Fabien; Aresta-Branco, Francisco; Bento, Fabio; Young, Simon A.; Pinto, Andreia; Van Den Abbeele, Jan; Ribeiro, Ruy M.; Dias, Sérgio; Smith, Terry K.; Figueiredo, Luisa M.

    2016-01-01

    This work was supported by 55007419 (HHMI) and 2151 (EMBO) to L.M.F., D.P.-N., F.B., and F.G.; FCT fellowships to S.T., F.R.-F., and F.A.-B. (SFRH/BPD/89833/2012, SFRH/BD/51286/2010, and SFRH/BD/80718/2011, respectively); Wellcome Trust grant (093228), MRC MR/M020118/1, and European Community Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED) to S.A.Y. and T.K.S.; and PAI 7/41 (Belspo) and ERC-NANOSYM to J.V.D.A. Trypanosoma brucei is an extracellular parasite t...

  8. Contribution of Glucose Transport to the Control of the Glycolytic Flux in Trypanosoma brucei

    Science.gov (United States)

    Bakker, Barbara M.; Walsh, Michael C.; Ter Kuile, Benno H.; Mensonides, Femke I. C.; Michels, Paul A. M.; Opperdoes, Fred R.; Westerhoff, Hans V.

    1999-08-01

    The rate of glucose transport across the plasma membrane of the bloodstream form of Trypanosoma brucei was modulated by titration of the hexose transporter with the inhibitor phloretin, and the effect on the glycolytic flux was measured. A rapid glucose uptake assay was developed to measure the transport activity independently of the glycolytic flux. Phloretin proved a competitive inhibitor. When the effect of the intracellular glucose concentration on the inhibition was taken into account, the flux control coefficient of the glucose transporter was between 0.3 and 0.5 at 5 mM glucose. Because the flux control coefficients of all steps in a metabolic pathway sum to 1, this result proves that glucose transport is not the rate-limiting step of trypanosome glycolysis. Under physiological conditions, transport shares the control with other steps. At glucose concentrations much lower than physiological, the glucose carrier assumed all control, in close agreement with model predictions.

  9. Domestic animals as potential reservoir hosts of Trypanosoma brucei gambiense in sleeping sickness foci in Cameroon

    Directory of Open Access Journals (Sweden)

    Njiokou F.

    2010-03-01

    Full Text Available An explanation of the endemic nature and/or the resurgence of Human African Trypanosomiasis (HAT in the historic foci in West and Central Africa may be the existence of an animal reservoir. In some HAT foci, pigs were found infected by Trypanosoma brucei gambiense but the implication of the other domestic animals was not quite evaluated. This study aims to determine the prevalence of T. b. gambiense in domestic animal species (goat, sheep, pig and dog commonly found in the four active HAT foci in Cameroon (Bipindi, Fontem, Campo and Doumé. Blood samples were collected from 307 pigs, 264 goats, 267 sheep and 37 dogs and used for parasitological (QBC, immunological (LiTat 1.3 CATT and molecular (PCR analyses. QBC detected trypanosomes in 3.88 % domestic animals while 22.7 % were sero-positive with LiTat 1.3 CATT tests. Of the 875 animals analysed, 174 (19.88 % harboured T. brucei s.l. DNA, found in each of the four types of animal and in the four localities. The infection rate significantly differed among the animal species (p < 0.0001 and localities (p < 0.0001. The PCR also revealed T. b. gambiense group 1 DNA in 27 (3.08 % domestic animals. The specific infection rates were as follows: sheep (6.74 %, goats (3.08 %, pigs (0.32 % and dogs (0 %. T. b. gambiense was found in 8 (3.92 % animals from Bipindi, 15 (4.83 % from Campo, 4 (2.59 % from Fontem-Center and none from Doumé. The infection rates significantly differed between the localities, and correlated with the intensity of HAT transmission in the foci.

  10. Population genetics of Trypanosoma brucei rhodesiense: clonality and diversity within and between foci.

    Directory of Open Access Journals (Sweden)

    Craig W Duffy

    2013-11-01

    Full Text Available African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda and Southern (Malawi Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics.

  11. Knockdown of Inner Arm Protein IC138 in Trypanosoma brucei Causes Defective Motility and Flagellar Detachment.

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    Corinne S Wilson

    Full Text Available Motility in the protozoan parasite Trypanosoma brucei is conferred by a single flagellum, attached alongside the cell, which moves the cell forward using a beat that is generated from tip-to-base. We are interested in characterizing components that regulate flagellar beating, in this study we extend the characterization of TbIC138, the ortholog of a dynein intermediate chain that regulates axonemal inner arm dynein f/I1. TbIC138 was tagged In situ-and shown to fractionate with the inner arm components of the flagellum. RNAi knockdown of TbIC138 resulted in significantly reduced protein levels, mild growth defect and significant motility defects. These cells tended to cluster, exhibited slow and abnormal motility and some cells had partially or fully detached flagella. Slight but significant increases were observed in the incidence of mis-localized or missing kinetoplasts. To document development of the TbIC138 knockdown phenotype over time, we performed a detailed analysis of flagellar detachment and motility changes over 108 hours following induction of RNAi. Abnormal motility, such as slow twitching or irregular beating, was observed early, and became progressively more severe such that by 72 hours-post-induction, approximately 80% of the cells were immotile. Progressively more cells exhibited flagellar detachment over time, but this phenotype was not as prevalent as immotility, affecting less than 60% of the population. Detached flagella had abnormal beating, but abnormal beating was also observed in cells with no flagellar detachment, suggesting that TbIC138 has a direct, or primary, effect on the flagellar beat, whereas detachment is a secondary phenotype of TbIC138 knockdown. Our results are consistent with the role of TbIC138 as a regulator of motility, and has a phenotype amenable to more extensive structure-function analyses to further elucidate its role in the control of flagellar beat in T. brucei.

  12. Secondary Metabolites from Vietnamese Marine Invertebrates with Activity against Trypanosoma brucei and T. cruzi

    Directory of Open Access Journals (Sweden)

    Nguyen Phuong Thao

    2014-06-01

    Full Text Available Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 < 5.0 μg/mL. Among the compounds isolated from these extracts, laevigatol B (1 from Lobophytum crassum and L. laevigatum, (24S-ergost-4-ene-3-one (2 from Sinularia dissecta, astropectenol A (3 from Astropecten polyacanthus, and cholest-8-ene-3β,5α,6β,7α-tetraol (4 from Diadema savignyi showed inhibitory activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM. Laevigatol B (1 and 5α-cholest-8(14-ene-3β,7α-diol (5 exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.

  13. Processing of the glycosomal matrix-protein import receptor PEX5 of Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Gualdrón-López, Melisa [Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Brussels (Belgium); Michels, Paul A.M., E-mail: paul.michels@uclouvain.be [Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Brussels (Belgium)

    2013-02-01

    Highlights: ► Most eukaryotic cells have a single gene for the peroxin PEX5. ► PEX5 is sensitive to in vitro proteolysis in distantly related organisms. ► TbPEX5 undergoes N-terminal truncation in vitro and possibly in vivo. ► Truncated TbPEX5 is still capable of binding PTS1-containing proteins. ► PEX5 truncation is physiologically relevant or an evolutionary conserved artifact. -- Abstract: Glycolysis in kinetoplastid protists such as Trypanosoma brucei is compartmentalized in peroxisome-like organelles called glycosomes. Glycosomal matrix-protein import involves a cytosolic receptor, PEX5, which recognizes the peroxisomal-targeting signal type 1 (PTS1) present at the C-terminus of the majority of matrix proteins. PEX5 appears generally susceptible to in vitro proteolytic processing. On western blots of T. brucei, two PEX5 forms are detected with apparent M{sub r} of 100 kDa and 72 kDa. 5′-RACE-PCR showed that TbPEX5 is encoded by a unique transcript that can be translated into a protein of maximally 72 kDa. However, recombinant PEX5 migrates aberrantly in SDS–PAGE with an apparent M{sub r} of 100 kDa, similarly as observed for the native peroxin. In vitro protease susceptibility analysis of native and {sup 35}S-labelled PEX5 showed truncation of the 100 kDa form at the N-terminal side by unknown parasite proteases, giving rise to the 72 kDa form which remains functional for PTS1 binding. The relevance of these observations is discussed.

  14. Magnetic switch for reactor control rod. [LMFBR

    Science.gov (United States)

    Germer, J.H.

    1982-09-30

    A magnetic reed switch assembly is described for activating an electromagnetic grapple utilized to hold a control rod in position above a reactor core. In normal operation the magnetic field of a permanent magnet is short-circuited by a magnetic shunt, diverting the magnetic field away from the reed switch. The magnetic shunt is made of a material having a Curie-point at the desired release temperature. Above that temperature the material loses its ferromagnetic properties, and the magnetic path is diverted to the reed switch which closes and short-circuits the control circuit for the control rod electro-magnetic grapple which allows the control rod to drop into the reactor core for controlling the reactivity of the core.

  15. HIGH STRENGTH CONTROL RODS FOR NEUTRONIC REACTORS

    Science.gov (United States)

    Lustman, B.; Losco, E.F.; Cohen, I.

    1961-07-11

    Nuclear reactor control rods comprised of highly compressed and sintered finely divided metal alloy panticles and fine metal oxide panticles substantially uniformly distributed theretbrough are described. The metal alloy consists essentially of silver, indium, cadmium, tin, and aluminum, the amount of each being present in centain percentages by weight. The oxide particles are metal oxides of the metal alloy composition, the amount of oxygen being present in certain percentages by weight and all the oxygen present being substantially in the form of metal oxide. This control rod is characterized by its high strength and resistance to creep at elevated temperatures.

  16. No gold standard estimation of the sensitivity and specificity of two molecular diagnostic protocols for Trypanosoma brucei spp. in Western Kenya.

    Directory of Open Access Journals (Sweden)

    Barend Mark de Clare Bronsvoort

    Full Text Available African animal trypanosomiasis is caused by a range of tsetse transmitted protozoan parasites includingTrypanosoma vivax, Trypanosoma congolense and Trypansoma brucei. In Western Kenya and other parts of East Africa two subspecies of T. brucei, T.b. brucei and the zoonoticT.b. rhodesiense, co-circulate in livestock. A range of polymerase chain reactions (PCR have been developed as important molecular diagnostic tools for epidemiological investigations of T. brucei s.l. in the animal reservoir and of its zoonotic potential. Quantification of the relative performance of different diagnostic PCRs is essential to ensure comparability of studies. This paper describes an evaluation of two diagnostic test systems for T. brucei using a T. brucei s.l. specific PCR [1] and a single nested PCR targeting the Internal Transcribed Spacer (ITS regions of trypanosome ribosomal DNA [2]. A Bayesian formulation of the Hui-Walter latent class model was employed to estimate their test performance in the absence of a gold standard test for detecting T.brucei s.l. infections in ear-vein blood samples from cattle, pig, sheep and goat populations in Western Kenya, stored on Whatman FTA cards. The results indicate that the system employing the T. brucei s.l. specific PCR (Se1=0.760 had a higher sensitivity than the ITS-PCR (Se2=0.640; both have high specificity (Sp1=0.998; Sp2=0.997. The true prevalences for livestock populations were estimated (pcattle=0.091, ppigs=0.066, pgoats=0.005, psheep=0.006, taking into account the uncertainties in the specificity and sensitivity of the two test systems. Implications of test performance include the required survey sample size; due to its higher sensitivity and specificity, the T. brucei s.l. specific PCR requires a consistently smaller sample size than the ITS-PCR for the detection of T. brucei s.l. However the ITS-PCR is able to simultaneously screen samples for other pathogenic trypanosomes and may thus be, overall, a better

  17. Scanning and three-dimensional electron microscopy methods for the study of Trypanosoma brucei and Leishmania mexicana flagella.

    Science.gov (United States)

    Gluenz, Eva; Wheeler, Richard John; Hughes, Louise; Vaughan, Sue

    2015-01-01

    Three-dimensional electron microscopy tools have revolutionized our understanding of cell structure and molecular complexes in biology. Here, we describe methods for studying flagellar ultrastructure and biogenesis in two unicellular parasites-Trypanosoma brucei and Leishmania mexicana. We describe methods for the preparation of these parasites for scanning electron microscopy cellular electron tomography, and serial block face scanning electron microscopy (SBFSEM). These parasites have a highly ordered cell shape and form, with a defined positioning of internal cytoskeletal structures and organelles. We show how knowledge of these can be used to dissect cell cycles in both parasites and identify the old flagellum from the new in T. brucei. Finally, we demonstrate the use of SBFSEM three-dimensional models for analysis of individual whole cells, demonstrating the excellent potential this technique has for future studies of mutant cell lines.

  18. In vitro investigation of Brazilian Cerrado plant extract activity against Plasmodium falciparum, Trypanosoma cruzi and T. brucei gambiense.

    Science.gov (United States)

    Charneau, Sébastien; de Mesquita, Mariana Laundry; Bastos, Izabela Marques Dourado; Santana, Jaime Martins; de Paula, José Elias; Grellier, Philippe; Espindola, Laila Salmen

    2016-06-01

    The threatened Brazilian Cerrado biome is an important biodiversity hotspot but still few explored that constitutes a potential reservoir of molecules to treat infectious diseases. We selected eight Cerrado plant species for screening against the erythrocytic stages of Plasmodium falciparum, human intracellular stages of Trypanosoma cruzi and bloodstream forms of T. brucei gambiense, and for their cytotoxicity upon the rat L6-myoblast cell line. Bioassays were performed with 37 hexane, ethyl acetate and ethanol extracts prepared from different plant organs. Activities against parasites were observed for 24 extracts: 9 with anti-P. falciparum, 4 with anti-T. cruzi and 11 with anti-T. brucei gambiense activities. High anti-protozoal activity (IC50 values Cerrado conservation and sustainable development.

  19. Inhibitors of the mitochondrial cytochrome b-c1 complex inhibit the cyanide-insensitive respiration of Trypanosoma brucei.

    Science.gov (United States)

    Turrens, J F; Bickar, D; Lehninger, A L

    1986-06-01

    The cyanide-insensitive respiration of bloodstream trypomastigote forms of Trypanosoma brucei (75 +/- 8 nmol O2 min-1(mg protein)-1) is completely inhibited by the mitochondrial ubiquinone-like inhibitors 2-hydroxy-3-undecyl-1,4-naphthoquinone (UHNQ) and 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT). The Ki values for UHDBT (30 nM) and UHNQ (2 microM) are much lower than the reported Ki for salicylhydroxamic acid (SHAM) (5 microM), a widely used inhibitor of the cyanide-insensitive oxidase. UHNQ also stimulated the glycerol-3-phosphate-dependent reduction of phenazine methosulfate, demonstrating that the site of UHNQ inhibition is on the terminal oxidase of the cyanide-insensitive respiration of T. brucei. These results suggest that a ubiquinone-like compound may act as an electron carrier between the two enzymatic components of the cyanide-insensitive glycerol-3-phosphate oxidase.

  20. TbFlabarin, a flagellar protein of Trypanosoma brucei, highlights differences between Leishmania and Trypanosoma flagellar-targeting signals.

    Science.gov (United States)

    Tetaud, Emmanuel; Lefebvre, Michèle; M'Bang-Benet, Diane-Ethna; Crobu, Lucien; Blancard, Corinne; Sterkers, Yvon; Pages, Michel; Bastien, Patrick; Merlin, Gilles

    2016-07-01

    TbFlabarin is the Trypanosoma brucei orthologue of the Leishmania flagellar protein LdFlabarin but its sequence is 33% shorter than LdFlabarin, as it lacks a C-terminal domain that is indispensable for LdFlabarin to localize to the Leishmania flagellum. TbFlabarin is mainly expressed in the procyclic forms of the parasite and localized to the flagellum, but only when two palmitoylable cysteines at positions 3 and 4 are present. TbFlabarin is more strongly attached to the membrane fraction than its Leishmania counterpart, as it resists complete solubilization with as much as 0.5% NP-40. Expression ablation by RNA interference did not change parasite growth in culture, its morphology or apparent motility. Heterologous expression showed that neither TbFlabarin in L. amazonensis nor LdFlabarin in T. brucei localized to the flagellum, revealing non-cross-reacting targeting signals between the two species.

  1. Comparative genomics reveals two novel RNAi factors in Trypanosoma brucei and provides insight into the core machinery.

    Directory of Open Access Journals (Sweden)

    Rebecca L Barnes

    Full Text Available The introduction ten years ago of RNA interference (RNAi as a tool for molecular exploration in Trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. In particular, a genome-wide RNAi screen has recently been combined with next-generation Illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. At present, this technology is restricted to RNAi-positive protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium falciparum. Therefore, elucidating the mechanism of RNAi and identifying the essential components of the pathway is fundamental for improving RNAi efficiency in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here we used comparative genomics of RNAi-positive and -negative trypanosomatid protozoans to identify the repertoire of factors in T. brucei. In addition to the previously characterized Argonaute 1 (AGO1 protein and the cytoplasmic and nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA Interference Factors 4 and 5 (TbRIF4 and TbRIF5. TbRIF4 is a 3'-5' exonuclease of the DnaQ superfamily and plays a critical role in the conversion of duplex siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi and appears to act as a TbDCL1 cofactor. The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites.

  2. T. brucei infection reduces B lymphopoiesis in bone marrow and truncates compensatory splenic lymphopoiesis through transitional B-cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Viki Bockstal

    2011-06-01

    Full Text Available African trypanosomes of the Trypanosoma brucei species are extracellular protozoan parasites that cause the deadly disease African trypanosomiasis in humans and contribute to the animal counterpart, Nagana. Trypanosome clearance from the bloodstream is mediated by antibodies specific for their Variant Surface Glycoprotein (VSG coat antigens. However, T. brucei infection induces polyclonal B cell activation, B cell clonal exhaustion, sustained depletion of mature splenic Marginal Zone B (MZB and Follicular B (FoB cells, and destruction of the B-cell memory compartment. To determine how trypanosome infection compromises the humoral immune defense system we used a C57BL/6 T. brucei AnTat 1.1 mouse model and multicolor flow cytometry to document B cell development and maturation during infection. Our results show a more than 95% reduction in B cell precursor numbers from the CLP, pre-pro-B, pro-B, pre-B and immature B cell stages in the bone marrow. In the spleen, T. brucei induces extramedullary B lymphopoiesis as evidenced by significant increases in HSC-LMPP, CLP, pre-pro-B, pro-B and pre-B cell populations. However, final B cell maturation is abrogated by infection-induced apoptosis of transitional B cells of both the T1 and T2 populations which is not uniquely dependent on TNF-, Fas-, or prostaglandin-dependent death pathways. Results obtained from ex vivo co-cultures of living bloodstream form trypanosomes and splenocytes demonstrate that trypanosome surface coat-dependent contact with T1/2 B cells triggers their deletion. We conclude that infection-induced and possibly parasite-contact dependent deletion of transitional B cells prevents replenishment of mature B cell compartments during infection thus contributing to a loss of the host's capacity to sustain antibody responses against recurring parasitemic waves.

  3. Trypanosoma brucei rhodesiense infection in a German traveller returning from the Masai Mara area, Kenya, January 2012.

    Science.gov (United States)

    Wolf, T; Wichelhaus, T; Gottig, S; Kleine, C; Brodt, H R; Just-Nuebling, G

    2012-03-08

    In January 2012, a case of Human African Trypanosomiasis (HAT) has been identified in Germany in a traveller returning from the Masai Mara area in Kenya. The 62-year-old man had travelled to the Masai Mara game park from 18 to 19 January 2012 and developed fever on 28 January. The infection with Trypanosoma brucei rhodesiense was confirmed by laboratory testing three days hereafter.

  4. A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Sharlow

    Full Text Available BACKGROUND: The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host. The first step in this metabolic pathway is mediated by hexokinase (TbHK, an enzyme essential to the parasite that transfers the gamma-phospho of ATP to a hexose. Here we describe the identification and confirmation of novel small molecule inhibitors of bacterially expressed TbHK1, one of two TbHKs expressed by T. brucei, using a high throughput screening assay. METHODOLOGY/PRINCIPAL FINDINGS: Exploiting optimized high throughput screening assay procedures, we interrogated 220,233 unique compounds and identified 239 active compounds from which ten small molecules were further characterized. Computation chemical cluster analyses indicated that six compounds were structurally related while the remaining four compounds were classified as unrelated or singletons. All ten compounds were approximately 20-17,000-fold more potent than lonidamine, a previously identified TbHK1 inhibitor. Seven compounds inhibited T. brucei blood stage form parasite growth (0.03brucei parasites, Leishmania promastigotes, and mammalian cell lines. Analysis of two structurally related compounds, ebselen and SID 17387000, revealed that both were mixed inhibitors of TbHK1 with respect to ATP. Additionally, both compounds inhibited parasite lysate-derived HK activity. None of the compounds displayed structural similarity to known hexokinase inhibitors or human African trypanosomiasis therapeutics. CONCLUSIONS/SIGNIFICANCE: The novel chemotypes identified here could represent leads for future therapeutic development against the African trypanosome.

  5. Evolutionary consequences of a large duplication event in Trypanosoma brucei: Chromosomes 4 and 8 are partial duplicons

    Directory of Open Access Journals (Sweden)

    Jackson Andrew P

    2007-11-01

    Full Text Available Abstract Background Gene order along the genome sequence of the human parasite Trypanosoma brucei provides evidence for a 0.5 Mb duplication, comprising the 3' regions of chromosomes 4 and 8. Here, the principal aim was to examine the contribution made by this duplication event to the T. brucei genome sequence, emphasising the consequences for gene content and the evolutionary change subsequently experienced by paralogous gene copies. The duplicated region may be browsed online at http://www.genedb.org/genedb/tryp/48dup_image.jsp Results Comparisons of trypanosomatid genomes demonstrated widespread gene loss from each duplicon, but also showed that 47% of duplicated genes were retained on both chromosomes as paralogous loci. Secreted and surface-expressed genes were over-represented among retained paralogs, reflecting a bias towards important factors at the host-parasite interface, and consistent with a dosage-balance hypothesis. Genetic divergence in both coding and regulatory regions of retained paralogs was bimodal, with a deficit in moderately divergent paralogs; in particular, non-coding sequences were either conserved or entirely remodelled. The conserved paralogs included examples of remarkable sequence conservation, but also considerable divergence of both coding and regulatory regions. Sequence divergence typically displayed strong negative selection; but several features, such as asymmetric evolutionary rates, positively-selected codons and other non-neutral substitutions, suggested that divergence of some paralogs was driven by functional change. The absence of orthologs to retained paralogs in T. congolense indicated that the duplication event was specific to T. brucei. Conclusion The duplication of this chromosomal region doubled the dosage of many genes. Rather than creating 'more of the same', these results show that paralogs were structurally modified according to various evolutionary trajectories. The retention of paralogs, and

  6. Modeling and simulation performance of sucker rod beam pump

    Energy Technology Data Exchange (ETDEWEB)

    Aditsania, Annisa, E-mail: annisaaditsania@gmail.com [Department of Computational Sciences, Institut Teknologi Bandung (Indonesia); Rahmawati, Silvy Dewi, E-mail: silvyarahmawati@gmail.com; Sukarno, Pudjo, E-mail: psukarno@gmail.com [Department of Petroleum Engineering, Institut Teknologi Bandung (Indonesia); Soewono, Edy, E-mail: esoewono@math.itb.ac.id [Department of Mathematics, Institut Teknologi Bandung (Indonesia)

    2015-09-30

    Artificial lift is a mechanism to lift hydrocarbon, generally petroleum, from a well to surface. This is used in the case that the natural pressure from the reservoir has significantly decreased. Sucker rod beam pumping is a method of artificial lift. Sucker rod beam pump is modeled in this research as a function of geometry of the surface part, the size of sucker rod string, and fluid properties. Besides its length, sucker rod string also classified into tapered and un-tapered. At the beginning of this research, for easy modeling, the sucker rod string was assumed as un-tapered. The assumption proved non-realistic to use. Therefore, the tapered sucker rod string modeling needs building. The numerical solution of this sucker rod beam pump model is computed using finite difference method. The numerical result shows that the peak of polished rod load for sucker rod beam pump unit C-456-D-256-120, for non-tapered sucker rod string is 38504.2 lb, while for tapered rod string is 25723.3 lb. For that reason, to avoid the sucker rod string breaks due to the overload, the use of tapered sucker rod beam string is suggested in this research.

  7. Modeling and simulation performance of sucker rod beam pump

    Science.gov (United States)

    Aditsania, Annisa; Rahmawati, Silvy Dewi; Sukarno, Pudjo; Soewono, Edy

    2015-09-01

    Artificial lift is a mechanism to lift hydrocarbon, generally petroleum, from a well to surface. This is used in the case that the natural pressure from the reservoir has significantly decreased. Sucker rod beam pumping is a method of artificial lift. Sucker rod beam pump is modeled in this research as a function of geometry of the surface part, the size of sucker rod string, and fluid properties. Besides its length, sucker rod string also classified into tapered and un-tapered. At the beginning of this research, for easy modeling, the sucker rod string was assumed as un-tapered. The assumption proved non-realistic to use. Therefore, the tapered sucker rod string modeling needs building. The numerical solution of this sucker rod beam pump model is computed using finite difference method. The numerical result shows that the peak of polished rod load for sucker rod beam pump unit C-456-D-256-120, for non-tapered sucker rod string is 38504.2 lb, while for tapered rod string is 25723.3 lb. For that reason, to avoid the sucker rod string breaks due to the overload, the use of tapered sucker rod beam string is suggested in this research.

  8. Piston rod seal for a Stirling engine

    Science.gov (United States)

    Shapiro, Wilbur

    1984-01-01

    In a piston rod seal for a Stirling engine, a hydrostatic bearing and differential pressure regulating valve are utilized to provide for a low pressure differential across a rubbing seal between the hydrogen and oil so as to reduce wear on the seal.

  9. Fabrication of preliminary fuel rods for SFR

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Ki; Oh, Seok Jin; Ko, Young Mo; Woo, Youn Myung; Kim, Ki Hwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-05-15

    Metal fuels was selected for fueling many of the first reactors in the US, including the Experimental Breeder Reactor-I (EBR-I) and the Experimental Breeder Reactor-II (EBR-II) in Idaho, the FERMI-I reactor, and the Dounreay Fast Reactor (DFR) in the UK. Metallic U.Pu.Zr alloys were the reference fuel for the US Integral Fast Reactor (IFR) program. Metallic fuel has advantages such as simple fabrication procedures, good neutron economy, high thermal conductivity, excellent compatibility with a Na coolant and inherent passive safety. U-Zr-Pu alloy fuels have been used for SFR (sodium-cooled fast reactor) related to the closed fuel cycle for managing minor actinides and reducing a high radioactivity levels since the 1980s. Fabrication technology of metallic fuel for SFR has been in development in Korea as a national nuclear R and D program since 2007. For the final goal of SFR fuel rod fabrication with good performance, recently, three preliminary fuel rods were fabricated. In this paper, the preliminary fuel rods were fabricated, and then the inspection for QC(quality control) of the fuel rods was performed

  10. Adjustable solitary waves in electroactive rods

    Science.gov (United States)

    Wang, Y. Z.; Zhang, C. L.; Dai, H.-H.; Chen, W. Q.

    2015-10-01

    This paper presents an asymptotic analysis of solitary waves propagating in an incompressible isotropic electroactive circular rod subjected to a biasing longitudinal electric displacement. Several asymptotic expansions are introduced to simplify the rod governing equations. The boundary conditions on the lateral surface of the rod are satisfied from the asymptotic point of view. In the limit of finite-small amplitude and long wavelength, a set of ten simplified one-dimensional nonlinear governing equations is established. To validate our approach and the derivation, we compare the linear dispersion relation with the one directly derived from the three-dimensional linear theory in the limit of long wavelength. Then, by the reductive perturbation method, we deduce the far-field equation (i.e. the KdV equation). Finally, the leading order of the electroelastic solitary wave solution is presented. Numerical examples are provided to show the influences of the biasing electric displacement and material constants on the solitary waves. It is found that the biasing electric displacement can modulate the velocity of solitary waves with a prescribed amplitude in the electroactive rod, a very interesting result which may promote the particular application of solitary waves in solids with multi-field coupling.

  11. Chemopreventive effect of methanolic extract of Azadirachta indica on experimental Trypanosoma brucei induced oxidative stress in dogs

    Directory of Open Access Journals (Sweden)

    Temidayo O Omobowale

    2015-01-01

    Full Text Available Introduction: The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals. Materials and Methods: Twenty-five apparently healthy dogs weighing between 3 and 8 kg were randomly divided into five groups with five dogs in each group. Ameliorative effect of A. indica on erythrocyte antioxidant status and markers of oxidative stress were assessed. Liver and kidney function tests were also performed. Results: Pre-treatment with methanolic extract of Azadirachta indica (MEAI at different doses did not significantly alter the values of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity in Trypanosoma brucei infection. Although, serum creatinine significantly (P 0.05 difference compared to the values obtained in pre-treated animals. Pre-treatment with 100 mg/kg and 200 mg/kg of A. indica significantly (P < 0.05 decreased serum myeloperoxidase activity at 2 weeks post-infection with T. brucei. Conclusion: From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection.

  12. Validation Test of CARR Safety Rod Driving Mechanism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>CARR safety Rods are driven by hydraulic force. The safety rod driving mechanism is designed by Tsinghua University and manufactured by Shenyang LIMING factory. Two sets of the mechanism are used for the validation test.

  13. Stimulus-evoked outer segment changes in rod photoreceptors

    Science.gov (United States)

    Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Lu, Yiming; Gai, Shaoyan; Yao, Xincheng

    2016-06-01

    Rod-dominated transient retinal phototropism (TRP) has been recently observed in freshly isolated mouse and frog retinas. Comparative confocal microscopy and optical coherence tomography revealed that the TRP was predominantly elicited from the rod outer segment (OS). However, the biophysical mechanism of rod OS dynamics is still unknown. Mouse and frog retinal slices, which displayed a cross-section of retinal photoreceptors and other functional layers, were used to test the effect of light stimulation on rod OSs. Time-lapse microscopy revealed stimulus-evoked conformational changes of rod OSs. In the center of the stimulated region, the length of the rod OS shrunk, while in the peripheral region, the rod OS swung toward the center region. Our experimental observation and theoretical analysis suggest that the TRP may reflect unbalanced rod disc-shape changes due to localized visible light stimulation.

  14. Longitudinal Vibrations of Rheological Rod With Variable Cross Section

    Institute of Scientific and Technical Information of China (English)

    Katica(Stevanovic)HEDRIH; AleksandarFILIPOVSKI

    1999-01-01

    Longitudinal vibrations of rheological rod with variable cross section are examined.Particular solutions and eigenfunction are accomplished for natural vibrations of the rod with hereditary material of standard hereditary body.Some examples are given.

  15. Sucker rod string design of the pumping systems

    Directory of Open Access Journals (Sweden)

    Chun Hua Liu

    2015-08-01

    Full Text Available The existing design of sucker rod string mainly focuses on the simplifying assumptions that rod string was exposed to simple tension loading. And its goal was to have equal modified stress at the top of each taper. The improved rod design was to have the same degree of safety at each section, and it used a dynamic force distribution that was proportional along the whole string. However, the available procedures did not provide the desired accuracy of its pertinent analysis, and the operators could not identify the specific phenomena that occur in CBM wells. In this paper, the mathematical models of rod loads and string length were developed based on the cyclic nature of rod string loading; the fatigue endurance method is used to design the single rod string; and the tapered rod string is designed to have an equal equivalent stress at the top of each section. Its application characteristics are demonstrated by the example of CBM wells in Ordos Basin. The interpretations of results show that the previous design gave the single rods a larger diameter and the top rods in the string a greater percent than the proposed method. The calculation should concern about inertial, vibration and friction forces to illustrate the elastic force waves travelling in the rod material with the speed of sound. The single string should be designed using fatigue endurance ratings due to asymmetric pulsating tension of rod loading; and the tapered string should involve a balanced design by setting the fatigue endurance at each section equal. A shorter stroke length gives a greater rod taper percentage and an increased load capacity results to an enhanced rod diameter. The rod diameter increases with the pump size and load capacity for the single string, and the rod taper percentage of the top rod strings increases with plunger diameter for the tapered string. The proposed research improves efficiency of the pumping system, assures good operating conditions, and reduces

  16. Investigation of control rod worth and nuclear end of life of BWR control rods

    Energy Technology Data Exchange (ETDEWEB)

    Magnusson, Per

    2008-01-15

    This work has investigated the Control Rod Worth (CRW) and Nuclear End of Life (NEOL) values for BWR control rods. A study of how different parameters affect NEOL was performed with the transport code PHOENIX4. It was found that NEOL, expressed in terms of {sup 10}B depletion, can be generalized beyond the conditions for which the rod is depleted, such as different power densities and void fractions, the corresponding variation in the NEOL will be about 0.2-0.4% {sup 10}B. It was also found that NEOL results for different fuel types and different fuel enrichments have a variation of about 2-3% in {sup 10}B depletion. A comparative study on NHOL and CRW was made between PHOENIX4 and the stochastic Monte Carlo code MCNP. It was found that there is a significant difference, both due to differences in the codes and to limitations in the geometrical modeling in PHOENIX4. Since MCNP is considered more physically correct, a methodology was developed to calculate the nuclear end of life of BWR control rods with MCNP. The advantages of the methodology are that it does not require other codes to perform the depletion of the absorber material, it can describe control rods of any design and it can deplete the control rod absorber material without burning the fuel. The disadvantage of the method is that is it time-consuming.

  17. 77 FR 1504 - Stainless Steel Wire Rod From India

    Science.gov (United States)

    2012-01-10

    ... COMMISSION Stainless Steel Wire Rod From India Determination On the basis of the record \\1\\ developed in the... antidumping duty order on stainless steel wire rod From India would be likely to lead to continuation or... contained in USITC Publication 4300 (January 2012), entitled Stainless Steel Wire Rod From...

  18. Carbon Inverse Opal Rods for Nonenzymatic Cholesterol Detection.

    Science.gov (United States)

    Zhong, Qifeng; Xie, Zhuoying; Ding, Haibo; Zhu, Cun; Yang, Zixue; Gu, Zhongze

    2015-11-18

    Carbon inverse opal rods made from silica photonic crystal rods are used for nonenzymatic cholesterol sensing. The characteristic reflection peak originating from the physical periodic structure works as sensing signals for quantitatively estimating cholesterol concentrations. Carbon inverse opal rods work both in cholesterol standard solutions and human serum. They are suitable for practical use in clinical diagnose.

  19. Rod Has High Tensile Strength And Low Thermal Expansion

    Science.gov (United States)

    Smith, D. E.; Everton, R. L.; Howe, E.; O'Malley, M.

    1996-01-01

    Thoriated tungsten extension rod fabricated to replace stainless-steel extension rod attached to linear variable-differential transformer in gap-measuring gauge. Threads formed on end of rod by machining with special fixtures and carefully chosen combination of speeds and feeds.

  20. High-yield production of hydrophobins RodA and RodB from Aspergillus fumigatus in Pichia pastoris

    DEFF Research Database (Denmark)

    Pedersen, Mona Højgaard; Borodina, Irina; Moresco, Jacob Lange;

    2011-01-01

    A as well as rRodB were able to convert a glass surface from hydrophilic to hydrophobic similar to native RodA, but only rRodB was able to decrease the hydrophobicity of a Teflon-like surface to the same extent as native RodA, while rRodA showed this ability to a lesser extent. Recombinant RodA and native......Hydrophobins are small fungal proteins with amphipatic properties and the ability to self-assemble on a hydrophobic/hydrophilic interface; thus, many technical applications for hydrophobins have been suggested. The pathogenic fungus Aspergillus fumigatus expresses the hydrophobins RodA and Rod...

  1. Changes in blood sugar levels of rats experimentally infected withTrypanosoma brucei and treated with imidocarb dipropionate and diminazene aceturate

    Institute of Scientific and Technical Information of China (English)

    Nwoha Rosemary Ijeoma Ogechi; Omamegbe Joseph Omalathebu

    2016-01-01

    Objective:To determine the effect ofTrypanosoma brucei (T. brucei) on blood sugar level of infected rats. Methods: The experiment was done with 42 albino rats grouped into 3 groups of 14 members each. Group A was uninfected (control group), Group B was infected withT. brucei and treated with diminazene aceturate, and Group C was infected withT. brucei and treated with imidocarb dipropionate. Blood samples were collected from the media canthus of the experimental rats on Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 for the assessment of change in blood sugar levels. The blood sugar levels were determined with a glucometer (Accu-chek active serialNo.GN:10023338). Results: By 4 to 5 days post infection, there was a significant increase (P 0.05) was observed in the groups when compared with the control group till Day 12 of the experiment. Conclusions:T. brucei caused a significant increase in blood sugar of infected rats.

  2. Transport proteins determine drug sensitivity and resistance in a protozoan parasite, Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Jane Claire Munday

    2015-03-01

    Full Text Available Drug resistance in pathogenic protozoa is very often caused by changes to the ‘transportome’ of the parasites. In Trypanosoma brucei, several transporters have been implicated in uptake of the main classes of drugs, diamidines and melaminophenyl arsenicals. The resistance mechanism had been thought to be due to loss of a transporter known to carry both types of agents: the aminopurine transporter P2, encoded by the gene TbAT1. However, although loss of P2 activity is well-documented as the cause of resistance to the veterinary diamidine diminazene aceturate (Berenil®, cross-resistance between the human-use arsenical melarsoprol and the diamidine pentamidine (MPXR is the result of loss of a separate High Affinity Pentamidine Transporter (HAPT1. A genome-wide RNAi library screen for resistance to pentamidine, published in 2012, gave the key to the genetic identity of HAPT1 by linking the phenomenon to a locus that contains the closely related T. brucei aquaglyceroporin genes TbAQP2 and TbAQP3. Further analysis determined that knockdown of only one pore, TbAQP2, produced the MPXR phenotype. TbAQP2 is an unconventional aquaglyceroporin with unique residues in the selectivity region of the pore, and it was found that in several MPXR lab strains the WT gene was either absent or replaced by a chimeric protein, recombined with parts of TbAQP3. Importantly, wild-type AQP2 was also absent in field isolates of T. b. gambiense, correlating with the outcome of melarsoprol treatment. Expression of a wild-type copy of TbAQP2 in even the most resistant strain completely reversed MPXR and re-introduced HAPT1 function and transport kinetics. Expression of TbAQP2 in Leishmania mexicana introduced a pentamidine transport activity indistinguishable from HAPT1. Although TbAQP2 has been shown to function as a classical aquaglyceroporin it is now clear that it is also a high affinity drug transporter, HAPT1. We discuss here a possible structural rationale for this

  3. Transport proteins determine drug sensitivity and resistance in a protozoan parasite, Trypanosoma brucei

    Science.gov (United States)

    Munday, Jane C.; Settimo, Luca; de Koning, Harry P.

    2015-01-01

    Drug resistance in pathogenic protozoa is very often caused by changes to the ‘transportome’ of the parasites. In Trypanosoma brucei, several transporters have been implicated in uptake of the main classes of drugs, diamidines and melaminophenyl arsenicals. The resistance mechanism had been thought to be due to loss of a transporter known to carry both types of agents: the aminopurine transporter P2, encoded by the gene TbAT1. However, although loss of P2 activity is well-documented as the cause of resistance to the veterinary diamidine diminazene aceturate (DA; Berenil®), cross-resistance between the human-use arsenical melarsoprol and the diamidine pentamidine (melarsoprol/pentamidine cross resistance, MPXR) is the result of loss of a separate high affinity pentamidine transporter (HAPT1). A genome-wide RNAi library screen for resistance to pentamidine, published in 2012, gave the key to the genetic identity of HAPT1 by linking the phenomenon to a locus that contains the closely related T. brucei aquaglyceroporin genes TbAQP2 and TbAQP3. Further analysis determined that knockdown of only one pore, TbAQP2, produced the MPXR phenotype. TbAQP2 is an unconventional aquaglyceroporin with unique residues in the “selectivity region” of the pore, and it was found that in several MPXR lab strains the WT gene was either absent or replaced by a chimeric protein, recombined with parts of TbAQP3. Importantly, wild-type AQP2 was also absent in field isolates of T. b. gambiense, correlating with the outcome of melarsoprol treatment. Expression of a wild-type copy of TbAQP2 in even the most resistant strain completely reversed MPXR and re-introduced HAPT1 function and transport kinetics. Expression of TbAQP2 in Leishmania mexicana introduced a pentamidine transport activity indistinguishable from HAPT1. Although TbAQP2 has been shown to function as a classical aquaglyceroporin it is now clear that it is also a high affinity drug transporter, HAPT1. We discuss here a

  4. Oligo(naphthylene–ethynylene) Molecular Rods

    DEFF Research Database (Denmark)

    Cramer, Jacob Roland; Ning, Yanxiao; Shen, Cai;

    2013-01-01

    Molecular rods designed for surface chirality studies have been synthesized in high yields. The molecules are composed of oligo(naphthylene–ethynylene) skeletons and functionalized at their two termini with carboxylic acids and hydrophobic groups. The molecular skeletons were constructed by means...... of palladium-catalyzed Sonogashira reactions between naphthyl halides and acetylenes. The triazene functionality was used as a protected iodine precursor to allow linear extension of the molecular rods during the synthe-ses. The carboxylic acid groups in the target molecules were protected as esters during...... the synthesis to keep the large aromatic molecules soluble during their syntheses. These rigid oligomers were designed to form lamella-like structures when adsorbed on a surface, through which multiple distinguishable surface conformations should be obtainable. Preliminary scanning tunneling microscopy imaging...

  5. Photonic mesophases from cut rod rotators

    Energy Technology Data Exchange (ETDEWEB)

    Stelson, Angela C.; Liddell Watson, Chekesha M., E-mail: cml66@cornell.edu [Materials Science and Engineering, Cornell University, Ithaca, New York 14853 (United States); Avendano, Carlos [Chemical Engineering and Analytical Science, The University of Manchester, Manchester M13 9PL (United Kingdom)

    2016-01-14

    The photonic band properties of random rotator mesophases are calculated using supercell methods applied to cut rods on a hexagonal lattice. Inspired by the thermodynamic mesophase for anisotropic building blocks, we vary the shape factor of cut fraction for the randomly oriented basis. We find large, stable bandgaps with high gap isotropy in the inverted and direct structures as a function of cut fraction, dielectric contrast, and filling fraction. Bandgap sizes up to 34.5% are maximized at high dielectric contrast for rods separated in a matrix. The bandgaps open at dielectric contrasts as low as 2.0 for the transverse magnetic polarization and 2.25 for the transverse electric polarization. Additionally, the type of scattering that promotes the bandgap is correlated with the effect of disorder on bandgap size. Slow light properties are investigated in waveguide geometry and slowdown factors up to 5 × 10{sup 4} are found.

  6. Instabilities of a rotating helical rod

    Science.gov (United States)

    Park, Yunyoung; Ko, William; Kim, Yongsam; Lim, Sookkyung

    2016-11-01

    Bacteria such as Escherichia coli and Vibrio alginolyticus have helical flagellar filament. By rotating a motor, which is located at the bottom end of the flagellar filament embedded in the cell body, CCW or CW, they swim forward or backward. We model a left-handed helix by the Kirchhoff rod theory and use regularized Stokes formulation to study an interaction between the surrounding fluid and the flagellar filament. We perform numerical studies focusing on relations between physical parameters and critical angular frequency of the motor, which separates overwhiring from twirling. We are also interested in the buckling instability of the hook, which is very flexible elastic rod. By measuring buckling angle, which is an angle between rotational axis and helical axis, we observe the effects of physical parameters on buckling of the hook.

  7. STUDY ON A HYDROPHOBIC-HYDROPHILIC GRADIENT ROD

    Institute of Scientific and Technical Information of China (English)

    Jun Ma; Bai-yu Li; Hai-yun Liu; Zhi-min Zheng; Jian Xu

    2004-01-01

    A hydrophobic-hydrophilic gradient rod with a length of 40 mm and a diameter of 3 mm was prepared by heating a polymethylsilsesquioxane rod in a cylindrical stove with temperature gradient. The rod was thus pyrolyzed under a temperature gradient condition. The organic end of the gradient rod appears hydrophobic with a contact angle of 109.9° while the other end is hydrophilic with a contact angle of 62.4°. The gradient chemical structure and the gradient microstructure along the rod were characterized by FTIR and SEM, respectively.

  8. Test Research on Special Sucker Rod for Screw Pump

    Institute of Scientific and Technical Information of China (English)

    Zhang Mingyi; Chen Mingzhan; Li Zhi

    2006-01-01

    @@ According to the statistics of straight thread sucker rods' application in screw pump in Daqing Oilfield before2000, the proportion of sucker rods' yearly breakaway reached to 41.6%, taking up 70% of the total wells that were checked. Thus it can be seen that the rods breakaway problem was becoming the main barrier restricting screw pump large-scale population and application. Since then,the development work on the special sucker rods for screw pump had been carried on. Through the analysis on the failure position and failure form of the sucker rods',the following conclusions arepresented:

  9. Hollow Sucker Rod Applied in Production Engineering

    Institute of Scientific and Technical Information of China (English)

    Wang Tongbin; Liu Liandong; Hu Daoming; Jia Yanshan

    1997-01-01

    @@ Working Principle A positive cycle system or a working channel can be formed by means of hollow sucker rod and its mating parts in the oil tube ofa well, through which heat carriers (such as hot water,hot oil and steam), chemicals and heating cable can be pumped or put into the well so as to lower the viscosity of crude, dissolve the paraffin building-up and open the conduit, thus leading to the smooth oil flow out of well.

  10. Rod Driven Frequency Entrainment and Resonance Phenomena

    Directory of Open Access Journals (Sweden)

    Christina Salchow

    2016-08-01

    Full Text Available A controversy exists on photic driving in the human visual cortex evoked by intermittent photic stimulation. Frequency entrainment and resonance phenomena are reported for frequencies higher than 12 Hz in some studies while missing in others. We hypothesized that this might be due to different experimental conditions, since both high and low intensity light stimulation were used. However, most studies do not report radiometric measurements, which makes it impossible to categorize the stimulation according to photopic, mesopic, and scotopic vision. Low intensity light stimulation might lead to scotopic vision, where rod perception dominates. In this study, we investigated photic driving for rod-dominated visual input under scotopic conditions. Twelve healthy volunteers were stimulated with low intensity light flashes at 20 stimulation frequencies, leading to rod activation only. The frequencies were multiples of the individual alpha frequency (α of each volunteer in the range from 0.40–2.30*α. 306-channel whole head magnetoencephalography recordings were analyzed in time, frequency, and spatiotemporal domains with the Topographic Matching Pursuit algorithm. We found resonance phenomena and frequency entrainment for stimulations at or close to the individual alpha frequency (0.90–1.10*α and half of the alpha frequency (0.40–0.55*α. No signs of resonance and frequency entrainment phenomena were revealed around 2.00*α. Instead, on-responses at the beginning and off-responses at the end of each stimulation train were observed for the first time in a photic driving experiment at frequencies of 1.30–2.30*α, indicating that the flicker fusion threshold was reached. All results, the resonance and entrainment as well as the fusion effects, provide evidence for rod-dominated photic driving in the visual cortex.

  11. Rod Driven Frequency Entrainment and Resonance Phenomena

    Science.gov (United States)

    Salchow, Christina; Strohmeier, Daniel; Klee, Sascha; Jannek, Dunja; Schiecke, Karin; Witte, Herbert; Nehorai, Arye; Haueisen, Jens

    2016-01-01

    A controversy exists on photic driving in the human visual cortex evoked by intermittent photic stimulation. Frequency entrainment and resonance phenomena are reported for frequencies higher than 12 Hz in some studies while missing in others. We hypothesized that this might be due to different experimental conditions, since both high and low intensity light stimulation were used. However, most studies do not report radiometric measurements, which makes it impossible to categorize the stimulation according to photopic, mesopic, and scotopic vision. Low intensity light stimulation might lead to scotopic vision, where rod perception dominates. In this study, we investigated photic driving for rod-dominated visual input under scotopic conditions. Twelve healthy volunteers were stimulated with low intensity light flashes at 20 stimulation frequencies, leading to rod activation only. The frequencies were multiples of the individual alpha frequency (α) of each volunteer in the range from 0.40 to 2.30∗α. Three hundred and six-channel whole head magnetoencephalography recordings were analyzed in time, frequency, and spatiotemporal domains with the Topographic Matching Pursuit algorithm. We found resonance phenomena and frequency entrainment for stimulations at or close to the individual alpha frequency (0.90–1.10∗α) and half of the alpha frequency (0.40–0.55∗α). No signs of resonance and frequency entrainment phenomena were revealed around 2.00∗α. Instead, on-responses at the beginning and off-responses at the end of each stimulation train were observed for the first time in a photic driving experiment at frequencies of 1.30–2.30∗α, indicating that the flicker fusion threshold was reached. All results, the resonance and entrainment as well as the fusion effects, provide evidence for rod-dominated photic driving in the visual cortex. PMID:27588002

  12. ELECTROMAGNETIC APPARATUS FOR MOVING A ROD

    Science.gov (United States)

    Young, J.N.

    1957-08-20

    An electromagnetic device for moving an object in a linear path by increments is described. The device is specifically adapted for moving a neutron absorbing control rod into and out of the core of a reactor and consists essentially of an extension member made of magnetic material connected to one end of the control rod and mechanically flexible to grip the walls of a sleeve member when flexed, a magnetic sleeve member coaxial with and slidable between limit stops along the flexible extension, electromagnetic coils substantially centrally located with respect to the flexible extension to flex the extension member into gripping engagement with the sleeve member when ener gized, moving electromagnets at each end of the sleeve to attract the sleeve when energized, and a second gripping electromagnet positioned along the flexible extension at a distance from the previously mentioned electromagnets for gripping the extension member when energized. In use, the second gripping electromagnet is deenergized, the first gripping electromagnet is energized to fix the extension member in the sleeve, and one of the moving electromagnets is energized to attract the sleeve member toward it, thereby moving the control rod.

  13. Evidence for loss of a partial flagellar glycolytic pathway during trypanosomatid evolution.

    Directory of Open Access Journals (Sweden)

    Robert W B Brown

    Full Text Available Classically viewed as a cytosolic pathway, glycolysis is increasingly recognized as a metabolic pathway exhibiting surprisingly wide-ranging variations in compartmentalization within eukaryotic cells. Trypanosomatid parasites provide an extreme view of glycolytic enzyme compartmentalization as several glycolytic enzymes are found exclusively in peroxisomes. Here, we characterize Trypanosoma brucei flagellar proteins resembling glyceraldehyde-3-phosphate dehydrogenase (GAPDH and phosphoglycerate kinase (PGK: we show the latter associates with the axoneme and the former is a novel paraflagellar rod component. The paraflagellar rod is an essential extra-axonemal structure in trypanosomes and related protists, providing a platform into which metabolic activities can be built. Yet, bioinformatics interrogation and structural modelling indicate neither the trypanosome PGK-like nor the GAPDH-like protein is catalytically active. Orthologs are present in a free-living ancestor of the trypanosomatids, Bodo saltans: the PGK-like protein from B. saltans also lacks key catalytic residues, but its GAPDH-like protein is predicted to be catalytically competent. We discuss the likelihood that the trypanosome GAPDH-like and PGK-like proteins constitute molecular evidence for evolutionary loss of a flagellar glycolytic pathway, either as a consequence of niche adaptation or the re-localization of glycolytic enzymes to peroxisomes and the extensive changes to glycolytic flux regulation that accompanied this re-localization. Evidence indicating loss of localized ATP provision via glycolytic enzymes therefore provides a novel contribution to an emerging theme of hidden diversity with respect to compartmentalization of the ubiquitous glycolytic pathway in eukaryotes. A possibility that trypanosome GAPDH-like protein additionally represents a degenerate example of a moonlighting protein is also discussed.

  14. Nuclear thermionic converter. [tungsten-thorium oxide rods

    Science.gov (United States)

    Phillips, W. M.; Mondt, J. F. (Inventor)

    1977-01-01

    Efficient nuclear reactor thermionic converter units are described which can be constructed at low cost and assembled in a reactor which requires a minimum of fuel. Each converter unit utilizes an emitter rod with a fluted exterior, several fuel passages located in the bulges that are formed in the rod between the flutes, and a collector receiving passage formed through the center of the rod. An array of rods is closely packed in an interfitting arrangement, with the bulges of the rods received in the recesses formed between the bulges of other rods, thereby closely packing the nuclear fuel. The rods are constructed of a mixture of tungsten and thorium oxide to provide high power output, high efficiency, high strength, and good machinability.

  15. Description and characterization of HBWR Series H-1 test rods

    Energy Technology Data Exchange (ETDEWEB)

    Wagoner, S.R.; Barner, J.O.; Welty, R.K.

    1979-06-01

    The as-built characterization results are presented for the HBWR Series H-1 test rods to be irradiated as part of the Fuel Performance Improvement Program (FPIP). The irradiation of these rods is to be conducted in the Halden Boiling Water Reactor (HBWR). Series H-1 consists of twelve rods for irradiation and six spares. Rod design types include (1) a reference dished pellet design, (2) an annular pellet design, (3) an annular pellet design combined with graphite-coated cladding, and (4) a packed-particle (vipac) design. The report, which describes the fabrication and detailed characterization results for the rods, is divided into four major sections: (1) experiment description, (2) process development required to fabricate the test rods, (3) methods and procedures used to fabricate and characterize the rods, and (4) a summary of the characterization results.

  16. Isothermal microcalorimetry, a new tool to monitor drug action against Trypanosoma brucei and Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Tanja Wenzler

    Full Text Available Isothermal microcalorimetry is an established tool to measure heat flow of physical, chemical or biological processes. The metabolism of viable cells produces heat, and if sufficient cells are present, their heat production can be assessed by this method. In this study, we investigated the heat flow of two medically important protozoans, Trypanosoma brucei rhodesiense and Plasmodium falciparum. Heat flow signals obtained for these pathogens allowed us to monitor parasite growth on a real-time basis as the signals correlated with the number of viable cells. To showcase the potential of microcalorimetry for measuring drug action on pathogenic organisms, we tested the method with three antitrypanosomal drugs, melarsoprol, suramin and pentamidine and three antiplasmodial drugs, chloroquine, artemether and dihydroartemisinin, each at two concentrations on the respective parasite. With the real time measurement, inhibition was observed immediately by a reduced heat flow compared to that in untreated control samples. The onset of drug action, the degree of inhibition and the time to death of the parasite culture could conveniently be monitored over several days. Microcalorimetry is a valuable element to be added to the toolbox for drug discovery for protozoal diseases such as human African trypanosomiasis and malaria. The method could probably be adapted to other protozoan parasites, especially those growing extracellularly.

  17. Dynamic modelling under uncertainty: the case of Trypanosoma brucei energy metabolism.

    Directory of Open Access Journals (Sweden)

    Fiona Achcar

    2012-01-01

    Full Text Available Kinetic models of metabolism require detailed knowledge of kinetic parameters. However, due to measurement errors or lack of data this knowledge is often uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei is a particularly well analysed example of a quantitative metabolic model, but so far it has been studied with a fixed set of parameters only. Here we evaluate the effect of parameter uncertainty. In order to define probability distributions for each parameter, information about the experimental sources and confidence intervals for all parameters were collected. We created a wiki-based website dedicated to the detailed documentation of this information: the SilicoTryp wiki (http://silicotryp.ibls.gla.ac.uk/wiki/Glycolysis. Using information collected in the wiki, we then assigned probability distributions to all parameters of the model. This allowed us to sample sets of alternative models, accurately representing our degree of uncertainty. Some properties of the model, such as the repartition of the glycolytic flux between the glycerol and pyruvate producing branches, are robust to these uncertainties. However, our analysis also allowed us to identify fragilities of the model leading to the accumulation of 3-phosphoglycerate and/or pyruvate. The analysis of the control coefficients revealed the importance of taking into account the uncertainties about the parameters, as the ranking of the reactions can be greatly affected. This work will now form the basis for a comprehensive Bayesian analysis and extension of the model considering alternative topologies.

  18. Flux Analysis of the Trypanosoma brucei Glycolysis Based on a Multiobjective-Criteria Bioinformatic Approach

    Directory of Open Access Journals (Sweden)

    Amine Ghozlane

    2012-01-01

    Full Text Available Trypanosoma brucei is a protozoan parasite of major of interest in discovering new genes for drug targets. This parasite alternates its life cycle between the mammal host(s (bloodstream form and the insect vector (procyclic form, with two divergent glucose metabolism amenable to in vitro culture. While the metabolic network of the bloodstream forms has been well characterized, the flux distribution between the different branches of the glucose metabolic network in the procyclic form has not been addressed so far. We present a computational analysis (called Metaboflux that exploits the metabolic topology of the procyclic form, and allows the incorporation of multipurpose experimental data to increase the biological relevance of the model. The alternatives resulting from the structural complexity of networks are formulated as an optimization problem solved by a metaheuristic where experimental data are modeled in a multiobjective function. Our results show that the current metabolic model is in agreement with experimental data and confirms the observed high metabolic flexibility of glucose metabolism. In addition, Metaboflux offers a rational explanation for the high flexibility in the ratio between final products from glucose metabolism, thsat is, flux redistribution through the malic enzyme steps.

  19. Identification and characterization of an unusual class I myosin involved in vesicle traffic in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Diana Spitznagel

    Full Text Available Myosins are a multimember family of motor proteins with diverse functions in eukaryotic cells. African trypanosomes possess only two candidate myosins and thus represent a useful system for functional analysis of these motors. One of these candidates is an unusual class I myosin (TbMyo1 that is expressed at similar levels but organized differently during the life cycle of Trypanosoma brucei. This myosin localizes to the polarized endocytic pathway in bloodstream forms of the parasite. This organization is actin dependent. Knock down of TbMyo1 results in a significant reduction in endocytic activity, a cessation in cell division and eventually cell death. A striking morphological feature in these cells is an enlargement of the flagellar pocket, which is consistent with an imbalance in traffic to and from the surface. In contrast TbMyo1 is distributed throughout procyclic forms of the tsetse vector and a loss of approximately 90% of the protein has no obvious effects on growth or morphology. These results reveal a life cycle stage specific requirement for this myosin in essential endocytic traffic and represent the first description of the involvement of a motor protein in vesicle traffic in these parasites.

  20. Identification and characterization of an unusual class I myosin involved in vesicle traffic in Trypanosoma brucei.

    Science.gov (United States)

    Spitznagel, Diana; O'Rourke, John F; Leddy, Neal; Hanrahan, Orla; Nolan, Derek P

    2010-01-01

    Myosins are a multimember family of motor proteins with diverse functions in eukaryotic cells. African trypanosomes possess only two candidate myosins and thus represent a useful system for functional analysis of these motors. One of these candidates is an unusual class I myosin (TbMyo1) that is expressed at similar levels but organized differently during the life cycle of Trypanosoma brucei. This myosin localizes to the polarized endocytic pathway in bloodstream forms of the parasite. This organization is actin dependent. Knock down of TbMyo1 results in a significant reduction in endocytic activity, a cessation in cell division and eventually cell death. A striking morphological feature in these cells is an enlargement of the flagellar pocket, which is consistent with an imbalance in traffic to and from the surface. In contrast TbMyo1 is distributed throughout procyclic forms of the tsetse vector and a loss of approximately 90% of the protein has no obvious effects on growth or morphology. These results reveal a life cycle stage specific requirement for this myosin in essential endocytic traffic and represent the first description of the involvement of a motor protein in vesicle traffic in these parasites.

  1. The Role of Folate Transport in Antifolate Drug Action in Trypanosoma brucei*

    Science.gov (United States)

    Dewar, Simon; Sienkiewicz, Natasha; Ong, Han B.; Wall, Richard J.; Horn, David

    2016-01-01

    The aim of this study was to identify and characterize mechanisms of resistance to antifolate drugs in African trypanosomes. Genome-wide RNAi library screens were undertaken in bloodstream form Trypanosoma brucei exposed to the antifolates methotrexate and raltitrexed. In conjunction with drug susceptibility and folate transport studies, RNAi knockdown was used to validate the functions of the putative folate transporters. The transport kinetics of folate and methotrexate were further characterized in whole cells. RNA interference target sequencing experiments identified a tandem array of genes encoding a folate transporter family, TbFT1–3, as major contributors to antifolate drug uptake. RNAi knockdown of TbFT1–3 substantially reduced folate transport into trypanosomes and reduced the parasite's susceptibly to the classical antifolates methotrexate and raltitrexed. In contrast, knockdown of TbFT1–3 increased susceptibly to the non-classical antifolates pyrimethamine and nolatrexed. Both folate and methotrexate transport were inhibited by classical antifolates but not by non-classical antifolates or biopterin. Thus, TbFT1–3 mediates the uptake of folate and classical antifolates in trypanosomes, and TbFT1–3 loss-of-function is a mechanism of antifolate drug resistance. PMID:27703008

  2. Crystal structures and inhibition of Trypanosoma brucei hypoxanthine–guanine phosphoribosyltransferase

    Science.gov (United States)

    Terán, David; Hocková, Dana; Česnek, Michal; Zíková, Alena; Naesens, Lieve; Keough, Dianne T.; Guddat, Luke W.

    2016-01-01

    Human African Trypanosomiasis (HAT) is a life-threatening infectious disease caused by the protozoan parasite, Trypanosoma brucei (Tbr). Due to the debilitating side effects of the current therapeutics and the emergence of resistance to these drugs, new medications for this disease need to be developed. One potential new drug target is 6-oxopurine phosphoribosyltransferase (PRT), an enzyme central to the purine salvage pathway and whose activity is critical for the production of the nucleotides (GMP and IMP) required for DNA/RNA synthesis within this protozoan parasite. Here, the first crystal structures of this enzyme have been determined, these in complex with GMP and IMP and with three acyclic nucleoside phosphonate (ANP) inhibitors. The Ki values for GMP and IMP are 30.5 μM and 77 μM, respectively. Two of the ANPs have Ki values considerably lower than for the nucleotides, 2.3 μM (with guanine as base) and 15.8 μM (with hypoxanthine as base). The crystal structures show that when two of the ANPs bind, they induce an unusual conformation change to the loop where the reaction product, pyrophosphate, is expected to bind. This and other structural differences between the Tbr and human enzymes suggest selective inhibitors for the Tbr enzyme can be designed. PMID:27786284

  3. Melarsoprol- and pentamidine-resistant Trypanosoma brucei rhodesiense populations and their cross-resistance.

    Science.gov (United States)

    Bernhard, Sonja C; Nerima, Barbara; Mäser, Pascal; Brun, Reto

    2007-11-01

    Resistance to melarsoprol and pentamidine was induced in bloodstream-form Trypanosoma brucei rhodesiense STIB 900 in vitro, and drug sensitivity was determined for melarsoprol, pentamidine and furamidine. The resistant populations were also inoculated into immunosuppressed mice to verify infectivity and to monitor whether rodent passage selects for clones with altered drug sensitivity. After proliferation in the mouse, trypanosomes were isolated and their IC(50) values to the three drugs were determined. To assess the stability of drug-induced resistance, drug pressure was ceased for 2 months and the drug sensitivity was determined again. Resistance was stable, with a few exceptions that are discussed. Drug IC(50)s indicated cross-resistance among all drugs, but to varying extents: resistance of the melarsoprol-selected and pentamidine-selected trypanosomes to pentamidine was the same, but the pentamidine-selected trypanosome population showed lower resistance to melarsoprol than the melarsoprol-selected trypanosomes. Interestingly, both resistant populations revealed the same intermediate cross-resistance to furamidine. Resistant trypanosome populations were characterised by molecular means, referring to the status of the TbAT1 gene. The melarsoprol-selected population apparently had lost TbAT1, whereas in the pentamidine-selected trypanosome population it was still present.

  4. Association of a novel preribosomal complex in Trypanosoma brucei determined by fluorescence resonance energy transfer.

    Science.gov (United States)

    Wang, Lei; Ciganda, Martin; Williams, Noreen

    2013-02-01

    We have previously reported that the trypanosome-specific proteins P34 and P37 form a unique preribosomal complex with ribosomal protein L5 and 5S rRNA in the nucleoplasm. We hypothesize that this novel trimolecular complex is necessary for stabilizing 5S rRNA in Trypanosoma brucei and is essential for the survival of the parasite. In vitro quantitative analysis of the association between the proteins L5 and P34 is fundamental to our understanding of this novel complex and thus our ability to exploit its unique characteristics. Here we used in vitro fluorescence resonance energy transfer (FRET) to analyze the association between L5 and P34. First, we demonstrated that FRET can be used to confirm the association between L5 and P34. We then determined that the binding constant for L5 and P34 is 0.60 ± 0.03 μM, which is in the range of protein-protein binding constants for RNA binding proteins. In addition, we used FRET to identify the critical regions of L5 and P34 involved in the protein-protein association. We found that the N-terminal APK-rich domain and RNA recognition motif (RRM) of P34 and the L18 domain of L5 are important for the association of the two proteins with each other. These results provide us with the framework for the discovery of ways to disrupt this essential complex.

  5. Fluorinated Sterols Are Suicide Inhibitors of Ergosterol Biosynthesis and Growth in Trypanosoma brucei.

    Science.gov (United States)

    Leaver, David J; Patkar, Presheet; Singha, Ujjal K; Miller, Matthew B; Haubrich, Brad A; Chaudhuri, Minu; Nes, W David

    2015-10-22

    Trypanosoma brucei, the causal agent for sleeping sickness, depends on ergosterol for growth. Here, we describe the effects of a mechanism-based inhibitor, 26-fluorolanosterol (26FL), which converts in vivo to a fluorinated substrate of the sterol C24-methyltransferase essential for sterol methylation and function of ergosterol, and missing from the human host. 26FL showed potent inhibition of ergosterol biosynthesis and growth of procyclic and bloodstream forms while having no effect on cholesterol biosynthesis or growth of human epithelial kidney cells. During exposure of cloned TbSMT to 26-fluorocholesta-5,7,24-trienol, the enzyme is gradually killed as a consequence of the covalent binding of the intermediate C25 cation to the active site (kcat/kinact = 0.26 min(-1)/0.24 min(-1); partition ratio of 1.08), whereas 26FL is non-productively bound. These results demonstrate that poisoning of ergosterol biosynthesis by a 26-fluorinated Δ(24)-sterol is a promising strategy for developing a new treatment for trypanosomiasis.

  6. Parasite development and host responses during the establishment of Trypanosoma brucei infection transmitted by tsetse fly.

    Science.gov (United States)

    Barry, J D; Emergy, D L

    1984-02-01

    Following inoculation of Trypanosoma brucei into large mammals by the tsetse fly a local skin reaction, the 'chancre', develops due to trypanosome proliferation. We have cannulated the afferent and efferent lymphatics of the draining lymph node in goats and examined the onset of a cellular reaction, the emigration of the parasite from the chancre and the development of both antigenic variation and the specific immune response. The chancre first became detectable by day 3 post-infection, peaked by day 6 and then subsided. Lymphocyte output increased 6- to 8-fold by day 10 and the number of lymphoblasts increased 50-fold in this period. Both then declined. Trypanosomes were detected in lymph 1-2 days before the chancre, peaked by days 5-6, declined during development of the chancre and then peaked again. The bloodstream population appeared by days 4-5 and displayed different kinetics from that in lymph. Recirculation of parasites through the lymphatics ensued. Lymph-borne trypanosome populations were highly pleomorphic. Parasites in lymph expressed firstly a mixture of the Variable Antigen Types (VATs) which are found characteristically in the tsetse fly, this being followed by a mixture of other VATs. The two groups overlapped in appearance. In the bloodstream the same sequence of events occurred although 2 or 3 days later. The specific antibody response, as measured by radioimmunoassay and agglutination, arose within a few days of the first detection of each VAT. Activities appeared first in the lymph and then in plasma.

  7. Synchronous expression of individual metacyclic variant surface glycoprotein genes in Trypanosoma brucei.

    Science.gov (United States)

    Ramey-Butler, Kiantra; Ullu, Elisabetta; Kolev, Nikolay G; Tschudi, Christian

    2015-01-01

    One distinctive feature of the Trypanosoma brucei life cycle is the presence of two discrete populations that are based on differential expression of variant surface glycoproteins (VSGs). Both are adapted to the environmental pressures they face and more importantly, both contribute directly to transmission. Metacyclics in the tsetse fly enable transmission to a new mammalian host, whereas bloodstream trypanosomes must avoid immune destruction to the extent that sufficient numbers are available for transmission, when the insect vector takes a blood meal. At present, there are few investigations on the molecular aspects of parasite biology in the tsetse vector and specifically about the activation of metacyclic VSG gene expression. Here we used an established in vitro differentiation system based on the overexpression of the RNA-binding protein 6 (RBP6), to monitor two metacyclic VSGs (VSG 397 and VSG 653) during development from procyclics to infectious metacyclic forms. We observed that activation of these two mVSGs was simultaneous both at the transcript and protein level, and manifested by the appearance of only one of the mVSGs in individual cells.

  8. Identification of a new EF-hand superfamily member from Trypanosoma brucei

    Science.gov (United States)

    Wong, S.; Kretsinger, R. H.; Campbell, D. A.

    1992-01-01

    We identified several open reading frames between the regions encoding calmodulin and ubiquitin-EP52/1 in the genome of Trypanosoma brucei. One of these, EFH5, encodes a protein 192 amino acids long. The EFH5 transcript is present in poly(A)+ mRNA and is present at similar levels in the mammalian bloodstream form and the insect procyclic form. EFH5 contains four EF-hand homolog domains, two of which are inferred to bind Ca2+ ions. We expressed EFH5 as a fusion protein in Escherichia coli and demonstrated calcium-binding activity of the fusion protein using the 45Ca-overlay technique. The function of EFH5 remains unknown; however, as the fourth EF-hand homolog identified in trypanosomes, it attests to the broad range of functions assumed by calcium functioning as a second messenger. EFH5, which is most closely related to LAV1-2 from Physarum, represents a distinct subfamily among the EF-hand-containing proteins.

  9. Rediscovery of Trypanosoma (Pycnomonas) suis, a tsetse-transmitted trypanosome closely related to T. brucei.

    Science.gov (United States)

    Hutchinson, Rachel; Gibson, Wendy

    2015-12-01

    The African tsetse-transmitted trypanosomes are considered to be a well-known group of parasitic protozoa, but in 2008 a novel and distinctive trypanosome related to Trypanosoma brucei was discovered among tsetse isolates from Msubugwe in Tanzania. The host range, distribution and potential pathogenicity of this new trypanosome remain to be elucidated; such studies would be facilitated by a sensitive and specific identification method. Here, we identified two highly repetitive elements in the genome of the new trypanosome: a 177 bp repeat, which was located predominantly on the highly abundant minichromosomes, and a 138 bp repeat, which was widely dispersed in the genome. A PCR test based on each repeat was specific for the new trypanosome and sensitive to Trypanosoma (Pycnomonas) suis. We also present data on the molecular karyotype and spliced leader (SL, miniexon) repeat of the new trypanosome, both of which distinguish T. suis from other, better-known African tsetse-transmitted trypanosomes. The rediscovery of T. suis opens new lines of research into the evolution and biology of the African trypanosomes.

  10. Between a Map and a Data Rod

    Science.gov (United States)

    Teng, W. L.; Rui, H.; Strub, R. F.; Vollmer, B.

    2015-12-01

    A "Digital Divide" has long stood between how NASA and other satellite-derived data are typically archived (time-step arrays or "maps") and how hydrology and other point-time series oriented communities prefer to access those data. In essence, the desired method of data access is orthogonal to the way the data are archived. Our approach to bridging the Divide is part of a larger NASA-supported "data rods" project to enhance access to and use of NASA and other data by the Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) Hydrologic Information System (HIS) and the larger hydrology community. Our main objective was to determine a way to reorganize data that is optimal for these communities. Two related objectives were to optimally reorganize data in a way that (1) is operational and fits in and leverages the existing Goddard Earth Sciences Data and Information Services Center (GES DISC) operational environment and (2) addresses the scaling up of data sets available as time series from those archived at the GES DISC to potentially include those from other Earth Observing System Data and Information System (EOSDIS) data archives. Through several prototype efforts and lessons learned, we arrived at a non-database solution that satisfied our objectives/constraints. We describe, in this presentation, how we implemented the operational production of pre-generated data rods and, considering the tradeoffs between length of time series (or number of time steps), resources needed, and performance, how we implemented the operational production of on-the-fly ("virtual") data rods. For the virtual data rods, we leveraged a number of existing resources, including the NASA Giovanni Cache and NetCDF Operators (NCO) and used data cubes processed in parallel. Our current benchmark performance for virtual generation of data rods is about a year's worth of time series for hourly data (~9,000 time steps) in ~90 seconds. Our approach is a specific

  11. Between a Map and a Data Rod

    Science.gov (United States)

    Teng, William; Rui, Hualan; Strub, Richard; Vollmer, Bruce

    2015-01-01

    A Digital Divide has long stood between how NASA and other satellite-derived data are typically archived (time-step arrays or maps) and how hydrology and other point-time series oriented communities prefer to access those data. In essence, the desired method of data access is orthogonal to the way the data are archived. Our approach to bridging the Divide is part of a larger NASA-supported data rods project to enhance access to and use of NASA and other data by the Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) Hydrologic Information System (HIS) and the larger hydrology community. Our main objective was to determine a way to reorganize data that is optimal for these communities. Two related objectives were to optimally reorganize data in a way that (1) is operational and fits in and leverages the existing Goddard Earth Sciences Data and Information Services Center (GES DISC) operational environment and (2) addresses the scaling up of data sets available as time series from those archived at the GES DISC to potentially include those from other Earth Observing System Data and Information System (EOSDIS) data archives. Through several prototype efforts and lessons learned, we arrived at a non-database solution that satisfied our objectivesconstraints. We describe, in this presentation, how we implemented the operational production of pre-generated data rods and, considering the tradeoffs between length of time series (or number of time steps), resources needed, and performance, how we implemented the operational production of on-the-fly (virtual) data rods. For the virtual data rods, we leveraged a number of existing resources, including the NASA Giovanni Cache and NetCDF Operators (NCO) and used data cubes processed in parallel. Our current benchmark performance for virtual generation of data rods is about a years worth of time series for hourly data (9,000 time steps) in 90 seconds. Our approach is a specific implementation of

  12. Determination of the rod-wire transition length in colloidal indium phosphide quantum rods.

    Science.gov (United States)

    Wang, Fudong; Buhro, William E

    2007-11-21

    Colloidal InP quantum rods (QRs) having controlled diameters and lengths are grown by the solution-liquid-solid method, from Bi nanoparticles in the presence of hexadecylamine and other conventional quantum dot surfactants. These quantum rods show band-edge photoluminescence after HF photochemical etching. Photoluminescence efficiency is further enhanced after the Bi tips are selectively removed from the QRs by oleic acid etching. The QRs are anisotropically 3D confined, the nature of which is compared to the corresponding isotropic 3D confinement in quantum dots and 2D confinement in quantum wires. The 3D-2D rod-wire transition length is experimentally determined to be 25 nm, which is about 2 times the bulk InP exciton Bohr radius (of approximately 11 nm).

  13. Sucker-rod pumping handbook production engineering fundamentals and long-stroke rod pumping

    CERN Document Server

    Takacs, Gabor

    2015-01-01

    Sucker-Rod Pumping Handbook presents the latest information on the most common form of production enhancement in today's oil industry, making up roughly two-thirds of the producing oilwell operations in the world. The book begins with an introduction to the main features of sucker rod pumping and an explanation and comparison of lift methods. It goes on to provide the technical and practical knowledge needed to introduce the new and practicing production engineer and operator to the equipment, technology, and applications required to maintain optimum operating conditions.

  14. New functions for parts of the Krebs cycle in procyclic Trypanosoma brucei, a cycle not operating as a cycle.

    Science.gov (United States)

    van Weelden, Susanne W H; van Hellemond, Jaap J; Opperdoes, Fred R; Tielens, Aloysius G M

    2005-04-01

    We investigated whether substrate availability influences the type of energy metabolism in procyclic Trypanosoma brucei. We show that absence of glycolytic substrates (glucose and glycerol) does not induce a shift from a fermentative metabolism to complete oxidation of substrates. We also show that glucose (and even glycolysis) is not essential for normal functioning and proliferation of pleomorphic procyclic T. brucei cells. Furthermore, absence of glucose did not result in increased degradation of amino acids. Variations in availability of glucose and glycerol did result, however, in adaptations in metabolism in such a way that the glycosome was always in redox balance. We argue that it is likely that, in procyclic cells, phosphoglycerate kinase is located not only in the cytosol, but also inside glycosomes, as otherwise an ATP deficit would occur in this organelle. We demonstrate that procyclic T. brucei uses parts of the Krebs cycle for purposes other than complete degradation of mitochondrial substrates. We suggest that citrate synthase plus pyruvate dehydrogenase and malate dehydrogenase are used to transport acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, a process we show to occur in proliferating procyclic cells. The part of the Krebs cycle consisting of alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase was used for the degradation of proline and glutamate to succinate. We also demonstrate that the subsequent enzymes of the Krebs cycle, succinate dehydrogenase and fumarase, are most likely used for conversion of succinate into malate, which can then be used in gluconeogenesis.

  15. Visual transduction in human rod photoreceptors.

    Science.gov (United States)

    Kraft, T W; Schneeweis, D M; Schnapf, J L

    1993-05-01

    1. Photocurrents were recorded with suction electrodes from rod photoreceptors of seven humans. 2. Brief flashes of light evoked transient outward currents of up to 20 pA. With increasing light intensity the peak response amplitude increased along an exponential saturation function. A half-saturating peak response was evoked by approximately sixty-five photoisomerizations. 3. Responses to brief dim flashes rose to a peak in about 200 ms. The waveform was roughly like the impulse response of a series of four to five low-pass filters. 4. The rising phases of the responses to flashes of increasing strength were found to fit with a biochemical model of phototransduction with an 'effective delay time' and 'characteristic time' of about 2 and 800 ms, respectively. 5. Spectral sensitivities were obtained over a wavelength range from 380 to 760 nm. The action spectrum, which peaked at 495 nm, followed the template described for photoreceptors in the macaque retina. Variation between rods in the position of the spectrum on the wavelength axis was small. 6. The scotopic luminosity function derived from human psychophysical experiments was found to agree well with the measured rod action spectrum after adjustments were made for lens absorption and photopigment self-screening in the intact eye. 7. Responses to steps of light rose monotonically to a maintained level, showing little or no relaxation. Nevertheless, the relationship between light intensity and steady-state response amplitude was shallower than that expected from simple response saturation. This is consistent with an adaptation mechanism acting on a rapid time scale. 8. Flash sensitivity fell with increasing intensities of background light according to Weber's law. Sensitivity was reduced twofold by lights evoking about 120 photoisomerizations per second. Background lights decreased the time to peak and the integration time of the flash response by up to 20%.

  16. Solitary waves on nonlinear elastic rods. I

    DEFF Research Database (Denmark)

    Sørensen, Mads Peter; Christiansen, Peter Leth; Lomdahl, P. S.

    1984-01-01

    Acoustic waves on elastic rods with circular cross section are governed by improved Boussinesq equations when transverse motion and nonlinearity in the elastic medium are taken into account. Solitary wave solutions to these equations have been found. The present paper treats the interaction between...... the solitary waves numerically. It is demonstrated that the waves behave almost like solitons in agreement with the fact that the improved Boussinesq equations are nearly integrable. Thus three conservation theorems can be derived from the equations. A new subsonic quasibreather is found in the case of a cubic...... nonlinearity. The balance between dispersion and nonlinearity in the equation is investigated....

  17. Transient waves in finite viscoelastic rods

    Energy Technology Data Exchange (ETDEWEB)

    Mainardi, F. (Bologna Univ. (Italy). Ist. di Fisica); Nervosi, R. (Bologna Univ. (Italy))

    1980-11-29

    A method based on the Laplace transform is presented to compute wave-front expansions for transient waves in finite viscoelastic rods using the creep or the relaxation representation. The response is related to the basic solution of the semi-infinite problem, for which a series expansion is obtained by a recursive procedure. The convergence is guaranteed in any space-time domain if the material functions are entirely of exponential type. However, for numerical computation an acceleration of convergence is required and the Pade approximants turn out to be successful as shown by some examples.

  18. Rod-like nano-light harvester.

    Science.gov (United States)

    Ling, Jun; Zheng, Zhicheng; Köhler, Anna; Müller, Axel H E

    2014-01-01

    Imitating the natural "energy cascade" architecture, we present a single-molecular rod-like nano-light harvester (NLH) based on a cylindrical polymer brush. Block copolymer side chains carrying (9,9-diethylfluoren-2-yl)methyl methacrylate units as light absorbing antennae (energy donors) are tethered to a linear polymer backbone containing 9-anthracenemethyl methacrylate units as emitting groups (energy acceptors). These NLHs exhibit very efficient energy absorption and transfer. Moreover, we manipulate the energy transfer by tuning the donor-acceptor distance.

  19. Brazilian methodology adopted about lightning rods

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Felipe [Comissao Nacional de Enegia Nuclear, Rio de Janeiro, RJ (Brazil). Div. de Rejeitos Radioativos]. E-mail: felipe@cnen.gov.br

    2005-07-01

    This paper describes the Brazilian experience concerning the suspension of the authorization for the production and installation of lightning rods containing radioactive material in the country and the main measures put into practice in order to safely remove and transport to temporary storage facilities all the existing devices Brazil that would be put out of use after the suspension. It is also presented the procedure established by the National Regulatory Body namely the Brazilian National Commission of Nuclear Energy- CNEN to be accomplished by the owners of this kind of devices. (author)

  20. 4-rod RFQ linac for ion implantation

    Energy Technology Data Exchange (ETDEWEB)

    Fujisawa, Hiroshi; Hamamoto, Nariaki; Inouchi, Yutaka [Nisshin Electric Co. Ltd., Kyoto (Japan)

    1997-03-01

    A 34 MHz 4-rod RFQ linac system has been upgraded in both its rf power efficiency and beam intensity. The linac is able to accelerate in cw operation 0.83 mA of a B{sup +} ion beam from 0.03 to 0.91 MeV with transmission of 61 %. The rf power fed to the RFQ is 29 kW. The unloaded Q-value of the RFQ has been improved approximately 61 % to 5400 by copper-plating stainless steel cooling pipes in the RFQ cavity. (author)

  1. Locally periodic Timoshenko rod: experiment and theory.

    Science.gov (United States)

    Díaz-de-Anda, A; Pimentel, A; Flores, J; Morales, A; Gutiérrez, L; Méndez-Sánchez, R A

    2005-05-01

    The flexural vibrations of a locally periodic rod, which consists of N unit cells, are discussed both from the experimental and theoretical points of view. Timoshenko's beam theory and the transfer matrix method are used to calculate the normal-mode frequencies and amplitudes. The theoretical values are then compared with the experimental ones, which are obtained using an electromagnetic acoustic transducer (EMAT). Good agreement between the numerical results and the experimental measurements is obtained. It is shown that as N grows, a band spectrum emerges.

  2. High-yield production of hydrophobins RodA and RodB from Aspergillus fumigatus in Pichia pastoris.

    Science.gov (United States)

    Pedersen, Mona Højgaard; Borodina, Irina; Moresco, Jacob Lange; Svendsen, Winnie Edith; Frisvad, Jens Christian; Søndergaard, Ib

    2011-06-01

    Hydrophobins are small fungal proteins with amphipatic properties and the ability to self-assemble on a hydrophobic/hydrophilic interface; thus, many technical applications for hydrophobins have been suggested. The pathogenic fungus Aspergillus fumigatus expresses the hydrophobins RodA and RodB on the surface of its conidia. RodA is known to be of importance to the pathogenesis of the fungus, while the biological role of RodB is currently unknown. Here, we report the successful expression of both hydrophobins in Pichia pastoris and present fed-batch fermentation yields of 200-300 mg/l fermentation broth. Protein bands of expected sizes were detected by SDS-PAGE and western blotting, and the identity was further confirmed by tandem mass spectrometry. Both proteins were purified using his-affinity chromatography, and the high level of purity was verified by silver-stained SDS-PAGE. Recombinant RodA as well as rRodB were able to convert a glass surface from hydrophilic to hydrophobic similar to native RodA, but only rRodB was able to decrease the hydrophobicity of a Teflon-like surface to the same extent as native RodA, while rRodA showed this ability to a lesser extent. Recombinant RodA and native RodA showed a similar ability to emulsify air in water, while recombinant RodB could also emulsify oil in water better than the control protein bovine serum albumin (BSA). This is to our knowledge the first successful expression of hydrophobins from A. fumigatus in a eukaryote host, which makes it possible to further characterize both hydrophobins. Furthermore, the expression strategy and fed-batch production using P. pastoris may be transferred to hydrophobins from other species.

  3. Vibration of the Package of Rods Linked by Spacer Grids

    Science.gov (United States)

    Zeman, V.; Hlaváč, Z.

    This paper deals with modelling and vibration analysis of the large package of identical parallel rods which are linked by transverse springs (spacer grids) placed on several level spacings. The vibration of rods is caused by the support plate motion. The rod discretization by FEM is based on Rayleigh beam theory. With respect to cyclic and central package rod symmetry, the system is decomposed to identical revolved rod segments. The modal synthesis method with condensation of the rod segments is used for modelling and determination of steady forced vibration of the whole system. The presented method is the first step to modelling of the nuclear fuel assembly vibration caused by kinematical excitation determined by motion of the support plates which are part of the reactor core.

  4. Stirring with ghost rods in a lid-driven cavity

    Science.gov (United States)

    Kumar, Pankaj; Chen, Jie; Stremler, Mark

    2009-11-01

    It has shown that passive fluid particles moving on periodic orbits can be used to `stir' a viscous fluid in a two-dimensional lid-driven cavity that exhibits a figure-eight flow pattern (Stremler & Chen 2007). Fluid motion in the vicinity of these particles produces ``ghost rod'' structures that behave like semi-permeable rods in the flow. Since these ghost rods are present due to the system dynamics, perturbations in the boundary conditions lead to variations in the existence and structure of the ghost rods. We discuss these variations and assess the role of ghost rods in mixing over a range of operating conditions for this system. The results suggest that ghost rods can play an important role in mixing for other counter-rotating flows.

  5. Trypanosoma brucei gambiense adaptation to different mammalian sera is associated with VSG expression site plasticity.

    Directory of Open Access Journals (Sweden)

    Carlos Cordon-Obras

    Full Text Available Trypanosoma brucei gambiense infection is widely considered an anthroponosis, although it has also been found in wild and domestic animals. Thus, fauna could act as reservoir, constraining the elimination of the parasite in hypo-endemic foci. To better understand the possible maintenance of T. b. gambiense in local fauna and investigate the molecular mechanisms underlying adaptation, we generated adapted cells lines (ACLs by in vitro culture of the parasites in different mammalian sera. Using specific antibodies against the Variant Surface Glycoproteins (VSGs we found that serum ACLs exhibited different VSG variants when maintained in pig, goat or human sera. Although newly detected VSGs were independent of the sera used, the consistent appearance of different VSGs suggested remodelling of the co-transcribed genes at the telomeric Expression Site (VSG-ES. Thus, Expression Site Associated Genes (ESAGs sequences were analysed to investigate possible polymorphism selection. ESAGs 6 and 7 genotypes, encoding the transferrin receptor (TfR, expressed in different ACLs were characterised. In addition, we quantified the ESAG6/7 mRNA levels and analysed transferrin (Tf uptake. Interestingly, the best growth occurred in pig and human serum ACLs, which consistently exhibited a predominant ESAG7 genotype and higher Tf uptake than those obtained in calf and goat sera. We also detected an apparent selection of specific ESAG3 genotypes in the pig and human serum ACLs, suggesting that other ESAGs could be involved in the host adaptation processes. Altogether, these results suggest a model whereby VSG-ES remodelling allows the parasite to express a specific set of ESAGs to provide selective advantages in different hosts. Finally, pig serum ACLs display phenotypic adaptation parameters closely related to human serum ACLs but distinct to parasites grown in calf and goat sera. These results suggest a better suitability of swine to maintain T. b. gambiense infection

  6. Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate.

    Science.gov (United States)

    Dawson, Alice; Gibellini, Federica; Sienkiewicz, Natasha; Tulloch, Lindsay B; Fyfe, Paul K; McLuskey, Karen; Fairlamb, Alan H; Hunter, William N

    2006-09-01

    The protozoan Trypanosoma brucei has a functional pteridine reductase (TbPTR1), an NADPH-dependent short-chain reductase that participates in the salvage of pterins, which are essential for parasite growth. PTR1 displays broad-spectrum activity with pterins and folates, provides a metabolic bypass for inhibition of the trypanosomatid dihydrofolate reductase and therefore compromises the use of antifolates for treatment of trypanosomiasis. Catalytic properties of recombinant TbPTR1 and inhibition by the archetypal antifolate methotrexate have been characterized and the crystal structure of the ternary complex with cofactor NADP+ and the inhibitor determined at 2.2 A resolution. This enzyme shares 50% amino acid sequence identity with Leishmania major PTR1 (LmPTR1) and comparisons show that the architecture of the cofactor binding site, and the catalytic centre are highly conserved, as are most interactions with the inhibitor. However, specific amino acid differences, in particular the placement of Trp221 at the side of the active site, and adjustment of the beta6-alpha6 loop and alpha6 helix at one side of the substrate-binding cleft significantly reduce the size of the substrate binding site of TbPTR1 and alter the chemical properties compared with LmPTR1. A reactive Cys168, within the active site cleft, in conjunction with the C-terminus carboxyl group and His267 of a partner subunit forms a triad similar to the catalytic component of cysteine proteases. TbPTR1 therefore offers novel structural features to exploit in the search for inhibitors of therapeutic value against African trypanosomiasis.

  7. 3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction.

    Directory of Open Access Journals (Sweden)

    Johanna L Höög

    2016-01-01

    Full Text Available Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (FC is a three-layered transmembrane junction that moves with the growing tip of a new flagellum and attaches it to the side of the old flagellum. The FC moves via an unknown molecular mechanism, independent of new flagellum growth. Here we describe the detailed 3D architecture of the FC suggesting explanations for how it functions and its mechanism of motility.We have used a combination of electron tomography and cryo-electron tomography to reveal the 3D architecture of the FC. Cryo-electron tomography revealed layers of repetitive filamentous electron densities between the two flagella in the interstitial zone. Though the FC does not change in length and width during the growth of the new flagellum, the interstitial zone thickness decreases as the FC matures. This investigation also shows interactions between the FC layers and the axonemes of the new and old flagellum, sufficiently strong to displace the axoneme in the old flagellum. We describe a novel filament, the flagella connector fibre, found between the FC and the axoneme in the old flagellum.The FC is similar to other cellular junctions in that filamentous proteins bridge the extracellular space and are anchored to underlying cytoskeletal structures; however, it is built between different portions of the same cell and is unique because of its intrinsic motility. The detailed description of its structure will be an important tool to use in attributing structure / function relationships as its molecular components are discovered in the future. The FC is involved in the inheritance of cell shape, which is important for the life cycle of this human parasite.

  8. Untreated human infections by Trypanosoma brucei gambiense are not 100% fatal.

    Directory of Open Access Journals (Sweden)

    Vincent Jamonneau

    Full Text Available The final outcome of infection by Trypanosoma brucei gambiense, the main agent of sleeping sickness, has always been considered as invariably fatal. While scarce and old reports have mentioned cases of self-cure in untreated patients, these studies suffered from the lack of accurate diagnostic tools available at that time. Here, using the most specific and sensitive tools available to date, we report on a long-term follow-up (15 years of a cohort of 50 human African trypanosomiasis (HAT patients from the Ivory Coast among whom 11 refused treatment after their initial diagnosis. In 10 out of 11 subjects who continued to refuse treatment despite repeated visits, parasite clearance was observed using both microscopy and polymerase chain reaction (PCR. Most of these subjects (7/10 also displayed decreasing serological responses, becoming progressively negative to trypanosome variable antigens (LiTat 1.3, 1.5 and 1.6. Hence, in addition to the "classic" lethal outcome of HAT, we show that alternative natural progressions of HAT may occur: progression to an apparently aparasitaemic and asymptomatic infection associated with strong long-lasting serological responses and progression to an apparently spontaneous resolution of infection (with negative results in parasitological tests and PCR associated with a progressive drop in antibody titres as observed in treated cases. While this study does not precisely estimate the frequency of the alternative courses for this infection, it is noteworthy that in the field national control programs encounter a significant proportion of subjects displaying positive serologic test results but negative results in parasitological testing. These findings demonstrate that a number of these subjects display such infection courses. From our point of view, recognising that trypanotolerance exists in humans, as is now widely accepted for animals, is a major step forward for future research in the field of HAT.

  9. Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei.

    Science.gov (United States)

    Mony, Binny M; MacGregor, Paula; Ivens, Alasdair; Rojas, Federico; Cowton, Andrew; Young, Julie; Horn, David; Matthews, Keith

    2014-01-30

    The protozoan parasites Trypanosoma brucei spp. cause important human and livestock diseases in sub-Saharan Africa. In mammalian blood, two developmental forms of the parasite exist: proliferative 'slender' forms and arrested 'stumpy' forms that are responsible for transmission to tsetse flies. The slender to stumpy differentiation is a density-dependent response that resembles quorum sensing in microbial systems and is crucial for the parasite life cycle, ensuring both infection chronicity and disease transmission. This response is triggered by an elusive 'stumpy induction factor' (SIF) whose intracellular signalling pathway is also uncharacterized. Laboratory-adapted (monomorphic) trypanosome strains respond inefficiently to SIF but can generate forms with stumpy characteristics when exposed to cell-permeable cAMP and AMP analogues. Exploiting this, we have used a genome-wide RNA interference library screen to identify the signalling components driving stumpy formation. In separate screens, monomorphic parasites were exposed to 8-(4-chlorophenylthio)-cAMP (pCPT-cAMP) or 8-pCPT-2'-O-methyl-5'-AMP to select cells that were unresponsive to these signals and hence remained proliferative. Genome-wide Ion Torrent based RNAi target sequencing identified cohorts of genes implicated in each step of the signalling pathway, from purine metabolism, through signal transducers (kinases, phosphatases) to gene expression regulators. Genes at each step were independently validated in cells naturally capable of stumpy formation, confirming their role in density sensing in vivo. The putative RNA-binding protein, RBP7, was required for normal quorum sensing and promoted cell-cycle arrest and transmission competence when overexpressed. This study reveals that quorum sensing signalling in trypanosomes shares similarities to fundamental quiescence pathways in eukaryotic cells, its components providing targets for quorum-sensing interference-based therapeutics.

  10. Loop-mediated isothermal amplification (LAMP method for rapid detection of Trypanosoma brucei rhodesiense.

    Directory of Open Access Journals (Sweden)

    Zablon Kithinji Njiru

    Full Text Available Loop-mediated isothermal amplification (LAMP of DNA is a novel technique that rapidly amplifies target DNA under isothermal conditions. In the present study, a LAMP test was designed from the serum resistance-associated (SRA gene of Trypanosoma brucei rhodesiense, the cause of the acute form of African sleeping sickness, and used to detect parasite DNA from processed and heat-treated infected blood samples. The SRA gene is specific to T. b. rhodesiense and has been shown to confer resistance to lysis by normal human serum. The assay was performed at 62 degrees C for 1 h, using six primers that recognised eight targets. The template was varying concentrations of trypanosome DNA and supernatant from heat-treated infected blood samples. The resulting amplicons were detected using SYTO-9 fluorescence dye in a real-time thermocycler, visual observation after the addition of SYBR Green I, and gel electrophoresis. DNA amplification was detected within 35 min. The SRA LAMP test had an unequivocal detection limit of one pg of purified DNA (equivalent to 10 trypanosomes/ml and 0.1 pg (1 trypanosome/ml using heat-treated buffy coat, while the detection limit for conventional SRA PCR was approximately 1,000 trypanosomes/ml. The expected LAMP amplicon was confirmed through restriction enzyme RsaI digestion, identical melt curves, and sequence analysis. The reproducibility of the SRA LAMP assay using water bath and heat-processed template, and the ease in results readout show great potential for the diagnosis of T. b. rhodesiense in endemic regions.

  11. A monoclonal antibody marker for the exclusion-zone filaments of Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Decossas Marion

    2008-07-01

    Full Text Available Abstract Background Trypanosoma brucei is a haemoflagellate pathogen of man, wild animals and domesticated livestock in central and southern Africa. In all life cycle stages this parasite has a single mitochondrion that contains a uniquely organised genome that is condensed into a flat disk-like structure called the kinetoplast. The kinetoplast is essential for insect form procyclic cells and therefore is a potential drug target. The kinetoplast is unique in nature because it consists of novel structural proteins and thousands of circular, interlocking, DNA molecules (kDNA. Secondly, kDNA replication is critically timed to coincide with nuclear S phase and new flagellum biogenesis. Thirdly, the kinetoplast is physically attached to the flagellum basal bodies via a structure called the tripartite attachment complex (TAC. The TAC consists of unilateral filaments (within the mitochondrion matrix, differentiated mitochondrial membranes and exclusion-zone filaments that extend from the distal end of the basal bodies. To date only one protein, p166, has been identified to be a component of the TAC. Results In the work presented here we provide data based on a novel EM technique developed to label and characterise cytoskeleton structures in permeabilised cells without extraction of mitochondrion membranes. We use this protocol to provide data on a new monoclonal antibody reagent (Mab 22 and illustrate the precise localisation of basal body-mitochondrial linker proteins. Mab 22 binds to these linker proteins (exclusion-zone filaments and provides a new tool for the characterisation of cytoskeleton mediated kinetoplast segregation. Conclusion The antigen(s recognised by Mab 22 are cytoskeletal, insensitive to extraction by high concentrations of non-ionic detergent, extend from the proximal region of basal bodies and bind to the outer mitochondrial membrane. This protein(s is the first component of the TAC exclusion-zone fibres to be identified. Mab 22

  12. Enhanced succinic acid production in Aspergillus saccharolyticus by heterologous expression of fumarate reductase from Trypanosoma brucei.

    Science.gov (United States)

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K; Lübeck, Peter S

    2016-02-01

    Aspergillus saccharolyticus exhibits great potential as a cell factory for industrial production of dicarboxylic acids. In the analysis of the organic acid profile, A. saccharolyticus was cultivated in an acid production medium using two different pH conditions. The specific activities of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact on the pattern and the amount of organic acids produced by A. saccharolyticus. The wild-type strain produced higher amount of malic acid and succinic acid in the pH buffered condition (pH 6.5) compared with the pH non-buffered condition. The enzyme assays showed that the rTCA branch was active in the acid production medium as well as the complete medium, but the measured enzyme activities were different depending on the media. Furthermore, a soluble NADH-dependent fumarate reductase gene (frd) from Trypanosoma brucei was inserted and expressed in A. saccharolyticus. The expression of the frd gene led to an enhanced production of succinic acid in frd transformants compared with the wild-type in both pH buffered and pH non-buffered conditions with highest amount produced in the pH buffered condition (16.2 ± 0.5 g/L). This study demonstrates the feasibility of increasing succinic acid production through the cytosolic reductive pathway by genetic engineering in A. saccharolyticus.

  13. Synthesis of homochiral tris-indanyl molecular rods

    DEFF Research Database (Denmark)

    Kjeldsen, Niels Due; Funder, Erik Daa; Gothelf, Kurt Vesterager

    2014-01-01

    Homochiral tris-indanyl molecular rods designed for supramolecular surface self-assembly were synthesized. The chiral indanol moiety was constructed via a Ti-mediated alkyne trimerization. Further manipulations resulted in a homochiral indanol monomer. This was employed as the precursor...... for successive Sonogashira and Ohira-Bestman reactions towards the homochiral tris-indanyl molecular rods. The molecular rods will be applied for scanning tunnelling microscopy studies of their surface self-assembly and chirality....

  14. Metallography and Microanalysis of Qinshan PhaseⅠ NPP Spent Fuel Rods

    Institute of Scientific and Technical Information of China (English)

    QIAN; Jin; BIAN; Wei; GUO; Li-na; GUO; Yi-fan; CHU; Feng-min; LIANG; Zheng-qiang

    2015-01-01

    Qinshan PhaseⅠNPP is a first domestic commercial PWR and its fuel rods and fuel assembly were designed and manufactured by China.In order to assess the irradiation properties of the fuel rods,8spent fuel rods which were drew out from 3fuel assemblies were transferred to CIAE hot cells for post irradiation examination(PIE)in 2014.The cladding material of the fuel

  15. Plastic Guidance Fins for Long Rod Projectiles .

    Directory of Open Access Journals (Sweden)

    Mark L. Bundy

    1997-10-01

    Full Text Available Projectile tail fins on long rod kinetic energy (KE penetrators serve the same purpose as fletchings (feathers on an arrow, namely, they help align the projectile axis with its velocity vector. This reduces the projectile's yaw and hence reduces its aerodynamic drag. In addition, a low yaw angle at target impact helps to maximise the projectile's target penetration. It is typical for projectiles to exit the gun muzzle and enter free flight at some ndn-zero yaw angle. Aerodynamic forces acting on yawed tail fins create a stabilising torque about the projectile's centre of gravity (CG. This torque can be increased by making the fin material lighter. Most conventional long rod penetrators fired from high performance guns have tail fins made from aluminium. However, aluminium can undergo catastrophic oxidation (rapid burning in-bore. Coating aluminium with Al/sub 2/O/sub 3/ {hardcoat prevents ignition of the substrate, provided solid propellant grain impacts do not chip the brittle hardcoat off the surface. Plastic is lighter than aluminium and less exothermic when oxidized. Therefore, other factors aside, it is conceivable that plastic fins could increase projectile stability while incurring less thermal erosion than aluminium. However, thermal loads are not the only concern when considering plastic as an alternative tail fin material. The mechanical strength of plastic is also a critical factor. This paper discusses some of the successes and failures of plastic fins, at least relatively thin fins, for use as KE stabilisers.

  16. Biophysical mechanism of transient retinal phototropism in rod photoreceptors

    Science.gov (United States)

    Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Gai, Shaoyan; Yao, Xincheng

    2016-03-01

    Oblique light stimulation evoked transient retinal phototropism (TRP) has been recently detected in frog and mouse retinas. High resolution microscopy of freshly isolated retinas indicated that the TRP is predominated by rod photoreceptors. Comparative confocal microscopy and optical coherence tomography (OCT) revealed that the TRP predominantly occurred from the photoreceptor outer segment (OS). However, biophysical mechanism of rod OS change is still unknown. In this study, frog retinal slices, which open a cross section of retinal photoreceptor and other functional layers, were used to test the effect of light stimulation on rod OS. Near infrared light microscopy was employed to monitor photoreceptor changes in retinal slices stimulated by a rectangular-shaped visible light flash. Rapid rod OS length change was observed after the stimulation delivery. The magnitude and direction of the rod OS change varied with the position of the rods within the stimulated area. In the center of stimulated region the length of the rod OS shrunk, while in the peripheral region the rod OS tip swung towards center region in the plane perpendicular to the incident stimulus light. Our experimental result and theoretical analysis suggest that the observed TRP may reflect unbalanced disc-shape change due to localized pigment bleaching. Further investigation is required to understand biochemical mechanism of the observed rod OS kinetics. Better study of the TRP may provide a noninvasive biomarker to enable early detection of age-related macular degeneration (AMD) and other diseases that are known to produce retinal photoreceptor dysfunctions.

  17. Vortex patterns in a superconducting-ferromagnetic rod

    Energy Technology Data Exchange (ETDEWEB)

    Romaguera, Antonio R. de C, E-mail: antonio.romaguera@df.ufrpe.b [Departamento de Fi' sica, Universidade Federal Rural de Pernambuco, 52171-900 Recife, Pernambuco (Brazil); Doria, Mauro M. [Departamento de Fi' sica dos Solidos, Universidade Federal do Rio de Janeiro, 21941-972 Rio de Janeiro (Brazil); Peeters, Francois M. [Departement Fysica, Universiteit Antwerpen, Groenenborgerlaan 171, B-2020 Antwerpen (Belgium)

    2010-10-01

    A superconducting rod with a magnetic moment on top develops vortices obtained here through 3D calculations of the Ginzburg-Landau theory. The inhomogeneity of the applied field brings new properties to the vortex patterns that vary according to the rod thickness. We find that for thin rods (disks) the vortex patterns are similar to those obtained in presence of a homogeneous magnetic field instead because they consist of giant vortex states. For thick rods novel patterns are obtained as vortices are curve lines in space that exit through the lateral surface.

  18. Rolls-Royce digital Rod Control System

    Energy Technology Data Exchange (ETDEWEB)

    Pouillot, M. [Rolls-Royce Civil Nuclear SAS (France)

    2010-07-01

    Full text of publication follows: Rolls-Royce has developed a new generation of Rod Control System, based on 40 years of experience. The fifth-generation Rod Control System (RCS) from Rolls-Royce offers a reliable, modular design with adaptability to your preferred platform, for modernization projects or new reactors. Flexible implementation provides the option for you to keep existing cabinets, which permits you to optimize installation approach. Main features for the power part: - Control Rod Drive Mechanism (CRDM) type: 3-coil. - Independent control of each sub-bank. - Each sub-bank is controlled by a cycler unit and 3 identical power racks, each including 4 identical power modules and a common power-supply module. - Coil-per-coil digital control: each power module embeds power-conversion, current-control, and current-monitoring functions for one coil. Control and monitoring are carried out by separate electronics in the module. Current is digitized and fully monitored by means of min-max templates. - A double-hold function is included: a power module assigned to a gripper will activate its coil if a fault risking to cause a reactor trip occurs. - Power modules are standardized, hot-pluggable and self-configured: a power module includes a set of parameters for each type of coil SG, MG, LC. The module recognizes the rack it is plugged in, and chooses automatically parameters to be used. Main benefits: - Reduced operational, maintenance, training, and inventory costs: standardization of power modules and integration of control and monitoring on the same PC-card lead to a drastic reduction of spare part types, and simplification of the system. - Easy maintenance: - Replacement of a power module solves nearly all failures due to current control or monitoring for a coil. It is done instantly thanks to hot-plug capability. - On the front plate of power-modules, LEDs provide useful information for diagnostic: current setpoint from cycler, output current bar

  19. The F(0F(1-ATP synthase complex contains novel subunits and is essential for procyclic Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Alena Zíková

    2009-05-01

    Full Text Available The mitochondrial F(0F(1 ATP synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little is known about its composition and role in Trypanosoma brucei, an early diverged eukaryotic pathogen. We purified the F(0F(1 ATP synthase by a combination of affinity purification, immunoprecipitation and blue-native gel electrophoresis and characterized its composition and function. We identified 22 proteins of which five are related to F(1 subunits, three to F(0 subunits, and 14 which have no obvious homology to proteins outside the kinetoplastids. RNAi silencing of expression of the F(1 alpha subunit or either of the two novel proteins showed that they are each essential for the viability of procyclic (insect stage cells and are important for the structural integrity of the F(0F(1-ATP synthase complex. We also observed a dramatic decrease in ATP production by oxidative phosphorylation after silencing expression of each of these proteins while substrate phosphorylation was not severely affected. Our procyclic T. brucei cells were sensitive to the ATP synthase inhibitor oligomycin even in the presence of glucose contrary to earlier reports. Hence, the two novel proteins appear essential for the structural organization of the functional complex and regulation of mitochondrial energy generation in these organisms is more complicated than previously thought.

  20. Complete coding sequence, sequence analysis and transmembrane topology modelling of Trypanosoma brucei rhodesiense putative oligosaccharyl transferase (TbOST II).

    Science.gov (United States)

    Baticados, Waren N; Inoue, Noboru; Sugimoto, Chihiro; Nagasawa, Hideyuki; Baticados, Abigail M

    2011-01-01

    The partial nucleotide sequence of putative Trypanosoma brucei rhodesiense oligosaccharyl transferase gene was previously reported. Here, we describe the determination of its full-length nucleotide sequence by Inverse PCR (IPCR), subsequent biological sequence analysis and transmembrane topology modelling. The full-length DNA sequence has an Open Reading Frame (ORF) of 2406 bp and encodes a polypeptide of 801 amino acid residues. Protein and DNA sequence analyses revealed that homologues within the genome of other kinetoplastid and various origins exist. Protein topology analysis predicted that Trypanosoma brucei rhodesiense putative oligosaccharyl transferase clone II (TbOST II) is a transmembrane protein with transmembrane helices in probably an N(cytosol)-C(cytosol) orientation. Data from the GenBank database assembly and sequence analyses in general clearly state that TbOST II is the STT3 subunit of OST in T.b. rhodesiense that necessitates further characterisation and functional studies with RNAi. TbOST II sequence had been deposited in the GenBank (accession number GU245937).

  1. In Silico Identification and in Vitro Activity of Novel Natural Inhibitors of Trypanosoma brucei Glyceraldehyde-3-phosphate-dehydrogenase

    Directory of Open Access Journals (Sweden)

    Fabian C. Herrmann

    2015-09-01

    Full Text Available As part of our ongoing efforts to identify natural products with activity against pathogens causing neglected tropical diseases, we are currently performing an extensive screening of natural product (NP databases against a multitude of protozoan parasite proteins. Within this project, we screened a database of NPs from a commercial supplier, AnalytiCon Discovery (Potsdam, Germany, against Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH, a glycolytic enzyme whose inhibition deprives the parasite of energy supply. NPs acting as potential inhibitors of the mentioned enzyme were identified using a pharmacophore-based virtual screening and subsequent docking of the identified hits into the active site of interest. In a set of 700 structures chosen for the screening, 13 (1.9% were predicted to possess significant affinity towards the enzyme and were therefore tested in an in vitro enzyme assay using recombinant TbGAPDH. Nine of these in silico hits (69% showed significant inhibitory activity at 50 µM, of which two geranylated benzophenone derivatives proved to be particularly active with IC50 values below 10 µM. These compounds also showed moderate in vitro activity against T. brucei rhodesiense and may thus represent interesting starting points for further optimization.

  2. SAS-4 Protein in Trypanosoma brucei Controls Life Cycle Transitions by Modulating the Length of the Flagellum Attachment Zone Filament.

    Science.gov (United States)

    Hu, Huiqing; Zhou, Qing; Li, Ziyin

    2015-12-18

    The evolutionarily conserved centriole/basal body protein SAS-4 regulates centriole duplication in metazoa and basal body duplication in flagellated and ciliated organisms. Here, we report that the SAS-4 homolog in the flagellated protozoan Trypanosoma brucei, TbSAS-4, plays an unusual role in controlling life cycle transitions by regulating the length of the flagellum attachment zone (FAZ) filament, a specialized cytoskeletal structure required for flagellum adhesion and cell morphogenesis. TbSAS-4 is concentrated at the distal tip of the FAZ filament, and depletion of TbSAS-4 in the trypomastigote form disrupts the elongation of the new FAZ filament, generating cells with a shorter FAZ associated with a longer unattached flagellum and repositioned kinetoplast and basal body, reminiscent of epimastigote-like morphology. Further, we show that TbSAS-4 associates with six additional FAZ tip proteins, and depletion of TbSAS-4 disrupts the enrichment of these FAZ tip proteins at the new FAZ tip, suggesting a role of TbSAS-4 in maintaining the integrity of this FAZ tip protein complex. Together, these results uncover a novel function of TbSAS-4 in regulating the length of the FAZ filament to control basal body positioning and life cycle transitions in T. brucei.

  3. Deviating the level of proliferating cell nuclear antigen in Trypanosoma brucei elicits distinct mechanisms for inhibiting proliferation and cell cycle progression.

    Science.gov (United States)

    Valenciano, Ana L; Ramsey, Aaron C; Mackey, Zachary B

    2015-01-01

    The DNA replication machinery is spatially and temporally coordinated in all cells to reproduce a single exact copy of the genome per division, but its regulation in the protozoan parasite Trypanosoma brucei is not well characterized. We characterized the effects of altering the levels of proliferating cell nuclear antigen, a key component of the DNA replication machinery, in bloodstream form T. brucei. This study demonstrated that tight regulation of TbPCNA levels was critical for normal proliferation and DNA replication in the parasite. Depleting TbPCNA mRNA reduced proliferation, severely diminished DNA replication, arrested the synthesis of new DNA and caused the parasites to accumulated in G2/M. Attenuating the parasite by downregulating TbPCNA caused it to become hypersensitive to hydroxyurea. Overexpressing TbPCNA in T. brucei arrested proliferation, inhibited DNA replication and prevented the parasite from exiting G2/M. These results indicate that distinct mechanisms of cell cycle arrest are associated with upregulating or downregulating TbPCNA. The findings of this study validate deregulating intra-parasite levels of TbPCNA as a potential strategy for therapeutically exploiting this target in bloodstream form T. brucei.

  4. A proteomics approach reveals molecular manipulators of distinct cellular processes in the salivary glands of Glossina m. morsitans in response to Trypanosoma b. brucei infections

    NARCIS (Netherlands)

    Kariithi, Henry M.; Boeren, Sjef; Murungi, Edwin K.; Vlak, Just M.; Abd-Alla, Adly M.M.

    2016-01-01

    Background: Glossina m. morsitans is the primary vector of the Trypanosoma brucei group, one of the causative agents of African trypanosomoses. The parasites undergo metacyclogenesis, i.e. transformation into the mammalian-infective metacyclic trypomastigote (MT) parasites, in the salivary glands

  5. Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign.

    Directory of Open Access Journals (Sweden)

    Rosario Diaz

    2014-10-01

    Full Text Available In the interest of identification of new kinase-targeting chemotypes for target and pathway analysis and drug discovery in Trypanosomal brucei, a high-throughput screen of 42,444 focused inhibitors from the GlaxoSmithKline screening collection was performed against parasite cell cultures and counter-screened against human hepatocarcinoma (HepG2 cells. In this way, we have identified 797 sub-micromolar inhibitors of T. brucei growth that are at least 100-fold selective over HepG2 cells. Importantly, 242 of these hit compounds acted rapidly in inhibiting cellular growth, 137 showed rapid cidality. A variety of in silico and in vitro physicochemical and drug metabolism properties were assessed, and human kinase selectivity data were obtained, and, based on these data, we prioritized three compounds for pharmacokinetic assessment and demonstrated parasitological cure of a murine bloodstream infection of T. brucei rhodesiense with one of these compounds (NEU-1053. This work represents a successful implementation of a unique industrial-academic collaboration model aimed at identification of high quality inhibitors that will provide the parasitology community with chemical matter that can be utilized to develop kinase-targeting tool compounds. Furthermore these results are expected to provide rich starting points for discovery of kinase-targeting tool compounds for T. brucei, and new HAT therapeutics discovery programs.

  6. Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign.

    Science.gov (United States)

    Diaz, Rosario; Luengo-Arratta, Sandra A; Seixas, João D; Amata, Emanuele; Devine, William; Cordon-Obras, Carlos; Rojas-Barros, Domingo I; Jimenez, Elena; Ortega, Fatima; Crouch, Sabrinia; Colmenarejo, Gonzalo; Fiandor, Jose Maria; Martin, Jose Julio; Berlanga, Manuela; Gonzalez, Silvia; Manzano, Pilar; Navarro, Miguel; Pollastri, Michael P

    2014-10-01

    In the interest of identification of new kinase-targeting chemotypes for target and pathway analysis and drug discovery in Trypanosomal brucei, a high-throughput screen of 42,444 focused inhibitors from the GlaxoSmithKline screening collection was performed against parasite cell cultures and counter-screened against human hepatocarcinoma (HepG2) cells. In this way, we have identified 797 sub-micromolar inhibitors of T. brucei growth that are at least 100-fold selective over HepG2 cells. Importantly, 242 of these hit compounds acted rapidly in inhibiting cellular growth, 137 showed rapid cidality. A variety of in silico and in vitro physicochemical and drug metabolism properties were assessed, and human kinase selectivity data were obtained, and, based on these data, we prioritized three compounds for pharmacokinetic assessment and demonstrated parasitological cure of a murine bloodstream infection of T. brucei rhodesiense with one of these compounds (NEU-1053). This work represents a successful implementation of a unique industrial-academic collaboration model aimed at identification of high quality inhibitors that will provide the parasitology community with chemical matter that can be utilized to develop kinase-targeting tool compounds. Furthermore these results are expected to provide rich starting points for discovery of kinase-targeting tool compounds for T. brucei, and new HAT therapeutics discovery programs.

  7. Analysis of cosmid clones of nuclear DNA from Trypanosome brucei shows that the genes for variant surface glycoproteins are clustered in the genome.

    NARCIS (Netherlands)

    D. Valerio (Dinko); T. de Lange; P. Borst (Piet); F.G. Grosveld (Frank); L.H.T. van der Ploeg

    1982-01-01

    textabstractTrypanosoma brucei contains more than a hundred genes coding for the different variant surface glycoproteins (VSGs). Activation of some of these genes involves the duplication of the gene (the basic copy or BC) and transposition of the duplicate to an expression site (yielding the expres

  8. Use of Supplemental Short Pre-Contoured Accessory Rods and Cobalt Chrome Alloy Posterior Rods Reduces Primary Rod Strain and Range of Motion Across the Pedicle Subtraction Osteotomy Level

    DEFF Research Database (Denmark)

    Hallager, Dennis Winge; Gehrchen, Martin; Dahl, Benny

    2016-01-01

    correct significant sagittal deformity of the lumbar spine; however, revision rates are high. To reduce rod strain and the incidence of rod fracture, clinical use of multi-rod construction, cobalt chrome (CoCr) alloy rods, and interbody spacers adjacent to PSO has been proposed. Investigating both motion...

  9. Patterns of rod proliferation in deep-sea fish retinae.

    Science.gov (United States)

    Fröhlich, E; Negishi, K; Wagner, H J

    1995-07-01

    In a sample of 37 species of deep-sea fish species from the sea floor of the Porcupine Seabight and the Gobal spur (North Atlantic) we investigated the overall structure of the retina with special respect for the organization of rods, their length and their arrangement in multiple banks. Using an immunocytochemical marker for cell proliferation (PCNA) we studied the mechanisms of rod proliferation, and, by means of serial section reconstruction followed their integration into the existing population of rods. Furthermore, in three different species we have observed growth related changes in retinal thickness, rod density and proliferation activity. We found evidence for two different principles for the organization of rods in these deep-sea fish retinae. In the first group of species represented by Nematonurus armatus and Coryphaenoides guentheri we found rods to be rather short (20-30 microns) and arranged in three and more banks. In these species rod proliferation occurred in a single band of cells immediately vitread of the external limiting membrane, thus showing a high degree of spatial and temporal order. In these species, young rods are inserted just sclerad of the external limiting membrane and the older outer segments pushed away from the incoming light towards the back of the eye. This may be linked to a progressive loss of function of the older rods and might represent an alternative mechanism to the disk shedding in other vertebrates. In the second population (e.g. Conocara macroptera, Alepocephalus agassizii) we observed considerably longer rod outer segments (60-80 microns) forming no more than two layers. These retinae had rod precursors arranged in disseminated clusters throughout the outer nuclear layer indicating the lack of clear spatio-temporal order in mitotic activity along with a more statistical pattern of integration of the newly formed outer segments. In our sample of species both populations were of about equal size suggesting that the two

  10. Investigation of axial power gradients near a control rod tip

    Energy Technology Data Exchange (ETDEWEB)

    Loberg, John, E-mail: John.Loberg@fysast.uu.se [Uppsala University, Department of Physics and Astronomy, Division of Applied Nuclear Physics, Box 525, SE-75120 Uppsala (Sweden); Osterlund, Michael, E-mail: Michael.Osterlund@fysast.uu.se [Uppsala University, Department of Physics and Astronomy, Division of Applied Nuclear Physics, Box 525, SE-75120 Uppsala (Sweden); Bejmer, Klaes-Hakan, E-mail: Klaes-Hakan.Bejmer@vattenfall.com [Vattenfall Nuclear Fuel AB, Jaemtlandsgatan 99, 162 60 Vaellingby, Stockholm (Sweden); Blomgren, Jan, E-mail: Jan.Blomgren@vattenfall.com [Vattenfall Nuclear Fuel AB, Jaemtlandsgatan 99, 162 60 Vaellingby, Stockholm (Sweden); Kierkegaard, Jesper, E-mail: Jesper.Kierkegaar@vattenfall.com [Vattenfall Nuclear Fuel AB, Jaemtlandsgatan 99, 162 60 Vaellingby, Stockholm (Sweden)

    2011-07-15

    Highlights: > Pin power gradients near BWR control rod tips have been investigated. > A control rod tip is modeled in MCNP and compared to simplified 2D/3D geometry. > Small nodes increases pin power gradients; standard nodes underestimates gradients. > The MCNP results are validated against axial gamma scan of a controlled fuel pin. - Abstract: Control rod withdrawal in BWRs induces large power steps in the adjacent fuel assemblies. This paper investigates how well a 2D/3D method, e.g., CASMO5/SIMULATE5 computes axial pin power gradients adjacent to an asymmetrical control-rod tip in a BWR. The ability to predict pin power gradients accurately is important for safety considerations whereas large powers steps induced by control rod withdrawal can cause Pellet Cladding Interaction. The computation of axial pin power gradients axially around a control rod tip is a challenging task for any nodal code. On top of that, asymmetrical control rod handles are present in some BWR designs. The lattice code CASMO requires diagonal symmetry of all control rod parts. This introduces an error in computed pin power gradients that has been evaluated by Monte Carlo calculations. The results show that CASMO5/SIMULATE5, despite the asymmetrical control rod handle, is able to predict the axial pin power gradient within 1%/cm for axial nodal sizes of 15-3.68 cm. However, a nodal size of 3.68 cm still causes underestimations of pin power gradients compared with 1 cm nodes. Furthermore, if conventional node sizes are used, {approx}15 cm, pin power gradients can be underestimated by over 50% compared with 1 cm nodes. The detailed axial pin power profiles from MCNP are corroborated by measured gamma scan data on fuel rods irradiated adjacent to control rods.

  11. Electric Fuel Rod Simulator Fabrication at ORNL

    Science.gov (United States)

    Ott, Larry J.; McCulloch, Reg

    2004-02-01

    Commercial vendors could not supply the high-quality, highly instrumented electric fuel rod simulators (FRS) required for large thermal-hydraulic safety-oriented experiments at the Oak Ridge National Laboratory (ORNL) in the 1970s and early 1980s. Staff at ORNL designed, developed, and manufactured the simulators utilized in these safety experiments. Important FRS design requirements include (1) materials of construction, (2) test power requirements and availability, (3) experimental test objectives, (4) supporting thermal analyses, and (5) extensive quality control throughout all phases of FRS fabrication. This paper will present an overview of these requirements (design, analytics, and quality control) as practiced at ORNL to produce a durable high-quality FRS.

  12. Axial thermal rotation of slender rods.

    Science.gov (United States)

    Li, Dichuan; Fakhri, Nikta; Pasquali, Matteo; Biswal, Sibani Lisa

    2011-05-06

    Axial rotational diffusion of rodlike polymers is important in processes such as microtubule filament sliding and flagella beating. By imaging the motion of small kinks along the backbone of chains of DNA-linked colloids, we produce a direct and systematic measurement of axial rotational diffusivity of rods both in bulk solution and near a wall. The measured diffusivities decrease linearly with the chain length, irrespective of the distance from a wall, in agreement with slender-body hydrodynamics theory. Moreover, the presence of small kinks does not affect the chain's axial diffusivity. Our system and measurements provide insights into fundamental axial diffusion processes of slender objects, which encompass a wide range of entities including biological filaments and linear polymer chains.

  13. Biomolecular rods and tubes in nanotechnology

    Science.gov (United States)

    Bittner, Alexander M.

    2005-02-01

    Biomolecules are vitally important elements in nanoscale science and also in future nanotechnology. Their shape and their chemical and physical functionality can give them a big advantage over inorganic and organic substances. While this becomes most obvious in proteins and peptides, with their complicated, but easily controlled chemistry, other biomolecular substances such as DNA, lipids and carbohydrates can also be important. In this review, the emphasis is on one-dimensional molecules and on molecules that self-assemble into linear structures, and on their potential applications. An important aspect is that biomolecules can act as templates, i.e. their shape and chemical properties can be employed to arrange inorganic substances such as metals or metal compounds on the nanometre scale. In particular, rod- and tube-like nanostructures can show physical properties that are different from those of the bulk material, and thus these structures are likely to be a basis for new technology.

  14. Optimized Control Rods of the BR2 Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Kalcheva, Silva; Koonen, E.

    2007-09-15

    At the present time the BR-2 reactor uses control elements with cadmium as neutron absorbing part. The lower section of the control element is a beryllium assembly cooled by light water. Due to the burn up of the lower end of the cadmium section during the reactor operation, the presently used rods for reactivity control of the BR-2 reactor have to be replaced by new ones. Considered are various types Control Rods with full active part of the following materials: cadmium (Cd), hafnium (Hf), europium oxide (Eu2O3) and gadolinium (Gd2O3). Options to decrease the burn up of the control rod material in the hot spot, such as use of stainless steel in the lower active part of the Control Rod are discussed. Comparison with the characteristics of the presently used Control Rods types is performed. The changing of the characteristics of different types Control Rods and the perturbation effects on the reactor neutronics during the BR-2 fuel cycle are investigated. The burn up of the Control Rod absorbing material, total and differential control rods worth, macroscopic and effective microscopic absorption cross sections, fuel and reactivity evolution are evaluated during approximately 30 operating cycles.

  15. Chitosan rod reinforced by self-crosslinking through thermal treatment

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Chitosan (CS) rods were reinforced at high temperatures to form network structure by self-crosslinking of amino groups.Properties of treated CS rods were studied by FTIR spectroscopy,intrinsic viscosity measurement,mechanical properties testing and water absorption measurement.The FTIR spectra indicated that the CS configuration was transformed from β-CS for untreated CS rods to α-CS for thermally treated CS rods.Meanwhile,the crosslinking also occurred between amino groups of CS.Due to the increase in the crosslinking degree,the intrinsic viscosity increased with the rising of temperature.It was found that the network structure enhanced the bending strength of CS rods,which reached 154.8 MPa when CS rods were treated at 140℃ for 2 h.Thermal treatment also reduced the water absorption of CS rods.Due to the improved mechanical properties,thermally treated CS rods could be used as a novel device for internal fixation of bone fracture.

  16. 49 CFR 236.794 - Rod, up-and-down.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Rod, up-and-down. 236.794 Section 236.794 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION..., up-and-down. A rod used for connecting the semaphore arm to the operating mechanism of a signal....

  17. Control rod drive for high temperature gas cooled reactor

    Institute of Scientific and Technical Information of China (English)

    DengJun-Xian; XuJi-Ming; 等

    1998-01-01

    This control rod drive is developed for HTR-10 high temperature gas cooled test reactor.The stepmotor is prefered to improve positioning of the control rod and the scram behavior.The preliminary test in 1600170 ambient temperature shows that the selected stepmotor and transmission system can meet the main operation function requirements of HTR-10.

  18. Numerical investigation of flow past a row of rectangular rods

    Directory of Open Access Journals (Sweden)

    S.Ul. Islam

    2016-09-01

    Full Text Available A numerical study of uniform flow past a row of rectangular rods with aspect ratio defined as R = width/height = 0.5 is performed using the Lattice Boltzmann method. For this study the Reynolds number (Re is fixed at 150, while spacings between the rods (g are taken in the range from 1 to 6. Depending on g, the flow is classified into four patterns: flip-flopping, nearly unsteady-inphase, modulated inphase-antiphase non-synchronized and synchronized. Sudden jumps in physical parameters were observed, attaining either maximum or minimum values, with the change in flow patterns. The mean drag coefficient (Cdmean of middle rod is higher than the second and fourth rod for flip-flopping pattern while in case of nearly unsteady-inphase the middle rod attains minimum drag coefficient. It is also found that the Strouhal number (St of first, second and fifth rod decreases as g increases while that of other two have mixed trend. The results further show that there exist secondary interaction frequencies together with primary vortex shedding frequency due to jet in the gap between rods for 1 ⩽ g ⩽ 3. For the average values of Cdmean and St, an empirical relation is also given as a function of gap spacing. This relation shows that the average values of Cdmean and St approach to those of single rectangular rod with increment in g.

  19. Switch isotropic/anisotropic wettability via dual-scale rods

    Directory of Open Access Journals (Sweden)

    Yang He

    2014-10-01

    Full Text Available It is the first time to demonstrate the comparison of isotropic/anisotropic wettability between dual-scale micro-nano-rods and single-scale micro-rods. Inspired by the natural structures of rice leaf, a series of micro-nano-rods and micro-rods with different geometric parameters were fabricated using micro-fabrication technology. Experimental measured apparent contact angles and advancing and receding contact angles from orthogonal orientations were characterized. The difference of contact angles from orthogonal orientation on dual-scale rods was much smaller than those on single-scale rods in both static and dynamic situation. It indicated that the dual-scale micro-nano-rods showed isotropic wettability, while single-scale micro-rods showed anisotropic wettability. The switch of isotropic/anisotropic wettability could be illustrated by different wetting state and contact line moving. It offers a facial way to switch isotropic/anisotropic wettability of the surface via dual-scale or single-scale structure.

  20. Probabilistic thermo-chemical analysis of a pultruded composite rod

    DEFF Research Database (Denmark)

    Baran, Ismet; Tutum, Cem Celal; Hattel, Jesper Henri

    2012-01-01

    In the present study the deterministic thermo-chemical pultrusion simulation of a composite rod taken from the literature [7] is used as a validation case. The predicted centerline temperature and cure degree profiles of the rod match well with those in the literature [7]. Following the validation...

  1. Switch isotropic/anisotropic wettability via dual-scale rods

    Science.gov (United States)

    He, Yang; Jiang, Chengyu; Wang, Shengkun; Ma, Zhibo; Yuan, Weizheng

    2014-10-01

    It is the first time to demonstrate the comparison of isotropic/anisotropic wettability between dual-scale micro-nano-rods and single-scale micro-rods. Inspired by the natural structures of rice leaf, a series of micro-nano-rods and micro-rods with different geometric parameters were fabricated using micro-fabrication technology. Experimental measured apparent contact angles and advancing and receding contact angles from orthogonal orientations were characterized. The difference of contact angles from orthogonal orientation on dual-scale rods was much smaller than those on single-scale rods in both static and dynamic situation. It indicated that the dual-scale micro-nano-rods showed isotropic wettability, while single-scale micro-rods showed anisotropic wettability. The switch of isotropic/anisotropic wettability could be illustrated by different wetting state and contact line moving. It offers a facial way to switch isotropic/anisotropic wettability of the surface via dual-scale or single-scale structure.

  2. Probabilistic thermo-chemical analysis of a pultruded composite rod

    NARCIS (Netherlands)

    Baran, Ismet; Tutum, Cem C.; Hattel, Jesper H.

    2012-01-01

    In the present study the deterministic thermo-chemical pultrusion simulation of a composite rod taken from the literature [7] is used as a validation case. The predicted centerline temperature and cure degree profiles of the rod match well with those in the literature [7]. Following the validation c

  3. Optimization of fuel rod enrichment distribution for BWR fuel assembly

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Yasushi; Hida, Kazuki; Sakurada, Koichi; Yamamoto, Munenari [Toshiba Corp., Kawasaki, Kanagawa (Japan). Nuclear Engineering Lab.

    1996-09-01

    A practical method was developed for determining the optimum fuel enrichment distribution within a boiling water reactor fuel assembly. The method deals with two different optimization problems, i.e. the combinatorial optimization problem of grouping fuel rods into a given number of rod groups with the same enrichment, and the problem of determining an optimal enrichment for each fuel rod under the resultant rod-grouping pattern. In solving these problems, the primary goal is to minimize a predefined objective function over a given exposure period. The objective function used here is defined by the linear combination C{sub 1}X + C{sub 2}X{sub G}, where X and X{sub G} stand, respectively, for control variables giving constraint to the local power peaking factor and the gadolinium rod power. C{sub 1} and C{sub 2} are user-definable weighting factors to accommodate design preferences. The algorithm for solving this combinatorial optimization problem starts by finding the optimal enrichment vector without any rod-grouping, and promising candidates of rod-grouping patterns are found by exhaustive enumeration based on the resulting fuel enrichment ordering. This latter problem is solved using the method of approximation programming. A practical application is shown for a contemporary 8 x 8 Pu mixed-oxide fuel assembly with 10 gadolinium-poisoned rods. (author)

  4. The use of yellow fluorescent hybrids to indicate mating in Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Ferris Vanessa

    2008-02-01

    Full Text Available Abstract Background Trypanosoma brucei undergoes genetic exchange in its insect vector, the tsetse fly, by an unknown mechanism. The difficulties of working with this experimental system of genetic exchange have hampered investigation, particularly because the trypanosome life cycle stages involved cannot be cultured in vitro and therefore must be examined in the insect. Searching for small numbers of hybrid trypanosomes directly in the fly has become possible through the incorporation of fluorescent reporter genes, and we have previously carried out a successful cross using a reporter-repressor strategy. However, we could not be certain that all fluorescent trypanosomes observed in that cross were hybrids, due to mutations of the repressor leading to spontaneous fluorescence, and we have therefore developed an alternative strategy. Results To visualize the production of hybrids in the fly, parental trypanosome clones were transfected with a gene encoding Green Fluorescent Protein (GFP or Red Fluorescent Protein (RFP. Co-infection of flies with red and green fluorescent parental trypanosomes produced yellow fluorescent hybrids, which were easily visualized in the fly salivary glands. Yellow trypanosomes were not seen in midgut or proventricular samples and first appeared in the glands as epimastigotes as early as 13 days after fly infection. Cloned progeny originating from individual salivary glands had yellow, red, green or no fluorescence and were confirmed as hybrids by microsatellite, molecular karyotype and kinetoplast (mitochondrial DNA analyses. Hybrid clones showed biparental inheritance of both nuclear and kinetoplast genomes. While segregation and reassortment of the reporter genes and microsatellite alleles were consistent with Mendelian inheritance, flow cytometry measurement of DNA content revealed both diploid and polyploid trypanosomes among the hybrid progeny clones. Conclusion The strategy of using production of yellow hybrids

  5. Semiconductor Quantum Rods as Single Molecule FluorescentBiological Labels

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Aihua; Gu, Weiwei; Boussert, Benjamine; Koski, Kristie; Gerion, Daniele; Manna, Liberato; Le Gros, Mark; Larabell, Carolyn; Alivisatos, A. Paul

    2006-05-29

    In recent years, semiconductor quantum dots have beenapplied with great advantage in a wide range of biological imagingapplications. The continuing developments in the synthesis of nanoscalematerials and specifically in the area of colloidal semiconductornanocrystals have created an opportunity to generate a next generation ofbiological labels with complementary or in some cases enhanced propertiescompared to colloidal quantum dots. In this paper, we report thedevelopment of rod shaped semiconductor nanocrystals (quantum rods) asnew fluorescent biological labels. We have engineered biocompatiblequantum rods by surface silanization and have applied them fornon-specific cell tracking as well as specific cellular targeting. Theproperties of quantum rods as demonstrated here are enhanced sensitivityand greater resistance for degradation as compared to quantum dots.Quantum rods have many potential applications as biological labels insituations where their properties offer advantages over quantumdots.

  6. Entropical Colloidal Interaction in Rod-like Molecules Solution

    Science.gov (United States)

    Hohlfeld, Evan B.; Lin, Keng-Hui; Zeri, Ana Carolina; Crocker, John C.; Yodh, Arjun G.

    2001-03-01

    We report direct measurements of the functional form of the depletion interaction between two colloidal spheres in a rod-like molecule suspension the line-scanned optical tweezer. The rod like moleculses are bacteriaphage fd with length (L) 880 nm and diameter(D) 6.5 nm and TMV with L 300 nm and D 200 nm. We probed different ratios of sphere radius R and rod length L and compared with theoretical models of Yaman^. The experimental data agrees with the model with slight discrepancy due to the flexibility of rod molecules. At high salt concentration, we also observed the steric repulsion due rod molecule stuck on the spheres. We gratefully acknowledge support from the NSF (DMR-9623441) and MRSEC (DMR-9632598). K. Yaman, C. Jeppesen and C.M. Marques, Europhys. Lett., 42, 221 (1998).

  7. Investigating the optical XNOR gate using plasmonic nano-rods

    Science.gov (United States)

    Akhlaghi, Majid; Kaboli, Milad

    2016-04-01

    In this paper, a coherent perfect absorption (CPA)-type XNOR gate based on plasmonic nano particle is proposed. It consists of two plasmonic nano rod arrays on top of two parallel arms with quartz substrate. The operation principle is based on the absorbable formation of a conductive path in the dielectric layer of a plasmonic nano-particles waveguide. Since the CPA efficiency depends strongly on the number of plasmonic nano-rod and the nano rod location, an efficient binary optimization method based the Particle Swarm Optimization (PSO) algorithm is used to design an optimized array of the plasmonic nano-rod in order to achieve the maximum absorption coefficient in the 'off' state and the minimum absorption coefficient in the 'on' state. In Binary PSO (BPSO), a group of birds consists a matrix with binary entries, control the presence ('1‧) or the absence ('0‧) of nano rod in the array.

  8. Jourdain Principle of a Super-Thin Elastic Rod Dynamics

    Institute of Scientific and Technical Information of China (English)

    XUE Yun; SHANG Hui-Lin

    2009-01-01

    A super thin elastic rod is modeled with a background of DNA super coiling structure, and its dynamics is discussed based on the Jourdain variation. The cross section of the rod is taken as the object of this study and two velocity spaces about arc coordinate and the time are obtained respectively. Virtual displacements of the section on the two velocity spaces are defined and can be expressed in terms of Jourdaln variation. Jourdain principles of a super thin elastic rod dynamics on arc coordinate and the time velocity space are established,respectively, which show that there are two ways to realize the constraint conditions. If the constitutive relation of the rod is linear, the Jourdaln principle takes the Euler-Lagrange form with generalized coordinates. The Kirchhoff equation, Lagrange equation and Appell equation can be derived from the present Jourdaln principle.While the rod subjected to a surface constraint, Lagrange equation with undetermined multipliers may be derived.

  9. Systematic parametric design/calculation of the piston rod unit

    Science.gov (United States)

    Kacani, V.

    2015-08-01

    In this article a modern and economic method for the strength calculation of the piston rod unit and its components under different operating conditions will be presented. Herefore the commercial FEA - Software will be linked with the company-owned calculation tools. The parametric user input will be followed by an automatic Pre- and Postprocessing. Afterwards the strength calculation is processed on all critical points of the piston rod connection, assisted by an extra module, based on general standards and special codes for reciprocating compressors. In this process most arrangements of the piston rod unit as well as the special geometries of the single-components (piston, piston rod and piston nut) can be considered easily. In this article the modeling of the notches, especially on the piston rod, piston as well as the piston nut will be covered in detail.

  10. Fatigue Life Improving of Drill Rod by Inclusion Control

    Science.gov (United States)

    Wang, Linzhu; Yang, Shufeng; Li, Jingshe; Liu, Wei; Zhou, Yinghao

    2016-08-01

    Large and hard inclusions often deteriorate the service performance and reduce the fatigue lifetime of drill rods. In this paper, the main reasons of the rupture of drill rods were analyzed by the examination of their fracture and it is found that the large inclusions were the main reason of breakage of rod drill. The inclusions were high of Ca content or Al2O3 rich. Smaller and better deformability inclusions were obtained by the optimization of refining slag, calcium treatment process and the flow control devices of tundish. Results of industrial experiment after optimization show that total oxygen content of drill rods decreased by more than 50%, macro-inclusions weight fraction decreased from about 4 mg/10 kg to about 0.3 mg/10 kg and the micro-inclusions average size decreased from 6 to 3.6 μm. The average using times of drill rods after optimization were increased by about 60%.

  11. Heterologous expression of hydrophobins RodA and RodB from Aspergillus fumigatus in host Pichia pastoris

    DEFF Research Database (Denmark)

    Pedersen, Mona Højgaard; Borodina, Irina; Frisvad, Jens Christian;

    Introduction: Hydrophobins are small amphipatic proteins present on the spore surface of filamentous fungi. They most likely play an important role in the attachment of spores to a solid phase. The pathogenic fungus Aspergillus fumigatus expresses the hydrophobins RodA and RodB on the surface...

  12. Optimization of fuel rod enrichment distribution to minimize rod power peaking throughout life within BWR fuel assembly

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Yasushi; Hida, Kazuki; Sakurada, Koichi; Yamamoto, Munenari [Toshiba Corp., Kawasaki, Kanagawa (Japan). Nuclear Engineering Lab.

    1997-01-01

    A practical method was developed for determining the optimum fuel enrichment distribution within a boiling water reactor fuel assembly. The method deals with two different optimization problems, i.e. a combinatorial optimization problem grouping fuel rods into a given number of rod groups with the same enrichment, and a problem determining an optimal enrichment for each fuel rod under the resultant rod-grouping pattern. In solving these problems, the primary goal is to minimize a predefined objective function over a given exposure period. The objective function used here is defined by a linear combination: C{sub 1}X+C{sub 2}X{sub G}, where X and X{sub G} stand for a control variable to give the constraint respectively for a local power peaking factor and a gadolinium rod power, and C{sub 1} and C{sub 2} are user-definable weighting factor to accommodate the design preference. The algorithm of solving the combinatorial optimization problem starts with finding the optimal enrichment vector without any rod-grouping, and promising candidates of rod-grouping patterns are found by exhaustive enumeration based on the resulting fuel enrichment ordering, and then the latter problem is solved by using the method of approximation programming. The practical application of the present method is shown for a contemporary 8x8 Pu mixed-oxide fuel assembly with 10 gadolinium-poisoned rods. (author)

  13. Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate with decreased susceptibility to pentamidine and melarsoprol.

    Directory of Open Access Journals (Sweden)

    Fabrice E Graf

    Full Text Available The predominant mechanism of drug resistance in African trypanosomes is decreased drug uptake due to loss-of-function mutations in the genes for the transporters that mediate drug import. The role of transporters as determinants of drug susceptibility is well documented from laboratory-selected Trypanosoma brucei mutants. But clinical isolates, especially of T. b. gambiense, are less amenable to experimental investigation since they do not readily grow in culture without prior adaptation. Here we analyze a selected panel of 16 T. brucei ssp. field isolates that (i have been adapted to axenic in vitro cultivation and (ii mostly stem from treatment-refractory cases. For each isolate, we quantify the sensitivity to melarsoprol, pentamidine, and diminazene, and sequence the genomic loci of the transporter genes TbAT1 and TbAQP2. The former encodes the well-characterized aminopurine permease P2 which transports several trypanocides including melarsoprol, pentamidine, and diminazene. We find that diminazene-resistant field isolates of T. b. brucei and T. b. rhodesiense carry the same set of point mutations in TbAT1 that was previously described from lab mutants. Aquaglyceroporin 2 has only recently been identified as a second transporter involved in melarsoprol/pentamidine cross-resistance. Here we describe two different kinds of TbAQP2 mutations found in T. b. gambiense field isolates: simple loss of TbAQP2, or loss of wild-type TbAQP2 allele combined with the formation of a novel type of TbAQP2/3 chimera. The identified mutant T. b. gambiense are 40- to 50-fold less sensitive to pentamidine and 3- to 5-times less sensitive to melarsoprol than the reference isolates. We thus demonstrate for the first time that rearrangements of the TbAQP2/TbAQP3 locus accompanied by TbAQP2 gene loss also occur in the field, and that the T. b. gambiense carrying such mutations correlate with a significantly reduced susceptibility to pentamidine and melarsoprol.

  14. Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate with decreased susceptibility to pentamidine and melarsoprol.

    Science.gov (United States)

    Graf, Fabrice E; Ludin, Philipp; Wenzler, Tanja; Kaiser, Marcel; Brun, Reto; Pyana, Patient Pati; Büscher, Philippe; de Koning, Harry P; Horn, David; Mäser, Pascal

    2013-01-01

    The predominant mechanism of drug resistance in African trypanosomes is decreased drug uptake due to loss-of-function mutations in the genes for the transporters that mediate drug import. The role of transporters as determinants of drug susceptibility is well documented from laboratory-selected Trypanosoma brucei mutants. But clinical isolates, especially of T. b. gambiense, are less amenable to experimental investigation since they do not readily grow in culture without prior adaptation. Here we analyze a selected panel of 16 T. brucei ssp. field isolates that (i) have been adapted to axenic in vitro cultivation and (ii) mostly stem from treatment-refractory cases. For each isolate, we quantify the sensitivity to melarsoprol, pentamidine, and diminazene, and sequence the genomic loci of the transporter genes TbAT1 and TbAQP2. The former encodes the well-characterized aminopurine permease P2 which transports several trypanocides including melarsoprol, pentamidine, and diminazene. We find that diminazene-resistant field isolates of T. b. brucei and T. b. rhodesiense carry the same set of point mutations in TbAT1 that was previously described from lab mutants. Aquaglyceroporin 2 has only recently been identified as a second transporter involved in melarsoprol/pentamidine cross-resistance. Here we describe two different kinds of TbAQP2 mutations found in T. b. gambiense field isolates: simple loss of TbAQP2, or loss of wild-type TbAQP2 allele combined with the formation of a novel type of TbAQP2/3 chimera. The identified mutant T. b. gambiense are 40- to 50-fold less sensitive to pentamidine and 3- to 5-times less sensitive to melarsoprol than the reference isolates. We thus demonstrate for the first time that rearrangements of the TbAQP2/TbAQP3 locus accompanied by TbAQP2 gene loss also occur in the field, and that the T. b. gambiense carrying such mutations correlate with a significantly reduced susceptibility to pentamidine and melarsoprol.

  15. The Aurora Kinase in Trypanosoma brucei plays distinctive roles in metaphase-anaphase transition and cytokinetic initiation.

    Directory of Open Access Journals (Sweden)

    Ziyin Li

    2009-09-01

    Full Text Available Aurora B kinase is an essential regulator of chromosome segregation with the action well characterized in eukaryotes. It is also implicated in cytokinesis, but the detailed mechanism remains less clear, partly due to the difficulty in separating the latter from the former function in a growing cell. A chemical genetic approach with an inhibitor of the enzyme added to a synchronized cell population at different stages of the cell cycle would probably solve this problem. In the deeply branched parasitic protozoan Trypanosoma brucei, an Aurora B homolog, TbAUK1, was found to control both chromosome segregation and cytokinetic initiation by evidence from RNAi and dominant negative mutation. To clearly separate these two functions, VX-680, an inhibitor of TbAUK1, was added to a synchronized T. brucei procyclic cell population at different cell cycle stages. The unique trans-localization pattern of the chromosomal passenger complex (CPC, consisting of TbAUK1 and two novel proteins TbCPC1 and TbCPC2, was monitored during mitosis and cytokinesis by following the migration of the proteins tagged with enhanced yellow fluorescence protein in live cells with time-lapse video microscopy. Inhibition of TbAUK1 function in S-phase, prophase or metaphase invariably arrests the cells in the metaphase, suggesting an action of TbAUK1 in promoting metaphase-anaphase transition. TbAUK1 inhibition in anaphase does not affect mitotic exit, but prevents trans-localization of the CPC from the spindle midzone to the anterior tip of the new flagellum attachment zone for cytokinetic initiation. The CPC in the midzone is dispersed back to the two segregated nuclei, while cytokinesis is inhibited. In and beyond telophase, TbAUK1 inhibition has no effect on the progression of cytokinesis or the subsequent G1, S and G2 phases until a new metaphase is attained. There are thus two clearly distinct points of TbAUK1 action in T. brucei: the metaphase-anaphase transition and

  16. Effects of supplementing Erythrina brucei leaf as a substitute for cotton seed meal on growth performance and carcass characteristics of Sidama goats fed basal diet of natural grass hay.

    Science.gov (United States)

    Yinnesu, Asmamaw; Nurfeta, Ajebu

    2012-03-01

    The replacement value of dried Erythrina brucei leaf for cotton seed meal (CSM) on growth performance and carcass characteristics was evaluated. Twenty-five yearling buck goats (15.8 ± 1.4 kg) were assigned into five treatments in a randomized complete block design: natural grass hay alone (T1) or supplemented with 100% CSM (T2), 67% CSM + 33% E. brucei (T3), 33% CSM + 67% E. brucei (T4), and 100% E. brucei (T5) on dry matter (DM) basis. Supplemented goats consumed more (P  0.05) by the proportion of the supplements. The highest (P goats supplemented with CSM alone, whereas the lowest intake was observed in the non-supplemented group. Total CP intake decreased (P goats gained more (P goats than in the non-supplemented ones, but similar (P > 0.05) among the supplemented group. The digestibility of CP was higher (P goats, except in those goats fed E. brucei alone, than the non-supplemented group. Slaughter weight, empty body weight, hot carcass weight, dressing percentage, rib eye muscle area, and total edible offals were higher (P goats than for the non-supplemented ones. It could be concluded that E. brucei could be used as a substitute to CSM under smallholder production systems.

  17. Anisotropy in CdSe quantum rods

    Energy Technology Data Exchange (ETDEWEB)

    Li, Liang-shi

    2003-09-01

    The size-dependent optical and electronic properties of semiconductor nanocrystals have drawn much attention in the past decade, and have been very well understood for spherical ones. The advent of the synthetic methods to make rod-like CdSe nanocrystals with wurtzite structure has offered us a new opportunity to study their properties as functions of their shape. This dissertation includes three main parts: synthesis of CdSe nanorods with tightly controlled widths and lengths, their optical and dielectric properties, and their large-scale assembly, all of which are either directly or indirectly caused by the uniaxial crystallographic structure of wurtzite CdSe. The hexagonal wurtzite structure is believed to be the primary reason for the growth of CdSe nanorods. It represents itself in the kinetic stabilization of the rod-like particles over the spherical ones in the presence of phosphonic acids. By varying the composition of the surfactant mixture used for synthesis we have achieved tight control of the widths and lengths of the nanorods. The synthesis of monodisperse CdSe nanorods enables us to systematically study their size-dependent properties. For example, room temperature single particle fluorescence spectroscopy has shown that nanorods emit linearly polarized photoluminescence. Theoretical calculations have shown that it is due to the crossing between the two highest occupied electronic levels with increasing aspect ratio. We also measured the permanent electric dipole moment of the nanorods with transient electric birefringence technique. Experimental results on nanorods with different sizes show that the dipole moment is linear to the particle volume, indicating that it originates from the non-centrosymmetric hexagonal lattice. The elongation of the nanocrystals also results in the anisotropic inter-particle interaction. One of the consequences is the formation of liquid crystalline phases when the nanorods are dispersed in solvent to a high enough

  18. Thermal post-bunkling analyses of functionally graded material rod

    Institute of Scientific and Technical Information of China (English)

    ZHAO Feng-qun; WANG Zhong-min; LIU Hong-zhao

    2007-01-01

    The non-linear governing differential equations of immovably simply supported functionally graded material (FGM) rod subjected to thermal loads were derived.The thermal post-buckling behaviors of FGM rod made of ZrO2 and Ti-6A1-4Vwere analyzed by shooting method. Firstly, the thermal post-buckling equilibrium paths of the FGM rod with different gradient index in the uniform temperature field were plotted,and compared with the behaviors of the homogeneous rods made of ZrO2 and Ti-6A1-4V materials, respectively. For given value of end rotation angles, the influence of gradient index on the thermal post-buckling behaviors of FGM rod was discussed. Secondly, the thermal post-buckling characteristics of the FGM rod were analyzed when the temperature difference parameter is changed while the bottom temperature parameter remains constant, and when the bottom temperature parameter is changed while the temperature difference parameter remains constant, and compared with the characteristics of the two homogeneous material rods.

  19. Crystal structures of Trypanosoma brucei oligopeptidase B broaden the paradigm of catalytic regulation in prolyl oligopeptidase family enzymes.

    Science.gov (United States)

    Canning, Peter; Rea, Dean; Morty, Rory E; Fülöp, Vilmos

    2013-01-01

    Oligopeptidase B cleaves after basic amino acids in peptides up to 30 residues. As a virulence factor in bacteria and trypanosomatid pathogens that is absent in higher eukaryotes, this is a promising drug target. Here we present ligand-free open state and inhibitor-bound closed state crystal structures of oligopeptidase B from Trypanosoma brucei, the causative agent of African sleeping sickness. These (and related) structures show the importance of structural dynamics, governed by a fine enthalpic and entropic balance, in substrate size selectivity and catalysis. Peptides over 30 residues cannot fit the enzyme cavity, preventing the complete domain closure required for a key propeller Asp/Glu to fix the catalytic His and Arg in the catalytically competent conformation. This size exclusion mechanism protects larger peptides and proteins from degradation. Similar bacterial prolyl endopeptidase and archael acylaminoacyl peptidase structures demonstrate this mechanism is conserved among oligopeptidase family enzymes across all three domains of life.

  20. Crystal structures of Trypanosoma brucei oligopeptidase B broaden the paradigm of catalytic regulation in prolyl oligopeptidase family enzymes.

    Directory of Open Access Journals (Sweden)

    Peter Canning

    Full Text Available Oligopeptidase B cleaves after basic amino acids in peptides up to 30 residues. As a virulence factor in bacteria and trypanosomatid pathogens that is absent in higher eukaryotes, this is a promising drug target. Here we present ligand-free open state and inhibitor-bound closed state crystal structures of oligopeptidase B from Trypanosoma brucei, the causative agent of African sleeping sickness. These (and related structures show the importance of structural dynamics, governed by a fine enthalpic and entropic balance, in substrate size selectivity and catalysis. Peptides over 30 residues cannot fit the enzyme cavity, preventing the complete domain closure required for a key propeller Asp/Glu to fix the catalytic His and Arg in the catalytically competent conformation. This size exclusion mechanism protects larger peptides and proteins from degradation. Similar bacterial prolyl endopeptidase and archael acylaminoacyl peptidase structures demonstrate this mechanism is conserved among oligopeptidase family enzymes across all three domains of life.

  1. Functional characterization of two paralogs that are novel RNA binding proteins influencing mitochondrial transcripts of Trypanosoma brucei.

    Science.gov (United States)

    Kafková, Lucie; Ammerman, Michelle L; Faktorová, Drahomíra; Fisk, John C; Zimmer, Sara L; Sobotka, Roman; Read, Laurie K; Lukes, Julius; Hashimi, Hassan

    2012-10-01

    A majority of Trypanosoma brucei proteins have unknown functions, a consequence of its independent evolutionary history within the order Kinetoplastida that allowed for the emergence of several unique biological properties. Among these is RNA editing, needed for expression of mitochondrial-encoded genes. The recently discovered mitochondrial RNA binding complex 1 (MRB1) is composed of proteins with several functions in processing organellar RNA. We characterize two MRB1 subunits, referred to herein as MRB8170 and MRB4160, which are paralogs arisen from a large chromosome duplication occurring only in T. brucei. As with many other MRB1 proteins, both have no recognizable domains, motifs, or orthologs outside the order. We show that they are both novel RNA binding proteins, possibly representing a new class of these proteins. They associate with a similar subset of MRB1 subunits but not directly with each other. We generated cell lines that either individually or simultaneously target the mRNAs encoding both proteins using RNAi. Their dual silencing results in a differential effect on moderately and pan-edited RNAs, suggesting a possible functional separation of the two proteins. Cell growth persists upon RNAi silencing of each protein individually in contrast to the dual knockdown. Yet, their apparent redundancy in terms of cell viability is at odds with the finding that only one of these knockdowns results in the general degradation of pan-edited RNAs. While MRB8170 and MRB4160 share a considerable degree of conservation, our results suggest that their recent sequence divergence has led to them influencing mitochondrial mRNAs to differing degrees.

  2. Mathematical modelling of polyamine metabolism in bloodstream-form Trypanosoma brucei: an application to drug target identification.

    Directory of Open Access Journals (Sweden)

    Xu Gu

    Full Text Available We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT and ornithine production (OrnPt have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.

  3. Regulators of Trypanosoma brucei cell cycle progression and differentiation identified using a kinome-wide RNAi screen.

    Directory of Open Access Journals (Sweden)

    Nathaniel G Jones

    2014-01-01

    Full Text Available The African trypanosome, Trypanosoma brucei, maintains an integral link between cell cycle regulation and differentiation during its intricate life cycle. Whilst extensive changes in phosphorylation have been documented between the mammalian bloodstream form and the insect procyclic form, relatively little is known about the parasite's protein kinases (PKs involved in the control of cellular proliferation and differentiation. To address this, a T. brucei kinome-wide RNAi cell line library was generated, allowing independent inducible knockdown of each of the parasite's 190 predicted protein kinases. Screening of this library using a cell viability assay identified ≥42 PKs that are required for normal bloodstream form proliferation in culture. A secondary screen identified 24 PKs whose RNAi-mediated depletion resulted in a variety of cell cycle defects including in G1/S, kinetoplast replication/segregation, mitosis and cytokinesis, 15 of which are novel cell cycle regulators. A further screen identified for the first time two PKs, named repressor of differentiation kinase (RDK1 and RDK2, depletion of which promoted bloodstream to procyclic form differentiation. RDK1 is a membrane-associated STE11-like PK, whilst RDK2 is a NEK PK that is essential for parasite proliferation. RDK1 acts in conjunction with the PTP1/PIP39 phosphatase cascade to block uncontrolled bloodstream to procyclic form differentiation, whilst RDK2 is a PK whose depletion efficiently induces differentiation in the absence of known triggers. Thus, the RNAi kinome library provides a valuable asset for functional analysis of cell signalling pathways in African trypanosomes as well as drug target identification and validation.

  4. The orthologue of Sjogren's syndrome nuclear autoantigen 1 (SSNA1 in Trypanosoma brucei is an immunogenic self-assembling molecule.

    Directory of Open Access Journals (Sweden)

    Helen P Price

    Full Text Available Primary Sjögren's Syndrome (PSS is a highly prevalent autoimmune disease, typically manifesting as lymphocytic infiltration of the exocrine glands leading to chronically impaired lacrimal and salivary secretion. Sjögren's Syndrome nuclear autoantigen 1 (SSNA1 or NA14 is a major specific target for autoantibodies in PSS but the precise function and clinical relevance of this protein are largely unknown. Orthologues of the gene are absent from many of the commonly used model organisms but are present in Chlamyodomonas reinhardtii (in which it has been termed DIP13 and most protozoa. We report the functional characterisation of the orthologue of SSNA1 in the kinetoplastid parasite, Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins which are predicted to be remote homologues of the actin-binding protein tropomyosin. We use comparative proteomic methods to identify potential interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to self-assemble into fibril-like structures both in vitro and in vivo, a property which may contribute to its immunogenicity. Endogenous TbDIP13 partially co-localises with acetylated α-tubulin in the insect procyclic stage of the parasite. However, deletion of the DIP13 gene in cultured bloodstream and procyclic stages of T. brucei has little effect on parasite growth or morphology, indicating either a degree of functional redundancy or a function in an alternative stage of the parasite life cycle.

  5. Crystal Structures of TbCatB and rhodesain, potential chemotherapeutic targets and major cysteine proteases of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Iain D Kerr

    Full Text Available BACKGROUND: Trypanosoma brucei is the etiological agent of Human African Trypanosomiasis, an endemic parasitic disease of sub-Saharan Africa. TbCatB and rhodesain are the sole Clan CA papain-like cysteine proteases produced by the parasite during infection of the mammalian host and are implicated in the progression of disease. Of considerable interest is the exploration of these two enzymes as targets for cysteine protease inhibitors that are effective against T. brucei. METHODS AND FINDINGS: We have determined, by X-ray crystallography, the first reported structure of TbCatB in complex with the cathepsin B selective inhibitor CA074. In addition we report the structure of rhodesain in complex with the vinyl-sulfone K11002. CONCLUSIONS: The mature domain of our TbCat*CA074 structure contains unique features for a cathepsin B-like enzyme including an elongated N-terminus extending 16 residues past the predicted maturation cleavage site. N-terminal Edman sequencing reveals an even longer extension than is observed amongst the ordered portions of the crystal structure. The TbCat*CA074 structure confirms that the occluding loop, which is an essential part of the substrate-binding site, creates a larger prime side pocket in the active site cleft than is found in mammalian cathepsin B-small molecule structures. Our data further highlight enhanced flexibility in the occluding loop main chain and structural deviations from mammalian cathepsin B enzymes that may affect activity and inhibitor design. Comparisons with the rhodesain*K11002 structure highlight key differences that may impact the design of cysteine protease inhibitors as anti-trypanosomal drugs.

  6. Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole.

    Directory of Open Access Journals (Sweden)

    Chiung-Kuang Chen

    Full Text Available BACKGROUND: Chagas Disease is the leading cause of heart failure in Latin America. Current drug therapy is limited by issues of both efficacy and severe side effects. Trypansoma cruzi, the protozoan agent of Chagas Disease, is closely related to two other major global pathogens, Leishmania spp., responsible for leishmaniasis, and Trypansoma brucei, the causative agent of African Sleeping Sickness. Both T. cruzi and Leishmania parasites have an essential requirement for ergosterol, and are thus vulnerable to inhibitors of sterol 14alpha-demethylase (CYP51, which catalyzes the conversion of lanosterol to ergosterol. Clinically employed anti-fungal azoles inhibit ergosterol biosynthesis in fungi, and specific azoles are also effective against both Trypanosoma and Leishmania parasites. However, modification of azoles to enhance efficacy and circumvent potential drug resistance has been problematic for both parasitic and fungal infections due to the lack of structural insights into drug binding. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structures for CYP51 from T. cruzi (resolutions of 2.35 A and 2.27 A, and from the related pathogen T. brucei (resolutions of 2.7 A and 2.6 A, co-crystallized with the antifungal drugs fluconazole and posaconazole. Remarkably, both drugs adopt multiple conformations when binding the target. The fluconazole 2,4-difluorophenyl ring flips 180 degrees depending on the H-bonding interactions with the BC-loop. The terminus of the long functional tail group of posaconazole is bound loosely in the mouth of the hydrophobic substrate binding tunnel, suggesting that the major contribution of the tail to drug efficacy is for pharmacokinetics rather than in interactions with the target. CONCLUSIONS/SIGNIFICANCE: The structures provide new insights into binding of azoles to CYP51 and mechanisms of potential drug resistance. Our studies define in structural detail the CYP51 therapeutic target in T. cruzi, and

  7. Trypanosoma brucei PUF9 regulates mRNAs for proteins involved in replicative processes over the cell cycle.

    Directory of Open Access Journals (Sweden)

    Stuart K Archer

    2009-08-01

    Full Text Available Many genes that are required at specific points in the cell cycle exhibit cell cycle-dependent expression. In the early-diverging model eukaryote and important human pathogen Trypanosoma brucei, regulation of gene expression in the cell cycle and other processes is almost entirely post-transcriptional. Here, we show that the T. brucei RNA-binding protein PUF9 stabilizes certain transcripts during S-phase. Target transcripts of PUF9--LIGKA, PNT1 and PNT2--were identified by affinity purification with TAP-tagged PUF9. RNAi against PUF9 caused an accumulation of cells in G2/M phase and unexpectedly destabilized the PUF9 target mRNAs, despite the fact that most known Puf-domain proteins promote degradation of their target mRNAs. The levels of the PUF9-regulated transcripts were cell cycle dependent, peaking in mid- to late- S-phase, and this effect was abolished when PUF9 was targeted by RNAi. The sequence UUGUACC was over-represented in the 3' UTRs of PUF9 targets; a point mutation in this motif abolished PUF9-dependent stabilization of a reporter transcript carrying the PNT1 3' UTR. LIGKA is involved in replication of the kinetoplast, and here we show that PNT1 is also kinetoplast-associated and its over-expression causes kinetoplast-related defects, while PNT2 is localized to the nucleus in G1 phase and redistributes to the mitotic spindle during mitosis. PUF9 targets may constitute a post-transcriptional regulon, encoding proteins involved in temporally coordinated replicative processes in early G2 phase.

  8. Gamma-ray spectroscopy on irradiated fuel rods

    Energy Technology Data Exchange (ETDEWEB)

    Terremoto, Luis Antonio Albiac [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Engenharia Nuclear], e-mail: laaterre@ipen.br

    2009-07-01

    The recording of gamma-ray spectra along an irradiated fuel rod allows the fission products to be qualitatively and quantitatively examined. Among all nondestructive examinations performed on irradiated fuel rods by gamma-ray spectroscopy, the most comprehensive one is the average burnup measurement, which is quantitative. Moreover, burnup measurements by means of gamma-ray spectroscopy are less time-consuming and waste-generating than burnup measurements by radiochemical, destructive methods. This work presents the theoretical foundations and experimental techniques necessary to measure, using nondestructive gamma-ray spectroscopy, the average burnup of irradiated fuel rods in a laboratory equipped with hot cells. (author)

  9. Treatment of defective fuel rods for interim storage

    Energy Technology Data Exchange (ETDEWEB)

    Muenchow, K.; Hummel, W. [AREVA NP GmbH, Erlangen (Germany)

    2013-07-01

    In this paper we look exclusively at the treatment of defective fuel rods for long-term dry interim storage at the nuclear power plant, in order to avoid off-site transports. AREVA has developed a technique that allows verifiably adequate drying of the defective fuel rods and reconstructs the barrier for retaining radioactive materials. This is done by individually encapsulating the defective fuel rods and achieving gas-tightness by seal welding. This guarantees the retention of radioactive materials during the storage period of at least 40 years in a transport and storage flask in an interim storage facility at site. (orig.)

  10. Phase diagram of colloid-rod system

    Science.gov (United States)

    Lai, S. K.; Xiao, Xuhui

    2010-01-01

    The semigrand ensemble theory [H. N. W. Lekkerkerker, W. C. K. Poon, P. N. Pusey, A. Stroobants, and P. B. Warren, Europhys. Lett. 20, 559 (1992)] in conjunction with the fundamental measure density functional theory [V. B. Warshavsky and X. Song, Phys. Rev. E 69, 061113 (2004)] are used to construct the Helmholtz free energy densities of a mixture of uncharged colloidal hard spheres and colloidal rods in its solid and liquid phases. Given these free energy density functions, we apply the free energy density minimization method [G. F. Wang and S. K. Lai, Phys. Rev. E 70, 051402 (2004)] to crosshatch the system's regions of phases in coexistence. The calculated results show that the triangular area bounded by gas-liquid, gas-solid, and liquid-solid coexisting two phases which has been called the coexistence region of gas-liquid-solid corresponds in fact to sets of two phases in coexistence. The phase boundaries which define our calculated coexistence domains compare very well with previous theoretical calculations. The relevance of the phase-diagram domains to three phases in coexistence will be discussed.

  11. Large-eddy simulation, fuel rod vibration and grid-to-rod fretting in pressurized water reactors

    Science.gov (United States)

    Christon, Mark A.; Lu, Roger; Bakosi, Jozsef; Nadiga, Balasubramanya T.; Karoutas, Zeses; Berndt, Markus

    2016-10-01

    Grid-to-rod fretting (GTRF) in pressurized water reactors is a flow-induced vibration phenomenon that results in wear and fretting of the cladding material on fuel rods. GTRF is responsible for over 70% of the fuel failures in pressurized water reactors in the United States. Predicting the GTRF wear and concomitant interval between failures is important because of the large costs associated with reactor shutdown and replacement of fuel rod assemblies. The GTRF-induced wear process involves turbulent flow, mechanical vibration, tribology, and time-varying irradiated material properties in complex fuel assembly geometries. This paper presents a new approach for predicting GTRF induced fuel rod wear that uses high-resolution implicit large-eddy simulation to drive nonlinear transient dynamics computations. The GTRF fluid-structure problem is separated into the simulation of the turbulent flow field in the complex-geometry fuel-rod bundles using implicit large-eddy simulation, the calculation of statistics of the resulting fluctuating structural forces, and the nonlinear transient dynamics analysis of the fuel rod. Ultimately, the methods developed here, can be used, in conjunction with operational management, to improve reactor core designs in which fuel rod failures are minimized or potentially eliminated. Robustness of the behavior of both the structural forces computed from the turbulent flow simulations and the results from the transient dynamics analyses highlight the progress made towards achieving a predictive simulation capability for the GTRF problem.

  12. Results of Post Irradiation Examinations of VVER Leaky Rods

    Energy Technology Data Exchange (ETDEWEB)

    Markov, D.; Perepelkin, S.; Polenok, V.; Zhitelev, V.; Mayorshina, G. [Head of Fuel Research Department, JSC ' SSC RIAR' , 433510, Dimitrovgrad-10, Ulyanovsk region (Russian Federation)

    2009-06-15

    The most important requirement imposed on fuel elements is to maintain integrity of fuel rod claddings under operation, storage and transportation, since it is directly related to the operational safety. However, failed rod claddings are sometimes observed under reactor operation. Identification and unloading of fuel assemblies with leaky rods from VVER is available only at the time of planned preventive maintenance. An unscheduled reactor shutdown due to the excess of coolant activity limit as well as a preterm unloading of the fuel assembly cause economic damage to nuclear plant. Therefore, models and calculation codes were developed to forecast coolant contamination and failed fuel rod behavior. Criteria based on calculations were set to determine the admissible number of the failed rods in core and the opportunity to continue the reactor operation or pre-term unloading of the fuel assembly with the failed rods. Nevertheless, to prevent the fuel rod failure (for unfailing operation) it is necessary to reveal disadvantages of the design, fabrication method and fuel operation conditions, and to eliminate defects. The most complete and significant information about spent fuel assemblies may be received following the post irradiation material examinations. In order to reveal failure origins and mechanism of changes in VVER fuel and failed rod cladding condition depending on the operation, the examinations of 12 VVER-1000 fuel assemblies and 3 VVER-440 fuel assemblies, operated under normal conditions up to the fuel burnup 13..47 MWd/kgU were carried out. To evaluate the rod cladding condition, reveal defects and determine their parameters, the ultrasonic control of cladding integrity, surface visual inspection, eddy current defectoscopy, measurement of geometrical parameters were applied. In separate cases we used the metallography, measured the hydrogen percentage and carried out the mechanical tests of o-ring samples. The pellet condition was evaluated in

  13. Rod-shaped carbon isotopes at extreme spin and isopin

    CERN Document Server

    Zhao, P W; Meng, J

    2014-01-01

    The anomalously deformed rod shape has been investigated in the framework of the cranking covariant density functional theory, and two mechanisms to stabilize such state with respect to the bending motion, extreme spin and isospin, are simultaneously discussed for the first time in a self-consistent and microscopic way. It has been known that adding valence neutrons and rotating the system play very important roles in the stability of the rod shape, and we have found their coherent effect; the sigma-orbitals (parallel to the symmetry axis) of the valence neutrons, important for the rod shape, are lowered by the rotation due to the Coriolis term. This provides a further strong hint that a rod shape could be realized in nuclei towards extreme spin and isopin.

  14. Vibrations of post-buckled rods: The singular inextensible limit

    KAUST Repository

    Neukirch, Sébastien

    2012-01-01

    The small-amplitude in-plane vibrations of an elastic rod clamped at both extremities are studied. The rod is modeled as an extensible, shearable, planar Kirchhoff elastic rod under large displacements and rotations, and the vibration frequencies are computed both analytically and numerically as a function of the loading. Of particular interest is the variation of mode frequencies as the load is increased through the buckling threshold. While for some modes there are no qualitative changes in the mode frequencies, other frequencies experience rapid variations after the buckling threshold, the thinner the rod, the more abrupt the variations. Eventually, a mismatch for half of the frequencies at buckling arises between the zero thickness limit of the extensible model and the inextensible model. © 2011 Elsevier Ltd. All rights reserved.

  15. Development of visual and tactile rod orientation in children.

    Science.gov (United States)

    Meerwaldt, J D; Schmitz, P I

    1988-09-15

    Two groups of neurologically normal children (total number 64), aged from 4 to 13 years, were examined with the rod orientation test. In the second group, the line orientation test and finger tapping were also studied in addition to the rod orientation test. On the rod orientation test, the mean error rates decreased with age in both groups, and from the age of 10 the children performed as well as normal adults. In the period (ages 4-7 years) in which the greatest change in performance on the visual part of the rod orientation test had taken place (63%), a much smaller change occurred in the tapping frequency (23%). Thus the development of motor skills does not seem to be directly related to the development of spatial perception. The line orientation test did not show any developmental profile.

  16. Design requirement on KALIMER control rod assembly duct

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, W.; Kang, H. Y.; Nam, C.; Kim, J. O.; Kim, Y. J

    1998-03-01

    This document establishes the design guidelines which are needs for designing the control rod assembly duct of the KALIMER as design requirements. it describes control rod assembly duct of the KALIMER and its requirements that includes functional requirements, performance requirements, interfacing systems, design limits and strength requirements, seismic requirements, structural requirements, environmental requirements, reliability and safety requirements, standard and codes, QA programs, and other requirements. The control rod system consists of three parts, which are drive mechanism, drive-line, and absorber bundle. This report deals with the absorber bundle and its outer duct only because the others are beyond the scope of fuel system design. The guidelines for design requirements intend to be used for an improved design of the control rod assembly duct of the KALIMER. (author). 19 refs.

  17. Site-specific growth of polymers on silica rods.

    Science.gov (United States)

    Peng, Bo; Soligno, Giuseppe; Kamp, Marlous; de Nijs, Bart; de Graaf, Joost; Dijkstra, Marjolein; van Roij, René; van Blaaderen, Alfons; Imhof, Arnout

    2014-12-28

    Colloids specifically developed for self-assembly (SA) into advanced functional materials have rapidly become more complex, as this complexity allows for more ways to optimize both the SA process and the properties of the resulting materials. For instance, by creating 'patchy' particles more open structures can be achieved through directional interactions. However, the number of ways in which site-specific chemistry can be achieved on particle surfaces is still limited. Here, we show how polymer patches can be specifically grown onto only the flat end of bullet-shaped silica rods by utilizing a subtle anisotropy in surface tension and shape caused by the growth mechanism of the rods. Conversely, if the bullet-shaped silica rods are used as 'Pickering-emulsion' stabilizers the same surface tension effects exclusively direct the orientation of the rods into a 'hedgehog-morphology'. Finally, we demonstrate how an external electric field can direct the particles in a 'vectorial' way.

  18. Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.

    Science.gov (United States)

    Martin, M B; Grimley, J S; Lewis, J C; Heath, H T; Bailey, B N; Kendrick, H; Yardley, V; Caldera, A; Lira, R; Urbina, J A; Moreno, S N; Docampo, R; Croft, S L; Oldfield, E

    2001-03-15

    We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC(50) activity values against parasite replication (e.g. o-risedronate, IC(50) = 220 nM for T. brucei rhodesiense; risedronate, IC(50) = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.

  19. Computer program for automatic generation of BWR control rod patterns

    Energy Technology Data Exchange (ETDEWEB)

    Taner, M.S.; Levine, S.H.; Hsia, M.Y. (Pennsylvania State Univ., University Park (United States))

    1990-01-01

    A computer program named OCTOPUS has been developed to automatically determine a control rod pattern that approximates some desired target power distribution as closely as possible without violating any thermal safety or reactor criticality constraints. The program OCTOPUS performs a semi-optimization task based on the method of approximation programming (MAP) to develop control rod patterns. The SIMULATE-E code is used to determine the nucleonic characteristics of the reactor core state.

  20. Percolation thresholds for rod-like particles: polydispersity effects

    Science.gov (United States)

    Chatterjee, Avik P.

    2008-06-01

    A model based upon excluded volume considerations is presented for the connectedness percolation thresholds in polydisperse systems of cylindrical rod-like nanoparticles. The dependence of the percolation threshold upon polydispersity index and number-averaged aspect ratio is examined for two different distribution functions for the rod radii and lengths. The importance of accounting for polydispersity is explored in the context of measurements of the elastic moduli and electrical conductance in fibre-filled nanocomposites.

  1. Oscillation of a rigid rod in the special relativity

    CERN Document Server

    Paiva, F M

    2012-01-01

    In the special relativity, a rigid rod slides upon itself, with one extremity oscillating harmonically. We discovered restrictions in the amplitude of the motion and in the length of the rod, essential to eliminate unphysical solutions. ------- Cxe la speciala relativeco, rigida stango movigxas sur si mem, kun unu fino oscilante harmonie. Ni malkovris limigajn kondicxojn pri la amplitudo de movado kaj pri la longo de stango, necesegaj por elimini ne-fizikajn solvojn.

  2. Effect of experimental single Ancylostoma caninum and mixed infections of Trypanosoma brucei and Trypanosoma congolense on the humoural immune response to anti-rabies vaccination in dogs

    Institute of Scientific and Technical Information of China (English)

    Nwoha Rosemary Ijeoma Ogechi; Anene Boniface Maduka

    2015-01-01

    Objective:To determine the effect of Ancylostoma caninum (A. caninum) and trypanosome parasites on the immune response to vaccination in dogs in endemic environments. Methods:Sixteen dogs for the experiment were grouped into 4 of 4 members each. Group I was the uninfected control one, and GPII was infected with A. caninum; GPIII was infected with A. caninum/Trypanosoma congolense (T. congolense), and GPIV was infected with Trypanosoma brucei (T. brucei)/A. caninum. The dogs were first vaccinated with antirabies vaccine before infecting GPII, GPIII and GPIV with A. caninum which were done 4 weeks after vaccination. By 2-week post-vaccination, trypanosome parasites were superimposed on both GPIII and GPIV. A secondary vaccination was given to GPI, GPII, GPIII, and GPIV by Week 12 of the experiment (4 weeks post treatment). Results:The prepatent period was (3.00 ± 1.40) days, in the conjunct infection of T. brucei/A. caninum. It was (9.00 ± 1.10) days, in conjunct T. congolense/A. caninum. The prepatent period of A. caninum was (14.0 ± 2.0) days in the single A. caninum group and (13.0 ± 1.0) days in the conjunct trypanosome/A. caninum. At the 1st week after vaccination, the antibody titer in all the vaccinated groups (GPI, GPII, GPIII, and GPIV) significantly increased (P Conclusions:It was therefore concluded that A. caninum, T. brucei and T. congolense induced immunosuppression in antirabies vaccination in dogs.

  3. Parasite-based screening and proteome profiling reveal orlistat, an FDA-approved drug, as a potential anti Trypanosoma brucei agent.

    Science.gov (United States)

    Yang, Peng-Yu; Wang, Min; Liu, Kai; Ngai, Mun Hong; Sheriff, Omar; Lear, Martin J; Sze, Siu Kwan; He, Cynthia Y; Yao, Shao Q

    2012-07-02

    Trypanosoma brucei is a parasite that causes African sleeping sickness in humans and nagana in livestock and is transmitted by the tsetse fly. There is an urgent need for the development of new drugs against African trypanosomiasis due to the lack of vaccines and effective drugs. Orlistat (also called tetrahydrolipstatin or THL) is an FDA-approved antiobesity drug targeting primarily the pancreatic and gastric lipases within the gastrointestinal tract. It shows potential activities against tumors, mycobacteria, and parasites. Herein, we report the synthesis and evaluation of an expanded set of orlistat-like compounds, some of which showed highly potent trypanocidal activities in both the bloodstream form (BSF) and the procyclic form (PCF) of T. brucei. Subsequent in situ parasite-based proteome profiling was carried out to elucidate potential cellular targets of the drug in both forms. Some newly identified targets were further validated by the labeling of recombinantly expressed enzymes in Escherichia coli lysates. Bioimaging experiments with a selected compound were carried out to study the cellular uptake of the drug in T. brucei. Results indicated that orlistat is much more efficiently taken up by the BSF than the PCF of T. brucei and has clear effects on the morphology of mitochondria, glycosomes, and the endoplasmic reticulum in both BSF and PCF cells. These results support specific effects of orlistat on these organelles and correlate well with our in situ proteome profiling. Given the economic challenges of de novo drug development for neglected diseases, we hope that our findings will stimulate further research towards the conversion of orlistat-like compounds into new trypanocidal drugs.

  4. Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi

    OpenAIRE

    Ward Pauline N; Worthey Elizabeth A; Parsons Marilyn; Mottram Jeremy C

    2005-01-01

    Abstract Background The trypanosomatids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, African sleeping sickness, and Chagas disease. These protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. However, the ways in which the parasites respond to their environment and coordi...

  5. An Examination Of Fracture Splitting Parameters Of Crackable Connecting Rods

    Directory of Open Access Journals (Sweden)

    Zafer Özdemir

    2000-06-01

    Full Text Available Fracture splitting method is an innovative processing technique in the field of automobile engine connecting rod (con/rod manufacturing. Compared with traditional method, this technique has remarkable advantages. Manufacturing procedures, equipment and tools investment can be decreased and energy consumption reduced remarkably. Furthermore, product quality and bearing capability can also be improved. It provides a high quality, high accuracy and low cost route for producing connecting rods (con/rods. With the many advantages mentioned above, this method has attracted manufacturers attention and has been utilized in many types of con/rod manufacturing. In this article, the method and the advantages it provides, such as materials, notches for fracture splitting, fracture splitting conditions and fracture splitting equipment are discussed in detail. The paper describes an analysis of examination of fracture splitting parameters and optik-SEM fractography of C70S6 crackable connectıng rod. Force and velocity parameters are investigated. That uniform impact force distrubition starting from the starting notch causes brittle and cleavage failure mode is obtained as a result. This induces to decrease the toughness.

  6. Finite Element Analysis and Design Optimization of Connecting Rod

    Directory of Open Access Journals (Sweden)

    Ashwini Mane

    2016-07-01

    Full Text Available The objective of this study is to improve the design of connecting rod of single cylinder four stroke Otto cycle engine by shape optimization. The main objective of this study is weight reduction of connecting rod and improving its performance without affecting its functionality. Finite element analysis is one of the most important tools of CAD/CAM CAE. For this study ANSYS analysis software is used for modeling, analysis and shape design optimization. Initially, according to design considerations maximum loads were calculated for various maximum operating loading conditions. Calculated loads used as a loading condition in various load steps of FEM analysis. Stresses generated across all the locations of connecting rod evaluated using ANSYS Workbench. For optimization ANSYS Shape optimization module is used and extracted the required shape of connecting rod. Final CAD model of optimized connecting rod is prepared in Design Modeler. Static structural analysis of modified design is performed and the results compared with baseline design. After result are validated with the help of Modified Goodman’s Diagram. From the shape optimization we could able to achieve 14.73% weight reduction in existing connecting rod. Since the optimized design is having sufficient life, the design is much improved as compared to the existing design

  7. KE-Rod Initial Velocity of Hollow Cylindrical Charge

    Directory of Open Access Journals (Sweden)

    Wang Shushan

    2011-01-01

    Full Text Available KE-rod warhead is a kind of forward interception warhead. To control the KE-rods to disperse uniformly, the hollow cylindrical charge is applied. Initial velocity is crucial to KE-rods distribution and the coordination between the fuze and the warhead. Therefore, based on the classical Gurney formula of cylindrical charge and tabulate interlayer charge, a mathematical model for calculating the KE-rod initial velocity of hollow cylindrical charge has been deduced based on certain assumptions, of which the basis theory is energy and momentum conservation. To validate this deduced equation, high-speed photography and metal-pass target experimental methods were applied simultaneously to test the initial velocity of designed KE-rod warhead. Testing results clearly indicate that the calculated results of the derived mathematical model coincides with the experimental  results, and with the increase in hollow radius, the calculated results become much closer to the experimental results. But the calculated results of classical Gurney formula are far above the experimental results, and the relative error increases with increase in the hollow diameter. The derived mathematical model with satisfactory accuracy is applicable to calculate the KE-rod initial velocity of hollow cylindrical charge in engineering applications.Defence Science Journal, 2011, 61(1, pp.25-29, DOI:http://dx.doi.org/10.14429/dsj.61.72

  8. Swimming in a suspension of rod-like molecules

    Science.gov (United States)

    Shi, Juan; Powers, Thomas

    2016-11-01

    In nature, it is common for microorganisms to swim in fluids with microstructure, such as mucus. Motivated by this fact, there have been many recent theoretical, computational, and experimental studies of idealized swimmers in a dilute solution of flexible polymers. Here we study this problem from a different point of view by considering swimmers in a dilute solution of rigid rod-like polymers. We study the prescribed swimming problem of Taylor's sheet in a dilute suspension of non-Brownian rods. Using a simple continuum constitutive law for the suspension that describes the stress in terms of velocity gradient and local rod orientation, we calculate swimming speed to second order in the amplitude of the wave. Due to stresses induced by the presence of the rods, the first-order flow field differs from that of the Newtonian case. We find that the swimming speed increases linearly with rod concentration: the presence of the rods always makes the swimmer go faster. We also consider the problem of a finite swimmer by studying a two-dimensional circular squirmer. The squirmer is defined as a circle with a prescribed tangential slip velocity that leads to propulsion. By varying the prescribed slip boundary condition, we study both pushers and pullers.

  9. Thermal hydraulics of rod bundles: The effect of eccentricity

    Energy Technology Data Exchange (ETDEWEB)

    Chauhan, Amit K., E-mail: amit_fmlab@yahoo.co.in [Fluid Mechanics Laboratory, Department of Applied Mechanics, Indian Institute of Technology Madras, Chennai 600036 (India); Prasad, B.V.S.S.S., E-mail: prasad@iitm.ac.in [Thermal Turbomachines Laboratory, Department of Mechanical Engineering, Indian Institute of Technology Madras, Chennai 600036 (India); Patnaik, B.S.V., E-mail: bsvp@iitm.ac.in [Fluid Mechanics Laboratory, Department of Applied Mechanics, Indian Institute of Technology Madras, Chennai 600036 (India)

    2013-10-15

    Highlights: • Present CFD investigation explores, whole bundle eccentricity for the first time. • Fluid flow and thermal characteristics in various subchannels are analyzed. • Mass flux distribution is particularly analyzed to study eccentricity effect. • Higher eccentricity resulted in a shoot up in rod surface temperature distribution. • Both tangential and radial flow in rod bundles has resulted due to eccentricity. -- Abstract: The effect of eccentricity on the fluid flow and heat transfer through a 19-rod bundle is numerically carried out. When the whole bundle shifts downwards with respect to the outer (pressure) tube, flow redistribution happens. This in turn is responsible for changes in mass flux, pressure and differential flow development in various subchannels. The heat flux imposed on the surface of the fuel rods and the mass flux through the subchannels determines the coolant outlet temperatures. The simulations are performed for a coolant flow Reynolds number of 4 × 10{sup 5}. For an eccentricity value of 0.7, the mass flux in the bottom most subchannel (l) was found to decrease by 10%, while the surface temperature of the fuel rod in the vicinity of this subchannel increased by 250% at the outlet section. Parameters of engineering interest including skin friction coefficient, Nusselt number, etc., have been systematically explored to study the effect of eccentricity on the rod bundle.

  10. Commissioning of a passive rod scanner at INB

    Energy Technology Data Exchange (ETDEWEB)

    Junqueira, Fabio da Silva; Oliveira, Carlos A.; Palheiros, Franklin, E-mail: carlossilva@inb.gov.br, E-mail: franklin@inb.gov.br [Industrias Nucleares do Brasil (INB), Resende, RJ (Brazil). Superintendencia de Engenharia do Combustivel; Fernandez, Pablo Jesus Piñer, E-mail: pineiro@tecnatom.es [Tecnatom, San Sebastian de los Reyes, Madrid (Spain)

    2015-07-01

    For the 21st reload for Angra 1, a shift from Standard to Advanced fuel design will be introduced, where the fuel assemblies under the new design will contain fuel rods with axial blanket, in line with ELETRONUCLEAR's requirement for a higher energy efficient reactor fuel. Additionally, fuel rods for Angra 2 and 3, using gadolinium type burnable poison, have to be submitted to inspections due to the demand for the same type of inspection, which cannot be certified at INB currently. In keeping with CNEN regulations, every fuel-assembly component must be inspected and certified by a qualified method. Nevertheless, INB lacks the means to perform the certification-required inspection aimed at determining the uranium enrichment and presence of gadolinium pellets inside the closed rods. Hence, the use is necessary of a scanner capable of inspecting differently enriched fuel rods and/or gadolinium pellets (axial blanket). This work aims to present the recent Passive Rod Scanner installed at INB with most advance technology in the area, making possible to completely fulfill Angra 1, 2 and 3 rods inspection at INB Resende site. (author)

  11. Rod internal pressure quantification and distribution analysis using Frapcon

    Energy Technology Data Exchange (ETDEWEB)

    Jessee, Matthew Anderson [ORNL; Wieselquist, William A [ORNL; Ivanov, Kostadin [Pennsylvania State University, University Park

    2015-09-01

    This report documents work performed supporting the Department of Energy (DOE) Office of Nuclear Energy (NE) Fuel Cycle Technologies Used Fuel Disposition Campaign (UFDC) under work breakdown structure element 1.02.08.10, ST Analysis. In particular, this report fulfills the M4 milestone M4FT- 15OR0810036, Quantify effects of power uncertainty on fuel assembly characteristics, within work package FT-15OR081003 ST Analysis-ORNL. This research was also supported by the Consortium for Advanced Simulation of Light Water Reactors (http://www.casl.gov), an Energy Innovation Hub (http://www.energy.gov/hubs) for Modeling and Simulation of Nuclear Reactors under U.S. Department of Energy Contract No. DE-AC05-00OR22725. The discharge rod internal pressure (RIP) and cladding hoop stress (CHS) distributions are quantified for Watts Bar Nuclear Unit 1 (WBN1) fuel rods by modeling core cycle design data, operation data (including modeling significant trips and downpowers), and as-built fuel enrichments and densities of each fuel rod in FRAPCON-3.5. A methodology is developed which tracks inter-cycle assembly movements and assembly batch fabrication information to build individual FRAPCON inputs for each evaluated WBN1 fuel rod. An alternate model for the amount of helium released from the zirconium diboride (ZrB2) integral fuel burnable absorber (IFBA) layer is derived and applied to FRAPCON output data to quantify the RIP and CHS for these types of fuel rods. SCALE/Polaris is used to quantify fuel rodspecific spectral quantities and the amount of gaseous fission products produced in the fuel for use in FRAPCON inputs. Fuel rods with ZrB2 IFBA layers (i.e., IFBA rods) are determined to have RIP predictions that are elevated when compared to fuel rod without IFBA layers (i.e., standard rods) despite the fact that IFBA rods often have reduced fill pressures and annular fuel pellets. The primary contributor to elevated RIP predictions at burnups less than and greater than 30 GWd

  12. AN INTRODUCTION TO THE CUISENAIRE RODS, AN APPROACH TO THE TEACHING OF ELEMENTARY MATHEMATICS.

    Science.gov (United States)

    HULL, WILLIAM P.

    CUISENAIRE RODS ARE COLORED, RECTANGULAR PIECES OF WOOD ONE UNIT WIDE AND ANY NUMBER OF UNITS LONG. THE COLOR OF THE ROD DEPENDS UPON ITS LENGTH. RODS CAN BE USED IN KINDERGARTEN THROUGH HIGH SCHOOL, BUT ARE PARTICULARILY HELPFUL IN THE EARLY GRADES. THE RODS CAN BE USED TO TEACH CHILDREN SUCH CONCEPTS AS…

  13. Control Rod Driveline Reactivity Feedback Model for Liquid Metal Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Young-Min; Jeong, Hae-Yong; Chang, Won-Pyo; Cho, Chung-Ho; Lee, Yong-Bum

    2008-01-15

    The thermal expansion of the control rod drivelines (CRDL) is one important passive mitigator under all unprotected accident conditions in the metal and oxide cores. When the CRDL are washed by hot sodium in the coolant outlet plenum, the CRDL thermally expands and causes the control rods to be inserted further down into the active core region, providing a negative reactivity feedback. Since the control rods are attached to the top of the vessel head and the core attaches to the bottom of the reactor vessel (RV), the expansion of the vessel wall as it heats will either lower the core or raise the control rods supports. This contrary thermal expansion of the reactor vessel wall pulls the control rods out of the core somewhat, providing a positive reactivity feedback. However this is not a safety factor early in a transient because its time constant is relatively large. The total elongated length is calculated by subtracting the vessel expansion from the CRDL expansion to determine the net control rod expansion into the core. The system-wide safety analysis code SSC-K includes the CRDL/RV reactivity feedback model in which control rod and vessel expansions are calculated using single-nod temperatures for the vessel and CRDL masses. The KALIMER design has the upper internal structures (UIS) in which the CRDLs are positioned outside the structure where they are exposed to the mixed sodium temperature exiting the core. A new method to determine the CRDL expansion is suggested. Two dimensional hot pool thermal hydraulic model (HP2D) originally developed for the analysis of the stratification phenomena in the hot pool is utilized for a detailed heat transfer between the CRDL mass and the hot pool coolant. However, the reactor vessel wall temperature is still calculated by a simple lumped model.

  14. Detection of single photons by toad and mouse rods.

    Science.gov (United States)

    Reingruber, Jürgen; Pahlberg, Johan; Woodruff, Michael L; Sampath, Alapakkam P; Fain, Gordon L; Holcman, David

    2013-11-26

    Amphibian and mammalian rods can both detect single photons of light even though they differ greatly in physical dimensions, mammalian rods being much smaller in diameter than amphibian rods. To understand the changes in physiology and biochemistry required by such large differences in outer segment geometry, we developed a computational approach, taking into account the spatial organization of the outer segment divided into compartments, together with molecular dynamics simulations of the signaling cascade. We generated simulations of the single-photon response together with intrinsic background fluctuations in toad and mouse rods. Combining this computational approach with electrophysiological data from mouse rods, we determined key biochemical parameters. On average around one phosphodiesterase (PDE) molecule is spontaneously active per mouse compartment, similar to the value for toad, which is unexpected due to the much smaller diameter in mouse. A larger number of spontaneously active PDEs decreases dark noise, thereby improving detection of single photons; it also increases cGMP turnover, which accelerates the decay of the light response. These constraints explain the higher PDE density in mammalian compared with amphibian rods that compensates for the much smaller diameter of mammalian disks. We further find that the rate of cGMP hydrolysis by light-activated PDE is diffusion limited, which is not the case for spontaneously activated PDE. As a consequence, in the small outer segment of a mouse rod only a few activated PDEs are sufficient to generate a signal that overcomes noise, which permits a shorter lifetime of activated rhodopsin and greater temporal resolution.

  15. Strategy for Fuel Rod Receipt, Characterization, Sample Allocation for the Demonstration Sister Rods

    Energy Technology Data Exchange (ETDEWEB)

    Marschman, Steven C. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Warmann, Stephan A. [Portage, Inc., Idaho Falls, ID (United States); Rusch, Chris [NAC International, Inc., Norcross, GA (United States)

    2014-03-01

    , inert gas backfilling, and transfer to an Independent Spent Fuel Storage Installation (ISFSI) for multi-year storage. To document the initial condition of the used fuel prior to emplacement in a storage system, “sister ” fuel rods will be harvested and sent to a national laboratory for characterization and archival purposes. This report supports the demonstration by describing how sister rods will be shipped and received at a national laboratory, and recommending basic nondestructive and destructive analyses to assure the fuel rods are adequately characterized for UFDC work. For this report, a hub-and-spoke model is proposed, with one location serving as the hub for fuel rod receipt and characterization. In this model, fuel and/or clad would be sent to other locations when capabilities at the hub were inadequate or nonexistent. This model has been proposed to reduce DOE-NE’s obligation for waste cleanup and decontamination of equipment.

  16. Alba-domain proteins of Trypanosoma brucei are cytoplasmic RNA-binding proteins that interact with the translation machinery.

    Directory of Open Access Journals (Sweden)

    Jan Mani

    Full Text Available Trypanosoma brucei and related pathogens transcribe most genes as polycistronic arrays that are subsequently processed into monocistronic mRNAs. Expression is frequently regulated post-transcriptionally by cis-acting elements in the untranslated regions (UTRs. GPEET and EP procyclins are the major surface proteins of procyclic (insect midgut forms of T. brucei. Three regulatory elements common to the 3' UTRs of both mRNAs regulate mRNA turnover and translation. The glycerol-responsive element (GRE is unique to the GPEET 3' UTR and regulates its expression independently from EP. A synthetic RNA encompassing the GRE showed robust sequence-specific interactions with cytoplasmic proteins in electromobility shift assays. This, combined with column chromatography, led to the identification of 3 Alba-domain proteins. RNAi against Alba3 caused a growth phenotype and reduced the levels of Alba1 and Alba2 proteins, indicative of interactions between family members. Tandem-affinity purification and co-immunoprecipitation verified these interactions and also identified Alba4 in sub-stoichiometric amounts. Alba proteins are cytoplasmic and are recruited to starvation granules together with poly(A RNA. Concomitant depletion of all four Alba proteins by RNAi specifically reduced translation of a reporter transcript flanked by the GPEET 3' UTR. Pulldown of tagged Alba proteins confirmed interactions with poly(A binding proteins, ribosomal protein P0 and, in the case of Alba3, the cap-binding protein eIF4E4. In addition, Alba2 and Alba3 partially cosediment with polyribosomes in sucrose gradients. Alba-domain proteins seem to have exhibited great functional plasticity in the course of evolution. First identified as DNA-binding proteins in Archaea, then in association with nuclear RNase MRP/P in yeast and mammalian cells, they were recently described as components of a translationally silent complex containing stage-regulated mRNAs in Plasmodium. Our results are

  17. Nuclear Fuel Test Rod Fabrication for Data Acquisition Test

    Energy Technology Data Exchange (ETDEWEB)

    Joung, Chang-Young; Hong, Jin-Tae; Kim, Ka-Hye; Huh, Sung-Ho [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    A nuclear fuel test rod must be fabricated with precise welding and assembly technologies, and confirmed for their soundness. Recently, we have developed various kinds of processing systems such as an orbital TIG welding system, a fiber laser welding system, an automated drilling system and a helium leak analyzer, which are able to fabricate the nuclear fuel test rods and rigs, and keep inspection systems to confirm the soundness of the nuclear fuel test rods and rids. The orbital TIG welding system can be used with two kinds of welding methods. One can perform the round welding for end-caps of a nuclear fuel test rod by an orbital head mounted in a low-pressure chamber. The other can do spot welding for a pin-hole of a nuclear fuel test rod in a high-pressure chamber to fill up helium gas of high pressure. The fiber laser welding system can weld cylindrical and 3 axis samples such as parts of a nuclear fuel test rod and instrumentation sensors which is moved by an index chuck and a 3 axis (X, Y, Z) servo stage controlled by the CNC program. To measure the real-time temperature change at the center of the nuclear fuel during the irradiation test, a thermocouple should be instrumented at that position. Therefore, a hole needs to be made at the center of fuel pellet to instrument the thermocouple. An automated drilling system can drill a fine hole into a fuel pellet without changing tools or breaking the work-piece. The helium leak analyzer (ASM-380 model of DEIXEN Co.) can check the leak of the nuclear fuel test rod filled with helium gas. This paper describes not only the assembly and fabrication methods used by the process systems, but also the results of the data acquisition test for the nuclear fuel test rod. A nuclear fuel test rod for the data acquisition test was fabricated using the welding and assembling echnologies acquired from previous tests.

  18. Plasmonic-cavity model for radiating nano-rod antennas

    DEFF Research Database (Denmark)

    Peng, Liang; Mortensen, N. Asger

    2014-01-01

    In this paper, we propose the analytical solution of nano-rod antennas utilizing a cylindrical harmonics expansion. By treating the metallic nano-rods as plasmonic cavities, we derive closed-form expressions for both the internal and the radiated fields, as well as the resonant condition and the ......In this paper, we propose the analytical solution of nano-rod antennas utilizing a cylindrical harmonics expansion. By treating the metallic nano-rods as plasmonic cavities, we derive closed-form expressions for both the internal and the radiated fields, as well as the resonant condition...... and the radiation efficiency. With our theoretical model, we show that besides the plasmonic resonances, efficient radiation takes advantage of (a) rendering a large value of the rods' radius and (b) a central-fed profile, through which the radiation efficiency can reach up to 70% and even higher in a wide...... frequency band. Our theoretical expressions and conclusions are general and pave the way for engineering and further optimization of optical antenna systems and their radiation patterns....

  19. Nano-rods of zinc oxide in nano-graphene

    Science.gov (United States)

    Ortiz, Pedro; Chavira, Elizabeth; Monroy, Marel; Elizalde, José; Santiago, Patricia; Sato, Roberto; Tejeda, Adriana; González, Guillermina; Novelo, Omar; Flores, Carlos

    2014-03-01

    It's of great interest to study the devices based on nano-ZnO and graphene, for their electromagnetic and optical properties to increase the efficiency of solar cells. The graphene multilayers synthesis was done by mechanosynthesis, grinding in a mechanical agate mortar. The zinc oxide nano-rods were synthesized from zinc acetate dihydrate, Ace, (Sigma Aldrich) and ethylene diamine, En, (Sigma Aldrich) with a 1:2 ratio of reagents En/Ace. The ZnO nano-rods in nano-tubes graphene were obtained by mechanosynthesis. The X-ray powder diffraction, shows the shift of C with PDF 12-0212 and ZnO, Zincite PDF 36-1451, both with hexagonal unit cell. The grain size and morphology of graphene (multilayers and nano-tubes), ZnO nano-rods and ZnO-graphene mixture (multilayers, nano-tubes) were observed by scanning electron microscope. Transmission electron microscope, corroborates shown in SEM. Raman spectroscopy, shows the shift of multilayer graphene and the ZnO nano-rods. In photoluminescence measurements, observe the change in intensity in the band defects. Magnetic properties characterization was carried out by Vibrating Sample Magnetometry. We conclude that graphite multilayers dislocated by cutting efforts, forming graphene nano-tubes and encapsulated ZnO nano-rods within graphene.

  20. Dysprosium titanate as an absorber material for control rods

    Science.gov (United States)

    Risovany, V. D.; Varlashova, E. E.; Suslov, D. N.

    2000-09-01

    Disprosium titanate is an attractive control rod material for the thermal neutron reactors. Its main advantages are: insignificant swelling, no out-gassing under neutron irradiation, rather high neutron efficiency, a high melting point (˜1870°C), non-interaction with the cladding at temperatures above 1000°C, simple fabrication and easily reprocessed non-radioactive waste. It can be used in control rods as pellets and powder. The disprosium titanate control rods have worked off in the MIR reactor for 17 years, in VVER-1000 - for 4 years without any operating problems. After post-irradiation examinations this type of control rod having high lifetime was recommended for the VVER and RBMK. The paper presents the examination results of absorber element dummies containing dysprosium titanate, irradiated in the SM reactor to the neutron fluence of 3.4×10 22 cm -2 ( E>0.1 MeV) and, also, the data on structure, thermal-physical properties of dysprosium titanate, efficiency of dysprosium titanate control rods.

  1. Simulation on the HTTR Control Rod Withdrawal Test

    Energy Technology Data Exchange (ETDEWEB)

    Jun, Ji Su; Tak, Nam-il; Lim, Hong Sik [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    This paper describes the GAMMA+ code simulation of HTTR control rod withdrawal test. The simulation is done to examine the effect of GAMMA+ code's single-zone and multi-zone point kinetics models on the prediction of the reactor power response during HTTR control rod withdrawal test. In addition, it has an objective to examine how the reactor power response is affected by the application of the fuel temperature coefficients on TRISO kernel or compact rod. The calculation results of reactivity response and reactor power response are compared with the test results which were obtained at the initial power of 15.2 MW with the amount of reactivity insertion by control rod withdrawal to 3.4e-04 (dk/k) in 6.59 seconds. All GAMMA+ simulation results on a HTTR CRW test showed good predictions with the measured data. In particular, TRISO Kernel Model where the fuel temperature coefficients applied on the TRISO particle produced a better prediction within a 1.5% measured data and made no difference between the single-zone model and the multi-zone point kinetics model. During the control rod withdrawal event which is a fast transient, the total reactivity is mainly affected by the inserted reactivity and the reactivity response due to the change of the fuel temperature and the graphite moderator temperature.

  2. Exploration of Multifocal Rod Electroretinograms Recording in Human

    Institute of Scientific and Technical Information of China (English)

    Changzheng Chen; Lezheng Wu; De-Zheng Wu; Shixian Long; Jiongji Liang; Futian Jiang; Libing Jiang

    2002-01-01

    Purpose:To test the feasibility of recording rod multifocal electroretinograms (ERG) in humans and observe appropriate recording conditions.Methods: Multifocal rod ERG were recorded using a stimulus array of 61 equalsized hexagons in two normal subjects after the dark adaptation. Flashes were blue (W47B). Blank frames between two successive flashes of hexagons varied from 0 to 14. Length of the m-sequence, bandwidth, flash frequency, flash intensities and background intensities were changed to obtain appropriate recording conditions for the clinical use.Results:Multifocal rod ERG were clearly recordable and well formed. They had an early implicit time, very small negative wave and a late implicit time, large positive wave. The positive wave was bimodal, whose timing and waveform were similar to the full-field rod ERG. The local response amplitudes can be suppressed with increase in flash frequency or background intensity, decrease in flash intensity or the size of stimulus elements.Conclusions: Multifocal rod ERG can be recorded in human and can provide topographical maps of retinal function that have clinical usage. 212-1 m-sequence length, 3F blank frames and 3~ 300 Hz bandwidth were suggested to appropriate recording conditions.

  3. Fault pseudotachylyte: a coseismic lightning rod

    Science.gov (United States)

    Ferre, E. C.; Conder, J. A.; MathanaSekaran, N.; Geissman, J. W.

    2013-12-01

    of melt during the formation of a pseudotachylite vein. The increase in melt temperature is the most important factor affecting electrical conductivity in the fault plane. When the melt temperature rises from 1300 to 2000K, its electrical conductivity increases about 80 times. This implies that once a continuous pseudotachylite sheet-like vein is formed during an earthquake, the vein has a much higher electrical conductivity than its host-rock. The dramatic increase in electrical conductivity along the pseudotachylite plane might be synchronous with the generation of the coseismic electrical current. Thus, regardless of its origin, any electrical current produced during an earthquake will travel along the pseudotachylite plane which acts as a lightning rod. The magnetization of a solid due to an electrical current results from Biot-Savart law which states that an electrical current generates a magnetic field. The solidification of the pseudotachylite vein does not happen at once but proceeds from the margin inwards as an electrical current may still pass through the conducting pseudotachylite. Therefore, the host-rock of the pseudotachylite vein or its solidified margin can be magnetized by a coseismic current.

  4. Nematic Ordering of Rigid Rods in a Gravitational Field

    CERN Document Server

    Baulin, V A; Baulin, Vladimir A.; Khokhlov, Alexei R.

    1999-01-01

    The isotropic-to-nematic transition in an athermal solution of long rigid rods subject to a gravitational (or centrifugal) field is theoretically considered in the Onsager approximation. The new feature emerging in the presence of gravity is a concentration gradient which coupled with the nematic ordering. For rodlike molecules this effect becomes noticeable at centrifugal acceleration g ~ 10^3--10^4 m/s^2, while for biological rodlike objects, such as tobacco mosaic virus, TMV, the effect is important even for normal gravitational acceleration conditions. Rods are concentrated near the bottom of the vessel which sometimes leads to gravity induced nematic ordering. The concentration range corresponding to phase separation increases with increasing g. In the region of phase separation the local rod concentration, as well as the order parameter, follow a step function with height.

  5. Characterisation of Plasma Filled Rod Pinch electron beam diode operation

    Science.gov (United States)

    MacDonald, James; Bland, Simon; Chittenden, Jeremy

    2016-10-01

    The plasma filled rod pinch diode (aka PFRP) offers a small radiographic spot size and a high brightness source. It operates in a very similar to plasma opening switches and dense plasma focus devices - with a plasma prefill, supplied via a number of simple coaxial plasma guns, being snowploughed along a thin rod cathode, before detaching at the end. The aim of this study is to model the PFRP and understand the factors that affect its performance, potentially improving future output. Given the dependence on the PFRP on the prefill, we are making detailed measurements of the density (1015-1018 cm-3), velocity, ionisation and temperature of the plasma emitted from a plasma gun/set of plasma guns. This will then be used to provide initial conditions to the Gorgon 3D MHD code, and the dynamics of the entire rod pinch process studied.

  6. Cognitive set influences on Witkin's Rod-and-Frame Test.

    Science.gov (United States)

    Reinking, R H

    1977-04-01

    Witkin's field-dependence theory is embroiled in conflict as research shows its primary assessment method, the Rod-and-frame Test, is influenced by situational events. This study explored the impact of an additional situational variable, locus of problem-solving data search, a cognitive set modified from Rotter's (1966) work. Two experimental groups of hospitalized alcoholics received standard Witkin instructions plus instructions emphasizing either an internal or external search for problem-solving cues. A control group received only Witkin's instructions. Aanlysis of variance showed the special instructions affected rod-and-frame scores in the predicted directions. The results were interpreted as indicating a need for a multi-factor approach to analyzing the complex relationships of the Rod-and-frame Test.

  7. Plasmonic-cavity model for radiating nano-rod antennas.

    Science.gov (United States)

    Peng, Liang; Mortensen, N Asger

    2014-01-23

    In this paper, we propose the analytical solution of nano-rod antennas utilizing a cylindrical harmonics expansion. By treating the metallic nano-rods as plasmonic cavities, we derive closed-form expressions for both the internal and the radiated fields, as well as the resonant condition and the radiation efficiency. With our theoretical model, we show that besides the plasmonic resonances, efficient radiation takes advantage of (a) rendering a large value of the rods' radius and (b) a central-fed profile, through which the radiation efficiency can reach up to 70% and even higher in a wide frequency band. Our theoretical expressions and conclusions are general and pave the way for engineering and further optimization of optical antenna systems and their radiation patterns.

  8. Two rods confined by positive plates: effective forces and charge distribution profiles

    Energy Technology Data Exchange (ETDEWEB)

    Odriozola, G; Jimenez-Angeles, F; Lozada-Cassou, M [Programa de IngenierIa Molecular, Instituto Mexicano del Petroleo, Lazaro Cardenas 152, 07730 Mexico, DF (Mexico)

    2006-09-13

    The effect of confinement on the interaction force between two negatively charged rods is studied through Monte Carlo simulations. Confinement is produced by two parallel, charged or uncharged plates. The system is immersed in a 0.1 M 1-1 restricted primitive model electrolyte. The effect on the rod-rod effective force by the plate charge distribution is analysed. A strong modification of the rod-rod effective force due to confinement is found, as compared to the bulk case. In particular, rod-rod attraction was found for plates having a charge equal to that of fully charged bilipid bilayers. In spite of the simplicity of the model, these results agree with some DNA-phospholipid experimental observations. On the other hand, for a model having the plate charges fixed on a grid, very long range, oscillatory rod-rod effective forces were obtained.

  9. Adaptive potentiation in rod photoreceptors after light exposure.

    Science.gov (United States)

    McKeown, Alex S; Kraft, Timothy W

    2014-06-01

    Photoreceptors adapt to changes in illumination by altering transduction kinetics and sensitivity, thereby extending their working range. We describe a previously unknown form of rod photoreceptor adaptation in wild-type (WT) mice that manifests as a potentiation of the light response after periods of conditioning light exposure. We characterize the stimulus conditions that evoke this graded hypersensitivity and examine the molecular mechanisms of adaptation underlying the phenomenon. After exposure to periods of saturating illumination, rods show a 10-35% increase in circulating dark current, an adaptive potentiation (AP) to light exposure. This potentiation grows as exposure to light is extended up to 3 min and decreases with longer exposures. Cells return to their initial dark-adapted sensitivity with a time constant of recovery of ∼7 s. Halving the extracellular Mg concentration prolongs the adaptation, increasing the time constant of recovery to 13.3 s, but does not affect the magnitude of potentiation. In rods lacking guanylate cyclase activating proteins 1 and 2 (GCAP(-/-)), AP is more than doubled compared with WT rods, and halving the extracellular Mg concentration does not affect the recovery time constant. Rods from a mouse expressing cyclic nucleotide-gated channels incapable of binding calmodulin also showed a marked increase in the amplitude of AP. Application of an insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitor (Tyrphostin AG1024) blocked AP, whereas application of an insulin receptor kinase inhibitor (HNMPA(AM)3) failed to do so. A broad-acting tyrosine phosphatase inhibitor (orthovanadate) also blocked AP. Our findings identify a unique form of adaptation in photoreceptors, so that they show transient hypersensitivity to light, and are consistent with a model in which light history, acting via the IGF-1R, can increase the sensitivity of rod photoreceptors, whereas the photocurrent overshoot is regulated by Ca-calmodulin and Ca(2

  10. Loop Mediated Isothermal Amplification for Detection of Trypanosoma brucei gambiense in Urine and Saliva Samples in Nonhuman Primate Model

    Directory of Open Access Journals (Sweden)

    Maina Ngotho

    2015-01-01

    Full Text Available Human African trypanosomiasis (HAT is a vector-borne parasitic zoonotic disease. The disease caused by Trypanosoma brucei gambiense is the most prevalent in Africa. Early diagnosis is hampered by lack of sensitive diagnostic techniques. This study explored the potential of loop mediated isothermal amplification (LAMP and polymerase chain reaction (PCR in the detection of T. b. gambiense infection in a vervet monkey HAT model. Six vervet monkeys were experimentally infected with T. b. gambiense IL3253 and monitored for 180 days after infection. Parasitaemia was scored daily. Blood, cerebrospinal fluid (CSF, saliva, and urine samples were collected weekly. PCR and LAMP were performed on serum, CSF, saliva, and urine samples. The detection by LAMP was significantly higher than that of parasitological methods and PCR in all the samples. The performance of LAMP varied between the samples and was better in serum followed by saliva and then urine samples. In the saliva samples, LAMP had 100% detection between 21 and 77 dpi, whereas in urine the detection it was slightly lower, but there was over 80% detection between 28 and 91 dpi. However, LAMP could not detect trypanosomes in either saliva or urine after 140 and 126 dpi, respectively. The findings of this study emphasize the importance of LAMP in diagnosis of HAT using saliva and urine samples.

  11. Loop Mediated Isothermal Amplification for Detection of Trypanosoma brucei gambiense in Urine and Saliva Samples in Nonhuman Primate Model.

    Science.gov (United States)

    Ngotho, Maina; Kagira, John Maina; Gachie, Beatrice Muthoni; Karanja, Simon Muturi; Waema, Maxwell Wambua; Maranga, Dawn Nyawira; Maina, Naomi Wangari

    2015-01-01

    Human African trypanosomiasis (HAT) is a vector-borne parasitic zoonotic disease. The disease caused by Trypanosoma brucei gambiense is the most prevalent in Africa. Early diagnosis is hampered by lack of sensitive diagnostic techniques. This study explored the potential of loop mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR) in the detection of T. b. gambiense infection in a vervet monkey HAT model. Six vervet monkeys were experimentally infected with T. b. gambiense IL3253 and monitored for 180 days after infection. Parasitaemia was scored daily. Blood, cerebrospinal fluid (CSF), saliva, and urine samples were collected weekly. PCR and LAMP were performed on serum, CSF, saliva, and urine samples. The detection by LAMP was significantly higher than that of parasitological methods and PCR in all the samples. The performance of LAMP varied between the samples and was better in serum followed by saliva and then urine samples. In the saliva samples, LAMP had 100% detection between 21 and 77 dpi, whereas in urine the detection it was slightly lower, but there was over 80% detection between 28 and 91 dpi. However, LAMP could not detect trypanosomes in either saliva or urine after 140 and 126 dpi, respectively. The findings of this study emphasize the importance of LAMP in diagnosis of HAT using saliva and urine samples.

  12. A single amino acid substitution in the group 1 Trypanosoma brucei gambiense haptoglobin-hemoglobin receptor abolishes TLF-1 binding.

    Directory of Open Access Journals (Sweden)

    E DeJesus

    Full Text Available Critical to human innate immunity against African trypanosomes is a minor subclass of human high-density lipoproteins, termed Trypanosome Lytic Factor-1 (TLF-1. This primate-specific molecule binds to a haptoglobin-hemoglobin receptor (HpHbR on the surface of susceptible trypanosomes, initiating a lytic pathway. Group 1 Trypanosoma brucei gambiense causes human African Trypanosomiasis (HAT, escaping TLF-1 killing due to reduced uptake. Previously, we found that group 1 T. b. gambiense HpHbR (TbgHpHbR mRNA levels were greatly reduced and the gene contained substitutions within the open reading frame. Here we show that a single, highly conserved amino acid in the TbgHpHbR ablates high affinity TLF-1 binding and subsequent endocytosis, thus evading TLF-1 killing. In addition, we show that over-expression of TbgHpHbR failed to rescue TLF-1 susceptibility. These findings suggest that the single substitution present in the TbgHpHbR directly contributes to the reduced uptake and resistance to TLF-1 seen in these important human pathogens.

  13. Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    Directory of Open Access Journals (Sweden)

    Darren J Creek

    2015-03-01

    Full Text Available Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

  14. Molecular Evidence of a Trypanosoma brucei gambiense Sylvatic Cycle in the Human African Trypanosomiasis Foci of Equatorial Guinea

    Directory of Open Access Journals (Sweden)

    Carlos eCordon-Obras

    2015-07-01

    Full Text Available Gambiense trypanosomiasis is considered an anthroponotic disease. Consequently, control programs are generally aimed at stopping transmission of Trypanosoma brucei gambiense (T. b. gambiense by detecting and treating human cases. However, the persistence of numerous foci despite efforts to eliminate this disease questions this strategy as unique tool to pursue the eradication. The role of animals as a reservoir of T. b. gambiense is still controversial, but could partly explain maintenance of the infection at hypo-endemic levels. In the present study, we evaluated the presence of T. b. gambiense in wild animals in Equatorial Guinea. The infection rate ranged from 0.8% in the insular focus of Luba to more than 12% in Mbini, a focus with a constant trickle of human cases. The parasite was detected in a wide range of animal species including four species never described previously as putative reservoirs. Our study comes to reinforce the hypothesis that animals may play a role in the persistence of T. b. gambiense transmission, being particularly relevant in low transmission settings. Under these conditions the integration of sustained vector control and medical interventions should be considered to achieve the elimination of Gambiense trypanosomiasis.

  15. A global comparison of the human and T. brucei degradomes gives insights about possible parasite drug targets.

    Directory of Open Access Journals (Sweden)

    Susan T Mashiyama

    Full Text Available We performed a genome-level computational study of sequence and structure similarity, the latter using crystal structures and models, of the proteases of Homo sapiens and the human parasite Trypanosoma brucei. Using sequence and structure similarity networks to summarize the results, we constructed global views that show visually the relative abundance and variety of proteases in the degradome landscapes of these two species, and provide insights into evolutionary relationships between proteases. The results also indicate how broadly these sequence sets are covered by three-dimensional structures. These views facilitate cross-species comparisons and offer clues for drug design from knowledge about the sequences and structures of potential drug targets and their homologs. Two protease groups ("M32" and "C51" that are very different in sequence from human proteases are examined in structural detail, illustrating the application of this global approach in mining new pathogen genomes for potential drug targets. Based on our analyses, a human ACE2 inhibitor was selected for experimental testing on one of these parasite proteases, TbM32, and was shown to inhibit it. These sequence and structure data, along with interactive versions of the protein similarity networks generated in this study, are available at http://babbittlab.ucsf.edu/resources.html.

  16. Determination of Ultimate Torque for Multiply Connected Cross Section Rod

    Directory of Open Access Journals (Sweden)

    V. L. Danilov

    2015-01-01

    Full Text Available The aim of this work is to determine load-carrying capability of the multiply cross-section rod. This calculation is based on the model of the ideal plasticity of the material, so that the desired ultimate torque is a torque at which the entire cross section goes into a plastic state.The article discusses the cylindrical multiply cross-section rod. To satisfy the equilibrium equation and the condition of plasticity simultaneously, two stress function Ф and φ are introduced. By mathematical transformations it has been proved that Ф is constant along the path, and a formula to find its values on the contours has been obtained. The paper also presents the rationale of the line of stress discontinuity and obtained relationships, which allow us to derive the equations break lines for simple interaction of neighboring circuits, such as two lines, straight lines and circles, circles and a different sign of the curvature.After substitution into the boundary condition at the end of the stress function Ф and mathematical transformations a formula is obtained to determine the ultimate torque for the multiply cross-section rod.Using the doubly connected cross-section and three-connected cross-section rods as an example the application of the formula of ultimate torque is studied.For doubly connected cross-section rod, the paper offers a formula of the torque versus the radius of the rod, the aperture radius and the distance between their centers. It also clearly demonstrates the torque dependence both on the ratio of the radii and on the displacement of hole. It is shown that the value of the torque is more influenced by the displacement of hole, rather than by the ratio of the radii.For the three-connected cross-section rod the paper shows the integration feature that consists in selection of a coordinate system. As an example, the ultimate torque is found by two methods: analytical one and 3D modeling. The method of 3D modeling is based on the Nadai

  17. Multistep ion exchange processes of gradient refractive index rod lens.

    Science.gov (United States)

    Lv, Hao; Liu, Aimei; Tong, Jufang; Yi, Xunong; Li, Qianguang; Wang, Xinmin; Ding, Yaoming

    2011-01-01

    A mathematical model for research on the refractive index profile (RIP) of multistep ion exchange processes (IEPs) of gradient refractive index rod lenses (GRINs) is established by the different initial condition and boundary condition, based on the Fickian diffusion equation. GRIN rod lenses have been fabricated using the three-step IEPs. Research results indicate that the experimental deviations of refractive index (DRI) are in good agreement with the theoretical data. The DRI of three-step IEPs is superior to the one- and two-step IEPs and smaller than 10(-5).

  18. The extraordinary radiation pattern of an optical rod antenna

    CERN Document Server

    Zhao, Chenglong

    2010-01-01

    We investigated the radiation pattern of an optical rod antenna and found that it had many features compared with its conventional radio-wave equivalents. After defining a parameter {\\Lambda} = {\\lambda}eff /{\\lambda}, which was the ratio of the effective wavelength of the rod antenna to the incident wavelength, we found that {\\Lambda} had a great influence on the radiation pattern. Even the radiation pattern with a higher resonant order is without side lobes and results in a sharper directivity, which provides new design flexibilities in improving the directivities of the optical antennas.

  19. The improvement of control rod in experimental fast reactor JOYO. The development of a sodium bonded type control rod

    Energy Technology Data Exchange (ETDEWEB)

    Soga, T.; Miyakawa, S.; Mitsugi, T. [Japan Nuclear Cycle Development Inst., Oarai Engineering Center, Irradiation Center, Irradiation and Administration Section, Oarai, Ibaraki (Japan)

    1999-06-01

    Currently, the lifetime of control rods in JOYO is limited by Absorber-Cladding Mechanical Interaction (ACMI) due to swelling of B{sub 4}C(boron carbide) pellets accelerated by relocation of pellet fragments. A sodium bonded type control rod was developed which improves the thermal conductivity by means of charging sodium into the gap between B{sub 4}C and cladding and by utilizing a shroud which wraps the pellet fragments in a thin tube. This new design will be able to enlarge the gap between B{sub 4}C and cladding, without heating B{sub 4}C or fragment relocation, thus extending the life of the control rod. The sodium bonded type will be fabricated as the ninth reload control rods in JOYO. (1) The specification of a sodium bonded type control rod was determined with the wide gap between B{sub 4}C and cladding. In the design simulation, main component temperature were below the maximum limit. And the local heating by helium bubble generated from B{sub 4}C in the sodium gap, was not a serious problem in the analysis which was considered. (2) A structural design for the sodium entrance into the pin was determined. A formula was developed which the limit for sodium charging given physical dimension of the structure and sodium property. Result from sodium out-pile experiments validated the theoretical formula. (3) The analysis of ACMI indicated a lifetime extension of the sodium bonded type by 4.6% in comparison with lifetime of the helium bonded type of 1.6%. This is due to the boron10 burn-up rate being three times higher in the sodium bonded type than in the helium bonded type. To achieve a target burn-up 10% in the future, it will be necessary to modify design based on irradiation data which will be obtained by practical use of the sodium bonded control rods in JOYO. (4) The effects due to Absorber-Cladding Chemical Interaction (ACCI) were reduced by controlling the cladding temperature and chromium coating to the cladding's inner surface. It was confirmed

  20. Intraoperative implant rod three-dimensional geometry measured by dual camera system during scoliosis surgery.

    Science.gov (United States)

    Salmingo, Remel Alingalan; Tadano, Shigeru; Abe, Yuichiro; Ito, Manabu

    2016-05-12

    Treatment for severe scoliosis is usually attained when the scoliotic spine is deformed and fixed by implant rods. Investigation of the intraoperative changes of implant rod shape in three-dimensions is necessary to understand the biomechanics of scoliosis correction, establish consensus of the treatment, and achieve the optimal outcome. The objective of this study was to measure the intraoperative three-dimensional geometry and deformation of implant rod during scoliosis corrective surgery.A pair of images was obtained intraoperatively by the dual camera system before rotation and after rotation of rods during scoliosis surgery. The three-dimensional implant rod geometry before implantation was measured directly by the surgeon and after surgery using a CT scanner. The images of rods were reconstructed in three-dimensions using quintic polynomial functions. The implant rod deformation was evaluated using the angle between the two three-dimensional tangent vectors measured at the ends of the implant rod.The implant rods at the concave side were significantly deformed during surgery. The highest rod deformation was found after the rotation of rods. The implant curvature regained after the surgical treatment.Careful intraoperative rod maneuver is important to achieve a safe clinical outcome because the intraoperative forces could be higher than the postoperative forces. Continuous scoliosis correction was observed as indicated by the regain of the implant rod curvature after surgery.

  1. Estimation and control in HTGR fuel rod fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Downing, D J; Bailey, M J

    1980-01-01

    A control algorithm has been derived for a HTGR Fuel Rod Fabrication Process utilizing the method of Box and Jenkins. The estimator is a Kalman filter and is compared with a Least Square estimator and a standard control chart. The effects of system delays are presented.

  2. Melting mechanism in monolayers of flexible rod-shaped molecules

    DEFF Research Database (Denmark)

    Hansen, Flemming Yssing; Taub, H.

    1992-01-01

    mechanism for melting in monolayers of flexible rod-shaped molecules. Melting requires the formation of vacancies in the monolayer by molecular motion perpendicular to the surface. This ‘‘footprint reduction’’ mechanism implies that strictly two-dimensional theories of melting are inapplicable...

  3. Scoring Rod-and-Frame Tests: Quantitative and Qualitative Considerations.

    Science.gov (United States)

    Haller, Otto; Edgington, Eugene S.

    1982-01-01

    Current scoring procedures depend on unrealistic assumptions about subjects' performance on the rod-and-frame test. A procedure is presented which corrects for constant error, is sensitive to response strategy and consistency, and examines qualitative and quantitative aspects of performance and individual differences in laterality bias as defined…

  4. Frequency resolved transverse mode instability in rod fiber amplifiers

    DEFF Research Database (Denmark)

    Johansen, Mette Marie; Laurila, Marko; Maack, Martin D.

    2013-01-01

    Frequency dynamics of transverse mode instabilities (TMIs) are investigated by testing three 285/100 rod fibers in a single-pass amplifier setup reaching up to ~200W of extracted output power without beam instabilities. The pump power is increased well above the TMI threshold to uncover output...

  5. Improvement Research of Control Rod Drive Mechanism in CARR

    Institute of Scientific and Technical Information of China (English)

    ZHU; Xue-wei; ZHEN; Jian-xiao; LUO; Zhong; YANG; Kun; WANG; Yi-shi; JIA; Yue-guang

    2013-01-01

    We take an improvement research of synchronization in process of control rod drive mechanism(CRDM)inversion.An experimental prototype is designed based on the structure and function of the CRDM,we take some experiments on this experimental prototype,such as maximum loading force experiment,coil temperature rise experiment and stiffness experiment,achieve important magnetic

  6. Coexistence of central nucleus, cores, and rods: Diagnostic relevance

    Science.gov (United States)

    Dhinakaran, Sathiyabama; Kumar, Rashmi Santhosh; Thakkar, Ravindra; Narayanappa, Gayathri

    2016-01-01

    Background: Congenital myopathies (CMs) though considered distinct disorders, simultaneous occurrence of central nucleus, nemaline rods, and cores in the same biopsy are scarcely reported. Objective: A retrospective reassessment of cases diagnosed as CMs to look for multiple pathologies missed, if any, during the initial diagnosis. Materials and Methods: Enzyme histochemical, and immunohistochemical-stained slides from 125 cases diagnosed as congenital myopathy were reassessed. Results: The study revealed 15 cases (12%) of congenital myopathy with more than one morphological feature. Central nucleus with cores (n = 11), central nucleus, nemaline rods and cores (n = 3), and nemaline rods with cores (n = 1). 4/11 cases were diagnosed as centronuclear myopathy (CNM) in the first instance; in addition, cores were revealed on reassessment. Discussion: The prevalence of CMs of all neuromuscular disorders is approximately 6 in 100,000 live births, with regional variations. Three main defined CMs include centro nuclear myopathy (CNM), nemaline rod myopathy (NRM), and central core disease (CCD). However, they are more diverse with overlapping clinical and histopathological features, thus broadening the spectra within each category of congenital myopathy. Conclusion: Identification of cases with overlap of pathological features has diagnostic relevance. PMID:27293330

  7. The Use of Coloured Rods in Teaching Primary Numberwork.

    Science.gov (United States)

    Vancouver Public Schools, WA.

    A review of research literature revealed that some researchers felt that the use of colored rods, such as the Cuisenaire materials, in teaching number work gave perceptual support to many relationships. Experiments conducted over 3 years attempted to test some of these relationships. During each year, experimental classes in grade one were…

  8. Stress Analysis of Single Spacer Grid Support considering Fuel Rod

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Y. G.; Jung, D. H.; Kim, J. H. [Chungnam National University, Daejeon (Korea, Republic of); Park, J. K.; Jeon, K. L. [Korea Nuclear Fuel, Daejeon (Korea, Republic of)

    2010-10-15

    Pressurized water reactor (PWR) nuclear fuel assembly is mainly composed of a top-end piece, a bottom-end piece, lots of fuel rods, and several spacer grids. Among them, the main function of spacer grid is protecting fuel rods from Fluid Induced Vibration (FIV). The cross section of spacer grid assembled by laser welding in upper and lower point. When the fuel rod inserted in spacer gird, spring and dimple and around of welded area got a stresses. The main hypothesis of this analysis is the boundary area of HAZ and base metal can get a lot of damage than other area by FIV. So, design factors of spacer grid mainly considered to preventing the fatigue failure in HAZ and spring and dimple of spacer grid. From previous researching, the environment in reactor verified. Pressure and temperature of light water observed 15MPa and 320 .deg. C, and vibration of the fuel rod observed within 0 {approx} 50Hz. In this study, mechanical properties of zirconium alloy that extracted from the test and the spacer grid model which used in the PWR were applied in stress analyzing. General-purpose finite element analysis program was used ANSYS Workbench 12.0.1 version. 3-D CAD program CATIA was used to create spacer grid model

  9. Research on overlaying welding rod of high hardness maraging steel

    Institute of Scientific and Technical Information of China (English)

    PAN Yong-ming; CHEN Shao-wei

    2006-01-01

    The development of new maraging steel overlaying welding rod,which contains Co,Mo,W and V alloy,solved the problems of poor homogeneity of hardness and mechanical process, prolonged the service life of wear-resistant components and increased the productive efficiency of repairing,greatly benefiting the national economy.

  10. Estimating modal instability threshold for photonic crystal rod fiber amplifiers

    DEFF Research Database (Denmark)

    Johansen, Mette Marie; Hansen, Kristian Rymann; Laurila, Marko;

    2013-01-01

    We present a semi-analytic numerical model to estimate the transverse modal instability (TMI) threshold for photonic crystal rod amplifiers. The model includes thermally induced waveguide perturbations in the fiber cross section modeled with finite element simulations, and the relative intensity...

  11. Phase behaviour of rod-like colloid + flexible polymer mixtures

    NARCIS (Netherlands)

    Lekkerkerker, H.N.W.; Stroobants, A.

    1994-01-01

    The effect of non-adsorbing, flexible polymer on the isotropic-nematic transition in dispersions of rod-like colloids is investigated. A widening of the biphasic gap is observed, in combination with a marked polymer partitioning between the coexisting phases. Under certain conditions, areas of isotr

  12. Flexible Stabilisation of the Degenerative Lumbar Spine Using PEEK Rods

    Directory of Open Access Journals (Sweden)

    Jacques Benezech

    2016-01-01

    Full Text Available Posterior lumbar interbody fusion using cages, titanium rods, and pedicle screws is considered today as the gold standard of surgical treatment of lumbar degenerative disease and has produced satisfying long-term fusion rates. However this rigid material could change the physiological distribution of load at the instrumental and adjacent segments, a main cause of implant failure and adjacent segment disease, responsible for a high rate of further surgery in the following years. More recently, semirigid instrumentation systems using rods made of polyetheretherketone (PEEK have been introduced. This clinical study of 21 patients focuses on the clinical and radiological outcomes of patients with lumbar degenerative disease treated with Initial VEOS PEEK®-Optima system (Innov’Spine, France composed of rods made from PEEK-OPTIMA® polymer (Invibio Biomaterial Solutions, UK without arthrodesis. With an average follow-up of 2 years and half, the chances of reoperation were significantly reduced (4.8%, quality of life was improved (ODI = 16%, and the adjacent disc was preserved in more than 70% of cases. Based on these results, combined with the biomechanical and clinical data already published, PEEK rods systems can be considered as a safe and effective alternative solution to rigid ones.

  13. Noise level analysis in buffer rod geometries for ultrasonic sensors.

    Science.gov (United States)

    Garcia-Alvarez, J; Yañez, Y; Prego, J L; Turo, A; Chavez, J A; Garcia, M J; Salazar, J

    2006-12-22

    This work presents an ultrasonic sensor for on-line batter monitoring with low-noise design considerations. The density and the compressibility of the batter vary as a function of mixing time and are strongly related to the quality of the final product. Traditionally, a batter sample of a fixed volume is removed and weighted in order to determine its density. This is a time consuming process. Benefits to the industry of on-line measuring techniques include better control of product quality, improving processing efficiencies and reduction in wastage. In this paper low-noise design considerations are accounted for an ultrasonic sensor based on a piezoceramic disk mounted between two reference buffer rods of acrylic resin to measure the acoustic impedance of the batter. Measuring the acoustic impedance changes of the batter its compressibility and density can be monitored. Spurious echoes generated at different parts of the buffer rods boundary strongly affect accuracy and reliability of the measurements, and are considered as noise. The influence of buffer rods geometry on noise level is studied using simulations and afterwards justified experimentally. Design aspects such as buffer rods length and radius, piezoceramic disk frequency and radius are discussed and their influence on noise level is shown. Finally, strategies for optimum geometry design of the ultrasonic sensor are given.

  14. Interface Defeat of Long Rods Impacting Oblique Silicon Carbide

    Science.gov (United States)

    2011-02-01

    Test data for gold rods impacting unconfined silicon carbide targets are reported. This work focuses on the dwell phenomenon exhibited by silicon ... carbide for targets at obliquity. Experiments are presented for obliquities of 30 deg, 45 deg and 60 deg, with and without cover plates. Results are compared to normal impact.

  15. Fabrication of control rods for the High Flux Isotope Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Sease, J.D.

    1998-03-01

    The High Flux Isotope Reactor (HFIR) is a research-type nuclear reactor that was designed and built in the early 1960s and has been in continuous operation since its initial criticality in 1965. Under current plans, the HFIR is expected to continue in operation until 2035. This report updates ORNL/TM-9365, Fabrication Procedure for HFIR Control Plates, which was mainly prepared in the early 1970's but was not issued until 1984, and reflects process changes, lessons learned in the latest control rod fabrication campaign, and suggested process improvements to be considered in future campaigns. Most of the personnel involved with the initial development of the processes and in part campaigns have retired or will retire soon. Because their unlikely availability in future campaigns, emphasis has been placed on providing some explanation of why the processes were selected and some discussions about the importance of controlling critical process parameters. Contained in this report is a description of the function of control rods in the reactor, the brief history of the development of control rod fabrication processes, and a description of procedures used in the fabrication of control rods. A listing of the controlled documents and procedures used in the last fabrication campaigns is referenced in Appendix A.

  16. Mathematical model of an integrated circuit cooling through cylindrical rods

    Directory of Open Access Journals (Sweden)

    Beltrán-Prieto Luis Antonio

    2017-01-01

    Full Text Available One of the main challenges in integrated circuits development is to propose alternatives to handle the extreme heat generated by high frequency of electrons moving in a reduced space that cause overheating and reduce the lifespan of the device. The use of cooling fins offers an alternative to enhance the heat transfer using combined a conduction-convection systems. Mathematical model of such process is important for parametric design and also to gain information about temperature distribution along the surface of the transistor. In this paper, we aim to obtain the equations for heat transfer along the chip and the fin by performing energy balance and heat transfer by conduction from the chip to the rod, followed by dissipation to the surrounding by convection. Newton's law of cooling and Fourier law were used to obtain the equations that describe the profile temperature in the rod and the surface of the chip. Ordinary differential equations were obtained and the respective analytical solutions were derived after consideration of boundary conditions. The temperature along the rod decreased considerably from the initial temperature (in contatct with the chip surface. This indicates the benefit of using a cilindrical rod to distribute the heat generated in the chip.

  17. Achieving anisotropy in metamaterials made of dielectric cylindrical rods

    DEFF Research Database (Denmark)

    Peng, Liang; Ran, Lixin; Mortensen, Asger

    2010-01-01

    We show that anisotropic negative effective dispersion relation can be achieved in pure dielectric rod-type metamaterials by turning from the symmetry of a square lattice to that of a rectangular one. Theoretical predictions and conclusions are verified by both numerical calculations and computer...

  18. Non-linear waves in heterogeneous elastic rods via homogenization

    KAUST Repository

    Quezada de Luna, Manuel

    2012-03-01

    We consider the propagation of a planar loop on a heterogeneous elastic rod with a periodic microstructure consisting of two alternating homogeneous regions with different material properties. The analysis is carried out using a second-order homogenization theory based on a multiple scale asymptotic expansion. © 2011 Elsevier Ltd. All rights reserved.

  19. Further Development of a Model for Rod Ricochet

    Science.gov (United States)

    2007-02-01

    constraint, a solution technique has been developed that avoids the complexity of an iterative solution that characterized the original work. The revised...simpler minimization constraint, a solution technique has been developed that avoids the complexity of an iterative solution that characterized the...1. Spark cinematography of a ricocheting rod projectile, [3]. S.B. Segletes / International Journal of Impact Engineering 34 (2007) 899

  20. Cholesteric order in systems of helical Yukawa rods

    Energy Technology Data Exchange (ETDEWEB)

    Wensink, H H; Jackson, G, E-mail: wensink@thphy.uni-duesseldorf.de [Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom)

    2011-05-18

    We consider the interaction potential between two chiral rod-like colloids which consist of a thin cylindrical backbone decorated with a helical charge distribution on the cylinder surface. For sufficiently slender helical rods a simple scaling expression is derived which relates the chiral 'twisting' potential to the microscopic properties of the particles, such as the internal helical pitch, charge density and electrostatic screening parameter. To predict the behaviour of the macroscopic cholesteric pitch of the fluid bulk phase we invoke a simple second-virial theory generalized to treat anisotropic states with weakly twisted director fields. It is shown that, while particles with weakly coiled helices always form a cholesteric phase whose helical sense is commensurate with that of the internal helix, more strongly coiled rods lead to the formation of a cholesteric state of opposite sense. The correlation between the helical symmetry at the microscopic and macroscopic scale is found to be very sensitive to the pitch of the Yukawa helix. Mixing helical particles of sufficiently disparate length and internal pitch may give rise to a demixing of the uniform cholesteric phase into two fractions with a different macroscopic pitch. Our findings could be relevant to the interpretation of experimental observations in systems of cellulose and chitin microfibres, DNA and fd virus rods.

  1. Periodicity effects of axial waves in elastic compound rods

    DEFF Research Database (Denmark)

    Nielsen, R. B.; Sorokin, S. V.

    2015-01-01

    Floquet analysis is applied to the Bernoulli-Euler model for axial waves in a periodic rod. Explicit asymptotic formulae for the stop band borders are given and the topology of the stop band pattern is explained. Eigenfrequencies of the symmetric unit cell are determined by the Phase-closure Prin...

  2. Prosthetic Hand For Holding Rods, Tools, And Handles

    Science.gov (United States)

    Belcher, Jewell G., Jr.; Vest, Thomas W.

    1995-01-01

    Prosthetic hand with quick-grip/quick-release lever broadens range of specialized functions available to lower-arm amputee by providing improved capabilities for gripping rods, tools, handles, and like. Includes two stationary lower fingers opposed by one pivoting upper finger. Lever operates in conjunction with attached bracket.

  3. Histone H3 Variant Regulates RNA Polymerase II Transcription Termination and Dual Strand Transcription of siRNA Loci in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    David Reynolds

    2016-01-01

    Full Text Available Base J, β-D-glucosyl-hydroxymethyluracil, is a chromatin modification of thymine in the nuclear DNA of flagellated protozoa of the order Kinetoplastida. In Trypanosoma brucei, J is enriched, along with histone H3 variant (H3.V, at sites involved in RNA Polymerase (RNAP II termination and telomeric sites involved in regulating variant surface glycoprotein gene (VSG transcription by RNAP I. Reduction of J in T. brucei indicated a role of J in the regulation of RNAP II termination, where the loss of J at specific sites within polycistronic gene clusters led to read-through transcription and increased expression of downstream genes. We now demonstrate that the loss of H3.V leads to similar defects in RNAP II termination within gene clusters and increased expression of downstream genes. Gene derepression is intensified upon the subsequent loss of J in the H3.V knockout. mRNA-seq indicates gene derepression includes VSG genes within the silent RNAP I transcribed telomeric gene clusters, suggesting an important role for H3.V in telomeric gene repression and antigenic variation. Furthermore, the loss of H3.V at regions of overlapping transcription at the end of convergent gene clusters leads to increased nascent RNA and siRNA production. Our results suggest base J and H3.V can act independently as well as synergistically to regulate transcription termination and expression of coding and non-coding RNAs in T. brucei, depending on chromatin context (and transcribing polymerase. As such these studies provide the first direct evidence for histone H3.V negatively influencing transcription elongation to promote termination.

  4. Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes

    Science.gov (United States)

    Laperchia, Claudia; Palomba, Maria; Seke Etet, Paul F.; Rodgers, Jean; Bradley, Barbara; Montague, Paul; Grassi-Zucconi, Gigliola; Bentivoglio, Marina

    2016-01-01

    Background The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications. Methodology Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM) periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses. Principal findings Trypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion. Conclusion These findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging. PMID:28002454

  5. Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance.

    Directory of Open Access Journals (Sweden)

    Rebecca E Symula

    Full Text Available Trypanosoma brucei rhodesiense (Tbr and T. b. gambiense (Tbg, causative agents of Human African Trypanosomiasis (sleeping sickness in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs, components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR. HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb, a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1 and not found in related taxa, which are either human serum susceptible (Tbb or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2. We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR function.

  6. Microgravity Flammability of PMMA Rods in Concurrent Flow

    Science.gov (United States)

    Olson, Sandra L.; Ferkul, Paul V.

    2015-01-01

    Microgravity experiments burning cast PMMA cylindrical rods in axial flow have been conducted aboard the International Space Station in the Microgravity Science Glovebox (MSG) facility using the Burning and Suppression of Solids (BASS) flow duct, as part of the BASS-II experiment. Twenty-four concurrent-flow tests were performed, focusing on finding flammability limits as a function of oxygen and flow speed. The oxygen was varied by using gaseous nitrogen to vitiate the working volume of the MSG. The speed of the flow parallel to the rod was varied using a fan at the entrance to the duct. Both blowoff and quenching limits were obtained at several oxygen concentrations. Each experiment ignited the rod at the initially hemispherical stagnation tip of the rod, and allowed the flame to develop and heat the rod at a sufficient flow to sustain burning. For blowoff limit tests, the astronaut quickly turned up the flow to obtain extinction. Complementary 5.18-second Zero Gravity Facility drop tests were conducted to compare blowoff limits in short and long duration microgravity. For quenching tests, the flow was incrementally turned down and the flame allowed to stabilize at the new flow condition for at least the solid-phase response time before changing it again. Quenching was observed when the flow became sufficiently weak that the flame could no longer provide adequate heat flux to compensate for the heat losses (conduction into the rod and radiation). A surface energy balance is presented that shows the surface radiative loss exceeds the conductive loss into the rod near the limit. The flammability boundary is shown to represent a critical Damkohler number, expressed in terms of the reaction rate divided by the stretch rate. For the blowoff branch, the boundary exhibits a linear dependence on oxygen concentration and stretch rate, indicating that the temperature at blowoff must be fairly constant. For the quenching branch, the dominance of the exponential nature of

  7. 2D model for melt progression through rods and debris

    Energy Technology Data Exchange (ETDEWEB)

    Fichot, F. [IPSN/DRS, CEA Cadarache, St. Paul-lez-Durance (France)

    2001-07-01

    During the degradation of a nuclear core in a severe accident scenario, the high temperatures reached lead to the melting of materials. The formation of liquid mixtures at various elevations is followed by the flow of molten materials through the core. Liquid mixture may flow under several configurations: axial relocation along the rods, horizontal motion over a plane surface such as the core support plate or a blockage of material, 2D relocation through a debris bed, etc.. The two-dimensional relocation of molten material through a porous debris bed, implemented for the simulation of late degradation phases, has opened a new way to the elaboration of the relocation model for the flow of liquid mixture along the rods. It is based on a volume averaging method, where wall friction and capillary effects are taken into account by introducing effective coefficients to characterize the solid matrix (rods, grids, debris, etc.). A local description of the liquid flow is necessary to derive the effective coefficients. Heat transfers are modelled in a similar way. The derivation of the conservation equations for the liquid mixture falling flow (momentum) in two directions (axial and radial-horizontal) and for the heat exchanges (energy) are the main points of this new model for simulating melt progression. In this presentation, the full model for the relocation and solidification of liquid materials through a rod bundle or a debris bed is described. It is implemented in the ICARE/CATHARE code, developed by IPSN in Cadarache. The main improvements and advantages of the new model are: A single formulation for liquid mixture relocation, in 2D, either through a rod bundle or a porous debris bed, Extensions to complex structures (grids, by-pass, etc..), The modeling of relocation of a liquid mixture over plane surfaces. (author)

  8. Coolant mixing in LMFBR rod bundles and outlet plenum mixing transients. Progress report, June 1, 1976--August 31, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Todreas, N.E.; Golay, M.W.; Wolf, L.

    1976-01-01

    Progress is summarized in the following areas: wrapped and bare rod bundle geometry, bare rod subchannel geometry, outlet plenum flow mixing, and theoretical determination of local temperature fields in rod bundles. (DG)

  9. Scram simulation of a control rod drive mechanism of a pressurized water reactor under seismic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, Katsuhisa; Shinohara, Yoshikazu; Ichinoo, Hiroyuki; Yoshikawa, Eiji; Nambu, Kiyoshi; Nomura, Tomonori.

    1987-03-01

    Control rod drop verification experiments of Mitsubishi pressurized water reactor under seismic conditions are performed to confirm the insertion function of control rods into the core. To evaluate these tests, computer simulations are performed. The scram time of control rods under seismic conditions was confirmed to meet the scram function. The behavior of the dropping control rods and the scram time obtained by the computer simulation show a very good correspondence with the results of verification experiments.

  10. Possibilities and limitations of rod-beam theories. [nonlinear distortion tensor and nonlinear stress tensors

    Science.gov (United States)

    Peterson, D.

    1979-01-01

    Rod-beam theories are founded on hypotheses such as Bernouilli's suggesting flat cross-sections under deformation. These assumptions, which make rod-beam theories possible, also limit the accuracy of their analysis. It is shown that from a certain order upward terms of geometrically nonlinear deformations contradict the rod-beam hypotheses. Consistent application of differential geometry calculus also reveals differences from existing rod theories of higher order. These differences are explained by simple examples.

  11. Linear motion device and method for inserting and withdrawing control rods

    Science.gov (United States)

    Smith, J.E.

    Disclosed is a linear motion device and more specifically a control rod drive mechanism (CRDM) for inserting and withdrawing control rods into a reactor core. The CRDM and method disclosed is capable of independently and sequentially positioning two sets of control rods with a single motor stator and rotor. The CRDM disclosed can control more than one control rod lead screw without incurring a substantial increase in the size of the mechanism.

  12. The miRNA and mRNA Signatures of Peripheral Blood Cells in Humans Infected with Trypanosoma brucei gambiense.

    Directory of Open Access Journals (Sweden)

    Smiths Lueong

    Full Text Available Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II and without (stage I brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II, 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology.

  13. Diverse effects on mitochondrial and nuclear functions elicited by drugs and genetic knockdowns in bloodstream stage Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Christal Worthen

    Full Text Available BACKGROUND: The options for treating the fatal disease human African trypanosomiasis are limited to a few drugs that are toxic or facing increasing resistance. New drugs that kill the causative agents, subspecies of Trypanosoma brucei, are therefore urgently needed. Little is known about the cellular mechanisms that lead to death of the pathogenic bloodstream stage. METHODOLOGY/PRINCIPAL FINDINGS: We therefore conducted the first side by side comparison of the cellular effects of multiple death inducers that target different systems in bloodstream form parasites, including six drugs (pentamidine, prostaglandin D(2, quercetin, etoposide, camptothecin, and a tetrahydroquinoline and six RNAi knockdowns that target distinct cellular functions. All compounds tested were static at low concentrations and killed at high concentrations. Dead parasites were rapidly quantified by forward and side scatter during flow cytometry, as confirmed by ethidium homodimer and esterase staining, making these assays convenient for quantitating parasite death. The various treatments yielded different combinations of defects in mitochondrial potential, reactive oxygen species, cell cycle, and genome segregation. No evidence was seen for phosphatidylserine exposure, a marker of apoptosis. Reduction in ATP levels lagged behind decreases in live cell number. Even when the impact on growth was similar at 24 hours, drug-treated cells showed dramatic differences in their ability to further proliferate, demonstrating differences in the reversibility of effects induced by the diverse compounds. CONCLUSIONS/SIGNIFICANCE: Parasites showed different phenotypes depending on the treatment, but none of them were clear predictors of whether apparently live cells could go on to proliferate after drugs were removed. We therefore suggest that clonal proliferation assays may be a useful step in selecting anti-trypanosomal compounds for further development. Elucidating the genetic or

  14. Functional and structural insights revealed by molecular dynamics simulations of an essential RNA editing ligase in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Rommie E Amaro

    Full Text Available RNA editing ligase 1 (TbREL1 is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme.

  15. Genetic character of drug resistance in Trpanosoma brucei%锥虫抗药性的遗传特性

    Institute of Scientific and Technical Information of China (English)

    廖党金; 沈杰

    2000-01-01

    @@ 锥虫病是由锥虫寄生于人和动物的血液而引起人和动物的一种疾病.锥虫抗药性的产生,可能给人和家畜带来较严重的后果[1],国外于1908年已注意到锥虫的抗药性问题[2、3],而我国于1988年第一次口头报道在云南用厂方推荐的安锥赛治疗剂量难以治愈家畜锥虫病,1991年沈杰等正式报道了我国伊氏锥虫云南株和安徽株对安锥赛已产生抗药性[4].迄今,报告产生抗药性的锥虫虫种有布氏锥虫(Trypanosoma brucei)等常见的8个种,其它未报告的锥虫并不意味着不产生抗药性.已报告产生抗药性的药物有苏拉明(Suramine)等30多种抗锥虫药物.抗药性是能遗传的,对锥虫抗药性的遗传特性的了解,能帮助我们正确地选择和使用药物、减少和避免抗药性的产生及怎样消除已有的抗药性具有极其重要的作用,其次也有助于锥虫的生理、生化及生物学研究.

  16. Crystal Structures of Trypanosoma brucei Sterol 14[alpha]-Demethylase and Implications for Selective Treatment of Human Infections

    Energy Technology Data Exchange (ETDEWEB)

    Lepesheva, Galina I.; Park, Hee-Won; Hargrove, Tatiana Y.; Vanhollebeke, Benoit; Wawrzak, Zdzislaw; Harp, Joel M.; Sundaramoorthy, Munirathinam; Nes, W. David; Pays, Etienne; Chaudhuri, Minu; Villalta, Fernando; Waterman, Michael R. (ULdB); (Vanderbilt); (TTU); (Toronto); (NWU); (Meharry)

    2010-01-25

    Sterol 14{alpha}-demethylase (14DM, the CYP51 family of cytochrome P450) is an essential enzyme in sterol biosynthesis in eukaryotes. It serves as a major drug target for fungal diseases and can potentially become a target for treatment of human infections with protozoa. Here we present 1.9 {angstrom} resolution crystal structures of 14DM from the protozoan pathogen Trypanosoma brucei, ligand-free and complexed with a strong chemically selected inhibitor N-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(5-phenyl-1,3,4-oxadi-azol-2-yl)benzamide that we previously found to produce potent antiparasitic effects in Trypanosomatidae. This is the first structure of a eukaryotic microsomal 14DM that acts on sterol biosynthesis, and it differs profoundly from that of the water-soluble CYP51 family member from Mycobacterium tuberculosis, both in organization of the active site cavity and in the substrate access channel location. Inhibitor binding does not cause large scale conformational rearrangements, yet induces unanticipated local alterations in the active site, including formation of a hydrogen bond network that connects, via the inhibitor amide group fragment, two remote functionally essential protein segments and alters the heme environment. The inhibitor binding mode provides a possible explanation for both its functionally irreversible effect on the enzyme activity and its selectivity toward the 14DM from human pathogens versus the human 14DM ortholog. The structures shed new light on 14DM functional conservation and open an excellent opportunity for directed design of novel antiparasitic drugs.

  17. 77 FR 59892 - Carbon and Certain Alloy Steel Wire Rod From Mexico: Affirmative Final Determination of...

    Science.gov (United States)

    2012-10-01

    ... International Trade Administration Carbon and Certain Alloy Steel Wire Rod From Mexico: Affirmative Final... mm to 5.0 mm. \\1\\ See Carbon and Certain Alloy Steel Wire Rod from Mexico: Affirmative Preliminary... on said entries.\\4\\ \\2\\ See Carbon and Certain Alloy Steel Wire Rod from Mexico: Initiation of...

  18. 76 FR 78882 - Carbon and Certain Alloy Steel Wire Rod From Mexico: Affirmative Preliminary Determination of...

    Science.gov (United States)

    2011-12-20

    ... International Trade Administration Carbon and Certain Alloy Steel Wire Rod From Mexico: Affirmative Preliminary... Administration, Department of Commerce. SUMMARY: We preliminarily determine that carbon and certain alloy steel wire rod (wire rod) with an actual diameter between 4.75 mm and 5.00 mm produced in Mexico and...

  19. 78 FR 2658 - Carbon and Certain Alloy Steel Wire Rod From Mexico: Rescission of Antidumping Duty...

    Science.gov (United States)

    2013-01-14

    ... International Trade Administration Carbon and Certain Alloy Steel Wire Rod From Mexico: Rescission of... its administrative review of the antidumping duty order on carbon and certain alloy steel wire rod (``wire rod'') from Mexico for the period October 1, 2011, through September 30, 2012. DATES:...

  20. 78 FR 71565 - Steel Threaded Rod from India: Postponement of Preliminary Determination of Antidumping Duty...

    Science.gov (United States)

    2013-11-29

    ... International Trade Administration Steel Threaded Rod from India: Postponement of Preliminary Determination of...'') published a notice of initiation of the antidumping duty investigation of steel threaded rod from India.\\1... later than December 20, 2013. \\1\\ See Steel Threaded Rod From India and Thailand: Initiation...

  1. Differential Effects of the Rod-and-Frame Illusion on the Timing of Forearm Rotations

    NARCIS (Netherlands)

    Lommertzen, J.; Zuijlen, A.M.J. van; Meulenbroek, R.G.J.; Lier, R.J. van

    2009-01-01

    The present study focused on the time course of the effects of the Rod-and-Frame Illusion (RFI) on the kinematics of targeted forearm rotations. Participants were asked to reproduce perceived rod orientations by propelling a hand-held cylinder forward while rotating it to the target orientation. Rod

  2. A Patient With Pyruvate Carboxylase Deficiency and Nemaline Rods on Muscle Biopsy

    DEFF Research Database (Denmark)

    Unal, Ozlem; Orhan, Diclehan; Ostergaard, Elsebet;

    2013-01-01

    and nemaline rods detected on muscle biopsy. The nemaline rods may be due to cellular energy shortage and altered energy metabolism in pyruvate carboxylase deficiency, similar to that in the previously reported patients. The mechanism of nemaline rod formation may be associated with the role of pyruvate...

  3. Use of Belcastro Rods to Teach Mathematical Concepts to Blind Students.

    Science.gov (United States)

    Belcastro, Frank P.

    1989-01-01

    The article suggests that Belcastro rods, which retain the basic properties of Cuisenaire rods but allow instant identification by touch, may be useful in teaching mathematical concepts to blind children. Drawings illustrate use of the rods in teaching such concepts as addition and subtraction. (Author/DB)

  4. Fabrication and characterization of terahertz anisotropic anti-rod dimer planar metamaterials

    DEFF Research Database (Denmark)

    Zalkovskij, Maksim; Malureanu, Radu; Novitsky, Andrey

    2012-01-01

    In this work we describe the fabrication and characterization of free-standing membranes with thick anti-rod dimers metamaterials for terahertz waves. Two different designs with parallel and V-shape anti-rods were analysed. Even though both structures consists of simple elements, namely anti......-rod dimers, they reveal interesting birefringent and dichroic transmission properties....

  5. Results of automatic system implementation for the friction control rods execution in Cofrentes nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Curiel, M. [Logistica y Acondicionamientos Industriales SAU, Sorolla Center, local 10, Av. de las Cortes Valencianas, 46015 Valencia (Spain); Palomo, M. J. [ISIRYM, Universidad Politecnica de Valencia, Camino de Vera s/n, Valencia (Spain); Urrea, M. [Iberdrola Generacion S. A., Central Nuclear Cofrentes, Carretera Almansa Requena s/n, 04662 Cofrentes, Valencia (Spain); Arnaldos, A., E-mail: m.curiel@lainsa.co [TITANIA Servicios Tecnologicos SL, Sorolla Center, local 10, Av. de las Cortes Valencianas No. 58, 46015 Valencia (Spain)

    2010-10-15

    The purpose of this presentation is to show the obtained results in Cofrentes nuclear power plant (Spain) of control rods Pcc/24 friction test procedure. In order to perform this, a control rod friction test system has been developed. Principally, this system consists on software and data acquisition hardware that obtains and analyzes the control rod pressure variation on which the test is being made. The Pcc/24 procedure objective is to detect an excessive friction in the control rod movement that could cause a control rod drive movement slower than usual. This test is necessary every time that an anomalous alteration is produced in the reactor core that could affect to a fuel rod, and it is executed before the time measure of control rods rapid scram test of the affected rods. This test has to be carried out to all the reactor control rods and takes valuable time during plant refuelling. So, by means of an automatic system to perform the test, we obtain an important time saving during refuelling. On the other hand, the on-line monitoring of the control rod insertion and changes in differential pressure, permits a control rod operation fast and safe validation. Moreover, an automatic individual report of every rod is generated by the system and a final global result report of the entire test developed in refuelling is generated. The mentioned reports can be attached directly to the procedure documents obtaining an office data processing important saving time. (Author)

  6. Results of automatic system implementation for the friction control rods execution in Cofrentes nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, M., E-mail: mpalomo@iqn.upv.es [Universidad Politecnica de Valencia (UPV) (Spain); Urrea, M., E-mail: matias.urrea@iberdrola.es [Iberdrola Generacion S.A. Valencia (Spain). C.N. Cofrentes; Curiel, M., E-mail: m.curiel@lainsa.com [Logistica y Acondicionamientos Industriales (LAINSA), Valencia (Spain); Arnaldos, A., E-mail: a.arnaldos@titaniast.com [TITANIA Servicios Teconologicos, Valencia (Spain)

    2011-07-01

    The purpose of this presentation is to show the obtained results in Cofrentes Nuclear Power Plant (Spain) of Control Rods PCC/24 Friction Test Procedure. In order to perform this, a Control Rod Friction Test System has been developed. Principally, this system consists on software and data acquisition hardware that obtains and analyzes the control rod pressure variation on which the test is being made. The PCC/24 Procedure objective is to detect an excessive friction in the control rod movement that could cause a CRD (Control Rod Drive) movement slower than usual. This test is necessary every time that an anomalous alteration is produced in the reactor core that could affect to a fuel rod, and it is executed before the time measure of control rods rapid scram test of the affected rods. This test has to be carried out to all the reactor control rods and takes valuable time during plant refuelling. So, by means of an automatic system to perform the test, we obtain an important time saving during refuelling. On the other hand, the on-line monitoring of the control rod insertion and changes in differential pressure, permits a control rod operation fast and safe validation. Moreover, an automatic individual report of every rod is generated by the system and a final global result report of the entire test developed in refuelling is generated. The mentioned reports can be attached directly to the procedure documents obtaining an office data processing important saving time.(author)

  7. Experimental fuel rod stored energy determination. STEED I project

    Energy Technology Data Exchange (ETDEWEB)

    Engman, U.; Malen, K. [Studsvik Nuclear AB, Nykoeping (Sweden)

    1999-06-01

    The objective of the STEED I (STored Energy/Enthalpy Determination) project was to evaluate an experimental method for producing accurate and reliable data concerning the stored energy in fuel rods during operation. The STEED data should provide useful information for LOCA evaluation, fuel design and thermo-mechanical modelling. Stored energy refers to the amount of heat, which at a certain time is stored within the fuel. Physical properties of the fuel that affect the quantity of stored energy are radial power profile, burnup, fuel geometry, fuel density and thermal conductivity and heat capacity of the fuel pellet, and the gas gap conductance. The quantity of stored energy is conveniently studied under transient conditions when all, or part of the stored heat is released. This work describes determination of the stored energy by evaluating scram tests. The R2 test reactor is well suited for this type of experiments, where the thermal response of different types of fuel rods can be evaluated and compared. Scrams have been performed with the intent to evaluate the fuel rod stored energy before the scram. Methods have been developed for evaluation of the stored energy from the scram response It was found that the time dependence for a large part of the heat release from the rod could be described by a single time constant. Evaluations of the time constant have been made from the data in different ways. The stored energy has been evaluated integrating the exponential decay. The integral of the exponential decay is the initial power multiplied by the time constant. This means that differences in the stored energy due to, for instance, rod properties or rod power dependence are best studied using the same time constant. The scram response was modelled with the TOODEE2 transient code. The calculations gave a time constant of about 4 s and very little power dependence. The experimental result is a time constant around 4 s. The small differences in the measurement results

  8. A Novel Basal Body Protein That Is a Polo-like Kinase Substrate Is Required for Basal Body Segregation and Flagellum Adhesion in Trypanosoma brucei.

    Science.gov (United States)

    Hu, Huiqing; Zhou, Qing; Li, Ziyin

    2015-10-01

    The Polo-like kinase (PLK) in Trypanosoma brucei plays multiple roles in basal body segregation, flagellum attachment, and cytokinesis. However, the mechanistic role of TbPLK remains elusive, mainly because most of its substrates are not known. Here, we report a new substrate of TbPLK, SPBB1, and its essential roles in T. brucei. SPBB1 was identified through yeast two-hybrid screening with the kinase-dead TbPLK as the bait. It interacts with TbPLK in vitro and in vivo, and is phosphorylated by TbPLK in vitro. SPBB1 localizes to both the mature basal body and the probasal body throughout the cell cycle, and co-localizes with TbPLK at the basal body during early cell cycle stages. RNAi against SPBB1 in procyclic trypanosomes inhibited basal body segregation, disrupted the new flagellum attachment zone filament, detached the new flagellum, and caused defective cytokinesis. Moreover, RNAi of SPBB1 confined TbPLK at the basal body and the bilobe structure, resulting in constitutive phosphorylation of TbCentrin2 at the bilobe. Altogether, these results identified a basal body protein as a TbPLK substrate and its essential role in promoting basal body segregation and flagellum attachment zone filament assembly for flagellum adhesion and cytokinesis initiation.

  9. Nucleolar accumulation of RNA binding proteins induced by Actinomycin D is functional in Trypanosoma cruzi and Leishmania mexicana but not in T. brucei.

    Directory of Open Access Journals (Sweden)

    Ezequiel Názer

    Full Text Available We have recently shown in T. cruzi that a group of RNA Binding Proteins (RBPs, involved in mRNA metabolism, are accumulated into the nucleolus in response to Actinomycin D (ActD treatment. In this work, we have extended our analysis to other members of the trypanosomatid lineage. In agreement with our previous study, the mechanism seems to be conserved in L. mexicana, since both endogenous RBPs and a transgenic RBP were relocalized to the nucleolus in parasites exposed to ActD. In contrast, in T. brucei, neither endogenous RBPs (TbRRM1 and TbPABP2 nor a transgenic RBP from T. cruzi were accumulated into the nucleolus under such treatment. Interestingly, when a transgenic TbRRM1 was expressed in T. cruzi and the parasites exposed to ActD, TbRRM1 relocated to the nucleolus, suggesting that it contains the necessary sequence elements to be targeted to the nucleolus. Together, both experiments demonstrate that the mechanism behind nucleolar localization of RBPs, which is present in T. cruzi and L. mexicana, is not functional in T. brucei, suggesting that it has been lost or retained differentially during the evolution of the trypanosomatid lineage.

  10. Deletion of a novel protein kinase with PX and FYVE-related domains increases the rate of differentiation of Trypanosoma brucei.

    Science.gov (United States)

    Vassella, E; Krämer, R; Turner, C M; Wankell, M; Modes, C; van den Bogaard, M; Boshart, M

    2001-07-01

    Growth control of African trypanosomes in the mammalian host is coupled to differentiation of a non-dividing life cycle stage, the stumpy bloodstream form. We show that a protein kinase with novel domain architecture is important for growth regulation. Zinc finger kinase (ZFK) has a kinase domain related to RAC and S6 kinases flanked by a FYVE-related zinc finger and a phox (PX) homology domain. To investigate the function of the kinase during cyclical development, a stable transformation procedure for bloodstream forms of differentiation-competent (pleomorphic) Trypanosoma brucei strains was established. Deletion of both allelic copies of ZFK by homologous recombination resulted in reduced growth of bloodstream-form parasites in culture, which was correlated with an increased rate of differentiation to the non-dividing stumpy form. Growth and differentiation rates were returned to wild-type level by ectopic ZFK expression. The phenotype is stage-specific, as growth of procyclic (insect form) trypanosomes was unaffected, and Deltazfk/Deltazfk clones were able to undergo full cyclical development in the tsetse fly vector. Deletion of ZFK in a differentiation-defective (monomorphic) strain of T. brucei did not change its growth rate in the bloodstream stage. This suggests a function of ZFK associated with the trypanosomes' decision between either cell cycle progression, as slender bloodstream form, or differentiation to the non-dividing stumpy form.

  11. Dynein Light Chain LC8 Is Required for RNA Polymerase I-Mediated Transcription in Trypanosoma brucei, Facilitating Assembly and Promoter Binding of Class I Transcription Factor A.

    Science.gov (United States)

    Kirkham, Justin K; Park, Sung Hee; Nguyen, Tu N; Lee, Ju Huck; Günzl, Arthur

    2016-01-01

    Dynein light chain LC8 is highly conserved among eukaryotes and has both dynein-dependent and dynein-independent functions. Interestingly, LC8 was identified as a subunit of the class I transcription factor A (CITFA), which is essential for transcription by RNA polymerase I (Pol I) in the parasite Trypanosoma brucei. Given that LC8 has never been identified with a basal transcription factor and that T. brucei relies on RNA Pol I for expressing the variant surface glycoprotein (VSG), the key protein in antigenic variation, we investigated the CITFA-specific role of LC8. Depletion of LC8 from mammalian-infective bloodstream trypanosomes affected cell cycle progression, reduced the abundances of rRNA and VSG mRNA, and resulted in rapid cell death. Sedimentation analysis, coimmunoprecipitation of recombinant proteins, and bioinformatic analysis revealed an LC8 binding site near the N terminus of the subunit CITFA2. Mutation of this site prevented the formation of a CITFA2-LC8 heterotetramer and, in vivo, was lethal, affecting assembly of a functional CITFA complex. Gel shift assays and UV cross-linking experiments identified CITFA2 as a promoter-binding CITFA subunit. Accordingly, silencing of LC8 or CITFA2 resulted in a loss of CITFA from RNA Pol I promoters. Hence, we discovered an LC8 interaction that, unprecedentedly, has a basal function in transcription.

  12. Implementation of CTRLPOS, a VENTURE module for control rod position criticality searches, control rod worth curve calculations, and general criticality searches

    Energy Technology Data Exchange (ETDEWEB)

    Smith, L.A.; Renier, J.P.

    1994-06-01

    A module in the VENTURE reactor analysis code system, CTRLPOS, is developed to position control rods and perform control rod position criticality searches. The module is variably dimensioned so that calculations can be performed with any number of control rod banks each having any number of control rods. CTRLPOS can also calculate control rod worth curves for a single control rod or a bank of control rods. Control rod depletion can be calculated to provide radiation source terms. These radiation source terms can be used to predict radiation doses to personnel and estimate the shielding and long-term storage requirements for spent control rods. All of these operations are completely automated. The numerous features of the module are discussed in detail. The necessary input data for the CTRLPOS module is explained. Several sample problems are presented to show the flexibility of the module. The results presented with the sample problems show that the CTRLPOS module is a powerful tool which allows a wide variety of calculations to be easily performed.

  13. Realization of Tapered Waveguide by Stretching the Rod Waveguide

    Institute of Scientific and Technical Information of China (English)

    XIA Ke-yu; YU Rong-jin; MENG Hua-mao

    2004-01-01

    By stretching the rod waveguide with different velocities in opposite directions,the tapered waveguide can be fabricated.In condition of taking no account of volume expansion caused by heating and under the assumptions of volume conservation,the rod waveguide can be stretched freely in the heated region without being stretched outside of the heated region. A model,which shows the relation of the transition shape and the two factors,that is the ratio of two velocity and the heated region length,is presented for the shape of the taper transition through mathematic deduction.Based on this model,a desired tapered waveguide can be fabricated.The tapered waveguide are widely used for fabricating tapered fiber couplers and sensors.In addition,the conclusion can be used for fabricating fused fiber coupler.

  14. Granular gases of rod-shaped grains in microgravity.

    Science.gov (United States)

    Harth, K; Kornek, U; Trittel, T; Strachauer, U; Höme, S; Will, K; Stannarius, R

    2013-04-05

    Granular gases are convenient model systems to investigate the statistical physics of nonequilibrium systems. In the literature, one finds numerous theoretical predictions, but only few experiments. We study a weakly excited dilute gas of rods, confined in a cuboid container in microgravity during a suborbital rocket flight. With respect to a gas of spherical grains at comparable filling fraction, the mean free path is considerably reduced. This guarantees a dominance of grain-grain collisions over grain-wall collisions. No clustering was observed, unlike in similar experiments with spherical grains. Rod positions and orientations were determined and tracked. Translational and rotational velocity distributions are non-Gaussian. Equipartition of kinetic energy between translations and rotations is violated.

  15. Test requirement for PIE of HANARO irradiated fuel rod

    Energy Technology Data Exchange (ETDEWEB)

    Lim, I. C.; Cho, Y. G

    2000-06-01

    Since the first criticality of HANARO reached in Feb. of 1995, the rod type U{sub 3}Si-A1 fuel imported from AECL has been used. From the under-water fuel inspection which has been conducted since 1997, a ballooning-rupture type abnormality was observed in several fuel rods. In order to find the root cause of this abnormality and to find the resolution, the post irradiation examination(PIE) was proposed as the best way. In this document, the information from the under-water inspection as well as the PIE requirements are described. Based on the information in this document, a detail test plan will be developed by the project team who shall conduct the PIE.

  16. Terahertz pinch harmonics enabled by single nano rods.

    Science.gov (United States)

    Park, Hyeong-Ryeol; Bahk, Young-Mi; Choe, Jong Ho; Han, Sanghoon; Choi, Seong Soo; Ahn, Kwang Jun; Park, Namkyoo; Park, Q-Han; Kim, Dai-Sik

    2011-11-21

    A pinch harmonic (or guitar harmonic) is a musical note produced by lightly pressing the thumb of the picking hand upon the string immediately after it is picked [J. Chem. Educ. 84, 1287 (2007)]. This technique turns off the fundamental and all overtones except those with a node at that location. Here we present a terahertz analogue of pinch harmonics, whereby a metallic nano rod placed at a harmonic node on a terahertz nanoresonator suppresses the fundamental mode, making the higher harmonics dominant. Strikingly, a skin depth-wide nano rod placed at the mid-point turns off all resonances. Our work demonstrates that terahertz electromagnetic waves can be tailored by nanoparticles strategically positioned, paving important path towards terahertz switching and detection applications.

  17. Experimental analysis of liquid-metal reactor scram rod kinematic characteristics

    Science.gov (United States)

    Konovalenko, F. D.; Kondrashov, S. I.

    2017-01-01

    This article represents the results of computational and experimental research of liquid-metal research reactor control rod kinematics. In this research liquid-metal coolant (sodium) was simulated by water. Investigation of control rod scram-mode movement duration and investigation of velocity of movable parts near the bump of damper are the purposes of this research. Also mathematic simulation of control rod movement in scram mode was performed. Computational results for some modes of water circulation comply with experimental results well. Results of this work will be used for tests of scram rod drive of above-named research reactor. It will significantly simplify the scram rod drive testing stand construction.

  18. Fabrication of free-standing PbSe micro-rods

    Science.gov (United States)

    Jain, S.; Mukherjee, S.; Guan, Z. P.; Ray, D.; Zhao, F.; Li, D.; Shi, Z.

    2007-07-01

    We have fabricated epitaxially grown PbSe micro-rods by the fold-back action of the thin film and have investigated the experimental factors affecting the size of the micro-rods. We observe that the initial layer thickness and the etching parameters of the sacrificial layer determined the final diameter of the rods. By individually mounting the rods on copper heat sink, we observe an approximately 100 times increase in photoluminescence (PL) intensity per surface area when compared to the bulk film before rolling into micro-rod. These results offer a promising future of microstructures to the technology of mid-infrared light-emitting devices.

  19. Pinch-off of rods by bulk diffusion

    DEFF Research Database (Denmark)

    Aagesen, L.K.; Johnson, A.E.; Fife, J.L.;

    2011-01-01

    The morphology of a rod embedded in a matrix undergoing pinching by interfacial-energy-driven bulk diffusion is determined near the point of pinching. We find a self-similar solution that gives a unique temporal power law and interfacial shape prior to pinching and self-similar solutions after pi......, and thus provide estimates of the time required for capillarity-driven break-up of microstructures from the detachment of secondary dendrite arms to polymer blends....

  20. Hydrodynamic behavior of a bare rod bundle. [LMFBR

    Energy Technology Data Exchange (ETDEWEB)

    Bartzis, J.G.; Todreas, N.E.

    1977-06-01

    The temperature distribution within the rod bundle of a nuclear reactor is of major importance in nuclear reactor design. However temperature information presupposes knowledge of the hydrodynamic behavior of the coolant which is the most difficult part of the problem due to complexity of the turbulence phenomena. In the present work a 2-equation turbulence model--a strong candidate for analyzing actual three dimensional turbulent flows--has been used to predict fully developed flow of infinite bare rod bundle of various aspect ratios (P/D). The model has been modified to take into account anisotropic effects of eddy viscosity. Secondary flow calculations have been also performed although the model seems to be too rough to predict the secondary flow correctly. Heat transfer calculations have been performed to confirm the importance of anisotropic viscosity in temperature predictions. All numerical calculations for flow and heat have been performed by two computer codes based on the TEACH code. Experimental measurements of the distribution of axial velocity, turbulent axial velocity, turbulent kinetic energy and radial Reynolds stresses were performed in the developing and fully developed regions. A 2-channel Laser Doppler Anemometer working on the Reference mode with forward scattering was used to perform the measurements in a simulated interior subchannel of a triangular rod array with P/D = 1.124. Comparisons between the analytical results and the results of this experiment as well as other experimental data in rod bundle array available in literature are presented. The predictions are in good agreement with the results for the high Reynolds numbers.

  1. Transmission efficiency measurement at the FNAL 4-rod RFQ

    Energy Technology Data Exchange (ETDEWEB)

    Carneiro, J. P. [Fermilab; Garcia, F. G. [Fermilab; Ostiguy, J. F. [Fermilab; Saini, A. [Fermilab; Zwaska, R. [Fermilab; Mustapha, B. [Argonne; Ostroumov, P. [Argonne

    2014-12-01

    This paper presents measurements of the beam transmission performed on the 4-rod RFQ currently under operation at Fermilab. The beam current has been measured at the RFQ exit as a function of the magnetic field strength in the two LEBT solenoids. This measurement is compared with scans performed on the FermiGrid with the beam dynamics code TRACK. A particular attention is given to the impact, on the RFQ beam transmission, of the space-charge neutralization in the LEBT.

  2. Dagang Subsurface Sucker Rod Pump and Its Fitting

    Institute of Scientific and Technical Information of China (English)

    Liu Chunyong

    1995-01-01

    @@ Petroleum Machinery Manufacturing Plant,Dagang Petroleum Administration is a manufacturer of subsurface sucker rod pump and its fittings. The plant is located in Tianjin,Bohai Bay, near communication hubs of Beijin and Tianjin port, covering an area of 286 000 square meter. Since the plant was established in 1974, it has been developed to be a modern enterprise of subsurface pump with enormous potentiality.

  3. Adaptive potentiation in rod photoreceptors after light exposure

    OpenAIRE

    McKeown, Alex S; Kraft, Timothy W.

    2014-01-01

    Photoreceptors adapt to changes in illumination by altering transduction kinetics and sensitivity, thereby extending their working range. We describe a previously unknown form of rod photoreceptor adaptation in wild-type (WT) mice that manifests as a potentiation of the light response after periods of conditioning light exposure. We characterize the stimulus conditions that evoke this graded hypersensitivity and examine the molecular mechanisms of adaptation underlying the phenomenon. After e...

  4. Gray Related Analysis on Shaped-charge Rod Penetrator Shaped

    Institute of Scientific and Technical Information of China (English)

    HUANG Zheng-xiang; ZHANG Xian-feng; CHEN Hui-wu

    2005-01-01

    The gray relation among the design parameters of the cumulative charge rod penetrator (CCRP) is analyzed adopting the gray systematic theory and method, and the gray related matrix among the parameters is obtained. The result parameters of CCRP and the main parameters of influencing the CCRP molding are obtained utilizing numerical simulation. This lays the foundation of CCRP design and provides a kind of effective research method.

  5. Minimum slugging velocity in fluidized beds containing vertical rods

    Energy Technology Data Exchange (ETDEWEB)

    Coronella, C.J.; Lee, S.Y.; Seader, J.D. (University of Utah, Salt Lake City, UT (United States). Dept. of Chemical Engineering)

    1994-09-01

    A new method for determining the onset of slugging in fluidized beds is presented. Pressure-drop fluctuations, measured from below the distributor to the gas exit line, are transformed to the frequency domain by the power spectral desity function (PSDF). The dominant frequency of the PSDF corresponds to the eruption frequency of bubbles or slugs. A fluidized bed is in the slugging regime when this dominant frequency, f[sub d], remains constant with changing gas velocity. This method is an improvement over previous methods because of the simple nature of the apparatus required, and because it is possible to locate the pressure probes so that they do not interfere with the fluidization or undergo rapid wear from the constant particle movement. This method was used to determine the gas velocity corresponding to the transition from the bubbling to the slugging regime for a 10cm diameter bed of sand fluidized with air and containing three 1.9cm diameter vertical rods at 5.2cm centre-to-centre triangular spacing and extending the length of the bed, and to compare the results with those from the same bed without any internal rods. The presence of the vertical rods inhibited the onset of the slugging regime, and significantly extended the bubbling regime to higher gas velocities. 32 refs., 12 figs.

  6. Elastic-plastic deformation of sandwich rod on elastic basis

    Institute of Scientific and Technical Information of China (English)

    GU Yu

    2008-01-01

    Sandwich composite material possesses advantages of both light weight and high strength.Although the mechanical behaviors of sandwich composite material with the influence of single external environment have been intensively studied,little work has been done in the study of mechanical property,in view of the nonlinear behavior of sandwich composites in the complicated external environments.In this paper,the problem about the bending of the three-layer elastic-plastic rod located on the elastic base,with a compressibly physical nonlinear core,has been studied.The mechanical response of the designed three-layer elements consisting of two bearing layers and a core has been examined.The complicated problem about curving of the three-layer rod located on the elastic base has been solved.The convergence of the proposed method of elastic solutions is examined to convince that the solution is acceptable.The calculated results indicate that the plasticity and physical nonlinearity of materials have a great influence on the deformation of the sandwich rod on the elastic basis.

  7. Glutamine deprivation initiates reversible assembly of mammalian rods and rings.

    Science.gov (United States)

    Calise, S John; Carcamo, Wendy C; Krueger, Claire; Yin, Joyce D; Purich, Daniel L; Chan, Edward K L

    2014-08-01

    Rods and rings (RR) are protein assemblies composed of cytidine triphosphate synthetase type 1 (CTPS1) and inosine monophosphate dehydrogenase type 2 (IMPDH2), key enzymes in CTP and GTP biosynthesis. Small-molecule inhibitors of CTPS1 or IMPDH2 induce RR assembly in various cancer cell lines within 15 min to hours. Since glutamine is an essential amide nitrogen donor in these nucleotide biosynthetic pathways, glutamine deprivation was examined to determine whether it leads to RR formation. HeLa cells cultured in normal conditions did not show RR, but after culturing in media lacking glutamine, short rods (5 μm) formed after 48 h. Upon supplementation with glutamine or guanosine, these RR underwent almost complete disassembly within 15 min. Inhibition of glutamine synthetase with methionine sulfoximine also increased RR assembly in cells deprived of glutamine. Taken together, our data support the hypothesis that CTP/GTP biosynthetic enzymes polymerize to form RR in response to a decreased intracellular level of glutamine. We speculate that rod and ring formation is an adaptive metabolic response linked to disruption of glutamine homeostasis.

  8. A measurement of a control rod drop using an LVDT

    Science.gov (United States)

    Choi, Myoung-Hwan; Kim, Ji-Ho; Huh, Hyung; Yu, Je-Yong; Sohn, Dong-Seong

    2010-03-01

    A control element drive mechanism is a reactor regulating system, which is to insert, withdraw, or maintain a control rod containing neutron-absorbing material within a reactor core to control the reactivity of the reactor. The ball-screw type CEDM for the small and medium research reactor has a spring-hydraulic damper to reduce the impact force due to the free drop of the CEDM. This paper describes the experimental results to obtain the drop characteristics of the CEDM. The tests are performed by using a full-scale structure except the control element assembly, and a drop time and displacement after an impact are measured by using an LVDT. The influences of the rod weight and the drop height on the drop behavior are also estimated on the basis of test results. In case of the longest stroke, the drop time of the control rod is within 4.5 seconds to meet the design requirement. The behavior after the impact shows a general damping motion of the spring-damper system, and the maximum displacement is measured as 15.6 mm.

  9. Model of ASTM Flammability Test in Microgravity: Iron Rods

    Science.gov (United States)

    Steinberg, Theodore A; Stoltzfus, Joel M.; Fries, Joseph (Technical Monitor)

    2000-01-01

    There is extensive qualitative results from burning metallic materials in a NASA/ASTM flammability test system in normal gravity. However, this data was shown to be inconclusive for applications involving oxygen-enriched atmospheres under microgravity conditions by conducting tests using the 2.2-second Lewis Research Center (LeRC) Drop Tower. Data from neither type of test has been reduced to fundamental kinetic and dynamic systems parameters. This paper reports the initial model analysis for burning iron rods under microgravity conditions using data obtained at the LERC tower and modeling the burning system after ignition. Under the conditions of the test the burning mass regresses up the rod to be detached upon deceleration at the end of the drop. The model describes the burning system as a semi-batch, well-mixed reactor with product accumulation only. This model is consistent with the 2.0-second duration of the test. Transient temperature and pressure measurements are made on the chamber volume. The rod solid-liquid interface melting rate is obtained from film records. The model consists of a set of 17 non-linear, first-order differential equations which are solved using MATLAB. This analysis confirms that a first-order rate, in oxygen concentration, is consistent for the iron-oxygen kinetic reaction. An apparent activation energy of 246.8 kJ/mol is consistent for this model.

  10. Spare the rods and spoil the retina: revisited.

    Science.gov (United States)

    Sivaprasad, S; Arden, G

    2016-02-01

    Visual function improves with oxygen inhalation in people with diabetes even in the absence of visible retinopathy. Rods consume the most oxygen in the retina due to the high metabolic activity required to maintain the dark current. Therefore, Arden hypothesized that in diabetes where oxygen supply may also be affected due to the changes in retinal vasculature, prevention of dark adaptation may be a viable option to prevent or decrease the rate of progression of diabetic retinopathy. Animal experiments have proven that the absence of rods decreases the development of retinal neovascularisation. The same principle applies to panretinal photocoagulation, an established treatment for proliferative diabetic retinopathy. Recently, a few clinical studies have also shown that preventing dark adaptation by suppressing rods with 500-nm light source at night decreases the rate of progression of early diabetic retinopathy and maculopathy in the short-term. We await the results of a large two-year multi-centre trial (CLEOPATRA trial) to evaluate the long-term effects of decreasing dark adaptation by applying a 500nm light source as a mask over eyes with non-central diabetic macular oedema.

  11. Actin-Interacting Protein 1 Contributes to Intranuclear Rod Assembly in Dictyostelium discoideum

    Science.gov (United States)

    Ishikawa-Ankerhold, Hellen C.; Daszkiewicz, Wioleta; Schleicher, Michael; Müller-Taubenberger, Annette

    2017-01-01

    Intranuclear rods are aggregates consisting of actin and cofilin that are formed in the nucleus in consequence of chemical or mechanical stress conditions. The formation of rods is implicated in a variety of pathological conditions, such as certain myopathies and some neurological disorders. It is still not well understood what exactly triggers the formation of intranuclear rods, whether other proteins are involved, and what the underlying mechanisms of rod assembly or disassembly are. In this study, Dictyostelium discoideum was used to examine appearance, stages of assembly, composition, stability, and dismantling of rods. Our data show that intranuclear rods, in addition to actin and cofilin, are composed of a distinct set of other proteins comprising actin-interacting protein 1 (Aip1), coronin (CorA), filactin (Fia), and the 34 kDa actin-bundling protein B (AbpB). A finely tuned spatio-temporal pattern of protein recruitment was found during formation of rods. Aip1 is important for the final state of rod compaction indicating that Aip1 plays a major role in shaping the intranuclear rods. In the absence of both Aip1 and CorA, rods are not formed in the nucleus, suggesting that a sufficient supply of monomeric actin is a prerequisite for rod formation. PMID:28074884

  12. Cladding corrosion and hydriding in irradiated defected zircaloy fuel rods (LWBR Development Program)

    Energy Technology Data Exchange (ETDEWEB)

    Clayton, J.C.

    1985-08-01

    Twenty-one LWBR irradiation test rods containing ThO/sub 2/-UO/sub 2/ fuel and Zircaloy cladding with holes or cracks operated successfully. Zircaloy cladding corrosion on the inside and outside diameter surfaces and hydrogen pickup in the cladding were measured. The observed outer surface Zircaloy cladding corrosion oxide thicknesses of the test rods were similar to thicknesses measured for nondefected irradiation test rods. An analysis model, which was developed to calculate outer surface oxide thickness of non-defected rods, gave results which were in reasonable agreement with the outer surface oxide thicknesses of defected rods. When the analysis procedure was modified to account for additional corrosion proportional to fission rate and to time, the calculated values agreed well with measured inner oxide corrosion film values. Hydrogen pickup in the defected rods was not directly proportional to local corrosion oxide weight gain as was the case for non-defected rods. 16 refs., 6 figs., 8 tabs.

  13. Analysis of Subchannel and Rod Bundle PSBT Experiments with CATHARE 3

    Directory of Open Access Journals (Sweden)

    M. Valette

    2012-01-01

    Full Text Available This paper presents the assessment of CATHARE 3 against PWR subchannel and rod bundle tests of the PSBT benchmark. Noticeable measurements were the following: void fraction in single subchannel and rod bundle, multiple liquid temperatures at subchannel exit in rod bundle, and DNB power and location in rod bundle. All these results were obtained both in steady and transient conditions. Void fraction values are satisfactory predicted by CATHARE 3 in single subchannels with the pipe module. More dispersed predictions of void values are obtained in rod bundles with the CATHARE 3 3D module at subchannel scale. Single-phase liquid mixing tests and DNB tests in rod bundle are also analyzed. After calibrating the mixing in liquid single phase with specific tests, DNB tests using void mixing give mitigated results, perhaps linked to inappropriate use of CHF lookup tables in such rod bundles with many spacers.

  14. Measurements of the coupling between the tumbling of rods and the velocity gradient tensor in turbulence

    CERN Document Server

    Ni, Rui; Ouellette, Nicholas T; Voth, Greg A

    2014-01-01

    We present simultaneous experimental measurements of the dynamics of anisotropic particles transported by a turbulent flow and the velocity gradient tensor of the flow surrounding them. We track both rod-shaped particles and small spherical flow tracers using stereoscopic particle tracking. By using scanned illumination, we are able to obtain a high enough seeding density of tracers to measure the full velocity gradient tensor near the rod. The alignment of rods with the vorticity and the eigenvectors of the strain rate show agreement with numerical simulations. A full description of the tumbling of rods in turbulence requires specifying a seven-dimensional joint probability density function (PDF) of five scalars characterizing the velocity gradient tensor and two scalars describing the relative orientation of the rod. If these seven parameters are known, then Jeffery's equation specifies the rod tumbling rate and any statistic of rod rotations can be obtained as a weighted average over the joint PDF. To look...

  15. Femoral non-elongating rodding in osteogenesis imperfecta - The importance of purchasing epiphyseal plate

    Directory of Open Access Journals (Sweden)

    Wei-Chun Li

    2015-04-01

    Full Text Available Background: Corrective osteotomy and intramedullary rodding are widely used in children with osteogenesis imperfecta (OI, but revision rodding is often required. This study aims to investigate the effect of purchasing distal femoral epiphysis on the longevity of fixation using non-elongating rod. Methods: We investigated children with Sillence type III or IV OI who received antegrade femoral Rush rod fixations at age between 4 and 10 years in our institution. The fixations were classified into group A in which the rod reached distal femoral epiphysis and group B in which the rod stopped at femoral metaphysis. Failure of fixation is defined as rod cutting out of the cortex or when revision surgery was performed. Calculation of longevity of each rod fixation and Kaplan-Meier survival analysis were performed and compared between the two groups. Results: Eighteen children had the first femoral rodding at a mean age of 6.9 years and received a total of 61 femoral roddings with a mean follow-up of 11.4 years. Group A included 38 roddings performed at a mean age of 7.1 years and group B included 23 roddings performed at a mean age of 6.6 years. Group A had less revision rate (58% vs. 87%, more chance of survival > 3 years (74% vs. 43%, and longer median survival time (80 months vs. 33 months than group B. Conclusions: Less revision rate and better 3-year and 5-year survival rate were proved in the roddings that purchased epiphysis. We emphasize on using the precise implant length to purchase distal femoral epiphysis when non-elongating rod is the only available implant for fixation in children with OI.

  16. Rhodopsin gene expression determines rod outer segment size and rod cell resistance to a dominant-negative neurodegeneration mutant.

    Directory of Open Access Journals (Sweden)

    Brandee A Price

    Full Text Available Two outstanding unknowns in the biology of photoreceptors are the molecular determinants of cell size, which is remarkably uniform among mammalian species, and the mechanisms of rod cell death associated with inherited neurodegenerative blinding diseases such as retinitis pigmentosa. We have addressed both questions by performing an in vivo titration with rhodopsin gene copies in genetically engineered mice that express only normal rhodopsin or an autosomal dominant allele, encoding rhodopsin with a disease-causing P23H substitution. The results reveal that the volume of the rod outer segment is proportional to rhodopsin gene expression; that P23H-rhodopsin, the most common rhodopsin gene disease allele, causes cell death via a dominant-negative mechanism; and that long term survival of rod cells carrying P23H-rhodopsin can be achieved by increasing the levels of wild type rhodopsin. These results point to promising directions in gene therapy for autosomal dominant neurodegenerative diseases caused by dominant-negative mutations.

  17. Multiple rod-cone and cone-rod photoreceptor transmutations in snakes: evidence from visual opsin gene expression.

    Science.gov (United States)

    Simões, Bruno F; Sampaio, Filipa L; Loew, Ellis R; Sanders, Kate L; Fisher, Robert N; Hart, Nathan S; Hunt, David M; Partridge, Julian C; Gower, David J

    2016-01-27

    In 1934, Gordon Walls forwarded his radical theory of retinal photoreceptor 'transmutation'. This proposed that rods and cones used for scotopic and photopic vision, respectively, were not fixed but could evolve into each other via a series of morphologically distinguishable intermediates. Walls' prime evidence came from series of diurnal and nocturnal geckos and snakes that appeared to have pure-cone or pure-rod retinas (in forms that Walls believed evolved from ancestors with the reverse complement) or which possessed intermediate photoreceptor cells. Walls was limited in testing his theory because the precise identity of visual pigments present in photoreceptors was then unknown. Subsequent molecular research has hitherto neglected this topic but presents new opportunities. We identify three visual opsin genes, rh1, sws1 and lws, in retinal mRNA of an ecologically and taxonomically diverse sample of snakes central to Walls' theory. We conclude that photoreceptors with superficially rod- or cone-like morphology are not limited to containing scotopic or photopic opsins, respectively. Walls' theory is essentially correct, and more research is needed to identify the patterns, processes and functional implications of transmutation. Future research will help to clarify the fundamental properties and physiology of photoreceptors adapted to function in different light levels.

  18. A core MRB1 complex component is indispensable for RNA editing in insect and human infective stages of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Michelle L Ammerman

    Full Text Available Uridine insertion/deletion RNA editing is a unique and vital process in kinetoplastids, required for creation of translatable open reading frames in most mitochondrially-encoded RNAs. Emerging as a key player in this process is the mitochondrial RNA binding 1 (MRB1 complex. MRB1 comprises an RNA-independent core complex of at least six proteins, including the GAP1/2 guide RNA (gRNA binding proteins. The core interacts in an RNA-enhanced or -dependent manner with imprecisely defined TbRGG2 subcomplexes, Armadillo protein MRB10130, and additional factors that comprise the dynamic MRB1 complex. Towards understanding MRB1 complex function in RNA editing, we present here functional characterization of the pentein domain-containing MRB1 core protein, MRB11870. Inducible RNAi studies demonstrate that MRB11870 is essential for proliferation of both insect vector and human infective stage T. brucei. MRB11870 ablation causes a massive defect in RNA editing, affecting both pan-edited and minimally edited mRNAs, but does not substantially affect mitochondrial RNA stability or processing of precursor transcripts. The editing defect in MRB1-depleted cells occurs at the initiation stage of editing, as pre-edited mRNAs accumulate. However, the gRNAs that direct editing remain abundant in the knockdown cells. To examine the contribution of MRB11870 to MRB1 macromolecular interactions, we tagged core complexes and analyzed their composition and associated proteins in the presence and absence of MRB11870. These studies demonstrated that MRB11870 is essential for association of GAP1/2 with the core, as well as for interaction of the core with other proteins and subcomplexes. Together, these data support a model in which the MRB1 core mediates functional interaction of gRNAs with the editing machinery, having GAP1/2 as its gRNA binding constituents. MRB11870 is a critical component of the core, essential for its structure and function.

  19. Murine Models for Trypanosoma brucei gambiense disease progression--from silent to chronic infections and early brain tropism.

    Directory of Open Access Journals (Sweden)

    Christiane Giroud

    Full Text Available Human African trypanosomiasis (HAT caused by Trypanosoma brucei gambiense remains highly prevalent in west and central Africa and is lethal if left untreated. The major problem is that the disease often evolves toward chronic or asymptomatic forms with low and fluctuating parasitaemia producing apparently aparasitaemic serological suspects who remain untreated because of the toxicity of the chemotherapy. Whether the different types of infections are due to host or parasite factors has been difficult to address, since T. b. gambiense isolated from patients is often not infectious in rodents thus limiting the variety of isolates.T. b. gambiense parasites were outgrown directly from the cerebrospinal fluid of infected patients by in vitro culture and analyzed for their molecular polymorphisms. Experimental murine infections showed that these isolates could be clustered into three groups with different characteristics regarding their in vivo infection properties, immune response and capacity for brain invasion. The first isolate induced a classical chronic infection with a fluctuating blood parasitaemia, an invasion of the central nervous system (CNS, a trypanosome specific-antibody response and death of the animals within 6-8 months. The second group induced a sub-chronic infection resulting in a single wave of parasitaemia after infection, followed by a low parasitaemia with no parasites detected by microscope observations of blood but detected by PCR, and the presence of a specific antibody response. The third isolate induced a silent infection characterised by the absence of microscopically detectable parasites throughout, but infection was detectable by PCR during the whole course of infection. Additionally, specific antibodies were barely detectable when mice were infected with a low number of this group of parasites. In both sub-chronic and chronic infections, most of the mice survived more than one year without major clinical symptoms

  20. Quantitative Mass Spectrometry-Based Analysis of β-D-Glucosyl-5-Hydroxymethyluracil in Genomic DNA of Trypanosoma brucei

    Science.gov (United States)

    Liu, Shuo; Ji, Debin; Cliffe, Laura; Sabatini, Robert; Wang, Yinsheng

    2014-10-01

    β-D-glucosyl-5-hydroxymethyluracil (base J) is a hyper-modified nucleobase found in the nuclear DNA of kinetoplastid parasites. With replacement of a fraction of thymine in DNA, J is localized primarily in telomeric regions of all organisms carrying this modified base. The biosynthesis of J occurs in two putative steps: first, a specific thymine in DNA is recognized and converted into 5-hydroxymethyluracil (5-HmU) by J-binding proteins (JBP1 and JBP2); a glucosyl transferase (GT) subsequently glucosylates the 5-HmU to yield J. Although several recent studies revealed the roles of internal J in regulating transcription in kinetoplastids, functions of telomeric J and proteins involved in J synthesis remain elusive. Assessing the functions of base J and understanding fully its biosynthesis necessitate the measurement of its level in cells and organisms. In this study, we reported a reversed-phase HPLC coupled with tandem mass spectrometry (LC-MS/MS) method, together with the use of a surrogate internal standard (β-D-glucosyl-5-hydroxymethyl-2'-deoxycytidine, 5-gHmdC), for the accurate detection of β-D-glucosyl-5-hydroxymethyl-2'-deoxyuridine (dJ) in Trypanosoma brucei DNA. For comparison, we also measured the level of the precursor for dJ synthesis [i.e. 5-hydroxymethyl-2'-deoxyuridine (5-HmdU)]. We found that base J was not detectable in the JBP-null cells whereas it replaced approximately 0.5% thymine in wild-type cells, which was accompanied with a markedly decreased level of 5-HmdU in JBP1/JBP2-null strain relative to the wild-type strain. These results provided direct evidence supporting that JBP proteins play an important role in oxidizing thymidine to form 5-HmdU, which facilitated the generation of dJ. This is the first report about the application of LC-MS/MS for the quantification of base J. The analytical method built a solid foundation for dissecting the molecular mechanisms of J biosynthesis and assessing the biological functions of base J in the

  1. 78 FR 28190 - Carbon and Certain Alloy Steel Wire Rod From Mexico: Final Results of Antidumping Duty...

    Science.gov (United States)

    2013-05-14

    ... International Trade Administration Carbon and Certain Alloy Steel Wire Rod From Mexico: Final Results of... carbon and certain alloy steel wire rod (wire rod) from Mexico. The period of review (POR) is October 1... (the Act). \\1\\ See Carbon and Certain Alloy Steel Wire Rod From Mexico: Preliminary Results...

  2. 77 FR 66954 - Carbon and Certain Alloy Steel Wire Rod From Mexico: Preliminary Results of Antidumping Duty...

    Science.gov (United States)

    2012-11-08

    ... International Trade Administration Carbon and Certain Alloy Steel Wire Rod From Mexico: Preliminary Results of... on carbon and certain alloy steel wire rod (wire rod) from Mexico. The period of review is October 1... Antidumping Duty Orders: Carbon and Certain Alloy Steel Wire Rod from Brazil, Indonesia, Mexico,...

  3. 77 FR 13545 - Carbon and Certain Alloy Steel Wire Rod From Mexico: Notice of Final Results of Antidumping Duty...

    Science.gov (United States)

    2012-03-07

    ... International Trade Administration Carbon and Certain Alloy Steel Wire Rod From Mexico: Notice of Final Results... duty order on carbon and certain alloy steel wire rod (wire rod) from Mexico.\\1\\ This review covers.... \\1\\ See Carbon and Certain Alloy Steel Wire Rod from Mexico: Notice of Preliminary Results...

  4. A genetically encoded reporter for real-time imaging of cofilin-actin rods in living neurons.

    Directory of Open Access Journals (Sweden)

    Jianjie Mi

    Full Text Available Filament bundles (rods of cofilin and actin (1:1 form in neurites of stressed neurons where they inhibit synaptic function. Live-cell imaging of rod formation is hampered by the fact that overexpression of a chimera of wild type cofilin with a fluorescent protein causes formation of spontaneous and persistent rods, which is exacerbated by the photostress of imaging. The study of rod induction in living cells calls for a rod reporter that does not cause spontaneous rods. From a study in which single cofilin surface residues were mutated, we identified a mutant, cofilinR21Q, which when fused with monomeric Red Fluorescent Protein (mRFP and expressed several fold above endogenous cofilin, does not induce spontaneous rods even during the photostress of imaging. CofilinR21Q-mRFP only incorporates into rods when they form from endogenous proteins in stressed cells. In neurons, cofilinR21Q-mRFP reports on rods formed from endogenous cofilin and induced by all modes tested thus far. Rods have a half-life of 30-60 min upon removal of the inducer. Vesicle transport in neurites is arrested upon treatments that form rods and recovers as rods disappear. CofilinR21Q-mRFP is a genetically encoded rod reporter that is useful in live cell imaging studies of induced rod formation, including rod dynamics, and kinetics of rod elimination.

  5. 78 FR 60850 - Carbon and Certain Alloy Steel Wire Rod From Brazil: Final Results of the Expedited Second Sunset...

    Science.gov (United States)

    2013-10-02

    ... International Trade Administration Carbon and Certain Alloy Steel Wire Rod From Brazil: Final Results of the... certain alloy steel wire rod (wire rod) from Brazil would be likely to lead to continuation or recurrence... Alloy Steel Wire Rod from Brazil, 67 FR 55805 (August 30, 2002). \\2\\ See Initiation of...

  6. Fed-batch production of the hydrophobins RodA and RodB from Aspergillus fumigatus in host Pichia pastoris

    DEFF Research Database (Denmark)

    Pedersen, Mona Højgaard; Borodina, Irina; Frisvad, Jens Christian;

    . The expression of the RodA and RodB genes was first studied in culture flasks in buffered complex methanol medium as protein production was dependent on the methanol-induced AOX1 promoter. Later production was scaled up to a 2 L fed-batch fermentor. Hydrophobins were purified using His-select Nickel Affinity gel....... The emulsifying properties of recombinant hydrophobins were investigated using oil-water emulsions studied by light microscopy. Results: Protein bands of expected size were detected by SDS-PAGE and western blotting in the fermentation broth. Fed-batch production yielded approximately 300 mg/L. rRodB showed good...... emulsifying properties. Conclusion: RodA and RodB from A. fumigatus were successfully produced by yeast host Pichia pastoris with good yields....

  7. Dynamic rod worth simulation study for a sodium-cooled TRU burner

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Ji; Ha, Pham Nhu Viet, E-mail: phamha@kaeri.re.kr; Lee, Min Jae; Kang, Chang Mu

    2015-12-15

    Highlights: • Dynamic rod worth calculation methodology for a sodium-cooled TRU burner was developed. • The spatial weighting functions were relatively insensitive to control rods position. • The simulated pseudo detector response agreed well with the calculated core power. • The simulated dynamic rod worths compared well against the simulated static values. • Impact of individual detector on the simulated dynamic worth was evaluated. - Abstract: This paper presents a preliminary dynamic rod worth simulation study for a TRU burner core mockup of the PGSFR (Korean Prototype Gen-IV Sodium-cooled Fast Reactor) named BFS-76-1A so as to establish a calculation methodology for evaluating the rod worth of the PGSFR. The simulation method was mainly based on a three-dimensional multi-group nodal diffusion transient code for fast reactors in which the rod drop simulation for the BFS-76-1A was performed and all the fuel assemblies were taken into account for the detector response calculation. Then the dynamic rod worths were inferred from the simulated detector responses using an inverse point kinetics model and compared against the simulated static worths. The results show good agreement between the simulated pseudo detector response and the calculated core power as well as between the simulated dynamic and static rod worths, and thus indicate that the dynamic rod worth simulation method developed in this work can be applied to the rod worth estimation and validation for the PGSFR.

  8. Analysis of High Temperature Reactor Control Rod Worth for the Initial and Full Core

    Science.gov (United States)

    Oktajianto, Hammam; Setiawati, Evi; Anam, Khoirul; Sugito, Heri

    2017-01-01

    Control rod is one important component in a nuclear reactor. In nuclear reactor operations the control rod functions to shut down the reactor. This research analyses ten control rods worth of HTR (High Temperature Reactor) at initial and full core. The HTR in this research adopts HTR-10 China and HTR- of pebble bed. Core calculations are performed by using MCNPX code after modelling the entire parts of core in condition of ten control rods fully withdrawn, all control rods in with 20 cm ranges of depth and the use of one control rod. Pebble bed and moderator balls are distributed in the core zone using a Body Centred Cubic (BCC) lattice by ratio of 57:43. The research results are obtained that the use of one control rod will decrease the reactor criticality of 2.04±0.12 %Δk/k at initial core and 1.57±0.10 %Δk/k at full core. The deeper control rods are in, the lesser criticality of reactor is with reactivity of ten control rods of 16.41±0.11 %Δk/k at initial core and 15.43±0.11 %Δk/k at full core. The results show that the use of ten control rods at full core will keep achieving subcritical condition even though the reactivity is smaller than reactivity at initial core.

  9. Morphological Diversity of the Rod Spherule: A Study of Serially Reconstructed Electron Micrographs.

    Directory of Open Access Journals (Sweden)

    Shuai Li

    Full Text Available Rod spherules are the site of the first synaptic contact in the retina's rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon. Retraction of the rod axon and spherule is often observed in disease processes and aging, and the retracted rod spherule superficially resembles rod spherules lacking an axon. We hypothesized that retracted spherules take on an axonless spherule morphology, which may be easier to maintain in a diseased state. To test our hypothesis, we quantified the spatial organization and subcellular structures of rod spherules with and without axons. We then compared them to the retracted spherules in a disease model, mice that overexpress Dscam (Down syndrome cell adhesion molecule, to gain a better understanding of the rod synapse in health and disease.We reconstructed serial EM images of wild type and DscamGoF (gain of function rod spherules at a resolution of 7 nm in the X-Y axis and 60 nm in the Z axis. Rod spherules with and without axons, and retracted spherules in the DscamGoF retina, were reconstructed. The rod spherule intracellular organelles, the invaginating dendrites of rod bipolar cells and horizontal cell axon tips were also reconstructed for statistical analysis.Stereotypical rod (R1 spherules occupy the outer two-thirds of the outer plexiform layer (OPL, where they present as spherical terminals with large mitochondria. This spherule group is highly uniform and composed more than 90% of the rod spherule population. Rod

  10. Rod monochromacy and the coevolution of cetacean retinal opsins.

    Directory of Open Access Journals (Sweden)

    Robert W Meredith

    2013-04-01

    Full Text Available Cetaceans have a long history of commitment to a fully aquatic lifestyle that extends back to the Eocene. Extant species have evolved a spectacular array of adaptations in conjunction with their deployment into a diverse array of aquatic habitats. Sensory systems are among those that have experienced radical transformations in the evolutionary history of this clade. In the case of vision, previous studies have demonstrated important changes in the genes encoding rod opsin (RH1, short-wavelength sensitive opsin 1 (SWS1, and long-wavelength sensitive opsin (LWS in selected cetaceans, but have not examined the full complement of opsin genes across the complete range of cetacean families. Here, we report protein-coding sequences for RH1 and both color opsin genes (SWS1, LWS from representatives of all extant cetacean families. We examine competing hypotheses pertaining to the timing of blue shifts in RH1 relative to SWS1 inactivation in the early history of Cetacea, and we test the hypothesis that some cetaceans are rod monochomats. Molecular evolutionary analyses contradict the "coastal" hypothesis, wherein SWS1 was pseudogenized in the common ancestor of Cetacea, and instead suggest that RH1 was blue-shifted in the common ancestor of Cetacea before SWS1 was independently knocked out in baleen whales (Mysticeti and in toothed whales (Odontoceti. Further, molecular evidence implies that LWS was inactivated convergently on at least five occasions in Cetacea: (1 Balaenidae (bowhead and right whales, (2 Balaenopteroidea (rorquals plus gray whale, (3 Mesoplodon bidens (Sowerby's beaked whale, (4 Physeter macrocephalus (giant sperm whale, and (5 Kogia breviceps (pygmy sperm whale. All of these cetaceans are known to dive to depths of at least 100 m where the underwater light field is dim and dominated by blue light. The knockout of both SWS1 and LWS in multiple cetacean lineages renders these taxa rod monochromats, a condition previously unknown among

  11. Rod monochromacy and the coevolution of cetacean retinal opsins.

    Science.gov (United States)

    Meredith, Robert W; Gatesy, John; Emerling, Christopher A; York, Vincent M; Springer, Mark S

    2013-04-01

    Cetaceans have a long history of commitment to a fully aquatic lifestyle that extends back to the Eocene. Extant species have evolved a spectacular array of adaptations in conjunction with their deployment into a diverse array of aquatic habitats. Sensory systems are among those that have experienced radical transformations in the evolutionary history of this clade. In the case of vision, previous studies have demonstrated important changes in the genes encoding rod opsin (RH1), short-wavelength sensitive opsin 1 (SWS1), and long-wavelength sensitive opsin (LWS) in selected cetaceans, but have not examined the full complement of opsin genes across the complete range of cetacean families. Here, we report protein-coding sequences for RH1 and both color opsin genes (SWS1, LWS) from representatives of all extant cetacean families. We examine competing hypotheses pertaining to the timing of blue shifts in RH1 relative to SWS1 inactivation in the early history of Cetacea, and we test the hypothesis that some cetaceans are rod monochomats. Molecular evolutionary analyses contradict the "coastal" hypothesis, wherein SWS1 was pseudogenized in the common ancestor of Cetacea, and instead suggest that RH1 was blue-shifted in the common ancestor of Cetacea before SWS1 was independently knocked out in baleen whales (Mysticeti) and in toothed whales (Odontoceti). Further, molecular evidence implies that LWS was inactivated convergently on at least five occasions in Cetacea: (1) Balaenidae (bowhead and right whales), (2) Balaenopteroidea (rorquals plus gray whale), (3) Mesoplodon bidens (Sowerby's beaked whale), (4) Physeter macrocephalus (giant sperm whale), and (5) Kogia breviceps (pygmy sperm whale). All of these cetaceans are known to dive to depths of at least 100 m where the underwater light field is dim and dominated by blue light. The knockout of both SWS1 and LWS in multiple cetacean lineages renders these taxa rod monochromats, a condition previously unknown among

  12. Rewetting of a low superheated rod with saturated water

    Energy Technology Data Exchange (ETDEWEB)

    Portillo, O.; Reyes, R.; Wayner, P.C. Jr.

    1999-07-01

    The study of the rewetting of a superheated surface has application in several technological fields. It is related to the control mechanism for loss of coolant accident (LOCA) in nuclear reactors. An adsorption model as the precursory mechanism for rewetting of a superheated surface is extended from its application to non-polar liquids to a polar fluid, and modeling calculations are compared with experimental data found in the literature. The adsorption model is based on interfacial forces acting at the tip of the rewetting front, the three-phase region. In this region, solid, liquid and vapor interfaces generate a contact angle that depends on the degree of superheat and describes the velocity of rewetting. The contact angle is a function of interfacial forces calculated through the disjoining pressure of the adsorbed film precursory of the rewetting. The influences of van der Waals and electrostatic intermolecular forces in the film thickness are analyzed. The authors find that the order of magnitude of the film thickness in the controlling region is of a few angstroms: thus, only van der Waals intermolecular forces define the interactions. For the prediction of the velocity of rewetting the temperature profile along the rod's surface is required and a one-dimensional and a two-dimensional heat conduction balances are solved. The thermophysical properties in the adsorption model are predicted by ASPEN PLUS data bank and from ASME steam tables. Variations of the predicted values have a strong influence on the results. The surface boundary condition on the rod contains an evaporative heat transfer coefficient that is calculated from the fitted experimental rewetting velocities and the two-dimensional temperature field in the rod. Using this calculation scheme the values of the evaporative heat transfer coefficient are obtained in the normal range of values. Therefore the adsorption model gives results that are consistent with experimental observations.

  13. SOLITARY WAVES IN FINITE DEFORMATION ELASTIC CIRCULAR ROD

    Institute of Scientific and Technical Information of China (English)

    LIU Zhi-fang; ZHANG Shan-yuan

    2006-01-01

    A new nonlinear wave equation of a finite deformation elastic circular rod simultaneously introducing transverse inertia and shearing strain was derived by means of Hamilton principle. The nonlinear equation includes two nonlinear terms caused by finite deformation and double geometric dispersion effects caused by transverse inertia and transverse shearing strain. Nonlinear wave equation and corresponding truncated nonlinear wave equation were solved by the hyperbolic secant function finite expansion method. The solitary wave solutions of these nonlinear equations were obtained. The necessary condition of these solutions existence was given also.

  14. NONLINEAR WAVES AND PERIODIC SOLUTION IN FINITE DEFORMATION ELASTIC ROD

    Institute of Scientific and Technical Information of China (English)

    Liu Zhifang; Zhang Shanyuan

    2006-01-01

    A nonlinear wave equation of elastic rod taking account of finite deformation, transverse inertia and shearing strain is derived by means of the Hamilton principle in this paper. Nonlinear wave equation and truncated nonlinear wave equation are solved by the Jacobi elliptic sine function expansion and the third kind of Jacobi elliptic function expansion method. The exact periodic solutions of these nonlinear equations are obtained, including the shock wave solution and the solitary wave solution. The necessary condition of exact periodic solutions, shock solution and solitary solution existence is discussed.

  15. Interaction modes between asymmetrically and oppositely charged rods.

    Science.gov (United States)

    Antila, Hanne S; Van Tassel, Paul R; Sammalkorpi, Maria

    2016-02-01

    The interaction of oppositely and asymmetrically charged rods in salt-a simple model of (bio)macromolecular assembly-is observed via simulation to exhibit two free energy minima, separated by a repulsive barrier. In contrast to similar minima in the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, the governing mechanism includes electrostatic attraction at large separation, osmotic repulsion at close range, and depletion attraction near contact. A model accounting for ion condensation and excluded volume is shown to be superior to a mean-field treatment in predicting the effect of charge asymmetry on the free-energy profile.

  16. Study on CAD/CAE System of Engine Connecting Rod

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The intensive competition of automotive market requ ir es shortening the product development circle and improving the product quality. Many of auto manufacturers in china have introduced some CAD/CAE/CAM systems in product development process, and have got some success. But the special and effi cient CAD system aimed at particular product is absent. This paper provides a CA D/CAE system that can realize the integration of CAD and CAE process for engine connecting rod development. The paper discusses som...

  17. Compact Dielectric-Rod White-Light Delay Lines

    Science.gov (United States)

    Maleki, Lute; Matsko, Andrey; Savchenkov, Anatoliy; Strekalov, Dmitry

    2008-01-01

    Optical delay lines of a proposed type would be made from rods of such dielectric materials as calcium fluoride, fused silica, or sapphire. These would offer advantages over prior optical delay lines, as summarized below. Optical delay lines are key components of opto-electronic microwave oscillators, narrow-band opto-electronic microwave filters, evanescent-field optical biochemical detectors, and some Fourier-Transform spectrum analyzers. Heretofore, optical delay lines used in such applications have been of two types: resonators and coiled long optical fibers, both of which have disadvantages: Resonators are compact, but excitation must be provided by narrow-band lasers. Wide-band (including noisy) laser light cannot be coupled efficiently to narrow-band resonators. When light is coupled into a narrowband resonator from a source of reasonably high power, a significant amount of optical energy circulates within the resonator, causing nonlinear loss and significant noise. Typically, a coil-type optical delay line is made of fused-silica fiber, which exhibits fundamental loss. To overcome the limit imposed by the optical loss in fused silica, it would be necessary to use fibers having crystalline cores. Although space is saved by winding fibers into coils, fiber-coil delay lines are still inconveniently bulky. The proposed compact dielectric-rod delay lines would exploit the special class of non-diffracting light beams that are denoted Bessel beams because their amplitudes are proportional to Bessel functions of the radii from their central axes. High-order Bessel beams can have large values of angular momentum. They can be generated with the help of whispering-gallery-mode optical resonators, as described, for example, in "Simplified Generation of High-Angular-Momentum Light Beams" (NPO-42965) NASA Tech Briefs, Vol. 31, No. 3 (March 2007), page 8a. In a delay line according to the proposal, the dielectric rod would be dimensioned to function as a multimode

  18. TREATMENT OF SHIN BONE FRACTURES USING EXTERNAL ROD APPARATUSES

    Directory of Open Access Journals (Sweden)

    D. E. Kupkenov

    2010-01-01

    Full Text Available Treatment results of 30 patients with diaphyseal fractures of shin bones are presented. All patients were treated by transosseus osteosynthesis tehnique with rod apparatus developed by author. Good outcome of treatment was received in 28 (93,3% patients, satisfactory - in 2 (6,7% in one - three years after operation. This method of treatment permits to perform a closed accurate reposition of bone fragments, to achieve the stable fixation for the whole period of treatment and to mobilize patients on second day after operation.

  19. RESORBABLE HIGH-STRENGTH ROD FOR FRACTURE INTERNAL FIXATION

    Institute of Scientific and Technical Information of China (English)

    杨团民; 刘淼; 杨爱玲; 石宗利; 邱希江; 李毅; 同志超; 韩月

    2004-01-01

    Objective To find an ideal biomaterial for internal fixation. Methods Forty rabbits with fracture of the femur diaphysis (superiorcondyle) were treated by intramedullary nailing of femur with composites rod of resorbable DL-polylactic acid (PDLLA)-calcium metaphosphate (CMP), while steinmann's pin as control. The fracture healing, the material degradation and its mechanical properties were studied by X-ray films, macroscopic, microscopic and electron microscopic observations. Results No significant inflammatory reaction was found, and all the osteotomies were healed, while material was resorbed. Conclusion The PDLLA-CMP has excellent biocompatibility and mechanical properties, and it can be a promising implant material in orthopaedics surgery.

  20. 3-(3-amino-3-carboxypropyl)-5,6-Dihydrouridine is one of two novel post-transcriptional modifications in tRNALys(UUU) from Trypanosoma brucei

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Español, Yaiza; Giessing, Anders M B;

    2011-01-01

    was MALDI-TOF MS of two independent digests of the tRNA, with RNase A and RNase T1, respectively. This revealed digestion products harbouring mass-changing modifications. Next, the modifications were mapped at the nucleotide level in the RNase products by tandem MS. Comparison with the sequence......tRNA is the most heavily modified of all RNA types, with typically 10-20% of the residues being post-transcriptionally altered. Unravelling the modification pattern of a tRNA is a challenging task; there are 92 currently known tRNA modifications [1], many of which are chemically similar....... Furthermore, the tRNA has to be investigated with single-nucleotide resolution in order to ensure complete mapping of all modifications. In the present work, we characterized tRNA(Lys) (UUU) from Trypanosoma brucei, and provide a complete overview of its post-transcriptional modifications. The first step...

  1. Eleganolone, a Diterpene from the French Marine Alga Bifurcaria bifurcata Inhibits Growth of the Human Pathogens Trypanosoma brucei and Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Anne-Marie Rusig

    2013-02-01

    Full Text Available Organic extracts of 20 species of French seaweed have been screened against Trypanosoma brucei rhodesiense trypomastigotes, the parasite responsible for sleeping sickness. These extracts have previously shown potent antiprotozoal activities in vitro against Plasmodium falciparum and Leishmania donovani. The selectivity of the extracts was also evaluated by testing cytotoxicity on a mammalian L6 cell line. The ethyl acetate extract of the brown seaweed, Bifurcaria bifurcata, showed strong trypanocidal activity with a mild selectivity index (IC50 = 0.53 µg/mL; selectivity index (SI = 11.6. Bio-guided fractionation led to the isolation of eleganolone, the main diterpenoid isolated from this species. Eleganolone contributes only mildly to the trypanocidal activity of the ethyl acetate extract (IC50 = 45.0 µM, SI = 4.0. However, a selective activity against P. falciparum erythrocytic stages in vitro has been highlighted (IC50 = 7.9 µM, SI = 21.6.

  2. Eleganolone, a Diterpene from the French Marine Alga Bifurcaria bifurcata Inhibits Growth of the Human Pathogens Trypanosoma brucei and Plasmodium falciparum

    Science.gov (United States)

    Gallé, Jean-Baptiste; Attioua, Barthélémy; Kaiser, Marcel; Rusig, Anne-Marie; Lobstein, Annelise; Vonthron-Sénécheau, Catherine

    2013-01-01

    Organic extracts of 20 species of French seaweed have been screened against Trypanosoma brucei rhodesiense trypomastigotes, the parasite responsible for sleeping sickness. These extracts have previously shown potent antiprotozoal activities in vitro against Plasmodium falciparum and Leishmania donovani. The selectivity of the extracts was also evaluated by testing cytotoxicity on a mammalian L6 cell line. The ethyl acetate extract of the brown seaweed, Bifurcaria bifurcata, showed strong trypanocidal activity with a mild selectivity index (IC50 = 0.53 µg/mL; selectivity index (SI) = 11.6). Bio-guided fractionation led to the isolation of eleganolone, the main diterpenoid isolated from this species. Eleganolone contributes only mildly to the trypanocidal activity of the ethyl acetate extract (IC50 = 45.0 µM, SI = 4.0). However, a selective activity against P. falciparum erythrocytic stages in vitro has been highlighted (IC50 = 7.9 µM, SI = 21.6). PMID:23442789

  3. 布氏锥虫葡糖基磷脂酰肌醇(GPI)的研究进展%RESEARCH PROSPECTS ON GLYCOSYLPHOSPHATIDYLINOSITOL (GPI) OF TRYPANOSOMA BRUCEI

    Institute of Scientific and Technical Information of China (English)

    原丽红; 林本夫; 王祥生; 李莲瑞

    2004-01-01

    布氏锥虫(Trypanosoma brucei)是一种原虫性寄生虫,通过采采蝇(tsets fly)的传播感染人和其它哺乳动物,导致人的昏睡病和家畜的那卡那病。布氏锥虫有两个截然不同的生活阶段,即血液期(bloodstream stage,寄生于哺乳动物血细胞内)和昆虫期(insect stage,又叫循环期或感染期,寄生于采采蝇的中肠内)。

  4. Photonic crystal rod fibers: Understanding a new class of active optical waveguides

    DEFF Research Database (Denmark)

    Laurila, Marko

    In this PhD thesis an experimental study of modal characterization methods on large mode area photonic crystal fibers (PCFs) is performed and the development of a new ytterbium-doped photonic bandgap PCF rod fiber is presented. The first focus of this work is to use modal characterization methods...... core modes and the cladding band as the underlying mechanics to ensure SM operation of the new rod fiber design (85 μm core diameter), which was developed during this thesis work. The second focus of this work is the study of the new ytterbiumdoped rod fiber design under active operation. Performance...... of the rod fiber is evaluated in high power laser and laser amplifier configurations. The high power rod amplifier setup including the seed source is developed and characterized. Results obtained from the rod fiber showed simultaneously SM, near diffraction limited output beam quality with high average power...

  5. Large-scale Flow Pulsation in Tight Square Arrayed Rod Bundles of Nuclear Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Hwan; Kim, Kyung Min; Cho, Hyung Hee [Yonsei University, Seoul (Korea, Republic of); Shin, Chang Hwan; In, Wang Kee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-05-15

    As a major component of modern nuclear reactor, the nuclear fuel rod bundles with liquid coolant have been studied by a lot of researchers to understand the flow structure between the fuel rods. Recently, rod arrays with much small pitch-to-diameter ratio have been being tried to increase performance of the nuclear reactor. The liquid coolant flowing axially through these small spaces between the rods is known to show some peculiar phenomena including large-scale, quasi-periodic flow pulsation. These flow pulsation phenomena dominate mixing process in the subchannels. Thus, precise understating of the flow structure is essential to predict thermal-hydraulic phenomena in nuclear rod bundles. In this present paper, the turbulent flow in tight square arrayed rod bundles is investigated with Hot-wire anemometry. Then, the measured velocity data are analyzed by using Fast Fourier Transform analysis to find characteristic frequency of the pulsation

  6. The Interaction Between Control Rods as Estimated by Second-Order One-Group Perturbation Theory

    Energy Technology Data Exchange (ETDEWEB)

    Persson, Rolf

    1966-10-15

    The interaction effect between control rods is an important problem for the reactivity control of a reactor. The approach of second order one-group perturbation theory is shown to be attractive due to its simplicity. Formulas are derived for the fully inserted control rods in a bare reactor. For a single rod we introduce a correction parameter b, which with good approximation is proportional to the strength of the absorber. For two and more rods we introduce an interaction function g(r{sub ij}), which is assumed to depend only on the distance r{sub ij} between the rods. The theoretical expressions are correlated with the results of several experiments in R0, ZEBRA and the Aagesta reactor, as well as with more sophisticated calculations. The approximate formulas are found to give quite good agreement with exact values, but in the case of about 8 or more rods higher-order effects are likely to be important.

  7. Mechanism of Action of Rare Earths in High Effective Fe Powder Welding Rods

    Institute of Scientific and Technical Information of China (English)

    Han Yongquan; Li Jianguo; Yao Qinghu; Liu Yan; Huang Lihong

    2007-01-01

    The optimum coating composition of alkali Fe powder welding rods was designed by orthogonal experiment with mix rates. A new kind of effective RE-Fe powder welding rod was prepared which could be used at the condition of direct and indirect current. The arc characteristics and stabilities of effective Fe powder welding rods containing RE were analyzed by HANNOVER analyzer. The efficiency of Fe powder welding rods was tested by weighting method. It wag found that the stability of Fe powder welding rods Wag improved when it was added with rare earths. The results of impact experiment at low temperatures and SEM analysis on impact break showed that the grain was refined, the welding joint was cleaned, and the mechanical properties of joint was enhanced with proper RE content. It was provided with good processing property for this effective RE-Fe powder welding rod, and its efficiency could arrive at 180%.

  8. Ti-Ni Rods with Variable Stiffness for Spine Stabilization: Manufacture and Biomechanical Evaluation

    Science.gov (United States)

    Brailovski, Vladimir; Facchinello, Yann; Brummund, Martin; Petit, Yvan; Mac-Thiong, Jean-Marc

    2016-03-01

    A new concept of monolithic spinal rods with variable flexural stiffness is proposed to reduce the risk of adjacent segment degeneration and vertebral fracture, while providing adequate stability to the spine. The variability of mechanical properties is generated by locally annealing Ti-Ni shape memory alloy rods. Ten-minute Joule effect annealing allows the restoration of the superelasticity in the heated portion of the rod. Such processing also generates a mechanical property gradient between the heated and the unheated zones. A numerical model simulating the annealing temperature and the distributions of the mechanical properties was developed to optimize the Joule-heating strategy and to modulate the rod's overall flexural stiffness. Subsequently, the rod model was included in a finite element model of a porcine lumbar spine to study the effect of the rod's stiffness profiles on the spinal biomechanics.

  9. The response of trypanosomes and other eukaryotes to ER stress and the spliced leader RNA silencing (SLS) pathway in Trypanosoma brucei.

    Science.gov (United States)

    Michaeli, Shulamit

    2015-01-01

    The unfolded protein response (UPR) is induced when the quality control machinery of the cell is overloaded with unfolded proteins or when one of the functions of the endoplasmic reticulum (ER) is perturbed. Here, I describe UPR in yeast and mammals, and compare it to what we know about pathogenic fungi and the parasitic protozoans from the order kinetoplastida, focusing on the novel pathway the spliced leader silencing (SLS) in Trypanosoma brucei. Trypanosomes lack conventional transcription regulation, and thus, lack most of the UPR machinery present in other eukaryotes. Trypanosome genes are transcribed in polycistronic units that are processed by trans-splicing and polyadenylation. In trans-splicing, which is essential for processing of each mRNA, an exon known as the spliced leader (SL) is added to all mRNAs from a small RNA, the SL RNA. Under severe ER stress, T. brucei elicits the SLS pathway. In SLS, the transcription of the SL RNA gene is extinguished, and the entire transcription complex dissociates from the SL RNA promoter. Induction of SLS is mediated by an ER-associated kinase (PK3) that migrates to the nucleus, where it phosphorylates the TATA-binding protein (TRF4), leading shut-off of SL RNA transcription. As a result, trans-splicing is inhibited and the parasites activate a programmed cell death (PCD) pathway. Despite the ability to sense the ER stress, the different eukaryotes, especially unicellular parasites and pathogenic fungi, developed a variety of unique and different ways to sense and adjust to this stress in a manner different from their host.

  10. Characterization of a Novel Class I Transcription Factor A (CITFA) Subunit That Is Indispensable for Transcription by the Multifunctional RNA Polymerase I of Trypanosoma brucei

    KAUST Repository

    Nguyen, T. N.

    2012-10-26

    Trypanosoma brucei is the only organism known to have evolved a multifunctional RNA polymerase I (pol I) system that is used to express the parasite\\'s ribosomal RNAs, as well as its major cell surface antigens, namely, the variant surface glycoprotein (VSG) and procyclin, which are vital for establishing successful infections in the mammalian host and the tsetse vector, respectively. Thus far, biochemical analyses of the T. brucei RNA pol I transcription machinery have elucidated the subunit structure of the enzyme and identified the class I transcription factor A (CITFA). CITFA binds to RNA pol I promoters, and its CITFA-2 subunit was shown to be absolutely essential for RNA pol I transcription in the parasite. Tandem affinity purification (TAP) of CITFA revealed the subunits CITFA-1 to -6, which are conserved only among kinetoplastid organisms, plus the dynein light chain DYNLL1. Here, by tagging CITFA-6 instead of CITFA-2, a complex was purified that contained all known CITFA subunits, as well as a novel proline-rich protein. Functional studies carried out in vivo and in vitro, as well as a colocalization study, unequivocally demonstrated that this protein is a bona fide CITFA subunit, essential for parasite viability and indispensable for RNA pol I transcription of ribosomal gene units and the active VSG expression site in the mammalian-infective life cycle stage of the parasite. Interestingly, CITFA-7 function appears to be species specific, because expression of an RNA interference (RNAi)-resistant CITFA-7 transgene from Trypanosoma cruzi could not rescue the lethal phenotype of silencing endogenous CITFA-7.

  11. The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice.

    Directory of Open Access Journals (Sweden)

    Stefan Magez

    Full Text Available African trypanosomes are extracellular parasitic protozoa, predominantly transmitted by the bite of the haematophagic tsetse fly. The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous interaction between antibodies and the parasite surface, covered by variant-specific surface glycoproteins. Early experimental studies have shown that B-cell responses can be strongly protective but are limited by their VSG-specificity. We have used B-cell (microMT and IgM-deficient (IgM(-/- mice to investigate the role of B-cells and IgM antibodies in parasitemia control and the in vivo induction of trypanosomiasis-associated anemia. These infection studies revealed that that the initial setting of peak levels of parasitemia in Trypanosoma brucei-infected microMT and IgM(-/- mice occurred independent of the presence of B-cells. However, B-cells helped to periodically reduce circulating parasites levels and were required for long term survival, while IgM antibodies played only a limited role in this process. Infection-associated anemia, hypothesized to be mediated by B-cell responses, was induced during infection in microMT mice as well as in IgM(-/- mice, and as such occurred independently from the infection-induced host antibody response. Antigenic variation, the main immune evasion mechanism of African trypanosomes, occurred independently from host antibody responses against the parasite's ever-changing antigenic glycoprotein coat. Collectively, these results demonstrated that in murine experimental T. brucei trypanosomiasis, B-cells were crucial for periodic peak parasitemia clearance, whereas parasite-induced IgM antibodies played only a limited role in the outcome of the infection.

  12. Structures of Trypanosoma brucei methionyl-tRNA synthetase with urea-based inhibitors provide guidance for drug design against sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Cho Yeow Koh

    2014-04-01

    Full Text Available Methionyl-tRNA synthetase of Trypanosoma brucei (TbMetRS is an important target in the development of new antitrypanosomal drugs. The enzyme is essential, highly flexible and displaying a large degree of changes in protein domains and binding pockets in the presence of substrate, product and inhibitors. Targeting this protein will benefit from a profound understanding of how its structure adapts to ligand binding. A series of urea-based inhibitors (UBIs has been developed with IC50 values as low as 19 nM against the enzyme. The UBIs were shown to be orally available and permeable through the blood-brain barrier, and are therefore candidates for development of drugs for the treatment of late stage human African trypanosomiasis. Here, we expand the structural diversity of inhibitors from the previously reported collection and tested for their inhibitory effect on TbMetRS and on the growth of T. brucei cells. The binding modes and binding pockets of 14 UBIs are revealed by determination of their crystal structures in complex with TbMetRS at resolutions between 2.2 Å to 2.9 Å. The structures show binding of the UBIs through conformational selection, including occupancy of the enlarged methionine pocket and the auxiliary pocket. General principles underlying the affinity of UBIs for TbMetRS are derived from these structures, in particular the optimum way to fill the two binding pockets. The conserved auxiliary pocket might play a role in binding tRNA. In addition, a crystal structure of a ternary TbMetRS•inhibitor•AMPPCP complex indicates that the UBIs are not competing with ATP for binding, instead are interacting with ATP through hydrogen bond. This suggests a possibility that a general 'ATP-engaging' binding mode can be utilized for the design and development of inhibitors targeting tRNA synthetases of other disease-causing pathogen.

  13. Cytosolic NADPH homeostasis in glucose-starved procyclic Trypanosoma brucei relies on malic enzyme and the pentose phosphate pathway fed by gluconeogenic flux.

    Science.gov (United States)

    Allmann, Stefan; Morand, Pauline; Ebikeme, Charles; Gales, Lara; Biran, Marc; Hubert, Jane; Brennand, Ana; Mazet, Muriel; Franconi, Jean-Michel; Michels, Paul A M; Portais, Jean-Charles; Boshart, Michael; Bringaud, Frédéric

    2013-06-21

    All living organisms depend on NADPH production to feed essential biosyntheses and for oxidative stress defense. Protozoan parasites such as the sleeping sickness pathogen Trypanosoma brucei adapt to different host environments, carbon sources, and oxidative stresses during their infectious life cycle. The procyclic stage develops in the midgut of the tsetse insect vector, where they rely on proline as carbon source, although they prefer glucose when grown in rich media. Here, we investigate the flexible and carbon source-dependent use of NADPH synthesis pathways in the cytosol of the procyclic stage. The T. brucei genome encodes two cytosolic NADPH-producing pathways, the pentose phosphate pathway (PPP) and the NADP-dependent malic enzyme (MEc). Reverse genetic blocking of those pathways and a specific inhibitor (dehydroepiandrosterone) of glucose-6-phosphate dehydrogenase together established redundancy with respect to H2O2 stress management and parasite growth. Blocking both pathways resulted in ∼10-fold increase of susceptibility to H2O2 stress and cell death. Unexpectedly, the same pathway redundancy was observed in glucose-rich and glucose-depleted conditions, suggesting that gluconeogenesis can feed the PPP to provide NADPH. This was confirmed by (i) a lethal phenotype of RNAi-mediated depletion of glucose-6-phosphate isomerase (PGI) in the glucose-depleted Δmec/Δmec null background, (ii) an ∼10-fold increase of susceptibility to H2O2 stress observed for the Δmec/Δmec/(RNAi)PGI double mutant when compared with the single mutants, and (iii) the (13)C enrichment of glycolytic and PPP intermediates from cells incubated with [U-(13)C]proline, in the absence of glucose. Gluconeogenesis-supported NADPH supply may also be important for nucleotide and glycoconjugate syntheses in the insect host.

  14. FDD-1 System On-line Monitoring Fuel Rod Failure of Nuclear Power Plant

    Institute of Scientific and Technical Information of China (English)

    CHENPeng; ZHANGYing-chao; JISong-tao; GAOYong-guang; YINZhen-guo; HANChuan-bin

    2003-01-01

    The FDD-1 system developed by CIAE for on-line monitoring fuel rod failure of nuclear power plant consists of γ-ray detector, γ-ray spectrum analyzer, computer, and an analysis code for evaluating the status of fuel rod failure. It would be determined that the fuel rod failure occurs when a large amount of γ activity increases in the primary system measured by γ-ray detector near the CVCS.

  15. Non-destructive Testing Dummy Nuclear Fuel Rods by Neutron Radiography

    Institute of Scientific and Technical Information of China (English)

    WEI; Guo-hai; HAN; Song-bai; HE; Lin-feng; WANG; Yu; WANG; Hong-li; LIU; Yun-tao; CHEN; Dong-feng

    2013-01-01

    As a unique non-destructive testing technique,neutron radiography can be used to measure nuclear fuel rods with radioactivity.The images of the dummy nuclear fuel rods were obtained at the CARR.Through imaging analysis methods,the structure defections,the hydrogen accumulation in the cladding and the 235U enrichment of the pellet were studied and analyzed.Experiences for non-destructive testing real PWR nuclear fuel rods by NR

  16. Considerations for sensitivity analysis, uncertainty quantification, and data assimilation for grid-to-rod fretting

    Energy Technology Data Exchange (ETDEWEB)

    Michael Pernice

    2012-10-01

    Grid-to-rod fretting is the leading cause of fuel failures in pressurized water reactors, and is one of the challenge problems being addressed by the Consortium for Advanced Simulation of Light Water Reactors to guide its efforts to develop a virtual reactor environment. Prior and current efforts in modeling and simulation of grid-to-rod fretting are discussed. Sources of uncertainty in grid-to-rod fretting are also described.

  17. Method of targeted delivery of laser beam to isolated retinal rods by fiber optics.

    Science.gov (United States)

    Sim, Nigel; Bessarab, Dmitri; Jones, C Michael; Krivitsky, Leonid

    2011-11-01

    A method of controllable light delivery to retinal rod cells using an optical fiber is described. Photo-induced current of the living rod cells was measured with the suction electrode technique. The approach was tested with measurements relating the spatial distribution of the light intensity to photo-induced current. In addition, the ion current responses of rod cells to polarized light at two different orientation geometries of the cells were studied.

  18. The results of postirradiation examinations of VVER-1000 and VVER-440 fuel rods

    Science.gov (United States)

    Dubrovin, K. P.; Ivanov, E. G.; Strijov, P. N.; Yakovlev, V. V.

    1991-02-01

    The paper presents the results of postirradiation examination of the fuel rods having different fuel-cladding gaps, pellet densities, pellet inner diameters and so on. The fuel rods were irradiated in the material science reactor (MR) of the Kurchatov Institute of Atomic Energy and at 4 unit of the Novo-Voronezh nuclear powerplant. Some data on fission gas release and rod geometry and compared with computer code predictions.

  19. Method of targeted delivery of laser beam to isolated retinal rods by fiber optics

    CERN Document Server

    Sim, Nigel; Jones, C Michael; Krivitsky, Leonid

    2013-01-01

    A method of controllable light delivery to retinal rod cells using an optical fiber is described. Photo-induced current of the living rod cells was measured with the suction electrode technique. The approach was tested with measurements relating the spatial distribution of the light intensity to photo-induced current. In addition, the ion current responses of rod cells to polarized light at two different orientation geometries of the cells were studied.

  20. Decontamination of control rod housing from Palisades Nuclear Power Station.

    Energy Technology Data Exchange (ETDEWEB)

    Kaminski, M.D.; Nunez, L.; Purohit, A.

    1999-05-03

    Argonne National Laboratory has developed a novel decontamination solvent for removing oxide scales formed on ferrous metals typical of nuclear reactor piping. The decontamination process is based on the properties of the diphosphonic acids (specifically 1-hydroxyethane-1,1-diphosphonic acid or HEDPA) coupled with strong reducing-agents (e.g., sodium formaldehyde sulfoxylate, SFS, and hydroxylamine nitrate, HAN). To study this solvent further, ANL has solicited actual stainless steel piping material that has been recently removed from an operating nuclear reactor. On March 3, 1999 ANL received segments of control rod housing from Consumers Energy's Palisades Nuclear Plant (Covert, MI) containing radioactive contamination from both neutron activation and surface scale deposits. Palisades Power plant is a PWR type nuclear generating plant. A total of eight segments were received. These segments were from control rod housing that was in service for about 6.5 years. Of the eight pieces that were received two were chosen for our experimentation--small pieces labeled Piece A and Piece B. The wetted surfaces (with the reactor's pressurized water coolant/moderator) of the pieces were covered with as a scale that is best characterized visually as a smooth, shiny, adherent, and black/brown in color type oxide covering. This tenacious oxide could not be scratched or removed except by aggressive mechanical means (e.g., filing, cutting).

  1. Protrusion of the Rod Electrode in the Electrospinning Process

    Directory of Open Access Journals (Sweden)

    Jan Valtera

    2015-01-01

    Full Text Available The paper focuses on the influence of the protrusion of the rod electrode on critical voltage in the DC electrospinning process. On the testing and industrial DC electrospinning devices, electrodes of any kind are extended towards the counter electrode. This provides the maximal, that is, supercritical, electric field intensity on the spinning-electrode orifice that is found to be higher than on the other supplementary parts. The principal study and experiments with basic apparatus were carried out and presented by Taylor in 1966. This study is focused on the arrangement closely related to the design of the real electrospinning device with respect to the safety and technological aspects. Results of the carried out experiments of the rod spinning-electrode are compared with the electrostatic simulation and analytical calculation. The presented effect of the electrode protrusion on the potential difference and the critical field strength introduces valuable information for the designers of electrospinning machines as well as for the setting up of the optimal technological parameters for producing modern nonwoven textile products.

  2. Geometric Nonlinear Computation of Thin Rods and Shells

    Science.gov (United States)

    Grinspun, Eitan

    2011-03-01

    We develop simple, fast numerical codes for the dynamics of thin elastic rods and shells, by exploiting the connection between physics, geometry, and computation. By building a discrete mechanical picture from the ground up, mimicking the axioms, structures, and symmetries of the smooth setting, we produce numerical codes that not only are consistent in a classical sense, but also reproduce qualitative, characteristic behavior of a physical system----such as exact preservation of conservation laws----even for very coarse discretizations. As two recent examples, we present discrete computational models of elastic rods and shells, with straightforward extensions to the viscous setting. Even at coarse discretizations, the resulting simulations capture characteristic geometric instabilities. The numerical codes we describe are used in experimental mechanics, cinema, and consumer software products. This is joint work with Miklós Bergou, Basile Audoly, Max Wardetzky, and Etienne Vouga. This research is supported in part by the Sloan Foundation, the NSF, Adobe, Autodesk, Intel, the Walt Disney Company, and Weta Digital.

  3. Multidimensional simulations of hydrides during fuel rod lifecycle

    Science.gov (United States)

    Stafford, D. S.

    2015-11-01

    In light water reactor fuel rods, waterside corrosion of zirconium-alloy cladding introduces hydrogen into the cladding, where it is slightly soluble. When the solubility limit is reached, the hydrogen precipitates into crystals of zirconium hydride which decrease the ductility of the cladding and may lead to cladding failure during dry storage or transportation events. The distribution of the hydride phase and the orientation of the crystals depend on the history of the spatial temperature and stress profiles in the cladding. In this work, we have expanded the existing hydride modeling capability in the BISON fuel performance code with the goal of predicting both global and local effects on the radial, azimuthal and axial distribution of the hydride phase. We compare results from 1D simulations to published experimental data. We demonstrate the new capability by simulating in 2D a fuel rod throughout a lifecycle that includes irradiation, short-term storage in the spent fuel pool, drying, and interim storage in a dry cask. Using the 2D simulations, we present qualitative predictions of the effects of the inter-pellet gap and the drying conditions on the growth of a hydride rim.

  4. Neutron strain scanning in straightened eutectoid steel rods

    Science.gov (United States)

    Martínez, M. L.; Borlado, C. R.; Mompeán, F. J.; Peng, R. L.; Daymond, M. R.; Ruiz, J.; García-Hernández, M.

    Neutron strain scanning has been performed on a neutectoid steel rod at a reactor-based source (REST diffractometer, at NFL) and at a pulsed source (ENGIN diffractometer, at ISIS). The rod is primarily obtained from a drawing process and has been subject to bending and straightening procedures, which induce residual stress. The material exhibits a pearlitic microstructure, with alternating ferrite (90 vol%) and cementite (10 vol%) layers. Strain profiles for the ferritic phase were measured on REST. Both phases were measured on ENGIN and analysed by single-peak (ferrite) and Rietveld refinement (ferrite and cementite) methods. The agreement between REST and ENGIN data is excellent for the three measured directions in the ferritic phase. Total stress profiles have been evaluated by combining phase stresses using the rule of mixtures. The experimental results compare well with analytical models for a two-phase material subject to bending and straightening operations under pure bending and unbending moments with perfect elastic behaviour up to the yield point and plastic Voce behaviour above.

  5. Research on the New One Rod Contraceptive Implant Containing Gestodene

    Institute of Scientific and Technical Information of China (English)

    Hai-lin CHEN; Jian-xing CHEN

    2007-01-01

    Objective To develop a new contraceptive implant containing gestodene featuring with only one rod for 5 years long effectiveness and safety.Methods Gestodene synthesis, polymer tube designation, in vitro or in vivo test, the pilot test was used for the establishing of minimum clinic dosage.Results It had a burst effect at beginning and become constantly releasing since 12th day. It had zero-order releasing, in vitro, the average releasing rate was 17. 0-19.1 μg/d,the safe dosage was 70.2 mg/kg, C1hr was 2.91 ± 1.25 ng/ml, Tmax was 8.86 ± 4.32 h,Cmax was 7.31 ±1.09 ng/ml, Tss was 14 d, Css was 4.16±0.48 ng/ml. Twenty-four hours later after removal of the implant, gestodene was almost cleaned out in the blood circulation and only trace amount of drug was detected after the removal.Conclusion One rod gestodene implant is a new long effective contraceptive and may be promising.

  6. Preparation and characterization of the rod-shaped stibnite

    Energy Technology Data Exchange (ETDEWEB)

    Ouni, B., E-mail: bachir.ouni@laposte.net [Unité de Physique des Dispositifs a Semi-conducteurs, Faculté des Sciences deTunis, Tunis El Manar University, 2092 Tunis (Tunisia); Zouini, M. [Laboratoire de Photovoltaïque, Centre de Recherches et des Technologies de l' Energie, Technopôle de Borj-Cédria, BP 95, Hammam-Lif 2050 (Tunisia); Lakhdar, M. Haj; Larbi, T. [Unité de Physique des Dispositifs a Semi-conducteurs, Faculté des Sciences deTunis, Tunis El Manar University, 2092 Tunis (Tunisia); Dimassi, W. [Laboratoire de Photovoltaïque, Centre de Recherches et des Technologies de l' Energie, Technopôle de Borj-Cédria, BP 95, Hammam-Lif 2050 (Tunisia); Amlouk, M. [Unité de Physique des Dispositifs a Semi-conducteurs, Faculté des Sciences deTunis, Tunis El Manar University, 2092 Tunis (Tunisia)

    2015-07-15

    Highlights: • A facile route to synthesize large-scale rod-like Sb{sub 2}S{sub 3} micro-wires was presented. • A deep analysis conjoint between band tails, band gap alteration and electrical model. • The band gap is 1.75 eV which may hold for solar energy conversion. - Abstract: Stibnite (Sb{sub 2}S{sub 3}) micro-wires have been grown on glass substrates by sulfuration of Sb thermal evaporated film in a vacuum sealed tube in presence of sulfur powder at 300 °C for 6 h. X-ray diffraction and Raman spectroscopy techniques indicate that the synthesized micro-wires have an orthorhombic structure. SEM micrographs show rod-shaped micro-wires with a typical length of several tens of micrometers and a diameter of the order of 0.5 μm. The absorption coefficient dependence on the photon energy in the UV–visible range revealed the existence of a direct transition with an energy band gap of about 1.7 eV. Moreover, the band tails and localized states which are related to the level of defects in the material will be presented. These parameters were determined from the exponential absorption profile. All these results have been evaluated and discussed in terms of alteration of band gap edge and electrical measurements.

  7. Trans-orbital orbitocranial penetrating injury by pointed iron rod

    Directory of Open Access Journals (Sweden)

    Vinod Kumar Tewari

    2015-01-01

    Full Text Available Trans-orbital orbitocranial penetrating injury (TOPI by a foreign body is an extremely rare compound head injury having a potential to cause major morbidity and mortality. Preoperative radiological imaging by CT scan is very important for operative guidance, but in remote area where CT scan is not available, the patient is generally referred to tertiary level. Here we present a case which was dealt successfully without CT scan, only on the basis of stable clinical status and X-rays. We present a case of a 35-year-old man who had an accidental injury (fall from height by rod. Immediate X-ray (anteroposterior and lateral views revealed that the pointed end of the foreign body (rod was inside the ipsilateral anterior fossa via basifrontal bone up to frontal vertex, not crossing the midline. CT scan was not available and his vitals with GCS were normal (15/15. He was operated with the help of an ophthalmic surgeon by right frontotemporal craniotomy. The patient was discharged on 10 th day without any neurological deficit except restricted right eyeball movement to superolateral and ptosis. The restricted eyeball movements recovered after third month of follow up with remnant ptosis for 2 years. This case highlights an unusual case, direct visualization and repair of brain structures with higher antibiotics can save the life even in remote areas where CT scan is still not available only on the basis of stable GCS and X-rays.

  8. Electric-field Induced Microdynamics of Charged Rods

    Directory of Open Access Journals (Sweden)

    Kyongok eKang

    2014-12-01

    Full Text Available Electric-field induced phase/state transitions are observed in AC electric fields with small amplitudes and low frequencies in suspensions of charged fibrous viruses (fd, which are model systems for highly charged rod-like colloids. Texture- and particle-dynamics in these field-induced states, and on crossing transition lines, are explored by image time-correlation and dynamic light scattering, respectively. At relatively low frequencies, starting from a system within the isotropic-nematic coexistence region, a transition from a nematic to a chiral nematic is observed, as well as a dynamical state where nematic domains melt and reform. These transitions are preliminary due to field-induced dissociation/association of condensed ions. At higher frequencies a uniform state is formed that is stabilized by hydrodynamic interactions through field-induced electro-osmotic flow where the rods align along the field direction. There is a point in the field-amplitude versus frequency plane where various transition lines meet. This point can be identified as a non-equilibrium critical point, in the sense that a length scale and a time scale diverge on approach of that point. The microscopic dynamics exhibits discontinuities on crossing transition lines that were identified independently by means of image and signal correlation spectroscopy.

  9. Pinch-off of rods by bulk diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Aagesen, L.K.; Johnson, A.E.; Fife, J.L. [Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208-3108 (United States); Voorhees, P.W., E-mail: p-voorhees@northwestern.edu [Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208-3108 (United States); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, IL 60208-3108 (United States); Miksis, M.J. [Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, IL 60208-3108 (United States); Poulsen, S.O.; Lauridsen, E.M. [Riso National Laboratory for Sustainable Energy, Technical University of Denmark, P.O. Box 49, DK-4000 Roskilde (Denmark); Marone, F. [Swiss Light Source, Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Stampanoni, M. [Swiss Light Source, Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Institute for Biomedical Engineering, University and ETH Zuerich, 8092 Zuerich (Switzerland)

    2011-07-15

    The morphology of a rod embedded in a matrix undergoing pinching by interfacial-energy-driven bulk diffusion is determined near the point of pinching. We find a self-similar solution that gives a unique temporal power law and interfacial shape prior to pinching and self-similar solutions after pinching. The theory is compared to experiments that employ in situ four-dimensional X-ray tomographic microscopy for rods of liquid or solid pinching by solute diffusion in the high-diffusivity liquid phase. The excellent agreement between experiment and theory confirms that the interfacial morphology near the singularity is universal both before and after pinching; the shape holds regardless of the material system and initial condition. This also implies that the predictions of the time-dependence of the process can be used to determine the time to pinching for a wide variety of physical systems, and thus provide estimates of the time required for capillarity-driven break-up of microstructures from the detachment of secondary dendrite arms to polymer blends.

  10. Numerical modelling of longitudinal vibrations of a sucker rod string

    Science.gov (United States)

    Shardakov, I. N.; Wasserman, I. N.

    2010-03-01

    A new technique for analyzing the dynamic behavior of a sucker rod string used in the oil well industry is presented. The main difficulty in the numerical calculation of the examined structure is a multivalued velocity—force relation determined by Coulomb's friction and by loads generated during operation of pump valves. Both the monotonic and nonmonotonic velocity—force relations are considered. A quasi-variational inequality formulation of the problem is proposed. The solution of the inequality amounts to finding the minimum of a convex nonsmooth functional at each time step by means of the Newmark difference time scheme, successive iterations and finite element discretization. The problem of functional minimization is reduced to construction of a sequence of smooth nonlinear programming problems by introducing the auxiliary variables and applying the augmented Lagrangian method. The proposed approach is used to study the longitudinal vibrations of sucker rod strings under near-real conditions. In such systems the most commonly occurring vibration modes are the stick-slip vibrations and the vibrations with natural force excited twice a cycle. The nonmonotonic character of the friction law leads to intensification of these vibrations. In the case of nonmonotonic friction law the stick-slip vibrations can occur even under the action of constant external forces.

  11. Generation of elastic stress waves at a T-junction of square rods

    Science.gov (United States)

    Yong, K. H.; Atkins, K. J.

    1983-06-01

    Fourier techniques have been used to predict transmitted and reflected waves at a T-joint in rods of square cross-section for an arbitrary longitudinal impulse approaching the joint in the terminating rod. Elementary and Timoshenko beam theory were used for longitudinal and flexural wave motions respectively. Good agreement is obtained between the predicted and experimental results for an input pulse with large wavelengths compared with the lateral dimensions of the rod. The results demonstrate the similarity to transverse impact of an infinite rod and the unidirectional translation of the joint as a valid model.

  12. Development of Tools for Treating an Irradiated Fuel Rod Assembly in the Pool of HANARO

    Energy Technology Data Exchange (ETDEWEB)

    Hong, J. T.; Ahn, S. H.; Kim, K. H.; Joung, C. Y. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-07-01

    To inspect a fuel rod during irradiation testing at the test loop of a research reactor, the test rig should be disassembled from the IPS (In-pile test section), and the targeted fuel rod assembly should be disassembled from the test rig and encapsulated in a cask to deliver the assembly to the hot cell. In addition, the fuel rod assembly under inspection in the hot cell should be delivered to the reactor pool and reassembled into the test rig to resume the irradiation test. Because the irradiated fuel rod is highly radioactive, all of the assembly and disassembly operations should be carried out in the reactor pool. Therefore, special tools need to be developed to treat the test rig in the pool of a research reactor. In this study, a new mechanically detachable fuel rod assembly has been developed for intermediate inspection during irradiation test at HANARO. A fuel rod assembly can be divided into two parts, such as an instrumented fuel rod assembly and a non-instrumented fuel rod assembly. In particular, an instrumented fuel rod assembly is assembled at the lower part of the test rig, and a non-instrumented fuel rod assembly is assembled at the bottom of the instrumented fuel rod assembly. The non-instrumented fuel rod assembly is locked in the test rig during irradiation test, and is easily disassembled from the instrumented fuel rod assembly by pushing the anchor button and twisting the non-instrumented fuel rod assembly. In addition, because a test rig is 5.4 meters long and the disassembling operation should be carried out at 6 meters deep in the pool of HANARO, tools to help disassemble and assemble the non-instrumented fuel rod assembly have also been developed. All components were designed to operate mechanically and are made of stainless steel and Al 6061 to minimize the effects from the radioactivity. The performance of the developed fuel rod assembly and tools have been verified through an out pile test.

  13. Process development and fabrication for sphere-pac fuel rods. [PWR; BWR

    Energy Technology Data Exchange (ETDEWEB)

    Welty, R.K.; Campbell, M.H.

    1981-06-01

    Uranium fuel rods containing sphere-pac fuel have been fabricated for in-reactor tests and demonstrations. A process for the development, qualification, and fabrication of acceptable sphere-pac fuel rods is described. Special equipment to control fuel contamination with moisture or air and the equipment layout needed for rod fabrication is described and tests for assuring the uniformity of the fuel column are discussed. Fuel retainers required for sphere-pac fuel column stability and instrumentation to measure fuel column smear density are described. Results of sphere-pac fuel rod fabrication campaigns are reviewed and recommended improvements for high throughput production are noted.

  14. Age-related decrease in rod bipolar cell density of the human retina: an immunohistochemical study

    Indian Academy of Sciences (India)

    P Aggarwal; T C Nag; S Wadhwa

    2007-03-01

    During normal ageing, the rods (and other neurones) undergo a significant decrease in density in the human retina from the fourth decade of life onward. Since the rods synapse with the rod bipolar cells in the outer plexiform layer, a decline in rod density (mainly due to death) may ultimately cause an associated decline of the neurones which, like the rod bipolar cells, are connected to them. The rod bipolar cells are selectively stained with antibodies to protein kinase C-. This study examined if rod bipolar cell density changes with ageing of the retina, utilizing donor human eyes (age: 6–91 years). The retinas were fixed and their temporal parts from the macula to the mid-periphery sectioned and processed for protein kinase C- immunohistochemistry. The density of the immunopositive rod bipolar cells was estimated in the mid-peripheral retina (eccentricity: 3–5 mm) along the horizontal temporal axis. The results show that while there is little change in the density of the rod bipolar cells from 6 to 35 years (2.2%), the decline during the period from 35 to 62 years is about 21% and between seventh and tenth decades, it is approximately 27%.

  15. Energy efficient one-pot synthesis of durable superhydrophobic coating through nylon micro-rods

    Science.gov (United States)

    Simovich, T.; Wu, A. H.; Lamb, R. N.

    2014-03-01

    A durable and superhydrophobic coating was fabricated at room temperature through encapsulating nylon micro-rods in a hydrophobic silica shell. This was achieved through the precipitation of miniemulsified nylon under high shear to generate micro-rods with high aspect ratio in the presence of methyltrimethoxysilane. The resultant coating structure resembles a network of highly entangled micro-rods that give rise to both surface roughness and hydrophobicity, resulting in contact angles greater than 155°. The embedded nylon polymer within the micro-rods imparts significant mechanical durability to the surface, resulting in a coating hardness of 2H using the pencil hardness test.

  16. Semi-analytical method for calculating aeroelastic effect of profiled rod flying at high velocity

    Directory of Open Access Journals (Sweden)

    Hui-jun Ning

    2015-03-01

    Full Text Available The key technique of a kinetic energy rod (KER warhead is to control the flight attitude of rods. The rods are usually designed to different shapes. A new conceptual KER named profiled rod which has large L/D ratio is described in this paper. The elastic dynamic equations of this profiled rod flying at high velocity after detonation are set up on the basis of Euler-Bernoulli beam, and the aeroelastic deformation of profiled rod is calculated by semi-analytical method for calculating the vibration characteristics of variable cross-section beam. In addition, the aeroelastic deformation of the undeformed profiled rod and the aeroelastic deformation of deformed profiled rod which is caused by the detonation of explosive are simulated by computational fluid dynamic and finite element method (CFD/FEM, respectively. A satisfactory agreement of these two methods is obtained by the comparison of two methods. The results show that the semi-analytical method for calculating the vibration characteristics of variable cross-section beam is applied to analyze the aeroelastic deformation of profiled rod flying at high velocity.

  17. Resizing buffer rods for ultrasound testing of food products with acoustic noise considerations.

    Science.gov (United States)

    García-Álvarez, Javier; García-Hernández, Miguel J; Novoa-Díaz, Daniel F; Turó Peroy, Antoni; Chávez Domínguez, Juan Antonio; Salazar Soler, Jordi

    2013-01-01

    Buffer rods can be used to perform non-destructive and on-line analysis of food and beverage products. These rods, usually solid cylinders, can be long and heavy for certain applications. In this paper, a resizing analytic procedure is described. Buffer rods designed following this new procedure can be several times shorter than the conventionally designed ones, optimising thus their weight and cost. The signal to noise ratio (SNR) of the resized buffers is also studied in order to determine their practical usability. To this effect, simulations and experiments are conducted using metal and plastic buffer rod materials appropriate for food and beverage testing such as aluminium and polyethylene.

  18. Diode-pumped tunable laser with dual Cri:LiSAF rods

    Institute of Scientific and Technical Information of China (English)

    Xie Guo-Qiang; Wang Tao; Zhu He-Yuan; Qian Lie-Jia

    2006-01-01

    We propose and demonstrate a simple approach to lower the thermal quenching effect and improve the output power of Cr:LiSAF lasers, which is accomplished by employing two laser rods. The resonator contains two laser rods and is designed by using two "X" folding cavities in cascade. A tunable laser output of ~ 180 mW has been achieved with the pump of single-striped laser diodes. Compared with lasers using single gain rod, the laser with dual rods shows less severe thermal effect and increases the output by more than two times.

  19. Analytical estimation of control rod shadowing effect for excess reactivity measurement of High Temperature Engineering Test Reactor (HTTR)

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Masaaki; Yamashita, Kiyonobu; Fujimoto, Nozomu; Nojiri, Naoki; Takeuchi, Mitsuo; Fujisaki, Shingo [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment; Tokuhara, Kazumi; Nakata, Tetsuo

    1998-05-01

    The control rod shadowing effect has been estimated analytically in application of the fuel addition method to excess reactivity measurement of High Temperature Engineering Test Reactor (HTTR). The movements of control rods in the procedure of the fuel addition method have been simulated in the analysis. The calculated excess reactivity obtained by the simulation depends on the combinations of measuring control rods and compensating control rods and varies from -10% to +50% in comparison with the excess reactivity calculated from the effective multiplication factor of the core where all control rods are fully withdrawn. The control rod shadowing effect is reduced by the use of plural number of measuring and compensation control rods because of the reduction in neutron flux deformation in the measuring procedure. As a result, following combinations of control rods are recommended; 1) Thirteen control rods of the center, first, and second rings will be used for the reactivity measurement. The reactivity of each control rod is measured by the use of the other twelve control rods for reactivity compensation. 2) Six control rods of the first ring will be used for the reactivity measurement. The reactivity of each control rod is measured by the use of the other five control rods for reactivity compensation. (author)

  20. 3-(Oxazolo[4,5-b]pyridin-2-yl)anilides as a novel class of potent inhibitors for the kinetoplastid Trypanosoma brucei, the causative agent for human African trypanosomiasis.

    Science.gov (United States)

    Ferrins, Lori; Rahmani, Raphaël; Sykes, Melissa L; Jones, Amy J; Avery, Vicky M; Teston, Eliott; Almohaywi, Basmah; Yin, JieXiang; Smith, Jason; Hyland, Chris; White, Karen L; Ryan, Eileen; Campbell, Michael; Charman, Susan A; Kaiser, Marcel; Baell, Jonathan B

    2013-08-01

    A whole organism high-throughput screen of approximately 87,000 compounds against Trypanosoma brucei brucei led to the recent discovery of several novel compound classes with low micromolar activity against this organism and without appreciable cytotoxicity to mammalian cells. Herein we report a structure-activity relationship (SAR) investigation around one of these hit classes, the 3-(oxazolo[4,5-b]pyridin-2-yl)anilides. Sharp SAR is revealed, with our most active compound (5) exhibiting an IC₅₀ of 91 nM against the human pathogenic strain T.b. rhodesiense and being more than 700 times less toxic towards the L6 mammalian cell line. Physicochemical properties are attractive for many compounds in this series. For the most potent representatives, we show that solubility and metabolic stability are key parameters to target during future optimisation.