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Sample records for brucei paraflagellar rod

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. Adhesion of Trypanosoma cruzi trypomastigotes to fibronectin or laminin modifies tubulin and paraflagellar rod protein phosphorylation.

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    Eliciane C Mattos

    Full Text Available BACKGROUND: The unicellular parasite Trypanosoma cruzi is the causative agent of Chagaś disease in humans. Adherence of the infective stage to elements of the extracellular matrix (ECM, as laminin and fibronectin, is an essential step in host cell invasion. Although members of the gp85/TS, as Tc85, were identified as laminin and fibronectin ligands, the signaling events triggered on the parasite upon binding to these molecules are largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Viable infective parasites were incubated with laminin, fibronectin or bovine serum albumin for different periods of time and the proteins were separated by bidimensional gels. The phosphoproteins were envisaged by specific staining and the spots showing phosphorylation levels significantly different from the control were excised and identified by MS/MS. The results of interest were confirmed by immunoblotting or immunoprecipitation and the localization of proteins in the parasite was determined by immunofluorescence. Using a host cell-free system, our data indicate that the phosphorylation contents of T. cruzi proteins encompassing different cellular functions are modified upon incubation of the parasite with fibronectin or laminin. CONCLUSIONS/SIGNIFICANCE: Herein it is shown, for the first time, that paraflagellar rod proteins and α-tubulin, major structural elements of the parasite cytoskeleton, are predominantly dephosphorylated during the process, probably involving the ERK1/2 pathway. It is well established that T. cruzi binds to ECM elements during the cell infection process. The fact that laminin and fibronectin induce predominantly dephosphorylation of the main cytoskeletal proteins of the parasite suggests a possible correlation between cytoskeletal modifications and the ability of the parasite to internalize into host cells.

  4. Flagellar adhesion in Trypanosoma brucei relies on interactions between different skeletal structures in the flagellum and cell body.

    Science.gov (United States)

    Rotureau, Brice; Blisnick, Thierry; Subota, Ines; Julkowska, Daria; Cayet, Nadège; Perrot, Sylvie; Bastin, Philippe

    2014-01-01

    The Trypanosoma brucei flagellum is an essential organelle anchored along the surface of the cell body through a specialized structure called the flagellum attachment zone (FAZ). Adhesion relies on the interaction of the extracellular portion of two transmembrane proteins, FLA1 and FLA1BP. Here, we identify FLAM3 as a novel large protein associated with the flagellum skeleton whose ablation inhibits flagellum attachment. FLAM3 does not contain transmembrane domains and its flagellar localization matches closely, but not exactly, that of the paraflagellar rod, an extra-axonemal structure present in the flagellum. Knockdown of FLA1 or FLAM3 triggers similar defects in motility and morphogenesis, characterized by the assembly of a drastically reduced FAZ filament. FLAM3 remains associated with the flagellum skeleton even in the absence of adhesion or a normal paraflagellar rod. However, the protein is dispersed in the cytoplasm when flagellum formation is inhibited. By contrast, FLA1 remains tightly associated with the FAZ filament even in the absence of a flagellum. In these conditions, the extracellular domain of FLA1 points to the cell surface. FLAM3 is essential for proper distribution of FLA1BP, which is restricted to the most proximal portion of the flagellum upon knockdown of FLAM3. We propose that FLAM3 is a key component of the FAZ connectors that link the axoneme to the adhesion zone, hence it acts in an equivalent manner to the FAZ filament complex, but on the side of the flagellum.

  5. INFECTED WITH TRYPANOSOMA BRUCEI BRUCEI

    African Journals Online (AJOL)

    v brucei infection where for example tant components of extra-cellular the parasite infectivity potential and toxicological effects have been sues in animal. They are ... homeostasis (1,2, 3). With a unique ability to main- tain the cellular contents and ions stable concentrations, Trypano- soma b. brucei, to which humans.

  6. Non-radioactive method for labelling Trypanosoma brucei brucei ...

    African Journals Online (AJOL)

    It was observed that (i) the biological activities of the T.brucei brucei like the motility, viability, and growth were not affected adversely by the biotinylation; (ii) as little as 100ug Sulfo-NHS-LC-Biotin was enough to label about 6x106 Trypanosoma Brucei Brucei; (iii) high temperature appears to have adverse effect on the ...

  7. 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 ...

  8. Hepatic response in Trypanosomia brucei brucei infected-rats ...

    African Journals Online (AJOL)

    Ethanol leaf extract of Tithonia diversifolia was investigated for its hepato-curative activity in Trypanosoma brucei brucei infected-rats. The phytochemical compositions of the plant extract were also evaluated. The leaf extract was administered 14 days post-infection at dose of 200 and 400 mg/kg orally once daily.

  9. SUMOylation in Trypanosoma brucei

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    Cornelia Andrea Klein

    2013-10-01

    Full Text Available Small ubiquitin like modifier (SUMO proteins are involved in many processes in eukaryotes. We here show that Trypanosoma brucei SUMO (Tb927.5.3210 modifies many proteins. The levels of SUMOylation were unaffected by temperature changes but were increased by severe oxidative stress. We obtained evidence that trypanosome homologues of the SUMO conjugating enzyme Ubc9 (Tb927.2.2460 and the SUMO-specific protease SENP (Tb927.9.2220 are involved in SUMOylation and SUMO removal, respectively.

  10. Malleable mitochondrion of Trypanosoma brucei.

    Science.gov (United States)

    Verner, Zdeněk; Basu, Somsuvro; Benz, Corinna; Dixit, Sameer; Dobáková, Eva; Faktorová, Drahomíra; Hashimi, Hassan; Horáková, Eva; Huang, Zhenqiu; Paris, Zdeněk; Peña-Diaz, Priscila; Ridlon, Lucie; Týč, Jiří; Wildridge, David; Zíková, Alena; Lukeš, Julius

    2015-01-01

    The importance of mitochondria for a typical aerobic eukaryotic cell is undeniable, as the list of necessary mitochondrial processes is steadily growing. Here, we summarize the current knowledge of mitochondrial biology of an early-branching parasitic protist, Trypanosoma brucei, a causative agent of serious human and cattle diseases. We present a comprehensive survey of its mitochondrial pathways including kinetoplast DNA replication and maintenance, gene expression, protein and metabolite import, major metabolic pathways, Fe-S cluster synthesis, ion homeostasis, organellar dynamics, and other processes. As we describe in this chapter, the single mitochondrion of T. brucei is everything but simple and as such rivals mitochondria of multicellular organisms. Copyright © 2015. Published by Elsevier Inc.

  11. Rodding Surgery

    Science.gov (United States)

    ... above-the-knee splint or lightweight plaster or fiberglass splint instead. Bracing may be used after the ... level. Potential Complications Complications from rodding surgery include risks related to:  General anesthesia,  Fractures during the procedure,  ...

  12. Non-cytochrome mediated mitochondrial ATP production in bloodstream form Trypanosoma brucei brucei

    NARCIS (Netherlands)

    Bienen, E. J.; Maturi, R. K.; Pollakis, G.; Clarkson, A. B.

    1993-01-01

    The life cycle of Trypanosoma brucei brucei involves a series of differentiation steps characterized by marked changes in mitochondrial development and function. The bloodstream forms of this parasite completely lack cytochromes and have not been considered to have any Krebs cycle function. It has

  13. What happens when Trypanosoma brucei leaves Africa.

    Science.gov (United States)

    Jensen, Robert E; Simpson, Larry; Englund, Paul T

    2008-10-01

    Julius Lukes and co-workers evaluated the evolutionary origin of Trypanosoma equiperdum and Trypanosoma evansi, parasites that cause horse and camel diseases. Although similar to T. brucei, the sleeping-sickness parasite, these trypanosomes do not cycle through the tsetse fly and have been able to spread beyond Africa. Transmission occurs sexually, or via blood-sucking flies or vampire bats. They concluded that these parasites, which resemble yeast petite mutants, are T. brucei sub-species, which have evolved recently through changes in mitochondrial DNA.

  14. Interaction between Trypanosoma brucei and Haemonchus ...

    African Journals Online (AJOL)

    In order to investigate the immunomodulatory influence of concurrent T. brucei and H. contortus infection in West African Dwarf (WAD) goats, 28 infected and 7 uninfected (control) of 8-9 months old male WAD goats were studied. The infected goats were separated into resistant (Class 1) and susceptible (Class 2) Faecal ...

  15. Haematology of experimental Trypanosoma brucei rhodesiense ...

    African Journals Online (AJOL)

    Haematological aberrations associated with human infective trypanosomes were investigated in the vervet monkey model of the Rhodesian sleeping sickness. Four monkeys were infected intravenously with 104 Trypanosoma brucei rhodesiense and monitored for changes in the blood profile using a haematological ...

  16. 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.

  17. Characterization of Trypanosoma brucei gambiense stocks isolated ...

    African Journals Online (AJOL)

    Characterization of Trypanosoma brucei gambiense stocks isolated from humans by RAPD fingerprinting in Côte d'Ivoire: another evidence for multiple infections. ... a given isoenzyme profile (zymodeme), confirming that this fingerprinting method has a higher discriminative power (faster molecular clock) than isoenzymes.

  18. 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.

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

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    Matyáš Síma

    2011-06-01

    Full Text Available 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.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.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.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.

  20. Trypanosoma brucei: two steps to spread out from Africa.

    Science.gov (United States)

    Lun, Zhao-Rong; Lai, De-Hua; Li, Feng-Jun; Lukes, Julius; Ayala, Francisco J

    2010-09-01

    Trypanosoma brucei equiperdum and Trypanosoma brucei evansi are typically considered separate species, although a recent study suggested that these organisms can be classified as subspecies of Trypanosoma brucei, which we also favor. Here we present a scenario that attempts to explain the continuing evolution of the dyskinetoplastic and akinetoplastic strains, as a consequence of loss of selective pressure(s) leading to the loss of kinetoplast DNA. Copyright 2010 Elsevier Ltd. All rights reserved.

  1. Identification of Trypanosoma evansi, Trypanosoma equiperdum and Trypanosoma brucei brucei using repetitive DNA probes.

    Science.gov (United States)

    Zhang, Z Q; Baltz, T

    1994-06-01

    The phylogenetic relatedness of 15 stocks of Trypanosoma evansi, three stocks of Trypanosoma equiperdum and one stock of Trypanosoma brucei brucei was determined using Southern blot analysis of restriction enzyme digested DNA, probed with two repetitive DNA sequences from T. b. brucei. A dendrogram derived by cluster analysis of restriction fragment length polymorphism (RFLP) revealed three groups of related stocks. Group 1 included 14 stocks of T. evansi and one stock of T. equiperdum. Group 2 included two stocks of T. equiperdum and one stock of T. evansi. Group 3 included the one stock of T. brucei brucei. Group 2 is more closely related to Group 3 than Group 1, by analysis of the banding patterns. Further analysis of the T. evansi in Group 1 revealed that the patterns of isolates from different provinces in China were identical, but differed from T. evansi isolated from Africa, South America and the Philippines. These results provide insight into the origins of T. evansi and suggest that RFLP may be a useful means of distinguishing closely related trypanosomes.

  2. Detection of Trypanosoma brucei gambiense and T. b. rhodesiense ...

    African Journals Online (AJOL)

    Detection of Trypanosoma brucei gambiense and T. b. rhodesiense in Glossina fuscipes fuscipes ( Diptera: Glossinidae ) and Stomoxys flies using the polymerase chain reaction (PCR) technique in southern Sudan.

  3. (Berenil(B)) in the Treatment of Experimental Trypanosoma brucei ...

    African Journals Online (AJOL)

    Dr Olaleye

    Animal welfare was observed in accordance with. International guidelines for the use of laboratory animals for biomedical research (EC, 1996). Trypanosomes: Trypanosoma brucei brucei (Federe strain) obtained from NITR, Vom, was used and the parasites were maintained by serial passages in rats. One millilitre of.

  4. The Effect of Garlic Extracts on Experimental Trypanosoma brucei ...

    African Journals Online (AJOL)

    The anti-trypanosomal effect of aqueous and methanolic extracts of garlic were studied in Trypanosoma brucei brucei infected rabbits. With the establishment of infection, parasitaemia, anaemia, leucopenia, neutropenia and lymphocytosis developed. There was decrease in total serum protein, albumin and increase in ...

  5. Pathogenicity of Trypanosoma brucei in African giant rats ...

    African Journals Online (AJOL)

    Pathogenicity of Trypanosoma brucei in African giant rats ( Cricetomys gambianus , Water House) ... The course of trypanosomosis was investigated over a period of two weeks in six African giant rats (Cricetomys gambianus) experimentally infected with Trypanosoma brucei. Six other rats served as uninfected control.

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

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    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.

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

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    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.

  8. 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.

  9. Mechanisms Mediating Antigenic Variation in Trypanosoma brucei

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    Rudenko Gloria

    1999-01-01

    Full Text Available Antigenic variation in Trypanosoma brucei is a highly sophisticated survival strategy involving switching between the transcription of one of an estimated thousand variant surface glycoprotein (VSG genes. Switching involves either transcriptional control, resulting in switching between different VSG expression sites; or DNA rearrangement events slotting previously inactive VSG genes into an active VSG expression site. In recent years, considerable progress has been made in techniques allowing us to genetically modify infective bloodstream form trypanosomes. This is allowing us to reengineer VSG expression sites, and look at the effect on the mechanisms subsequently used for antigenic variation. We can now begin a dissection of a highly complicated survival strategy mediated by many different mechanisms operating simultaneously.

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

    National Research Council Canada - National Science Library

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

    2015-01-01

    .... 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...

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

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    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.

  12. 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.

  13. Why Rods and Cocci

    Indian Academy of Sciences (India)

    Bacteria exhibit a wide variety of shapes but the commonly studied species of bacteria are generally either spherical in shape which are called cocci (singular coccus) or have a cylindrical shape and are called rods or bacilli (singular bacillus). In reality rods and cocci are the ends of a continuum. Sonle of the cocci are.

  14. 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.

  15. Mechanism of Trypanosoma brucei gambiense resistance to human serum

    DEFF Research Database (Denmark)

    Uzureau, Pierrick; Uzureau, Sophie; Lecordier, Laurence

    2013-01-01

    The African parasite Trypanosoma brucei gambiense accounts for 97% of human sleeping sickness cases. T. b. gambiense resists the specific human innate immunity acting against several other tsetse-fly-transmitted trypanosome species such as T. b. brucei, the causative agent of nagana disease......GP), which prevents APOL1 toxicity and induces stiffening of membranes upon interaction with lipids. Two additional features contribute to resistance to TLFs: reduction of sensitivity to APOL1 requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S substitution. According...

  16. Nucleoside analysis of DNA from Trypanosoma brucei and Trypanosoma equiperdum.

    Science.gov (United States)

    Crozatier, M; De Brij, R J; Den Engelse, L; Johnson, P J; Borst, P

    1988-11-01

    We have digested trypanosome DNA with a combination of pancreatic DNase I, nuclease P1 and bovine alkaline phosphatase and fractionated the resulting nucleosides on a Supelcosil LC-18-S column by high pressure liquid chromatography. We find less than 0.1% unusual nucleosides, both in Trypanosoma brucei and in a Trypanosoma equiperdum stock, in contrast to a previous report of an unusual nucleoside replacing dC at 1.3% of total nucleosides in T. equiperdum. Our results agree with previous suggestions that the modification of inactive telomeric expression sites for variant-specific surface glycoprotein genes in T. brucei only affects a very small fraction of the total DNA.

  17. Control rod testing apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Gaunt, R.R.; Ashman, C.M.

    1987-06-02

    A control rod testing apparatus is described comprising: a first guide means having a vertical cylindrical opening for grossly guiding a control rod; a second guide means having a vertical cylindrical opening for grossly guiding a control rod. The first and second guide means are supported at axially spaced locations with the openings coaxial; and a substantially cylindrical subassembly having a vertical cylindrical opening therethrough. The subassembly is trapped coaxial with and between the first and second guide means, and the subassembly radially floats with respect to the first and second guide means.

  18. Nitroheterocyclic drug resistance mechanisms in Trypanosoma brucei.

    Science.gov (United States)

    Wyllie, Susan; Foth, Bernardo J; Kelner, Anna; Sokolova, Antoaneta Y; Berriman, Matthew; Fairlamb, Alan H

    2016-03-01

    The objective of this study was to identify the mechanisms of resistance to nifurtimox and fexinidazole in African trypanosomes. Bloodstream-form Trypanosoma brucei were selected for resistance to nifurtimox and fexinidazole by stepwise exposure to increasing drug concentrations. Clones were subjected to WGS to identify putative resistance genes. Transgenic parasites modulating expression of genes of interest were generated and drug susceptibility phenotypes determined. Nifurtimox-resistant (NfxR) and fexinidazole-resistant (FxR) parasites shared reciprocal cross-resistance suggestive of a common mechanism of action. Previously, a type I nitroreductase (NTR) has been implicated in nitro drug activation. WGS of resistant clones revealed that NfxR parasites had lost >100 kb from one copy of chromosome 7, rendering them hemizygous for NTR as well as over 30 other genes. FxR parasites retained both copies of NTR, but lost >70 kb downstream of one NTR allele, decreasing NTR transcription by half. A single knockout line of NTR displayed 1.6- and 1.9-fold resistance to nifurtimox and fexinidazole, respectively. Since NfxR and FxR parasites are ∼6- and 20-fold resistant to nifurtimox and fexinidazole, respectively, additional factors must be involved. Overexpression and knockout studies ruled out a role for a putative oxidoreductase (Tb927.7.7410) and a hypothetical gene (Tb927.1.1050), previously identified in a genome-scale RNAi screen. NTR was confirmed as a key resistance determinant, either by loss of one gene copy or loss of gene expression. Further work is required to identify which of the many dozens of SNPs identified in the drug-resistant cell lines contribute to the overall resistance phenotype. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  19. Effects of Morinda lucida leaf extract on Trypanosoma brucei brucei infection in mice.

    Science.gov (United States)

    Asuzu, I U; Chineme, C N

    1990-10-01

    The dried leaves of Morinda lucida were extracted with 50% methanol and the extract was recovered in a 9.7% w/w yield. Acute toxicity tests were performed in mice and the intraperitoneal LD50 of the extract was 2000 mg/kg. The extract induced purgation in mice from the first hour after oral administration and reached its peak between the third and fourth hour. The purgation was not dose-dependent. M. lucida leaf extract i.p. significantly suppressed the level of parasitemia after Trypanosoma brucei infection in mice. Suppression of existing parasitemia appeared dose-dependent with 1000 mg/kg i.p. producing the maximum effect. The best trypanocidal activity was obtained when treatment with M. lucida extract commenced simultaneously with trypanosome inoculation.

  20. Axial Rod Coupling Design

    National Research Council Canada - National Science Library

    Smith, David R

    2003-01-01

    .... The axial rod and coupling has been designed to withstand external survival loads ( 8.3 kN (1,870 lb) for Ring 5), and to maintain its length to within 7 microns after disassembly and reassembly...

  1. Immunomodulatory activity of Buchholzia coriacea seed methanol extract on Trypanosoma brucei brucei infected mice.

    Science.gov (United States)

    Eze, James I; Ekelozie, Chioma F; Nweze, Nwakego E

    2017-12-01

    The seeds of Buchholzia coriacea Engler (Capparaceae) are used in Eastern Nigeria to treat feverish conditions, and to treat malaria and sleeping sickness that cause fever. The current study assesses the immunomodulatory activity of Buchholzia coriacea seed extract on Trypanosoma brucei brucei infected mice. Delayed hypersensitivity reaction, humoral antibody response and in-vivo leucocyte mobilization tests were assessed in three different experiments to determine the effect of the extract on immune response. Seventy-five (75) mice (25 mice per experiment) were used for the study and were each infected with 1.00 × 106 trypanosomes intra-peritoneally. Groups A, B and C were given 250, 500 and 1000 mg/kg of the extract, respectively, group D received 7.5 mg/kg body weight of levamisole and group E was the control. Sheep RBCs were used as antigen. The acute toxicity tests did not cause clinical signs or death within 24 h post treatment at all the doses tested. The extract inhibited delayed hypersensitivity reaction by 20.9 and 20.8% at 250 and 500 mg/kg, respectively, while at 1000 mg/kg, the paw size increased (-101.9%) when compared with the control. The extract elevated the antibody titre from 1.60 ± 0.40 for control to 8.00 ± 3.58 for 500 mg/kg group. The extract increased in total leucocytes counts. The extract has a very wide safety margin and was able to improve immune response. The results of the present study showed that Buchholzia coriacea seed methanol extract possesses immunostimulatory activity on trypanosome-infected mice.

  2. ( Nigella sativa ) oil on Trypanosoma brucei -infected rats

    African Journals Online (AJOL)

    The effect of black seed oil (Nigella sativa oil) on parasitaemia, some serum and liver enzymes as well as some haematological parameters in Trypanosoma brucei-infected rats were investigated. The results show there was low parasitaemia and extension of life span of rats from 12 days of the infected untreated (control) ...

  3. The genome of the African trypanosome Trypanosoma brucei.

    Science.gov (United States)

    Berriman, Matthew; Ghedin, Elodie; Hertz-Fowler, Christiane; Blandin, Gaëlle; Renauld, Hubert; Bartholomeu, Daniella C; Lennard, Nicola J; Caler, Elisabet; Hamlin, Nancy E; Haas, Brian; Böhme, Ulrike; Hannick, Linda; Aslett, Martin A; Shallom, Joshua; Marcello, Lucio; Hou, Lihua; Wickstead, Bill; Alsmark, U Cecilia M; Arrowsmith, Claire; Atkin, Rebecca J; Barron, Andrew J; Bringaud, Frederic; Brooks, Karen; Carrington, Mark; Cherevach, Inna; Chillingworth, Tracey-Jane; Churcher, Carol; Clark, Louise N; Corton, Craig H; Cronin, Ann; Davies, Rob M; Doggett, Jonathon; Djikeng, Appolinaire; Feldblyum, Tamara; Field, Mark C; Fraser, Audrey; Goodhead, Ian; Hance, Zahra; Harper, David; Harris, Barbara R; Hauser, Heidi; Hostetler, Jessica; Ivens, Al; Jagels, Kay; Johnson, David; Johnson, Justin; Jones, Kristine; Kerhornou, Arnaud X; Koo, Hean; Larke, Natasha; Landfear, Scott; Larkin, Christopher; Leech, Vanessa; Line, Alexandra; Lord, Angela; Macleod, Annette; Mooney, Paul J; Moule, Sharon; Martin, David M A; Morgan, Gareth W; Mungall, Karen; Norbertczak, Halina; Ormond, Doug; Pai, Grace; Peacock, Chris S; Peterson, Jeremy; Quail, Michael A; Rabbinowitsch, Ester; Rajandream, Marie-Adele; Reitter, Chris; Salzberg, Steven L; Sanders, Mandy; Schobel, Seth; Sharp, Sarah; Simmonds, Mark; Simpson, Anjana J; Tallon, Luke; Turner, C Michael R; Tait, Andrew; Tivey, Adrian R; Van Aken, Susan; Walker, Danielle; Wanless, David; Wang, Shiliang; White, Brian; White, Owen; Whitehead, Sally; Woodward, John; Wortman, Jennifer; Adams, Mark D; Embley, T Martin; Gull, Keith; Ullu, Elisabetta; Barry, J David; Fairlamb, Alan H; Opperdoes, Fred; Barrell, Barclay G; Donelson, John E; Hall, Neil; Fraser, Claire M; Melville, Sara E; El-Sayed, Najib M

    2005-07-15

    African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.

  4. Roles of triosephosphate isomerase and aerobic metabolism in Trypanosoma brucei.

    NARCIS (Netherlands)

    Helfert, S.; Estevez, A.M.; Bakker, B.M.; Michels, P.A.M.; Clayton, C.

    2001-01-01

    Kinetoplastid protozoa compartmentalize the first seven enzymes of glycolysis and two enzymes of glycerol metabolism in a microbody, the glycosome. While in its mammalian host, Trypanosoma brucei depends entirely on glucose for ATP generation. Under aerobic conditions, most of the glucose is

  5. Population genetic structure and cladistic analysis of Trypanosoma brucei isolates

    NARCIS (Netherlands)

    Agbo, E.C.; Clausen, P.H.; Buscher, P.; Majiwa, P.A.O.; Pas, te M.F.W.; Claassen, E.

    2003-01-01

    Using a novel multilocus DNA marker analysis method, we studied the population genetic structure of Trypansoma brucei stocks and derived clones isolated from animal and rhodesiense sleeping sickness patients during a national sleeping sickness control program in Mukono district, Uganda. We then

  6. Role of cytokines in Trypanosoma brucei-induced anaemia: A ...

    African Journals Online (AJOL)

    the blood-brain barrier. The subspecies Trypanosoma brucei rhodesiense in eastern and southern Africa generally causes a more acute form of ... The persistence of anaemia beyond the initial wave of parasitaemia (after which low numbers of parasites are in circulation) indicates that anaemia may be directly induced.

  7. 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.

  8. Crystal structure of arginine methyltransferase 6 from Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Chongyuan Wang

    Full Text Available Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6 is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH. The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6.

  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. REACTOR CONTROL ROD OPERATING SYSTEM

    Science.gov (United States)

    Miller, G.

    1961-12-12

    A nuclear reactor control rod mechanism is designed which mechanically moves the control rods into and out of the core under normal conditions but rapidly forces the control rods into the core by catapultic action in the event of an emergency. (AEC)

  11. Effect of diminazene aceturate, levamisole and vitamin C combination therapy in rats experimentally infected with Trypanosoma brucei brucei.

    Science.gov (United States)

    Chekwube, Adieme Ijeoma; Onyema, Ezeh Ikenna; Ikenna, Ugochukwu Emmanuel; Ezeokonkwo, Romanus Chukwuduruo

    2014-06-01

    To investigate the effect of diminazene aceturate (DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei. Thirty adult male albino rats, randomly assigned into 6 groups (A-F) of 5 rats each were used. They were either infected with 1×10(6) trypanosomes intraperitoneally (groups A-E) or uninfected (group F). The different groups were treated respectively as follows: group A-with 3.5 mg/kg DA; group B-3.5 mg/kg DA and 7.5 mg/kg levamisole; group C-3.5 mg/kg DA and 100 mg/kg vitamin C; and group D-3.5 mg/kg DA and 7.5 mg/kg levamisole and 100 mg/kg vitamin C. Group E was left untreated. Parameters assessed include: rectal temperature, body weight changes, packed cell volume (PCV), Haemoglobin concentration (Hb), total leucocyte count (TLC) differential leucocyte count (DLC), parasitaemia, clinical signs and survivability. Average pre-patent period of 5 days was recorded. Parasites in the blood were cleared in all treated groups (A-D) within 48 hours post treatment (PT). Untreated rats in group E died between 25 and 32 days post infection (PI). Relapse was not recorded in all the treated groups (A-D). The initial reduction in PCV, Hb, TLC and increases in rectal temperature following infection were reversed by the treatments. The rats that received drug combinations (groups B, C and D) showed faster and higher recovery rates than the uninfected control and group A. Levamisole and/or Vitamin C combination with DA were more effective in the treatment of rats infected with Trypanosoma brucei brucei. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  12. Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei.

    Science.gov (United States)

    Lai, De-Hua; Hashimi, Hassan; Lun, Zhao-Rong; Ayala, Francisco J; Lukes, Julius

    2008-02-12

    Trypanosoma brucei is a kinetoplastid flagellate, the agent of human sleeping sickness and ruminant nagana in Africa. Kinetoplastid flagellates contain their eponym kinetoplast DNA (kDNA), consisting of two types of interlocked circular DNA molecules: scores of maxicircles and thousands of minicircles. Maxicircles have typical mitochondrial genes, most of which are translatable only after RNA editing. Minicircles encode guide RNAs, required for decrypting the maxicircle transcripts. The life cycle of T. brucei involves a bloodstream stage (BS) in vertebrates and a procyclic stage (PS) in the tsetse fly vector. Partial [dyskinetoplastidy (Dk)] or total [akinetoplastidy (Ak)] loss of kDNA locks the trypanosome in the BS form. Transmission between vertebrates becomes mechanical without PS and tsetse mediation, allowing the parasite to spread outside the African tsetse belt. Trypanosoma equiperdum and Trypanosoma evansi are agents of dourine and surra, diseases of horses, camels, and water buffaloes. We have characterized representative strains of T. equiperdum and T. evansi by numerous molecular and classical parasitological approaches. We show that both species are actually strains of T. brucei, which lost part (Dk) or all (Ak) of their kDNA. These trypanosomes are not monophyletic clades and do not qualify for species status. They should be considered two subspecies, respectively T. brucei equiperdum and T. brucei evansi, which spontaneously arose recently. Dk/Ak trypanosomes may potentially emerge repeatedly from T. brucei.

  13. 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.

  14. 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

  15. 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.

  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. 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.

  18. In or out? On the tightness of glycosomal compartmentalizatin of metabolites and enzymes in Trypanosoma brucei.

    NARCIS (Netherlands)

    Haanstra, J.R.; Bakker, B.M.; Michels, P.A.M.

    2014-01-01

    Trypanosomatids sequester large parts of glucose metabolism inside specialised peroxisomes, called glycosomes. Many studies have shown that correct glycosomal compartmentalization of glycolytic enzymes is essential for bloodstream-form Trypanosoma brucei. The recent finding of pore-forming

  19. 1H, 13C and 15N resonance assignment of Urm1 from Trypanosoma brucei.

    Science.gov (United States)

    Zhang, Wen; Ding, Husheng; Zhang, Jiahai; Tu, Xiaoming

    2008-06-01

    Urm1 (ubiquitin-related modifier), involved in diverse biological processes in yeast, is proved to be a "molecular fossil" in ubiquitin superfamily. Here we report the resonance assignment of Urm1 from Trypanosoma brucei.

  20. A Flagellar Pocket Membrane Fraction from Trypanosoma brucei rhodesiense: Immunogold Localization and Nonvariant Immunoprotection

    Science.gov (United States)

    1988-01-01

    membrane components. specific glycoproteins from Trypanosoma equiperdum variants. Exp. Parasitol. 64:1-11. FEBS Lett. 82:93-96. 20. Melton, D. W., D. S...Fraction from Trypanosoma brucei rhodesiense: Immunogold Localization and Nonvariant Immunoprotection JOHN G. OLENICK,* RUTH WOLFF,’ ROBERT K. NAUMAN...obtained for each of three distinct variable antigenic types (VATs) of a serodeme of Trypanosoma brucei rhodesiense Wellcome strain. Products of

  1. The Phosphoproteome of Bloodstream Form Trypanosoma brucei, Causative Agent of African Sleeping Sickness

    OpenAIRE

    Nett, Isabelle R. E.; Martin, David M. A.; Miranda-Saavedra, Diego; Lamont, Douglas; Barber, Jonathan D.; Mehlert, Angela; Ferguson, Michael A. J.

    2009-01-01

    The protozoan parasite Trypanosoma brucei is the causative agent of human African sleeping sickness and related animal diseases, and it has over 170 predicted protein kinases. Protein phosphorylation is a key regulatory mechanism for cellular function that, thus far, has been studied in T.brucei principally through putative kinase mRNA knockdown and observation of the resulting phenotype. However, despite the relatively large kinome of this organism and the demonstrated essentiality of severa...

  2. Steroid Alkaloids from Holarrhena africana with Strong Activity against Trypanosoma brucei rhodesiense

    OpenAIRE

    Charles Okeke Nnadi; Ngozi Justina Nwodo; Marcel Kaiser; Reto Brun; Thomas J. Schmidt

    2017-01-01

    In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, “sleeping sickness”), we have investigated extracts from the leaves and bark of the West African Holarrhena africana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatogr...

  3. Characterization of Trypanosoma brucei dihydroorotate dehydrogenase as a possible drug target; structural, kinetic and RNAi studies.

    Science.gov (United States)

    Arakaki, Tracy L; Buckner, Frederick S; Gillespie, J Robert; Malmquist, Nicholas A; Phillips, Margaret A; Kalyuzhniy, Oleksandr; Luft, Joseph R; Detitta, George T; Verlinde, Christophe L M J; Van Voorhis, Wesley C; Hol, Wim G J; Merritt, Ethan A

    2008-04-01

    Nucleotide biosynthesis pathways have been reported to be essential in some protozoan pathogens. Hence, we evaluated the essentiality of one enzyme in the pyrimidine biosynthetic pathway, dihydroorotate dehydrogenase (DHODH) from the eukaryotic parasite Trypanosoma brucei through gene knockdown studies. RNAi knockdown of DHODH expression in bloodstream form T. brucei did not inhibit growth in normal medium, but profoundly retarded growth in pyrimidine-depleted media or in the presence of the known pyrimidine uptake antagonist 5-fluorouracil (5-FU). These results have significant implications for the development of therapeutics to combat T. brucei infection. Specifically, a combination therapy including a T. brucei-specific DHODH inhibitor plus 5-FU may prove to be an effective therapeutic strategy. We also show that this trypanosomal enzyme is inhibited by known inhibitors of bacterial Class 1A DHODH, in distinction to the sensitivity of DHODH from human and other higher eukaryotes. This selectivity is supported by the crystal structure of the T. brucei enzyme, which is reported here at a resolution of 1.95 A. Additional research, guided by the crystal structure described herein, is needed to identify potent inhibitors of T. brucei DHODH.

  4. 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...

  5. Role of centrins 2 and 3 in organelle segregation and cytokinesis in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Angamuthu Selvapandiyan

    Full Text Available Centrins are calcium binding proteins involved in cell division in eukaryotes. Previously, we have shown that depletion of centrin1 in Trypanosoma brucei (T. brucei displayed arrested organelle segregation resulting in loss of cytokinesis. In this study we analyzed the role of T. brucei centrin2 (TbCen2 and T. brucei 3 (TbCen3 in the early events of T. brucei procyclic cell cycle. Both the immunofluorescence assay and electron microscopy showed that TbCen2 and 3-deficient cells were enlarged in size with duplicated basal bodies, multinuclei and new flagella that are detached along the length of the cell body. In both TbCen2 and TbCen3 depleted cells segregation of the organelles i.e. basal bodies, kinetoplast and nucleus was disrupted. Further analysis of the cells with defective organelle segregation identified three different sub configurations of organelle mis-segregations (Type 1-3. In addition, in majority of the TbCen2 depleted cells and in nearly half of the TbCen3 depleted cells, the kinetoplasts were enlarged and undivided. The abnormal segregations ultimately led to aborted cytokinesis and hence affected growth in these cells. Therefore, both centrin2 and 3 are involved in organelle segregation similar to centrin1 as was previously observed. In addition, we identified their role in kinetoplast division which may be also linked to overall mis-segregation.

  6. 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; Vincendeau, Philippe; Robinson, Derrick R

    2016-11-01

    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 (pnifurtimox-eflornithine combinations showed similar improvement in mice survival (p≤0.001). Our results provide support for a CYP51 targeting based treatment in HAT. Thus posaconazole used in combination may represent a therapeutic alternative for trypanosomiasis.

  7. Advanced gray rod control assembly

    Science.gov (United States)

    Drudy, Keith J; Carlson, William R; Conner, Michael E; Goldenfield, Mark; Hone, Michael J; Long, Jr., Carroll J; Parkinson, Jerod; Pomirleanu, Radu O

    2013-09-17

    An advanced gray rod control assembly (GRCA) for a nuclear reactor. The GRCA provides controlled insertion of gray rod assemblies into the reactor, thereby controlling the rate of power produced by the reactor and providing reactivity control at full power. Each gray rod assembly includes an elongated tubular member, a primary neutron-absorber disposed within the tubular member said neutron-absorber comprising an absorber material, preferably tungsten, having a 2200 m/s neutron absorption microscopic capture cross-section of from 10 to 30 barns. An internal support tube can be positioned between the primary absorber and the tubular member as a secondary absorber to enhance neutron absorption, absorber depletion, assembly weight, and assembly heat transfer characteristics.

  8. High-throughput Gene Tagging in Trypanosoma brucei.

    Science.gov (United States)

    Dyer, Philip; Dean, Samuel; Sunter, Jack

    2016-08-12

    Improvements in mass spectrometry, sequencing and bioinformatics have generated large datasets of potentially interesting genes. Tagging these proteins can give insights into their function by determining their localization within the cell and enabling interaction partner identification. We recently published a fast and scalable method to generate Trypanosoma brucei cell lines that express a tagged protein from the endogenous locus. The method was based on a plasmid we generated that, when coupled with long primer PCR, can be used to modify a gene to encode a protein tagged at either terminus. This allows the tagging of dozens of trypanosome proteins in parallel, facilitating the large-scale validation of candidate genes of interest. This system can be used to tag proteins for localization (using a fluorescent protein, epitope tag or electron microscopy tag) or biochemistry (using tags for purification, such as the TAP (tandem affinity purification) tag). Here, we describe a protocol to perform the long primer PCR and the electroporation in 96-well plates, with the recovery and selection of transgenic trypanosomes occurring in 24-well plates. With this workflow, hundreds of proteins can be tagged in parallel; this is an order of magnitude improvement to our previous protocol and genome scale tagging is now possible.

  9. 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.

  10. 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.

  11. Ligand tunnels in T. brucei and human CYP51: Insights for parasite-specific drug design.

    Science.gov (United States)

    Yu, Xiaofeng; Nandekar, Prajwal; Mustafa, Ghulam; Cojocaru, Vlad; Lepesheva, Galina I; Wade, Rebecca C

    2016-01-01

    Cytochrome P450 sterol 14α-demethylase (CYP51) is an essential enzyme for sterol biosynthesis and a target for anti-parasitic drug design. However, the design of parasite-specific drugs that inhibit parasitic CYP51 without severe side effects remains challenging. The active site of CYP51 is situated in the interior of the protein. Here, we characterize the potential ligand egress routes and mechanisms in Trypanosoma brucei and human CYP51 enzymes. We performed Random Acceleration Molecular Dynamics simulations of the egress of four different ligands from the active site of models of soluble and membrane-bound T. brucei CYP51 and of soluble human CYP51. In the simulations, tunnel 2f, which leads to the membrane, was found to be the predominant ligand egress tunnel for all the ligands studied. Tunnels S, 1 and W, which lead to the cytosol, were also used in T. brucei CYP51, whereas tunnel 1 was the only other tunnel used significantly in human CYP51. The common tunnels found previously in other CYPs were barely used. The ligand egress times were shorter for human than T. brucei CYP51, suggesting lower barriers to ligand passage. Two gating residues, F105 and M460, in T. brucei CYP51 that modulate the opening of tunnels 2f and S were identified. Although the main egress tunnel was the same, differences in the tunnel-lining residues, ligand passage and tunnel usage were found between T. brucei and human CYP51s. The results provide a basis for the design of selective anti-parasitic agents targeting the ligand tunnels. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Isolation and analysis of the genetic diversity of repertoires of VSG expression site containing telomeres from Trypanosoma brucei gambiense, T. b. brucei and T. equiperdum

    Directory of Open Access Journals (Sweden)

    Becker Marion

    2008-08-01

    Full Text Available Abstract Background African trypanosomes (including Trypanosoma brucei are unicellular parasites which multiply in the mammalian bloodstream. T. brucei has about twenty telomeric bloodstream form Variant Surface Glycoprotein (VSG expression sites (BESs, of which one is expressed at a time in a mutually exclusive fashion. BESs are polycistronic transcription units, containing a variety of families of expression site associated genes (ESAGs in addition to the telomeric VSG. These polymorphic ESAG families are thought to play a role in parasite-host adaptation, and it has been proposed that ESAG diversity might be related to host range. Analysis of the genetic diversity of these telomeric gene families has been confounded by the underrepresentation of telomeric sequences in standard libraries. We have previously developed a method to selectively isolate sets of trypanosome BES containing telomeres using Transformation associated recombination (TAR cloning in yeast. Results Here we describe the isolation of repertoires of BES containing telomeres from three trypanosome subspecies: Trypanosoma brucei gambiense DAL 972 (causative agent of West-African trypanosomiasis, T. b. brucei EATRO 2340 (a nonhuman infective strain and T. equiperdum STIB 818 (which causes a sexually transmitted disease in equines. We have sequenced and analysed the genetic diversity at four BES loci (BES promoter region, ESAG6, ESAG5 and ESAG2 from these three trypanosome BES repertoires. Conclusion With the exception of ESAG2, the BES sequence repertoires derived from T. b. gambiense are both less diverse than and nearly reciprocally monophyletic relative to those from T. b. brucei and T. equiperdum. Furthermore, although we find evidence for adaptive evolution in all three ESAG repertoires in T. b. brucei and T. equiperdum, only ESAG2 appears to be under diversifying selection in T. b. gambiense. This low level of variation in the T. b. gambiense BES sequence repertoires is

  13. Isolation and analysis of the genetic diversity of repertoires of VSG expression site containing telomeres from Trypanosoma brucei gambiense, T. b. brucei and T. equiperdum.

    Science.gov (United States)

    Young, Rosanna; Taylor, Jesse E; Kurioka, Ayako; Becker, Marion; Louis, Edward J; Rudenko, Gloria

    2008-08-12

    African trypanosomes (including Trypanosoma brucei) are unicellular parasites which multiply in the mammalian bloodstream. T. brucei has about twenty telomeric bloodstream form Variant Surface Glycoprotein (VSG) expression sites (BESs), of which one is expressed at a time in a mutually exclusive fashion. BESs are polycistronic transcription units, containing a variety of families of expression site associated genes (ESAGs) in addition to the telomeric VSG. These polymorphic ESAG families are thought to play a role in parasite-host adaptation, and it has been proposed that ESAG diversity might be related to host range. Analysis of the genetic diversity of these telomeric gene families has been confounded by the underrepresentation of telomeric sequences in standard libraries. We have previously developed a method to selectively isolate sets of trypanosome BES containing telomeres using Transformation associated recombination (TAR) cloning in yeast. Here we describe the isolation of repertoires of BES containing telomeres from three trypanosome subspecies: Trypanosoma brucei gambiense DAL 972 (causative agent of West-African trypanosomiasis), T. b. brucei EATRO 2340 (a nonhuman infective strain) and T. equiperdum STIB 818 (which causes a sexually transmitted disease in equines). We have sequenced and analysed the genetic diversity at four BES loci (BES promoter region, ESAG6, ESAG5 and ESAG2) from these three trypanosome BES repertoires. With the exception of ESAG2, the BES sequence repertoires derived from T. b. gambiense are both less diverse than and nearly reciprocally monophyletic relative to those from T. b. brucei and T. equiperdum. Furthermore, although we find evidence for adaptive evolution in all three ESAG repertoires in T. b. brucei and T. equiperdum, only ESAG2 appears to be under diversifying selection in T. b. gambiense. This low level of variation in the T. b. gambiense BES sequence repertoires is consistent both with the relatively narrow host range

  14. 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.

  15. Rod and lamellar growth of eutectic

    Directory of Open Access Journals (Sweden)

    M. Trepczyńska-Łent

    2010-04-01

    Full Text Available The paper presents adaptation problem of lamellar growth of eutectic. The formation of rod eutectic microstructure was investigated systematically. A new rod eutectic configuration was observed in which the rods form with elliptical cylindrical shape. A new interpretation of the eutectic growth theory was proposed.

  16. 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...

  17. 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).

  18. Arterial blood pressure changes in acute T. brucei infection of dogs ...

    African Journals Online (AJOL)

    The aim of this study is to find out the usefulness of serial arterial blood pressure measurements in predicting severity and outcome of acute Trypanosoma brucei infection in dogs. Twenty adult dogs of mixed sexes and aged between 2 and 5 years were used for this study. The dogs were of good cardiac health and were ...

  19. 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

  20. Phosphatidylinositol 4-kinase III-beta is required for Golgi maintenance and cytokinesis in Trypanosoma brucei.

    Science.gov (United States)

    Rodgers, Melissa J; Albanesi, Joseph P; Phillips, Margaret A

    2007-07-01

    The parasitic protozoan Trypanosoma brucei contains two type III phosphatidylinositol 4-kinases (alpha and beta). We have cloned the gene encoding the T. brucei type III phosphatidylinositol 4-kinase beta (TbPI4KIII-beta), expressed the protein in COS-7 cells, and confirmed that the protein catalyzes the phosphorylation of phosphatidylinositol. Depletion of TbPI4KIII-beta in procyclic T. brucei by RNA interference (RNAi) resulted in inhibition of cell growth and a distorted cellular morphology. RNAi cells had a distorted Golgi apparatus, and lysosomal and flagellar pocket proteins were mislocalized. Ultrastructural analysis revealed the internal accumulation of a heterogeneous population of vesicles, abnormal positioning of organelles, and a loss of cell polarity. Scanning electron microcopy revealed a twisted phenotype, and dividing cells often exhibited a detached daughter flagellum and lacked a cleavage furrow. Cell cycle analysis confirmed that cells depleted of TbPI4KIII-beta have a postmitotic cytokinesis block that occurs after a single round of mitosis, suggestive of a specific cell cycle block. In summary, TbPI4KIII-beta is an essential protein in procyclic T. brucei, required for maintenance of Golgi structure, protein trafficking, normal cellular shape, and cytokinesis.

  1. The Flagellar Arginine Kinase in Trypanosoma brucei Is Important for Infection in Tsetse Flies.

    Directory of Open Access Journals (Sweden)

    Cher-Pheng Ooi

    Full Text Available African trypanosomes are flagellated parasites that cause sleeping sickness. Parasites are transmitted from one mammalian host to another by the bite of a tsetse fly. Trypanosoma brucei possesses three different genes for arginine kinase (AK including one (AK3 that encodes a protein localised to the flagellum. AK3 is characterised by the presence of a unique amino-terminal insertion that specifies flagellar targeting. We show here a phylogenetic analysis revealing that flagellar AK arose in two independent duplication events in T. brucei and T. congolense, the two species of African trypanosomes that infect the tsetse midgut. In T. brucei, AK3 is detected in all stages of parasite development in the fly (in the midgut and in the salivary glands as well as in bloodstream cells, but with predominance at insect stages. Genetic knockout leads to a slight reduction in motility and impairs parasite infectivity towards tsetse flies in single and competition experiments, both phenotypes being reverted upon expression of an epitope-tagged version of AK3. We speculate that this flagellar arginine kinase is important for T. brucei infection of tsetse, especially in the context of mixed infections and that its flagellar targeting relies on a system equivalent to that discovered for calflagins, a family of trypanosome flagellum calcium binding proteins.

  2. The Flagellar Arginine Kinase in Trypanosoma brucei Is Important for Infection in Tsetse Flies.

    Science.gov (United States)

    Ooi, Cher-Pheng; Rotureau, Brice; Gribaldo, Simonetta; Georgikou, Christina; Julkowska, Daria; Blisnick, Thierry; Perrot, Sylvie; Subota, Ines; Bastin, Philippe

    2015-01-01

    African trypanosomes are flagellated parasites that cause sleeping sickness. Parasites are transmitted from one mammalian host to another by the bite of a tsetse fly. Trypanosoma brucei possesses three different genes for arginine kinase (AK) including one (AK3) that encodes a protein localised to the flagellum. AK3 is characterised by the presence of a unique amino-terminal insertion that specifies flagellar targeting. We show here a phylogenetic analysis revealing that flagellar AK arose in two independent duplication events in T. brucei and T. congolense, the two species of African trypanosomes that infect the tsetse midgut. In T. brucei, AK3 is detected in all stages of parasite development in the fly (in the midgut and in the salivary glands) as well as in bloodstream cells, but with predominance at insect stages. Genetic knockout leads to a slight reduction in motility and impairs parasite infectivity towards tsetse flies in single and competition experiments, both phenotypes being reverted upon expression of an epitope-tagged version of AK3. We speculate that this flagellar arginine kinase is important for T. brucei infection of tsetse, especially in the context of mixed infections and that its flagellar targeting relies on a system equivalent to that discovered for calflagins, a family of trypanosome flagellum calcium binding proteins.

  3. Particle-bound enzymes in the bloodstream form of Trypanosoma brucei

    NARCIS (Netherlands)

    Opperdoes, F. R.; Borst, P.; Spits, H.

    1977-01-01

    We have screened the bloodstream form of Trypanosoma brucei for the presence of enzymes that could serve as markers for the microbodies and the highly repressed mitochondrion of this organism. None of seven known microbody enzymes were detected at all, but glycerol-3-phosphate oxidase, ATPase,

  4. 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

  5. Contribution of glucose transport to the control of the glycolytic flux in Trypanosoma brucei.

    NARCIS (Netherlands)

    Bakker, B.M.; Walsh, M.C.; ter Kuile, B.; Mensonides, F.I.C.; Michels, P.A.M.; Opperdoes, F.R.; Westerhoff, H.V.

    1999-01-01

    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

  6. The promoter for a variant surface glycoprotein gene expression site in Trypanosoma brucei

    NARCIS (Netherlands)

    Zomerdijk, J. C.; Ouellette, M.; ten Asbroek, A. L.; Kieft, R.; Bommer, A. M.; Clayton, C. E.; Borst, P.

    1990-01-01

    The variant-specific surface glycoprotein (VSG) gene 221 of Trypanosoma brucei is transcribed as part of a 60 kb expression site (ES). We have identified the promoter controlling this multigene transcription unit by the use of 221 chromosome-enriched DNA libraries and VSG gene 221 expression site

  7. Maf1 is a negative regulator of transcription in Trypanosoma brucei.

    Science.gov (United States)

    Romero-Meza, Gabriela; Vélez-Ramírez, Daniel E; Florencio-Martínez, Luis E; Román-Carraro, Fiordaliso C; Manning-Cela, Rebeca; Hernández-Rivas, Rosaura; Martínez-Calvillo, Santiago

    2017-02-01

    RNA polymerase III (Pol III) produces small RNA molecules that play essential roles in mRNA processing and translation. Maf1, originally described as a negative regulator of Pol III transcription, has been studied from yeast to human. Here we characterized Maf1 in the parasitic protozoa Trypanosoma brucei (TbMaf1), representing the first report to analyse Maf1 in an early-diverged eukaryote. While Maf1 is generally encoded by a single-copy gene, the T. brucei genome contains two almost identical TbMaf1 genes. The TbMaf1 protein has the three conserved sequences and is predicted to fold into a globular structure. Unlike in yeast, TbMaf1 localizes to the nucleus in procyclic forms of T. brucei under normal growth conditions. Cell lines that either downregulate or overexpress TbMaf1 were generated, and growth curve analysis with them suggested that TbMaf1 participates in the regulation of cell growth of T. brucei. Nuclear run-on and chromatin immunoprecipitation analyses demonstrated that TbMaf1 represses Pol III transcription of tRNA and U2 snRNA genes by associating with their promoters. Interestingly, 5S rRNA levels do not change after TbMaf1 ablation or overexpression. Notably, our data also revealed that TbMaf1 regulates Pol I transcription of procyclin gene and Pol II transcription of SL RNA genes. © 2016 John Wiley & Sons Ltd.

  8. 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

  9. Deletion of the Trypanosoma brucei Superoxide Dismutase Gene sodb1 Increases Sensitivity to Nifurtimox and Benznidazole▿

    Science.gov (United States)

    Prathalingham, S. Radhika; Wilkinson, Shane R.; Horn, David; Kelly, John M.

    2007-01-01

    It has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. However, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide. PMID:17145786

  10. Deletion of the Trypanosoma brucei superoxide dismutase gene sodb1 increases sensitivity to nifurtimox and benznidazole.

    Science.gov (United States)

    Prathalingham, S Radhika; Wilkinson, Shane R; Horn, David; Kelly, John M

    2007-02-01

    It has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. However, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide.

  11. Trypanosoma brucei Infection in a herd of sedentary cattle in Danja ...

    African Journals Online (AJOL)

    Trypanosoma brucei Infection in a herd of sedentary cattle in Danja Local Government Area, Katsina State, Northern Nigeria– A possible resurgence of Tsetse flies ... resulted in advocacy for pastoralists to settle down into productive cattle production compared to the nomadic behavior which does not enhance productivity.

  12. 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...

  13. Aquaglyceroporins Are the Entry Pathway of Boric Acid in Trypanosoma brucei.

    Science.gov (United States)

    Marsiccobetre, Sabrina; Rodríguez-Acosta, Alexis; Lang, Florian; Figarella, Katherine; Uzcátegui, Néstor L

    2017-05-01

    The boron element possesses a range of different effects on living beings. It is essential to beneficial at low concentrations, but toxic at excessive concentrations. Recently, some boron-based compounds have been identified as promising molecules against Trypanosoma brucei, the causative agent of sleeping sickness. However, until now, the boron metabolism and its access route into the parasite remained elusive. The present study addressed the permeability of T. brucei aquaglyceroporins (TbAQPs) for boric acid, the main natural boron species. To this end, the three TbAQPs were expressed in Saccharomyces cerevisiae and Xenopus laevis oocytes. Our findings in both expression systems showed that all three TbAQPs are permeable for boric acid. Especially TbAQP2 is highly permeable for this compound, displaying one of the highest conductances reported for a solute in these channels. Additionally, T. brucei aquaglyceroporin activities were sensitive to pH. Taken together, these results establish that TbAQPs are channels for boric acid and are highly efficient entry pathways for boron into the parasite. Our findings stress the importance of studying the physiological functions of boron and their derivatives in T. brucei, as well as the pharmacological implications of their uptake by trypanosome aquaglyceroporins. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Paula Ana Iribarren

    Full Text Available 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.

  15. BAPTA-AM decreases cellular pH, inhibits acidocalcisome acidification and autophagy in amino acid-starved T. brucei.

    Science.gov (United States)

    Li, Feng-Jun; Tan, Kevin S W; He, Cynthia Y

    2017-04-01

    To investigate the role of Ca2+ signaling in starvation-induced autophagy in Trypanosoma brucei, the causative agent of human African trypanosomiasis, we used cell-permeant Ca2+ chelator BAPTA-AM and cell impermeant chelator EGTA, and examined the potential involvement of several intracellular Ca2+ signaling pathways in T. brucei autophagy. The results showed an unexpected effect of BAPTA-AM in decreasing cellular pH and inhibiting acidocalcisome acidification in starved cells. The implication of these results in the role of Ca2+ signaling and cellular/organellar pH in T. brucei autophagy is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Fuel rod assembly to manifold attachment

    Science.gov (United States)

    Donck, Harry A.; Veca, Anthony R.; Snyder, Jr., Harold J.

    1980-01-01

    A fuel element is formed with a plurality of fuel rod assemblies detachably connected to an overhead support with each of the fuel rod assemblies having a gas tight seal with the support to allow internal fission gaseous products to flow without leakage from the fuel rod assemblies into a vent manifold passageway system on the support. The upper ends of the fuel rod assemblies are located at vertically extending openings in the support and upper threaded members are threaded to the fuel rod assemblies to connect the latter to the support. The preferred threaded members are cap nuts having a dome wall encircling an upper threaded end on the fuel rod assembly and having an upper sealing surface for sealing contact with the support. Another and lower seal is achieved by abutting a sealing surface on each fuel rod assembly with the support. A deformable portion on the cap nut locks the latter against inadvertent turning off the fuel rod assembly. Orienting means on the fuel rod and support primarily locates the fuel rods azimuthally for reception of a deforming tool for the cap nut. A cross port in the fuel rod end plug discharges into a sealed annulus within the support, which serves as a circumferential chamber, connecting the manifold gas passageways in the support.

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

    Directory of Open Access Journals (Sweden)

    Frédéric-Antoine Dauchy

    2016-11-01

    Full Text Available 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 (p<0.05, suggesting cytokinesis dysfunction. The survival of CYP51RNAi Doxycycline-treated mice (p = 0.053 and of CYP51RNAi 5-day pre-induced Doxycycline-treated mice (p = 0.008 were improved compared to WT showing a CYP51 RNAi effect on trypanosomal virulence in mice. The posaconazole concentrations that inhibited parasite growth by 50% (IC50 were 8.5, 2.7, 1.6 and 0.12 μM for T. b. brucei 427 90-13, T. b. brucei Antat 1.1, T. b. gambiense Feo (Feo/ITMAP/1893 and T. b. gambiense Biyamina (MHOM/SD/82, respectively. During infection with these last three virulent strains, posaconazole-eflornithine and nifurtimox-eflornithine combinations showed similar improvement in mice survival (p≤0.001. Our results provide support for a CYP51 targeting based treatment in HAT. Thus posaconazole used in combination may represent a therapeutic

  18. The phosphoproteome of bloodstream form Trypanosoma brucei, causative agent of African sleeping sickness.

    Science.gov (United States)

    Nett, Isabelle R E; Martin, David M A; Miranda-Saavedra, Diego; Lamont, Douglas; Barber, Jonathan D; Mehlert, Angela; Ferguson, Michael A J

    2009-07-01

    The protozoan parasite Trypanosoma brucei is the causative agent of human African sleeping sickness and related animal diseases, and it has over 170 predicted protein kinases. Protein phosphorylation is a key regulatory mechanism for cellular function that, thus far, has been studied in T.brucei principally through putative kinase mRNA knockdown and observation of the resulting phenotype. However, despite the relatively large kinome of this organism and the demonstrated essentiality of several T. brucei kinases, very few specific phosphorylation sites have been determined in this organism. Using a gel-free, phosphopeptide enrichment-based proteomics approach we performed the first large scale phosphorylation site analyses for T.brucei. Serine, threonine, and tyrosine phosphorylation sites were determined for a cytosolic protein fraction of the bloodstream form of the parasite, resulting in the identification of 491 phosphoproteins based on the identification of 852 unique phosphopeptides and 1204 phosphorylation sites. The phosphoproteins detected in this study are predicted from their genome annotations to participate in a wide variety of biological processes, including signal transduction, processing of DNA and RNA, protein synthesis, and degradation and to a minor extent in metabolic pathways. The analysis of phosphopeptides and phosphorylation sites was facilitated by in-house developed software, and this automated approach was validated by manual annotation of spectra of the kinase subset of proteins. Analysis of the cytosolic bloodstream form T. brucei kinome revealed the presence of 44 phosphorylated protein kinases in our data set that could be classified into the major eukaryotic protein kinase groups by applying a multilevel hidden Markov model library of the kinase catalytic domain. Identification of the kinase phosphorylation sites showed conserved phosphorylation sequence motifs in several kinase activation segments, supporting the view that

  19. Compact Hybrid Laser Rod and Laser System

    Science.gov (United States)

    Busch, George E. (Inventor); Amzajerdian, Farzin (Inventor); Pierrottet, Diego F. (Inventor)

    2017-01-01

    A hybrid fiber rod includes a fiber core and inner and outer cladding layers. The core is doped with an active element. The inner cladding layer surrounds the core, and has a refractive index substantially equal to that of the core. The outer cladding layer surrounds the inner cladding layer, and has a refractive index less than that of the core and inner cladding layer. The core length is about 30 to 2000 times the core diameter. A hybrid fiber rod laser system includes an oscillator laser, modulating device, the rod, and pump laser diode(s) energizing the rod from opposite ends. The rod acts as a waveguide for pump radiation but allows for free-space propagation of laser radiation. The rod may be used in a laser resonator. The core length is less than about twice the Rayleigh range. Degradation from single-mode to multi-mode beam propagation is thus avoided.

  20. Essential Assembly Factor Rpf2 Forms Novel Interactions within the 5S RNP in Trypanosoma brucei.

    Science.gov (United States)

    Kamina, Anyango D; Jaremko, Daniel; Christen, Linda; Williams, Noreen

    2017-01-01

    Ribosome biogenesis is a highly complex and conserved cellular process that is responsible for making ribosomes. During this process, there are several assembly steps that function as regulators to ensure proper ribosome formation. One of these steps is the assembly of the 5S ribonucleoprotein particle (5S RNP) in the central protuberance of the 60S ribosomal subunit. In eukaryotes, the 5S RNP is composed of 5S rRNA, ribosomal proteins L5 and L11, and assembly factors Rpf2 and Rrs1. Our laboratory previously showed that in Trypanosoma brucei, the 5S RNP is composed of 5S rRNA, L5, and trypanosome-specific RNA binding proteins P34 and P37. In this study, we characterize an additional component of the 5S RNP, the T. brucei homolog of Rpf2. This is the first study to functionally characterize interactions mediated by Rpf2 in an organism other than fungi. T. brucei Rpf2 (TbRpf2) was identified from tandem affinity purification using extracts prepared from protein A-tobacco etch virus (TEV)-protein C (PTP)-tagged L5, P34, and P37 cell lines, followed by mass spectrometry analysis. We characterized the binding interactions between TbRpf2 and the previously characterized members of the T. brucei 5S RNP. Our studies show that TbRpf2 mediates conserved binding interactions with 5S rRNA and L5 and that TbRpf2 also interacts with trypanosome-specific proteins P34 and P37. We performed RNA interference (RNAi) knockdown of TbRpf2 and showed that this protein is essential for the survival of the parasites and is critical for proper ribosome formation. These studies provide new insights into a critical checkpoint in the ribosome biogenesis pathway in T. brucei. IMPORTANCETrypanosoma brucei is the parasitic protozoan that causes African sleeping sickness. Ribosome assembly is essential for the survival of this parasite through the different host environments it encounters during its life cycle. The assembly of the 5S ribonucleoprotein particle (5S RNP) functions as one of the

  1. 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.

  2. Aparasitemic serological suspects in Trypanosoma brucei gambiense human African trypanosomiasis : a potential human reservoir of parasites ?

    OpenAIRE

    Koffi, Mathurin; Solano, Philippe; Denizot, M.; Courtin, D.; Garcia, André; Lejon, V.; Buscher, P.; Cuny, Gérard; Jamonneau, Vincent

    2006-01-01

    The serological and parasitological tests used for Trypanosoma brucei gambiense human African trypanosomiasis (HAT) diagnosis have low specificity and sensitivity, respectively, and in the field, control program teams are faced with subjects with positive serology but negative parasitology who remain untreated. The aim of this work was to explore, using PCR tool, the significance of these aparasitemic serological suspects. Since discordant PCR results have been observed earlier with different...

  3. Differential virulence and tsetse fly transmissibility of Trypanosoma congolense and Trypanosoma brucei strains

    Directory of Open Access Journals (Sweden)

    Purity K. Gitonga

    2017-01-01

    Full Text Available African animal trypanosomiasis causes significant economic losses in sub-Saharan African countries because of livestock mortalities and reduced productivity. Trypanosomes, the causative agents, are transmitted by tsetse flies (Glossina spp.. In the current study, we compared and contrasted the virulence characteristics of five Trypanosoma congolense and Trypanosoma brucei isolates using groups of Swiss white mice (n = 6. We further determined the vectorial capacity of Glossina pallidipes, for each of the trypanosome isolates. Results showed that the overall pre-patent (PP periods were 8.4 ± 0.9 (range, 4–11 and 4.5 ± 0.2 (range, 4–6 for T. congolense and T. brucei isolates, respectively (p < 0.01. Despite the longer mean PP, T. congolense–infected mice exhibited a significantly (p < 0.05 shorter survival time than T. brucei–infected mice, indicating greater virulence. Differences were also noted among the individual isolates with T. congolense KETRI 2909 causing the most acute infection of the entire group with a mean ± standard error survival time of 9 ± 2.1 days. Survival time of infected tsetse flies and the proportion with mature infections at 30 days post-exposure to the infective blood meals varied among isolates, with subacute infection–causing T. congolense EATRO 1829 and chronic infection–causing T. brucei EATRO 2267 isolates showing the highest mature infection rates of 38.5% and 23.1%, respectively. Therefore, our study provides further evidence of occurrence of differences in virulence and transmissibility of eastern African trypanosome strains and has identified two, T. congolense EATRO 1829 and T. brucei EATRO 2267, as suitable for tsetse infectivity and transmissibility experiments.

  4. 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

  5. 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.

  6. Mapping of branch sites in trans-spliced pre-mRNAs of Trypanosoma brucei.

    Science.gov (United States)

    Patzelt, E; Perry, K L; Agabian, N

    1989-01-01

    The process of trans splicing is essential to the maturation of all mRNAs in the Trypanosomatidae, a family of protozoan parasites, and to specific mRNAs in several species of nematode. In Trypanosoma brucei, a 39-nucleotide (nt) leader sequence originating from a small, 139-nt donor RNA (the spliced leader [SL] RNA) is spliced to the 5' end of mRNAs. An intermediate in this trans-splicing process is a Y structure which contains the 3' 100 nt of the SL RNA covalently linked to the pre-mRNA via a 2'-5' phosphodiester bond at the branch point residue. We mapped the branch points in T. brucei alpha- and beta-tubulin pre-mRNAs. The primary branch acceptors for the alpha- and beta-tubulins are 44 and 56 nt upstream of the 3' splice sites, respectively, and are A residues. Minor branch acceptors were detected 42 and 49 nt upstream of the alpha-tubulin splice site and 58 nt upstream of the splice site in beta-tubulin. The regions surrounding these branch points lack homology to the consensus sequences determined for mammalian cells and yeasts; there is also no conservation among the sequences themselves. Thus, the identified sequences suggest that the mechanism of branch point recognition in T. brucei differs from the mechanism of recognition by U2 RNA that has been proposed for other eucaryotes. Images PMID:2479824

  7. The inositol pyrophosphate synthesis pathway in Trypanosoma brucei is linked to polyphosphate synthesis in acidocalcisomes.

    Science.gov (United States)

    Cordeiro, Ciro D; Saiardi, Adolfo; Docampo, Roberto

    2017-10-01

    Inositol pyrophosphates are novel signaling molecules possessing high-energy pyrophosphate bonds and involved in a number of biological functions. Here, we report the correct identification and characterization of the kinases involved in the inositol pyrophosphate biosynthetic pathway in Trypanosoma brucei: inositol polyphosphate multikinase (TbIPMK), inositol pentakisphosphate 2-kinase (TbIP5K) and inositol hexakisphosphate kinase (TbIP6K). TbIP5K and TbIP6K were not identifiable by sequence alone and their activities were validated by enzymatic assays with the recombinant proteins or by their complementation of yeast mutants. We also analyzed T. brucei extracts for the presence of inositol phosphates using polyacrylamide gel electrophoresis and high-performance liquid chromatography. Interestingly, we could detect inositol phosphate (IP), inositol 4,5-bisphosphate (IP2 ), inositol 1,4,5-trisphosphate (IP3 ), and inositol hexakisphosphate (IP6 ) in T. brucei different stages. Bloodstream forms unable to produce inositol pyrophosphates, due to downregulation of TbIPMK expression by conditional knockout, have reduced levels of polyphosphate and altered acidocalcisomes. Our study links the inositol pyrophosphate pathway to the synthesis of polyphosphate in acidocalcisomes, and may lead to better understanding of these organisms and provide new targets for drug discovery. © 2017 John Wiley & Sons Ltd.

  8. Molecular variation of Trypanosoma brucei subspecies as revealed by AFLP fingerprinting.

    Science.gov (United States)

    Agbo, E E C; Majiwa, P A O; Claassen, H J H M; te Pas, M F W

    2002-04-01

    Genetic analysis of Trypanosoma spp. depends on the detection of variation between strains. We have used the amplified fragment length polymorphism (AFLP) technique to develop a convenient and reliable method for genetic characterization of Trypanosome (sub)species. AFLP accesses multiple independent sites within the genome and would allow a better definition of the relatedness of different Trypanosome (sub)species. Nine isolates (3 from each T. brucei subspecies) were tested with 40 AFLP primer combinations to identify the most appropriate pairs of restriction endonucleases and selective primers. Primers based on the recognition sequences of EcoRI and BglII were chosen and used to analyse 31 T. brucei isolates. Similarity levels calculated with the Pearson correlation coefficient ranged from 15 to 98%, and clusters were determined using the unweighted pair-group method using arithmetic averages (UPGMA). At the intraspecific level, AFLP fingerprints were grouped by numerical analysis in 2 main clusters, allowing a clear separation of T. b. gambiense (cluster I) from T. b. brucei and T. b. rhodesiense isolates (cluster II). Interspecies evaluation of this customized approach produced heterogeneous AFLP patterns, with unique genetic markers, except for T. evansi and T. equiperdum, which showed identical patterns and clustered together.

  9. 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.

  10. NIMA-related kinase TbNRKC is involved in basal body separation in Trypanosoma brucei.

    Science.gov (United States)

    Pradel, Lydie C; Bonhivers, Mélanie; Landrein, Nicolas; Robinson, Derrick R

    2006-05-01

    The NIMA-related kinase 2 (NEK 2) has important cell cycle functions related to centriole integrity and splitting. Trypanosoma brucei does not possess centrioles, however, cytokinesis is coupled to basal body separation events. Here we report the first functional characterisation of a T. brucei basal body-cytoskeletal NIMA-related kinase (NRK) protein, TbNRKC. The TbNRKC kinase domain has high amino acid identity with the human NEK1 kinase domain (50%) but also shares 42% identity with human NEK2. TbNRKC is expressed in bloodstream and procyclic cells and functions as a bona fide kinase in vitro. Remarkably, RNAi knockdown of TbNRKC and overexpression of kinase-dead TbNRKC in procyclic forms induces the accumulation of cells with four basal bodies, whereas overexpression of active protein produces supernumary basal bodies and blocks cytokinesis. TbNRKC is located on mature and immature basal bodies and is the first T. brucei NRK to be found associated with the basal body cytokinesis pathway.

  11. Tipping Time of a Quantum Rod

    Science.gov (United States)

    Parrikar, Onkar

    2010-01-01

    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…

  12. Computing Temperatures In Optically Pumped Laser Rods

    Science.gov (United States)

    Farrukh, Usamah O.

    1991-01-01

    Computer program presents new model solving temperature-distribution problem for laser rods of finite length and calculates both radial and axial components of temperature distributions in these rods. Contains several self-checking schemes to prevent over-writing of memory blocks and to provide simple tracing of information in case of trouble. Written in Microsoft FORTRAN 77.

  13. Self-contact for rods on cylinders

    NARCIS (Netherlands)

    G.H.M. van der Heijden; M.A. Peletier (Mark); R. Planqué (Robert)

    2004-01-01

    textabstractWe study self-contact phenomena in elastic rods that are constrained to lie on a cylinder. By choosing a particular set of variables to describe the rod centerline the variational setting is made particularly simple: the strain energy is a second-order functional of a single scalar

  14. A Pre-clinical Animal Model of Trypanosoma brucei Infection Demonstrating Cardiac Dysfunction.

    Directory of Open Access Journals (Sweden)

    Charlotte S McCarroll

    2015-05-01

    Full Text Available African trypanosomiasis (AT, caused by Trypanosoma brucei species, results in both neurological and cardiac dysfunction and can be fatal if untreated. Research on the pathogenesis and treatment of the disease has centred to date on the characteristic neurological symptoms, whereas cardiac dysfunction (e.g. ventricular arrhythmias in AT remains largely unstudied. Animal models of AT demonstrating cardiac dysfunction similar to that described in field cases of AT are critically required to transform our understanding of AT-induced cardiac pathophysiology and identify future treatment strategies. We have previously shown that T. brucei can interact with heart muscle cells (cardiomyocytes to induce ventricular arrhythmias in ex vivo adult rat hearts. However, it is unknown whether the arrhythmias observed ex vivo are also present during in vivo infection in experimental animal models. Here we show for the first time the characterisation of ventricular arrhythmias in vivo in two animal models of AT infection using electrocardiographic (ECG monitoring. The first model utilised a commonly used monomorphic laboratory strain, Trypanosoma brucei brucei Lister 427, whilst the second model used a pleomorphic laboratory strain, T. b. brucei TREU 927, which demonstrates a similar chronic infection profile to clinical cases. The frequency of ventricular arrhythmias and heart rate (HR was significantly increased at the endpoint of infection in the TREU 927 infection model, but not in the Lister 427 infection model. At the end of infection, hearts from both models were isolated and Langendorff perfused ex vivo with increasing concentrations of the β-adrenergic agonist isoproterenol (ISO. Interestingly, the increased frequency of arrhythmias observed in vivo in the TREU 927 infection model was lost upon isolation of the heart ex vivo, but re-emerged with the addition of ISO. Our results demonstrate that TREU 927 infection modifies the substrate of the myocardium

  15. Estimation of irradiated control rod worth

    Energy Technology Data Exchange (ETDEWEB)

    Varvayanni, M., E-mail: melina@ipta.demokritos.g [NCSR ' DEMOKRITOS' , PO Box 60228, 15310 Aghia Paraskevi (Greece); Catsaros, N. [NCSR ' DEMOKRITOS' , PO Box 60228, 15310 Aghia Paraskevi (Greece); Antonopoulos-Domis, M. [School of Electrical and Computer Engineering, Aristotle University of Thessaloniki, Thessaloniki (Greece)

    2009-11-15

    When depleted control rods are planned to be used in new core configurations, their worth has to be accurately predicted in order to deduce key design and safety parameters such as the available shutdown margin. In this work a methodology is suggested for the derivation of the distributed absorbing capacity of a depleted rod, useful in the case that the level of detail that is known about the irradiation history of the control rod does not allow an accurate calculation of the absorber's burnup. The suggested methodology is based on measurements of the rod's worth carried out in the former core configuration and on corresponding calculations based on the original (before first irradiation) absorber concentration. The methodology is formulated for the general case of the multi-group theory; it is successfully tested for the one-group approximation, for a depleted control rod of the Greek Research Reactor, containing five neutron absorbers. The computations reproduce satisfactorily the irradiated rod worth measurements, practically eliminating the discrepancy of the total rod worth, compared to the computations based on the nominal absorber densities.

  16. 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.

  17. Magnetically controlled growing rods for scoliosis surgery.

    Science.gov (United States)

    Metkar, Umesh; Kurra, Swamy; Quinzi, David; Albanese, Stephen; Lavelle, William F

    2017-02-01

    Early onset scoliosis can be both a disfiguring as well as a life threatening condition. When more conservative treatments fail, pediatric spinal surgeons are forced to consider operative interventions. Traditionally, these interventions have involved the insertion of a variety of implants into the patient with a limited number of anchor points controlling the spine. In the past, these pediatric patients have had multiple surgeries for elective lengthening of these devices to facilitate their growth while attempting to control the scoliosis. These patients often experience a physical and emotional toll from their multiple repeated surgeries. Growing spine techniques have also had a noted high complication rate due to implant dislodgement and infections. Recently, the development of non-invasively, self-lengthening growing rods has occurred. These devices have the potential to allow for the devices to be lengthened magnetically in a conscious patient in the surgeon's office. Areas covered: This review summarized previously published articles in the English literature using a key word search in PubMed for: 'magnetically controlled growing rods', 'Magec rods', 'magnetic growing rods' and 'growing rods'. Expert commentary: Magnetically controlled growing rods have an advantage over growing rods in lengthening the growing spine in the absence of repetitive surgeries.

  18. Induced Current Measurement of Rod Vibrations

    Science.gov (United States)

    Sawicki, Charles A.

    2003-01-01

    The longitudinal normal modes of vibration of rods are similar to the modes seen in pipes open at both ends. A maximum of particle displacement exists at both ends and an integral number (n) of half wavelengths fit into the rod length. The frequencies fn of the normal modes is given by Eq. (1), where L is the rod length and V is the wave velocity: fn = nV/2L. Many methods have been used to measure the velocity of these waves. The Kundt's tube method commonly used in student labs will not be discussed here. A simpler related method has been described by Nicklin.2 Kluk3 measured velocities in a wide range of materials using a frequency counter and microphone to study sounds produced by impacts. Several earlier methods4,5 used phonograph cartridges complete with needles to detect vibrations in excited rods. A recent interesting experiment6 used wave-induced changes in magnetization produced in an iron rod by striking one end. The travel time, measured as the impulsive wave reflects back and forth, gave the wave velocity for the iron rod. In the method described here, a small magnet is attached to the rod with epoxy, and vibrations are detected using the current induced in a few loops of wire. The experiment is simple and yields very accurate velocity values.

  19. Immunization with recombinant actin from Trypanosoma evansi induces protective immunity against T. evansi, T. equiperdum and T. b. brucei infection.

    Science.gov (United States)

    Li, San-Qiang; Yang, Wu-Biao; Lun, Zhao-Rong; Ma, Ling-Jun; Xi, Shou-Min; Chen, Qun-Li; Song, Xiao-Wei; Kang, Jian; Yang, Lan-Ze

    2009-01-01

    Actin gene of Trypanosoma evansi (STIB 806) was cloned and expressed in Escherichia coli. The predicted amino acid sequence of T. evansi actin shows 100%, 98.7%, and 93.1%, homology with Trypanosoma equiperdum, Trypanosoma brucei brucei, and Trypanosoma cruzi. Recombinant actin was expressed as inclusion bodies in E. coli. It was purified and renatured for immunological studies. Mice immunized with the renatured recombinant actin were protected from lethal challenge with T. evansi STIB 806, T. equiperdum STIB 818, and T. b. brucei STIB 940, showing 63.3%, 56.7%, and 53.3% protection, respectively. Serum collected from the rabbit immunized with recombinant actin inhibited the growth of T. evansi, T. equiperdum, and T. b. brucei in vitro cultivation. Serum from mice and rabbits immunized with recombinant actin only recognized T. evansi actin but not mouse actin. The results of this study suggest that the recombinant T. evansi actin induces protective immunity against T. evansi, T. equiperdum, and T. b. brucei infection and may be useful in the development of a vaccine with other cytoskeletal proteins to prevent animal trypanosomiasis caused by these three trypanosome species.

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

    Science.gov (United States)

    Omobowale, Temidayo O; Oyagbemi, Ademola A; Oyewunmi, Oyefunbi A; Adejumobi, Olumuyiwa A

    2015-01-01

    The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals. 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. 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 indica, after 2 weeks of T. brucei infection. However, the reduced glutathione (GSH) content of the erythrocyte increased significantly in animals pre-treated with 50 mg/kg and 200 mg/kg of A. indica respectively. Markers of oxidative stress such as malondialdehyde and hydrogen peroxide generated were higher in animals infected with T. brucei with no significant (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. From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection.

  1. The nucleotide sequence of the variable region in Trypanosoma brucei completes the sequence analysis of the maxicircle component of mitochondrial kinetoplast DNA

    NARCIS (Netherlands)

    Sloof, P.; de Haan, A.; Eier, W.; van Iersel, M.; Boel, E.; van Steeg, H.; Benne, R.

    1992-01-01

    The nucleotide sequence of two non-contiguous DNA fragments of 4.0 and 2.2 kb, respectively, of the kinetoplast maxicircle of Trypanosoma brucei brucei EATRO strain 427 has been determined, completing the sequence analysis of the so-called variable region (see also de Vries et al., 1988, Mol.

  2. PCR approach for the detection of Trypanosoma brucei and T. equiperdum and their differentiation from T. evansi based on maxicircle kinetoplast DNA.

    Science.gov (United States)

    Li, Feng-Jun; Gasser, Robin B; Lai, De-Hua; Claes, Filip; Zhu, Xing-Quan; Lun, Zhao-Rong

    2007-02-01

    The goal of this study was to develop a PCR approach based on the sequence of maxicircle kinetoplast DNA (kDNA) of Trypanosoma brucei to distinguish T. brucei/T. equiperdum from T. evansi and to evaluate its diagnostic use for their detection in blood samples. Primers derived from the sequence of the maxicircle kDNA of T. brucei, encoding the NADH dehydrogenase subunit 5 (nad5) gene, were used to test the PCR-amplification from T. brucei (including T. b. brucei and T. b. rhodesiense), T. equiperdum, T. evansi, T. vivax and T. congolense. A primer pair to a nuclear DNA region incorporated into a separate PCR was employed to control for the presence of amplifiable genomic DNA (representing the subgenus Trypanozoon) in each sample subjected to the PCR. Products of approximately 395bp were amplified from all T. brucei and T. equiperdum samples tested using the nad5-PCR, but not from T. evansi DNA samples or any of the control samples representing T. vivax, T. congolense, or host. The current PCR approach allows the rapid differentiation of T. brucei/T.equiperdum from T. evansi and can detect the equivalent of 20-25 cells of T. brucei or T. equiperdum in purified genomic DNA or infected blood samples.

  3. Bijels stabilized using rod-like particles.

    Science.gov (United States)

    Hijnen, Niek; Cai, Dongyu; Clegg, Paul S

    2015-06-14

    Bicontinuous interfacially jammed emulsion gels, in short 'bijels', rely on a trapped layer of colloidal particles for their stability. These structures have traditionally been created using spherical colloidal particles. Here we show for the first time the use of rod-shape particles to stabilize bijels. We show that domain size decreases more rapidly with particle concentration in the case of rods compared to spheres. Large-scale analysis and detailed examination of images show that the packing fraction of rods is much higher than expected, in part, due to the role of 'flippers'.

  4. The rod as an instrument of discipline

    OpenAIRE

    Milton Luiz Torres; Centro Universitário Adventista de São Paulo, São Paulo, SP

    2013-01-01

    Both in biblical literature as in ancient extrabiblical literature, the use of the rod appears primarily related to the capacity or to the authority of the one who holds it. It is, above all, an instrument of power. This article investigates the implications of using the rod as a tool of correction and discipline, taking into account the symbolism, culture and literary tradition associated with the use of that instrument of discipline for correction and transformation of those subjected to it...

  5. 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....

  6. 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.

  7. Microelectrophoresis of Silica Rods Using Confocal Microscopy

    Science.gov (United States)

    2017-01-01

    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 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. PMID:28045541

  8. 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.

  9. The Phosphoarginine Energy-Buffering System of Trypanosoma brucei Involves Multiple Arginine Kinase Isoforms with Different Subcellular Locations

    Science.gov (United States)

    Wadforth, Cath; Harley, Maggie; Colasante, Claudia

    2013-01-01

    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. PMID:23776565

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

    Directory of Open Access Journals (Sweden)

    Jason Carnes

    2015-01-01

    Full Text Available 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.

  11. 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.

  12. Genome-wide analysis of chromatin structures in Trypanosoma brucei using high-resolution MNase-ChIP-seq.

    Science.gov (United States)

    Wedel, Carolin; Siegel, T Nicolai

    2017-09-01

    Specific DNA-protein interactions are the basis for many important cellular mechanisms like the regulation of gene expression or replication. Knowledge about the precise genomic locations of DNA-protein interactions is important because it provides insight into the regulation of these processes. Recently, we have adapted an approach that combines micrococcal nuclease (MNase) digestion of chromatin with chromatin immunoprecipitation in Trypanosoma brucei. Here, we describe in detail how this method can be used to map the genome-wide distribution of nucleosomes or other DNA-binding proteins at high resolution in T. brucei. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Pyrimidine Salvage Enzymes Are Essential for De Novo Biosynthesis of Deoxypyrimidine Nucleotides in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Christopher Leija

    2016-11-01

    Full Text Available The human pathogenic parasite Trypanosoma brucei possess both de novo and salvage routes for the biosynthesis of pyrimidine nucleotides. Consequently, they do not require salvageable pyrimidines for growth. Thymidine kinase (TK catalyzes the formation of dTMP and dUMP and is one of several salvage enzymes that appear redundant to the de novo pathway. Surprisingly, we show through analysis of TK conditional null and RNAi cells that TK is essential for growth and for infectivity in a mouse model, and that a catalytically active enzyme is required for its function. Unlike humans, T. brucei and all other kinetoplastids lack dCMP deaminase (DCTD, which provides an alternative route to dUMP formation. Ectopic expression of human DCTD resulted in full rescue of the RNAi growth phenotype and allowed for selection of viable TK null cells. Metabolite profiling by LC-MS/MS revealed a buildup of deoxypyrimidine nucleosides in TK depleted cells. Knockout of cytidine deaminase (CDA, which converts deoxycytidine to deoxyuridine led to thymidine/deoxyuridine auxotrophy. These unexpected results suggested that T. brucei encodes an unidentified 5'-nucleotidase that converts deoxypyrimidine nucleotides to their corresponding nucleosides, leading to their dead-end buildup in TK depleted cells at the expense of dTTP pools. Bioinformatics analysis identified several potential candidate genes that could encode 5'-nucleotidase activity including an HD-domain protein that we show catalyzes dephosphorylation of deoxyribonucleotide 5'-monophosphates. We conclude that TK is essential for synthesis of thymine nucleotides regardless of whether the nucleoside precursors originate from the de novo pathway or through salvage. Reliance on TK in the absence of DCTD may be a shared vulnerability among trypanosomatids and may provide a unique opportunity to selectively target a diverse group of pathogenic single-celled eukaryotes with a single drug.

  14. Knockdown of asparagine synthetase A renders Trypanosoma brucei auxotrophic to asparagine.

    Directory of Open Access Journals (Sweden)

    Inês Loureiro

    Full Text Available Asparagine synthetase (AS catalyzes the ATP-dependent conversion of aspartate into asparagine using ammonia or glutamine as nitrogen source. There are two distinct types of AS, asparagine synthetase A (AS-A, known as strictly ammonia-dependent, and asparagine synthetase B (AS-B, which can use either ammonia or glutamine. The absence of AS-A in humans, and its presence in trypanosomes, suggested AS-A as a potential drug target that deserved further investigation. We report the presence of functional AS-A in Trypanosoma cruzi (TcAS-A and Trypanosoma brucei (TbAS-A: the purified enzymes convert L-aspartate into L-asparagine in the presence of ATP, ammonia and Mg(2+. TcAS-A and TbAS-A use preferentially ammonia as a nitrogen donor, but surprisingly, can also use glutamine, a characteristic so far never described for any AS-A. TbAS-A knockdown by RNAi didn't affect in vitro growth of bloodstream forms of the parasite. However, growth was significantly impaired when TbAS-A knockdown parasites were cultured in medium with reduced levels of asparagine. As expected, mice infections with induced and non-induced T. brucei RNAi clones were similar to those from wild-type parasites. However, when induced T. brucei RNAi clones were injected in mice undergoing asparaginase treatment, which depletes blood asparagine, the mice exhibited lower parasitemia and a prolonged survival in comparison to similarly-treated mice infected with control parasites. Our results show that TbAS-A can be important under in vivo conditions when asparagine is limiting, but is unlikely to be suitable as a drug target.

  15. Chemical characterisation of Nigerian red propolis and its biological activity against Trypanosoma Brucei.

    Science.gov (United States)

    Omar, Ruwida M K; Igoli, John; Gray, Alexander I; Ebiloma, Godwin Unekwuojo; Clements, Carol; Fearnley, James; Ebel, Ru Angeli Edrada; Zhang, Tong; De Koning, Harry P; Watson, David G

    2016-01-01

    A previous study showed the unique character of Nigerian red propolis from Rivers State, Nigeria (RSN), with regards to chemical composition and activity against Trypanosoma brucei in comparison with other African propolis. To carry out fractionation and biological testing of Nigerian propolis in order to isolate compounds with anti-trypanosomal activity. To compare the composition of the RSN propolis with the composition of Brazilian red propolis. Profiling was carried out using HPLC-UV-ELSD and HPLC-Orbitrap-FTMS on extracts of two samples collected from RSN with data extraction using MZmine software. Isolation was carried out by normal phase and reversed phase MPLC. Elucidation of the compounds with a purity > 95% was performed by 1D/2D NMR HRMS and HRLC-MS(n) . Ten phenolic compounds were isolated or in the case of liquiritigenin partially purified. Data for nine of these correlated with literature reports of known compounds i.e. one isoflavanone, calycosin (1); two flavanones, liquiritigenin (2) and pinocembrin (5); an isoflavan, vestitol (3); a pterocarpan, medicarpin (4); two prenylflavanones, 8-prenylnaringenin (7) and 6-prenylnaringenin (8); and two geranyl flavonoids, propolin D (9) and macarangin (10). The tenth was elucidated as a previously undescribed dihydrobenzofuran (6). The isolated compounds were tested against Trypanosoma brucei and displayed moderate to high activity. Some of the compounds tested had similar activity against wild type T. brucei and two strains displaying pentamidine resistance. Nigerian propolis from RSN has some similarities with Brazilian red propolis. The propolis displayed anti-trypanosomal activity at a potentially useful level. Copyright © 2015 John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    Nikolay G Kolev

    2010-09-01

    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.

  17. Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells.

    Directory of Open Access Journals (Sweden)

    Deborah Frenkel

    2016-07-01

    Full Text Available After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/- retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK cell-mediated cytotoxicity: i B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR-/- and FcγRIIIa deficient (CD16-/- C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell-mediated cytotoxicity; ii administration of NK1.1 specific IgG2a (mAb PK136 but not irrelevant IgG2a (myeloma M9144 prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv purified NK cells from naïve C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei

  18. Variation of G-rich mitochondrial transcripts among stocks of Trypanosoma brucei.

    Science.gov (United States)

    Jasmer, D P; Feagin, J E; Payne, M; Stuart, K

    1987-01-15

    We have compared maxicircle transcripts from eight stocks of subspecies of Trypanosoma brucei. Transcripts from the rRNA and protein genes have a constant size among stocks and exhibit only minor variation in abundance. In contrast, four of the G+C rich sequences encode multiple transcripts that very markedly in size or abundance. Maxicircle nucleotide sequence comparison of three stocks shows very limited sequence divergence suggesting that sequence divergence may not explain the transcript variability. These results suggest that the G-rich transcripts do not encode proteins and that their variability among stocks may result from posttranscriptional processing events.

  19. 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.

  20. 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.

  1. Radiological characterization of spent control rod assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Lepel, E.A.; Robertson, D.E.; Thomas, C.W.; Pratt, S.L.; Haggard, D.L. [Pacific Northwest Lab., Richland, WA (United States)

    1995-10-01

    This document represents the final report of an ongoing study to provide radiological characterizations, classifications, and assessments in support of the decommissioning of nuclear power stations. This report describes the results of non-destructive and laboratory radionuclide measurements, as well as waste classification assessments, of BWR and PWR spent control rod assemblies. The radionuclide inventories of these spent control rods were determined by three separate methodologies, including (1) direct assay techniques, (2) calculational techniques, and (3) by sampling and laboratory radiochemical analyses. For the BWR control rod blade (CRB) and PWR burnable poison rod assembly (BPRA), {sup 60}Co and {sup 63}Ni, present in the stainless steel cladding, were the most abundant neutron activation products. The most abundant radionuclide in the PWR rod cluster control assembly (RCCA) was {sup 108m}Ag (130 yr halflife) produced in the Ag-In-Cd alloy used as the neutron poison. This radionuclide will be the dominant contributor to the gamma dose rate for many hundreds of years. The results of the direct assay methods agree very well ({+-}10%) with the sampling/radiochemical measurements. The results of the calculational methods agreed fairly well with the empirical measurements for the BPRA, but often varied by a factor of 5 to 10 for the CRB and the RCCA assemblies. If concentration averaging and encapsulation, as allowed by 10CFR61.55, is performed, then each of the entire control assemblies would be classified as Class C low-level radioactive waste.

  2. Broadband Vibration Attenuation Using Hybrid Periodic Rods

    Directory of Open Access Journals (Sweden)

    S. Asiri

    2008-12-01

    Full Text Available This paper presents both theoretically and experimentally a new kind of a broadband vibration isolator. It is a table-like system formed by four parallel hybrid periodic rods connected between two plates. The rods consist of an assembly of periodic cells, each cell being composed of a short rod and piezoelectric inserts. By actively controlling the piezoelectric elements, it is shown that the periodic rods can efficiently attenuate the propagation of vibration from the upper plate to the lower one within critical frequency bands and consequently minimize the effects of transmission of undesirable vibration and sound radiation. In such a system, longitudinal waves can propagate from the vibration source in the upper plate to the lower one along the rods only within specific frequency bands called the "Pass Bands" and wave propagation is efficiently attenuated within other frequency bands called the "Stop Bands". The spectral width of these bands can be tuned according to the nature of the external excitation. The theory governing the operation of this class of vibration isolator is presented and their tunable filtering characteristics are demonstrated experimentally as functions of their design parameters. This concept can be employed in many applications to control the wave propagation and the force transmission of longitudinal vibrations both in the spectral and spatial domains in an attempt to stop/attenuate the propagation of undesirable disturbances.

  3. Friction measuring device for control rod

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Tomomi.

    1994-03-18

    In the present invention, judgment for friction of control rods conducted upon periodical inspection of a BWR type power plant is conducted by automatic analysis and evaluation by digitalizing data of an operation pressure and an differential pressure of control rods. That is, a differential pressure detection means detects a pressure and a differential pressure of driving water of a control rod driving source. A data processing device conducts digital analysis and store data from the differential pressure detection means, as well as compares the data with set values to automatically judge the friction of the control rod to diagnose abnormality based on the changing trend of the analyzed data. According to the device of the present invention, data measured for the friction of a great number of control rods can be analyzed and judged automatically in a short period of time. Accordingly, evaluation can be conducted accurately even by less skilled operators. Further, when an abnormality is detected, the diagnosis thereof is conducted, so that the operation is simplified and an operator's burden upon inspection can be mitigated. (I.S.).

  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. Structural and functional insight into ADF/cofilin from Trypanosoma brucei.

    Science.gov (United States)

    Dai, Kun; Liao, Shanhui; Zhang, Jiahai; Zhang, Xuecheng; Tu, Xiaoming

    2013-01-01

    The ADF/cofilin family has been characterized as a group of actin-binding proteins critical for controlling the assembly of actin within the cells. In this study, the solution structure of the ADF/cofilin from Trypanosoma brucei (TbCof) was determined by NMR spectroscopy. TbCof adopts the conserved ADF/cofilin fold with a central β-sheet composed of six β-strands surrounded by five α-helices. Isothermal titration calorimetry experiments denoted a submicromolar affinity between TbCof and G-actin, and the affinity between TbCof and ADP-G-actin was five times higher than that between TbCof and ATP-G-actin at low ionic strength. The results obtained from electron microscopy and actin filament sedimentation assays showed that TbCof depolymerized but did not co-sediment with actin filaments and its ability of F-actin depolymerization was pH independent. Similar to actin, TbCof was distributed throughout the cytoplasm. All our data indicate a structurally and functionally conserved ADF/cofilin from Trypanosoma brucei.

  6. Structural and Functional Association of Trypanosoma brucei MIX Protein with Cytochrome c Oxidase Complex ▿ †

    Science.gov (United States)

    Zíková, Alena; Panigrahi, Aswini K.; Uboldi, Alessandro D.; Dalley, Rachel A.; Handman, Emanuela; Stuart, Kenneth

    2008-01-01

    A mitochondrial inner membrane protein, designated MIX, seems to be essential for cell viability. The deletion of both alleles was not possible, and the deletion of a single allele led to a loss of virulence and aberrant mitochondrial segregation and cell division in Leishmania major. However, the mechanism by which MIX exerts its effect has not been determined. We show here that MIX is also expressed in the mitochondrion of Trypanosoma brucei, and using RNA interference, we found that its loss leads to a phenotype that is similar to that described for Leishmania. The loss of MIX also had a major effect on cytochrome c oxidase activity, on the mitochondrial membrane potential, and on the production of mitochondrial ATP by oxidative phosphorylation. Using a tandem affinity purification tag, we found that MIX is associated with a multiprotein complex that contains subunits of the mitochondrial cytochrome c oxidase complex (respiratory complex IV), the composition of which was characterized in detail. The specific function of MIX is unknown, but it appears to be important for the function of complex IV and for mitochondrial segregation and cell division in T. brucei. PMID:18776036

  7. Base J and H3.V Regulate Transcriptional Termination in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Danae Schulz

    2016-01-01

    Full Text Available Trypanosoma brucei is a protozoan parasite that lacks many transcription factors found in other eukaryotes, such as those whose binding demarcates enhancers. T. brucei retains histone variants and modifications, however, and it is hypothesized that it relies on epigenetic marks to define transcription-related boundaries. The histone H3 variant (H3.V and an alternate nucleotide, base J (ß-D-glucosyl-hydroxymethyluracil, are two chromatin marks found at both transcription termination sites (TTSs and telomeres. Here, we report that the absence of both base J and H3.V result in transcription readthrough and the appearance of antisense transcripts near TTSs. Additionally, we find that maintaining the transcriptional silencing of pol I-transcribed telomeric Variant Surface Glycoprotein (VSG genes appears to be dependent on deposition of H3.V alone. Our study reveals that gene expression depends on different epigenetic cues depending on chromosomal location and on the transcribing polymerase. This work provides insight into how these signals may have evolved into the more nuanced and fine-tuned gene regulatory mechanisms observed in other model systems.

  8. Tail characteristics of Trypanosoma brucei mitochondrial transcripts are developmentally altered in a transcript-specific manner.

    Science.gov (United States)

    Gazestani, Vahid H; Hampton, Marshall; Shaw, Aubie K; Salavati, Reza; Zimmer, Sara L

    2018-02-01

    The intricate life cycle of Trypanosoma brucei requires extensive regulation of gene expression levels of the mtRNAs for adaptation. Post-transcriptional gene regulatory programs, including unencoded mtRNA 3' tail additions, potentially play major roles in this adaptation process. Intriguingly, T. brucei mitochondrial transcripts possess two distinct unencoded 3' tails, each with a differing functional role; i.e., while one type is implicated in RNA stability (in-tails), the other type appears associated with translation (ex-tails). We examined the degree to which tail characteristics differ among cytochrome c oxidase subunits I and III (CO1 and CO3), and NADH dehydrogenase subunit 1 (ND1) transcripts, and to what extent these characteristics differ developmentally. We found that CO1, CO3 and ND1 transcripts possess longer in-tails in the mammalian life stage. By mathematically modelling states of in-tail and ex-tail addition, we determined that the typical length at which an in-tail is extended to become an ex-tail differs by transcript and, in the case of ND1, by life stage. To the best of our knowledge, we provide the first evidence that developmental differences exist in tail length distributions of mtRNAs, underscoring the potential involvement of in-tail and ex-tail populations in mitochondrial post-transcriptional regulation mechanisms. Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  9. 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.

  10. 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.

  11. Secondary metabolites from Vietnamese marine invertebrates with activity against Trypanosoma brucei and T. cruzi.

    Science.gov (United States)

    Thao, Nguyen Phuong; No, Joo Hwan; Luyen, Bui Thi Thuy; Yang, Gyongseon; Byun, Soo Young; Goo, Junghyun; Kim, Kyung Tae; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Van Minh, Chau; Schmidt, Thomas J; Kang, Jong Seong; Kim, Young Ho

    2014-06-11

    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 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.

  12. 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.

  13. Bent Telescopic Rods in Patients With Osteogenesis Imperfecta.

    Science.gov (United States)

    Lee, R Jay; Paloski, Michael D; Sponseller, Paul D; Leet, Arabella I

    2016-09-01

    Telescopic rods require alignment of 2 rods to enable lengthening. A telescopic rod converts functionally into a solid rod if either rod bends, preventing proper engagement. Our goal was to characterize implant bending as a mode of failure of telescopic rods used in the treatment of osteogenesis imperfecta in children. We conducted a retrospective review of our osteogenesis imperfecta database for patients treated with intramedullary telescopic rods at our institution from 1992 through 2010 and identified 12 patients with bent rods. The 6 boys and 6 girls had an average age at the time of initial surgery of 3.1 years (range, 1.8 to 8.3 y) and a total of 51 telescoping rods. Clinic notes, operative reports, and radiographs were reviewed. The rods were analyzed for amount of lengthening, characteristics of bending, presence of cut out, or disengagement from an anchor point. Bends in the rods were characterized by their location on the implant component. The bent and straight rods were compared. Data were analyzed with the Mann-Whitney test (statistical significance set at P≤0.05). Of the 51 telescoping rods, 17 constructs (33%) bent. The average interval between surgery and rod bending was 4.0 years (range, 0.9 to 8.2 y). Before bending, 11 of 17 telescoping rods had routine follow-up radiographs for review. In 10 of the rods, bending was present when early signs of rod failure were first detected. Rod bending did not seem to be related to rod size. There was no area on the rod itself that seemed more susceptible to bending. Rod bending can be an early sign of impending rod failure. When rod bending is first noted, it may predispose the rod to other subsequent failures such as loss of proximal and distal fixation and cut out. Rod bending should be viewed as an indicator for closer monitoring of the patient and discussions regarding future need for rod exchange. Level III-retrospective review.

  14. Color dissociation artifacts in double Maddox rod cyclodeviation testing.

    Science.gov (United States)

    Simons, K; Arnoldi, K; Brown, M H

    1994-12-01

    The double Maddox rod test, based on a red Maddox rod in front of one eye and a clear Maddox rod in front of the other, is used to measure cyclodeviation, typically in patients with superior oblique muscle pareses. Discrepant results between the double Maddox rod test and other torsion measures, and reports of "paradoxic" cyclodeviation in the normal eye of some patients with superior oblique paresis, suggest the two-color format of the double Maddox rod test may produce artifactual torsion measures. Forty patients with superior oblique paresis were tested twice using the double Maddox rod test, reversing the red and white Maddox rods between eyes for the second test, and 18 were tested further with same-color red or clear Maddox rods in front of both eyes. With the standard double Maddox rod test, 33 (83%) of 40 patients localized their cyclodeviation to the eye viewing through the red Maddox rod, irrespective of laterality of the paresis or fixation preference. In all 33 patients, laterality of the perceived torsion changed between eyes when testing was repeated with red and white Maddox rods interchanged between eyes. With same-color Maddox rods before both eyes, 17 (94%) of 18 patients localized extorsion to the paretic eye. There was 7.6:1 ratio of luminance transmission and a 1.6:1 ratio of grating spatial frequency bandpass in the plano meridian between the clear and red Maddox rods, which appear to be responsible for the double Maddox rod test artifact. The traditional double Maddox rod test may produce artifactual cyclodeviation measurements. An alternative version of the test, based on same-color Maddox rods in front of both eyes, is proposed. The relatively high spatial frequency bandpass characteristics of the plano meridian of the Maddox rod (as high as 20/25 Snellen equivalent resolution through the clear Maddox rod) also suggests double Maddox rod testing should be conducted in a dark room to avoid biases from visual environment cues.

  15. 1H, 13C and 15N resonance assignments for a putative ADF/Cofilin from Trypanosoma brucei.

    Science.gov (United States)

    Dai, Kun; Yuan, Guangfa; Liao, Shanhui; Zhang, Jiahai; Tu, Xiaoming

    2011-10-01

    Actin-depolymerizing factor (ADF)/cofilin proteins are a family of actin-binding proteins expressed in almost all eukaryotic cells, and play a significant role in regulating actin-filament dynamics. Here we report the resonance assignments of a putative ADF/cofilin from Trypanosoma brucei for further understanding of the relationship between its structure and function.

  16. Variations in maxi-circle and mini-circle sequences in kinetoplast DNAs from different Trypanosoma brucei strains.

    NARCIS (Netherlands)

    P. Borst (Piet); F. Fase-Fowler; J.H.J. Hoeijmakers (Jan); A.C.C. Frasch

    1980-01-01

    textabstractWe have compared a total of 30 recognition sites for eight restriction endonucleases on the 20-kilobase-pair maxi-circle of kinetoplast DNAs from five different Trypanosoma brucei strains. In addition to three polymorphic sites were have found a 5 kilobase-pair region that is not cleaved

  17. THE CYTOSOLIC AND GLYCOSOMAL GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE FROM TRYPANOSOMA-BRUCEI - KINETIC-PROPERTIES AND COMPARISON WITH HOMOLOGOUS ENZYMES

    NARCIS (Netherlands)

    LAMBEIR, AM; LOISEAU, AM; KUNTZ, DA; VELLIEUX, FM; MICHELS, PAM; OPPERDOES, FR

    1991-01-01

    The protozoan haemoflagellate Trypanosoma brucei has two NAD-dependent glyceraldehyde-3-phosphate dehydrogenase isoenzymes, each with a different localization within the cell. One isoenzyme is found in the cytosol, as in other eukaryotes, while the other is found in the glycosome, a microbody-like

  18. 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...

  19. Haematological indices in Trypanosoma brucei brucei (Federe isolate infected Nigerian donkeys (Equus asinus treated with homidium and isometamidium chloride of ciprofloxacin in broiler chickens after single intravenous and intraingluvial administration

    Directory of Open Access Journals (Sweden)

    Queen Nneka Oparah

    2017-03-01

    Full Text Available The efficacy of intramuscular administration of Homidium chloride (Novidium® and Isometamidium chloride (Sécuridium® in Nigerian donkeys (Equus asinus experimentally infected with T. b. brucei (Federe isolate was investigated. Changes in haematological and serum biochemical indices were evaluated using clinical haematology and biochemistry methods. Red blood cell (RBC count for the negative control group was significantly higher than for the positive control, Novidium® and Sécuridium®-treatment groups. Haemoglobin (Hb concentration significantly reduced in the infected untreated group compared with other groups. Packed cell volume (PCV was significantly different between negative and positive controls, and also between the infected untreated and treatment groups. There was significant reduction in platelet counts post-infection and post-treatment. Mean corpuscular volume (MCV increased significantly in the treatment groups while mean corpuscular haemoglobin concentration (MCHC significantly reduced only in the Sécuridium®-treatment group. Lymphocyte count for infected untreated was non-significantly higher than for the uninfected controls, but treatment with both trypanocides recorded further increases, which were higher compared with that of the uninfected group. Post infection and treatment, aspartate aminotransferase (AST levels increased significantly. There were non-significant differences in electrolyte ion concentrations across the groups except for chloride ion which recorded a significant reduction in the Novidium®-treatment group. This experiment revealed that Nigerian donkeys infected with T. brucei brucei (Federe isolate developed symptoms of trypanosomosis; anaemia, lymphocytosis and thrombocytopenia. Treatment with the trypanocides ameliorated effects of the infection, and results suggest that immunosuppression may not be a substantial clinical manifestation of T. brucei brucei (Federe isolate trypanosomosis in Nigerian

  20. Sensitivity study of control rod depletion coefficients

    OpenAIRE

    Blomberg, Joel

    2015-01-01

    This report investigates the sensitivity of the control rod depletion coefficients, Sg, to different input parameters and how this affects the accumulated 10B depletion, β. Currently the coefficients are generated with PHOENIX4, but the geometries can be more accurately simulated in McScram. McScram is used to calculate Control Rod Worth, which in turn is used to calculate Nuclear End Of Life, and Sg cannot be generated in the current version of McScram. Therefore, it is also analyzed whether...

  1. Pattern selection dynamics in rod eutectics

    Science.gov (United States)

    Serefoglu, Melis

    The cooperative or diffusively coupled growth of multiple phases during solidification is one of the most widely observed and generally important classes of phase transformations in materials. Technologically, low melting temperature and small freezing range contribute to excellent casting fluidity and fine composite structures give rise to favorable properties. Both of these features contribute to the wide application of eutectic alloys in the casting, welding, and soldering of engineered components. Despite the broad-based technological importance, many fundamental questions regarding eutectic solidification remain unanswered, severely limiting our ability to employ computational methods in the prediction of microstructure for the effective design of new materials and processes. At the core of the most persistent questions, lie problems involving multicomponent thermodynamics, solid-liquid and solid-solid interfacial phenomena, morphological stability, chemical and thermal diffusion, and nucleation phenomena. In the current study, pattern selection dynamics in rod eutectics are investigated using systematic directional solidification experiments and phase field simulations. Directional solidification of a succinonitrile-camphor (SCN-DC) transparent alloy in thin slab geometries of various thicknesses reveals two main points. First, a velocity is indentified at which a transition in array basis vectors is observed in specimens with many rows of rods (i.e. bulk). This transition amounts to a 90 degree rotation of the rod array, shifting from alignment of 1st nearest neighbors to alignment of 2nd nearest neighbors along the slide wall. Second, significant array distortion is observed with decreasing slide thickness, delta, which ultimately leads to a single-row (quasi-3D) morphology where delta/lambda is on the order of unity. In our analysis of these observations, we use a geometrical model to describe the rod arrangement as a function of slide thickness, providing

  2. Sulfhydryl reagent susceptibility in proteins with high sequence similarity--triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi and Leishmania mexicana.

    Science.gov (United States)

    Garza-Ramos, G; Cabrera, N; Saavedra-Lira, E; Tuena de Gómez-Puyou, M; Ostoa-Saloma, P; Pérez-Montfort, R; Gómez-Puyou, A

    1998-05-01

    The amino acid sequence of triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana have an identity of 68%. Using the numbering system for the T. brucei enzyme, in their aligned sequences, the T. cruzi and leishmanial enzymes have cysteine residues at positions 14, 40, 117 and 126. T. brucei triosephosphate isomerase has cysteine residues at positions 14, 40 and 126, and a valine residue at position 117. Dithionitrobenzoic acid and methylmethane thiosulfonate inhibited the three enzymes, but T. cruzi triosephosphate isomerase was more than 100-fold more sensitive. The sensitivity of wild type triosephosphate isomerase from T. cruzi and T. brucei to the reagents was equal to that of the Cys117Val and Val117Cys mutant enzymes, respectively. Triosephosphate isomerases that have cysteine residues at positions 40 and 126, but lack a cysteine residue at position 14 are insensitive to methylmethane thiosulfonate. Thus, sulfhydryl reagents act on Cys14. At stoichiometric concentrations, the reagents inhibited the three enzymes as a consequence of structural alterations as measured by binding of 8-anilino-1-napthalenesulfonic acid to previously buried hydrophobic regions. However, the times for half-maximal alterations were 10 min, 15 hours and over 30 hours for T. cruzi, T. brucei and L. mexicana triosephosphate isomerase, respectively. The effect of pH on the action of the sulfhydryl reagents and molecular modeling showed no differences in the solvent accessibility of Cys14. As Cys14 forms part of the dimer interface, the data indicate that, in the three enzymes, barriers of different magnitude hinder the interaction between the sulfhydryl reagents and Cys14. The barrier is lower in T. cruzi triosephosphate isomerase which makes its dimer interface more susceptible for perturbation.

  3. Molecular profiles of Trypanosoma brucei, T. evansi and T. equiperdum stocks revealed by the random amplified polymorphic DNA method.

    Science.gov (United States)

    Lun, Zhao-Rong; Li, An-Xing; Chen, Xiao-Guang; Lu, Li-Xin; Zhu, Xing-Quan

    2004-03-01

    A total of 20 random primers (10-mers) were used to amplify RAPD markers from the genomic DNA of four Trypanosoma brucei stocks from East and West Africa, four T. evansi stocks from Africa, Asia and South America and one T. equiperdum stock from Asia. Between 65 and 88 reproducible fragments ranging from 0.25 to 2.15 kb were generated from these stocks depending on the stock/primer combination. The similarity coefficient (SC) among the stocks of T. brucei from Kenya, Nigeria, Tanzania and Zambia ranged from 62.9% to 74.0% (average: 67.6%). The SC among the stocks of T. evansi from Kenya, China and Brazil was 76.4%-95.5% (average: 86.4%), while the SC between T. evansi stock from China and Brazil was 95.5%. For T. evansi and T. equiperdum, the SC among the stocks ranged from 81.2% to 94.4% (average: 87.6%). As for the SC among the stocks of T. brucei and T. evansi, it was found to be from 54.7% to 80.3% (average: 68.0%) and the SC among stocks of T. brucei and T. equiperdum was from 59.4% to 76.9% (average: 68.1%). Our results indicate that the stocks of T. evansi from China and from Brazil are more closely related to the stock of T. equiperdum from China than to the stocks of T. evansi isolated from Kenya and to the stocks of T. brucei. In addition, our results further support the hypothesis that T. evansi stocks from China and Brazil could have arisen from a single lineage. The possible evolution of T. evansi and T. equiperdum is also discussed.

  4. ATG24 Represses Autophagy and Differentiation and Is Essential for Homeostasy of the Flagellar Pocket in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Ana Brennand

    Full Text Available We have previously identified homologs for nearly half of the approximately 30 known yeast Atg's in the genome database of the human sleeping sickness parasite Trypanosoma brucei. So far, only a few of these homologs have their role in autophagy experimentally confirmed. Among the candidates was the ortholog of Atg24 that is involved in pexophagy in yeast. In T. brucei, the peroxisome-like organelles named glycosomes harbor core metabolic processes, especially glycolysis. In the autotrophic yeast, autophagy is essential for adaptation to different nutritional environments by participating in the renewal of the peroxisome population. We hypothesized that autophagic turnover of the parasite's glycosomes plays a role in differentiation during its life cycle, which demands adaptation to different host environments and associated dramatic changes in nutritional conditions. We therefore characterized T. brucei ATG24, the T. brucei ortholog of yeast Atg24 and mammalian SNX4, and found it to have a regulatory role in autophagy and differentiation as well as endocytic trafficking. ATG24 partially localized on endocytic membranes where it was recruited via PI3-kinase III/VPS34. ATG24 silencing severely impaired receptor-mediated endocytosis of transferrin, but not adsorptive uptake of a lectin, and caused a major enlargement of the flagellar pocket. ATG24 silencing approximately doubled the number of autophagosomes, suggesting a role in repressing autophagy, and strongly accelerated differentiation, in accordance with a role of autophagy in parasite differentiation. Overexpression of the two isoforms of T. brucei ATG8 fused to GFP slowed down differentiation, possibly by a dominant-negative effect. This was overcome by ATG24 depletion, further supporting its regulatory role.

  5. An in vitro biomechanical comparison of single-rod, dual-rod, and dual-rod with transverse connector in anterior thoracolumbar instrumentation.

    Science.gov (United States)

    Reddy, Chandan G; Magnetta, Michael; Dahdaleh, Nader S; Demmer, Matthew; Iyamah, Kingsley Abode; Lim, Tae-Hong; Torner, James C; Hitchon, Patrick W

    2012-04-01

    After thoracolumbar corpectomy, standard anterolateral instrumentation may consist of dual rods with cross-connectors. However, when the vertebral bodies are small or involved with disease, only 1 rod may be possible. To compare the biomechanics of an in vitro L1 corpectomy model using 1 rod, 2 rods, or 2 rods with 2 cross-connectors. Eight fresh frozen human cadaveric spines were potted from T9 to L3. Pure moments of 1.5, 3, and 4.5 Nm were applied, and the motion of the spine was measured using 3 infrared cameras. Loads were applied in flexion and extension, right and left lateral bending, and right and left axial rotation. Each spine was first tested in the intact state. After performing an L1 corpectomy and replacement with a carbon fiber reinforced polymer cage, 3 constructs were tested: single rod (1R), dual rod (2R), and dual rod with 2 transverse connectors (CC). Analysis of variance suggests significant main effects of load (P < .0001), axis (P = .022), construct (P =.0019), and individual spine (P < .0001). Overall, the single-rod construct is significantly less rigid than the intact spine in axial rotation. There is no significant difference between the intact spine and either the dual-rod construct or the dual-rod cross-connector construct. In our in vitro model of anterior spinal stabilization after corpectomy and grafting, a single-rod construct is significantly less rigid than the intact spine. Addition of a second rod returns the rigidity of the spine to the intact state. A dual-rod cross-connector construct is significantly more rigid than a single-rod construct.

  6. Static in situ test of the axial power shaping rod and shim safety control rod mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Soberano, F T; Gannon, J A; Parlee, K A

    1982-08-01

    There are eight Axial Power Shaping Rods (APSRs) and 61 Shim Safety Control Rods (SSCRs) within the Three Mile Island (TMI) Unit 2 reactor core. This report describes the test results for all eight APSRs and three SSCRs. The tests were performed in situ from the Control Rod Drive (CRD) system logic cabinets and the transformer cabinets located in the cable spreading room. The tests were intended to determine the condition of the Absolute Position Indicators (APIs), the stator thermocouples, and the stators, and to assess each components' survival of the TMI-2 accident.

  7. Oligo(naphthylene–ethynylene) Molecular Rods

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  8. 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.

  9. 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.

  10. Further evidence from SSCP and ITS DNA sequencing support Trypanosoma evansi and Trypanosoma equiperdum as subspecies or even strains of Trypanosoma brucei

    OpenAIRE

    Wen, Y; Lun, Z; Zhu, X; Hide, G; Lai, D

    2016-01-01

    The subgenus Trypanozoon includes three species Trypanosoma brucei, Trypanosoma evansi and Trypanosoma equiperdum, which are morphologically identical and indistinguishable even using some molecular methods. In this study, PCR-based single strand conformation polymorphism (PCR-SSCP) was used to analyze the ribosomal DNA of the Trypanozoon species. Data indicate different patterns of ITS2 fragments between T. brucei, T. evansi and T. equiperdum by SSCP. Furthermore, analysis of total ITS seque...

  11. Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK

    Directory of Open Access Journals (Sweden)

    Pablo Wessig

    2015-01-01

    Full Text Available We developed a new type of molecular rods consisting of two (or more rigid units linked by a flexible joint. Consequently we called these constructs articulated rods (ARs. The syntheses of ARs were carried out by a flexible and modular approach providing access to a number of compounds with various functionalizations in terminal positions. First applications were presented with pyrene, cinnamoyl and anthracenyl labelled ARs.

  12. Trypanosoma brucei FKBP12 differentially controls motility and cytokinesis in procyclic and bloodstream forms.

    Science.gov (United States)

    Brasseur, Anaïs; Rotureau, Brice; Vermeersch, Marjorie; Blisnick, Thierry; Salmon, Didier; Bastin, Philippe; Pays, Etienne; Vanhamme, Luc; Pérez-Morga, David

    2013-02-01

    FKBP12 proteins are able to inhibit TOR kinases or calcineurin phosphatases upon binding of rapamycin or FK506 drugs, respectively. The Trypanosoma brucei FKBP12 homologue (TbFKBP12) was found to be a cytoskeleton-associated protein with specific localization in the flagellar pocket area of the bloodstream form. In the insect procyclic form, RNA interference-mediated knockdown of TbFKBP12 affected motility. In bloodstream cells, depletion of TbFKBP12 affected cytokinesis and cytoskeleton architecture. These last effects were associated with the presence of internal translucent cavities limited by an inside-out configuration of the normal cell surface, with a luminal variant surface glycoprotein coat lined up by microtubules. These cavities, which recreated the streamlined shape of the normal trypanosome cytoskeleton, might represent unsuccessful attempts for cell abscission. We propose that TbFKBP12 differentially affects stage-specific processes through association with the cytoskeleton.

  13. 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. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    DEFF Research Database (Denmark)

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K.

    2015-01-01

    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......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...... 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...

  15. Extracellular Vesicles from Trypanosoma brucei Mediate Virulence Factor Transfer and Cause Host Anemia.

    Science.gov (United States)

    Szempruch, Anthony J; Sykes, Steven E; Kieft, Rudo; Dennison, Lauren; Becker, Allison C; Gartrell, Anzio; Martin, William J; Nakayasu, Ernesto S; Almeida, Igor C; Hajduk, Stephen L; Harrington, John M

    2016-01-14

    Intercellular communication between parasites and with host cells provides mechanisms for parasite development, immune evasion, and disease pathology. Bloodstream African trypanosomes produce membranous nanotubes that originate from the flagellar membrane and disassociate into free extracellular vesicles (EVs). Trypanosome EVs contain several flagellar proteins that contribute to virulence, and Trypanosoma brucei rhodesiense EVs contain the serum resistance-associated protein (SRA) necessary for human infectivity. T. b. rhodesiense EVs transfer SRA to non-human infectious trypanosomes, allowing evasion of human innate immunity. Trypanosome EVs can also fuse with mammalian erythrocytes, resulting in rapid erythrocyte clearance and anemia. These data indicate that trypanosome EVs are organelles mediating non-hereditary virulence factor transfer and causing host erythrocyte remodeling, inducing anemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Compositional compartmentalization of the nuclear genomes of Trypanosoma brucei and Trypanosoma equiperdum.

    Science.gov (United States)

    Isacchi, A; Bernardi, G; Bernardi, G

    1993-12-06

    High molecular weight DNA preparations from Trypanosoma brucei and Trypanosoma equiperdum were fractionated by preparative centrifugation in a Cs2SO4 density gradient in the presence of BAMD, bis(acetatomercurimethyl)dioxane, a sequence-specific DNA ligand. Analytical centrifugation in CsCl of the DNA fractions so obtained showed that both DNAs had a bimodal distribution with two major peaks banding at 1.702-1.703 and 1.708 g/cm3 and representing 1/3 and 2/3 of total DNA, respectively. Several minor components were also detected. These results indicate that a compositional compartmentalization is not only found in the genome of vertebrates and plants, as already described, but also in those of protozoa such as Trypanosomes.

  17. 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

    2017-04-01

    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. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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.

  20. Trypanocidal action of bisphosphonium salts through a mitochondrial target in bloodstream form Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Abdulsalam A.M. Alkhaldi

    2016-04-01

    Full Text Available Lipophilic bisphosphonium salts are among the most promising antiprotozoal leads currently under investigation. As part of their preclinical evaluation we here report on their mode of action against African trypanosomes, the etiological agents of sleeping sickness. The bisphosphonium compounds CD38 and AHI-9 exhibited rapid inhibition of Trypanosoma brucei growth, apparently the result of cell cycle arrest that blocked the replication of mitochondrial DNA, contained in the kinetoplast, thereby preventing the initiation of S-phase. Incubation with either compound led to a rapid reduction in mitochondrial membrane potential, and ATP levels decreased by approximately 50% within 1 h. Between 4 and 8 h, cellular calcium levels increased, consistent with release from the depolarized mitochondria. Within the mitochondria, the Succinate Dehydrogenase complex (SDH was investigated as a target for bisphosphonium salts, but while its subunit 1 (SDH1 was present at low levels in the bloodstream form trypanosomes, the assembled complex was hardly detectable. RNAi knockdown of the SDH1 subunit produced no growth phenotype, either in bloodstream or in the procyclic (insect forms and we conclude that in trypanosomes SDH is not the target for bisphosphonium salts. Instead, the compounds inhibited ATP production in intact mitochondria, as well as the purified F1 ATPase, to a level that was similar to 1 mM azide. Co-incubation with azide and bisphosphonium compounds did not inhibit ATPase activity more than either product alone. The results show that, in T. brucei, bisphosphonium compounds do not principally act on succinate dehydrogenase but on the mitochondrial FoF1 ATPase.

  1. Trypanocidal action of bisphosphonium salts through a mitochondrial target in bloodstream form Trypanosoma brucei

    Science.gov (United States)

    Alkhaldi, Abdulsalam A.M.; Martinek, Jan; Panicucci, Brian; Dardonville, Christophe; Zíková, Alena; de Koning, Harry P.

    2015-01-01

    Lipophilic bisphosphonium salts are among the most promising antiprotozoal leads currently under investigation. As part of their preclinical evaluation we here report on their mode of action against African trypanosomes, the etiological agents of sleeping sickness. The bisphosphonium compounds CD38 and AHI-9 exhibited rapid inhibition of Trypanosoma brucei growth, apparently the result of cell cycle arrest that blocked the replication of mitochondrial DNA, contained in the kinetoplast, thereby preventing the initiation of S-phase. Incubation with either compound led to a rapid reduction in mitochondrial membrane potential, and ATP levels decreased by approximately 50% within 1 h. Between 4 and 8 h, cellular calcium levels increased, consistent with release from the depolarized mitochondria. Within the mitochondria, the Succinate Dehydrogenase complex (SDH) was investigated as a target for bisphosphonium salts, but while its subunit 1 (SDH1) was present at low levels in the bloodstream form trypanosomes, the assembled complex was hardly detectable. RNAi knockdown of the SDH1 subunit produced no growth phenotype, either in bloodstream or in the procyclic (insect) forms and we conclude that in trypanosomes SDH is not the target for bisphosphonium salts. Instead, the compounds inhibited ATP production in intact mitochondria, as well as the purified F1 ATPase, to a level that was similar to 1 mM azide. Co-incubation with azide and bisphosphonium compounds did not inhibit ATPase activity more than either product alone. The results show that, in T. brucei, bisphosphonium compounds do not principally act on succinate dehydrogenase but on the mitochondrial FoF1 ATPase. PMID:27054061

  2. Protein functional links in Trypanosoma brucei, identified by gene fusion analysis

    Directory of Open Access Journals (Sweden)

    Trimpalis Philip

    2011-07-01

    Full Text Available Abstract Background Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Results In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. Conclusions This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs.

  3. Sucker rod string design of the pumping systems

    Directory of Open Access Journals (Sweden)

    Chun Hua Liu

    2015-05-01

    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

  4. Dependence of control rod worth on fuel burnup

    Energy Technology Data Exchange (ETDEWEB)

    Savva, P., E-mail: savvapan@ipta.demokritos.g [NCSR ' DEMOKRITOS' , PoB 60228, 15310 Aghia Paraskevi (Greece); Varvayanni, M., E-mail: melina@ipta.demokritos.g [NCSR ' DEMOKRITOS' , PoB 60228, 15310 Aghia Paraskevi (Greece); Catsaros, N., E-mail: nicos@ipta.demokritos.g [NCSR ' DEMOKRITOS' , PoB 60228, 15310 Aghia Paraskevi (Greece)

    2011-02-15

    Research highlights: Diffusion and MC calculations for rod worth dependence on burnup and Xe in reactors. One-step rod withdrawal/insertion are used for rod worth estimation. The study showed that when Xe is present the rods worth is significantly reduced. Rod worth variation with burnup depends on rod position in core. Rod worth obtained with MC code is higher than that obtained from deterministic. - Abstract: One important parameter in the design and the analysis of a nuclear reactor core is the reactivity worth of the control rods, i.e. their efficiency to absorb excess reactivity. The control rod worth is affected by parameters such as the fuel burnup in the rod vicinity, the Xe concentration in the core, the operational time of the rod and its position in the core. In the present work, two different computational approaches, a deterministic and a stochastic one, were used for the determination of the rods worth dependence on the fuel burnup level and the Xe concentration level in a conceptual, symmetric reactor core, based on the MTR fuel assemblies used in the Greek Research Reactor (GRR-1). For the deterministic approach the neutronics code system composed by the SCALE modules NITAWL and XSDRN and the diffusion code CITATION was used, while for the stochastic one the Monte Carlo code TRIPOLI was applied. The study showed that when Xe is present in the core, the rods worth is significantly reduced, while the rod worth variation with increasing burnup depends on the rods position in the core grid. The rod worth obtained with the use of the Monte Carlo code is higher than the one obtained from the deterministic code.

  5. Distributed Mode Filtering Rod Fiber Amplifier With Improved Mode Stability

    DEFF Research Database (Denmark)

    Laurila, Marko; Alkeskjold, Thomas Tanggaard; Broeng, Jes

    2012-01-01

    We report 216W of average output power from a photonic crystal rod fiber amplifier. We demonstrate 44% power improvement before onset of the mode instability by operating the rod fiber in a leaky guiding regime.......We report 216W of average output power from a photonic crystal rod fiber amplifier. We demonstrate 44% power improvement before onset of the mode instability by operating the rod fiber in a leaky guiding regime....

  6. 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

  7. ROD INTERNAL PRESSURE QUANTIFICATION AND DISTRIBUTION ANALYSIS USING FRAPCON

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-01

    The discharge rod internal pressure (RIP) and cladding hoop stress (CHS) distributions are quantified forWatts BarNuclearUnit 1 (WBN1) fuel rods by modeling core cycle design data, intercycle assembly movements, operation data (including modeling significant trips and downpowers), and as-built fuel enrichments and densities of each fuel rod in FRAPCON-3.5. An alternate model for the amount of helium released from zirconium diboride (ZrB2) integral fuel burnable absorber (IFBA) layers is derived and applied to FRAPCON output data to quantify the RIP and CHS for these fuel rods. SCALE/Polaris is used to quantify fuel rod-specific 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 blankets. Cumulative distribution functions (CDFs) are prepared from the distribution of RIP predictions for all standard and IFBA rods. The provided CDFs allow for the determination of the portion of WBN1 fuel rods that exceed a specified RIP limit. Lastly, improvements to the computational methodology of FRAPCON are proposed.

  8. Measurement of the Speed of Sound in a Metal Rod.

    Science.gov (United States)

    Mak, Se-yuen; Ng, Yee-kong; Wu, Kam-wah

    2000-01-01

    Suggests two improved methods to measure the speed of sound in a metal rod. One employs a fast timer to measure the time required for a compression pulse to travel along the rod from end to end, and a second uses a microphone to measure the frequency of the fundamental mode of a freely suspending singing rod. (Author/ASK)

  9. 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 India...

  10. On the Vortex Sound from Rotating Rods

    Science.gov (United States)

    Yudin, E. Y.

    1947-01-01

    The motion of different bodies imersed in liquid or gaseous media is accompanied by characteristic sound which is excited by the formation of unstable surfaces of separation behind the body, usually disintegrating into a system of discrete vortices(such as the Karman vortex street due to the flow about an infintely long rod, etc.).In the noise from fans,pumps,and similar machtnery, vortexnQif3eI?Yequently predominates. The purpose of this work is to elucidate certain questions of the dependence ofthis sound upon the aerodynamic parameters and the tip speed of the rotating rods,or blades. Although scme material is given below,insufficientto calculate the first rough approximation to the solution of this question,such as the mechanics of vortex formation,never the less certain conclusions maybe found of practical application for the reduction of noise from rotating blades.

  11. Composites reinforcement by rods a SAS study

    CERN Document Server

    Urban, V; Pyckhout-Hintzen, W; Richter, D; Straube, E

    2002-01-01

    The mechanical properties of composites are governed by size, shape and dispersion degree of so-called reinforcing particles. Polymeric fillers based on thermodynamically driven microphase separation of block copolymers offer the opportunity to study a model system of controlled rod-like filler particles. We chose a triblock copolymer (PBPSPB) and carried out SAS measurements with both X-rays and neutrons, in order to characterize separately the hard phase and the cross-linked PB matrix. The properties of the material depend strongly on the way that stress is carried and transferred between the soft matrix and the hard fibers. The failure of the strain-amplification concept and the change of topological contributions to the free energy and scattering factor have to be addressed. In this respect the composite shows a similarity to a two-network system, i.e. interpenetrating rubber and rod-like filler networks. (orig.)

  12. Reduced Mitochondrial Membrane Potential Is a Late Adaptation of Trypanosoma brucei brucei to Isometamidium Preceded by Mutations in the γ Subunit of the F1Fo-ATPase.

    Directory of Open Access Journals (Sweden)

    Anthonius A Eze

    2016-08-01

    Full Text Available Isometamidium is the main prophylactic drug used to prevent the infection of livestock with trypanosomes that cause Animal African Trypanosomiasis. As well as the animal infective trypanosome species, livestock can also harbor the closely related human infective subspecies T. b. gambiense and T. b. rhodesiense. Resistance to isometamidium is a growing concern, as is cross-resistance to the diamidine drugs diminazene and pentamidine.Two isometamidium resistant Trypanosoma brucei clones were generated (ISMR1 and ISMR15, being 7270- and 16,000-fold resistant to isometamidium, respectively, which retained their ability to grow in vitro and establish an infection in mice. Considerable cross-resistance was shown to ethidium bromide and diminazene, with minor cross-resistance to pentamidine. The mitochondrial membrane potentials of both resistant cell lines were significantly reduced compared to the wild type. The net uptake rate of isometamidium was reduced 2-3-fold but isometamidium efflux was similar in wild-type and resistant lines. Fluorescence microscopy and PCR analysis revealed that ISMR1 and ISMR15 had completely lost their kinetoplast DNA (kDNA and both lines carried a mutation in the nuclearly encoded γ subunit gene of F1 ATPase, truncating the protein by 22 amino acids. The mutation compensated for the loss of the kinetoplast in bloodstream forms, allowing near-normal growth, and conferred considerable resistance to isometamidium and ethidium as well as significant resistance to diminazene and pentamidine, when expressed in wild type trypanosomes. Subsequent exposure to either isometamidium or ethidium led to rapid loss of kDNA and a further increase in isometamidium resistance.Sub-lethal exposure to isometamidium gives rise to viable but highly resistant trypanosomes that, depending on sub-species, are infective to humans and cross-resistant to at least some diamidine drugs. The crucial mutation is in the F1 ATPase γ subunit, which

  13. 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

    2010-01-01

    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

  14. 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.

  15. 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.

  16. Diagnosis of human trypanosomiasis, due to Trypanosoma brucei gambiense in central Africa, by the polymerase chain reaction

    OpenAIRE

    Penchenier, Laurent; Simo, G.; Grébaut, Pascal; Nkinin, S.; Laveissière, Claude; Herder, Stéphane

    2000-01-01

    During a mass screening of sleeping sickness conducted in 1998 and 1999, and involving 27,932 persons in Cameroon and the Central African Republic, we tested the polymerase chain reaction (PCR) on whole blood for the diagnosis of human African trypanosomiasis due to #Trypanosoma brucei gambiense$. The 1858 samples obtained were from 4 groups : 155 infected patients, 1432 serological suspects detected by the card agglutination test for trypanosomiasis (CATT), 222 negative controls living in th...

  17. 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.

  18. Apocytochrome b and other mitochondrial DNA sequences are differentially expressed during the life cycle of Trypanosoma brucei.

    OpenAIRE

    Feagin, J E; Jasmer, D P; Stuart, K

    1985-01-01

    Cytochromes and Krebs cycle enzymes are not detected in bloodstream forms of Trypanosoma brucei but are present in procyclic forms. We have analyzed transcription of mitochondrial sequences which contain the apocytochrome b gene and several other open reading frames (ORFs). Multiple transcripts map to individual DNA sequences located on both DNA strands. Larger low abundance transcripts map to multiple ORFs and may be precursor RNAs. Small abundant transcripts map to G + C rich sequences that...

  19. 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

    2010-04-01

    Full Text Available 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.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.The novel chemotypes identified here could represent leads for future therapeutic development against the African trypanosome.

  20. The orphan nuclear hormone receptor ERRβ controls rod photoreceptor survival

    Science.gov (United States)

    Onishi, Akishi; Peng, Guang-Hua; Poth, Erin M.; Lee, Daniel A.; Chen, Jichao; Alexis, Uel; de Melo, Jimmy; Chen, Shiming; Blackshaw, Seth

    2010-01-01

    Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor estrogen-related receptor β (ERRβ) as selectively expressed in rod photoreceptors. Overexpression of ERRβ induces expression of rod-specific genes in retinas of wild-type as well as Nrl−/− mice, which lack rod photoreceptors. Mutation of ERRβ results in dysfunction and degeneration of rods, whereas inverse agonists of ERRβ trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERRβ. ERRβ coordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing ERRβ activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that ERRβ is a critical regulator of rod photoreceptor function and survival, and suggest that ERRβ agonists may be useful in the treatment of certain retinal dystrophies. PMID:20534447

  1. 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

  2. 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.

  3. Outcomes of support rod usage in loop stoma formation.

    Science.gov (United States)

    Whiteley, Ian; Russell, Michael; Nassar, Natasha; Gladman, Marc A

    2016-06-01

    Traditionally, support rods have been used when creating loop stomas in the hope of preventing retraction. However, their effectiveness has not been clearly established. This study aimed to investigate the rate of stoma rod usage and its impact on stoma retraction and complication rates. A prospective cohort of 515 consecutive patients who underwent loop ileostomy/colostomy formation at a tertiary referral colorectal unit in Sydney, Australia were studied. Mortality and unplanned return to theatre rates were calculated. The primary outcome measure of interest was stoma retraction, occurring within 30 days of surgery. Secondary outcome measures included early stoma complications. The 10-year temporal trends for rod usage, stoma retraction, and complications were examined. Mortality occurred in 23 patients (4.1 %) and unplanned return to theatre in 4 patients (0.8 %). Stoma retraction occurred in four patients (0.78 %), all without rods. However, the rate of retraction was similar, irrespective of whether rods were used (P = 0.12). There was a significant decline in the use of rods during the study period (P stoma retraction rates. Early complications occurred in 94/432 patients (21.8 %) and were more likely to occur in patients with rods (64/223 versus 30/209 without rods, P Stoma retraction is a rare complication and its incidence is not significantly affected by the use of support rods. Further, complications are common post-operatively, and the rate appears higher when rods are used. The routine use of rods warrants judicious application. WHAT DOES THIS PAPER ADD TO THE LITERATURE?: It remains unclear whether support rods prevent stoma retraction. This study, the largest to date, confirms that stoma retraction is a rare complication and is not significantly affected by the use of rods. Consequently, routine rod usage cannot be recommended, particularly as it is associated with increased stoma complications.

  4. Extracellular-signal regulated kinase 8 of Trypanosoma brucei uniquely phosphorylates its proliferating cell nuclear antigen homolog and reveals exploitable properties.

    Science.gov (United States)

    Valenciano, Ana L; Knudsen, Giselle M; Mackey, Zachary B

    2016-10-17

    The Trypanosoma brucei subspecies T. brucei gambiense and T. brucei rhodesiense are vector-borne pathogens that cause sleeping sickness also known as Human African Trypanosomiasis (HAT), which is fatal if left untreated. The drugs that treat HAT are ineffective and cause toxic side effects. One strategy for identifying safer and more effective HAT drugs is to therapeutically exploit essential gene targets in T. brucei. Genes that make up a basic mitogen-activated protein kinase (MAPK) network are present in T. brucei. Tb927.10.5140 encodes an essential MAPK that is homologous to the human extracellular-signal regulated kinase 8 (HsERK8) which forms a tight complex with the replication factor proliferating cell nuclear antigen (PCNA) to stabilize intracellular PCNA levels. Here we demonstrate that (TbPCNA) is uniquely phos-phorylated on serine (S) and threonine (T) residues in T. brucei and that TbERK8 phosphorylates TbPCNA at each of these residues. The ability of an ERK8 homolog to phosphorylate a PCNA homolog is a novel biochemical property that is first demonstrated here in T. brucei and may be unique to this pathogen. We demonstrate that the potent HsERK8 inhibitor Ro318220, has an IC50 for TbERK8 that is several hundred times higher than its reported IC50 for HsERK8. This indicated that the active sites of TbERK8 and HsERK8 can be selectively inhibited, which provides a rational basis for discovering inhibitors that specifically target this essential parasite MAPK to kill the parasite.

  5. 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.

  6. Channel-forming activities in the glycosomal fraction from the bloodstream form of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Melisa Gualdron-López

    Full Text Available BACKGROUND: Glycosomes are a specialized form of peroxisomes (microbodies present in unicellular eukaryotes that belong to the Kinetoplastea order, such as Trypanosoma and Leishmania species, parasitic protists causing severe diseases of livestock and humans in subtropical and tropical countries. The organelles harbour most enzymes of the glycolytic pathway that is responsible for substrate-level ATP production in the cell. Glycolysis is essential for bloodstream-form Trypanosoma brucei and enzymes comprising this pathway have been validated as drug targets. Glycosomes are surrounded by a single membrane. How glycolytic metabolites are transported across the glycosomal membrane is unclear. METHODS/PRINCIPAL FINDINGS: We hypothesized that glycosomal membrane, similarly to membranes of yeast and mammalian peroxisomes, contains channel-forming proteins involved in the selective transfer of metabolites. To verify this prediction, we isolated a glycosomal fraction from bloodstream-form T. brucei and reconstituted solubilized membrane proteins into planar lipid bilayers. The electrophysiological characteristics of the channels were studied using multiple channel recording and single channel analysis. Three main channel-forming activities were detected with current amplitudes 70-80 pA, 20-25 pA, and 8-11 pA, respectively (holding potential +10 mV and 3.0 M KCl as an electrolyte. All channels were in fully open state in a range of voltages ±150 mV and showed no sub-conductance transitions. The channel with current amplitude 20-25 pA is anion-selective (P(K+/P(Cl-∼0.31, while the other two types of channels are slightly selective for cations (P(K+/P(Cl- ratios ∼1.15 and ∼1.27 for the high- and low-conductance channels, respectively. The anion-selective channel showed an intrinsic current rectification that may suggest a functional asymmetry of the channel's pore. CONCLUSIONS/SIGNIFICANCE: These results indicate that the membrane of glycosomes

  7. Steroid Alkaloids from Holarrhena africana with Strong Activity against Trypanosoma brucei rhodesiense.

    Science.gov (United States)

    Nnadi, Charles Okeke; Nwodo, Ngozi Justina; Kaiser, Marcel; Brun, Reto; Schmidt, Thomas J

    2017-07-06

    In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, "sleeping sickness"), we have investigated extracts from the leaves and bark of the West African Holarrhenaafricana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid. Impressive activities (IC50 in µM) against Tbr were recorded for 3β-holaphyllamine (0.40 ± 0.28), 3α-holaphyllamine (0.37 ± 0.16), 3β-dihydroholaphyllamine (0.67 ± 0.03), N-methylholaphyllamine (0.08 ± 0.01), conessimine (0.17 ± 0.08), conessine (0.42 ± 0.09), isoconessimine (0.17 ± 0.11) and holarrhesine (0.12 ± 0.08) with selectivity indices ranging from 13 to 302. Based on comparison of the structures of this congeneric series of steroid alkaloids and their activities, structure-activity relationships (SARs) could be established. It was found that a basic amino group at position C-3 of the pregnane or pregn-5-ene steroid nucleus is required for a significant anti-trypanosomal activity. The mono-methylated amino group at C-3 represents an optimum for activity. ∆(5,6) unsaturation slightly increased the activity while hydrolysis of C-12β ester derivatives led to a loss of activity. An additional amino group at C-20 engaged in a pyrrolidine ring closed towards C-18 significantly increased the selectivity index of the compounds. Our findings provide useful empirical data for further development of steroid alkaloids as a novel class of anti-trypanosomal compounds which represent a promising starting point towards new drugs to combat human African trypanosomiasis.

  8. Steroid Alkaloids from Holarrhena africana with Strong Activity against Trypanosoma brucei rhodesiense

    Directory of Open Access Journals (Sweden)

    Charles Okeke Nnadi

    2017-07-01

    Full Text Available In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, “sleeping sickness”, we have investigated extracts from the leaves and bark of the West African Holarrhena africana (syn. Holarrhena floribunda; Apocynaceae. The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT. Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid. Impressive activities (IC50 in µM against Tbr were recorded for 3β-holaphyllamine (0.40 ± 0.28, 3α-holaphyllamine (0.37 ± 0.16, 3β-dihydroholaphyllamine (0.67 ± 0.03, N-methylholaphyllamine (0.08 ± 0.01, conessimine (0.17 ± 0.08, conessine (0.42 ± 0.09, isoconessimine (0.17 ± 0.11 and holarrhesine (0.12 ± 0.08 with selectivity indices ranging from 13 to 302. Based on comparison of the structures of this congeneric series of steroid alkaloids and their activities, structure-activity relationships (SARs could be established. It was found that a basic amino group at position C-3 of the pregnane or pregn-5-ene steroid nucleus is required for a significant anti-trypanosomal activity. The mono-methylated amino group at C-3 represents an optimum for activity. ∆5,6 unsaturation slightly increased the activity while hydrolysis of C-12β ester derivatives led to a loss of activity. An additional amino group at C-20 engaged in a pyrrolidine ring closed towards C-18 significantly increased the selectivity index of the compounds. Our findings provide useful empirical data for further development of steroid alkaloids as a novel class of anti-trypanosomal compounds which represent a promising starting point towards new drugs to combat human African trypanosomiasis.

  9. The ATLAS tile calorimeter ROD injector and multiplexer board

    Energy Technology Data Exchange (ETDEWEB)

    Valero, A., E-mail: alberto.valero@cern.c [Instituto de Fisica Corpuscular, Universidad de Valencia-CSIC, Paterna, 46071 Valencia (Spain); Castillo, V.; Ferrer, A. [Instituto de Fisica Corpuscular, Universidad de Valencia-CSIC, Paterna, 46071 Valencia (Spain); Gonzalez, V. [Departamento de Ingenieria electronica, Universidad de Valencia, Burjassot, 46100 Valencia (Spain); Hernandez, Y.; Higon, E. [Instituto de Fisica Corpuscular, Universidad de Valencia-CSIC, Paterna, 46071 Valencia (Spain); Sanchis, E. [Departamento de Ingenieria electronica, Universidad de Valencia, Burjassot, 46100 Valencia (Spain); Solans, C. [Instituto de Fisica Corpuscular, Universidad de Valencia-CSIC, Paterna, 46071 Valencia (Spain); Torres, J. [Departamento de Ingenieria electronica, Universidad de Valencia, Burjassot, 46100 Valencia (Spain); Valls, J.A. [Instituto de Fisica Corpuscular, Universidad de Valencia-CSIC, Paterna, 46071 Valencia (Spain)

    2011-02-11

    The ATLAS Tile Calorimeter is a sampling detector composed by cells made of iron-scintillator tiles. The calorimeter cell signals are digitized in the front-end electronics and transmitted to the Read-Out Drivers (RODs) at the first level trigger rate. The ROD receives triggered data from up to 9856 channels and provides the energy, phase and quality factor of the signals to the second level trigger. The back-end electronics is divided into four partitions containing eight RODs each. Therefore, a total of 32 RODs are used to process and transmit the data of the TileCal detector. In order to emulate the detector signals in the production and commissioning of ROD modules a board called ROD Injector and Multiplexer Board (RIMBO) was designed. In this paper, the RIMBO main functional blocks, PCB design and the different operation modes are described. It is described the crucial role of the board within the TileCal ROD test-bench in order to emulate the front-end electronics during the validation of ROD boards as well as during the evaluation of the ROD signal reconstruction algorithms. Finally, qualification and performance results for the injection operation mode obtained during the Tile Calorimeter ROD production tests are presented.

  10. Improvement on the visualization of cytoskeletal structures of protozoan parasites using high-resolution field emission scanning electron microscopy (FESEM).

    Science.gov (United States)

    Sant'Anna, Celso; Campanati, Loraine; Gadelha, Catarina; Lourenço, Daniela; Labati-Terra, Letícia; Bittencourt-Silvestre, Joana; Benchimol, Marlene; Cunha-e-Silva, Narcisa Leal; De Souza, Wanderley

    2005-07-01

    The association of high resolution field emission scanning electron microscopy (FESEM), with a more efficient system of secondary electron (SE) collection and in-lens specimen position, provided a great improvement in the specimen's topographical contrast and in the generation of high-resolution images. In addition, images obtained with the use of the high-resolution backscattered electrons (BSE) detector provided a powerful tool for immunocytochemical analysis of biological material. In this work, we show the contribution of the FESEM to the detailed description of cytoskeletal structures of the protozoan parasites Herpetomonas megaseliae, Trypanosoma brucei and Giardia lamblia. High-resolution images of detergent extracted H. megaseliae and T. brucei showed the profile of the cortical microtubules, also known as sub-pellicular microtubules (SPMT), and protein bridges cross-linking them. Also, it was possible to visualize fine details of the filaments that form the lattice-like structure of the paraflagellar rod (PFR) and its connection with the axoneme. In G. lamblia, it was possible to observe the intricate structure of the adhesive disk, funis (a microtubular array) and other cytoskeletal structures poorly described previously. Since most of the stable cytoskeletal structures of this protozoan rely on tubulin, we used the BSE images to accurately map immunolabeled tubulin in its cytoskeleton. Our results suggest that the observation of detergent extracted parasites using FESEM associated to backscattered analysis of immunolabeled specimens represents a new approach for the study of parasite cytoskeletal elements and their protein associations.

  11. Rod strain after pedicle subtraction osteotomy

    DEFF Research Database (Denmark)

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

    2016-01-01

    Pedicle subtraction osteotomy (PSO) can provide major sagittal correction for adult spinal deformity, sometimes achieving correction greater than 308. Surgeons have reported failure rates up to 30% within 2 years, increasing to 46% after 4 to 5 years (SDC Figure 1, http://links.lww.com/BRS/B87......). Revision following failure is difficult on the patient. PSO has achieved positive outcomes, but when used to correct posture in older patients with spinal deformity and fixed sagittal imbalance, rod breakage often leads to multiple surgical revisions. These complications must be avoided....

  12. Rodded shutdown system for a nuclear reactor

    Science.gov (United States)

    Golden, Martin P.; Govi, Aldo R.

    1978-01-01

    A top mounted nuclear reactor diverse rodded shutdown system utilizing gas fed into a pressure bearing bellows region sealed at the upper extremity to an armature. The armature is attached to a neutron absorber assembly by a series of shafts and connecting means. The armature is held in an uppermost position by an electromagnet assembly or by pressurized gas in a second embodiment. Deenergizing the electromagnet assembly, or venting the pressurized gas, causes the armature to fall by the force of gravity, thereby lowering the attached absorber assembly into the reactor core.

  13. 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)

  14. Nonlinear localized elastoplastic waves in a rod

    Science.gov (United States)

    Erofeev, V. I.; Leonteva, A. V.; Malkhanov, A. O.

    2017-11-01

    It has been shown that longitudinal nonlinear stationary elastic-plastic waves can be formed in a rod. Waves can be both periodic and solitary (solitons), which is determined by the index of strain hardening of the material.The velocity of propagation of such waves is less than the speed of the elastic shear wave. Along with classical solitons, so-called “embedded solitons” can be formed, that is, double solitons, one of which with a smaller amplitude and widthis located inside the other with a larger amplitude and width.

  15. Uspon silovatelja: etnicitet, rod i nasilje

    OpenAIRE

    Mežnarić, Silva

    1993-01-01

    Članak raspravlja o uporabi silovanja kao politike u slučajevima kada se, do tragičnih posljedica, ukrštaju nasilje, rod i etnicitet. Prvo se ispituje kampanja srbijanskih medija 1990. na Kosovu protiv Albanaca kao silovatelja; zatim se analizira upotreba silovanja u prinudnom etničkom čišćenju prilikom srpske agresije na Bosnu, 1992-1993. Pokazuje se da je kampanja na Kosovu bila predigra stvarnom silovanju u Bosni. U oba je slučaja silovanje poslužilo u ograđivanju teritorija i definiranju ...

  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...

  17. Polysomes of Trypanosoma brucei: Association with Initiation Factors and RNA-Binding Proteins.

    Directory of Open Access Journals (Sweden)

    Cornelia Klein

    Full Text Available We report here the results of experiments designed to identify RNA-binding proteins that might be associated with Trypanosoma brucei polysomes. After some preliminary mass spectrometry of polysomal fractions, we investigated the distributions of selected tagged proteins using sucrose gradients and immunofluorescence. As expected, the polysomal fractions contained nearly all annotated ribosomal proteins, the translation-associated protein folding complex, and many translation factors, but also many other abundant proteins. Results suggested that cap-binding proteins EIF4E3 and EIF4E4 were associated with both free and membrane-bound polysomes. The EIF4E binding partners EIF4G4 and EIF4G3 were present but the other EIF4E and EIF4G paralogues were not detected. The dominant EIF4E in the polysomal fraction is EIF4E4 and very few polysomal mRNAs are associated with EIF4G. Thirteen potential mRNA-binding proteins were detected in the polysomes, including the known polysome-associated protein RBP42. The locations of two of the other proteins were tested after epitope tagging: RBP29 was in the nucleus and ZC3H29 was in the cytoplasm. Quantitative analyses showed that specific association of an RNA-binding protein with the polysome fraction in sucrose gradients will not be detected if the protein is in more than 25-fold molar excess over its target binding sites.

  18. 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.

  19. Functional analysis of TOEFAZ1 uncovers protein domains essential for cytokinesis in Trypanosoma brucei.

    Science.gov (United States)

    Sinclair-Davis, Amy N; McAllaster, Michael R; de Graffenried, Christopher L

    2017-10-09

    The parasite Trypanosoma brucei is highly polarized, including a flagellum that is attached along the cell surface by the flagellum attachment zone (FAZ). During cell division, the new FAZ positions the cleavage furrow, which ingresses from the anterior tip of the cell towards the posterior. We recently identified Tip Of the Extending FAZ protein 1 (TOEFAZ1) as an essential protein in trypanosome cytokinesis. We analyzed the localization and function of TOEFAZ1 domains using overexpression and RNAi complementation. TOEFAZ1 comprises three domains with separable functions: an N-terminal α-helical domain that may be involved in FAZ recruitment, a central intrinsically disordered domain that retains the morphogenic kinase TbPLK at the new FAZ tip, and a C-terminal zinc finger domain necessary for TOEFAZ1 oligomerization. Both the N-terminal and C-terminal domains are essential for TOEFAZ1 function, but TbPLK retention at the FAZ is not necessary for cytokinesis. The feasibility of alternate cytokinetic pathways that do not employ TOEFAZ1 are also assessed. Our results show that TOEFAZ1 is a multimeric scaffold for recruiting proteins that control the timing and location of cleavage furrow ingression. © 2017. Published by The Company of Biologists Ltd.

  20. Spliced leader trapping reveals widespread alternative splicing patterns in the highly dynamic transcriptome of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Daniel Nilsson

    2010-08-01

    Full Text Available Trans-splicing of leader sequences onto the 5'ends of mRNAs is a widespread phenomenon in protozoa, nematodes and some chordates. Using parallel sequencing we have developed a method to simultaneously map 5'splice sites and analyze the corresponding gene expression profile, that we term spliced leader trapping (SLT. The method can be applied to any organism with a sequenced genome and trans-splicing of a conserved leader sequence. We analyzed the expression profiles and splicing patterns of bloodstream and insect forms of the parasite Trypanosoma brucei. We detected the 5' splice sites of 85% of the annotated protein-coding genes and, contrary to previous reports, found up to 40% of transcripts to be differentially expressed. Furthermore, we discovered more than 2500 alternative splicing events, many of which appear to be stage-regulated. Based on our findings we hypothesize that alternatively spliced transcripts present a new means of regulating gene expression and could potentially contribute to protein diversity in the parasite. The entire dataset can be accessed online at TriTrypDB or through: http://splicer.unibe.ch/.

  1. 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.

  2. 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.

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

    Science.gov (United States)

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

    2016-04-20

    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-silencing reporter strain, we observed that chromatin of the active BES remains open for at least 24 hours after blocking transcription. This conformation is independent of the cell-cycle stage, but dependent upon TDP1, a high mobility group box protein. For two days after BES silencing, we detected a transient and reversible derepression of several silent BESs within the population, suggesting that cells probe other BESs before commitment to one, which is complete by 48 hours. FACS sorting and subsequent subcloning confirmed that probing cells are switching intermediates capable of returning to the original BES, switch to the probed BES or to a different BES. We propose that regulation of BES chromatin structure is an epigenetic mechanism important for successful antigenic switching. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Duplicated paralogous genes subject to positive selection in the genome of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Richard D Emes

    2008-05-01

    Full Text Available Whole genome studies have highlighted duplicated genes as important substrates for adaptive evolution. We have investigated adaptive evolution in this class of genes in the human parasite Trypanosoma brucei, as indicated by the ratio of non-synonymous (amino-acid changing to synonymous (amino acid retaining nucleotide substitution rates.We have identified duplicated genes that are most rapidly evolving in this important human parasite. This is the first attempt to investigate adaptive evolution in this species at the codon level. We identify 109 genes within 23 clusters of paralogous gene expansions to be subject to positive selection.Genes identified include surface antigens in both the mammalian and insect host life cycle stage suggesting that competitive interaction is not solely with the adaptive immune system of the mammalian host. Also surface transporters related to drug resistance and genes related to developmental progression are detected. We discuss how adaptive evolution of these genes may highlight lineage specific processes essential for parasite survival. We also discuss the implications of adaptive evolution of these targets for parasite biology and control.

  5. COMPUTER MODEL OF TEMPERATURE DISTRIBUTION IN OPTICALLY PUMPED LASER RODS

    Science.gov (United States)

    Farrukh, U. O.

    1994-01-01

    Managing the thermal energy that accumulates within a solid-state laser material under active pumping is of critical importance in the design of laser systems. Earlier models that calculated the temperature distribution in laser rods were single dimensional and assumed laser rods of infinite length. This program presents a new model which solves the temperature distribution problem for finite dimensional laser rods and calculates both the radial and axial components of temperature distribution in these rods. The modeled rod is either side-pumped or end-pumped by a continuous or a single pulse pump beam. (At the present time, the model cannot handle a multiple pulsed pump source.) The optical axis is assumed to be along the axis of the rod. The program also assumes that it is possible to cool different surfaces of the rod at different rates. The user defines the laser rod material characteristics, determines the types of cooling and pumping to be modeled, and selects the time frame desired via the input file. The program contains several self checking schemes to prevent overwriting memory blocks and to provide simple tracing of information in case of trouble. Output for the program consists of 1) an echo of the input file, 2) diffusion properties, radius and length, and time for each data block, 3) the radial increments from the center of the laser rod to the outer edge of the laser rod, and 4) the axial increments from the front of the laser rod to the other end of the rod. This program was written in Microsoft FORTRAN77 and implemented on a Tandon AT with a 287 math coprocessor. The program can also run on a VAX 750 mini-computer. It has a memory requirement of about 147 KB and was developed in 1989.

  6. Grey Rod Test in HANARO Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Choo, K. N.; Kim, B. G.; Kang, Y. H. (and others)

    2008-08-15

    Westinghouse/KAERI/KNF agreed to perform an irradiation test in the HANARO reactor to obtain irradiation data on the new grey rods that will be part of an AP1000 system. As a preliminary test, two samples containing pure Ag (Reference) and Ag-In-Cd materials provided by Westinghouse Electric Company (WEC) were inserted in a KNF irradiation capsule of 07M-13N. The specimens were irradiated for 95.19days (4 cycles) in the CT test hole of the HANARO of a 30MW thermal output to have a fast neutron fluence of 1.11x10{sup 21}(n/cm{sup 2}) (E>1.0MeV). This report provides all the test conditions and data obtained during the irradiation test of the grey rods in HANARO requested by Westinghouse. The test was prepared according to the meeting minutes (June 26, 2007) and the on-going subject test was stopped midway by the request of Westinghouse.

  7. Steam by-pass reciprocating rod pump

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, B. [Weatherford, Edmonton, AB (Canada)

    2008-07-01

    This article presented the design details of Weatherford's steam by-pass reciprocating rod rod pump which was designed to work under specific well conditions and individual applications, including Imperial Oil's Cold Lake bitumen recovery project located 230 km northeast of Edmonton, Alberta. Imperial Oil uses a cyclic steam stimulation (CSS) process to enhance bitumen recovery from the Clearwater oil sand reservoir. A typical wellbore reach can be up to 700 m and 80 degrees deviation at a target depth of 455 m TVD. These long well bore reaches along with high bottomhole angles and high produced fluid viscosities complicate the design of the artificial lift, which is essentially a modified conventional API pump. The hold-down section is a friction ring design incorporating stainless steel friction rings to provide positive holding force. The steam by-pass coupling is a reduced-diameter tube fitting between the API pump and the friction ring hold-down section. Three stages of the Imperial Cold Lake operation were described, namely the steam injection stage, soak phase stage and production stage. Typically, the steam by-pass pump is suspended in the tubing for the entire cycle. This presentation reviewed the operating steps of the pump, whose average run time in the field is about 15 months, depending on the potential for scaling or sand influx. tab., figs.

  8. Push rod for moving mine cars

    Energy Technology Data Exchange (ETDEWEB)

    Shtokman, I.G.; Apukhtin, A.S.; Dudnik, M.Z.; Remizov, I.P.; Shakhtar, P.S.

    1981-01-01

    In the operation of the known pushrods for haulage of cars on horizontal shafts, it becomes necessary to slow down the moving cars. In normal working modes, braking of the cars is guaranteed by counter engagement of the linear motors. However when emergency situations develop, for example if there is some lack of voltage in the network, it becomes necessary to brake the cars which this device cannot guarantee. The purpose of the invention is to brake the cars with disconnection of power. The goal is achieved because the push rod containing a frame with inductors attached to it installed on the sides of the rail path opposite each other, in which the cabs of the cars fill the role of the rotor, the support stands are connected to the inductors by means of springs, and the frame with inductors is hinged to the support stand and has mechanism for regulating the gap between the inductors and the cars, made in the form of rollers attached to the frame for interaction with the outer sidewalls of the car is equipped with friction elements installed on the frame and electromagnets with spring-rods installed on the support stands arranged with the possibility of interacting with the frame, and each friction element is arranged with the possibility of interacting with the rollers.

  9. Application of polyimide actuator rod seals

    Science.gov (United States)

    Watermann, A. W.; Gay, B. F.; Robinson, E. D.; Srinath, S. K.; Nelson, W. G.

    1972-01-01

    Development of polyimide two-stage hydraulic actuator rod seals for application in high-performance aircraft was accomplished. The significant portion of the effort was concentrated on optimization of the chevron and K-section second-stage seal geometries to satisfy the requirements for operation at 450 K (350 F) with dynamic pressure loads varying between 200 psig steady-state and 1500 psig impulse cycling. Particular significance was placed on reducing seal gland dimension by efficiently utilizing the fatigue allowables of polyimide materials. Other objectives included investigation of pressure balancing techniques for first-stage polyimide rod seals for 4000 psig 450 K(350 F) environment and fabrication of a modular retainer for the two-stage combination. Seals were fabricated in 0.0254 m (1.0in.) and 0.0635 m (2.5in.) sizes and tested for structural integrity, frictional resistance, and endurance life. Test results showed that carefully designed second stages using polyimides could be made to satisfy the dynamic return pressure requirements of applications in high-performance aircraft. High wear under full system pressure indicated that further research is necessary to obtain an acceptable first-stage design. The modular retainer was successfully tested and showed potential for new actuator applications.

  10. On the Wave Stresses in the Rods of Anvil Hammers

    Directory of Open Access Journals (Sweden)

    V. M. Sinitskiy

    2014-01-01

    Full Text Available With operating anvil hammers, there are rigid impacts of die tools, and as a result, almost instantaneous impact stops of the falling parts of hammer. Such operating conditions lead to the accelerated breakdowns of rods because of significant wave stresses arising in them. Common differential and integral methods to estimate wave stresses are widespread in engineering practice. However, to use them a researcher has to possess certain skills and special software. We consider the method for estimating the wave stresses in the rods of anvil hammers based on Laplace transforms (LT of wave equation. The article shows a procedure to set up and solve differential wave equations by operator method. These equations describe the wave propagation process of strains and stresses in the rods of anvil hammers with rigid impact and taking into account a damping rod connection with the head of hammer. The method takes into consideration an influence of both piston and rod weights and of mechanical and geometrical characteristics of rod on the stress value in the placement of rod in hammer head. Results analysis shows that a sufficiently efficient method for practical improving the durability of rods is the method of damping impact load on the rod through setting the damping devices in the form either of elastic "pad" of one or another design or of hydraulic shock absorbers in the placement of its connection with the hammer head. In this case there is a change of the wave front, it becomes flatter. It is shown that the stresses in the rod are proportional to the amount of wave stresses because of the own impact of rod and piston, which make a total weight of the system. Effect of piston weight on the stresses value at the rod during impact is directly proportional to the ratio of its weight to the rod weight. The geometric parameters of rod and the speed of the falling parts before the impact also influence on the value of stresses in the rod.The represented

  11. 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.

  12. TileCal ROD Hardware and Software Requirements

    CERN Document Server

    Castelo, J; Cuenca, C; Ferrer, A; Fullana, E; Higón, E; Iglesias, C; Munar, A; Poveda, J; Ruiz-Martínez, A; Salvachúa, B; Solans, C; Valls, J A

    2005-01-01

    In this paper we present the specific hardware and firmware requirements and modifications to operate the Liquid Argon Calorimeter (LiArg) ROD motherboard in the Hadronic Tile Calorimeter (TileCal) environment. Although the use of the board is similar for both calorimeters there are still some differences in the operation of the front-end associated to both detectors which make the use of the same board incompatible. We review the evolution of the design of the ROD from the early prototype stages (ROD based on commercial and Demonstrator boards) to the production phases (ROD final board based on the LiArg design), with emphasis on the different operation modes for the TileCal detector. We start with a short review of the TileCal ROD system functionality and then we detail the different ROD hardware requirements for options, the baseline (ROD Demo board) and the final (ROD final high density board). We also summarize the performance parameters of the ROD motherboard based on the final high density option and s...

  13. Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense.

    Science.gov (United States)

    Baltz, T; Baltz, D; Giroud, C; Crockett, J

    1985-05-01

    A semi-defined medium for the cultivation of bloodstream forms of the African trypanosome brucei subgroup was developed. Out of 14 different strains tested, 10 could be cultured including Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense. The presence of a reducing agent (2-mercaptoethanol or thioglycerol) was found to be essential for growth. The standard medium consisted of Hepes buffered minimum essential medium with Earle's salts supplemented with 0.2 mM 2-mercaptoethanol, 2 mM pyruvate and 10% inactivated serum either from rabbit (T. brucei, T. equiperdum, T. evansi and T. rhodesiense) or human (T. gambiense). Although a general medium could be defined for the long-term maintenance of trypanosome cultures, the initiation to culture nevertheless required particular conditions for the different strains. The cultured trypanosomes had all the characteristics of the in vivo bloodstream forms including: morphology, infectivity, antigenic variation and glucose metabolism.

  14. Further evidence from SSCP and ITS DNA sequencing support Trypanosoma evansi and Trypanosoma equiperdum as subspecies or even strains of Trypanosoma brucei.

    Science.gov (United States)

    Wen, Yan-Zi; Lun, Zhao-Rong; Zhu, Xing-Quan; Hide, Geoff; Lai, De-Hua

    2016-07-01

    The subgenus Trypanozoon includes three species Trypanosoma brucei, Trypanosoma evansi and Trypanosoma equiperdum, which are morphologically identical and indistinguishable even using some molecular methods. In this study, PCR-based single strand conformation polymorphism (PCR-SSCP) was used to analyze the ribosomal DNA of the Trypanozoon species. Data indicate different patterns of ITS2 fragments between T. brucei, T. evansi and T. equiperdum by SSCP. Furthermore, analysis of total ITS sequences within these three members of the subgenus Trypanozoon showed a high degree of homology using phylogenetic analysis but were polyphyletic in haplotype networks. These data provide novel nuclear evidence to further support the notion that T. evansi and T. equiperdum should be subspecies or even strains of T. brucei. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. 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

    proteins with the signal sequence of alfa-mating factor from Saccharomyces cerevisia known to work well for protein secretion from P. pastoris and the pPICZB plasmids had proteins cloned with their native signal sequences. The plasmids were linearized, transformed into P. pastoris strain X33...... and transformants were selected by zeocin resistance. The presence of the RodA and RodB genes in the transformants was confirmed by colony PCR. The expression of RodA and RodB genes was induced by growing cells in culture flasks for three days in buffered complex methanol medium as protein production was dependent...

  16. Diagnostic accuracy of loopamp Trypanosoma brucei detection kit for diagnosis of human African trypanosomiasis in clinical samples.

    Directory of Open Access Journals (Sweden)

    Patrick Mitashi

    Full Text Available BACKGROUND: Molecular methods have great potential for sensitive parasite detection in the diagnosis of human African trypanosomiasis (HAT, but the requirements in terms of laboratory infrastructure limit their use to reference centres. A recently developed assay detects the Trypanozoon repetitive insertion mobile element (RIME DNA under isothermal amplification conditions and has been transformed into a ready-to-use kit format, the Loopamp Trypanosoma brucei. In this study, we have evaluated the diagnostic performance of the Loopamp Trypanosoma brucei assay (hereafter called LAMP in confirmed T.b. gambiense HAT patients, HAT suspects and healthy endemic controls from the Democratic Republic of the Congo (DRC. METHODOLOGY/PRINCIPAL FINDINGS: 142 T.b. gambiense HAT patients, 111 healthy endemic controls and 97 HAT suspects with unconfirmed status were included in this retrospective evaluation. Reference standard tests were parasite detection in blood, lymph or cerebrospinal fluid. Archived DNA from blood of all study participants was analysed in duplicate with LAMP. Sensitivity of LAMP in parasitologically confirmed cases was 87.3% (95% CI 80.9-91.8% in the first run and 93.0% (95% CI 87.5-96.1% in the second run. Specificity in healthy controls was 92.8% (95% CI 86.4-96.3% in the first run and 96.4% (95% CI 91.1-98.6% in the second run. Reproducibility was excellent with a kappa value of 0.81. CONCLUSIONS/SIGNIFICANCE: In this laboratory-based study, the Loopamp Trypanosoma brucei Detection Kit showed good diagnostic accuracy and excellent reproducibility. Further studies are needed to assess the feasibility of its routine use for diagnosis of HAT under field conditions.

  17. 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.

  18. Trypanosoma brucei TbIF1 inhibits the essential F1-ATPase in the infectious form of the parasite.

    Directory of Open Access Journals (Sweden)

    Brian Panicucci

    2017-04-01

    Full Text Available The mitochondrial (mt FoF1-ATP synthase of the digenetic parasite, Trypanosoma brucei, generates ATP during the insect procyclic form (PF, but becomes a perpetual consumer of ATP in the mammalian bloodstream form (BF, which lacks a canonical respiratory chain. This unconventional dependence on FoF1-ATPase is required to maintain the essential mt membrane potential (Δψm. Normally, ATP hydrolysis by this rotary molecular motor is restricted to when eukaryotic cells experience sporadic hypoxic conditions, during which this compulsory function quickly depletes the cellular ATP pool. To protect against this cellular treason, the highly conserved inhibitory factor 1 (IF1 binds the enzyme in a manner that solely inhibits the hydrolytic activity. Intriguingly, we were able to identify the IF1 homolog in T. brucei (TbIF1, but determined that its expression in the mitochondrion is tightly regulated throughout the life cycle as it is only detected in PF cells. TbIF1 appears to primarily function as an emergency brake in PF cells, where it prevented the restoration of the Δψm by FoF1-ATPase when respiration was chemically inhibited. In vitro, TbIF1 overexpression specifically inhibits the hydrolytic activity but not the synthetic capability of the FoF1-ATP synthase in PF mitochondria. Furthermore, low μM amounts of recombinant TbIF1 achieve the same inhibition of total mt ATPase activity as the FoF1-ATPase specific inhibitors, azide and oligomycin. Therefore, even minimal ectopic expression of TbIF1 in BF cells proved lethal as the indispensable Δψm collapsed due to inhibited FoF1-ATPase. In summary, we provide evidence that T. brucei harbors a natural and potent unidirectional inhibitor of the vital FoF1-ATPase activity that can be exploited for future structure-based drug design.

  19. Trypanosoma brucei RAP1 maintains telomere and subtelomere integrity by suppressing TERRA and telomeric RNA:DNA hybrids.

    Science.gov (United States)

    Nanavaty, Vishal; Sandhu, Ranjodh; Jehi, Sanaa E; Pandya, Unnati M; Li, Bibo

    2017-06-02

    Trypanosoma brucei causes human African trypanosomiasis and regularly switches its major surface antigen, VSG, thereby evading the host's immune response. VSGs are monoallelically expressed from subtelomeric expression sites (ESs), and VSG switching exploits subtelomere plasticity. However, subtelomere integrity is essential for T. brucei viability. The telomeric transcript, TERRA, was detected in T. brucei previously. We now show that the active ES-adjacent telomere is transcribed. We find that TbRAP1, a telomere protein essential for VSG silencing, suppresses VSG gene conversion-mediated switching. Importantly, TbRAP1 depletion increases the TERRA level, which appears to result from longer read-through into the telomere downstream of the active ES. Depletion of TbRAP1 also results in more telomeric RNA:DNA hybrids and more double strand breaks (DSBs) at telomeres and subtelomeres. In TbRAP1-depleted cells, expression of excessive TbRNaseH1, which cleaves the RNA strand of the RNA:DNA hybrid, brought telomeric RNA:DNA hybrids, telomeric/subtelomeric DSBs and VSG switching frequency back to WT levels. Therefore, TbRAP1-regulated appropriate levels of TERRA and telomeric RNA:DNA hybrid are fundamental to subtelomere/telomere integrity. Our study revealed for the first time an important role of a long, non-coding RNA in antigenic variation and demonstrated a link between telomeric silencing and subtelomere/telomere integrity through TbRAP1-regulated telomere transcription. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Nuclear reactor shutdown control rod assembly

    Science.gov (United States)

    Bilibin, Konstantin

    1988-01-01

    A temperature responsive, self-actuated nuclear reactor shutdown control rod assembly 10. The upper end 18 of a lower drive line 17 fits within the lower end of an upper drive line 12. The lower end (not shown) of the lower drive line 17 is connected to a neutron absorber. During normal temperature conditions the lower drive line 17 is supported by detent means 22,26. When an overtemperature condition occurs thermal actuation means 34 urges ring 26 upwardly sufficiently to allow balls 22 to move radially outwardly thereby allowing lower drive line 17 to move downwardly toward the core of the nuclear reactor resulting in automatic reduction of the reactor powder.

  1. 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.

  2. Tunable attractions directing nonequilibrium states in dispersions of hard rods

    NARCIS (Netherlands)

    Bruggen, M.P.B. van; Lekkerkerker, H.N.W.

    2000-01-01

    The effect of attractive interactions on the phase behavior of colloidal hard rods has been studied by the addition of nonadsorbing polymer. In these rod-polymer mixtures, four pathways of phase separation can be distinguished: nucleation and growth, spinodal decomposition, aggregation, and

  3. 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.

  4. 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.

  5. 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

  6. Rapid calibaration of the control rod of miniature neutron source ...

    African Journals Online (AJOL)

    An innovative method of combining the well-known computer codes WIMS and CITATION in an interactive Windows environment to calculate the control rod worth and generate the calibration data/curve of single-contr-ol rod miniature source reactor (MNSR) types has been developed and tested. In the scheme, once ...

  7. Ultrasonic detection of cracks in uniaxial glass fibre rods

    CSIR Research Space (South Africa)

    Loveday, PW

    2006-01-01

    Full Text Available propagation in the rods. The authors attempt to model the excitation and transmission of waves along undamaged as well as damaged rods in order to predict the received signals, and we compare the model results with experimental data. Specially developed...

  8. 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. ...

  9. Damage development in rod-on-rod impact test on 1100 pure aluminum

    Science.gov (United States)

    Iannitti, G.; Bonora, N.; Bourne, N.; Ruggiero, A.; Testa, G.

    2017-01-01

    Stress triaxiality plays a major role in the nucleation and growth of ductile damage in metals and alloys. Although, the mechanisms responsible for ductile failure are the same at low and high strain rate, in impact dynamics, in addition to time resolved stress triaxiality and plastic strain accumulation, pressure also contributes to establish the condition for ductile failure to occur. In this work, ductile damage development in 1100 commercially pure aluminum was investigated by means of rod-on-rod (ROR) impact tests. Based on numerical simulations, using a continuum damage mechanics (CDM) model that accounts for the role of pressure on damage parameters and stochastic variability of such parameters, the impact velocity for no damage, incipient and fully developed damage were estimated. ROR tests at selected velocities were performed and damage distribution and extent were investigated by sectioning of soft recovered samples. Comparison between numerical simulations and experimental results is presented and discussed.

  10. 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.

  11. Glucose uptake occurs by facilitated diffusion in procyclic forms of Trypanosoma brucei.

    Science.gov (United States)

    Wille, U; Seyfang, A; Duszenko, M

    1996-02-15

    The glucose transporter of Trypanosoma brucei procyclic forms was characterized and compared with its bloodstream form counterpart. Measuring the glucose consumption enzymatically, we determined a saturable uptake process of relatively high affinity (Km = 80 microM, Vmax = 4 nmol min-1 10(-8) cells), which showed substrate inhibition at glucose concentrations above 1.5 mM (Ki = 21 mM). Control experiments measuring deoxy-D-[3H]Glc uptake under zero-trans conditions indicated that substrate inhibition occurred on the level of glycolysis. Temperature-dependent kinetics revealed a temperature quotient of Q10 = 2.33 and an activation energy of Ea = 64 kJ mol-1. As shown by trans-stimulation experiments, glucose uptake was stereospecific for the D isomer, whereas L-glucose was not recognized. Inhibitor studies using either the uncoupler carbonylcyanide-4-(trifluoromethoxy)phenylhydrazone (5 microM), the H+/ATPase inhibitor N,N'-dicyclohexylcarbodiimide (20 microM), the ionophor monensin (1 microM), or the Na+/K+-ATPase inhibitor ouabain (1 mM) showed insignificant effects on transport efficiency. The procyclic glucose transporter was subsequently enriched in a plasma-membrane fraction and functionally reconstituted into proteoliposomes. Using Na+-free conditions in the absence of a proton gradient, the specific activity of D-[14C]glucose transport was determined as 2.9 nmol min-1 (mg protein)-1 at 0.2 mM glucose. From these cumulative results, we conclude that glucose uptake by the procyclic insect form of the parasite occurs by facilitated diffusion, similar to the hexose-transport system expressed in bloodstream forms. However, the markedly higher substrate affinity indicates a differential expression of different transporter isoforms throughout the lifecycle.

  12. Regulation of Trypanosoma brucei Total and Polysomal mRNA during Development within Its Mammalian Host.

    Directory of Open Access Journals (Sweden)

    Paul Capewell

    Full Text Available The gene expression of Trypanosoma brucei has been examined extensively in the blood of mammalian hosts and in forms found in the midgut of its arthropod vector, the tsetse fly. However, trypanosomes also undergo development within the mammalian bloodstream as they progress from morphologically 'slender forms' to transmissible 'stumpy forms' through morphological intermediates. This transition is temporally progressive within the first wave of parasitaemia such that gene expression can be monitored in relatively pure slender and stumpy populations as well as during the progression between these extremes. The development also represents the progression of cells from translationally active forms adapted for proliferation in the host to translationally quiescent forms, adapted for transmission. We have used metabolic labelling to quantitate translational activity in slender forms, stumpy forms and in forms undergoing early differentiation to procyclic forms in vitro. Thereafter we have examined the cohort of total mRNAs that are enriched throughout development in the mammalian bloodstream (slender, intermediate and stumpy forms, irrespective of strain, revealing those that exhibit consistent developmental regulation rather than sample specific changes. Transcripts that cosediment with polysomes in stumpy forms and slender forms have also been enriched to identify transcripts that escape translational repression prior to transmission. Combined, the expression and polysomal association of transcripts as trypanosomes undergo development in the mammalian bloodstream have been defined, providing a resource for trypanosome researchers. This facilitates the identification of those that undergo developmental regulation in the bloodstream and therefore those likely to have a role in the survival and capacity for transmission of stumpy forms.

  13. 3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction

    Science.gov (United States)

    Höög, Johanna L.; Lacomble, Sylvain; Bouchet-Marquis, Cedric; Briggs, Laura; Park, Kristin; Hoenger, Andreas; Gull, Keith

    2016-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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

  14. Virulence and pathogenicity of three Trypanosoma brucei rhodesiense stabilates in a Swiss white mouse model

    Directory of Open Access Journals (Sweden)

    Christopher Kariuki

    2015-05-01

    Full Text Available Background: A key objective in basic research on human African trypanosomiasis (HAT is developing a cheap and reliable experimental model of the disease for use in pathogenesis and drug studies.Objective: With a view to improving current models, a study was undertaken to characterise the virulence and pathogenicity of three Trypanosoma brucei rhodesiense stabilates, labelled as International Livestock Research Institute (ILRI-2918, ILRI-3953, and Institute of Primate Research (IPR-001, infected into Swiss white mice.Methods: Swiss white mice were infected intraperitoneally with trypanosomes and observedfor parasitaemia using wet blood smears obtained by tail snipping. Induction of late-stagedisease was undertaken using diminazene aceturate (40 mg/kg, Berenil with curativetreatment done using melarsoprol (3.6 mg/kg, Arsobal.Results: The prepatent period for the stabilates ranged from three to four days with mean peak parasitaemia ranging from Log10 6.40 to 8.36. First peak parasitaemia for all stabilates varied between six and seven days post infection (DPI followed by secondary latency in ILRI-2918 (15–17 DPI and IPR-001 (17–19 DPI. Survival times ranged from six DPI (ILRI-3953 to 86 DPI (IPR-001. Hindleg paresis was observed in both ILRI-3953 (at peak parasitaemia and ILRI-2918 (after relapse parasitaemia. Mice infected with IPR-001 survived until 54 DPI when curative treatment was undertaken.Conclusions: This study demonstrated that the stabilates ILRI-2918 and ILRI-3953 were unsuitable for modelling late-stage HAT in mice. The stabilate IPR-001 demonstrated the potential to induce chronic trypanosomiasis in Swiss white mice for use in development of a late-stage model of HAT.

  15. Interfacial colloidal rod dynamics: Coefficients, simulations, and analysis

    Science.gov (United States)

    Yang, Yuguang; Bevan, Michael A.

    2017-08-01

    Colloidal rod diffusion near a wall is modeled and simulated based on a constrained Stokesian dynamic model of chains-of-spheres. By modeling colloidal rods as chains-of-spheres, complete diffusion tensors are computed for colloidal rods in bulk media and near interfaces, including hydrodynamic interactions, translation-rotation coupling, and all diffusion modes in the particle and lab frames. Simulated trajectories based on the chain-of-spheres diffusion tensor are quantified in terms of typical experimental quantities such as mean squared positional and angular displacements as well as autocorrelation functions. Theoretical expressions are reported to predict measured average diffusivities as well as the crossover from short-time anisotropic translational diffusion along the rod's major axis to isotropic diffusion. Diffusion modes are quantified in terms of closed form empirical fits to model results to aid their use in interpretation and prediction of experiments involving colloidal rod diffusion in interfacial and confined systems.

  16. RODMOD: a code for control rod positioning. [LMFBR

    Energy Technology Data Exchange (ETDEWEB)

    Vondy, D.R.; Fowler, T.B.

    1978-11-01

    The report documents a computer code which has been implemented to position control rods according to a prescribed schedule during the calculation of a reactor history. Control rods may be represented explicitly with or without internal black absorber conditions in selected energy groups, or fractional insertion may be done, or both, in a problem. There is provision for control rod follower, movement of materials through a series of zones in a closed loop, and shutdown rod insertion and subsequent removal to allow the reactor history calculation to be continued. This code is incorporated in the system containing the VENTURE diffusion theory neutronics and the BURNER exposure codes for routine use. The implemented automated procedures cause the prescribed control rod insertion schedule to be applied without the access of additional user input data during the calculation of a reactor operating history.

  17. Study of the anti-sand sucker rod pump

    Science.gov (United States)

    Wei, Hangxin; Lv, Bingxin; Xi, Wenkui; Yi, Peng

    2017-06-01

    In order to solve the problem of sand stuck in the sucker rod pump, an anti-sand sucker rod pump is designed. The anti-sand sucker rod pump includes the conventional sucker rod pump and the swirl flow device. The sand particles can be separated from the oil in the swirl flow device, so the plunger of the sucker rod pump cannot be stuck. The motion equation of the sand particles in oil is deduced. The virtual model of the swirl flow device is built in GAMBIT software. And simulation of solid-liquid two phase flow is simulated in software FLUENT. The simulation results show that the swirl flow device can realize the sand particles separation from the oil completely. So the pump can have the effect of anti-sands.

  18. Buckling of a thin rod under cylindrical constraint

    Science.gov (United States)

    Miller, Jay; Su, Tianxiang; Wicks, Nathan; Pabon, Jahir; Bertoldi, Katia; Reis, Pedro

    2013-03-01

    We investigate the buckling and post-buckling behavior of a thin elastic rod, under cylindrical constraint, with distributed loading. Our precision model experiments consist of injecting a custom-fabricated rod into a transparent glass pipe. Under imposed velocity (leading to frictional axial loading), a portion of the initially straight rod first buckles into a sinusoidal mode and eventually undergoes a secondary instability into a helical configuration. The buckling and post-buckling behavior is found to be highly dependent on the system's geometry, namely the injected rod length and the aspect ratio of the rod to pipe diameter, as well as material parameters. We quantify the critical loads for this sequence of instabilities, contrast our results with numerical experiments and rationalize the observed behavior through scaling arguments.

  19. 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.

  20. Dynamic behavior of upper hydraulic drive control rod

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaotian [Institute of Nuclear and New Energy Technology, Beijing 100084 (China)]. E-mail: lixiaotian@tsinghua.edu.cn; He Shuyan [Institute of Nuclear and New Energy Technology, Beijing 100084 (China)

    2006-12-15

    A 200 MW nuclear heating reactor (NHR) was developed based on the 5 MW testing heating reactor (THR-5). In order to improve its features, the INET was used to optimize its structure design. One task was to design the upper hydraulic drive control rod, which is located at the upper part of the reactor core, so that the fuel rod in each corner of the bundle will not be removed as they are in the THR-5. A program based on the method of characteristics was run to investigate the dynamic behavior of the upper hydraulic control rod drive system. The steady-state and dynamic characteristics of the control rod were studied. The influence of the reactor temperature and structure parameters on the operation reliability was investigated. Finally the optimal design parameters of the upper hydraulic drive control rod were obtained.

  1. Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation

    Directory of Open Access Journals (Sweden)

    O. S. Adeyemi

    2014-01-01

    Full Text Available Current chemotherapies against trypanosomiasis are beset with diverse challenges, a situation which underscores the numerous research efforts aimed at finding newer and effective treatments. Arginine kinase of trypanosome has been validated as target for drug development against trypanosomiasis. The present study investigated the interaction between a recombinant form of the arginine kinase (rTbAK of trypanosome and gallotannin. The interaction between gallotannin and recombinant arginine kinase of Trypanosoma brucei caused significant decrease of enzyme activity. Kinetic analysis revealed the interaction to be of noncompetitive inhibition. Further thermodynamic analysis showed that the interaction between gallotannin and the recombinant arginine kinase was nonspontaneous and involved hydrophobic forces. The Ksv values and the FRET analysis suggest that static quenching of fluorescence intensity by gallotannin was static. Data revealed inhibitory interactions between gallotannin and rTbAK of trypanosome. Although the mechanism of inhibition is not clear yet, molecular docking studies are ongoing to clearly define the inhibitory interactions between the gallotannin and rTbAK. The knowledge of such binding properties would enrich development of selective inhibitors for the arginine kinase of Trypanosoma brucei.

  2. 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.

  3. Proximity Interactions among Basal Body Components in Trypanosoma brucei Identify Novel Regulators of Basal Body Biogenesis and Inheritance

    Directory of Open Access Journals (Sweden)

    Hung Quang Dang

    2017-01-01

    Full Text Available The basal body shares similar architecture with centrioles in animals and is involved in nucleating flagellar axonemal microtubules in flagellated eukaryotes. The early-branching Trypanosoma brucei possesses a motile flagellum nucleated from the basal body that consists of a mature basal body and an adjacent pro-basal body. Little is known about the basal body proteome and its roles in basal body biogenesis and flagellar axoneme assembly in T. brucei. Here, we report the identification of 14 conserved centriole/basal body protein homologs and 25 trypanosome-specific basal body proteins. These proteins localize to distinct subdomains of the basal body, and several of them form a ring-like structure surrounding the basal body barrel. Functional characterization of representative basal body proteins revealed distinct roles in basal body duplication/separation and flagellar axoneme assembly. Overall, this work identified novel proteins required for basal body duplication and separation and uncovered new functions of conserved basal body proteins in basal body duplication and separation, highlighting an unusual mechanism of basal body biogenesis and inheritance in this early divergent eukaryote.

  4. 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 < 10 μg/mL) without obvious cytotoxicity to L6 cells was observed for eight extracts from plants: Connarus suberosus, Blepharocalyx salicifolius, Psidium laruotteanum and Myrsine guianensis. Overall, studies of plant extracts will contribute to increase the biodiversity knowledge essential for Cerrado conservation and sustainable development.

  5. In Silico Prediction and Experimental Evaluation of Furanoheliangolide Sesquiterpene Lactones as Potent Agents against Trypanosoma brucei rhodesiense

    Science.gov (United States)

    Da Costa, Fernando B.; Lopes, Norberto P.; Kaiser, Marcel; Brun, Reto

    2014-01-01

    As a continuation of our earlier study on the in vitro antiprotozoal activity of 40 natural sesquiterpene lactones (STLs), we extended the set of tested compounds from our laboratories to 59. On the basis of this extended data set, further enriched by literature data for 10 compounds tested under the same conditions, our quantitative structure-activity relationship (QSAR) analyses for activity against T. brucei rhodesiense (etiologic agent of human African trypanosomiasis, or sleeping sickness) were continued, and the QSAR model thus obtained with 69 structures was used to predict the activity of a virtual library of 1,750 STL structures. As a major result from these calculations, furanoheliangolide-type compounds, a subclass of STLs hitherto untested against T. brucei rhodesiense, were predicted to have an exceptionally high level of in vitro activity. Four representative compounds of this type, goyazensolide, 4,5-dihydro-2′,3′-epoxy-15-deoxygoyazensolide, budlein A, and 4,15-isoatriplicolide tiglate, were therefore tested. They displayed 50% inhibitory concentrations (IC50s) of 0.07, 0.20, 0.07, and 0.015 μM, respectively, so that the in silico prediction was experimentally confirmed. 4,15-Isoatriplicolide tiglate is the most potent STL against T. b. rhodesiense found. Furanoheliangolide STLs were thus identified as interesting leads against this parasite which deserve more detailed investigations. PMID:24165182

  6. Anisotropy in CdSe quantum rods

    Energy Technology Data Exchange (ETDEWEB)

    Li, Liang-shi [Univ. of California, Berkeley, CA (United States)

    2003-01-01

    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

  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

  8. The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase of Trypanosomatidae and the glycocomal redox balance of insect stages of Trypanosoma brucei and Leishmania spp.

    NARCIS (Netherlands)

    Guerra, D.G.; Decottignies, A.; Bakker, B.M.; Michels, P.A.M.

    2006-01-01

    The genes for the mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase were identified in Trypanosoma brucei and Leishmania major genomes. We have expressed the L. major gene in Saccharomyces cerevisiae and confirmed the subcellular localization and activity of the produced enzyme. Using

  9. Trypanosoma brucei TBRGG1, a mitochondrial oligo(U)-binding protein that co-localizes with an in vitro RNA editing activity

    NARCIS (Netherlands)

    Vanhamme, L.; Perez-Morga, D.; Marchal, C.; Speijer, D.; Lambert, L.; Geuskens, M.; Alexandre, S.; Ismaïli, N.; Göringer, U.; Benne, R.; Pays, E.

    1998-01-01

    We report the characterization of a Trypanosoma brucei 75-kDa protein of the RGG (Arg-Gly-Gly) type, termed TBRGG1. Dicistronic and monocistronic transcripts of the TBRGG1 gene were produced by both alternative splicing and polyadenylation. TBRGG1 was found in two or three forms that differ in their

  10. Discovery of novel Trypanosoma brucei phosphodiesterase B1 inhibitors by virtual screening against the unliganded TbrPDEB1 crystal structure

    NARCIS (Netherlands)

    Jansen, C.; Wang, H.; Kooistra, A.J.; de Graaf, C.; Orrling, K.M.; Tenor, H.; Seebeck, T.; de Esch, I.J.P.; Ke, H.; Leurs, R.

    2013-01-01

    Trypanosoma brucei cyclic nucleotide phosphodiesterase B1 (TbrPDEB1) and TbrPDEB2 have recently been validated as new therapeutic targets for human African trypanosomiasis by both genetic and pharmacological means. In this study we report the crystal structure of the catalytic domain of the

  11. Trypanosoma brucei Plimmer & Bradford, 1899 is a synonym of T. evansi (Steel, 1885) according to current knowledge and by application of nomenclature rules.

    Science.gov (United States)

    Molinari, Jesús; Moreno, S Andrea

    2018-02-06

    Proper application of the principles of biological nomenclature is fundamental for scientific and technical communication about organisms. As other scientific disciplines, taxonomy inherently is open to change, thus species names cannot be final and immutable. Nevertheless, altering the names of organisms of high economical, medical, or veterinary importance can become a complex challenge between the scientific need to have correct classifications, and the practical ideal of having fixed classifications. Trypanosoma evansi (Steel, 1885), T. brucei Plimmer & Bradford, 1899 and T. equiperdum Doflein, 1901 are important parasites of mammals. According to current knowledge, the three names are synonyms of a single trypanosome species, the valid name of which should be T. evansi by the mandatory application of the Principle of Priority of zoological nomenclature. Subspecies known as T. brucei brucei Plimmer & Bradford, 1899, T. b. gambiense Dutton, 1902 and T. b. rhodesiense Stephens & Fantham, 1910 should be referred to respectively as T. evansi evansi (Steel, 1885), T. e. gambiense and T. e. rhodesiense. The polyphyletic groupings so far known as T. evansi and T. equiperdum should be referred respectively to as surra- and dourine-causing strains of T. e. evansi. Likewise, trypanosomes so far known as T. b. brucei should be referred to as nagana-causing strains of T. e. evansi. Though it modifies the scientific names of flagship human and animal parasites, the amended nomenclature proposed herein should be adopted because it reflects phylogenetic and biological advancements, fixes errors, and is simpler than the existing classificatory system.

  12. 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...

  13. Dynamics of entangled rod-coil block copolymers

    Science.gov (United States)

    Wang, Muzhou; Timachova, Ksenia; Alexander-Katz, Alfredo; Likhtman, Alexei E.; Olsen, Bradley D.

    2014-03-01

    Polymer science is exploring advanced materials which combine functional domains such as proteins and semiconducting polymers with traditional flexible polymers onto the same molecule. While many studies have focused on equilibrium structure-property relationships, little is known about how the conformational restrictions of rigid domains affect dynamical phenomena such as mechanical properties, processing pathways, and self-assembly kinetics. We have recently introduced a reptation theory for entangled rod-coil block copolymers as a model for this wider class of functional polymeric materials. The theory hypothesizes that the motion of rod-coils is slowed relative to rod and coil homopolymers because of a mismatch between the curvature of the rod and coil entanglement tubes. This effect leads to activated reptation and arm retraction as two relaxation mechanisms that govern the short and long rod regimes, respectively. These results were verified by tracer diffusion measurements using molecular dynamics simulation and forced Rayleigh scattering in both the rod-coil diblock and coil-rod-coil triblock configurations. The tracer diffusion results were then compared to experimental self-diffusion measurements which require a consideration of the motion of the surrounding chains.

  14. Numerical simulation of the sucker-rod pumping system

    Directory of Open Access Journals (Sweden)

    Oldrich Joel Romero

    2014-11-01

    Full Text Available The sucker rod pump is an artificial lift method frequently applied in onshore petroleum wells. This system can be described using a numerical simulation based on the behavior of a rod string. In the past, the elastic behavior of the rod string made it difficult to model the system. However, since the 1960s and with the advent of digital computers, it has been modeled numerically. The rod string be-haves like a slender bar, and thus, the propagation of elastic waves along the bar can be represented by a one-dimensional equation. Gibbs (1963 presented a mathematical model based on the wave equation, which is described on the basis of the analysis of forces on the rod string and is incorporated into a boundary value problem involving partial differential equations. The use of the finite differ-ence method allows for a numerical solution by the discretization of the wave equation developed in the mathematical formulation with appropriate boundary and initial conditions. This work presents a methodology for implementing an academic computer code that allows simulation of the upstroke and downstroke motion of the rod string described by the wave equation under ideal operating conditions, assuming a harmonic motion of the rod at one end and downhole pump at the other end. The goal of this study is to generate the downhole dynamometer card, an important and consolidated tool that controls the pump system by diagnosing oper-ational conditions of the downhole pump.

  15. Thermal-recovery of modal instability in rod fiber amplifiers

    DEFF Research Database (Denmark)

    Jørgensen, Mette Marie; Laurila, Marko; Noordegraaf, Danny

    2013-01-01

    We investigate the temporal dynamics of Modal instabilities (MI) in ROD fiber amplifiers using a 100 μm core rod fiber in a single-pass amplifier configuration, and we achieve ~200W of extracted output power before the onset of MI. Above the MI threshold, we investigate the temporal dynamics of b...... and thermally annealed between each test series. We find that the MI threshold degrades as it is reached multiple times, but is recovered by thermal annealing. We also find that the test history of the rods affects the temporal dynamics....

  16. Plasmonic rod dimers as elementary planar chiral meta-atoms

    CERN Document Server

    Zhukovsky, Sergei V; Chigrin, Dmitry N

    2011-01-01

    Electromagnetic response of metallic rod dimers is theoretically calculated for arbitrary planar arrangement of rods in the dimer. It is shown that dimers without an in-plane symmetry axis exhibit elliptical dichroism and act as "atoms" in planar chiral metamaterials. Due to a very simple geometry of the rod dimer, such planar metamaterials are much easier in fabrication than conventional split-ring or gammadion-type structures, and lend themselves to a simple analytical treatment based on coupled dipole model. Dependencies of metamaterial's directional asymmetry on the dimer's geometry are established analytically and confirmed in numerical simulations.

  17. Review of FFTF and CRBRP control rod systems designs

    Energy Technology Data Exchange (ETDEWEB)

    Pitterle, T. A.; Lagally, H. O.

    1977-10-04

    The evolution of the primary control rod system design for FFTF and CRBR, beginning with the initial choice of the basic concepts, is described. The significant component and systems tests are reviewed together with the test results which referenced the development of the CRBR primary control rod system design. Modifications to the concepts and detail designs of the FFTF control rod system were required principally to satisfy the requirements of CRBR, and at the same time incorporating design refinements shown desirable by the tests.

  18. Trypanosoma brucei: analysis of cytoplasmic Ca2+ during differentiation of bloodstream stages in vitro.

    Science.gov (United States)

    Stojdl, D F; Clarke, M W

    1996-06-01

    The highly regulated intracellular concentration of calcium (Ca2+) is a well-described regulator of diverse cellular events, including cell cycle control. In the present study we have addressed the regulation of cytosolic Ca2+ in differentiation events in the life cycle of the protozoan parasite Trypanosoma brucei. Bloodstream form (BSF) trypanosomes include the mitotically active long slender forms (LS) which differentiate to two nondividing stages--intermediate (INT) which transform into short stumpy (SS) forms. An axenic in vitro culture system was used to cultivate LS to a density greater than 1.0 x 10(6) cells/ml/day. Populations of the intermediate BSF (INT) and SS were derived from cultured LS by treatment with difluoromethyl ornithine (DFMO, 100 microM) for 2 and 4 days, respectively. A semiquantitative reverse transcriptase-coupled polymerase chain reaction protocol (SQ-RT-PCR) was developed to objectively distinguish the three BSF by monitoring the relative levels of stage-specific mRNAs--cytochrome oxidase II (COXII), variant surface glycoprotein, and procyclin during the differentiation of LS to SS, showing an increase in COXII and procyclin mRNA expression during this process of differentiation. Basal cytosolic Ca2+ levels [Ca2+]i of populations of LS, INT, and SS were studied using Indo-1 dual emission fluorometry. [Ca2+]i was maximal in dividing LS cells and was shown to decrease coincidentally with early events in the process of differentiation to INT and SS. Thapsigargin (1 microM), reported to cause the release of Ca2+ from the endoplasmic reticulum, elevated [Ca2+]i by about 30-60 nM in all BSF; however, the total thapsigargin-releasable stores decreased in parallel with the decrease in basal [Ca2+]i. Control treatments verified that elevations in [Ca2+]i in response to thapsigargin were intracellular in origin. These results may reflect the cessation of cytosolic Ca2+ transients involved in the regulation of mitosis as the parasite exits from

  19. 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

  20. 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

  1. 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

    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 Rod...... 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...

  2. 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 succe......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....

  3. Motion simulation of hydraulic driven safety rod using FSI method

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jaeho; Kim, Sanghaun; Yoo, Yeonsik; Cho, Yeonggarp; Kim, Jong In [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-05-15

    Hydraulic driven safety rod which is one of them is being developed by Division for Reactor Mechanical Engineering, KAERI. In this paper the motion of this rod is simulated by fluid structure interaction (FSI) method before manufacturing for design verification and pump sizing. A newly designed hydraulic driven safety rod which is one of reactivity control mechanism is simulated using FSI method for design verification and pump sizing. The simulation is done in CFD domain with UDF. The pressure drop is changed slightly by flow rates. It means that the pressure drop is mainly determined by weight of moving part. The simulated velocity of piston is linearly proportional to flow rates so the pump can be sized easily according to the rising and drop time requirement of the safety rod using the simulation results.

  4. 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.

  5. The ATLAS LARG ROD G-Links Cooling System

    CERN Document Server

    Hubaut, F; Repain, P; Rossel, F; Vincent, D

    2004-01-01

    In this note is described the water cooling system that will be implemented on the ROD boards of the liquid argon calorimeter detectors in order to guarantee a proper behavior of the optical reception of the data.

  6. 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.

  7. CHF prediction in rod bundles using round tube data

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Wallen F.; Veloso, Maria A.F.; Pereira, Cláubia; Costa, Antonella L., E-mail: wallenfds@yahoo.com.br, E-mail: mdora@nuclear.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear

    2017-07-01

    The present work concerns the use of 1995 CHF table for uniformly heated round tubes, developed jointly by Canadian and Russian researchers, for the prediction of critical heat fluxes in rod bundles geometries. Comparisons between measured and calculated critical heat fluxes indicate that this table could be applied to rod bundles provided that a suitable correction factor is employed. The tolerance limits associated with the departure from nucleate boiling ratio (DNBR) are evaluated by using statistical analysis. (author)

  8. Apparatus for injection casting metallic nuclear energy fuel rods

    Science.gov (United States)

    Seidel, Bobby R.; Tracy, Donald B.; Griffiths, Vernon

    1991-01-01

    Molds for making metallic nuclear fuel rods are provided which present reduced risks to the environment by reducing radioactive waste. In one embodiment, the mold is consumable with the fuel rod, and in another embodiment, part of the mold can be re-used. Several molds can be arranged together in a cascaded manner, if desired, or several long cavities can be integrated in a monolithic multiple cavity re-usable mold.

  9. Colloidal rods and spheres in partially miscible binary liquids

    OpenAIRE

    Hijnen, Niek

    2013-01-01

    Different scenarios for assembling rod-like and spherical colloidal particles using binary mixtures of partially miscible liquids were investigated experimentally. Suitable rod-like colloids were developed first. The subsequent studies of colloids in binary liquids consisted, on one hand, of systems where particles were partially wetted by both phases and, on the other hand, of systems where particles were completely wetted by the minority phase. A simple method to prepare l...

  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 ...... noise (RIN) of the seed laser, which seeds mode coupling between the fundamental and higher order mode. The TMI threshold is predicted to ~370 W – 440 W depending on RIN for the distributed modal filtering rod fiber....

  11. 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.

  12. Performance of the NRX shut-off rods

    Energy Technology Data Exchange (ETDEWEB)

    Manson, R.E.

    1965-08-15

    A new type of shut-off rod of electromechanical design was developed by the American Machine and Foundry Company for use in the NRX reactor following the accident of 1952. The new rods were installed in May, 1956, as part of the control system conversion program which was completed in 1958. Some problems were encountered with limit switch adjustment but minor modifications in design led to much improved operation. he performance of the rods also improved as more experience was gained in the maintenance and adjustment of the various headgear components. Each headgear is now overhauled once a year on a routine basis. The present design of shut-off rod is considered to be very satisfactory. There has only been one occasion when a shut-off rod has failed to come fully down on a trip. Rods have failed to operate correctly on five other occasions but these occurred during shutdown periods or when the reactor was being shutdown manually. (author)

  13. Toggle rod stabilisation of coxofemoral luxation in 14 cats.

    Science.gov (United States)

    Pratesi, A; Grierson, J; Moores, A P

    2012-05-01

    To describe the surgical technique and to report outcomes in cats with coxofemoral luxation treated with open reduction and toggle rod stabilisation. Retrospective study of cats with coxofemoral luxation stabilised via the toggle rod method. Short-term follow-up included clinical examination and radiographs. Long-term follow-up was via owner questionnaire. Fourteen cats were included. All of the cats had reported unilateral craniodorsal hip luxation. Nine cats (64·3%) had additional orthopaedic injuries. Luxations were stabilised with a 3·2-mm toggle rod (2·7-mm toggle rod in one cat) and two loops of four-metric polydioxanone (five-metric polydioxanone in one cat and three loops of four-metric polydioxanone in two cats). Success rate, in terms of maintenance of reduction, was 86%. Reluxation occurred in two cats (14%), both of which had multiple limb injuries. Eleven owner questionnaires (mean follow-up time 15·5 months) reported a functional outcome of "very good" to "excellent". Although the diameter of the pelvic canal was reduced by the presence of the toggle rod (mean narrowing 16.2%), none of the cats had defaecatory issues. Toggle rod stabilisation is an effective method for the treatment of coxofemoral luxation in cats. Injuries to multiple limbs may be a risk factor for reluxation. © 2012 British Small Animal Veterinary Association.

  14. Vibrational Power Flow Analysis of Rods and Beams

    Science.gov (United States)

    Wohlever, James Christopher; Bernhard, R. J.

    1988-01-01

    A new method to model vibrational power flow and predict the resulting energy density levels in uniform rods and beams is investigated. This method models the flow of vibrational power in a manner analogous to the flow of thermal power in a heat conduction problem. The classical displacement solutions for harmonically excited, hysteretically damped rods and beams are used to derive expressions for the vibrational power flow and energy density in the rod and beam. Under certain conditions, the power flow in these two structural elements will be shown to be proportional to the energy density gradient. Using the relationship between power flow and energy density, an energy balance on differential control volumes in the rod and beam leads to a Poisson's equation which models the energy density distribution in the rod and beam. Coupling the energy density and power flow solutions for rods and beams is also discussed. It is shown that the resonant behavior of finite structures complicates the coupling of solutions, especially when the excitations are single frequency inputs. Two coupling formulations are discussed, the first based on the receptance method, and the second on the travelling wave approach used in Statistical Energy Analysis. The receptance method is the more computationally intensive but is capable of analyzing single frequency excitation cases. The traveling wave approach gives a good approximation of the frequency average of energy density and power flow in coupled systems, and thus, is an efficient technique for use with broadband frequency excitation.

  15. 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)

  16. 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

  17. Age-related decrease in rod bipolar cell density of the human retina ...

    Indian Academy of Sciences (India)

    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 ...

  18. 75 FR 21658 - Carbon and Certain Alloy Steel Wire Rod From Trinidad and Tobago

    Science.gov (United States)

    2010-04-26

    ... Certain Alloy Steel Wire Rod From Trinidad and Tobago AGENCY: United States International Trade Commission... Investigation No. 731-TA-961 concerning carbon and certain alloy steel wire rod (``wire rod'') from Trinidad and... value. Caribbean Ispat Ltd., a Trinidadian producer and exporter of wire rod now known as Mittal Steel...

  19. Programmed Cell Death in Procyclic Form Trypanosoma brucei rhodesiense - Identification of Differentially Expressed Genes during Con A Induced Death

    Directory of Open Access Journals (Sweden)

    Welburn Susan C

    1999-01-01

    Full Text Available Trypanosoma brucei rhodesiense can be induced to undergo apoptosis after stimulation with Con A. As cell death in these parasites is associated with de novo gene expression we have applied a differential display technique, Randomly Amplified Differential Expressed Sequence-Polymerase Chain Reaction (RADES-PCR to the study of gene expression during Con A induced cell death in these organisms. Twenty-two differentially displayed products have been cloned and sequenced. These represent the first endogenous genes to be identified as implicated in cellular death in trypanosomatids (the most primitive eukaryote in which apoptosis has been described. Evidence for an ancestral death machinery, `proto-apoptosis' in single celled organisms is discussed.

  20. High-confidence glycosome proteome for procyclic form Trypanosoma brucei by epitope-tag organelle enrichment and SILAC proteomics.

    Science.gov (United States)

    Güther, Maria Lucia S; Urbaniak, Michael D; Tavendale, Amy; Prescott, Alan; Ferguson, Michael A J

    2014-06-06

    The glycosome of the pathogenic African trypanosome Trypanosoma brucei is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed.

  1. Characterization of control rod worths and fuel rod power peaking factors in the university of Utah TRIGA Mark I reactor

    Directory of Open Access Journals (Sweden)

    Alroumi Fawaz

    2016-01-01

    Full Text Available Control rod reactivity (worths for the three control rods and fuel rod power peaking factors in the University of Utah research reactor (100 kW TRIGA Mark I are characterized using the AGENT code system and the results described in this paper. These values are compared to the MCNP6 and existing experimental measurements. In addition, the eigenvalue, neutron spatial flux distributions and reaction rates are analyzed and discussed. The AGENT code system is widely benchmarked for various reactor types and complexities in their geometric arrangements of the assemblies and reactor core material distributions. Thus, it is used as a base methodology to evaluate neutronics variables of the research reactor at the University of Utah. With its much shorter computation time than MCNP6, AGENT provides agreement with the MCNP6 within a 0.5 % difference for the eigenvalue and a maximum difference of 10% in the power peaking factor values. Differential and integral control rod worths obtained by AGENT show well agreement with MCNP6 and the theoretical model. However, regulating the control rod worth is somewhat overestimated by both MCNP6 and AGENT models when compared to the experimental/theoretical values. In comparison to MCNP6, the total control rod worths and shutdown margin obtained with AGENT show better agreement to the experimental values.

  2. A Multi-Stage Wear Model for Grid-to-Rod Fretting of Nuclear Fuel Rods

    Energy Technology Data Exchange (ETDEWEB)

    Blau, Peter Julian [ORNL

    2014-01-01

    The wear of fuel rod cladding against the supporting structures in the cores of pressurized water nuclear reactors (PWRs) is an important and potentially costly tribological issue. Grid-to-rod fretting (GTRF), as it is known, involves not only time-varying contact conditions, but also elevated temperatures, flowing hot water, aqueous tribo-corrosion, and the embrittling effects of neutron fluences. The multi-stage, closed-form analytical model described in this paper relies on published out-of-reactor wear and corrosion data and a set of simplifying assumptions to portray the conversion of frictional work into wear depth. The cladding material of interest is a zirconium-based alloy called Zircaloy-4, and the grid support is made of a harder and more wear-resistant material. Focus is on the wear of the cladding. The model involves an incubation stage, a surface oxide wear stage, and a base alloy wear stage. The wear coefficient, which is a measure of the efficiency of conversion of frictional work into wear damage, can change to reflect the evolving metallurgical condition of the alloy. Wear coefficients for Zircaloy-4 and for a polyphase zirconia layer were back-calculated for a range of times required to wear to a critical depth. Inputs for the model, like the friction coefficient, are taken from the tribology literature in lieu of in-reactor tribological data. Concepts of classical fretting were used as a basis, but are modified to enable the model to accommodate the complexities of the PWR environment. Factors like grid spring relaxation, pre-oxidation of the cladding, multiple oxide phases, gap formation, impact, and hydrogen embrittlement are part of the problem definition but uncertainties in their relative roles limits the ability to validate the model. Sample calculations of wear depth versus time in the cladding illustrate how GTRF wear might occur in a discontinuous fashion during months-long reactor operating cycles. A means to account for grid/rod gaps

  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. Spliced leader RNA silencing (SLS - a programmed cell death pathway in Trypanosoma brucei that is induced upon ER stress

    Directory of Open Access Journals (Sweden)

    Michaeli Shulamit

    2012-05-01

    Full Text Available Abstract Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite cycles between its insect (procyclic form and mammalian hosts (bloodstream form. Trypanosomes lack conventional transcription regulation, and their 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, the spliced leader (SL is added to all mRNAs from a small RNA, the SL RNA. Trypanosomes lack the machinery for the unfolded protein response (UPR, which in other eukaryotes is induced under endoplasmic reticulum (ER stress. Trypanosomes respond to such stress by changing the stability of mRNAs, which are essential for coping with the stress. However, under severe ER stress that is induced by blocking translocation of proteins to the ER, treatment of cells with chemicals that induce misfolding in the ER, or extreme pH, trypanosomes elicit the spliced leader silencing (SLS pathway. In SLS, the transcription of the SL RNA gene is extinguished, and tSNAP42, a specific SL RNA transcription factor, fails to bind to its cognate promoter. SLS leads to complete shut-off of trans-splicing. In this review, I discuss the UPR in mammals and compare it to the ER stress response in T. brucei leading to SLS. I summarize the evidence supporting the notion that SLS is a programmed cell death (PCD pathway that is utilized by the parasites to substitute for the apoptosis observed in higher eukaryotes under prolonged ER stress. I present the hypothesis that SLS evolved to expedite the death process, and rapidly remove from the population unfit parasites that, by elimination via SLS, cause minimal damage to the parasite population.

  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

    2010-06-01

    Full Text Available 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.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.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

    Science.gov (United States)

    Chen, Chiung-Kuang; Leung, Siegfried S. F.; Guilbert, Christophe; Jacobson, Matthew P.; McKerrow, James H.; Podust, Larissa M.

    2010-01-01

    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 14α-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 Å and 2.27 Å), and from the related pathogen T. brucei (resolutions of 2.7 Å and 2.6 Å), 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° 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 offer a starting point for

  7. 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.

  8. 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.

  9. 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....

  10. On Cherenkov light production by irradiated nuclear fuel rods

    Science.gov (United States)

    Branger, E.; Grape, S.; Jacobsson Svärd, S.; Jansson, P.; Andersson Sundén, E.

    2017-06-01

    Safeguards verification of irradiated nuclear fuel assemblies in wet storage is frequently done by measuring the Cherenkov light in the surrounding water produced due to radioactive decays of fission products in the fuel. This paper accounts for the physical processes behind the Cherenkov light production caused by a single fuel rod in wet storage, and simulations are presented that investigate to what extent various properties of the rod affect the Cherenkov light production. The results show that the fuel properties have a noticeable effect on the Cherenkov light production, and thus that the prediction models for Cherenkov light production which are used in the safeguards verifications could potentially be improved by considering these properties. It is concluded that the dominating source of the Cherenkov light is gamma-ray interactions with electrons in the surrounding water. Electrons created from beta decay may also exit the fuel and produce Cherenkov light, and e.g. Y-90 was identified as a possible contributor to significant levels of the measurable Cherenkov light in long-cooled fuel. The results also show that the cylindrical, elongated fuel rod geometry results in a non-isotropic Cherenkov light production, and the light component parallel to the rod's axis exhibits a dependence on gamma-ray energy that differs from the total intensity, which is of importance since the typical safeguards measurement situation observes the vertical light component. It is also concluded that the radial distributions of the radiation sources in a fuel rod will affect the Cherenkov light production.

  11. Control rod worth calculations using deterministic and stochastic methods

    Energy Technology Data Exchange (ETDEWEB)

    Varvayanni, M. [NCSR ' DEMOKRITOS' , PO Box 60228, 15310 Aghia Paraskevi (Greece); Savva, P., E-mail: melina@ipta.demokritos.g [NCSR ' DEMOKRITOS' , PO Box 60228, 15310 Aghia Paraskevi (Greece); Catsaros, N. [NCSR ' DEMOKRITOS' , PO Box 60228, 15310 Aghia Paraskevi (Greece)

    2009-11-15

    Knowledge of the efficiency of a control rod to absorb excess reactivity in a nuclear reactor, i.e. knowledge of its reactivity worth, is very important from many points of view. These include the analysis and the assessment of the shutdown margin of new core configurations (upgrade, conversion, refuelling, etc.) as well as several operational needs, such as calibration of the control rods, e.g. in case that reactivity insertion experiments are planned. The control rod worth can be assessed either experimentally or theoretically, mainly through the utilization of neutronic codes. In the present work two different theoretical approaches, i.e. a deterministic and a stochastic one are used for the estimation of the integral and the differential worth of two control rods utilized in the Greek Research Reactor (GRR-1). For the deterministic approach the neutronics code system SCALE (modules NITAWL/XSDRNPM) and CITATION is used, while the stochastic one is made using the Monte Carlo code TRIPOLI. Both approaches follow the procedure of reactivity insertion steps and their results are tested against measurements conducted in the reactor. The goal of this work is to examine the capability of a deterministic code system to reliably simulate the worth of a control rod, based also on comparisons with the detailed Monte Carlo simulation, while various options are tested with respect to the deterministic results' reliability.

  12. Nonlinear stiffness profiles of external fixators constructed with composite rods.

    Science.gov (United States)

    Carlson, Kimberly R; Kraus, Karl H; Kowaleski, Michael P

    2006-12-01

    To determine if composite connecting rods confer nonlinear stiffness characteristics on unilateral and bilateral external skeletal fixators (ESF) in cranial-caudal bending and axial loading. Mechanical testing performed on models. Six models of 6-pin ESF constructs composed of birch dowels, a commercial ESF system, and composite connecting rods. Unilateral and bilateral ESF configurations were assembled using either specially designed composite titanium and silicone (composite group) or solid titanium (solid group) connecting rods. Mechanical testing was performed in axial loading and 4-point cranial-caudal bending. Stiffness was determined at a low and high-load range, and was considered increasing and nonlinear if the stiffness at high loads was greater than at low loads. The stiffness of the solid group was linear in all testing modes and configurations. Bilateral composite fixators had a nonlinear increasing stiffness in axial loading and cranial-caudal bending. Unilateral composite fixators had a nonlinear increasing stiffness in axial loading, but not cranial-caudal bending. Solid connecting rods conferred a higher stiffness in all testing modes and configurations. Composite connecting rods resulted in nonlinear increasing axial and bending stiffness in bilateral fixators, and in axial load in unilateral fixators. Conventional ESF can be constructed so that the stiffness increases as load increases. This provides the surgeon with additional options to control the local mechanical environment of a healing fracture, which may be used to enhance fracture healing.

  13. Quasi-static and dynamic response of viscoelastic helical rods

    Science.gov (United States)

    Temel, Beytullah; Fırat Çalim, Faruk; Tütüncü, Naki

    2004-04-01

    In this study, the dynamic behaviour of cylindrical helical rods made of linear viscoelastic materials are investigated in the Laplace domain. The governing equations for naturally twisted and curved spatial rods obtained using the Timoshenko beam theory are rewritten for cylindrical helical rods. The curvature of the rod axis, effect of rotary inertia, and shear and axial deformations are considered in the formulation. The material of the rod is assumed to be homogeneous, isotropic and linear viscoelastic. In the viscoelastic material case, according to the correspondence principle, the material constants are replaced with their complex counterparts in the Laplace domain. Ordinary differential equations in scalar form obtained in the Laplace domain are solved numerically using the complementary functions method to calculate the dynamic stiffness matrix of the problem. In the solutions, the Kelvin model is employed. The solutions obtained are transformed to the real space using the Durbin's numerical inverse Laplace transform method. Numerical results for quasi-static and dynamic response of viscoelastic models are presented in the form of graphics.

  14. Combustion of solid carbon rods in zero and normal gravity

    Science.gov (United States)

    Spuckler, C. M.; Kohl, F. J.; Miller, R. A.; Stearns, C. A.; De Witt, K. J.

    1979-01-01

    In order to investigate the mechanism of carbon combustion, normal and zero gravity experiments were conducted in which spectroscopic carbon rods were resistance ignited and burned in an oxygen environment. Direct mass spectrometric sampling was used in the normal gravity tests to measure gas phase concentrations. The gas sampling probe was positioned near the circumference of the horizontally mounted carbon rods, either at the top or at angles of 45 or 90 deg from the top, and yielded concentration profiles of CO2, CO, and O2 as a function of distance from the carbon surface. The experimental concentrations were compared to those predicted by a stagnant film model. Zero gravity droptower tests were conducted in order to assess the effect of convection on the normal gravity combustion process. The ratio of flame diameter to rod diameter as a function of time for oxygen pressures of 5, 10, 15, and 20 psia was obtained for three different diameter rods. It was found that this ratio was inversely proportional to both the oxygen pressure and the rod diameter.

  15. 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.

  16. The acidocalcisome vacuolar transporter chaperone 4 catalyzes the synthesis of polyphosphate in insect-stages of Trypanosoma brucei and T. cruzi.

    Science.gov (United States)

    Ulrich, Paul N; Lander, Noelia; Kurup, Samarchith P; Reiss, Laura; Brewer, Jessica; Soares Medeiros, Lia C; Miranda, Kildare; Docampo, Roberto

    2014-01-01

    Polyphosphate is a polymer of inorganic phosphate found in both prokaryotes and eukaryotes. Polyphosphate typically accumulates in acidic, calcium-rich organelles known as acidocalcisomes, and recent research demonstrated that vacuolar transporter chaperone 4 catalyzes its synthesis in yeast. The human pathogens Trypanosoma brucei and T. cruzi possess vacuolar transporter chaperone 4 homologs. We demonstrate that T. cruzi vacuolar transporter chaperone 4 localizes to acidocalcisomes of epimastigotes by immunofluorescence and immuno-electron microscopy and that the recombinant catalytic region of the T. cruzi enzyme is a polyphosphate kinase. RNA interference of the T. brucei enzyme in procyclic form parasites reduced short chain polyphosphate levels and resulted in accumulation of pyrophosphate. These results suggest that this trypanosome enzyme is an important component of a polyphosphate synthase complex that utilizes ATP to synthesize and translocate polyphosphate to acidocalcisomes in insect stages of these parasites. © 2013 The Author(s) Journal of Eukaryotic Microbiology © 2013 International Society of Protistologists.

  17. Analysis of Explanted Magnetically Controlled Growing Rods From Seven UK Spinal Centers.

    Science.gov (United States)

    Joyce, Thomas J; Smith, Simon L; Rushton, Paul R P; Bowey, Andrew J; Gibson, Michael J

    2018-01-01

    Analysis of explanted MAGnetic Expansion Control (MAGEC) growing rods. To analyze explanted MAGEC rods used in management of early onset scoliosis and identify the mode of failure in such cases. Magnetically controlled growing rods are increasingly used as the option of choice for early onset scoliosis. However, being more complex than conventional growing rods they are perhaps more likely to succumb to multifarious failure modes. In addition, metallosis has been reported around failed MAGEC rods. Explanted MAGEC rods from seven UK spinal centers were obtained for independent analysis. Thirty-four MAGEC rods, from 18 children, explanted for reasons including failure of rod lengthening and maximum rod distraction reached, were cut open to allow internal components to be evaluated and assessed. Externally, all MAGEC rods showed localized marks, which were termed "growth marks" as they indicated growth of the rod in vivo, on the extending bar component. After cutting open, titanium wear debris was found inside all 34 (100%) MAGEC rods. Ninety-one percent (31/34) of MAGEC rods showed measurable wear of the extending bar, towards the magnet end. Substantial damage to the radial bearing was seen inside 74% (25/34) of MAGEC rods while O-ring seal failure was seen in 53% (18/34) of cases. In 44% (15/34) of MAGEC rods the drive pin was fractured but this was felt to be an effect of rod failure, not a cause. The combination of high volumes of titanium wear debris alongside O-ring seal damage likely accounts for the metallosis reported clinically around some MAGEC rods. Based on this explant data, a failure mechanism in MAGEC rods due to the natural off axis loading in the spine was proposed. This is the largest data set reporting a complete analysis of explanted MAGEC rods to date. 4.

  18. Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs

    Science.gov (United States)

    Munday, Jane C.; Eze, Anthonius A.; Baker, Nicola; Glover, Lucy; Clucas, Caroline; Aguinaga Andrés, David; Natto, Manal J.; Teka, Ibrahim A.; McDonald, Jennifer; Lee, Rebecca S.; Graf, Fabrice E.; Ludin, Philipp; Burchmore, Richard J. S.; Turner, C. Michael R.; Tait, Andy; MacLeod, Annette; Mäser, Pascal; Barrett, Michael P.; Horn, David; De Koning, Harry P.

    2014-01-01

    Objectives Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. Methods The TbAQP2 loci of isogenic pairs of drug-susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. Results All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. Conclusions TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporter. PMID:24235095

  19. Trypanosoma brucei TbIF1 inhibits the essential Finf1/inf-ATPase in the infectious form of the parasite

    Czech Academy of Sciences Publication Activity Database

    Panicucci, Brian; Gahura, Ondřej; Zíková, Alena

    2017-01-01

    Roč. 11, č. 4 (2017), č. článku e0005552. ISSN 1935-2735 R&D Projects: GA MŠk(CZ) EE2.3.30.0032; GA ČR GA17-22248S Institutional support: RVO:60077344 Keywords : mt * TblF1 * Trypanosoma brucei Subject RIV: EE - Microbiology, Virology Impact factor: 3.834, year: 2016

  20. Preparation of nanometer-scale rod array of hydroxyapatite crystal.

    Science.gov (United States)

    Hayakawa, Satoshi; Li, Yaqi; Tsuru, Kanji; Osaka, Akiyoshi; Fujii, Eiji; Kawabata, Koji

    2009-07-01

    Fabrication of nano- or micro-structured scaffolds to mimic structural and three-dimensional details of natural bone or teeth has been the subject of much interest, and this study proposes a new strategy for self-assembling one-dimensional hydroxyapatite (HAp) nanorods into organized superstructures. A nanometer-scale rod array of HAp having preferred orientation to the c-axis was successfully prepared simply by soaking calcium-containing silicate glass substrates in Na(2)HPO(4) aqueous solution at 80 degrees C for various periods. Those HAp rods grew perpendicularly to the glass surface, and the crystallites covered the glass surface uniformly, resulting in a "dental enamel-like" rod array structure consisting of "pine-leaf-like" structure units.

  1. Simulations of optical sensors fabricated from metallic rods couplers

    Energy Technology Data Exchange (ETDEWEB)

    Singh, M. R. [Department of Physics and Astronomy, Western University Ontario, London, Ontario N6A 3K7 (Canada); Balakrishanan, Shankar [Department of Physics and Astronomy, Western University Ontario, London, Ontario, Canada, N6A 3K7 and Lawson Health Research Institute, 268, Grosvenor Street, London, Ontario N6A 4V2 (Canada)

    2014-03-31

    We have developed the optical sensing mechanism of photonic couplers fabricated from the periodically arranged metallic rods. The metallic rod lattice is embedded between two dielectric material waveguides. This structure is called metallic coupler. Using the transfer matrix method, expressions for the reflection and transmission coefficients of electromagnetic wave propagating in waveguides have been obtained. We found that for certain energies, the electromagnetic wave is totally reflected from the coupler. Similarly, for a certain energy range the light is totally transmitted. It has also been found that by changing the periodicity of the metallic rods, the transmitted energy can be reflected. The periodicity of the metallic lattice can be modified by applying an external stress or pressure. In other words, the system can be used as stress and pressure sensors. The present findings can be used to make new types photonic sensors.

  2. 3-D rod ejection analysis using a conservative methodology

    Energy Technology Data Exchange (ETDEWEB)

    Park, Min Ho; Park, Jin Woo; Park, Guen Tae; Um, Kil Sup; Ryu, Seok Hee; Lee, Jae Il; Choi, Tong Soo [KEPCO, Daejeon (Korea, Republic of)

    2016-05-15

    The point kinetics model which simplifies the core phenomena and physical specifications is used for the conventional rod ejection accident analysis. The point kinetics model is convenient to assume conservative core parameters but this simplification loses large amount of safety margin. The CHASER system couples the three-dimensional core neutron kinetics code ASTRA, the sub-channel analysis code THALES and the fuel performance analysis code FROST. The validation study for the CHASER system is addressed using the NEACRP three-dimensional PWR core transient benchmark problem. A series of conservative rod ejection analyses for the APR1400 type plant is performed for both hot full power (HFP) and hot zero power (HZP) conditions to determine the most limiting cases. The conservative rod ejection analysis methodology is designed to properly consider important phenomena and physical parameters.

  3. 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.

  4. The ATLAS liquid argon calorimeters Read Out Driver (ROD) system

    CERN Document Server

    Henry-Coüannier, F

    2000-01-01

    The electronic Readout chain for the Liquid Argon calorimeters of the ATLAS detector is briefly presented. Special attention is given to the Read Out Drivers (ROD) which will receive the triggered data from approximately 200,000 calorimeter cells at a 100 kHz event rate. In the ROD boards the energy will be computed for each cell from discrete samples of the waveform using optimal filtering algorithms running in fast digital signal processors. The monitoring of the calorimeter data will also be performed at the ROD level. Performances expected in ATLAS which have been evaluated from simulation studies are presented. A demonstrator system currently under construction is described and performances of the Processing Units (DSP daughter boards) are presented. 4 Refs.

  5. Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK-Cyclin Complex in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Séverine Monnerat

    Full Text Available The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively.

  6. Detection of Trypanosoma brucei in field-captured tsetse flies and identification of host species fed on by the infected flies.

    Science.gov (United States)

    Konnai, Satoru; Mekata, Hirohisa; Odbileg, Raadan; Simuunza, Martin; Chembensof, Mwelwa; Witola, William Harold; Tembo, Mwase Enala; Chitambo, Harrison; Inoue, Noboru; Onuma, Misao; Ohashi, Kazuhiko

    2008-08-01

    The prevalence of trypanosome infections in tsetse flies in the Chiawa area of Lower Zambezi in Zambia, with endemic trypanosomosis, was determined by a polymerase chain reaction (PCR) method that allowed the detection of trypanosome DNA and determination of the type of animal host fed on by the tsetse fly Glossina pallidipes, using tsetse-derived DNA extracts as templates. Ninety G. pallidipes (82 females and 8 males; 18.3%) of the 492 flies captured by baited biconical traps tested positive for the presence of Trypanosoma brucei species genomic DNA. Of the 90 T. brucei-positive flies, 47 (52.2%) also tested positive for vertebrate mitochondrial DNA. Sequence analysis of the vertebrate mitochondrial DNA amplicons established that they originated from 8 different vertebrate species, namely, human (Homo sapiens), African elephant (Loxodonta cyclotis), African buffalo (Syncerus caffer), waterbuck (Kobus ellipsiprymnus), roan antelope (Hippotragus equinus), greater kudu (Tragelaphus strepsiceros), warthog (Phacochoerus africanus), and goat (Capra hircus). Furthermore, to investigate the prevalence of trypanosome infections in domestic goats in the same area where trypanosomes had been detected in tsetse files, a total of 86 goats were randomly selected from 6 different herds. Among the selected goats, 36 (41.9%) were found to be positive for T. brucei species. This combined detection method would be an ideal approach not only for mass screening for infection prevalence in tsetse populations, but also for the prediction of natural reservoirs in areas endemic for trypanosomosis.

  7. Immunization with recombinant beta-tubulin from Trypanosoma evansi induced protection against T. evansi, T. equiperdum and T. b. brucei infection in mice.

    Science.gov (United States)

    Li, S-Q; Fung, M-C; Reid, S A; Inoue, N; Lun, Z-R

    2007-04-01

    The beta-tubulin gene of Trypanosoma evansi (STIB 806) was cloned and expressed in Escherichia coli. The predicted amino acid sequence of T. evansi beta-tubulin shows 100%, 99.8%, 99.1%, and 98.6% homology with T. equiperdum, T. b. brucei, T. cruzi and T. danilewskyi, respectively, but is diverse from that of T. cyclops, showing only 51.6% of homology. Recombinant beta-tubulin was expressed as inclusion bodies in E. coli. It was purified and renatured for immunological studies. Mice immunized with the renatured recombinant beta-tubulin were protected from lethal challenge with T. evansi STIB 806, T. equiperdum STIB 818 and T. b. brucei STIB 940, showing 83.3%, 70% and 76.7% protection, respectively. Serum collected from the rabbit immunized with recombinant beta-tubulin inhibited the growth of T. evansi, T. equiperdum and T. b. brucei in vitro. Serum from mice and rabbits immunized with recombinant beta-tubulin recognized only T. evansi beta-tubulin and not mouse beta-tubulin. The results of this study demonstrated that the recombinant T. evansi beta-tubulin is a potential candidate for the development of a vaccine to prevent animal trypanosomiasis caused by these three trypanosome species.

  8. An experimental study on mechanical properties of GFRP braid-pultruded composite rods

    Directory of Open Access Journals (Sweden)

    2009-09-01

    Full Text Available In this work, a conventional textile braiding machine was modified and added to a pultrusion line in order to produce glass fiber reinforced composite rods by braiding-pultrusion technique. Braid-pultruded (BP rods were produced with three braid roving linear densities and also with three different braid angles. To study the influence of overbraiding on mechanical properties of pultruded rods, unidirectional (UD rods, without braided fabric, were produced, as well. All rod types were subjected to tensile, bending and torsion tests. The experimental results showed that BP rods have considerably higher shear modulus, but lower tensile modulus and flexural rigidity than those of UD pultruded rods, when fiber volume fraction is kept constant. Moreover, rods produced with higher braid roving linear densities had better torsional, but lower tensile and flexural properties. The highest shear modulus was observed in BP rods with braid angle of 45°.

  9. New models of droplet deposition and entrainment for prediction of CHF in cylindrical rod bundles

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Haibin, E-mail: hb-zhang@xjtu.edu.cn [School of Chemical Engineering and Technology, Xi’an Jiaotong University, Xi’an 710049 (China); Department of Chemical Engineering, Imperial College, London SW7 2BY (United Kingdom); Hewitt, G.F. [Department of Chemical Engineering, Imperial College, London SW7 2BY (United Kingdom)

    2016-08-15

    Highlights: • New models of droplet deposition and entrainment in rod bundles is developed. • A new phenomenological model to predict the CHF in rod bundles is described. • The present model is well able to predict CHF in rod bundles. - Abstract: In this paper, we present a new set of model of droplet deposition and entrainment in cylindrical rod bundles based on the previously proposed model for annuli (effectively a “one-rod” bundle) (2016a). These models make it possible to evaluate the differences of the rates of droplet deposition and entrainment for the respective rods and for the outer tube by taking into account the geometrical characteristics of the rod bundles. Using these models, a phenomenological model to predict the CHF (critical heat flux) for upward annular flow in vertical rod bundles is described. The performance of the model is tested against the experimental data of Becker et al. (1964) for CHF in 3-rod and 7-rod bundles. These data include tests in which only the rods were heated and data for simultaneous uniform and non-uniform heating of the rods and the outer tube. It was shown that the predicted CHFs by the present model agree well with the experimental data and with the experimental observation that dryout occurred first on the outer rods in 7-rod bundles. It is expected that the methodology used will be generally applicable in the prediction of CHF in rod bundles.

  10. 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......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...

  11. 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

  12. Functional allocation of synaptic contacts in microcircuits from rods via rod bipolar to AII amacrine cells in the mouse retina.

    Science.gov (United States)

    Tsukamoto, Yoshihiko; Omi, Naoko

    2013-10-15

    Retinal microcircuits for night vision at the absolute threshold are required to relay a single-photon rod signal reliably to ganglion cells via rod bipolar (RB) cells and AII amacrine cells. To assess the noise reduction of intercellular signal transmission in this rod-specific pathway, we quantified its synaptic connectivity by 3D reconstruction of a series of electron micrographs. In most cases (94%), each rod made ribbon synaptic contacts onto two adjacent RB cells. Conversely, each RB cell was contacted by 25 rods. Each RB axon terminal contacted four or five AII amacrine cells via 53 ribbon synapses. Thus, the signal from one rod may be represented as 106 replicates at two RB axons. Moreover, the two adjacent RB cells contacted two to four AII amacrine cells in common, where the signals relayed by two RB cells were reunited. In more detail, over 50% of each RB output was directed predominantly to a single, preferred AII amacrine cell, although each RB cell also separately contacted another one to three AII amacrine cells. Most of the replicate signals at two RB axons were collected on a few AII amacrine cells via reunions, dominant connections, and electrical coupling by AII-AII gap junctions. Thus the original signal may be reliably represented by signal amplification with focal accumulation without gathering unnecessary noise from a wide surrounding area. This allocation of RB-AII synaptic contacts may serve as the structural basis for the physiological properties of the AII single-photon response that include high amplification, local adaptation, and regenerative acceleration. Copyright © 2013 Wiley Periodicals, Inc.

  13. 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

  14. Microstructure analysis and comparison of tungsten alloy rod and [001] oriented columnar-grained tungsten rod ballistic penetrators

    Energy Technology Data Exchange (ETDEWEB)

    Pappu, S.; Kennedy, C.; Murr, L.E. [Texas Univ., El Paso, TX (United States). Dept. of Metallurgical and Materials Engineering; Magness, L.S. [US Army Research Lab., Aberdeen Proving Ground, MD (United States); Kapoor, D. [US Army Armament, Research, Development, and Engineering Center (ARDEC), Picatinny Arsenal, NJ (United States)

    1999-04-01

    Tungsten heavy alloy (WHA) penetrator rods (93% W particles in a matrix of 4.9% Ni and 2.1% Fe) were compared with [001] columnar-grained W penetrator rods in the as-fabricated condition, and after penetration into thick targets at impact velocities of 1 and 1.5 km s{sup -1}, respectively. Light metallography and transmission electron microscopy revealed the initial W microstructures to be similar arrangements of predominantly a left angle 111 right angle /2 screw dislocations. The in-target (deformed) microstructures were characterized by recovered and elongated sub-grains having misorientations ranging from 1 to 5 . (orig.) 22 refs.

  15. Antitrypanosomal compounds from the essential oil and extracts of Keetia leucantha leaves with inhibitor activity on Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase.

    Science.gov (United States)

    Bero, J; Beaufay, C; Hannaert, V; Hérent, M-F; Michels, P A; Quetin-Leclercq, J

    2013-02-15

    Keetia leucantha is a West African tree used in traditional medicine to treat several diseases among which parasitic infections. The dichloromethane extract of leaves was previously shown to possess growth-inhibitory activities on Plasmodium falciparum, Trypanosoma brucei brucei and Leishmania mexicana mexicana with low or no cytotoxicity (>100 μg/ml on human normal fibroblasts) (Bero et al. 2009, 2011). In continuation of our investigations on the antitrypanosomal compounds from this dichloromethane extract, we analyzed by GC-FID and GC-MS the essential oil of its leaves obtained by hydrodistillation and the major triterpenic acids in this extract by LC-MS. Twenty-seven compounds were identified in the oil whose percentages were calculated using the normalization method. The essential oil, seven of its constituents and the three triterpenic acids were evaluated for their antitrypanosomal activity on Trypanosoma brucei brucei bloodstream forms (Tbb BSF) and procyclic forms (Tbb PF) to identify an activity on the glycolytic process of trypanosomes. The oil showed an IC(50) of 20.9 μg/ml on Tbb BSF and no activity was observed on Tbb PF. The best antitrypanosomal activity was observed for ursolic acid with IC(50) of 2.5 and 6.5 μg/ml respectively on Tbb BSF and Tbb PF. The inhibitory activity on a glycolytic enzyme of T. brucei, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was also evaluated for betulinic acid, olenaolic acid, ursolic acid, phytol, α-ionone and β-ionone. The three triterpenic acids and β-ionone showed inhibitory activities on GAPDH with oleanolic acid being the most active with an inhibition of 72.63% at 20 μg/ml. This paper reports for the first time the composition and antitrypanosomal activity of the essential oil of Keetia leucantha. Several of its constituents and three triterpenic acids present in the dichloromethane leaves extract showed a higher antitrypanosomal activity on bloodstream forms of Tbb as compared to procyclic forms

  16. The Evolutionary Linguist's Divining-rod: Restrictive Theory

    African Journals Online (AJOL)

    KATEVG

    The Evolutionary Linguist's Divining-rod: Restrictive Theory 51 course, to be complemented by a theory which characterizes – in an equally constrained way – the products of adaptation by natural selection. Indeed, on certain theories of evolutionary processes an entity is considered an exaptation if it lacks the properties of ...

  17. Boiling water reactor radiation shielded Control Rod Drive Housing Supports

    Energy Technology Data Exchange (ETDEWEB)

    Baversten, B.; Linden, M.J. [ABB Combustion Engineering Nuclear Operations, Windsor, CT (United States)

    1995-03-01

    The Control Rod Drive (CRD) mechanisms are located in the area below the reactor vessel in a Boiling Water Reactor (BWR). Specifically, these CRDs are located between the bottom of the reactor vessel and above an interlocking structure of steel bars and rods, herein identified as CRD Housing Supports. The CRD Housing Supports are designed to limit the travel of a Control Rod and Control Rod Drive in the event that the CRD vessel attachement went to fail, allowing the CRD to be ejected from the vessel. By limiting the travel of the ejected CRD, the supports prevent a nuclear overpower excursion that could occur as a result of the ejected CRD. The Housing Support structure must be disassembled in order to remove CRDs for replacement or maintenance. The disassembly task can require a significant amount of outage time and personnel radiation exposure dependent on the number and location of the CRDs to be changed out. This paper presents a way to minimize personal radiation exposure through the re-design of the Housing Support structure. The following paragraphs also delineate a method of avoiding the awkward, manual, handling of the structure under the reactor vessel during a CRD change out.

  18. Porous tantalum rods for treating osteonecrosis of the femoral head.

    Science.gov (United States)

    Liu, Z H; Guo, W S; Li, Z R; Cheng, L M; Zhang, Q D; Yue, D B; Shi, Z C; Wang, B L; Sun, W; Zhang, N F

    2014-10-20

    This study evaluated the outcomes of using porous tantalum rods for the treatment of osteonecrosis of the femoral head (ONFH). We performed core decompression and inserted porous tantalum implants in 149 patients (168 consecutive hips) with ONFH. Hips had large (65), medium (64), or small (39) lesions; 63 lesions were lateral, 68 were central, and 35 were medial. Conversion to total hip arthroplasty (THA) was the end point of this survey. A total of 130 cases (138 hips) were followed. The mean follow-up time was 38.46 ± 5.76 months; 43 hips (31%) were converted to or needed THA. Of the 43 hips requiring THA, 33 had large lesions, including 1 medial, 3 central, and 29 lateral lesions; 9 had medium, lateral lesions, and 1 hip had a small, lateral lesion. Bone grafting was used in 59 hips, with 3 hips failing; 40 of 79 hips without bone grafts failed. The sum distances between the tops of the rods and the lateral lesion boundaries (SDTL, mm) were measured in anteroposterior and lateral radiographs. In the failure and spared groups, the average SDTLs were 7.65 ± 2.759 and 0.83 ± 2.286 mm, respectively. The survival of porous tantalum rods used for treating early-stage ONFH was affected by the size and location of the lesion, whether or not a bone graft was used, as well as the distance between top of the rod and the lateral boundary of the lesion.

  19. Effect of Cuisenaire Rods' approach on students' interest in decimal ...

    African Journals Online (AJOL)

    This study explored the effectiveness of Cuisenaire Rods' approach in arousing students' interest in decimal fractions. Two research questions were posed and three hypotheses were formulated to guide the study. A sample of 200 JS3 students from a randomly selected schools in Makurdi Metropolis of Benue State, served ...

  20. 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.

  1. Phase behaviour of rod-like colloid + flexible polymer mixtures

    NARCIS (Netherlands)

    Lekkerkerker, H.N.W.; Stroobants, A.

    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

  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. Alignment of rod-shaped gold particles by electric fields

    NARCIS (Netherlands)

    Zande, B.M.I. van der; Koper, G.J.M.; Lekkerkerker, H.N.W.

    1999-01-01

    The electro-optical response of colloidal dispersions of rod-shaped gold particles is studied for various aspect ratios (2.6 < L/d < 49; d = 15 nm) by monitoring the absorbance spectra in the visible wavelength regime. The absorbance spectra strongly depend on the degree of orientational order of

  4. 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.

  5. On the resonant behavior of longitudinally vibrating accreting rods

    CSIR Research Space (South Africa)

    Shatalov, M

    2012-09-01

    Full Text Available subjected to longitudinal vibrations. This problem is described it terms of the linear classical, Rayleigh-Love and Rayleigh-Bishop models. It is assumed that the rod is fixed at one end and free at the other end and its length is increasing. For solution...

  6. Electric Field Driven Self-Assembly of Colloidal Rods

    Science.gov (United States)

    Juarez, Jaime; Chaudhary, Kundan; Chen, Qian; Granick, Steve; Lewis, Jennifer

    2012-02-01

    The ability to assemble anisotropic colloidal building blocks into ordered configurations is of both scientific and technological importance. We are studying how electric field-induced interactions guide the self-assembly of these blocks into well aligned microstructures. Specifically, we present observations of the assembly of colloidal silica rods (L/D ˜ 4) within planar electrode cells as a function of different electric field parameters. Results from video microscopy and image analysis demonstrate that aligned microstructures form due to the competition between equilibrium interactions of induced dipoles and non-equilibrium processes (i.e., electro-osmosis). Under the appropriate electric field conditions (˜ kHZ AC fields), aligned colloidal rod fluids form over large areas on the electrode surface. The superposition of a DC electric field to this aligned colloidal rod fluid initiates their condensation into a vertically oriented crystalline phase. Ongoing work is now focused on exploring how temporal changes to electric fields influence colloidal rod dynamics and, hence, the assembly kinetics of aligned colloidal monolayers.

  7. Longitudinal vibrations of a Rayleigh-Bishop rod

    CSIR Research Space (South Africa)

    Fedotov, IA

    2010-01-01

    Full Text Available In this work, for analyzing the longitudinal vibrations of a conic rod, the authors used the Rayleigh–Bishop model, which generalizes the Rayleigh model and takes into account both lateral displacements and the shear stress in the transverse cross...

  8. Cross-correlated imaging of distributed mode filtering rod fiber

    DEFF Research Database (Denmark)

    Laurila, Marko; Barankov, Roman; Jørgensen, Mette Marie

    2013-01-01

    We analyze the modal properties of an 85μm core distributed mode filtering rod fiber using cross-correlated (C2) imaging. We evaluate suppression of higher-order modes (HOMs) under severely misaligned mode excitation and identify a single-mode regime where HOMs are suppressed by more than 20dB....

  9. The Rod and Bottle System: A Problem in Statics

    Science.gov (United States)

    MacInnes, Iain

    2005-11-01

    The rod and bottle system (sometimes called the "wine butler"), shown in Fig. 1, is a common statics demonstration in the introductory level physics course. One is immediately attracted to it by the craftsmanship in wood. Thomas Carlyle wrote, "Two men I honour, and no third. The scholar and the craftsman."2 This paper presents an analytic treatment of the system.

  10. Rigid rod spaced fullerene as building block for nanoclusters

    Indian Academy of Sciences (India)

    By using phenylacetylene based rigid-rod linkers (PhA), we have successfully synthesized two fullerene derivatives, C60-PhA and C60-PhA-C60. The absorption spectral features of C60, as well as that of the phenylacetylene moiety are retained in the monomeric forms of these fullerene derivatives, ruling out the possibility ...

  11. Hemispherical-rod microlens as a variant fractional Fourier transformer.

    Science.gov (United States)

    Dragoman, D; Brenner, K H; Dragoman, M; Bähr, J; Krackhardt, U

    1998-10-01

    It is shown that a hemispherical-rod microlens can act as a fractional Fourier transform device with a continuously varying degree of fractionality. It is believed to be the first proposed device to perform such a task; its most immediate applications include optical tomography.

  12. Nonlinear optical properties of rigid-rod polymers

    Science.gov (United States)

    Trimmer, Mark S.; Wang, Ying

    1992-01-01

    The purpose of this research project was to integrate enhanced third order nonlinear optical (NLO) properties, especially high x(exp (3)) (greater than 10(exp -8) esu), into Maxdem's novel conjugated rigid-rod polymers while retaining their desirable processing, mechanical, and thermal properties. This work primarily involved synthetic approaches to optimized materials.

  13. Auer rod-like inclusions in non blast cells.

    Science.gov (United States)

    Chapuis, Alexandra; Chebrek, Safia; Lefrand, Hélène; Chesnais, Anne-Laure; Granier, Guillaume; Zerazhi, Hacène; André-Kerneïs, Elisabeth

    2017-11-21

    We report a 69-year-old adult case with a monoclonal gammopathy incidentally discovered, associated with a moderate thrombocytopenia of 90 G/L. Study of blood smear revealed the presence of tumor cells presenting Auer rod-like inclusions, although there were not blast cells. Blood cytology as well as immunophenotyping allowed us to make the diagnosis of malignant hemopathy.

  14. 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.

  15. A Rod-Sparing Retinopathy in Bardet-Biedl Syndrome

    Directory of Open Access Journals (Sweden)

    Cynthia S. Chiu

    2015-01-01

    Full Text Available Bardet-Biedl syndrome is a continuum of disorders characterized by systemic and ocular findings. Retinal abnormalities typically present as diffuse photoreceptor degeneration. Here, we report a novel case that suggests a rod-sparing variant of Bardet-Biedl syndrome.

  16. 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.

  17. SCADOP: Phenomenological modeling of dryout in nuclear fuel rod bundles

    Energy Technology Data Exchange (ETDEWEB)

    Dasgupta, Arnab, E-mail: arnie@barc.gov.in; Chandraker, D.K., E-mail: dineshkc@barc.gov.in; Vijayan, P.K., E-mail: vijayanp@barc.gov.in

    2015-11-15

    Highlights: • Phenomenological model for annular flow dryout is presented. • The model evaluates initial entrained fraction using a new methodology. • The history effect in annular flow is predicted and validated. • Rod bundle dryout is predicted using subchannel methodology. • Model is validated against experimental dryout data in tubes and rod bundles. - Abstract: Analysis and prediction of dryout is of important consequence to safety of nuclear fuel clusters of boiling water type of reactors. Traditionally, experimental correlations are used for dryout predictions. Since these correlations are based on operating parameters and do not aim to model the underlying phenomena, there has been a proliferation of the correlations, each catering to some specific bundle geometry under a specific set of operating conditions. Moreover, such experiments are extremely costly. In general, changes in tested bundle geometry for improvement in thermal-hydraulic performance would require re-experimentation. Understanding and modeling the basic processes leading to dryout in flow boiling thus has great incentive. Such a model has the ability to predict dryout in any rod bundle geometry, unlike the operating parameter based correlation approach. Thus more informed experiments can be carried out. A good model can, reduce the number of experiments required during the iterations in bundle design. In this paper, a phenomenological model as indicated above is presented. The model incorporates a new methodology to estimate the Initial Entrained Fraction (IEF), i.e., entrained fraction at the onset of annular flow. The incorporation of this new methodology is important since IEF is often assumed ad-hoc and sometimes also used as a parameter to tune the model predictions to experimental data. It is highlighted that IEF may be low under certain conditions against the general perception of a high IEF due to influence of churn flow. It is shown that the same phenomenological model is

  18. p53 selectively regulates developmental apoptosis of rod photoreceptors.

    Directory of Open Access Journals (Sweden)

    Linda Vuong

    Full Text Available Retinal cells become post-mitotic early during post-natal development. It is likely that p53, a well-known cell cycle regulator, is involved in regulating the genesis, differentiation and death of retinal cells. Furthermore, retinal cells are under constant oxidative stress that can result in DNA damage, due to the extremely high level of metabolic activity associated with phototransduction. If not repaired, this damage may result in p53-dependent cell death and ensuing vision loss. In this study, the role of p53 during retinal development and in the post-mitotic retina is investigated. A previously described super p53 transgenic mouse that expresses an extra copy of the mouse p53 gene driven by its endogenous promoter is utilized. Another transgenic mouse (HIP that expresses the p53 gene in rod and cone photoreceptors driven by the human interphotoreceptor retinoid binding protein promoter was generated. The electroretinogram (ERG of the super p53 mouse exhibited reduced rod-driven scotopic a and b wave and cone-driven photopic b wave responses. This deficit resulted from a reduced number of rod photoreceptors and inner nuclear layer cells. However, the reduced photopic signal arose only from lost inner retinal neurons, as cone numbers did not change. Furthermore, cell loss was non-progressive and resulted from increased apoptosis during retinal developmental as determined by TUNEL staining. In contrast, the continuous and specific expression of p53 in rod and cone photoreceptors in the mature retinas of HIP mice led to the selective loss of both rods and cones. These findings strongly support a role for p53 in regulating developmental apoptosis in the retina and suggest a potential role, either direct or indirect, for p53 in the degenerative photoreceptor loss associated with human blinding disorders.

  19. COST IMPACT OF ROD CONSOLIDATION ON THE VIABILITY ASSESSMENT DESIGN

    Energy Technology Data Exchange (ETDEWEB)

    D. Lancaster

    1999-03-29

    The cost impact to the Civilian Radioactive Waste Management System of using rod consolidation is evaluated. Previous work has demonstrated that the fuel rods of two assemblies can be packed into a canister that can fit into the same size space as that used to store a single assembly. The remaining fuel assembly hardware can be compacted into the same size canisters with a ratio of 1 hardware canister per each 6 to 12 assemblies. Transportation casks of the same size as currently available can load twice the number of assemblies by placing the compacted assemblies in the slots currently designed for a single assembly. Waste packages similarly could contain twice the number of assemblies; however, thermal constraints would require considering either a low burnup or cooling. The analysis evaluates the impact of rod consolidation on CRWMS costs for consolidation at prior to transportation and for consolidation at the Monitored Geological Repository surface facility. For this study, no design changes were made to either the transport casks or waste packages. Waste package designs used for the Viability Assessment design were employed but derated to make the thermal limits. A logistics analysis of the waste was performed to determine the number of each waste package with each loading. A review of past rod consolidation experience found cost estimates which range from $10/kgU to $32/kgU. $30/kgU was assumed for rod consolidation costs prior to transportation. Transportation cost savings are about $17/kgU and waste package cost savings are about $21/kgU. The net saving to the system is approximately $500 million if the consolidation is performed prior to transportation. If consolidation were performed at the repository surface facilities, it would cost approximately $15/kgU. No transportation savings would be realized. The net savings for consolidation at the repository site would be about $400 million dollars.

  20. Biosynthesis of Zinc Oxide Nano-rods Using Xanthomonas campestris

    Directory of Open Access Journals (Sweden)

    Zahra sadat Mahdi

    2017-06-01

    Full Text Available Introduction: one dimensional nanocrystals especially nano-rods have attracted a great deal of attention due to their unique properties and wide applications in industry. Chemical and physical methods which are currently used to produce zinc oxide nano- rods, often leave toxic chemicals on surface of nanoparticles limiting their applications for health and medical purposes. Therefore, biological synthesis of zinc oxide nanoparticles has been considered as an environmentally friendly process and a potential alternative to chemical and physical methods. Materials and methods: Nano-rods of zinc oxide were produced by Xanthomonas campestris using zinc nitrate hexa hydrate as substrate, in a shaker incubator at 37 ° C and pH 7. The powder produced was then calcined at 600 ° C for 2 hours after drying. The synthesized ZnO nanoparticles were characterized using FTIR, XRD, SEM, EDX and UV–vis spectroscopy. Results: FTIR analysis was used to identify functional groups involved in the biosynthesis of ZnO NPs. The peak observed at 563 cm-1 corresponds to the stretching vibrations of ZnO NPs. XRD analysis revealed that the hexagonal ZnO nanoparticles synthesized were pure and crystalline in nature. The morphology and size of the powder were investigated using SEM analysis and the results showed that ZnO nano-rods have a diameter ranging from 122–200 nm with an average length about 300 nm. EDX analysis was performed for determination of the elemental composition and purity of samples. The recorded EDX spectrum revealed the high purity of the synthesized ZnO nano-rods without detection of any impurities. The absorption peak at 376 nm indicating the presence of zinc oxide nanoparticles was further confirmed by UV-Vis spectroscopy. Discussion and conclusion: The current research work describes a low-cost, unreported, nontoxic, simple, safe and eco-friendly method for the biosynthesis of zinc oxide nanoparticle using xanthomonas campestris as the reducing

  1. Correlated and uncorrelated invisible temporal white noise alters mesopic rod signaling.

    Science.gov (United States)

    Hathibelagal, Amithavikram R; Feigl, Beatrix; Kremers, Jan; Zele, Andrew J

    2016-03-01

    We determined how rod signaling at mesopic light levels is altered by extrinsic temporal white noise that is correlated or uncorrelated with the activity of one (magnocellular, parvocellular, or koniocellular) postreceptoral pathway. Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. Psychometric (Weibull) functions were measured for incremental rod pulses (50 to 250 ms) in the presence (or absence; control) of perceptually invisible subthreshold extrinsic noise. Uncorrelated (rod) noise facilitates rod detection. Correlated postreceptoral pathway noise produces differential changes in rod detection thresholds and decreases the slope of the psychometric functions. We demonstrate that invisible extrinsic noise changes rod-signaling characteristics within the three retinogeniculate pathways at mesopic illumination depending on the temporal profile of the rod stimulus and the extrinsic noise type.

  2. Burnout data for flow of boiling water in vertical round ducts, annuli and rod clusters

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Kurt M.; Hernborg, Gunnar; Bode, Manfred; Eriksson, O.

    1965-07-01

    The present report contains the tables of the burnout data obtained for flow in vertical channels at the Heat Engineering Laboratory of AB Atomenergi in Sweden. The data covers measurements in round ducts, annuli, 3-rod and 7-rod clusters.

  3. 78 FR 33103 - Carbon and Certain Alloy Steel Wire Rod From Brazil, Indonesia, Mexico, Moldova, Trinidad and...

    Science.gov (United States)

    2013-06-03

    ... Certain Alloy Steel Wire Rod From Brazil, Indonesia, Mexico, Moldova, Trinidad and Tobago, and Ukraine... countervailing duty order on carbon and certain alloy steel wire rod (``wire rod'') from Brazil and the...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. IL-6 is Upregulated in Late-Stage Disease in Monkeys Experimentally Infected with Trypanosoma brucei rhodesiense

    Directory of Open Access Journals (Sweden)

    Dawn Nyawira Maranga

    2013-01-01

    Full Text Available The management of human African trypanosomiasis (HAT is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. The search for novel biomarkers is, therefore, essential in the fight against HAT. The current study aimed at investigating the potential of IL-6 as an adjunct parameter for HAT stage determination in vervet monkey model. Four adult vervet monkeys (Chlorocebus aethiops were experimentally infected with Trypanosoma brucei rhodesiense and treated subcuratively at 28 days after infection (dpi to induce late stage disease. Three noninfected monkeys formed the control group. Cerebrospinal fluid (CSF and blood samples were obtained at weekly intervals and assessed for various biological parameters. A typical HAT-like infection was observed. The late stage was characterized by significant (P<0.05 elevation of CSF IL-6, white blood cell count, and total protein starting 35 dpi with peak levels of these parameters coinciding with relapse parasitaemia. Brain immunohistochemical staining revealed an increase in brain glial fibrillary acidic protein expression indicative of reactive astrogliosis in infected animals which were euthanized in late-stage disease. The elevation of IL-6 in CSF which accompanied other HAT biomarkers indicates onset of parasite neuroinvasion and show potential for use as an adjunct late-stage disease biomarker in the Rhodesian sleeping sickness.

  10. IL-6 is Upregulated in Late-Stage Disease in Monkeys Experimentally Infected with Trypanosoma brucei rhodesiense

    Science.gov (United States)

    Nyawira Maranga, Dawn; Kagira, John Maina; Kinyanjui, Christopher Kariuki; Muturi Karanja, Simon; Wangari Maina, Naomi; Ngotho, Maina

    2013-01-01

    The management of human African trypanosomiasis (HAT) is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. The search for novel biomarkers is, therefore, essential in the fight against HAT. The current study aimed at investigating the potential of IL-6 as an adjunct parameter for HAT stage determination in vervet monkey model. Four adult vervet monkeys (Chlorocebus aethiops) were experimentally infected with Trypanosoma brucei rhodesiense and treated subcuratively at 28 days after infection (dpi) to induce late stage disease. Three noninfected monkeys formed the control group. Cerebrospinal fluid (CSF) and blood samples were obtained at weekly intervals and assessed for various biological parameters. A typical HAT-like infection was observed. The late stage was characterized by significant (P < 0.05) elevation of CSF IL-6, white blood cell count, and total protein starting 35 dpi with peak levels of these parameters coinciding with relapse parasitaemia. Brain immunohistochemical staining revealed an increase in brain glial fibrillary acidic protein expression indicative of reactive astrogliosis in infected animals which were euthanized in late-stage disease. The elevation of IL-6 in CSF which accompanied other HAT biomarkers indicates onset of parasite neuroinvasion and show potential for use as an adjunct late-stage disease biomarker in the Rhodesian sleeping sickness. PMID:24194772

  11. 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.

  12. Similarity in variable antigen type composition of Trypanosoma brucei rhodesiense populations in different sites within the mouse host.

    Science.gov (United States)

    Turner, C M; Hunter, C A; Barry, J D; Vickerman, K

    1986-01-01

    Trypanosoma brucei rhodesiense subpopulations in different sites within the body of infected mice were isolated and enumerated on day 6 of cyclically transmitted infections. Most trypanosomes were in the blood vasculature and spleen but approximately 6% occurred in lymph nodes and about 9% were extravascular. Most of the extravascular trypanosomes were in the peritoneal and pleural cavities; significant numbers also occurred in the brain and kidneys. Six major variable antigen types (VATs) were detected by immunofluorescence using specific antisera and monoclonal antibodies. The prevalence of each VAT was essentially the same in subpopulations in the blood, mesenteric and inguinal lymph nodes, brain, kidneys and peritoneal and pleural cavities. This similarity of VAT composition in different subpopulations is probably caused by high rates of dynamic interchange of trypanosomes between sites. Extravascular trypanosomes, therefore, form a significant proportion of the total population in acute infections of mice but they do not appear to play any special role in the population biology of antigenic variation at this stage of infection.

  13. Control rod system useable for fuel handling in a gas-cooled nuclear reactor

    Science.gov (United States)

    Spurrier, Francis R.

    1976-11-30

    A control rod and its associated drive are used to elevate a complete stack of fuel blocks to a position above the core of a gas-cooled nuclear reactor. A fuel-handling machine grasps the control rod and the drive is unlatched from the rod. The stack and rod are transferred out of the reactor, or to a new location in the reactor, by the fuel-handling machine.

  14. 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.

  15. 49 CFR 230.96 - Main, side, and valve motion rods.

    Science.gov (United States)

    2010-10-01

    ... bore of main rod bearings shall not exceed pin diameters more than 3/32 inch at front or back end. The total lost motion at both ends shall not exceed 5/32 inch. (g) Side rod bearings. The bore of side rod.... The total amount of side motion of each rod on its crank pin shall not exceed 1/4 inch. (e) Oil and...

  16. Crossover between activated reptation and arm retraction mechanisms in entangled rod-coil block copolymers

    Science.gov (United States)

    Wang, Muzhou; Likhtman, Alexei E.; Olsen, Bradley D.

    2015-11-01

    Using a coarse-grained slip-spring model, the dynamics of rod-coil block copolymers is explored over a wide parameter space to fully capture the crossover between the short rod (activated reptation) and long rod (arm retraction) limits. An analytical, closed-form expression for curvilinear diffusion by activated reptation was derived by separating the drag into individual components for the rod and coil block. Curvilinear diffusion in the intermediate rod regime, where both mechanisms are important, was then found to be faster than predicted when both mechanisms are independently combined. The discrepancy in the crossover regime arises because the rod-coil copolymer's exploration of space is not accurately described by either a coil homopolymer (assumed by activated reptation) or a rod homopolymer (assumed by arm retraction). This effect is explored by tracking the rod orientation as the polymer reptates, confirming that the polymer reptates along a path that becomes more rodlike as the rod fraction is increased. Thus, activated reptation under-predicts diffusion because the rod can choose reptation paths that are more extended than the coil homopolymer by renewal of the entanglement tube from the ends. Arm retraction under-predicts diffusion because minor rotations of the rod allow some motion before full retractions of the coil block. Finally, more familiar 3-dimensional center-of-mass diffusion measurements are related to the curvilinear diffusion analysis because the ratio of these two quantities varies smoothly between the coil and rod homopolymer limits as the reptation path becomes more extended.

  17. Simultaneous contribution of two rod pathways to AII amacrine and cone bipolar cell light responses.

    Science.gov (United States)

    Trexler, E Brady; Li, Wei; Massey, Stephen C

    2005-03-01

    Rod signals traverse several synapses en route to cone bipolar cells. In one pathway, rods communicate directly with cones via gap junctions. In a second pathway, signals flow rods-rod bipolars-AII amacrines-cone bipolars. The relative contribution of each pathway to retinal function is not well understood. Here we have examined this question from the perspective of the AII amacrine. AIIs form bidirectional electrical synapses with on cone bipolars. Consequently, as on cone bipolars are activated by outer plexiform inputs, they too should contribute to the AII response. Rod bipolar inputs to AIIs were blocked by AMPA receptor antagonists, revealing a smaller, non-AMPA component of the light response. This small residual response did not reverse between -70 and +70 mV and was blocked by carbenoxolone, suggesting that the current arose in on cone bipolars and was transmitted to AIIs via gap junctions. The residual component was evident for stimuli 2 log units below cone threshold and was prolonged for bright stimuli, demonstrating that it was rod driven. Because the rod bipolar-AII pathway was blocked, the rod-driven residual current likely was generated via the rod-cone pathway activation of on cone bipolars. Thus for a large range of intensities, rod signals reach the inner retina by both rod bipolar-AII and rod-cone coupling pathways.

  18. 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 of...

  19. 78 FR 44532 - Steel Threaded Rod From India: Initiation of Countervailing Duty Investigation

    Science.gov (United States)

    2013-07-24

    ... International Trade Administration Steel Threaded Rod From India: Initiation of Countervailing Duty... (``CVD'') petition concerning imports of steel threaded rod from India, filed in proper form by All...., (collectively hereinafter ``Petitioners'').\\1\\ Petitioners are domestic producers of steel threaded rod. On July...

  20. 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 Anti...

  1. 75 FR 32503 - Stainless Steel Wire Rod From Italy, Japan, Korea, Spain, and Taiwan

    Science.gov (United States)

    2010-06-08

    ... COMMISSION Stainless Steel Wire Rod From Italy, Japan, Korea, Spain, and Taiwan Determinations On the basis...)), that revocation of the antidumping duty orders on stainless steel wire rod from Italy, Japan, Korea... contained in USITC Publication 4154 (May 2010), entitled Stainless Steel Wire Rod from Italy, Japan, Korea...

  2. 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)

  3. 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)

  4. Kinematic Analysis of Continuum Robot Consisted of Driven Flexible Rods

    Directory of Open Access Journals (Sweden)

    Yingzhong Tian

    2016-01-01

    Full Text Available This paper presents the kinematic analysis of a continuum bionic robot with three flexible actuation rods. Since the motion of the end-effector is actuated by the deformation of the rods, the robot structure is with high elasticity and good compliance and the kinematic analysis of the robot requires special treatment. We propose a kinematic model based on the geometry with constant curvature. The analysis consists of two independent mappings: a general mapping for the kinematics of all robots and a specific mapping for this kind of robots. Both of those mappings are developed for the single section and for the multisections. We aim at providing a guide for kinematic analysis of the similar manipulators through this paper.

  5. High-power rod-type photonic crystal fiber laser

    Science.gov (United States)

    Limpert, J.; Deguil-Robin, N.; Manek-Hönninger, I.; Salin, F.; Röser, F.; Liem, A.; Schreiber, T.; Nolte, S.; Zellmer, H.; Tünnermann, A.; Broeng, J.; Petersson, A.; Jakobsen, C.

    2005-02-01

    We report on a novel ytterbium-doped fiber design that combines the advantages of rod and fiber gain media. The fiber design has outer dimensions of a rod laser, meaning a diameter in the range of a few millimeters and a length of just a few tens of centimeters, and includes two important waveguide structures, one for pump radiation and one for laser radiation. We obtained 120-W output power in single-mode beam quality from a 48-cm-long fiber cane that corresponds to an extracted power of 250 W/m. The fiber has significantly reduced nonlinearity, which therefore allows for scalability in the performance of a high-peak-power fiber laser and amplifier system.

  6. The readout driver (ROD) for the ATLAS liquid argon calorimeters

    CERN Document Server

    Efthymiopoulos, I

    2001-01-01

    The Readout Driver (ROD) for the Liquid Argon calorimeter of the ATLAS detector is described. Each ROD module receives triggered data from 256 calorimeter cells via two fiber-optics 1.28 Gbit/s links with a 100 kHz event rate (25 kbit/event). Its principal function is to determine the precise energy and timing of the signal from discrete samples of the waveform, taken each period of the LHC clock (25 ns). In addition, it checks, histograms, and formats the digital data stream. A demonstrator system, consisting of a motherboard and several daughter-board processing units (PUs) was constructed and is currently used for tests in the lab. The design of this prototype board is presented here. The board offers maximum modularity and allows the development and testing of different PU designs based on today's leading integer and floating point DSPs. (3 refs).

  7. Fuel rod crud deposition: effects of heat load

    Energy Technology Data Exchange (ETDEWEB)

    Barrera, Facundo

    1999-05-15

    Anomalous diameter changes have been observed on the fuel rods of the in-pile test assembly IFA-585. These diameter changes are described in the HWR-407 [1], where it is suggested that crud deposition is their cause. The present report continues the study of the causes of crud deposition on the fuel rods, by analysing its dependence with the heat load. It is observed that crud deposition is less favoured on the cladding at axial positions of pellet-pellet interfaces, and that this is directly correlated with the fact that heat flux is lower at pellet-pellet interfaces. A finite element model is built to analyse the heat flux on the cladding at the surroundings of pellet-pellet interfaces. Also, an empirical formula is derived for the dependence of crud deposition rate with heat loading, taking into account the differences in heat flux on the surroundings of pellet-pellet interfaces (author) (ml)

  8. Measurement of secondary flow vortices on a rod bundle

    Energy Technology Data Exchange (ETDEWEB)

    Vonka, V.

    1988-02-01

    Secondary flow vortices in infinite rod bundles have been predicted by a number of theoretical analyses. Nevertheless experimental verification was difficult, since the magnitude of the secondary velocities appeared to be less than the accuracy of the experimental techniques used. Only indications of the maximum velocity magnitude have been available but no report on successful direct measurement is known to the author. At ECN, laser Doppler velocimetry is successfully used for measurement of secondary flow vortices in two regular subchannels of a triangularly arranged bare rod bundle with pitch-to-diameter ratio P/D-1.3 under the Reynolds number conditions 60,000 and 175,000. One single secondary vortex, having the average tangential velocity slightly less than 0.1% of the mean bulk velocity, is resolved per minimum symmetry sector of the bundle geometry. Ensemble averages are made to obtain quantitative description of the vortex and to form a data base for comparison with calculations.

  9. High-power dual-rod Yb:YAG laser

    Energy Technology Data Exchange (ETDEWEB)

    Honea, Eric C.; Beach, Raymond J.; Mitchell, Scott C.; Skidmore, Jay A.; Emanuel, Mark A.; Sutton, Steven B.; Payne, Stephen A.; Avizonis, Petras V.; Monroe, Robert S.; Harris, Dennis G.

    2000-06-01

    We describe a diode-pumped Yb:YAG laser that produces 1080 W of power cw with 27.5% optical optical efficiency and 532 W Q -switched with M{sup 2}=2.2 and 17% optical-optical efficiency. The laser uses two composite Yb:YAG rods separated by a 90 degree sign quartz rotator for bifocusing compensation. A microlensed diode array end pumps each rod, using a hollow lens duct for pump delivery. By changing resonator parameters we can adjust the fundamental mode size and the output beam quality. Using a flattened Gaussian intensity profile to calculate the mode-fill efficiency and clipping losses, we compare experimental data with modeled output power versus beam quality. (c) 2000 Optical Society of America.

  10. The Attenuation of Torsional Strain Wave in a PMMA Rod

    OpenAIRE

    田辺, 裕治; 前川, 一郎; 半田, 晋一; 原, 利昭; Tanabe, Yuji; Maekawa, Ichiro; Handa, Shinichi; Hara, Toshiaki

    1990-01-01

    In order to clarify the strain attenuation during shear wave propagation, impact torsion experiments are carried out using a PMMA rod specimen. The strain pulses measured by strain gages are complicated due to the superposition of many reflected and transmitted waves from the supported end of the specimen. To obtain data from such pulses for determining a viscoelastic model, a method which modifies the pulse form is developed taking into account wave propagation behavior in the experimental s...

  11. 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....

  12. 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.

  13. Critical Power in 7-Rod Tight Lattice Bundle

    Science.gov (United States)

    Liu, Wei; Kureta, Masatoshi; Akimoto, Hajime

    The Reduced-Moderation Water Reactor (RMWR) has recently becomes of great concern. The RMWR is expected to promote the effective utilization of uranium recourse. The RMWR is based on water-cooled reactor technology, with achieved under lower core water volume and water flow rate. In comparison with the current light water reactors whose water-to-fuel volume ratio is about 2-3, in the RMWR, this value is reduced to less than 0.5. Thereby, there is a need to research its cooling characteristics. Experimental research on critical power in tight lattice bundle that simulates the RMWR has been carried out in Japan Atomic Energy Research Institute (JAERI). The bundle consists one center rod and six peripheral rods. The 7 rods are arranged on a 14.3mm equilateral triangular pitch. Each rod is 13mm in outside diameter. An axial 12-step power distribution is employed to simulate the complicate heating condition in RMWR. Experiments are carried out under G=100-1400kg/m2s, Pex=2-8.5MPa. Effects of mass velocity, inlet temperature, pressure, radial peaking factor and axial peaking factor on critical power and critical quality are discussed. Compared with axial uniform heating condition, the axial non-uniform heating condition causes an obvious decrease in critical quality. Arai correlation, which is the only correlation that has been optimized for tight lattice condition, is verified with the present experimental data. The correlation is found to be able to give reasonable prediction only around RMWR nominal operating condition.

  14. 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.

  15. THE CALCULATION OF MULTICOMPONENT ROD SYSTEMS BY DECOMPOSITION METHOD

    Directory of Open Access Journals (Sweden)

    O. S. Raspopov

    2008-12-01

    Full Text Available For decomposition of two- and three-dimensional rod systems the effective algorithm of dividing a system into blocks and the appropriate technique of coding for states of each from subsystems are developed. It is shown that the structure of multi-dimensional models can be set by means of space matrices based on the research of topological properties of the system graph.

  16. Features of electric drive sucker rod pumps for oil production

    Science.gov (United States)

    Gizatullin, F. A.; Khakimyanov, M. I.; Khusainov, F. F.

    2018-01-01

    This article is about modes of operation of electric drives of downhole sucker rod pumps. Downhole oil production processes are very energy intensive. Oil fields contain many oil wells; many of them operate in inefficient modes with significant additional losses. Authors propose technical solutions to improve energy performance of a pump unit drives: counterweight balancing, reducing of electric motor power, replacing induction motors with permanent magnet motors, replacing balancer drives with chain drives, using of variable frequency drives.

  17. First Test Results of the 4-ROD Crab Cavity

    CERN Document Server

    Ambattu, P; Burt, G; Calaga, R; Capatina, O; Calatroni, S; Ciapala, E; Doherty, D; Ferreira, L; Jensen, E; Hall, B; Lingwood, C; Maesen, P; Mongelluzzo, A; Renaglia, T; Therasse, M

    2013-01-01

    The first compact prototype crab cavity with the 4rod geometry has undergone surface treatment and cold testing. Due to the complex geometry and unique fabrication procedure, RF validation of the field at beyond the nominal operating voltage at a sufficiently high Q0 is an important pre-requisite. Preliminary results of the first cold tests are presented along with cavity performance at different stages of the cavity processing is described.

  18. Characterization of Emericella nidulans RodA and DewA hydrophobin mutants

    DEFF Research Database (Denmark)

    Jensen, Britt Guillaume; Nielsen, Jakob Blæsbjerg; Pedersen, Mona Højgaard

    Hydrophobins are small amphiphilic proteins containing an eight cysteine pattern only found in filamentous fungi. They are involved in the attachment of hyphae to hydrophobic structures and the formation of aerial structures. Five Emericella nidulans mutant strains were examined to study the two...... hydrophobins RodA and DewA. Individual knock-out mutants rodAΔ, dewAΔ and the double deletion strain rodAΔdewAΔ were constructed. Furthermore, two strains containing a point mutation in the first of the cysteines of RodA (rodA-C57G), where one was coupled to the dewA deletion, were included. The reference...

  19. Modal properties of the flexural vibrating package of rods linked by spacer grids

    Directory of Open Access Journals (Sweden)

    Zeman V.

    2011-06-01

    Full Text Available The paper deals with the modelling and modal analysis of the large package of identical parallel rods linked by transverse springs (spacer grids placed on several level spacings. The rod discretization by finite element method is based on Rayleigh beam theory. For the cyclic and central symmetric package of rods (such as fuel rods in nuclear fuel assembly the system decomposition on the identical revolved rod segments was applied. A modal synthesis method with condensation is used for modelling of the whole system. The presented method is the first step for modelling the nuclear fuel assembly vibration caused by excitation determined by the support plate motion of the reactor core.

  20. Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes.

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    2016-12-01

    Full Text Available 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.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.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.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.

  1. 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.

  2. Digital gene expression analysis of two life cycle stages of the human-infective parasite, Trypanosoma brucei gambiense reveals differentially expressed clusters of co-regulated genes

    Directory of Open Access Journals (Sweden)

    Wildridge David

    2010-02-01

    Full Text Available Abstract Background The evolutionarily ancient parasite, Trypanosoma brucei, is unusual in that the majority of its genes are regulated post-transcriptionally, leading to the suggestion that transcript abundance of most genes does not vary significantly between different life cycle stages despite the fact that the parasite undergoes substantial cellular remodelling and metabolic changes throughout its complex life cycle. To investigate this in the clinically relevant sub-species, Trypanosoma brucei gambiense, which is the causative agent of the fatal human disease African sleeping sickness, we have compared the transcriptome of two different life cycle stages, the potentially human-infective bloodstream forms with the non-human-infective procyclic stage using digital gene expression (DGE analysis. Results Over eleven million unique tags were generated, producing expression data for 7360 genes, covering 81% of the genes in the genome. Compared to microarray analysis of the related T. b. brucei parasite, approximately 10 times more genes with a 2.5-fold change in expression levels were detected. The transcriptome analysis revealed the existence of several differentially expressed gene clusters within the genome, indicating that contiguous genes, presumably from the same polycistronic unit, are co-regulated either at the level of transcription or transcript stability. Conclusions DGE analysis is extremely sensitive for detecting gene expression differences, revealing firstly that a far greater number of genes are stage-regulated than had previously been identified and secondly and more importantly, this analysis has revealed the existence of several differentially expressed clusters of genes present on what appears to be the same polycistronic units, a phenomenon which had not previously been observed in microarray studies. These differentially regulated clusters of genes are in addition to the previously identified RNA polymerase I polycistronic

  3. Activation and deactivation of vibronic channels in intact phycocyanin rods

    Science.gov (United States)

    Nganou, C.; David, L.; Meinke, R.; Adir, N.; Maultzsch, J.; Mkandawire, M.; Pouhè, D.; Thomsen, C.

    2014-02-01

    We investigated the excitation modes of the light-harvesting protein phycocyanin (PC) from Thermosynechococcus vulcanus in the crystalline state using UV and near-infrared Raman spectroscopy. The spectra revealed the absence of a hydrogen out-of-plane wagging (HOOP) mode in the PC trimer, which suggests that the HOOP mode is activated in the intact PC rod, while it is not active in the PC trimer. Furthermore, in the PC trimer an intense mode at 984 cm-1 is assigned to the C-C stretching vibration while the mode at 454 cm-1 is likely due to ethyl group torsion. In contrast, in the similar chromophore phytochromobilin the C5,10,15-D wag mode at 622 cm-1 does not come from a downshift of the HOOP. Additionally, the absence of modes between 1200 and 1300 cm-1 rules out functional monomerization. A correlation between phycocyanobilin (PCB) and phycoerythrobilin (PEB) suggests that the PCB cofactors of the PC trimer appear in a conformation similar to that of PEB. The conformation of the PC rod is consistent with that of the allophycocyanin (APC) trimer, and thus excitonic flow is facilitated between these two independent light-harvesting compounds. This excitonic flow from the PC rod to APC appears to be modulated by the vibration channels during HOOP wagging, C = C stretching, and the N-H rocking in-plan vibration.

  4. 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.

  5. 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.

  6. Development of examination technique for oxide layer thickness measurement of irradiated fuel rods

    Energy Technology Data Exchange (ETDEWEB)

    Koo, D. S.; Park, S. W.; Kim, J. H.; Seo, H. S.; Min, D. K.; Kim, E. K.; Chun, Y. B.; Bang, K. S

    1999-06-01

    Technique for oxide layer thickness measurement of irradiated fuel rods was developed to measure oxide layer thickness and study characteristic of fuel rods. Oxide layer thickness of irradiated fuels were measured, analyzed. Outer oxide layer thickness of 3 cycle-irradiated fuel rods were 20 - 30 {mu}m, inner oxide layer thickness 0 - 10 {mu}m and inner oxide layer thickness on cracked cladding about 30 {mu}m. Oxide layer thickness of 4 cycle-irradiated fuel rods were about 2 times as thick as those of 1 cycle-irradiated fuel rods. Oxide layer on lower region of irradiated fuel rods was thin and oxide layer from lower region to upper region indicated gradual increase in thickness. Oxide layer thickness from 2500 to 3000 mm showed maximum and oxide layer thickness from 3000 to top region of irradiated fuel rods showed decreasing trend. Inner oxide layer thicknesses of 4 cycle-irradiated fuel rod were about 8 {mu}m at 750 - 3500 mm from the bottom end of fuel rod. Outer oxide layer thickness were about 8 {mu}m at 750 - 1000 mm from the bottom end of fuel rod. These indicated gradual increase up to upper region from the bottom end of fuel rod. These indicated gradual increase up to upper region from the bottom end of fuel. Oxide layer thickness technique will apply safety evaluation and study of reactor fuels. (author). 6 refs., 14 figs.

  7. Comparative biochemical and pathological changes in some laboratory animals experimentally infected with Trypanosoma brucei and their responses to diminazene diaceturate (Veriben® therapy

    Directory of Open Access Journals (Sweden)

    Amina Ibrahim

    2015-12-01

    Full Text Available Objective: To compare the biochemical and pathological changes of Trypanosoma brucei brucei infected mice, rats and rabbits, and study the chemotherapeutic effects according to standard criteria. Methods: A total of 20 Balb/c Albino mice, 20 Wister Albino rats and 20 New Zealand rabbits, all adults and of both sexes were used in the study. Each rodent group was divided into four groups (A, B, C and D of five animals each. Animals in Groups A and C were individually infected with 0.5 mL of blood from donor rats containing 1.5 ××106 Trypanasoma brucei brucei, while Groups B and D remained uninfected. The animals were later treated like this: Group A (infected and untreated control, Group B (uninfected and untreated control, Group C (infected and treated and Group D (uninfected and treated. The treatment was administered on Day 12 after infection. Results: The prepatent period for mice and rats was 4 days while that for rabbits was 8 days. There was a significant (P < 0.05 increase in levels of liver enzymes and serum metabolites which were more marked among the mice and rats than rabbits. These changes were modulated to their preinfection values in the infected treated animals. At necropsy, all animals showed splenomegaly, hepatomegaly and nephritis. However, cardiomegaly was exclusive to the rabbits. Histopathologically, degenerative changes were observed in both the liver and kidneys which were more severe among mice and rats and moderate in rabbits. Spleen of mice showed giant macrophages, while that of the rats showed epithelioid giant cells. However, spleen of rabbits showed haemosiderosis and eosinophilic infiltrations. Hydrophobic degeneration, necrosis and mononuclear cell infiltrations in the myocardium were observed only among rabbits. Conclusions: Diminazene diaceturate was able to ameliorate the various biochemical and pathological changes which were suggestive of severe liver and kidney dysfunctions with greater intensity occurring

  8. 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.

  9. The rod pathway of the microbat retina has bistratified rod bipolar cells and tristratified AII amacrine cells.

    Science.gov (United States)

    Müller, Brigitte; Butz, Elisabeth; Peichl, Leo; Haverkamp, Silke

    2013-01-16

    We studied the retinal rod pathway of Carollia perspicillata and Glossophaga soricina, frugivorous microbats of the phyllostomid family. Protein kinase Cα (PKCα) immunolabeling revealed abundant rod bipolar cells (RBCs) with axon terminals in the innermost sublamina of the inner plexiform layer (IPL), which is typical for mammals. Extraordinarily, the RBC axons showed additional synaptic contacts in a second sublamina further out in the IPL. Dye injections of PKCα-prelabeled RBCs of C. perspicillata confirmed the bistratified axon morphology. The functional partition of the IPL into ON and OFF sublayers was shown by using antibodies against vesicular glutamate transporter 1 [labeling all ON and OFF bipolar cell (BC) axon terminals] and G-protein γ13 (labeling all ON BCs). The ON sublayer occupied 75% of the IPL thickness, including both strata of the RBC axons. RBC output onto putative AII amacrine cells (ACs), the crucial interneurons of the rod pathway, was identified by calretinin, PKCα, and CtBP2 triple immunolabeling. Dye injections of calretinin-prelabeled ACs revealed tristratification of the AII ACs corresponding to the bistratified RBCs. Triple immunolabeling for PKCα, nitric oxide synthetase (NOS), and either GABA(C) or CtBP2 indicated GABAergic feedback onto RBCs via NOS-immunoreactive ACs. AII output analysis showed glycineric synapses with glycine receptor α1 expression between AII cells and OFF cone BCs and connexin 36-labeled gap junctions between AII cells and ON cone BCs. We conclude that microbats have a well developed rod pathway with great similarities to that of other mammals, but with an unusual IPL stratification pattern of RBCs and AIIs.

  10. Interaction between the flagellar pocket collar and the hook complex via a novel microtubule-binding protein in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Anna Albisetti

    2017-11-01

    Full Text Available Trypanosoma brucei belongs to a group of unicellular, flagellated parasites that are responsible for human African trypanosomiasis. An essential aspect of parasite pathogenicity is cytoskeleton remodelling, which occurs during the life cycle of the parasite and is accompanied by major changes in morphology and organelle positioning. The flagellum originates from the basal bodies and exits the cell body through the flagellar pocket (FP but remains attached to the cell body via the flagellum attachment zone (FAZ. The FP is an invagination of the pellicular membrane and is the sole site for endo- and exocytosis. The FAZ is a large complex of cytoskeletal proteins, plus an intracellular set of four specialised microtubules (MtQ that elongate from the basal bodies to the anterior end of the cell. At the distal end of the FP, an essential, intracellular, cytoskeletal structure called the flagellar pocket collar (FPC circumvents the flagellum. Overlapping the FPC is the hook complex (HC (a sub-structure of the previously named bilobe that is also essential and is thought to be involved in protein FP entry. BILBO1 is the only functionally characterised FPC protein and is necessary for FPC and FP biogenesis. Here, we used a combination of in vitro and in vivo approaches to identify and characterize a new BILBO1 partner protein-FPC4. We demonstrate that FPC4 localises to the FPC, the HC, and possibly to a proximal portion of the MtQ. We found that the C-terminal domain of FPC4 interacts with the BILBO1 N-terminal domain, and we identified the key amino acids required for this interaction. Interestingly, the FPC4 N-terminal domain was found to bind microtubules. Over-expression studies highlight the role of FPC4 in its association with the FPC, HC and FPC segregation. Our data suggest a tripartite association between the FPC, the HC and the MtQ.

  11. Trypanosoma brucei gambiense Infections in Mice Lead to Tropism to the Reproductive Organs, and Horizontal and Vertical Transmission.

    Directory of Open Access Journals (Sweden)

    Nicolas Biteau

    2016-01-01

    Full Text Available Trypanosoma brucei gambiense, transmitted by the tsetse fly, is the main causative agent of Human African trypanosomosis in West Africa and poses a significant health risk to 70 million people. Disease progression varies depending on host immunity, but usually begins with a haemo-lymphatic phase, followed by parasite invasion of the central nervous system. In the current study, the tropism of T. b. gambiense 1135, causing a low level chronic 'silent' infection, was monitored in a murine model using bioluminescence imaging and PCR. A tropism to the reproductive organs, in addition to the central nervous system, after 12-18 months of infection was observed. Bioluminescent analysis of healthy females crossed with infected males showed that 50%, 62.5% and 37.5% of the female mice were subsequently positive for parasites in their ovaries, uteri and brain respectively. Although PCR confirmed the presence of parasites in the uterus of one of these mice, the blood of all mice was negative by PCR and LAMP. Subsequently, bioluminescent imaging of the offspring of infected female mice crossed with healthy males indicated parasites were present in the reproductive organs of both male (80% and female (60% offspring. These findings imply that transmission of T. b. gambiense 1135 occurs horizontally, most probably via sexual contact, and vertically in a murine model, which raises the possibility of a similar transmission in humans. This has wide reaching implications. Firstly, the observations made in this study are likely to be valid for wild animals acting as a reservoir for T. b. gambiense. Also, the reproductive organs may act as a refuge for parasites during drug treatment in a similar manner to the central nervous system. This could leave patients at risk of a relapse, ultimately allowing them to act as a reservoir for subsequent transmission by tsetse and possibly, horizontally and vertically.

  12. Trypanosoma brucei rhodesiense transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis.

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    John K Thuita

    Full Text Available We have investigated the pathogenicity of tsetse (Glossina pallidipes-transmitted cloned strains of Trypanosoma brucei rhodesiense in vervet monkeys. Tsetse flies were confirmed to have mature trypanosome infections by xenodiagnosis, after which nine monkeys were infected via the bite of a single infected fly. Chancres developed in five of the nine (55.6% monkeys within 4 to 8 days post infection (dpi. All nine individuals were successfully infected, with a median pre-patent period of 4 (range = 4-10 days, indicating that trypanosomes migrated from the site of fly bite to the systemic circulation rapidly and independently of the development of the chancre. The time lag to detection of parasites in cerebrospinal fluid (CSF was a median 16 (range = 8-40 days, marking the onset of central nervous system (CNS, late stage disease. Subsequently, CSF white cell numbers increased above the pre-infection median count of 2 (range = 0-9 cells/microl, with a positive linear association between their numbers and that of CSF trypanosomes. Haematological changes showed that the monkeys experienced an early microcytic-hypochromic anaemia and severe progressive thrombocytopaenia. Despite a 3-fold increase in granulocyte numbers by 4 dpi, leucopaenia occurred early (8 dpi in the monkey infection, determined mainly by reductions in lymphocyte numbers. Terminally, leucocytosis was observed in three of nine (33% individuals. The duration of infection was a median of 68 (range = 22-120 days. Strain and individual differences were observed in the severity of the clinical and clinical pathology findings, with two strains (KETRI 3741 and 3801 producing a more acute disease than the other two (KETRI 3804 and 3928. The study shows that the fly-transmitted model accurately mimics the human disease and is therefore a suitable gateway to understanding human African trypanosomiasis (HAT; sleeping sickness.

  13. 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.

  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

    2007-11-01

    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. Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo.

    Science.gov (United States)

    Priotto, Gerardo; Kasparian, Serena; Ngouama, Daniel; Ghorashian, Sara; Arnold, Ute; Ghabri, Salah; Karunakara, Unni

    2007-12-01

    Human African trypanosomiasis caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are either highly toxic or impracticable in field conditions. We compared the efficacy and safety of the nifurtimox-eflornithine drug combination with the standard eflornithine regimen for the treatment of second-stage disease. A randomized, open-label, active-control, phase III clinical trial comparing 2 arms was conducted at the Sleeping Sickness Treatment Center, which was run by Medecins Sans Frontieres, in Nkayi, Bouenza Province, Republic of Congo. Patients were screened for inclusion and randomly assigned to receive eflornithine alone (400 mg/kg per day given intravenously every 6 h for 14 days) or eflornithine (400 mg/kg per day given intravenously every 12 h for 7 days) plus nifurtimox (15 mg/kg per day given orally every 8 h for 10 days). Patients were observed for 18 months. The study's outcomes were cure and adverse events attributable to treatment. A total of 103 patients with second-stage disease were enrolled. Cure rates were 94.1% for the eflornithine group and 96.2% for the nifurtimox-eflornithine group. Drug reactions were frequent in both arms, and severe reactions affected 25.5% of patients in the eflornithine group and 9.6% of those in the nifurtimox-eflornithine group, resulting in 2 and 1 treatment suspensions, respectively. There was 1 death in the eflornithine arm and no deaths in the nifurtimox-eflornithine arm. The nifurtimox-eflornithine combination appears to be a promising first-line therapy for second-stage sleeping sickness. If our findings are corroborated by ongoing findings from additional sites (a multicenter extension of this study), the new nifurtimox-eflornithine combination therapy will mark a major and multifaceted advance over current therapies.

  16. Magnetic controlled growth rods versus conventional growing rod systems in the treatment of early onset scoliosis: a cost comparison.

    Science.gov (United States)

    Rolton, Daniel; Richards, Joanna; Nnadi, Colin

    2015-07-01

    To evaluate the cost differences between a conventional growth rod system (CGRS) and magnetic controlled growth rods (MCGR) in treating early onset scoliosis (EOS) over a projected 5 year period. We hypothesise that the high initial outlay for MCGR would be recouped from fewer admissions and surgical procedures over the lifetime of the implant. The costs of all aspects of treatment for 14 patients undergoing conversion from CGRS to MGRS were collected over a 3 year period. The costs of all aspects of each treatment including clinic visits, hospital stay, theatre and complications were calculated and projected over the lifetime of each device. The initial outlay for insertion for MCGR was £12,913 more than the CGRS. There were significant cost savings for each lengthening which projected over the 5 year lifetime amounted to a cost saving of over £8,000 per patient. Magnetic controlled growth rods reduce the need for multiple invasive procedures in the management of EOS. The implant has a significant projected cost saving in comparison to CGRS.

  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. © 2016 The Author(s).

  18. Reduction of intradiscal pressure by the use of polycarbonate-urethane rods as compared to titanium rods in posterior thoracolumbar spinal fixation.

    Science.gov (United States)

    Jacobs, Eva; Roth, Alex K; Arts, Jacobus J; van Rhijn, Lodewijk W; Willems, Paul C

    2017-08-21

    Loss of sagittal alignment and balance in adult spinal deformity can cause severe pain, disability and progressive neurological deficit. When conservative treatment has failed, spinal fusion using rigid instrumentation is currently the salvage treatment to stop further curve progression. However, fusion surgery is associated with high revision rates due to instrumentation failure and proximal junctional failure, especially if patients also suffer from osteoporosis. To address these drawbacks, a less rigid rod construct is proposed, which is hypothesized to provide a more gradual transition of force and load distribution over spinal segments in comparison to stiff titanium rods. In this study, the effect of variation in rod stiffness on the intradiscal pressure (IDP) of fixed spinal segments during flexion-compression loading was assessed. An ex vivo multisegment (porcine) flexion-compression spine test comparing rigid titanium rods with more flexible polycarbonate-urethane (PCU) rods was used. An increase in peak IDP was found for both the titanium and PCU instrumentation groups as compared to the uninstrumented controls. The peak IDP for the spines instrumented with the PCU rods was significantly lower in comparison to the titanium instrumentation group. These results demonstrated the differences in mechanical load transfer characteristics between PCU and titanium rod constructs when subjected to flexion-compression loading. The concept of stabilization with a less rigid rod may be an alternative to fusion with rigid instrumentation, with the aim of decreasing mechanical stress on the instrumented segments and the possible benefit of a decrease in the incidence of screw pullout.

  19. 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 Five-Year...

  20. 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 of...

  1. 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... certain alloy steel wire rod. The product is currently classified under the Harmonized Tariff Schedule of...

  2. 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 of...

  3. Diverse patterns of expression of the cytochrome c oxidase subunit I gene and unassigned reading frames 4 and 5 during the life cycle of Trypanosoma brucei.

    Science.gov (United States)

    Jasmer, D P; Feagin, J E; Stuart, K

    1985-01-01

    Transcription of a maxicircle segment from Trypanosoma brucei 164 that contains nucleotide (nt) sequences corresponding to cytochrome c oxidase subunit I (COI) and unassigned reading frames (URFs) 4 and 5 of other mitochondrial systems was investigated. Two major transcripts that differ in size by ca. 200 nt map to each of the COI and URF4 genes, while a single major transcript maps to URF5. In total RNA, the larger COI transcript is more abundant in procyclic forms (PFs) than in bloodstream forms (BFs), the smaller COI and both URF4 transcripts have similar abundances in both forms, and the single URF5 transcript is more abundant in BF than PF. These patterns of expression differ in poly(A)+ RNA as a result of a higher proportion of poly(A)+ mitochondrial transcripts in PFs than in BFs. In addition, small (300- to 500-nt) RNAs that are transcribed from C-rich sequences located between putative protein-coding genes also exhibit diverse patterns of expression between life cycle stages and differences in polyadenylation in PFs compared with BFs. These observations suggest that multiple processes regulate the differential expression of mitochondrial genes in T. brucei. Images PMID:2427925

  4. Trypanosoma brucei Inhibition by Essential Oils from Medicinal and Aromatic Plants Traditionally Used in Cameroon (Azadirachta indica, Aframomum melegueta, Aframomum daniellii, Clausena anisata, Dichrostachys cinerea and Echinops giganteus).

    Science.gov (United States)

    Kamte, Stephane L Ngahang; Ranjbarian, Farahnaz; Campagnaro, Gustavo Daniel; Nya, Prosper C Biapa; Mbuntcha, Hélène; Woguem, Verlaine; Womeni, Hilaire Macaire; Ta, Léon Azefack; Giordani, Cristiano; Barboni, Luciano; Benelli, Giovanni; Cappellacci, Loredana; Hofer, Anders; Petrelli, Riccardo; Maggi, Filippo

    2017-07-06

    Essential oils are complex mixtures of volatile components produced by the plant secondary metabolism and consist mainly of monoterpenes and sesquiterpenes and, to a minor extent, of aromatic and aliphatic compounds. They are exploited in several fields such as perfumery, food, pharmaceutics, and cosmetics. Essential oils have long-standing uses in the treatment of infectious diseases and parasitosis in humans and animals. In this regard, their therapeutic potential against human African trypanosomiasis (HAT) has not been fully explored. In the present work, we have selected six medicinal and aromatic plants ( Azadirachta indica , Aframomum melegueta , Aframomum daniellii , Clausena anisata , Dichrostachys cinerea , and Echinops giganteus ) traditionally used in Cameroon to treat several disorders, including infections and parasitic diseases, and evaluated the activity of their essential oils against Trypanosma brucei TC221. Their selectivity was also determined with Balb/3T3 (mouse embryonic fibroblast cell line) cells as a reference. The results showed that the essential oils from A. indica , A . daniellii , and E. giganteus were the most active ones, with half maximal inhibitory concentration (IC 50 ) values of 15.21, 7.65, and 10.50 µg/mL, respectively. These essential oils were characterized by different chemical compounds such as sesquiterpene hydrocarbons, monoterpene hydrocarbons, and oxygenated sesquiterpenes. Some of their main components were assayed as well on T. brucei TC221, and their effects were linked to those of essential oils.

  5. Rhodopsin mutant P23H destabilizes rod photoreceptor disk membranes.

    Directory of Open Access Journals (Sweden)

    Mohammad Haeri

    Full Text Available Mutations in rhodopsin cause retinitis pigmentosa in humans and retinal degeneration in a multitude of other animals. We utilized high-resolution live imaging of the large rod photoreceptors from transgenic frogs (Xenopus to compare the properties of fluorescently tagged rhodopsin, Rho-EGFP, and Rho(P23H-EGFP. The mutant was abnormally distributed both in the inner and outer segments (OS, accumulating in the OS to a concentration of ∼0.1% compared to endogenous opsin. Rho(P23H-EGFP formed dense fluorescent foci, with concentrations of mutant protein up to ten times higher than other regions. Wild-type transgenic Rho-EGFP did not concentrate in OS foci when co-expressed in the same rod with Rho(P23H-EGFP. Outer segment regions containing fluorescent foci were refractory to fluorescence recovery after photobleaching, while foci in the inner segment exhibited recovery kinetics similar to OS regions without foci and Rho-EGFP. The Rho(P23H-EGFP foci were often in older, more distal OS disks. Electron micrographs of OS revealed abnormal disk membranes, with the regular disk bilayers broken into vesiculotubular structures. Furthermore, we observed similar OS disturbances in transgenic mice expressing Rho(P23H, suggesting such structures are a general consequence of mutant expression. Together these results show that mutant opsin disrupts OS disks, destabilizing the outer segment possibly via the formation of aggregates. This may render rods susceptible to mechanical injury or compromise OS function, contributing to photoreceptor loss.

  6. 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.

  7. 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

  8. Electrical responses of rods in the retina of Bufo marinus

    Science.gov (United States)

    Cervetto, L.; Pasino, E.; Torre, V.

    1977-01-01

    1. Intracellular responses to flashes and steps of light have been recorded from the outer segment and the cell body of rods in the retina of the Bufo marinus. The identification of the origin of recorded responses has been confirmed by intracellular marking. 2. Responses to flashes delivered in darkness or superimposed on a background were analysed. Responses recorded from outer segments conform to the principle of `spectral univariance'. The shape of the response is not affected by enlarging the spot diameter from 150 to 1000 μm. 3. The membrane potential measured in darkness at the outer segments varied from -15 to -25 mV. Injection of steady hyperpolarizing currents increases the size of the response to light; depolarizing currents reduce the response. The mean value of the input resistance is 97 ± 30 MΩ in darkness and increases by 20-30% during illumination. 4. The responses obtained from the cell body of rods have the same shape, time course and spectral sensitivity of those recorded at the outer segment. Injection of steady current at the cell body produces different effects than at the outer segment: hyperpolarizing currents reduce the amplitude of the response to light; depolarizing currents increase the response. 5. The experimental data are fitted according to a model similar to that used to describe the responses of turtle cones (Baylor & Hodgkin, 1974; Baylor, Hodgkin & Lamb, 1974a, b). 6. The model reproduces the electrical responses of the rod outer segment to a variety of stimuli: (a) brief flashes and steps of light in dark adapted conditions; (b) bright flashes superimposed on background illuminations; (c) pairs of flashes delivered at different time intervals. Responses to hyperpolarizing steps of current are also reproduced by the model. ImagesABCD PMID:406383

  9. RNA interference analyses suggest a transcript-specific regulatory role for mitochondrial RNA-binding proteins MRP1 and MRP2 in RNA editing and other RNA processing in Trypanosoma brucei

    NARCIS (Netherlands)

    Vondrusková, Eva; van den Burg, Janny; Zíková, Alena; Ernst, Nancy Lewis; Stuart, Kenneth; Benne, Rob; Lukes, Julius

    2005-01-01

    Mitochondrial RNA-binding proteins MRP1 and MRP2 occur in a heteromeric complex that appears to play a role in U-insertion/deletion editing in trypanosomes. Reduction in the levels of MRP1 (gBP21) and/or MRP2 (gBP25) mRNA by RNA interference in procyclic Trypanosoma brucei resulted in severe growth

  10. Rod progenitor cells in the mature zebrafish retina.

    Science.gov (United States)

    Morris, Ann C; Scholz, Tamera; Fadool, James M

    2008-01-01

    The zebrafish is an excellent model organism in which to study the retina's response to photoreceptor degeneration and/or acute injury. While much has been learned about the retinal stem and progenitor cells that mediate the damage response, several questions remain that cannot be addressed by acute models of injury. The development of genetic models, such as the XOPS-mCFP transgenic line, should further efforts to understand the nature of the signals that promote rod progenitor proliferation and differentiation following photoreceptor loss. This in turn may help to refine future approaches in higher vertebrates aimed at enhancing retinal progenitor cell activity for therapeutic purposes.

  11. Breaking of rod-shaped model material during compression

    Directory of Open Access Journals (Sweden)

    Lukas Kulaviak

    2017-01-01

    Full Text Available The breakage of a model anisometric dry granular material caused by uniaxial compression was studied. The bed of uniform rod-like pasta particles (8 mm long, aspect ratio 1:8 was compressed (Gamlen Tablet Press and their size distribution was measured after each run (Dynamic Image Analysing. The compression dynamics was recorded and the effect of several parameters was tested (rate of compression, volume of granular bed, pressure magnitude and mode of application. Besides the experiments, numerical modelling of the compressed breakable material was performed as well, employing the DEM approach (Discrete Element Method. The comparison between the data and the model looks promising.

  12. Elasticity of the Rod-Shaped Gram-Negative Eubacteria

    Science.gov (United States)

    Boulbitch, A.; Quinn, B.; Pink, D.

    2000-12-01

    We report a theoretical calculation of the elasticity of the peptidoglycan network, the only stress-bearing part of rod-shaped Gram-negative eubacteria. The peptidoglycan network consists of elastic peptides and inextensible glycan strands, and it has been proposed that the latter form zigzag filaments along the circumference of the cylindrical bacterial shell. The zigzag geometry of the glycan strands gives rise to nonlinear elastic behavior. The four elastic moduli of the peptidoglycan network depend on its stressed state. For a bacterium under physiological conditions the elasticity is proportional to the bacterial turgor pressure. Our results are in good agreement with recent measurements.

  13. Breaking of rod-shaped model material during compression

    Science.gov (United States)

    Lukas, Kulaviak; Vera, Penkavova; Marek, Ruzicka; Miroslav, Puncochar; Petr, Zamostny; Zdenek, Grof; Frantisek, Stepanek; Marek, Schongut; Jaromir, Havlica

    2017-06-01

    The breakage of a model anisometric dry granular material caused by uniaxial compression was studied. The bed of uniform rod-like pasta particles (8 mm long, aspect ratio 1:8) was compressed (Gamlen Tablet Press) and their size distribution was measured after each run (Dynamic Image Analysing). The compression dynamics was recorded and the effect of several parameters was tested (rate of compression, volume of granular bed, pressure magnitude and mode of application). Besides the experiments, numerical modelling of the compressed breakable material was performed as well, employing the DEM approach (Discrete Element Method). The comparison between the data and the model looks promising.

  14. Simultaneous Processing Method for Micro-Rods and Holes Using EDM

    Science.gov (United States)

    Yamazaki, Minoru; Mori, Noritosi; Suzuki, Takemi; Kunieda, Masanori

    This paper describes a new method for micro-EDM drilling which utilizes the wear of rod electrodes. With this method, a pair of micro rod and micro hole can be machined in a single process, while with conventional methods, the micro rod electrode needs to be formed before machining the micro hole. Processing conditions were optimized for the new method to obtain higher aspect ratio for the micro rods. Results of experiments also showed the following: 1) This method can be applied to AISI1045, AISI304 and Kovar and any electrode diameter size. 2) From the second process, if machining many holes using the same electrode, the electrode shape can be regenerated with excellent repeatability and holes processed efficiently. 3) The influence of carbon adhering to the tip region of the rod electrode is large, which is why the rod electrode becomes needle sharp.

  15. 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.

  16. 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...

  17. 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.

  18. Expression of Trypanosoma brucei gambiense Antigens in Leishmania tarentolae. Potential for Use in Rapid Serodiagnostic Tests (RDTs.

    Directory of Open Access Journals (Sweden)

    Barrie Rooney

    2015-12-01

    Full Text Available The development of rapid serodiagnostic tests for sleeping sickness and other diseases caused by kinetoplastids relies on the affordable production of parasite-specific recombinant antigens. Here, we describe the production of recombinant antigens from Trypanosoma brucei gambiense (T.b. gambiense in the related species Leishmania tarentolae (L. tarentolae, and compare their diagnostic sensitivity and specificity to native antigens currently used in diagnostic kits against a panel of human sera. A number of T.b. gambiense protein antigen candidates were chosen for recombinant expression in L. tarentolae based on current diagnostics in field use and recent findings on immunodiagnostic antigens found by proteomic profiling. In particular, the extracellular domains of invariant surface glycoprotein 65 (ISG65, variant surface glycoproteins VSG LiTat 1.3 and VSG LiTat 1.5 were fused with C-terminal histidine tags and expressed as soluble proteins in the medium of cultured, recombinant L. tarentolae. Using affinity chromatography, on average 10 mg/L of recombinant protein was purified from cultures and subsequently tested against a panel of sera from sleeping sickness patients from controls, i.e. persons without sleeping sickness living in HAT endemic countries. The evaluation on sera from 172 T.b. gambiense human African trypanosomiasis (HAT patients and from 119 controls showed very high diagnostic potential of the two recombinant VSG and the rISG65 fragments with areas under the curve between 0.97 and 0.98 compared to 0.98 and 0.99 with native VSG LiTat 1.3 and VSG LiTat 1.5 (statistically not different. Evaluation on sera from 78 T.b. rhodesiense HAT patients and from 100 controls showed an acceptable diagnostic potential of rISG65 with an area under the curve of 0.83. These results indicate that a combination of these recombinant antigens has the potential to be used in next generation rapid serodiagnostic tests. In addition, the L. tarentolae

  19. 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.

  20. Dimensional Analysis and Extended Hydrodynamic Theory Applied to Long-Rod Penetration of Ceramics

    Science.gov (United States)

    2016-07-01

    ARL-RP-0572 ● JULY 2016 US Army Research Laboratory Dimensional Analysis and Extended Hydrodynamic Theory Applied to Long-Rod...Dimensional Analysis and Extended Hydrodynamic Theory Applied to Long-Rod Penetration of Ceramics by John D Clayton Weapons and Materials Research...TITLE AND SUBTITLE Dimensional Analysis and Extended Hydrodynamic Theory Applied to Long- Rod Penetration of Ceramics 5a. CONTRACT NUMBER 5b. GRANT

  1. An analysis of the temperature distribution in finite solid-state laser rods

    Energy Technology Data Exchange (ETDEWEB)

    Farrukh, U.O. (Hampton Univ., Hampton, VA 23668 (US)); Buoncristiani, A.M.; Byvik, C.E. (NASA Langley Research Center, Hampton, VA 23665 (US))

    1988-11-01

    An expression for the time-dependent temperature distribution in a finite solid-state laser rod, for an arbitrary distribution of pump energy, has been derived. The specific case of end pumping by circular (constant) or Gaussian beams is included. This formulation was employed to predict the time evolution of temperature in Ti:sapphire laser rods and in Nd:YAG rods of specific dimensions.

  2. An analysis of the temperature distribution in finite solid-state laser rods

    Science.gov (United States)

    Farrukh, Usamah O.; Buoncristiani, A. Martin; Byvik, Charles E.

    1988-01-01

    An expression for the time-dependent temperature distribution in a finite solid-state laser rod, for an arbitrary distribution of pump energy, has been derived. The specific case of end pumping by circular (constant) or Gaussian beams is included. This formulation was used to predict the time evolution of temperature in Ti:sapphire laser rods and in Nd:YAG rods of specific dimensions.

  3. 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.

  4. Experimental Study on Surrogate Nuclear Fuel Rods under Reversed Cyclic Bending

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong [ORNL; Wang, Jy-An John [ORNL

    2017-01-01

    The mechanical behavior of spent nuclear fuel (SNF) rods under reversed cyclic bending or bending fatigue must be understood to evaluate their vibration integrity in a transportation environment. This is especially important for high-burnup fuels (>45 GWd/MTU), which have the potential for increased structural damage. It has been demonstrated that the bending fatigue of SNF rods can be effectively studied using surrogate rods. In this investigation, surrogate rods made of stainless steel (SS) 304 cladding and aluminum oxide pellets were tested under load or moment control at a variety of amplitude levels at 5 Hz using the Cyclic Integrated Reversible-Bending Fatigue Tester developed at Oak Ridge National Laboratory. The behavior of the rods was further characterized using flexural rigidity and hysteresis data, and fractography was performed on the failed rods. The proposed surrogate rods captured many of the characteristics of deformation and failure mode observed in SNF, including the linear-to-nonlinear deformation transition and large residual curvature in static tests, PPI and PCMI failure mechanisms, and large variation in the initial structural condition. Rod degradation was measured and characterized by measuring the flexural rigidity; the degradation of the rigidity depended on both the moment amplitude applied and the initial structural condition of the rods. It was also shown that a cracking initiation site can be located on the internal surface or the external surface of cladding. Finally, fatigue damage to the bending rods can be described in terms of flexural rigidity, and the fatigue life of rods can be predicted once damage model parameters are properly evaluated. The developed experimental approach, test protocol, and analysis method can be used to study the vibration integrity of SNF rods in the future.

  5. 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.

  6. 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.

  7. Numerical analysis of MHD flow structure behind a square rod

    Energy Technology Data Exchange (ETDEWEB)

    Satake, M. [Advanced Fusion Reactor Engineering Laboratory, Department of Quantum Science and Energy Engineering, Graduate School of Engineering, Tohoku University (Japan)]. E-mail: msata@karma.qse.tohoku.ac.jp; Yuki, K. [Advanced Fusion Reactor Engineering Laboratory, Department of Quantum Science and Energy Engineering, Graduate School of Engineering, Tohoku University (Japan); Chiba, S. [Advanced Fusion Reactor Engineering Laboratory, Department of Quantum Science and Energy Engineering, Graduate School of Engineering, Tohoku University (Japan); Hashizume, H. [Advanced Fusion Reactor Engineering Laboratory, Department of Quantum Science and Energy Engineering, Graduate School of Engineering, Tohoku University (Japan)

    2006-02-15

    In a liquid blanket system, the large MHD pressure drop for liquid lithium and/or LiPb makes it difficult to remove high heat load. Since the MHD pressure drop is proportional to the flow velocity, it is necessary to remove the high heat load under low velocity conditions. Meanwhile, in case of molten salt Flibe, which is a high Prandtl number fluid, it is also important to enhance the heat transfer performance. In this study, MHD flow structure behind a square rod inserted in a parallel channel to enhance the heat transfer is simulated numerically to clarify the interaction between the flow structure and the magnetic field by using a low-Reynolds number k-{epsilon} turbulent model and including MHD effects. The laminar flow analysis indicates that the disappearance of twin vortices and the change of the Karman's vortex street to the twin vortices occur around a Ha/Re {sub h} ratio of 0.7 and 0.07-0.09, respectively. The turbulent flow analysis confirms that installing the rod near the heating wall contributes to enhancing the heat transfer even in the presence of a magnetic field, although the turbulent kinetic energy decreases with increasing Hartmann number.

  8. Structural analysis of fuel rod applied to pressurized water reactors

    Energy Technology Data Exchange (ETDEWEB)

    Faria, Danilo P.; Pinheiro, Andre Ricardo M.; Lotto, André A., E-mail: danilo.pinheiro@marinha.mil.br [Centro Tecnológico da Marinha em São Paulo (CTMSP), São Paulo, SP (Brazil)

    2017-07-01

    The design of fuel assemblies applied to Pressurized Water Reactors (PWR) has several requirements and acceptance criteria that must be attended for licensing. In the case of PWR fuel rods, an important mechanical structural requirement is to keep the radial stability when submitted to the coolant external pressure. In the framework of the Accident Tolerant Fuel (ATF) program new materials have been studied to replace zirconium based alloys as cladding, including iron-based alloys. In this sense, efforts have been made to evaluate the behavior of these materials under PWR conditions. The present work aims to evaluate the collapse cold pressure of a stainless steel thin-walled tube similar to that used as cladding material of fuel rods by means of the comparison of numeric data, and experimental results. As a result of the simulations, it was observed that the collapse pressure has a value intermediate value between those found by regulatory requirements and analytical calculations. The experiment was carried out for the validation of the computational model using test specimens of thin-walled tubes considering empty tube. The test specimens were sealed at both ends by means of welding. They were subjected to a high pressure device until the collapse of the tubes. Preliminary results obtained from experiments with the empty test specimens indicate that the computational model can be validated for stainless steel cladding, considering the difference between collapse pressure indicated in the regulatory document and the actual limit pressure concerning to radial instability of tubes with the studied characteristics. (author)

  9. 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.

  10. 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.

  11. Hardened plungers and piston rods for high-pressure compressors

    Energy Technology Data Exchange (ETDEWEB)

    1942-07-07

    This report was a summary of information on dimensions, materials, and operating conditions, as well as experience in the use of piston rods and plungers at Gelsenkirchen. The surface hardening of these parts and their resulting life and wear were of prime importance. Nitriding hardening was one of the best processes for the production of wearproof surfaces. Case hardening and autogeneous hardening had been found satisfactory. Heat hardening had been found to be a cheap process in many applications. Surfaces could be obtained by hard chrome plating which would have the same or higher wear resistance as nitriding and excel in the depth of hardness. However, the heat hardening alone produced hard layers which had sufficiently good properties for plungers and piston rods of the booster compressors, gas-circulation pumps, paste presses, compressors and possibly pressure-release machines. This plant possessed a hardening installation which offered the advantage of production of most of the required equipment right at the works. This was particularly important if a grinding machine was available. This arrangement had to be supplemented with a shaft furnace in which parts could be heated to remove stresses before and after machining. 5 tables.

  12. Comparative Study Between Cobalt Chrome and Titanium Alloy Rods for Multilevel Spinal Fusion: Proximal Junctional Kyphosis More Frequently Occurred in Patients Having Cobalt Chrome Rods.

    Science.gov (United States)

    Han, Sanghyun; Hyun, Seung-Jae; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

    2017-07-01

    The use of titanium alloy (Ti) rods is frequently associated with rod fracture after spinal fixation. To address this issue, cobalt chrome (CoCr) rods, which are advantageous because of their greater strength and resistance to fatigue relative to Ti rods, have been introduced. The purpose of the present study was to compare radiographic outcomes after the use of Ti versus CoCr rods in a matched cohort of patients undergoing posterior spinal fusion for treatment of spinal instability. We retrospectively reviewed data from patients who had undergone spinal fusion involving more than 3 levels at a single institution between 2004 and 2015. Patients were matched for age, diagnosis, 3-column osteotomy, levels fused, and T score. Fifty patients with Ti rods were identified and appropriately matched to 50 consecutive patients with CoCr rods. The distributions of age at surgery, sex, diagnosis, 3-column osteotomy, levels fused, number of patients with previous surgical procedures, and T score did not significantly differ between the 2 groups. However, there were significant differences in length of follow-up (CoCr, 25.0 vs. Ti, 28.5 months; P < 0.001), fusion rate (CoCr, 45 [90%] vs. Ti, 33 [66%]; P = 0.004), occurrence of rod breakage (CoCr, 0 vs. T, 8 [16%]; P = 0.006), and junctional kyphosis (CoCr, 24 [46%] vs. Ti, 9 [18%]; P = 0.003). Our findings indicate that the use of CoCr rods is effective in ensuring stability of the posterior spinal construct and accomplishment of spinal fusion. Furthermore, our results indicate that junctional kyphosis may occur more frequently in CoCr systems than in Ti systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Fuel rod pressure in nuclear power reactors: Statistical evaluation of the fuel rod internal pressure in LWRs with application to lift-off probability

    Energy Technology Data Exchange (ETDEWEB)

    Jelinek, Tomas

    2001-02-01

    In this thesis, a methodology for quantifying the risk of exceeding the Lift-off limit in nuclear light water power reactors is outlined. Due to fission gas release, the pressure in the gap between the fuel pellets and the cladding increases with burnup of the fuel. An increase in the fuel-clad gap due to clad creep would be expected to result in positive feedback, in the form of higher fuel temperatures, leading to more fission gas release, higher rod pressure, etc, until the cladding breaks. An increase in the fuel-clad gap that leads to this positive feedback is a phenomenon called Lift-off and is a limitation that must be considered in the fuel core management. Lift-off is a consequence of very high internal fuel rod pressure. The internal fuel rod pressure is therefore used as a Lift-off indicator. The internal fuel rod pressure is closely connected to the fission gas release into the fuel rod plenum and is thus used to increase the database. It is concluded that the dominating error source in the prediction of the pressure in Boiling Water Reactors (BWR), is the power history. There is a bias in the fuel pressure prediction that is dependent on the fuel rod position in the fuel assembly for BWRs. A methodology to quantify the risk of the fuel rod internal pressure exceeding a certain limit is developed; the risk is dependent of the pressure prediction and the fuel rod position. The methodology is based on statistical treatment of the discrepancies between predicted and measured fuel rod internal pressures. Finally, a methodology to estimate the Lift-off probability of the whole core is outlined.

  14. 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, Poul Martin; Dahl, Benny

    2016-01-01

    and rod strain is necessary to determine the biomechanical efficacy of these techniques. METHODS: Five specimens (T12-S1) underwent PSO at L3 with pedicle screw stabilization at L1-S1. Pedicle subtraction was adjusted to achieve a final lordosis of 70°. Flexion-extension (FE), lateral bending, and axial...... surface strain on the primary rod, irrespective of construct (P devices minimally affected motion...

  15. Repulsion between oppositely charged rod-shaped macromolecules: Role of overcharging and ionic confinement

    Science.gov (United States)

    Antila, Hanne S.; Van Tassel, Paul R.; Sammalkorpi, Maria

    2017-09-01

    The interaction between two oppositely charged rod-shaped macro-ions in a micro-ion solution is investigated via Monte Carlo simulations of the primitive model. The focus is on the asymmetry in rod and/or ion charge, i.e., conditions where oppositely charged objects can repel one another. For equally and oppositely charged rods with asymmetric z:1 micro-ions, repulsion may be induced by overcharging one of the rods with the z valent ions. For asymmetrically charged rods in a symmetric z:z micro-ion solution, a repulsive interaction—at separation of the order of one ion diameter—can arise via an unbalanced osmotic pressure contribution from the ionic atmosphere in the inter-rod space, and an attractive interaction—at a smaller separation—may occur due to a "squeezing out" of the micro-ions from the space between the rods (with a consequent gain in entropy). The thermodynamics of each mechanism is investigated in terms of rod charge and size and micro-ion valence, size, and concentration. Our findings contribute to the understanding of the complex role of charge asymmetry on the interaction of, for example, oppositely charged polyelectrolytes, functionalized nanotubes, and rod-like biomolecules, e.g., viruses.

  16. Mechanical stability of talin rod controls cell migration and substrate sensing

    National Research Council Canada - National Science Library

    Rolle Rahikainen; Magdaléna von Essen; Markus Schaefer; Lei Qi; Latifeh Azizi; Conor Kelly; Teemu O Ihalainen; Bernhard Wehrle-Haller; Martin Bastmeyer; Cai Huang; Vesa P Hytönen

    2017-01-01

    .... Here, by utilizing computationally designed mutations, we demonstrate that stepwise destabilization of the talin rod R3 subdomain decreases cellular traction force generation, which affects talin...

  17. Domain Size Control in Self-Assembling Rod-Coil Block Copolymer And Homopolymer Blends

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Y.; Olsen, B.D.; Ganesan, V.; Segalman, R.A.; /UC, Berkeley /LBL, Berkeley /Texas U.

    2007-07-13

    The addition of homopolymers to a self-assembling rod-coil block copolymer is demonstrated to be a flexible route toward domain size control. Molecular weight matched rod-like homopolymers interdigitate with the rod-blocks within their respective lamellae. As a result of the interdigitation, the coil blocks must rearrange to occupy more interfacial area resulting in an unprecedented decrease in domain spacing with increasing rod homopolymers. Conversely coil homopolymers were locally solubilized within the coil microdomain resulting in an increase of domain spacing with increasing coil homopolymers. The mechanisms of homopolymers solubilization are in qualitative agreement with predictions made by self-consistent mean-field theory (SCFT) calculations.

  18. Adjuster rod aging in Darlington's CANDU reactors: behaviour, measurement and implications for operation

    Energy Technology Data Exchange (ETDEWEB)

    Banica, C.; Sullivan, Aaron, E-mail: constantin.banica@opg.com [Darlington Nuclear Generating Station, Ontario Power Generation, Bowmanville, ON (Canada)

    2015-07-01

    Presented are the simulation methodology and the results of reactivity worth measurements performed on adjuster rods in an equilibrium Darlington (large CANDU) core. Simulation had predicted the effect of neutron irradiation on device properties for adjuster rods of different construction and in-core residence times. The expected difference in the rate of irradiation-induced reactivity worth loss in rods containing titanium versus all stainless steel has been confirmed by comparing measured reactivity values for adjuster rods that differ in material construction and in-core service times. Also discussed are the method for conducting the measurements, and the accuracy of pre-simulation results. (author)

  19. Fuel-rod temperature transients during LWR degraded-core accidents

    Energy Technology Data Exchange (ETDEWEB)

    Briscoe, F; Rivard, J B; Young, M F

    1982-01-01

    Heat transfer models of fuel rods and coolant have been developed in support of LWR damaged fuel studies underway at Sandia National Laboratories for the NRC. A one-dimensional, full-length model simulates a PWR fuel rod; a two-dimensional, 0.5 m model simulates 9-rod bundle experiments to be performed in the Annular Core Research Reactor. The models include zircaloy oxidation, heat transfer by convecting steam/hydrogen flow, and radiation between surfaces through an absorbing/emitting gas. Characteristics of the one-dimensional reactor fuel rod model for two types of accident sequence are reported, as well as comparisons with MARCH code results.

  20. 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.

  1. 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...

  2. Models for fuel rod behaviour at high burnup

    Energy Technology Data Exchange (ETDEWEB)

    Jernkvist, Lars O.; Massih, Ali R. [Quantum Technologies AB, Uppsala Science Park, Uppsala (Sweden)

    2004-12-01

    This report deals with release of fission product gases and irradiation-induced restructuring in uranium dioxide nuclear fuel. Waterside corrosion of zirconium alloy clad tubes to light water reactor fuel rods is also discussed. Computational models, suitable for implementation in the FRAPCON-3.2 computer code, are proposed for these potentially life-limiting phenomena. Hence, an integrated model for the calculation or thermal fission gas release by intragranular diffusion, gas trapping in grain boundaries, irradiation-induced re-solution, grain boundary saturation, and grain boundary sweeping in UO{sub 2} fuel, under time varying temperature loads, is formulated. After a brief review of the status of thermal fission gas release modelling, we delineate the governing equations for the aforementioned processes. Grain growth kinetic modelling is briefly reviewed and pertinent data on grain growth of high burnup fuel obtained during power ramps in the Third Risoe Fission Gas Release Project are evaluated. Sample computations are performed, which clearly show the connection between fission gas release and gram growth as a function of time at different isotherms. Models are also proposed for the restructuring of uranium dioxide fuel at high burnup, the so-called rim formation, and its effect on fuel porosity build-up, fuel thermal conductivity and fission gas release. These models are assessed by use of recent experimental data from the High Burnup Rim Project, as well as from post irradiation examinations of high-burnup fuel, irradiated in power reactors. Moreover, models for clad oxide growth and hydrogen pickup in PWRs, applicable to Zircaloy-4, ZIRLO or M5 cladding, are formulated, based on recent in-reactor corrosion data for high-burnup fuel rods. Our evaluation of these data indicates that the oxidation rate of ZIRLO-type materials is about 20% lower than for standard Zircaloy-4 cladding under typical PWR conditions. Likewise, the oxidation rate of M5 seems to be

  3. Fuel rod under power oscillations; calculations with the ENIGMA code

    Energy Technology Data Exchange (ETDEWEB)

    Ranta-Puska, Kari

    1999-05-15

    Power oscillations in a BWR may result from a series of events starting from a re-circulation pump trip or can be initiated during start-up at low-flow conditions by other perturbations. Whole core and regional oscillations have been observed. Severe consequences may be anticipated if the instability diverges and the reactor protection system fails (no scram) in all phases of the incident (ATWS). Power peaks higher than ten times of the pre-transient power level have been speculated to appear. Low-magnitude oscillations have been observed at the TVO plant, Olkiluoto 1987, and at the Lasalle-2 plant, 1988, and in other BWRs world-wide. Typically, a boiling water reactor has an unstable operational point at low flow and high power conditions. The physical phenomenon behind the instability is density wave oscillations leading to boiling boundary oscillations and void fraction fluctuations across the heated channel. These in turn, make the fission power vary. The typical frequency of the oscillations seems to be of the order of 0.5 Hz, and thus the power peak for a fuel rod is considerably wider than a RIA-pulse, for instance. Large oscillations can result in elevated fuel temperatures, accelerated fission gas release and additional internal loads on the cladding. These effects may be more severe for a high burnup rod with a large fission gas inventory and a closed gap. Therefore, an experiment has been proposed to be conducted at Halden reactor for simulating the fuel rod response under power oscillations. As there is lack of knowledge also on the relevant boundary conditions, pre-calculations with various input options have been performed and are further suggested. Calculations with FRAPTRAN code have shown the importance of the cladding-coolant heat transfer to the fuel temperature. The applicability of the ENIGMA code to this kind of transients was confirmed. To support the planning of the proposed Halden test, estimates on fuel and cladding temperatures as well as

  4. Ultrasonic Structural Health Monitoring to Assess the Integrity of Spinal Growing Rods In Vitro.

    Science.gov (United States)

    Oetgen, Matthew E; Goodley, Addison; Yoo, Byungseok; Pines, Darryll J; Hsieh, Adam H

    2016-01-01

    Rod fracture is a common complication of growing rods and can result in loss of correction, patient discomfort, and unplanned revision surgery. The ability to quantitate rod integrity at each lengthening would be advantageous to avoid this complication. We investigate the feasibility of applying structural health monitoring to evaluate the integrity of growing rods in vitro. Single-rod titanium 4.5-mm growing rod constructs (n = 9), one screw proximally and one distally connected by in-line connectors, were assembled with pedicle screws fixed in polyethylene blocks. Proximal and distal ends were loaded and constructs subjected to cyclic axial compression (0-100 N at 1 Hz), with incrementally increasing maximum compressive loads of 10 N every 9k cycles until failure. Four piezoceramic transducers (PZTs) were mounted along the length the constructs to interrogate the integrity of the rods with an ultrasonic, guided lamb wave approach. Every 9k cycles, an 80 V excitatory voltage was applied to a PZT to generate high-frequency vibrations, which, after propagating through the construct, was detected by the remaining PZTs. Amplitude differences between pre- and postload waveform signals were calculated until rod failure. Average construct lifetime was 88,991 ± 13,398 cycles. All constructs failed due to rod fracture within 21 mm (mean = 15 ± 4.5 mm) of a screw or connector. Amplitude differences between pre- and postload increased in a stepwise fashion as constructs were cycled. Compared to baseline, we found a 1.8 ± 0.6-fold increase in amplitude 18k cycles before failure, a 2.2 ± 1.0-fold increase in amplitude 9k cycles before failure, and a 2.75 ± 1.5-fold increase in amplitude immediately before rod fracture. We describe a potential method for assessing the structural integrity of growing rods using ultrasonic structural health monitoring. These preliminary data demonstrate the ability of periodic rod assessment to detect structural changes in cycled growing

  5. Computational fluid dynamics (CFD) round robin benchmark for a pressurized water reactor (PWR) rod bundle

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Shin K., E-mail: paengki1@tamu.edu; Hassan, Yassin A.

    2016-05-15

    Highlights: • The capabilities of steady RANS models were directly assessed for full axial scale experiment. • The importance of mesh and conjugate heat transfer was reaffirmed. • The rod inner-surface temperature was directly compared. • The steady RANS calculations showed a limitation in the prediction of circumferential distribution of the rod surface temperature. - Abstract: This study examined the capabilities and limitations of steady Reynolds-Averaged Navier–Stokes (RANS) approach for pressurized water reactor (PWR) rod bundle problems, based on the round robin benchmark of computational fluid dynamics (CFD) codes against the NESTOR experiment for a 5 × 5 rod bundle with typical split-type mixing vane grids (MVGs). The round robin exercise against the high-fidelity, broad-range (covering multi-spans and entire lateral domain) NESTOR experimental data for both the flow field and the rod temperatures enabled us to obtain important insights into CFD prediction and validation for the split-type MVG PWR rod bundle problem. It was found that the steady RANS turbulence models with wall function could reasonably predict two key variables for a rod bundle problem – grid span pressure loss and the rod surface temperature – once mesh (type, resolution, and configuration) was suitable and conjugate heat transfer was properly considered. However, they over-predicted the magnitude of the circumferential variation of the rod surface temperature and could not capture its peak azimuthal locations for a central rod in the wake of the MVG. These discrepancies in the rod surface temperature were probably because the steady RANS approach could not capture unsteady, large-scale cross-flow fluctuations and qualitative cross-flow pattern change due to the laterally confined test section. Based on this benchmarking study, lessons and recommendations about experimental methods as well as CFD methods were also provided for the future research.

  6. Measurement of nuclear fuel rod deformation using an image processing technique

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jai Wan; Choi, Young Soo; Jeong, Kyung Min [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Shin, Jung Cheol [KEPCO Nuclear Fuel, Daejeon (Korea, Republic of)

    2011-03-15

    In this paper, a deformation measurement technology for nuclear fuel rods is proposed. The deformation measurement system includes a high-definition CMOS image sensor, a lens, a semiconductor laser line beam marker, and optical and mechanical accessories. The basic idea of the proposed deformation measurement system is to illuminate the outer surface of a fuel rod with a collimated laser line beam at an angle of 45 degrees or higher. For this method, it is assumed that a nuclear fuel rod and the optical axis of the image sensor for observing the rod are vertically composed. The relative motion of the fuel rod in the horizontal direction causes the illuminated laser line beam to move vertically along the surface of the fuel rod. The resulting change of the laser line beam position on the surface of the fuel rod is imaged as a parabolic beam in the high definition CMOS image sensor. An ellipse model is then extracted from the parabolic beam pattern. The center coordinates of the ellipse model are taken as the feature of the deformed fuel rod. The vertical offset of the feature point of the nuclear fuel rod is derived based on the displacement of the offset in the horizontal direction. Based on the experimental results for a nuclear fuel rod sample with a formation of surface crud, an inspection resolution of 50 is achieved using the proposed method. In terms of the degree of precision, this inspection resolution is an improvement of more than 300% from a 150 {mu}m resolution, which is the conventional measurement criteria required for the deformation of neutron irradiated fuel rods

  7. Analytical Solution to the Pneumatic Transient Rod System at ACRR

    Energy Technology Data Exchange (ETDEWEB)

    Fehr, Brandon Michael [Georgia Inst. of Technology, Atlanta, GA (United States)

    2016-01-08

    The ACRR pulse is pneumatically driven by nitrogen in a system of pipes, valves and hoses up to the connection of the pneumatic system and mechanical linkages of the transient rod (TR). The main components of the TR pneumatic system are the regulator, accumulator, solenoid valve and piston-cylinder assembly. The purpose of this analysis is to analyze the flow of nitrogen through the TR pneumatic system in order to develop a motion profile of the piston during the pulse and be able to predict the pressure distributions inside both the cylinder and accumulators. The predicted pressure distributions will be validated against pressure transducer data, while the motion profile will be compared to proximity switch data. By predicting the motion of the piston, pulse timing will be determined and provided to the engineers/operators for verification. The motion profile will provide an acceleration distribution to be used in Razorback to more accurately predict reactivity insertion into the system.

  8. Characterization of the mouse rod transducin alpha subunit gene.

    Science.gov (United States)

    Raport, C J; Dere, B; Hurley, J B

    1989-05-05

    A genomic clone spanning the mouse rod transducin alpha subunit (Tr alpha) gene has been isolated by screening a mouse genomic library with a bovine Tr alpha cDNA clone. The coding region of the mouse Tr alpha gene reveals an 88.7% nucleotide identify and 99.7% amino acid identity with bovine Tr alpha. The mouse Tr alpha gene is composed of 8 exons and 7 introns within its coding region. These introns are in the same locations as introns in human Gi alpha genes, that encode G proteins closely related to transducin. Primer extension, RNA sequencing, and S1 nuclease protection analyses indicate that the mouse Tr alpha gene transcription start site is 84 bases upstream of the initiation codon. Northern blot analysis shows that the mouse Tr alpha is expressed in the retina, but not in brain, kidney, liver, or heart.

  9. Simulations of electrothermal instability growth in solid aluminum rods

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Kyle J.; Yu, Edmund P.; Sinars, Daniel B.; Cuneo, Michael E.; Slutz, Stephen A.; Nakhleh, Charles; Herrmann, Mark C. [Sandia National Laboratories, P.O. Box 5800, Albuquerque, New Mexico 87185-1186 (United States); Koning, Joseph M.; Marinak, Michael M. [Lawrence Livermore National Laboratory, University of California, Livermore, California 94551 (United States)

    2013-05-15

    A recent publication [K. J. Peterson et al., Phys. Plasmas 19, 092701 (2012)] describes simulations and experiments of electrothermal instability growth on well characterized initially solid aluminum and copper rods driven with a 20 MA, 100 ns rise time current pulse on Sandia National Laboratories Z accelerator. Quantitative analysis of the high precision radiography data obtained in the experiments showed excellent agreement with simulations and demonstrated levels of instability growth in dense matter that could not be explained by magneto-Rayleigh-Taylor instabilities alone. This paper extends the previous one by examining the nature of the instability growth in 2D simulations in much greater detail. The initial instability growth in the simulations is shown via several considerations to be predominantly electrothermal in nature and provides a seed for subsequent magneto-Rayleigh-Taylor growth.

  10. Normal-stress coefficients and rod climbing in colloidal dispersions

    Science.gov (United States)

    Farage, T. F. F.; Reinhardt, J.; Brader, J. M.

    2013-10-01

    We calculate tractable microscopic expressions for the low-shear normal-stress coefficients of colloidal dispersions. Although restricted to the low rate regime, the presented formulas are valid for all volume fractions below the glass transition and for any interaction potential. Numerical results are presented for a system of colloids interacting via a hard-core attractive Yukawa potential, for which we explore the interplay between attraction strength and volume fraction. We show that the normal-stress coefficients exhibit nontrivial features close to the critical point and at high volume fractions in the vicinity of the reentrant glass transition. Finally, we exploit our formulas to make predictions about rod-climbing effects in attractive colloidal dispersions.

  11. A model of rod outer segment derived lipofuscin.

    Science.gov (United States)

    Hiramitsu, T; Ishihama, H

    1995-01-01

    The rod outer segments (ROS) from pig eyes were incubated with ferrous iron and albumin. The fluorescent lipid peroxides formed in the reaction were extracted with chloroform-methanol, ethanol-ether or water. After centrifugation, the fluorescence intensities of the supernatant and the aqueous solution of the sediments were measured with a Fluorospectrophotometer. The sediments were observed with a fluorescence microscope. The fluorescence spectra has an excitation maximum at 365 nm and an emission maximum at 430-440 nm. The fluorescence intensities were greater in the water soluble fraction than in the organic solevent fraction. The fluorescence microscopy showed the blue emitting fluorophores. The fluorophores from ROS peroxidized with ferrous iron have different properties from the lipofuscin in human RPE extracted with the organic solvents.

  12. Asynchronous oscillations of rigid rods drive viscous fluid to swirl

    Science.gov (United States)

    Hayashi, Rintaro; Takagi, Daisuke

    2017-12-01

    We present a minimal system for generating flow at low Reynolds number by oscillating a pair of rigid rods in silicone oil. Experiments show that oscillating them in phase produces no net flow, but a phase difference alone can generate rich flow fields. Tracer particles follow complex trajectory patterns consisting of small orbital movements every cycle and then drifting or swirling in larger regions after many cycles. Observations are consistent with simulations performed using the method of regularized Stokeslets, which reveal complex three-dimensional flow structures emerging from simple oscillatory actuation. Our findings reveal the basic underlying flow structure around oscillatory protrusions such as hairs and legs as commonly featured on living and nonliving bodies.

  13. Mechanical Design of AM Fabricated Prismatic Rods under Torsion

    Directory of Open Access Journals (Sweden)

    Manzhirov Alexander V.

    2017-01-01

    Full Text Available We study the stress-strain state of viscoelastic prismatic rods fabricated or repaired by additive manufacturing technologies under torsion. An adequate description of the processes involved is given by methods of a new scientific field, mechanics of growing solids. Three main stages of the deformation process (before the beginning of growth, in the course of growth, and after the termination of growth are studied. Two versions of statement of two problems are given: (i given the torque, find the stresses, displacements, and torsion; (ii given the torsion, find the stresses, displacements, and torque. Solution methods using techniques of complex analysis are presented. The results can be used in mechanical and instrument engineering.

  14. iRODS: A Distributed Data Management Cyberinfrastructure for Observatories

    Science.gov (United States)

    Rajasekar, A.; Moore, R.; Vernon, F.

    2007-12-01

    Rule-Oriented Data System (iRODS) (http://irods.sdsc.edu) provides the mechanisms needed to describe not only management policies, but also to track how the policies are applied and their execution results. The iRODS data grid maps management policies to rules that control the execution of the remote micro-services. As an example, a rule can be created that automatically creates a replica whenever a file is added to a specific collection, or extracts its metadata automatically and registers it in a searchable catalog. For the replication operation, the persistent state information consists of the replica location, the creation date, the owner, the replica size, etc. The mechanism used by iRODS for providing policy virtualization is based on well-defined functions, called micro-services, which are chained into alternative workflows using rules. A rule engine, based on the event-condition-action paradigm executes the rule-based workflows after an event. Rules can be deferred to a pre-determined time or executed on a periodic basis. As the data management policies evolve, the iRODS system can implement new rules, new micro-services, and new state information (metadata content) needed to manage the new policies. Each sub- collection can be managed using a different set of policies. The discussion of the concepts in rule-based policy virtualization and its application to long-term and large-scale data management for observatories such as ORION and NEON will be the basis of the paper.

  15. GENERATION OF A COMPOSITE GLASS-METAL ROD: PRACTICAL RESULTS

    Directory of Open Access Journals (Sweden)

    Gridasova Ekaterina Alexandrovna

    2012-10-01

    Full Text Available Glass has a high compressive strength and low impact strength. The strength of glass in compression is a lot higher than the strength of glass in tension, and it varies within the range of 500-1,250 MPa. Whenever the glass is in compression, it can compete with the properties of metal in terms of its strength. The tensile strength of glass under tension is 30-50 MPa. The reason for that is the fact that the strength of glass is strongly dependent on the state of its surface. Methods of increasing the strength of glass have been the subject of research projects implemented at Far Eastern Federal University. The objective is to apply compressive stresses that would prevent any defects in the surface layer and harden the surface to improve the glass resistance to mechanical stresses and isolate it from the environment. Creation of a composite rod made of glass grade C49-1 (3С5Na and steel E235C (ISO standard manufactured through the employment of diffusion bonding represents a practical result of the research. Its analysis has proven the presence of full contact, absence of cracks and poor penetration alongside the welding zone. Microscopy methods of analysis have demonstrated the presence of the transition zone in the points of interface of materials. The results of the spectral analysis prove the penetration of Fe-cations into the glass down to the depth of 30 microns. The chemical analysis of the zone of diffusion proves that the crystalline structure, or fayalite (Fe2SiO4, is formed in the glass. The rod strength analysis has demonstrated its high compressive

  16. Amelogenin-Ameloblastin Spatial Interaction around Maturing Enamel Rods

    Science.gov (United States)

    Mazumder, P.; Prajapati, S.; Bapat, R.; Moradian-Oldak, J.

    2016-01-01

    Amelogenin and ameloblastin are 2 extracellular matrix proteins that are essential for the proper development of enamel. We recently reported that amelogenin and ameloblastin colocalized during the secretory stage of enamel formation when nucleation of enamel crystallites occurs. Direct interactions between the 2 proteins have been also demonstrated in our in vitro studies. Here, we explore interactions between their fragments during enamel maturation. We applied in vivo immunofluorescence imaging, quantitative co-localization analysis, and a new FRET (fluorescence resonance energy transfer) technique to demonstrate ameloblastin and amelogenin interaction in the maturing mouse enamel. Using immunochemical analysis of protein samples extracted from 8-d-old (P8) first molars from mice as a model for maturation-stage enamel, we identified the ~17-kDa ameloblastin (Ambn-N) and the TRAP (tyrosine-rich amelogenin peptide) fragments. We used Ambn-N18 and Ambn-M300 antibodies raised against the N-terminal and C-terminal segments of ameloblastin, as well as Amel-FL and Amel-C19 antibodies against full-length recombinant mouse amelogenin (rM179) and C-terminal amelogenin, respectively. In transverse sections, co-localization images of N-terminal fragments of amelogenin and ameloblastin around the prism boundary revealed the “fish net” pattern of the enamel matrix. Using in vivo FRET microscopy, we further demonstrated spatial interactions between amelogenin and ameloblastin N-terminal fragments. In the maturing mouse enamel, the association of these residual protein fragments created a discontinuity between enamel rods, which we suggest is important for support and maintenance of enamel rods and eventual contribution to unique enamel mechanical properties. We present data that support cooperative functions of enamel matrix proteins in mediating the structural hierarchy of enamel and that contribute to our efforts to design and develop enamel biomimetic material. PMID

  17. Slip-spring model of entangled rod-coil block copolymers

    Science.gov (United States)

    Wang, Muzhou; Likhtman, Alexei E.; Olsen, Bradley D.

    2015-03-01

    Understanding the dynamics of rod-coil block copolymers is important for optimal design of functional nanostructured materials for organic electronics and biomaterials. Recently, we proposed a reptation theory of entangled rod-coil block copolymers, predicting the relaxation mechanisms of activated reptation and arm retraction that slow rod-coil dynamics relative to coil and rod homopolymers, respectively. In this work, we introduce a coarse-grained slip-spring model of rod-coil block copolymers to further explore these mechanisms. First, parameters of the coarse-grained model are tuned to match previous molecular dynamics simulation results for coils, rods, and block copolymers. For activated reptation, rod-coil copolymers are shown to disfavor configurations where the rod occupies curved portions of the entanglement tube of randomly varying curvature created by the coil ends. The effect of these barriers on diffusion is quantitatively captured by considering one-dimensional motion along an entanglement tube with a rough free energy potential. Finally, we analyze the crossover between the two mechanisms. The resulting dynamics from both mechanisms acting in combination is faster than from each one individually.

  18. Truss beam having convex-curved rods, shear web panels, and self-aligning adapters

    Science.gov (United States)

    Fernandez, Ian M. (Inventor)

    2013-01-01

    A truss beam comprised of a plurality of joined convex-curved rods with self-aligning adapters (SAA) adhesively attached at each end of the truss beam is disclosed. Shear web panels are attached to adjacent pairs of rods, providing buckling resistance for the truss beam. The rods are disposed adjacent to each other, centered around a common longitudinal axis, and oriented so that adjacent rod ends converge to at least one virtual convergence point on the common longitudinal axis, with the rods' curvature designed to increase prevent buckling for the truss beam. Each SAA has longitudinal bores that provide self-aligning of the rods in the SAA, the self-aligning feature enabling creation of strong adhesive bonds between each SAA and the rods. In certain embodiments of the present invention, pultruded unidirectional carbon fiber rods are coupled with carbon fiber shear web panels and metal SAA(s), resulting in a lightweight, low-cost but strong truss beam that is highly resistant to buckling.

  19. Large Deformation of an Elastic Rod with Structural Anisotropy Subjected to Fluid Flow

    Science.gov (United States)

    Hassani, Masoud; Mureithi, Njuki; Gosselin, Frederick

    2015-11-01

    In the present work, we seek to understand the fundamental mechanisms of three-dimensional reconfiguration of plants by studying the large deformation of a flexible rod in fluid flow. Flexible rods made of Polyurethane foam and reinforced with Nylon fibers are tested in a wind tunnel. The rods have bending-torsion coupling which induces a torsional deformation during asymmetric bending. A mathematical model is also developed by coupling the Kirchhoff rod theory with a semi-empirical drag formulation. Different alignments of the material frame with respect to the flow direction and a range of structural properties are considered to study their effect on the deformation of the flexible rod and its drag scaling. Results show that twisting causes the flexible rods to reorient and bend with the minimum bending rigidity. It is also found that the drag scaling of the rod in the large deformation regime is not affected by torsion. Finally, using a proper set of dimensionless numbers, the state of a bending and twisting rod is characterized as a beam undergoing a pure bending deformation.

  20. Investigation of wave propagation in double cylindrical rods considering the effect of prestress

    Science.gov (United States)

    Li, Chunlei; Han, Qiang; Liu, Yijie; Liu, Xiucheng; Wu, Bin

    2015-09-01

    This paper presents the investigation of guided wave propagation in prestressed double-cylinder structure. Based on Hertzian contact theory, the interaction between two rods is treated as a plane strain problem and the stress state in the waveguide under the static load is obtained. The stress state is considered as a prestressed configuration for elastic wave propagation analysis in double cylindrical rods. The elastodynamic equation of the prestressed structure is established with the updated Lagrangian formulation and the wave finite element (WFE) method. Firstly, the equation is verified by the application on an aluminum rod compared with the Euler-Bernoulli beam theory. Then, dispersion curves for single rod and double cylindrical rods without prestress are computed. Besides, at the dimensionless frequency 0.25 the propagating modes in double cylindrical rods are identified with mode shapes and displacement vectors. The guided waves in double rods consist of the modes different from single rod. Particularly, there exist two kinds of torsional-like modes, one of which has a twist center and the other has two. The latter changes obviously with the increase of prestress in the waveguide. At low frequencies, torsional-like modes are very sensitive to the variation of prestress; in addition, the prestress configuration has little influence on propagating modes at mid-frequencies but some at high frequencies.

  1. Rapid kinetics of endocytosis at rod photoreceptor synapses depends upon endocytic load and calcium

    Science.gov (United States)

    CORK, KARLENE M.; THORESON, WALLACE B.

    2015-01-01

    Release from rods is triggered by the opening of L-type Ca2+ channels that lie beneath synaptic ribbons. After exocytosis, vesicles are retrieved by compensatory endocytosis. Previous work showed that endocytosis is dynamin-dependent in rods but dynamin-independent in cones. We hypothesized that fast endocytosis in rods may also differ from cones in its dependence upon the amount of Ca2+ influx and/or endocytic load. We measured exocytosis and endocytosis from membrane capacitance (Cm) changes evoked by depolarizing steps in voltage clamped rods from tiger salamander retinal slices. Similar to cones, the time constant for endocytosis in rods was quite fast, averaging endocytosis kinetics in rods slowed after increasing Ca2+ channel activation with longer step durations or more strongly depolarized voltage steps. Endocytosis kinetics also slowed as Ca2+ buffering was decreased by replacing BAPTA (10 or 1 mM) with the slower Ca2+ buffer EGTA (5 or 0.5 mM) in the pipette solution. These data provide further evidence that endocytosis mechanisms differ in rods and cones and suggest that endocytosis in rods is regulated by both endocytic load and local Ca2+ levels. PMID:24735554

  2. Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope

    Science.gov (United States)

    Dubra, Alfredo; Sulai, Yusufu; Norris, Jennifer L.; Cooper, Robert F.; Dubis, Adam M.; Williams, David R.; Carroll, Joseph

    2011-01-01

    The rod photoreceptors are implicated in a number of devastating retinal diseases. However, routine imaging of these cells has remained elusive, even with the advent of adaptive optics imaging. Here, we present the first in vivo images of the contiguous rod photoreceptor mosaic in nine healthy human subjects. The images were collected with three different confocal adaptive optics scanning ophthalmoscopes at two different institutions, using 680 and 775 nm superluminescent diodes for illumination. Estimates of photoreceptor density and rod:cone ratios in the 5°–15° retinal eccentricity range are consistent with histological findings, confirming our ability to resolve the rod mosaic by averaging multiple registered images, without the need for additional image processing. In one subject, we were able to identify the emergence of the first rods at approximately 190 μm from the foveal center, in agreement with previous histological studies. The rod and cone photoreceptor mosaics appear in focus at different retinal depths, with the rod mosaic best focus (i.e., brightest and sharpest) being at least 10 μm shallower than the cones at retinal eccentricities larger than 8°. This study represents an important step in bringing high-resolution imaging to bear on the study of rod disorders. PMID:21750765

  3. Effects of Hardness on Pintle Rod Performance in the Universal and Retained Gas Samplers

    Energy Technology Data Exchange (ETDEWEB)

    BOGER, R.M.

    1999-11-18

    Interaction between hardness of the pintle rods and the retainer rings used in the core samplers is investigated. It is found that ordinary Rockwell C measurements are not sufficient and superficial hardness instruments are recommended to verify hardness since in-production hardness of pintle rods is found to vary widely and probably leads to some premature release of pistons in samplers.

  4. Millijoule Pulse Energy Second Harmonic Generation With Single-Stage Photonic Bandgap Rod Fiber Laser

    DEFF Research Database (Denmark)

    Laurila, Marko; Saby, Julien; Alkeskjold, Thomas Tanggaard

    2011-01-01

    In this paper, we demonstrate, for the first time, a single-stage Q-switched single-mode (SM) ytterbium-doped rod fiber laser delivering record breaking pulse energies at visible and UV light. We use a photonic bandgap rod fiber with a mode field diameter of 59μm based on a new distributed...

  5. Design and testing of a four rod crab cavity for High Luminosity LHC

    Directory of Open Access Journals (Sweden)

    B. Hall

    2017-01-01

    Full Text Available A 4-rod deflecting structure is proposed as a possible crab cavity design for the LHC high luminosity upgrade. Crab cavities are required for the LHC luminosity upgrade to provide a greater bunch overlap in the presence of a crossing angle, but must fit in the existing limited space. The structure has two parallel sections consisting of two longitudinally opposing quarter-wave rods, where each rod has the opposite charge from each of its nearest neighbors. The structure is transversely compact because the frequency is dependent on the rod lengths rather than the cavity radius. Simulations were undertaken to investigate the effect of rod shape on surface fields, higher order multipole terms and induced wakefields in order to obtain the optimal rod shape. The simulation results presented show that the addition of focus electrodes or by shaping the rods the sextupole contribution of the cavity voltage can be negated; the sextupole contribution is 321.57  mTm/m^{2}, E_{peak}=27.7  MV/m, and B_{peak}=63.9  mT at the design voltage of 3 MV. The damping requirements for the LHC are critical and suitable couplers to damp all modes but the operating mode are presented. The results of various testing cycles of the first SRF 4 rod prototype cavity are presented and show that the cavity has reached the required transverse voltage of 3 MV.

  6. 78 FR 2658 - Carbon and Certain Alloy Steel Wire Rod From Mexico: Rescission of Antidumping Duty...

    Science.gov (United States)

    2013-01-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE 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...

  7. 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... Certain Alloy Steel Wire Rod from Brazil, Indonesia, Mexico, Moldova, Trinidad and Tobago, and Ukraine, 67...

  8. Isotropic-nematic phase separation in asymmetrical rod-plate mixtures

    NARCIS (Netherlands)

    Wensink, H.H.; Vroege, G.J.; Lekkerkerker, H.N.W.

    2001-01-01

    Recent experiments on mixtures of rodlike and platelike colloidal particles have uncovered the phase behavior of strongly asymmetrical rod-plate mixtures. In these mixtures, in which the excluded volume of the platelets is much larger than that of the rods, an extended isotropic (I)–plate-rich

  9. Exploratory movements determine cue weighting in haptic length perception of handheld rods

    NARCIS (Netherlands)

    Debats, N.B.; van der Langenberg, R.W.; Kingma, I.; Smeets, J.B.J.; Beek, P.J.

    2010-01-01

    In the present study, we sought to unravel how exploratory movements affect length perception of rods that are held in and wielded by hand. We manipulated the mechanical rod properties - mass (m), first moment of mass distribution (M), major principal moment of inertia (I

  10. Effects of a telescopic intramedullary rod for treating patients with osteogenesis imperfecta of the femur

    Science.gov (United States)

    Rosemberg, D. L.; Goiano, E. O.; Akkari, M.; Santili, C.

    2018-01-01

    Abstract Purpose To introduce a new model of telescopic intramedullary rod (TIR), evaluate its effects on treating patients presenting with moderate and severe osteogenesis imperfecta (OI) and to compare the findings with those of other telescopic rods. Methods A total of 21 patients (nine girls and 12 boys; mean age at first operation, 6.6 years, 1.52 to 13.18) who underwent 52 femoral operations were monitored during a mean of 9.96 years (3.39 to 14.54). Patient characteristics, telescoping rod capability and its complications were examined. Results According to the Sillence classification, we investigated one patient with type I, nine with type III and 11 with type IV OI. Revision rates at up to five years (36%) were inferior to those found for the Fassier-Duval rod (46%). The main cause of revision was fracture (15 patients), followed by rod migration (nine), and infection (two). The rod exhibited higher telescopic capacity in boys than girls. Type III most commonly required an operation; the age group with the highest number of procedures was five to ten years. Male migration was the main cause of rod migration. Conclusion The TIR has a satisfactory cost-benefit ratio with less complication rates and low production costs. The TIR is a feasible alternative to the commonly used Fassier-Duval rod. Level of Evidence IV PMID:29456761

  11. Demonstrating the Conservation of Angular Momentum Using Model Cars Moving along a Rotating Rod

    Science.gov (United States)

    Abdul-Razzaq, Wathiq; Golubovic, Leonardo

    2013-01-01

    We have developed an exciting non-traditional experiment for our introductory physics laboratories to help students to understand the principle of conservation of angular momentum. We used electric toy cars moving along a long rotating rod. As the cars move towards the centre of the rod, the angular velocity of this system increases.…

  12. Mutations in PCDH21 cause autosomal recessive cone-rod dystrophy

    DEFF Research Database (Denmark)

    Østergaard, Elsebet; Batbayli, M; Dunø, Morten

    2010-01-01

    Cone-rod dystrophy is a retinal dystrophy with early loss of cone photoreceptors and a parallel or subsequent loss of rod photoreceptors. It may be syndromic, but most forms are non-syndromic with autosomal dominant, autosomal recessive or X-linked recessive inheritance....

  13. Reflectance Spectra of Peacock Feathers and the Turning Angles of Melanin Rods in Barbules.

    Science.gov (United States)

    Okazaki, Toshio

    2018-02-01

    I analyzed the association between the reflectance spectra and melanin rod arrangement in barbules of the eyespot of peacock feathers. The reflectance spectra from the yellow-green feather of the eyespot indicated double peaks of 430 and 540 nm. The maximum reflectance spectrum of the blue feather was 480 nm, and that of the dark blue feather was 420 nm. The reflectance spectra from brown feathers indicated double peaks of 490 and 610 nm. Transmission electron microscopic analysis confirmed that melanin rods were arranged fanwise in the outer layer toward the barbule tips. In addition, using polarized light microscope, I attempted to determine whether the turning angles of melanin rods in the barbules reflected different colors. The turning angle of the polarizing axis of the barbules was supported by that of the melanin rods, observed using transmission electron microscopic images. To compare the turning angle of melanin rods in the respective barbules, I calculated the opening width of the fanwise melanin rods by dividing the width of the barbules by the turning angle of the polarizing axis of barbules and obtained a positive correlation between the reflectance spectra and opening width of the fanwise melanin rods. Moreover, the widely spreading reflection from the barbules may occur because of the fanwise melanin rod arrangement.

  14. Effects of fuel relocation on reflood in a partially-blocked rod bundle

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byoung Jae [School of Mechanical Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Kim, Jongrok; Kim, Kihwan; Bae, Sung Won [Thermal-Hydraulic Safety Research Division, Korea Atomic Energy Research Division, 111 Daedeok-daero, Yuseong-gu, Daejeon 34057 (Korea, Republic of); Moon, Sang-Ki, E-mail: skmoon@kaeri.re.kr [Thermal-Hydraulic Safety Research Division, Korea Atomic Energy Research Division, 111 Daedeok-daero, Yuseong-gu, Daejeon 34057 (Korea, Republic of)

    2017-02-15

    Ballooning of the fuel rods has been an important issue, since it can influence the coolability of the rod bundle in a large-break loss-of-coolant accident (LBLOCA). Numerous past studies have investigated the effect of blockage geometry on the heat transfer in a partially blocked rod bundle. However, they did not consider the occurrence of fuel relocation and the corresponding effect on two-phase heat transfer. Some fragmented fuel particles located above the ballooned region may drop into the enlarged volume of the balloon. Accordingly, the fuel relocation brings in a local power increase in the ballooned region. The present study’s objective is to investigate the effect of the fuel relocation on the reflood under a LBLOCA condition. Toward this end, experiments were performed in a 5 × 5 partially-blocked rod bundle. Two power profiles were tested: one is a typical cosine shape and the other is the modified shape considering the effect of the fuel relocation. For a typical power shape, the peak temperature in the ballooned rods was lower than that in the intact rods. On the other hand, for the modified power shape, the peak temperature in the ballooned rods was higher than that in the intact rods. Numerical simulations were also performed using the MARS code. The tendencies of the peak clad temperatures were well predicted.

  15. Power Maneuvering of Pressurized Water Reactors with Axially Variable Strength Control Rods

    Science.gov (United States)

    Kim, Ung-Soo; Seong, Poong-Hyun

    2004-02-01

    In this research, axially variable strength control rods (AVSCRs) are developed to solve the problems related to the axial power distribution of a reactor during power maneuvering of pressurized water reactors (PWRs). The control rods are classified into two types: multipurpose control rods and regulating control rods. Two multipurpose control rod banks (AVSCR1, AVSCR2) are newly developed; conventional axially uniform strength control rods are adopted as regulating control rod banks to minimize the design change. The newly developed AVSCRs are axially three-sectioned and their worth shapes are optimized to obtain appropriate moving characteristics related to the variation of the axial offset (AO) according to the motion of the AVSCRs. The operation strategy for the power maneuvering is developed in consideration of the moving characteristics of the AVSCRs. This strategy consists of simple logics, and no use of reactivity compensation by boron is considered. Finally, the AVSCRs are applied to the power maneuvering with a typical 100-50-100%, 2-6-2-14 h pattern of daily load-follow for all burn-up state of the core. From the application results, it is shown that the use of AVSCRs makes it possible to regulate AO within the target band during the power maneuvering with only control rods. Consequently, power maneuvering is accomplished without reactivity compensation by a change in boron concentration, and the AVSCRs can cover the entire burn-up states of the reactor core.

  16. 85 μm core rod fiber amplifier delivering 350 W/m

    DEFF Research Database (Denmark)

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

    2016-01-01

    An improved version of the distributed modal filtering (DMF) rod fiber is tested in a high power setup delivering 350 W/m of extracted signal average power limited by the available pump power. The rod fiber is thoroughly tested to record the transverse modal instability (TMI) behavior and also...

  17. A uniquely shaped rod improves curve correction in surgical treatment of adolescent idiopathic scoliosis

    DEFF Research Database (Denmark)

    Gehrchen, Poul Martin; Ohrt-Nissen, Søren; Hallager, Dennis Winge

    2016-01-01

    Study Design. A retrospective cohort study.  Objective. The aim of this study is to determine the initial curve correction in patients surgically treated for adolescent idiopathic scoliosis (AIS) using either beam-like rods (BRs) or traditional circular rods (CRs).  Summary of Background Data...

  18. Fission gas release during power change. Re-irradiation test of LWR fuel rod at JMTR

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Jinichi; Furuta, Teruo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Endo, Yasuichi; Ishii, Tadahiko; Shimizu, Michio

    1995-11-01

    A full length rod irradiated at Tsuruga unit 1 was refablicated to short length rods, and rod inner pressure gauges were re-instrumented to the rods. Re-irradiation tests to study the fission gas release during power change were carried out by means of BOCA/OSF-1 facility at JMTR. In the tests, steady state operation at 40kW/m, power cycling and daily load follow operations between 20 and 40kW/m were conducted for the same high power holding time, and the rod inner pressure change during the tests was measured. The rod inner pressure increase was observed during power change, especially during power reduction. The rod inner pressure increase during a power cycling depended on the length of the high power operation just before the power cycling. The width of the rod inner pressure increase during a power cycling decreased gradually as the power cycling was repeated continuously. When steady state operation and power cycling were repeated at the power levels of 30, 35 and 40kW/m, the power cycling accelerated the fission gas release compared with the steady state operation. The fission gas release during power reduction is estimated to be the release from FP gas bubbles on the grain boundary caused by the thermal stress in the pellet during power reduction. (author).

  19. Blocking Synthesis of the Variant Surface Glycoprotein Coat in Trypanosoma brucei Leads to an Increase in Macrophage Phagocytosis Due to Reduced Clearance of Surface Coat Antibodies.

    Directory of Open Access Journals (Sweden)

    Jackie L Y Cheung

    2016-11-01

    Full Text Available The extracellular bloodstream form parasite Trypanosoma brucei is supremely adapted to escape the host innate and adaptive immune system. Evasion is mediated through an antigenically variable Variant Surface Glycoprotein (VSG coat, which is recycled at extraordinarily high rates. Blocking VSG synthesis triggers a precytokinesis arrest where stalled cells persist for days in vitro with superficially intact VSG coats, but are rapidly cleared within hours in mice. We therefore investigated the role of VSG synthesis in trypanosome phagocytosis by activated mouse macrophages. T. brucei normally effectively evades macrophages, and induction of VSG RNAi resulted in little change in phagocytosis of the arrested cells. Halting VSG synthesis resulted in stalled cells which swam directionally rather than tumbling, with a significant increase in swim velocity. This is possibly a consequence of increased rigidity of the cells due to a restricted surface coat in the absence of VSG synthesis. However if VSG RNAi was induced in the presence of anti-VSG221 antibodies, phagocytosis increased significantly. Blocking VSG synthesis resulted in reduced clearance of anti-VSG antibodies from the trypanosome surface, possibly as a consequence of the changed motility. This was particularly marked in cells in the G2/ M cell cycle stage, where the half-life of anti-VSG antibody increased from 39.3 ± 4.2 seconds to 99.2 ± 15.9 seconds after induction of VSG RNAi. The rates of internalisation of bulk surface VSG, or endocytic markers like transferrin, tomato lectin or dextran were not significantly affected by the VSG synthesis block. Efficient elimination of anti-VSG-antibody complexes from the trypanosome cell surface is therefore essential for trypanosome evasion of macrophages. These experiments highlight the essentiality of high rates of VSG recycling for the rapid removal of host opsonins from the parasite surface, and identify this process as a key parasite

  20. The orthologue of Sjögren'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.