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Sample records for brucei rhodesiense diagnostic

  1. 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.

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

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    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.

  3. Relationship between Trypanosoma brucei rhodesiense genetic diversity and clinical spectrum among sleeping sickness patients in Uganda.

    Science.gov (United States)

    Kato, Charles D; Mugasa, Claire M; Nanteza, Ann; Matovu, Enock; Alibu, Vincent P

    2017-10-27

    Human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense in East and southern Africa is reported to be clinically diverse. We tested the hypothesis that this clinical diversity is associated with a variation in trypanosome genotypes. Trypanosome DNA isolated from HAT patients was genotyped using 7 microsatellite markers directly from blood spotted FTA cards following a whole genome amplification. All markers were polymorphic and identified 17 multi-locus genotypes with 56% of the isolates having replicate genotypes. We did not observe any significant clustering between isolates and bootstrap values across major tree nodes were insignificant. When genotypes were compared among patients with varying clinical presentation or outcome, replicate genotypes were observed at both extremes showing no significant association between genetic diversity and clinical outcome. Our study shows that T. b. rhodesiense isolates are homogeneous within a focus and that observed clinical diversity may not be associated with parasite genetic diversity. Other factors like host genetics and environmental factors might be involved in determining clinical diversity. Our study may be important in designing appropriate control measures that target the parasite.

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

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    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.

  5. 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

    and 140 days post-infection (dpi) respectively. Matched serum and CSF samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) and IL-10 were quantified by ELISA. RESULTS: There was no detectable immunospecific IgM and IgG in the CSF before 49 dpi. CSF IgM and Ig......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...... curative treatment was given. After curative treatment, there was rapid and significant drop in serum IgM and IL-10 concentration as well as CSF WCC. However, the CSF IgM and IgG remained detectable to the end of the study. CONCLUSIONS: Serum and CSF concentrations of immunospecific IgM and CSF IgG changes...

  6. Coenzyme Q10 prevented full blown splenomegaly and decreased melarsoprol-induced reactive encephalopathy in mice infected with Trypanosoma brucei rhodesiense

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    James Nyabuga Nyariki

    2015-03-01

    Full Text Available Objective: To establish the modulatory effects of coenzyme Q10 on experimental trypanosome infections in mice and evaluate the risk of occurrence and severity of melarsoprol-induced post treatment reactive encephalopathy (PTRE. Methods: Female Swiss white mice were orally administered with 200 mg/kg of coenzyme Q10 after which they were intraperitoneally inoculated with Trypanasoma brucei rhodesiense (T. b. rhodesiense. The resultant infection was allowed to develop and simulate all phases of human African trypanosomiasis and PTRE. Parasitaemia development, packed cell volume, haematological and pathological changes were determined. Results: A histological study in the brain tissue of T. b. rhodesiense infected mice demonstrated neuroinflammatory pathology which was highly amplified in the PTRE-induced groups. A prominent reduction in the severity of the neuroinflammatory response was detected when coenzyme-Q10 was administered. Furthermore, the mean tissue weight of spleen to body ratio in coenzyme Q10 supplemented group was significantly (P<0.05 different compared to un-supplemented groups, and clearly indicated that coenzyme Q10 prevented full blown splenomegaly pathogenesis by T. b. rhodesiense. A significant (P<0.05 increase in hemoglobin levels and red blood cells was observed in coenzyme Q10 mice compared to those infected and un-supplemented with coenzyme Q10. Conclusions: The capacity of coenzyme Q10 to alter the pathogenesis of T. b. rhodesiense infection in mice and following treatment with melarsoprol, may find application by rendering humans and animals less susceptible to deleterious effects of trypanosome infection such as splenomegaly and melarsoprol-induced PTRE and neurotoxicity.

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

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    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

  8. 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.

  9. Estimating the burden of rhodesiense sleeping sickness during an outbreak in Serere, eastern Uganda

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    Coleman Paul G

    2008-03-01

    Full Text Available Abstract Background Zoonotic sleeping sickness, or HAT (Human African Trypanosomiasis, caused by infection with Trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. Previous assessments of the disease burden expressed as Disability-Adjusted Life Years (DALYs for this infection have not distinguished T.b. rhodesiense from infection with the related, but clinically distinct Trypanosoma brucei gambiense form. T.b. rhodesiense occurs focally, and it is important to assess the burden at the scale at which resource-allocation decisions are made. Methods The burden of T.b. rhodesiense was estimated during an outbreak of HAT in Serere, Uganda. We identified the unique characteristics affecting the burden of rhodesiense HAT such as age, severity, level of under-reporting and duration of hospitalisation, and use field data and empirical estimates of these to model the burden imposed by this and other important diseases in this study population. While we modelled DALYs using standard methods, we also modelled uncertainty of our parameter estimates through a simulation approach. We distinguish between early and late stage HAT morbidity, and used disability weightings appropriate for the T.b. rhodesiense form of HAT. We also use a model of under-reporting of HAT to estimate the contribution of un-reported mortality to the overall disease burden in this community, and estimate the cost-effectiveness of hospital-based HAT control. Results Under-reporting accounts for 93% of the DALY estimate of rhodesiense HAT. The ratio of reported malaria cases to reported HAT cases in the same health unit was 133:1, however, the ratio of DALYs was 3:1. The age productive function curve had a close correspondence with the HAT case distribution, and HAT cases occupied more patient admission time in Serere during 1999 than all other infectious diseases other than malaria. The DALY estimate for HAT in Serere shows that the burden is much greater

  10. Identification of compounds with anti-proliferative activity against Trypanosoma brucei brucei strain 427 by a whole cell viability based HTS campaign.

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    Melissa L Sykes

    Full Text Available Human African Trypanosomiasis (HAT is caused by two trypanosome sub-species, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Drugs available for the treatment of HAT have significant issues related to difficult administration regimes and limited efficacy across species and disease stages. Hence, there is considerable need to find new alternative and less toxic drugs. An approach to identify starting points for new drug candidates is high throughput screening (HTS of large compound library collections. We describe the application of an Alamar Blue based, 384-well HTS assay to screen a library of 87,296 compounds against the related trypanosome subspecies, Trypanosoma brucei brucei bloodstream form lister 427. Primary hits identified against T.b. brucei were retested and the IC(50 value compounds were estimated for T.b. brucei and a mammalian cell line HEK293, to determine a selectivity index for each compound. The screening campaign identified 205 compounds with greater than 10 times selectivity against T.b. brucei. Cluster analysis of these compounds, taking into account chemical and structural properties required for drug-like compounds, afforded a panel of eight compounds for further biological analysis. These compounds had IC(50 values ranging from 0.22 µM to 4 µM with associated selectivity indices ranging from 19 to greater than 345. Further testing against T.b. rhodesiense led to the selection of 6 compounds from 5 new chemical classes with activity against the causative species of HAT, which can be considered potential candidates for HAT early drug discovery. Structure activity relationship (SAR mining revealed components of those hit compound structures that may be important for biological activity. Four of these compounds have undergone further testing to 1 determine whether they are cidal or static in vitro at the minimum inhibitory concentration (MIC, and 2 estimate the time to kill.

  11. Crystal structures of T. b. rhodesiense adenosine kinase complexed with inhibitor and activator: implications for catalysis and hyperactivation.

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    Sabine Kuettel

    2011-05-01

    Full Text Available BACKGROUND: The essential purine salvage pathway of Trypanosoma brucei bears interesting catalytic enzymes for chemotherapeutic intervention of Human African Trypanosomiasis. Unlike mammalian cells, trypanosomes lack de novo purine synthesis and completely rely on salvage from their hosts. One of the key enzymes is adenosine kinase which catalyzes the phosphorylation of ingested adenosine to form adenosine monophosphate (AMP utilizing adenosine triphosphate (ATP as the preferred phosphoryl donor. METHODS AND FINDINGS: Here, we present the first structures of Trypanosoma brucei rhodesiense adenosine kinase (TbrAK: the structure of TbrAK in complex with the bisubstrate inhibitor P(1,P(5-di(adenosine-5'-pentaphosphate (AP5A at 1.55 Å, and TbrAK complexed with the recently discovered activator 4-[5-(4-phenoxyphenyl-2H-pyrazol-3-yl]morpholine (compound 1 at 2.8 Å resolution. CONCLUSIONS: The structural details and their comparison give new insights into substrate and activator binding to TbrAK at the molecular level. Further structure-activity relationship analyses of a series of derivatives of compound 1 support the observed binding mode of the activator and provide a possible mechanism of action with respect to their activating effect towards TbrAK.

  12. Sensitivity and Specificity of a Prototype Rapid Diagnostic Test for the Detection of Trypanosoma brucei gambiense Infection: A Multi-centric Prospective Study.

    Science.gov (United States)

    Bisser, Sylvie; Lumbala, Crispin; Nguertoum, Etienne; Kande, Victor; Flevaud, Laurence; Vatunga, Gedeao; Boelaert, Marleen; Büscher, Philippe; Josenando, Theophile; Bessell, Paul R; Biéler, Sylvain; Ndung'u, Joseph M

    2016-04-01

    A major challenge in the control of human African trypanosomiasis (HAT) is lack of reliable diagnostic tests that are rapid and easy to use in remote areas where the disease occurs. In Trypanosoma brucei gambiense HAT, the Card Agglutination Test for Trypanosomiasis (CATT) has been the reference screening test since 1978, usually on whole blood, but also in a 1/8 dilution (CATT 1/8) to enhance specificity. However, the CATT is not available in a single format, requires a cold chain for storage, and uses equipment that requires electricity. A solution to these challenges has been provided by rapid diagnostic tests (RDT), which have recently become available. A prototype immunochromatographic test, the SD BIOLINE HAT, based on two native trypanosomal antigens (VSG LiTat 1.3 and VSG LiTat 1.5) has been developed. We carried out a non-inferiority study comparing this prototype to the CATT 1/8 in field settings. The prototype SD BIOLINE HAT, the CATT Whole Blood and CATT 1/8 were systematically applied on fresh blood samples obtained from 14,818 subjects, who were prospectively enrolled through active and passive screening in clinical studies in three endemic countries of central Africa: Angola, the Democratic Republic of the Congo and the Central African Republic. One hundred and forty nine HAT cases were confirmed by parasitology. The sensitivity and specificity of the prototype SD BIOLINE HAT was 89.26% (95% confidence interval (CI) = 83.27-93.28) and 94.58% (95% CI = 94.20-94.94) respectively. The sensitivity and specificity of the CATT on whole blood were 93.96% (95% CI = 88.92-96.79) and 95.91% (95% CI = 95.58-96.22), and of the CATT 1/8 were 89.26% (95% CI = 83.27-93.28) and 98.88% (95% CI = 98.70-99.04) respectively. After further optimization, the prototype SD BIOLINE HAT could become an alternative to current screening methods in primary healthcare settings in remote, resource-limited regions where HAT typically occurs.

  13. 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 Trypanoso...ma_brucei_S.png Trypanosoma_brucei_NS.png http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Trypanoso...ma+brucei&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 ...

  14. The activity of aminoglycoside antibiotics against Trypanosoma brucei.

    Science.gov (United States)

    Maina, N W; Kinyanjui, B; Onyango, J D; Auma, J E; Croj, S

    1998-01-01

    The trypanocidal activity of four aminoglycosides was determined against Trypanosoma brucei in vitro. The drug activity in descending order, was as follows; paromomycin kanamycin>gentamycin > neomycin. Paromomycin bad the highest activity and the concentration that inhibited 50% of trypanosome growth (IC50) was 11.4microM. The effect of paromomycin on the causative agents of the East African form of sleeping sickness - T.b. rhodesiense KETRI 265, 2285, 2545, 2562 and EATRO 110,112, 1152 was subsequently assessed. Variations sensitivities between the trypanosome populations were observed and IC50 values ranging from 13.01 to 43.06 microM recorded. However, when paromomycin was administered intraperitoneally (i.p) at 500 mg/kg, it was not effective in curing mice infected with T. b. rhodesienseKETRI 2545 the most drug-sensitive isolate in vitro. Lack of in vivo activity may be because the trypanosome is an extracellular parasite. The pharmacokinetics of paromomycin in the mouse model need to be determined.

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

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    Nwoha Rosemary Ijeoma Ogechi

    2015-02-01

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

  16. Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.

    Science.gov (United States)

    Giroud, Maude; Dietzel, Uwe; Anselm, Lilli; Banner, David; Kuglstatter, Andreas; Benz, Jörg; Blanc, Jean-Baptiste; Gaufreteau, Delphine; Liu, Haixia; Lin, Xianfeng; Stich, August; Kuhn, Bernd; Schuler, Franz; Kaiser, Marcel; Brun, Reto; Schirmeister, Tanja; Kisker, Caroline; Diederich, François; Haap, Wolfgang

    2018-04-26

    Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei ( T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors ( K i < 10 nM), preventing the cell-growth of Trypanosoma brucei rhodesiense (IC 50 < 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic acid (Cys-SOH) during crystallization. The P-glycoprotein efflux ratio was measured and the in vivo brain penetration in rats determined. When tested in vivo in acute HAT model, the compounds permitted up to 16.25 (vs 13.0 for untreated controls) mean days of survival.

  17. Response of Tripanosoma brucei brucei –induced anaemia to a ...

    African Journals Online (AJOL)

    A study was therefore carried out to determine the effect of the preparation on packed cell volume (PCV) and haemoglobin (Hb) concentrations in anaemic rabbits. The PCV and Hb concentrations of healthy rabbits infected with Trypanosoma brucei brucei were monitored for 49 days. T. b. brucei produced a significant ...

  18. Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei.

    Science.gov (United States)

    Zimmermann, Stefanie; Oufir, Mouhssin; Leroux, Alejandro; Krauth-Siegel, R Luise; Becker, Katja; Kaiser, Marcel; Brun, Reto; Hamburger, Matthias; Adams, Michael

    2013-11-15

    In mice cynaropicrin (CYN) potently inhibits the proliferation of Trypanosoma brucei-the causative agent of Human African Trypanosomiasis-by a so far unknown mechanism. We hypothesized that CYNs α,β-unsaturated methylene moieties act as Michael acceptors for glutathione (GSH) and trypanothione (T(SH)2), the main low molecular mass thiols essential for unique redox metabolism of these parasites. The analysis of this putative mechanism and the effects of CYN on enzymes of the T(SH)2 redox metabolism including trypanothione reductase, trypanothione synthetase, glutathione-S-transferase, and ornithine decarboxylase are shown. A two step extraction protocol with subsequent UPLC-MS/MS analysis was established to quantify intra-cellular CYN, T(SH)2, GSH, as well as GS-CYN and T(S-CYN)2 adducts in intact T. b. rhodesiense cells. Within minutes of exposure to CYN, the cellular GSH and T(SH)2 pools were entirely depleted, and the parasites entered an apoptotic stage and died. CYN also showed inhibition of the ornithine decarboxylase similar to the positive control eflornithine. Significant interactions with the other enzymes involved in the T(SH)2 redox metabolism were not observed. Alongside many other biological activities sesquiterpene lactones including CYN have shown antitrypanosomal effects, which have been postulated to be linked to formation of Michael adducts with cellular nucleophiles. Here the interaction of CYN with biological thiols in a cellular system in general, and with trypanosomal T(SH)2 redox metabolism in particular, thus offering a molecular explanation for the antitrypanosomal activity is demonstrated. At the same time, the study provides a novel extraction and analysis protocol for components of the trypanosomal thiol metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Trypanosoma brucei gambiense: HMI-9 medium containing methylcellulose and human serum supports the continuous axenic in vitro propagation of the bloodstream form.

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    Van Reet, N; Pyana, P P; Deborggraeve, S; Büscher, P; Claes, F

    2011-07-01

    Trypanosoma brucei (T.b.) gambiense causes the chronic form of human African trypanosomiasis or sleeping sickness. One of the major problems with studying T.b. gambiense is the difficulty to isolate it from its original host and the difficult adaptation to in vivo and in vitro mass propagation. The objective of this study was to evaluate if an established method for axenic culture of pleomorphic bloodstream form T.b. brucei strains, based on methylcellulose containing HMI-9 medium, also facilitated the continuous in vitro propagation of other bloodstream form Trypanozoon strains, in particular of T.b. gambiense. Bloodstream form trypanosomes from one T.b. brucei, two T.b. rhodesiense, one T. evansi and seven T.b. gambiense strains were isolated from mouse blood and each was concurrently cultivated in liquid and methylcellulose-containing HMI-9 based medium, either with or without additional human serum supplementation, for over 10 consecutive sub passages. Although HMI-9 based medium supplemented with 1.1% (w/v) methylcellulose supported the continuous cultivation of all non-gambiense strains better than liquid media could, the in vitro cultivation of all gambiense strains was only achieved in HMI-9 based medium containing 1.1% (w/v) methylcellulose, 15% (v/v) fetal calf serum and 5% (v/v) heat-inactivated human serum. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Malleable Mitochondrion of Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

    Roč. 315, 2015 Feb 07 (2015), s. 73-151 ISSN 1937-6448 R&D Projects: GA ČR GAP302/12/2513; GA MŠk LL1205; GA MŠk(CZ) EE2.3.30.0032; GA MŠk LH12104; GA ČR GAP305/12/2261 EU Projects: European Commission(XE) 316304 Institutional support: RVO:60077344 Keywords : Kinetoplast * Metabolism * Mitochondrial transport * Mitochondrion * RNA import * T. brucei * Trypanosome * kDNA Subject RIV: EE - Microbiology, Virology Impact factor: 3.752, year: 2015

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

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    Fabian C. Herrmann

    2015-09-01

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

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

    Science.gov (United States)

    Herrmann, Fabian C; Lenz, Mairin; Jose, Joachim; Kaiser, Marcel; Brun, Reto; Schmidt, Thomas J

    2015-09-03

    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. Factors influencing passive surveillance for T. b. rhodesiense human african trypanosomiasis in Uganda.

    Science.gov (United States)

    Acup, Christine; Bardosh, Kevin Louis; Picozzi, Kim; Waiswa, Charles; Welburn, Susan Christina

    2017-01-01

    Sleeping sickness or Human African Trypanosomiasis (HAT) is a neglected tropical disease of public health importance across much of Sub-Saharan Africa. In Uganda, chronic T. b. gambiense HAT (gHAT) and acute T. b. rhodesiense HAT (rHAT) occur in two large but discrete geographical foci. Both forms are difficult to diagnose, expensive to treat and ultimately fatal in the absence of treatment. The area affected by zoonotic rHAT has been steadily expanding, placing a high burden on local health systems. HAT is a disease of neglected populations and is notorious for being under-reported. Here we examine the factors that influence passive rHAT surveillance within the district health system in four Ugandan districts into which the disease had recently been introduced, focusing on staff knowledge, infrastructure and data management. A mixed methods study was undertaken between 2011 and 2013 in Dokolo, Kaberamaido, Soroti and Serere districts to explore health facility capacity and clinical service provision, diagnostic capacity, HAT knowledge and case reporting. Structured interviews were undertaken with 86 medical personnel, including clinicians, nurses, midwives and technicians across 65 HC-II and HC-III medical facilities, where the health infrastructure was also directly observed. Eleven semi-structured interviews were undertaken with medical staff in each of the three designated HAT treatment facilities (Dokolo, Lwala and Serere HC-IV) in the area. HAT treatment centre case records, collected between 2009 and 2012, were analyzed. Most medical staff in HC-II and HC-III facilities had been made aware of HAT from radio broadcasts, newspapers and by word of mouth, suggestive of a lack of formal training. Key knowledge as regards the causative agent, clinical signs and that HAT drugs are provided free of charge was lower amongst HC-II than HC-III staff. Many respondents did not know whether HAT was endemic in their district. In rHAT specialist treatment centres, staff

  4. 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

  5. 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.

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

    Czech Academy of Sciences Publication Activity Database

    Šíma, Matyáš; Havelková, Helena; Quan, L.; Svobodová, M.; Jarošíková, T.; Vojtíšková, Jarmila; Stassen, A. P. M.; Demant, P.; Lipoldová, Marie

    2011-01-01

    Roč. 5, č. 6 (2011), e1173 ISSN 1935-2735 R&D Projects: GA AV ČR IAA500520606; GA MŠk(CZ) LC06009 Grant - others:NIH-NCI(US) 1R01CA127162-01 Institutional research plan: CEZ:AV0Z50520514 Keywords : Trypanosoma brucei brucei * mouse recombinant congenic strains * Tbbr Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.716, year: 2011

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

    African Journals Online (AJOL)

    Trypanosoma brucei gambiense was isolated twice from each of 23 patients in Côte d'Ivoire. Genetic characterization using RAPD (Random Primed Amplified Polymorphic DNA) showed additional variability within a given isoenzyme profile (zymodeme), confirming that this fingerprinting method has a higher discriminative ...

  8. 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 ...

  9. 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.

  10. Comparative Genomics of Glossina palpalis gambiensis and G. morsitans morsitans to Reveal Gene Orthologs Involved in Infection by Trypanosoma brucei gambiense.

    Science.gov (United States)

    Hamidou Soumana, Illiassou; Tchicaya, Bernadette; Rialle, Stéphanie; Parrinello, Hugues; Geiger, Anne

    2017-01-01

    Blood-feeding Glossina palpalis gambiense (Gpg) fly transmits the single-celled eukaryotic parasite Trypanosoma brucei gambiense (Tbg), the second Glossina fly African trypanosome pair being Glossina morsitans / T .brucei rhodesiense. Whatever the T. brucei subspecies, whereas the onset of their developmental program in the zoo-anthropophilic blood feeding flies does unfold in the fly midgut, its completion is taking place in the fly salivary gland where does emerge a low size metacyclic trypomastigote population displaying features that account for its establishment in mammals-human individuals included. Considering that the two Glossina - T. brucei pairs introduced above share similarity with respect to the developmental program of this African parasite, we were curious to map on the Glossina morsitans morsitans (Gmm), the Differentially Expressed Genes (DEGs) we listed in a previous study. Briefly, using the gut samples collected at days 3, 10, and 20 from Gpg that were fed or not at day 0 on Tbg-hosting mice, these DGE lists were obtained from RNA seq-based approaches. Here, post the mapping on the quality controlled DEGs on the Gmm genome, the identified ortholog genes were further annotated, the resulting datasets being compared. Around 50% of the Gpg DEGs were shown to have orthologs in the Gmm genome. Under one of the three Glossina midgut sampling conditions, the number of DEGs was even higher when mapping on the Gmm genome than initially recorded. Many Gmm genes annotated as "Hypothetical" were mapped and annotated on many distinct databases allowing some of them to be properly identified. We identify Glossina fly candidate genes encoding (a) a broad panel of proteases as well as (b) chitin-binding proteins, (c) antimicrobial peptide production-Pro3 protein, transferrin, mucin, atttacin, cecropin, etc-to further select in functional studies, the objectives being to probe and validated fly genome manipulation that prevents the onset of the developmental

  11. Studies on the glycosome of Trypanosoma brucei

    International Nuclear Information System (INIS)

    Aman, R.A.

    1985-01-01

    Glycosomes (microbodies) have been purified from bloodstream form Trypanosoma brucei by an improved procedure involving freezing and thawing live organisms in 15% glycerol prior to cell disruption. Highly purified organelles of bloodstream form T. brucei contain 11 major proteins of which 8 tentatively identified glycolytic enzymes make up about 90% of the total glycosomal protein. Treatment of these intact isolated organelles with the bisimidoester dimethylsuberimidate (DMSI) resulted in crosslinking of all glycosomal proteins into a large complex suggestive of juxtapositioning of the glycosomal proteins. The crosslinked complex was capable of catalyzing the multienzyme conversion of glucose to glycerol-3-phosphate but did not possess any special kinetic features different from those of the unaggregated enzymes represented by solubilized glycosomes. The multienzyme reaction had a lab phase associated with it and [ 14 C]-glucose label incorporation into sugar phosphate intermediates was effectively competed by unlabeled intermediates. Glycosomes were also purified from culture form T. brucei by several different procedures. Comparison of highly purified organelles from the two different life stages of the organism showed reduced specific activities and contents of the early glycolytic enzymes in organelles from the culture form with a decrease from 87% to 35% of the contribution of glycolytic enzymes to the total glycosomal protein

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

    Directory of Open Access Journals (Sweden)

    Georges C. Accrombessi

    2011-02-01

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

  13. In vivo trypanocidal activity of Nymphaea lotus Linn. methanol extract against Trypanosoma brucei brucei

    Directory of Open Access Journals (Sweden)

    Muhammad Haruna Garba

    2015-10-01

    Full Text Available Objective: To evaluate the antitrypanosomal potentials of methanol extract of Nymphaea lotus Linn. (N. lotus with the aim of obtaining a new lead for formulating safe, inexpensive, nontoxic and readily available trypanocidal drugs. Methods: Seventy percent (v/v (methanol/water crude extract of N. lotus was evaluated for antitrypanosomal activity in experimental trypanosomiasis using Trypanosoma brucei bruceiinfected mice. Infected mice in different groups were administered intraperitoneally 100, 200, 300 and 400 mg/kg body weight/day of the crude for two weeks, while a positive control group was treated with standard drug, berenil. Results: The crude extract at a dose of 100 mg/kg body weight/day was more effective than the higher doses in completely clearing parasites from the blood of mice infected with Trypanosoma brucei brucei. Pre-treatment of healthy mice with the crude extract for 5 days before infection did not prevent the establishment of the infection, indicating that the extract had no prophylactic activity. Subinoculation of the blood and cerebrospinal fluid drawn from the cured mice into healthy mice failed to produce any infection within 50 days post inoculation. Administration of 1 000 mg/kg body weight of the crude extract led to the death of 50% of the experimental animals indicating a high level of toxicity of the extract at higher doses. Conclusions: This study has demonstrated the potency of the crude extract of N. lotus in treating experimental trypanosomiasis at lower doses.

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

    African Journals Online (AJOL)

    species Trypanosoma brucei that are transmitted by a tsetse fly (Glossina spp.) ... of autologous immunoglobulin antibodies on the red cell surfaces and also to ... development for the detection and management of anaemia in trypanosomiasis.

  15. Some liver function indices and blood parameters in T. brucei ...

    African Journals Online (AJOL)

    JTEkanem

    symptoms of African sleeping sickness9. Despite the prolific research ... is a disease for which both man and other animals whether ... on some symptoms caused by T. brucei infection. .... immune response is insufficient to clear infection21-23.

  16. Characterization of recombinant Trypanosoma brucei gambiense Translationally Controlled Tumor Protein (rTbgTCTP) and its interaction with Glossina midgut bacteria.

    Science.gov (United States)

    Bossard, Géraldine; Bartoli, Manon; Fardeau, Marie-Laure; Holzmuller, Philippe; Ollivier, Bernard; Geiger, Anne

    2017-09-03

    In humans, sleeping sickness (i.e. Human African Trypanosomiasis) is caused by the protozoan parasites Trypanosoma brucei gambiense (Tbg) in West and Central Africa, and T. b. rhodesiense in East Africa. We previously showed in vitro that Tbg is able to excrete/secrete a large number of proteins, including Translationally Controlled Tumor Protein (TCTP). Moreover, the tctp gene was described previously to be expressed in Tbg-infected flies. Aside from its involvement in diverse cellular processes, we have investigated a possible alternative role within the interactions occurring between the trypanosome parasite, its tsetse fly vector, and the associated midgut bacteria. In this context, the Tbg tctp gene was synthesized and cloned into the baculovirus vector pAcGHLT-A, and the corresponding protein was produced using the baculovirus Spodoptera frugicola (strain 9) / insect cell system. The purified recombinant protein rTbgTCTP was incubated together with bacteria isolated from the gut of tsetse flies, and was shown to bind to 24 out of the 39 tested bacteria strains belonging to several genera. Furthermore, it was shown to affect the growth of the majority of these bacteria, especially when cultivated under microaerobiosis and anaerobiosis. Finally, we discuss the potential for TCTP to modulate the fly microbiome composition toward favoring trypanosome survival.

  17. Regulation and spatial organization of PCNA in Trypanosoma brucei

    International Nuclear Information System (INIS)

    Kaufmann, Doris; Gassen, Alwine; Maiser, Andreas; Leonhardt, Heinrich; Janzen, Christian J.

    2012-01-01

    Highlights: ► Characterization of the proliferating cell nuclear antigen in Trypanosoma brucei (TbPCNA). ► TbPCNA is a suitable marker to detect replication in T. brucei. ► 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.

  18. Regulation and spatial organization of PCNA in Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-23

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

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

    Directory of Open Access Journals (Sweden)

    Ya Nan Sun

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Nathan Habila

    2010-01-01

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

  1. Troglitazone induces differentiation in Trypanosoma brucei

    International Nuclear Information System (INIS)

    Denninger, Viola; Figarella, Katherine; Schoenfeld, Caroline; Brems, Stefanie; Busold, Christian; Lang, Florian; Hoheisel, Joerg; Duszenko, Michael

    2007-01-01

    Trypanosoma brucei, a protozoan parasite causing sleeping sickness, is transmitted by the tsetse fly and undergoes a complex lifecycle including several defined stages within the insect vector and its mammalian host. In the latter, differentiation from the long slender to the short stumpy form is induced by a yet unknown factor of trypanosomal origin. Here we describe that some thiazolidinediones are also able to induce differentiation. In higher eukaryotes, thiazolidinediones are involved in metabolism and differentiation processes mainly by binding to the intracellular receptor peroxisome proliferator activated receptor γ. Our studies focus on the effects of troglitazone on bloodstream form trypanosomes. Differentiation was monitored using mitochondrial markers (membrane potential, succinate dehydrogenase activity, inhibition of oxygen uptake by KCN, amount of cytochrome transcripts), morphological changes (Transmission EM and light microscopy), and transformation experiments (loss of the Variant Surface Glycoprotein coat and increase of dihydroliponamide dehydrogenase activity). To further investigate the mechanisms responsible for these changes, microarray analyses were performed, showing an upregulation of expression site associated gene 8 (ESAG8), a potential differentiation regulator

  2. Analytical purification of a 60-kDa target protein of artemisinin detected in Trypanosoma brucei brucei

    Directory of Open Access Journals (Sweden)

    Benetode Konziase

    2015-12-01

    Full Text Available Here we describe the isolation and purity determination of Trypanosoma brucei (T. b. brucei candidate target proteins of artemisinin. The candidate target proteins were detected and purified from their biological source (T. b. brucei lysate using the diazirine-free biotinylated probe 5 for an affinity binding to a streptavidin-tagged resin and, subsequently, the labeled target proteins were purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. We herein showed the electrophoresis gel and the immunoblotting film containing the 60-kDa trypanosomal candidate target protein of artemisinin as a single band, which was visualized on-gel by the reverse-staining method and on a Western blotting film by enhanced chemiluminescence. The data provided in this article are related to the original research article “Biotinylated probes of artemisinin with labeling affinity toward Trypanosoma brucei brucei target proteins”, by Konziase (Anal. Biochem., vol. 482, 2015, pp. 25–31. http://dx.doi.org/10.1016/j.ab.2015.04.020.

  3. Diagnostics

    DEFF Research Database (Denmark)

    Donné, A.J.H.; Costley, A.E.; Barnsley, R.

    2007-01-01

    of the measurements—time and spatial resolutions, etc—will in some cases be more stringent. Many of the measurements will be used in the real time control of the plasma driving a requirement for very high reliability in the systems (diagnostics) that provide the measurements. The implementation of diagnostic systems...... on ITER is a substantial challenge. Because of the harsh environment (high levels of neutron and gamma fluxes, neutron heating, particle bombardment) diagnostic system selection and design has to cope with a range of phenomena not previously encountered in diagnostic design. Extensive design and R......&D is needed to prepare the systems. In some cases the environmental difficulties are so severe that new diagnostic techniques are required. The starting point in the development of diagnostics for ITER is to define the measurement requirements and develop their justification. It is necessary to include all...

  4. Triacylglycerol Storage in Lipid Droplets in Procyclic Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Stefan Allmann

    Full Text Available Carbon storage is likely to enable adaptation of trypanosomes to nutritional challenges or bottlenecks during their stage development and migration in the tsetse. Lipid droplets are candidates for this function. This report shows that feeding of T. brucei with oleate results in a 4-5 fold increase in the number of lipid droplets, as quantified by confocal fluorescence microscopy and by flow cytometry of BODIPY 493/503-stained cells. The triacylglycerol (TAG content also increased 4-5 fold, and labeled oleate is incorporated into TAG. Fatty acid carbon can thus be stored as TAG in lipid droplets under physiological growth conditions in procyclic T. brucei. β-oxidation has been suggested as a possible catabolic pathway for lipids in T. brucei. A single candidate gene, TFEα1 with coding capacity for a subunit of the trifunctional enzyme complex was identified. TFEα1 is expressed in procyclic T. brucei and present in glycosomal proteomes, Unexpectedly, a TFEα1 gene knock-out mutant still expressed wild-type levels of previously reported NADP-dependent 3-hydroxyacyl-CoA dehydrogenase activity, and therefore, another gene encodes this enzymatic activity. Homozygous Δtfeα1/Δtfeα1 null mutant cells show a normal growth rate and an unchanged glycosomal proteome in procyclic T. brucei. The decay kinetics of accumulated lipid droplets upon oleate withdrawal can be fully accounted for by the dilution effect of cell division in wild-type and Δtfeα1/Δtfeα1 cells. The absence of net catabolism of stored TAG in procyclic T. brucei, even under strictly glucose-free conditions, does not formally exclude a flux through TAG, in which biosynthesis equals catabolism. Also, the possibility remains that TAG catabolism is completely repressed by other carbon sources in culture media or developmentally activated in post-procyclic stages in the tsetse.

  5. In vitro susceptibility of Trypanosoma brucei brucei to selected essential oils and their major components.

    Science.gov (United States)

    Costa, Sonya; Cavadas, Cláudia; Cavaleiro, Carlos; Salgueiro, Lígia; do Céu Sousa, Maria

    2018-07-01

    Aiming for discovering effective and harmless antitrypanosomal agents, 17 essential oils and nine major components were screened for their effects on T. b. brucei. The essential oils were obtained by hydrodistillation from fresh plant material and analyzed by GC and GC-MS. The trypanocidal activity was assessed using blood stream trypomastigotes cultures of T. b. brucei and the colorimetric resazurin method. The MTT test was used to assess the cytotoxicity of essential oils on macrophage cells and Selectivity Indexes were calculated. Of the 17 essential oils screened three showed high trypanocidal activity (IC 50  oils had no cytotoxic effects on macrophage cells showing the highest values of Selectivity Index (63.4, 9.0 and 11.8, respectively). The oils of Distichoselinum tenuifolium, Lavandula viridis, Origanum virens, Seseli tortuosom, Syzygium aromaticum, and Thymbra capitata also exhibited activity (IC 50 of 10-25 μg/mL) but showed cytotoxicity on macrophages. Of the nine compounds tested, α-pinene (IC 50 of 2.9 μg/mL) and citral (IC 50 of 18.9 μg/mL) exhibited the highest anti-trypanosomal activities. Citral is likely the active component of C. citratus and α-pinene is responsible for the antitrypanosomal effects of J. oxycedrus. The present work leads us to propose the J. oxycedrus, C. citratus and L. luisieri oils as valuable sources of new molecules for African Sleeping Sickness treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. 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)...

  7. What controls glycolysis in bloodstream form Trypanosoma brucei?

    NARCIS (Netherlands)

    Bakker, B.M.; Michels, P.A.M.; Opperdoes, F.R.; Westerhoff, H.V.

    1999-01-01

    On the basis of the experimentally determined kinetic properties of the trypanosomal enzymes, the question is addressed of which step limits the glycolytic flux in bloodstream form Trypanosoma brucei. There appeared to be no single answer; in the physiological range, control shifted between the

  8. Serum Iron and Nitric Oxide Production in Trypanosoma brucei ...

    African Journals Online (AJOL)

    JTEkanem

    reduction in the serum iron status and a modulation of nitric oxide synthase activity of T. brucei infected rats. ... inflammation and tissue damage15. ... The serum iron level was determined ... concentration or of total nitrate and nitrite ... 15. 16. 17. 18. Days. S e ru m iro n lev e l mg. /ml. Infected treated. Infected untreated. 0.

  9. Wild chimpanzees are infected by Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Jirků, M.; Votýpka, J.; Petrželková, Klára Judita; Jirků-Pomajbíková, K.; Kriegová, E.; Vodička, R.; Lankester, F.; Leendertz, S. A. J.; Wittig, R. M.; Boesch, C.; Modrý, D.; Ayala, F. J.; Leendertz, F. H.; Lukeš, J.

    2015-01-01

    Roč. 4, č. 3 (2015), s. 277-282 ISSN 0020-7519 Institutional support: RVO:68081766 Keywords : Trypanosomes * Chimpanzee * Non-human primates * Transmission * Diagnostics Subject RIV: EG - Zoology Impact factor: 4.242, year: 2015

  10. Development of resazurin-based assay in 384-well format for high throughput whole cell screening of Trypanosoma brucei rhodesiense strain STIB 900 for the identification of potential anti-trypanosomal agents.

    Science.gov (United States)

    Lim, Kah Tee; Zahari, Zuriati; Amanah, Azimah; Zainuddin, Zafarina; Adenan, Mohd Ilham

    2016-03-01

    To accelerate the discovery of novel leads for the treatment of Human African Trypanosomiasis (HAT), it is necessary to have a simple, robust and cost-effective assay to identify positive hits by high throughput whole cell screening. Most of the fluorescence assay was made in black plate however in this study the HTS assay developed in 384-well format using clear plate and black plate, for comparison. The HTS assay developed is simple, sensitive, reliable and reproducible in both types of plates. Assay robustness and reproducibility were determined under the optimized conditions in 384-well plate was well tolerated in the HTS assay, including percentage of coefficient of variation (% CV) of 4.68% and 4.74% in clear and black 384-well plate, signal-to-background ratio (S/B) of 12.75 in clear 384-well plate and 12.07 in black 384-well plate, Z' factor of 0.79 and 0.82 in clear 384-well plate and black 384-well plate, respectively and final concentration of 0.30% dimethylsulfoxide (DMSO) in both types of plate. Drug sensitivity was found to be comparable to the reported anti-trypanosomal assay in 96-well format. The reproducibility and sensitivity of this assay make it compliant to automated liquid handler use in HTS applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Meiosis and Haploid Gametes in the Pathogen Trypanosoma brucei

    OpenAIRE

    Peacock, Lori; Bailey, Mick; Carrington, Mark; Gibson, Wendy

    2014-01-01

    Summary In eukaryote pathogens, sex is an important driving force in spreading genes for drug resistance, pathogenicity, and virulence [1]. For the parasitic trypanosomes that cause African sleeping sickness, mating occurs during transmission by the tsetse vector [2, 3] and involves meiosis [4], but haploid gametes have not yet been identified. Here, we show that meiosis is a normal part of development in the insect salivary glands for all subspecies of Trypanosoma brucei, including the human...

  12. Trypanosoma brucei Mitochondrial Respiratome: Composition and Organization in Procyclic Form

    Czech Academy of Sciences Publication Activity Database

    Acestor, N.; Zíková, Alena; Dalley, R. A.; Anupama, A.; Panigrahi, A. K.; Stuart, K. D.

    2011-01-01

    Roč. 10, č. 9 (2011), s. 1-14 ISSN 1535-9476 R&D Projects: GA ČR GP204/09/P563 Institutional research plan: CEZ:AV0Z60220518 Keywords : SUCCINATE DEHYDROGENASE * EDITED MESSENGER-RNA * COMPLEX-I * TRYPANOSOMA-BRUCEI * UBIQUINONE OXIDOREDUCTASE * TAP-TAG * PROTEIN INTERACTION * ALTERNATIVE OXIDASE * STATISTICAL-MODEL * MASS-SPECTROMETRY Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.398, year: 2011

  13. Trypanosoma brucei solanesyl-diphosphate synthase localizes to the mitochondrion

    Czech Academy of Sciences Publication Activity Database

    Lai, D.-H.; Bontempi, E. J.; Lukeš, Julius

    2012-01-01

    Roč. 183, č. 2 (2012), s. 189-192 ISSN 0166-6851 R&D Projects: GA ČR(CZ) GAP305/11/2179 Institutional support: RVO:60077344 Keywords : Trypanosoma brucei * Sleeping sickness * Ubiquinone * Solanesyl-diphosphate synthase * Digitonin permeabilization * In situ tagging Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.734, year: 2012 http://www.sciencedirect.com/science/article/pii/S0166685112000539

  14. 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.

  15. 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.

  16. The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.

    Science.gov (United States)

    Carvalho, Luis; Martínez-García, Marta; Pérez-Victoria, Ignacio; Manzano, José Ignacio; Yardley, Vanessa; Gamarro, Francisco; Pérez-Victoria, José M

    2015-10-01

    The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca(2+), and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Wild chimpanzees are infected by Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Jirků, Milan; Votýpka, Jan; Petrželková, Klára Judita; Jirků-Pomajbíková, K.; Kriegová, Eva; Vodička, R.; Lankester, F.; Leendertz, S. A. J.; Wittig, R. M.; Boesch, C.; Modrý, David; Ayala, F. J.; Leendertz, F. H.; Lukeš, Julius

    2015-01-01

    Roč. 4, č. 3 (2015), s. 277-282 ISSN 2213-2244 R&D Projects: GA MŠk(CZ) EE2.3.30.0032 EU Projects: European Commission(XE) 316304 Institutional support: RVO:60077344 Keywords : Trypanosomes * Chimpanzee * Non-human primates * Transmission * Diagnostics Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine

  18. Intraclonal mating occurs during tsetse transmission of Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Ferris Vanessa

    2009-09-01

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

  19. The flagellum of Trypanosoma brucei: new tricks from an old dog

    Science.gov (United States)

    Ralston, Katherine S.; Hill, Kent L.

    2010-01-01

    African trypanosomes, i.e. Trypanosoma brucei and related sub-species, are devastating human and animal pathogens that cause significant human mortality and limit sustained economic development in sub-Saharan Africa. Trypanosoma brucei is a highly motile protozoan parasite and coordinated motility is central to both disease pathogenesis in the mammalian host and parasite development in the tsetse fly vector. Since motility is critical for parasite development and pathogenesis, understanding unique aspects of the T. brucei flagellum may uncover novel targets for therapeutic intervention in African sleeping sickness. Moreover, studies of conserved features of the T. brucei flagellum are directly relevant to understanding fundamental aspects of flagellum and cilium function in other eukaryotes, making T. brucei an important model system. The T. brucei flagellum contains a canonical 9 + 2 axoneme, together with additional features that are unique to kinetoplastids and a few closely-related organisms. Until recently, much of our knowledge of the structure and function of the trypanosome flagellum was based on analogy and inference from other organisms. There has been an explosion in functional studies in T. brucei in recent years, revealing conserved as well as novel and unexpected structural and functional features of the flagellum. Most notably, the flagellum has been found to be an essential organelle, with critical roles in parasite motility, morphogenesis, cell division and immune evasion. This review highlights recent discoveries on the T. brucei flagellum. PMID:18472102

  20. 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.

  1. 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.

  2. 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.

  3. 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.

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

    KAUST Repository

    Wang, Jim Jing-Yan; Gao, Xin

    2014-01-01

    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

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

    DEFF Research Database (Denmark)

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

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

  6. Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

    Science.gov (United States)

    Gazestani, Vahid H; Salavati, Reza

    2015-01-01

    Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

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

    Directory of Open Access Journals (Sweden)

    James P J Hall

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

  8. 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.

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

    Science.gov (United States)

    Laperchia, Claudia; Palomba, Maria; Seke Etet, Paul F; Rodgers, Jean; Bradley, Barbara; Montague, Paul; Grassi-Zucconi, Gigliola; Kennedy, Peter G E; Bentivoglio, Marina

    2016-12-01

    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.

  10. Characterization of Trypanosoma brucei brucei S-adenosyl-L-methionine decarboxylase and its inhibition by Berenil, pentamidine and methylglyoxal bis(guanylhydrazone).

    Science.gov (United States)

    Bitonti, A J; Dumont, J A; McCann, P P

    1986-01-01

    Trypanosoma brucei brucei S-adenosyl-L-methionine (AdoMet) decarboxylase was found to be relatively insensitive to activation by putrescine as compared with the mammalian enzyme, being stimulated by only 50% over a 10,000-fold range of putrescine concentrations. The enzyme was not stimulated by up to 10 mM-Mg2+. The Km for AdoMet was 30 microM, similar to that of other eukaryotic AdoMet decarboxylases. T.b. brucei AdoMet decarboxylase activity was apparently irreversibly inhibited in vitro by Berenil and reversibly by pentamidine and methylglyoxal bis(guanylhydrazone). Berenil also inhibited trypanosomal AdoMet decarboxylase by 70% within 4 h after administration to infected rats and markedly increased the concentration of putrescine in trypanosomes that were exposed to the drug in vivo. Spermidine and spermine blocked the curative effect of Berenil on model mouse T.b. brucei infections. This effect of the polyamines was probably not due to reversal of Berenil's inhibitory effects on the AdoMet decarboxylase. PMID:3800910

  11. Mating compatibility in the parasitic protist Trypanosoma brucei.

    Science.gov (United States)

    Peacock, Lori; Ferris, Vanessa; Bailey, Mick; Gibson, Wendy

    2014-02-21

    Genetic exchange has been described in several kinetoplastid parasites, but the most well-studied mating system is that of Trypanosoma brucei, the causative organism of African sleeping sickness. Sexual reproduction takes place in the salivary glands (SG) of the tsetse vector and involves meiosis and production of haploid gametes. Few genetic crosses have been carried out to date and consequently there is little information about the mating compatibility of different trypanosomes. In other single-celled eukaryotes, mating compatibility is typically determined by a system of two or more mating types (MT). Here we investigated the MT system in T. brucei. We analysed a large series of F1, F2 and back crosses by pairwise co-transmission of red and green fluorescent cloned cell lines through experimental tsetse flies. To analyse each cross, trypanosomes were cloned from fly SG containing a mixture of both parents, and genotyped by microsatellites and molecular karyotype. To investigate mating compatibility at the level of individual cells, we directly observed the behaviour of SG-derived gametes in intra- or interclonal mixtures of red and green fluorescent trypanosomes ex vivo. Hybrid progeny were found in all F1 and F2 crosses and most of the back crosses. The success of individual crosses was highly variable as judged by the number of hybrid clones produced, suggesting a range of mating compatibilities among F1 progeny. As well as hybrids, large numbers of recombinant genotypes resulting from intraclonal mating (selfers) were found in some crosses. In ex vivo mixtures, red and green fluorescent trypanosome gametes were observed to pair up and interact via their flagella in both inter- and intraclonal combinations. While yellow hybrid trypanosomes were frequently observed in interclonal mixtures, such evidence of cytoplasmic exchange was rare in the intraclonal mixtures. The outcomes of individual crosses, particularly back crosses, were variable in numbers of both

  12. Exosome secretion affects social motility in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Dror Eliaz

    2017-03-01

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

  13. Meiosis and haploid gametes in the pathogen Trypanosoma brucei.

    Science.gov (United States)

    Peacock, Lori; Bailey, Mick; Carrington, Mark; Gibson, Wendy

    2014-01-20

    In eukaryote pathogens, sex is an important driving force in spreading genes for drug resistance, pathogenicity, and virulence. For the parasitic trypanosomes that cause African sleeping sickness, mating occurs during transmission by the tsetse vector and involves meiosis, but haploid gametes have not yet been identified. Here, we show that meiosis is a normal part of development in the insect salivary glands for all subspecies of Trypanosoma brucei, including the human pathogens. By observing insect-derived trypanosomes during the window of peak expression of meiosis-specific genes, we identified promastigote-like (PL) cells that interacted with each other via their flagella and underwent fusion, as visualized by the mixing of cytoplasmic red and green fluorescent proteins. PL cells had a short, wide body, a very long anterior flagellum, and either one or two kinetoplasts, but only the anterior kinetoplast was associated with the flagellum. Measurement of nuclear DNA contents showed that PL cells were haploid relative to diploid metacyclics. Trypanosomes are among the earliest diverging eukaryotes, and our results support the hypothesis that meiosis and sexual reproduction are ubiquitous in eukaryotes and likely to have been early innovations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii.

    Science.gov (United States)

    Lun, Zhao-Rong; Lai, De-Hua; Wen, Yan-Zi; Zheng, Ling-Ling; Shen, Ji-Long; Yang, Ting-Bo; Zhou, Wen-Liang; Qu, Liang-Hu; Hide, Geoff; Ayala, Francisco J

    2015-07-21

    Cancer is a general name for more than 100 malignant diseases. It is postulated that all cancers start from a single abnormal cell that grows out of control. Untreated cancers can cause serious consequences and deaths. Great progress has been made in cancer research that has significantly improved our knowledge and understanding of the nature and mechanisms of the disease, but the origins of cancer are far from being well understood due to the limitations of suitable model systems and to the complexities of the disease. In view of the fact that cancers are found in various species of vertebrates and other metazoa, here, we suggest that cancer also occurs in parasitic protozoans such as Trypanosoma brucei, a blood parasite, and Toxoplasma gondii, an obligate intracellular pathogen. Without treatment, these protozoan cancers may cause severe disease and death in mammals, including humans. The simpler genomes of these single-cell organisms, in combination with their complex life cycles and fascinating life cycle differentiation processes, may help us to better understand the origins of cancers and, in particular, leukemias.

  15. 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.

  16. Neural Damage in Experimental Trypanosoma brucei gambiense Infection: The Suprachiasmatic Nucleus

    Directory of Open Access Journals (Sweden)

    Chiara Tesoriero

    2018-02-01

    Full Text Available Trypanosoma brucei (T. b. gambiense is the parasite subspecies responsible for most reported cases of human African trypanosomiasis (HAT or sleeping sickness. This severe infection leads to characteristic disruption of the sleep-wake cycle, recalling attention on the circadian timing system. Most animal models of the disease have been hitherto based on infection of laboratory rodents with the T. b. brucei subspecies, which is not infectious to humans. In these animal models, functional, rather than structural, alterations of the master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN, have been reported. Information on the SCN after infection with the human pathogenic T. b. gambiense is instead lacking. The present study was aimed at the examination of the SCN after T. b. gambiense infection of a susceptible rodent, the multimammate mouse, Mastomys natalensis, compared with T. b. brucei infection of the same host species. The animals were examined at 4 and 8 weeks post-infection, when parasites (T. b. gambiense or T. b. brucei were detected in the brain parenchyma, indicating that the disease was in the encephalitic stage. Neuron and astrocyte changes were examined with Nissl staining, immunophenotyping and quantitative analyses. Interestingly, significant neuronal loss (about 30% reduction was documented in the SCN during the progression of T. b. gambiense infection. No significant neuronal density changes were found in the SCN of T. b. brucei-infected animals. Neuronal cell counts in the hippocampal dentate gyrus of T. b. gambiense-infected M. natalensis did not point out significant changes, indicating that no widespread neuron loss had occurred in the brain. Marked activation of astrocytes was detected in the SCN after both T. b. gambiense and T. b. brucei infections. Altogether the findings reveal that neurons of the biological clock are highly susceptible to the infection caused by human pathogenic African trypanosomes

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

    International Nuclear Information System (INIS)

    Alloatti, Andres; Gupta, Shreedhara; Gualdron-Lopez, Melisa; Nguewa, Paul A.; Altabe, Silvia G.; Deumer, Gladys; Wallemacq, Pierre; Michels, Paul A.M.; Uttaro, Antonio D.

    2011-01-01

    Highlights: → Inhibiting Δ9 desaturase drastically changes T. brucei's fatty-acid composition. → Isoxyl specifically inhibits the Δ9 desaturase causing a growth arrest. → RNA interference of desaturase expression causes a similar effect. → Feeding T. brucei-infected mice with Isoxyl decreases the parasitemia. → 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 50 ) of PCF was 1.0 ± 0.2 μM for Isoxyl and 5 ± 2 μM for 10-TS, whereas BSF appeared more susceptible with EC 50 values 0.10 ± 0.03 μM (Isoxyl) and 1.0 ± 0.6 μM (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.

  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. 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

  20. 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

  1. Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation

    Science.gov (United States)

    Dobson, Rachel; Stockdale, Christopher; Lapsley, Craig; Wilkes, Jonathan; McCulloch, Richard

    2011-01-01

    Homologous recombination in Trypanosoma brucei is used for moving variant surface glycoprotein (VSG) genes into expression sites during immune evasion by antigenic variation. A major route for such VSG switching is gene conversion reactions in which RAD51, a universally conserved recombinase, catalyses homology-directed strand exchange. In any eukaryote, RAD51-directed strand exchange in vivo is mediated by further factors, including RAD51-related proteins termed Rad51 paralogues. These appear to be ubiquitously conserved, although their detailed roles in recombination remain unclear. In T. brucei, four putative RAD51 paralogue genes have been identified by sequence homology. Here we show that all four RAD51 paralogues act in DNA repair, recombination and RAD51 subnuclear dynamics, though not equivalently, while mutation of only one RAD51 paralogue gene significantly impedes VSG switching. We also show that the T. brucei RAD51 paralogues interact, and that the complexes they form may explain the distinct phenotypes of the mutants as well as observed expression interdependency. Finally, we document the Rad51 paralogues that are encoded by a wide range of protists, demonstrating that the Rad51 paralogue repertoire in T. brucei is unusually large among microbial eukaryotes and that one member of the protein family corresponds with a key, conserved eukaryotic Rad51 paralogue. PMID:21615552

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

    Czech Academy of Sciences Publication Activity Database

    Alkhaldi, A.A.M.; Martínek, Jan; Panicucci, Brian; Dardonville, C.; Zíková, Alena; de Koning, H.P.

    2016-01-01

    Roč. 6, č. 1 (2016), s. 23-34 ISSN 2211-3207 R&D Projects: GA MŠk LL1205 Institutional support: RVO:60077344 Keywords : Trypanosoma brucei * mitochondrion * FoF1 ATPase * succinate dehydrogenase * phosphonium salt * SDH complex Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.809, year: 2016

  3. 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 . IMPORTANCE Trypanosoma 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

  4. Novel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei.

    Science.gov (United States)

    Pham, ThanhTruc; Walden, Madeline; Butler, Christopher; Diaz-Gonzalez, Rosario; Pérez-Moreno, Guiomar; Ceballos-Pérez, Gloria; Gomez-Pérez, Veronica; García-Hernández, Raquel; Zecca, Henry; Krakoff, Emma; Kopec, Brian; Ichire, Ogar; Mackenzie, Caden; Pitot, Marika; Ruiz, Luis Miguel; Gamarro, Francisco; González-Pacanowska, Dolores; Navarro, Miguel; Dounay, Amy B

    2017-08-15

    In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Mitochondrial tRNA import in Trypanosoma brucei is independent of thiolation and the Rieske protein

    Czech Academy of Sciences Publication Activity Database

    Paris, Zdeněk; RUBIO, M. A. T.; Lukeš, Julius; Alfonzo, J. D.

    2009-01-01

    Roč. 15, č. 7 (2009), s. 1398-1406 ISSN 1355-8382 R&D Projects: GA ČR GA204/06/1558; GA MŠk LC07032; GA MŠk 2B06129 Institutional research plan: CEZ:AV0Z60220518 Keywords : T. brucei * tRNA import * 2-thiolation * RIC * Rieske * Fe-S cluster Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.198, year: 2009

  6. A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity.

    Directory of Open Access Journals (Sweden)

    Géraldine De Muylder

    2013-10-01

    Full Text Available In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity.

  7. Neural Damage in Experimental Trypanosoma brucei gambiense Infection: Hypothalamic Peptidergic Sleep and Wake-Regulatory Neurons

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    2018-02-01

    Full Text Available Neuron populations of the lateral hypothalamus which synthesize the orexin (OX/hypocretin or melanin-concentrating hormone (MCH peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT, also called sleeping sickness, caused by extracellular Trypanosoma brucei (T. b. parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T. b. brucei subspecies. No information is available, however, on these peptidergic neurons after systemic infection with T. b. gambiense, the etiological agent of 97% of HAT cases. The present study was aimed at the investigation of immunohistochemically characterized OX and MCH neurons after T. b. gambiense or T. b. brucei infection of a susceptible rodent, the multimammate mouse, Mastomysnatalensis. Cell counts and evaluation of OX fiber density were performed at 4 and 8 weeks post-infection, when parasites had entered the brain parenchyma from the periphery. A significant decrease of OX neurons (about 44% reduction and MCH neurons (about 54% reduction was found in the lateral hypothalamus and perifornical area at 8 weeks in T. b. gambiense-infected M. natalensis. A moderate decrease (21% and 24% reduction, respectively, which did not reach statistical significance, was found after T. b. brucei infection. In two key targets of diencephalic orexinergic innervation, the peri-suprachiasmatic nucleus (SCN region and the thalamic paraventricular nucleus (PVT, densitometric analyses showed a significant progressive decrease in the density of orexinergic fibers in both infection paradigms, and especially during T. b. gambiense infection. Altogether the findings provide novel information showing that OX and MCH neurons are highly vulnerable to chronic

  8. 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

  9. Structure of a Trypanosoma brucei α/β-hydrolase fold protein with unknown function

    International Nuclear Information System (INIS)

    Merritt, Ethan A.; Holmes, Margaret; Buckner, Frederick S.; Van Voorhis, Wesley C.; Quartly, Erin; Phizicky, Eric M.; Lauricella, Angela; Luft, Joseph; DeTitta, George; Neely, Helen; Zucker, Frank; Hol, Wim G. J.

    2008-01-01

    T. brucei gene Tb10.6k15.0140 codes for an α/β-hydrolase fold protein of unknown function. The 2.2 Å crystal structure shows that members of this sequence family retain a conserved Ser residue at the expected site of a catalytic nucleophile, but that trypanosomatid sequences lack structural homologs for the other expected residues of the catalytic triad. The structure of a structural genomics target protein, Tbru020260AAA from Trypanosoma brucei, has been determined to a resolution of 2.2 Å using multiple-wavelength anomalous diffraction at the Se K edge. This protein belongs to Pfam sequence family PF08538 and is only distantly related to previously studied members of the α/β-hydrolase fold family. Structural superposition onto representative α/β-hydrolase fold proteins of known function indicates that a possible catalytic nucleophile, Ser116 in the T. brucei protein, lies at the expected location. However, the present structure and by extension the other trypanosomatid members of this sequence family have neither sequence nor structural similarity at the location of other active-site residues typical for proteins with this fold. Together with the presence of an additional domain between strands β6 and β7 that is conserved in trypanosomatid genomes, this suggests that the function of these homologs has diverged from other members of the fold family

  10. Exploring the Trypanosoma brucei Hsp83 potential as a target for structure guided drug design.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Pizarro

    Full Text Available Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp, while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF. Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite.

  11. Identification of TOEFAZ1-interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis.

    Science.gov (United States)

    Hilton, Nicholas A; Sladewski, Thomas E; Perry, Jenna A; Pataki, Zemplen; Sinclair-Davis, Amy N; Muniz, Richard S; Tran, Holly L; Wurster, Jenna I; Seo, Jiwon; de Graffenried, Christopher L

    2018-05-21

    The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly-polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. brucei cytokinetic machinery. We performed a proximity-dependent biotinylation (BioID) screen using TOEFAZ1 as a means to identify additional proteins that are involved in cytokinesis. Using quantitative proteomic methods, we identified nearly 500 TOEFAZ1-proximal proteins and characterized 59 in further detail. Among the candidates, we identified an essential putative phosphatase that regulates the expression level and localization of both TOEFAZ1 and TbPLK, a previously uncharacterized protein that is necessary for the assembly of a new cell posterior, and a microtubule plus-end directed orphan kinesin that is required for completing cleavage furrow ingression. The identification of these proteins provides new insight into T. brucei cytokinesis and establishes TOEFAZ1 as a key component of this essential and uniquely-configured process in kinetoplastids. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

  12. Novel sterol metabolic network of Trypanosoma brucei procyclic and bloodstream forms

    Science.gov (United States)

    Nes, Craigen R.; Singha, Ujjal K.; Liu, Jialin; Ganapathy, Kulothungan; Villalta, Fernando; Waterman, Michael R.; Lepesheva, Galina I.; Chaudhuri, Minu; Nes, W. David

    2012-01-01

    Trypanosoma brucei is the protozoan parasite that causes African trypanosomiasis, a neglected disease of people and animals. Co-metabolite analysis, labelling studies using [methyl-2H3]-methionine and substrate/product specificities of the cloned 24-SMT (sterol C24-methyltransferase) and 14-SDM (sterol C14-demethylase) from T. brucei afforded an uncommon sterol metabolic network that proceeds from lanosterol and 31-norlanosterol to ETO [ergosta-5,7,25(27)-trien-3β-ol], 24-DTO [dimethyl ergosta-5,7,25(27)-trienol] and ergosterol [ergosta-5,7,22(23)-trienol]. To assess the possible carbon sources of ergosterol biosynthesis, specifically 13C-labelled specimens of lanosterol, acetate, leucine and glucose were administered to T. brucei and the 13C distributions found were in accord with the operation of the acetate–mevalonate pathway, with leucine as an alternative precursor, to ergostenols in either the insect or bloodstream form. In searching for metabolic signatures of procyclic cells, we observed that the 13C-labelling treatments induce fluctuations between the acetyl-CoA (mitochondrial) and sterol (cytosolic) synthetic pathways detected by the progressive increase in 13C-ergosterol production (control sterol synthesis that is further fluctuated in the cytosol, yielding distinct sterol profiles in relation to cell demands on growth. PMID:22176028

  13. Adenylate Cyclases of Trypanosoma brucei, Environmental Sensors and Controllers of Host Innate Immune Response.

    Science.gov (United States)

    Salmon, Didier

    2018-04-25

    Trypanosoma brucei , etiological agent of Sleeping Sickness in Africa, is the prototype of African trypanosomes, protozoan extracellular flagellate parasites transmitted by saliva ( Salivaria ). In these parasites the molecular controls of the cell cycle and environmental sensing are elaborate and concentrated at the flagellum. Genomic analyses suggest that these parasites appear to differ considerably from the host in signaling mechanisms, with the exception of receptor-type adenylate cyclases (AC) that are topologically similar to receptor-type guanylate cyclase (GC) of higher eukaryotes but control a new class of cAMP targets of unknown function, the cAMP response proteins (CARPs), rather than the classical protein kinase A cAMP effector (PKA). T. brucei possesses a large polymorphic family of ACs, mainly associated with the flagellar membrane, and these are involved in inhibition of the innate immune response of the host prior to the massive release of immunomodulatory factors at the first peak of parasitemia. Recent evidence suggests that in T. brucei several insect-specific AC isoforms are involved in social motility, whereas only a few AC isoforms are involved in cytokinesis control of bloodstream forms, attesting that a complex signaling pathway is required for environmental sensing. In this review, after a general update on cAMP signaling pathway and the multiple roles of cAMP, I summarize the existing knowledge of the mechanisms by which pathogenic microorganisms modulate cAMP levels to escape immune defense.

  14. Adenylate Cyclases of Trypanosoma brucei, Environmental Sensors and Controllers of Host Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Didier Salmon

    2018-04-01

    Full Text Available Trypanosoma brucei, etiological agent of Sleeping Sickness in Africa, is the prototype of African trypanosomes, protozoan extracellular flagellate parasites transmitted by saliva (Salivaria. In these parasites the molecular controls of the cell cycle and environmental sensing are elaborate and concentrated at the flagellum. Genomic analyses suggest that these parasites appear to differ considerably from the host in signaling mechanisms, with the exception of receptor-type adenylate cyclases (AC that are topologically similar to receptor-type guanylate cyclase (GC of higher eukaryotes but control a new class of cAMP targets of unknown function, the cAMP response proteins (CARPs, rather than the classical protein kinase A cAMP effector (PKA. T. brucei possesses a large polymorphic family of ACs, mainly associated with the flagellar membrane, and these are involved in inhibition of the innate immune response of the host prior to the massive release of immunomodulatory factors at the first peak of parasitemia. Recent evidence suggests that in T. brucei several insect-specific AC isoforms are involved in social motility, whereas only a few AC isoforms are involved in cytokinesis control of bloodstream forms, attesting that a complex signaling pathway is required for environmental sensing. In this review, after a general update on cAMP signaling pathway and the multiple roles of cAMP, I summarize the existing knowledge of the mechanisms by which pathogenic microorganisms modulate cAMP levels to escape immune defense.

  15. Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness.

    Science.gov (United States)

    Abdeen, Sanofar; Salim, Nilshad; Mammadova, Najiba; Summers, Corey M; Goldsmith-Pestana, Karen; McMahon-Pratt, Diane; Schultz, Peter G; Horwich, Arthur L; Chapman, Eli; Johnson, Steven M

    2016-11-01

    Trypanosoma brucei are protozoan parasites that cause African sleeping sickness in humans (also known as Human African Trypanosomiasis-HAT). Without treatment, T. brucei infections are fatal. There is an urgent need for new therapeutic strategies as current drugs are toxic, have complex treatment regimens, and are becoming less effective owing to rising antibiotic resistance in parasites. We hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a viable anti-trypanosomal strategy as parasites rely on these stress response elements for their development and survival. We recently discovered several hundred inhibitors of the prototypical HSP60/10 chaperonin system from Escherichia coli, termed GroEL/ES. One of the most potent GroEL/ES inhibitors we discovered was compound 1. While examining the PubChem database, we found that a related analog, 2e-p, exhibited cytotoxicity to Leishmania major promastigotes, which are trypanosomatids highly related to Trypanosoma brucei. Through initial counter-screening, we found that compounds 1 and 2e-p were also cytotoxic to Trypanosoma brucei parasites (EC 50 =7.9 and 3.1μM, respectively). These encouraging initial results prompted us to develop a library of inhibitor analogs and examine their anti-parasitic potential in vitro. Of the 49 new chaperonin inhibitors developed, 39% exhibit greater cytotoxicity to T. brucei parasites than parent compound 1. While many analogs exhibit moderate cytotoxicity to human liver and kidney cells, we identified molecular substructures to pursue for further medicinal chemistry optimization to increase the therapeutic windows of this novel class of chaperonin-targeting anti-parasitic candidates. An intriguing finding from this study is that suramin, the first-line drug for treating early stage T. brucei infections, is also a potent inhibitor of GroEL/ES and HSP60/10 chaperonin systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Nwoha Rosemary Ijeoma Ogechi

    2016-01-01

    Full Text Available Objective: To determine the effect of Trypanosoma brucei (T. brucei on blood sugar level of infected rats. Methods: The experiment was done with 42 albino rats grouped into 3 groups of 14 members each. Group A was uninfected (control group, Group B was infected with T. brucei and treated with diminazene aceturate, and Group C was infected with T. brucei and treated with imidocarb dipropionate. Blood samples were collected from the media canthus of the experimental rats on Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 for the assessment of change in blood sugar levels. The blood sugar levels were determined with a glucometer (Accu-chek active serial No. GN: 10023338. Results: By 4 to 5 days post infection, there was a significant increase (P 0.05 was observed in the groups when compared with the control group till Day 12 of the experiment. Conclusions: T. brucei caused a significant increase in blood sugar of infected rats.

  17. Overview of the Diagnostic Methods Used in the Field for Human African Trypanosomiasis: What Could Change in the Next Years?

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    Julien Bonnet

    2015-01-01

    Full Text Available Sleeping sickness is a parasitic infection caused by two species of trypanosomes (Trypanosoma brucei gambiense and rhodesiense, transmitted by the tsetse fly. The disease eventually affects the central nervous system, resulting in severe neurological symptoms. Without treatment, death is inevitable. During the first stage of the disease, infected patients are mildly symptomatic and early detection of infection allows safer treatment (administered on an outpatient basis which can avoid death; routine screening of the exposed population is necessary, especially in areas of high endemicity. The current therapeutic treatment of this disease, especially in stage 2, can cause complications and requires a clinical surveillance for several days. A good stage diagnosis of the disease is the cornerstone for delivering the adequate treatment. The task faced by the medical personnel is further complicated by the lack of support from local health infrastructure, which is at best weak, but often nonexistent. Therefore it is crucial to look for new more efficient technics for the diagnosis of stage which are also best suited to use in the field, in areas not possessing high-level health facilities. This review, after an overview of the disease, summarizes the current diagnosis procedures and presents the advances in the field.

  18. The miRNA and mRNA Signatures of Peripheral Blood Cells in Humans Infected with Trypanosoma brucei gambiense.

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    Smiths Lueong

    Full Text Available Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II and without (stage I brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II, 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology.

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

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    Jean Rodgers

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

  20. Handling uncertainty in dynamic models: the pentose phosphate pathway in Trypanosoma brucei.

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    Eduard J Kerkhoven

    Full Text Available Dynamic models of metabolism can be useful in identifying potential drug targets, especially in unicellular organisms. A model of glycolysis in the causative agent of human African trypanosomiasis, Trypanosoma brucei, has already shown the utility of this approach. Here we add the pentose phosphate pathway (PPP of T. brucei to the glycolytic model. The PPP is localized to both the cytosol and the glycosome and adding it to the glycolytic model without further adjustments leads to a draining of the essential bound-phosphate moiety within the glycosome. This phosphate "leak" must be resolved for the model to be a reasonable representation of parasite physiology. Two main types of theoretical solution to the problem could be identified: (i including additional enzymatic reactions in the glycosome, or (ii adding a mechanism to transfer bound phosphates between cytosol and glycosome. One example of the first type of solution would be the presence of a glycosomal ribokinase to regenerate ATP from ribose 5-phosphate and ADP. Experimental characterization of ribokinase in T. brucei showed that very low enzyme levels are sufficient for parasite survival, indicating that other mechanisms are required in controlling the phosphate leak. Examples of the second type would involve the presence of an ATP:ADP exchanger or recently described permeability pores in the glycosomal membrane, although the current absence of identified genes encoding such molecules impedes experimental testing by genetic manipulation. Confronted with this uncertainty, we present a modeling strategy that identifies robust predictions in the context of incomplete system characterization. We illustrate this strategy by exploring the mechanism underlying the essential function of one of the PPP enzymes, and validate it by confirming the model predictions experimentally.

  1. Functional characterisation and drug target validation of a mitotic kinesin-13 in Trypanosoma brucei.

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    Kuan Yoow Chan

    2010-08-01

    Full Text Available Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation. Therefore, in humans, kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies. Phylogenetic analyses have assigned five of the approximately fifty kinesin motor proteins coded by Trypanosoma brucei genome to the Kinesin-13 family. Kinesins of this family have unusual biochemical properties because they do not transport cargo along microtubules but are able to depolymerise microtubules at their ends, therefore contributing to the regulation of microtubule length. In other eukaryotic genomes sequenced to date, only between one and three Kinesin-13s are present. We have used immunolocalisation, RNAi-mediated protein depletion, biochemical in vitro assays and a mouse model of infection to study the single mitotic Kinesin-13 in T. brucei. Subcellular localisation of all five T. brucei Kinesin-13s revealed distinct distributions, indicating that the expansion of this kinesin family in kinetoplastids is accompanied by functional diversification. Only a single kinesin (TbKif13-1 has a nuclear localisation. Using active, recombinant TbKif13-1 in in vitro assays we experimentally confirm the depolymerising properties of this kinesin. We analyse the biological function of TbKif13-1 by RNAi-mediated protein depletion and show its central role in regulating spindle assembly during mitosis. Absence of the protein leads to abnormally long and bent mitotic spindles, causing chromosome mis-segregation and cell death. RNAi-depletion in a mouse model of infection completely prevents infection with the parasite. Given its essential role in mitosis, proliferation and survival of the parasite and the availability of a simple in vitro activity assay, TbKif13-1 has been identified as an excellent potential drug target.

  2. 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.

  3. SHORT COMMUNICATION

    African Journals Online (AJOL)

    2007-05-02

    May 2, 2007 ... caused by morphologically indistinguishable subspecies of Trypanosoma brucei. The two forms are West African sleeping sickness, caused by. T. brucei gambiense and East African sleeping sickness, caused by T. brucei rhodesiense. In Tanzania HAT is one of the major public health problems and was ...

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

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    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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which...... binds the haptoglobin-hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome...... immunity against the parasite....

  6. Metabolic reprogramming during the Trypanosoma brucei life cycle [version 2; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Terry K. Smith

    2017-05-01

    Full Text Available Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites. This review highlights some of these metabolic changes in this early divergent eukaryotic model organism.

  7. Metabolic reprogramming during the Trypanosoma brucei life cycle [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Terry K. Smith

    2017-05-01

    Full Text Available Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites. This review highlights some of these metabolic changes in this early divergent eukaryotic model organism.

  8. 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.

  9. Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei.

    Science.gov (United States)

    Ooi, Cher-Pheng; Smith, Terry K; Gluenz, Eva; Wand, Nadina Vasileva; Vaughan, Sue; Rudenko, Gloria

    2018-06-01

    The predominant secretory cargo of bloodstream form Trypanosoma brucei is variant surface glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of endoplasmic reticulum exit sites (ERES) in post-mitotic cells dropped from 3.9 ± 0.6 to 2.7 ± 0.1 eight hours after blocking VSG synthesis. The secretory pathway was still functional in these stalled cells, as monitored using Cathepsin L. Rates of phospholipid and glycosylphosphatidylinositol-anchor biosynthesis remained relatively unaffected, except for the level of sphingomyelin which increased. However, both endoplasmic reticulum and Golgi morphology became distorted, with the Golgi cisternae becoming significantly dilated, particularly at the trans-face. Membrane accumulation in these structures is possibly caused by reduced budding of nascent vesicles due to the drastic reduction in the total amount of secretory cargo, that is, VSG. These data argue that the total flux of secretory cargo impacts upon the biogenesis and maintenance of secretory structures and organelles in T. brucei, including the ERES and Golgi. © 2018 The Authors. Traffic published by John Wiley & Sons Ltd.

  10. The Chemical Characterization of Nigerian Propolis samples and Their Activity Against Trypanosoma brucei.

    Science.gov (United States)

    Omar, Ruwida; Igoli, John O; Zhang, Tong; Gray, Alexander I; Ebiloma, Godwin U; Clements, Carol J; Fearnley, James; Edrada Ebel, RuAngeli; Paget, Tim; de Koning, Harry P; Watson, David G

    2017-04-19

    Profiling of extracts from twelve propolis samples collected from eight regions in Nigeria was carried out using high performance liquid chromatography (LC) coupled with evaporative light scattering (ELSD), ultraviolet detection (UV) and mass spectrometry (MS), gas chromatography mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). Principal component analysis (PCA) of the processed LC-MS data demonstrated the varying chemical composition of the samples. Most of the samples were active against Trypanosoma b. brucei with the highest activity being in the samples from Southern Nigeria. The more active samples were fractionated in order to isolate the component(s) responsible for their activity using medium pressure liquid chromatography (MPLC). Three xanthones, 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, 1,3,7-trihydroxy-4,8-di-(3-methylbut-2-enyl)xanthone a previously undescribed xanthone and three triterpenes: ambonic acid, mangiferonic acid and a mixture of α-amyrin with mangiferonic acid (1:3) were isolated and characterised by NMR and LC-MS. These compounds all displayed strong inhibitory activity against T.b. brucei but none of them had higher activity than the crude extracts. Partial least squares (PLS) modelling of the anti-trypanosomal activity of the sample extracts using the LC-MS data indicated that high activity in the extracts, as judged from LCMS 2 data, could be correlated to denticulatain isomers in the extracts.

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

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    Jason Carnes

    Full Text Available 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.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.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.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  13. Studies on the localization of Trypanosoma brucei in the female reproductive tract of bka mice and hooded lister rats

    International Nuclear Information System (INIS)

    Chipepa, J.A.S.; Brown, H.; Holmes, P.

    1991-01-01

    A study was conducted to establish whether Trypanosoma brucei migrated preferentially to the reproductive tracts of female BKA mice, or Hooded Lister rats and lodged there as the site of choice compared to other organs. Blood flow to the reproductive tracts, the liver and spleen was measured using red blood cells labelled with chromium- 51. The distribution of trypanosomes labelled with 75 Se-methionine. The average percentage of the blood flow to the reproductive tract was 0.21Plus or minus0.08 in mice, while the mean concentration of trypanosomes there was 0.30% in both mice and rats. Blood flow to the liver was lower than the percentage distribution of Se-labelled T.Brucei(5.17Plus or minus1.34 versus 8.1Plus or Minus1.2). There were, on the contrary, less labelled trypanosomes as compared to the mean blood flow to the spleen (0.54% plus or minus0.18 versus 2.10%pPlus or minus0.88). After 24 hours there were adequate numbers of T. brucei in the reproductive tract to cause parasitaemia in recipient mice. From these preliminary data it was concluded that T. brucei did not lodge in the reproductive organ system a site of choice. (author). 9 refs., 3 tabs

  14. 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

  15. Mitochondrial translation factors of Trypanosoma brucei: elongation factor-Tu has a unique subdomain that is essential for its function

    Czech Academy of Sciences Publication Activity Database

    Cristodero, M.; Mani, J.; Oeljeklaus, S.; Aeberhard, L.; Hashimi, Hassan; Ramrath, D.J.F.; Lukeš, Julius; Warscheid, B.; Schneider, A.

    2013-01-01

    Roč. 90, č. 4 (2013), s. 744-755 ISSN 0950-382X R&D Projects: GA ČR GAP305/12/2261 Institutional support: RVO:60077344 Keywords : mitochondrial translation * Trypanosoma brucei * EF-Tu Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.026, year: 2013

  16. Adaptations in the glucose metabolism of procyclic Trypanosoma brucei isolates from Tsetse flies and during differentiation of bloodstream forms.

    NARCIS (Netherlands)

    van Grinsven, K.W.A.; van den Abbeele, J.; van den Bossche, P.; van Hellemond, J.J.; Tielens, A.G.M.

    2009-01-01

    Procyclic forms of Trypanosoma brucei isolated from the midguts of infected tsetse flies, or freshly transformed from a strain that is close to field isolates, do not use a complete Krebs cycle. Furthermore, short stumpy bloodstream forms produce acetate and are apparently metabolically preadapted

  17. 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

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

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    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.

  19. Characterization of a Novel Class I Transcription Factor A (CITFA) Subunit That Is Indispensable for Transcription by the Multifunctional RNA Polymerase I of Trypanosoma brucei

    KAUST Repository

    Nguyen, T. N.; Nguyen, B. N.; Lee, J. H.; Panigrahi, A. K.; Gunzl, A.

    2012-01-01

    Trypanosoma brucei is the only organism known to have evolved a multifunctional RNA polymerase I (pol I) system that is used to express the parasite's ribosomal RNAs, as well as its major cell surface antigens, namely, the variant surface

  20. 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.

  1. 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...... of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact...

  2. Trypanosoma brucei gambiense trypanosomiasis in Terego county, northern Uganda, 1996: a lot quality assurance sampling survey.

    Science.gov (United States)

    Hutin, Yvan J F; Legros, Dominique; Owini, Vincent; Brown, Vincent; Lee, Evan; Mbulamberi, Dawson; Paquet, Christophe

    2004-04-01

    We estimated the pre-intervention prevalence of Trypanosoma brucei gambiense (Tbg) trypanosomiasis using the lot quality assurance sampling (LQAS) methods in 14 parishes of Terego County in northern Uganda. A total of 826 participants were included in the survey sample in 1996. The prevalence of laboratory confirmed Tbg trypanosomiasis adjusted for parish population sizes was 2.2% (95% confidence interval =1.1-3.2). This estimate was consistent with the 1.1% period prevalence calculated on the basis of cases identified through passive and active screening in 1996-1999. Ranking of parishes in four categories according to LQAS analysis of the 1996 survey predicted the prevalences observed during the first round of active screening in the population in 1997-1998 (P LQAS were validated by the results of the population screening, suggesting that these survey methods may be useful in the pre-intervention phase of sleeping sickness control programs.

  3. Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans.

    Directory of Open Access Journals (Sweden)

    Amy F Savage

    Full Text Available African trypanosomes, the causative agents of sleeping sickness in humans and nagana in animals, have a complex digenetic life cycle between a mammalian host and an insect vector, the blood-feeding tsetse fly. Although the importance of the insect vector to transmit the disease was first realized over a century ago, many aspects of trypanosome development in tsetse have not progressed beyond a morphological analysis, mainly due to considerable challenges to obtain sufficient material for molecular studies. Here, we used high-throughput RNA-Sequencing (RNA-Seq to profile Trypanosoma brucei transcript levels in three distinct tissues of the tsetse fly, namely the midgut, proventriculus and salivary glands. Consistent with current knowledge and providing a proof of principle, transcripts coding for procyclin isoforms and several components of the cytochrome oxidase complex were highly up-regulated in the midgut transcriptome, whereas transcripts encoding metacyclic VSGs (mVSGs and the surface coat protein brucei alanine rich protein or BARP were extremely up-regulated in the salivary gland transcriptome. Gene ontology analysis also supported the up-regulation of biological processes such as DNA metabolism and DNA replication in the proventriculus transcriptome and major changes in signal transduction and cyclic nucleotide metabolism in the salivary gland transcriptome. Our data highlight a small repertoire of expressed mVSGs and potential signaling pathways involving receptor-type adenylate cyclases and members of a surface carboxylate transporter family, called PADs (Proteins Associated with Differentiation, to cope with the changing environment, as well as RNA-binding proteins as a possible global regulators of gene expression.

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

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    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.

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

    International Nuclear Information System (INIS)

    Gualdrón-López, Melisa; Michels, Paul A.M.

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-01

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

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

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    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.

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

    Science.gov (United States)

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

    1986-06-01

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

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

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    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.

  10. Dynamics of Mitochondrial RNA-Binding Protein Complex in Trypanosoma brucei and Its Petite Mutant under Optimized Immobilization Conditions

    Czech Academy of Sciences Publication Activity Database

    Huang, Zhenqiu; Kaltenbrunner, S.; Šimková, Eva; Staněk, David; Lukeš, Julius; Hashimi, Hassan

    2014-01-01

    Roč. 13, č. 9 (2014), s. 1232-1240 ISSN 1535-9778 R&D Projects: GA ČR GAP305/12/2261; GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 ; RVO:68378050 Keywords : mitochondrion * Trypanosoma brucei * YFP Subject RIV: EB - Genetics ; Molecular Biology; EB - Genetics ; Molecular Biology (UMG-J) Impact factor: 2.820, year: 2014

  11. The F1 -ATPase from Trypanosoma brucei is elaborated by three copies of an additional p18-subunit.

    Science.gov (United States)

    Gahura, Ondřej; Šubrtová, Karolína; Váchová, Hana; Panicucci, Brian; Fearnley, Ian M; Harbour, Michael E; Walker, John E; Zíková, Alena

    2018-02-01

    The F-ATPases (also called the F 1 F o -ATPases or ATP synthases) are multi-subunit membrane-bound molecular machines that produce ATP in bacteria and in eukaryotic mitochondria and chloroplasts. The structures and enzymic mechanisms of their F 1 -catalytic domains are highly conserved in all species investigated hitherto. However, there is evidence that the F-ATPases from the group of protozoa known as Euglenozoa have novel features. Therefore, we have isolated pure and active F 1 -ATPase from the euglenozoan parasite, Trypanosoma brucei, and characterized it. All of the usual eukaryotic subunits (α, β, γ, δ, and ε) were present in the enzyme, and, in addition, two unique features were detected. First, each of the three α-subunits in the F 1 -domain has been cleaved by proteolysis in vivo at two sites eight residues apart, producing two assembled fragments. Second, the T. brucei F 1 -ATPase has an additional subunit, called p18, present in three copies per complex. Suppression of expression of p18 affected in vitro growth of both the insect and infectious mammalian forms of T. brucei. It also reduced the levels of monomeric and multimeric F-ATPase complexes and diminished the in vivo hydrolytic activity of the enzyme significantly. These observations imply that p18 plays a role in the assembly of the F 1 domain. These unique features of the F 1 -ATPase extend the list of special characteristics of the F-ATPase from T. brucei, and also, demonstrate that the architecture of the F 1 -ATPase complex is not strictly conserved in eukaryotes. © 2017 Federation of European Biochemical Societies.

  12. Proteome remodelling during development from blood to insect-form Trypanosoma brucei quantified by SILAC and mass spectrometry

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    Gunasekera Kapila

    2012-10-01

    Full Text Available Abstract Background Trypanosoma brucei is the causative agent of human African sleeping sickness and Nagana in cattle. In addition to being an important pathogen T. brucei has developed into a model system in cell biology. Results Using Stable Isotope Labelling of Amino acids in Cell culture (SILAC in combination with mass spectrometry we determined the abundance of >1600 proteins in the long slender (LS, short stumpy (SS mammalian bloodstream form stages relative to the procyclic (PC insect-form stage. In total we identified 2645 proteins, corresponding to ~30% of the total proteome and for the first time present a comprehensive overview of relative protein levels in three life stages of the parasite. Conclusions We can show the extent of pre-adaptation in the SS cells, especially at the level of the mitochondrial proteome. The comparison to a previously published report on monomorphic in vitro grown bloodstream and procyclic T. brucei indicates a loss of stringent regulation particularly of mitochondrial proteins in these cells when compared to the pleomorphic in vivo situation. In order to better understand the different levels of gene expression regulation in this organism we compared mRNA steady state abundance with the relative protein abundance-changes and detected moderate but significant correlation indicating that trypanosomes possess a significant repertoire of translational and posttranslational mechanisms to regulate protein abundance.

  13. Anti-Parasitic Activities of Allium sativum and Allium cepa against Trypanosoma b. brucei and Leishmania tarentolae.

    Science.gov (United States)

    Krstin, Sonja; Sobeh, Mansour; Braun, Markus Santhosh; Wink, Michael

    2018-04-21

    Background: Garlics and onions have been used for the treatment of diseases caused by parasites and microbes since ancient times. Trypanosomiasis and leishmaniasis are a concern in many areas of the world, especially in poor countries. Methods: Trypanosoma brucei brucei and Leishmania tarentolae were used to investigate the anti-parasitic effects of dichloromethane extracts of Allium sativum (garlic) and Allium cepa (onion) bulbs. As a confirmation of known antimicrobial activities, they were studied against a selection of G-negative, G-positive bacteria and two fungi. Chemical analyses were performed using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (LC-ESI-MS/MS). Results: Chemical analyses confirmed the abundance of several sulfur secondary metabolites in garlic and one (zwiebelane) in the onion extract. Both extracts killed both types of parasites efficiently and inhibited the Trypanosoma brucei trypanothione reductase irreversibly. In addition, garlic extract decreased the mitochondrial membrane potential in trypanosomes. Garlic killed the fungi C. albicans and C. parapsilosis more effectively than the positive control. The combinations of garlic and onion with common trypanocidal and leishmanicidal drugs resulted in a synergistic or additive effect in 50% of cases. Conclusion: The mechanism for biological activity of garlic and onion appears to be related to the amount and the profile of sulfur-containing compounds. It is most likely that vital substances inside the parasitic cell, like trypanothione reductase, are inhibited through disulfide bond formation between SH groups of vital redox compounds and sulfur-containing secondary metabolites.

  14. Trypanosoma brucei metabolite indolepyruvate decreases HIF-1α and glycolysis in macrophages as a mechanism of innate immune evasion.

    Science.gov (United States)

    McGettrick, Anne F; Corcoran, Sarah E; Barry, Paul J G; McFarland, Jennifer; Crès, Cécile; Curtis, Anne M; Franklin, Edward; Corr, Sinéad C; Mok, K Hun; Cummins, Eoin P; Taylor, Cormac T; O'Neill, Luke A J; Nolan, Derek P

    2016-11-29

    The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard. The bloodstream form of T. brucei excretes significant amounts of aromatic ketoacids, including indolepyruvate, a transamination product of tryptophan. This study demonstrates that this process is essential in bloodstream forms, is mediated by a specialized isoform of cytoplasmic aminotransferase and, importantly, reveals an immunomodulatory role for indolepyruvate. Indolepyruvate prevents the LPS-induced glycolytic shift in macrophages. This effect is the result of an increase in the hydroxylation and degradation of the transcription factor hypoxia-inducible factor-1α (HIF-1α). The reduction in HIF-1α levels by indolepyruvate, following LPS or trypanosome activation, results in a decrease in production of the proinflammatory cytokine IL-1β. These data demonstrate an important role for indolepyruvate in immune evasion by T. brucei.

  15. Major surface glycoproteins of insect forms of Trypanosoma brucei are not essential for cyclical transmission by tsetse.

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    Erik Vassella

    Full Text Available Procyclic forms of Trypanosoma brucei reside in the midgut of tsetse flies where they are covered by several million copies of glycosylphosphatidylinositol-anchored proteins known as procyclins. It has been proposed that procyclins protect parasites against proteases and/or participate in tropism, directing them from the midgut to the salivary glands. There are four different procyclin genes, each subject to elaborate levels of regulation. To determine if procyclins are essential for survival and transmission of T. brucei, all four genes were deleted and parasite fitness was compared in vitro and in vivo. When co-cultured in vitro, the null mutant and wild type trypanosomes (tagged with cyan fluorescent protein maintained a near-constant equilibrium. In contrast, when flies were infected with the same mixture, the null mutant was rapidly overgrown in the midgut, reflecting a reduction in fitness in vivo. Although the null mutant is patently defective in competition with procyclin-positive parasites, on its own it can complete the life cycle and generate infectious metacyclic forms. The procyclic form of T. brucei thus differs strikingly from the bloodstream form, which does not tolerate any perturbation of its variant surface glycoprotein coat, and from other parasites such as Plasmodium berghei, which requires the circumsporozoite protein for successful transmission to a new host.

  16. The γ-tubulin complex in Trypanosoma brucei: molecular composition, subunit interdependence and requirement for axonemal central pair protein assembly

    Science.gov (United States)

    Zhou, Qing; Li, Ziyin

    2015-01-01

    The γ-tubulin complex constitutes a key component of the microtubule-organizing center and nucleates microtubule assembly. This complex differs in complexity in different organisms: the budding yeast contains the γ-tubulin small complex (γTuSC) composed of γ-tubulin, GCP2 and GCP3, whereas animals contain the γ-tubulin ring complex (γTuRC) composed of γTuSC and three additional proteins, GCP4, GCP5 and GCP6. In Trypanosoma brucei, the composition of the γ-tubulin complex remains elusive, and it is not known whether it also regulates assembly of the subpellicular microtubules and the spindle microtubules. Here we report that the γ-tubulin complex in T. brucei is composed of γ-tubulin and three GCP proteins, GCP2-GCP4, and is primarily localized in the basal body throughout the cell cycle. Depletion of GCP2 and GCP3, but not GCP4, disrupted the axonemal central pair microtubules, but not the subpellicular microtubules and the spindle microtubules. Furthermore, we showed that the γTuSC is required for assembly of two central pair proteins and that γTuSC subunits are mutually required for stability. Together, these results identified an unusual γ-tubulin complex in T. brucei, uncovered an essential role of γTuSC in central pair protein assembly, and demonstrated the interdependence of individual γTuSC components for maintaining a stable complex. PMID:26224545

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

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    Ward Pauline N

    2005-09-01

    Full Text Available Abstract Background The trypanosomatids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, African sleeping sickness, and Chagas disease. These protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. However, the ways in which the parasites respond to their environment and coordinate intracellular processes are poorly understood. As a part of an effort to understand parasite signaling functions, we report the results of a genome-wide analysis of protein kinases (PKs of these three trypanosomatids. Results Bioinformatic searches of the trypanosomatid genomes for eukaryotic PKs (ePKs and atypical PKs (aPKs revealed a total of 176 PKs in T. brucei, 190 in T. cruzi and 199 in L. major, most of which are orthologous across the three species. This is approximately 30% of the number in the human host and double that of the malaria parasite, Plasmodium falciparum. The representation of various groups of ePKs differs significantly as compared to humans: trypanosomatids lack receptor-linked tyrosine and tyrosine kinase-like kinases, although they do possess dual-specificity kinases. A relative expansion of the CMGC, STE and NEK groups has occurred. A large number of unique ePKs show no strong affinity to any known group. The trypanosomatids possess few ePKs with predicted transmembrane domains, suggesting that receptor ePKs are rare. Accessory Pfam domains, which are frequently present in human ePKs, are uncommon in trypanosomatid ePKs. Conclusion Trypanosomatids possess a large set of PKs, comprising approximately 2% of each genome, suggesting a key role for phosphorylation in parasite biology. Whilst it was possible to place most of the trypanosomatid ePKs into the seven established groups using bioinformatic analyses, it has not been

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

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    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

  19. Glycolipid precursors for the membrane anchor of Trypanosoma brucei variant surface glycoproteins. II. Lipid structures of phosphatidylinositol-specific phospholipase C sensitive and resistant glycolipids

    International Nuclear Information System (INIS)

    Mayor, S.; Menon, A.K.; Cross, G.A.

    1990-01-01

    A common diagnostic feature of glycosylinositol phospholipid (GPI)-anchored proteins is their release from the membrane by a phosphatidylinositol-specific phospholipase C (PI-PLC). However, some GPI-anchored proteins are resistant to this enzyme. The best characterized example of this subclass is the human erythrocyte acetylcholinesterase, where the structural basis of PI-PLC resistance has been shown to be the acylation of an inositol hydroxyl group(s). Both PI-PLC-sensitive and resistant GPI-anchor precursors (P2 and P3, respectively) have been found in Trypanosoma brucei, where the major surface glycoprotein is anchored by a PI-PLC-sensitive glycolipid anchor. The accompanying paper shows that P2 and P3 have identical glycans, indistinguishable from the common core glycan found on all the characterized GPI protein anchors. This paper shows that the single difference between P2 and P3, and the basis for the PI-PLC insusceptibility of P3, is a fatty acid, ester-linked to the inositol residue in P3. The inositol-linked fatty acid can be removed by treatment with mild base to restore PI-PLC sensitivity. Biosynthetic labeling experiments with [3H]palmitic acid and [3H]myristic acid show that [3H]palmitic acid specifically labels the inositol residue in P3 while [3H]myristic acid labels the diacylglycerol portion. Possible models to account for the simultaneous presence of PI-PLC-resistant and sensitive glycolipids are discussed in the context of available information on the biosynthesis of GPI-anchors

  20. Differential Editosome Protein Function between Life Cycle Stages of Trypanosoma brucei.

    Science.gov (United States)

    McDermott, Suzanne M; Guo, Xuemin; Carnes, Jason; Stuart, Kenneth

    2015-10-09

    Uridine insertion and deletion RNA editing generates functional mitochondrial mRNAs in Trypanosoma brucei. The mRNAs are differentially edited in bloodstream form (BF) and procyclic form (PF) life cycle stages, and this correlates with the differential utilization of glycolysis and oxidative phosphorylation between the stages. The mechanism that controls this differential editing is unknown. Editing is catalyzed by multiprotein ∼20S editosomes that contain endonuclease, 3'-terminal uridylyltransferase, exonuclease, and ligase activities. These editosomes also contain KREPB5 and KREPA3 proteins, which have no functional catalytic motifs, but they are essential for parasite viability, editing, and editosome integrity in BF cells. We show here that repression of KREPB5 or KREPA3 is also lethal in PF, but the effects on editosome structure differ from those in BF. In addition, we found that point mutations in KREPB5 or KREPA3 differentially affect cell growth, editosome integrity, and RNA editing between BF and PF stages. These results indicate that the functions of KREPB5 and KREPA3 editosome proteins are adjusted between the life cycle stages. This implies that these proteins are involved in the processes that control differential editing and that the 20S editosomes differ between the life cycle stages. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

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    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.

  2. Identification and characterization of a stage specific membrane protein involved in flagellar attachment in Trypanosoma brucei.

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    Katherine Woods

    Full Text Available Flagellar attachment is a visibly striking morphological feature of African trypanosomes but little is known about the requirements for attachment at a molecular level. This study characterizes a previously undescribed membrane protein, FLA3, which plays an essential role in flagellar attachment in Trypanosoma brucei. FLA3 is heavily N-glycosylated, locates to the flagellar attachment zone and appears to be a bloodstream stage specific protein. Ablation of the FLA3 mRNA rapidly led to flagellar detachment and a concomitant failure of cytokinesis in the long slender bloodstream form but had no effect on the procyclic form. Flagellar detachment was obvious shortly after induction of the dsRNA and the newly synthesized flagellum was often completely detached after it emerged from the flagellar pocket. Within 12 h most cells possessed detached flagella alongside the existing attached flagellum. These results suggest that proteins involved in attachment are not shared between the new and old attachment zones. In other respects the detached flagella appear normal, they beat rapidly although directional motion was lost, and they possess an apparently normal axoneme and paraflagellar rod structure. The flagellar attachment zone appeared to be disrupted when FLA3 was depleted. Thus, while flagellar attachment is a constitutive feature of the life cycle of trypanosomes, attachment requires stage specific elements at the protein level.

  3. Three Redox States of Trypanosoma brucei Alternative Oxidase Identified by Infrared Spectroscopy and Electrochemistry

    Science.gov (United States)

    Maréchal, Amandine; Kido, Yasutoshi; Kita, Kiyoshi; Moore, Anthony L.; Rich, Peter R.

    2009-01-01

    Electrochemistry coupled with Fourier transform infrared (IR) spectroscopy was used to investigate the redox properties of recombinant alternative ubiquinol oxidase from Trypanosoma brucei, the organism responsible for African sleeping sickness. Stepwise reduction of the fully oxidized resting state of recombinant alternative ubiquinol oxidase revealed two distinct IR redox difference spectra. The first of these, signal 1, titrates in the reductive direction as an n = 2 Nernstian component with an apparent midpoint potential of 80 mV at pH 7.0. However, reoxidation of signal 1 in the same potential range under anaerobic conditions did not occur and only began with potentials in excess of 500 mV. Reoxidation by introduction of oxygen was also unsuccessful. Signal 1 contained clear features that can be assigned to protonation of at least one carboxylate group, further perturbations of carboxylic and histidine residues, bound ubiquinone, and a negative band at 1554 cm−1 that might arise from a radical in the fully oxidized protein. A second distinct IR redox difference spectrum, signal 2, appeared more slowly once signal 1 had been reduced. This component could be reoxidized with potentials above 100 mV. In addition, when both signals 1 and 2 were reduced, introduction of oxygen caused rapid oxidation of both components. These data are interpreted in terms of the possible active site structure and mechanism of oxygen reduction to water. PMID:19767647

  4. Overproduction, purification, crystallization and preliminary X-ray diffraction analysis of Trypanosoma brucei gambiense glycerol kinase

    International Nuclear Information System (INIS)

    Balogun, Emmanuel Oluwadare; Inaoka, Daniel Ken; Kido, Yasutoshi; Shiba, Tomoo; Nara, Takeshi; Aoki, Takashi; Honma, Teruki; Tanaka, Akiko; Inoue, Masayuki; Matsuoka, Shigeru; Michels, Paul A. M.; Harada, Shigeharu; Kita, Kiyoshi

    2010-01-01

    Glycerol kinase from human African trypanosomes has been purified and crystallized for X-ray structure analysis. In the bloodstream forms of human trypanosomes, glycerol kinase (GK; EC 2.7.1.30) is one of the nine glycosomally compartmentalized enzymes that are essential for energy metabolism. In this study, a recombinant Trypanosoma brucei gambiense GK (rTbgGK) with an N-terminal cleavable His 6 tag was overexpressed, purified to homogeneity and crystallized by the sitting-drop vapour-diffusion method using PEG 400 as a precipitant. A complete X-ray diffraction data set to 2.75 Å resolution indicated that the crystals belonged to the orthorhombic space group P2 1 2 1 2 1 , with unit-cell parameters a = 63.84, b = 121.50, c = 154.59 Å. The presence of two rTbgGK molecules in the asymmetric unit gives a Matthews coefficient (V M ) of 2.5 Å 3 Da −1 , corresponding to 50% solvent content

  5. γ-Tubulin complex in Trypanosoma brucei: molecular composition, subunit interdependence and requirement for axonemal central pair protein assembly.

    Science.gov (United States)

    Zhou, Qing; Li, Ziyin

    2015-11-01

    γ-Tubulin complex constitutes a key component of the microtubule-organizing center and nucleates microtubule assembly. This complex differs in complexity in different organisms: the budding yeast contains the γ-tubulin small complex (γTuSC) composed of γ-tubulin, gamma-tubulin complex protein (GCP)2 and GCP3, whereas animals contain the γ-tubulin ring complex (γTuRC) composed of γTuSC and three additional proteins, GCP4, GCP5 and GCP6. In Trypanosoma brucei, the composition of the γ-tubulin complex remains elusive, and it is not known whether it also regulates assembly of the subpellicular microtubules and the spindle microtubules. Here we report that the γ-tubulin complex in T. brucei is composed of γ-tubulin and three GCP proteins, GCP2-GCP4, and is primarily localized in the basal body throughout the cell cycle. Depletion of GCP2 and GCP3, but not GCP4, disrupted the axonemal central pair microtubules, but not the subpellicular microtubules and the spindle microtubules. Furthermore, we showed that the γTuSC is required for assembly of two central pair proteins and that γTuSC subunits are mutually required for stability. Together, these results identified an unusual γ-tubulin complex in T. brucei, uncovered an essential role of γTuSC in central pair protein assembly, and demonstrated the interdependence of individual γTuSC components for maintaining a stable complex. © 2015 John Wiley & Sons Ltd.

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

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    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.

  7. Processing of metacaspase 2 from Trypanosoma brucei (TbMCA2) broadens its substrate specificity.

    Science.gov (United States)

    Gilio, Joyce M; Marcondes, Marcelo F; Ferrari, Débora; Juliano, Maria A; Juliano, Luiz; Oliveira, Vitor; Machado, Maurício F M

    2017-04-01

    Metacaspases are members of the cysteine peptidase family and may be implicated in programmed cell death in plants and lower eukaryotes. These proteases exhibit calcium-dependent activity and specificity for arginine residues at P 1 . In contrast to caspases, they do not require processing or dimerization for activity. Indeed, unprocessed metacaspase-2 of Trypanosoma brucei (TbMCA2) is active; however, it has been shown that cleavages at Lys 55 and Lys 268 increase TbMCA2 hydrolytic activity on synthetic substrates. The processed TbMCA2 comprises 3 polypeptide chains that remain attached by non-covalent bonds. Replacement of Lys 55 and Lys 268 with Gly via site-directed mutagenesis results in non-processed but enzymatically active mutant, TbMCA2 K55/268G. To investigate the importance of this processing for the activity and specificity of TbMCA2, we performed activity assays comparing the non-processed mutant (TbMCA2 K55/268G) with the processed TbMCA2 form. Significant differences between TbMCA2 WT (processed form) and TbMCA2 K55/268G (non-processed form) were observed. Specifically, we verified that although non-processed TbMCA2 is active when assayed with small synthetic substrates, the TbMCA2 form does not exhibit hydrolytic activity on large substrates such as azocasein, while processed TbMCA2 is able to readily digest this protein. Such differences can be relevant for understanding the physiological regulation and function of TbMCA2. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. 3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction.

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    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.

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

    Science.gov (United States)

    Cordon-Obras, Carlos; Cano, Jorge; González-Pacanowska, Dolores; Benito, Agustin; Navarro, Miguel; Bart, Jean-Mathieu

    2013-01-01

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

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

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    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.

  11. Independent Analysis of the Flagellum Surface and Matrix Proteomes Provides Insight into Flagellum Signaling in Mammalian-infectious Trypanosoma brucei*

    Science.gov (United States)

    Oberholzer, Michael; Langousis, Gerasimos; Nguyen, HoangKim T.; Saada, Edwin A.; Shimogawa, Michelle M.; Jonsson, Zophonias O.; Nguyen, Steven M.; Wohlschlegel, James A.; Hill, Kent L.

    2011-01-01

    The flagellum of African trypanosomes is an essential and multifunctional organelle that functions in motility, cell morphogenesis, and host-parasite interaction. Previous studies of the trypanosome flagellum have been limited by the inability to purify flagella without first removing the flagellar membrane. This limitation is particularly relevant in the context of studying flagellum signaling, as signaling requires surface-exposed proteins in the flagellar membrane and soluble signaling proteins in the flagellar matrix. Here we employ a combination of genetic and mechanical approaches to purify intact flagella from the African trypanosome, Trypanosoma brucei, in its mammalian-infectious stage. We combined flagellum purification with affinity-purification of surface-exposed proteins to conduct independent proteomic analyses of the flagellum surface and matrix fractions. The proteins identified encompass a broad range of molecular functionalities, including many predicted to function in signaling. Immunofluorescence and RNA interference studies demonstrate flagellum localization and function for proteins identified and provide insight into mechanisms of flagellum attachment and motility. The flagellum surface proteome includes many T. brucei-specific proteins and is enriched for proteins up-regulated in the mammalian-infectious stage of the parasite life-cycle. The combined results indicate that the flagellum surface presents a diverse and dynamic host-parasite interface that is well-suited for host-parasite signaling. PMID:21685506

  12. Endogenous sterol biosynthesis is important for mitochondrial function and cell morphology in procyclic forms of Trypanosoma brucei.

    Science.gov (United States)

    Pérez-Moreno, Guiomar; Sealey-Cardona, Marco; Rodrigues-Poveda, Carlos; Gelb, Michael H; Ruiz-Pérez, Luis Miguel; Castillo-Acosta, Víctor; Urbina, Julio A; González-Pacanowska, Dolores

    2012-10-01

    Sterol biosynthesis inhibitors are promising entities for the treatment of trypanosomal diseases. Insect forms of Trypanosoma brucei, the causative agent of sleeping sickness, synthesize ergosterol and other 24-alkylated sterols, yet also incorporate cholesterol from the medium. While sterol function has been investigated by pharmacological manipulation of sterol biosynthesis, molecular mechanisms by which endogenous sterols influence cellular processes remain largely unknown in trypanosomes. Here we analyse by RNA interference, the effects of a perturbation of three specific steps of endogenous sterol biosynthesis in order to dissect the role of specific intermediates in proliferation, mitochondrial function and cellular morphology in procyclic cells. A decrease in the levels of squalene synthase and squalene epoxidase resulted in a depletion of cellular sterol intermediates and end products, impaired cell growth and led to aberrant morphologies, DNA fragmentation and a profound modification of mitochondrial structure and function. In contrast, cells deficient in sterol methyl transferase, the enzyme involved in 24-alkylation, exhibited a normal growth phenotype in spite of a complete abolition of the synthesis and content of 24-alkyl sterols. Thus, the data provided indicates that while the depletion of squalene and post-squalene endogenous sterol metabolites results in profound cellular defects, bulk 24-alkyl sterols are not strictly required to support growth in insect forms of T. brucei in vitro. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  13. TbPIF5 is a Trypanosoma brucei mitochondrial DNA helicase involved in processing of minicircle Okazaki fragments.

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    Beiyu Liu

    2009-09-01

    Full Text Available Trypanosoma brucei's mitochondrial genome, kinetoplast DNA (kDNA, is a giant network of catenated DNA rings. The network consists of a few thousand 1 kb minicircles and several dozen 23 kb maxicircles. Here we report that TbPIF5, one of T. brucei's six mitochondrial proteins related to Saccharomyces cerevisiae mitochondrial DNA helicase ScPIF1, is involved in minicircle lagging strand synthesis. Like its yeast homolog, TbPIF5 is a 5' to 3' DNA helicase. Together with other enzymes thought to be involved in Okazaki fragment processing, TbPIF5 localizes in vivo to the antipodal sites flanking the kDNA. Minicircles in wild type cells replicate unidirectionally as theta-structures and are unusual in that Okazaki fragments are not joined until after the progeny minicircles have segregated. We now report that overexpression of TbPIF5 causes premature removal of RNA primers and joining of Okazaki fragments on theta structures. Further elongation of the lagging strand is blocked, but the leading strand is completed and the minicircle progeny, one with a truncated H strand (ranging from 0.1 to 1 kb, are segregated. The minicircles with a truncated H strand electrophorese on an agarose gel as a smear. This replication defect is associated with kinetoplast shrinkage and eventual slowing of cell growth. We propose that TbPIF5 unwinds RNA primers after lagging strand synthesis, thus facilitating processing of Okazaki fragments.

  14. 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

  15. The 2’-O-ribose methyltransferase for cap 1 of spliced leader RNA and U1 small nuclear RNA in Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Zamudio, J. R.; Mittra, B.; Foldynová-Trantírková, Silvie; Zeiner, G. M.; Lukeš, Julius; Bujnicki, J. M.; Sturm, N. R.; Campbell, D. A.

    2007-01-01

    Roč. 27, č. 17 (2007), s. 6084-6092 ISSN 0270-7306 R&D Projects: GA MŠk 2B06129; GA MŠk LC07032 Institutional research plan: CEZ:AV0Z60220518 Keywords : methylation * Trypanosoma brucei * methyltransferase * RNA interference Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.420, year: 2007

  16. Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in Trypanosoma brucei

    Science.gov (United States)

    Smith, Joseph T.; Singha, Ujjal K.; Misra, Smita

    2018-01-01

    ABSTRACT The small Tim proteins belong to a group of mitochondrial intermembrane space chaperones that aid in the import of mitochondrial inner membrane proteins with internal targeting signals. Trypanosoma brucei, the protozoan parasite that causes African trypanosomiasis, possesses multiple small Tim proteins that include homologues of T. brucei Tim9 (TbTim9) and Tim10 (TbTim10) and a unique small Tim that shares homology with both Tim8 and Tim13 (TbTim8/13). Here, we found that these three small TbTims are expressed as soluble mitochondrial intermembrane space proteins. Coimmunoprecipitation and mass spectrometry analysis showed that the small TbTims stably associated with each other and with TbTim17, the major component of the mitochondrial inner membrane translocase in T. brucei. Yeast two-hybrid analysis indicated direct interactions among the small TbTims; however, their interaction patterns appeared to be different from those of their counterparts in yeast and humans. Knockdown of the small TbTims reduced cell growth and decreased the steady-state level of TbTim17 and T. brucei ADP/ATP carrier (TbAAC), two polytopic mitochondrial inner membrane proteins. Knockdown of small TbTims also reduced the matured complexes of TbTim17 in mitochondria. Depletion of any of the small TbTims reduced TbTim17 import moderately but greatly hampered the stability of the TbTim17 complexes in T. brucei. Altogether, our results revealed that TbTim9, TbTim10, and TbTim8/13 interact with each other, associate with TbTim17, and play a crucial role in the integrity and maintenance of the levels of TbTim17 complexes. IMPORTANCE Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite’s mitochondrion represents a useful source for potential chemotherapeutic targets. Similarly to yeast and humans, mitochondrial functions depend on the import of proteins that are encoded in the nucleus and made in the cytosol. Even though the machinery involved in this

  17. Dynamics of gamete production and mating in the parasitic protist Trypanosoma brucei.

    Science.gov (United States)

    Peacock, Lori; Bailey, Mick; Gibson, Wendy

    2016-07-20

    Sexual reproduction in Plasmodium falciparum and Trypanosoma brucei occurs in the insect vector and is important in generating hybrid strains with different combinations of parental characteristics. Production of hybrid parasite genotypes depends on the likelihood of co-infection of the vector with multiple strains. In mosquitoes, existing infection with Plasmodium facilitates the establishment of a second infection, although the asynchronicity of gamete production subsequently prevents mating. In the trypanosome/tsetse system, flies become increasingly refractory to infection as they age, so the likelihood of a fly acquiring a second infection also decreases. This effectively restricts opportunities for trypanosome mating to co-infections picked up by the fly on its first feed, unless an existing infection increases the chance of successful second infection as in the Plasmodium/mosquito system. Using green and red fluorescent trypanosomes, we compared the rates of trypanosome infection and hybrid production in flies co-infected on the first feed, co-infected on a subsequent feed 18 days after emergence, or fed sequentially with each trypanosome clone 18 days apart. Infection rates were highest in the midguts and salivary glands (SG) of flies that received both trypanosome clones in their first feed, and were halved when the infected feed was delayed to day 18. In flies fed the two trypanosome clones sequentially, the second clone often failed to establish a midgut infection and consequently was not present in the SG. Nevertheless, hybrids were recovered from all three groups of infected flies. Meiotic stages and gametes were produced continuously from day 11 to 42 after the infective feed, and in sequentially infected flies, the co-occurrence of gametes led to hybrid formation. We found that a second trypanosome strain can establish infection in the tsetse SG 18 days after the first infected feed, with co-mingling of gametes and production of trypanosome hybrids

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

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    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

  19. Single-subunit oligosaccharyltransferases of Trypanosoma brucei display different and predictable peptide acceptor specificities.

    Science.gov (United States)

    Jinnelov, Anders; Ali, Liaqat; Tinti, Michele; Güther, Maria Lucia S; Ferguson, Michael A J

    2017-12-08

    Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, Tb STT3A and Tb STT3B, are expressed in the bloodstream form of the parasite. These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities, and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N -glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. Here, we show by blue-native gel electrophoresis and stable isotope labeling in cell culture proteomics that the Tb STT3A and Tb STT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase H and peptide: N -glycosidase-F digestions. This allowed us to assess the relative occupancies of numerous N -glycosylation sites by endoglycosidase H-resistant N -glycans originating from Man 5 GlcNAc 2 -PP-dolichol transferred by Tb STT3A, and endoglycosidase H-sensitive N -glycans originating from Man 9 GlcNAc 2 -PP-dolichol transferred by Tb STT3B. Using machine learning, we assessed the features that best define Tb STT3A and Tb STT3B substrates in vivo and built an algorithm to predict the types of N -glycan most likely to predominate at all the putative N -glycosylation sites in the parasite proteome. Finally, molecular modeling was used to suggest why Tb STT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N -glycosylation to provide protein sequence-specific N -glycan modifications. Data are available via ProteomeXchange with identifiers PXD007236, PXD007267

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

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    Ziyin Li

    2009-09-01

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

  1. A role for Sar1 and ARF1 GTPases during Golgi biogenesis in the protozoan parasite Trypanosoma brucei

    Science.gov (United States)

    Yavuz, Sevil; Warren, Graham

    2017-01-01

    A single Golgi stack is duplicated and partitioned into two daughter cells during the cell cycle of the protozoan parasite Trypanosoma brucei. The source of components required to generate the new Golgi and the mechanism by which it forms are poorly understood. Using photoactivatable GFP, we show that the existing Golgi supplies components directly to the newly forming Golgi in both intact and semipermeabilized cells. The movement of a putative glycosyltransferase, GntB, requires the Sar1 and ARF1 GTPases in intact cells. In addition, we show that transfer of GntB from the existing Golgi to the new Golgi can be recapitulated in semipermeabilized cells and is sensitive to the GTP analogue GTPγS. We suggest that the existing Golgi is a key source of components required to form the new Golgi and that this process is regulated by small GTPases. PMID:28495798

  2. 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.

  3. Sleep and rhythm changes at the time of Trypanosoma brucei invasion of the brain parenchyma in the rat.

    Science.gov (United States)

    Seke Etet, Paul F; Palomba, Maria; Colavito, Valeria; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Bertini, Giuseppe

    2012-05-01

    Human African trypanosomiasis (HAT), or sleeping sickness, is a severe disease caused by Trypanosoma brucei (T.b.). The disease hallmark is sleep alterations. Brain involvement in HAT is a crucial pathogenetic step for disease diagnosis and therapy. In this study, a rat model of African trypanosomiasis was used to assess changes of sleep-wake, rest-activity, and body temperature rhythms in the time window previously shown as crucial for brain parenchyma invasion by T.b. to determine potential biomarkers of this event. Chronic radiotelemetric monitoring in Sprague-Dawley rats was used to continuously record electroencephalogram, electromyogram, rest-activity, and body temperature in the same animals before (baseline recording) and after infection. Rats were infected with T.b. brucei. Data were acquired from 1 to 20 d after infection (parasite neuroinvasion initiates at 11-13 d post-infection in this model), and were compared to baseline values. Sleep parameters were manually scored from electroencephalographic-electromyographic tracings. Circadian rhythms of sleep time, slow-wave activity, rest-activity, and body temperature were studied using cosinor rhythmometry. Results revealed alterations of most of the analyzed parameters. In particular, sleep pattern and sleep-wake organization plus rest-activity and body temperature rhythms exhibited early quantitative and qualitative alterations, which became marked around the time interval crucial for parasite neuroinvasion or shortly after. Data derived from actigrams showed close correspondence with those from hypnograms, suggesting that rest-activity could be useful to monitor sleep-wake alterations in African trypanosomiasis.

  4. 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; GA MŠk LL1205 Institutional support: RVO:60077344 Keywords : mt * TblF1 * Trypanosoma brucei Subject RIV: EE - Microbiology, Virology OBOR OECD: Infectious Diseases Impact factor: 3.834, year: 2016

  5. Molecular Diagnostics

    OpenAIRE

    Choe, Hyonmin; Deirmengian, Carl A.; Hickok, Noreen J.; Morrison, Tiffany N.; Tuan, Rocky S.

    2015-01-01

    Orthopaedic infections are complex conditions that require immediate diagnosis and accurate identification of the causative organisms to facilitate appropriate management. Conventional methodologies for diagnosis of these infections sometimes lack accuracy or sufficient rapidity. Current molecular diagnostics are an emerging area of bench-to-bedside research in orthopaedic infections. Examples of promising molecular diagnostics include measurement of a specific biomarker in the synovial fluid...

  6. 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

  7. Companion diagnostics

    DEFF Research Database (Denmark)

    Jørgensen, Jan Trøst; Hersom, Maria

    2016-01-01

    of disease mechanisms, things are slowly changing. Within the last few years, we have seen an increasing number of predictive biomarker assays being developed to guide the use of targeted cancer drugs. This type of assay is called companion diagnostics and is developed in parallel to the drug using the drug-diagnostic...... co-development model. The development of companion diagnostics is a relatively new discipline and in this review, different aspects will be discussed including clinical and regulatory issues. Furthermore, examples of drugs, such as the ALK and PD-1/PD-L1 inhibitors, that have been approved recently....... Despite having discussed personalized medicine for more than a decade, we still see that most drug prescriptions for severe chronic diseases are largely based on 'trial and error' and not on solid biomarker data. However, with the advance of molecular diagnostics and a subsequent increased understanding...

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

    Directory of Open Access Journals (Sweden)

    Jan Mani

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

  9. Plasma Diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Zaveryaev, V [Kurchatov Institute, Moscow (Russian Federation); others, and

    2012-09-15

    The success in achieving peaceful fusion power depends on the ability to control a high temperature plasma, which is an object with unique properties, possibly the most complicated object created by humans. Over years of fusion research a new branch of science has been created, namely plasma diagnostics, which involves knowledge of almost all fields of physics, from electromagnetism to nuclear physics, and up-to-date progress in engineering and technology (materials, electronics, mathematical methods of data treatment). Historically, work on controlled fusion started with pulsed systems and accordingly the methods of plasma parameter measurement were first developed for short lived and dense plasmas. Magnetically confined hot plasmas require the creation of special experimental techniques for diagnostics. The diagnostic set is the most scientifically intensive part of a plasma device. During many years of research operation some scientific tasks have been solved while new ones arose. New tasks often require significant changes in the diagnostic system, which is thus a very flexible part of plasma machines. Diagnostic systems are designed to solve several tasks. As an example here are the diagnostic tasks for the International Thermonuclear Experimental Reactor - ITER: (1) Measurements for machine protection and basic control; (2) Measurements for advanced control; (3) Additional measurements for performance evaluation and physics. Every new plasma machine is a further step along the path to the main goal - controlled fusion - and nobody knows in advance what new phenomena will be met on the way. So in the planning of diagnostic construction we should keep in mind further system upgrading to meet possible new scientific and technical challenges. (author)

  10. Cell-cycle synchronisation of bloodstream forms of Trypanosoma brucei using Vybrant DyeCycle Violet-based sorting.

    Science.gov (United States)

    Kabani, Sarah; Waterfall, Martin; Matthews, Keith R

    2010-01-01

    Studies on the cell-cycle of Trypanosoma brucei have revealed several unusual characteristics that differ from the model eukaryotic organisms. However, the inability to isolate homogenous populations of parasites in distinct cell-cycle stages has limited the analysis of trypanosome cell division and complicated the understanding of mutant phenotypes with possible impact on cell-cycle related events. Although hydroxyurea-induced cell-cycle arrest in procyclic and bloodstream forms has been applied recently with success, such block-release protocols can complicate the analysis of cell-cycle regulated events and have the potential to disrupt important cell-cycle checkpoints. An alternative approach based on flow cytometry of parasites stained with Vybrant DyeCycle Orange circumvents this problem, but is restricted to procyclic form parasites. Here, we apply Vybrant Dyecycle Violet staining coupled with flow cytometry to effectively select different cell-cycle stages of bloodstream form trypanosomes. Moreover, the sorted parasites remain viable, although synchrony is rapidly lost. This method enables cell-cycle enrichment of populations of trypanosomes in their mammal infective stage, particularly at the G1 phase.

  11. 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.

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

    Science.gov (United States)

    Mashiyama, Susan T; Koupparis, Kyriacos; Caffrey, Conor R; McKerrow, James H; Babbitt, Patricia C

    2012-01-01

    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.

  13. 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.

  14. 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.

  15. Diagnostic development

    International Nuclear Information System (INIS)

    Barnett, C.F.; Brisson, D.A.; Greco, S.E.

    1978-01-01

    During the past year the far-infrared or submillimeter diagnostic research program resulted in three major developments: (1) an optically pumped 0.385-μm D 2 O-laser oscillator-amplifier system was operated at a power level of 1 MW with a line width of less than 50 MHz; (2) a conical Pyrex submillimeter laser beam dump with a retention efficiency greater than 10 4 was developed for the ion temperature Thompson scattering experiment; and (3) a new diagnostic technique was developed that makes use of the Faraday rotation of a modulated submillimeter laser beam to determine plasma current profile. Measurements of the asymmetric distortion of the H/sub α/ (6563 A) spectral line profile show that the effective toroidal drift velocity, dv/sub two vertical bars i/dT/sub i/, may be used as an indicator of plasma quality and as a complement to other ion temperature diagnostics

  16. Diagnostic dilemma

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Dobrovolny, Robert; Nazarenko, Irina

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of a-galactosidase A (a-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased a-Gal A activity. However, in female heterozygotes, the a-Gal A activity can range from low t...... on enzyme replacement therapy. Thus, gene dosage analyses can detect large deletions (>50bp) in suspect heterozygotes for X-linked and autosomal dominant diseases that are "sequencing cryptic," resolving molecular diagnostic dilemmas....... to normal due to random X-chromosomal inactivation, and diagnostic confirmation requires identification of the family's a-Gal A gene mutation. In a young female who had occasional acroparesthesias, corneal opacities, and 15 to 50% of the lower limit of normal leukocyte a-Gal A activity, a-Gal A sequencing...... in two expert laboratories did not identify a confirmatory mutation, presenting a diagnostic dilemma. A renal biopsy proved diagnostic and renewed efforts to detect an a-Gal A mutation. Subsequent gene dosage analyses identified a large a-Gal A deletion confirming her heterozygosity, and she was started...

  17. RNA-Seq analysis validates the use of culture-derived Trypanosoma brucei and provides new markers for mammalian and insect life-cycle stages.

    Science.gov (United States)

    Naguleswaran, Arunasalam; Doiron, Nicholas; Roditi, Isabel

    2018-04-02

    Trypanosoma brucei brucei, the parasite causing Nagana in domestic animals, is closely related to the parasites causing sleeping sickness, but does not infect humans. In addition to its importance as a pathogen, the relative ease of genetic manipulation and an innate capacity for RNAi extend its use as a model organism in cell and infection biology. During its development in its mammalian and insect (tsetse fly) hosts, T. b. brucei passes through several different life-cycle stages. There are currently four life-cycle stages that can be cultured: slender forms and stumpy forms, which are equivalent to forms found in the mammal, and early and late procyclic forms, which are equivalent to forms in the tsetse midgut. Early procyclic forms show coordinated group movement (social motility) on semi-solid surfaces, whereas late procyclic forms do not. RNA-Seq was performed on biological replicates of each life-cycle stage. These constitute the first datasets for culture-derived slender and stumpy bloodstream forms and early and late procyclic forms. Expression profiles confirmed that genes known to be stage-regulated in the animal and insect hosts were also regulated in culture. Sequence reads of 100-125 bases provided sufficient precision to uncover differential expression of closely related genes. More than 100 transcripts showed peak expression in stumpy forms, including adenylate cyclases and several components of inositol metabolism. Early and late procyclic forms showed differential expression of 73 transcripts, a number of which encoded proteins that were previously shown to be stage-regulated. Moreover, two adenylate cyclases previously shown to reduce social motility are up-regulated in late procyclic forms. This study validates the use of cultured bloodstream forms as alternatives to animal-derived parasites and yields new markers for all four stages. In addition to underpinning recent findings that early and late procyclic forms are distinct life-cycle stages

  18. Peptide-targeted delivery of a pH sensor for quantitative measurements of intraglycosomal pH in live Trypanosoma brucei.

    Science.gov (United States)

    Lin, Sheng; Morris, Meredith T; Ackroyd, P Christine; Morris, James C; Christensen, Kenneth A

    2013-05-28

    Studies of dynamic changes in organelles of protozoan parasite Trypanosoma brucei have been limited, in part because of the difficulty of targeting analytical probes to specific subcellular compartments. Here we demonstrate application of a ratiometric probe for pH quantification in T. brucei glycosomes. The probe consists of a peptide encoding the peroxisomal targeting sequence (F-PTS1, acetyl-CKGGAKL) coupled to fluorescein, which responds to pH. When incubated with living parasites, the probe is internalized within vesicular structures that colocalize with a glycosomal marker. Inhibition of uptake of F-PTS1 at 4 °C and pulse-chase colocalization with fluorescent dextran suggested that the probe is initially taken up by non-receptor-mediated endocytosis but is subsequently transported separately from dextran and localized within glycosomes, prior to the final fusion of labeled glycosomes and lysosomes as part of glycosomal turnover. Intraorganellar measurements and pH calibration with F-PTS1 in T. brucei glycosomes indicate that the resting glycosomal pH under physiological conditions is 7.4 ± 0.2. However, incubation in glucose-depleted buffer triggered mild acidification of the glycosome over a period of 20 min, with a final observed pH of 6.8 ± 0.3. This glycosomal acidification was reversed by reintroduction of glucose. Coupling of ratiometric fluorescent sensors and reporters to PTS peptides offers an invaluable tool for monitoring in situ glycosomal response(s) to changing environmental conditions and could be applied to additional kinetoplastid parasites.

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

    Directory of Open Access Journals (Sweden)

    Nwoha Rosemary Ijeoma Ogechi

    2015-06-01

    Full Text Available Objective: To determine the effect of Ancylostoma caninum (A. caninum and trypanosome parasites on the immune response to vaccination in dogs in endemic environments. Methods: Sixteen dogs for the experiment were grouped into 4 of 4 members each. Group I was the uninfected control one, and GPII was infected with A. caninum; GPIII was infected with A. caninum/Trypanosoma congolense (T. congolense, and GPIV was infected with Trypanosoma brucei (T. brucei/A. caninum. The dogs were first vaccinated with antirabies vaccine before infecting GPII, GPIII and GPIV with A. caninum which were done 4 weeks after vaccination. By 2-week post-vaccination, trypanosome parasites were superimposed on both GPIII and GPIV. A secondary vaccination was given to GPI, GPII, GPIII, and GPIV by Week 12 of the experiment (4 weeks post treatment. Results: The prepatent period was (3.00 ± 1.40 days, in the conjunct infection of T. brucei/ A. caninum. It was (9.00 ± 1.10 days, in conjunct T. congolense/A. caninum. The prepatent period of A. caninum was (14.0 ± 2.0 days in the single A. caninum group and (13.0 ± 1.0 days in the conjunct trypanosome/A. caninum. At the 1st week after vaccination, the antibody titer in all the vaccinated groups (GPI, GPII, GPIII, and GPIV significantly increased (P < 0.05 and peaked at the 3rd week after vaccination. Following infections, there were marked significant decreases (P < 0.05 in the antibody production against rabies in GPII, GPIII and GPIV. The significant decrease (P < 0.05 in antibody titer was highest in the conjunct groups (GPIII and GPIV compared to the single infection (GPII. Treatment with diminazene aceturate and mebendazole did not significantly improve antibody response in the dogs. A secondary vaccination administered at the 12th week after the primary vaccination significantly increased (P < 0.05 the antibody titer with a peak at the 3rd week after the secondary vaccination. Conclusions: It was therefore concluded

  20. 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.

  1. 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.

  2. Isolation of Trypanosoma brucei gambiense from cured and relapsed sleeping sickness patients and adaptation to laboratory mice.

    Directory of Open Access Journals (Sweden)

    Patient Pati Pyana

    Full Text Available BACKGROUND: Sleeping sickness due to Trypanosoma brucei (T.b. gambiense is still a major public health problem in some central African countries. Historically, relapse rates around 5% have been observed for treatment with melarsoprol, widely used to treat second stage patients. Later, relapse rates of up to 50% have been recorded in some isolated foci in Angola, Sudan, Uganda and Democratic Republic of the Congo (DRC. Previous investigations are not conclusive on whether decreased sensitivity to melarsoprol is responsible for these high relapse rates. Therefore we aimed to establish a parasite collection isolated from cured as well as from relapsed patients for downstream comparative drug sensitivity profiling. A major constraint for this type of investigation is that T.b. gambiense is particularly difficult to isolate and adapt to classical laboratory rodents. METHODOLOGY/PRINCIPAL FINDINGS: From 360 patients treated in Dipumba hospital, Mbuji-Mayi, D.R. Congo, blood and cerebrospinal fluid (CSF was collected before treatment. From patients relapsing during the 24 months follow-up, the same specimens were collected. Specimens with confirmed parasite presence were frozen in liquid nitrogen in a mixture of Triladyl, egg yolk and phosphate buffered glucose solution. Isolation was achieved by inoculation of the cryopreserved specimens in Grammomys surdaster, Mastomys natalensis and SCID mice. Thus, 85 strains were isolated from blood and CSF of 55 patients. Isolation success was highest in Grammomys surdaster. Forty strains were adapted to mice. From 12 patients, matched strains were isolated before treatment and after relapse. All strains belong to T.b. gambiense type I. CONCLUSIONS AND SIGNIFICANCE: We established a unique collection of T.b. gambiense from cured and relapsed patients, isolated in the same disease focus and within a limited period. This collection is available for genotypic and phenotypic characterisation to investigate the

  3. Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography.

    Science.gov (United States)

    Patterson, Stephen; Alphey, Magnus S; Jones, Deuan C; Shanks, Emma J; Street, Ian P; Frearson, Julie A; Wyatt, Paul G; Gilbert, Ian H; Fairlamb, Alan H

    2011-10-13

    Trypanothione reductase (TryR) is a genetically validated drug target in the parasite Trypanosoma brucei , the causative agent of human African trypanosomiasis. Here we report the discovery, synthesis, and development of a novel series of TryR inhibitors based on a 3,4-dihydroquinazoline scaffold. In addition, a high resolution crystal structure of TryR, alone and in complex with substrates and inhibitors from this series, is presented. This represents the first report of a high resolution complex between a noncovalent ligand and this enzyme. Structural studies revealed that upon ligand binding the enzyme undergoes a conformational change to create a new subpocket which is occupied by an aryl group on the ligand. Therefore, the inhibitor, in effect, creates its own small binding pocket within the otherwise large, solvent exposed active site. The TryR-ligand structure was subsequently used to guide the synthesis of inhibitors, including analogues that challenged the induced subpocket. This resulted in the development of inhibitors with improved potency against both TryR and T. brucei parasites in a whole cell assay.

  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. 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

  6. Thyroid diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Scriba, P C; Boerner, W; Emrich, S; Gutekunst, R; Herrmann, J; Horn, K; Klett, M; Krueskemper, H L; Pfannenstiel, P; Pickardt, C R

    1985-03-01

    None of the in-vitro and in-vivo methods listed permits on unambiguous diagnosis when applied alone, owing to the fact that similar or even identical findings are obtained for various individual parameters in different thyroid diseases. Further, especially the in-vitro tests are also subject to extrathyroidal effects which may mask the typical findings. The limited and varying specificity and sensitivity of the tests applied, as well as the falsification of results caused by the patients' idiosyncracies and the methodology, make it necessary to interpret and evaluate the in-vivo and in-vitro findings only if the clinical situation (anamnesis and physical examination) is known. For maximum diagnostic quality of the tests, the initial probability of the assumed type of thyroid disease must be increased (formulation of the clinical problem). The concepts of exclusion diagnosis and identification must be distinguished as well as the diagnosis of functional disturbances on the one hand and of thyroid diseases on the other. Both of this requires a qualified, specific and detailed anamnesis and examination procedure, and the clinical examination remains the obligatory basis of clinical diagnostics. In case of inexplicable discrepancies between the clinical manifestations and the findings obtained with specific methods, or between the findings obtained with a specific method, the patient should be referred to an expert institution, or the expert institution should be consulted.

  7. Thyroid diagnostics

    International Nuclear Information System (INIS)

    Scriba, P.C.; Boerner, W.; Emrich, S.; Gutekunst, R.; Herrmann, J.; Horn, K.; Klett, M.; Krueskemper, H.L.; Pfannenstiel, P.; Pickardt, C.R.; Reiners, C.; Reinwein, D.; Schleusener, H.

    1985-01-01

    None of the in-vitro and in-vivo methods listed permits on unambiguous diagnosis when applied alone, owing to the fact that similar or even identical findings are obtained for various individual parameters in different thyroid diseases. Further, especially the in-vitro tests are also subject to extrathyroidal effects which may mask the typical findings. The limited and varying specificity and sensitivity of the tests applied, as well as the falsification of results caused by the patients' idiosyncracies and the methodology, make it necessary to interpret and evaluate the in-vivo and in-vitro findings only if the clinical situation (anamnesis and physical examination) is known. For maximum diagnostic quality of the tests, the initial probability of the assumed type of thyroid disease must be increased (formulation of the clinical problem). The concepts of exclusion diagnosis and identification must be distinguished as well as the diagnosis of functional disturbances on the one hand and of thyroid diseases on the other. Both of this requires a qualified, specific and detailed anamnesis and examination procedure, and the clinical examination remains the obligatory basis of clinical diagnostics. In case of inexplicable discrepancies between the clinical manifestations and the findings obtained with specific methods, or between the findings obtained with a specific method, the patient should be referred to an expert institution, or the expert institution should be consulted. (orig./MG) [de

  8. Ambient diagnostics

    CERN Document Server

    Cai, Yang

    2014-01-01

    Part I. FundamentalsIntroductionWhat is Ambient Diagnostics?Diagnostic ModelsMultimedia IntelligenceCrowd SourcingSoft SensorsScience of SimplicityPersonal DiagnosesBasic AlgorithmsBasic ToolsSummaryProblemsTransformationEarly Discoveries of Heartbeat PatternsTransforms, Features, and AttributesSequential FeaturesSpatiotemporal FeaturesShape FeaturesImagery FeaturesFrequency Domain FeaturesMulti-Resolution FeaturesSummaryProblemsPattern RecognitionSimilarities and DistancesClustering MethodsClassification MethodsClassifier Accuracy MeasuresSummaryProblemsPart II. Multimedia IntelligenceSound RecognitionMicrophone AppsModern Acoustic Transducers (Microphones)Frequency Response CharacteristicsDigital Audio File FormatsHeart Sound SensingLung Sound SensingSnore MeterSpectrogram (STFT)Ambient Sound AnalysisSound RecognitionRecognizing Asthma SoundPeak ShiftFeature CompressionRegroupingNoise IssuesFuture ApplicationsSummaryProblemsColor SensorsColor SensingHuman Color VisionColor SensorsColor Matching ExperimentsC...

  9. Diagnostic accuracy of organ electrodermal diagnostics | Szopinski ...

    African Journals Online (AJOL)

    Objective. To estimate the diagnostic accuracy as well as the scope of utilisation of a new bio-electronic method of organ diagnostics. Design. Double-blind comparative study of the diagnostic results obtained by means of organ electrodermal diagnostics (OED) and clinical diagnoses, as a criterion standard. Setting.

  10. A core MRB1 complex component is indispensable for RNA editing in insect and human infective stages of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Michelle L Ammerman

    Full Text Available Uridine insertion/deletion RNA editing is a unique and vital process in kinetoplastids, required for creation of translatable open reading frames in most mitochondrially-encoded RNAs. Emerging as a key player in this process is the mitochondrial RNA binding 1 (MRB1 complex. MRB1 comprises an RNA-independent core complex of at least six proteins, including the GAP1/2 guide RNA (gRNA binding proteins. The core interacts in an RNA-enhanced or -dependent manner with imprecisely defined TbRGG2 subcomplexes, Armadillo protein MRB10130, and additional factors that comprise the dynamic MRB1 complex. Towards understanding MRB1 complex function in RNA editing, we present here functional characterization of the pentein domain-containing MRB1 core protein, MRB11870. Inducible RNAi studies demonstrate that MRB11870 is essential for proliferation of both insect vector and human infective stage T. brucei. MRB11870 ablation causes a massive defect in RNA editing, affecting both pan-edited and minimally edited mRNAs, but does not substantially affect mitochondrial RNA stability or processing of precursor transcripts. The editing defect in MRB1-depleted cells occurs at the initiation stage of editing, as pre-edited mRNAs accumulate. However, the gRNAs that direct editing remain abundant in the knockdown cells. To examine the contribution of MRB11870 to MRB1 macromolecular interactions, we tagged core complexes and analyzed their composition and associated proteins in the presence and absence of MRB11870. These studies demonstrated that MRB11870 is essential for association of GAP1/2 with the core, as well as for interaction of the core with other proteins and subcomplexes. Together, these data support a model in which the MRB1 core mediates functional interaction of gRNAs with the editing machinery, having GAP1/2 as its gRNA binding constituents. MRB11870 is a critical component of the core, essential for its structure and function.

  11. Ethyl Pyruvate Emerges as a Safe and Fast Acting Agent against Trypanosoma brucei by Targeting Pyruvate Kinase Activity.

    Directory of Open Access Journals (Sweden)

    Netsanet Worku

    Full Text Available Human African Trypanosomiasis (HAT also called sleeping sickness is an infectious disease in humans caused by an extracellular protozoan parasite. The disease, if left untreated, results in 100% mortality. Currently available drugs are full of severe drawbacks and fail to escape the fast development of trypanosoma resistance. Due to similarities in cell metabolism between cancerous tumors and trypanosoma cells, some of the current registered drugs against HAT have also been tested in cancer chemotherapy. Here we demonstrate for the first time that the simple ester, ethyl pyruvate, comprises such properties.The current study covers the efficacy and corresponding target evaluation of ethyl pyruvate on T. brucei cell lines using a combination of biochemical techniques including cell proliferation assays, enzyme kinetics, phasecontrast microscopic video imaging and ex vivo toxicity tests. We have shown that ethyl pyruvate effectively kills trypanosomes most probably by net ATP depletion through inhibition of pyruvate kinase (Ki = 3.0±0.29 mM. The potential of ethyl pyruvate as a trypanocidal compound is also strengthened by its fast acting property, killing cells within three hours post exposure. This has been demonstrated using video imaging of live cells as well as concentration and time dependency experiments. Most importantly, ethyl pyruvate produces minimal side effects in human red cells and is known to easily cross the blood-brain-barrier. This makes it a promising candidate for effective treatment of the two clinical stages of sleeping sickness. Trypanosome drug-resistance tests indicate irreversible cell death and a low incidence of resistance development under experimental conditions.Our results present ethyl pyruvate as a safe and fast acting trypanocidal compound and show that it inhibits the enzyme pyruvate kinase. Competitive inhibition of this enzyme was found to cause ATP depletion and cell death. Due to its ability to easily cross

  12. SNS Diagnostics

    International Nuclear Information System (INIS)

    Shea, T.J.; Cameron, P.; Doolittle, L.; Power, J.

    2000-01-01

    The Spallation Neutron Source (SNS) Project is a collaborative effort to build the next generation neutron science facility at Oak Ridge, TN. The facility will deliver a 2 MW proton beam to a liquid mercury target. Neutrons from this target will be moderated and sent to several state-of-the-art instruments. Six national laboratories are involved in SNS construction. Berkeley (LBNL) will build the front end that produces a 2.5 MeV, 52 mA H-beam. Los Alamos (LANL) is responsible for the 1 GeV linac with a superconducting section provided by Thomas Jefferson (JLab). Brookhaven (BNL) is building the transfer lines and accumulator ring. Oak Ridge (ORNL) and Argonne (ANL) have responsibility for the target and instruments. All activities are coordinated by the SNS project office at Oak Ridge. The high beam power, a desired availability of 95%, and an aggressive commissioning schedule lead to some interesting challenges in beam diagnostics

  13. Diagnostic thoracoscopy

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2002-01-01

    Full Text Available Diagnostic thoracoscopy in patients with pleural effusion of unclear origin mostly provides the correct diagnosis. Results from published reports of previous researches are not uniform. In 47 male and 20 female patients with pleural effusion of unknown etiology, after receiving negative results obtained from cytological finding of pleural effusion and percutaneous needle biopsy, thoracoscopy with biopsy of one or both pleurae was performed. Procedure was done in local anesthesia using Stortz rigid thoracoscope. In 37 patients with malignant disease (primary or metastatic diagnosis was confirmed histopathologically in 31 patient (81.12%. In 27 patients with inflammatory pleural disease diagnosis was confirmed histopathologically in 22 patients (81.4%. Among 11 patients with specific pleural effusions, tuberculosis was confirmed in 10 (90.91%. Normal finding in cases of spontaneous pneumothorax and pulmonary embolism was taken as a positive result. Total number of positive findings was 55 (82.10%. In one patient, the third spontaneous pneumothorax was the indication for thoracoscopy, and after numerous bullae were seen during the procedure, talcum powder pleurodesis was done. In four patients low intensity subcutaneous emphysema occurred one day after thoracoscopy. It can be concluded that thoracoscopy in local anesthesia out of the operating room is good and practical method for solving the unclear pleural effusions, with neglectable rate of complications.

  14. Mitigation diagnostics

    International Nuclear Information System (INIS)

    Hall, S.T.

    1990-01-01

    This paper reports that experience in the remediation of schools and other large buildings has shown the importance of the effects of both the location of geologic sources and HVAC-induced distribution of indoor radon. In general, elevated radon in areas of schools with evenly distributed HVAC pressures are correlated with maximum soil radon emanations. However, strong or unequal HVAC effects can redistribute indoor radon to areas away from the direct source. Effective remediation required a complete understanding of both contributions. In some schools, highest indoor radon levels were located near large return ducts and were attributed to proximity to negative HVAC pressure. Successful sub-slab depressurization systems were installed, however, in rooms with lower indoor but greatest sub-slab radon levels, closest to the source. This shows the inadequacy of using indoor radon levels alone as a basis for remediation. Wings of two other schools with radon problems have equivalent window fan coil units in rooms of equal size and no central HVAC system. Highest indoor radon levels correlated well with highest sub-slab radon levels due to the equivalent effects of the window units. Diagnostic tests in other schools have revealed: blockwall radon transport to upper floors; high blockwall radon adjacent to sub-slab sources; and elevated indoor radon over crawlspace being drawn upward by HVAC-induced negative pressure, determined from indoor to outdoor micromanometer measurements

  15. Characterization of a Novel Class I Transcription Factor A (CITFA) Subunit That Is Indispensable for Transcription by the Multifunctional RNA Polymerase I of Trypanosoma brucei

    KAUST Repository

    Nguyen, T. N.

    2012-10-26

    Trypanosoma brucei is the only organism known to have evolved a multifunctional RNA polymerase I (pol I) system that is used to express the parasite\\'s ribosomal RNAs, as well as its major cell surface antigens, namely, the variant surface glycoprotein (VSG) and procyclin, which are vital for establishing successful infections in the mammalian host and the tsetse vector, respectively. Thus far, biochemical analyses of the T. brucei RNA pol I transcription machinery have elucidated the subunit structure of the enzyme and identified the class I transcription factor A (CITFA). CITFA binds to RNA pol I promoters, and its CITFA-2 subunit was shown to be absolutely essential for RNA pol I transcription in the parasite. Tandem affinity purification (TAP) of CITFA revealed the subunits CITFA-1 to -6, which are conserved only among kinetoplastid organisms, plus the dynein light chain DYNLL1. Here, by tagging CITFA-6 instead of CITFA-2, a complex was purified that contained all known CITFA subunits, as well as a novel proline-rich protein. Functional studies carried out in vivo and in vitro, as well as a colocalization study, unequivocally demonstrated that this protein is a bona fide CITFA subunit, essential for parasite viability and indispensable for RNA pol I transcription of ribosomal gene units and the active VSG expression site in the mammalian-infective life cycle stage of the parasite. Interestingly, CITFA-7 function appears to be species specific, because expression of an RNA interference (RNAi)-resistant CITFA-7 transgene from Trypanosoma cruzi could not rescue the lethal phenotype of silencing endogenous CITFA-7.

  16. Structures of Trypanosoma brucei methionyl-tRNA synthetase with urea-based inhibitors provide guidance for drug design against sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Cho Yeow Koh

    2014-04-01

    Full Text Available Methionyl-tRNA synthetase of Trypanosoma brucei (TbMetRS is an important target in the development of new antitrypanosomal drugs. The enzyme is essential, highly flexible and displaying a large degree of changes in protein domains and binding pockets in the presence of substrate, product and inhibitors. Targeting this protein will benefit from a profound understanding of how its structure adapts to ligand binding. A series of urea-based inhibitors (UBIs has been developed with IC50 values as low as 19 nM against the enzyme. The UBIs were shown to be orally available and permeable through the blood-brain barrier, and are therefore candidates for development of drugs for the treatment of late stage human African trypanosomiasis. Here, we expand the structural diversity of inhibitors from the previously reported collection and tested for their inhibitory effect on TbMetRS and on the growth of T. brucei cells. The binding modes and binding pockets of 14 UBIs are revealed by determination of their crystal structures in complex with TbMetRS at resolutions between 2.2 Å to 2.9 Å. The structures show binding of the UBIs through conformational selection, including occupancy of the enlarged methionine pocket and the auxiliary pocket. General principles underlying the affinity of UBIs for TbMetRS are derived from these structures, in particular the optimum way to fill the two binding pockets. The conserved auxiliary pocket might play a role in binding tRNA. In addition, a crystal structure of a ternary TbMetRS•inhibitor•AMPPCP complex indicates that the UBIs are not competing with ATP for binding, instead are interacting with ATP through hydrogen bond. This suggests a possibility that a general 'ATP-engaging' binding mode can be utilized for the design and development of inhibitors targeting tRNA synthetases of other disease-causing pathogen.

  17. 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.

  18. Methanolic leaf extract of Moringa oleifera improves the survivability rate, weight gain and histopathological changes of Wister rats infected with Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    A. Aremu

    2018-04-01

    Full Text Available Trypanosomosis is a major disease of Man and animals. This study investigated the effect of Moringa oleifera leaf extract on the survivability rate, weight gain and histopathological changes of Wister rats experimentally infected with Trypanosoma brucei. A total of thirty (30 rats randomly divided into six groups (A-F. Rats in group A remain untreated and uninfected while rates in group F were infected and untreated. Rats in groups B and C were treated with Moringa oleifera leave extract orally at 200 mg/kg for 14 days pre-infection and the treatment continued in B but not in C. Rats in groups D and E were treated with the extract orally for ninety days at 200 mg/kg (pre-infection and the treatment continued in D but not in E. The weight changes in all rats were monitored weekly. Rats in B-F groups were infected with 3 × 106 of Trypanosoma brucei per mL of blood. The results showed that all the infected rats died but the treated group survived extra two days when compared with the untreated group. The percentage weight gain of rats in groups B and C was high (23.9% and 21.1% respectively as against negative control (17.2%. The groups with chronic administration of the extract (D and E had a lower percentage weight gains (64.3% and 60.3% respectively when compared with negative control (71.8%. The histopathology results showed that the extract was a potent ameliorative agent that reduced neuronal degeneration and congestion in the brain and the spleen of the infected rats respectively. In conclusion, Moringa Oleifera leave extract has mitigative effects on the pathogenesis of trypanosomosis. Keywords: Histopathology, Moringa, Survivability, Trypanosoma, Weight, Wister rats

  19. Challenges in the diagnosis and management of sleeping sickness ...

    African Journals Online (AJOL)

    Blood and cerebrospinal fluid (CSF) samples were examined for the presence of trypanosomes using wet film, Field\\'s stain and concentration techniques. Typanosoma brucei rhodesiense were detected in both the blood and CSF samples. The patient was treated successfully with melarsoprol. The results of this case study ...

  20. Detection of human-infective trypanosomes in acutely-infected Jack ...

    African Journals Online (AJOL)

    A diagnosis of acute canine African trypanosomosis was made by microscopic examination of blood smear. Loop-mediated isothermal amplification (LAMP) analysis, using primers specifically targeting the human serum resistanceassociated (SRA) gene, revealed a monolytic infection with Trypanosoma brucei rhodesiense ...

  1. Lectures in plasma diagnostics

    International Nuclear Information System (INIS)

    Hutchinson, I.H.

    1990-06-01

    This paper discusses the following topics on plasma diagnostics: Electric probes in flowing and magnetized plasmas; Electron cyclotron emission absorption; Magnetic diagnostics; Spectroscopy; and Thomson Scattering

  2. Multiple evolutionary origins of Trypanosoma evansi in Kenya.

    Directory of Open Access Journals (Sweden)

    Christine M Kamidi

    2017-09-01

    Full Text Available Trypanosoma evansi is the parasite causing surra, a form of trypanosomiasis in camels and other livestock, and a serious economic burden in Kenya and many other parts of the world. Trypanosoma evansi transmission can be sustained mechanically by tabanid and Stomoxys biting flies, whereas the closely related African trypanosomes T. brucei brucei and T. b. rhodesiense require cyclical development in tsetse flies (genus Glossina for transmission. In this study, we investigated the evolutionary origins of T. evansi. We used 15 polymorphic microsatellites to quantify levels and patterns of genetic diversity among 41 T. evansi isolates and 66 isolates of T. b. brucei (n = 51 and T. b. rhodesiense (n = 15, including many from Kenya, a region where T. evansi may have evolved from T. brucei. We found that T. evansi strains belong to at least two distinct T. brucei genetic units and contain genetic diversity that is similar to that in T. brucei strains. Results indicated that the 41 T. evansi isolates originated from multiple T. brucei strains from different genetic backgrounds, implying independent origins of T. evansi from T. brucei strains. This surprising finding further suggested that the acquisition of the ability of T. evansi to be transmitted mechanically, and thus the ability to escape the obligate link with the African tsetse fly vector, has occurred repeatedly. These findings, if confirmed, have epidemiological implications, as T. brucei strains from different genetic backgrounds can become either causative agents of a dangerous, cosmopolitan livestock disease or of a lethal human disease, like for T. b. rhodesiense.

  3. Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme

    Directory of Open Access Journals (Sweden)

    Alcione Silva de Carvalho

    2014-06-01

    Full Text Available Megazol (7 is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8 in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7 for nitrogen (in the triazole in 8, the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7.

  4. Diagnostic reasoning strategies and diagnostic success.

    Science.gov (United States)

    Coderre, S; Mandin, H; Harasym, P H; Fick, G H

    2003-08-01

    Cognitive psychology research supports the notion that experts use mental frameworks or "schemes", both to organize knowledge in memory and to solve clinical problems. The central purpose of this study was to determine the relationship between problem-solving strategies and the likelihood of diagnostic success. Think-aloud protocols were collected to determine the diagnostic reasoning used by experts and non-experts when attempting to diagnose clinical presentations in gastroenterology. Using logistic regression analysis, the study found that there is a relationship between diagnostic reasoning strategy and the likelihood of diagnostic success. Compared to hypothetico-deductive reasoning, the odds of diagnostic success were significantly greater when subjects used the diagnostic strategies of pattern recognition and scheme-inductive reasoning. Two other factors emerged as independent determinants of diagnostic success: expertise and clinical presentation. Not surprisingly, experts outperformed novices, while the content area of the clinical cases in each of the four clinical presentations demonstrated varying degrees of difficulty and thus diagnostic success. These findings have significant implications for medical educators. It supports the introduction of "schemes" as a means of enhancing memory organization and improving diagnostic success.

  5. Genetic and structural study of DNA-directed RNA polymerase II of Trypanosoma brucei, towards the designing of novel antiparasitic agents

    Directory of Open Access Journals (Sweden)

    Louis Papageorgiou

    2017-03-01

    Full Text Available Trypanosoma brucei brucei (TBB belongs to the unicellular parasitic protozoa organisms, specifically to the Trypanosoma genus of the Trypanosomatidae class. A variety of different vertebrate species can be infected by TBB, including humans and animals. Under particular conditions, the TBB can be hosted by wild and domestic animals; therefore, an important reservoir of infection always remains available to transmit through tsetse flies. Although the TBB parasite is one of the leading causes of death in the most underdeveloped countries, to date there is neither vaccination available nor any drug against TBB infection. The subunit RPB1 of the TBB DNA-directed RNA polymerase II (DdRpII constitutes an ideal target for the design of novel inhibitors, since it is instrumental role is vital for the parasite’s survival, proliferation, and transmission. A major goal of the described study is to provide insights for novel anti-TBB agents via a state-of-the-art drug discovery approach of the TBB DdRpII RPB1. In an attempt to understand the function and action mechanisms of this parasite enzyme related to its molecular structure, an in-depth evolutionary study has been conducted in parallel to the in silico molecular designing of the 3D enzyme model, based on state-of-the-art comparative modelling and molecular dynamics techniques. Based on the evolutionary studies results nine new invariant, first-time reported, highly conserved regions have been identified within the DdRpII family enzymes. Consequently, those patches have been examined both at the sequence and structural level and have been evaluated in regard to their pharmacological targeting appropriateness. Finally, the pharmacophore elucidation study enabled us to virtually in silico screen hundreds of compounds and evaluate their interaction capabilities with the enzyme. It was found that a series of chlorine-rich set of compounds were the optimal inhibitors for the TBB DdRpII RPB1 enzyme. All

  6. Genotypic status of the TbAT1/P2 adenosine transporter of Trypanosoma brucei gambiense isolates from Northwestern Uganda following melarsoprol withdrawal.

    Directory of Open Access Journals (Sweden)

    Anne J N Kazibwe

    Full Text Available BACKGROUND: The development of arsenical and diamidine resistance in Trypanosoma brucei is associated with loss of drug uptake by the P2 purine transporter as a result of alterations in the corresponding T. brucei adenosine transporter 1 gene (TbAT1. Previously, specific TbAT1 mutant type alleles linked to melarsoprol treatment failure were significantly more prevalent in T. b. gambiense from relapse patients at Omugo health centre in Arua district. Relapse rates of up to 30% prompted a shift from melarsoprol to eflornithine (alpha-difluoromethylornithine, DFMO as first-line treatment at this centre. The aim of this study was to determine the status of TbAT1 in recent isolates collected from T. b. gambiense sleeping sickness patients from Arua and Moyo districts in Northwestern Uganda after this shift in first-line drug choice. METHODOLOGY AND RESULTS: Blood and cerebrospinal fluids of consenting patients were collected for DNA preparation and subsequent amplification. All of the 105 isolates from Omugo that we successfully analysed by PCR-RFLP possessed the TbAT1 wild type allele. In addition, PCR/RFLP analysis was performed for 74 samples from Moyo, where melarsoprol is still the first line drug; 61 samples displayed the wild genotype while six were mutant and seven had a mixed pattern of both mutant and wild-type TbAT1. The melarsoprol treatment failure rate at Moyo over the same period was nine out of 101 stage II cases that were followed up at least once. Five of the relapse cases harboured mutant TbAT1, one had the wild type, while no amplification was achieved from the remaining three samples. CONCLUSIONS/SIGNIFICANCE: The apparent disappearance of mutant alleles at Omugo may correlate with melarsoprol withdrawal as first-line treatment. Our results suggest that melarsoprol could successfully be reintroduced following a time lag subsequent to its replacement. A field-applicable test to predict melarsoprol treatment outcome and identify

  7. Procedures in diagnostic radiology

    International Nuclear Information System (INIS)

    Doyle, T.; Hare, W.S.C.; Thomson, K.; Tess, B.

    1989-01-01

    This book outlines the various procedures necessary for the successful practice of diagnostic radiology. Topics covered are: general principles, imaging of the urinary and gastrointestinal tracts, vascular radiology, arthrography, and miscellaneous diagnostic radiologic procedures

  8. Diagnostic Algorithm Benchmarking

    Science.gov (United States)

    Poll, Scott

    2011-01-01

    A poster for the NASA Aviation Safety Program Annual Technical Meeting. It describes empirical benchmarking on diagnostic algorithms using data from the ADAPT Electrical Power System testbed and a diagnostic software framework.

  9. RNA-seq de novo Assembly Reveals Differential Gene Expression in Glossina palpalis gambiensis Infected with Trypanosoma brucei gambiense vs. Non-Infected and Self-Cured Flies.

    Science.gov (United States)

    Hamidou Soumana, Illiassou; Klopp, Christophe; Ravel, Sophie; Nabihoudine, Ibouniyamine; Tchicaya, Bernadette; Parrinello, Hugues; Abate, Luc; Rialle, Stéphanie; Geiger, Anne

    2015-01-01

    Trypanosoma brucei gambiense (Tbg), causing the sleeping sickness chronic form, completes its developmental cycle within the tsetse fly vector Glossina palpalis gambiensis (Gpg) before its transmission to humans. Within the framework of an anti-vector disease control strategy, a global gene expression profiling of trypanosome infected (susceptible), non-infected, and self-cured (refractory) tsetse flies was performed, on their midguts, to determine differential genes expression resulting from in vivo trypanosomes, tsetse flies (and their microbiome) interactions. An RNAseq de novo assembly was achieved. The assembled transcripts were mapped to reference sequences for functional annotation. Twenty-four percent of the 16,936 contigs could not be annotated, possibly representing untranslated mRNA regions, or Gpg- or Tbg-specific ORFs. The remaining contigs were classified into 65 functional groups. Only a few transposable elements were present in the Gpg midgut transcriptome, which may represent active transpositions and play regulatory roles. One thousand three hundred and seventy three genes differentially expressed (DEGs) between stimulated and non-stimulated flies were identified at day-3 post-feeding; 52 and 1025 between infected and self-cured flies at 10 and 20 days post-feeding, respectively. The possible roles of several DEGs regarding fly susceptibility and refractoriness are discussed. The results provide new means to decipher fly infection mechanisms, crucial to develop anti-vector control strategies.

  10. Transcriptome and proteome analyses and the role of atypical calpain protein and autophagy in the spliced leader silencing pathway in Trypanosoma brucei.

    Science.gov (United States)

    Hope, Ronen; Egarmina, Katarina; Voloshin, Konstantin; Waldman Ben-Asher, Hiba; Carmi, Shai; Eliaz, Dror; Drori, Yaron; Michaeli, Shulamit

    2016-10-01

    Under persistent ER stress, Trypanosoma brucei parasites induce the spliced leader silencing (SLS) pathway. In SLS, transcription of the SL RNA gene, the SL donor to all mRNAs, is extinguished, arresting trans-splicing and leading to programmed cell death (PCD). In this study, we investigated the transcriptome following silencing of SEC63, a factor essential for protein translocation across the ER membrane, and whose silencing induces SLS. The proteome of SEC63-silenced cells was analyzed with an emphasis on SLS-specific alterations in protein expression, and modifications that do not directly result from perturbations in trans-splicing. One such protein identified is an atypical calpain SKCRP7.1/7.2. Co-silencing of SKCRP7.1/7.2 and SEC63 eliminated SLS induction due its role in translocating the PK3 kinase. This kinase initiates SLS by migrating to the nucleus and phosphorylating TRF4 leading to shut-off of SL RNA transcription. Thus, SKCRP7.1 is involved in SLS signaling and the accompanying PCD. The role of autophagy in SLS was also investigated; eliminating autophagy through VPS34 or ATG7 silencing demonstrated that autophagy is not essential for SLS induction, but is associated with PCD. Thus, this study identified factors that are used by the parasite to cope with ER stress and to induce SLS and PCD. © 2016 John Wiley & Sons Ltd.

  11. Veterinary Molecular Diagnostics

    NARCIS (Netherlands)

    Roest, H.I.J.; Engelsma, M.Y.; Weesendorp, E.; Bossers, A.; Elbers, A.R.W.

    2017-01-01

    In veterinary molecular diagnostics, samples originating from animals are tested. Developments in the farm animals sector and in our societal attitude towards pet animals have resulted in an increased demand for fast and reliable diagnostic techniques. Molecular diagnostics perfectly matches this

  12. Characterisation of the wildlife reservoir community for human and animal trypanosomiasis in the Luangwa Valley, Zambia.

    Directory of Open Access Journals (Sweden)

    Neil E Anderson

    2011-06-01

    Full Text Available Animal and human trypanosomiasis are constraints to both animal and human health in Sub-Saharan Africa, but there is little recent evidence as to how these parasites circulate in wild hosts in natural ecosystems. The Luangwa Valley in Zambia supports high densities of tsetse flies (Glossina species and is recognised as an historical sleeping sickness focus. The objective of this study was to characterise the nature of the reservoir community for trypanosomiasis in the absence of influence from domesticated hosts.A cross-sectional survey of trypanosome prevalence in wildlife hosts was conducted in the Luangwa Valley from 2005 to 2007. Samples were collected from 418 animals and were examined for the presence of Trypanosoma brucei s.l., T. b. rhodesiense, Trypanosoma congolense and Trypanosoma vivax using molecular diagnostic techniques. The overall prevalence of infection in all species was 13.9% (95% confidence interval [CI]: 10.71-17.57%. Infection was significantly more likely to be detected in waterbuck (Kobus ellipsiprymnus (Odds ratio [OR]=10.5, 95% CI: 2.36-46.71, lion (Panthera leo (OR=5.3, 95% CI: 1.40-19.69, greater kudu (Tragelaphus strepsiceros (OR=4.7, 95% CI: 1.41-15.41 and bushbuck (Tragelaphus scriptus (OR=4.5, 95% CI: 1.51-13.56. Bushbucks are important hosts for T. brucei s.l. while the Bovidae appear the most important for T. congolense. The epidemiology of T. vivax was less clear, but parasites were detected most frequently in waterbuck. Human infective T. b. rhodesiense were identified for the first time in African buffalo (Syncerus caffer and T. brucei s.l. in leopard (Panthera pardus. Variation in infection rates was demonstrated at species level rather than at family or sub-family level. A number of significant risk factors interact to influence infection rates in wildlife including taxonomy, habitat and blood meal preference.Trypanosoma parasites circulate within a wide and diverse host community in this bio

  13. Diagnostic Development on NSTX

    International Nuclear Information System (INIS)

    A.L. Roquemore; D. Johnson; R. Kaita; et al

    1999-01-01

    Diagnostics are described which are currently installed or under active development for the newly commissioned NSTX device. The low aspect ratio (R/a less than or equal to 1.3) and low toroidal field (0.1-0.3T) used in this device dictate adaptations in many standard diagnostic techniques. Technical summaries of each diagnostic are given, and adaptations, where significant, are highlighted

  14. TFTR diagnostic vacuum controller

    International Nuclear Information System (INIS)

    Olsen, D.; Persons, R.

    1981-01-01

    The TFTR diagnostic vacuum controller (DVC) provides in conjunction with the Central Instrumentation Control and Data Acquisition System (CICADA), control and monitoring for the pumps, valves and gauges associated with each individual diagnostic vacuum system. There will be approximately 50 systems on TFTR. Two standard versions of the controller (A and B) wil be provided in order to meet the requirements of two diagnostic manifold arrangements. All pump and valve sequencing, as well as protection features, will be implemented by the controller

  15. Proteomic Analysis of Intact Flagella of Procyclic Trypanosoma brucei Cells Identifies Novel Flagellar Proteins with Unique Sub-localization and Dynamics*

    Science.gov (United States)

    Subota, Ines; Julkowska, Daria; Vincensini, Laetitia; Reeg, Nele; Buisson, Johanna; Blisnick, Thierry; Huet, Diego; Perrot, Sylvie; Santi-Rocca, Julien; Duchateau, Magalie; Hourdel, Véronique; Rousselle, Jean-Claude; Cayet, Nadège; Namane, Abdelkader; Chamot-Rooke, Julia; Bastin, Philippe

    2014-01-01

    Cilia and flagella are complex organelles made of hundreds of proteins of highly variable structures and functions. Here we report the purification of intact flagella from the procyclic stage of Trypanosoma brucei using mechanical shearing. Structural preservation was confirmed by transmission electron microscopy that showed that flagella still contained typical elements such as the membrane, the axoneme, the paraflagellar rod, and the intraflagellar transport particles. It also revealed that flagella severed below the basal body, and were not contaminated by other cytoskeletal structures such as the flagellar pocket collar or the adhesion zone filament. Mass spectrometry analysis identified a total of 751 proteins with high confidence, including 88% of known flagellar components. Comparison with the cell debris fraction revealed that more than half of the flagellum markers were enriched in flagella and this enrichment criterion was taken into account to identify 212 proteins not previously reported to be associated to flagella. Nine of these were experimentally validated including a 14-3-3 protein not yet reported to be associated to flagella and eight novel proteins termed FLAM (FLAgellar Member). Remarkably, they localized to five different subdomains of the flagellum. For example, FLAM6 is restricted to the proximal half of the axoneme, no matter its length. In contrast, FLAM8 is progressively accumulating at the distal tip of growing flagella and half of it still needs to be added after cell division. A combination of RNA interference and Fluorescence Recovery After Photobleaching approaches demonstrated very different dynamics from one protein to the other, but also according to the stage of construction and the age of the flagellum. Structural proteins are added to the distal tip of the elongating flagellum and exhibit slow turnover whereas membrane proteins such as the arginine kinase show rapid turnover without a detectible polarity. PMID:24741115

  16. Proteomic analysis of intact flagella of procyclic Trypanosoma brucei cells identifies novel flagellar proteins with unique sub-localization and dynamics.

    Science.gov (United States)

    Subota, Ines; Julkowska, Daria; Vincensini, Laetitia; Reeg, Nele; Buisson, Johanna; Blisnick, Thierry; Huet, Diego; Perrot, Sylvie; Santi-Rocca, Julien; Duchateau, Magalie; Hourdel, Véronique; Rousselle, Jean-Claude; Cayet, Nadège; Namane, Abdelkader; Chamot-Rooke, Julia; Bastin, Philippe

    2014-07-01

    Cilia and flagella are complex organelles made of hundreds of proteins of highly variable structures and functions. Here we report the purification of intact flagella from the procyclic stage of Trypanosoma brucei using mechanical shearing. Structural preservation was confirmed by transmission electron microscopy that showed that flagella still contained typical elements such as the membrane, the axoneme, the paraflagellar rod, and the intraflagellar transport particles. It also revealed that flagella severed below the basal body, and were not contaminated by other cytoskeletal structures such as the flagellar pocket collar or the adhesion zone filament. Mass spectrometry analysis identified a total of 751 proteins with high confidence, including 88% of known flagellar components. Comparison with the cell debris fraction revealed that more than half of the flagellum markers were enriched in flagella and this enrichment criterion was taken into account to identify 212 proteins not previously reported to be associated to flagella. Nine of these were experimentally validated including a 14-3-3 protein not yet reported to be associated to flagella and eight novel proteins termed FLAM (FLAgellar Member). Remarkably, they localized to five different subdomains of the flagellum. For example, FLAM6 is restricted to the proximal half of the axoneme, no matter its length. In contrast, FLAM8 is progressively accumulating at the distal tip of growing flagella and half of it still needs to be added after cell division. A combination of RNA interference and Fluorescence Recovery After Photobleaching approaches demonstrated very different dynamics from one protein to the other, but also according to the stage of construction and the age of the flagellum. Structural proteins are added to the distal tip of the elongating flagellum and exhibit slow turnover whereas membrane proteins such as the arginine kinase show rapid turnover without a detectible polarity. © 2014 by The

  17. Structure determination of glycogen synthase kinase-3 from Leishmania major and comparative inhibitor structure-activity relationships with Trypanosoma brucei GSK-3

    Energy Technology Data Exchange (ETDEWEB)

    Ojo, Kayode K; Arakaki, Tracy L; Napuli, Alberto J; Inampudi, Krishna K; Keyloun, Katelyn R; Zhang, Li; Hol, Wim G.J.; Verlind, Christophe L.M.J.; Merritt, Ethan A; Van Voorhis, Wesley C [UWASH

    2012-04-24

    Glycogen synthase kinase-3 (GSK-3) is a drug target under intense investigation in pharmaceutical companies and constitutes an attractive piggyback target for eukaryotic pathogens. Two different GSKs are found in trypanosomatids, one about 150 residues shorter than the other. GSK-3 short (GeneDB: Tb927.10.13780) has previously been validated genetically as a drug target in Trypanosoma brucei by RNAi induced growth retardation; and chemically by correlation between enzyme and in vitro growth inhibition. Here, we report investigation of the equivalent GSK-3 short enzymes of L. major (LmjF18.0270) and L. infantum (LinJ18_V3.0270, identical in amino acid sequences to LdonGSK-3 short) and a crystal structure of LmajGSK-3 short at 2 Å resolution. The inhibitor structure-activity relationships (SARs) of L. major and L. infantum are virtually identical, suggesting that inhibitors could be useful for both cutaneous and visceral leishmaniasis. Leishmania spp. GSK-3 short has different inhibitor SARs than TbruGSK-3 short, which can be explained mostly by two variant residues in the ATP-binding pocket. Indeed, mutating these residues in the ATP-binding site of LmajGSK-3 short to the TbruGSK-3 short equivalents results in a mutant LmajGSK-3 short enzyme with SAR more similar to that of TbruGSK-3 short. The differences between human GSK-3β (HsGSK-3β) and LmajGSK-3 short SAR suggest that compounds which selectively inhibit LmajGSK-3 short may be found.

  18. Psychologists' diagnostic processes during a diagnostic interview

    NARCIS (Netherlands)

    Groenier, Marleen; Beerthuis, Vos R.J.; Pieters, Julius Marie; Witteman, C.L.M.; Witteman, Cilia L.M.; Swinkels, Jan A.

    2011-01-01

    In mental health care, psychologists assess clients’ complaints, analyze underlying problems, and identify causes for these problems, to make treatment decisions. We present a study on psychologists’ diagnostic processes, in which a mixed-method approach was employed. We aimed to identify a common

  19. Diagnostic nerve ultrasonography

    International Nuclear Information System (INIS)

    Baeumer, T.; Grimm, A.; Schelle, T.

    2017-01-01

    For the diagnostics of nerve lesions an imaging method is necessary to visualize peripheral nerves and their surrounding structures for an etiological classification. Clinical neurological and electrophysiological investigations provide functional information about nerve lesions. The information provided by a standard magnetic resonance imaging (MRI) examination is inadequate for peripheral nerve diagnostics; however, MRI neurography is suitable but on the other hand a resource and time-consuming method. Using ultrasonography for peripheral nerve diagnostics. With ultrasonography reliable diagnostics of entrapment neuropathies and traumatic nerve lesions are possible. The use of ultrasonography for neuropathies shows that a differentiation between different forms is possible. Nerve ultrasonography is an established diagnostic tool. In addition to the clinical examination and clinical electrophysiology, structural information can be obtained, which results in a clear improvement in the diagnostics. Ultrasonography has become an integral part of the diagnostic work-up of peripheral nerve lesions in neurophysiological departments. Nerve ultrasonography is recommended for the diagnostic work-up of peripheral nerve lesions in addition to clinical and electrophysiological investigations. It should be used in the clinical work-up of entrapment neuropathies, traumatic nerve lesions and spacy-occupying lesions of nerves. (orig.) [de

  20. Ongoing experiments: diagnostics requirements

    International Nuclear Information System (INIS)

    Dickerman, C.E.

    1976-01-01

    The paper reviews the fuel motion diagnostics needs for ongoing LMFBR safety experiments over approximately the next five years, with the discussion centered on TREAT. Brief comments on the direction in which clad motion diagnostics requirements are expected to develop are also presented

  1. Clinical diagnostic ultrasound

    International Nuclear Information System (INIS)

    Barnett, E.; Morley, P.

    1986-01-01

    This textbook on diagnostic ultrasound covers the main systems, with emphasis being placed on the clinical application of diagnostic ultrasound in everyday practice. It provides not only a textbook for postgraduates (particularly FRCR candidates), but also a reference work for practitioners of clinical ultrasound and clinicians generally

  2. Gearbox vibration diagnostic analyzer

    Science.gov (United States)

    1992-01-01

    This report describes the Gearbox Vibration Diagnostic Analyzer installed in the NASA Lewis Research Center's 500 HP Helicopter Transmission Test Stand to monitor gearbox testing. The vibration of the gearbox is analyzed using diagnostic algorithms to calculate a parameter indicating damaged components.

  3. Diagnostics on Z (invited)

    International Nuclear Information System (INIS)

    Nash, T. J.; Derzon, M. S.; Chandler, G. A.; Fehl, D. L.; Leeper, R. J.; Porter, J. L.; Spielman, R. B.; Ruiz, C.; Cooper, G.; McGurn, J.

    2001-01-01

    The 100 ns, 20 MA pinch-driver Z is surrounded by an extensive set of diagnostics. There are nine radial lines of sight set at 12 o above horizontal and each of these may be equipped with up to five diagnostic ports. Instruments routinely fielded viewing the pinch from the side with these ports include x-ray diode arrays, photoconducting detector arrays, bolometers, transmission grating spectrometers, time-resolved x-ray pinhole cameras, x-ray crystal spectrometers, calorimeters, silicon photodiodes, and neutron detectors. A diagnostic package fielded on axis for viewing internal pinch radiation consists of nine lines of sight. This package accommodates virtually the same diagnostics as the radial ports. Other diagnostics not fielded on the axial or radial ports include current B-dot monitors, filtered x-ray scintillators coupled by fiber optics to streak cameras, streaked visible spectroscopy, velocity interferometric system for any reflector, bremsstrahlung cameras, and active shock breakout measurement of hohlraum temperature. The data acquisition system is capable of recording up to 500 channels and the data from each shot is available on the Internet. A major new diagnostic presently under construction is the BEAMLET backlighter. We will briefly describe each of these diagnostics and present some of the highest-quality data from them

  4. Cable Diagnostic Focused Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Hartlein, R.A.; Hampton, R.N.

    2010-12-30

    This report summarizes an extensive effort made to understand how to effectively use the various diagnostic technologies to establish the condition of medium voltage underground cable circuits. These circuits make up an extensive portion of the electric delivery infrastructure in the United States. Much of this infrastructure is old and experiencing unacceptable failure rates. By deploying efficient diagnostic testing programs, electric utilities can replace or repair circuits that are about to fail, providing an optimal approach to improving electric system reliability. This is an intrinsically complex topic. Underground cable systems are not homogeneous. Cable circuits often contain multiple branches with different cable designs and a range of insulation materials. In addition, each insulation material ages differently as a function of time, temperature and operating environment. To complicate matters further, there are a wide variety of diagnostic technologies available for assessing the condition of cable circuits with a diversity of claims about the effectiveness of each approach. As a result, the benefits of deploying cable diagnostic testing programs have been difficult to establish, leading many utilities to avoid the their use altogether. This project was designed to help address these issues. The information provided is the result of a collaborative effort between Georgia Tech NEETRAC staff, Georgia Tech academic faculty, electric utility industry participants, as well as cable system diagnostic testing service providers and test equipment providers. Report topics include: •How cable systems age and fail, •The various technologies available for detecting potential failure sites, •The advantages and disadvantages of different diagnostic technologies, •Different approaches for utilities to employ cable system diagnostics. The primary deliverables of this project are this report, a Cable Diagnostic Handbook (a subset of this report) and an online

  5. Plasma diagnostic reflectometry

    International Nuclear Information System (INIS)

    Cohen, B.I.; Afeyan, B.B.; Garrison, J.C.; Kaiser, T.B.; Luhmann, N.C. Jr.; Domier, C.W.; Chou, A.E.; Baang, S.

    1996-01-01

    Theoretical and experimental studies of plasma diagnostic reflectometry have been undertaken as a collaborative research project between the Lawrence Livermore National Laboratory (LLNL) and the University of California Department of Applied Science Plasma Diagnostics Group under the auspices of the Laboratory Directed Research and Development Program at LLNL. Theoretical analyses have explored the basic principles of reflectometry to understand its limitations, to address specific gaps in the understanding of reflectometry measurements in laboratory experiments, and to explore extensions of reflectometry such as ultra-short-pulse reflectometry. The theory has supported basic laboratory reflectometry experiments where reflectometry measurements can be corroborated by independent diagnostic measurements

  6. Melarsoprol sensitivity profile of Trypanosoma brucei gambiense isolates from cured and relapsed sleeping sickness patients from the Democratic Republic of the Congo.

    Directory of Open Access Journals (Sweden)

    Patient Pyana Pati

    2014-10-01

    Full Text Available Sleeping sickness caused by Trypanosoma brucei (T.b. gambiense constitutes a serious health problem in sub-Sahara Africa. In some foci, alarmingly high relapse rates were observed in patients treated with melarsoprol, which used to be the first line treatment for patients in the neurological disease stage. Particularly problematic was the situation in Mbuji-Mayi, East Kasai Province in the Democratic Republic of the Congo with a 57% relapse rate compared to a 5% relapse rate in Masi-Manimba, Bandundu Province. The present study aimed at investigating the mechanisms underlying the high relapse rate in Mbuji-Mayi using an extended collection of recently isolated T.b. gambiense strains from Mbuji-Mayi and from Masi-Manimba.Forty five T.b. gambiense strains were used. Forty one were isolated from patients that were cured or relapsed after melarsoprol treatment in Mbuji-Mayi. In vivo drug sensitivity tests provide evidence of reduced melarsoprol sensitivity in these strains. This reduced melarsoprol sensitivity was not attributable to mutations in TbAT1. However, in all these strains, irrespective of the patient treatment outcome, the two aquaglyceroporin (AQP 2 and 3 genes are replaced by chimeric AQP2/3 genes that may be associated with resistance to pentamidine and melarsoprol. The 4 T.b. gambiense strains isolated in Masi-Manimba contain both wild-type AQP2 and a different chimeric AQP2/3. These findings suggest that the reduced in vivo melarsoprol sensitivity of the Mbuji-Mayi strains and the high relapse rates in that sleeping sickness focus are caused by mutations in the AQP2/AQP3 locus and not by mutations in TbAT1.We conclude that mutations in the TbAQP2/3 locus of the local T.b. gambiense strains may explain the high melarsoprol relapse rates in the Mbuji-Mayi focus but other factors must also be involved in the treatment outcome of individual patients.

  7. Equipment for radiation diagnostics

    International Nuclear Information System (INIS)

    Tschunt, E.; Platz, W.

    1976-01-01

    The invention relates to an improvement of the line type of the plotter in an X-ray diagnostics apparatus enabling the production of distinguishable recordings by means of a single plot type. The construction is described explicitly. (UWI) [de

  8. National Convective Weather Diagnostic

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Current convective hazards identified by the National Convective Weather Detection algorithm. The National Convective Weather Diagnostic (NCWD) is an automatically...

  9. Diagnostic radiology: I

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    This chapter describes the historic development of diagnostic equipment for radiology. The problems associated with fluoroscope design are detailed and the current uses of updated technology, particularly digitization, are considered. Numerous historical photographs are included. 13 refs

  10. Prenatal Genetic Diagnostic Tests

    Science.gov (United States)

    ... are available for many inherited disorders. The main disadvantage is that diagnostic testing carries a very small ... chromosomes, arranged in order of size. Microarray: A technology that examines all of a person’s genes to ...

  11. Molecular diagnostics of periodontitis

    OpenAIRE

    Izabela Korona-Głowniak; Radosław Siwiec; Marcin Berger; Anna Malm; Jolanta Szymańska

    2017-01-01

    The microorganisms that form dental plaque are the main cause of periodontitis. Their identification and the understanding of the complex relationships and interactions that involve these microorganisms, environmental factors and the host’s health status enable improvement in diagnostics and targeted therapy in patients with periodontitis. To this end, molecular diagnostics techniques (both techniques based on the polymerase chain reaction and those involving nucleic acid analysis via hybridi...

  12. Optics/Optical Diagnostics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Optics/Optical Diagnostics Laboratory supports graduate instruction in optics, optical and laser diagnostics and electro-optics. The optics laboratory provides...

  13. LHD neutron diagnostics

    International Nuclear Information System (INIS)

    Isobe, M.; Ogawa, K.; Kobuchi, T.

    2015-01-01

    The Large Helical Device (LHD) project will step into a next stage, i.e. experiment by using deuterium gases after two years of preparation. A comprehensive set of neutron and γ-ray diagnostics is going to be installed on the LHD towards extension of energetic-particle (EP) physics research in heliotron plasmas. Conceptual design of fusion products diagnostics for the LHD was made in late 1990s. After conclusion of agreements for the LHD deuterium experiment with local government bodies, development of FPs diagnostics has begun lately. Because there are a lot of tasks to do, all Japan fusion neutron and γ-ray diagnostics team has been organized in the collaboration framework of National Institute for Fusion Science. FPs diagnostics system on the LHD will consist of 1) wide dynamic range neutron flux monitor (NFM), 2) neutron activation system (NAS), 3) vertical neutron camera (VNC). In addition to these, we are developing a directional scintillating fiber detector, an artificial diamond detector and a γ-ray scintillation detector for confinement study of MeV ions. A neutron energy spectrometer prototype is also being developed and tested in KSTAR. In this paper, roles of NFM, NAS and VNC and current status of implementation onto the LHD are briefly described. (author)

  14. Pitfalls in diagnostic radiology

    Energy Technology Data Exchange (ETDEWEB)

    Peh, Wilfred C.G. (ed.) [Khoo Teck Puat Hospital (Singapore). Dept. of Diagnostic Radiology

    2015-04-01

    Only textbook to focus primarily on the topic of pitfalls in diagnostic radiology. Highlights the pitfalls in a comprehensive and systematic manner. Written by experts in different imaging modalities and subspecialties from reputable centers across the world. The practice of diagnostic radiology has become increasingly complex, with the use of numerous imaging modalities and division into many subspecialty areas. It is becoming ever more difficult for subspecialist radiologists, general radiologists, and residents to keep up with the advances that are occurring year on year, and this is particularly true for less familiar topics. Failure to appreciate imaging pitfalls often leads to diagnostic error and misinterpretation, and potential medicolegal problems. Diagnostic errors may be due to various factors such as inadequate imaging technique, imaging artifacts, failure to recognize normal structures or variants, lack of correlation with clinical and other imaging findings, and poor training or inexperience. Many, if not most, of these factors are potentially recognizable, preventable, or correctable. This textbook, written by experts from reputable centers across the world, systematically and comprehensively highlights the pitfalls that may occur in diagnostic radiology. Both pitfalls specific to different modalities and techniques and those specific to particular organ systems are described with the help of numerous high-quality illustrations. Recognition of these pitfalls is crucial in helping the practicing radiologist to achieve a more accurate diagnosis.

  15. Pitfalls in diagnostic radiology

    International Nuclear Information System (INIS)

    Peh, Wilfred C.G.

    2015-01-01

    Only textbook to focus primarily on the topic of pitfalls in diagnostic radiology. Highlights the pitfalls in a comprehensive and systematic manner. Written by experts in different imaging modalities and subspecialties from reputable centers across the world. The practice of diagnostic radiology has become increasingly complex, with the use of numerous imaging modalities and division into many subspecialty areas. It is becoming ever more difficult for subspecialist radiologists, general radiologists, and residents to keep up with the advances that are occurring year on year, and this is particularly true for less familiar topics. Failure to appreciate imaging pitfalls often leads to diagnostic error and misinterpretation, and potential medicolegal problems. Diagnostic errors may be due to various factors such as inadequate imaging technique, imaging artifacts, failure to recognize normal structures or variants, lack of correlation with clinical and other imaging findings, and poor training or inexperience. Many, if not most, of these factors are potentially recognizable, preventable, or correctable. This textbook, written by experts from reputable centers across the world, systematically and comprehensively highlights the pitfalls that may occur in diagnostic radiology. Both pitfalls specific to different modalities and techniques and those specific to particular organ systems are described with the help of numerous high-quality illustrations. Recognition of these pitfalls is crucial in helping the practicing radiologist to achieve a more accurate diagnosis.

  16. Polychromatic holographic plasma diagnostics

    International Nuclear Information System (INIS)

    Zhiglinskij, A.G.; Morozov, A.O.

    1992-01-01

    Review of holographic interferometry properties is performed and advantages of this method by plasma diagnostics are indicated. Main results obtained by the method of holographic interferometry in studies of various-type plasmas are considered. Special attention is paid to multiwave plasma diagnostics, the necessity of which is related as a rule to multicomponent composition of plasma. The eight laser and gas-discharge sources and holographic schemes, which make it possible to realize plasma polychromatic and holographic interferometry, are considered. The advantages of the method are demonstrated by examples of polychromatic holographic diagnostics of arc discharge and discharge in a hollow cathode. Review of theoretical works determining the applicability area of resonance polychromatic interferometry is carried out

  17. Reversed field pinch diagnostics

    International Nuclear Information System (INIS)

    Weber, P.G.

    1986-01-01

    The Reversed Field Pinch (RFP) is a toroidal, axisymmetric magnetic confinement configuration characterized by a magnetic field configuration in which the toroidal magnetic field is of similar strength to the poloidal field, and is reversed at the edge compared to the center. The RFP routinely operates at high beta, and is a strong candidate for a compact fusion device. Relevant attributes of the configuration will be presented, together with an overview of present and planned experiments and their diagnostics. RFP diagnostics are in many ways similar to those of other magnetic confinement devices (such as tokamaks); these lectures will point out pertinent differences, and will present some diagnostics which provide special insights into unique attributes of the RFP

  18. Metabolomics for laboratory diagnostics.

    Science.gov (United States)

    Bujak, Renata; Struck-Lewicka, Wiktoria; Markuszewski, Michał J; Kaliszan, Roman

    2015-09-10

    Metabolomics is an emerging approach in a systems biology field. Due to continuous development in advanced analytical techniques and in bioinformatics, metabolomics has been extensively applied as a novel, holistic diagnostic tool in clinical and biomedical studies. Metabolome's measurement, as a chemical reflection of a current phenotype of a particular biological system, is nowadays frequently implemented to understand pathophysiological processes involved in disease progression as well as to search for new diagnostic or prognostic biomarkers of various organism's disorders. In this review, we discussed the research strategies and analytical platforms commonly applied in the metabolomics studies. The applications of the metabolomics in laboratory diagnostics in the last 5 years were also reviewed according to the type of biological sample used in the metabolome's analysis. We also discussed some limitations and further improvements which should be considered taking in mind potential applications of metabolomic research and practice. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Corpuscular plasma diagnostics

    International Nuclear Information System (INIS)

    Afrosimov, V.; Petrov, M.

    1984-01-01

    An elementary explanation is presented of the physical principles and important methods of corpuscular plasma diagnostics. The invaluable role of corpuscular methods for measuring the hot plasma ion component in thermonuclear facilities, especially hydrogen ions in tokamaks, is emphasized. All corpuscular methods employ analysis of fast neutral atoms and therefore the mechanism of their creation inside a hot plasma is explained first. The ammount of information obtainable from spectra of fast neutrals is discussed. Multichannel analyzers developed at the FTI A.F. Ioffe in Leningrad are described in detail. Classical passive corpuscular diagnostics are examined as are active methods using artifitial beams of hydrogen atoms. The method used for obtaining local values of ion temperature and density is explained. Corpuscular spectroscopic diagnostics and its application for measuring impurities is mentioned. (J.U.)

  20. [Cytology in uropathological diagnostics].

    Science.gov (United States)

    Gaisa, N T; Lindemann-Docter, K

    2015-11-01

    Cytology in uropathological diagnostics is mainly performed for oncological purposes. The assessment of malignancy by urothelial cell morphology is therefore decisive; however, cytology is only sensitive enough to detect high-grade tumor cells and the different low-grade tumors cannot be reliably diagnosed. Thus, the four-tier classification system of cytological findings (i.e. negative, atypical cells but significance uncertain, suspicious and positive) refers to high-grade tumor cells only. Furthermore, for valid cytological diagnostics not only the cytological specimen but also clinical information on cystoscopy findings and, if applicable, a biopsy should be evaluated together. In difficult differential diagnostic settings, e.g. differentiation between reactive versus neoplastic atypia or difficult to access lesions in the upper urinary tract, additional fluorescence in situ hybridization of cytological preparations might be helpful. At the moment there are no indications for further immunocytology or additional biomarker tests.

  1. ORION laser target diagnostics

    International Nuclear Information System (INIS)

    Bentley, C. D.; Edwards, R. D.; Andrew, J. E.; James, S. F.; Gardner, M. D.; Comley, A. J.; Vaughan, K.; Horsfield, C. J.; Rubery, M. S.; Rothman, S. D.; Daykin, S.; Masoero, S. J.; Palmer, J. B.; Meadowcroft, A. L.; Williams, B. M.; Gumbrell, E. T.; Fyrth, J. D.; Brown, C. R. D.; Hill, M. P.; Oades, K.

    2012-01-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  2. ORION laser target diagnostics.

    Science.gov (United States)

    Bentley, C D; Edwards, R D; Andrew, J E; James, S F; Gardner, M D; Comley, A J; Vaughan, K; Horsfield, C J; Rubery, M S; Rothman, S D; Daykin, S; Masoero, S J; Palmer, J B; Meadowcroft, A L; Williams, B M; Gumbrell, E T; Fyrth, J D; Brown, C R D; Hill, M P; Oades, K; Wright, M J; Hood, B A; Kemshall, P

    2012-10-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  3. Nova diagnostics summary

    International Nuclear Information System (INIS)

    Slivinsky, V.W.; Drake, R.P.

    1985-01-01

    The authors intend that Nova be the best diagnosed ICF research facility in operation today. The authors experience in providing advanced diagnostics for previous laser systems will be extended at Nova, and will be challenged by the development of new instrumentation to diagnose the more advanced targets made possible by this powerful laser. Previous experience has shown that to understand target performance, the authors must have as complete a set of diagnostics as possible. The Nova diagnostics are divided into two sets: the basic set required for the initial Nova experiments and the more advanced set for later, generally more complex, experiments. The basic set will be operational for the first Nova shots; it was a Nova line item funded with Nova construction money. This basic set is presented in a table

  4. Angiography - interventional diagnostic applications

    International Nuclear Information System (INIS)

    Schild, H.

    1994-01-01

    The angiography system is very different from the other systems used in diagnostic radiology. The invasivity of angiography requires special, high standards in theoretical and practical training and experience both of beginners and experienced personnel. This textbook fully meets the demand for in-depth and exhaustive information, as it presents: - The fundamentals and techniques of angiography, the vascular anatomy, and many hints and tips of great help in practice. - A comprehensive survey of diagnostic problems and examination approaches, including neuro-angiography, with 221 reproductions of original angiographs, and additional schematic representations. - A special chapter devoted to indication and relevant techniques for the major vascular interventional examinations. - A great number of tables explain at a glance standard examination techniques, indications and diagnostic criteria. (orig./CB) [de

  5. The role of domestic animals in the epidemiology of human African trypanosomiasis in Ngorongoro conservation area, Tanzania.

    Science.gov (United States)

    Ruiz, Juan P; Nyingilili, Hamisi S; Mbata, Geofrey H; Malele, Imna I

    2015-10-06

    Trypanosomiasis is a neglected tropical disease caused by the trypanosome parasite and transmitted by the tsetse fly vector. In Sub-saharan Africa, both the human and animal variants of the disease are a great obstacle towards agriculture, development, and health. In order to better understand and therefore combat Trypanosomiasis, characterizing disease hotspots across species is critical. In this study, 193 samples from cattle, sheep, and goats were collected from eight sites. Samples were taken from animals belonging mostly to Maasai herdsmen in the Ngorongoro Crater Conservation Area (NCA) and analysed for the presence of trypanosomiasis infection using PCR techniques. Those that tested positive for T. brucei parasite were further tested using SRA LAMP technique to check for T. brucei rhodesiense, the human infective subspecies of parasite. Our study found a high incidence of Trypanosoma brucei infections across species. Of animals tested, 47 % of cattle, 91.7 % of sheep, and 60.8 % of goats were infected. Most of the infections were of the T. brucei species. We also identified sheep and goats as carriers of the T. brucei rhodesiense subspecies, which causes acute human trypanosomiasis. Together, these results point toward the need for stricter control strategies in the area to prevent disease outbreak.

  6. Beam Instrumentation and Diagnostics

    CERN Document Server

    Strehl, Peter

    2006-01-01

    This treatise covers all aspects of the design and the daily operations of a beam diagnostic system for a large particle accelerator. A very interdisciplinary field, it involves contributions from physicists, electrical and mechanical engineers and computer experts alike so as to satisfy the ever-increasing demands for beam parameter variability for a vast range of operation modi and particles. The author draws upon 40 years of research and work, most of them spent as the head of the beam diagnostics group at GSI. He has illustrated the more theoretical aspects with many real-life examples that will provide beam instrumentation designers with ideas and tools for their work.

  7. Diagnostic Imaging Workshop

    International Nuclear Information System (INIS)

    Sociedad Argentina de Fisica Medica

    2012-01-01

    The American Association of Physicist in Medicine (AAPM), the International Organization for Medical Physics (IOMP) and the Argentina Society of Medical Physics (SAFIM) was organized the Diagnostic Imaging Workshop 2012, in the city of Buenos Aires, Argentina. This workshop was an oriented training and scientific exchange between professionals and technicians who work in medical physics, especially in the areas of diagnostic imaging, nuclear medicine and radiotherapy, with special emphasis on the use of multimodal imaging for radiation treatment, planning as well of quality assurance associates.

  8. Structure-activity relationship study of sesquiterpene lactones and their semi-synthetic amino derivatives as potential antitrypanosomal products

    CSIR Research Space (South Africa)

    Zimmermann, S

    2014-03-01

    Full Text Available Stefanie Zimmermann 1,2, Gerda Fouché 3, Maria De Mieri 1, Yukiko Yoshimoto 4, Toyonobu Usuki 4, Rudzani Nthambeleni 3, Christopher J. Parkinson 5, Christiaan van der Westhuyzen 3, Marcel Kaiser 2,6, Matthias Hamburger 1 and Michael Adams 1,* 1... 1. Introduction Sleeping sickness, or human African trypanosomiasis (HAT), is a deadly protozoal disease caused by Trypanosoma brucei species spread by tsetse flies (Glossina spp.). The two human pathogenic subspecies, T. b. rhodesiense (95...

  9. Electron beam diagnostics study

    International Nuclear Information System (INIS)

    Garganne, P.

    1989-08-01

    This paper summarizes the results of a study on beam diagnostics, using carbon wire scanners and optical transition radiation (DTR) monitors. The main consideration consists in the material selection, taking their thermal properties and their effect on the beam into account [fr

  10. Molecular Beacons in Diagnostics

    OpenAIRE

    Tyagi, Sanjay; Kramer, Fred Russell

    2012-01-01

    Recent technical advances have begun to realize the potential of molecular beacons to test for diverse infections in clinical diagnostic laboratories. These include the ability to test for, and quantify, multiple pathogens in the same clinical sample, and to detect antibiotic resistant strains within hours. The design principles of molecular beacons have also spawned a variety of allied technologies.

  11. Diagnostic radiation and pregnancy

    International Nuclear Information System (INIS)

    Collins, L.; Fitzgerald, P.

    1983-01-01

    Accidental irradiation of the embryo or fetus in the first trimester is a problem which will occasionally occur. The value of a proper estimation of the radiation dose is emphasised. Very rarely does a single diagnostic procedure result in a uterine dose as high as 50 mGy. An accidental irradiation should rarely be cause for termination of a pregnancy

  12. Diagnostic imaging of craniopharyngioma

    International Nuclear Information System (INIS)

    Gradzki, J.; Nowak, S.; Paprzycki, W.

    1993-01-01

    40 patients have been examined with operational and histological confirmation of craniopharyngioma. CT image and X-ray plane of skull were performed in case all of these patients. TMR was conformed to examine 4 patients. X-ray planes was compared to CT. CT permits tumor cyst detection. The efficacy of mentioned above diagnostic techniques was compared with surgical findings. (author)

  13. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1996-04-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at LLNL from the early 1960's to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400 ns pulses. The Advanced Test Accelerator (ATA) built at Livermore's Site 300 produced 10,000 Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and LBNL. This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high current, short pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail

  14. Diagnostic studies in amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke Pier Cornelis

    2007-01-01

    In this thesis two diagnostic techniques are studied in amyloidosis. Systemic amyloidosis is characterized by deposition of amyloid fibrils (tiny fibres) throughout the body resulting in damage of vital organs. Amyloid can be detected in a tissue specimen stained with Congo red: red-stained amyloid

  15. 1968 Prototype Diagnostic Test.

    Science.gov (United States)

    Veterans Administration Hospital, Bedford, MA.

    This true-false diagnostic test was used for pretesting of employees at a Veterans Administration Hospital. The test is comprised of 20 items. An alternate test--Classification Questionnaire--was used for testing after remedial training. (For related document, see TM 002 334.) (DB)

  16. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1997-01-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at Lawrence Livermore National Laboratory (LLNL) from the early 1960s to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400-ns pulses. The Advanced Test Accelerator (ATA) built at Livermore close-quote s Site 300 produced 10,000-Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and Lawrence Berkeley National Laboratory (LBNL). This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high-current, short-pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail. copyright 1997 American Institute of Physics

  17. It's diagnostics, stupid.

    Science.gov (United States)

    Bernards, René

    2010-04-02

    To stem the spiraling cost of cancer treatment, a concerted effort is urgently needed to develop molecular diagnostics to better identify the patients that respond to expensive targeted therapies. Opportunities and obstacles in the development of such drug response biomarkers are discussed here. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Diagnostics for pellet experiments

    International Nuclear Information System (INIS)

    Johnson, R.R.

    1978-01-01

    The target diagnostics which are being used and planned in current laser driven ICF Experiments are described. Most of these diagnostics can be easily applied to future ion-beam fusion experiments. The status of laser fusion diagnostics has been much improved in the last 5 years and further improvements can be expected and should be available when the first ICF experiments using ion beams are performed. As an example, x-ray temporal and spatial resolutions are now approximately 5 psec and 3 μm, which is approximately a factor of 4 better than the resolution reported in the first implosion experiments. As one plans ahead for ion-beam fusion experiments it should be emphasized that high yield experiments are easier to diagnose provided adequate shielding is employed. However, in the event that the first high yield experiments fail it will be necessary to have diagnostics available to determine where the problems lie. In laser fusion it is interesting to note that higher laser powers are required now for breakeven experiments than first anticipated, mainly because some aspects of the laser-interaction physics were not recognized until the experiments were carefully diagnosed. Thus as has been pointed out, it may be necessary to increase the energy of the ion-beam driver to enable us to do breakeven experiments with high confidence

  19. Flowfield modeling and diagnostics

    International Nuclear Information System (INIS)

    Gupta, A.K.; Lilley, D.G.

    1985-01-01

    This textbook is devoted solely to flowfield modeling and diagnostics; their practical use, recent and current research, and projected developments and trends. It provides an account of the use of a broad range of techniques in industrial and research practice, both with and without combustion. Application ideas are complemented by details about experimental and modeling techniques

  20. Serbia : Systematic Country Diagnostic

    OpenAIRE

    World Bank Group

    2015-01-01

    This Systematic Country Diagnostic (SCD) aims to identify the major constraints on and opportunities for sustaining poverty reduction and shared prosperity in Serbia. The SCD serves as the analytic foundation on which the World Bank Group and the Government of Serbia will define a new Country Partnership Framework for FY2016 to FY2020. It is based on the best possible analysis, drawing on ...

  1. Diagnostic and interventional radiology

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, Thomas J. [Klinikum der Johann Wolfgang Goethe-Universitaet, Frankfurt am Main (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Reith, Wolfgang [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Klinik fuer Diagnostische und Interventionelle Neuroradiologie; Rummeny, Ernst J. (ed.) [Technische Univ. Muenchen Klinikum rechts der Isar, Muenchen (Germany). Inst. fuer Radiologie

    2016-08-01

    This exceptional book covers all aspects of diagnostic and interventional radiology within one volume, at a level appropriate for the specialist. From the basics through diagnosis to intervention: the reader will find a complete overview of all areas of radiology. The clear, uniform structure, with chapters organized according to organ system, facilitates the rapid retrieval of information. Features include: Presentation of the normal radiological anatomy Classification of the different imaging procedures according to their diagnostic relevance Imaging diagnosis with many reference images Precise description of the interventional options The inclusion of many instructive aids will be of particular value to novices in decision making: Important take home messages and summaries of key radiological findings smooth the path through the jungle of facts Numerous tables on differential diagnosis and typical findings in the most common diseases offer a rapid overview and orientation Diagnostic flow charts outline the sequence of diagnostic evaluation All standard procedures within the field of interventional radiology are presented in a clinically relevant and readily understandable way, with an abundance of illustrations. This is a textbook, atlas, and reference in one: with more than 2500 images for comparison with the reader's own findings. This comprehensive and totally up-to-date book provides a superb overview of everything that the radiology specialist of today needs to know.

  2. Tune-Based Halo Diagnostics

    International Nuclear Information System (INIS)

    Cameron, Peter

    2003-01-01

    Tune-based halo diagnostics can be divided into two categories -- diagnostics for halo prevention, and diagnostics for halo measurement. Diagnostics for halo prevention are standard fare in accumulators, synchrotrons, and storage rings, and again can be divided into two categories -- diagnostics to measure the tune distribution (primarily to avoid resonances), and diagnostics to identify instabilities (which will not be discussed here). These diagnostic systems include kicked (coherent) tune measurement, phase-locked loop (PLL) tune measurement, Schottky tune measurement, beam transfer function (BTF) measurements, and measurement of transverse quadrupole mode envelope oscillations. We refer briefly to tune diagnostics used at RHIC and intended for the SNS, and then present experimental results. Tune-based diagnostics for halo measurement (as opposed to prevention) are considerably more difficult. We present one brief example of tune-based halo measurement

  3. Beyond Diagnostic Accuracy: The Clinical Utility of Diagnostic Tests

    NARCIS (Netherlands)

    Bossuyt, Patrick M. M.; Reitsma, Johannes B.; Linnet, Kristian; Moons, Karel G. M.

    2012-01-01

    Like any other medical technology or intervention, diagnostic tests should be thoroughly evaluated before their introduction into daily practice. Increasingly, decision makers, physicians, and other users of diagnostic tests request more than simple measures of a test's analytical or technical

  4. Human and animal Trypanosomes in Côte d'Ivoire form a single breeding population.

    Directory of Open Access Journals (Sweden)

    Paul Capewell

    Full Text Available Trypanosoma brucei is the causative agent of African Sleeping Sickness in humans and contributes to the related veterinary disease, Nagana. T. brucei is segregated into three subspecies based on host specificity, geography and pathology. T. b. brucei is limited to animals (excluding some primates throughout sub-Saharan Africa and is non-infective to humans due to trypanolytic factors found in human serum. T. b. gambiense and T. b. rhodesiense are human infective sub-species. T. b. gambiense is the more prevalent human, causing over 97% of human cases. Study of T. b. gambiense is complicated in that there are two distinct groups delineated by genetics and phenotype. The relationships between the two groups and local T. b. brucei are unclear and may have a bearing on the evolution of the human infectivity traits.A collection of sympatric T. brucei isolates from Côte d'Ivoire, consisting of T. b. brucei and both groups of T. b. gambiense have previously been categorized by isoenzymes, RFLPs and Blood Incubation Infectivity Tests. These samples were further characterized using the group 1 specific marker, TgSGP, and seven microsatellites. The relationships between the T. b. brucei and T. b. gambiense isolates were determined using principal components analysis, neighbor-joining phylogenetics, STRUCTURE, FST, Hardy-Weinberg equilibrium and linkage disequilibrium.Group 1 T. b. gambiense form a clonal genetic group, distinct from group 2 and T. b. brucei, whereas group 2 T. b. gambiense are genetically indistinguishable from local T. b. brucei. There is strong evidence for mating within and between group 2 T. b. gambiense and T. b. brucei. We found no evidence to support the hypothesis that group 2 T. b. gambiense are hybrids of group 1 and T. b. brucei, suggesting that human infectivity has evolved independently in groups 1 and 2 T. b. gambiense.

  5. Cancer pancreatis, diagnostic procedures

    International Nuclear Information System (INIS)

    Graadal, Oe.; Schlichting, E.; Aasen, A.O.; Stadaas, J.O.

    1990-01-01

    151 patients treated for carcinoma of the pancreas at Ullevaal Hospital (Oslo University) during the period 1980-89 were studied. The most common initial symptom was abdominal pain. Other frequent debut symptoms were loss of weight and jaundice. ERCP and PTC were found to be the best diagnostic procedures. CT or ultrasonography were normal in 10-20% of the patients. Nearly all tumors of the pancreas were found by the ERCP procedure. Also angiography was used to evaluate operability of the pancreas tumor, but was found to be a very uncertain diagnostic method. This method will not be used in the future evaluation of patients with cancer of the pancreas. 13 refs., 1 fig., 2 tabs

  6. Inertial confinement fusion diagnostics

    International Nuclear Information System (INIS)

    Coleman, L.W.

    1986-10-01

    The concept and goals of ICF will be briefly reviewed and the new 100 kJ class Nova laser facility will be described. Experimental results obtained to date with Nova will be summarized, and the discussions of diagnostics will use examples on the present capabilities of Nova and new developments that are underway. The classes of diagnostic systems to be discussed fall into three basic categories: optical, x-ray, and particle. Examples of highly space resolved, time resolved, and spectrally resolved techniques as well as schemes involving combinations of these capabilities will be presented. A brief summary of the sophisticated acquisition and analysis system in use for Nova data will be provided

  7. Nanodevices in diagnostics

    Science.gov (United States)

    Hu, Ye; Fine, Daniel H.; Tasciotti, Ennio; Bouamrani, Ali; Ferrari, Mauro

    2010-01-01

    The real-time, personalized and highly sensitive early-stage diagnosis of disease remains an important challenge in modern medicine. With the ability to interact with matter at the nanoscale, the development of nanotechnology architectures and materials could potentially extend subcellular and molecular detection beyond the limits of conventional diagnostic modalities. At the very least, nanotechnology should be able to dramatically accelerate biomarker discovery, as well as facilitate disease monitoring, especially of maladies presenting a high degree of molecular and compositional heterogeneity. This article gives an overview of several of the most promising nanodevices and nanomaterials along with their applications in clinical practice. Significant work to adapt nanoscale materials and devices to clinical applications involving large interdisciplinary collaborations is already underway with the potential for nanotechnology to become an important enabling diagnostic technology. PMID:20229595

  8. Nanobiosensors in diagnostics

    Directory of Open Access Journals (Sweden)

    Alejandro Chamorro-Garcia

    2016-11-01

    Full Text Available Medical diagnosis has been greatly improved thanks to the development of new techniques capable of performing very sensitive detection and quantifying certain parameters. These parameters can be correlated with the presence of specific molecules and their quantity. Unfortunately, these techniques are demanding, expensive, and often complicated. On the other side, progress in other fields of science and technology has contributed to the rapid growth of nanotechnology. Although being an emerging discipline, nanotechnology has raised huge interest and expectations. Most of the enthusiasm comes from new possibilities and properties of nanomaterials. Biosensors (simple, robust, sensitive, cost-effective combined with nanomaterials, also called nanobiosensors, are serving as bridge between advanced detection/diagnostics and daily/routine tests. Here we review some of the latest applications of nanobiosensors in diagnostics field.

  9. Diagnostic radiation risks

    Energy Technology Data Exchange (ETDEWEB)

    Sherwood, T [Addenbrooke' s Hospital, Cambridge (UK)

    1980-04-01

    A brief discussion on diagnostic radiation risks is given. First some fundamental facts on the concepts and units of radiation measurement are clarified. Medical diagnostic radiation doses are also compared to the radiation doses received annually by man from natural background radiation. The controversy concerning the '10-day rule' in X-raying women of child-bearing age is discussed; it would appear that the risk of malformation in an unborn child due to X-radiation is very much less than the natural level of risk of malformation. The differences in the radiographic techniques and thus the different X-ray doses needed to make adequate X-ray images of different parts of the body are considered. The radiation burden of nuclear medicine investigations compared to X-ray procedures is also discussed. Finally, the problems of using volunteers in radiation research are aired.

  10. Diagnostics and structure

    International Nuclear Information System (INIS)

    Vial, J.C.

    1986-01-01

    The structure of prominences and the diagnostic techniques used to evaluate their physical parameters are discussed. These include electron temperature, various densities (n sub p, n sub e, n sub l), ionization degree, velocities, and magnetic field vector. UV and radio measurements have already evidenced the existence of different temperature regions, corresponding to different geometrical locations, e.g., the so called Prominence-Corona (P-C) interface. Velocity measurements are important for considering formation and mass balance of prominences but there are conflicting velocity measurements which have led to the basic question: what structure is actually observed at a given wavelength; what averaging is performed within the projected slit area during the exposure time? In optically thick lines, the question of the formation region of the radiation along the line of sight is also not a trivial one. The same is true for low resolution measurements of the magnetic field. Coupling diagnostics with structure is now a general preoccupation

  11. FEL components and diagnostics

    International Nuclear Information System (INIS)

    Carr, R.

    1997-01-01

    FEL hardware includes undulators, alignment systems, electron beam diagnostics, and mechanical and vacuum systems. While most FEL close-quote s employ conventional undulators, there is some interest in novel types, particularly where conventional designs cannot be used, as at very short periods and high fields. For these areas, superconducting technology is indicated. The most serious issue facing long FEL undulators is that of alignment; mechanical techniques may not be accurate enough, and beam-based strategies must be considered. To maintain alignment and control the electron trajectory, beam position monitors with micron precision are required. Beam size monitors are also required to assure control of emittance. The talks given in the working group sessions touch on undulators, alignment, and electron beam diagnostics, and they are summarized here. copyright 1997 American Institute of Physics

  12. Litigations in diagnostic radiology

    International Nuclear Information System (INIS)

    Patil, Ranjit

    2014-01-01

    There are various regulatory bodies at the international and national level, which lay down norms for radiation protection. These are the International Commission for Radiation Protection (ICRP) the National Commission for Radiation Protection (NCRP) in America, and the Atomic Energy Regulatory Board (AERB) in India. These bodies recommend norms on various radiation issues. Radiography and radiology are two key tools for diagnosing and treating diseases. Recently there are concerns about the effect of ionizing radiation on man and the frequent use of diagnostic radiographs. The professionals are expected to conduct their actions according to guidelines which reflect new information and changing technology in diagnostic radiography. Failure to do so may have severe legal consequences. Patient protection is a matter of normal course but knowledge and awareness of the legal issues is important to avoid legal hassles. Implications of the radiation protection guidelines are discussed. (author)

  13. STELLA Experiment - Microbunch Diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    He, P.; Liu, Y.; Cline, D. B.; Babzien, M.; Gallardo, J. C.; Kusche, K. P.; Pogorelsky, I. V.; Skaritka, J.; van Steenbergen, A.; Yakimenko, V.; Kimura, W. D.

    1998-07-01

    A microbunch diagnostic system is built at the Accelerator Test Facility (ATF) of Brookhaven National Laboratory for monitoring microbunches (10-fs bunch length) produced by the Inverse Free Electron Laser accelerator in Staged Electron Laser Acceleration experiment. It is similar to one already demonstrated at the ATF. With greatly improved beam optics conditions higher order harmonic coherent transition radiation will be measurable to determine the microbunch length and shape.

  14. Advanced diagnostic graphics

    International Nuclear Information System (INIS)

    Bray, M.A.; Petersen, R.J.; Clark, M.T.; Gertman, D.I.

    1981-01-01

    This paper reports US NRC-sponsored research at the Idaho National Engineering Laboratory (INEL) involving evaluation of computer-based diagnostic graphics. The specific targets of current evaluations are multivariate data display formats which may be used in Safety Parameter Display Systems (SPDS) being developed for nuclear power plant control rooms. The purpose of the work is to provide a basis for NRC action in regulating licensee SPDSs or later computer/cathode ray tube (CRT) applications in nuclear control rooms

  15. Molecular diagnostics in endodontics

    OpenAIRE

    Rechenberg, Dan-Krister; Zehnder, Matthias

    2014-01-01

    Recent systematic reviews have substantiated the fact that current testing methods to assess the inflammatory state of the pulp and the periapical tissues are of limited value. Consequently, it may be time to search for alternative routes in endodontic diagnostics. Molecular assessment methods could be the future. However, in the field of endodontics, the research in that direction is only about to evolve. Because pulpal and periradicular diseases are related to opportunistic infections, diag...

  16. Molecular Diagnostics of ?-Thalassemia

    OpenAIRE

    Atanasovska, B; Bozhinovski, G; Chakalova, L; Kocheva, S; Karanfilski, O; Plaseska-Karanfiska, D

    2012-01-01

    A high-quality hemoglobinopathy diagnosis is based on the results of a number of tests including assays for molecular identification of causative mutations. We describe the current diagnostic strategy for the identification of ?-thalassemias and hemoglobin (Hb) variants at the International Reference Laboratory for Haemoglobinopathies, Research Centre for Genetic Engineering and Biotechnology (RCGEB) ?Georgi D. Efremov,? Skopje, Republic of Macedonia. Our overall approach and most of the meth...

  17. Equipment for isotope diagnostics

    International Nuclear Information System (INIS)

    Platz, W.

    1976-01-01

    The invention concerns an improvement of equipment for isotope diagnostics allowing to mark special intensity ranges of the recorded measurements by means of different colors. For undisturbed operation it is of advantage to avoid electric circuits between movable and unmovable parts of the color recorder. According to the invention, long gear wheels of glass fiber-reinforced polyamide are used for these connections. (ORU) [de

  18. RFQ1 diagnostic devices

    International Nuclear Information System (INIS)

    Chidley, B.G.; Arbique, G.M.; de Jong, M.S.; McMichael, G.E.; Michel, W.L.; Smith, B.H.

    1991-01-01

    The diagnostic devices in use on RFQ1 will be described. They consist of a double-slit emittance-measuring unit, a 45 degree deflection energy-analysis magnet, parametric current transformers, optical beam sensors, beam-stop current monitors, and an x-ray end-point analyzer. All of these devices are able to operate up to the full output current of RFQ1 (75 mA cw at 0.6 MeV)

  19. Idiopathic chondrolysis - diagnostic difficulties

    International Nuclear Information System (INIS)

    Kozlowski, K.; Scougall, J.; Royal Alexandra Hospital for Children, Sydney

    1984-01-01

    Four cases of idiopathic chondrolysis of the hip in three white girls and one Maori girl are reported. The authors stress the causes why a disease with characteristic clinical and radiographic appearances and normal biochemical findings presents diagnostic difficulties. It is suspected that idiopathic chondrolysis is a metabolic disorder of chondrocytes, triggered by environment circumstances in susceptible individuals. Idiopathic chondrolysis is probably one of the most common causes of coxarthrosis in women. (orig.)

  20. Radiological diagnostics in hyperparathyroidism

    International Nuclear Information System (INIS)

    Moedder, U.; Kuhn, F.P.; Gruetzner, G.

    1991-01-01

    The most important radiologically detectable effects of the primary and secondary hyperparathyroidism of the skeletal system and the periarticular soft tissue structures are presented. In the following sensitivity and specificity of radiological imaging - sonography, scintigraphy, computed tomography, magnetic resonance imaging, arteriography and selective venous sampling - in the preoperative diagnostic of the parathyroid adenomas are discussed. Therefore, radiological imaging can be omitted before primary surgery. It was only in secondary surgery that radiological process proved useful and a guide during surgical intervention. (orig.) [de

  1. Thioaptamer Diagnostic System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — AM Biotechnologies (AM) will develop a diagnostic system in response to SBIR Topic X10.01 Reusable Diagnostic Lab Technology that will simultaneously detect and...

  2. Molecular diagnostics of periodontitis.

    Science.gov (United States)

    Korona-Głowniak, Izabela; Siwiec, Radosław; Berger, Marcin; Malm, Anna; Szymańska, Jolanta

    2017-01-28

    The microorganisms that form dental plaque are the main cause of periodontitis. Their identification and the understanding of the complex relationships and interactions that involve these microorganisms, environmental factors and the host's health status enable improvement in diagnostics and targeted therapy in patients with periodontitis. To this end, molecular diagnostics techniques (both techniques based on the polymerase chain reaction and those involving nucleic acid analysis via hybridization) come increasingly into use. On the basis of a literature review, the following methods are presented: polymerase chain reaction (PCR), real-time polymerase chain reaction (real-time PCR), 16S rRNA-encoding gene sequencing, checkerboard and reverse-capture checkerboard hybridization, microarrays, denaturing gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE), as well as terminal restriction fragment length polymorphism (TRFLP) and next generation sequencing (NGS). The advantages and drawbacks of each method in the examination of periopathogens are indicated. The techniques listed above allow fast detection of even small quantities of pathogen present in diagnostic material and prove particularly useful to detect microorganisms that are difficult or impossible to grow in a laboratory.

  3. Molecular diagnostics of periodontitis

    Directory of Open Access Journals (Sweden)

    Izabela Korona-Głowniak

    2017-01-01

    Full Text Available The microorganisms that form dental plaque are the main cause of periodontitis. Their identification and the understanding of the complex relationships and interactions that involve these microorganisms, environmental factors and the host’s health status enable improvement in diagnostics and targeted therapy in patients with periodontitis. To this end, molecular diagnostics techniques (both techniques based on the polymerase chain reaction and those involving nucleic acid analysis via hybridization come increasingly into use. On the basis of a literature review, the following methods are presented: polymerase chain reaction (PCR, real-time polymerase chain reaction (real-time PCR, 16S rRNA-encoding gene sequencing, checkerboard and reverse-capture checkerboard hybridization, microarrays, denaturing gradient gel electrophoresis (DGGE, temperature gradient gel electrophoresis (TGGE, as well as terminal restriction fragment length polymorphism (TRFLP and next generation sequencing (NGS. The advantages and drawbacks of each method in the examination of periopathogens are indicated. The techniques listed above allow fast detection of even small quantities of pathogen present in diagnostic material and prove particularly useful to detect microorganisms that are difficult or impossible to grow in a laboratory.

  4. XML Diagnostics Description Standard

    International Nuclear Information System (INIS)

    Neto, A.; Fernandes, H.; Varandas, C.; Lister, J.; Yonekawa, I.

    2006-01-01

    A standard for the self-description of fusion plasma diagnostics will be presented, based on the Extensible Markup Language (XML). The motivation is to maintain and organise the information on all the components of a laboratory experiment, from the hardware to the access security, to save time and money when problems arises. Since there is no existing standard to organise this kind of information, every Association stores and organises each experiment in different ways. This can lead to severe problems when the organisation schema is poorly documented or written in national languages. The exchange of scientists, researchers and engineers between laboratories is a common practice nowadays. Sometimes they have to install new diagnostics or to update existing ones and frequently they lose a great deal of time trying to understand the currently installed system. The most common problems are: no documentation available; the person who understands it has left; documentation written in the national language. Standardisation is the key to solving all the problems mentioned. From the commercial information on the diagnostic (component supplier; component price) to the hardware description (component specifications; drawings) to the operation of the equipment (finite state machines) through change control (who changed what and when) and internationalisation (information at least in the native language and in English), a common XML schema will be proposed. This paper will also discuss an extension of these ideas to the self-description of ITER plant systems, since the problems will be identical. (author)

  5. SNS Diagnostics Timing Integration

    CERN Document Server

    Long, Cary D; Murphy, Darryl J; Pogge, James; Purcell, John D; Sundaram, Madhan

    2005-01-01

    The Spallation Neutron Source (SNS) accelerator systems will deliver a 1.0 GeV, 1.4 MW proton beam to a liquid mercury target for neutron scattering research. The accelerator complex consists of a 1 GeV linear accelerator, an accumulator ring and associated transport lines. The SNS diagnostics platform is PC-based running Windows XP Embedded for its OS and LabVIEW as its programming language. Coordinating timing among the various diagnostics instruments with the generation of the beam pulse is a challenging task that we have chosen to divide into three phases. First, timing was derived from VME based systems. In the second phase, described in this paper, timing pulses are generated by an in house designed PCI timing card installed in ten diagnostics PCs. Using fan-out modules, enough triggers were generated for all instruments. This paper describes how the Timing NAD (Network Attached Device) was rapidly developed using our NAD template, LabVIEW's PCI driver wizard, and LabVIEW Channel Access library. The NAD...

  6. Radiological diagnostics of skeletal tumors

    International Nuclear Information System (INIS)

    Uhl, M.; Herget, G.W.

    2008-01-01

    The book contains contributions concerning the following topics: 1. introduction and fundamentals: WHO classification of bone tumors, imaging diagnostics and their function; localization, typical clinical and radiological criteria, TNM classification and status classification, invasive tumor diagnostics; 2. specific tumor diagnostics: chondrogenic bone tumors, osseous tumors, connective tissue bony tumors, osteoclastoma, osteomyelogenic bone tumors, vascular bone tumors, neurogenic bone tumors, chordoma; adamantinoma of the long tubular bone; tumor-like lesions, bony metastases, bone granulomas, differential diagnostics: tumor-like lesions

  7. The architecture of diagnostic research

    DEFF Research Database (Denmark)

    Colli, Agostino; Fraquelli, Mirella; Casazza, Giovanni

    2014-01-01

    The diagnostic research process can be divided into five phases, designed to establish the clinical utility of a new diagnostic test - the index test. The aim of the present review is to illustrate the study designs that are appropriate for each diagnostic phase, using clinical examples regarding...

  8. 2012 HIV Diagnostics Conference: the molecular diagnostics perspective.

    Science.gov (United States)

    Branson, Bernard M; Pandori, Mark

    2013-04-01

    2012 HIV Diagnostic Conference Atlanta, GA, USA, 12-14 December 2012. This report highlights the presentations and discussions from the 2012 National HIV Diagnostic Conference held in Atlanta (GA, USA), on 12-14 December 2012. Reflecting changes in the evolving field of HIV diagnostics, the conference provided a forum for evaluating developments in molecular diagnostics and their role in HIV diagnosis. In 2010, the HIV Diagnostics Conference concluded with the proposal of a new diagnostic algorithm which included nucleic acid testing to resolve discordant screening and supplemental antibody test results. The 2012 meeting, picking up where the 2010 meeting left off, focused on scientific presentations that assessed this new algorithm and the role played by RNA testing and new developments in molecular diagnostics, including detection of total and integrated HIV-1 DNA, detection and quantification of HIV-2 RNA, and rapid formats for detection of HIV-1 RNA.

  9. MAST magnetic diagnostics

    Science.gov (United States)

    Edlington, T.; Martin, R.; Pinfold, T.

    2001-01-01

    The mega-ampere spherical tokamak (MAST) experiment is a new, large, low aspect ratio device (R=0.7-0.8 m, a=0.5-0.65 m, maximum BT˜0.63 T at R=0.7 m) operating its first experimental physics campaign. Designed to study a wide variety of plasma shapes with up to 2 MA of plasma current with an aspect ratio down to 1.3, the poloidal field (PF) coils used for plasma formation, equilibrium and shaping are inside the main vacuum vessel. For plasma control and to investigate a wide range of plasma phenomena, an extensive set of magnetic diagnostics have been installed inside the vacuum vessel. More than 600 vacuum compatible, bakeable diagnostic coils are configured in a number of discrete arrays close to the plasma edge with about half the coils installed behind the graphite armour tiles covering the center column. The coil arrays measure the toroidal and poloidal variation in the equilibrium field and its high frequency fluctuating components. Internal coils also measure currents in the PF coils, plasma current, stored energy and induced currents in the mechanical support structures of the coils and graphite armour tiles. The latter measurements are particularly important when halo currents are induced following a plasma termination, for example, when the plasma becomes vertically unstable. The article describes the MAST magnetic diagnostic coil set and their calibration. The way in which coil signals are used to control the plasma equilibrium is described and data from the first MAST experimental campaign presented. These coil data are used as input to the code EFIT [L. Lao et al., Nucl. Fusion 25, 1611 (1985)], for measurement of halo currents in the vacuum vessel structure and for measurements of the structure of magnetic field fluctuations near the plasma edge.

  10. Planetary Transmission Diagnostics

    Science.gov (United States)

    Lewicki, David G. (Technical Monitor); Samuel, Paul D.; Conroy, Joseph K.; Pines, Darryll J.

    2004-01-01

    This report presents a methodology for detecting and diagnosing gear faults in the planetary stage of a helicopter transmission. This diagnostic technique is based on the constrained adaptive lifting algorithm. The lifting scheme, developed by Wim Sweldens of Bell Labs, is a time domain, prediction-error realization of the wavelet transform that allows for greater flexibility in the construction of wavelet bases. Classic lifting analyzes a given signal using wavelets derived from a single fundamental basis function. A number of researchers have proposed techniques for adding adaptivity to the lifting scheme, allowing the transform to choose from a set of fundamental bases the basis that best fits the signal. This characteristic is desirable for gear diagnostics as it allows the technique to tailor itself to a specific transmission by selecting a set of wavelets that best represent vibration signals obtained while the gearbox is operating under healthy-state conditions. However, constraints on certain basis characteristics are necessary to enhance the detection of local wave-form changes caused by certain types of gear damage. The proposed methodology analyzes individual tooth-mesh waveforms from a healthy-state gearbox vibration signal that was generated using the vibration separation (synchronous signal-averaging) algorithm. Each waveform is separated into analysis domains using zeros of its slope and curvature. The bases selected in each analysis domain are chosen to minimize the prediction error, and constrained to have the same-sign local slope and curvature as the original signal. The resulting set of bases is used to analyze future-state vibration signals and the lifting prediction error is inspected. The constraints allow the transform to effectively adapt to global amplitude changes, yielding small prediction errors. However, local wave-form changes associated with certain types of gear damage are poorly adapted, causing a significant change in the

  11. Biotechnology in diagnostics

    International Nuclear Information System (INIS)

    Koprowski, H.; Ferrone, S.; Albertini, A.

    1985-01-01

    In recent years much progress has been made in the area of biotechnology. The cellular and molecular cloning methodology to develop monoclonal antibodies and DNA probes have been extensively utilized in basic and clinical research. These investigations have provided the necessary information to apply these reagents to diagnostic problems. The RIA 85 meeting focused on the application of monoclonal antibodies and DNA probes in laboratory medicine. The papers presented at this meeting clearly indicate that biotechnology has already had a significant impact on clinical medicine. (Auth.)

  12. Bouveret's Syndrome: diagnostic considerations

    International Nuclear Information System (INIS)

    Cooper, S.G.; Sherman, S.B.; Steinhardt, J.E.; Wilson, J.M. Jr.; Richman, A.H.

    1987-01-01

    Bouveret's syndrome is a rare disease entity manifested by the formation of a cholecystoduodenal or choledochoduodenal fistula with passage of a gallstone into the duodenal bulb and subsequent obstruction of the gastric outlet. To date, no report of this entity using computed tomographic (CT) imaging is available. This article presents a case of Bouveret's syndrome with the classic findings on upper gastrointestinal (GI) tract series and a description of the CT manifestations. The literature is reviewed with discussion of the diagnostic approach to patients with Bouveret's syndrome

  13. FASTBUS Snoop Diagnostic Module

    International Nuclear Information System (INIS)

    Walz, H.V.; Downing, R.

    1980-11-01

    Development of the FASTBUS Snoop Module, undertaken as part of the prototype program for the new interlaboratory data bus standard, is described. The Snoop Module resides on a FASTBUS crate segment and provides diagnostic monitoring and testing capability. Communication with a remote host computer is handled independent of FASTBUS through a serial link. The module consists of a high-speed ECL front-end to monitor and single-step FASTBUS cycles, a master-slave interface, and a control microprocessor with serial communication ports. Design details and performance specifications of the prototype module are reported. 9 figures, 1 table

  14. Isotope diagnostics apparatus

    International Nuclear Information System (INIS)

    Herrschaft, H.

    1976-01-01

    The invention relates to a measuring probe for an isotope diagnostics apparatus to determine the distribution of radioactive substances in a body by measuring the radiation emanating from this body by means of a multiplicity of measuring probes directed simultaneously towards areas of measuring surfae and carried in guidances of a holding block. The measuring results of the individual probes are recorded separately, thus allowing the possibility of being evaluated separately, too. Measuring probes of this kind are used in multi-channel measuring objects and are useful particularly for determining the regional cerebral blood flow. (orig./ORU) [de

  15. Vibration control, machine diagnostics

    International Nuclear Information System (INIS)

    1990-01-01

    Changing vibrations announce damage in the form of wear or cracks on components of, e.g., engine rotors, pumps, power plant turbo sets, rounding-up tools, or marine diesel engines. Therefore, machine diagnostics use frequency analyses, system tests, trend analyses as well as expert systems to localize or estimate the causes of these damages and malfunctions. Data acquisistion, including not only sensors, but also reliable and redundant data processing systems and analyzing systems, play an important role. The lectures pertaining to the data base are covered in detail. (DG) [de

  16. Diagnostic radiology 1987

    International Nuclear Information System (INIS)

    Margulis, A.R.; Gooding, C.A.

    1987-01-01

    This is the latest version of the continuing education course on diagnostic radiology given yearly by the Department of Radiology at the University of California, San Francisco. The lectures are grouped into sections on gastrointestinal radiology, mammography, uroradiology, magnetic resonance, hepatobiliary radiology, pediatric radiology, ultrasound, interventional radiology, chest radiology, nuclear medicine, cardiovascular radiology, and skeletal radiology. Each section contains four to eight topics. Each of these consists of text that represents highlights in narrative form, selected illustrations, and a short bibliography. The presentation gives a general idea of what points were made in the lecture

  17. Nuclear power plant diagnostics

    International Nuclear Information System (INIS)

    Hollo, E.; Siklossy, P.

    1982-01-01

    The cooling circuit vibration diagnostic system of the Block 1 of the Paks nuclear power station is described. The automatic online vibration monitoring system consisting presently of 42 acceleration sensors and 9 pressure fluctuation sensors, which could be extended, performs both global and local inspection of the primary cooling circuit and its components. The offline data processing system evaluates the data for failure mode analysis. The software under development will be appropriate for partial preliminary identification of failure reasons during their initial phases. The installation experiences and the preliminary results during the hot operational testing of Block 1 are presented. (Sz.J.)

  18. Thermal diagnostics for LTP

    International Nuclear Information System (INIS)

    Lobo, Alberto; Nofrarias, M; Sanjuan, J

    2005-01-01

    This is a short note reporting on the current state of development of the temperature sensors which are part of the LTP Diagnostics Subsystem on board the LISA Pathfinder mission (LPF). A thermal insulator has been designed which ensures sufficient stability of a set of eight NTC sensors (negative temperature coefficient of resistance or thermistors), and the front-end electronics has also been designed and manufactured. Tests have been performed which nearly approach the goal of a global stability of 10 -5 K Hz -1/2

  19. Diagnostic Technologies in Practice

    Science.gov (United States)

    Steinberg, Malcolm; Kwag, Michael; Chown, Sarah A.; Doupe, Glenn; Trussler, Terry; Rekart, Michael; Gilbert, Mark

    2015-01-01

    Diagnosing HIV-positive gay men through enhanced testing technologies that detect acute HIV infection (AHI) or recent HIV infection provides opportunities for individual and population health benefits. We recruited 25 men in British Columbia who received an acute (n = 13) or recent (n = 12) HIV diagnosis to engage in a longitudinal multiple-methods study over one year or longer. Our thematic analysis of baseline qualitative interviews revealed insights within men’s accounts of technologically mediated processes of HIV discovery and diagnosis. Our analysis illuminated the dialectic of new HIV technologies in practice by considering the relationship between advances in diagnostics (e.g., nucleic acid amplification tests) and the users of these medical technologies in clinical settings (e.g., clients and practitioners). Technological innovations and testing protocols have shifted experiences of learning of one’s HIV-positive status; these innovations have created new diagnostic categories that require successful interpretation and translation to be rendered meaningful, to alleviate uncertainty, and to support public health objectives. PMID:25201583

  20. Shiva optical diagnostics

    International Nuclear Information System (INIS)

    Rienecker, F.; Kobierecki, M.; Ozarski, R.; Seppala, L.; Manes, K.; Merritt, B.

    1977-01-01

    In the laser fusion program at Lawrence Livermore Laboratory, no target experiment is complete unless it is complemented by careful measurements of the laser pulse that irradiates the target. For this purpose, an incident beam diagnostics (IBD) package has been designed for the Shiva laser. The package will furnish data on items such as the total energy and the focusable energy out of the laser chain, and the spatial and temporal energy and power distribution at the target plane. Understanding laser-plasma interactions requires knowledge of the amount of 1.06 μm light energy that is scattered in various directions from the target. The light energy that is scattered toward the beam focusing lens is analyzed by a reflected beam diagnostic (RBD) package containing a calorimeter, a multiple image camera and a TV camera. This paper describes the detailed design and operation of the IBD and RBD packages as tools to align spatial filters and targets, as well as to diagnose the laser beams and target reflectivity

  1. Laser fusion diagnostics

    International Nuclear Information System (INIS)

    Coleman, L.W.

    1978-01-01

    The current status of the capability of laser fusion diagnostics is reviewed. Optical and infrared streak cameras provide one time resolution measurement capability of less than 10 ps, while x-ray streak cameras provide 15 ps time resolution in the range of about 1--30 keV presently. Time integrated spatial resolutions of 1 μm are provided with a variety of optical techniques. Ultraviolet holographic interferometry has measured electron densities above 10 21 cm -3 with 1 μm spatial resolution and 15 ps temporal resolution. X-ray microscopes provide 3 μm time integrated resolution and the x-ray streak pinhole camera has 6 μm spatial resolution. Development of the framing camera has thus far provided 50 μm spatial resolution with 125 ps frame duration and the third order reconstruction of zone plate images has provided 3 μm resolutions for alpha particles. Time integrated measurements of x-rays span the range shown. Finally, the new Shiva neutron spectrometer increases the energy resolution capability of that technique to 25 keV for 14-MeV neutrons. These combined capabilities provide a unique set of diagnostics for the detailed measurement of the interaction of laser light with targets and a subsequent performance of those targets

  2. Reflectometry diagnostics on TCV

    Science.gov (United States)

    Molina Cabrera, Pedro; Coda, Stefano; Porte, Laurie; Offeddu, Nicola; Tcv Team

    2017-10-01

    Both profile reflectometer and Doppler back-scattering (DBS) diagnostics are being developed for the TCV Tokamak using a steerable quasi-optical launcher and universal polarizers. First results will be presented. A pulse reflectometer is being developed to complement Thomson Scattering measurements of electron density, greatly increasing temporal resolution and also effectively enabling fluctuation measurements. Pulse reflectometry consists of sending short pulses of varying frequency and measuring the roundtrip group-delay with precise chronometers. A fast arbitrary waveform generator is used as a pulse source feeding frequency multipliers that bring the pulses to V-band. A DBS diagnostic is currently operational in TCV. DBS may be used to infer the perpendicular velocity and wave number spectrum of electron density fluctuations in the 3-15 cm-1 wave-number range. Off-the-shelf transceiver modules, originally used for VNA measurements, are being used in a Doppler radar configuration. See author list of S. Coda et al., 2017 Nucl. Fusion 57 102011.

  3. Radiation hardening of diagnostics

    International Nuclear Information System (INIS)

    Siemon, R.E.

    1991-01-01

    The world fusion program has advanced to the stage where it is appropriate to construct a number of devices for the purpose of burning DT fuel. In these next-generation experiments, the expected flux and fluence of 14 MeV neutrons and associated gamma rays will pose a significant challenge to the operation and diagnostics of the fusion device. Radiation effects include structural damage to materials such as vacuum windows and seals, modifications to electrical properties such as electrical conductivity and dielectric strength and impaired optical properties such as reduced transparency and luminescence of windows and fiber optics during irradiation. In preparation for construction and operation of these new facilities, the fusion diagnostics community needs to work with materials scientists to develop a better understanding of radiation effects, and to undertake a testing program aimed at developing workable solutions for this multi-faceted problem. A unique facility to help in this regard is the Los Alamos Spallation Radiation Effects Facility, a neutron source located at the beam stop of the world's most powerful accelerator, the Los Alamos Meson Physics Facility (LAMPF). The LAMPF proton beam generates 10 16 neutrons per second because of ''spallation'' reactions when the protons collide with the copper nuclei in the beam stop

  4. Climate Model Diagnostic Analyzer

    Science.gov (United States)

    Lee, Seungwon; Pan, Lei; Zhai, Chengxing; Tang, Benyang; Kubar, Terry; Zhang, Zia; Wang, Wei

    2015-01-01

    The comprehensive and innovative evaluation of climate models with newly available global observations is critically needed for the improvement of climate model current-state representation and future-state predictability. A climate model diagnostic evaluation process requires physics-based multi-variable analyses that typically involve large-volume and heterogeneous datasets, making them both computation- and data-intensive. With an exploratory nature of climate data analyses and an explosive growth of datasets and service tools, scientists are struggling to keep track of their datasets, tools, and execution/study history, let alone sharing them with others. In response, we have developed a cloud-enabled, provenance-supported, web-service system called Climate Model Diagnostic Analyzer (CMDA). CMDA enables the physics-based, multivariable model performance evaluations and diagnoses through the comprehensive and synergistic use of multiple observational data, reanalysis data, and model outputs. At the same time, CMDA provides a crowd-sourcing space where scientists can organize their work efficiently and share their work with others. CMDA is empowered by many current state-of-the-art software packages in web service, provenance, and semantic search.

  5. Thioaptamer Diagnostic System (TDS)

    Science.gov (United States)

    Yang, Xianbin

    2015-01-01

    AM Biotechnologies, LLC, in partnership with Sandia National Laboratories, has developed a diagnostic device that quickly detects sampled biomarkers. The TDS quickly quantifies clinically relevant biomarkers using only microliters of a single sample. The system combines ambient-stable, long shelf-life affinity assays with handheld, microfluidic gel electrophoresis affinity assay quantification technology. The TDS is easy to use, operates in microgravity, and permits simultaneous quantification of 32 biomarkers. In Phase I of the project, the partners demonstrated that a thioaptamer assay used in the microfluidic instrument could quantify a specific biomarker in serum in the low nanomolar range. The team also identified novel affinity agents to bone-specific alkaline phosphatase (BAP) and demonstrated their ability to detect BAP with the microfluidic instrument. In Phase II, AM Biotech expanded the number of ambient affinity agents and demonstrated a TDS prototype. In the long term, the clinical version of the TDS will provide a robust, flight-tested diagnostic capability for space exploration missions.

  6. Encyclopedia of diagnostic imaging

    International Nuclear Information System (INIS)

    Baert, A.L.

    2008-01-01

    The simple A to Z format provides easy access to relevant information in the field of imaging. Extensive cross references between keywords and related articles enable efficient searches in a user-friendly manner. Fully searchable and hyperlinked electronic online edition. The aim of this comprehensive encyclopedia is to provide detailed information on diagnostic radiology contributing to the broad field of imaging. The wide range of entries are written by leading experts. They will provide basic and clinical scientists in academia, practice and industry with valuable information about the field of diagnostic imaging. Those in related fields, students, teachers, and interested laypeople will also benefit from the important and relevant information on the most recent developments. Please note that this publication is available as print only or online only or print + online set. Save 75% of the online list price when purchasing the bundle. For more information on the online version please type the publication title into the search box above, then click on the eReference version in the results list. (orig.)

  7. Plasma diagnostics on large tokamaks

    International Nuclear Information System (INIS)

    Orlinskij, D.V.; Magyar, G.

    1988-01-01

    The main tasks of the large tokamaks which are under construction (T-15 and Tore Supra) and of those which have already been built (TFTR, JET, JT-60 and DIII-D) together with their design features which are relevant to plasma diagnostics are briefly discussed. The structural features and principal characteristics of the diagnostic systems being developed or already being used on these devices are also examined. The different diagnostic methods are described according to the physical quantities to be measured: electric and magnetic diagnostics, measurements of electron density, electron temperature, the ion components of the plasma, radiation loss measurements, spectroscopy of impurities, edge diagnostics and study of plasma stability. The main parameters of the various diagnostic systems used on the six large tokamaks are summarized in tables. (author). 351 refs, 44 figs, 22 tabs

  8. Cognitive aspect of diagnostic errors.

    Science.gov (United States)

    Phua, Dong Haur; Tan, Nigel C K

    2013-01-01

    Diagnostic errors can result in tangible harm to patients. Despite our advances in medicine, the mental processes required to make a diagnosis exhibits shortcomings, causing diagnostic errors. Cognitive factors are found to be an important cause of diagnostic errors. With new understanding from psychology and social sciences, clinical medicine is now beginning to appreciate that our clinical reasoning can take the form of analytical reasoning or heuristics. Different factors like cognitive biases and affective influences can also impel unwary clinicians to make diagnostic errors. Various strategies have been proposed to reduce the effect of cognitive biases and affective influences when clinicians make diagnoses; however evidence for the efficacy of these methods is still sparse. This paper aims to introduce the reader to the cognitive aspect of diagnostic errors, in the hope that clinicians can use this knowledge to improve diagnostic accuracy and patient outcomes.

  9. Generator for radiological diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Seissl, J; Broenner, K; Krause, H

    1978-10-02

    A generator is described for X-ray diagnostics, with a high-voltage transformer with a primary coil connected or with the grid and a secondary coil feeding the X-ray tube and with a rectifier bridge situated in the primary circuit of the high-voltage transformer. The direct current branch of the rectifier bridge contains a filter capacitor and a thyristor which is opened and closed by means of a pulse duty factor determining the capacitor voltage and thus the voltage of the X-ray tube. An LC-tuned circuit is connected to the thyristor whose capacity is discharged to the conductive thyristor so that the thyristor is quenched via a free-wheel diode arranged in parallel to the thyristor. In this way, a high switching frequency of the thyristor and, consequently, a low ripple of the X-ray tube voltage is obtained.

  10. Molecular diagnostic PCR handbook

    International Nuclear Information System (INIS)

    Viljoen, G.J.; Crowther, J.R.; Nel, L.H.

    2005-01-01

    The uses of nucleic acid-directed methods have increased significantly in the past five years and have made important contributions to disease control country programmes for improving national and international trade. These developments include the more routine use of PCR as a diagnostic tool in veterinary diagnostic laboratories. However, there are many problems associated with the transfer and particularly, the application of this technology. These include lack of consideration of: the establishment of quality-assured procedures, the required set-up of the laboratory and the proper training of staff. This can lead to a situation where results are not assured. This book gives a comprehensive account of the practical aspects of PCR and strong consideration is given to ensure its optimal use in a laboratory environment. This includes the setting-up of a PCR laboratory; Good Laboratory Practice and standardised PCR protocols to detect animal disease pathogens. Examples of Standard Operating Procedures as used in individual specialist laboratories and an outline of training materials necessary for PCR technology transfer are presented. The difficulties, advantages and disadvantages in PCR applications are explained and placed in context with other test systems. Emphasis is placed on the use of PCR for detection of pathogens, with a particular focus on diagnosticians and scientists from the developing world. It is hoped that this book will enable readers from various disciplines and levels of expertise to better judge the merits of PCR and to increase their skills and knowledge in order to assist in a more logical, efficient and assured use of this technology

  11. Oral vs. salivary diagnostics

    Science.gov (United States)

    Marques, Joana; Corby, Patricia M.; Barber, Cheryl A.; Abrams, William R.; Malamud, Daniel

    2015-05-01

    The field of "salivary diagnostics" includes studies utilizing samples obtained from a variety of sources within the oral cavity. These samples include; whole unstimulated saliva, stimulated whole saliva, duct saliva collected directly from the parotid, submandibular/sublingual glands or minor salivary glands, swabs of the buccal mucosa, tongue or tonsils, and gingival crevicular fluid. Many publications state "we collected saliva from subjects" without fully describing the process or source of the oral fluid. Factors that need to be documented in any study include the time of day of the collection, the method used to stimulate and collect the fluid, and how much fluid is being collected and for how long. The handling of the oral fluid during and post-collection is also critical and may include addition of protease or nuclease inhibitors, centrifugation, and cold or frozen storage prior to assay. In an effort to create a standard protocol for determining a biomarker's origin we carried out a pilot study collecting oral fluid from 5 different sites in the mouth and monitoring the concentrations of pro- and anti-inflammatory cytokines detected using MesoScaleDiscovery (MSD) electrochemiluminesence assays. Our data suggested that 3 of the cytokines are primarily derived from the submandibular gland, while 7 of the cytokines come from a source other than the major salivary glands such as the minor salivary glands or cells in the oral mucosae. Here we review the literature on monitoring biomarkers in oral samples and stress the need for determining the blood/saliva ratio when a quantitative determination is needed and suggest that the term oral diagnostic be used if the source of an analyte in the oral cavity is unknown.

  12. Nova target diagnostics control system

    International Nuclear Information System (INIS)

    Severyn, J.R.

    1985-01-01

    During the past year the Nova target diagnostics control system was finished and put in service. The diagnostics loft constructed to the north of the target room provides the environmental conditions required to collect reliable target diagnostic data. These improvements include equipment cooling and isolation of the power source with strict control of instrumentation grounds to eliminate data corruption due to electromagnetic pulses from the laser power-conditioning system or from target implosion effects

  13. Picosecond image-converter diagnostics

    International Nuclear Information System (INIS)

    Schelev, M.Ya.

    1975-01-01

    A brief review is presented of the improvements in picosecond image-converter diagnostics carried out since the previous Congress in 1972. The account is given under the following headings: picosecond image converter cameras for visible and x-ray radiation diagnostics; Nd:glass and ruby mode-locked laser measurements; x-ray plasma emission diagnostics; computer treatment of pictures produced by picosecond cameras. (U.K.)

  14. Quantitative Structure ‒ Antiprotozoal Activity Relationships of Sesquiterpene Lactones

    Directory of Open Access Journals (Sweden)

    Reto Brun

    2009-06-01

    Full Text Available Prompted by results of our previous studies where we found high activity of some sesquiterpene lactones (STLs against Trypanosoma brucei rhodesiense (which causes East African sleeping sickness, we have now conducted a structure-(in-vitro-activity study on a set of 40 STLs against T. brucei rhodesiense, T. cruzi, Leishmania donovani and Plasmodium falciparum. Furthermore, cytotoxic activity against L6 rat skeletal myoblast cells was assessed. Some of the compounds possess high activity, especially against T. brucei (e.g. helenalin and some of its esters with IC50-values of 0.05-0.1 µM, which is about 10 times lower than their cytotoxic activity. It was found that all investigated antiprotozoal activities are significantly correlated with cytotoxicity and the major determinants for activity are a,b-unsaturated structural elements, also known to be essential for other biological activities of STLs. It was observed, however, that certain compounds are considerably more toxic against protozoa than against mammalian cells while others are more cytotoxic than active against the protozoa. A comparative QSAR analysis was therefore undertaken, in order to discern the antiparasitic activity of STLs against T. brucei and cytotoxicity. Both activities were found to depend to a large extent on the same structural elements and molecular properties. The observed variance in the biological data can be explained in terms of subtle variations in the relative influences of various molecular descriptors.

  15. PLS-Prediction and Confirmation of Hydrojuglone Glucoside as the Antitrypanosomal Constituent of Juglans Spp.

    Directory of Open Access Journals (Sweden)

    Therese Ellendorff

    2015-05-01

    Full Text Available Naphthoquinones (NQs occur naturally in a large variety of plants. Several NQs are highly active against protozoans, amongst them the causative pathogens of neglected tropical diseases such as human African trypanosomiasis (sleeping sickness, Chagas disease and leishmaniasis. Prominent NQ-producing plants can be found among Juglans spp. (Juglandaceae with juglone derivatives as known constituents. In this study, 36 highly variable extracts were prepared from different plant parts of J. regia, J. cinerea and J. nigra. For all extracts, antiprotozoal activity was determined against the protozoans Trypanosoma cruzi, T. brucei rhodesiense and Leishmania donovani. In addition, an LC-MS fingerprint was recorded for each extract. With each extract’s fingerprint and the data on in vitro growth inhibitory activity against T. brucei rhodesiense a Partial Least Squares (PLS regression model was calculated in order to obtain an indication of compounds responsible for the differences in bioactivity between the 36 extracts. By means of PLS, hydrojuglone glucoside was predicted as an active compound against T. brucei and consequently isolated and tested in vitro. In fact, the pure compound showed activity against T. brucei at a significantly lower cytotoxicity towards mammalian cells than established antiprotozoal NQs such as lapachol.

  16. Challenges in the diagnosis and management of sleeping sickness in Tanzania: a case report.

    Science.gov (United States)

    Sindato, C; Kibona, S N; Nkya, G M; Mbilu, T J N K; Manga, C; Kaboya, J S; Rawille, F

    2008-07-01

    In Tanzania sleeping sickness presents a serious threat to human health with a country-wide average of 400 cases reported annually. Both wild and domestic animals have been found to play a significant role in the epidemiology of sleeping sickness. Serengeti National Park in northern Tanzania, has experienced a number of sleeping sickness epidemics since 1922. The epidemics were associated with abundant game animals in the areas and Glossina swynnertoni was incriminated as the main vector. However since 2001 there has been no case of sleeping sickness reported from the park. This case report highlights on the possibility of resurgence and challenges in the diagnosis and management of sleeping sickness in Serengeti. A 38 years old Tanzanian man working in the Serengeti National Park who had experienced various tsetse bites was presented with a febrile condition and history of unsuccessful case management at different health facilities. Blood and cerebrospinal fluid (CSF) samples were examined for the presence oftrypanosomes using wet film, Field's stain and concentration techniques. Typanosoma brucei rhodesiense were detected in both the blood and CSF samples. The patient was treated successfully with melarsoprol. The results of this case study highlight the possibility of resurgence of sleeping sickness in the park hence calls for the need to create more awareness among the community and clinicians. There is need for early reporting to health facility and strengthening the diagnostic capacity of healthcare facilities in and around national parks endemic for sleeping sickness.

  17. Plant diagnostics in power stations

    International Nuclear Information System (INIS)

    Sturm, A.; Doering, D.

    1985-01-01

    The method of noise diagnostics is dealt with as a part of plant diagnostics in nuclear power stations. The following special applications are presented: (1) The modular noise diagnostics system is used for monitoring primary coolant circuits and detecting abnormal processes due to mechanical vibrations, loose parts or leaks. (2) The diagnostics of machines and plants with antifriction bearings is based on bearing vibration measurements. (3) The measurement of the friction moment by means of acoustic emission analysis is used for evaluating the operational state of slide bearings

  18. Team building and diagnostic training

    International Nuclear Information System (INIS)

    Bulmer, S.

    1987-01-01

    While developing a commercial training program to improve teamwork in control room crews, General Electric's Nuclear Training Services made an important discovery. Traditional training methods for developing teamwork and enhancing diagnostics capabilities are incomplete. Traditional methods generally help, but fail to fulfill the long-term needs of most teams. Teamwork has been treated as a short-term performance problem. Traditional diagnostic training suffers from a similar problem. Too often, it covers only the basic principles of decision-making, ignoring the development of expert diagnostic capabilities. In response to this discovery, they have developed comprehensive training in Team Building and Diagnostics

  19. Cognitive diagnostic assessment via Bayesian evaluation of informative diagnostic hypotheses.

    NARCIS (Netherlands)

    Hoijtink, Herbert; Béland, Sébastien; Vermeulen, Jorine A.

    2014-01-01

    There exist diverse approaches that can be used for cognitive diagnostic assessment, such as mastery testing, constrained latent class analysis, rule space methodology, diagnostic cognitive modeling, and person-fit analysis. Each of these approaches can be used within 1 of the 4 psychometric

  20. Cognitive Diagnostic Assessment via Bayesian Evaluation of Informative Diagnostic Hypotheses

    NARCIS (Netherlands)

    Hoitink, Herbert; Beland, Sebastien; Vermeulen, Jorine

    2014-01-01

    There exist diverse approaches that can be used for cognitive diagnostic assessment, such as mastery testing, constrained latent class analysis, rule space methodology, diagnostic cognitive modeling, and person-fit analysis. Each of these approaches can be used within 1 of the 4 psychometric

  1. Plasma diagnostics discharge parameters and chemistry

    CERN Document Server

    Auciello, Orlando

    1989-01-01

    Plasma Diagnostics, Volume 1: Discharge Parameters and Chemistry covers seven chapters on the important diagnostic techniques for plasmas and details their use in particular applications. The book discusses optical diagnostic techniques for low pressure plasmas and plasma processing; plasma diagnostics for electrical discharge light sources; as well as Langmuir probes. The text also describes the mass spectroscopy of plasmas, microwave diagnostics, paramagnetic resonance diagnostics, and diagnostics in thermal plasma processing. Electrical engineers, nuclear engineers, microwave engineers, che

  2. Regression models of reactor diagnostic signals

    International Nuclear Information System (INIS)

    Vavrin, J.

    1989-01-01

    The application is described of an autoregression model as the simplest regression model of diagnostic signals in experimental analysis of diagnostic systems, in in-service monitoring of normal and anomalous conditions and their diagnostics. The method of diagnostics is described using a regression type diagnostic data base and regression spectral diagnostics. The diagnostics is described of neutron noise signals from anomalous modes in the experimental fuel assembly of a reactor. (author)

  3. Dual Processing and Diagnostic Errors

    Science.gov (United States)

    Norman, Geoff

    2009-01-01

    In this paper, I review evidence from two theories in psychology relevant to diagnosis and diagnostic errors. "Dual Process" theories of thinking, frequently mentioned with respect to diagnostic error, propose that categorization decisions can be made with either a fast, unconscious, contextual process called System 1 or a slow, analytical,…

  4. Laser-aided plasma diagnostics

    NARCIS (Netherlands)

    Donne, A. J. H.; Barth, C. J.

    2008-01-01

    This paper will focus on two types of laser-aided diagnostics: Thomson scattering and laser-induced fluorescence. Thomson scattering is a very powerful diagnostic, which is applied at nearly every magnetic confinement device. Depending on the experimental conditions different plasma parameters can

  5. Student Interpretations of Diagnostic Feedback

    Science.gov (United States)

    Doe, Christine

    2015-01-01

    Diagnostic assessment is increasingly being recognized as a potentially beneficial tool for teaching and learning (Jang, 2012). There have been calls in the research literature for students to receive diagnostic feedback and for researchers to investigate how such feedback is used by students. Therefore, this study examined how students…

  6. Technical diagnostics of steam turbines

    International Nuclear Information System (INIS)

    Vlckova, B.; Drahy, J.

    1987-01-01

    This paper deals with practical experience in application of technical diagnostics methods to steam turbines, in particular using pedestal and shaft vibration measurements as well as estimation of bearing metal temperature and ultrasound emission signals. An estimation of effectiveness of the diagnostics methods used is given on the basis of experimental investigations made on a 30-MW turbine. (author)

  7. Psychometric perspectives on diagnostic systems

    NARCIS (Netherlands)

    Borsboom, D.

    2008-01-01

    The author identifies four conceptualizations of the relation between symptoms and disorders as utilized in diagnostic systems such as the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994): A constructivist perspective, which holds

  8. Diagnostic evaluation of rhabdomyolysis.

    Science.gov (United States)

    Nance, Jessica R; Mammen, Andrew L

    2015-06-01

    Rhabdomyolysis is characterized by severe acute muscle injury resulting in muscle pain, weakness, and/or swelling with release of myofiber contents into the bloodstream. Symptoms develop over hours to days after an inciting factor and may be associated with dark pigmentation of the urine. Serum creatine kinase and urine myoglobin levels are markedly elevated. Clinical examination, history, laboratory studies, muscle biopsy, and genetic testing are useful tools for diagnosis of rhabdomyolysis, and they can help differentiate acquired from inherited causes of rhabdomyolysis. Acquired causes include substance abuse, medication or toxic exposures, electrolyte abnormalities, endocrine disturbances, and autoimmune myopathies. Inherited predisposition to rhabdomyolysis can occur with disorders of glycogen metabolism, fatty acid β-oxidation, and mitochondrial oxidative phosphorylation. Less common inherited causes of rhabdomyolysis include structural myopathies, channelopathies, and sickle-cell disease. This review focuses on the differentiation of acquired and inherited causes of rhabdomyolysis and proposes a practical diagnostic algorithm. Muscle Nerve 51: 793-810, 2015. © 2015 Wiley Periodicals, Inc.

  9. Laboratory diagnostics of malaria

    Science.gov (United States)

    Siahaan, L.

    2018-03-01

    Even now, malaria treatment should only be administered after laboratory confirmation. There are several principal methods for diagnosing malaria. All these methods have their disadvantages.Presumptive treatment of malaria is widely practiced where laboratory tests are not readily available. Microscopy of Giemsa-stained thick and thin blood films remains the gold standard for the diagnosis of malaria infection. The technique of slide preparation, staining and reading are well known and standardized, and so is the estimate of the parasite density and parasite stages. Microscopy is not always available or feasible at primary health services in limited resource settings due to cost, lack of skilled manpower, accessories and reagents required. Rapid diagnostic tests (RDTs) are potential tools for parasite-based diagnosis since the tests are accurate in detecting malaria infections and are easy to use. The test is based on the capture of parasite antigen that released from parasitized red blood cells using monoclonal antibodies prepared against malaria antigen target. Polymerase Chain Reaction (PCR), depend on DNA amplification approaches and have higher sensitivity than microscopy. PCR it is not widely used due to the lack of a standardized methodology, high costs, and the need for highly-trained staff.

  10. Moyamoya disease: Diagnostic imaging

    International Nuclear Information System (INIS)

    Tarasów, Eugeniusz; Kułakowska, Alina; Łukasiewicz, Adam; Kapica-Topczewska, Katarzyna; Korneluk-Sadzyńska, Alicja; Brzozowska, Joanna; Drozdowski, Wiesław

    2011-01-01

    Moyamoya disease is a progressive vasculopathy leading to stenosis of the main intracranial arteries. The incidence of moyamoya disease is high in Asian countries; in Europe and North America, the prevalence of the disease is considerably lower. Clinically, the disease may be of ischaemic, haemorrhagic and epileptic type. Cognitive dysfunction and behavioral disturbance are atypical symptoms of moyamoya disease. Characteristic angiographic features of the disease include stenosis or occlusion of the arteries of the circle of Willis, as well as the development of collateral vasculature. Currently, magnetic resonance angiography and CT angiography with multi-row systems are the main imaging methods of diagnostics of the entire range of vascular changes in moyamoya disease. The most common surgical treatment combines the direct arterial anastomosis between the superficial temporal artery and middle cerebral, and the indirect synangiosis involving placement of vascularised tissue in the brain cortex, in order to promote neoangiogenesis. Due to progressive changes, correct and early diagnosis is of basic significance in selecting patients for surgery, which is the only effective treatment of the disease. An appropriate qualification to surgery should be based on a comprehensive angiographic and imaging evaluation of brain structures. Despite the rare occurrence of moyamoya disease in European population, it should be considered as one of causes of ischaemic or haemorrhagic strokes, especially in young patients

  11. Radiologic diagnostics of dementia

    International Nuclear Information System (INIS)

    Essig, M.; Schoenberg, S.O.

    2003-01-01

    Dementia is one of the most common diseases in the elderly population and is getting more and more important with the ageing of the population. A radiologic structural examination with CT or MRI is meanwhile a standard procedure in the diagnostic work up of patients with dementia syndrome. Radiology enables an early diagnosis and a differential diagnosis between different causes of dementia. Because structural changes occur only late in the disease process, a more detailed structural analysis using volumetric techniques or the use of functional imaging techniques is mandatory. These days, structural imaging uses MRI which enables to detect early atrophic changes at the medial temporal lobe with focus on the amygdala hippocampal complex. These changes are also present in the normal ageing process. In patients with Alzheimer's disease, however, they are more rapid and more pronounced. The use of functional imaging methods such as perfusion MRI, diffusion MRI or fMRI allow new insights into the pathophysiologic changes of dementia. The article gives an overview of the current status of structural imaging and an outlook into the potential of functional imaging methods. Detailed results of structural and functional imaging are presented in other articles of this issue. (orig.) [de

  12. Recent diagnostic developments on LHD

    International Nuclear Information System (INIS)

    Sudo, S.; Nagayama, Y.; Peterson, B.J.

    2003-01-01

    Standard diagnostics for fundamental plasma parameters and for plasma physics are routinely utilized for daily operation and physics study in the large helical device (LHD) with high reliability. Diagnostics for steady state plasma are intensively developed, especially for T e , n e (YAG laser Thomson, CO 2 laser polarimeter), data acquisition in steady state, heat resistant probes. To clarify the plasma property of the helical structure, 2-D or 3-D diagnostics are intensively developed: Tangential cameras (Fast SX TV, Photon counting CCD, H α TV); Tomography (Tangential SX CCD, Bolometer); Imaging (Bolometer, ECE, Reflectometer). Divertor and edge physics are one of important key issues for steady state operation. Diagnostics for neutral flux (H α array, Zeeman spectroscopy) and n e (Fast scanning probe, Li beam probe, Pulsed radar reflectometer). In addition to these, advanced diagnostics are being intensively developed with national and international collaborations in LHD. (author)

  13. The engineering of JET diagnostics

    International Nuclear Information System (INIS)

    Walker, C.I.; Dillon, S.F.; Hammond, N.P.; Hancock, C.J.; Lam, N.; McCarron, E.J.; Prior, P.C.S.; Reid, J.; Sanders, S.; Tellier, X.; Tiscornia, A.J.; Whitfield, G.A.H.; Wilson, C.H.; Wilson, D.J.

    1995-01-01

    There are some 62 identifiably different diagnostic systems on JET. 22 were installed new at the last, Pumped Divertor, shutdown and a further 22 which were modified, upgraded or repositioned. This paper describes some of the engineering aspects peculiar to the renewed diagnostic systems, reviews their construction and installation and gives an overview of the design of presently installed diagnostic equipment at the Torus. Examples are considered that illustrate the breakdown into a categorisation based on their installation method. This is useful for discussion of many of the associated engineering problems of method and quality control of manufacture, vulnerability, access for installation and maintenance and ultimately system safety and reliability. The function and measured plasma parameter of specific diagnostics is covered in other papers and is not attempted here, neither is a full catalogue of Diagnostics on JET. (orig.)

  14. ITER diagnostic system: Vacuum interface

    International Nuclear Information System (INIS)

    Patel, K.M.; Udintsev, V.S.; Hughes, S.; Walker, C.I.; Andrew, P.; Barnsley, R.; Bertalot, L.; Drevon, J.M.; Encheva, A.; Kashchuk, Y.; Maquet, Ph.; Pearce, R.; Taylor, N.; Vayakis, G.; Walsh, M.J.

    2013-01-01

    Diagnostics play an essential role for the successful operation of the ITER tokamak. They provide the means to observe control and to measure plasma during the operation of ITER tokamak. The components of the diagnostic system in the ITER tokamak will be installed in the vacuum vessel, in the cryostat, in the upper, equatorial and divertor ports, in the divertor cassettes and racks, as well as in various buildings. Diagnostic components that are placed in a high radiation environment are expected to operate for the life of ITER. There are approx. 45 diagnostic systems located on ITER. Some diagnostics incorporate direct or independently pumped extensions to maintain their necessary vacuum conditions. They require a base pressure less than 10 −7 Pa, irrespective of plasma operation, and a leak rate of less than 10 −10 Pa m 3 s −1 . In all the cases it is essential to maintain the ITER closed fuel cycle. These directly coupled diagnostic systems are an integral part of the ITER vacuum containment and are therefore subject to the same design requirements for tritium and active gas confinement, for all normal and accidental conditions. All the diagnostics, whether or not pumped, incorporate penetration of the vacuum boundary (i.e. window assembly, vacuum feedthrough etc.) and demountable joints. Monitored guard volumes are provided for all elements of the vacuum boundary that are judged to be vulnerable by virtue of their construction, material, load specification etc. Standard arrangements are made for their construction and for the monitoring, evacuating and leak testing of these volumes. Diagnostic systems are incorporated at more than 20 ports on ITER. This paper will describe typical and particular arrangements of pumped diagnostic and monitored guard volume. The status of the diagnostic vacuum systems, which are at the start of their detailed design, will be outlined and the specific features of the vacuum systems in ports and extensions will be described

  15. ITER diagnostic system: Vacuum interface

    Energy Technology Data Exchange (ETDEWEB)

    Patel, K.M., E-mail: Kaushal.Patel@iter.org [ITER Organization, Route de Vinon sur Verdon, 13115 St Paul-Lez-Durance (France); Udintsev, V.S.; Hughes, S.; Walker, C.I.; Andrew, P.; Barnsley, R.; Bertalot, L. [ITER Organization, Route de Vinon sur Verdon, 13115 St Paul-Lez-Durance (France); Drevon, J.M. [Bertin Technologies, BP 22, 13762 Aix-en Provence cedex 3 (France); Encheva, A. [ITER Organization, Route de Vinon sur Verdon, 13115 St Paul-Lez-Durance (France); Kashchuk, Y. [Institution “PROJECT CENTER ITER”, 1, Akademika Kurchatova pl., Moscow (Russian Federation); Maquet, Ph. [Bertin Technologies, BP 22, 13762 Aix-en Provence cedex 3 (France); Pearce, R.; Taylor, N.; Vayakis, G.; Walsh, M.J. [ITER Organization, Route de Vinon sur Verdon, 13115 St Paul-Lez-Durance (France)

    2013-10-15

    Diagnostics play an essential role for the successful operation of the ITER tokamak. They provide the means to observe control and to measure plasma during the operation of ITER tokamak. The components of the diagnostic system in the ITER tokamak will be installed in the vacuum vessel, in the cryostat, in the upper, equatorial and divertor ports, in the divertor cassettes and racks, as well as in various buildings. Diagnostic components that are placed in a high radiation environment are expected to operate for the life of ITER. There are approx. 45 diagnostic systems located on ITER. Some diagnostics incorporate direct or independently pumped extensions to maintain their necessary vacuum conditions. They require a base pressure less than 10{sup −7} Pa, irrespective of plasma operation, and a leak rate of less than 10{sup −10} Pa m{sup 3} s{sup −1}. In all the cases it is essential to maintain the ITER closed fuel cycle. These directly coupled diagnostic systems are an integral part of the ITER vacuum containment and are therefore subject to the same design requirements for tritium and active gas confinement, for all normal and accidental conditions. All the diagnostics, whether or not pumped, incorporate penetration of the vacuum boundary (i.e. window assembly, vacuum feedthrough etc.) and demountable joints. Monitored guard volumes are provided for all elements of the vacuum boundary that are judged to be vulnerable by virtue of their construction, material, load specification etc. Standard arrangements are made for their construction and for the monitoring, evacuating and leak testing of these volumes. Diagnostic systems are incorporated at more than 20 ports on ITER. This paper will describe typical and particular arrangements of pumped diagnostic and monitored guard volume. The status of the diagnostic vacuum systems, which are at the start of their detailed design, will be outlined and the specific features of the vacuum systems in ports and extensions

  16. Plasma diagnostics for tokamaks and stellarators

    Energy Technology Data Exchange (ETDEWEB)

    Stott, P E; Sanchez, J

    1994-07-01

    A collection of papers on plasma diagnostics is presented. The papers show the state of the art developments in a series of techniques: Magnetic diagnostics, Edge diagnostics, Langmuir probes, Spectroscopy, Microwave and FIR diagnostics as well as Thomson Scattering. Special interest was focused on those diagnostics oriented to fluctuations measurements in the plasma. (Author) 451 refs.

  17. Plasma diagnostics for tokamaks and stellarators

    International Nuclear Information System (INIS)

    Stott, P.E.; Sanchez, J.

    1994-01-01

    A collection of papers on plasma diagnostics is presented. The papers show the state of the art developments in a series of techniques: magnetic diagnostics, Edge diagnostics, Langmuir probes, Spectroscopy, Microwave and FIR diagnostics as well as Thomson Sattering. Special interest was focused on those diagnostics oriented to fluctuations measurements in the plasma

  18. Imaging systems for medical diagnostics

    International Nuclear Information System (INIS)

    Krestel, E.

    1990-01-01

    This book provides physicians and clinical physicists with detailed information on today's imaging modalities and assists them in selecting the optimal system for each clinical application. Physicists, engineers and computer specialists engaged in research and development and sales departments will also find this book to be of considerable use. It may also be employed at universities, training centers and in technical seminars. The physiological and physical fundamentals are explained in part 1. The technical solutions contained in part 2 illustrate the numerous possibilities available in X-ray diagnostics, computed tomography, nuclear medical diagnostics, magnetic resonance imaging, sonography and biomagnetic diagnostics. (orig.)

  19. [Diagnostic laparoscopy in acute abdomen].

    Science.gov (United States)

    Keller, R; Kleemann, M; Hildebrand, P; Roblick, U J; Bruch, H-P

    2006-11-01

    Acute abdomen is not a disease in itself but a description of a complex of symptoms combined with severe abdominal pain developed within a time frame of less than 24 h. All strategies for the management of acute abdomen underline the need for an interdisciplinary approach to diagnosis and therapy. This requires focused and intelligent use of efficient diagnostic procedures. Diagnostic laparoscopy may be a key to solving the diagnostic dilemma of unspecific acute abdomen. Furthermore, it allows not only direct inspection of the abdominal cavity but also surgical intervention, if needed. In particular the rate of negative laparotomies can be reduced.

  20. Screening diagnostic program breast cancer

    International Nuclear Information System (INIS)

    Portnoj, L.M.; Zhakova, I.I.; Budnikova, N.V.; Rukhlyadko, E.D.

    1995-01-01

    The authors propose their screening program for detection of breast cancer. It includes the entire complex of present-day screening diagnostic methods, starting from an original system for the formation of groups at risk of breast cancer and completed by the direct diagnostic model of detection of the condition, oriented at a differentiated approach to the use of mammographic techniques. The proposed organizational and methodologic screening measures are both economic and diagnostically effective, thus meeting the principal requirements to screening programs. Screening of 8541 risk-groups patients helped detect 867 nodular formations, 244 of which were cancer and 623 benign formations. 8 refs., 3 figs.,

  1. Mammary carcinoma diagnostics and therapy

    International Nuclear Information System (INIS)

    Fischer, Uwe; Baum, Friedemann

    2014-01-01

    The book on mammary carcinoma diagnostics and therapy covers the following issues: development, anatomy and physiology of the mammary glands, pathology of benign and malign mammary gland changes, non-imaging diagnostics; mammography; ultrasonic mammography; magnetic resonance tomography of the mammary glands; imaging diagnostics findings; mammary interventions; examination concepts; operative therapy of the mammary carcinoma; chemotherapy of the mammary carcinoma; radio-oncological therapy of the mammary carcinoma; logistics in a medical center for mammary gland diseases; logistics in an interdisciplinary center for mammary diseases; dialogue conduction and psycho-social attendance.

  2. Diagnostics for the National Compact Stellarator Experiment

    International Nuclear Information System (INIS)

    Stratton, B.C.; Johnson, D.; Feder, R.; Fredrickson, E.; Neilson, H.; Takahashi, H.; Zarnstorf, M.; Cole, M.; Goranson, P.; Lazarus, E.; Nelson, B.

    2003-01-01

    The status of planning of the National Compact Stellarator Experiment (NCSX) diagnostics is presented, with the emphasis on resolution of diagnostics access issues and on diagnostics required for the early phases of operation

  3. Diagnostics of Gun Barrel Propellants

    National Research Council Canada - National Science Library

    Lederman, S

    1983-01-01

    A preliminary investigation of the applicability of the spontaneous Raman diagnostic technique to the determination of the temperature of the propellant gases in the vicinity of the muzzle of a 2Omm...

  4. Microfluidic technology for molecular diagnostics.

    Science.gov (United States)

    Robinson, Tom; Dittrich, Petra S

    2013-01-01

    Molecular diagnostics have helped to improve the lives of millions of patients worldwide by allowing clinicians to diagnose patients earlier as well as providing better ongoing therapies. Point-of-care (POC) testing can bring these laboratory-based techniques to the patient in a home setting or to remote settings in the developing world. However, despite substantial progress in the field, there still remain many challenges. Progress in molecular diagnostics has benefitted greatly from microfluidic technology. This chapter aims to summarise the more recent advances in microfluidic-based molecular diagnostics. Sections include an introduction to microfluidic technology, the challenges of molecular diagnostics, how microfluidic advances are working to solve these issues, some alternative design approaches, and detection within these systems.

  5. Thioaptamer Diagnostic System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — AM Biotechnologies (AM) in partnership with Sandia National Laboratories will develop a Thioaptamer Diagnostic System (TDS) in response to Topic X10.01 Reusable...

  6. Calibration issues for neutron diagnostics

    International Nuclear Information System (INIS)

    Sadler, G.J.; Adams, J.M.; Barnes, C.W.

    1997-10-01

    In order for ITER to meet its operational and programmatic goals, it will be necessary to measure a wide range of plasma parameters. Some of the required parameters e.g., neutron yield, fusion power and power density, ion temperature profile in the core plasma, and characteristics of confined and escaping alpha particle populations are best measured by fusion product diagnostic techniques. To make these measurements, ITER will have dedicated diagnostic systems, including radial and vertical neutron cameras, neutron and gamma ray spectrometers, internal and external fission chambers, a neutron activation system, and diagnostics for confined and escaping alpha particles. Engineering integration of many of these systems is in progress, and other systems are under investigation. This paper summarizes the present state of design of fusion product diagnostic systems for ITER and discusses expected measurement capability

  7. Environmental sensing and combustion diagnostics

    International Nuclear Information System (INIS)

    Santoleri, J.J.

    1991-01-01

    This book contains proceedings of Environmental Sensing and Combustion Diagnostics. Topics covered include: Incineration Systems Applications, Permitting, And Monitoring Overview; Infrared Techniques Applied to Incineration Systems; Continuous Emission Monitors; Analyzers and Sensors for Process Control And Environmental Monitoring

  8. The Downside of Diagnostic Imaging

    Science.gov (United States)

    An article about radiation exposure during computed tomography and nuclear imaging procedures and the risk of cancer. Several studies released in 2009 have helped to quantify the risk and the growing use of these diagnostic imaging methods.

  9. Saliva Preservative for Diagnostic Purposes

    Science.gov (United States)

    Pierson, Duane L.; Mehta, Satish K.

    2012-01-01

    Saliva is an important body fluid for diagnostic purposes. Glycoproteins, glucose, steroids, DNA, and other molecules of diagnostic value are found in saliva. It is easier to collect as compared to blood or urine. Unfortunately, saliva also contains large numbers of bacteria that can release enzymes, which can degrade proteins and nucleic acids. These degradative enzymes destroy or reduce saliva s diagnostic value. This innovation describes the formulation of a chemical preservative that prevents microbial growth and inactivates the degradative enzymes. This extends the time that saliva can be stored or transported without losing its diagnostic value. Multiple samples of saliva can be collected if needed without causing discomfort to the subject and it does not require any special facilities to handle after it is collected.

  10. Recent diagnostic developments on LHD

    International Nuclear Information System (INIS)

    Sudo, S; Ozaki, T; Ashikawa, N; Emoto, M; Goto, M; Hamada, Y; Ida, K; Ido, T; Iguchi, H; Inagaki, S; Isobe, M; Kawahata, K; Khlopenkov, K; Kobuchi, T; Liang, Y; Masuzaki, S; Minami, T; Morita, S; Muto, S; Nagayama, Y; Nakanishi, H; Narihara, K; Nishizawa, A; Ohdachi, S; Osakabe, M; Peterson, B J; Sakakibara, S; Sasao, M; Sato, K; Shoji, M; Tamura, N; Tanaka, K; Toi, K; Tokuzawa, T; Watanabe, K; Watanabe, T; Yamada, I; Goncharov, P; Ejiri, A; Okajima, S; Mase, A; Tsuji-Iio, S; Akiyama, T; Lyon, J F; Vyacheslavov, L N; Sanin, A

    2003-01-01

    The recent diagnostic developments on the large helical device (LHD) are described briefly. LHD is the largest helical machine with all superconducting coils, and its purpose is to prove the ability of a helical system to confine a fusion-relevant plasma in steady state. According to the missions of LHD research, the diagnostic devices are categorized as follows: diagnostics for (i) high nτ E T plasmas and transport physics; (ii) magnetohydrodynamic stability; (iii) long pulse operation and divertor function; and (iv) energetic particles. These are briefly described focusing on the recent developments of the devices. Since the LHD experiment started in March 1998, five series of experimental campaigns have been carried out. The LHD diagnostics during these periods were operated successfully, and contributed to the analysis of the experimental results

  11. Laser Diagnostics for Reacting Flows

    National Research Council Canada - National Science Library

    Hanson, Ronald K

    2007-01-01

    ... (UV) or infrared (IR) wavelengths. The cw lasers were spectrally narrow, allowing study of innovative diagnostics based on spectral lineshapes, while the pulsed lasers provided intense bursts of photons needed for techniques based on LIF...

  12. Gonad shielding in diagnostic radiology

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    The use of gonad shielding is an important radiation protection technique, intended to reduce unnecessary x-ray exposure of the gonads of patients from diagnostic x-ray procedures. The types of gonad shields in use are discussed as are the types of diagnostic examinations that should include gonad shielding. It was found that when properly used, most shields provided substantial gonad dose reductions

  13. Novel uses of detonator diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, John R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wilde, Zakary Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tasker, Douglas George [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Francois, Elizabeth Green [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Nakamoto, Teagan Kanakanui Junichi [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Smith, Dalton Kay [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Trujillo, Christopher J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-09-15

    A novel combination of diagnostics is being used to research the physics of detonator initiation. The explosive PETN (Pentaerythritol tetranitrate) commonly used in detonators, is also a piezo-electric material that, when sufficiently shocked, emits an electromagnetic field in the radio frequency (RF) range, along crystal fracture planes. In an effort to capture this RF signal, a new diagnostic was created. A copper foil, used as an RF antenna, was wrapped around a foam fixture encompassing a PETN pellet. Rogowski coils were used to obtain the change in current with respect to time (di/dt) the detonator circuit, in and polyvinylidene difluoride (PVDF) stress sensors were used to capture shockwave arrival time. The goal of these experiments is to use these diagnostics to study the reaction response of a PETN pellet of known particle size to shock loading with various diagnostics including an antenna to capture RF emissions. Our hypothesis is that RF feedback may signify the rate of deflagration to detonation transition (DDT) or lack thereof. The new diagnostics and methods will be used to determine the timing of start of current, bridge burst, detonator breakout timing and RF generated from detonation. These data will be compared to those of currently used diagnostics in order to validate the accuracy of these new methods. Future experiments will incorporate other methods of validation including dynamic radiography, optical initiation and use of magnetic field sensors.

  14. Diagnostic criteria in MR neurography

    International Nuclear Information System (INIS)

    Baeumer, P.

    2017-01-01

    Peripheral neuropathies are frequent and can mostly be correctly diagnosed by clinical examination and electrophysiology; however, diagnostically difficult cases are sometimes encountered especially with respect to precise localization of nerve lesions. Imaging of the peripheral nervous system has been shown to provide additional useful diagnostic information. In addition to the more widely available nerve sonography, magnetic resonance neurography (MRN) is the method of choice in diagnostically complex cases. The most important pulse sequence is a T2-weighted fat-saturated pulse sequence with high in-plane resolution and detects increased T2-weighted signals of nerve fascicles as a highly sensitive sign for nerve lesions. Further established diagnostic criteria are nerve caliber and, less commonly used, contrast agent uptake. The spatial pattern of nerve lesions aids in the diagnostic classification of neuropathies. Functional imaging techniques, such as diffusion tensor imaging (DTI) and nerve perfusion are currently under examination with respect to the clinical potential. If all other diagnostic methods, including clinical examination, electrophysiology and nerve sonography do not arrive at an unambiguous diagnosis of a peripheral neuropathy, MRN should be used. The special value of MRN is demonstrated particularly in complex nerve lesions, such as traumatic plexopathies and in partial fascicular neuropathies and many other indications. (orig.) [de

  15. Diagnostic planning in JT-60 project

    International Nuclear Information System (INIS)

    Matoba, Tohru; Suzuki, Yasuo; Funahashi, Akimasa; Itagaki, Tokiyoshi

    1977-08-01

    The diagnostic plans of JT-60 were made along with design of the main machine. Basic requirements of the diagnostic program are (1) multiple measurement of respective plasma parameters, (2) efficient usage of the discharge, (3) capable data acquisition system, (4) high reliability of the diagnostic equipments, and (5) systematic development of new diagnostic techniques. Dimensions of the diagnostic ports were determined in detailed design of the vacuum vessel, anticipating the possible diagnostic methods. The proposed diagnostic systems and the plans are shown in table and figures respectively. Problems in the diagnostics are also described. (auth.)

  16. Constraints to estimating the prevalence of trypanosome infections in East African zebu cattle

    Directory of Open Access Journals (Sweden)

    Cox Andrew P

    2010-09-01

    Full Text Available Abstract Background In East Africa, animal trypanosomiasis is caused by many tsetse transmitted protozoan parasites including Trypanosoma vivax, T. congolense and subspecies of T. brucei s.l. (T. b. brucei and zoonotic human infective T. b. rhodesiense that may co-circulate in domestic and wild animals. Accurate species-specific prevalence measurements of these parasites in animal populations are complicated by mixed infections of trypanosomes within individual hosts, low parasite densities and difficulties in conducting field studies. Many Polymerase Chain Reaction (PCR based diagnostic tools are available to characterise and quantify infection in animals. These are important for assessing the contribution of infections in animal reservoirs and the risk posed to humans from zoonotic trypanosome species. New matrices for DNA capture have simplified large scale field PCR analyses but few studies have examined the impact of these techniques on prevalence estimations. Results The Whatman FTA matrix has been evaluated using a random sample of 35 village zebu cattle from a population naturally exposed to trypanosome infection. Using a generic trypanosome-specific PCR, prevalence was systematically evaluated. Multiple PCR samples taken from single FTA cards demonstrated that a single punch from an FTA card is not sufficient to confirm the infectivity status of an individual animal as parasite DNA is unevenly distributed across the card. At low parasite densities in the host, this stochastic sampling effect results in underestimation of prevalence based on single punch PCR testing. Repeated testing increased the estimated prevalence of all Trypanosoma spp. from 9.7% to 86%. Using repeat testing, a very high prevalence of pathogenic trypanosomes was detected in these local village cattle: T. brucei (34.3%, T. congolense (42.9% and T. vivax (22.9%. Conclusions These results show that, despite the convenience of Whatman FTA cards and specific PCR based

  17. Constraints to estimating the prevalence of trypanosome infections in East African zebu cattle.

    Science.gov (United States)

    Cox, Andrew P; Tosas, Olga; Tilley, Aimee; Picozzi, Kim; Coleman, Paul; Hide, Geoff; Welburn, Susan C

    2010-09-06

    In East Africa, animal trypanosomiasis is caused by many tsetse transmitted protozoan parasites including Trypanosoma vivax, T. congolense and subspecies of T. brucei s.l. (T. b. brucei and zoonotic human infective T. b. rhodesiense) that may co-circulate in domestic and wild animals. Accurate species-specific prevalence measurements of these parasites in animal populations are complicated by mixed infections of trypanosomes within individual hosts, low parasite densities and difficulties in conducting field studies. Many Polymerase Chain Reaction (PCR) based diagnostic tools are available to characterise and quantify infection in animals. These are important for assessing the contribution of infections in animal reservoirs and the risk posed to humans from zoonotic trypanosome species. New matrices for DNA capture have simplified large scale field PCR analyses but few studies have examined the impact of these techniques on prevalence estimations. The Whatman FTA matrix has been evaluated using a random sample of 35 village zebu cattle from a population naturally exposed to trypanosome infection. Using a generic trypanosome-specific PCR, prevalence was systematically evaluated. Multiple PCR samples taken from single FTA cards demonstrated that a single punch from an FTA card is not sufficient to confirm the infectivity status of an individual animal as parasite DNA is unevenly distributed across the card. At low parasite densities in the host, this stochastic sampling effect results in underestimation of prevalence based on single punch PCR testing. Repeated testing increased the estimated prevalence of all Trypanosoma spp. from 9.7% to 86%. Using repeat testing, a very high prevalence of pathogenic trypanosomes was detected in these local village cattle: T. brucei (34.3%), T. congolense (42.9%) and T. vivax (22.9%). These results show that, despite the convenience of Whatman FTA cards and specific PCR based detection tools, the chronically low parasitaemias in

  18. Far infrared fusion plasma diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Luhmann, N.C. Jr.; Peebles, W.A.

    1990-01-01

    Over the last several years, reflectometry has grown in importance as a diagnostic for both steady-state density Profiles as well as for the investigation of density fluctuations and turbulence. As a diagnostic for density profile measurement, it is generally believed to be well understood in the tokamak environment. However, its use as a fluctuation diagnostic is hampered by a lack of quantitative experimental understanding of its wavenumber sensitivity and spatial resolution. Several researchers, have theoretically investigated these questions. However, prior to the UCLA laboratory investigation, no group has experimentally investigated these questions. Because of the reflectometer's importance to the world effort in understanding plasma turbulence and transport, UCLA has, over the last year, made its primary Task IIIA effort the resolution of these questions. UCLA has taken the lead in a quantitative experimental understanding of reflectometer data as applied to the measurement of density fluctuations. In addition to this, work has proceeded on the design, construction, and installation of a reflectometer system on UCLA's CCT tokamak. This effort will allow a comparison between the improved confinement regimes (H-mode) observed on both the DIII-D and CCT machines with the goal of achieving a physics understanding of the phenomena. Preliminary investigation of a new diagnostic technique to measure density profiles as a function of time has been initiated at UCLA. The technique promises to be a valuable addition to the range of available plasma diagnostics. Work on advanced holographic reflectometry technique as applied to fluctuation diagnostics has awaited a better understanding of the reflectometer signal itself as discussed above. Efforts to ensure the transfer of the diagnostic developments have continued with particular attention devoted to the preliminary design of a multichannel FIR interferometer for MST.

  19. Mobile diagnostics: next-generation technologies for in vitro diagnostics.

    Science.gov (United States)

    Shin, Joonchul; Chakravarty, Sudesna; Choi, Wooseok; Lee, Kyungyeon; Han, Dongsik; Hwang, Hyundoo; Choi, Jaekyu; Jung, Hyo-Il

    2018-03-26

    The emergence of a wide range of applications of smartphones along with advances in 'liquid biopsy' has significantly propelled medical research particularly in the field of in vitro diagnostics (IVD). Herein, we have presented a detailed analysis of IVD, its associated critical concerns and probable solutions. It also demonstrates the transition in terms of analytes from minimally invasive (blood) to non-invasive (urine, saliva and sweat) and depicts how the different features of a smartphone can be integrated for specific diagnostic purposes. This review basically highlights recent advances in the applications of smartphone-based biosensors in IVD taking into account the following factors: accuracy and portability; quantitative and qualitative analysis; and centralization and decentralization tests. Furthermore, the critical concerns and future direction of diagnostics based on smartphones are also discussed.

  20. Diagnostic challenges of childhood asthma.

    Science.gov (United States)

    Bakirtas, Arzu

    2017-01-01

    Diagnosis of asthma in childhood is challenging. Both underdiagnosis and overdiagnosis of asthma are important issues. The present review gives information about challenging factors for an accurate diagnosis of childhood asthma. Although underdiagnosis of asthma in childhood has always been the most important diagnostic problem, overdiagnosis of asthma has also been increasingly recognized. This is probably due to diagnosis of asthma based on symptoms and signs alone. Demonstration of variable airflow obstruction by lung function tests is the most common asthma diagnostic tests used in practice and is therefore strongly recommended in children who can cooperate. Recently, an asthma guideline combining the clinical and economic evidences with sensitivity and specificity of diagnostic procedures was developed to improve accuracy of diagnosis and to avoid overdiagnosis. This guideline provided an algorithmic clinical and cost-effective approach and included fractional exhaled nitric oxide measurement as one of the diagnostic tests in addition to lung function. Diagnosis of asthma in children should be made by combining relevant history with at least two confirmatory diagnostic tests whenever possible. Diagnosis based on short-period treatment trials should be limited to young children who are unable to cooperate with these tests.

  1. MOLECULAR DIAGNOSTICS OF YERSINIA RUCKERI

    Directory of Open Access Journals (Sweden)

    Yu. Rud

    2014-06-01

    Full Text Available Purpose. The analysis of nucleotide sequences of the 16S rDNA gene of virulent strains of Yersinia ruckeri and to develop the method of molecular diagnostic of enteric redmouth disease. Methodology. By the method of CLUSTALW algorithm in MEGA software version 6.0 the nucleotide sequences of the 16S rDNA gene of virulent strains of Yersinia ruckeri were analysed. For development of molecular diagnostic of Y. ruckeri the method of polymerase chain reaction (PCR was used. Primer selection was carried out in software VectorNTI11 and on-line-service BLAST. The PCR products were investigated by the methods of sequencing and nucleotide analysis. Findings. Based on PCR assay the method of molecular diagnostic of enteric redmouth disease agent, bacterium Y. ruckeri was developed. It was shown that specific oligonucleotide primers generated PCR products in size of 600 base pairs. PCR products were investigated by the sequencing that showed right targeting of primers in reaction. Originality. Among high-conservative gene of 16S rDNA of Y. ruckeri the fragment of DNA was determined to which the specific primers for rapid diagnostic of virulent strains were selected. Practical Value. Rapid diagnostic of yersiniosis will allow to identify an agent of this infectious disease, bacterium Y. ruckeri, and to provide the prophylactic or medical measures in the fish farming of Ukraine.

  2. Diagnostics in Japan's microgravity experiments

    Science.gov (United States)

    Kadota, Toshikazu

    1995-01-01

    The achievement of the combustion research under microgravity depends substantially on the availability of diagnostic systems. The non-intrusive diagnostic systems are potentially applicable for providing the accurate, realistic and detailed information on momentum, mass and energy transport, complex gas phase chemistry, and phase change in the combustion field under microgravity. The non-intrusive nature of optical instruments is essential to the measurement of combustion process under microgravity which is very nervous to any perturbation. However, the implementation of the non-intrusive combustion diagnostic systems under microgravity is accompanied by several constraints. Usually, a very limited space is only available for constructing a highly sophisticated system which is so sensitive that it is easily affected by the magnitude of the gravitational force, vibration and heterogeneous field of temperature and density of the environments. The system should be properly adjusted prior to the experiment. Generally, it is quite difficult to tune the instruments during measurements. The programmed sequence of operation should also be provided. Extensive effort has been toward the development of non-intrusive diagnostic systems available for the combustion experiments under microgravity. This paper aims to describe the current art and the future strategy on the non-intrusive diagnostic systems potentially applicable to the combustion experiments under microgravity in Japan.

  3. Diagnostics for the ATA beam propagation experiments

    International Nuclear Information System (INIS)

    Fessenden, T.J.; Atchison, W.L.; Barletta, W.A.

    1981-11-01

    This report contains a discussion of the diagnostics required for the beam propagation experiment to be done with the ATA accelerator. Included are a list of the diagnostics needed; a description of the ATA experimental environment; the status of beam diagnostics available at Livermore including recent developments, and a prioritized list of accelerator and propagation diagnostics under consideration or in various stages of development

  4. Potential hazards of diagnostic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Houston, C S; Shokeir, M H

    1977-03-01

    There are no precise data for determining the extent of somatic damage from small doses of radiation used in diagnostic radiology. Diagnostic radiation given to pregnant women, knowingly or unknowingly, should rarely reach teratogenic levels causing brain and eye abnormalities. Evidence suggests that it does increase the risk of childhood malignancy, especially leukemia. Although rapidly growing tissues seem most susceptible, all radiation probably carries a very small risk of carcinogenesis. Genetic damage is equally difficult to estimate. Diagnostic radiation of females, even in childhood, may be related to an increased incidence of Down's syndrome in older mothers. Radiation also causes point mutations, which may explain the increase of some genetic abnormalities in progeny of older fathers. Whenever an abdominal or pelvic radiograph is ordered before the end of the reproductive period, there must be a potential benefit to balance the small risk involved.

  5. Molecular diagnostics of neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Megha eAgrawal

    2015-09-01

    Full Text Available Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer’s and Parkinson’s disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

  6. Diagnostic accuracy in virtual dermatopathology

    DEFF Research Database (Denmark)

    Mooney, E.; Kempf, W.; Jemec, G.B.E.

    2012-01-01

    Background Virtual microscopy is used for teaching medical students and residents and for in-training and certification examinations in the United States. However, no existing studies compare diagnostic accuracy using virtual slides and photomicrographs. The objective of this study was to compare...... diagnostic accuracy of dermatopathologists and pathologists using photomicrographs vs. digitized images, through a self-assessment examination, and to elucidate assessment of virtual dermatopathology. Methods Forty-five dermatopathologists and pathologists received a randomized combination of 15 virtual...... slides and photomicrographs with corresponding clinical photographs and information in a self-assessment examination format. Descriptive data analysis and comparison of groups were performed using a chi-square test. Results Diagnostic accuracy in dermatopathology using virtual dermatopathology...

  7. Molecular diagnostics of neurodegenerative disorders.

    Science.gov (United States)

    Agrawal, Megha; Biswas, Abhijit

    2015-01-01

    Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer's and Parkinson's disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

  8. CT guided diagnostic foot injections

    International Nuclear Information System (INIS)

    Saifuddin, A.; Abdus-Samee, M.; Mann, C.; Singh, D.; Angel, J.C.

    2005-01-01

    AIM: To describe a CT technique for guiding diagnostic and therapeutic injections in the hind- and mid-foot. MATERIALS AND METHODS: Over a period of 50 months, 28 individuals were referred for diagnostic and therapeutic hind- and mid-foot injections before possible arthrodesis. A CT technique was developed that allowed entry into the various joints using a vertical approach. Numbers of joints injected were as follows: posterior subtalar, 21; talonavicular, 4; calcaneonavicular, calcaneocuboid, navicular-cuneiform and 5th metatarsocuboid joints, 1 each. RESULTS: All injections but one were technically successful. Significant relief of symptoms was noted by 16 participants, whereas for 9 there was no improvement and for 3 a partial response was achieved. CONCLUSION: CT is a simple and safe alternative to fluoroscopy for guiding diagnostic and therapeutic foot injections, and may be the technique of choice in cases of disordered anatomy

  9. Enhanced NIF neutron activation diagnostics.

    Science.gov (United States)

    Yeamans, C B; Bleuel, D L; Bernstein, L A

    2012-10-01

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the (89)Zr/(89 m)Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  10. A revolution in diagnostic imaging.

    Science.gov (United States)

    Mamula, Paul W

    2003-03-01

    In November 1966, Sandy Koufax, the star left-handed pitcher of the Los Angeles Dodgers, retired after spending his final season coping with traumatic arthritis in his elbow, the compounded effects of a sliding injury to his pitching arm the previous season and 12 years of hard throwing.1 Had his career begun a few years later, he might have been able to benefit from the advances in diagnostic imaging and treatment that were introduced at that time. Modern arthroscopy and computed tomography (CT) did not become available until the mid 1970s,2 and the first elbow reconstruction was done by Frank Jobe, MD, about 10 years after Koufax retired.1 Arthroscopy was first used as a diagnostic tool, but it later became a surgical tool, affecting treatment of knees, then, later, shoulders. Since 1973, when The Physician and Sportsmedicine was launched, we have witnessed a revolution in diagnostic imaging and are continuing to see an evolution of modalities.

  11. Fetal exposure in diagnostic radiology

    International Nuclear Information System (INIS)

    Baker, M.L.; Vandergrift, J.F.; Dalrymple, G.V.

    1979-01-01

    The problem of possible radiation damage to the fetus or embryo as a result of diagnostic radiography during pregnancy, particularly in the early stages, is discussed. Recommendations of therapeutic abortion after fetal exposure require an adequate knowledge of the doses involved. In the absence of actual dose measurements or estimates, approximate exposure levels may be determined from the literature. A summary of published values for radiography involving the lower abdomen is given. Data is also presented from a series of fetal exposures resulting mostly from routine diagnostic radiography when pregnancy was not known at the time but was established later. Results of actual dose measurements using a phantom and of dose calculations based on published values are in reasonable agreement indicating that literature values of dose provide a satisfactory alternative to measurement. These data suggest that diagnostic radiography rarely, if ever, results in fetal exposures high enough to justify therapeutic abortion. (author)

  12. Dual processing and diagnostic errors.

    Science.gov (United States)

    Norman, Geoff

    2009-09-01

    In this paper, I review evidence from two theories in psychology relevant to diagnosis and diagnostic errors. "Dual Process" theories of thinking, frequently mentioned with respect to diagnostic error, propose that categorization decisions can be made with either a fast, unconscious, contextual process called System 1 or a slow, analytical, conscious, and conceptual process, called System 2. Exemplar theories of categorization propose that many category decisions in everyday life are made by unconscious matching to a particular example in memory, and these remain available and retrievable individually. I then review studies of clinical reasoning based on these theories, and show that the two processes are equally effective; System 1, despite its reliance in idiosyncratic, individual experience, is no more prone to cognitive bias or diagnostic error than System 2. Further, I review evidence that instructions directed at encouraging the clinician to explicitly use both strategies can lead to consistent reduction in error rates.

  13. Optical beam diagnostics on PEP

    International Nuclear Information System (INIS)

    Sabersky, A.P.

    1981-02-01

    In designing the PEP optical diagnostics we have been able to build on the experience gained with SPEAR. Most of the problems at SPEAR could be traced to the optical diagnostic system being inside the tunnel. A machine shutdown is required for any maintenance or modification. This implies that in order to make such an instrument successful, a large engineering effort must be mounted to ensure 100% operation at startup. The functions that do not work at startup may never be made to work; this has happened at several machines. Experimental setups are likewise risky and time consuming. A point which has been borne out in both SPEAR and PEP is that the mechanical part of the instrument, the special vacuum chamber, the optical mounts, the alignment and adjustments, require approximately 60% of the effort and cost of the optical diagnostics. It is far better to economize on detectors and electronics than on mechanical and optical essentials

  14. Calibration issues for neutron diagnostics

    International Nuclear Information System (INIS)

    Sadler, G.J.; Adams, J.M.; Barnes, C.W.

    1997-01-01

    The performance of diagnostic systems are limited by their weakest constituents, including their calibration issues. Neutron diagnostics are notorious for problems encountered while determining their absolute calibrations, due mainly to the nature of the neutron transport problem. In order to facilitate the determination of an accurate and precise calibration, the diagnostic design should be such as to minimize the scattered neutron flux. ITER will use a comprehensive set of neutron diagnostics--comprising radial and vertical neutron cameras, neutron spectrometers, a neutron activation system and internal and external fission chambers--to provide accurate measurements of fusion power and power densities as a function of time. The calibration of such an important diagnostic system merits careful consideration. Some thoughts have already been given to this subject during the conceptual design phase in relation to the time-integrated neutron activation and time-dependent neutron yield monitors. However, no overall calibration strategy has been worked out so far. This paper represents a first attempt to address this vital issue. Experience gained from present large tokamaks (JET, TFTR and JT60U) and proposals for ITER are reviewed. The need to use a 14-MeV neutron generator as opposed to radioactive sources for in-situ calibration of D-T diagnostics will be stressed. It is clear that the overall absolute determination of fusion power will have to rely on a combination of nuclear measuring techniques, for which the provision of accurate and independent calibrations will constitute an ongoing process as ITER moves from one phase of operation to the next

  15. First Wall and Operational Diagnostics

    International Nuclear Information System (INIS)

    Lasnier, C; Allen, S; Boedo, J; Groth, M; Brooks, N; McLean, A; LaBombard, B; Sharpe, J; Skinner, C; Whyte, D; Rudakov, D; West, W; Wong, C

    2006-01-01

    In this chapter we review numerous diagnostics capable of measurements at or near the first wall, many of which contribute information useful for safe operation of a tokamak. There are sections discussing infrared cameras, visible and VUV cameras, pressure gauges and RGAs, Langmuir probes, thermocouples, and erosion and deposition measurements by insertable probes and quartz microbalance. Also discussed are dust measurements by electrostatic detectors, laser scattering, visible and IR cameras, and manual collection of samples after machine opening. In each case the diagnostic is discussed with a view toward application to a burning plasma machine such as ITER

  16. Diagnostic nerve ultrasonography; Diagnostische Nervensonographie

    Energy Technology Data Exchange (ETDEWEB)

    Baeumer, T. [Universitaet zu Luebeck CBBM, Haus 66, Institut fuer Neurogenetik, Luebeck (Germany); Grimm, A. [Universitaetsklinikum Tuebingen, Klinik und Poliklinik fuer Neurologie, Tuebingen (Germany); Schelle, T. [Staedtisches Klinikum Dessau, Neurologische Klinik, Dessau (Germany)

    2017-03-15

    For the diagnostics of nerve lesions an imaging method is necessary to visualize peripheral nerves and their surrounding structures for an etiological classification. Clinical neurological and electrophysiological investigations provide functional information about nerve lesions. The information provided by a standard magnetic resonance imaging (MRI) examination is inadequate for peripheral nerve diagnostics; however, MRI neurography is suitable but on the other hand a resource and time-consuming method. Using ultrasonography for peripheral nerve diagnostics. With ultrasonography reliable diagnostics of entrapment neuropathies and traumatic nerve lesions are possible. The use of ultrasonography for neuropathies shows that a differentiation between different forms is possible. Nerve ultrasonography is an established diagnostic tool. In addition to the clinical examination and clinical electrophysiology, structural information can be obtained, which results in a clear improvement in the diagnostics. Ultrasonography has become an integral part of the diagnostic work-up of peripheral nerve lesions in neurophysiological departments. Nerve ultrasonography is recommended for the diagnostic work-up of peripheral nerve lesions in addition to clinical and electrophysiological investigations. It should be used in the clinical work-up of entrapment neuropathies, traumatic nerve lesions and spacy-occupying lesions of nerves. (orig.) [German] Fuer die Diagnostik von Nervenlaesionen ist ein bildgebendes Verfahren zur Darstellung des peripheren Nervs und seiner ihn umgebenden Strukturen fuer eine aetiologische Einordnung erforderlich. Mit der klinisch-neurologischen Untersuchung und Elektrophysiologie ist eine funktionelle Aussage ueber die Nervenlaesion moeglich. In der Standard-MRT-Untersuchung wird der periphere Nerv nur unzureichend gut dargestellt. Die MRT-Neurographie ist ein sehr gutes, aber auch zeit- und ressourcenintensives Verfahren. Nutzung des Ultraschalls fuer die

  17. Differential diagnostics of bullous dermatoses

    Directory of Open Access Journals (Sweden)

    A. A. Kubanov

    2016-01-01

    Full Text Available Bullous dermatoses are the diseases characterized by vesication and erosion of skin and/or mucos coats, production of autoantibodies against the structural components of epidermis and/or derma. The most frequent diseases of these disorders are pemphigus, bullous pemphigoid, dermatitis herpetiformis, beningn familial chronic pemphigus (Gougerot Hailey-Hailey disease.Diagnostics of bullous dermatoses is based on assessement of clinical signs, results of cytological and histological studies and immunological tests. However none of the current diagnostic methods allows to reveal bullous dermatosis severally and with absolute certainty. Consequently it is necessary to perform wide range of clinical and laboratory tests for early diagnosis and treatment order.

  18. An edge over diagnostic setup

    Directory of Open Access Journals (Sweden)

    Sridhar Kannan

    2017-01-01

    Full Text Available Diagnostic setup proposed by H.D. Kingsley serves as a practical aid in treatment planning and diagnosis. These setups have some inherent shortcomings. A simple technique of duplication of the setups in dental stone can solve problems encountered before as well as provide many other advantages over the conventional procedure. The diagnostic setup is prepared by the conventional method [Figure 1]. An alginate impression is then taken of the setups and poured in dental stone to obtain the derived treatment model [Figure 2]. The same setup can now be further modified for alternate lines of treatment. Subsequently models could then be obtained as required [Figure 3].

  19. Diagnostic imaging in internal medicine

    International Nuclear Information System (INIS)

    Eisenberg, R.L.

    1985-01-01

    This book examines medical diagnostic techniques. Topics considered include biological considerations in the approach to clinical medicines; infectious diseases; disorders of the heart; disorders of the vascular system; disorders of the respiratory system; diseases of the kidneys and urinary tract; disorders of the alimentary tract; disorders of the hepatobiliary system and pancreas; disorders of the hematopoietic system; disorders of bone and bone mineralization; disorders of the joints, connective tissues, and striated muscles; disorders of the nervous system; miscellaneous disorders; and procedures in diagnostic imaging

  20. Optical diagnostics of intermittent flows

    DEFF Research Database (Denmark)

    Okulov, V.L.; Naumov, I.V.; Sørensen, Jens Nørkær

    2007-01-01

    The efficiency of combined use of different optical techniques for flow diagnostics is demonstrated with the practically important case of intense swirling flows. It is shown that, when applied separately, commonly used optical measuring techniques, such as laser Doppler anemometry and particle...... is for the first time applied for diagnostics of the flow pattern in a closed cylinder with a rotating end face with the aim of studying the changeover from the steady axisymmetric to unsteady asymmetric flow over a wide range of flow parameters. It is found that such a transition is notable for azimuthal...

  1. Mjollnir Rotational Line Scan Diagnostics.

    Science.gov (United States)

    1981-05-19

    using long cavity. M8 Removable Pellicle Beam Splitter for He-Ne Lineup Beam. Removed before HF or DF laser is turned on. 27 A 27 * A r of the chopper...three probe laser lines, however three lines were sequentially measured to verify the diagnostic equipment. Two of the three lines have been monitored

  2. Heuristics Reasoning in Diagnostic Judgment.

    Science.gov (United States)

    O'Neill, Eileen S.

    1995-01-01

    Describes three heuristics--short-cut mental strategies that streamline information--relevant to diagnostic reasoning: accessibility, similarity, and anchoring and adjustment. Analyzes factors thought to influence heuristic reasoning and presents interventions to be tested for nursing practice and education. (JOW)

  3. Diagnostic interface problems on TFTR

    International Nuclear Information System (INIS)

    Goldfarb, S.

    1977-01-01

    Diagnostic equipment on TFTR has functional interfaces with many machine systems. Salient requirements include plasma access, environmental resistance to thermal, magnetic and radiation effects, automated data acquisition and controls, remote handling and personnel safety. Problems imposed by these requirements and the solutions being considered are described

  4. Diagnostic errors in pediatric radiology

    International Nuclear Information System (INIS)

    Taylor, George A.; Voss, Stephan D.; Melvin, Patrice R.; Graham, Dionne A.

    2011-01-01

    Little information is known about the frequency, types and causes of diagnostic errors in imaging children. Our goals were to describe the patterns and potential etiologies of diagnostic error in our subspecialty. We reviewed 265 cases with clinically significant diagnostic errors identified during a 10-year period. Errors were defined as a diagnosis that was delayed, wrong or missed; they were classified as perceptual, cognitive, system-related or unavoidable; and they were evaluated by imaging modality and level of training of the physician involved. We identified 484 specific errors in the 265 cases reviewed (mean:1.8 errors/case). Most discrepancies involved staff (45.5%). Two hundred fifty-eight individual cognitive errors were identified in 151 cases (mean = 1.7 errors/case). Of these, 83 cases (55%) had additional perceptual or system-related errors. One hundred sixty-five perceptual errors were identified in 165 cases. Of these, 68 cases (41%) also had cognitive or system-related errors. Fifty-four system-related errors were identified in 46 cases (mean = 1.2 errors/case) of which all were multi-factorial. Seven cases were unavoidable. Our study defines a taxonomy of diagnostic errors in a large academic pediatric radiology practice and suggests that most are multi-factorial in etiology. Further study is needed to define effective strategies for improvement. (orig.)

  5. Optical diagnostics for plasma etching

    NARCIS (Netherlands)

    Bisschops, T.H.J.; Kroesen, G.M.W.; Veldhuizen, van E.M.; de Zeeuw, C.J.H.; Timmermans, C.J.

    1985-01-01

    Several optical diagnostics were used to det. plasma properties and etch rates in an single wafer etch reactor. Results of UV-visible spectroscopy and IR absorption spectroscopy, indicating different mol. species and their densities are presented. The construction of an interferometer to det. the

  6. Local Sensitivity and Diagnostic Tests

    NARCIS (Netherlands)

    Magnus, J.R.; Vasnev, A.L.

    2004-01-01

    In this paper we confront sensitivity analysis with diagnostic testing.Every model is misspecified, but a model is useful if the parameters of interest (the focus) are not sensitive to small perturbations in the underlying assumptions. The study of the e ect of these violations on the focus is

  7. Diagnostic imaging of shoulder impingement

    International Nuclear Information System (INIS)

    Merl, T.; Weinhardt, H.; Oettl, G.; Lenz, M.; Riel, K.A.

    1996-01-01

    Magnetic resonance imaging is a method that has been advancing in the last few years to the modality of choice for diagnostic evaluation of the bone joints, as the method is capable of imaging not only the ossous but also the soft tissue components of the joint. MRI likewise has become an accepted method for diagnostic evaluation of syndromes of the shoulder, with high diagnostic accuracy in detecting rotator cuff lesions, or as an efficient MRI arthrography for evaluation of the instability or lesions of the labrocapsular complex. In the evaluation of early stages of shoulder impingement, the conventional MRI technique as a static technique yields indirect signs which in many cases do not provide the diagnostic certainty required in order to do justice to the functional nature of the syndrome. In these cases, functional MRI for imaging of the arm in abducted position and in rotational movement may offer a chance to early detect impingement and thus identify patients who will profit from treatment at an early stage [de

  8. Diagnostic Criteria for Pediatric MS

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-06-01

    Full Text Available Investigators at Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital of Chicago review the diagnostic criteria for pediatric multiple sclerosis, the differential diagnosis, the 2010 McDonald criteria, and Callen criteria.

  9. Diagnostic imaging of exotic pets

    International Nuclear Information System (INIS)

    Silverman, S.

    1993-01-01

    Radiographic, ultrasonographic, and computed tomographic (CT) imaging are important diagnostic modalities in exotic pets. The use of appropriate radiographic equipment, film-screen combinations, and radiographic projections enhances the information obtained from radiographs. Both normal findings and common radiographic abnormalities are discussed. The use of ultrasonography and CT scanning for exotic small mammals and reptiles is described

  10. A Diagnostic Ultrasound Imaging System

    International Nuclear Information System (INIS)

    Lee, Seong Woo

    1999-01-01

    The ability to see the internal organs of the human body in a noninvasive way is a powerful diagnostic tool of modern medicine. Among these imaging modalities such as X-ray, MRI, and ultrasound. MRI and ultrasound are presenting much less risk of undesirable damage of both patient and examiner. In fact, no deleterious effects have been reported as a result of clinical examination by using MRI and ultrasound diagnostic equipment. As a result, their market volume has been rapidly increased. MRI has a good resolution. but there are a few disadvantages such as high price. non-real-time imaging capability. and expensive diagnostic cost. On the other hand, the ultrasound imaging system has inherently poor resolution as compared with X-ray and MRI. In spite of its poor resolution, the ultrasound diagnostic equipment is lower in price and has an ability of real-time imaging as compared with the others. As a result, the ultrasound imaging system has become general and essential modality for imaging the internal organs of human body. In this review various researches and developments to enhance the resolution of the ultrasound images are explained and future trends of the ultrasound imaging technology are described

  11. Diagnosis of asthma: diagnostic testing.

    Science.gov (United States)

    Brigham, Emily P; West, Natalie E

    2015-09-01

    Asthma is a heterogeneous disease, encompassing both atopic and non-atopic phenotypes. Diagnosis of asthma is based on the combined presence of typical symptoms and objective tests of lung function. Objective diagnostic testing consists of 2 components: (1) demonstration of airway obstruction, and (2) documentation of variability in degree of obstruction. A review of current guidelines and literature was performed regarding diagnostic testing for asthma. Spirometry with bronchodilator reversibility testing remains the mainstay of asthma diagnostic testing for children and adults. Repetition of the test over several time points may be necessary to confirm airway obstruction and variability thereof. Repeated peak flow measurement is relatively simple to implement in a clinical and home setting. Bronchial challenge testing is reserved for patients in whom the aforementioned testing has been unrevealing but clinical suspicion remains, though is associated with low specificity. Demonstration of eosinophilic inflammation, via fractional exhaled nitric oxide measurement, or atopy, may be supportive of atopic asthma, though diagnostic utility is limited particularly in nonatopic asthma. All efforts should be made to confirm the diagnosis of asthma in those who are being presumptively treated but have not had objective measurements of variability in the degree of obstruction. Multiple testing modalities are available for objective confirmation of airway obstruction and variability thereof, consistent with a diagnosis of asthma in the appropriate clinical context. Providers should be aware that both these characteristics may be present in other disease states, and may not be specific to a diagnosis of asthma. © 2015 ARS-AAOA, LLC.

  12. Electronic DNA detection and diagnostics

    NARCIS (Netherlands)

    De, Arpita

    2013-01-01

    The Nanopill project is an ambitious undertaking with the objective to develop an early-warning cancer diagnostic pill that is ingested by the patient. The Nanopill collects intestinal fluid as the pill travels down the intestinal tract, and tests for the presence of a free floating hyper-methylated

  13. Cell Analysis and Early Diagnostics

    NARCIS (Netherlands)

    Subramaniam, Vinod; Jones, Val

    2006-01-01

    In an era of aging populations and rising health-care costs, the shift of medical paradigms towards rapid, accurate, early diagnoses of diseases is inevitable. In addition to further development of ultrasensitive in vitro tests, the focus of attention in both diagnostics and the early drug discovery

  14. Maximum entropy beam diagnostic tomography

    International Nuclear Information System (INIS)

    Mottershead, C.T.

    1985-01-01

    This paper reviews the formalism of maximum entropy beam diagnostic tomography as applied to the Fusion Materials Irradiation Test (FMIT) prototype accelerator. The same formalism has also been used with streak camera data to produce an ultrahigh speed movie of the beam profile of the Experimental Test Accelerator (ETA) at Livermore. 11 refs., 4 figs

  15. Maximum entropy beam diagnostic tomography

    International Nuclear Information System (INIS)

    Mottershead, C.T.

    1985-01-01

    This paper reviews the formalism of maximum entropy beam diagnostic tomography as applied to the Fusion Materials Irradiation Test (FMIT) prototype accelerator. The same formalism has also been used with streak camera data to produce an ultrahigh speed movie of the beam profile of the Experimental Test Accelerator (ETA) at Livermore

  16. Laser Diagnostics for Reacting Flows

    Science.gov (United States)

    2010-01-11

    the high-temperature kinetics of n-heptane pyrolysis . The two-wavelength temperature and vapor concentration diagnostic designed for n- dodecane was...features ranging from 1338 nm to 1469 nm and one laser tuned to a CO2 transition near 1997 nm were combined onto a single mode optical fiber ( Corning

  17. Gonad shielding in diagnostic radiology

    International Nuclear Information System (INIS)

    1975-06-01

    The use of gonad shielding is an important radiation protection technique, intended to reduce unnecessary x-ray exposure of the gonads of patients from diagnostic x-ray procedures. This pamphlet will provide physicians and radiologic technologists with information which will aid their appropriate use of gonad shielding

  18. When Diagnostic Labels Mask Trauma

    Science.gov (United States)

    Foltz, Robert; Dang, Sidney; Daniels, Brian; Doyle, Hillary; McFee, Scott; Quisenberry, Carolyn

    2013-01-01

    A growing body of research shows that many seriously troubled children and adolescents are reacting to adverse life experiences. Yet traditional diagnostic labels are based on checklists of surface symptoms. Distracted by disruptive behavior, the common response is to medicate, punish, or exclude rather than respond to needs of youth who have…

  19. Dynamic behaviour of diagnostic assemblies

    International Nuclear Information System (INIS)

    Pecinka, L.

    1980-01-01

    The methodology is shown of calculating the frequency spectrum of a diagnostic assembly. The oscillations of the assembly as a whole, of a fuel rod bundle, the assembly jacket and of the individual rods in the bundle were considered. The manufacture is suggested of a model assembly which would be used for testing forced vibrations using an experimental water loop. (M.S.)

  20. Recent trend of diagnostic radiology

    International Nuclear Information System (INIS)

    Kim, S.Y.; Kim, H.K.

    1979-01-01

    Present status and recent trend of diagnostic radiology have been reviewed. The interrelationships and Characteristics of various fields of radiology such as computed tomography, X-ray radiology, and nuclear medicine were discussed. The mevit of computed tomography and the promising use of short lived, accelerator produced radionuclides, and radiotherapy in nuclear medicine were emphasized. (author)

  1. ITER diagnostics ex-vessel engineering services

    Energy Technology Data Exchange (ETDEWEB)

    Arumugam, A.P., E-mail: arun.prakash@iter.org; Walker, C.I.; Andrew, P.; Barnsley, R.; Beltran, D.; Bertalot, L.; Dammann, A.; Direz, M.F.; Drevon, J.M.; Encheva, A.; Giacomin, T.; Hourtoule, J.; Kuehn, I.; Lanza, R.; Levesy, B.; Maquet, P.; Patel, K.M.; Patisson, L.; Pitcher, C.S.; Portales, M.; and others

    2013-10-15

    Highlights: • This paper describes about the ITER diagnostics ex-vessel engineering services. • It describes various diagnostics systems, its location and its environment. • Diagnostics interfaces with other services such as the buildings, HVAC, electrical services, cooling water, vacuum, liquid and gas distribution. • All the interfaces with these services are identified and defined. • Buildings services for diagnostics, such as penetrations, local shielding, embedment and temperature control are discussed. -- Abstract: Extensive diagnostics systems will be installed on the ITER machine to provide the measurements necessary to control, evaluate and optimize plasma performance in ITER and to further the understanding of plasma physics. These include measurements of temperature, density, impurity concentration, and particle and energy confinement times. ITER diagnostic systems extend from the center of the Tokamak to the various diagnostic areas, where they are controlled and acquired data is processed. This mainly includes the areas such as ports, port cells, gallery, diagnostics enclosures and cubicle areas. The diagnostics port plugs encloses the front end of the diagnostic systems and the diagnostics building houses the diagnostics equipment, instrumentation and control cubicles. There are several systems providing services to diagnostics. These mainly include ITER buildings, electrical power services, cooling water services, Heating Ventilation and Air Conditioning (HVAC), vacuum services, liquid and gas distribution services, cable engineering, de-tritiation systems, control cubicles, etc. Requirements of these service systems have to be defined, even though many of the diagnostics are at an early stage of development. It is a real challenge to define and to design diagnostics systems considering the constraints imposed by these service systems. This paper summarizes the provision of these services to the individual diagnostics and diagnostics areas

  2. ITER diagnostics ex-vessel engineering services

    International Nuclear Information System (INIS)

    Arumugam, A.P.; Walker, C.I.; Andrew, P.; Barnsley, R.; Beltran, D.; Bertalot, L.; Dammann, A.; Direz, M.F.; Drevon, J.M.; Encheva, A.; Giacomin, T.; Hourtoule, J.; Kuehn, I.; Lanza, R.; Levesy, B.; Maquet, P.; Patel, K.M.; Patisson, L.; Pitcher, C.S.; Portales, M.

    2013-01-01

    Highlights: • This paper describes about the ITER diagnostics ex-vessel engineering services. • It describes various diagnostics systems, its location and its environment. • Diagnostics interfaces with other services such as the buildings, HVAC, electrical services, cooling water, vacuum, liquid and gas distribution. • All the interfaces with these services are identified and defined. • Buildings services for diagnostics, such as penetrations, local shielding, embedment and temperature control are discussed. -- Abstract: Extensive diagnostics systems will be installed on the ITER machine to provide the measurements necessary to control, evaluate and optimize plasma performance in ITER and to further the understanding of plasma physics. These include measurements of temperature, density, impurity concentration, and particle and energy confinement times. ITER diagnostic systems extend from the center of the Tokamak to the various diagnostic areas, where they are controlled and acquired data is processed. This mainly includes the areas such as ports, port cells, gallery, diagnostics enclosures and cubicle areas. The diagnostics port plugs encloses the front end of the diagnostic systems and the diagnostics building houses the diagnostics equipment, instrumentation and control cubicles. There are several systems providing services to diagnostics. These mainly include ITER buildings, electrical power services, cooling water services, Heating Ventilation and Air Conditioning (HVAC), vacuum services, liquid and gas distribution services, cable engineering, de-tritiation systems, control cubicles, etc. Requirements of these service systems have to be defined, even though many of the diagnostics are at an early stage of development. It is a real challenge to define and to design diagnostics systems considering the constraints imposed by these service systems. This paper summarizes the provision of these services to the individual diagnostics and diagnostics areas

  3. Modern diagnostic capabilities for vasospastic angina diagnostics (intracoronary provocative testing

    Directory of Open Access Journals (Sweden)

    А. А. Обединский

    2017-04-01

    Full Text Available This review is devoted to a topical problem of modern cardiology – techniques of diagnosing vasospastic angina. The results of retrospective and prospective studies on the efficacy and safety of vasospastic angina diagnostics are reviewed. The literature on the prevalence, progression and treatment of this pathology is discussed.Received 13 January 2017. Accepted 6 February 2017.Financing: The study did not have sponsorship.Conflict of interest: The authors declare no conflict of interest.

  4. Development of JT-60 diagnostics system

    International Nuclear Information System (INIS)

    Suzuki, Yasuo

    1988-01-01

    The various kinds of plasma diagnostics have been developed and utilized in the JT-60 experiments. The features of JT-60 diagnostics system and the historical proceeding of the development are described in this paper. Taking account of the design consideration, JT-60 diagnostics system is sorted out into eight groups, which include six diagnostics systems, the data processing system and diagnostics supporting system. The all devices in the JT-60 diagnostics system were instrumented on schedule in the end of the fiscal year of 1985 and have contributed to JT-60 experiments. (author)

  5. Diagnostics

    International Nuclear Information System (INIS)

    Borer, J.; Jung, R.

    1984-01-01

    All the non interacting monitors used for the p-anti p instrumentation can be related to the use of the wall image current as induced by relativistic charged particle bunches circulating in a metallic pipe or vacuum chamber. The monitors are then classified by their type of beam coupling impedance. This allows a more generalized approach of the design of the so-called pickups. (orig./HSI)

  6. DIFFERENTIAL DIAGNOSTICS OF PROSTATE TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    E. V. Brizhatyuk

    2017-01-01

    Full Text Available Prostate tuberculosis is difficult to be diagnosed, especially if lesions are limited only by this organ. The article analyses the experience of differential diagnostics of prostate tuberculosis based on the data of examination of 84 patients. 45 of them were diagnosed with prostate tuberculosis, and 39 patients were diagnosed with chronic bacterial prostatitis. Pathognomonic diagnostics criteria of prostate tuberculosis were the following: detection of tuberculous mycobacteria in the prostatic fluid or ejaculate, signs of granulomatous prostatitis with areas of cavernous necrosis in prostate biopsy samples, and prostate cavities visualized by X-ray or ultrasound examinations. Should the above criteria be absent, the disease can be diagnosed based on the combination of indirect signs: symptoms of prostate inflammation with active tuberculosis of the other localization; large prostate calcification, extensive hyperechoic area of the prostate, spermatocystic lesions, leucospermia and hemospermia, failure of the adequate non-specific anti-bacterial therapy.

  7. Information engineering for molecular diagnostics.

    Science.gov (United States)

    Sorace, J. M.; Ritondo, M.; Canfield, K.

    1994-01-01

    Clinical laboratories are beginning to apply the recent advances in molecular biology to the testing of patient samples. The emerging field of Molecular Diagnostics will require a new Molecular Diagnostics Laboratory Information System which handles the data types, samples and test methods found in this field. The system must be very flexible in regards to supporting ad-hoc queries. The requirements which are shaping the developments in this field are reviewed and a data model developed. Several queries which demonstrate the data models ability to support the information needs of this area have been developed and run. These results demonstrate the ability of the purposed data model to meet the current and projected needs of this rapidly expanding field. PMID:7949937

  8. Advances in medical diagnostic technology

    CERN Document Server

    Lai, Khin Wee; Mohamad Salim, Maheza Irna; Ong, Sang-Bing; Utama, Nugraha Priya; Myint, Yin Mon; Mohd Noor, Norliza; Supriyanto, Eko

    2014-01-01

    This book provides the most recent findings and knowledge in advanced diagnostics technology, covering a wide spectrum including brain activity analysis, breast and lung cancer detection, echocardiography, computer aided skeletal assessment to mitochondrial biology imaging at the cellular level. The authors explored magneto acoustic approaches and tissue elasticity imaging for the purpose of breast cancer detection. Perspectives in fetal echocardiography from an image processing angle are included. Diagnostic imaging in the field of mitochondrial diseases as well as the use of Computer-Aided System (CAD) are also discussed in the book. This book will be useful for students, lecturers or professional researchers in the field of biomedical sciences and image processing.

  9. Patient dosimetry in diagnostic radiology

    International Nuclear Information System (INIS)

    Rweyemamu, M.

    2013-04-01

    The objective of this project was to review patient dosimetry aiming at reducing the patient dose during diagnostic procedures while maintaining the best image quality in order to protect patients from ionizing radiation. CT examination was selected in this study to represent imaging protocols with high patient doses used in diagnostic radiology. Dosimetric parameters in CT which are CTDI, CTDIW, DLP, MSAD, organ dose and effective dose were discussed. Parameters such as tube current, tube voltage, filtration, scan volume and slice thickness were found to affect patient dose, therefore proper management of these factors was recommended. For optimization of protection of the patient, application of the “as low as reasonably achievable” (ALARA) principle was recommended as an important key for avoiding overexposure and minimizing patient doses. Also it was recommended that CT examinations should be performed if and only if is the only suitable option when weighed against other options which do not involve ionizing radiation exposure. (author)

  10. CIT diagnostic computer interface studies

    International Nuclear Information System (INIS)

    Rauch, W.; Hayes, S.; Lowrance, J.; Oliaro, G.; Sauthoff, N.; Sichta, P.; Stark, W.

    1987-01-01

    This paper presents the on-going work performed in proposing instrumentation equipment and communications networks for the Diagnostic Data Acquisition and Diagnostic Instrumentation and Control System for the Compact Ignition Torus (CIT), which will begin operation in 1993. Consideration is given to the system criteria and requirements and their influence on the appropriate application of instrumentation and communication technologies to the system. This paper concentrates on the investigation of the bus communication technologies as they apply to the CIT data acquisition system. It compares CAMAC, VME, and FASTBUS as standards for data acquisition. The paper describes the connectivity between VAX equipment and CAMAC and VME instrumentation systems. Instrumentation and communication functionality and performance levels are presented as factors important to the overall data acquisition system performance

  11. Novette diagnostic support. Final report

    International Nuclear Information System (INIS)

    Cirigliano, R.; Franco, E.; Koppel, L.; Rodrigues, B.; Smith, J.

    1985-02-01

    The primary research areas were the following: (1) contribute x-ray diagnostic, experimental, and data reduction and analysis support for the Novette DANTE x-ray spectrometer experiments. This effort was expanded to improve the overall quality of the Novette database; (2) experimental and calculational characterization of the x-ray imaging properties of an ellipsoidal x-ray collection optic serving as a sensitivity enhancing component of the Transmission Grating Streak Spectrometer; (3) performance simulation of the x-ray dispersion properties of candidate x-ray laser cavity, normal incidence end-mirror optics; (4) contribute x-ray diagnostic, experimental, and data reduction and analysis support for the Novette Henway crystal spectrometer and the MCPIGS microchannel plate intensified grazing incident spectrometer experiments; and (5) perform a technical performance vs cost evaluation of commercially available hardware required to perform the NOVA neutron time-of-flight experiments

  12. Diagnostic agent for radioimmunological determinations

    International Nuclear Information System (INIS)

    Updike, S.J.

    1978-01-01

    The invention concerns a diagnostic agent for radioimmunological determinations. According to the invention, a binding protein (protein globulins, antibodies) of an aqueous solution specific for the substance to be determined is incorporated in gel particles of a strongly hydrophilic insoluble gel of controlled pore size. After subsequent drying of the system, a radioactively labelled form of the substance to be determined from a non-aqueous medium is included. The mixture is dried again. The diagnostic agent forred can be well stored and is very stable. There is no loss of activity of the specific bonding protein when drying according to the invented method. The described reagent can be effectively applied to the determination of many antigens and haptens: The gel is rehydrated by the sample to be investigated; as a result of this, the non-bonded tracer is set free and competes with the non-labelled substance for the bonding position. (VJ) [de

  13. Molecular Diagnostic Tests for Microsporidia

    Directory of Open Access Journals (Sweden)

    Kaya Ghosh

    2009-01-01

    Full Text Available The Microsporidia are a ubiquitous group of eukaryotic obligate intracellular parasites which were recognized over 100 years ago with the description of Nosema bombycis, a parasite of silkworms. It is now appreciated that these organisms are related to the Fungi. Microsporidia infect all major animal groups most often as gastrointestinal pathogens; however they have been reported from every tissue and organ, and their spores are common in environmental sources such as ditch water. Several different genera of these organisms infect humans, but the majority of infections are due to either Enterocytozoon bieneusi or Encephalitozoon species. These pathogens can be difficult to diagnose, but significant progress has been made in the last decade in the development of molecular diagnostic reagents for these organisms. This report reviews the molecular diagnostic tests that have been described for the identification of the microsporidia that infect humans.

  14. [Diagnostic workup of fragrance allergy].

    Science.gov (United States)

    Geier, J; Uter, W

    2015-09-01

    The diagnostic workup of contact allergy to fragrances must not be limited to patch testing with the two well-established fragrance mixes. False-positive reactions to these mixes occur in up to 50 % of the patch tested patients. For the diagnostic work-up of positive reactions, and in cases of suspected fragrance allergy, patch testing with the single mix components and additional fragrances is mandatory. Frequently sensitizing fragrance materials are the 14 components of the two fragrance mixes and tree moss (Evernia furfuracea), ylang ylang oil (I + II; Cananga odorata), lemongrass oil (Cymbopogon schoenanthus), sandalwood oil (Santalum album), jasmine absolute (Jasminum spp.), and, less frequently, clove oil (Eugenia caryophyllus), cedarwood oil (Cedrus atlantica/deodara, Juniperus virginiana), Neroli oil (Citrus aurantium amara flower oil), salicylaldehyde, narcissus absolute (Narcissus spp.), and patchouli oil (Pogostemon cablin).

  15. Nuclear power plant diagnostic system

    International Nuclear Information System (INIS)

    Prokop, K.; Volavy, J.

    1982-01-01

    Basic information is presented on diagnostic systems used at nuclear power plants with PWR reactors. They include systems used at the Novovoronezh nuclear power plant in the USSR, at the Nord power plant in the GDR, the system developed at the Hungarian VEIKI institute, the system used at the V-1 nuclear power plant at Jaslovske Bohunice in Czechoslovakia and systems of the Rockwell International company used in US nuclear power plants. These diagnostic systems are basically founded on monitoring vibrations and noise, loose parts, pressure pulsations, neutron noise, coolant leaks and acoustic emissions. The Rockwell International system represents a complex unit whose advantage is the on-line evaluation of signals which gives certain instructions for the given situation directly to the operator. The other described systems process signals using similar methods. Digitized signals only serve off-line computer analyses. (Z.M.)

  16. SALIVA AS A DIAGNOSTIC FLUID

    Directory of Open Access Journals (Sweden)

    Pezelj-Ribarić Sonja

    2015-12-01

    Full Text Available Saliva is a readily available oral fluid with many functions, from digestion, maintenance of oral tissues' integrity, to caries prevention. Changes regarding its secretion may be divided into qualitative and quantitative: both of them are a consequence of certain conditions/diseases (e.g. internal factors or nutrients/drugs ingested (e.g. external factors. During the last 15 years, technological advances gave a significant momentum to utilization of saliva as a diagnostic tool. Analysis of saliva, just like the blood analysis, has two main objectives: to identify the subjects suffering from a certain disorder, and to follow the development and progress of therapy. This paper provides an overview of possibilities for the use of saliva for diagnostic purposes and gives specific examples of some clinical investigations, with the final aim to stimulate the use of this noninvasive means for the health care promotion.

  17. Beam diagnostic instruments of TARN

    International Nuclear Information System (INIS)

    Watanabe, Shin-ichi.

    1987-09-01

    The paper summarizes the beam diagnostic instruments of the low energy ion accumulation ring; TARN. With these monitors, position, profiles, bunch structure, intensity, emittance and momentum spread were measured to evaluate the injection and stacking experiments. The monitors provide the sensitivity of a few μA for the nondestructive and a few nA for the destructive monitors. Discussions on monitor probe and electronics are presented on the basis of an achievement of the beam stacking experiments. (author)

  18. Diagnostic Strategy in APR1400

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dongyoung; Kim, Jonghyun [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

    2013-05-15

    These features may bring out changes in operator tasks, changing the characteristics of tasks, or creating new tasks. Diagnostic strategy for identifying anomaly may be different especially in APR1400 from that in the analog control room due to the change of human-system interface, i.e. alarm system and display system. Since the first plant of APR1400 is being built at this moment, it is not known what strategies the operators will adopt in diagnosis tasks in the new operating environment. In this light, this paper aims at investigating operator's diagnostic strategies which are appropriate for APR1400. In order to collect data, several different approaches which are complementary are used to identify diagnostic strategies in the digital control room: analysis on audio/video recording of operation, observation in the simulator, and interview with the operators. The result shows that the digital control room introduces new strategies in the diagnosis, compared with the analog control room, and also changed the characteristics of strategies, mostly, by getting more support from the computerized system. This paper investigated how the digitalized control room may influence operator's diagnostic strategies. Several different approaches, i. e., audio/video record, observation of training, and the interview with operators, were used to gather information about the operator's behaviors. As a conclusion, this paper figured out that the digital control room introduces new strategies in the diagnosis, compared with the analog control room, and also changed the characteristics of the strategies, mostly, by getting more support from the computerized system. The operators interviewed also commented that the diagnosis in the APR1400 is quicker, more correct, and easier, compared with the analog control room.

  19. Appropriate use of diagnostic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, P.E.S.; Cockshott, W.P.

    1984-11-16

    This article discusses ways in which more appropriate use can be made of roentgenography with a resulting decrease in radiation doses to the patient population. The authors recommend that fewer films be made and that traditional roentgenography be replaced with endoscopy, ultrasound, computerized tomography, or angiography where appropriate. They also recommend that medical schools and medical subspecialty groups study the World Health Organization document which provides indications for diagnostic imaging, the choice of procedure and the limitations of each.

  20. Recent advances in diagnostic microbiology.

    Science.gov (United States)

    Bravo, Lulette Tricia C; Procop, Gary W

    2009-07-01

    The past decade has seen a surge in the development of a variety of molecular diagnostics designed to rapidly identify or characterize medically important microorganisms. We briefly review important advances in molecular microbiology, and then discuss specific assays that have been implemented in clinical microbiology laboratories throughout the country. We also discuss emerging methods and technologies that will soon be more widely used for the prompt and accurate detection of the agents of infectious diseases.

  1. Diagnostic Strategy in APR1400

    International Nuclear Information System (INIS)

    Kim, Dongyoung; Kim, Jonghyun

    2013-01-01

    These features may bring out changes in operator tasks, changing the characteristics of tasks, or creating new tasks. Diagnostic strategy for identifying anomaly may be different especially in APR1400 from that in the analog control room due to the change of human-system interface, i.e. alarm system and display system. Since the first plant of APR1400 is being built at this moment, it is not known what strategies the operators will adopt in diagnosis tasks in the new operating environment. In this light, this paper aims at investigating operator's diagnostic strategies which are appropriate for APR1400. In order to collect data, several different approaches which are complementary are used to identify diagnostic strategies in the digital control room: analysis on audio/video recording of operation, observation in the simulator, and interview with the operators. The result shows that the digital control room introduces new strategies in the diagnosis, compared with the analog control room, and also changed the characteristics of strategies, mostly, by getting more support from the computerized system. This paper investigated how the digitalized control room may influence operator's diagnostic strategies. Several different approaches, i. e., audio/video record, observation of training, and the interview with operators, were used to gather information about the operator's behaviors. As a conclusion, this paper figured out that the digital control room introduces new strategies in the diagnosis, compared with the analog control room, and also changed the characteristics of the strategies, mostly, by getting more support from the computerized system. The operators interviewed also commented that the diagnosis in the APR1400 is quicker, more correct, and easier, compared with the analog control room

  2. Novel Nonlinear Laser Diagnostic Techniques

    Science.gov (United States)

    1993-07-01

    a thermometric probe of reactive flows. Since the two-photon pump laser couples a Doppler broadened ground state velocity distribution to the excited...rism, and passed unfocused into an aluminum cell con- in frequency space. Regions for line fitting are found by taining 99% pure NO. The gas mixture...of ASE as a More recently, ASE has prompted interest as an thermometric probe of combustion environments optical diagnostic of combustion environments

  3. The sleepy teenager - diagnostic challenges

    OpenAIRE

    Anne-Marie eLandtblom; Anne-Marie eLandtblom; Anne-Marie eLandtblom; Anne-Marie eLandtblom; Maria eEngström

    2014-01-01

    The sleepy teenager is a diagnostic challenge because the problems may be physiological or pathological, with behavioural, social and pychological expressions. It is of great importance that health staff that encounter young people with sleep disturbance have good knowledge about the diseases that must be excluded. Narcolepsy, periodic hypersomnia like Kleine Levin syndrome, delayed sleep phase syndrome and obstructive sleep apnoea syndrome, depression and substance use as well as fatigue f...

  4. Patient dosimetry in diagnostic radiology

    International Nuclear Information System (INIS)

    Shrimpton, P.C.

    2000-01-01

    Full text: X-ray examinations remain an essential and widely used diagnostic tool in medicine and hence the most significant source of exposure to man-made radiation for populations. Patterns of practice in diagnostic radiology continue to evolve, with overall growth in the numbers of procedures worldwide and, particularly in developed countries, increasing importance for complex procedures such as computed tomography (CT) and interventional techniques. In order to maximise the benefits from x-rays relative to the associated radiation risks, there is a need to ensure the prior justification of all examinations and the optimisation of patient protection such that doses are as low as reasonably practicable to meet specific clinical requirements. Accordingly, patient dosimetry is a fundamental requirement in diagnostic radiology. Detailed measurements for the assessment of risks or comparison of different types of procedure require the estimation of organ and effective doses. Such comprehensive dosimetry necessarily involves the simulation of clinical practice using anthropomorphic phantoms, with either measurements in a physical phantom or calculations utilising a mathematical phantom. Simpler measurements for the routine monitoring of dose in x-ray departments can be based on practical quantities such as entrance surface dose, dose-area product and, for CT, weighted CT dose index and dose-length product. Widescale surveys reveal significant variations between departments in the typical doses for a given type of procedure and potential scope for dose reductions. In order to promote improvements in practice, the results of periodic dose surveys in departments should be compared with appropriate standards, such as diagnostic reference levels for adult and paediatric patients, that are set nationally or locally for the purposes of promoting critical review of the equipment and techniques in use. Patient dosimetry should form an essential element of routine quality

  5. Infrared laser diagnostics for ITER

    International Nuclear Information System (INIS)

    Hutchinson, D.P.; Richards, R.K.; Ma, C.H.

    1995-01-01

    Two infrared laser-based diagnostics are under development at ORNL for measurements on burning plasmas such as ITER. The primary effort is the development of a CO 2 laser Thomson scattering diagnostic for the measurement of the velocity distribution of confined fusion-product alpha particles. Key components of the system include a high-power, single-mode CO 2 pulsed laser, an efficient optics system for beam transport and a multichannel low-noise infrared heterodyne receiver. A successful proof-of-principle experiment has been performed on the Advanced Toroidal Facility (ATF) stellerator at ORNL utilizing scattering from electron plasma frequency satellites. The diagnostic system is currently being installed on Alcator C-Mod at MIT for measurements of the fast ion tail produced by ICRH heating. A second diagnostic under development at ORNL is an infrared polarimeter for Faraday rotation measurements in future fusion experiments. A preliminary feasibility study of a CO 2 laser tangential viewing polarimeter for measuring electron density profiles in ITER has been completed. For ITER plasma parameters and a polarimeter wavelength of 10.6 microm, a Faraday rotation of up to 26 degree is predicted. An electro-optic polarization modulation technique has been developed at ORNL. Laboratory tests of this polarimeter demonstrated a sensitivity of ≤ 0.01 degree. Because of the similarity in the expected Faraday rotation in ITER and Alcator C-Mod, a collaboration between ORNL and the MIT Plasma Fusion Center has been undertaken to test this polarimeter system on Alcator C-Mod. A 10.6 microm polarimeter for this measurement has been constructed and integrated into the existing C-Mod multichannel two-color interferometer. With present experimental parameters for C-Mod, the predicted Faraday rotation was on the order of 0.1 degree. Significant output signals were observed during preliminary tests. Further experiment and detailed analyses are under way

  6. Biomedical photonics handbook biomedical diagnostics

    CERN Document Server

    Vo-Dinh, Tuan

    2014-01-01

    Shaped by Quantum Theory, Technology, and the Genomics RevolutionThe integration of photonics, electronics, biomaterials, and nanotechnology holds great promise for the future of medicine. This topic has recently experienced an explosive growth due to the noninvasive or minimally invasive nature and the cost-effectiveness of photonic modalities in medical diagnostics and therapy. The second edition of the Biomedical Photonics Handbook presents fundamental developments as well as important applications of biomedical photonics of interest to scientists, engineers, manufacturers, teachers, studen

  7. new possibilities in diagnostic radiology

    OpenAIRE

    Scheel, Michael

    2014-01-01

    Diffusion Tensor Imaging (DTI) allows a non-invasive diffusion-based tissue characterization and thus offers completely new possibilities in the field of diagnostic radiology. On the one hand, this method allows an improved detection of pathological changes at the microstructural level, which are frequently not detectable in conventional MRI methods. On the other hand new strategies for therapy monitoring are feasible by quantification of diffusion parameters (e.g., Parallel, Radial and Mean ...

  8. Algorithm of Functional Musculoskeletal Disorders Diagnostics

    OpenAIRE

    Alexandra P. Eroshenko

    2012-01-01

    The article scientifically justifies the algorithm of complex diagnostics of functional musculoskeletal disorders during resort treatment, aimed at the optimal application of modern methods of physical rehabilitation (correction programs formation), based on diagnostic methodologies findings

  9. Algorithm of Functional Musculoskeletal Disorders Diagnostics

    Directory of Open Access Journals (Sweden)

    Alexandra P. Eroshenko

    2012-04-01

    Full Text Available The article scientifically justifies the algorithm of complex diagnostics of functional musculoskeletal disorders during resort treatment, aimed at the optimal application of modern methods of physical rehabilitation (correction programs formation, based on diagnostic methodologies findings

  10. Myasthenia Gravis: Tests and Diagnostic Methods

    Science.gov (United States)

    ... Focus on MG Newsletter MG Quarterly Test & Diagnostic methods In addition to a complete medical and neurological ... How can I help? About MGFA Test & Diagnostic methods Treatment for MG FAQ's Upcoming Events 2018 MG ...

  11. Diagnostics for PLX-alpha

    Science.gov (United States)

    Gilmore, Mark; Hsu, Scott

    2015-11-01

    The goal of the Plasma Liner eXperiment PLX-alpha at Los Alamos National Laboratory is to establish the viability of creating a spherically imploding plasma liner for MIF and HED applications, using a spherical array of supersonic plasma jets launched by innovative contoured-gap coaxial plasma guns. PLX- α experiments will focus in particular on establishing the ram pressure and uniformity scalings of partial and fully spherical plasma liners. In order to characterize these parameters experimentally, a suite of diagnostics is planned, including multi-camera fast imaging, a 16-channel visible interferometer (upgraded from 8 channels) with reconfigurable, fiber-coupled front end, and visible and VUV high-resolution and survey spectroscopy. Tomographic reconstruction and data fusion techniques will be used in conjunction with interferometry, imaging, and synthetic diagnostics from modeling to characterize liner uniformity in 3D. Diagnostic and data analysis design, implementation, and status will be presented. Supported by the Advanced Research Projects Agency - Energy - U.S. Department of Energy.

  12. Diagnostic radiation and chromosome aberrations

    International Nuclear Information System (INIS)

    Patil, S.R.; Hecht, F.; Lubs, H.A.; Kimberling, W.; Brown, J.; Gerald, P.S.; Summitt, R.L.

    1977-01-01

    Some evidence is presented suggesting that diagnostic X-rays may be important in the origin of a new chromosomal abnormality other than Down syndrome. Chromosome analyses have been carried out on 4342 children, seven or eight years old. Maternal diagnostic irradiation in the year before conception and up to third lunar month of the index pregnancy was recorded, before the chromosome study began, together with a large amount of family and clinical data. Information on X-ray exposure was supplied by the mothers, s o radiation dosage could not be estimated. 21 children (including a pair of twins and a pair of siblings) born to 19 mothers had chromosomal aberrations. The mothers of six children with inherited translocations, rearrangements and XYY karyotypes were excluded, and 3 (23%) of the remaining 13 mothers had received abdominal and pelvic X-ray exposures. In the whole sample, however, only 6% of the mothers had diagnostic irradiation. Two of these mothers, aged sixteen and twenty, gave birth to a child each with de-novo autosomal translocations, and the third mother, aged thirty-two, had a child with a complex mosaicism involving one X chromosome. Although the sample size of the mothers with chromosomally abnormal children is small, the results are significant. (U.K.)

  13. The interpretation of diagnostic tests

    International Nuclear Information System (INIS)

    Lamk, M.; Lamki, M.D.

    1987-01-01

    The progress of nuclear and other diagnostic imaging is near rampant. With almost every issue of the major journals in this field, a new diagnostic test, or at least a new utility of an old test is described. Before we accept these innovations, we have to have a clear understanding of the clinical performance of the test. The major criteria are the sensitivity and the specificity of the test. From these derived other statistical parameters such as accuracy or efficiency of that test; also, the receiver operating characteristic (ROC) curves may then be evaluated and used in comparison of different tests. When we know the prevalence of the disease tested in the population we are investigating, we can then derive the predictive value of a positive or a negative result. This introduction tries to explain these parameters to help the reader understand the literature dealing with the subject of efficacy of imaging procedures. It is not intended as a critical review of the literature on the subject or a comprehensive overview of the subject matter. The benefit derived from explaination of statistical concepts to physicians is documented in a recent publication. Explaination of these basic statistical parameters will be followed by a demonstration of the utility of multiple testing with these parameters. The reader is thereby introduced to relevant statistical concepts that must be grasped for full comprehension of published results of a new diagnostic imaging modality, or before clinical decision making

  14. Diagnostic and therapeutic peroral cholangioscopy

    Directory of Open Access Journals (Sweden)

    Jong Ho Moon

    2012-01-01

    Full Text Available Peroral cholangioscopy (POC provides direct visualization of the bile duct and facilitates diagnostic or therapeutic intervention. The currently available single-operator POC systems are "Mother-baby" scope system, SpyGlass direct visualization system, and direct POC using a regular ultra-slim upper endoscope. Direct POC using an ultra-slim upper endoscope having a larger 2-mm working channel can provide a valuable and economic solution for evaluating bile-duct lesions. Main diagnostic procedures under direct POC are visual characterization and optically guided target biopsy for the indeterminate bile duct lesion. Image-enhanced endoscopy such as narrow-band imaging has shown promise for more detailed evaluation of mucosal abnormality and can be performed under direct POC. Intracorporeal lithotripsy such as electrohydraulic lithotripsy or laser lithotripsy is a main therapeutic intervention of direct POC for patients with bile duct stones that are resistant to conventional endoscopic stone-removal procedures. Besides, tumor ablation therapy, such as photodynamic therapy and argon plasma coagulation may be also performed using direct POC. Further developments of the endoscope and specialized accessories or devices are expected to facilitate diagnostic and therapeutic role of this cholangioscopic procedure.

  15. Intelligent neural network diagnostic system

    International Nuclear Information System (INIS)

    Mohamed, A.H.

    2010-01-01

    Recently, artificial neural network (ANN) has made a significant mark in the domain of diagnostic applications. Neural networks are used to implement complex non-linear mappings (functions) using simple elementary units interrelated through connections with adaptive weights. The performance of the ANN is mainly depending on their topology structure and weights. Some systems have been developed using genetic algorithm (GA) to optimize the topology of the ANN. But, they suffer from some limitations. They are : (1) The computation time requires for training the ANN several time reaching for the average weight required, (2) Slowness of GA for optimization process and (3) Fitness noise appeared in the optimization of ANN. This research suggests new issues to overcome these limitations for finding optimal neural network architectures to learn particular problems. This proposed methodology is used to develop a diagnostic neural network system. It has been applied for a 600 MW turbo-generator as a case of real complex systems. The proposed system has proved its significant performance compared to two common methods used in the diagnostic applications.

  16. Health Risks of Diagnostic Radiology

    International Nuclear Information System (INIS)

    Al-Oraby, M.N.A.

    2014-01-01

    Exposure to ionizing radiation during diagnostic radiologic procedures carries small but real risks. Children, young adults and pregnant women are especially vulnerable. Exposure of patients to diagnostic energy levels of ionizing radiation should be kept to the minimum necessary to provide useful clinical information and allay patients concerns about radiation-related risks. Computerized Tomography (CT) accounts for two thirds of the cumulative patient dose from diagnostic radiological procedures and the cumulative dose from CT is rising as technological advances increase the number of indications and the capabilities of CT. Carcinogenesis and teratogenesis are the main concerns with ionizing radiation. The risk increases as the radiation dose increases. There is no minimum threshold and the risk is cumulative: a dose of 1 mSv once a year for 10 years is equivalent to a single dose of 10 mSv. Whenever practical, choose an imaging test that uses less radiation or no radiation and lengthen the periods between follow-up imaging tests. Some patients may avoid screening mammography because of fear of radiation-induced cancer, yet this test uses a very small radiation dose (0.6 mSv, much less than the annual dose from background radiation, 3.6 mSv). (author)

  17. Diagnostic guidlines for occupational epicondylitis

    Directory of Open Access Journals (Sweden)

    Patrycja Krawczyk-Szulc

    2015-07-01

    Full Text Available Making final decisions on the occupational etiology of musculoskeletal diseases is often difficult and problematic at every stage of the diagnostic procedure. Taking into account the need to facilitate decision-making about the causal relationship between the diagnosed disease entity and the working conditions guidelines for the recognition of work-related musculoskeletal diseases have been developed. This paper presents the guidelines for the diagnosis of occupational etiology of humeral epicondylitis, one of the most common occupational disease of the musculoskeletal system in Poland. The developed guidelines have been based on the literature data concerning occupational risk factors of humeral epicondylitis, workload classification, including repetitive movements, awkward postures, and force. Some criteria applied in ergonomic evaluation methods were also included. The presented diagnostic guidelines define approximate benchmarks for stating (after excluding non-occupational etiology that the identified humeral epicondylitis, is related to the way of working. Crucial work factors that should be analyzed include an operating time of movements overloading tendons connecting to the epicondyle, repetition and force used to perform occupational activities. The developed guidelines are aimed to facilitate occupational physicians diagnostic and certification procedures in case of humeral epicondylitis and determination whether there is a likelihood of its occupational etiology. Med Pr 2015;66(3:443–450

  18. Diagnostic radiation and chromosome aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Patil, S R; Hecht, F [Dept. of Pediatrics, Child Development and Rehabilitation Center, Univ. of Oregon Health Sciences Center, Portland, Oregon (USA); Lubs, H A; Kimberling, W; Brown, J; Gerald, P S; Summitt, R L

    1977-01-15

    Some evidence is presented suggesting that diagnostic X-rays may be important in the origin of a new chromosomal abnormality other than Down syndrome. Chromosome analyses have been carried out on 4342 children, seven or eight years old. Maternal diagnostic irradiation in the year before conception and up to third lunar month of the index pregnancy was recorded, before the chromosome study began, together with a large amount of family and clinical data. Information on X-ray exposure was supplied by the mothers, so radiation dosage could not be estimated. 21 children (including a pair of twins and a pair of siblings) born to 19 mothers had chromosomal aberrations. The mothers of six children with inherited translocations, rearrangements and XYY karyotypes were excluded, and 3 (23%) of the remaining 13 mothers had received abdominal and pelvic X-ray exposures. In the whole sample, however, only 6% of the mothers had diagnostic irradiation. Two of these mothers, aged sixteen and twenty, gave birth to a child each with de-novo autosomal translocations, and the third mother, aged thirty-two, had a child with a complex mosaicism involving one X chromosome. Although the sample size of the mothers with chromosomally abnormal children is small, the results are significant.

  19. Radiation exposure in diagnostic medicine

    International Nuclear Information System (INIS)

    Haehnel, S.; Michalczak, H.; Reinoehl-Kompa, S.

    1995-01-01

    This volume includes the manuscripts of the papers read at the conference as well as a summary and assessment of its results. The scientific discussions were centred upon the following issues: - International surveys and comparisons of rdiation exposures in diagnostic radiology and nuclear medicine, frequency of the individual diagnostic procedures and age distribution of patients examined; - policies and regulations for the radiation protection of patients, charcteristic dosimetric values and practical usefulness of the effective dose concept during medical examinations; - assessments of the relative benefits and risks and measures to reduce the radiation exposure in the light of quality assurance aspects. The main objective of this conference not only was to evaluate the risks from diagnostic radiology and nuclear medicine but also to encourgage a critical analysis and adjustment of examination routines followed in everyday practice. Among the measures recommended were quality assurance, maintenace of international standards, development of guidelines, introduction of standard doses, improved training and professional education of personnel as well as surveys and analyses of certain examination procedures associated with substantial radiation exposure. (orig./MG) [de

  20. Diagnostic interventions in nuclear medicine

    International Nuclear Information System (INIS)

    Thrall, J.H.; Swanson, D.P.

    1989-01-01

    Diagnostic interventions in nuclear medicine may be defined as the coadministration of a nonradioactive drug or application of a physical stimulus or physiologic maneuver to enhance the diagnostic utility of a nuclear medicine test. The rationale for each interventional maneuver follows from the physiology or metabolism of the particular organ or organ system under evaluation. Diagnostic inference is drawn from the pattern of change in the biodistribution of the tracer in response to the intervention-induced change in metabolism or function. In current practice, the most commonly performed interventional maneuvers are aimed at studies of the heart, genitourinary system, hepatobiliary system, and gastrointestinal tract. The single most commonly performed interventional study in the United States is the stress Thallium-201 myocardial perfusion scan aimed at the diagnosis of coronary artery disease. The stress portion of the study is accomplished with dynamic leg exercise on a treadmill and is aimed at increasing myocardial oxygen demands. Areas of myocardium distal to hemodynamically significant lesions in the coronary arteries become ischemic at peak stress due to the inability of the stenotic vessel to respond to the oxygen demand/blood flow needs of the myocardium. Ischemic areas are readily recognized as photopenic defects on scans obtained immediately after exercise, with normalization upon delayed imaging. Diuresis renography is aimed at the differential diagnosis of hydroureteronephrosis. By challenging the urinary tract collecting structures with an augmented urine flow, dilated, unobstructed systems can be differentiated from systems with significant mechanical obstruction. 137 references

  1. Portable Diagnostics and Rapid Germination

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, Zachary Spencer [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-12-01

    In the Bioenergy and Defense Department of Sandia National Laboratories, characterization of the BaDx (Bacillus anthracis diagnostic cartridge) was performed and rapid germination chemistry was investigated. BaDx was tested with complex sample matrixes inoculated with Bacillus anthracis, and the trials proved that BaDx will detect Bacillus anthracis in a variety of the medium, such as dirt, serum, blood, milk, and horse fluids. The dimensions of the device were altered to accommodate an E. coli or Listeria lateral flow immunoassay, and using a laser printer, BaDx devices were manufactured to identify E. coli and Listeria. Initial testing with E. coli versions of BaDx indicate that the device will be viable as a portable diagnostic cartridge. The device would be more effective with faster bacteria germination; hence studies were performed the use of rapid germination chemistry. Trials with calcium dipicolinic acid displayed increased cell germination, as shown by control studies using a microplate reader. Upon lyophilization the rapid germination chemistry failed to change growth patterns, indicating that the calcium dipicolinic acid was not solubilized under the conditions tested. Although incompatible with the portable diagnostic device, the experiments proved that the rapid germination chemistry was effective in increasing cell germination.

  2. Copper laser diagnostics and kinetics support

    International Nuclear Information System (INIS)

    1981-12-01

    In the effort MSNW participated with the LINL copper-Vapor Laser Program by providing a useful plasma diagnostic for interpretation of Copper-vapor laser kinetics. MSNW developed and delivered a pulsed interferometric diagnostic package to LLNL. Moreover MSNW provided personal services at the request and direction of LLL in the implementation of the diagnostic and interpretation of the data

  3. Climate Prediction Center: ENSO Diagnostic Discussion

    Science.gov (United States)

    Organization Search Go Search the CPC Go Expert Assessments ENSO Diagnostic Discussion Archive About Us Our Assessments > ENSO Diagnostic Discussion El Niño/Southern Oscillation (ENSO) Diagnostic Discussion PDF : English Version Spanish Version Adobe PDF Reader (Click icon for Adobe PDF Reader) Word: English Version

  4. MFTF-B plasma-diagnostic system

    International Nuclear Information System (INIS)

    Throop, A.L.; Goerz, D.A.; Thomas, S.R.

    1981-01-01

    This paper describes the current design status of the plasma diagnostic system for MFTF-B. In this paper we describe the system requirement changes which have occurred as a result of the funded rescoping of the original MFTF facility into MFTF-B. We outline the diagnostic instruments which are currently planned, and present an overview of the diagnostic system

  5. Complications in diagnostic imaging. 2. ed.

    International Nuclear Information System (INIS)

    Ansell, G.; Wilkins, R.A.; Medical Research Council, Harrow

    1987-01-01

    Thirty-seven chapters review various complications which may arise for patients and staff in medical diagnostic imaging. Five of these chapters are indexed separately covering topics on the complications of using radiopharmaceuticals, safety considerations in magnetic resonance imaging, radiation hazards of diagnostic radiology and medico-legal problems involving diagnostic radiology in both the UK and the USA. (UK)

  6. Relating faults in diagnostic reasoning with diagnostic errors and patient harm.

    NARCIS (Netherlands)

    Zwaan, L.; Thijs, A.; Wagner, C.; Wal, G. van der; Timmermans, D.R.M.

    2012-01-01

    Purpose: The relationship between faults in diagnostic reasoning, diagnostic errors, and patient harm has hardly been studied. This study examined suboptimal cognitive acts (SCAs; i.e., faults in diagnostic reasoning), related them to the occurrence of diagnostic errors and patient harm, and studied

  7. Summary from working group on noninterceptive diagnostics

    International Nuclear Information System (INIS)

    Chamberlin, D.D.

    1985-01-01

    The working group for noninterceptive diagnostics spent much of its time comparing diagnostic techniques from different fields and their possible application to high-power injectors. The group included backgrounds from electron beam diagnostics, fusion power diagnostics, cw ion source and transport design, and ion beam of diagnostics. The probability of success for adapting techniques from these different areas is quite difficult to judge, short of a detailed examination of each application. Unexpected flaws or unforeseen noise sources can eliminate an idea that would otherwise appear promising. The report presents several ideas that were discussed, with an indication of those ideas most likely to succeed if implemented

  8. Radiogenomics: Creating a link between molecular diagnostics and diagnostic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Rutman, Aaron M. [Department of Radiology, University of California San Diego Medical Center, San Diego, CA 92103 (United States); Kuo, Michael D. [Department of Radiology, University of California San Diego Medical Center, San Diego, CA 92103 (United States); Center for Translational Medical Systems, University of California San Diego Medical Center, San Diego, CA 92103 (United States)], E-mail: mkuo@ucsd.edu

    2009-05-15

    Studies employing high-throughput biological techniques have recently contributed to an improved characterization of human cancers, allowing for novel sub-classification, better diagnostic accuracy, and more precise prognostication. However, requirement of surgical procurement of tissue among other things limits the clinical application of such methods in everyday patient care. Radiographic imaging is routine in clinical practice but is currently histopathology based. The use of routine radiographic imaging provides a potential platform for linking specific imaging traits with specific gene expression patterns that inform the underlying cellular pathophysiology; imaging features could then serve as molecular surrogates that contribute to the diagnosis, prognosis, and likely gene-expression-associated treatment response of various forms of human cancer. This review focuses on high-throughput methods such as microarray analysis of gene expression, their role in cancer research, and in particular, on novel methods of associating gene expression patterns with radiographic imaging phenotypes, known as 'radiogenomics.' These findings underline a potential future role of both diagnostic and interventional radiologists in genetic assessment of cancer patients with radiographic imaging studies.

  9. Radiogenomics: Creating a link between molecular diagnostics and diagnostic imaging

    International Nuclear Information System (INIS)

    Rutman, Aaron M.; Kuo, Michael D.

    2009-01-01

    Studies employing high-throughput biological techniques have recently contributed to an improved characterization of human cancers, allowing for novel sub-classification, better diagnostic accuracy, and more precise prognostication. However, requirement of surgical procurement of tissue among other things limits the clinical application of such methods in everyday patient care. Radiographic imaging is routine in clinical practice but is currently histopathology based. The use of routine radiographic imaging provides a potential platform for linking specific imaging traits with specific gene expression patterns that inform the underlying cellular pathophysiology; imaging features could then serve as molecular surrogates that contribute to the diagnosis, prognosis, and likely gene-expression-associated treatment response of various forms of human cancer. This review focuses on high-throughput methods such as microarray analysis of gene expression, their role in cancer research, and in particular, on novel methods of associating gene expression patterns with radiographic imaging phenotypes, known as 'radiogenomics.' These findings underline a potential future role of both diagnostic and interventional radiologists in genetic assessment of cancer patients with radiographic imaging studies.

  10. Paradigm Shifts in Ophthalmic Diagnostics.

    Science.gov (United States)

    Sebag, J; Sadun, Alfredo A; Pierce, Eric A

    2016-08-01

    Future advances in ophthalmology will see a paradigm shift in diagnostics from a focus on dysfunction and disease to better measures of psychophysical function and health. Practical methods to define genotypes will be increasingly important and non-invasive nanotechnologies are needed to detect molecular changes that predate histopathology. This is not a review nor meant to be comprehensive. Specific topics have been selected to illustrate the principles of important paradigm shifts that will influence the future of ophthalmic diagnostics. It is our impression that future evaluation of vision will go beyond visual acuity to assess ocular health in terms of psychophysical function. The definition of disease will incorporate genotype into what has historically been a phenotype-centric discipline. Non-invasive nanotechnologies will enable a paradigm shift from disease detection on a cellular level to a sub-cellular molecular level. Vision can be evaluated beyond visual acuity by measuring contrast sensitivity, color vision, and macular function, as these provide better insights into the impact of aging and disease. Distortions can be quantified and the psychophysical basis of vision can be better evaluated than in the past by designing tests that assess particular macular cell function(s). Advances in our understanding of the genetic basis of eye diseases will enable better characterization of ocular health and disease. Non-invasive nanotechnologies can assess molecular changes in the lens, vitreous, and macula that predate visible pathology. Oxygen metabolism and circulatory physiology are measurable indices of ocular health that can detect variations of physiology and early disease. This overview of paradigm shifts in ophthalmology suggests that the future will see significant improvements in ophthalmic diagnostics. The selected topics illustrate the principles of these paradigm shifts and should serve as a guide to further research and development. Indeed

  11. Diagnostics of vector magnetic fields

    Science.gov (United States)

    Stenflo, J. O.

    1985-01-01

    It is shown that the vector magnetic fields derived from observations with a filter magnetograph will be severely distorted if the spatially unresolved magnetic structure is not properly accounted for. Thus the apparent vector field will appear much more horizontal than it really is, but this distortion is strongly dependent on the area factor and the temperature line weakenings. As the available fluxtube models are not sufficiently well determined, it is not possible to correct the filter magnetograph observations for these effects in a reliable way, although a crude correction is of course much better than no correction at all. The solution to this diagnostic problem is to observe simultaneously in suitable combinations of spectral lines, and/or use Stokes line profiles recorded with very high spectral resolution. The diagnostic power of using a Fourier transform spectrometer for polarimetry is shown and some results from I and V spectra are illustrated. The line asymmetries caused by mass motions inside the fluxtubes adds an extra complication to the diagnostic problem, in particular as there are indications that the motions are nonstationary in nature. The temperature structure appears to be a function of fluxtube diameter, as a clear difference between plage and network fluxtubes was revealed. The divergence of the magnetic field with height plays an essential role in the explanation of the Stokes V asymmetries (in combination with the mass motions). A self consistent treatment of the subarcsec field geometry may be required to allow an accurate derivation of the spatially averaged vector magnetic field from spectrally resolved data.

  12. DEMO diagnostics and burn control

    Energy Technology Data Exchange (ETDEWEB)

    Biel, Wolfgang, E-mail: w.biel@fz-juelich.de [Institute of Energy and Climate Research, Forschungszentrum Jülich GmbH, Jülich (Germany); Department of Applied Physics, Ghent University (Belgium); Baar, Marco de [FOM-Institute DIFFER, Nieuwegein (Netherlands); Eindhoven University of Technology (Netherlands); Dinklage, Andreas [Max-Planck-Institut für Plasmaphysik, Greifswald (Germany); Felici, Federico [Eindhoven University of Technology (Netherlands); König, Ralf [Max-Planck-Institut für Plasmaphysik, Greifswald (Germany); Meister, Hans; Treutterer, Wolfgang [Max-Planck-Institut für Plasmaphysik, Garching (Germany); Wenninger, Ronald [Max-Planck-Institut für Plasmaphysik, Garching (Germany); EFDA Power Plant Physics and Technology, Garching (Germany)

    2015-10-15

    Highlights: • An initial concept for the DEMO diagnostic and control system is presented. • A preliminary list of control functions and candidate diagnostics is developed. • Challenges regarding disruptions, power exhaust and radiation control are highlighted. • The need for introducing realistic control margins is emphasized. • On outline of the future R&D plan is presented. - Abstract: The development of the control system for a tokamak demonstration fusion reactor (DEMO) faces unprecedented challenges. First, the requirements for control reliability and accuracy are more stringent than on existing fusion devices: any loss of plasma control on DEMO may result in a disruption which could damage the inner wall of the machine, while operating the device with larger margins against the operational limits would lead to a reduction of the electrical output power. Second, the performance of DEMO control is limited by space restrictions for the implementation of components (optimization of the tritium breeding rate), by lifetime issues for the front-end parts (neutron and gamma radiation, erosion and deposition acting on all components) and by slow, weak and indirect action of the available actuators (plasma shaping, heating and fuelling). The European DEMO conceptual design studies include the development of a reliable control system, since the details of the achievable plasma scenario and the machine design may depend on the actual performance of the control system. In the first phase of development, an initial understanding of the prime choices of diagnostic methods applicable to DEMO, implementation and performance issues, the interrelation with the plasma scenario definition, and the planning of necessary future R&D have been obtained.

  13. Safety of Medical Diagnostic Ultrasound

    International Nuclear Information System (INIS)

    Breyer, B.

    1998-01-01

    Large numbers of people (both sick and healthy) are routinely exposed to ultrasound waves. We shall discuss wave parameters and scanner properties that are relevant to the safety aspect. This includes central pulse frequency, pulse length, intensity (ISPTA and others), focusing, pulse repetition frequency, pulse pressure, etc. Since the transmitted ultrasound power has steadily been increasing during the last two decades, the problems are becoming more serious with time. Doppler methods have gained importance and 'popularity, which additionally increases ultrasound power requirements since the reflectivity of red blood cells is so small that the backscattered pressure is about 100 times less than that from soft tissue structures in the body. Main mechanisms that can potentially present hazard are heating and cavitation. The basic parameter used to assess thermal hazard is ISPTA and the optimal predictor of cavitation hazard is the peak rarefractional pressure. The hazard of heating-up can be summarized in saying that temperatures up to 38.5 o C are safe, while temperatures above 41 o C are definitely not. Care must be taken to stay within the safe zone. However, there does not exist a confirmed report of any type of hazardous effects on humans using intensities presently applied in diagnostic ultrasound scanners. Taking this into account, various international bodies have put limits to the application of ultrasound, which is best summarized in the FDA (USA) regulation that diagnostic apparatus may have an output of maximally 720 mW/cm 2 (derated) provided thermal and mechanical properties are indicated (onscreen) by properly defined Thermal Indices (TI) and Mechanical Index (MI). These aspects shall be discussed in some detail. We shall give the rules for the operator to apply ultrasound with minimal hazard. The general conclusion is that diagnostic ultrasound, as presently known, may be used whenever a qualified expert expects essential medical benefit for the

  14. Diagnostic imaging of the hand

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, Rainer [Hospital for Cardiovascular Diseases, Bad Neustadt an der Saale (Germany). Dept. of Radiology; Lanz, Ulrich [Perlach Hospital, Munich (Germany). Dept. of Hand Surgery

    2008-07-01

    With its complex anatomy and specialized biomechanics, the human hand has always presented physicians with a unique challenge when it comes to diagnosing and treating the diseases that afflict it. And while recent decades have seen a rapid increase in the number of therapeutic options, many diseases and injuries of the hand are still commonly misinterpreted. In diagnostic imaging of the hand, an interdisciplinary team, comprisingspecialists in radiology, surgery, and rheumatology, presents a comprehensive,reliable guide to this topographically intricate area. Highlights include: - More than 1000 high-quality illustrations - All state-of-the-art imaging modalities-including multidetector CT, with 2D displays and 3D reconstructions, and contrast-enhanced MRI with multi-channel, phased-array coils - An overview of all currently used methods of examination - A detailed presentation of the anatomic and functional foundations necessary for diagnosis - Full coverage of all disorders of the hand - Systematic treatment of each disease's definition, pathogenesis, and clinical symptoms, according to a graduated diagnostic plan - Easy-to-use format, featuring crisp images and line drawings seamlessly integrated with concise text, summary tables, and handy checklists - A heavily cross-referenced appendix of differential diagnosis tables - Emphasis on interdisciplinary consultation throughout designed to help both radiologists and clinicians develop the most efficient and effective strategies for evaluating and treating patients, Diagnostic imaging of the hand will leave specialists of all levels with a fresh appreciation for - and a richer understanding of - the expanding array of cutting-edge alternatives for diagnosing and treating disorders of the hand. (orig.)

  15. Diagnostic imaging of the hand

    International Nuclear Information System (INIS)

    Schmitt, Rainer; Lanz, Ulrich

    2008-01-01

    With its complex anatomy and specialized biomechanics, the human hand has always presented physicians with a unique challenge when it comes to diagnosing and treating the diseases that afflict it. And while recent decades have seen a rapid increase in the number of therapeutic options, many diseases and injuries of the hand are still commonly misinterpreted. In diagnostic imaging of the hand, an interdisciplinary team, comprisingspecialists in radiology, surgery, and rheumatology, presents a comprehensive,reliable guide to this topographically intricate area. Highlights include: - More than 1000 high-quality illustrations - All state-of-the-art imaging modalities-including multidetector CT, with 2D displays and 3D reconstructions, and contrast-enhanced MRI with multi-channel, phased-array coils - An overview of all currently used methods of examination - A detailed presentation of the anatomic and functional foundations necessary for diagnosis - Full coverage of all disorders of the hand - Systematic treatment of each disease's definition, pathogenesis, and clinical symptoms, according to a graduated diagnostic plan - Easy-to-use format, featuring crisp images and line drawings seamlessly integrated with concise text, summary tables, and handy checklists - A heavily cross-referenced appendix of differential diagnosis tables - Emphasis on interdisciplinary consultation throughout designed to help both radiologists and clinicians develop the most efficient and effective strategies for evaluating and treating patients, Diagnostic imaging of the hand will leave specialists of all levels with a fresh appreciation for - and a richer understanding of - the expanding array of cutting-edge alternatives for diagnosing and treating disorders of the hand. (orig.)

  16. Estimating the economic and social consequences for patients diagnosed with human African trypanosomiasis in Muchinga, Lusaka and Eastern Provinces of Zambia (2004–2014)

    OpenAIRE

    Mwiinde, Allan Mayaba; Simuunza, Martin; Namangala, Boniface; Chama-Chiliba, Chitalu Miriam; Machila, Noreen; Anderson, Neil; Shaw, Alexandra; Welburn, Susan C.

    2017-01-01

    Background Acute human African trypanosomiasis (rHAT) caused by Trypanosoma brucei rhodesiense is associated with high mortality and is fatal if left untreated. Only a few studies have examined the psychological, social and economic impacts of rHAT. In this study, mixed qualitative and quantitative research methods were used to evaluate the socio-economic impacts of rHAT in Mambwe, Rufunsa, Mpika and Chama Districts of Zambia. Methods Individuals diagnosed with rHAT from 2004 to 2014 were tra...

  17. Epidemiology of human African trypanosomiasis

    Directory of Open Access Journals (Sweden)

    Franco JR

    2014-08-01

    Full Text Available Jose R Franco,1 Pere P Simarro,1 Abdoulaye Diarra,2 Jean G Jannin1 1World Health Organization, Control of Neglected Tropical Diseases, Innovative and Intensified Disease Management, Geneva, Switzerland; 2World Health Organization, Inter Country Support Team for Central Africa, Regional Office for Africa, Libreville, Gabon Abstract: Human African trypanosomiasis (HAT, or sleeping sickness, is caused by Trypanosoma brucei gambiense, which is a chronic form of the disease present in western and central Africa, and by Trypanosoma brucei rhodesiense, which is an acute disease located in eastern and southern Africa. The rhodesiense form is a zoonosis, with the occasional infection of humans, but in the gambiense form, the human being is regarded as the main reservoir that plays a key role in the transmission cycle of the disease. The gambiense form currently assumes that 98% of the cases are declared; the Democratic Republic of the Congo is the most affected country, with more than 75% of the gambiense cases declared. The epidemiology of the disease is mediated by the interaction of the parasite (trypanosome with the vectors (tsetse flies, as well as with the human and animal hosts within a particular environment. Related to these interactions, the disease is confined in spatially limited areas called “foci”, which are located in Sub-Saharan Africa, mainly in remote rural areas. The risk of contracting HAT is, therefore, determined by the possibility of contact of a human being with an infected tsetse fly. Epidemics of HAT were described at the beginning of the 20th century; intensive activities have been set up to confront the disease, and it was under control in the 1960s, with fewer than 5,000 cases reported in the whole continent. The disease resurged at the end of the 1990s, but renewed efforts from endemic countries, cooperation agencies, and nongovernmental organizations led by the World Health Organization succeeded to raise awareness and

  18. Evaluation of an ethnopharmacologically selected Bhutanese medicinal plants for their major classes of phytochemicals and biological activities.

    Science.gov (United States)

    Wangchuk, Phurpa; Keller, Paul A; Pyne, Stephen G; Taweechotipatr, Malai; Tonsomboon, Aunchalee; Rattanajak, Roonglawan; Kamchonwongpaisan, Sumalee

    2011-09-01

    As many as 229 medicinal plants have been currently used in the Bhutanese Traditional Medicine (BTM) as a chief ingredient of polyherbal formulations and these plants have been individually indicated for treating various types of infections including malaria, tumor, and microbial. We have focused our study only on seven species of these plants. We aim to evaluate the antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities of the seven medicinal plants of Bhutan selected using an ethno-directed bio-rational approach. This study creates a scientific basis for their use in the BTM and gives foundation for further phytochemical and biological evaluations which can result in the discovery of new drug lead compounds. A three stage process was conducted which consisted of: (1) an assessment of a pharmacopoeia and a formulary book of the BTM for their mode of plant uses; (2) selecting 25 anti-infective medicinal plants based on the five established criteria, collecting them, and screening for their major classes of phytochemicals using appropriate test protocols; and (3) finally analyzing the crude extracts of the seven medicinal plants, using the standard test protocols, for their antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities as directed by the ethnopharmacological uses of each plant. Out of 25 medicinal plants screened for their major classes of phytochemicals, the majority contained tannins, alkaloids and flavonoids. Out of the seven plant species investigated for their biological activities, all seven of them exhibited mild antimicrobial properties, five plants gave significant in vitro antiplasmodial activities, two plants gave moderate anti-Trypanosoma brucei rhodesiense activity, and one plant showed mild cytotoxicity. Meconopsis simplicifolia showed the highest antiplasmodial activity with IC(50) values of 0.40 μg/ml against TM4/8.2 strain (a wild type chloroquine and

  19. [Radiological diagnostics in CUP syndrome].

    Science.gov (United States)

    Kazmierczak, P M; Nikolaou, K; Rominger, A; Graser, A; Reiser, M F; Cyran, C C

    2014-02-01

    Imaging plays an essential role in the therapeutic management of cancer of unknown primary (CUP) patients for localizing the primary tumor, for the identification of tumor entities for which a dedicated therapy regimen is available and for the characterization of clinicopathological subentities that direct the subsequent diagnostic and therapeutic strategy. Modalities include conventional x-ray, computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound as well as positron emission tomography (PET)-CT and MRI-PET. In whole body imaging CT has a high sensitivity for tumor entities which frequently present as a metastasized cancer illness. According to the current literature CT is diagnostic in 86% of patients with pancreatic carcinoma, in 36% of patients with colon carcinoma and in 74% of patients with lung carcinoma. Additionally a meta-analysis showed that for patients with squamous cell carcinoma and cervical lymph node metastases a positive diagnosis was possible in 22% of the cases using CT, in 36% using MRI and in 28-57% using 18F-fluorodeoxyglucose PET-CT ((18)F-FDG PET-CT). In addition, MRI plays an important role in the localization of primary occult tumors (e.g. breast and prostate) because of its high soft tissue contrast and options for functional imaging. At the beginning of the diagnostic algorithm stands the search for a possible primary tumor and CT of the neck, thorax and abdomen is most frequently used for whole body staging. Subsequent organ-specific imaging examinations follow, e.g. mammography in women with axillary lymphadenopathy. For histological and immunohistochemical characterization of tumor tissue, imaging is also applied to identify the most accessible and representative tumor manifestation for biopsy. Tumor biopsy may be guided by CT, MRI or ultrasound and MRI also plays a central role in the localization of primary occult tumors because of superior soft tissue contrast and options for functional imaging (perfusion

  20. Vibration diagnostics instrumentation for ILC

    Energy Technology Data Exchange (ETDEWEB)

    Bertolini, A.

    2007-06-15

    The future e{sup -}e{sup +} 500 GeV International Linear Collider will rely on unprecedented nanometer scale particle beam size at the interaction point, in order to achieve the design luminosity. Tight tolerances on static and dynamic alignment of the accelerator cavities and optical components are demanded to transport and focus the high energy electron and positron beams with reasonable position jitter and low emittance. A brief review of techniques and devices evaluated and developed so far for the vibration diagnostics of the machine is presented in this paper. (orig.)

  1. Intensified CCD for ultrafast diagnostics

    International Nuclear Information System (INIS)

    Cheng, J.; Tripp, G.; Coleman, L.

    1978-01-01

    Many of the present laser fusion diagnostics are recorded on either ultrafast streak cameras or on oscilloscopes. For those experiments in which a large volume of data is accumulated, direct computer processing of the information becomes important. We describe an approach which uses a RCA 52501 back-thinned CCD sensor to obtain direct electron readouts for both the streak camera and the CRT. Performance of the 100 GHz streak camera and the 4 GHz CRT are presented. Design parameters and computer interfacing for both systems are described in detail

  2. Diagnostic imaging of the pancreas

    International Nuclear Information System (INIS)

    Araki, Tsutomu; Itai, Yuji

    1981-01-01

    Diagnostic imaging of the pancreas, ultrasonography (US), computed tomography (CT), radionuclide (RN) scintigraphy, angiography, and endoscopic retrograde pancreaticography (ERP). First three noninvasive methods, were the most effective to diagnose psudo-cyst or cystoadenoma. Especially, CT gives the clear image of inflammation and shows pancreatic stones and calcification, with high sensitivity. As for pancreatic carcinomas there was no noninvasive methods to apply at an early stage. In order to diagnose the cancer the combination of angiography and ERP was preferable. The problem was how to select the candidates for the investigation of combined method out of the patients with negative CT or US. (Tsunoda, M.)

  3. Vibration diagnostics instrumentation for ILC

    International Nuclear Information System (INIS)

    Bertolini, A.

    2007-06-01

    The future e - e + 500 GeV International Linear Collider will rely on unprecedented nanometer scale particle beam size at the interaction point, in order to achieve the design luminosity. Tight tolerances on static and dynamic alignment of the accelerator cavities and optical components are demanded to transport and focus the high energy electron and positron beams with reasonable position jitter and low emittance. A brief review of techniques and devices evaluated and developed so far for the vibration diagnostics of the machine is presented in this paper. (orig.)

  4. A new diagnostic for spheromaks

    International Nuclear Information System (INIS)

    Boyd, D.A.

    1986-01-01

    Electron cyclotron emission from a spheromak plasma may be able to provide information about the confining magnetic field of the system. Emission generated in the extraordinary mode wit hits electric vector perpendicular to the local magnetic field at sufficiently high frequency will propagate out of the plasma while retaining the original orientation if its electric vector. Thus, a measurement of the orientation of the emergent electric vector and the emission frequency will allow one to deduce the orientation and strength of the magnetic field at the radiation source. In this paper, simple models of the Maryland spheromak are used to examine the practicality of such a diagnostic

  5. Interface language for diagnostic control

    International Nuclear Information System (INIS)

    Matone, J.T.

    1985-01-01

    The neutron multichannel collimator diagnostic on TFTR is run with the help of a keyboard-entered interface language. The language allows the user to interact with the real-time control and data analysis systems in a consistent and efficient manner. It uses a vocabulary that can be abbreviated into one character commands which the proficient user may concatenate into command words. This allows the user to progress quickly from a novice to an expert operating mode. A similar type interface language could be applied to many interactive applications accepting keyboard inputs

  6. [Pedophilia. Prevalence, etiology, and diagnostics].

    Science.gov (United States)

    Mokros, A; Osterheider, M; Nitschke, J

    2012-03-01

    Pedophilia is a disorder of sexual preference that increases the risk for committing sexual offenses against children. Consequently, pedophilia is not only relevant in psychiatric therapy and prognostics, but also greatly influences the public attitude towards criminality. Public opinion seems to equate pedophilia with child sexual abuse and vice versa which leads to stigmatization of patients and may impede treatment. The present paper provides information on recent studies on the potential origins of the disorder and introduces new diagnostic methods. Moreover, the article presents estimates on the prevalence of pedophilic sexual interest.

  7. [Diagnostic aspects of pharyngeal tumors].

    Science.gov (United States)

    Savin, A A; Kradinov, A I; Vasil'ev, A Iu; Rogozhin, V A; Ivankov, A P

    1999-01-01

    In the work there are summarized the results of the examination of the 28 patients suffering with the pharynx tumors (angiophybroma of the pharynx, tumor of rhinopharynx with spreading to the cells of ethmoidal labyrinth and maxillary sinus, tumor of the pharynx spreading upon the rhinopharynx and intracranially) aged from 14 till 62. There are described the methods of roentgenologic investigation, computed and magnetic resonance tomography. There are shown the possibilities of different diagnostic methods in pharynx tumors, in estimation of the localization specification, prevalence, structure, degree of invasion into the neoplasms gathering round the cells, as well as the definition of the bony destruction.

  8. Artificial intelligence methods for diagnostic

    International Nuclear Information System (INIS)

    Dourgnon-Hanoune, A.; Porcheron, M.; Ricard, B.

    1996-01-01

    To assist in diagnosis of its nuclear power plants, the Research and Development Division of Electricite de France has been developing skills in Artificial Intelligence for about a decade. Different diagnostic expert systems have been designed. Among them, SILEX for control rods cabinet troubleshooting, DIVA for turbine generator diagnosis, DIAPO for reactor coolant pump diagnosis. This know how in expert knowledge modeling and acquisition is direct result of experience gained during developments and of a more general reflection on knowledge based system development. We have been able to reuse this results for other developments such as a guide for auxiliary rotating machines diagnosis. (authors)

  9. Reporting of Diagnostic Cytogenetic Results.

    Science.gov (United States)

    Giersch, Anne B S; Bieber, Frederick R; Dubuc, Adrian M; Fletcher, Jonathan A; Ligon, Azra H; Mason-Suares, Heather; Morton, Cynthia C; Weremowicz, Stanislawa; Xiao, Sheng; Dal Cin, Paola

    2016-04-01

    This appendix, developed by the staff at the Center for Advanced Molecular Diagnostics in the Department of Pathology at the Brigham and Women's Hospital, includes a comprehensive list of current "macros" or standardized statements used to facilitate reporting of cytogenetic results. These are provided as a useful reference for other laboratories. The statements are organized under the general categories of constitutional or acquired abnormalities and subdivided into analysis type (GTG-banding, FISH, or chromosomal microarray). Multi-specimen usage macros are included that can be applied to two or more specimen types. Copyright © 2016 John Wiley & Sons, Inc.

  10. Granulomatous mastitis - a diagnostic dilemma.

    Science.gov (United States)

    Mote, Dajiram G; Gungi, Raghavendra P; Satyanarayana, V; Premsunder, T

    2008-10-01

    Granulomatous lobular mastitis is a rare benign breast disease. It is characterized by chronic, non-caseating granulomatous lobulitis. It may be misdiagnosed as a carcinoma of the breast and may lead to mastectomy. Diagnostic criteria include-A) Granulomatous infl ammation with multinucleated giant cells, epithelioid histiocytes. B) It is centered on lobules with minor ductal and periductal infl ammation. C) It nearly always follows the pregnancy. A case of GLM, which was treated with local excision and postoperative steroid therapy is being reported to increase awareness amongst surgeons and pathologist.

  11. Radiation risk of diagnostical procedures

    International Nuclear Information System (INIS)

    Pohlit, W.

    1986-01-01

    The environmental radiation burden of man in Germany is about 1 mGy (Milligray) per year. This is, of course, also valid for children. Due to diagnostical procedures this burden is increased to about 1.3 mGy. The question arises wether this can be neglected, or important consequences have to be drawn. To give a clear answer, the action of ionizing radiation in living cells and in organisms is explained in detail. Many of the radiation actions at the DNA can soon be repaired by the cell, if the radiation dose was small. Some damage, however will remain irreparable for the cell and consequently leads to cell death, to mutations or to cell transformation. The number of these lesion increases or decreases linearily with radiation dose. Therefore, it must be expected that the risk of tumour induction is increased to above the normal background even by the smallest doses. This small but not negligible risk has to be compared with other risks of civilization or with other medical risks. But also the benefit and the efficacy of diagnostic procedures have to be considered. (orig./HSCH) [de

  12. Tuberculosis diagnostics: Challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Vijay Nema

    2012-01-01

    Full Text Available Tuberculosis (TB has been a disease affecting almost all parts of the world since ages. Lot many efforts came in the past for improving diagnosis and treatment. Also, an effective vaccine has been sought after for long. With the emergence of resistant strains of Mycobacterium tuberculosis, the causal organisms of tuberculosis, and complexities emerging due to other associated infections and disease conditions, there is a desperate need for further research input in the field. Be it the better medication and care or better resistance management, proper diagnostics holds the key to success. It has been observed that a high burden of the disease was accompanied by resource limitations and poor research set-up. The scenario remained like this for several decades. With the refreshed vision of resourceful countries and funding agencies, funding is being provided in many areas of research in tuberculosis diagnosis and treatment. This review has been written with an aim to bring forth the limitations of available methods in the field of diagnostics and making researchers aware about the changing scenario with better funding opportunities and support. The author visualizes an enthusiasm from all over the world for the development of better modalities and urges scientists to join the struggle at this very perfect time to take the challenge and come forward with innovations in this field.

  13. Studies on WWER core diagnostics

    International Nuclear Information System (INIS)

    Lunin, G.L.; Mitin, V.I.; Bulavin, V.V.

    1987-01-01

    The reliability and safety of nuclear power plants have decisive meaning under the situation that nuclear power generation steadily increases, and among various measures aiming at ensuring the reliability and safety in the operation of nuclear power plants, the countermeasures for protecting reactor core, main process equipment and high pressure circuits from damage have the important role, and the monitoring of condition and the organization of forecast, which are carried out continuously or periodically during the operation of nuclear power stations using the diagnostic expert system specially developed for the purpose, are included in them. Such monitoring enables the early detection of mechanical damage, increase of vibration, defects caused during operation and so on in reactor cores and primary and secondary circuits, and the continuous watching of defect developments. Also boiling in a core is detected, the place of abnormality occurrence is identified, and the intensity and characteristics of boiling are determined, thus the occurrence of dangerous condition is prevented. The developments of an in-core monitoring system and noise diagnostic systems are reported. (Kako, I.)

  14. Diagnostic and therapeutic radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Russell, W J [Radiation Effects Research Foundation, Hiroshima (Japan)

    1975-09-01

    Diagnostic and therapeutic radiology were studied as possible contaminants in the evaluations of A-bomb survivors in the ABCC-JNIH Adult Health Study for radiation effects. Hiroshima and Nagasaki subjects received X-ray examinations elsewhere within three months of their ABCC visits at rates of 23 and 12%, respectively. Medical X-ray examinations were more frequent among survivors than comparison subjects. Hiroshima and Nagasaki radiologic practice steadily increased since 1948, and differed markedly by city. From 1946-70 the Hiroshima and Nagasaki X-ray bone marrow doses were 2,300 and 1,000 g-rads, respectively. By 1970, cumulated medical X-ray doses approximated A-bomb doses at distances from the hypocenters of 2,000 m in Hiroshima and 2,800 m in Nagasaki. ABCC X-ray examination doses per subject are routinely updated for comparison with A-bomb doses. Each subject's reported fluoroscopy, photofluorography and radiation therapy exposure elsewhere are for future reference. Dental radiography, though increasing, was not currently an important contributor to survivors' overall exposure. Radiation therapy exposures of 137 subjects were confirmed, and doses estimated for most. Two-thirds the treatments were for malignancies; therapy differed markedly by city; and five cancers possibly arose from earlier radiation therapy. This underscores the importance of considering diagnostic and therapeutic radiology when attributing diseases to the atomic bombs.

  15. Patient dosimetry in diagnostic radiology

    Directory of Open Access Journals (Sweden)

    Ciraj-Bjelac Olivera F.

    2003-01-01

    Full Text Available The objective of this work is to assess patient organ doses, effective doses and entrance surface doses in conventional diagnostic radiology procedures for standard adult patient. The survey consists of measurements of doses delivered to 239 patients in nine types of X-ray examinations. Three types of data were collected: X-ray machine data, patient data, and output measurements. Entrance surface dose was assessed based on the survey data and subsequently, using conversion coefficients, the organ doses and effective doses were calculated. Values of the entrance surface dose and the effective dose were estimated to be 0.4 to 5.8 mGy and 0.03 to 3.00 mSv for different examinations. Derived doses were compared with recommended general diagnostic reference levels. The impact of examination parameters on dose values was discussed. Except for posterior-anterior chest examination, all estimated doses are lower than stated reference levels. Survey data are aimed at helping development of national quality control and radiation protection programmed for medical exposures.

  16. Molecular diagnostics for human leptospirosis.

    Science.gov (United States)

    Waggoner, Jesse J; Pinsky, Benjamin A

    2016-10-01

    The definitive diagnosis of leptospirosis, which results from infection with spirochetes of the genus Leptospira, currently relies on the use of culture, serological testing (microscopic agglutination testing), and molecular detection. The purpose of this review is to describe new molecular diagnostics for Leptospira and discuss advancements in the use of available methods. Efforts have been focused on improving the clinical sensitivity of Leptospira detection using molecular methods. In this review, we describe a reoptimized pathogenic species-specific real-time PCR (targeting lipL32) that has demonstrated improved sensitivity, findings by two groups that real-time reverse-transcription PCR assays targeting the 16S rrs gene can improve detection, and two new loop-mediated amplification techniques. Quantitation of leptospiremia, detection in different specimen types, and the complementary roles played by molecular detection and microscopic agglutination testing will be discussed. Finally, a protocol for Leptospira strain subtyping using variable number tandem repeat targets and high-resolution melting will be described. Molecular diagnostics have an established role for the diagnosis of leptospirosis and provide an actionable diagnosis in the acute setting. The use of real-time reverse-transcription PCR for testing serum/plasma and cerebrospinal fluid, when available, may improve the detection of Leptospira without decreasing clinical specificity.

  17. Molecular diagnostics of myeloproliferative neoplasms.

    Science.gov (United States)

    Langabeer, Stephen E; Andrikovics, Hajnalka; Asp, Julia; Bellosillo, Beatriz; Carillo, Serge; Haslam, Karl; Kjaer, Lasse; Lippert, Eric; Mansier, Olivier; Oppliger Leibundgut, Elisabeth; Percy, Melanie J; Porret, Naomi; Palmqvist, Lars; Schwarz, Jiri; McMullin, Mary F; Schnittger, Susanne; Pallisgaard, Niels; Hermouet, Sylvie

    2015-10-01

    Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations, and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Thematic plan on diagnostic radiology

    International Nuclear Information System (INIS)

    2003-01-01

    Due to the vital importance of diagnostic radiology in both the diagnosis and management of disease processes, there is a need for a greater coherent international effort to help the developing nations create strategies for the incorporation of imaging into their healthcare systems. To meet the needs of such countries, a comprehensive programme is required to take into consideration the availability of local expertise (medical and technical), the infrastructure (stable electrical supply, water and air-conditioning) and the disease pattern or burden. In short, the total solution requires coordinating the International Atomic Energy Agency efforts with those of other partners. The Agency already has programmes in nuclear medicine and radiation therapy supported by activities in dosimetry and medical physics. Through the Technical Co-operation fund the Agency already supports projects in some areas of diagnostic imaging, dosimetry and radiation protection, but it lacks a comprehensive programme to provide a systematic approach focusing on the medical aspects of imaging science and including all the imaging technologies. Member States require the Agency's assistance in this area since no single UN organisation has the resources or the expertise to do the entire job without help. This document presents the proposed programme strategy and action plan

  19. New tuberculosis diagnostics and rollout

    Directory of Open Access Journals (Sweden)

    Ruth McNerney

    2015-03-01

    Full Text Available Early detection and effective treatment are crucial for tuberculosis control, but global case detection rates remain low. The diagnosis of paediatric and extrapulmonary disease is problematic and there are, as yet, no rapid screening tests to assist active case finding in the community. Progress has been made in clinic-based detection tools with the introduction of Xpert MTB/RIF, a nucleic acid amplification test that combines sample processing and analysis in a single instrument to provide a diagnostic result and detection of resistance to rifampicin in under 2 h. Enthusiasm for Xpert MTB/RIF has been high and global rollout has been facilitated by donor agencies. However, concerns remain about access and sustainability due to the high cost and infrastructure requirements. Although more sensitive than smear microscopy, early studies suggest the impact of the new test on case detection rates and patient survival has been limited. Alternative technologies are being developed, including non-sputum-based tests to assist the detection of extrapulmonary disease. Evaluation studies are needed to provide evidence of the impact of the new technologies on patient outcomes. This will enable appropriate placement of new diagnostic products in the healthcare system to support the control and eventual eradication of tuberculosis disease.

  20. Prostate carcinoma: current diagnostic strategy

    International Nuclear Information System (INIS)

    Schwarzschild, Monica Maria Agata Stiepcich; Ferraz, Maria Lucia Cardoso Gomes; Oliveira, Jose Marcelo Amatuzzi; Andriolo, Adagmar

    2001-01-01

    Prostate cancer is the second cause of cancer death in men in the Western world. Despite progress in the treatment of advanced disease, it is recognized that the only possibility of reduction in prostate cancer death is nearly diagnosis when the disease is localized. In the present study our aim was to review the current strategy for diagnosis of prostate carcinoma. Prostate-specific antigen (PSA) is a valuable tumor marker and has demonstrated effectiveness in detecting prostate carcinoma, monitoring therapeutic efficacy, and disclosing disease recurrence. However, alternative methods are been proposed just as the free to total PSA ratio, PSA density, PSA velocity, which could improve the diagnostic sensibility and the specificity. Image diagnostic methods include transrectal ultra sound, computerized tomography, magnetic resonance image, and bone cintigraphy. The ultra sound is the best approach to guide the prostate biopsy and, together with the magnetic resonance is still useful for loco regional graduation. Computerized tomography as magnetic resonance image can be used for identification of linfonodal involvement. Bone cintigraphy is the best method for the identification of metastatic disease. (author)

  1. Interprofessional working in diagnostic radiography

    International Nuclear Information System (INIS)

    Strudwick, Ruth M.; Day, Jane

    2014-01-01

    This paper considers interprofessional working within one diagnostic imaging department. The literature is still divided about the long-term impact of interprofessional learning in pre-registration health and social care education, and its impact on the quality of care provided. When reading the literature about interprofessional working the main topics considered by other authors are team working, communication between professionals, stereotyping and tribalism. The results presented are from an ethnographic study in one department with participant observation and semi-structured interviews. The three main aspects discussed in this paper are; tribalism and culture within the diagnostic radiography profession, communication between different professional groups, and a lack of understanding of the roles of other professional groups. It was evident from the results of this study that tribalism and culture, and a lack of understanding were significant barriers to interprofessional working. It was felt by the authors that pre-registration and post-registration interprofessional education could be significant in changing the culture of the NHS in the future as more professionals learn from and about one another

  2. Diagnostic imaging in fertility disorders

    International Nuclear Information System (INIS)

    Winfield, A.C.; Fleischer, A.C.

    1987-01-01

    Some 10%-15% of married couples are affected by a fertility disorder. The number of infertile couples seeking medical assistance has increased dramatically in the past decade. The roles of diagnostic imaging with radiography and US (conventional and transvaginal) is emphasized in the assessment of couples with fertility disorders and an unexpectedly higher incidence of fetal wastage secondary to unsuspected uterine anomalies. The most frequently utilized radiographic examination in infertile patients is hysterosalpingography (HSG). Techniques and complications of HSG are illustrated. The normal anatomy, variants, and congenital anomalies of the uterus and fallopian tubes are demonstrated, as are the numerous abnormalities such as filling defects of the uterine cavity, synechiae, effects of maternal diethylstilbestrol exposure, inflammatory tubal disease, and the more common HSG findings following uterine and tubal surgery. The role of diagnostic imaging in male infertility, including vasography and varicocele detection, are addressed. Conventional and transvaginal US in the management of gynecologic fertility disorders are examined, with an emphasis on follicular monitoring, guided follicular aspirations, endometrial evaluations, and evaluation of other disorders (such as endometriosis) associated with infertility

  3. Ultrasound diagnostics of thyroid diseases

    International Nuclear Information System (INIS)

    Kharchenko, Vladimir P.; Kotlyarov, Peter M.; Mogutov, Mikhail S.; Sencha, Alexander N.; Patrunov, Yury N.; Belyaev, Denis V.; Alexandrov, Yury K.

    2010-01-01

    This book is based on the authors' extensive practical experience in the use of modern ultrasound, and other radiological methods, in the diagnosis of thyroid diseases. The authors have analyzed more than 100,000 ultrasound examinations performed between 1995 and 2008 in patients with thyroid and parathyroid disease, as well as many thousands of diagnostic and therapeutic ultrasound-guided minimally invasive procedures. The opening chapters include discussion of current ultrasound techniques, pitfalls, and the specifics of ultrasound examination of the thyroid in children. Detailed attention is then devoted to findings in the normal thyroid and in the presence of diffuse and focal changes. Further chapters focus on such topics as ultrasound examination after thyroid surgery and ultrasound diagnosis of parathyroid disease, recurrent goiter, and neck masses. Ultrasound-guided minimally invasive techniques, such as fine-needle aspiration biopsy, percutaneous laser ablation, and ethanol and glucocorticoid injections, are considered in depth. This up-to-date and richly illustrated book will interest and assist specialists in ultrasound diagnostics, radiologists, endocrinologists, and neck surgeons. (orig.)

  4. Software diagnostic aids on Aladdin

    International Nuclear Information System (INIS)

    Eisert, D.E.; Stott, J.P.

    1990-01-01

    The upgrade of the Aladdin control system included many enhancements in the software. Some of the new diagnostic aids provided are: intelligent temporary logging of all readbacks for at least the previous 12 hours, permanent logging of specified readbacks into disk files, temporary logging of beam positions at an operator-specified interval, an alarm system for all devices, including range limits for analogue readbacks that should remain fixed and window limits which automatically track readbacks that should decay or increase monotonically, automated checklists to verify the devices are within the specified operating range for a particular phase of operation, latched digital signals to capture momentary changes. The software has been designed to alert the operator when something is wrong, without generating a flood of unimportant messages, and to make it possible to observe and record readbacks over a range of time scales. The latter capability is essential for tracking down marginal components and correlating observed problems with possible causes. The algorithms used for these diagnostic aids, and how well they perform their desired tasks, are described in this paper. (orig.)

  5. Diagnostic tools in ocular allergy.

    Science.gov (United States)

    Leonardi, A; Doan, S; Fauquert, J L; Bozkurt, B; Allegri, P; Marmouz, F; Rondon, C; Jedrzejczak, M; Hellings, P; Delgado, L; Calder, V

    2017-10-01

    Ocular allergy (OA) includes a group of common and less frequent hypersensitivity disorders frequently misdiagnosed and not properly managed. The diagnosis of OA is usually based on clinical history and signs and symptoms, with the support of in vivo and in vitro tests when identification of the specific allergen is required. To date, no specific test is available for the diagnosis of the whole spectrum of the different forms of OA. The lack of recommendations on diagnosis of OA is considered a medical need not only for allergists but also for ophthalmologists. This position paper aims to provide a comprehensive overview of the currently available tools for diagnosing OA to promote a common nomenclature and procedures to be used by different specialists. Questionnaires, sign and symptom grading scales, tests, and potential biomarkers for OA are reviewed. We also identified several unmet needs in the diagnostic tools to generate interest, increase understanding, and inspire further investigations. Tools, recommendations, and algorithms for the diagnosis of OA are proposed for use by both allergists and ophthalmologists. Several unmet needs in the diagnostic tools should be further improved by specific clinical research in OA. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  6. Iron-associated biology of Trypanosoma brucei.

    Czech Academy of Sciences Publication Activity Database

    Basu, Somsuvro; Horáková, Eva; Lukeš, Julius

    2016-01-01

    Roč. 1860, č. 2 (2016), s. 363-370 ISSN 0304-4165 R&D Projects: GA ČR(CZ) GA14-23986S; GA ČR GAP305/12/2261; GA MŠk(CZ) EE2.3.30.0032 EU Projects: European Commission(XE) COST Action CM1307; European Commission(XE) 316304 - MODBIOLIN Grant - others:AV ČR(CZ) M200961204 Institutional support: RVO:60077344 Keywords : iron * Fe/S cluster * heme * Trypanosoma * TAO Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.702, year: 2016

  7. Proposed Diagnostic Criteria for Smartphone Addiction.

    Science.gov (United States)

    Lin, Yu-Hsuan; Chiang, Chih-Lin; Lin, Po-Hsien; Chang, Li-Ren; Ko, Chih-Hung; Lee, Yang-Han; Lin, Sheng-Hsuan

    2016-01-01

    Global smartphone penetration has led to unprecedented addictive behaviors. The aims of this study are to develop diagnostic criteria of smartphone addiction and to examine the discriminative ability and the validity of the diagnostic criteria. We developed twelve candidate criteria for characteristic symptoms of smartphone addiction and four criteria for functional impairment caused by excessive smartphone use. The participants consisted of 281 college students. Each participant was systematically assessed for smartphone-using behaviors by psychiatrist's structured diagnostic interview. The sensitivity, specificity, and diagnostic accuracy of the candidate symptom criteria were analyzed with reference to the psychiatrists' clinical global impression. The optimal model selection with its cutoff point of the diagnostic criteria differentiating the smartphone addicted subjects from non-addicted subjects was then determined by the best diagnostic accuracy. Six symptom criteria model with optimal cutoff point were determined based on the maximal diagnostic accuracy. The proposed smartphone addiction diagnostic criteria consisted of (1) six symptom criteria, (2) four functional impairment criteria and (3) exclusion criteria. Setting three symptom criteria as the cutoff point resulted in the highest diagnostic accuracy (84.3%), while the sensitivity and specificity were 79.4% and 87.5%, respectively. We suggested determining the functional impairment by two or more of the four domains considering the high accessibility and penetration of smartphone use. The diagnostic criteria of smartphone addiction demonstrated the core symptoms "impaired control" paralleled with substance related and addictive disorders. The functional impairment involved multiple domains provide a strict standard for clinical assessment.

  8. Outcomes After Diagnostic Hip Injection.

    Science.gov (United States)

    Lynch, T Sean; Steinhaus, Michael E; Popkin, Charles A; Ahmad, Christopher S; Rosneck, James

    2016-08-01

    To provide a comprehensive review of outcomes associated with local anesthetic (LA) or LA and corticosteroid (CS) diagnostic hip injections, and how well response predicts subsequent operative success. A systematic review from database (PubMed, Medline, Scopus, Embase) inception to January 2015 for English-language articles reporting primary patient outcomes data was performed, excluding studies with >50% underlying osteoarthritis. Studies were assessed by 2 reviewers who collected pertinent data. Seven studies were included, reporting on a total 337 patients undergoing diagnostic hip injection. The mean age was 34.4 years, with 5 studies reporting 94 (35.2%) males and 173 (64.8%) females. One study examined the rate of pain relief with LA (92.5%); 2 CS studies reported relief on a scale from 0% to 100% (no to complete relief), ranging from 61% to 82.3%; and 3 studies used 10-point pain scales, with a CS study noting a pain score of 1.0, an LA study with a score of 3.03, and 1 study using either CS or LA scores of 3 to 5.6. Duration of pain relief was 9.8 (CS) and 2.35 days (LA). By pathology, greatest relief was achieved in acetabular chondral injury (93.3%) and least in cam impingement (81.6%), with clinical and imaging findings being unreliable predictors of relief. One study showed nonresponse to be a strong predictor of negative surgical outcome for femoroacetabular impingement. Diagnostic hip injections provide substantial pain relief for patients with various hip pathologies, with limited data to suggest greatest relief for those with chondral injury. Clinical and imaging findings are unreliable predictors of injection response, and nonresponse to injection is a strong negative predictor of surgical outcome. Future research should focus on elucidating differences by underlying pathology and predicting future operative success. Level IV, systematic review. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights

  9. Summary Report on Synchronization, Diagnostics and Instrumentation

    International Nuclear Information System (INIS)

    Arne Freyberger

    2005-01-01

    The proceedings of Working Group 4 of the 2005 Energy Recovery Linac (ERL) workshop are summarized. Working Group 4 dealt with the challenging topic of beam diagnostics for ERL machines. Energy Recovery Linacs represent a challenge for beam diagnostics from several perspectives; invasive versus non-invasive diagnostics, longitudinal and transverse beam diagnostics, overall machine timing/synchronization and machine protection. Beam diagnostics for an ERL can benefit strongly from the experience at third generation light sources, recirculating linacs and presently operating ERLs. During the workshop there were presentations from all these communities, representing a large range operation experience in beam diagnostics. A brief summary Working Group 4 discussion is presented in this paper

  10. Irradiation effects on plasma diagnostic components

    International Nuclear Information System (INIS)

    Nishitani, Takeo; Iida, Toshiyuki; Ikeda, Yujiro

    1998-10-01

    One of the most important issues to develop the diagnostics for the experimental thermonuclear reactor such as ITER is the irradiation effects on the diagnostics components. Typical neutron flux and fluence on the first wall are 1 MW/m 2 and 1 MWa/m 2 , respectively for ITER. In such radiation condition, most of the present diagnostics could not survive so that those will be planed to be installed far from the vacuum vessel. However, some diagnostics sensors such as bolometers and magnetic probes still have to be install inside vessel. And many transmission components for lights, wave and electric signals are inevitable even inside vessel. As a part of this R and D program of the ITER Engineering Design Activities (EDA), we carried out the irradiation tests on the basic materials of the transmission components and in-vessel diagnostics sensors in order to identify radiation hardened materials that can be used for diagnostic systems. (J.P.N.)

  11. [Cognitive errors in diagnostic decision making].

    Science.gov (United States)

    Gäbler, Martin

    2017-10-01

    Approximately 10-15% of our diagnostic decisions are faulty and may lead to unfavorable and dangerous outcomes, which could be avoided. These diagnostic errors are mainly caused by cognitive biases in the diagnostic reasoning process.Our medical diagnostic decision-making is based on intuitive "System 1" and analytical "System 2" diagnostic decision-making and can be deviated by unconscious cognitive biases.These deviations can be positively influenced on a systemic and an individual level. For the individual, metacognition (internal withdrawal from the decision-making process) and debiasing strategies, such as verification, falsification and rule out worst-case scenarios, can lead to improved diagnostic decisions making.

  12. Image diagnostic of colonic diseases - controversial questions

    International Nuclear Information System (INIS)

    Pomakov, P.; Rizov, A.; Stancheva, I.

    2013-01-01

    In the system of colonic diseases' diagnostic algorithm, fibrocolonoscopy (FCS) is defined as 'Golden Standard'. By this reason some X-ray diagnostic methods - irrigography, etc. are currently not being used in a number of health institutions. The aim of this study is a comparative analysis of FCS and irrigography diagnostic efficacy in various colonic diseases. For 10-years period, in cooperation with a gastroenterologist-gastroscopist, 2151 patients with various colonic diseases were evaluated by FCS and irrigography with pharmaco-diagnostics/when necessary. Advantage of FCS was established in diagnosing diseases with patho-morfologic changes on the inner surface of the colon - benign and malignant neoplastic processes, chronic inflammatory diseases, etc. At the same time functional changes - irritated colon syndrome, changes in defecation act, etc., are not an object of diagnosis through FCS. Correction in colonic diseases diagnostic algorithm is necessary. FCS should be mandatory. If result is negative - irrigography with pharmaco-diagnostics should be done. (authors)

  13. Implementation of Rapid Molecular Infectious Disease Diagnostics: the Role of Diagnostic and Antimicrobial Stewardship.

    Science.gov (United States)

    Messacar, Kevin; Parker, Sarah K; Todd, James K; Dominguez, Samuel R

    2017-03-01

    New rapid molecular diagnostic technologies for infectious diseases enable expedited accurate microbiological diagnoses. However, diagnostic stewardship and antimicrobial stewardship are necessary to ensure that these technologies conserve, rather than consume, additional health care resources and optimally affect patient care. Diagnostic stewardship is needed to implement appropriate tests for the clinical setting and to direct testing toward appropriate patients. Antimicrobial stewardship is needed to ensure prompt appropriate clinical action to translate faster diagnostic test results in the laboratory into improved outcomes at the bedside. This minireview outlines the roles of diagnostic stewardship and antimicrobial stewardship in the implementation of rapid molecular infectious disease diagnostics. Copyright © 2017 American Society for Microbiology.

  14. Microbial Diagnostic Array Workstation (MDAW: a web server for diagnostic array data storage, sharing and analysis

    Directory of Open Access Journals (Sweden)

    Chang Yung-Fu

    2008-09-01

    Full Text Available Abstract Background Microarrays are becoming a very popular tool for microbial detection and diagnostics. Although these diagnostic arrays are much simpler when compared to the traditional transcriptome arrays, due to the high throughput nature of the arrays, the data analysis requirements still form a bottle neck for the widespread use of these diagnostic arrays. Hence we developed a new online data sharing and analysis environment customised for diagnostic arrays. Methods Microbial Diagnostic Array Workstation (MDAW is a database driven application designed in MS Access and front end designed in ASP.NET. Conclusion MDAW is a new resource that is customised for the data analysis requirements for microbial diagnostic arrays.

  15. Rational use of diagnostic radiology

    International Nuclear Information System (INIS)

    Racoveanu, N.T.; Volodin, V.

    1992-01-01

    Radiologists in USA and UK have since early 1970 questioned the efficacy of various radiological investigations and produced substantial evidence that more rational approaches are necessary. WHO initiated, in 1977, a programme which has issued four technical reports giving practical recommendations on how to rationalise the use of radiological examinations. Three main directions are considered: (1) Abandonment of routine radiological examinations, as procedures with no clinical or epidemiologic significance and which represent a waste of resources and patient dose. (2) Patient selection for various radiological investigations based on clinical criteria (high, intermediate, low yield). Selected patients have an increased prevalence of the given disease and the predictive value of radiological investigation is much higher. (3) Use of diagnostic algorithms with higher cost/efficiency and risk/benefit ratios, improving the outcome of radiological examinations. (author)

  16. Rational use of diagnostic radiology

    International Nuclear Information System (INIS)

    Racoveanu, N.T.; Volodin, V.

    1992-01-01

    The escalating number of radiodiagnostic investigations has, as a consequence, an increase in medical irradiation of patients and of cost of radiological services. Radiologists in USA and UK have since early 1970 questioned the efficacy of various radiological investigations and produced substantial evidence that more rational approaches are necessary. WHO initiated, in 1977, a programme in this direction which has issued four technical reports which give practical recommendations on how to rationalize the use of radiological examinations. Three main directions are considered: (1) Abandonment of routine radiological examinations, as procedures with no clinical or epidemiologic significance and which represent a waste of resources and patient dose. (2) Patient selection for various radiological investigations based on clinical criteria (high, intermediate, low yield). Selected patients have an increased prevalence of the given disease and the predictive value of radiological investigation is much higher. (3) Use of diagnostic algorithms with higher cost/efficiency and risk/benefit ratios, improving the outcome of radiological examinations

  17. Spark gap produced plasma diagnostics

    International Nuclear Information System (INIS)

    Chang, H.Y.

    1990-01-01

    A Spark Gap (Applied voltage : 2-8KV, Capacitor : 4 Micro F. Dia of the tube : 1 inch, Electrode distance : .3 ∼.5 inch) was made to generate a small size dynamic plasma. To measure the plasma density and temperature as a function of time and position, we installed and have been installing four detection systems - Mach-Zehnder type Interferometer for the plasma refractivity, Expansion speed detector using two He-Ne laser beams, Image Processing using Lens and A Optical-Fiber Array for Pointwise Radiation Sensing, Faraday Rotation of a Optical Fiber to measure the azimuthal component of B-field generated by the plasma drift. These systems was used for the wire explosion diagnostics, and can be used for the Laser driven plasma also

  18. Diagnostic Ultrasound in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael

    2014-01-01

    SUMMARYBackground and purpose Colorectal cancer is a common disease in Denmark with considerable morbidity and mortality. Although survival in recent years has improved, Denmark still has the lowest 5-year survival compared to the other Nordic countries. The treatment of patients depends on local...... the potential to contribute to the staging of colorectal cancer. The purpose of these studies was to determine the usefulness of ultrasound diagnostics in patients with colorectal cancer.The purpose of the TRUS studies was to compare staging of rectal carcinomas using digital rectal exploration...... of 295 patients with primary colorectal cancer we found a sensitivity of preoperative ultrasound, surgical exploration, and intraoperative ultrasound of 70%, 84%, and 97%, respectively, based on a patient-by-patient comparison (p

  19. Computer-based diagnostic decisionmaking.

    Science.gov (United States)

    Miller, R A

    1987-12-01

    The three decisionmaking aids described by the authors attack the generic problem of "see no evil, hear no evil, speak no evil"--improving the detection, diagnosis, and therapy of psychiatric disorders in the primary care setting. The three systems represent interventions at different steps in the process of providing appropriate care to psychiatric patients. The DSPW system of Robins and Marcus offers the potential of increasing the recognition of psychiatric disease in the physician's office. Politser's IDS program is representative of the sort of sophisticated microcomputer-based decisionmaking support tools that will become available to physicians in the not-too-distant future. Erdman's study of the impact of explanation capabilities on the acceptability of therapy recommending systems points out the need for careful scientific evaluations of features added to diagnostic and therapeutic systems.

  20. Diagnostic Management of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dabizzi, Emanuele [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States); Assef, Mauricio Saab [Faculdade de Ciências Médicas da Santa Casa de São Paulo, Rua Dr. Cesário Motta Jr. #61 Cep: 01221-020, São Paulo (Brazil); Raimondo, Massimo, E-mail: raimondo.massimo@mayo.edu [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States)

    2011-01-31

    Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used.