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Sample records for prpsc remains unknown

  1. Histidines in the octapeptide repeat of PrPC react with PrPSc at an acidic pH.

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    Cruite, Justin T; Abalos, Gil C; Bellon, Anne; Solforosi, Laura

    2011-03-15

    Cellular PrP is actively cycled between the cell surface and the endosomal pathway. The exact site and mechanism of conversion from PrP(C) to PrP(Sc) remain unknown. We have previously used recombinant antibodies containing grafts of PrP sequence to identify three regions of PrP(C) (aa23-27, 98-110, and 136-158) that react with PrP(Sc) at neutral pH. To determine if any regions of PrP(C) react with PrP(Sc) at an acidic pH similar to that of an endosomal compartment, we tested our panel of grafted antibodies for the ability to precipitate PrP(Sc) in a range of pH conditions. At pH near or lower than 6, PrP-grafted antibodies representing the octapeptide repeat react strongly with PrP(Sc) but not PrP(C). Modified grafts in which the histidines of the octarepeat were replaced with alanines did not react with PrP(Sc). PrP(Sc) precipitated by the octapeptide at pH 5.7 was able to seed conversion of normal PrP to PrP(Sc) in vitro. However, modified PrP containing histidine to alanine substitutions within the octapeptide repeats was still converted to PrP(Sc) in N2a cells. These results suggest that once PrP has entered the endosomal pathway, the acidic environment facilitates the binding of PrP(Sc) to the octarepeat of PrP(C) by the change in charge of the histidines within the octarepeat.

  2. Mechanisms of action of brief alcohol interventions remain largely unknown – A narrative review

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    Jacques eGaume

    2014-08-01

    Full Text Available A growing body of evidence has shown efficacy of brief intervention (BI for hazardous and harmful alcohol use in primary health care settings. Evidence for efficacy in other settings, and effectiveness when implemented at larger scale is disappointing. Indeed, BI comprises varying content, and exploring BI content and mechanisms of action may be a promising way to enhance efficacy and effectiveness.We searched Medline and PsychInfo, as well as references of retrieved publications for original research or reviews on active ingredients (or components, or mechanisms of face-to-face BIs (and its subtypes, including brief advice and brief motivational interviewing [BMI] for alcohol. Overall, BI active ingredients have been scarcely investigated, almost only within BMI, and mostly among Emergency Room patients, young adults, and US college students. This body of research has shown that personalized feedback may be an effective component; specific MI techniques showed mixed findings; decisional balance findings tended to suggest a potential detrimental effect; while change plan exercises, advice to reduce or stop drinking, presenting alternative change options, and moderation strategies are promising but need further study. Client change talk is a potential mediator of BMI effects; change in norm perceptions and enhanced discrepancy between current behavior and broader life goals and values have received preliminary support; readiness to change was only partially supported as a mediator; while enhanced awareness of drinking, perceived risks/benefits of alcohol use, alcohol treatment seeking, and self-efficacy were seldom studied and have as yet found no significant support as such.Research is obviously limited and has provided no clear and consistent evidence on the mechanisms of alcohol BI. How BI achieves the effects seen in randomized trials remains mostly unknown and should be investigated to inform the development of more effective interventions.

  3. The Structure of PrPSc Prions

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    Holger Wille

    2018-02-01

    Full Text Available PrPSc (scrapie isoform of the prion protein prions are the infectious agent behind diseases such as Creutzfeldt–Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (deer, elk, moose, and reindeer, as well as goat and sheep scrapie. PrPSc is an alternatively folded variant of the cellular prion protein, PrPC, which is a regular, GPI-anchored protein that is present on the cell surface of neurons and other cell types. While the structure of PrPC is well studied, the structure of PrPSc resisted high-resolution determination due to its general insolubility and propensity to aggregate. Cryo-electron microscopy, X-ray fiber diffraction, and a variety of other approaches defined the structure of PrPSc as a four-rung β-solenoid. A high-resolution structure of PrPSc still remains to be solved, but the four-rung β-solenoid architecture provides a molecular framework for the autocatalytic propagation mechanism that gives rise to the alternative conformation of PrPSc. Here, we summarize the current knowledge regarding the structure of PrPSc and speculate about the molecular conversion mechanisms that leads from PrPC to PrPSc.

  4. A simple metric sexing method for unknown skeletal remains: the Sacro-Clavicular Index (SCI).

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    Trautmann, Martin; Trautmann, Iris

    2014-01-01

    Sex diagnosis on human skeletal remains from forensic or archaeological contexts is often hampered by poor preservation or completeness. The successful application of most identification methods demands the presence of skull or pelvis, since most reliable sex-determining features can be found here; unfortunately, because of their fragile anatomy, these bones are frequently damaged or destroyed. To compensate for this, we tested the effectiveness of two often well preserved postcranial structures as instrument of sexing skeletal individuals. Preliminary results are promising.

  5. Plasminogen: A cellular protein cofactor for PrPSc propagation.

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    Mays, Charles E; Ryou, Chongsuk

    2011-01-01

    The biochemical essence of prion replication is the molecular multiplication of the disease-associated misfolded isoform of prion protein (PrP), termed PrPSc, in a nucleic acid-free manner. PrP(Sc) is generated by the protein misfolding process facilitated by conformational conversion of the host-encoded cellular PrP to PrP(Sc). Evidence suggests that an auxiliary factor may play a role in PrP(Sc) propagation. We and others previously discovered that plasminogen interacts with PrP, while its functional role for PrPSc propagation remained undetermined. In our recent in vitro PrP conversion study, we showed that plasminogen substantially stimulates PrP(Sc) propagation in a concentration-dependent manner by accelerating the rate of PrP(Sc) generation, while depletion of plasminogen, destabilization of its structure, and interference with the PrP-plasminogen interaction hinder PrP(Sc) propagation. Further investigation in cell culture models confirmed an increase of PrP(Sc) formation by plasminogen. Although molecular basis of the observed activity for plasminogen remain to be addressed, our results demonstrate that plasminogen is the first cellular protein auxiliary factor proven to stimulate PrP(Sc) propagation.

  6. Infectivity-associated PrPSc and disease duration-associated PrPSc of mouse BSE prions

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    Miyazawa, Kohtaro; Okada, Hiroyuki; Masujin, Kentaro; Iwamaru, Yoshifumi; Yokoyama, Takashi

    2015-01-01

    ABSTRACT Disease-related prion protein (PrPSc), which is a structural isoform of the host-encoded cellular prion protein, is thought to be a causative agent of transmissible spongiform encephalopathies. However, the specific role of PrPSc in prion pathogenesis and its relationship to infectivity remain controversial. A time-course study of prion-affected mice was conducted, which showed that the prion infectivity was not simply proportional to the amount of PrPSc in the brain. Centrifugation (20,000 ×g) of the brain homogenate showed that most of the PrPSc was precipitated into the pellet, and the supernatant contained only a slight amount of PrPSc. Interestingly, mice inoculated with the obtained supernatant showed incubation periods that were approximately 15 d longer than those of mice inoculated with the crude homogenate even though both inocula contained almost the same infectivity. Our results suggest that a small population of fine PrPSc may be responsible for prion infectivity and that large, aggregated PrPSc may contribute to determining prion disease duration. PMID:26555211

  7. Ionic strength and transition metals control PrPSc protease resistance and conversion-inducing activity.

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    Nishina, Koren; Jenks, Samantha; Supattapone, Surachai

    2004-09-24

    The essential component of infectious prions is a misfolded protein termed PrPSc, which is produced by conformational change of a normal host protein, PrPC. It is currently unknown whether PrPSc molecules exist in a unique conformation or whether they are able to undergo additional conformational changes. Under commonly used experimental conditions, PrPSc molecules are characteristically protease-resistant and capable of inducing the conversion of PrPC molecules into new PrPSc molecules. We describe the effects of ionic strength, copper, and zinc on the conformation-dependent protease resistance and conversion-inducing activity of PrPSc molecules in scrapie-infected hamster brains. In the absence of divalent cations, PrPSc molecules were > 20-fold more sensitive to proteinase K digestion in low ionic strength buffers than in high ionic strength buffers. Addition of micromolar concentrations of copper or zinc ions restored the protease resistance of PrPSc molecules under conditions of low ionic strength. These transition metals also controlled the conformation of purified truncated PrP-(27-30) molecules at low ionic strength, confirming that the N-terminal octapeptide repeat region of PrPSc is not required for binding to copper or zinc ions. The protease-sensitive and protease-resistant conformations of PrPSc were reversibly interchangeable, and only the protease-resistant conformation of PrPSc induced by high ionic strength was able to induce the formation of new protease-resistant PrP (PrPres) molecules in vitro. These findings show that PrPSc molecules are structurally interconvertible and that only a subset of PrPSc conformations are able to induce the conversion of other PrP molecules. Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc.

  8. Alternative fates of newly formed PrPSc upon prion conversion on the plasma membrane.

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    Goold, Rob; McKinnon, Chris; Rabbanian, Samira; Collinge, John; Schiavo, Giampietro; Tabrizi, Sarah J

    2013-08-15

    Prion diseases are fatal neurodegenerative diseases characterised by the accumulation of misfolded prion protein (PrP(Sc)) in the brain. They are caused by the templated misfolding of normal cellular protein, PrP(C), by PrP(Sc). We have recently generated a unique cell system in which epitope-tagged PrP(C) competent to produce bona fide PrP(Sc) is expressed in neuroblastoma cells. Using this system we demonstrated that PrP(Sc) forms on the cell surface within minutes of prion exposure. Here, we describe the intracellular trafficking of newly formed PrP(Sc). After formation in GM1-enriched lipid microdomains at the plasma membrane, PrP(Sc) is rapidly internalised to early endosomes containing transferrin and cholera toxin B subunit. Following endocytosis, PrP(Sc) intracellular trafficking diverges: some is recycled to the plasma membrane via Rab11-labelled recycling endosomes; the remaining PrP(Sc) is subject to retromer-mediated retrograde transport to the Golgi. This pathway leads to lysosomal degradation, and we show that this is the dominant PrP(Sc) degradative mechanism in the early stages of prion infection.

  9. Exploration of the main sites for the transformation of normal prion protein (PrPC into pathogenic prion protein (PrPsc

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    Liu Xi-Lin

    2017-03-01

    Full Text Available Introduction: The functions and mechanisms of prion proteins (PrPC are currently unknown, but most experts believe that deformed or pathogenic prion proteins (PrPSc originate from PrPC, and that there may be plural main sites for the conversion of normal PrPC into PrPSc. In order to better understand the mechanism of PrPC transformation to PrPSc, the most important step is to determine the replacement or substitution site.

  10. Pilot study to establish a nasal tip prediction method from unknown human skeletal remains for facial reconstruction and skull photo superimposition as applied to a Japanese male populations.

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    Utsuno, Hajime; Kageyama, Toru; Uchida, Keiichi; Kibayashi, Kazuhiko; Sakurada, Koichi; Uemura, Koichi

    2016-02-01

    Skull-photo superimposition is a technique used to identify the relationship between the skull and a photograph of a target person: and facial reconstruction reproduces antemortem facial features from an unknown human skull, or identifies the facial features of unknown human skeletal remains. These techniques are based on soft tissue thickness and the relationships between soft tissue and the skull, i.e., the position of the ear and external acoustic meatus, pupil and orbit, nose and nasal aperture, and lips and teeth. However, the ear and nose region are relatively difficult to identify because of their structure, as the soft tissues of these regions are lined with cartilage. We attempted to establish a more accurate method to determine the position of the nasal tip from the skull. We measured the height of the maxilla and mid-lower facial region in 55 Japanese men and generated a regression equation from the collected data. We obtained a result that was 2.0±0.99mm (mean±SD) distant from the true nasal tip, when applied to a validation set consisting of another 12 Japanese men. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  11. Effects of different experimental conditions on the PrPSc core generated by protease digestion: implications for strain typing and molecular classification of CJD.

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    Notari, Silvio; Capellari, Sabina; Giese, Armin; Westner, Ingo; Baruzzi, Agostino; Ghetti, Bernardino; Gambetti, Pierluigi; Kretzschmar, Hans A; Parchi, Piero

    2004-04-16

    The discovery of molecular subtypes of the pathological prion protein PrPSc has provided the basis for a novel classification of human transmissible spongiform encephalopathies (TSEs) and a potentially powerful method for strain typing. However, there is still a significant disparity regarding the understanding and nomenclature of PrPSc types. In addition, it is still unknown whether a specific PrPSc type is associated with each TSE phenotypic variant. In sporadic Creutzfeldt-Jakob disease (sCJD), five disease phenotypes are known, but only two major types of PrPSc, types 1 and 2, have been consistently reproduced. We further analyzed PrPSc properties in sCJD and variant CJD using a high resolution gel electrophoresis system and varying experimental conditions. We found that pH varies among CJD brain homogenates in standard buffers, thereby influencing the characteristics of protease-treated PrPSc. We also show that PrPSc type 1 and type 2 are heterogeneous species which can be further distinguished into five molecular subtypes that fit the current histopathological classification of sCJD variants. Our results shed light on previous disparities in PrPSc typing, provide a refined classification of human PrPSc types, and support the notion that the pathological TSE phenotype is related to PrPSc structure.

  12. The N-Terminal Sequence of Prion Protein Consists an Epitope Specific to the Abnormal Isoform of Prion Protein (PrPSc)

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    Masujin, Kentaro; Kaku-Ushiki, Yuko; Miwa, Ritsuko; Okada, Hiroyuki; Shimizu, Yoshihisa; Kasai, Kazuo; Matsuura, Yuichi; Yokoyama, Takashi

    2013-01-01

    The conformation of abnormal prion protein (PrPSc) differs from that of cellular prion protein (PrPC), but the precise characteristics of PrPSc remain to be elucidated. To clarify the properties of native PrPSc, we attempted to generate novel PrPSc-specific monoclonal antibodies (mAbs) by immunizing PrP-deficient mice with intact PrPSc purified from bovine spongiform encephalopathy (BSE)-affected mice. The generated mAbs 6A12 and 8D5 selectivity precipitated PrPSc from the brains of prion-affected mice, sheep, and cattle, but did not precipitate PrPC from the brains of healthy animals. In histopathological analysis, mAbs 6A12 and 8D5 strongly reacted with prion-affected mouse brains but not with unaffected mouse brains without antigen retrieval. Epitope analysis revealed that mAbs 8D5 and 6A12 recognized the PrP subregions between amino acids 31–39 and 41–47, respectively. This indicates that a PrPSc-specific epitope exists in the N-terminal region of PrPSc, and mAbs 6A12 and 8D5 are powerful tools with which to detect native and intact PrPSc. We found that the ratio of proteinase K (PK)-sensitive PrPSc to PK-resistant PrPSc was constant throughout the disease time course. PMID:23469131

  13. Co-existence of distinct prion types enables conformational evolution of human PrPSc by competitive selection.

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    Haldiman, Tracy; Kim, Chae; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Qing, Liuting; Cohen, Mark L; Langeveld, Jan; Telling, Glenn C; Kong, Qingzhong; Safar, Jiri G

    2013-10-11

    The unique phenotypic characteristics of mammalian prions are thought to be encoded in the conformation of pathogenic prion proteins (PrP(Sc)). The molecular mechanism responsible for the adaptation, mutation, and evolution of prions observed in cloned cells and upon crossing the species barrier remains unsolved. Using biophysical techniques and conformation-dependent immunoassays in tandem, we isolated two distinct populations of PrP(Sc) particles with different conformational stabilities and aggregate sizes, which frequently co-exist in the most common human prion disease, sporadic Creutzfeldt-Jakob disease. The protein misfolding cyclic amplification replicates each of the PrP(Sc) particle types independently and leads to the competitive selection of those with lower initial conformational stability. In serial propagation with a nonglycosylated mutant PrP(C) substrate, the dominant PrP(Sc) conformers are subject to further evolution by natural selection of the subpopulation with the highest replication rate due to its lowest stability. Cumulatively, the data show that sporadic Creutzfeldt-Jakob disease PrP(Sc) is not a single conformational entity but a dynamic collection of two distinct populations of particles. This implies the co-existence of different prions, whose adaptation and evolution are governed by the selection of progressively less stable, faster replicating PrP(Sc) conformers.

  14. Co-existence of Distinct Prion Types Enables Conformational Evolution of Human PrPSc by Competitive Selection*

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    Haldiman, Tracy; Kim, Chae; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Qing, Liuting; Cohen, Mark L.; Langeveld, Jan; Telling, Glenn C.; Kong, Qingzhong; Safar, Jiri G.

    2013-01-01

    The unique phenotypic characteristics of mammalian prions are thought to be encoded in the conformation of pathogenic prion proteins (PrPSc). The molecular mechanism responsible for the adaptation, mutation, and evolution of prions observed in cloned cells and upon crossing the species barrier remains unsolved. Using biophysical techniques and conformation-dependent immunoassays in tandem, we isolated two distinct populations of PrPSc particles with different conformational stabilities and aggregate sizes, which frequently co-exist in the most common human prion disease, sporadic Creutzfeldt-Jakob disease. The protein misfolding cyclic amplification replicates each of the PrPSc particle types independently and leads to the competitive selection of those with lower initial conformational stability. In serial propagation with a nonglycosylated mutant PrPC substrate, the dominant PrPSc conformers are subject to further evolution by natural selection of the subpopulation with the highest replication rate due to its lowest stability. Cumulatively, the data show that sporadic Creutzfeldt-Jakob disease PrPSc is not a single conformational entity but a dynamic collection of two distinct populations of particles. This implies the co-existence of different prions, whose adaptation and evolution are governed by the selection of progressively less stable, faster replicating PrPSc conformers. PMID:23974118

  15. Structural studies of PrPSc

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    Vázquez Fernández, Ester

    2013-01-01

    Elucidation of the structure of PrPSc continues to be one major challenge in prion research. Molecular basis of the biology of prion protein, such as the molecular mechanism of prion replication and aggregation, the species barrier and the pathogenesis of neurodegeneration will not be understood until the structure is solved. Given that high-resolution techniques such as NMR or X-ray crystallography cannot be used, a number of lower resolution analytical approaches have been attempted.

  16. Plasminogen: A cellular protein cofactor for PrPSc propagation

    OpenAIRE

    Mays, Charles E; Ryou, Chongsuk

    2011-01-01

    The biochemical essence of prion replication is the molecular multiplication of the disease-associated misfolded isoform of prion protein (PrP), termed PrPSc, in a nucleic acid-free manner. PrPSc is generated by the protein misfolding process facilitated by conformational conversion of the host-encoded cellular PrP to PrPSc. Evidence suggests that an auxiliary factor may play a role in PrPSc propagation. We and others previously discovered that plasminogen interacts with PrP, while its functi...

  17. Mouse-adapted ovine scrapie prion strains are characterized by different conformers of PrPSc.

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    Thackray, Alana M; Hopkins, Lee; Klein, Michael A; Bujdoso, Raymond

    2007-11-01

    The agent responsible for prion disease may exist in different forms, commonly referred to as strains, with each carrying the specific information that determines its own distinct biological properties, such as incubation period and lesion profile. Biological strain typing of ovine scrapie isolates by serial passage in conventional mice has shown some diversity in ovine prion strains. However, this biological diversity remains poorly supported by biochemical prion strain typing. The protein-only hypothesis predicts that variation between different prion strains in the same host is manifest in different conformations adopted by PrPSc. Here we have investigated the molecular properties of PrPSc associated with two principal Prnp(a) mouse-adapted ovine scrapie strains, namely, RML and ME7, in order to establish biochemical prion strain typing strategies that may subsequently be used to discriminate field cases of mouse-passaged ovine scrapie isolates. We used a conformation-dependent immunoassay and a conformational stability assay, together with Western blot analysis, to demonstrate that RML and ME7 PrPSc proteins show distinct biochemical and physicochemical properties. Although RML and ME7 PrPSc proteins showed similar resistance to proteolytic digestion, they differed in their glycoform profiles and levels of proteinase K (PK)-sensitive and PK-resistant isoforms. In addition, the PK-resistant core (PrP27-30) of ME7 was conformationally more stable following exposure to guanidine hydrochloride or Sarkosyl than was RML PrP27-30. Our data show that mouse-adapted ovine scrapie strains can be discriminated by their distinct conformers of PrPSc, which provides a basis to investigate their diversity at the molecular level.

  18. Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

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    Kim, Chae; Haldiman, Tracy; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Sy, Man-Sun; Cohen, Mark; Safar, Jiri G

    2011-09-01

    The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD), are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc)) using novel conformational methods derived from a conformation-dependent immunoassay (CDI). In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc), we identified an extensive array of PrP(Sc) structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc) correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc) structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc) suggests that these conformers play an important role in the pathogenesis of sCJD.

  19. Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

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    Chae Kim

    2011-09-01

    Full Text Available The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD, are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc using novel conformational methods derived from a conformation-dependent immunoassay (CDI. In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc, we identified an extensive array of PrP(Sc structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc suggests that these conformers play an important role in the pathogenesis of sCJD.

  20. Prions adhere to soil minerals and remain infectious.

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    Christopher J Johnson

    2006-04-01

    Full Text Available An unidentified environmental reservoir of infectivity contributes to the natural transmission of prion diseases (transmissible spongiform encephalopathies [TSEs] in sheep, deer, and elk. Prion infectivity may enter soil environments via shedding from diseased animals and decomposition of infected carcasses. Burial of TSE-infected cattle, sheep, and deer as a means of disposal has resulted in unintentional introduction of prions into subsurface environments. We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc with common soil minerals. In this study, we demonstrated substantial PrP(Sc adsorption to two clay minerals, quartz, and four whole soil samples. We quantified the PrP(Sc-binding capacities of each mineral. Furthermore, we observed that PrP(Sc desorbed from montmorillonite clay was cleaved at an N-terminal site and the interaction between PrP(Sc and Mte was strong, making desorption of the protein difficult. Despite cleavage and avid binding, PrP(Sc bound to Mte remained infectious. Results from our study suggest that PrP(Sc released into soil environments may be preserved in a bioavailable form, perpetuating prion disease epizootics and exposing other species to the infectious agent.

  1. Small protease sensitive oligomers of PrPSc in distinct human prions determine conversion rate of PrP(C).

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    Kim, Chae; Haldiman, Tracy; Surewicz, Krystyna; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Sy, Man-Sun; Cohen, Mark; Kong, Qingzhong; Telling, Glenn C; Surewicz, Witold K; Safar, Jiri G

    2012-01-01

    The mammalian prions replicate by converting cellular prion protein (PrP(C)) into pathogenic conformational isoform (PrP(Sc)). Variations in prions, which cause different disease phenotypes, are referred to as strains. The mechanism of high-fidelity replication of prion strains in the absence of nucleic acid remains unsolved. We investigated the impact of different conformational characteristics of PrP(Sc) on conversion of PrP(C) in vitro using PrP(Sc) seeds from the most frequent human prion disease worldwide, the Creutzfeldt-Jakob disease (sCJD). The conversion potency of a broad spectrum of distinct sCJD prions was governed by the level, conformation, and stability of small oligomers of the protease-sensitive (s) PrP(Sc). The smallest most potent prions present in sCJD brains were composed only of∼20 monomers of PrP(Sc). The tight correlation between conversion potency of small oligomers of human sPrP(Sc) observed in vitro and duration of the disease suggests that sPrP(Sc) conformers are an important determinant of prion strain characteristics that control the progression rate of the disease.

  2. Small protease sensitive oligomers of PrPSc in distinct human prions determine conversion rate of PrP(C.

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    Chae Kim

    Full Text Available The mammalian prions replicate by converting cellular prion protein (PrP(C into pathogenic conformational isoform (PrP(Sc. Variations in prions, which cause different disease phenotypes, are referred to as strains. The mechanism of high-fidelity replication of prion strains in the absence of nucleic acid remains unsolved. We investigated the impact of different conformational characteristics of PrP(Sc on conversion of PrP(C in vitro using PrP(Sc seeds from the most frequent human prion disease worldwide, the Creutzfeldt-Jakob disease (sCJD. The conversion potency of a broad spectrum of distinct sCJD prions was governed by the level, conformation, and stability of small oligomers of the protease-sensitive (s PrP(Sc. The smallest most potent prions present in sCJD brains were composed only of∼20 monomers of PrP(Sc. The tight correlation between conversion potency of small oligomers of human sPrP(Sc observed in vitro and duration of the disease suggests that sPrP(Sc conformers are an important determinant of prion strain characteristics that control the progression rate of the disease.

  3. Small Protease Sensitive Oligomers of PrPSc in Distinct Human Prions Determine Conversion Rate of PrPC

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    Kim, Chae; Haldiman, Tracy; Surewicz, Krystyna; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Sy, Man-Sun; Cohen, Mark; Kong, Qingzhong; Telling, Glenn C.; Surewicz, Witold K.; Safar, Jiri G.

    2012-01-01

    The mammalian prions replicate by converting cellular prion protein (PrPC) into pathogenic conformational isoform (PrPSc). Variations in prions, which cause different disease phenotypes, are referred to as strains. The mechanism of high-fidelity replication of prion strains in the absence of nucleic acid remains unsolved. We investigated the impact of different conformational characteristics of PrPSc on conversion of PrPC in vitro using PrPSc seeds from the most frequent human prion disease worldwide, the Creutzfeldt-Jakob disease (sCJD). The conversion potency of a broad spectrum of distinct sCJD prions was governed by the level, conformation, and stability of small oligomers of the protease-sensitive (s) PrPSc. The smallest most potent prions present in sCJD brains were composed only of∼20 monomers of PrPSc. The tight correlation between conversion potency of small oligomers of human sPrPSc observed in vitro and duration of the disease suggests that sPrPSc conformers are an important determinant of prion strain characteristics that control the progression rate of the disease. PMID:22876179

  4. PK-sensitive PrPSc is infectious and shares basic structural features with PK-resistant PrPSc

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    One of the main characteristics of the transmissible isoform of the prion protein (PrPSc) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrPSc following Western blot or ELISA. More recently, researchers determ...

  5. Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis.

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    Sevillano, Alejandro M; Fernández-Borges, Natalia; Younas, Neelam; Wang, Fei; R Elezgarai, Saioa; Bravo, Susana; Vázquez-Fernández, Ester; Rosa, Isaac; Eraña, Hasier; Gil, David; Veiga, Sonia; Vidal, Enric; Erickson-Beltran, Melissa L; Guitián, Esteban; Silva, Christopher J; Nonno, Romolo; Ma, Jiyan; Castilla, Joaquín; R Requena, Jesús

    2018-01-01

    Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and that individual PrPSc subunits stack to form amyloid fibers. We recently used limited proteolysis to map the β-strands and connecting loops that make up the PrPSc solenoid. Using high resolution SDS-PAGE followed by epitope analysis, and mass spectrometry, we identified positions ~116/118, 133-134, 141, 152-153, 162, 169 and 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such sites likely define loops and/or borders of β-strands, helping us to predict the threading of the β-solenoid. We have now extended this approach to recombinant PrPSc (recPrPSc). The term recPrPSc refers to bona fide recombinant prions prepared by PMCA, exhibiting infectivity with attack rates of ~100%. Limited proteolysis of mouse and bank vole recPrPSc species yielded N-terminally truncated PK-resistant fragments similar to those seen in brain-derived PrPSc, albeit with varying relative yields. Along with these fragments, doubly N- and C-terminally truncated fragments, in particular ~89/97-152, were detected in some recPrPSc preparations; similar fragments are characteristic of atypical strains of brain-derived PrPSc. Our results suggest a shared architecture of recPrPSc and brain PrPSc prions. The observed differences, in particular the distinct yields of specific PK-resistant fragments, are likely due to differences in threading which result in the specific biochemical characteristics of recPrPSc. Furthermore, recombinant PrPSc offers exciting opportunities for structural studies unachievable with brain-derived PrPSc.

  6. Inhibitors of the mitogen-activated protein kinase kinase 1/2 signaling pathway clear prion-infected cells from PrPSc.

    Science.gov (United States)

    Nordström, Elin K; Luhr, Katarina M; Ibáñez, Carlos; Kristensson, Krister

    2005-09-14

    Prions represent a unique class of infectious agents in which the normal cellular prion protein (PrPC) is converted to an abnormal isoform (PrPSc), which accumulates in the brain and constitutes the major, if not the only, component of the infectious particle. Factors that still remain to be identified may facilitate the conversion of PrPC to PrPSc. In the present study, we first demonstrated that a growth factor of the neurotrophin family, brain-derived neurotrophic factor (BDNF), stimulates the formation of PrPSc in a gonadotropin-releasing hormone-secreting neuronal cell line (GT1-1 cells) infected with the Rocky Mountain Laboratory (RML) strain of scrapie as determined by Western blot analysis. We then observed that the prion-infected cells can be cleared from PrPSc by treatment with three inhibitors of mitogen-activated protein kinase kinase 1/2 (MEK1/2) [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene and 2-(2-amino-3-methyoxyphenyl)-4H-1-benzopyran-4-one, as well as alpha-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl) benzeneacetonitrile, which passes the blood-brain barrier], a component of one of the intracellular signaling pathways activated by BDNF. The MEK1/2 inhibitors were also efficient in clearing PrPSc from prion-infected GT1-1 cells stimulated to accumulate high levels of PrPSc by enhanced serum concentrations in the medium or by the use of a serum-free neuron-specific neurobasal medium. PrPSc did not reappear in the cultures within 5 weeks after completion of treatment. We conclude that inhibitors of the MEK1/2 pathway can efficiently and probably irreversibly clear PrP(Sc) from prion-infected cells. The MEK pathway may therefore be a suitable target for therapeutic intervention in prion diseases.

  7. Inhibition of cholesterol recycling impairs cellular PrPSc propagation

    OpenAIRE

    Gilch, Sabine; Bach, Christian; Lutzny, Gloria; Vorberg, Ina; Sch?tzl, Hermann M.

    2009-01-01

    The infectious agent in prion diseases consists of an aberrantly folded isoform of the cellular prion protein (PrPc), termed PrPSc, which accumulates in brains of affected individuals. Studies on prion-infected cultured cells indicate that cellular cholesterol homeostasis influences PrPSc propagation. Here, we demonstrate that the cellular PrPSc content decreases upon accumulation of cholesterol in late endosomes, as induced by NPC-1 knock-down or treatment with U18666A. PrPc trafficking, lip...

  8. Modulation of Glycosaminoglycans Affects PrPSc Metabolism but Does Not Block PrPSc Uptake.

    Science.gov (United States)

    Wolf, Hanna; Graßmann, Andrea; Bester, Romina; Hossinger, André; Möhl, Christoph; Paulsen, Lydia; Groschup, Martin H; Schätzl, Hermann; Vorberg, Ina

    2015-10-01

    Mammalian prions are unconventional infectious agents composed primarily of the misfolded aggregated host prion protein PrP, termed PrP(Sc). Prions propagate by the recruitment and conformational conversion of cellular prion protein into abnormal prion aggregates on the cell surface or along the endocytic pathway. Cellular glycosaminoglycans have been implicated as the first attachment sites for prions and cofactors for cellular prion replication. Glycosaminoglycan mimetics and obstruction of glycosaminoglycan sulfation affect prion replication, but the inhibitory effects on different strains and different stages of the cell infection have not been thoroughly addressed. We examined the effects of a glycosaminoglycan mimetic and undersulfation on cellular prion protein metabolism, prion uptake, and the establishment of productive infections in L929 cells by two mouse-adapted prion strains. Surprisingly, both treatments reduced endogenous sulfated glycosaminoglycans but had divergent effects on cellular PrP levels. Chemical or genetic manipulation of glycosaminoglycans did not prevent PrP(Sc) uptake, arguing against their roles as essential prion attachment sites. However, both treatments effectively antagonized de novo prion infection independently of the prion strain and reduced PrP(Sc) formation in chronically infected cells. Our results demonstrate that sulfated glycosaminoglycans are dispensable for prion internalization but play a pivotal role in persistently maintained PrP(Sc) formation independent of the prion strain. Recently, glycosaminoglycans (GAGs) became the focus of neurodegenerative disease research as general attachment sites for cell invasion by pathogenic protein aggregates. GAGs influence amyloid formation in vitro. GAGs are also found in intra- and extracellular amyloid deposits. In light of the essential role GAGs play in proteinopathies, understanding the effects of GAGs on protein aggregation and aggregate dissemination is crucial for

  9. Sodium valproate does not augment Prpsc in murine neuroblastoma cells.

    Science.gov (United States)

    Legendre, C; Casagrande, F; Andrieu, T; Dormont, D; Clayette, P

    2007-10-01

    Sodium valproate (VPA) has been reported to increase the accumulation of the pathologic isoform of prion protein (PrPsc) in scrapie-infected murine neuroblastoma cells. In this study, the effect of VPA on PrPsc accumulation was investigated in murine N2a neuroblastoma cells chronically infected with scrapie strain 22L (N2a-22L). No accumulation of PrPsc was detected after short-term (3 days) or long-term (21 days) treatment of N2a-22L cells with 4.8, 12, 18 or 24 microM VPA. Higher VPA concentrations (240 and 600 microM) also failed to augment PrPsc expression. In conclusion, in our experimental conditions, no deleterious effect was induced by VPA on prions replication.

  10. Recombinant PrPSc shares structural features with brain-derived PrPSc suggesting that they have a similar architecture: Insights from limited proteolysis

    Science.gov (United States)

    An extensive body of experimental and spectroscopic evidence supports the hypothesis that PrPSc is a multimer of 4-rung ß-solenoids, and that individual PrPSc solenoids stack to form amyloid fibers. We recently used limited proteolysis to map the ß-strands and connecting loops that make up the PrPSc...

  11. Heterogeneity of the Abnormal Prion Protein (PrPSc) of the Chandler Scrapie Strain.

    Science.gov (United States)

    Kasai, Kazuo; Iwamaru, Yoshifumi; Masujin, Kentaro; Imamura, Morikazu; Mohri, Shirou; Yokoyama, Takashi

    2013-02-18

    The pathological prion protein, PrPSc, displays various sizes of aggregates. In this study, we investigated the conformation, aggregation stability and proteinase K (PK)-sensitivity of small and large PrPSc aggregates of mouse-adapted prion strains. We showed that small PrPSc aggregates, previously thought to be PK-sensitive, are resistant to PK digestion. Furthermore, we showed that small PrPSc aggregates of the Chandler scrapie strain have greater resistance to PK digestion and aggregation-denaturation than large PrPSc aggregates of this strain. We conclude that this strain consists of heterogeneous PrPSc.

  12. The N-terminal cleavage site of PrPSc from BSE differs from that of PrPSc from scrapie.

    Science.gov (United States)

    Hayashi, Hiroko K; Yokoyama, Takashi; Takata, Masuhiro; Iwamaru, Yoshifumi; Imamura, Morikazu; Ushiki, Yuko K; Shinagawa, Morikazu

    2005-03-25

    Heterogeneity in transmissible spongiform encephalopathy is thought to have derived from conformational variation in an abnormal isoform of the prion protein (PrPSc). To characterize PrPSc in bovine spongiform encephalopathy (BSE) and scrapie, we analyzed the newly generated N-terminus of PrPSc isoforms by digestion with proteinase K (PK). With a lower concentration of PK, the terminal amino acid of BSE PrPSc converged at N96. Under the same conditions, however, the terminal amino acid of scrapie PrPSc was G81 or G85. Furthermore, with an increase of PK concentration, the N-terminal amino acid was shifted and converged at G89. The results suggest that the PK cleavage site of BSE PrPSc is uniform and is different from the cleavage site of scrapie PrPSc.

  13. Fever of unknown origin

    NARCIS (Netherlands)

    Mulders-Manders, C.; Simon, A.; Bleeker-Rovers, C.P.

    2015-01-01

    More than 50 years after the first definition of fever of unknown origin (FUO), it still remains a diagnostic challenge. Evaluation starts with the identification of potential diagnostic clues (PDCs), which should guide further investigations. In the absence of PDCs a standardised diagnostic

  14. Immunoreactivity of specific epitopes of PrPSc is enhanced by pretreatment in a hydrated autoclave.

    Science.gov (United States)

    Yokoyama, T; Momotani, E; Kimura, K; Yuasa, N

    1996-01-01

    An abnormal protein (PrPSc) accumulates in animals affected with scrapie. Immunoblotting procedures have been used widely to detect PrPSc. Blotted membranes were subjected to pretreatment in a hydrated autoclave, and the subsequent immunoreactivity of PrPSc was examined. The immunoreactivity of PrPSc to antisera against the synthetic peptides of the mouse PrP amino acid sequences 199 to 208 and 213 to 226 was enhanced by the pretreatment. However, the reactivity to antisera of peptide sequences 100 to 115 and 165 to 174 was not affected. The antibody-binding ability of the specific epitopes which are located close to the C-terminal end of PrP27-30 the proteinase-resistant portion of PrPSc, was enhanced by pretreatment in a hydrated autoclave. This pretreatment increased the sensitivity of PrPSc, and it would be useful for diagnosis of scrapie. PMID:8807215

  15. Prion inhibition with multivalent PrPSc binding compounds.

    Science.gov (United States)

    Mays, Charles E; Joy, Shaon; Li, Lei; Yu, Linghui; Genovesi, Sacha; West, Frederick G; Westaway, David

    2012-10-01

    Quinacrine and related heterocyclic compounds have antiprion activity. Since the infectious pathogen of prion diseases is composed of multimeric PrP(Sc) assemblies, we hypothesized that this antiprion property could be enhanced by attaching multiple quinacrine-derived chloroquinoline or acridine moieties to a scaffold. In addition to exploring Congo red dye and tetraphenylporphyrin tetracarboxylic acid scaffolds, which already possess intrinsic prion-binding ability; trimesic acid was used in this role. In practice, Congo red itself could not be modified with chloroquinoline or acridine units, and a modified dicarboxyl analog was also unreactive. The latter also lacked antiprion activity in infected cultured cells. While addition of chloroquinoline to a tetraphenylporphyrin tetracarboxylic acid scaffold resulted in some reduction of PrP(Sc), moieties attached to a trimesic acid scaffold exhibited sub-micromolar IC(50)'s as well as a toxicity profile superior to quinacrine. Antiprion activity of these molecules was influenced by the length, polarity, and rigidity associated with the variable linear or cyclic polyamine tethers, and in some instances was modulated by host-cell and/or strain type. Unexpectedly, several compounds in our series increased PrP(Sc) levels. Overall, inhibitory and enhancing properties of these multivalent compounds offer new avenues for structure-based investigation of prion biology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. PrPSc in Salivary Glands of Scrapie-Affected Sheep▿

    OpenAIRE

    Vascellari, Marta; Nonno, Romolo; Mutinelli, Franco; Bigolaro, Michela; Di Bari, Michele Angelo; Melchiotti, Erica; Marcon, Stefano; D'Agostino, Claudia; Vaccari, Gabriele; Conte, Michela; De Grossi, Luigi; Rosone, Francesca; Giordani, Francesco; Agrimi, Umberto

    2007-01-01

    The salivary glands of scrapie-affected sheep and healthy controls were investigated for the presence of the pathological prion protein (PrPSc). PrPSc was detected in major (parotid and mandibular) and minor (buccal, labial, and palatine) salivary glands of naturally and experimentally infected sheep. Using Western blotting, the PrPSc concentration in glands was estimated to be 0.02 to 0.005% of that in brain. Immunohistochemistry revealed intracellular depositions of PrPSc in ductal and acin...

  17. Alternative fates of newly formed PrPSc upon prion conversion on the plasma membrane

    OpenAIRE

    Goold, Rob; McKinnon, Chris; Rabbanian, Samira; Collinge, John; Schiavo, Giampietro; Tabrizi, Sarah J.

    2013-01-01

    Prion diseases are fatal neurodegenerative diseases characterised by the accumulation of misfolded prion protein (PrPSc) in the brain. They are caused by the templated misfolding of normal cellular protein, PrPC, by PrPSc. We have recently generated a unique cell system in which epitope-tagged PrPC competent to produce bona fide PrPSc is expressed in neuroblastoma cells. Using this system we demonstrated that PrPSc forms on the cell surface within minutes of prion exposure. Here, we describe ...

  18. Biology of PrPsc accumulation in two natural scrapie-infected sheep flocks.

    Science.gov (United States)

    Caplazi, Patrick; O'Rourke, Katherine; Wolf, Cynthia; Shaw, Daniel; Baszler, Timothy V

    2004-11-01

    Sheep scrapie is a prion disease that requires interaction of exogenous prions with host prion protein (PrP) supporting prion formation. Disease is associated with deposition of a host-generated conformational variant of PrP, PrPsc, in a variety of tissues, including brain, resulting in fatal spongiform encephalopathy. Efficiency of PrPsc formation is determined by polymorphisms in the PrP-coding sequence. This article adds to previous data of natural sheep scrapie, concentrating on the effect of host genotype and age on PrPsc accumulation patterns during preclinical and clinical disease. Two entire scrapie-infected, predominantly Suffolk-cross, sheep flocks euthanized for regulatory purposes were genotyped and analyzed for PrPsc deposition in various tissues using single- and dual-label immunohistochemistry. Scrapie, as defined by PrPsc deposition, occurred in 13/80 sheep. Preclinical disease was evident in nearly 70% of infected sheep, ranging in age from 14 months to 7 years. PrPsc accumulated systemically in the nervous tissue, various lymphoid tissues, both alimentary tract related and non-alimentary tract related, and the placenta. Clinical neurological illness was always associated with spongiform encephalopathy and PrPsc deposition in the brain. Only 6 of 9 sheep with preclinical scrapie had PrPsc deposition in the brain but widespread PrPsc deposition in peripheral lymphoid tissue, supporting previous data showing peripheral PrPsc accumulation preceding deposition in the brain. PrPsc colocalized with a marker for follicular dendritic cells throughout the lymphoid system. PrPsc also accumulated in the peripheral nervous system, particularly the nervous supply of the gastrointestinal tract. Abundant PrPsc was evident in trophoblast cells of placentomes but not in the endometrium, myometrium, or associated nervous plexus. PrPsc deposits were not observed in the mammary parenchyma or bone marrow. Scrapie susceptibility was defined genetically by PrP codon 171

  19. Distribution of Peripheral PrPSc in Sheep with Naturally Acquired Scrapie

    Science.gov (United States)

    Garza, María Carmen; Monzón, Marta; Marín, Belén; Badiola, Juan José; Monleón, Eva

    2014-01-01

    Accumulation of prion protein (PrPSc) in the central nervous system is the hallmark of transmissible spongiform encephalopathies. However, in some of these diseases such as scrapie or chronic wasting disease, the PrPSc can also accumulate in other tissues, particularly in the lymphoreticular system. In recent years, PrPSc in organs other than nervous and lymphoid have been described, suggesting that distribution of this protein in affected individuals may be much larger than previously thought. In the present study, 11 non-nervous/non-lymphoid organs from 16 naturally scrapie infected sheep in advanced stages of the disease were examined for the presence of PrPSc. Fourteen infected sheep were of the ARQ/ARQ PRNP genotype and 2 of the VRQ/VRQ, where the letters A, R, Q, and V represent the codes for amino-acids alanine, arginine, glutamine and valine, respectively. Adrenal gland, pancreas, heart, skin, urinary bladder and mammary gland were positive for PrPSc by immunohistochemistry and IDEXX HerdChek scrapie/BSE Antigen EIA Test in at least one animal. Lung, liver, kidney and skeletal muscle exhibited PrPSc deposits by immunohistochemistry only. To our knowledge, this is the first report regarding the presence of PrPSc in the heart, pancreas and urinary bladder in naturally acquired scrapie infections. In some other organs examined, in which PrPSc had been previously detected, PrPSc immunolabeling was observed to be associated with new structures within those organs. The results of the present study illustrate a wide dissemination of PrPSc in both ARQ/ARQ and VRQ/VRQ infected sheep, even when the involvement of the lymphoreticular system is scarce or absent, thus highlighting the role of the peripheral nervous system in the spread of PrPSc. PMID:24828439

  20. Methionine Sulfoxides on PrPSc: A Prion-Specific Covalent Signature

    NARCIS (Netherlands)

    Canello, T.; Engelstein, R.; Moshel, O.; Xanthopoulos, K.; Langeveld, J.P.M.; Sklaviadis, T.; Gasset, M.; Gabizon, R.

    2008-01-01

    Prion diseases are fatal neurodegenerative disorders believed to be transmitted by PrPSc, an aberrant form of the membrane protein PrPC. In the absence of an established form-specific covalent difference, the infectious properties of PrPSc were uniquely ascribed to the self-perpetuation properties

  1. Isolation and characterization of a proteinase K-sensitive PrPSc fraction.

    Science.gov (United States)

    Pastrana, Miguel A; Sajnani, Gustavo; Onisko, Bruce; Castilla, Joaquín; Morales, Rodrigo; Soto, Claudio; Requena, Jesús R

    2006-12-26

    Recent studies have shown that a sizable fraction of PrPSc present in prion-infected tissues is, contrary to previous conceptions, sensitive to digestion by proteinase K (PK). This finding has important implications in the context of diagnosis of prion disease, as PK has been extensively used in attempts to distinguish between PrPSc and PrPC. Even more importantly, PK-sensitive PrPSc (sPrPSc) might be essential to understand the process of conversion and aggregation of PrPC leading to infectivity. We have isolated a fraction of sPrPSc. This material was obtained by differential centrifugation at an intermediate speed of Syrian hamster PrPSc obtained through a conventional procedure based on ultracentrifugation in the presence of detergents. PK-sensitive PrPSc is completely degraded under standard conditions (50 mug/mL of proteinase K at 37 degrees C for 1 h) and can also be digested with trypsin. Centrifugation in a sucrose gradient showed sPrPSc to correspond to the lower molecular weight fractions of the continuous range of oligomers that constitute PrPSc. PK-sensitive PrPSc has the ability to convert PrPC into protease-resistant PrPSc, as assessed by the protein misfolding cyclic amplification assay (PMCA). Limited proteolysis of sPrPSc using trypsin allows for identification of regions that are particularly susceptible to digestion, i.e., are partially exposed and flexible; we have identified as such the regions around residues K110, R136, R151, K220, and R229. PK-sensitive PrPSc isolates should prove useful for structural studies to help understand fundamental issues of the molecular biology of PrPSc and in the quest to design tests to detect preclinical prion disease.

  2. Proteinase K and the structure of PrPSc: The good, the bad and the ugly.

    Science.gov (United States)

    Silva, Christopher J; Vázquez-Fernández, Ester; Onisko, Bruce; Requena, Jesús R

    2015-09-02

    Infectious proteins (prions) are, ironically, defined by their resistance to proteolytic digestion. A defining characteristic of the transmissible isoform of the prion protein (PrP(Sc)) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrP(Sc) by Western blot, ELISA or immunohistochemical detection. PK digestion has also been used to detect differences in prion strains. Thus, PK has been a crucial tool to detect and, thereby, control the spread of prions. PK has also been used as a tool to probe the structure of PrP(Sc). Mass spectrometry and antibodies have been used to identify PK cleavage sites in PrP(Sc). These results have been used to identify the more accessible, flexible stretches connecting the β-strand components in PrP(Sc). These data, combined with physical constraints imposed by spectroscopic results, were used to propose a qualitative model for the structure of PrP(Sc). Assuming that PrP(Sc) is a four rung β-solenoid, we have threaded the PrP sequence to satisfy the PK proteolysis data and other experimental constraints. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Analysis of prion strains by PrPSc profiling in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Schoch, Gaby; Seeger, Harald; Bogousslavsky, Julien; Tolnay, Markus; Janzer, Robert Charles; Aguzzi, Adriano; Glatzel, Markus

    2006-02-01

    Prion diseases are a group of invariably fatal neurodegenerative disorders affecting humans and a wide range of mammals. An essential part of the infectious agent, termed the prion, is composed of an abnormal isoform (PrPSc) of a host-encoded normal cellular protein (PrPC). The conversion of PrPC to PrPSc is thought to play a crucial role in the development of prion diseases and leads to PrPSc deposition, mainly in the central nervous system. Sporadic Creutzfeldt-Jakob disease (sCJD), the most common form of human prion disease, presents with a marked clinical heterogeneity. This diversity is accompanied by a molecular signature which can be defined by histological, biochemical, and genetic means. The molecular classification of sCJD is an important tool to aid in the understanding of underlying disease mechanisms and the development of therapy protocols. Comparability of classifications is hampered by disparity of applied methods and inter-observer variability. To overcome these difficulties, we developed a new quantification protocol for PrPSc by using internal standards on each Western blot, which allows for generation and direct comparison of individual PrPSc profiles. By studying PrPSc profiles and PrPSc type expression within nine defined central nervous system areas of 50 patients with sCJD, we were able to show distinct PrPSc distribution patterns in diverse subtypes of sCJD. Furthermore, we were able to demonstrate the co-existence of more than one PrPSc type in individuals with sCJD in about 20% of all patients and in more than 50% of patients heterozygous for a polymorphism on codon 129 of the gene encoding the prion protein (PRNP). PrPSc profiling represents a valuable tool for the molecular classification of human prion diseases and has important implications for their diagnosis by brain biopsy. Our results show that the co-existence of more than one PrPSc type might be influenced by genetic and brain region-specific determinants. These findings

  4. Fate of pathological prion (PrP(sc)92-138) in soil and water: prion-clay nanoparticle molecular dynamics.

    Science.gov (United States)

    Chapron, Yves; Charlet, Laurent; Sahai, Nita

    2014-01-01

    Pathogenic prion protein scrapie (PrP(sc)) may contaminate soils for decades and remain in water in colloidal suspension, providing infection pathways for animals through the inhalation of ingested dust and soil particles, and drinking water. We used molecular dynamics simulations to understand the strong binding mechanism of this pathogenic peptide with clay mineral surfaces and compared our results to experimental works. We restricted our model to the moiety PrP(92-138), which is a portion of the whole PrP(sc) molecule responsible for infectivity and modeled it using explicit solvating water molecules in contact with a pyrophyllite cleavage plane. Pyrophyllite is taken as a model for common soil clay, but it has no permanent structural charge. However, partial residual negative charges occur on the cleavage plane slab surface due to a slab charge unbalance. The charge is isotropic in 2D and it was balanced with K(+) ions. After partially removing potassium ions, the peptide anchors to the clay surface via up to 10 hydrogen bonds, between protonated lysine or histidine residues and the oxygen atoms of the siloxane cavities. Our results provide insight to the mechanism responsible for the strong association between the PrP(sc) peptide and clay nanoparticles and the associations present in contaminated soil and water which may lead to the infection of animals.

  5. Microglia in the degenerating brain are capable of phagocytosis of beads and of apoptotic cells, but do not efficiently remove PrPSc, even upon LPS stimulation.

    Science.gov (United States)

    Hughes, Martina M; Field, Robert H; Perry, V Hugh; Murray, Carol L; Cunningham, Colm

    2010-12-01

    Despite the phagocytic machinery available to microglia the aberrant amyloid proteins produced during Alzheimer's and prion disease, amyloid-β and PrP(Sc), are inefficiently cleared. We have shown that microglia in the ME7 model of prion disease show morphological evidence of activation, synthesize low levels of pro-inflammatory cytokines and are primed to produce exaggerated responses to subsequent inflammatory challenges. Whether these microglia engage in significant phagocytic activity in the disease per se, or upon subsequent inflammatory challenge is not clear. In the present study we show transcriptional activation of a large number of scavenger receptors (SRs), matrix metalloproteinases (MMPs), oxidative enzymes, and cathepsins in ME7 animals. Hippocampally-injected inert latex beads (6 μm) are efficiently phagocytosed by microglia of ME7 prion-diseased animals, but not by microglia in normal animals. Stimulation of ME7 animals with systemic bacterial endotoxin (lipopolysaccharide, LPS) induced further increases in SR-A2, MMP3, and urokinase plasminogen activator receptor (uPAR) but decreased, or did not alter, transcription of most phagocytosis-related genes examined and did not enhance clearance of deposited PrP(Sc). Furthermore, intracerebral injection with LPS (0.5 μg) induced marked microglial production of IL-1β, robust cellular infiltration and marked apoptosis but also did not induce further clearance of PrP(Sc). These data indicate that microglia in the prion-diseased brain are capable of phagocytosis per se, but show limited efficacy in removing PrP(Sc) even upon marked escalation of CNS inflammation. Furthermore, microglia/macrophages remain IL-1β-negative during phagocytosis of apoptotic cells. The data demonstrate that phagocytic activity and pro-inflammatory microglial phenotype do not necessarily correlate.

  6. Fluorescent Immunoassay Development for PrPSc Detection and Antemortem Diagnosis of TSEs

    National Research Council Canada - National Science Library

    Carp, Richard I

    2005-01-01

    The overall goal of our study is to develop methods of high-sensitivity and high-specificity for the antemortem diagnosis of prion diseases by detecting PrPSc in biological fluids using fluorescent immunoassay...

  7. Fluorescent Immunoassay Development for PrP(Sc) Detection and Antemortem Diagnosis of TSEs

    National Research Council Canada - National Science Library

    Carp, Richard I

    2004-01-01

    The overall goal of our study is to develop methods of high-sensitivity and high-specificity for the antemortem diagnosis of prion diseases by detecting PrPsc in biological fluids using fluorescent immunoassay...

  8. Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc.

    Science.gov (United States)

    Ferrucci, M; Ryskalin, L; Biagioni, F; Gambardella, S; Busceti, C L; Falleni, A; Lazzeri, G; Fornai, F

    2017-07-01

    The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blue, immune- histochemistry and immune-gold electron microscopy. To analyze whether METH administration produces PrPsc aggregates we used antibodies directed against PrP following exposure to proteinase K or sarkosyl which digest folded PrPc but misfolded PrPsc. We fond that METH triggers PrPsc aggregates in DA-containing cells while METH is not effective in primary striatal neurons which do not produce DA. In the latter cells exogenous DA is needed to trigger PrPsc accumulation similarly to what happens in DA containing cells under the effects of METH. The present findings, while fostering novel molecular mechanisms involving prion proteins, indicate that, cell pathology similar to prion disorders can be mimicked via a DA-dependent mechanism by a drug of abuse.

  9. Assessment of strain-specific PrP(Sc elongation rates revealed a transformation of PrP(Sc properties during protein misfolding cyclic amplification.

    Directory of Open Access Journals (Sweden)

    Nuria Gonzalez-Montalban

    Full Text Available Prion replication is believed to consist of two components, a growth or elongation of infectious isoform of the prion protein (PrP(Sc particles and their fragmentation, a process that provides new replication centers. The current study introduced an experimental approach that employs Protein Misfolding Cyclic Amplification with beads (PMCAb and relies on a series of kinetic experiments for assessing elongation rates of PrP(Sc particles. Four prion strains including two strains with short incubation times to disease (263K and Hyper and two strains with very long incubation times (SSLOW and LOTSS were tested. The elongation rate of brain-derived PrP(Sc was found to be strain-specific. Strains with short incubation times had higher rates than strains with long incubation times. Surprisingly, the strain-specific elongation rates increased substantially for all four strains after they were subjected to six rounds of serial PMCAb. In parallel to an increase in elongation rates, the percentages of diglycosylated PrP glycoforms increased in PMCAb-derived PrP(Sc comparing to those of brain-derived PrP(Sc. These results suggest that PMCAb selects the same molecular features regardless of strain initial characteristics and that convergent evolution of PrP(Sc properties occurred during in vitro amplification. These results are consistent with the hypothesis that each prion strain is comprised of a variety of conformers or 'quasi-species' and that change in the prion replication environment gives selective advantage to those conformers that replicate most effectively under specific environment.

  10. Assessment of Strain-Specific PrPSc Elongation Rates Revealed a Transformation of PrPSc Properties during Protein Misfolding Cyclic Amplification

    Science.gov (United States)

    Gonzalez-Montalban, Nuria; Baskakov, Ilia V.

    2012-01-01

    Prion replication is believed to consist of two components, a growth or elongation of infectious isoform of the prion protein (PrPSc) particles and their fragmentation, a process that provides new replication centers. The current study introduced an experimental approach that employs Protein Misfolding Cyclic Amplification with beads (PMCAb) and relies on a series of kinetic experiments for assessing elongation rates of PrPSc particles. Four prion strains including two strains with short incubation times to disease (263K and Hyper) and two strains with very long incubation times (SSLOW and LOTSS) were tested. The elongation rate of brain-derived PrPSc was found to be strain-specific. Strains with short incubation times had higher rates than strains with long incubation times. Surprisingly, the strain-specific elongation rates increased substantially for all four strains after they were subjected to six rounds of serial PMCAb. In parallel to an increase in elongation rates, the percentages of diglycosylated PrP glycoforms increased in PMCAb-derived PrPSc comparing to those of brain-derived PrPSc. These results suggest that PMCAb selects the same molecular features regardless of strain initial characteristics and that convergent evolution of PrPSc properties occurred during in vitro amplification. These results are consistent with the hypothesis that each prion strain is comprised of a variety of conformers or ‘quasi-species’ and that change in the prion replication environment gives selective advantage to those conformers that replicate most effectively under specific environment. PMID:22815972

  11. A novel method for preclinical detection of PrPSc in blood.

    Science.gov (United States)

    Rubenstein, Richard; Chang, Binggong; Gray, Perry; Piltch, Martin; Bulgin, Marie S; Sorensen-Melson, Sharon; Miller, Michael W

    2010-07-01

    In this study, we demonstrate that a moderate amount of protein misfolding cyclic amplification (PMCA) coupled to a novel surround optical fibre immunoassay (SOFIA) detection scheme can be used to detect the disease-associated form of the prion protein (PrP(Sc)) in protease-untreated plasma from preclinical and clinical scrapie sheep, and white-tailed deer with chronic wasting disease, following natural and experimental infection. PrP(Sc), resulting from a conformational change of the normal (cellular) form of prion protein (PrP(C)), is considered central to neuropathogenesis and serves as the only reliable molecular marker for prion disease diagnosis. While the highest levels of PrP(Sc) are present in the central nervous system, the development of a reasonable diagnostic assay requires the use of body fluids that characteristically contain exceedingly low levels of PrP(Sc). PrP(Sc) has been detected in the blood of sick animals by means of PMCA technology. However, repeated cycling over several days, which is necessary for PMCA of blood material, has been reported to result in decreased specificity (false positives). To generate an assay for PrP(Sc) in blood that is both highly sensitive and specific, we have utilized limited serial PMCA (sPMCA) with SOFIA. We did not find any enhancement of sPMCA with the addition of polyadenylic acid nor was it necessary to match the genotypes of the PrP(C) and PrP(Sc) sources for efficient amplification.

  12. Inhibition of PrPSc formation by synthetic O-sulfated glycopyranosides and their polymers.

    Science.gov (United States)

    Yamaguchi, Satoko; Nishida, Yoshihiro; Sasaki, Kenji; Kambara, Mikie; Kim, Chan-Lan; Ishiguro, Naotaka; Nagatsuka, Takehiro; Uzawa, Hirotaka; Horiuchi, Motohiro

    2006-10-20

    Sulfated glycosaminoglycans (GAGs) and sulfated glycans inhibit formation of the abnormal isoform of prion protein (PrPSc) in prion-infected cells and prolong the incubation time of scrapie-infected animals. Sulfation of GAGs is not tightly regulated and possible sites of sulfation are randomly modified, which complicates elucidation of the fundamental structures of GAGs that mediate the inhibition of PrPSc formation. To address the structure-activity relationship of GAGs in the inhibition of PrPSc formation, we screened the ability of various regioselectively O-sulfated glycopyranosides to inhibit PrPSc formation in prion-infected cells. Among the glycopyranosides and their polymers examined, monomeric 4-sulfo-N-acetyl-glucosamine (4SGN), and two glycopolymers, poly-4SGN and poly-6-sulfo-N-acetyl-glucosamine (poly-6SGN), inhibited PrPSc formation with 50% effective doses below 20 microg/ml, and their inhibitory effect became more evident with consecutive treatments. Structural comparisons suggested that a combination of an N-acetyl group at C-2 and an O-sulfate group at either O-4 or O-6 on glucopyranoside might be involved in the inhibition of PrPSc formation. Furthermore, polymeric but not monomeric 6SGN inhibited PrPSc formation, suggesting the importance of a polyvalent configuration in its effect. These results indicate that the synthetic sulfated glycosides are useful not only for the analysis of structure-activity relationship of GAGs but also for the development of therapeutics for prion diseases.

  13. PrPSc spreading patterns in the brain of sheep linked to different prion types.

    Science.gov (United States)

    Wemheuer, Wiebke M; Benestad, Sylvie L; Wrede, Arne; Wemheuer, Wilhelm E; Brenig, Bertram; Bratberg, Bjørn; Schulz-Schaeffer, Walter J

    2011-02-15

    Scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform encephalopathy in cattle (BSE) and Creutzfeldt-Jakob disease in humans. According to the prion hypothesis, the pathological isoform (PrPSc) of the cellular prion protein (PrPc) comprises the essential, if not exclusive, component of the transmissible agent. Currently, two types of scrapie disease are known--classical and atypical/Nor98 scrapie. In the present study we examine 24 cases of classical and 25 cases of atypical/Nor98 scrapie with the sensitive PET blot method and validate the results with conventional immunohistochemistry. The sequential detection of PrPSc aggregates in the CNS of classical scrapie sheep implies that after neuroinvasion a spread from spinal cord and obex to the cerebellum, diencephalon and frontal cortex via the rostral brainstem takes place. We categorize the spread of PrPSc into four stages: the CNS entry stage, the brainstem stage, the cruciate sulcus stage and finally the basal ganglia stage. Such a sequential development of PrPSc was not detectable upon analysis of the present atypical/Nor98 scrapie cases. PrPSc distribution in one case of atypical/Nor98 scrapie in a presumably early disease phase suggests that the spread of PrPSc aggregates starts in the di- or telencephalon. In addition to the spontaneous generation of PrPSc, an uptake of the infectious agent into the brain, that bypasses the brainstem and starts its accumulation in the thalamus, needs to be taken into consideration for atypical/Nor98 scrapie.

  14. TSE strain differentiation in mice by immunohistochemical PrP(Sc) profiles and triplex Western blot.

    Science.gov (United States)

    van Keulen, Lucien J M; Langeveld, Jan P M; Dolstra, Corry H; Jacobs, Jorg; Bossers, Alex; van Zijderveld, Fred G

    2015-10-01

    TSE strains are routinely identified by their incubation period and vacuolation profile in the brain after intracerebral inoculation and serial passaging in inbred mouse lines. There are some major drawbacks to this method that are related to the variation in vacuolation that exists in the brains of mice infected with the same TSE strain and to variation between observers and laboratories in scoring vacuolation and determining the final incubation period. We investigated the potential of PrP(Sc) immunohistochemistry and triplex Western blotting as possible alternative methods to differentiate between TSE strains. TSE reference strains ME7, 87A/87V, 22A/22C, 79A/79V and 301C/301V were intracerebrally inoculated in RIII or VM inbred mice that differ in their PrP genotype. Immunohistochemical PrP(Sc) profiles were drawn up by scanning light microscopy both on coronal and sagittal sections. On the basis of the localization of PrP(Sc) in the cerebral cortex, hippocampus, and cerebellar cortex and the overall type of PrP(Sc) staining, all TSE strains could be well differentiated from each other through their typical strain dependent characteristics. In addition, Western blot showed that the combination of glycosylation profile and 12B2 epitope content of PrP(Sc) allowed to distinguish between all reference strains except for ME7 and 22A in VM mice. TSE strains in mice can be identified on the basis of their PrP(Sc) profile alone. The potential to identify TSE strains in ruminants with these PrP(Sc) profiles after a single primary passage in mice will be the topic of future studies. © 2014 British Neuropathological Society.

  15. Sc237 hamster PrPSc and Sc237-derived mouse PrPSc generated by interspecies in vitro amplification exhibit distinct pathological and biochemical properties in tga20 transgenic mice.

    Science.gov (United States)

    Yoshioka, Miyako; Imamura, Morikazu; Okada, Hiroyuki; Shimozaki, Noriko; Murayama, Yuichi; Yokoyama, Takashi; Mohri, Shirou

    2011-05-01

    Prions are the infectious agents responsible for transmissible spongiform encephalopathy, and are primarily composed of the pathogenic form (PrP(Sc)) of the host-encoded prion protein (PrP(C)). Recent studies have revealed that protein misfolding cyclic amplification (PMCA), a highly sensitive method for PrP(Sc) detection, can overcome the species barrier in several xenogeneic combinations of PrP(Sc) seed and PrP(C) substrate. Although these findings provide valuable insight into the origin and diversity of prions, the differences between PrP(Sc) generated by interspecies PMCA and by in vivo cross-species transmission have not been described. This study investigated the histopathological and biochemical properties of PrP(Sc) in the brains of tga20 transgenic mice inoculated with Sc237 hamster scrapie prion and PrP(Sc) from mice inoculated with Sc237-derived mouse PrP(Sc), which had been generated by interspecies PMCA using Sc237 as seed and normal mouse brain homogenate as substrate. Tga20 mice overexpressing mouse PrP(C) were susceptible to Sc237 after primary transmission. PrP(Sc) in the brains of mice inoculated with Sc237-derived mouse PrP(Sc) and in the brains of mice inoculated with Sc237 differed in their lesion profiles and accumulation patterns, Western blot profiles, and denaturant resistance. In addition, these PrP(Sc) exhibited distinctive virulence profiles upon secondary passage. These results suggest that different in vivo and in vitro environments result in propagation of PrP(Sc) with different biological properties. © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

  16. Accumulation profiles of PrPSc in hemal nodes of naturally and experimentally scrapie-infected sheep

    Science.gov (United States)

    2013-01-01

    Background In classical scrapie, the disease-associated abnormal isoform (PrPSc) of normal prion protein accumulates principally in the nervous system and lymphoid tissues of small ruminants. Lymph nodes traffic leukocytes via lymphatic and blood vasculatures but hemal nodes lack lymphatic vessels and thus traffic leukocytes only via the blood. Although PrPSc accumulation profiles are well-characterized in ovine lymphoid tissues, there is limited information on such profiles in hemal nodes. Therefore, the objective of this study was to compare the follicular accumulation of PrPSc within hemal nodes and lymph nodes by prion epitope mapping and western blot studies. Results Our studies found that PrPSc accumulation in 82% of animals’ abdominal hemal nodes when PrPSc is detected in both mesenteric and retropharyngeal lymph nodes collected from preclinical and clinical, naturally and experimentally (blood transfusion) scrapie-infected sheep representing all three major scrapie-susceptible Prnp genotypes. Abdominal hemal nodes and retropharyngeal lymph nodes were then used to analyze immune cell phenotypes and PrPSc epitope mapping by immunohistochemistry and PrPSc banding patterns by western blot. Similar patterns of PrPSc accumulation were detected within the secondary follicles of hemal nodes and retropharyngeal lymph nodes, where cellular labeling was mostly associated with macrophages and follicular dendritic cells. The pattern of PrPSc accumulation within hemal nodes and retropharyngeal lymph nodes also did not differ with respect to epitope mapping with seven mAbs (N-terminus, n = 4; globular domain, n = 2; C-terminus, n = 1) in all three Prnp genotypes. Western blot analysis of hemal node and retropharyngeal lymph node homogenates revealed identical three banding patterns of proteinase K resistant PrPSc. Conclusion Despite the anatomical difference in leukocyte trafficking between lymph nodes and hemal nodes, the follicles of hemal nodes appear to

  17. Re-assessment of PrP(Sc distribution in sporadic and variant CJD.

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    Richard Rubenstein

    Full Text Available Human prion diseases are fatal neurodegenerative disorders associated with an accumulation of PrP(Sc in the central nervous system (CNS. Of the human prion diseases, sporadic Creutzfeldt-Jakob disease (sCJD, which has no known origin, is the most common form while variant CJD (vCJD is an acquired human prion disease reported to differ from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. Peripheral tissue involvement in prion disease, as judged by PrP(Sc accumulation in the tonsil, spleen, and lymph node has been reported in vCJD as well as several animal models of prion diseases. However, this distribution of PrP(Sc has not been consistently reported for sCJD. We reexamined CNS and non-CNS tissue distribution and levels of PrP(Sc in both sCJD and vCJD. Using a sensitive immunoassay, termed SOFIA, we also assessed PrP(Sc levels in human body fluids from sCJD as well as in vCJD-infected humanized transgenic mice (Tg666. Unexpectedly, the levels of PrP(Sc in non-CNS human tissues (spleens, lymph nodes, tonsils from both sCJD and vCJD did not differ significantly and, as expected, were several logs lower than in the brain. Using protein misfolding cyclic amplification (PMCA followed by SOFIA, PrP(Sc was detected in cerebrospinal fluid (CSF, but not in urine or blood, in sCJD patients. In addition, using PMCA and SOFIA, we demonstrated that blood from vCJD-infected Tg666 mice showing clinical disease contained prion disease-associated seeding activity although the data was not statistically significant likely due to the limited number of samples examined. These studies provide a comparison of PrP(Sc in sCJD vs. vCJD as well as analysis of body fluids. Further, these studies also provide circumstantial evidence that in human prion diseases, as in the animal prion diseases, a direct comparison and intraspecies correlation cannot be made between the levels of PrP(Sc and infectivity.

  18. Prion Infectivity Plateaus and Conversion to Symptomatic Disease Originate from Falling Precursor Levels and Increased Levels of Oligomeric PrPSc Species.

    Science.gov (United States)

    Mays, Charles E; van der Merwe, Jacques; Kim, Chae; Haldiman, Tracy; McKenzie, Debbie; Safar, Jiri G; Westaway, David

    2015-12-01

    In lethal prion neurodegenerative diseases, misfolded prion proteins (PrP(Sc)) replicate by redirecting the folding of the cellular prion glycoprotein (PrP(C)). Infections of different durations can have a subclinical phase with constant levels of infectious particles, but the mechanisms underlying this plateau and a subsequent exit to overt clinical disease are unknown. Using tandem biophysical techniques, we show that attenuated accumulation of infectious particles in presymptomatic disease is preceded by a progressive fall in PrP(C) level, which constricts replication rate and thereby causes the plateau effect. Furthermore, disease symptoms occurred at the threshold associated with increasing levels of small, relatively less protease-resistant oligomeric prion particles (oPrP(Sc)). Although a hypothetical lethal isoform of PrP cannot be excluded, our data argue that diminishing residual PrP(C) levels and continuously increasing levels of oPrP(Sc) are crucial determinants in the transition from presymptomatic to symptomatic prion disease. Prions are infectious agents that cause lethal brain diseases; they arise from misfolding of a cell surface protein, PrP(C) to a form called PrP(Sc). Prion infections can have long latencies even though there is no protective immune response. Accumulation of infectious prion particles has been suggested to always reach the same plateau in the brain during latent periods, with clinical disease only occurring when hypothetical toxic forms (called PrP(L) or TPrP) begin to accumulate. We show here that infectivity plateaus arise because PrP(C) precursor levels become downregulated and that the duration of latent periods can be accounted for by the level of residual PrP(C), which transduces a toxic effect, along with the amount of oligomeric forms of PrP(Sc). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Immunolocalisation of PrPSc in scrapie-infected N2a mouse neuroblastoma cells by light and electron microscopy.

    Science.gov (United States)

    Veith, Nathalie M; Plattner, Helmut; Stuermer, Claudia A O; Schulz-Schaeffer, Walter J; Bürkle, Alexander

    2009-01-01

    The causative agent of transmissible spongiform encephalopathies (TSE) is PrPSc, an infectious, misfolded isoform of the cellular prion protein (PrPC). The localisation and trafficking of PrPSc and sites of conversion from PrPC to PrPSc are under debate, particularly since most published work did not discriminate between PrPC and PrPSc. Here we describe the localisation of PrPC and PrPSc in a scrapie-infected neuroblastoma cell line, ScN2a, by light and electron microscopic immunolocalisation. After eliminating PrPC with proteinase K, PrPSc was detected at the plasma membrane, endocytosed via clathrin-coated pits and delivered to early endosomes. Finally, PrPSc was detected in late endosomes/lysosomes. As we detected PrPSc at the cell surface, in early endosomes and in late endosomes/lysosomes, i.e. locations where PrPC is also present, our data imply that the conversion process could take place at the plasma membrane and/or along the endocytic pathway. Finally, we observed the release of PrPC/PrPSc via exocytotic pathways, i.e. via exosomes and as an opaque electron-dense mass which may represent a mechanism of intercellular spreading of infectious prions.

  20. Accumulation of pathological prion protein PrPSc in the skin of animals with experimental and natural scrapie.

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    Achim Thomzig

    2007-05-01

    Full Text Available Prion infectivity and its molecular marker, the pathological prion protein PrP(Sc, accumulate in the central nervous system and often also in lymphoid tissue of animals or humans affected by transmissible spongiform encephalopathies. Recently, PrP(Sc was found in tissues previously considered not to be invaded by prions (e.g., skeletal muscles. Here, we address the question of whether prions target the skin and show widespread PrP(Sc deposition in this organ in hamsters perorally or parenterally challenged with scrapie. In hamsters fed with scrapie, PrP(Sc was detected before the onset of symptoms, but the bulk of skin-associated PrP(Sc accumulated in the clinical phase. PrP(Sc was localized in nerve fibres within the skin but not in keratinocytes, and the deposition of PrP(Sc in skin showed no dependence from the route of infection and lymphotropic dissemination. The data indicated a neurally mediated centrifugal spread of prions to the skin. Furthermore, in a follow-up study, we examined sheep naturally infected with scrapie and detected PrP(Sc by Western blotting in skin samples from two out of five animals. Our findings point to the skin as a potential reservoir of prions, which should be further investigated in relation to disease transmission.

  1. Cellular Trafficking of the Pathogenic Prion Protein PrPSc and Phenotypic Characterisation of Deletion Mutants in the Hydrophobic Domain of the Normal Prion Protein PrPC

    OpenAIRE

    Veith, Nathalie Monika

    2008-01-01

    The localisation of the pathogenic prion protein PrPSc was investigated with light and electron microscopy. The PrPSc specific antibody 15B3 was tested for its efficiency in immuncytochemistry. Subsequently, an appropriate method was found to stain PrPSc selectively. PrPSc was detected in clathrin coated pits, early endosomes, late endosomes/lysosomes nad exosomes. PrPSc could not be observed in lipid droplets.In the next part of the thesis different mutants of the prion protein carrying micr...

  2. 4-hydroxytamoxifen leads to PrPSc clearance by conveying both PrPC and PrPSc to lysosomes independently of autophagy.

    Science.gov (United States)

    Marzo, Ludovica; Marijanovic, Zrinka; Browman, Duncan; Chamoun, Zeina; Caputo, Anna; Zurzolo, Chiara

    2013-03-15

    Prion diseases are fatal neurodegenerative disorders involving the abnormal folding of a native cellular protein, named PrP(C), to a malconformed aggregation-prone state, enriched in beta sheet secondary structure, denoted PrP(Sc). Recently, autophagy has garnered considerable attention as a cellular process with the potential to counteract neurodegenerative diseases of protein aggregation such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. Stimulation of autophagy by chemical compounds has also been shown to reduce PrP(Sc) in infected neuronal cells and prolong survival times in mouse models. Consistent with previous reports, we demonstrate that autophagic flux is increased in chronically infected cells. However, in contrast to recent findings we show that autophagy does not cause a reduction in scrapie burden. We report that in infected neuronal cells different compounds known to stimulate autophagy are ineffective in increasing autophagic flux and in reducing PrP(Sc). We further demonstrate that tamoxifen and its metabolite 4-hydroxytamoxifen lead to prion degradation in an autophagy-independent manner by diverting the trafficking of both PrP and cholesterol to lysosomes. Our data indicate that tamoxifen, a well-characterized, widely available pharmaceutical, may have applications in the therapy of prion diseases.

  3. PrP glycoforms are associated in a strain-specific ratio in native PrPSc.

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    Khalili-Shirazi, Azadeh; Summers, Linda; Linehan, Jacqueline; Mallinson, Gary; Anstee, David; Hawke, Simon; Jackson, Graham S; Collinge, John

    2005-09-01

    Prion diseases involve conversion of host-encoded cellular prion protein (PrPC) to a disease-related isoform (PrPSc). Using recombinant human beta-PrP, a panel of monoclonal antibodies was produced that efficiently immunoprecipitated native PrPSc and recognized epitopes between residues 93-105, indicating for the first time that this region is exposed in both human vCJD and mouse RML prions. In contrast, monoclonal antibodies raised to human alpha-PrP were more efficient in immunoprecipitating PrPC than PrPSc, and some of them could also distinguish between different PrP glycoforms. Using these monoclonal antibodies, the physical association of PrP glycoforms was studied in normal brain and in the brains of humans and mice with prion disease. It was shown that while PrPC glycoforms can be selectively immunoprecipitated, the differentially glycosylated molecules of native PrPSc are closely associated and always immunoprecipitate together. Furthermore, the ratio of glycoforms comprising immunoprecipitated native PrPSc from diverse prion strains was similar to those observed on denaturing Western blots. These studies are consistent with the view that the proportion of each glycoform incorporated into PrPSc is probably controlled in a strain-specific manner and that each PrPSc particle contains a mixture of glycoforms.

  4. Live imaging of prions reveals nascent PrPSc in cell-surface, raft-associated amyloid strings and webs.

    Science.gov (United States)

    Rouvinski, Alexander; Karniely, Sharon; Kounin, Maria; Moussa, Sanaa; Goldberg, Miri D; Warburg, Gabriela; Lyakhovetsky, Roman; Papy-Garcia, Dulce; Kutzsche, Janine; Korth, Carsten; Carlson, George A; Godsave, Susan F; Peters, Peter J; Luhr, Katarina; Kristensson, Krister; Taraboulos, Albert

    2014-02-03

    Mammalian prions refold host glycosylphosphatidylinositol-anchored PrP(C) into β-sheet-rich PrP(Sc). PrP(Sc) is rapidly truncated into a C-terminal PrP27-30 core that is stable for days in endolysosomes. The nature of cell-associated prions, their attachment to membranes and rafts, and their subcellular locations are poorly understood; live prion visualization has not previously been achieved. A key obstacle has been the inaccessibility of PrP27-30 epitopes. We overcame this hurdle by focusing on nascent full-length PrP(Sc) rather than on its truncated PrP27-30 product. We show that N-terminal PrP(Sc) epitopes are exposed in their physiological context and visualize, for the first time, PrP(Sc) in living cells. PrP(Sc) resides for hours in unexpected cell-surface, slow moving strings and webs, sheltered from endocytosis. Prion strings observed by light and scanning electron microscopy were thin, micrometer-long structures. They were firmly cell associated, resisted phosphatidylinositol-specific phospholipase C, aligned with raft markers, fluoresced with thioflavin, and were rapidly abolished by anti-prion glycans. Prion strings and webs are the first demonstration of membrane-anchored PrP(Sc) amyloids.

  5. Generation of monoclonal antibody that distinguishes PrPSc from PrPC and neutralizes prion infectivity.

    Science.gov (United States)

    Horiuchi, Motohiro; Karino, Ayako; Furuoka, Hidefumi; Ishiguro, Naotaka; Kimura, Kumiko; Shinagawa, Morikazu

    2009-11-25

    To establish PrP(Sc)-specific mAbs, we immunized Prnp(-/-) mice with PrP(Sc) purified from prion-infected mice. Using this approach, we obtained mAb 6H10, which reacted with PrP(Sc) treated with proteinase K, but not with PrP(Sc) pretreated with more than 3 M GdnHCl. In contrast, reactivity of pan-PrP mAbs increased with increasing concentrations of GdnHCl used for pretreatment of PrP(Sc). In histoblot analysis, mAb 6H10 showed a positive reaction on a non-denatured histoblot but reactivity was lower when the histoblot was pretreated by autoclaving. Epitope analysis suggested that the extreme C-terminus of PrP is likely to be part of the epitope for mAb 6H10. MAb 6H10 immunoprecipitated PrP(Sc) from brains of mice, sheep, and cattle infected with prions. Furthermore, pretreatment of purified PrP(Sc) with mAb 6H10 reduced the infectious titer more than 1 log. Taken together, these results suggest that mAb 6H10 recognizes a conformational epitope on PrP(Sc) that is related to prion infectivity.

  6. Sporadic Creutzfeldt-Jakob disease: the extent of microglia activation is dependent on the biochemical type of PrPSc.

    Science.gov (United States)

    Puoti, Gianfranco; Giaccone, Giorgio; Mangieri, Michela; Limido, Lucia; Fociani, Paolo; Zerbi, Pietro; Suardi, Silvia; Rossi, Giacomina; Iussich, Selina; Capobianco, Raffaella; Di Fede, Giuseppe; Marcon, Gabriella; Cotrufo, Roberto; Filippini, Graziella; Bugiani, Orso; Tagliavini, Fabrizio

    2005-10-01

    In prion-related encephalopathies, microglial activation occurs early and is dependent on accumulation of disease-specific forms of the prion protein (PrPSc) and may play a role in nerve cell death. Previously, we found that different types of PrPSc (i.e. type 1 and type 2) coexisted in approximately 25% of patients with sporadic Creutzfeldt-Jakob disease (CJD); and a close relationship was detected between PrPSc type, the pattern of PrP immunoreactivity, and extent of spongiform degeneration. To investigate whether microglial reaction is related to the biochemical type and deposition pattern of PrPSc, we carried out a neuropathologic and biochemical study on 26 patients with sporadic CJD, including all possible genotypes at codon 129 of the prion protein gene. By quantitative analysis, we demonstrated that strong microglial activation was associated with type 1 PrPSc and diffuse PrP immunoreactivity, whereas type 2 PrPSc and focal PrP deposits were accompanied by mild microglia reaction. These findings support the view that the phenotypic heterogeneity of sporadic CJD is largely determined by the physicochemical properties of distinct PrPSc conformers.

  7. How do PrPSc Prions Spread between Host Species, and within Hosts?

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    Neil A. Mabbott

    2017-11-01

    Full Text Available Prion diseases are sub-acute neurodegenerative diseases that affect humans and some domestic and free-ranging animals. Infectious prion agents are considered to comprise solely of abnormally folded isoforms of the cellular prion protein known as PrPSc. Pathology during prion disease is restricted to the central nervous system where it causes extensive neurodegeneration and ultimately leads to the death of the host. The first half of this review provides a thorough account of our understanding of the various ways in which PrPSc prions may spread between individuals within a population, both horizontally and vertically. Many natural prion diseases are acquired peripherally, such as by oral exposure, lesions to skin or mucous membranes, and possibly also via the nasal cavity. Following peripheral exposure, some prions accumulate to high levels within the secondary lymphoid organs as they make their journey from the site of infection to the brain, a process termed neuroinvasion. The replication of PrPSc prions within secondary lymphoid organs is important for their efficient spread to the brain. The second half of this review describes the key tissues, cells and molecules which are involved in the propagation of PrPSc prions from peripheral sites of exposure (such as the lumen of the intestine to the brain. This section also considers how additional factors such as inflammation and aging might influence prion disease susceptibility.

  8. Small molecules and antibodies: a means of distinguishing between PrPC and PrPSc

    Science.gov (United States)

    PrPSc and PrPC are isoforms, since they possess identical covalent structures and identical post-translational modifications. The same amino acid may react differently with the same chemical reagent in an isoform-dependent manner. The site of covalent modification can be identified by mass spectrom...

  9. Distinguishing between PrPC and PrPSc using small molecule reagents(Abstract)

    Science.gov (United States)

    Background/Introduction. The structural difference between PrPSc and PrPC is entirely conformational: they are isoforms. Both isoforms possess identical covalent structures and identical post-translational modifications. This means that the same amino acid can react differently with the same chemica...

  10. Probing the structure of GPI-less PrPSc by limited proteolysis(Abstract)

    Science.gov (United States)

    Limited proteolysis is a very useful tool to pinpoint flexible regions within scrapie prion protein (PrPSc), but due to carbohydrate and glysosylphosphatidylinositol (GPI) moieties, and limitations of the analytical techniques, until now it was impossible to characterize accurately these regions. To...

  11. Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies

    Science.gov (United States)

    Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of BSE exist...

  12. Distinguishing between PrPC and PrPSc using small molecule reagents

    Science.gov (United States)

    Background/Introduction. The structural difference between PrPSc and PrPC is entirely conformational: they are isoforms. Both isoforms possess identical covalent structures and identical post-translational modifications. This means that the same amino acid can react differently with the same chemic...

  13. Ultra-efficient PrP(Sc amplification highlights potentialities and pitfalls of PMCA technology.

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    Gian Mario Cosseddu

    2011-11-01

    Full Text Available In order to investigate the potential of voles to reproduce in vitro the efficiency of prion replication previously observed in vivo, we seeded protein misfolding cyclic amplification (PMCA reactions with either rodent-adapted Transmissible Spongiform Encephalopathy (TSE strains or natural TSE isolates. Vole brain homogenates were shown to be a powerful substrate for both homologous or heterologous PMCA, sustaining the efficient amplification of prions from all the prion sources tested. However, after a few serial automated PMCA (saPMCA rounds, we also observed the appearance of PK-resistant PrP(Sc in samples containing exclusively unseeded substrate (negative controls, suggesting the possible spontaneous generation of infectious prions during PMCA reactions. As we could not definitively rule out cross-contamination through a posteriori biochemical and biological analyses of de novo generated prions, we decided to replicate the experiments in a different laboratory. Under rigorous prion-free conditions, we did not observe de novo appearance of PrP(Sc in unseeded samples of M109M and I109I vole substrates, even after many consecutive rounds of saPMCA and working in different PMCA settings. Furthermore, when positive and negative samples were processed together, the appearance of spurious PrP(Sc in unseeded negative controls suggested that the most likely explanation for the appearance of de novo PrP(Sc was the occurrence of cross-contamination during saPMCA. Careful analysis of the PMCA process allowed us to identify critical points which are potentially responsible for contamination events. Appropriate technical improvements made it possible to overcome PMCA pitfalls, allowing PrP(Sc to be reliably amplified up to extremely low dilutions of infected brain homogenate without any false positive results even after many consecutive rounds. Our findings underline the potential drawback of ultrasensitive in vitro prion replication and warn on cautious

  14. Enzymatic degradation of PrPSc by a protease secreted from Aeropyrum pernix K1.

    Science.gov (United States)

    Snajder, Marko; Vilfan, Tanja; Cernilec, Maja; Rupreht, Ruth; Popović, Mara; Juntes, Polona; Serbec, Vladka Čurin; Ulrih, Nataša Poklar

    2012-01-01

    An R30 fraction from the growth medium of Aeropyrum pernix was analyzed for the protease that can digest the pathological prion protein isoform (PrP(Sc)) from different species (human, bovine, deer and mouse). Degradation of the PrP(Sc) isoform by the R30 fraction and the purified protease was evaluated using the 6H4 anti-PrP monoclonal antibody. Fragments from the N-terminal and C-terminal of PrP(Sc) were also monitored by Western blotting using the EB8 anti-PrP monoclonal antibody, and by dot blotting using the C7/5 anti-PrP monoclonal antibody, respectively. For detection of smaller peptides from incomplete digestion of PrP(Sc), the EB8 monoclonal antibody was used after precipitation with sodium phosphotungstate. Characterization of the purified active protease from the R30 fraction was achieved, through purification by fast protein liquid chromatography, and identification by tandem mass spectrometry the serine metalloprotease pernisine. SDS-PAGE and zymography show the purified pernisine plus its proregion with a molecular weight of ca. 45 kDa, and the mature purified pernisine as ca. 23 kDa. The purified pernisine was active between 58 °C and 99 °C, and between pH 3.5 and 8.0. The temperature and pH optima of the enzymatic activity of the purified pernisine in the presence of 1 mM CaCl(2) were 105 °C ± 0.5 °C and pH 6.5 ± 0.2, respectively. Our study has identified and characterized pernisine as a thermostable serine metalloprotease that is secreted from A. pernix and that can digest the pathological prion protein PrP(Sc).

  15. Enzymatic degradation of PrPSc by a protease secreted from Aeropyrum pernix K1.

    Directory of Open Access Journals (Sweden)

    Marko Snajder

    Full Text Available BACKGROUND: An R30 fraction from the growth medium of Aeropyrum pernix was analyzed for the protease that can digest the pathological prion protein isoform (PrP(Sc from different species (human, bovine, deer and mouse. METHODOLOGY/PRINCIPAL FINDINGS: Degradation of the PrP(Sc isoform by the R30 fraction and the purified protease was evaluated using the 6H4 anti-PrP monoclonal antibody. Fragments from the N-terminal and C-terminal of PrP(Sc were also monitored by Western blotting using the EB8 anti-PrP monoclonal antibody, and by dot blotting using the C7/5 anti-PrP monoclonal antibody, respectively. For detection of smaller peptides from incomplete digestion of PrP(Sc, the EB8 monoclonal antibody was used after precipitation with sodium phosphotungstate. Characterization of the purified active protease from the R30 fraction was achieved, through purification by fast protein liquid chromatography, and identification by tandem mass spectrometry the serine metalloprotease pernisine. SDS-PAGE and zymography show the purified pernisine plus its proregion with a molecular weight of ca. 45 kDa, and the mature purified pernisine as ca. 23 kDa. The purified pernisine was active between 58 °C and 99 °C, and between pH 3.5 and 8.0. The temperature and pH optima of the enzymatic activity of the purified pernisine in the presence of 1 mM CaCl(2 were 105 °C ± 0.5 °C and pH 6.5 ± 0.2, respectively. CONCLUSIONS/SIGNIFICANCE: Our study has identified and characterized pernisine as a thermostable serine metalloprotease that is secreted from A. pernix and that can digest the pathological prion protein PrP(Sc.

  16. PrPSc formation and clearance as determinants of prion tropism.

    Science.gov (United States)

    Shikiya, Ronald A; Langenfeld, Katie A; Eckland, Thomas E; Trinh, Jonathan; Holec, Sara A M; Mathiason, Candace K; Kincaid, Anthony E; Bartz, Jason C

    2017-03-01

    Prion strains are characterized by strain-specific differences in neuropathology but can also differ in incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) and drowsy (DY) strains of hamster-adapted transmissible mink encephalopathy (TME) differ in tissue tropism and susceptibility to infection by extraneural routes of infection. Notably, DY TME is not detected in the secondary lymphoreticular system (LRS) tissues of infected hosts regardless of the route of inoculation. We found that similar to the lymphotropic strain HY TME, DY TME crosses mucosal epithelia, enters draining lymphatic vessels in underlying laminae propriae, and is transported to LRS tissues. Since DY TME causes disease once it enters the peripheral nervous system, the restriction in DY TME pathogenesis is due to its inability to establish infection in LRS tissues, not a failure of transport. To determine if LRS tissues can support DY TME formation, we performed protein misfolding cyclic amplification using DY PrPSc as the seed and spleen homogenate as the source of PrPC. We found that the spleen environment can support DY PrPSc formation, although at lower rates compared to lymphotropic strains, suggesting that the failure of DY TME to establish infection in the spleen is not due to the absence of a strain-specific conversion cofactor. Finally, we provide evidence that DY PrPSc is more susceptible to degradation when compared to PrPSc from other lymphotrophic strains. We hypothesize that the relative rates of PrPSc formation and clearance can influence prion tropism.

  17. Analyses of N-linked glycans of PrPSc revealed predominantly 2,6-linked sialic acid residues.

    Science.gov (United States)

    Katorcha, Elizaveta; Baskakov, Ilia V

    2017-11-01

    Mammalian prions (PrPSc ) consist of misfolded, conformationally altered, self-replicating states of the sialoglycoprotein called prion protein or PrPC . Recent studies revealed that the sialylation status of PrPSc plays a major role in evading innate immunity and infecting a host. Establishing the type of linkage by which sialic acid residues are attached to galactose is important, as it helps to identify the sialyltransferases responsible for sialylating PrPC and outline strategies for manipulating the sialyation status of PrPSc . Using enzymatic treatment with sialidases and lectin blots, this study demonstrated that in N-linked glycans of PrPSc , the sialic acid residues are predominantly alpha 2,6-linked. High percentages of alpha 2,6-linked sialic acids were observed in PrPSc of three prion strains 22L, RML, and ME7, as well as PrPSc from brain, spleen, or N2a cells cultured in vitro. Moreover, the variation in the percentage of alpha 2,3- versus 2,6-linked sialic acid was found to be relatively minor between brain-, spleen-, or cell-derived PrPSc , suggesting that the type of linkage is independent of tissue type. Based on the current results, we propose that sialyltransferases of St6Gal family, which is responsible for attaching sialic acids via alpha 2,6-linkages to N-linked glycans, controls sialylation of PrPC and PrPSc . © 2017 Federation of European Biochemical Societies.

  18. Recent advances in cell-free PrPSc amplification technique.

    Science.gov (United States)

    Atarashi, Ryuichiro

    2009-01-01

    The development of amplification technology for abnormal forms of prion protein in vitro has had a great impact on the field of prion research. This novel technology has generated new possibilities for understanding the molecular basis of prions and for developing an early diagnostic test for prion diseases. This review provides an overview of recent progress in cell-free PrPSc amplification techniques.

  19. Dynamics and genetics of PrPSc placental accumulation in sheep.

    Science.gov (United States)

    Lacroux, C; Corbière, F; Tabouret, G; Lugan, S; Costes, P; Mathey, J; Delmas, J M; Weisbecker, J L; Foucras, G; Cassard, H; Elsen, J M; Schelcher, F; Andréoletti, O

    2007-03-01

    Placentae from scrapie-affected ewes are an important source of contamination. This study confirmed that scrapie-incubating ewes bearing susceptible genotypes could produce both abnormal prion protein (PrPSc)-positive and -negative placentae, depending only on the PRP genotype of the fetus. The results also provided evidence indicating that scrapie-incubating ARR/VRQ ewes may be unable to accumulate prions in the placenta, whatever the genotype of their progeny. Multinucleated trophoblast cells appeared to play a key role in placental PrPSc accumulation. PrPSc accumulation began in syncytiotrophoblasts before disseminating to uninucleated trophoblasts. As these result from trophoblast/uterine epithelial cell fusion, syncytiotrophoblast cells expressed maternal and fetal PrPC, whilst uninucleated trophoblast cells only expressed fetal PrPC. In ARR/VRQ scrapie-infected ewes, expression of the ARR allele by syncytiotrophoblasts appeared to prevent initiation of PrPSc placental deposition. The absence of prions in affected ARR/VRQ sheep placentae reinforces strongly the interest in ARR selection for scrapie control.

  20. Short-term study of the uptake of PrPSc by the Peyer’s patches in hamsters after oral exposure to scrapie

    DEFF Research Database (Denmark)

    Bergström, Ann-Louise; Jensen, Tim Kåre; Heegaard, Peter M. H.

    2006-01-01

    The disease-associated prion protein (PrPSc) has been detected in the ileal Peyer's patches of lambs as early as one week after oral exposure to scrapie. In hamsters, the earliest reported time of PrPSc detection in the Peyer's patches after oral exposure to scrapie is 69 days post...... of the scrapie agent. PrPSc was demonstrated in the Peyer's patches only a few days after exposure, i.e., much earlier than previously reported. This study Supports the view that the Peyer's patches constitute at least one of the primary entry sites of PrPSc after oral exposure to scrapie....

  1. Qualitative and Quantitative Detection of PrPSc Based on the Controlled Release Property of Magnetic Microspheres Using Surface Plasmon Resonance (SPR

    Directory of Open Access Journals (Sweden)

    Zhichao Lou

    2018-02-01

    Full Text Available Prion protein (PrPSc has drawn widespread attention due to its pathological potential to prion diseases. In this work, we constructed a novel surface plasmon resonance (SPR detection assay involving magnetic microspheres (MMs and its controlled release property, for selective capture, embedding, concentration, and SPR detection of PrPSc with high sensitivity and specificity. Aptamer-modified magnetic particles (AMNPs were used to specifically capture PrPSc. Amphiphilic copolymer was used to embed the labeled PrPSc and form magnetic microspheres to isolate PrPSc from the external environment. Static magnetic and alternating magnetic fields were used to concentrate and control release the embedded PrPSc, respectively. Finally, the released AMNPs-labeled PrPSc was detected by SPR which was equipped with a bare gold sensing film. A good linear relationship was obtained between SPR responses and the logarithm of PrPSc concentrations over a range of 0.01–1000 ng/mL. The detection sensitivity for PrPSc was improved by 10 fold compared with SPR direct detection format. The specificity of the present biosensor was also determined by PrPC and other reagents as controls. This proposed approach could also be used to isolate and detect other highly pathogenic biomolecules with similar structural characteristics by altering the corresponding aptamer in the AMNPs conjugates.

  2. The Strain-Encoded Relationship between PrPSc Replication, Stability and Processing in Neurons is Predictive of the Incubation Period of Disease

    Science.gov (United States)

    Ayers, Jacob I.; Schutt, Charles R.; Shikiya, Ronald A.; Aguzzi, Adriano; Kincaid, Anthony E.; Bartz, Jason C.

    2011-01-01

    Prion strains are characterized by differences in the outcome of disease, most notably incubation period and neuropathological features. While it is established that the disease specific isoform of the prion protein, PrPSc, is an essential component of the infectious agent, the strain-specific relationship between PrPSc properties and the biological features of the resulting disease is not clear. To investigate this relationship, we examined the amplification efficiency and conformational stability of PrPSc from eight hamster-adapted prion strains and compared it to the resulting incubation period of disease and processing of PrPSc in neurons and glia. We found that short incubation period strains were characterized by more efficient PrPSc amplification and higher PrPSc conformational stabilities compared to long incubation period strains. In the CNS, the short incubation period strains were characterized by the accumulation of N-terminally truncated PrPSc in the soma of neurons, astrocytes and microglia in contrast to long incubation period strains where PrPSc did not accumulate to detectable levels in the soma of neurons but was detected in glia similar to short incubation period strains. These results are inconsistent with the hypothesis that a decrease in conformational stability results in a corresponding increase in replication efficiency and suggest that glia mediated neurodegeneration results in longer survival times compared to direct replication of PrPSc in neurons. PMID:21437239

  3. Quantification of surviving cerebellar granule neurones and abnormal prion protein (PrPSc) deposition in sporadic Creutzfeldt-Jakob disease supports a pathogenic role for small PrPSc deposits common to the various molecular subtypes.

    Science.gov (United States)

    Faucheux, B A; Morain, E; Diouron, V; Brandel, J-P; Salomon, D; Sazdovitch, V; Privat, N; Laplanche, J-L; Hauw, J-J; Haïk, S

    2011-08-01

    Neuronal death is a major neuropathological hallmark in prion diseases. The association between the accumulation of the disease-related prion protein (PrP(Sc) ) and neuronal loss varies within the wide spectrum of prion diseases and their experimental models. In this study, we investigated the relationships between neuronal loss and PrP(Sc) deposition in the cerebellum from cases of the six subtypes of sporadic Creutzfeldt-Jakob disease (sCJD; n=100) that can be determined according to the M129V polymorphism of the human prion protein gene (PRNP) and PrP(Sc) molecular types. The numerical density of neurones was estimated with a computer-assisted image analysis system and the accumulation of PrP(Sc) deposits was scored. The scores of PrP(Sc) immunoreactive deposits of the punctate type (synaptic type) were correlated with neurone counts - the higher the score the higher the neuronal loss - in all sCJD subtypes. Large 5- to 50-µm-wide deposits (focal type) were found in sCJD-MV2 and sCJD-VV2 subtypes, and occasionally in a few cases of the other studied groups. By contrast, the highest scores for 5- to 50-µm-wide deposits observed in sCJD-MV2 subtype were not associated with higher neuronal loss. In addition, these scores were inversely correlated with neuronal counts in the sCJD-VV2 subtype. These results support a putative pathogenic role for small PrP(Sc) deposits common to the various sCJD subtypes. Furthermore, the observation of a lower loss of neurones associated with PrP(Sc) type-2 large deposits is consistent with a possible 'protective' role of aggregated deposits in both sCJD-MV2 and sCJD-VV2 subtypes. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

  4. Cancer of unknown primary

    DEFF Research Database (Denmark)

    Dyrvig, Anne-Kirstine; Yderstræde, Knud Bonnet; Gerke, Oke

    2017-01-01

    Cancer of unknown primary (CUP) ranges within top 10 cancers in both incidence and mortality. As primary identification is crucial to choosing treatment, guidelines on CUP emphasize the diagnostic strategy. Whether guidelines are complied with, or if they are indeed helpful, is however unclear. We...... to procedures and patient survival. The cohort was investigated in terms of validity of diagnosis through cross-referencing with the Cancer Registry (CR), which served as gold standard for cancer diagnoses and patients' cancer histories.The NPR cohort consisted of 542 patients (275 males, 264 females) of whom...... after 4 years.The validity of a CUP diagnosis in NPR was low when using data from CR as reference. More than half the suspected CUP patients had a previous cancer diagnosis with CUP being the most frequent. Patients were diagnosed in compliance with guidelines indicating high external validity, but less...

  5. [Badminton--unknown sport].

    Science.gov (United States)

    Zekan-Petrinović, Lidija

    2007-01-01

    For a long time, badminton was considered to be only a slow and light game for children, a game that is played outdoors and is structurally undemanding.Today, it is not an unknown and unrecognised sport, especially after it was included into the Olympics Games in 1992. Badminton is one of the oldest sports in the world. It is suitable for all ages (for children and elderly equally), women and men and even handicapped persons. Beginners can start playing badminton matches early because the basics are learned quickly. As a recreational activity, badminton is very popular in Zagreb. In the last 10 years, a number of halls specialized for badminton or offering badminton as one of available sports activities have been opened in Zagreb. At present, there are over 70 professional playgrounds for training of top contestants but also for the citizens who can play recreational badminton.

  6. Designing towards the unknown

    DEFF Research Database (Denmark)

    Wilde, Danielle; Underwood, Jenny

    2018-01-01

    interdisciplinary teams with time and resource constraints need to deliver concrete outcomes on schedule. The Poetic Kinaesthetic Interface project (PKI) engages with this problematic directly. In PKI we use unfolding processes—informed by participatory, speculative and critical design—in emergent actions...... the research potential to far-ranging possibilities. In this article we unpack the motivations driving the PKI project. We present our mixed-methodology, which entangles textile crafts, design interactions and materiality to shape an embodied enquiry. Our research outcomes are procedural and methodological....... PKI brings together diverse human, non-human, known and unknown actors to discover where the emergent assemblages might lead. Our approach is re-invigorating—as it demands re-envisioning of—the design process....

  7. Physics: unknown radiation

    CERN Document Server

    Grenier, E; Liksonov, V I; Tsinoiev, V G

    2002-01-01

    This article reports experiments concerning the study of the electrical explosion of a titanium foil in water. During the electrical discharge a strong luminescence appears, the analysis of spectra shows the presence of new chemical elements and this presence is confirmed by the mass-spectrometry measurements performed on the precipitates found after the discharge. This experiment has been repeated about 200 times and the results are consistent an show an average titanium transmutation rate of 4%. Neither gamma nor neutron radiation have been detected but an unknown radiation, sensitive to magnetic fields, has been detected through tracks left on RF-ZMP fluo-graphical films covered with a 10 mu m-thick emulsion layer. The assumption of a radiation made up of magnetic monopoles is supported by the author. (A.C.)

  8. Fish remains and humankind

    Directory of Open Access Journals (Sweden)

    Andrew K G Jones

    1997-08-01

    Full Text Available The four papers in this issue represent a trawl of the reports presented to the Fourth meeting of the International Council for Archaeozoology (ICAZ Fish Remains Working Group, which met at the University of York in 1987. The conference discussed material from many parts of the world - from Australasia to the north-west coast of America - and many eras, ranging in date from the early Pleistocene to the 1980s. It demonstrated both the variety of work being carried out and the growing interest in ancient fish remains. Internet Archaeology plans to publish other batches of papers from this conference. These reports will demonstrate the effort being made to distinguish between assemblages of fish remains which have been deposited by people and those which occur in ancient deposits as a result of the action of other agents. To investigate this area, experiments with modern material and observations of naturally occurring fish bone assemblages are supplemented with detailed analysis of ancient and modern fish remains. The papers published here illustrate the breadth of research into osteology, biogeography, documentary research, and the practicalities of recovering fish remains. Read, digest and enjoy them! Using the Internet for publishing research papers is not only ecologically sound (saving paper, etc. it disseminates scholarship to anyone anywhere on the planet with access to what is gradually becoming necessary technology in the late 20th century. Hopefully, future groups of papers will include video and audio material recorded at the conference, and so enable those who could not attend to gain further insights into the meeting and the scholarship underpinning this area of research.

  9. In vitro amplification of PrPSc derived from the brain and blood of sheep infected with scrapie.

    Science.gov (United States)

    Thorne, Leigh; Terry, Linda A

    2008-12-01

    Scrapie is a fatal, naturally transmissible, neurodegenerative prion disease that affects sheep and goats and is characterized by the accumulation of a misfolded protein, PrPSc, converted from host-encoded PrPc, in the central nervous system of affected animals. Highly efficient in vitro conversion of host PrPc to PrPSc has been achieved in models of scrapie and in natural prion diseases by protein misfolding cyclic amplification (PMCA). Here, we demonstrate amplification, by serial PMCA, of PrPSc from individual sources of scrapie-infected sheep. Efficiency of amplification was affected by the pairing of the source of PrPSc with the control brain substrate of different genotypes of PrP. In line with previous studies, efficiency of amplification was greatly enhanced with the addition of a synthetic polyanion, polyadenylic acid (PolyA), facilitating rapid detection of low levels of PrPSc from body fluids such as blood. To this end PrPSc was amplified, in a 3 day PMCA assay, from blood leukocyte preparations from VRQ/VRQ scrapie-affected sheep at clinical end point. While PolyA-assisted PMCA resulted in spontaneous conversion of PrPc, we were able to distinguish blood samples from unaffected and affected sheep under controlled conditions. This study demonstrates that highly efficient amplification of PrPSc can be achieved for ovine scrapie from both brain and blood from naturally infected sheep and shows potential applications for improvements in current diagnostics and pre-mortem testing.

  10. PrPSc accumulation in fetal cotyledons of scrapie-resistant lambs is influenced by fetus location in the uterus.

    Science.gov (United States)

    Alverson, Janet; O'Rourke, Katherine I; Baszler, Timothy V

    2006-04-01

    Placentae from scrapie-infected ewes have been shown to accumulate PrPSc when the genotype of the fetus is of a susceptible genotype (VRQ/VRQ, ARQ/VRQ or ARQ/ARQ). Cotyledons from fetuses of genotypes ARR/ARR, ARQ/ARR and ARQ/VRR have previously been shown to be resistant to PrPSc accumulation. By using ewes from a naturally infected scrapie flock, cotyledons from fetuses of multiple births of different genotypes were examined. PrPSc was detected in fetal cotyledons of genotype ARQ/ARQ, but not in cotyledons from their dizygotic twin of genotype ARQ/ARR. This confirms earlier reports of single fetuses of these genotypes, but is the first description of such a finding in twin fetuses, one of each genotype. It is also demonstrated that cotyledons from sibling fetuses of genotypes ARQ/VRQ and ARQ/ARQ have different patterns of PrPSc accumulation depending on whether the dam is of genotype ARQ/ARQ or ARQ/VRQ. Lastly, it is shown that cotyledons from fetuses with resistant genotypes are weakly positive for PrPSc when they have shared the same pregnant uterine horn with a fetus of a susceptible genotype with cotyledons positive for the detection of PrPSc. Additionally, a PCR product for the Sry gene, a product specific to males, was found in cotyledons from female fetuses that had shared a uterine horn with a male fetus. This indicates that some sharing of fetal blood occurs between placentomes and fetuses residing in the same uterine horn, which can result in PrPSc accumulation in cotyledons with resistant genotypes.

  11. Influence of Mabs on PrP(Sc formation using in vitro and cell-free systems.

    Directory of Open Access Journals (Sweden)

    Binggong Chang

    Full Text Available PrP(Sc is believed to serve as a template for the conversion of PrP(C to the abnormal isoform. This process requires contact between the two proteins and implies that there may be critical contact sites that are important for conversion. We hypothesized that antibodies binding to either PrP(cor PrP(Sc would hinder or prevent the formation of the PrP(C-PrP(Sc complex and thus slow down or prevent the conversion process. Two systems were used to analyze the effect of different antibodies on PrP(Sc formation: (i neuroblastoma cells persistently infected with the 22L mouse-adapted scrapie stain, and (ii protein misfolding cyclic amplification (PMCA, which uses PrP(Sc as a template or seed, and a series of incubations and sonications, to convert PrP(C to PrP(Sc. The two systems yielded similar results, in most cases, and demonstrate that PrP-specific monoclonal antibodies (Mabs vary in their ability to inhibit the PrP(C-PrP(Sc conversion process. Based on the numerous and varied Mabs analyzed, the inhibitory effect does not appear to be epitope specific, related to PrP(C conformation, or to cell membrane localization, but is influenced by the targeted PrP region (amino vs carboxy.

  12. Immunohistochemistry for PrPSc in natural scrapie reveals patterns which are associated with the PrP genotype.

    Science.gov (United States)

    Spiropoulos, J; Casalone, C; Caramelli, M; Simmons, M M

    2007-08-01

    Immunohistochemistry for PrPSc is used widely in scrapie diagnosis. In natural scrapie cases the use of immunohistochemistry (IHC) has revealed the existence of up to 12 different morphological types of immunostained deposits. The significance of this pattern variability in relation to genotype has not been studied extensively in natural disease. In this study we recorded in detail PrPSc patterns at the obex level of the medulla oblongata from 163 animals derived from 55 flocks which presented through passive surveillance in the UK and Italy. A strong association was seen between PrPSc patterns and PrP genotype, particularly in relation to codon 136. In a blind assessment of this association we were able to predict, with over 80% accuracy, the genotype of 151 scrapie cases which were presented through passive surveillance from 13 farms. The genotype of these cases was ARQ/ARQ or VRQ/VRQ. The association of PrPsc patterns with genotype was generally stronger in those farms where all the affected animals belonged to a single genotype compared with farms where both genotypes were identified, with the exception of one farm in which the genotype of all affected sheep was ARQ/ARQ and the PrPSc patterns were of the VRQ/VRQ type. Our observations support the hypothesis that the observed association between specific IHC patterns and genotypes may in fact be strain driven but in natural disease individual scrapie strains may demonstrate a genotypic tropism.

  13. Sporadic fatal insomnia with spongiform degeneration in the thalamus and widespread PrPSc deposits in the brain.

    Science.gov (United States)

    Piao, Yue-Shan; Kakita, Akiyoshi; Watanabe, Hiroyuki; Kitamoto, Tetsuyuki; Takahashi, Hitoshi

    2005-06-01

    We report a case of human prion disease of 29 months duration in a 74-year-old Japanese man. The disease started with progressive sleeplessness and dementia. MRI showed gradually progressive cerebral atrophy. Neuronal loss, spongiform change and gliosis were evident in the thalamus and cerebral cortex, as well as in the striatum and amygdaloid nucleus. In the cerebellar cortex, mild-to-moderate depletion of Pukinje cells and spongiform change were observed. Mild neuronal loss in the inferior olivary nucleus was also seen. Immunohistochemistry revealed widespread perivacuolar deposits of abnormal prion protein (PrPsc) in the cerebral cortex, thalamus, basal ganglia, and brainstem, and minimal plaque-like deposits of PrPSc in the cerebellar cortex. In the cerebellar plaque-like deposits, the presence of amyloid fibrils was confirmed ultrastructurally. The entire pathology appeared to lie halfway between those of CJD and fatal insomnia, and further demonstrated the relationship between spongiform degeneration and PrPSc deposits, especially in the diseased thalamus. By immunoblotting, the thalamus was shown to contain the lowest amount of PrPSc among the brain regions examined. The PrPSc of type 2, in which the ratio of the three glycoforms was compatible with that of sporadic fatal insomnia (MM2-thalamic variant) reported previously, was also demonstrated. Analysis of the prion protein gene (PRNP) showed no mutation, and homozygosity for methionine at codon 129. In conclusion, we considered that this patient had been suffering from sporadic, pathologically atypical fatal insomnia.

  14. A refined method for molecular typing reveals that co-occurrence of PrPSc types in Creutzfeldt-Jakob disease is not the rule

    NARCIS (Netherlands)

    Notari, S.; Capellari, S.; Langeveld, J.P.M.; Giese, A.; Strammiello, R.; Gambetti, P.; Kretzschmar, H.A.; Parchi, P.

    2007-01-01

    Molecular typing in Creutzfeldt¿Jakob disease (CJD) relies on the detection of distinct protease-resistant prion protein (PrPSc) core fragments, which differ in molecular mass or glycoform ratio. However, the definition and correct identification of CJD cases with a co-occurrence of PrPSc types

  15. Detection of PrPSc in Formalin Fixed Paraffin Embedded Tissue by Western Blot Differentiates Classical Scrapie, Nor98 Scrapie, and BSE

    Science.gov (United States)

    Transmissible spongiform encephalopathies including bovine spongiform encephalopathy and scrapie are fatal neurodegenerative disorders associated with the presence of an infectious abnormal isoform of normal mammalian proteins called prions (PrP**Sc). Identification of PrP**Sc in the CNS is typicall...

  16. Pachydermodactyly: An Unknown Entity.

    Science.gov (United States)

    Tolis, Konstantinos; Stavropoulos, Nikolaos; Mavrogenis, Andreas; Spyridonos, Sarantis

    2016-08-01

    Pachydermodactyly is a rare benign disease that usually affects the dorsal skin and subcutaneous tissue of the proximal interphalangeal joints of the index, middle, ring, and little fingers; the thumb is usually spared. Hyperkeratosis on the dorsal side of the affected areas is common. We present a case of a 19-year-old man who was diagnosed with pachydermodactyly after evaluation of a painless, progressive swelling and hyperkeratosis at the proximal interphalangeal and distal interphalangeal joints of all fingers, bilaterally, for 6 years before presentation. Conservative treatment was prescribed and the patient remains asymptomatic. Given the benign and nonprogressive course of the disease, symptomatic treatment alone is all that is usually required. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  17. Detection and localisation of PrP(Sc in the liver of sheep infected with scrapie and bovine spongiform encephalopathy.

    Directory of Open Access Journals (Sweden)

    Sally J Everest

    Full Text Available Prions are largely contained within the nervous and lymphoid tissue of transmissible spongiform encephalopathy (TSE infected animals. However, following advances in diagnostic sensitivity, PrP(Sc, a marker for prion disease, can now be located in a wide range of viscera and body fluids including muscle, saliva, blood, urine and milk, raising concerns that exposure to these materials could contribute to the spread of disease in humans and animals. Previously we demonstrated low levels of infectivity in the liver of sheep experimentally challenged with bovine spongiform encephalopathy. In this study we show that PrP(Sc accumulated in the liver of 89% of sheep naturally infected with scrapie and 100% of sheep challenged with BSE, at both clinical and preclinical stages of the disease. PrP(Sc was demonstrated in the absence of obvious inflammatory foci and was restricted to isolated resident cells, most likely Kupffer cells.

  18. Peptide aptamers expressed in the secretory pathway interfere with cellular PrPSc formation.

    Science.gov (United States)

    Gilch, Sabine; Kehler, Claudia; Schätzl, Hermann M

    2007-08-10

    Prion diseases are rare and obligatory fatal neurodegenerative disorders caused by the accumulation of a misfolded isoform (PrPSc) of the host-encoded prion protein (PrPc). Prophylactic and therapeutic regimens against prion diseases are very limited. To extend such strategies we selected peptide aptamers binding to PrP from a combinatorial peptide library presented on the Escherichia coli thioredoxin A (trxA) protein as a scaffold. In a yeast two-hybrid screen employing full-length murine PrP (aa 23-231) as a bait we identified three peptide aptamers that reproducibly bind to PrP. Treatment of prion-infected cells with recombinantly expressed aptamers added to the culture medium abolished PrPSc conversion with an IC50 between 350 and 700 nM. For expression in eukaryotic cells, peptide aptamers were fused to an N-terminal signal peptide for entry of the secretory pathway. The C terminus was modified by a glycosyl-phosphatidyl-inositol-(GPI) anchoring signal, a KDEL retention motif and the transmembrane and cytosolic domain of LAMP-I, respectively. These peptide aptamers retained their binding properties to PrPc and, depending on peptide sequence and C-terminal modification, interfered with endogenous PrPSc conversion upon expression in prion-infected cells. Notably, infection of cell cultures could be prevented by expression of KDEL peptide aptamers. For the first time, we show that trxA-based peptide aptamers can be targeted to the secretory pathway, thereby not losing the affinity for their target protein. Beside their inhibitory effect on prion conversion, these molecules could be used as fundament for rational drug design.

  19. Early Generation of New PrPSc on Blood Vessels after Brain Microinjection of Scrapie in Mice.

    Science.gov (United States)

    Chesebro, Bruce; Striebel, James; Rangel, Alejandra; Phillips, Katie; Hughson, Andrew; Caughey, Byron; Race, Brent

    2015-09-22

    Aggregation of misfolded host proteins in the central nervous system is believed to be important in the pathogenic process in several neurodegenerative diseases of humans, including prion diseases, Alzheimer's disease, and Parkinson's disease. In these diseases, protein misfolding and aggregation appear to expand through a process of seeded polymerization. Prion diseases occur in both humans and animals and are experimentally transmissible orally or by injection, thus providing a controllable model of other neurodegenerative protein misfolding diseases. In rodents and ruminants, prion disease has a slow course, lasting months to years. Although prion infectivity has been detected in brain tissue at 3 to 4 weeks postinfection (p.i.), the details of early prion replication in the brain are not well understood. Here we studied the localization and quantitation of PrPSc generation in vivo starting at 30 min postmicroinjection of scrapie into the brain. In C57BL mice at 3 days p.i., generation of new PrPSc was detected by immunohistochemistry and immunoblot assays, and at 7 days p.i., new generation was confirmed by real-time quaking-induced conversion assay. The main site of new PrPSc generation was near the outer basement membrane of small and medium blood vessels. The finding and localization of replication at this site so early after injection have not been reported previously. This predominantly perivascular location suggested that structural components of the blood vessel basement membrane or perivascular astrocytes might act as cofactors in the initial generation of PrPSc. The location of PrPSc replication at the basement membrane also implies a role for the brain interstitial fluid drainage in the early infection process. Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and prion diseases, of humans are characterized by misfolding and aggregation of certain proteins, resulting in the destruction of brain tissue. In these diseases

  20. Detection of Bovine Spongiform Encephalopathy-Specific PrPSc by Treatment with Heat and Guanidine Thiocyanate

    OpenAIRE

    Meyer, Rudolf K; Oesch, Bruno; Fatzer, Rosmarie; Zurbriggen, Andreas; Vandevelde, Marc

    1999-01-01

    The conversion of a ubiquitous cellular protein (PrPC), an isoform of the prion protein (PrP), to the pathology-associated isoform PrPSc is one of the hallmarks of transmissible spongiform encephalopathies such as bovine spongiform encephalopathy (BSE). Accumulation of PrPSc has been used to diagnose BSE. Here we describe a quantitative enzyme-linked immunosorbent assay (ELISA) that involves antibodies against epitopes within the protease-resistant core of the PrP molecule to measure the amou...

  1. Ovine wet carcass syndrome of unknown aetiology

    African Journals Online (AJOL)

    plicating cachexia, inflammatory processes, lymphoedema, cardiac failure, glycogen storage or myxoedema in the pathogenesis of the syndrome. In conclusion, despite intensive investigation the aeti- ology of the wet carcase syndrome remains unknown. At present the possibility of a histamine reaction due to insect bites is ...

  2. Atypical PrPsc distribution in goats naturally affected with scrapie.

    Science.gov (United States)

    Sofianidis, G; Psychas, V; Billinis, C; Spyrou, V; Argyroudis, S; Vlemmas, I

    2008-01-01

    The brain and spinal cord of 48 goats from two Greek herds in which scrapie had been reported were examined. All animals were symptomless at the time of euthanasia. Notably, no lesions were observed either at the level of the obex or at other regions of the brain and spinal cord. Immunohistochemical examination revealed PrPsc labelling of the linear and fine punctuate types, mainly in the cerebral cortices, of 36 goats. Twenty-seven of them were negative by ELISA (designed to detect proteinase-resistant PrP) at the level of the obex but positive in a pooled brain sample, and the majority carried PrP genotypes associated with scrapie susceptibility. Surprisingly, in 16 of the 27 animals, PrPsc deposits were detected only in the rostral parts of the brain. In addition, nine animals which were ELISA-positive at the level of the obex exhibited positive immunoreactivity, but not in the dorsal vagal nucleus. The findings indicate that this unusual scrapie type may have been underdiagnosed previously and may be of importance in scrapie surveillance programmes.

  3. Temporal resolution of PrPSc transport, PrPSc accumulation, activation of glia and neuronal death in retinas from C57Bl/6 mice inoculated with RML scrapie: Relevance to biomarkers of prion disease progression

    Science.gov (United States)

    Currently, there is a lack of pathologic landmarks to objectively evaluate the progression of prion disease in vivo. The goal of this work was to determine the temporal relationship between transport of misfolded prion protein to the retina from the brain, accumulation of PrPSc in the retina, the re...

  4. A naturally occurring C-terminal fragment of the prion protein (PrP) delays disease and acts as a dominant-negative inhibitor of PrPSc formation.

    Science.gov (United States)

    Westergard, Laura; Turnbaugh, Jessie A; Harris, David A

    2011-12-23

    The cellular prion protein (PrPC) undergoes constitutive proteolytic cleavage between residues 111/112 to yield a soluble N-terminal fragment (N1) and a membrane-anchored C-terminal fragment (C1). The C1 fragment represents the major proteolytic fragment of PrPC in brain and several cell types. To explore the role of C1 in prion disease, we generated Tg(C1) transgenic mice expressing this fragment (PrP(Δ23-111)) in the presence and absence of endogenous PrP. In contrast to several other N-terminally deleted forms of PrP, the C1 fragment does not cause a spontaneous neurological disease in the absence of endogenous PrP. Tg(C1) mice inoculated with scrapie prions remain healthy and do not accumulate protease-resistant PrP, demonstrating that C1 is not a substrate for conversion to PrPSc (the disease-associated isoform). Interestingly, Tg(C1) mice co-expressing C1 along with wild-type PrP (either endogenous or encoded by a second transgene) become ill after scrapie inoculation, but with a dramatically delayed time course compared with mice lacking C1. In addition, accumulation of PrPSc was markedly slowed in these animals. Similar effects were produced by a shorter C-terminal fragment of PrP(Δ23-134). These results demonstrate that C1 acts as dominant-negative inhibitor of PrPSc formation and accumulation of neurotoxic forms of PrP. Thus, C1, a naturally occurring fragment of PrPC, might play a modulatory role during the course of prion diseases. In addition, enhancing production of C1, or exogenously administering this fragment, represents a potential therapeutic strategy for the treatment of prion diseases.

  5. Imaging an unknown object in an unknown medium

    NARCIS (Netherlands)

    Snieder, R; Wapenaar, C.P.A.

    2016-01-01

    Imaging an unknown object in a medium that is known, such as a medium with constant velocity, is not difficult because one knows exactly where the waves are when they interact with the object. It is much more challenging to image an object in an unknown medium, because in that case one may know the

  6. Characterization of intracellular dynamics of inoculated PrP-res and newly generated PrPSc during early stage prion infection in Neuro2a cells

    Science.gov (United States)

    Yamasaki, Takeshi; Baron, Gerald S; Suzuki, Akio; Hasebe, Rie; Horiuchi, Motohiro

    2014-01-01

    Summary To clarify the cellular mechanisms for the establishment of prion infection, we analyzed the intracellular dynamics of inoculated and newly generated abnormal isoform of prion protein (PrPSc) in Neuro2a cells. Within 24 h after inoculation, the newly generated PrPSc was evident at the plasma membrane, in early endosomes, and in late endosomes, but this PrPSc was barely evident in lysosomes; in contrast, the majority of the inoculated PrPSc was evident in late endosomes and lysosomes. However, during the subsequent 48 h, the newly generated PrPSc increased remarkably in early endosomes and recycling endosomes. Overexpression of wild-type and mutant Rab proteins showed that membrane trafficking along not only the endocytic-recycling pathway but also the endo-lysosomal pathway is involved in de novo PrPSc generation. These results suggest that the trafficking of exogenously introduced PrPSc from the endo-lysosomal pathway to the endocytic-recycling pathway is important for the establishment of prion infection. PMID:24503096

  7. New insights into early sequential PrPsc accumulation in scrapie infected mouse brain evidenced by the use of streptomycin sulfate.

    Science.gov (United States)

    Bencsik, Anna A; Leclere, Edwige; Perron, Hervé; Moussa, Aly

    2008-05-01

    To investigate the amplifying potentialities of streptomycin sulfate in the immunohistochemical (IHC) detection of the abnormal prion protein (PrPsc), we used a sequential brain sampling from C506M3 scrapie strain inoculated C57Bl/6 mice. The weekly removed brains, from 7 to 63 days post intra-cranial inoculation were analysed using PrPsc IHC. The introduction of streptomycin sulfate, a technique developed for accurate cellular and regional mapping of PrPsc deposition in several animal TSEs, revealed a substantial amplifying effect and a clear specific PrPsc detection as early as 28 days post inoculation. The location of the first detected PrPsc deposits suggests a possible involvement of the cerebrospinal fluid in the early dissemination of the infectious agent. The meaning of these newly accessible PrPsc deposits is discussed in relation to a possible nascent form of PrPsc molecules detected in situ for the first time. Altogether, these findings argue that this method can be highly useful to study the early stages after infection with prion agents.

  8. It Remains Unknown Whether Filaggrin Gene Mutations Evolved to Increase Cutaneous Synthesis of Vitamin D

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Elias, Peter M

    2017-01-01

    encountered in Northern Europeans. Importantly, FLG mutation carriers have 10% increased serum vitamin D concentrations compared to controls. Based on these observations, we have proposed that this latitude-dependent gradient of FLG mutations across Europe, Asia and Africa could have provided an evolutionary......About 8-10% of normal Northern Europeans are heterozygous carriers of common FLG mutations, while only 1-4% of southern Europeans display these mutations, and only very rarely are mutations detected in African populations. Although mutations are found in Asians, they are different from those...

  9. Co-existence of Distinct Prion Types Enables Conformational Evolution of Human PrPSc by Competitive Selection

    NARCIS (Netherlands)

    Haldiman, T.; Kim, C.; Cohen, Y.; Chen, W.; Blevins, J.; Qing, L.; Cohen, M.L.; Langeveld, J.P.M.; Telling, G.C.; Kong, Q.; Safar, J.G.

    2013-01-01

    The unique phenotypic characteristics of mammalian prions are thought to be encoded in the conformation of pathogenic prion proteins (PrPSc). The molecular mechanism responsible for the adaptation, mutation, and evolution of prions observed in cloned cells and upon crossing the species barrier

  10. Transmission of the agent of sheep scrapie to deer results in PrPSc with two distinct molecular profiles

    Science.gov (United States)

    The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (I...

  11. High titers of transmissible spongiform encephalopathy infectivity associated with extremely low levels of PrPSc in vivo.

    Science.gov (United States)

    Barron, Rona M; Campbell, Susan L; King, Declan; Bellon, Anne; Chapman, Karen E; Williamson, R Anthony; Manson, Jean C

    2007-12-07

    Diagnosis of transmissible spongiform encephalopathy (TSE) disease in humans and ruminants relies on the detection in post-mortem brain tissue of the protease-resistant form of the host glycoprotein PrP. The presence of this abnormal isoform (PrP(Sc)) in tissues is taken as indicative of the presence of TSE infectivity. Here we demonstrate conclusively that high titers of TSE infectivity can be present in brain tissue of animals that show clinical and vacuolar signs of TSE disease but contain low or undetectable levels of PrP(Sc). This work questions the correlation between PrP(Sc) level and the titer of infectivity and shows that tissues containing little or no proteinase K-resistant PrP can be infectious and harbor high titers of TSE infectivity. Reliance on protease-resistant PrP(Sc) as a sole measure of infectivity may therefore in some instances significantly underestimate biological properties of diagnostic samples, thereby undermining efforts to contain and eradicate TSEs.

  12. Relationships between PrPSc stability and incubation time for United States scrapie strains in a natural host system

    Science.gov (United States)

    Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrP**C) into a beta-rich conformer (PrP**Sc) that accumulates into higher-order structures in the brain and other ti...

  13. The region approximately between amino acids 81 and 137 of proteinase K-resistant PrPSc is critical for the infectivity of the Chandler prion strain.

    Science.gov (United States)

    Shindoh, Ryo; Kim, Chan-Lan; Song, Chang-Hyun; Hasebe, Rie; Horiuchi, Motohiro

    2009-04-01

    Although the major component of the prion is believed to be the oligomer of PrP(Sc), little information is available concerning regions on the PrP(Sc) molecule that affect prion infectivity. During the analysis of PrP(Sc) molecules from various prion strains, we found that PrP(Sc) of the Chandler strain showed a unique property in the conformational-stability assay, and this property appeared to be useful for studying the relationship between regions of the PrP(Sc) molecule and prion infectivity. Thus, we analyzed PrP(Sc) of the Chandler strain in detail and analyzed the infectivities of the N-terminally denatured and truncated forms of proteinase K-resistant PrP. The N-terminal region of PrP(Sc) of the Chandler strain showed region-dependent resistance to guanidine hydrochloride (GdnHCl) treatment. The region approximately between amino acids (aa) 81 and 137 began to be denatured by treatment with 1.5 M GdnHCl. Within this stretch, the region comprising approximately aa 81 to 90 was denatured almost completely by 2 M GdnHCl. Furthermore, the region approximately between aa 90 and 137 was denatured completely by 3 M GdnHCl. However, the C-terminal region thereafter was extremely resistant to the GdnHCl treatment. This property was not observed in PrP(Sc) molecules of other prion strains. Denaturation of the region between aa 81 and 137 by 3 M GdnHCl significantly prolonged the incubation periods in mice compared to that for the untreated control. More strikingly, the denaturation and removal of this region nearly abolished the infectivity. This finding suggests that the conformation of the region between aa 81 and 137 of the Chandler strain PrP(Sc) molecule is directly associated with prion infectivity.

  14. Provenance of unknown plutonium material.

    Science.gov (United States)

    Nicolaou, G

    2008-10-01

    The determination of the provenance of 'unknown' plutonium material is demonstrated through a simulation study based on an isotopic fingerprinting approach. Plutonium of known provenance was considered as the 'unknown' nuclear material in order to evaluate the potential of the approach and verify its predictive capabilities. Factor analysis was used to compare the Pu isotopic composition of the 'unknown' material with Pu isotopic compositions simulating well known spent fuels from a range of commercial nuclear power stations. The provenance of the 'unknown material' is assigned to the commercial fuel with which exhibits the highest degree of similarity with respect to the Pu composition. The approach appears promising since it accurately predicted the provenance of the one 'unknown' sample considered; nevertheless, the approach is still at the development stage. Important challenging issues related to the simulation uncertainties and its testing on real laboratory samples have to be explored prior to evaluating the potential of the approach.

  15. Research advances in liver failure of unknown etiology

    Directory of Open Access Journals (Sweden)

    ZHU Bing

    2015-09-01

    Full Text Available A high proportion of the causes of liver failure remain unknown. This paper reviews the progress in the epidemiology, etiology, treatment, and prognosis of liver failure of unknown etiology. The possible causes of liver failure of unknown etiology may include occult hepatitis B virus infection, herpesvirus infection, transfusion-transmitted virus infection, hepatitis G virus infection, human parvovirus Bl9 infection, autoimmune and hepatitis. Aciclovir can be considered in the empirical treatment for patients with liver failure of unknown etiology. The mortality in patients with liver failure of unknown etiology is high. The research on the etiology and treatments should be strengthened.

  16. SIGNAL DETECTION WITH UNKNOWN PARAMETERS

    Directory of Open Access Journals (Sweden)

    Y. A. Sidorkina

    2015-01-01

    Full Text Available The likelihood ratio of the pulse signal with unknown time position while detecting and detecting the signal with unknown frequency, are considered. Is shown that an FFT algorithm should be performed while detecting the signal with unknown frequency, the maximum value of all spectral samples should be found and compared to the detection threshold. Upon detection of a pulse signal with unknown time position a fast convolution algorithm should be performed, the maximum value of all the spectral inverse FFT samples should be found and compared to the detection threshold. The effectiveness of this algorithm is determined by the sampling distribution of the maximum values of random variables distributed according to Rayleigh.

  17. Characterization of prion protein (PrP)-derived peptides that discriminate full-length PrPSc from PrPC.

    Science.gov (United States)

    Lau, Anthony L; Yam, Alice Y; Michelitsch, Melissa M D; Wang, Xuemei; Gao, Carol; Goodson, Robert J; Shimizu, Robert; Timoteo, Gulliver; Hall, John; Medina-Selby, Angelica; Coit, Doris; McCoin, Colin; Phelps, Bruce; Wu, Ping; Hu, Celine; Chien, David; Peretz, David

    2007-07-10

    On our initial discovery that prion protein (PrP)-derived peptides were capable of capturing the pathogenic prion protein (PrP(Sc)), we have been interested in how these peptides interact with PrP(Sc). After screening peptides from the entire human PrP sequence, we found two peptides (PrP(19-30) and PrP(100-111)) capable of binding full-length PrP(Sc) in plasma, a medium containing a complex mixture of other proteins including a vast excess of the normal prion protein (PrP(C)). The limit of detection for captured PrP(Sc) was calculated to be 8 amol from a approximately 10(5)-fold dilution of 10% (wt/vol) human variant Creutzfeldt-Jakob disease brain homogenate, with >3,800-fold binding specificity to PrP(Sc) over PrP(C). Through extensive analyses, we show that positively charged amino acids play an important, but not exclusive, role in the interaction between the peptides and PrP(Sc). Neither hydrophobic nor polar interactions appear to correlate with binding activity. The peptide-PrP(Sc) interaction was not sequence-specific, but amino acid composition affected binding. Binding occurs through a conformational domain that is only present in PrP(Sc), is species-independent, and is not affected by proteinase K digestion. These and other findings suggest a mechanism by which cationic domains of PrP(C) may play a role in the recruitment of PrP(C) to PrP(Sc).

  18. Enrichment of PrPSc in formalin-fixed, paraffin-embedded tissues prior to analysis by Western blot.

    Science.gov (United States)

    Nicholson, Eric M

    2011-07-01

    Diagnosis of prion disease is primarily through immunodetection of the infectious agent. Typically, 2 distinct procedures are recommended for a definitive diagnosis, with immunohistochemistry and Western blot providing the most information as to the specific isolate in question. In the past, these approaches required formalin-fixed, paraffin-embedded tissue and fresh or frozen tissue, respectively; however, methods have been developed that allow for use of fixed tissue for Western blot. The present study describes a method of enriching PrP(Sc) in formalin-fixed, paraffin-embedded tissues prior to Western blot analysis for the detection of PrP(Sc). With this modified procedure, 5 times the previously reported sample size may be used for analysis, greatly enhancing the sensitivity of this procedure.

  19. Anti-prion drug mPPIg5 inhibits PrP(C conversion to PrP(Sc.

    Directory of Open Access Journals (Sweden)

    James M McCarthy

    Full Text Available Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE in cattle and Creutzfeldt-Jakob disease (CJD in humans. The 'protein only hypothesis' advocates that PrP(Sc, an abnormal isoform of the cellular protein PrP(C, is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrP(Sc in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrP(C to PrP(Sc conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future.

  20. Anti-Prion Drug mPPIg5 Inhibits PrPC Conversion to PrPSc

    Science.gov (United States)

    McCarthy, James M.; Franke, Markus; Resenberger, Ulrike K.; Waldron, Sibeal; Simpson, Jeremy C.; Tatzelt, Jörg; Appelhans, Dietmar; Rogers, Mark S.

    2013-01-01

    Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The ‘protein only hypothesis’ advocates that PrPSc, an abnormal isoform of the cellular protein PrPC, is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrPSc in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrPC to PrPSc conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future. PMID:23383136

  1. Monoclonal and polyclonal antibodies for ante- and post-mortem detection of PrPSc in sheep

    Directory of Open Access Journals (Sweden)

    Michele Dietrich Moura Costa

    2015-04-01

    Full Text Available Scrapie is a disease that affects sheep and goats and is characterized by the accumulation of an abnormal isoform (PrPSc of the cellular prion protein, PrPC, in the central nervous system (CNS and in lymphoid tissues. Detection of PrPSc in these tissues can be attempted by a variety of techniques, including immunohistochemistry (IHC and western blotting (WB, for which a wide range of monoclonal and polyclonal antibodies are commercially available. The objective of this study was to test and compare the efficacy of monoclonal antibodiesF89/160.1.5, F99/97.6.1, and P4 and polyclonal antibodies M52 and R486 in the detection of PrPSc in lymphoid and CNS tissue samples by using IHC. Positive and negative control samples of sheep brain and tonsils were provided by the Animal Health and Veterinary Laboratories Agency (AHVLA, UK. The IHC examination of CNS samples with both monoclonal and polyclonal antibodies confirmed the granular deposition of PrPSc in the neurons of the positive control tissues. However, while the monoclonal antibodies did not produce positive reactions in the negative controls, the polyclonal antibodies showed some non-specific staining. The testing of positive control tonsil samples with polyclonal and monoclonal antibodies identified positive control-specific reactions, whereas the negative control tissues were IHC-negative with all antibodies, although P4 and the polyclonal antibodies produced some background staining. In summary, although the polyclonal antibodies may be more accessible, their use is not advisable because of possible false positive reactions. The polyclonal antibody M52 was able to identify PrPC in brain and spleen samples by WB but other lymphoid tissues were negative.

  2. The architecture of PrPSc: Threading secondary structure elements into the 4-rung ß-solenoid scaffold

    Science.gov (United States)

    Aims: We propose to exploit the wealth of theoretical and experimental constraints to develop a structure of the infectious prion (hamster PrP27-30). Recent cryo-EM based evidence has determined that PrPSc is a 4-rung ß-solenoid (Vázquez-Fernández et al. 2016, PLoS Pathog. 12(9): e1005835). This ev...

  3. Transcriptome analysis of CNS immediately before and after the detection of PrP(Sc) in SSBP/1 sheep scrapie.

    Science.gov (United States)

    Gossner, Anton G; Hopkins, John

    2014-10-10

    Sheep scrapie is a transmissible spongiform encephalopathy (TSE), progressive and fatal neurodegenerative diseases of the central nervous system (CNS) linked to the accumulation of misfolded prion protein, PrP(Sc). New Zealand Cheviot sheep, homozygous for the VRQ genotype of the PRNP gene are most susceptible with an incubation period of 193 days with SSBP/1 scrapie. However, the earliest time point that PrP(Sc) can be detected in the CNS is 125 days (D125). The aim of this study was to quantify changes to the transcriptome of the thalamus and obex (medulla) at times immediately before (D75) and after (D125) PrP(Sc) was detected. Affymetrix gene arrays were used to quantify gene expression in the thalamus and Illumina DGE-tag profiling for obex. Ingenuity Pathway Analysis was used to help describe the biological processes of scrapie pathology. Neurological disease and Cancer were common Bio Functions in each tissue at D75; inflammation and cell death were major processes at D125. Several neurological receptors were significantly increased at D75 (e.g. CHRNA6, GRM1, HCN2), which might be clues to the molecular basis of psychiatric changes associated with TSEs. No genes were significantly differentially expressed at both D75 and D125 and there was no progression of events from earlier to later time points. This implies that there is no simple linear progression of pathological or molecular events. There seems to be a step-change between D75 and D125, correlating with the detection of PrP(Sc), resulting in the involvement of different pathological processes in later TSE disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  4. A new method for the characterization of strain-specific conformational stability of protease-sensitive and protease-resistant PrPSc.

    Science.gov (United States)

    Pirisinu, Laura; Di Bari, Michele; Marcon, Stefano; Vaccari, Gabriele; D'Agostino, Claudia; Fazzi, Paola; Esposito, Elena; Galeno, Roberta; Langeveld, Jan; Agrimi, Umberto; Nonno, Romolo

    2010-09-14

    Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrP(Sc), a disease-associated isoform of the host-encoded cellular protein (PrP(C)). Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrP(Sc). However, PrP(Sc) is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrP(Sc) aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrP(C) and PrP(Sc) by means of differential centrifugation. The conformational solubility and stability assay (CSSA) was then developed by measuring PrP(Sc) solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl](1/2) values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl](1/2) values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M), followed by sheep scrapie (2.2 M) and by MM2 sCJD (1.6 M). In order to test the ability of CSSA to characterise protease-sensitive PrP(Sc), we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrP(Sc) aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrP(Sc) conformational stabilities of protease-resistant and protease-sensitive PrP(Sc) and that it is a valuable tool for

  5. A new method for the characterization of strain-specific conformational stability of protease-sensitive and protease-resistant PrPSc.

    Directory of Open Access Journals (Sweden)

    Laura Pirisinu

    Full Text Available Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrP(Sc, a disease-associated isoform of the host-encoded cellular protein (PrP(C. Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrP(Sc. However, PrP(Sc is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrP(Sc aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrP(C and PrP(Sc by means of differential centrifugation. The conformational solubility and stability assay (CSSA was then developed by measuring PrP(Sc solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl](1/2 values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl](1/2 values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M, followed by sheep scrapie (2.2 M and by MM2 sCJD (1.6 M. In order to test the ability of CSSA to characterise protease-sensitive PrP(Sc, we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrP(Sc aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrP(Sc conformational stabilities of protease-resistant and protease-sensitive PrP(Sc and that it is a valuable tool

  6. Relationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system.

    Science.gov (United States)

    Vrentas, Catherine E; Greenlee, Justin J; Tatum, Trudy L; Nicholson, Eric M

    2012-01-01

    Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrP(C)) into a â-rich conformer (PrP(Sc)) that accumulates into higher-order structures in the brain and other tissues. Distinct strains of TSEs exist, characterized by different pathologic profiles upon passage into rodents and representing distinct conformations of PrP(Sc). One biochemical method of distinguishing strains is the stability of PrP(Sc) as determined by unfolding in guanidine hydrochloride (GdnHCl), which is tightly and positively correlated with the incubation time of disease upon passage into mice. Here, we utilize a rapid, protease-free version of the stability assay to characterize naturally occurring scrapie samples, including a fast-acting scrapie inoculum for which incubation time is highly dependent on the amino acid at codon 136 of the prion protein. We utilize the stability methodology to identify the presence of two distinct isolates in the inoculum, and compare isolate properties to those of a host-stabilized reference scrapie isolate (NADC 13-7) in order to assess the stability/incubation time correlation in a natural host system. We demonstrate the utility of the stability methodology in characterizing TSE isolates throughout serial passage in livestock, which is applicable to a range of natural host systems, including strains of bovine spongiform encephalopathy and chronic wasting disease.

  7. Immunohistochemical study of PrPSc distribution in neural and extraneural tissues of two cats with feline spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Wunderlin Sabina S

    2009-03-01

    Full Text Available Abstract Background Two domestic shorthair cats presenting with progressive hind-limb ataxia and increased aggressiveness were necropsied and a post mortem diagnosis of Feline Spongiform Encephalopathy (FSE was made. A wide spectrum of tissue samples was collected and evaluated histologically and immunohistologically for the presence of PrPSc. Results Histopathological examination revealed a diffuse vacuolation of the grey matter neuropil with the following areas being most severely affected: corpus geniculatum medialis, thalamus, gyrus dentatus of the hippocampus, corpus striatum, and deep layers of the cerebral and cerebellar cortex as well as in the brain stem. In addition, a diffuse glial reaction involving astrocytes and microglia and intraneuronal vacuolation in a few neurons in the brain stem was present. Heavy PrPSc immunostaining was detected in brain, retina, optic nerve, pars nervosa of the pituitary gland, trigeminal ganglia and small amounts in the myenteric plexus of the small intestine (duodenum, jejunum and slightly in the medulla of the adrenal gland. Conclusion The PrPSc distribution within the brain was consistent with that described in other FSE-affected cats. The pattern of abnormal PrP in the retina corresponded to that found in a captive cheetah with FSE, in sheep with scrapie and was similar to nvCJD in humans.

  8. Identification of unknown nuclear material

    Energy Technology Data Exchange (ETDEWEB)

    Nicolaou, G. [University of Thrace, Department of Electrical and Computer Engineering, Laboratory of Nuclear Technology, Kimmerria Campus, 67100 Xanthi (Greece)

    2010-07-01

    Aim: provenance determination of unknown nuclear material: - demonstrated for spent nuclear fuel; - information sought for unknown: fuel type, reactor type where fuel was irradiated, final burnup; Using an isotopic finger-printing method: - U, Pu or Pu isotopics or fission products; - simulations of fuel evolution during irradiation, using ORIGEN; - multivariate statistical tools. Fuel considered: simulated commercial spent fuel for a range of burnups: - PWR UO{sub 2} 3.1% and 3.5% {sup 235}U, - PWR thermal MOX, - BWR UO{sub 2} 3.2% {sup 235}U, - CANDU-N natural U, - CANDU-S UO{sub 2} 3.2% {sup 235}U, - fast Reactor MOX; simulated commercial spent fuel for a range of burnups: - PWR UO{sub 2} 3.1% and 3.5% {sup 235}U, - PWR thermal MOX, - BWR UO{sub 2} 3.2% {sup 235}U, - CANDU-N natural U, - CANDU-S UO{sub 2} 3.2% {sup 235}U, - fast Reactor MOX; 'unknown' spent fuel: - PWR 1: UO{sub 2} 3.1% {sup 235}U (26 GWd/t), - PWR 2: UO{sub 2} 3.1% {sup 235}U (32 GWd/t). Procedures: U, Pu or Pu isotopic compositions or fission products: - isotopic composition of unknown spent fuel, - simulated for commercial spent fuel from a range of nuclear power reactors {yields} comparison of compositions through factor analysis {yields} unknown has the provenance of the commercial spent fuel with which it exhibits the most similar composition. In conclusion: different reactor-fuel types well resolved; fuel and reactor type accurately predicted; burnup predicted to within 5% of declared; different reactor-fuel types. (authors)

  9. Protein misfolding cyclic amplification corroborates the absence of PrP(Sc) accumulation in placenta from foetuses with the ARR/ARQ genotype in natural scrapie.

    Science.gov (United States)

    Garza, María Carmen; Eraña, Hasier; Castilla, Joaquín; Acín, Cristina; Vargas, Antonia; Badiola, Juan José; Monleón, Eva

    2017-05-01

    Ovine scrapie is a worldwide spread prion disease that is transmitted horizontally under field conditions. Placenta from scrapie-infected ewes is an important source of infection, since this tissue can accumulate high amounts of PrP(Sc) depending on the foetal genotype. Therefore, placentas carrying susceptible foetuses can accumulate PrP(Sc) but there is not PrP(Sc) accumulation in presence of foetuses with at least one ARR haplotype. In scrapie eradication programs, ARR/ARR males are used for breeding to increase the resistant progeny and reduce the horizontal transmission of the disease through the placenta. The development of highly sensitive techniques, that allow the detection of minimal amounts of PrP(Sc), has caused many secretions/excretions and tissues that had previously been deemed negative to be relabeled as positive for PrP(Sc). This has raised concerns about the possible presence of minimal amounts of PrP(Sc) in placentas from ARR foetuses that conventional techniques had indicated were negative. In the present study we examined 30 placentas from a total of 23 gestations; 15 gestations resulted from naturally ARQ/ARQ scrapie-infected ewes mated with ARR/ARR rams. The absence of PrP(Sc) in placentas carrying the foetal ARR haplotype (n=19) was determined by IDEXX HerdChek scrapie/BSE Antigen EIA Test, Prionics(®)-Check WESTERN and corroborated by the highly sensitive Protein Misfolding Cyclic Amplification technique (PMCA). By immunohistochemistry, several unspecific stainings that might mislead a diagnosis were observed. The results of the present study support that using ARR/ARR males in scrapie eradication programs efficiently decreases the spreading of the agent in the environment via shed placentas. Copyright © 2017. Published by Elsevier B.V.

  10. Chronic Traumatic Encephalopathy: Known Causes, Unknown Effects.

    Science.gov (United States)

    Iacono, Diego; Shively, Sharon B; Edlow, Brian L; Perl, Daniel P

    2017-05-01

    Chronic traumatic encephalopathy (CTE) is a neuropathologic diagnosis typically made in human brains with a history of repetitive traumatic brain injury (rTBI). It remains unknown whether CTE occurs exclusively after rTBI, or whether a single TBI (sTBI) can cause CTE. Similarly, it is unclear whether impact (eg, motor vehicle accidents) and non-impact (eg, blasts) types of energy transfer trigger divergent or common pathologies. While it is established that a history of rTBI increases the risk of multiple neurodegenerative diseases (eg, dementia, parkinsonism, and CTE), the possible pathophysiologic and molecular mechanisms underlying these risks have yet to be elucidated. Published by Elsevier Inc.

  11. Function analysis of unknown genes

    DEFF Research Database (Denmark)

    Rogowska-Wrzesinska, A.

    2002-01-01

      This thesis entitled "Function analysis of unknown genes" presents the use of proteome analysis for the characterisation of yeast (Saccharomyces cerevisiae) genes and their products (proteins especially those of unknown function). This study illustrates that proteome analysis can be used...... be obtained using proteome analysis. Chapter 1 and 2 provide the basic theoretical aspects of proteome analysis, its principles, the main techniques involved and their use in the studies of the molecular biology of yeast cells. Chapter 3 presents the methods and tools involved in proteome analysis and used...... to multiple drug resistance in yeast. It analyses the cellular response to the overexpression of the Pdr5p - an ABC transporter protein that is responsible for resistance of yeast cells to several drugs and chemical compounds. It shows that the overexpression of Pdr5p triggers a strong cell stress response...

  12. Inflammation in Heart Failure: known knowns and unknown unknowns.

    Science.gov (United States)

    Cocco, Giuseppe; Jerie, Paul; Amiet, Philipp; Pandolfi, Stefano

    2017-08-01

    The review deals with inflammation in heart failure (HF). Many data show that systemic inflammation is frequent in HF and implicate that inflammation contributes to damage and dysfunction of the cardiovascular system. Areas Covered: Experimental data have been mainly obtained in acute laboratory animal models. It is questionable whether animals' data can be translated into clinical settings with patients with chronic HF who have concomitant pathologies. The idea of a common inflammatory pathway that characterizes all different forms of clinical HF is unrealistic. It seems realistic that inflammation differs in non-cardiac and cardiac diseases. Research therapeutic options address the use of inhibitors of cytokines, of agents antagonizing oxidative stress, of MMP and of PI3K signaling pathways. Expert Opinion: Considering the many unknowns in our knowledge it is not surprising that early trials aimed to antagonize inflammation in HF have been disappointing. We are far away from having solid therapeutic schedules to use immunomodulation in all subtypes of HF. However, modern trials on HF due to virus infections have proven that immunomodulation is therapeutically effective. We should wisely use the known facts and accept that we have many unknowns. By appropriate selection of the subtypes of HF we may be able to find the appropriate therapy against inflammation in HF.

  13. Sialylation of prion protein controls the rate of prion amplification, the cross-species barrier, the ratio of PrPSc glycoform and prion infectivity.

    Science.gov (United States)

    Katorcha, Elizaveta; Makarava, Natallia; Savtchenko, Regina; D'Azzo, Alessandra; Baskakov, Ilia V

    2014-09-01

    The central event underlying prion diseases involves conformational change of the cellular form of the prion protein (PrP(C)) into the disease-associated, transmissible form (PrP(Sc)). Pr(PC) is a sialoglycoprotein that contains two conserved N-glycosylation sites. Among the key parameters that control prion replication identified over the years are amino acid sequence of host PrP(C) and the strain-specific structure of PrPSc. The current work highlights the previously unappreciated role of sialylation of PrP(C) glycans in prion pathogenesis, including its role in controlling prion replication rate, infectivity, cross-species barrier and PrP(Sc) glycoform ratio. The current study demonstrates that undersialylated PrP(C) is selected during prion amplification in Protein Misfolding Cyclic Amplification (PMCAb) at the expense of oversialylated PrP(C). As a result, PMCAb-derived PrP(Sc) was less sialylated than brain-derived PrP(Sc). A decrease in PrPSc sialylation correlated with a drop in infectivity of PMCAb-derived material. Nevertheless, enzymatic de-sialylation of PrP(C) using sialidase was found to increase the rate of PrP(Sc) amplification in PMCAb from 10- to 10,000-fold in a strain-dependent manner. Moreover, de-sialylation of PrP(C) reduced or eliminated a species barrier of for prion amplification in PMCAb. These results suggest that the negative charge of sialic acid controls the energy barrier of homologous and heterologous prion replication. Surprisingly, the sialylation status of PrP(C) was also found to control PrP(Sc) glycoform ratio. A decrease in Pr(PC) sialylation levels resulted in a higher percentage of the diglycosylated glycoform in PrP(Sc). 2D analysis of charge distribution revealed that the sialylation status of brain-derived PrP(C) differed from that of spleen-derived PrP(C). Knocking out lysosomal sialidase Neu1 did not change the sialylation status of brain-derived PrP(C), suggesting that Neu1 is not responsible for desialylation of Pr

  14. Sialylation of prion protein controls the rate of prion amplification, the cross-species barrier, the ratio of PrPSc glycoform and prion infectivity.

    Directory of Open Access Journals (Sweden)

    Elizaveta Katorcha

    2014-09-01

    Full Text Available The central event underlying prion diseases involves conformational change of the cellular form of the prion protein (PrP(C into the disease-associated, transmissible form (PrP(Sc. Pr(PC is a sialoglycoprotein that contains two conserved N-glycosylation sites. Among the key parameters that control prion replication identified over the years are amino acid sequence of host PrP(C and the strain-specific structure of PrPSc. The current work highlights the previously unappreciated role of sialylation of PrP(C glycans in prion pathogenesis, including its role in controlling prion replication rate, infectivity, cross-species barrier and PrP(Sc glycoform ratio. The current study demonstrates that undersialylated PrP(C is selected during prion amplification in Protein Misfolding Cyclic Amplification (PMCAb at the expense of oversialylated PrP(C. As a result, PMCAb-derived PrP(Sc was less sialylated than brain-derived PrP(Sc. A decrease in PrPSc sialylation correlated with a drop in infectivity of PMCAb-derived material. Nevertheless, enzymatic de-sialylation of PrP(C using sialidase was found to increase the rate of PrP(Sc amplification in PMCAb from 10- to 10,000-fold in a strain-dependent manner. Moreover, de-sialylation of PrP(C reduced or eliminated a species barrier of for prion amplification in PMCAb. These results suggest that the negative charge of sialic acid controls the energy barrier of homologous and heterologous prion replication. Surprisingly, the sialylation status of PrP(C was also found to control PrP(Sc glycoform ratio. A decrease in Pr(PC sialylation levels resulted in a higher percentage of the diglycosylated glycoform in PrP(Sc. 2D analysis of charge distribution revealed that the sialylation status of brain-derived PrP(C differed from that of spleen-derived PrP(C. Knocking out lysosomal sialidase Neu1 did not change the sialylation status of brain-derived PrP(C, suggesting that Neu1 is not responsible for desialylation of Pr

  15. Parasite remains in archaeological sites

    Directory of Open Access Journals (Sweden)

    Françoise Bouchet

    2003-01-01

    Full Text Available Organic remains can be found in many different environments. They are the most significant source for paleoparasitological studies as well as for other paleoecological reconstruction. Preserved paleoparasitological remains are found from the driest to the moistest conditions. They help us to understand past and present diseases and therefore contribute to understanding the evolution of present human sociality, biology, and behavior. In this paper, the scope of the surviving evidence will be briefly surveyed, and the great variety of ways it has been preserved in different environments will be discussed. This is done to develop to the most appropriated techniques to recover remaining parasites. Different techniques applied to the study of paleoparasitological remains, preserved in different environments, are presented. The most common materials used to analyze prehistoric human groups are reviewed, and their potential for reconstructing ancient environment and disease are emphasized. This paper also urges increased cooperation among archaeologists, paleontologists, and paleoparasitologists.

  16. Fever of unknown origin in elderly patients.

    Science.gov (United States)

    Knockaert, D C; Vanneste, L J; Bobbaers, H J

    1993-11-01

    To describe the spectrum of diseases that may give rise to fever of unknown origin in elderly patients and to delineate the diagnostic approach in these patients. Subgroup analysis of a prospectively collected case series followed more than 2 years. General Internal Medicine Service based at University hospital, Leuven, Belgium. Forty-seven consecutive patients, older than 65 years, meeting the classic criteria of fever of unknown origin. The final diagnosis established and the clinical value of diagnostic procedures. Infections, tumors and multisystem diseases (encompassing rheumatic diseases, connective tissue disorders, vasculitis including temporal arteritis, polymyalgia rheumatica, and sarcoidosis) were found in 12 (25%), six (12%) and 15 patients (31%), respectively. Drug-related fever was the cause in three patients (6%), miscellaneous conditions were found in five patients (10%), and six patients (12%) remained undiagnosed. Microbiologic investigations were diagnostic in eight cases (16%), serologic tests yielded one diagnosis, immunologic investigations had a diagnostic value in four cases, standard X-rays yielded a diagnostic contribution in 10 cases, ultrasonography and computed tomography were diagnostic in 11 cases, Gallium scintigraphy had a diagnostic contribution in 17 cases, and biopsies yielded the final diagnosis in 18 cases. Multisystem diseases emerged as the most frequent cause of fever of unknown origin in the elderly, and temporal arteritis was the most frequent specific diagnosis. Infections, particularly tuberculosis, remain an important group. The percentage of tumors was higher in our elderly patients than in the younger ones but still clearly lower than in other recent series of FUO in adults. The number of undiagnosed cases was significantly lower in elderly patients than in younger individuals (P < or = 0.01). The investigation of elderly patients with FUO should encompass routine temporal artery biopsy and extensive search for

  17. Carcinoma Telangiectaticum of Unknown Primary

    Directory of Open Access Journals (Sweden)

    Demet Çiçek

    2008-07-01

    Full Text Available Carcinoma telangiectaticum is an unusual type of cutaneous metastasis originating from various malignant tumors and characterized by telangiectases. This disorder appears with the spread of malignant cells to the skin via superficial lymphatics. It presents as small pink to purplish pseudovesicles, purpuric papules, plaques and telangiectases. A 58-year-old female patient with extensive internal organ metastasis, the primary of which could not be determined, was consulted for bluish lesion on her abdomen, while she was receiving cisplatinum and etoposide combination chemotherapy and radiotherapy. Histopathologic examination revealed that the superficial lymphatics in dermis were attacked by tumoral cells. Final diagnosis was established by clinical and histopathological findings as carcinoma telangiectaticum due to metastasis of a malignant tumor of unknown origin. Unfortunately our patient succumbed during her chemotherapy.

  18. Striving for the unknown normal

    DEFF Research Database (Denmark)

    Nielsen, Mikka

    the ADHD diagnosis both answers and produces existential questions on what counts as normal behaviour and emotions. The diagnosis helps the diagnosed to identify, accept and handle problems by offering concrete explanations and solutions to diffuse experienced problems. But the diagnostic process......-analysing situation trying to answer: What is ADHD and what is me and my personal features? When are the drugs having the right effect? And since I have never been normal then how would I know what behavioural ideal I am striving for? Moreover, the public questioning of the diagnosis calls the individual...... to constantly claiming recognition of the diagnosis. I end by discussing the moral implications of this striving for the unknown normal and ask if the pathologization of inattentive and hyperactive behaviour is to be addressed as a problematic moral issue or if we have a moral obligation to help people who...

  19. Motif-grafted antibodies containing the replicative interface of cellular PrP are specific for PrPSc.

    Science.gov (United States)

    Moroncini, Gianluca; Kanu, Nnennaya; Solforosi, Laura; Abalos, Gil; Telling, Glenn C; Head, Mark; Ironside, James; Brockes, Jeremy P; Burton, Dennis R; Williamson, R Anthony

    2004-07-13

    Prion diseases are closely associated with the conversion of the cellular prion protein (PrPC) to an abnormal conformer (PrPSc) [Prusiner, S. B. (1998) Proc. Natl. Acad. Sci. USA 95, 13363-13383]. Monoclonal antibodies that bind epitopes comprising residues 96-104 and 133-158 of PrPC potently inhibit this process, presumably by preventing heterodimeric association of PrPC and PrPSc, and suggest that these regions of PrPC may be critical components of the PrPC-PrPSc replicative interface. We reasoned that transplanting PrP sequence corresponding to these regions into a suitable carrier molecule, such as an antibody, could impart specific recognition of disease-associated forms of PrP. To test this hypothesis, polypeptides containing PrP sequence between residues 89-112 or 136-158 were used to replace the extended heavy chain complementarity-determining region 3 of an IgG antibody specific for the envelope glycoprotein of HIV-1. Herein the resulting engineered PrP-IgGs are shown to bind specifically to infective fractions of PrP in mouse, human, and hamster prion-infected tissues, but not to PrPC, other cellular components, or the HIV-1 envelope. PrPSc reactivity was abolished when the sequence of the PrP 89-112 and 136-158 grafts was mutated, scrambled, or N-terminally truncated. Our findings suggest that residues within the 89-112 and 136-158 segments of PrPC are key components of one face of the PrPC-PrPSc complex. PrPSc-specific antibodies produced by the approach described may find widespread application in the study of prion biology and replication and in the detection of infectious prions in human and animal materials.

  20. Cholesterol transporter ATP-binding cassette A1 (ABCA1) is elevated in prion disease and affects PrPC and PrPSc concentrations in cultured cells.

    Science.gov (United States)

    Kumar, Rajeev; McClain, Denise; Young, Rebecca; Carlson, George A

    2008-06-01

    Prion diseases are transmissible neurodegenerative disorders of prion protein (PrP) conformation. Prion replication by conversion of benign PrPC isoforms into disease-specific PrPSc isoforms is intimately involved in prion disease pathogenesis and may be initiated in cholesterol-rich caveolae-like domains (CLD). Concentrations of the cholesterol transporter ATP-binding cassette A1 protein (ABCA1) are elevated in pre-clinical scrapie prion-infected mice and in prion-infected cells in vitro. Elevation of ABCA1 in prion-infected brain is not a direct consequence of local PrPSc accumulation, indeed levels of ABCA1 are comparable in brain regions that differ dramatically in the amount of PrPSc. Similarly, ABCA1 concentrations are identical in normal mice, transgenic mice overexpressing PrP and PrP knockout mice. In contrast, PrPC and PrPSc levels, but not Prnp mRNA, were increased by overexpression of ABCA1 in N2a neuroblastoma cells and scrapie prion-infected N2a cells (ScN2a). Conversely, RNAi-mediated knock down of Abca1 expression decreased the concentrations of PrPC in N2a cells and of PrPSc in ScN2a cells. These results suggest that ABCA1's effects on PrPC levels are post-translational and may reflect an increase in of PrPC stability, mediated either indirectly by increasing membrane cholesterol and CLD formation or by other functions of ABCA1. The increased supply of PrPC available for conversion would lead to increased PrPSc formation.

  1. Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification.

    Science.gov (United States)

    Parchi, Piero; Strammiello, Rosaria; Notari, Silvio; Giese, Armin; Langeveld, Jan P M; Ladogana, Anna; Zerr, Inga; Roncaroli, Federico; Cras, Patrich; Ghetti, Bernardino; Pocchiari, Maurizio; Kretzschmar, Hans; Capellari, Sabina

    2009-11-01

    Six subtypes of sporadic Creutzfeldt-Jakob disease with distinctive clinico-pathological features have been identified largely based on two types of the abnormal prion protein, PrP(Sc), and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein. The existence of affected subjects showing mixed phenotypic features and concurrent PrP(Sc) types has been reported but with inconsistencies among studies in both results and their interpretation. The issue currently complicates diagnosis and classification of cases and also has implications for disease pathogenesis. To explore the issue in depth, we carried out a systematic regional study in a large series of 225 cases. PrP(Sc) types 1 and 2 concurrence was detected in 35% of cases and was higher in MM than in MV or VV subjects. The deposition of either type 1 or 2, when concurrent, was not random and always characterized by the coexistence of phenotypic features previously described in the pure subtypes. PrP(Sc) type 1 accumulation and related pathology predominated in MM and MV cases, while the type 2 phenotype prevailed in VVs. Neuropathological examination best identified the mixed types 1 and 2 features in MMs and most MVs, and also uniquely revealed the co-occurrence of pathological variants sharing PrP(Sc) type 2. In contrast, molecular typing best detected the concurrent PrP(Sc) types in VV subjects and MV cases with kuru plaques. The present data provide an updated disease classification and are of importance for future epidemiologic and transmission studies aimed to identify etiology and extent of strain variation in sporadic Creutzfeldt-Jakob disease.

  2. Prion Seeding Activities of Mouse Scrapie Strains with Divergent PrPSc Protease Sensitivities and Amyloid Plaque Content Using RT-QuIC and eQuIC

    OpenAIRE

    Vascellari, Sarah; Orrù, Christina D.; Hughson, Andrew G.; King, Declan; Barron, Rona; Wilham, Jason M.; Baron, Gerald S.; Race, Brent; Pani, Alessandra; Caughey, Byron

    2012-01-01

    Different transmissible spongiform encephalopathy (TSE)-associated forms of prion protein (e.g. PrP(Sc)) can vary markedly in ultrastructure and biochemical characteristics, but each is propagated in the host. PrP(Sc) propagation involves conversion from its normal isoform, PrP(C), by a seeded or templated polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and eQuIC prion assays which use recombinant PrP (rPrP(Sen)) as a substrate. These ultrasensitive detection assay...

  3. Carcinomatous Meningitis from Unknown Primary Carcinoma

    Directory of Open Access Journals (Sweden)

    L. Favier

    2009-10-01

    Full Text Available Carcinomatous meningitis (CM occurs in 3 to 8% of cancer patients. Patients present with a focal symptom, and multifocal signs are often found following neurological examination. The gold standard for diagnosis remains the demonstration of carcinomatous cells in the cerebrospinal fluid on cytopathological examination. Despite the poor prognosis, palliative treatment could improve quality of life and, in some cases, overall survival. We report on a patient who presented with vertigo, tinnitus and left-sided hearing loss followed by progressive diffuse facial nerve paralysis. Lumbar cerebrospinal fluid confirmed the diagnosis of CM. However, no primary tumor was discovered, even after multiple invasive investigations. This is the first reported case in the English-language medical literature of CM resulting from a carcinoma of unknown primary origin.

  4. New hominin remains from Uzbekistan.

    Science.gov (United States)

    Glantz, Michelle; Viola, Bence; Wrinn, Patrick; Chikisheva, Tatiana; Derevianko, Anatoly; Krivoshapkin, Andrei; Islamov, Uktur; Suleimanov, Rustam; Ritzman, Terrence

    2008-08-01

    Although the Paleolithic occupations of Uzbekistan and the neighboring foothill regions of Tajikistan and Kazakhstan are well-documented, almost no hominin fossil material has been discovered in the area since Teshik-Tash 1 in 1938. Here we describe and offer a preliminary comparative framework for hominin remains that were recovered in 2003 from two Middle Paleolithic sites in Uzbekistan, Obi-Rakhmat Grotto and Anghilak Cave. The description of Teshik-Tash as a Neandertal and the preponderance of lithic assemblages identified as Mousterian in character has supported the interpretation of the region as the eastern-most extent of the Neandertal range. The material from Obi-Rakhmat (OR-1), a subadult represented by part of a permanent maxillary dentition and a fragmentary cranium, expresses a relatively Neandertal-like dentition coupled with more ambiguous cranial anatomy. The remains from Anghilak Cave include a non-diagnostic, diminutive right fifth metatarsal (AH-1). These findings are important additions to the Central Asia hominin fossil record.

  5. Plasma membrane invaginations containing clusters of full-length PrPSc are an early form of prion-associated neuropathology in vivo.

    Science.gov (United States)

    Godsave, Susan F; Wille, Holger; Pierson, Jason; Prusiner, Stanley B; Peters, Peter J

    2013-06-01

    During prion disease, cellular prion protein (PrP(C)) is refolded into a pathogenic isoform (PrP(Sc)) that accumulates in the central nervous system and causes neurodegeneration and death. We used immunofluorescence, quantitative cryo-immunogold EM, and tomography to detect nascent, full-length PrP(Sc) in the hippocampus of prion-infected mice from early preclinical disease stages onward. Comparison of uninfected and infected brains showed that sites containing full-length PrP(Sc) could be recognized in the neuropil by bright spots and streaks of immunofluorescence on semi-thin (200-nm) sections, and by clusters of cryo-immunogold EM labeling. PrP(Sc) was found mainly on neuronal plasma membranes, most strikingly on membrane invaginations and sites of cell-to-cell contact, and was evident by 65 days postinoculation, or 54% of the incubation period to terminal disease. Both axons and dendrites in the neuropil were affected. We hypothesize that closely apposed plasma membranes provide a favorable environment for prion conversion and intercellular prion transfer. Only a small proportion of clustered PrP immunogold labeling was found at synapses, indicating that synapses are not targeted specifically in prion disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Relationship of PrPSc molecular properties with incubation time in a natural prion disease host: a characterization of three isolates of U.S. sheep scrapie

    Science.gov (United States)

    Determination of aspects of tertiary and quaternary structure of PrPSc associated with differences in disease presentation in the host is a key area of interest in the prion field. Previously, we determined that a U.S. scrapie isolate (136-VDEP) with a short incubation time upon passage in sheep als...

  7. Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

    NARCIS (Netherlands)

    Parchi, P.; Strammiello, R.; Notari, S.; Giese, A.; Langeveld, J.P.M.; Ladogana, A.; Zerr, I.; Roncaroli, F.; Cras, P.; Ghetti, B.; Pocchiari, M.; Kretzschmar, H.; Capellari, S.

    2009-01-01

    Six subtypes of sporadic Creutzfeldt-Jakob disease with distinctive clinico-pathological features have been identified largely based on two types of the abnormal prion protein, PrPSc, and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein. The existence of affected subjects

  8. A new method for the Characterization of Strain-Specific Conformational Stability of Protease-Sensitive and Protease Resistant PrPSc

    NARCIS (Netherlands)

    Pirisinu, L.; Bari, Di M.; Marcon, S.; Vaccari, G.; Agostino, D' C.; Fazzi, P.; Esposito, E.; Cardone, F.; Langeveld, J.P.M.; Agrimi, U.; Nonno, R.

    2010-01-01

    Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrPSc, a disease-associated isoform of the host-encoded cellular protein (PrPC). Molecular strain typing approaches

  9. PrPc does not mediate internalization of PrPSc but is required at an early stage for de novo prion infection of Rov cells.

    Science.gov (United States)

    Paquet, Sophie; Daude, Nathalie; Courageot, Marie-Pierre; Chapuis, Jérôme; Laude, Hubert; Vilette, Didier

    2007-10-01

    We have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing PrPc protein and permissive to infection by a sheep scrapie agent. We demonstrate that abnormal PrP (PrPSc) and prion infectivity are efficiently internalized in Rov cells, whether or not PrPc is expressed. At odds with earlier studies implicating cellular heparan sulfates in PrPSc internalization, we failed to find any involvement of such molecules in Rov cells, indicating that prions can enter target cells by several routes. We further show that PrPSc taken up in the absence of PrPc was unable to promote efficient prion multiplication once PrPc expression was restored in the cells. This observation argues that interaction of PrPSc with PrPc has to occur early, in a specific subcellular compartment(s), and is consistent with the view that the first prion multiplication events may occur at the cell surface.

  10. PrPc Does Not Mediate Internalization of PrPSc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells▿

    Science.gov (United States)

    Paquet, Sophie; Daude, Nathalie; Courageot, Marie-Pierre; Chapuis, Jérôme; Laude, Hubert; Vilette, Didier

    2007-01-01

    We have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing PrPc protein and permissive to infection by a sheep scrapie agent. We demonstrate that abnormal PrP (PrPSc) and prion infectivity are efficiently internalized in Rov cells, whether or not PrPc is expressed. At odds with earlier studies implicating cellular heparan sulfates in PrPSc internalization, we failed to find any involvement of such molecules in Rov cells, indicating that prions can enter target cells by several routes. We further show that PrPSc taken up in the absence of PrPc was unable to promote efficient prion multiplication once PrPc expression was restored in the cells. This observation argues that interaction of PrPSc with PrPc has to occur early, in a specific subcellular compartment(s), and is consistent with the view that the first prion multiplication events may occur at the cell surface. PMID:17626095

  11. Prions amplify through degradation of the VPS10P sorting receptor sortilin

    Science.gov (United States)

    Tomita, Mitsuru; Yano, Masashi; Hara, Hideyuki; Nykjaer, Anders

    2017-01-01

    Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells. PMID:28665987

  12. Prions amplify through degradation of the VPS10P sorting receptor sortilin.

    Directory of Open Access Journals (Sweden)

    Keiji Uchiyama

    2017-06-01

    Full Text Available Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells.

  13. Prions amplify through degradation of the VPS10P sorting receptor sortilin.

    Science.gov (United States)

    Uchiyama, Keiji; Tomita, Mitsuru; Yano, Masashi; Chida, Junji; Hara, Hideyuki; Das, Nandita Rani; Nykjaer, Anders; Sakaguchi, Suehiro

    2017-06-01

    Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells.

  14. Skeletal sexing standards of human remains in Turkey

    OpenAIRE

    Gulhan, O

    2017-01-01

    The identification of victims involved in mass fatality incidents, as well as the identification of unknown individuals in criminal cases has become an increasingly important issue nowadays. Sex assessment represents a key point in forensic evaluations due to its significance in providing biological identity. Even though the availability of documented skeletal remains to forensic practitioners is a common practice in many countries, in Turkey, contemporary documented skeletal remains are not ...

  15. Glimepiride reduces the expression of PrPc, prevents PrPSc formation and protects against prion mediated neurotoxicity in cell lines.

    Directory of Open Access Journals (Sweden)

    Clive Bate

    Full Text Available BACKGROUND: A hallmark of the prion diseases is the conversion of the host-encoded cellular prion protein (PrP(C into a disease related, alternatively folded isoform (PrP(Sc. The accumulation of PrP(Sc within the brain is associated with synapse loss and ultimately neuronal death. Novel therapeutics are desperately required to treat neurodegenerative diseases including the prion diseases. PRINCIPAL FINDINGS: Treatment with glimepiride, a sulphonylurea approved for the treatment of diabetes mellitus, induced the release of PrP(C from the surface of prion-infected neuronal cells. The cell surface is a site where PrP(C molecules may be converted to PrP(Sc and glimepiride treatment reduced PrP(Sc formation in three prion infected neuronal cell lines (ScN2a, SMB and ScGT1 cells. Glimepiride also protected cortical and hippocampal neurones against the toxic effects of the prion-derived peptide PrP82-146. Glimepiride treatment significantly reduce both the amount of PrP82-146 that bound to neurones and PrP82-146 induced activation of cytoplasmic phospholipase A(2 (cPLA(2 and the production of prostaglandin E(2 that is associated with neuronal injury in prion diseases. Our results are consistent with reports that glimepiride activates an endogenous glycosylphosphatidylinositol (GPI-phospholipase C which reduced PrP(C expression at the surface of neuronal cells. The effects of glimepiride were reproduced by treatment of cells with phosphatidylinositol-phospholipase C (PI-PLC and were reversed by co-incubation with p-chloromercuriphenylsulphonate, an inhibitor of endogenous GPI-PLC. CONCLUSIONS: Collectively, these results indicate that glimepiride may be a novel treatment to reduce PrP(Sc formation and neuronal damage in prion diseases.

  16. Does hypertension remain after kidney transplantation?

    Directory of Open Access Journals (Sweden)

    Gholamreza Pourmand

    2015-05-01

    Full Text Available Hypertension is a common complication of kidney transplantation with the prevalence of 80%. Studies in adults have shown a high prevalence of hypertension (HTN in the first three months of transplantation while this rate is reduced to 50- 60% at the end of the first year. HTN remains as a major risk factor for cardiovascular diseases, lower graft survival rates and poor function of transplanted kidney in adults and children. In this retrospective study, medical records of 400 kidney transplantation patients of Sina Hospital were evaluated. Patients were followed monthly for the 1st year, every two months in the 2nd year and every three months after that. In this study 244 (61% patients were male. Mean ± SD age of recipients was 39.3 ± 13.8 years. In most patients (40.8% the cause of end-stage renal disease (ESRD was unknown followed by HTN (26.3%. A total of 166 (41.5% patients had been hypertensive before transplantation and 234 (58.5% had normal blood pressure. Among these 234 individuals, 94 (40.2% developed post-transplantation HTN. On the other hand, among 166 pre-transplant hypertensive patients, 86 patients (56.8% remained hypertensive after transplantation. Totally 180 (45% patients had post-transplantation HTN and 220 patients (55% didn't develop HTN. Based on the findings, the incidence of post-transplantation hypertension is high, and kidney transplantation does not lead to remission of hypertension. On the other hand, hypertension is one of the main causes of ESRD. Thus, early screening of hypertension can prevent kidney damage and reduce further problems in renal transplant recipients.

  17. Unknown Risks: Parental Hesitation about Vaccination.

    Science.gov (United States)

    Blaisdell, Laura L; Gutheil, Caitlin; Hootsmans, Norbert A M; Han, Paul K J

    2016-05-01

    This qualitative study of a select sample of vaccine-hesitant parents (VHPs) explores perceived and constructed personal judgments about the risks and uncertainties associated with vaccines and vaccine-preventable diseases (VPDs) and how these subjective risk judgments influence parents' decisions about childhood vaccination. The study employed semistructured focus group interviews with 42 VHPs to elicit parents' perceptions and thought processes regarding the risks associated with vaccination and nonvaccination, the sources of these perceptions, and their approach to decision making about vaccination for their children. VHPs engage in various reasoning processes and tend to perceive risks of vaccination as greater than the risks of VPDs. At the same time, VHPs engage in other reasoning processes that lead them to perceive ambiguity in information about the harms of vaccination-citing concerns about the missing, conflicting, changing, or otherwise unreliable nature of information. VHPs' refusal of vaccination may reflect their aversion to both the risk and ambiguity they perceive to be associated with vaccination. Mitigating this vaccine hesitancy likely requires reconstructing the risks and ambiguities associated with vaccination-a challenging task that requires providing parents with meaningful evidence-based information on the known risks of vaccination versus VPDs and explicitly acknowledging the risks that remain truly unknown. © The Author(s) 2015.

  18. Mouse Prion Protein (PrP) Segment 100 to 104 Regulates Conversion of PrPC to PrPSc in Prion-Infected Neuroblastoma Cells

    Science.gov (United States)

    Hara, Hideyuki; Okemoto-Nakamura, Yuko; Shinkai-Ouchi, Fumiko; Hanada, Kentaro; Yamakawa, Yoshio

    2012-01-01

    Prion diseases are characterized by the replicative propagation of disease-associated forms of prion protein (PrPSc; PrP refers to prion protein). The propagation is believed to proceed via two steps; the initial binding of the normal form of PrP (PrPC) to PrPSc and the subsequent conversion of PrPC to PrPSc. We have explored the two-step model in prion-infected mouse neuroblastoma (ScN2a) cells by focusing on the mouse PrP (MoPrP) segment 92-GGTHNQWNKPSKPKTN-107, which is within a region previously suggested to be part of the binding interface or shown to differ in its accessibility to anti-PrP antibodies between PrPC and PrPSc. Exchanging the MoPrP segment with the corresponding chicken PrP segment (106-GGSYHNQKPWKPPKTN-121) revealed the necessity of MoPrP residues 99 to 104 for the chimeras to achieve the PrPSc state, while segment 95 to 98 was replaceable with the chicken sequence. An alanine substitution at position 100, 102, 103, or 104 of MoPrP gave rise to nonconvertible mutants that associated with MoPrPSc and interfered with the conversion of endogenous MoPrPC. The interference was not evoked by a chimera (designated MCM2) in which MoPrP segment 95 to 104 was changed to the chicken sequence, though MCM2 associated with MoPrPSc. Incubation of the cells with a synthetic peptide composed of MoPrP residues 93 to 107 or alanine-substituted cognates did not inhibit the conversion, whereas an anti-P8 antibody recognizing the above sequence in PrPC reduced the accumulation of PrPSc after 10 days of incubation of the cells. These results suggest the segment 100 to 104 of MoPrPC plays a key role in conversion after binding to MoPrPSc. PMID:22398286

  19. The biomechanical mechanism of how strength and power training improves walking speed in old adults remains unknown

    NARCIS (Netherlands)

    Beijersbergen, C. M. I.; Granacher, U.; Vandervoort, A. A.; DeVita, P.; Hortobagyi, T.

    Maintaining and increasing walking speed in old age is clinically important because this activity of daily living predicts functional and clinical state. We reviewed evidence for the biomechanical mechanisms of how strength and power training increase gait speed in old adults. A systematic search

  20. Detection of PrPSc in lung and mammary gland is favored by the presence of Visna/maedi virus lesions in naturally coinfected sheep.

    Science.gov (United States)

    Salazar, Eider; Monleón, Eva; Bolea, Rosa; Acín, Cristina; Pérez, Marta; Alvarez, Neila; Leginagoikoa, Iratxe; Juste, Ramón; Minguijón, Esmeralda; Reina, Ramsés; Glaria, Idoia; Berriatua, Eduardo; de Andrés, Damián; Badiola, Juan José; Amorena, Beatriz; Luján, Lluís

    2010-01-01

    There are few reports on the pathogenesis of scrapie (Sc) and Visna/maedi virus (VMV) coinfections. The aim of this work was to study in vivo as well as post mortem both diseases in 91 sheep. Diagnosis of Sc and VMV infections allowed the distribution of animals into five groups according to the presence (+) or absence (-) of infection by Sc and VMV: Sc-/VMV-, Sc-/VMV+, Sc+/VMV- and Sc+/VMV+. The latter was divided into two subgroups, with and without VMV-induced lymphoid follicle hyperplasia (LFH), respectively. In both the lung and mammary gland, PrPSc deposits were found in the germinal center of hyperplasic lymphoid follicles in the subgroup of Sc+/VMV+ having VMV-induced LFH. This detection was always associated with (and likely preceded by) PrPSc observation in the corresponding lymph nodes. No PrPSc was found in other VMV-associated lesions. Animals suffering from scrapie had a statistically significantly lower mean age than the scrapie free animals at the time of death, with no apparent VMV influence. ARQ/ARQ genotype was the most abundant among the 91 ewes and the most frequent in scrapie-affected sheep. VMV infection does not seem to influence the scrapie risk group distribution among animals from the five groups established in this work. Altogether, these data indicate that certain VMV-induced lesions can favor PrPSc deposits in Sc non-target organs such as the lung and the mammary gland, making this coinfection an interesting field that warrants further research for a better comprehension of the pathogenesis of both diseases. © The authors, INRA/EDP Sciences, 2010.

  1. Prion Strain Differences in Accumulation of PrPSc on Neurons and Glia Are Associated with Similar Expression Profiles of Neuroinflammatory Genes: Comparison of Three Prion Strains.

    Science.gov (United States)

    Carroll, James A; Striebel, James F; Rangel, Alejandra; Woods, Tyson; Phillips, Katie; Peterson, Karin E; Race, Brent; Chesebro, Bruce

    2016-04-01

    Misfolding and aggregation of host proteins are important features of the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, frontotemporal dementia and prion diseases. In all these diseases, the misfolded protein increases in amount by a mechanism involving seeded polymerization. In prion diseases, host prion protein is misfolded to form a pathogenic protease-resistant form, PrPSc, which accumulates in neurons, astroglia and microglia in the CNS. Here using dual-staining immunohistochemistry, we compared the cell specificity of PrPSc accumulation at early preclinical times post-infection using three mouse scrapie strains that differ in brain regional pathology. PrPSc from each strain had a different pattern of cell specificity. Strain 22L was mainly associated with astroglia, whereas strain ME7 was mainly associated with neurons and neuropil. In thalamus and cortex, strain RML was similar to 22L, but in substantia nigra, RML was similar to ME7. Expression of 90 genes involved in neuroinflammation was studied quantitatively using mRNA from thalamus at preclinical times. Surprisingly, despite the cellular differences in PrPSc accumulation, the pattern of upregulated genes was similar for all three strains, and the small differences observed correlated with variations in the early disease tempo. Gene upregulation correlated with activation of both astroglia and microglia detected in early disease prior to vacuolar pathology or clinical signs. Interestingly, the profile of upregulated genes in scrapie differed markedly from that seen in two acute viral CNS diseases (LaCrosse virus and BE polytropic Friend retrovirus) that had reactive gliosis at levels similar to our prion-infected mice.

  2. An assessment of the efficiency of PrPsc detection in rectal mucosa and third-eyelid biopsies from animals infected with scrapie.

    Science.gov (United States)

    Monleón, Eva; Garza, Ma Carmen; Sarasa, Rocío; Alvarez-Rodriguez, Javier; Bolea, Rosa; Monzón, Marta; Vargas, M Antonia; Badiola, Juan José; Acín, Cristina

    2011-01-27

    In classical scrapie, detection of PrPsc on lymphoreticular system is used for the in vivo and post mortem diagnosis of the disease. However, the sensitivity of this methodology is not well characterised because the magnitude and duration of lymphoid tissue involvement can vary considerably. The aim of the present study was to evaluate the efficiency of detecting PrPsc in rectal mucosa and third-eyelid biopsies. A total of 474 genetically susceptible sheep and 24 goats from three scrapie infected flocks were included in this study. A sample from rectal mucosa and a sample from third-eyelid lymphoid tissue were collected from each animal. Biopsy samples were fixed in formaldehyde and processed for immunohistochemical examination. Animals with negative biopsy results were studied more closely through a post mortem examination of central nervous and lymphoreticular systems and if there was a positive result, additional biopsy sections were further tested. The sensitivity of rectal mucosa and third-eyelid assays were 36% and 40% respectively on initial examination but increased to 48% and 44% respectively after retesting. The results of this field study show a high percentage of infected animals that do not have detectable levels of PrPsc in the biopsied lymphoid tissue, due mainly to the relatively high number of animals with minimal or no involvement of lymphoid tissue in the pathogenesis of the disease. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Controlled unknown quantum operations on hybrid systems

    Science.gov (United States)

    He, Yong; Luo, Ming-Xing

    2016-12-01

    Any unknown unitary operations conditioned on a control system can be deterministically performed if ancillary subspaces are available for the target systems [Zhou X Q, et al. 2011 Nat. Commun. 2 413]. In this paper, we show that previous optical schemes may be extended to general hybrid systems if unknown operations are provided by optical instruments. Moreover, a probabilistic scheme is proposed when the unknown operation may be performed on the subspaces of ancillary high-dimensional systems. Furthermore, the unknown operations conditioned on the multi-control system may be reduced to the case with a control system using additional linear circuit complexity. The new schemes may be more flexible for different systems or hybrid systems. Project supported by the National Natural Science Foundation of China (Grant Nos. 61303039 and 61201253), Chunying Fellowship, and Fundamental Research Funds for the Central Universities, China (Grant No. 2682014CX095).

  4. Fever of unknown origin in rheumatic diseases.

    Science.gov (United States)

    Zenone, Thierry

    2007-12-01

    Noninfectious inflammatory diseases (connective tissue diseases, vasculitis syndromes, granulomatous diseases) emerged as the most frequent cause of fever of unknown origin in western countries. Among these diseases, giant cell arteritis and polymyalgia rheumatica are the most frequent specific diagnosis in the elderly and adult-onset Still's disease the most frequent in younger patients. This article focuses on noninfectious inflammatory diseases as a cause of classic fever of unknown origin (mainly rheumatic diseases, such as vasculitis and connective tissue diseases).

  5. Ciguatera: recent advances but the risk remains.

    Science.gov (United States)

    Lehane, L; Lewis, R J

    2000-11-01

    Ciguatera is an important form of human poisoning caused by the consumption of seafood. The disease is characterised by gastrointestinal, neurological and cardiovascular disturbances. In cases of severe toxicity, paralysis, coma and death may occur. There is no immunity, and the toxins are cumulative. Symptoms may persist for months or years, or recur periodically. The epidemiology of ciguatera is complex and of central importance to the management and future use of marine resources. Ciguatera is an important medical entity in tropical and subtropical Pacific and Indian Ocean regions, and in the tropical Caribbean. As reef fish are increasingly exported to other areas, it has become a world health problem. The disease is under-reported and often misdiagnosed. Lipid-soluble, polyether toxins known as ciguatoxins accumulated in the muscles of certain subtropical and tropical marine finfish cause ciguatera. Ciguatoxins arise from biotransformation in the fish of less polar ciguatoxins (gambiertoxins) produced by Gambierdiscus toxicus, a marine dinoflagellate that lives on macroalgae, usually attached to dead coral. The toxins and their metabolites are concentrated in the food chain when carnivorous fish prey on smaller herbivorous fish. Humans are exposed at the end of the food chain. More than 400 species of fish can be vectors of ciguatoxins, but generally only a relatively small number of species are regularly incriminated in ciguatera. Ciguateric fish look, taste and smell normal, and detection of toxins in fish remains a problem. More than 20 precursor gambiertoxins and ciguatoxins have been identified in G. toxicus and in herbivorous and carnivorous fish. The toxins become more polar as they undergo oxidative metabolism and pass up the food chain. The main Pacific ciguatoxin (P-CTX-1) causes ciguatera at levels=0.1 microg/kg in the flesh of carnivorous fish. The main Caribbean ciguatoxin (C-CTX-1) is less polar and 10-fold less toxic than P-CTX-1. Ciguatoxins

  6. Prion seeding activities of mouse scrapie strains with divergent PrPSc protease sensitivities and amyloid plaque content using RT-QuIC and eQuIC.

    Science.gov (United States)

    Vascellari, Sarah; Orrù, Christina D; Hughson, Andrew G; King, Declan; Barron, Rona; Wilham, Jason M; Baron, Gerald S; Race, Brent; Pani, Alessandra; Caughey, Byron

    2012-01-01

    Different transmissible spongiform encephalopathy (TSE)-associated forms of prion protein (e.g. PrP(Sc)) can vary markedly in ultrastructure and biochemical characteristics, but each is propagated in the host. PrP(Sc) propagation involves conversion from its normal isoform, PrP(C), by a seeded or templated polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and eQuIC prion assays which use recombinant PrP (rPrP(Sen)) as a substrate. These ultrasensitive detection assays have been developed for TSE prions of several host species and sample tissues, but not for murine models which are central to TSE pathogenesis research. Here we have adapted RT-QuIC and eQuIC to various murine prions and evaluated how seeding activity depends on glycophosphatidylinositol (GPI) anchoring and the abundance of amyloid plaques and protease-resistant PrP(Sc) (PrP(Res)). Scrapie brain dilutions up to 10(-8) and 10(-13) were detected by RT-QuIC and eQuIC, respectively. Comparisons of scrapie-affected wild-type mice and transgenic mice expressing GPI anchorless PrP showed that, although similar concentrations of seeding activity accumulated in brain, the heavily amyloid-laden anchorless mouse tissue seeded more rapid reactions. Next we compared seeding activities in the brains of mice with similar infectivity titers, but widely divergent PrP(Res) levels. For this purpose we compared the 263K and 139A scrapie strains in transgenic mice expressing P101L PrP(C). Although the brains of 263K-affected mice had little immunoblot-detectable PrP(Res), RT-QuIC indicated that seeding activity was comparable to that associated with a high-PrP(Res) strain, 139A. Thus, in this comparison, RT-QuIC seeding activity correlated more closely with infectivity than with PrP(Res) levels. We also found that eQuIC, which incorporates a PrP(Sc) immunoprecipitation step, detected seeding activity in plasma from wild-type and anchorless PrP transgenic mice inoculated with 22L, 79A and/or RML

  7. Prion seeding activities of mouse scrapie strains with divergent PrPSc protease sensitivities and amyloid plaque content using RT-QuIC and eQuIC.

    Directory of Open Access Journals (Sweden)

    Sarah Vascellari

    Full Text Available Different transmissible spongiform encephalopathy (TSE-associated forms of prion protein (e.g. PrP(Sc can vary markedly in ultrastructure and biochemical characteristics, but each is propagated in the host. PrP(Sc propagation involves conversion from its normal isoform, PrP(C, by a seeded or templated polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and eQuIC prion assays which use recombinant PrP (rPrP(Sen as a substrate. These ultrasensitive detection assays have been developed for TSE prions of several host species and sample tissues, but not for murine models which are central to TSE pathogenesis research. Here we have adapted RT-QuIC and eQuIC to various murine prions and evaluated how seeding activity depends on glycophosphatidylinositol (GPI anchoring and the abundance of amyloid plaques and protease-resistant PrP(Sc (PrP(Res. Scrapie brain dilutions up to 10(-8 and 10(-13 were detected by RT-QuIC and eQuIC, respectively. Comparisons of scrapie-affected wild-type mice and transgenic mice expressing GPI anchorless PrP showed that, although similar concentrations of seeding activity accumulated in brain, the heavily amyloid-laden anchorless mouse tissue seeded more rapid reactions. Next we compared seeding activities in the brains of mice with similar infectivity titers, but widely divergent PrP(Res levels. For this purpose we compared the 263K and 139A scrapie strains in transgenic mice expressing P101L PrP(C. Although the brains of 263K-affected mice had little immunoblot-detectable PrP(Res, RT-QuIC indicated that seeding activity was comparable to that associated with a high-PrP(Res strain, 139A. Thus, in this comparison, RT-QuIC seeding activity correlated more closely with infectivity than with PrP(Res levels. We also found that eQuIC, which incorporates a PrP(Sc immunoprecipitation step, detected seeding activity in plasma from wild-type and anchorless PrP transgenic mice inoculated with 22L, 79A and/or RML

  8. CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils.

    Science.gov (United States)

    Spinner, Daryl S; Kascsak, Regina B; Lafauci, Giuseppe; Meeker, Harry C; Ye, Xuemin; Flory, Michael J; Kim, Jae Il; Schuller-Levis, Georgia B; Levis, William R; Wisniewski, Thomas; Carp, Richard I; Kascsak, Richard J

    2007-06-01

    Prion diseases are characterized by conversion of the cellular prion protein (PrP(C)) to a protease-resistant conformer, the srapie form of PrP (PrP(Sc)). Humoral immune responses to nondenatured forms of PrP(Sc) have never been fully characterized. We investigated whether production of antibodies to PrP(Sc) could occur in PrP null (Prnp(-/-)) mice and further, whether innate immune stimulation with the TLR9 agonist CpG oligodeoxynucleotide (ODN) 1826 could enhance this process. Whether such stimulation could raise anti-PrP(Sc) antibody levels in wild-type (Prnp(+/+)) mice was also investigated. Prnp(-/-) and Prnp(+/+) mice were immunized with nondenatured 139A scrapie-associated fibrils (SAF), with or without ODN 1826, and were tested for titers of PrP-specific antibodies. In Prnp(-/-) mice, inclusion of ODN 1826 in the immunization regime increased anti-PrP titers more than 13-fold after two immunizations and induced, among others, antibodies to an N-terminal epitope, which were only present in the immune repertoire of mice receiving ODN 1826. mAb 6D11, derived from such a mouse, reacts with the N-terminal epitope QWNK in native and denatured forms of PrP(Sc) and recombinant PrP and exhibits a K(d) in the 10(-)(11) M range. In Prnp(+/+) mice, ODN 1826 increased anti-PrP levels as much as 84% after a single immunization. Thus, ODN 1826 potentiates adaptive immune responses to PrP(Sc) in 139A SAF-immunized mice. These results represent the first characterization of humoral immune responses to nondenatured, infectious PrP(Sc) and suggest methods for optimizing the generation of mAbs to PrP(Sc), many of which could be used for diagnosis and treatment of prion diseases.

  9. Designing towards the Unknown: Engaging with Material and Aesthetic Uncertainty

    Directory of Open Access Journals (Sweden)

    Danielle Wilde

    2017-12-01

    Full Text Available New materials with new capabilities demand new ways of approaching design. Destabilising existing methods is crucial to develop new methods. Yet, radical destabilisation—where outcomes remain unknown long enough that new discoveries become possible—is not easy in technology design where complex interdisciplinary teams with time and resource constraints need to deliver concrete outcomes on schedule. The Poetic Kinaesthetic Interface project (PKI engages with this problematic directly. In PKI we use unfolding processes—informed by participatory, speculative and critical design—in emergent actions, to design towards unknown outcomes, using unknown materials. The impossibility of this task is proving as useful as it is disruptive. At its most potent, it is destabilising expectations, aesthetics and processes. Keeping the researchers, collaborators and participants in a state of unknowing, is opening the research potential to far-ranging possibilities. In this article we unpack the motivations driving the PKI project. We present our mixed-methodology, which entangles textile crafts, design interactions and materiality to shape an embodied enquiry. Our research outcomes are procedural and methodological. PKI brings together diverse human, non-human, known and unknown actors to discover where the emergent assemblages might lead. Our approach is re-invigorating—as it demands re-envisioning of—the design process.

  10. Multidimensional procurement auctions with unknown weights

    DEFF Research Database (Denmark)

    Greve, Thomas

    the principal and the agents leads to unclear reaction strategies. I show that an unknown weight on the principal’s valuation of quality leads to the production of to much quality and to high informational rent. A problem that can be reduced using a revelation mechanism. Having an unknown weight on quality...... gives rise to an analysis of a principal that can not fully commit to the outcome induced by the scoring rule. Therefore, my result apply to contract theory and it’s problems with imperfect commitment....

  11. Protocol for counterfactually transporting an unknown qubit

    Directory of Open Access Journals (Sweden)

    Hatim eSalih

    2016-01-01

    Full Text Available Quantum teleportation circumvents the uncertainty principle using dual channels: a quantum one consisting of previously-shared entanglement, and a classical one, together allowing the disembodied transport of an unknown quantum state over distance. It has recently been shown that a classical bit can be counterfactually communicated between two parties in empty space, Alice and Bob. Here, by using our dual version of the chained quantum Zeno effect to achieve a counterfactual CNOT gate, we propose a protocol for transporting an unknown qubit counterfactually, that is without any physical particles travelling between Alice and Bob—no classical channel and no previously-shared entanglement.

  12. Protocol for counterfactually transporting an unknown qubit

    Science.gov (United States)

    Salih, Hatim

    2015-12-01

    Quantum teleportation circumvents the uncertainty principle using dual channels: a quantum one consisting of previously-shared entanglement, and a classical one, together allowing the disembodied transport of an unknown quantum state over distance. It has recently been shown that a classical bit can be counterfactually communicated between two parties in empty space, “Alice” and “Bob”. Here, by using our “dual” version of the chained quantum Zeno effect to achieve a counterfactual CNOT gate, we propose a protocol for transporting an unknown qubit counterfactually, that is without any physical particles travelling between Alice and Bob—no classical channel and no previously-shared entanglement.

  13. Scott's Lake Excavation Letters on Human Remains

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This is two letters written about the repatriation of Santee Indian human remains and funerary objects to Santee Sioux Tribe. Includes an inventory of human remains...

  14. Climate change - clouds remain the misty factor

    NARCIS (Netherlands)

    Jonker, H.; Russchenberg, H.; Muller, M.

    2007-01-01

    Clouds are the great unknown quantity in predictions about climate change. For aeons they have been drifting quietly across the sky, but scientists still dont know exactly how they are formed and why they eventually come down again as rain. High time to take a closer look at clouds, say researchers

  15. Method for genetic identification of unknown organisms

    Energy Technology Data Exchange (ETDEWEB)

    Colston, Jr., Billy W.; Fitch, Joseph P.; Hindson, Benjamin J.; Carter, Chance J.; Beer, Neil Reginald

    2016-08-23

    A method of rapid, genome and proteome based identification of unknown pathogenic or non-pathogenic organisms in a complex sample. The entire sample is analyzed by creating millions of emulsion encapsulated microdroplets, each containing a single pathogenic or non-pathogenic organism sized particle and appropriate reagents for amplification. Following amplification, the amplified product is analyzed.

  16. Christian Petzold’s melodramas : From unknown woman to reciprocal unknownness in Phoenix, Wolfsburg, and Barbara

    NARCIS (Netherlands)

    Staat, W.

    2016-01-01

    Stanley Cavell’s theory of film melodrama is used for Christian Petzold’s Phoenix, Wolfsburg, and Barbara. Key for Cavell’s understanding of classical Hollywood melodrama is his notion of the ‘unknown woman.’ Remarkably, Petzold’s more contemporary melodramas feature unknown, i.e. unacknowledged,

  17. Subcritical Water Hydrolysis Effectively Reduces the In Vitro Seeding Activity of PrPSc but Fails to Inactivate the Infectivity of Bovine Spongiform Encephalopathy Prions.

    Science.gov (United States)

    Murayama, Yuichi; Yoshioka, Miyako; Okada, Hiroyuki; Takata, Eri; Masujin, Kentaro; Iwamaru, Yoshifumi; Shimozaki, Noriko; Yamamura, Tomoaki; Yokoyama, Takashi; Mohri, Shirou; Tsutsumi, Yuji

    2015-01-01

    The global outbreak of bovine spongiform encephalopathy (BSE) has been attributed to the recycling of contaminated meat and bone meals (MBMs) as feed supplements. The use of MBMs has been prohibited in many countries; however, the development of a method for inactivating BSE prions could enable the efficient and safe use of these products as an organic resource. Subcritical water (SCW), which is water heated under pressure to maintain a liquid state at temperatures below the critical temperature (374°C), exhibits strong hydrolytic activity against organic compounds. In this study, we examined the residual in vitro seeding activity of protease-resistant prion protein (PrPSc) and the infectivity of BSE prions after SCW treatments. Spinal cord homogenates prepared from BSE-infected cows were treated with SCW at 230-280°C for 5-7.5 min and used to intracerebrally inoculate transgenic mice overexpressing bovine prion protein. Serial protein misfolding cyclic amplification (sPMCA) analysis detected no PrPSc in the SCW-treated homogenates, and the mice treated with these samples survived for more than 700 days without any signs of disease. However, sPMCA analyses detected PrPSc accumulation in the brains of all inoculated mice. Furthermore, secondary passage mice, which inoculated with brain homogenates derived from a western blotting (WB)-positive primary passage mouse, died after an average of 240 days, similar to mice inoculated with untreated BSE-infected spinal cord homogenates. The PrPSc accumulation and vacuolation typically observed in the brains of BSE-infected mice were confirmed in these secondary passage mice, suggesting that the BSE prions maintained their infectivity after SCW treatment. One late-onset case, as well as asymptomatic but sPMCA-positive cases, were also recognized in secondary passage mice inoculated with brain homogenates from WB-negative but sPMCA-positive primary passage mice. These results indicated that SCW-mediated hydrolysis was

  18. Melanoma of unknown origin: a case series.

    LENUS (Irish Health Repository)

    Kelly, J

    2010-12-01

    The natural history of metastatic melanoma involving lymph nodes, in the absence of a known primary site (cutaneous, ocular or mucosal) has, to date, been poorly defined; and the optimal management of this rare subtype of disease is therefore unclear. Melanomas of unknown primary site (MUP) are estimated to comprise between 3.7 and 6% of all melanomas (Anbari et al. in Cancer 79:1861-1821, 1997).

  19. Fever of unknown origin (FUO) revised.

    Science.gov (United States)

    Unger, Manuel; Karanikas, Georgios; Kerschbaumer, Andreas; Winkler, Stefan; Aletaha, Daniel

    2016-11-01

    Fever of unknown origin (FUO) was originally characterised in 1961 by Petersdorf and Beeson as a disease condition of temperature exceeding 38.3 °C on at least three occasions over a period of at least three weeks, with no diagnosis made despite one week of inpatient investigation. However, since underlying diseases are often reported for classical FUO, these presentations may not be considered to be of "unknown origin". Rather, the aetiology of prolonged fever may resolve, or not resolve. The definition of fever with unresolved cause (true FUO) is difficult, as it is a moving target, given the constant advancement of imaging and biomarker analysis. Therefore, the prevalence of fever with unresolved cause (FUO) is unknown.In this review, we report such a case of prolonged fever, which initially has presented as classical FUO, and discuss current literature. Furthermore, we will give an outlook, how a prospective study on FUO will allow to solve outstanding issues like the utility of different diagnostic investigations, and the types and prevalence of various underlying diseases.

  20. Mammalian Remains from Indian Sites on Aruba

    NARCIS (Netherlands)

    Hooijer, D.A.

    1960-01-01

    Mr. H. R. VAN HEEKEREN and Mr. C. J. DU RY, of the Rijksmuseum voor Volkenkunde at Leiden, entrusted me with the identification of some animal remains collected from Indian sites on Aruba by Professor J. P. B. DE JOSSELIN DE JONG in 1923. These remains relate for the most part to marine turtles

  1. Luminescence of thermally altered human skeletal remains

    NARCIS (Netherlands)

    Krap, Tristan; Nota, Kevin; Wilk, Leah; van de Goot, Frank; Ruijter, Jan; Duijst, Wilma; Oostra, Roelof Jan

    2017-01-01

    Literature on luminescent properties of thermally altered human remains is scarce and contradictory. Therefore, the luminescence of heated bone was systemically reinvestigated. A heating experiment was conducted on fresh human bone, in two different media, and cremated human remains were recovered

  2. EDITORIAL MALARIA DIAGNOSIS Malaria remains the most ...

    African Journals Online (AJOL)

    hi-tech

    2005-03-02

    Mar 2, 2005 ... Malaria remains the most significant parasitic disease affecting man. Prompt and accurate diagnosis of malaria is the key to cost effective management (1). Since the identification of Plasmodium parasites in human blood in 1880, the diagnosis of malaria has remained a hot bed of scientific discussion.

  3. The Difficulty of Sexing Skeletons from Unknown Populations

    Directory of Open Access Journals (Sweden)

    Ingrid Sierp

    2015-01-01

    Full Text Available Determination of sex from skeletal remains is performed using a number of methods developed by biological anthropology. They must be evaluated for consistency and for their performance in a forensic setting. Twenty skeletons of varied provenance had their sex determined by 15 existing methods of forensic anthropology (7 metric and 8 morphological. The methods were evaluated for their consistency in determination of sex. No single individual was identified as belonging to one sex exclusively. Ambiguous results were obtained by metric methods for fourteen individuals (70% and by morphological methods for only five individuals (25% (Chi-squared = 4.3, df = 1, P<0.05. Methods which use the size of bones as an indicator of sex perform poorly on skeletal remains of individuals of unknown provenance. Methods which combine morphologic and metric techniques, that is, geometric morphometric analysis, may result in greater levels of consistency.

  4. Remaining Life Expectancy With and Without Polypharmacy

    DEFF Research Database (Denmark)

    Wastesson, Jonas W; Canudas-Romo, Vladimir; Lindahl-Jacobsen, Rune

    2016-01-01

    OBJECTIVES: To investigate the remaining life expectancy with and without polypharmacy for Swedish women and men aged 65 years and older. DESIGN: Age-specific prevalence of polypharmacy from the nationwide Swedish Prescribed Drug Register (SPDR) combined with life tables from Statistics Sweden...... was used to calculate the survival function and remaining life expectancy with and without polypharmacy according to the Sullivan method. SETTING: Nationwide register-based study. PARTICIPANTS: A total of 1,347,564 individuals aged 65 years and older who had been prescribed and dispensed a drug from July 1...... to September 30, 2008. MEASUREMENTS: Polypharmacy was defined as the concurrent use of 5 or more drugs. RESULTS: At age 65 years, approximately 8 years of the 20 remaining years of life (41%) can be expected to be lived with polypharmacy. More than half of the remaining life expectancy will be spent...

  5. Mass Remaining During Evaporation of Sessile Drop

    Science.gov (United States)

    2008-09-01

    oscillations in the mass remaining. • TRANSFORM ED t TRUEt TRUEtCont 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 TIMI (Hr) Figure 13. Effect of 3 min...2.5 2.55 2.8 TIMI (Hr) 2.86 2.1 275 2.8 Figure 14. Mass Remaining vs. Time Expanded Scale The assumed sinusoidal variation of the friction velocity

  6. To Know The Way To The Unknown

    DEFF Research Database (Denmark)

    Boysen, Mikkel Snorre Wilms

    2017-01-01

    , in various ways, expertise plays an important part in creative processes. However, the case studies also indicate that expertise sometimes leads to an entrenched perspective, in the sense that knowledge and experience may work as a path into the well-known rather than into the unknown. In this article......, these issues are explored with reference to different theoretical approaches to creativity and learning, including actor-network theory, the theory of blind variation and selective retention, and Csikszentmihalyi’s system model. Finally, some educational aspects and implications of this are discussed....

  7. TOURISM PROMOTION FOR UNKNOWN AREAS IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Fotache Lacramioara

    2013-12-01

    Full Text Available The paper is an effort to unknown areas identity affirmation, through collaborative development of advertising mix, with an emphasis on virtual platforms as admissible solution for increasing visibility. Based upon comparative effective analysis of categories of communication particularities, it is suggested a positioning strategic solution, via virtual advertising platform as unique, integrated, complex and very attractive tourism product promotion, fitted for the internal and international tourism circuit. The active promotion of the specified territorial identity will launch a brand with an impact among tourists by using marketing techniques and innovating technical means and prioritizing tourism as a principal vector of local and regional development.

  8. Exposure of RML scrapie agent to a sodium percarbonate-based product and sodium dodecyl sulfate renders PrPSc protease sensitive but does not eliminate infectivity.

    Science.gov (United States)

    Smith, Jodi D; Nicholson, Eric M; Foster, Gregory H; Greenlee, Justin J

    2013-01-11

    Prions, the causative agents of the transmissible spongiform encephalopathies, are notoriously difficult to inactivate. Current decontamination recommendations by the World Health Organization include prolonged exposure to 1 N sodium hydroxide or > 20,000 ppm sodium hypochlorite, or autoclaving. For decontamination of large stainless steel surfaces and equipment as in abattoirs, for example, these methods are harsh or unsuitable. The current study was designed to evaluate the effectiveness of a commercial product containing sodium percarbonate to inactivate prions. Samples of mouse brain infected with a mouse-adapted strain of the scrapie agent (RML) were exposed to a sodium percarbonate-based product (SPC-P). Treated samples were evaluated for abnormal prion protein (PrPSc)-immunoreactivity by western blot analysis, and residual infectivity by mouse bioassay. Exposure to a 21% solution of SPC-P or a solution containing either 2.1% or 21% SPC-P in combination with sodium dodecyl sulfate (SDS) resulted in increased proteinase K sensitivity of PrPSc. Limited reductions in infectivity were observed depending on treatment condition. A marginal effect on infectivity was observed with SPC-P alone, but an approximate 2-3 log10 reduction was observed with the addition of SDS, though exposure to SDS alone resulted in an approximate 2 log10 reduction. This study demonstrates that exposure of a mouse-adapted scrapie strain to SPC-P does not eliminate infectivity, but does render PrPSc protease sensitive.

  9. The interpretation of disease phenotypes to identify TSE strains in mice: characterisation of BSE using PrPSc distribution patterns in the brain.

    Science.gov (United States)

    Corda, Erica; Beck, Katy E; Sallis, Rosemary E; Vickery, Christopher M; Denyer, Margaret; Webb, Paul R; Bellworthy, Susan J; Spencer, Yvonne I; Simmons, Marion M; Spiropoulos, John

    2012-12-17

    In individual animals affected by transmissible spongiform encephalopathies, different disease phenotypes can be identified which are attributed to different strains of the agent. In the absence of reliable technology to fully characterise the agent, classification of disease phenotype has been used as a strain typing tool which can be applied in any host. This approach uses standardised data on biological parameters, established for a single host, to allow comparison of different prion sources. Traditionally prion strain characterisation in wild type mice is based on incubation periods and lesion profiles after the stabilisation of the agent into the new host which requires serial passages. Such analysis can take many years, due to prolonged incubation periods. The current study demonstrates that the PrPSc patterns produced by one serial passage in wild type mice of bovine or ovine BSE were consistent, stable and showed minimal and predictable differences from mouse-stabilised reference strains. This biological property makes PrPSc deposition pattern mapping a powerful tool in the identification and definition of TSE strains on primary isolation, making the process of characterisation faster and cheaper than a serial passage protocol. It can be applied to individual mice and therefore it is better suited to identify strain diversity within single inocula in case of co-infections or identify strains in cases where insufficient mice succumb to disease for robust lesion profiles to be constructed. The detailed description presented in this study provides a reference document for identifying BSE in wild type mice.

  10. Variation in Chst8 gene expression level affects PrPC to PrPSc conversion efficiency in prion-infected Mov cells.

    Science.gov (United States)

    Martin, Renaud; Chantepie, Sandrine; Chapuis, Jérôme; Le-Duc, Aurélien; Maftah, Abderrahman; Papy-Garcia, Dulcé; Laude, Hubert; Petit, Jean-Michel; Gallet, Paul-François

    2011-10-28

    The conversion of the endogenous cellular prion protein to an abnormally folded isoform is a hallmark of transmissible spongiform encephalopathies. It occurs when a misfolded prion protein contacts the cellular PrP. Among the molecular partners suggested to be involved in the misfolding process, the glycosaminoglycans seem to be good candidates. The present study was aimed to examine a possible link between PrP conversion efficiency and transcript level of Chst8 gene that encodes the carbohydrate N-acetylgalactosamine 4-O-sulfotransferase 8. Mov cells expressing ovine PrP were transfected with shRNA directed against Chst8 transcripts. Resulting clones were characterized for their Chst8 and Prnp transcript levels, and for their content in sulfated glycosaminoglycans, more particularly sulfated chondroitins. Unexpectedly, the decreased amount of Chst8 transcript induced an increase of the chondroitin sulfate percentage among total GAGs, with an increased amount of 4-O-sulfation of GalNAc residues. Upon to infection by a sheep prion, a slight amount of PrP(Sc) was observed, which rapidly disappeared upon subpassaging. Together, these findings indicate that the Chst8 transcript level affects the glycosaminoglycan environment of the cellular prion protein, and as a consequence its ability for conversion into PrP(Sc). Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Fish remains and humankind: part two

    Directory of Open Access Journals (Sweden)

    Andrew K G Jones

    1998-07-01

    Full Text Available The significance of aquatic resources to past human groups is not adequately reflected in the published literature - a deficiency which is gradually being acknowledged by the archaeological community world-wide. The publication of the following three papers goes some way to redress this problem. Originally presented at an International Council of Archaeozoology (ICAZ Fish Remains Working Group meeting in York, U.K. in 1987, these papers offer clear evidence of the range of interest in ancient fish remains across the world. Further papers from the York meeting were published in Internet Archaeology 3 in 1997.

  12. Oral inoculation of neonatal Suffolk sheep with the agent of classical scrapie results in PrPSc accumulation in sheep with the PRNP ARQ/ARQ but not the ARQ/ARR genotype

    Science.gov (United States)

    Background Scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent. Findings This study reports the failure to detect PrPSc in nervous or lymphoid tis...

  13. The Unknown Component Problem Theory and Applications

    CERN Document Server

    Villa, Tiziano; Brayton, Robert K; Mishchenko, Alan; Petrenko, Alexandre; Sangiovanni-Vincentelli, Alberto

    2012-01-01

    The Problem of the Unknown Component: Theory and Applications addresses the issue of designing a component that, combined with a known part of a system, conforms to an overall specification. The authors tackle this problem by solving abstract equations over a language. The most general solutions are studied when both synchronous and parallel composition operators are used. The abstract equations are specialized to languages associated with important classes of automata used for modeling systems. The book is a blend of theory and practice, which includes a description of a software package with applications to sequential synthesis of finite state machines. Specific topologies interconnecting the components, exact and heuristic techniques, and optimization scenarios are studied. Finally the scope is enlarged to domains like testing, supervisory control, game theory and synthesis for special omega languages. The authors present original results of the authors along with an overview of existing ones.

  14. Adresse inconnue / Address unknown / Suchwiin Bulmyeong

    Directory of Open Access Journals (Sweden)

    Serge Gruzinski

    2005-03-01

    Full Text Available Tous les films asiatiques parlent de métissage, même ceux qui se présentent comme de vastes fresques historiques perdues dans le temps. Les emprunts aux traditions hollywoodiennes et européennes n'ont cessé d'enrichir une cinématographie aussi ancienne que celle du monde occidental. Dans Adresse inconnue (Address unknown le cinéaste coréen Kim Ki-duk explore l'expérience du métissage et le corps du métis à la frontière entre Corée du Nord et Corée du sud. Fils d'un GI américain et noir et d...

  15. Information gain when measuring an unknown qubit

    Science.gov (United States)

    Björk, Gunnar

    2018-01-01

    In quantum information the fundamental information-containing system is the qubit. A measurement of a single qubit can at most yield one classical bit. However, a dichotomous measurement of an unknown qubit will yield much less information about the qubit state. We use Bayesian inference to compute how much information one progressively gets by making sucessive, individual measurements on an ensemble of identically prepared qubits. Perhaps surprisingly, even if the measurements are arranged so that each measurement yields one classical bit, that is, the two possible measurement outcomes are a priori equiprobable, it takes almost a handful of measurements before one has gained one bit of information about the gradually concentrated qubit probability density. We also show that by following a strategy that reaps the maximum information per measurement, we are led to a mutually unbiased basis as our measurement bases. This is a pleasing, although not entirely surprising, result.

  16. Education Through Exploration: Evaluating the Unknown

    Science.gov (United States)

    Anbar, A. D.

    2015-12-01

    Mastery of the peculiar and powerful practices of science is increasingly important for the average citizen. With the rise of the Internet, most of human knowledge is at our fingertips. As content becomes a commodity, success and survival aren't about who knows the most, but who is better able to explore the unknown, actively applying and extending knowledge through critical thinking and hypothesis-driven problem-solving. This applies to the economic livelihoods of individuals and to society at large as we grapple with climate change and other science-infused challenges. Unfortunately, science is too often taught as an encyclopedic collection of settled facts to be mastered rather than as a process of exploration that embraces curiosity, inquiry, testing, and communication to reduce uncertainty about the unknown. This problem is exacerbated by the continued prevalence of teacher-centric pedagogy, which promotes learning-from-authority and passive learning. The initial wave of massively open online courses (MOOCs) generally mimic this teaching style in virtual form. It is hypothesized that emerging digital teaching technologies can help address this challenge at Internet scale in "next generation" MOOCs and flipped classroom experiences. Interactive simulations, immersive virtual field trips, gamified elements, rapid adaptive feedback, intelligent tutoring systems, and personalized pathways, should motivate and enhance learning. Through lab-like projects and tutorials, students should be able to construct knowledge from interactive experiences, modeling the authentic practice of science while mastering complex concepts. Freed from lecturing, teaching staff should be available for direct and intense student-teacher interactions. These claims are difficult to evaluate with traditional assessment instruments, but digital technologies provide powerful new ways to evaluate student learning and learn from student behaviors. We will describe ongoing experiences with such

  17. The annuity puzzle remains a puzzle

    NARCIS (Netherlands)

    Peijnenburg, Kim; Nijman, Theo; Werker, Bas J. M.

    We examine incomplete annuity menus, background risk, bequest motives, and default risk as possible drivers of divergence from full annuitization. Contrary to what is often suggested in the literature, we find that full annuitization remains optimal if saving is possible after retirement. This holds

  18. Predicting the remaining service life of concrete

    Energy Technology Data Exchange (ETDEWEB)

    Clifton, J.F.

    1991-11-01

    Nuclear power plants are providing, currently, about 17 percent of the U.S. electricity and many of these plants are approaching their licensed life of 40 years. The U.S. Nuclear Regulatory Commission and the Department of Energy`s Oak Ridge National Laboratory are carrying out a program to develop a methodology for assessing the remaining safe-life of the concrete components and structures in nuclear power plants. This program has the overall objective of identifying potential structural safety issues, as well as acceptance criteria, for use in evaluations of nuclear power plants for continued service. The National Institute of Standards and Technology (NIST) is contributing to this program by identifying and analyzing methods for predicting the remaining life of in-service concrete materials. This report examines the basis for predicting the remaining service lives of concrete materials of nuclear power facilities. Methods for predicting the service life of new and in-service concrete materials are analyzed. These methods include (1) estimates based on experience, (2) comparison of performance, (3) accelerated testing, (4) stochastic methods, and (5) mathematical modeling. New approaches for predicting the remaining service lives of concrete materials are proposed and recommendations for their further development given. Degradation processes are discussed based on considerations of their mechanisms, likelihood of occurrence, manifestations, and detection. They include corrosion, sulfate attack, alkali-aggregate reactions, frost attack, leaching, radiation, salt crystallization, and microbiological attack.

  19. The case for fencing remains intact.

    Science.gov (United States)

    Packer, C; Swanson, A; Canney, S; Loveridge, A; Garnett, S; Pfeifer, M; Burton, A C; Bauer, H; MacNulty, D

    2013-11-01

    Creel et al. argue against the conservation effectiveness of fencing based on a population measure that ignores the importance of top predators to ecosystem processes. Their statistical analyses consider, first, only a subset of fenced reserves and, second, an incomplete examination of 'costs per lion.' Our original conclusions remain unaltered. © 2013 John Wiley & Sons Ltd/CNRS.

  20. Kadav Moun PSA (:60) (Human Remains)

    Centers for Disease Control (CDC) Podcasts

    2010-02-18

    This is an important public health announcement about safety precautions for those handling human remains. Language: Haitian Creole.  Created: 2/18/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 2/18/2010.

  1. Juveniles' Motivations for Remaining in Prostitution

    Science.gov (United States)

    Hwang, Shu-Ling; Bedford, Olwen

    2004-01-01

    Qualitative data from in-depth interviews were collected in 1990-1991, 1992, and 2000 with 49 prostituted juveniles remanded to two rehabilitation centers in Taiwan. These data are analyzed to explore Taiwanese prostituted juveniles' feelings about themselves and their work, their motivations for remaining in prostitution, and their difficulties…

  2. [Remaining solvents in dry cleaned over clothes].

    Science.gov (United States)

    Tashiro, H; Fujishiro, K; Matsuno, K; Kawamoto, T; Okubo, T

    1999-03-01

    We examined remaining solvents in dry cleaned trousers to estimate the magnitude of environmental pollution. A cleaning solvent of petroleum hydrocarbon was analyzed by means of capillary column mass spectrum gas chromatography. Principal ingredients were identified to be nonane, decane and undecane. The same main components were detected in dry cleaned trousers. Total amounts of evaporated vapor from a pair of trousers (480 g) in 5 days after dry cleaning were nonane (0.73 mg), decane (1.53 mg) and undecane (1.09 mg). The levels on the fifth day were 5%(nonane), 18%(decane) and 32%(undecane) of the first day's concentration, respectively. The half times of the remaining solvents were 1.0 day (nonane), 1.7 days (decane) and 2.7 days (undecane), respectively.

  3. SMART POINT CLOUD: DEFINITION AND REMAINING CHALLENGES

    OpenAIRE

    Poux, Florent; Neuville, Romain; Hallot, Pierre; Billen, Roland

    2016-01-01

    Dealing with coloured point cloud acquired from terrestrial laser scanner, this paper identifies remaining challenges for a new data structure: the smart point cloud. This concept arises with the statement that massive and discretized spatial information from active remote sensing technology is often underused due to data mining limitations. The generalisation of point cloud data associated with the heterogeneity and temporality of such datasets is the main issue regarding structure, segmenta...

  4. [Professional confidentiality: speak out or remain silent? ].

    Science.gov (United States)

    Daubigney, Jean-claude

    2014-01-01

    People who work with children, in their daily tasks, must choose whether to disclose information entrusted to them. However, they are subject to the law, which authorises or imposes speaking out or remaining silent. In terms of ethics, they can seek the best possible response while respecting professional secrecy when meeting an individual, in a situation, in a place or at a particular time. They must then take responsibility for that decision.

  5. Weight references for burned human skeletal remains from Portuguese samples.

    Science.gov (United States)

    Gonçalves, David; Cunha, Eugénia; Thompson, Tim J U

    2013-09-01

    Weight is often one of the few recoverable data when analyzing human cremains but references are still rare, especially for European populations. Mean weights for skeletal remains were thus documented for Portuguese modern cremations of both recently deceased individuals and dry skeletons, and the effect of age, sex, and the intensity of combustion was investigated using both multivariate and univariate statistics. The cremains from fresh cadavers were significantly heavier than the ones from dry skeletons regardless of sex and age cohort (p skeletal weight. The effect of the intensity of combustion in cremains weight was unclear. These weight references may, in some cases, help estimating the minimum number of individuals, the completeness of the skeletal assemblage, and the sex of an unknown individual. © 2013 American Academy of Forensic Sciences.

  6. Management of neuroendocrine tumors of unknown primary.

    Science.gov (United States)

    Alexandraki, Krystallenia; Angelousi, Anna; Boutzios, Georgios; Kyriakopoulos, Georgios; Rontogianni, Dimitra; Kaltsas, Gregory

    2017-12-04

    Neuroendocrine neoplams (NENs) are mostly relatively indolent malignancies but a significant number have metastatic disease at diagnosis mainly to the liver. Although in the majority of such cases the primary origin of the tumor can be identified, in approximately 11-22% no primary tumor is found and such cases are designated as NENs of unknown primary origin (UPO). This has significant therapeutic implications with respect to potentially resectable hepatic disease and/or application of appropriate medical therapy, either chemotherapeutic agents or targeted treatment, as the response to various treatments varies according to the origin of the primary tumor. This lack of tumor specific orientated treatment may also account for the relatively poorer prognosis of NENs of UPO compared to metastatic NENs with a known primary site. In the majority of cases the primary tumors are located in the small bowel and the lung, but a number may still elude detection. Occasionally the presence of a functional syndrome may direct to the specific tissue of origin but in the majority of cases a number of biochemical, imaging, histopathological and molecular modalities are utilized to help identify the primary origin of the tumor and direct treatment accordingly. Several diagnostic algorithms have recently been developed to help localize an occult primary tumor; however, in a number of cases no lesion is identified even after prolonged follow-up. It is expected that the delineation of the molecular signature of the different NENs may help identify such cases and provide appropriate treatment.

  7. A Physician’s Nightmare: Fever of Unknown Origin

    Directory of Open Access Journals (Sweden)

    Sana Din

    2016-01-01

    Full Text Available Fever of unknown origin (FUO remains to be a challenge despite advancement in diagnostic technologies and procedures. FUO is considered when fever presents intermittently without an explanation. It has been linked to various etiologies, which makes it difficult to diagnose. We present the case of 18-month-old female with recurrent fever, splenomegaly, abdominal pain, and constipation. The workup for her symptoms revealed wandering spleen. Wandering spleen is a result from excessive laxity or absence of splenic ligaments. The patient underwent splenectomy and was advised to continue on Senna, Miralax, and high fiber diet. Her mother reported that the fever is no longer present and there is marked improvement in her constipation and abdominal pain after splenectomy.

  8. Cancer of unknown primary origin: a case report

    Directory of Open Access Journals (Sweden)

    Elisa De Carlo

    2013-03-01

    Full Text Available Carcinoma of unknown primary origin (CUP accounts for 2-10% of all malignancies. The apparent absence of the primary tumour, the development of early, uncommon systemic metastases and the resistance to therapy and poor prognosis are hallmarks of this heterogeneous clinical entity and are a challenge for physicians. The diagnostic workup of patients with CUP includes a large amount of histopathological examination, as well as the use of imaging techniques that often fail to identify the primary tumour. Therefore, the optimal workup and treatment for these patients remains to be determined. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for "lost" CUP origin and guide the further treatment approach. We report the case of a 66-year-old man, with mediastinal lymph nodes metastasis of carcinoma and neurological syndrome with diplopia and balance disorders, in which many exams have been performed without finding the primary tumour.

  9. Distribution of albatross remains in the Far East regions during the Holocene, based on zooarchaeological remains.

    Science.gov (United States)

    Eda, Masaki; Higuchi, Hiroyoshi

    2004-07-01

    Many albatross remains have been found in the Japanese Islands and the surrounding areas, such as Sakhalin and South Korea. These remains are interesting for two reasons: numerous sites from which albatross remains have been found are located in coastal regions of the Far East where no albatrosses have been distributed recently, and there are some sites in which albatross remains represent a large portion of avian remains, although albatrosses are not easily preyed upon by human beings. We collected data on albatross remains from archaeological sites in the Far East regions during the Holocene and arranged the remains geographically, temporally and in terms of quantity. Based on these results, we showed that coastal areas along the Seas of Okhotsk and Japan have rarely been used by albatrosses in Modern times, though formerly there were many albatrosses. We proposed two explanations for the shrinkage of their distributional range: excessive hunting in the breeding areas, and distributional changes of prey for albatrosses.

  10. Shotgun microbial profiling of fossil remains

    DEFF Research Database (Denmark)

    Der Sarkissian, Clio; Ermini, Luca; Jónsson, Hákon

    2014-01-01

    Millions to billions of DNA sequences can now be generated from ancient skeletal remains thanks to the massive throughput of next-generation sequencing platforms. Except in cases of exceptional endogenous DNA preservation, most of the sequences isolated from fossil material do not originate from...... community profiling of the seven specimens revealed site-specific environmental signatures. These microbial communities appear to comprise mainly organisms that colonized the fossils recently. Our approach significantly extends the amount of useful data that can be recovered from ancient specimens using...

  11. Neanderthal infant and adult infracranial remains from Marillac (Charente, France).

    Science.gov (United States)

    Dolores Garralda, María; Maureille, Bruno; Vandermeersch, Bernard

    2014-09-01

    At the site of Marillac, near the Ligonne River in Marillac-le-Franc (Charente, France), a remarkable stratigraphic sequence has yielded a wealth of archaeological information, palaeoenvironmental data, as well as faunal and human remains. Marillac must have been a sinkhole used by Neanderthal groups as a hunting camp during MIS 4 (TL date 57,600 ± 4,600BP), where Quina Mousterian lithics and fragmented bones of reindeer predominate. This article describes three infracranial skeleton fragments. Two of them are from adults and consist of the incomplete shafts of a right radius (Marillac 24) and a left fibula (Marillac 26). The third fragment is the diaphysis of the right femur of an immature individual (Marillac 25), the size and shape of which resembles those from Teshik-Tash and could be assigned to a child of a similar age. The three fossils have been compared with the remains of other Neanderthals or anatomically Modern Humans (AMH). Furthermore, the comparison of the infantile femora, Marillac 25 and Teshik-Tash, with the remains of several European children from the early Middle Ages clearly demonstrates the robustness and rounded shape of both Neanderthal diaphyses. Evidence of peri-mortem manipulations have been identified on all three bones, with spiral fractures, percussion pits and, in the case of the radius and femur, unquestionable cutmarks made with flint implements, probably during defleshing. Traces of periostosis appear on the fibula fragment and on the immature femoral diaphysis, although their aetiology remains unknown. Copyright © 2014 Wiley Periodicals, Inc.

  12. Human prion protein (PrP) 219K is converted to PrPSc but shows heterozygous inhibition in variant Creutzfeldt-Jakob disease infection.

    Science.gov (United States)

    Hizume, Masaki; Kobayashi, Atsushi; Teruya, Kenta; Ohashi, Hiroaki; Ironside, James W; Mohri, Shirou; Kitamoto, Tetsuyuki

    2009-02-06

    Prion protein gene (PRNP) E219K is a human polymorphism commonly occurring in Asian populations but is rarely found in patients with sporadic Creutzfeldt-Jakob disease (CJD). Thus the polymorphism E219K has been considered protective against sporadic CJD. The corresponding mouse prion protein (PrP) polymorphism variant (mouse PrP 218K) is not converted to the abnormal isoform (PrP(Sc)) and shows a dominant negative effect on wild-type PrP conversion. To define the conversion activity of this human molecule, we herein established knock-in mice with human PrP 219K and performed a series of transmission experiments with human prions. Surprisingly, the human PrP 219K molecule was converted to PrP(Sc) in variant CJD infection, and the conversion occurred more efficiently than PrP 219E molecule. Notably the knock-in mice with PRNP codon 219E/K showed the least efficient conversion compared with their hemizygotes with PRNP codon 219E/0 or codon 219K/0, or homozygotes with PRNP codon 219E/E or codon 219K/K. This phenomenon indicated heterozygous inhibition. This heterozygous inhibition was observed also in knock-in mice with PRNP codon 129M/V genotype. In addition to variant CJD infection, the human PrP 219K molecule is conversion-competent in transmission experiments with sporadic CJD prions. Therefore, the protective effect of PRNP E219K against sporadic CJD might be due to heterozygous inhibition.

  13. Prion protein gene variability in Spanish goats. Inference through susceptibility to classical scrapie strains and pathogenic distribution of peripheral PrP(sc..

    Directory of Open Access Journals (Sweden)

    Cristina Acín

    Full Text Available Classical scrapie is a neurological disorder of the central nervous system (CNS characterized by the accumulation of an abnormal, partially protease resistant prion protein (PrP(sc in the CNS and in some peripheral tissues in domestic small ruminants. Whereas the pathological changes and genetic susceptibility of ovine scrapie are well known, caprine scrapie has been less well studied. We report here a pathological study of 13 scrapie-affected goats diagnosed in Spain during the last 9 years. We used immunohistochemical and biochemical techniques to discriminate between classical and atypical scrapie and bovine spongiform encephalopathy (BSE. All the animals displayed PrP(sc distribution patterns and western blot characteristics compatible with classical scrapie. In addition, we determined the complete open reading frame sequence of the PRNP in these scrapie-affected animals. The polymorphisms observed were compared with those of the herd mates (n = 665 and with the frequencies of healthy herds (n = 581 of native Spanish goats (Retinta, Pirenaica and Moncaina and other worldwide breeds reared in Spain (Saanen, Alpine and crossbreed. In total, sixteen polymorphic sites were identified, including the known amino acid substitutions at codons G37V, G127S, M137I, I142M, H143R, R151H, R154H, R211Q, Q222K, G232W, and P240S, and new polymorphisms at codons G74D, M112T, R139S, L141F and Q215R. In addition, the known 42, 138 and 179 silent mutations were detected, and one new one is reported at codon 122. The genetic differences observed in the population studied have been attributed to breed and most of the novel polymorphic codons show frequencies lower than 5%. This work provides the first basis of polymorphic distribution of PRNP in native and worldwide goat breeds reared in Spain.

  14. Estimation of symmetrical components and their orthogonal components under unknown frequencies and unknown biases

    Science.gov (United States)

    Chu, Zhaobi; Zhang, Rui; Chen, Bo; Li, Hua

    2017-07-01

    An algorithm to estimate symmetrical components, orthogonal components and amplitudes of each sinusoidal component in three-phase power system signal under unknown frequencies and unknown biases is presented. The algorithm consists of a signal transformation, a biased adaptive orthogonal decomposition (BAOD) and a symmetrical component estimation. The BAOD can be regarded as a combination of a low pass filter and a number of three-phase frequency estimators in parallel. The symmetrical component estimation employs addition and multiplication rather than operations of trigonometry, division and phase shift. The decomposition property and the convergence property were investigated by Lyapunov theorem, integral manifold of slow adaptation and average method. Two design parameters, bandwidth parameter and frequency adaptive gains, give different effects on the convergence property of frequency adaptation and amplitude estimation independently. Simulation results demonstrate the performance of the method.

  15. The knowns and unknowns of chimpanzee culture.

    Science.gov (United States)

    Gruber, Thibaud; Reynolds, Vernon; Zuberbühler, Klaus

    2010-05-01

    Claims of culture in chimpanzees appeared soon after the launch of the first field studies in africa.1 The notion of chimpanzee 'material cultures' was coined,2 and this was followed by a first formal comparison, which revealed an astonishing degree of behavioural diversity between the different study communities, mainly in terms of tool use.3 Although this behavioural diversity is still undisputed, the question of chimpanzee cultures has remained controversial.4-6 The debate has less to do with the definition of culture (most animal behaviour researchers accept the notion for behaviour that is 'transmitted repeatedly through social or observational learning to become a population-level characteristic' 3), but more with whether some key criteria are met.

  16. SMART POINT CLOUD: DEFINITION AND REMAINING CHALLENGES

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    F. Poux

    2016-10-01

    Full Text Available Dealing with coloured point cloud acquired from terrestrial laser scanner, this paper identifies remaining challenges for a new data structure: the smart point cloud. This concept arises with the statement that massive and discretized spatial information from active remote sensing technology is often underused due to data mining limitations. The generalisation of point cloud data associated with the heterogeneity and temporality of such datasets is the main issue regarding structure, segmentation, classification, and interaction for an immediate understanding. We propose to use both point cloud properties and human knowledge through machine learning to rapidly extract pertinent information, using user-centered information (smart data rather than raw data. A review of feature detection, machine learning frameworks and database systems indexed both for mining queries and data visualisation is studied. Based on existing approaches, we propose a new 3-block flexible framework around device expertise, analytic expertise and domain base reflexion. This contribution serves as the first step for the realisation of a comprehensive smart point cloud data structure.

  17. The Human Remains from HMS Pandora

    Directory of Open Access Journals (Sweden)

    D.P. Steptoe

    2002-04-01

    Full Text Available In 1977 the wreck of HMS Pandora (the ship that was sent to re-capture the Bounty mutineers was discovered off the north coast of Queensland. Since 1983, the Queensland Museum Maritime Archaeology section has carried out systematic excavation of the wreck. During the years 1986 and 1995-1998, more than 200 human bone and bone fragments were recovered. Osteological investigation revealed that this material represented three males. Their ages were estimated at approximately 17 +/-2 years, 22 +/-3 years and 28 +/-4 years, with statures of 168 +/-4cm, 167 +/-4cm, and 166cm +/-3cm respectively. All three individuals were probably Caucasian, although precise determination of ethnicity was not possible. In addition to poor dental hygiene, signs of chronic diseases suggestive of rickets and syphilis were observed. Evidence of spina bifida was seen on one of the skeletons, as were other skeletal anomalies. Various taphonomic processes affecting the remains were also observed and described. Compact bone was observed under the scanning electron microscope and found to be structurally coherent. Profiles of the three skeletons were compared with historical information about the 35 men lost with the ship, but no precise identification could be made. The investigation did not reveal the cause of death. Further research, such as DNA analysis, is being carried out at the time of publication.

  18. Cetaceans and Marine Debris: The Great Unknown

    Directory of Open Access Journals (Sweden)

    Mark Peter Simmonds

    2012-01-01

    Full Text Available Plastics and other marine debris have been found in the gastrointestinal tracts of cetaceans, including instances where large quantities of material have been found that are likely to cause impairment to digestive processes and other examples, where other morbidity and even death have resulted. In some instances, debris may have been ingested as a result of the stranding process and, in others, it may have been ingested when feeding. Those species that are suction or “ram” feeders may be most at risk. There is also evidence of entanglement of cetaceans in marine debris. However, it is usually difficult to distinguish entanglement in active fishing gear from that in lost or discarded gear. The overall significance of the threat from ingested plastics and other debris remains unclear for any population or species of cetaceans, although there are concerns for some taxa, including at the population level, and marine debris in the oceans continues to grow. Further research including the compilation of unpublished material and the investigation of important habitat areas is strongly recommended.

  19. Ghost Remains After Black Hole Eruption

    Science.gov (United States)

    2009-05-01

    NASA's Chandra X-ray Observatory has found a cosmic "ghost" lurking around a distant supermassive black hole. This is the first detection of such a high-energy apparition, and scientists think it is evidence of a huge eruption produced by the black hole. This discovery presents astronomers with a valuable opportunity to observe phenomena that occurred when the Universe was very young. The X-ray ghost, so-called because a diffuse X-ray source has remained after other radiation from the outburst has died away, is in the Chandra Deep Field-North, one of the deepest X-ray images ever taken. The source, a.k.a. HDF 130, is over 10 billion light years away and existed at a time 3 billion years after the Big Bang, when galaxies and black holes were forming at a high rate. "We'd seen this fuzzy object a few years ago, but didn't realize until now that we were seeing a ghost", said Andy Fabian of the Cambridge University in the United Kingdom. "It's not out there to haunt us, rather it's telling us something - in this case what was happening in this galaxy billions of year ago." Fabian and colleagues think the X-ray glow from HDF 130 is evidence for a powerful outburst from its central black hole in the form of jets of energetic particles traveling at almost the speed of light. When the eruption was ongoing, it produced prodigious amounts of radio and X-radiation, but after several million years, the radio signal faded from view as the electrons radiated away their energy. HDF 130 Chandra X-ray Image of HDF 130 However, less energetic electrons can still produce X-rays by interacting with the pervasive sea of photons remaining from the Big Bang - the cosmic background radiation. Collisions between these electrons and the background photons can impart enough energy to the photons to boost them into the X-ray energy band. This process produces an extended X-ray source that lasts for another 30 million years or so. "This ghost tells us about the black hole's eruption long after

  20. Focal foveal atrophy of unknown etiology: Clinical pictures and possible underlying causes

    Directory of Open Access Journals (Sweden)

    Tzu-Yun Kao

    2015-03-01

    Conclusion: This is the first report of clinical presentations for patients with focal foveal atrophy of unknown etiology. OCT aided in the diagnosis and assessment of the degree of retinal structural abnormalities, but the real etiology of foveal atrophy remains unclear.

  1. Vaginal symptoms of unknown etiology - a study in dutch general-practice

    NARCIS (Netherlands)

    Dekker, Janny H.; Boeke, A. Joan P.; Janssens, J; van Eijk, J.Th.M.

    Vaginal symptoms are frequently presented by women to general practitioners. In many cases, the aetiology of these symptoms remains unknown. This study focused on the factors associated with microbiologically unexplained vaginal symptoms, the course of symptoms and signs in these cases, and factors

  2. Control design for the SISO system with the unknown order and the unknown relative degree.

    Science.gov (United States)

    Zhao, Chunzhe; Li, Donghai

    2014-07-01

    For the uncertain system whose order, relative degree and parameters are unknown in the control design, new research is still in need on the parameter tuning and close-loop stability. During the last 10 years, much progress is made in the application and theory research of the active disturbance rejection control (ADRC) for the uncertain system. In this study, the necessary and sufficient conditions are established for building the ADRC for the minimum-phase system and the open-loop stable system when the plant parameters, orders and relative degrees are unknown, the corresponding ideal dynamics are analyzed, and the theoretical results are verified by the simulations. Considering the wide application and the long history of the PID/PI controller, a method is given to design ADRC quickly based on the existing (generalized or conventional) PID/PI controller. A plenty of simulations are made to illustrate this PID/PI-based design method and the corresponding close-loop performances. The simulation examples include the minimum/nonminimum-phase plants, the stable/integrating plants, the high/low-order plant, and the plants with time delays. Such plants are from a wider scope than the theoretical result, and representative of many kinds of the industrial processes. That leads to a new way to simplify the ADRC design via absorbing the engineering experience in designing the PID/PI controller. © 2013 ISA. Published by ISA. All rights reserved.

  3. Variable levels of 37-kDa/67-kDa laminin receptor (RPSA) mRNA in ovine tissues: potential contribution to the regulatory processes of PrPSc propagation?

    Science.gov (United States)

    Qiao, Jun-Wen; Su, Xiao-Ou; Li, Yu-Xing; Yang, Jian-Min; Wang, Yi-Qin; Kouadir, Mohammed; Zhou, Xiang-Mei; Yang, Li-Feng; Yin, Xiao-Min; Zhao, De-Ming

    2009-01-01

    The 37-kDa laminin receptor precursor/67-kDa laminin receptor (LRP/LR, also known as ribosomal protein SA, RPSA) has been reported to be involved in cancer development and prion internalization. Previous studies have shown that the LRP/LR is expressed in a wide variety of tissues. In particular, expression of LRP/LR mRNA may be closely related to the degree of PrP(Sc) propagation. This study presents a detailed investigation of the LRP/LR mRNA expression levels in eleven normal ovine tissues. Using real-time quantitative PCR, the highest LRP/LR expression was found in neocortex (p < 0.05). Slightly lower levels were found in the heart and obex. Intermediate levels were seen in hippocampus, cerebellum, spleen, thalamus, mesenteric lymph node, and the lowest levels were present in liver, kidney, and lung. In general, the LRP/LR mRNA levels were much higher in neuronal tissues than in peripheral tissues. The observation that differences in LRP/LR mRNA expression levels are consistent with the corresponding variation in PrP(Sc) accumulation suggests that the 37-kDa/67-kDa laminin receptor may be involved in the regulation of PrP(Sc) propagation.

  4. Identification of an unknown extraneous contaminant in pharmaceutical product analysis.

    Science.gov (United States)

    Lin, Mingxiang; Li, Min; Rustum, Abu

    2007-12-21

    During the content uniformity test of a drug product (tablet formulation), an unknown peak was observed in the HPLC chromatograms. Upon further investigation, it was determined that the unknown peak was originated from an external source and, therefore, the drug product is free of this unknown peak. The next step was to identify the structure of this unknown peak in order to determine the source of this contaminant species. In this paper, we wish to present the strategy and the results of the experiments that led to the identification of this unknown peak. LC-PDA/UV and LC-MS(n) analyses were conducted to obtain the UV spectrum, molecular weight and MS(n) fragmentation pathways of the unknown peak. The MS analysis revealed certain structural features of the unknown species and a number of model compounds that contain such features were then examined for their UV absorbance profiles in an attempt to establish the functional group connectivity within the unknown species. A careful examination of these results in conjunction with the determination of the high-resolution molecular weight led to a short list of potential candidates for the unknown species, among which the most likely one was 1,3-diphenylguanidine. The identification of the unknown contaminant was confirmed by spiking experiments using the authentic compound. The potential source of this contaminant was also identified as derived from the safety filler of the pipette bulb used to prepare the sample solutions during the drug analysis.

  5. Chronic kidney disease of unknown etiology in Sri Lanka.

    Science.gov (United States)

    Rajapakse, Senaka; Shivanthan, Mitrakrishnan Chrishan; Selvarajah, Mathu

    2016-07-01

    In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1-22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization.

  6. Ultrastructural mitochondrial alterations in equine myopathies of unknown origin.

    Science.gov (United States)

    Van Driessche, K; Ducatelle, R; Chiers, K; Van Coster, R; van der Kolk, J H; van der Kolk, H

    2015-03-01

    Very few mitochondrial myopathies have been described in horses. To examine the ultrastructure of muscle mitochondria in equine cases of myopathy of unknown origin. Biopsies of vastus lateralis of the Musculus quadriceps femoris were taken predominantly immediately post mortem and processed for transmission electron microscopy. As a result, electron micrographs of 90 horses in total were available for analysis comprising 4 control horses, 16 horses suffering from myopathy and 70 otherwise diseased horses. Following a thorough clinical and laboratory work-up, four out of five patients that did not fit into the usual algorithm to detect known causes of myopathy showed ultrastructural mitochondrial alterations. Small mitochondria with zones with complete disruption of cristae associated with lactic acidemia were detected in a 17-year-old pony mare, extremely long and slender mitochondria with longitudinal cristae in a 5-year-old Quarter horse stallion, a mixture of irregular extremely large mitochondria (measuring 2500 by 800 nm) next to smaller ones in an 8-year-old Hanoverian mare and round mitochondria with only few cristae in a 11-year-old pony gelding. It remains uncertain whether the subsarcolemmal mitochondrial accumulations observed in the fifth patient have any pathological significance. Ultrastructural alterations in mitochondria were detected in at least four horses. To conclude that these are due to mitochondrial dysfuntions, biochemical tests should be performed. The possibility of a mitochondrial myopathy should be included in the differential diagnosis of muscle weakness.

  7. Anaerobic oxidation of methane: progress with an unknown process.

    Science.gov (United States)

    Knittel, Katrin; Boetius, Antje

    2009-01-01

    Methane is the most abundant hydrocarbon in the atmosphere, and it is an important greenhouse gas, which has so far contributed an estimated 20% of postindustrial global warming. A great deal of biogeochemical research has focused on the causes and effects of the variation in global fluxes of methane throughout earth's history, but the underlying microbial processes and their key agents remain poorly understood. This is a disturbing knowledge gap because 85% of the annual global methane production and about 60% of its consumption are based on microbial processes. Only three key functional groups of microorganisms of limited diversity regulate the fluxes of methane on earth, namely the aerobic methanotrophic bacteria, the methanogenic archaea, and their close relatives, the anaerobic methanotrophic archaea (ANME). The ANME represent special lines of descent within the Euryarchaeota and appear to gain energy exclusively from the anaerobic oxidation of methane (AOM), with sulfate as the final electron acceptor according to the net reaction: CH(4) + SO(42-) ---> HCO(3-) + HS(-) + H(2)O. This review summarizes what is known and unknown about AOM on earth and its key catalysts, the ANME clades and their bacterial partners.

  8. Challenges of the Unknown: Clinical Application of Microbial Metagenomics

    Directory of Open Access Journals (Sweden)

    Graham Rose

    2015-01-01

    Full Text Available Availability of fast, high throughput and low cost whole genome sequencing holds great promise within public health microbiology, with applications ranging from outbreak detection and tracking transmission events to understanding the role played by microbial communities in health and disease. Within clinical metagenomics, identifying microorganisms from a complex and host enriched background remains a central computational challenge. As proof of principle, we sequenced two metagenomic samples, a known viral mixture of 25 human pathogens and an unknown complex biological model using benchtop technology. The datasets were then analysed using a bioinformatic pipeline developed around recent fast classification methods. A targeted approach was able to detect 20 of the viruses against a background of host contamination from multiple sources and bacterial contamination. An alternative untargeted identification method was highly correlated with these classifications, and over 1,600 species were identified when applied to the complex biological model, including several species captured at over 50% genome coverage. In summary, this study demonstrates the great potential of applying metagenomics within the clinical laboratory setting and that this can be achieved using infrastructure available to nondedicated sequencing centres.

  9. Highly efficient DNA extraction method from skeletal remains

    Directory of Open Access Journals (Sweden)

    Irena Zupanič Pajnič

    2011-03-01

    Full Text Available Background: This paper precisely describes the method of DNA extraction developed to acquire high quality DNA from the Second World War skeletal remains. The same method is also used for molecular genetic identification of unknown decomposed bodies in routine forensic casework where only bones and teeth are suitable for DNA typing. We analysed 109 bones and two teeth from WWII mass graves in Slovenia. Methods: We cleaned the bones and teeth, removed surface contaminants and ground the bones into powder, using liquid nitrogen . Prior to isolating the DNA in parallel using the BioRobot EZ1 (Qiagen, the powder was decalcified for three days. The nuclear DNA of the samples were quantified by real-time PCR method. We acquired autosomal genetic profiles and Y-chromosome haplotypes of the bones and teeth with PCR amplification of microsatellites, and mtDNA haplotypes 99. For the purpose of traceability in the event of contamination, we prepared elimination data bases including genetic profiles of the nuclear and mtDNA of all persons who have been in touch with the skeletal remains in any way. Results: We extracted up to 55 ng DNA/g of the teeth, up to 100 ng DNA/g of the femurs, up to 30 ng DNA/g of the tibias and up to 0.5 ng DNA/g of the humerus. The typing of autosomal and YSTR loci was successful in all of the teeth, in 98 % dekalof the femurs, and in 75 % to 81 % of the tibias and humerus. The typing of mtDNA was successful in all of the teeth, and in 96 % to 98 % of the bones. Conclusions: We managed to obtain nuclear DNA for successful STR typing from skeletal remains that were over 60 years old . The method of DNA extraction described here has proved to be highly efficient. We obtained 0.8 to 100 ng DNA/g of teeth or bones and complete genetic profiles of autosomal DNA, Y-STR haplotypes, and mtDNA haplotypes from only 0.5g bone and teeth samples.

  10. Establishing quantitative real-time quaking-induced conversion (qRT-QuIC) for highly sensitive detection and quantification of PrPSc in prion-infected tissues.

    Science.gov (United States)

    Shi, Song; Mitteregger-Kretzschmar, Gerda; Giese, Armin; Kretzschmar, Hans A

    2013-08-02

    PrPSc, the only known constituent of prions, the infectious agents causing prion diseases, can be detected by real-time quaking-induced conversion (RT-QuIC). However, there is no efficient method to quantify the amount of PrPSc by RT-QuIC. Here we introduce quantitative RT-QuIC (qRT-QuIC) to quantify with high accuracy minute amounts of PrPSc in the brain and various peripheral tissues at levels far below detection by in vivo transmission. PrPSc is relatively resistant to treatment with proteinase K (PK). However, as there can also be a fraction of pathological PrP that is digested by PK, we use the term PrP27-30 to denote to the amount of PrPSc that can be detected by immunoblot after PK treatment. qRT-QuIC is based upon the quantitative correlation between the seeded amount of PrP27-30 and the lag time to the start of the conversion reaction detected by RT-QuIC. By seeding known amounts of PrP27-30 quantified by immunoblot into qRT-QuIC a standard calibration curve can be obtained. Based on this calibration curve, seeded undetermined amounts of PrP27-30 can be directly calculated. qRT-QuIC allowed to quantify PrP27-30 concentrations at extremely low levels as low as 10-15.5 g PrP27-30, which corresponds to 0.001 LD50 units obtained by in vivo i.c. transmission studies. We find that PrP27-30 concentration increases steadily in the brain after inoculation and can be detected at various time points during the incubation period in peripheral organs (spleen, heart, muscle, liver, kidney) in two experimental scrapie strains (RML, ME7) in the mouse. We suggest that an automatic quantitative system to measure disease progression as well as prion contamination of organs, blood and food product is feasible. Moreover, the concept of qRT-QuIC should be applicable to measure other disease-associated proteins rich in β-pleated structures (amyloid) that bind ThT and that show seeded aggregation.

  11. The new right for all Colombians to retain their telephone numbers (a right which remains unknown if it is not demanded

    Directory of Open Access Journals (Sweden)

    Mauro Flórez Calderón

    2005-05-01

    Full Text Available Recognising rights and their evolution in terms of their varied classification and interpretation has followed a long and tortuous path throughout the ages. Body and soul originally belonged to the state; the middle ages saw mooring to the land for ever. The Petition of Right in 1628 (determining that no man could be arrested or detained without ludicial formality, the Habeas Corpus Act of 1679 (the corner-stone of English public freedom and the French Constituent Assembly’s rights of man and citizens rights in 1789 represent the most important milestones on the way. Contemporary rights would include the right to information, monetary stability and a user’s right to retain his/her telephone number (1995. The present article’s oblect is to broadcast this new users’ right, establish the state of the art, alert people to possible difficulties and propose some strategies for implementing such rights.

  12. 16 CFR 303.14 - Products containing unknown fibers.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Products containing unknown fibers. 303.14... RULES AND REGULATIONS UNDER THE TEXTILE FIBER PRODUCTS IDENTIFICATION ACT § 303.14 Products containing unknown fibers. (a) Where a textile fiber product is made from miscellaneous scraps, rags, odd lots...

  13. 37 CFR 381.9 - Unknown copyright owners.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Unknown copyright owners. 381.9 Section 381.9 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS... EDUCATIONAL BROADCASTING § 381.9 Unknown copyright owners. If PBS and its stations, NPR and its stations, or...

  14. 37 CFR 253.9 - Unknown copyright owners.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Unknown copyright owners. 253.9 Section 253.9 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT... NONCOMMERCIAL EDUCATIONAL BROADCASTING § 253.9 Unknown copyright owners. If PBS and its stations, NPR and its...

  15. 37 CFR 382.7 - Unknown copyright owners.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Unknown copyright owners. 382.7 Section 382.7 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS... SATELLITE DIGITAL AUDIO RADIO SERVICES Preexisting Subscription Services § 382.7 Unknown copyright owners...

  16. 37 CFR 260.7 - Unknown copyright owners.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Unknown copyright owners. 260.7 Section 260.7 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT... TRANSMISSIONS OF SOUND RECORDINGS AND MAKING OF EPHEMERAL PHONORECORDS § 260.7 Unknown copyright owners. If the...

  17. Known unknowns: indirect energy effects of information and communication technology

    Science.gov (United States)

    Horner, Nathaniel C.; Shehabi, Arman; Azevedo, Inês L.

    2016-10-01

    Background. There has been sustained and growing interest in characterizing the net energy impact of information and communication technology (ICT), which results from indirect effects offsetting (or amplifying) the energy directly consumed by ICT equipment. These indirect effects may be either positive or negative, and there is considerable disagreement as to the direction of this sign as well as the effect magnitude. Literature in this area ranges from studies focused on a single service (such as e-commerce versus traditional retail) to macroeconomic studies attempting to characterize the overall impact of ICT. Methods. We review the literature on the indirect energy effect of ICT found via Google Scholar, our own research, and input from other researchers in the field. The various studies are linked to an effect taxonomy, which is synthesized from several different hierarchies present in the literature. References are further grouped according to ICT service (e.g., e-commerce, telework) and summarized by scope, method, and quantitative and qualitative findings. Review results. Uncertainty persists in understanding the net energy effects of ICT. Results of indirect energy effect studies are highly sensitive to scoping decisions and assumptions made by the analyst. Uncertainty increases as the impact scope broadens, due to complex and interconnected effects. However, there is general agreement that ICT has large energy savings potential, but that the realization of this potential is highly dependent on deployment details and user behavior. Discussion. While the overall net effect of ICT is likely to remain unknown, this review suggests several guidelines for improving research quality in this area, including increased data collection, enhancing traditional modeling studies with sensitivity analysis, greater care in scoping, less confidence in characterizing aggregate impacts, more effort on understanding user behavior, and more contextual integration across the

  18. Treatment of Regional Metastatic Melanoma of Unknown Primary Origin

    Directory of Open Access Journals (Sweden)

    Elke J. A. H. van Beek

    2015-08-01

    Full Text Available (1 Background: The purpose of this retrospective study was to evaluate the recurrence and survival rates of metastatic melanoma of unknown primary origin (MUP, in order to further refine current recommendations for the surgical treatment; (2 Methods: Medical data of all MUP patients registered between 2000 and 2011, were analyzed. Seventy-eight patients were categorized in either lymph node (axilla, groin, head-and neck or subcutaneous MUP. Axillary node MUPs were generally treated with dissections of levels I-III, inguinal node MUPs with combined superficial and deep groin dissections, and head-and-neck node MUPs with neck dissections to various extents, based on lymph drainage patterns. Subcutaneous lesions were excised with 1–2 cm margins. The primary outcome was treatment outcomes in terms of (locoregional recurrence and survival rates; (3 Results: Lymph node MUP recurred regionally in 11% of patients, with an overall recurrence rate of 45%. In contrast, subcutaneous MUP recurred locally in 65% of patients with an overall recurrence rate of 78%. This latter group had a significantly shorter disease-free interval than patients with lymph node MUP (p = 0.000. In the entire study population, 5-year and 10-year overall survival rates were 56% and 47% respectively, with no differences observed between the various subgroups; (4 Conclusion: The relatively low regional recurrence rate after regional lymph node dissection (11% supports its current status as standard surgical treatment for lymph node MUP. Subcutaneous MUP, on the contrary, appears to recur both locally (65% and overall (78% at a significantly higher rate, suggesting a different biological behavior. However, wide local excision remains the best available option for this specific group.

  19. Grasping Unknown Objects in an Early Cognitive Vision System

    DEFF Research Database (Denmark)

    Popovic, Mila

    2011-01-01

    Grasping of unknown objects presents an important and challenging part of robot manipulation. The growing area of service robotics depends upon the ability of robots to autonomously grasp and manipulate a wide range of objects in everyday environments. Simple, non task-specific grasps of unknown...... presents a system for robotic grasping of unknown objects us- ing stereo vision. Grasps are defined based on contour and surface information provided by the Early Cognitive Vision System, that organizes visual informa- tion into a biologically motivated hierarchical representation. The contributions...

  20. Adaptive interferometric null testing for unknown freeform optics metrology.

    Science.gov (United States)

    Huang, Lei; Choi, Heejoo; Zhao, Wenchuan; Graves, Logan R; Kim, Dae Wook

    2016-12-01

    We report an adaptive interferometric null testing method for overcoming the dynamic range limitations of conventional null testing approaches during unknown freeform optics metrology or optics manufacturing processes that require not-yet-completed surface measurements to guide the next fabrication process. In the presented adaptive method, a deformable mirror functions as an adaptable null component for an unknown optical surface. The optimal deformable mirror's shape is determined by the stochastic parallel gradient descent algorithm and controlled by a deflectometry system. An adaptive interferometric null testing setup was constructed, and its metrology data successfully demonstrated superb adaptive capability in measuring an unknown surface.

  1. The Ven. Charles Theophilus Hahn, a hitherto unknown Edwardian botanical illustrator in Natal, 1908—1916

    Directory of Open Access Journals (Sweden)

    J. P. Rourke

    1992-10-01

    Full Text Available A brief biographical sketch is given of the Rev. C.T. Hahn, an English-born, Oxford-educated Anglican missionary in Zululand who painted some 235 watercolours of Natal flora between 1908 and 1913. Hahn (who later changed his name to Headley was one of the most productive of the early botanical illustrators in Natal but as a collection of his paintings has only recently been discovered, his work has until hitherto remained unknown.

  2. Effects of Memory Colour on Colour Constancy for Unknown Coloured Objects

    OpenAIRE

    Jeroen J M Granzier; Gegenfurtner, Karl R.

    2012-01-01

    The perception of an object's colour remains constant despite large variations in the chromaticity of the illumination—colour constancy. Hering suggested that memory colours, the typical colours of objects, could help in estimating the illuminant's colour and therefore be an important factor in establishing colour constancy. Here we test whether the presence of objects with diagnostical colours (fruits, vegetables, etc) within a scene influence colour constancy for unknown coloured objects in...

  3. Fever of unknown origin − diagnostic methods in a European developing country

    OpenAIRE

    Bosilkovski Mile; Dimzova Marija; Stevanović Milena; Semenakova-Cvetkovska Vesna; Vasileva-Duganovska Maja

    2016-01-01

    Background/Aim. Fewer of unknown origin (FUO) remains amongst the most difficult diagnostic dilemmas in contemporary medicine. The aim of this study was to determine the causes of FUO and to identify the methods of diagnosis in patients with FUO in a tertiary care setting in the Republic of Macedonia. Methods. Retrospectively histories of 123 immunocompetent patients older than 14 years with classical FUO that had been examined at the University Hospital fo...

  4. The Unknown Computer Viruses Detection Based on Similarity

    Science.gov (United States)

    Liu, Zhongda; Nakaya, Naoshi; Koui, Yuuji

    New computer viruses are continually being generated and they cause damage all over the world. In general, current anti-virus software detects viruses by matching a pattern based on the signature; thus, unknown viruses without any signature cannot be detected. Although there are some static analysis technologies that do not depend on signatures, virus writers often use code obfuscation techniques, which make it difficult to execute a code analysis. As is generally known, unknown viruses and known viruses share a common feature. In this paper we propose a new static analysis technology that can circumvent code obfuscation to extract the common feature and detect unknown viruses based on similarity. The results of evaluation experiments demonstrated that this technique is able to detect unknown viruses without false positives.

  5. Metastatic cervical carcinoma from an unknown primary: literature review

    National Research Council Canada - National Science Library

    Arrangoiz, Rodrigo; Galloway, Tom J; Papavasiliou, Pavlos; Ridge, John A; Lango, Miriam N

    2014-01-01

    Carcinoma of an unknown primary (CUP) encompasses a heterogeneous group of tumors for which no primary site can be detected following a thorough history, physical examination, and noninvasive and invasive testing...

  6. Using the Wheatstone Bridge to Compute Unknown Resistances.

    Science.gov (United States)

    Schlenker, Richard M.

    This document presents a secondary level physics unit which introduces students to the Wheatstone Bridge, its use in determining the value of unknown resistors, and the effects of wiring resistors in series or in parallel. (SL)

  7. Bone metastases of unknown origin: epidemiology and principles of management

    National Research Council Canada - National Science Library

    Piccioli, Andrea; Maccauro, Giulio; Spinelli, Maria Silvia; Biagini, Roberto; Rossi, Barbara

    2015-01-01

    ... % of patients present with bone metastases of unknown origin, where the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination...

  8. Persistent Surveillance of Transient Events with Unknown Statistics

    Science.gov (United States)

    2016-12-18

    stochastic and transient, their exact time of occurrence cannot be known apriori . Hence, the monitoring process requires the robot to visit each location and...unknown apriori . These relaxed assumptions are in contrast to previous problem definitions such as those in [1], [2], [3], where the statistics of...and the canonical problem of prediction with expert advice where the best expert is unknown apriori . An even more profound relationship and similarity

  9. Fast and Automatic Detection and Segmentation of Unknown Objects

    OpenAIRE

    Kootstra, Gert; Bergström, Niklas; Kragic, Danica

    2010-01-01

    This paper focuses on the fast and automatic detection and segmentation of unknown objects in unknown environments. Many existing object detection and segmentation methods assume prior knowledge about the object or human interference. However, an autonomous system operating in the real world will often be confronted with previously unseen objects. To solve this problem, we propose a segmentation approach named Automatic Detection And Segmentation (ADAS). For the detection of objects, we use s...

  10. Stochastic Online Learning in Dynamic Networks under Unknown Models

    Science.gov (United States)

    2016-08-02

    Stochastic Online Learning in Dynamic Networks under Unknown Models This research aims to develop fundamental theories and practical algorithms for...12211 Research Triangle Park, NC 27709-2211 Online learning , multi-armed bandit, dynamic networks REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S... Online Learning in Dynamic Networks under Unknown Models Report Title This research aims to develop fundamental theories and practical algorithms for

  11. Dissociation between transmissible spongiform encephalopathy (TSE) infectivity and proteinase K-resistant PrP(Sc) levels in peripheral tissue from a murine transgenic model of TSE disease.

    Science.gov (United States)

    Dobie, Karen; Barron, Rona

    2013-05-01

    Most current diagnostic tests for transmissible spongiform encephalopathies (TSE) rely on the presence of proteinase K (PK)-resistant PrP(Sc) (PrP-res) in postmortem tissues as an indication of TSE disease. However, a number of studies have highlighted a discrepancy between TSE infectivity and PrP-res levels in both natural and experimental cases of TSE disease. Previously, we have shown high TSE infectivity levels in the brain tissue of mice that have a clinical TSE disease with associated vacuolar pathology but little or no detectable PrP-res. Here, the levels of TSE infectivity and PrP-res within a peripheral tissue of this mouse model were investigated. Biochemical analysis showed that low levels of PrP-res were present in the spleen tissue in comparison to the levels observed in the spleen of mice infected with ME7 or 79A. However, upon subpassage of brain and spleen tissue from clinically ill mice with little or no PrP-res detectable, similar short incubation periods to disease were observed, indicating that infectivity levels were similarly high in both tissues. Thus, the discrepancy between PrP-res and TSE infectivity was also present in the peripheral tissues of this disease model. This result indicates that peripheral tissues can contain higher levels of infectivity given the correct combination of host species, PrP genotype, and TSE agent. Therefore, the assumption that the levels of peripheral infectivity are lower than those in the central nervous system is not always correct, and this could have implications for current food safety regulations.

  12. Chinese Unknown Word Recognition for PCFG-LA Parsing

    Directory of Open Access Journals (Sweden)

    Qiuping Huang

    2014-01-01

    Full Text Available This paper investigates the recognition of unknown words in Chinese parsing. Two methods are proposed to handle this problem. One is the modification of a character-based model. We model the emission probability of an unknown word using the first and last characters in the word. It aims to reduce the POS tag ambiguities of unknown words to improve the parsing performance. In addition, a novel method, using graph-based semisupervised learning (SSL, is proposed to improve the syntax parsing of unknown words. Its goal is to discover additional lexical knowledge from a large amount of unlabeled data to help the syntax parsing. The method is mainly to propagate lexical emission probabilities to unknown words by building the similarity graphs over the words of labeled and unlabeled data. The derived distributions are incorporated into the parsing process. The proposed methods are effective in dealing with the unknown words to improve the parsing. Empirical results for Penn Chinese Treebank and TCT Treebank revealed its effectiveness.

  13. Charting the Unknown: A Hunt in the Dark

    Science.gov (United States)

    Mohlabeng, Gopolang Mokoka

    Astrophysical and cosmological observations have pointed strongly to the existence of dark matter in the Universe, yet its nature remains elusive. It may be hidden in a vast unknown parameter space in which exhaustively searching for a signal is not feasible. We are, therefore, compelled to consider a robust program based on a wide range of new theoretical ideas and complementary strategies for detection. The aim of this dissertation is to investigate the phenomenology of diverse dark sectors with the objective of understanding and characterizing dark matter. We do so by exploring dark matter phenomenology under three main frameworks of study: (I) the model dependent approach, (II) model independent approach and (III) considering simplified models. In each framework we focus on unexplored and well motivated dark matter scenarios as well as their prospects of detection at current and future experiments. First, we concentrate on the model dependent method where we consider minimal dark matter in the form of mixed fermionic stable states in a gauge extension of the standard model. In particular, we incorporate the fermion mixings governed by gauge invariant interactions with the heavier degrees of freedom. We find that the manner of mixing has an impact on the detectability of the dark matter at experiments. Pursuing this model dependent direction, we explore a space-time extension of the standard model which houses a vector dark matter candidate. We incorporate boundary terms arising from the topology of the model and find that these control the way dark matter may interact with baryonic matter. Next we investigate the model independent approach in which we examine a non-minimal dark sector in the form of boosted dark matter. In this study, we consider an effective field theory involving two stable fermionic states. We probe the sensitivity of this type of dark matter coming from the galactic center and the center of the Sun, and investigate its detection prospects

  14. A novel approach for scrapie-associated prion (PrPSc) detection in blood using the competitive affinity of an aggregate-specific antibody and streptavidin to PrPSc.

    Science.gov (United States)

    Soutyrine, Andrei; Huang, Hongsheng; Andrievskaia, Olga; Walther, Ines; Mitchell, Gordon

    2017-08-01

    Scrapie is a fatal neurodegenerative disorder affecting sheep and goats, originating from exposure to disease-associated prions (PrP Sc ). An ante-mortem screening test that can detect native PrP Sc in body fluids remains unavailable due to insufficient sensitivity of current detection methods that involve proteinase or denaturation treatments. We adopted an approach to detect PrP Sc in whole blood using a simple proteinase- and denaturation-independent immunoassay, based on the competitive affinity of an aggregate-specific monoclonal antibody and streptavidin to PrP Sc . First, we demonstrated the ability of native PrP Sc to bind to streptavidin and the inhibition of this interaction by 15B3 antibody (P<0.05). This led to a new two-step assay that involved capturing native prions from infected blood on a solid-state matrix and detection of PrP Sc aggregates by evaluating the conformation-dependent conjugate catalytic activity ratio in samples against a pre-determined threshold. This test showed capacity for detecting scrapie prions in 500μl of sheep whole blood spiked with scrapie brain homogenate containing approximately 5ng of total brain protein, and estimated to have 500fg of PrP Sc . The test also discriminated between blood samples from scrapie-negative (6 sheep, 4 goats) and scrapie-infected animals (3 experimentally infected sheep, 7 naturally infected goats). Collectively, with the proposed high-throughput sample-processing platform, these initial studies provide insights into the development of a large-scale screening test for the routine diagnosis of scrapie. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  15. Biomarkers for Ectopic Pregnancy and Pregnancy of Unknown Location

    Science.gov (United States)

    Senapati, Suneeta; Barnhart, Kurt T.

    2013-01-01

    Early pregnancy failure is the most common complication of pregnancy, and 1–2% of all pregnancies will be ectopic. As one of the leading causes of maternal morbidity and mortality, diagnosing ectopic pregnancy and determining the fate of a pregnancy of unknown location are of great clinical concern. Several serum and plasma biomarkers for ectopic pregnancy have been investigated independently and in combination. The following is a review of the state of biomarker discovery and development for ectopic pregnancy and pregnancy of unknown location. PMID:23290746

  16. Fever of unknown origin, giant cell arteritis, and aortic dissection.

    Science.gov (United States)

    Hofheinz, K; Bertz, S; Wacker, J; Schett, G; Manger, B

    2017-02-01

    Giant cell arteritis is one of the most frequent causes of pyrexia of unknown origin after infectious or malignant causes have been ruled out. In this case report we describe a 66-year old female patient, who after five weeks of remitting fever developed a life-threatening, painless severe aortic dissection. The timely use of modern imaging technologies such as magnetic resonance angiography or positron emission computed tomography could in the future be of help to recognize aortic involvement early and to avoid this devastating complication in patients with fever of unknown origin.

  17. Prediction of Primary Tumors in Cancers of Unknown Primary

    DEFF Research Database (Denmark)

    Søndergaard, Dan; Nielsen, Svend; Pedersen, Christian N S

    2017-01-01

    A cancer of unknown primary (CUP) is a metastatic cancer for which standard diagnostic tests fail to identify the location of the primary tumor. CUPs account for 3-5% of cancer cases. Using molecular data to determine the location of the primary tumor in such cases can help doctors make the right...... treatment choice and thus improve the clinical outcome. In this paper, we present a new method for predicting the location of the primary tumor using gene expression data: locating cancers of unknown primary (LoCUP). The method models the data as a mixture of normal and tumor cells and thus allows correct...

  18. PrP-C1 fragment in cattle brains reveals features of the transmissible spongiform encephalopathy associated PrPsc.

    Science.gov (United States)

    Serra, Fabienne; Müller, Joachim; Gray, John; Lüthi, Ramona; Dudas, Sandor; Czub, Stefanie; Seuberlich, Torsten

    2017-03-15

    Three different types of bovine spongiform encephalopathy (BSE) are known and supposedly caused by distinct prion strains: the classical (C-) BSE type that was typically found during the BSE epidemic, and two relatively rare atypical BSE types, termed H-BSE and L-BSE. The three BSE types differ in the molecular phenotype of the disease associated prion protein, namely the N-terminally truncated proteinase K (PK) resistant prion protein fragment (PrP res ). In this study, we report and analyze yet another PrP res type (PrP res-2011 ), which was found in severely autolytic brain samples of two cows in the framework of disease surveillance in Switzerland in 2011. Analysis of brain tissues from these animals by PK titration and PK inhibitor assays ruled out the process of autolysis as the cause for the aberrant PrP res profile. Immunochemical characterization of the PrP fragments present in the 2011 cases by epitope mapping indicated that PrP res-2011 corresponds in its primary sequence to the physiologically occurring PrP-C1 fragment. However, high speed centrifugation, sucrose gradient assay and NaPTA precipitation revealed biochemical similarities between PrP res-2011 and the disease-associated prion protein found in BSE affected cattle in terms of detergent insolubility, PK resistance and PrP aggregation. Although it remains to be established whether PrP res-2011 is associated with a transmissible disease, our results point out the need of further research on the role the PrP-C1 aggregation and misfolding in health and disease. Copyright © 2017. Published by Elsevier B.V.

  19. 7 CFR 160.29 - Containers to remain intact.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Containers to remain intact. 160.29 Section 160.29... STANDARDS FOR NAVAL STORES Analysis, Inspection, and Grading on Request § 160.29 Containers to remain intact... the containers holding such naval stores remain intact as sampled until the analysis, classification...

  20. Adaptive fuzzy prescribed performance control for MIMO nonlinear systems with unknown control direction and unknown dead-zone inputs.

    Science.gov (United States)

    Shi, Wuxi; Luo, Rui; Li, Baoquan

    2017-01-01

    In this study, an adaptive fuzzy prescribed performance control approach is developed for a class of uncertain multi-input and multi-output (MIMO) nonlinear systems with unknown control direction and unknown dead-zone inputs. The properties of symmetric matrix are exploited to design adaptive fuzzy prescribed performance controller, and a Nussbaum-type function is incorporated in the controller to estimate the unknown control direction. This method has two prominent advantages: it does not require the priori knowledge of control direction and only three parameters need to be updated on-line for this MIMO systems. It is proved that all the signals in the resulting closed-loop system are bounded and that the tracking errors converge to a small residual set with the prescribed performance bounds. The effectiveness of the proposed approach is validated by simulation results. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  1. Detection of unknown occult primary tumors using positron emission tomography

    NARCIS (Netherlands)

    Kole, AC; Nieweg, OE; Pruim, J; Hoekstra, HJ; Roodenburg, JLN; Vaalburg, W; Vermey, A; Schraffordt Koops, H.

    1998-01-01

    BACKGROUND. The potential of positron emission tomography (PET) with F-18-fluoro-2-deoxy-D-glucose (FDG) to detect primary tumors after unsuccessful conventional diagnostic workup was assessed in patients with metastatic disease from an unknown primary tumor. METHODS. Twenty-nine patients with

  2. Prevalence and predictors of unknown HIV status among women ...

    African Journals Online (AJOL)

    Introduction: Knowledge of a person's HIV status during pregnancy is critical for prevention of mother to child transmission of HIV. Objectives: To determine the prevalence and factors associated with unknown HIV status among women delivering in Mulago Hospital. Methods: This was a cross-sectional study of women that ...

  3. Severe scratcher-reaction: an unknown health hazard?

    Directory of Open Access Journals (Sweden)

    Carsten Sauer Mikkelsen

    2015-03-01

    Full Text Available Tattoos are well known to cause skin problems and the number of reported adverse reactions after tattooing has increased. Illegally imported tattoo ink is unrestrained and can contain unknown ingredients and contamination thereby posing a serious health hazard. We present a case illustrating the risk of pronounced phototoxic allergic reaction and other severe complications after using home kit tattoo ink.

  4. RBF neural network based H∞ synchronization for unknown chaotic ...

    Indian Academy of Sciences (India)

    MS received 9 February 2010; accepted 24 May 2010. Abstract. In this paper, we propose a new H∞ synchronization strategy, called a. Radial Basis Function Neural Network H∞ synchronization (RBFNNHS) strategy, for unknown chaotic systems in the presence of external disturbance. In the pro- posed framework, a ...

  5. Bayesian Compressed Sensing with Unknown Measurement Noise Level

    DEFF Research Database (Denmark)

    Hansen, Thomas Lundgaard; Jørgensen, Peter Bjørn; Pedersen, Niels Lovmand

    2013-01-01

    In sparse Bayesian learning (SBL) approximate Bayesian inference is applied to find sparse estimates from observations corrupted by additive noise. Current literature only vaguely considers the case where the noise level is unknown a priori. We show that for most state-of-the-art reconstruction...

  6. Inventory control in case of unknown demand and control parameters

    NARCIS (Netherlands)

    Janssen, E.

    2010-01-01

    This thesis deals with unknown demand and control parameters in inventory control. Inventory control involves decisions on what to order when and in what quantity. These decisions are based on information about the demand. Models are constructed using complete demand information; these models ensure

  7. Fast grasping of unknown objects using principal component analysis

    Science.gov (United States)

    Lei, Qujiang; Chen, Guangming; Wisse, Martijn

    2017-09-01

    Fast grasping of unknown objects has crucial impact on the efficiency of robot manipulation especially subjected to unfamiliar environments. In order to accelerate grasping speed of unknown objects, principal component analysis is utilized to direct the grasping process. In particular, a single-view partial point cloud is constructed and grasp candidates are allocated along the principal axis. Force balance optimization is employed to analyze possible graspable areas. The obtained graspable area with the minimal resultant force is the best zone for the final grasping execution. It is shown that an unknown object can be more quickly grasped provided that the component analysis principle axis is determined using single-view partial point cloud. To cope with the grasp uncertainty, robot motion is assisted to obtain a new viewpoint. Virtual exploration and experimental tests are carried out to verify this fast gasping algorithm. Both simulation and experimental tests demonstrated excellent performances based on the results of grasping a series of unknown objects. To minimize the grasping uncertainty, the merits of the robot hardware with two 3D cameras can be utilized to suffice the partial point cloud. As a result of utilizing the robot hardware, the grasping reliance is highly enhanced. Therefore, this research demonstrates practical significance for increasing grasping speed and thus increasing robot efficiency under unpredictable environments.

  8. A Size Exclusion Chromatography Laboratory with Unknowns for Introductory Students

    Science.gov (United States)

    McIntee, Edward J.; Graham, Kate J.; Colosky, Edward C.; Jakubowski, Henry V.

    2015-01-01

    Size exclusion chromatography is an important technique in the separation of biological and polymeric samples by molecular weight. While a number of laboratory experiments have been published that use this technique for the purification of large molecules, this is the first report of an experiment that focuses on purifying an unknown small…

  9. Editoria: EBOLA: Fear of the unknown | Comoro | Tanzania Journal ...

    African Journals Online (AJOL)

    Tanzania Journal of Health Research. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 3, No 2 (2001) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Editoria: EBOLA: Fear of the unknown. C. Comoro, J.

  10. Prevalence and predictors of unknown HIV status among women ...

    African Journals Online (AJOL)

    The labour ward on 5C admits high risk women and re- ferrals from the formal and informal health sector. There are about 2300 deliveries at ward 5C per month. The HIV status of every woman is identified at admission, those with unknown HIV status receive HCT and if positive, are given emergency ARVs for PMTCT.

  11. Anal Cancer debuting as Cancer of Unknown Primary

    DEFF Research Database (Denmark)

    Sveistrup, Joen; Loft, Annika; Engelholm, Svend Aage

    2011-01-01

    Anal cancer usually presents with a visible or palpable tumour. In this case we describe a 54-year old man diagnosed with Cancer of Unknown Primary (CUP) with a single inguinal node as the only finding. Thorough examination failed to identify any primary tumour. The patient was treated with lymph...

  12. Urine biomarkers of kidney injury among adolescents in Nicaragua, a region affected by an epidemic of chronic kidney disease of unknown aetiology

    National Research Council Canada - National Science Library

    Ramírez-Rubio, Oriana; Amador, Juan José; Kaufman, James S; Weiner, Daniel E; Parikh, Chirag R; Khan, Usman; McClean, Michael D; Laws, Rebecca L; López-Pilarte, Damaris; Friedman, David J; Kupferman, Joseph; Brooks, Daniel R

    2016-01-01

    ...; however, the aetiology remains unknown. Because individuals are frequently diagnosed with CKD in early adulthood, we measured biomarkers of kidney injury among adolescents in different regions of Nicaragua to assess whether kidney damage...

  13. Bayesian source term determination with unknown covariance of measurements

    Science.gov (United States)

    Belal, Alkomiet; Tichý, Ondřej; Šmídl, Václav

    2017-04-01

    Determination of a source term of release of a hazardous material into the atmosphere is a very important task for emergency response. We are concerned with the problem of estimation of the source term in the conventional linear inverse problem, y = Mx, where the relationship between the vector of observations y is described using the source-receptor-sensitivity (SRS) matrix M and the unknown source term x. Since the system is typically ill-conditioned, the problem is recast as an optimization problem minR,B(y - Mx)TR-1(y - Mx) + xTB-1x. The first term minimizes the error of the measurements with covariance matrix R, and the second term is a regularization of the source term. There are different types of regularization arising for different choices of matrices R and B, for example, Tikhonov regularization assumes covariance matrix B as the identity matrix multiplied by scalar parameter. In this contribution, we adopt a Bayesian approach to make inference on the unknown source term x as well as unknown R and B. We assume prior on x to be a Gaussian with zero mean and unknown diagonal covariance matrix B. The covariance matrix of the likelihood R is also unknown. We consider two potential choices of the structure of the matrix R. First is the diagonal matrix and the second is a locally correlated structure using information on topology of the measuring network. Since the inference of the model is intractable, iterative variational Bayes algorithm is used for simultaneous estimation of all model parameters. The practical usefulness of our contribution is demonstrated on an application of the resulting algorithm to real data from the European Tracer Experiment (ETEX). This research is supported by EEA/Norwegian Financial Mechanism under project MSMT-28477/2014 Source-Term Determination of Radionuclide Releases by Inverse Atmospheric Dispersion Modelling (STRADI).

  14. Capecitabine and oxaliplatin as second-line treatment in patients with carcinoma of unknown primary site

    DEFF Research Database (Denmark)

    Møller, Anne Kirstine Hundahl; Pedersen, Karen Damgaard; Abildgaard, Julie Rafn

    2010-01-01

    Treatment of patients with carcinoma of unknown primary site (CUP) remains a challenge, and no effective second-line treatment has been identified. In CUP patients who are non-responsive or relapse early after first-line platinum/taxane-based regimens, it is likely that gastrointestinal (GI) tract...... tumours may be overrepresented. These patients could be candidates for GI tract-directed therapy. We here report the results obtained with oxaliplatin and capecitabine as second-line therapy in 25 recurrent/refractory CUP patients following first-line treatment with paclitaxel, cisplatin and gemcitabine....

  15. Quadrotor Control in the Presence of Unknown Mass Properties

    Science.gov (United States)

    Duivenvoorden, Rikky Ricardo Petrus Rufino

    Quadrotor UAVs are popular due to their mechanical simplicity, as well as their capability to hover and vertically take-off and land. As applications diversify, quadrotors are increasingly required to operate under unknown mass properties, for example as a multirole sensor platform or for package delivery operations. The work presented here consists of the derivation of a generalized quadrotor dynamic model without the typical simplifying assumptions on the first and second moments of mass. The maximum payload capacity of a quadrotor in hover, and the observability of the unknown mass properties are discussed. A brief introduction of L1 adaptive control is provided, and three different L 1 adaptive controllers were designed for the Parrot AR.Drone quadrotor. Their tracking and disturbance rejection performance was compared to the baseline nonlinear controller in experiments. Finally, the results of the combination of L1 adaptive control with iterative learning control are presented, showing high performance trajectory tracking under uncertainty.

  16. Towards high-speed autonomous navigation of unknown environments

    Science.gov (United States)

    Richter, Charles; Roy, Nicholas

    2015-05-01

    In this paper, we summarize recent research enabling high-speed navigation in unknown environments for dynamic robots that perceive the world through onboard sensors. Many existing solutions to this problem guarantee safety by making the conservative assumption that any unknown portion of the map may contain an obstacle, and therefore constrain planned motions to lie entirely within known free space. In this work, we observe that safety constraints may significantly limit performance and that faster navigation is possible if the planner reasons about collision with unobserved obstacles probabilistically. Our overall approach is to use machine learning to approximate the expected costs of collision using the current state of the map and the planned trajectory. Our contribution is to demonstrate fast but safe planning using a learned function to predict future collision probabilities.

  17. Learning Unknown Structure in CRFs via Adaptive Gradient Projection Method

    Directory of Open Access Journals (Sweden)

    Wei Xue

    2016-08-01

    Full Text Available We study the problem of fitting probabilistic graphical models to the given data when the structure is not known. More specifically, we focus on learning unknown structure in conditional random fields, especially learning both the structure and parameters of a conditional random field model simultaneously. To do this, we first formulate the learning problem as a convex minimization problem by adding an l_2-regularization to the node parameters and a group l_1-regularization to the edge parameters, and then a gradient-based projection method is proposed to solve it which combines an adaptive stepsize selection strategy with a nonmonotone line search. Extensive simulation experiments are presented to show the performance of our approach in solving unknown structure learning problems.

  18. Renal disease masquerading as pyrexia of unknown origin

    Directory of Open Access Journals (Sweden)

    D Korivi

    2013-01-01

    Full Text Available Pyrexia of unknown origin is a challenging clinical problem. Infections, malignancies, and connective tissue diseases form the major etiologies for this condition. We report a case of a 57-year-old diabetic male who presented with fever of unknown origin for several months. The course of investigations led to a kidney biopsy which clinched the cause of his fever as well as the underlying diagnosis. The light microscopy findings of expansile storiform fibrosis with a dense inflammatory infiltrate suggested the diagnosis which was confirmed by positive staining of Immunoglobulin G4, the dense lympho-plasmacytic infiltrate and elevated serum IgG4 concentrations. A course of steroids followed by mycophenolate mofetil as maintenance immunosuppression rendered the patient afebrile with improvement of renal function.

  19. Evaluation of Unknown Tube Well Depth Using Electrical Resistivity Method

    Directory of Open Access Journals (Sweden)

    Zainal Abidin Mohd Hazreek

    2017-01-01

    Full Text Available Electrical resistivity method has increasingly adopted in engineering, environmental, mining and archaeological studies. Systematic and proper studies of unknown civil engineering structure evaluation particularly on tube well depth was rarely being established. Conventionally, camera test or string with weight approach has been used to evaluate unknown tube well depth thus exposed to several restriction due to its expensive and time consuming. Hence, this study focused on evaluation of unknown tube well depth using indirect test with particular reference to electrical resistivity method (ERM.A single spread line of electrical resistivity survey was performed using ABEM SAS 4000 equipment set based on Wenner and Pole-dipole array in line with the tube well position. Electrical resistivity raw data was processed using RES2DINV software producing electrical resistivity tomography (ERT of the subsurface profile studied. Then, electrical resistivity value (ERV obtained from RES2DINV analyses (ERT was extracted and analysed using plotted graph (depth versus ERV specifically at tube well position based on electrical resistivity spread line performed. It was found that both array have shown some good similarity results in term of tube well depth (20 m thus able to verify the result interpreted. Both array have shown some good similarity of ERV representing groundwater (ERV = 10 – 100 Ωm and soil with water (ERV > 100 Ωm at depth of 0 – 20 m and >20 m respectively. All those interpretation have shown good agreement based on verification thru established ERV of earth materials references, geological map and nearest available boreholes data. Hence, this study has shown that the application of ERM was applicable in evaluation of unknown tube well depth which efficient in term of cost, time and environmental sustainable.

  20. Renovation of the Tomb of the Unknown Soldier, Baghdad, Iraq

    Science.gov (United States)

    2010-01-13

    animals, including some of the “ pet ” lions kept by Uday and Qusay Hussein. Also located near the Tomb of the Unknown in the Al Zarwaa Park is an...the following: 4 x 800 amp automatic transfer switches main power boards sub-distribution board for the different facilities main feeder ...repairing the 3-phase diesel generator and installing automatic transfer switches, main power boards, main feeder cables, and interior and exterior

  1. Stability Analysis of Fractional Differential Equations with Unknown Parameters

    OpenAIRE

    Koksal, Mehmet Emir

    2017-01-01

    In this paper, the stability of fractional differential equations (FDEs) with unknown parameters is studied. FDEs bring many advantages to model the physical systems in the nature or man-made systems in the industry. Because this representation has a property between linear differential equations and nonlinear differential equations. Therefore, the designer may use the FDEs to model complex systems instead of nonlinear differential equations which have hard mathematical background. Using the ...

  2. Modal Parameter Identification from Responses of General Unknown Random Inputs

    OpenAIRE

    Ibrahim, S. R.; Asmussen, J. C.; Brincker, Rune

    1995-01-01

    Modal parameter identification from ambient responses due to a general unknown random inputs is investigated. Existing identification techniques which are based on assumptions of white noise and or stationary random inputs are utilized even though the inputs conditions are not satisfied. This is accomplished via adding. In cascade. A force cascade conversion to the structures system under consideration. The input to the force conversion system is white noise and the output of which is the act...

  3. Localized hepatic tuberculosis presenting as fever of unknown origin

    Directory of Open Access Journals (Sweden)

    Teresa Cristina Abreu Ferrari

    Full Text Available Localized hepatic tuberculosis is a rare clinical form of tuberculosis infection; it has signs and symptoms related only to hepatic injury, with minimal or no extrahepatic involvement. It frequently presents as a non-specific syndrome, with systemic manifestations, which can sometimes result in a diagnostic dilemma. A high index of suspicion is required and a definitive diagnosis can be very difficult. We report a case of localized hepatic tuberculosis that presented as fever of unknown origin.

  4. General Unknown Screening by Ion Trap LC/MS/MS

    Science.gov (United States)

    2010-04-01

    are collected at autopsy and sent to CAMI’s Forensic Toxicology Research Laboratory for toxicological analysis of various postmortem fluids and... Forensic Toxicology, General Unknown Screening, LC/MS Document is available to the public through the Defense Technical Information...resulting in an acid/ neutral and a base vial from each specimen. rEsulTs ANd dIsCussION This study established the LOD for 359 forensically

  5. Bird remains from the Maastrichtian type area (Late Cretaceous)

    NARCIS (Netherlands)

    Dyke, Gareth J.; Schulp, A. S.; Jagt, J. W M

    2008-01-01

    Remains of Late Cretaceous birds are rare, which is especially true for Europe and the type area of the Maastrichtian Stage (southeast Netherlands, northeast Belgium) in particular. In the present paper, we record new remains (isolated tarsometatarsus and radius) that document the presence of both

  6. Detection of unknown primary head and neck tumors by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Braams, J.W.; Roodenburg, J.L.N. [Groningen Univ. Hospital, Dept. of Oral and Maxillofacial Surgery, Groningen (Netherlands); Pruim, J.; Vaalburg, W.; Kole, A.C. [Groningen Univ. Hospital, PET center, Groningen (Netherlands); Vermey, A. [Groningen Univ. Hospital, Dept. of Surgical Oncology, Groningen (Netherlands); Nikkels, P.G.J. [Groningen Univ. Hospital, Dept. of Pathology, Groningen (Netherlands)

    1997-04-01

    The purpose of this study was to investigate the potential of using positron emission tomography (PET) with {sup 18}F-labeled fluoro-2-deoxy-D-glucose (FDG) to detect unknown primary tumors of cervical metastases. Thirteen patients with various histologic types of cervical metastases of unknown primary origin were studied. Patients received 185-370 MBq FDG intravenously and were scanned from 30 min after injection onward. Whole-body scans were made with a Siemens ECAT 951/31 PET camera. PET identified the primary tumor in four patients: plasmocytoma, squamous cell cacinoma of the oropharynx, squamous cell carcinoma of the larynx, and bronchial carcinoma, respectively. All known metastatic tumor sites were visualized. PET did not identify a primary tumor in one patient in whom a squamous cell carcinoma at the base of the tongue was found in a latr phase. In the remaining eight patients, a primary lesion was never found. The follow up ranged from 18 to 30 months. A previously unknown primary tumor can be identified with FDG-PET in approximately 30% of patients with cervical metastases. PET can reveal useful information that results in more appropriate treatment, and it can be of value in guiding endoscopic biopsies for histologic diagnosis. (au).

  7. Restoring accents in unknown biomedical words: application to the French MeSH thesaurus.

    Science.gov (United States)

    Zweigenbaum, Pierre; Grabar, Natalia

    2002-12-04

    In languages with diacritic marks, such as French, there remain instances of textual or terminological resources that are available in electronic form without diacritic marks, which hinders their use in natural language interfaces. In a specialized domain such as medicine, it is often the case that some words are not found in the available electronic lexicons. The issue of accenting unknown words then arises: it is the theme of this work. We propose two internal methods for accenting unknown words, which both learn on a reference set of accented words the contexts of occurrence of the various accented forms of a given letter. One method is adapted from part-of-speech tagging, the other is based on finite state transducers. We show experimental results for letter e on the French version of the Medical Subject Headings thesaurus. With the best training set, the tagging method obtains a precision-recall breakeven point of 84.2+/-4.4% and the transducer method 83.8+/-4.5% (with a baseline at 64%) for the unknown words that contain this letter. A consensus combination of both increases precision to 92.0+/-3.7% with a recall of 75%. We perform an error analysis and discuss further steps that might help improve over the current performance.

  8. Study of sexual dimorphism of Malaysian crania: an important step in identification of the skeletal remains

    Science.gov (United States)

    Ibrahim, Abdelnasser; Alias, Aspalilah; Swarhib, Mohamed; Abu Bakar, Siti Noorain; Das, Srijit

    2017-01-01

    Sex determination is one of the main steps in the identification of human skeletal remains. It constitutes an initial step in personal identification from the skeletal remains. The aim of the present study was to provide the population-specific sex discriminating osteometric standards to aid human identification. The present study was conducted on 87 (174 sides) slices of crania using postmortem computed tomography in 45 males and 42 females, aged between 18 and 75 years. About 22 parameters of crania were measured using Osirix software 3-D Volume Rendering. Results showed that all parameters were significantly higher in males than in females except for orbital height of the left eye by independent t test (Pforensic tool for identification of unknown crania. PMID:28713610

  9. Study of sexual dimorphism of Malaysian crania: an important step in identification of the skeletal remains.

    Science.gov (United States)

    Ibrahim, Abdelnasser; Alias, Aspalilah; Nor, Faridah Mohd; Swarhib, Mohamed; Abu Bakar, Siti Noorain; Das, Srijit

    2017-06-01

    Sex determination is one of the main steps in the identification of human skeletal remains. It constitutes an initial step in personal identification from the skeletal remains. The aim of the present study was to provide the population-specific sex discriminating osteometric standards to aid human identification. The present study was conducted on 87 (174 sides) slices of crania using postmortem computed tomography in 45 males and 42 females, aged between 18 and 75 years. About 22 parameters of crania were measured using Osirix software 3-D Volume Rendering. Results showed that all parameters were significantly higher in males than in females except for orbital height of the left eye by independent t test (Ppopulation. The results of the present study can be used as a forensic tool for identification of unknown crania.

  10. Descriptions of the dental remains of Homo floresiensis

    National Research Council Canada - National Science Library

    KAIFU, YOUSUKE; KONO, REIKO T; SUTIKNA, THOMAS; SAPTOMO, E. WAHYU; JATMIKO; AWE, ROKUS DUE; BABA, HISAO

    2015-01-01

    Dental remains of Homo floresiensis excavated during 2002–2004 at Liang Bua, Flores, Indonesia, consist of one partial maxillary dentition, two nearly complete mandibular dentitions, and four isolated teeth...

  11. A Bayesian Framework for Remaining Useful Life Estimation

    Data.gov (United States)

    National Aeronautics and Space Administration — The estimation of remaining useful life (RUL) of a faulty component is at the center of system prognostics and health management. It gives operators a potent tool in...

  12. [The identification of unknown corpses by x-ray comparison].

    Science.gov (United States)

    Riepert, T; Schweden, F; Schild, H; Rittner, C

    1995-03-01

    Between 1987 and 1993, 30 unknown bodies were identified by means of pre- and postmortem radiographs at the Forensic Institute in Mainz. Our experience indicates that radiological identification comprises a useful, rapid and cheap method, at least as valuable as dactyloscopy or odontological comparisons. The ages of available radiographs were up to 25 years; the most suitable regions are the skull (11), pelvis and lumbar spine (6), lower femur and knee (5) and distal leg with the ankle joint (5). In respect of the problem of objectifying the probability of identity, possibilities for solutions are shown.

  13. Anal Cancer debuting as Cancer of Unknown Primary

    DEFF Research Database (Denmark)

    Sveistrup, Joen; Loft, Annika; Engelholm, Svend Aage

    2011-01-01

    Anal cancer usually presents with a visible or palpable tumour. In this case we describe a 54-year old man diagnosed with Cancer of Unknown Primary (CUP) with a single inguinal node as the only finding. Thorough examination failed to identify any primary tumour. The patient was treated with lymph...... node dissection and not until nearly two years after initial diagnosis, was the primary tumour found, and the patient was diagnosed with anal cancer. The patient was treated with chemoradiotherapy and 45 months after initial diagnosis there is still no sign of relapse. This case illustrates, that anal...

  14. Fault tolerant control of wind turbines using unknown input observers

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Stoustrup, Jakob

    2012-01-01

    This paper presents a scheme for accommodating faults in the rotor and generator speed sensors in a wind turbine. These measured values are important both for the wind turbine controller as well as the supervisory control of the wind turbine. The scheme is based on unknown input observers, which ...... are also used to detect and isolate these faults. The scheme is tested on a known benchmark for FDI and FTC of wind turbines. Tests on this benchmark model show a clear potential of the proposed scheme....

  15. Method for recovering elemental silicon from cutting remains.

    OpenAIRE

    Ulset, Torgeir; Julrud, Stein; Cassayre, Laurent; Chamelot, Pierre; Massot, Laurent; Taxil, Pierre

    2008-01-01

    This invention relates to a method for recovering elemental silicon cutting remains containing silicon particles, wherein the method comprises manufacturing solid anodes from the cutting remains, arranging one or more manufactured anode (s) in an electrolytic cell with a molten salt electrolyte and one or more cathode (s), and applying a potential difference between the one or more anode (s) and cathode (s) to obtain an oxidation of metallic silicon in the one or more anode (s), tran...

  16. Range image registration using a photometric metric under unknown lighting.

    Science.gov (United States)

    Thomas, Diego; Sugimoto, Akihiro

    2013-09-01

    Based on the spherical harmonics representation of image formation, we derive a new photometric metric for evaluating the correctness of a given rigid transformation aligning two overlapping range images captured under unknown, distant, and general illumination. We estimate the surrounding illumination and albedo values of points of the two range images from the point correspondences induced by the input transformation. We then synthesize the color of both range images using albedo values transferred using the point correspondences to compute the photometric reprojection error. This way allows us to accurately register two range images by finding the transformation that minimizes the photometric reprojection error. We also propose a practical method using the proposed photometric metric to register pairs of range images devoid of salient geometric features, captured under unknown lighting. Our method uses a hypothesize-and-test strategy to search for the transformation that minimizes our photometric metric. Transformation candidates are efficiently generated by employing the spherical representation of each range image. Experimental results using both synthetic and real data demonstrate the usefulness of the proposed metric.

  17. Shading-based Surface Detail Recovery under General Unknown Illumination.

    Science.gov (United States)

    Xu, Di; Duan, Qi; Zheng, Jianmin; Zhang, Juyong; Cai, Jianfei; Cham, Tat-Jen

    2017-02-17

    Reconstructing the shape of a 3D object from multi-view images under unknown, general illumination is a fundamental problem in computer vision and high quality reconstruction is usually challenging especially when fine detail is needed and the albedo of the object is non-uniform. This paper introduces vertex overall illumination vectors to model the illumination effect and presents a total variation (TV) based approach for recovering surface details using shading and multi-view stereo (MVS). Behind the approach are the two important observations: (1) the illumination over the surface of an object often appears to be piece wise smooth and (2) the recovery of surface orientation is not sufficient for reconstructing the surface, which was often overlooked previously. Thus we propose to use TV to regularize the overall illumination vectors and use visual hull to constrain partial vertices. The reconstruction is formulated as a constrained TV-minimization problem that simultaneously treats the shape and illumination vectors as unknowns. An augmented Lagrangian method is proposed to quickly solve the TV-minimization problem. As a result, our approach is robust, stable and is able to efficiently recover high quality of surface details even when starting with a coarse model obtained using MVS. These advantages are demonstrated by extensive experiments on the state-of-the-art MVS database, which includes challenging objects with varying albedo.

  18. The random exploration graph for optimal exploration of unknown environments

    Directory of Open Access Journals (Sweden)

    Alfredo Toriz Palacios

    2017-01-01

    Full Text Available The exploration of an unknown environment by a robot system is a well-studied problem in robotics; however, although many of the proposals made in this field represent efficient tools in terms of exploration paradigm, most of them are not efficient for time critical applications since the robot may visit the same place more than once during backtracking. In this way and considering these limitations, this article presents a novel approach called the random exploration graph, which addresses the problem of exploring unknown environments by building a graph structure created incrementally by the random choice of the free frontier in the observation range of the robot. In addition, the random exploration graph algorithm uses a new concept called “frontier control” introduced in this work, used to store nodes left behind in the graph structure that have not been fully explored and that will be used to guide the exploration process in an efficient way, when the algorithm needs to go back to previously visited areas to continue exploration. The frontier control concept next to the versatility of the graph structure used for the exploration process is the main contribution of this work.

  19. Reactive Path Planning Approach for Docking Robots in Unknown Environment

    Directory of Open Access Journals (Sweden)

    Peng Cui

    2017-01-01

    Full Text Available Autonomous robots need to be recharged and exchange information with the host through docking in the long-distance tasks. Therefore, feasible path is required in the docking process to guide the robot and adjust its pose. However, when there are unknown obstacles in the work area, it becomes difficult to determine the feasible path for docking. This paper presents a reactive path planning approach named Dubins-APF (DAPF to solve the path planning problem for docking in unknown environment with obstacles. In this proposed approach the Dubins curves are combined with the designed obstacle avoidance potential field to plan the feasible path. Firstly, an initial path is planned and followed according to the configurations of the robot and the docking station. Then when the followed path is evaluated to be infeasible, the intermediate configuration is calculated as well as the replanned path based on the obstacle avoidance potential field. The robot will be navigated to the docking station with proper pose eventually via the DAPF approach. The proposed DAPF approach is efficient and does not require the prior knowledge about the environment. Simulation results are given to validate the effectiveness and feasibility of the proposed approach.

  20. Three-dimensional cinematography with control object of unknown shape.

    Science.gov (United States)

    Dapena, J; Harman, E A; Miller, J A

    1982-01-01

    A technique for reconstruction of three-dimensional (3D) motion which involves a simple filming procedure but allows the deduction of coordinates in large object volumes was developed. Internal camera parameters are calculated from measurements of the film images of two calibrated crosses while external camera parameters are calculated from the film images of points in a control object of unknown shape but at least one known length. The control object, which includes the volume in which the activity is to take place, is formed by a series of poles placed at unknown locations, each carrying two targets. From the internal and external camera parameters, and from locations of the images of point in the films of the two cameras, 3D coordinates of the point can be calculated. Root mean square errors of the three coordinates of points in a large object volume (5m x 5m x 1.5m) were 15 mm, 13 mm, 13 mm and 6 mm, and relative errors in lengths averaged 0.5%, 0.7% and 0.5%, respectively.

  1. Learned navigation in unknown terrains: A retraction method

    Science.gov (United States)

    Rao, Nageswara S. V.; Stoltzfus, N.; Iyengar, S. Sitharama

    1989-01-01

    The problem of learned navigation of a circular robot R, of radius delta (is greater than or equal to 0), through a terrain whose model is not a-priori known is considered. Two-dimensional finite-sized terrains populated by an unknown (but, finite) number of simple polygonal obstacles are also considered. The number and locations of the vertices of each obstacle are unknown to R. R is equipped with a sensor system that detects all vertices and edges that are visible from its present location. In this context two problems are covered. In the visit problem, the robot is required to visit a sequence of destination points, and in the terrain model acquisition problem, the robot is required to acquire the complete model of the terrain. An algorithmic framework is presented for solving these two problems using a retraction of the freespace onto the Voronoi diagram of the terrain. Algorithms are then presented to solve the visit problem and the terrain model acquisition problem.

  2. Using endocarp-remains of seeds of wild apricot Prunus armeniaca to identify rodent seed predators

    Directory of Open Access Journals (Sweden)

    Hongmao ZHANG, Wei WANG

    2009-12-01

    Full Text Available Some rodent-dispersed seeds have a hard seed-coat (e.g. woody endocarp. Specific scrapes or dental marks on the hard seed-coat left by rodents when they eat these seeds can be used to identify seed predators. In this study we measured the morphological traits of endocarp-remains of seeds of wild apricot Prunus armeniaca used by Chinese white-bellied rats Niviventor confucianus and Korean field mice Apodemus peninsulae. We established their Fisher′s linear discriminant functions to separate endocarp-remains between the two predators. A total of 90.0 % of the endocarp-remains left by Korean field mice and 88.0 % of those left by Chinese white-bellied rats were correctly classified. The overall percentage of correct classification was 89.0 %. One hundred and sixty endocarp-remains of unknown what species predated them were classified using the functions. The method may allow more reliable quantitative studies of the effects of Chinese white-bellied rats and Korean field mice on seed consumption and dispersal of wild apricot and this study might be used for reference in other studies of seed predators identification on hard seeds [Current Zoology 55 (6: 396 –400, 2009].

  3. Forensic considerations when dealing with incinerated human dental remains.

    Science.gov (United States)

    Reesu, Gowri Vijay; Augustine, Jeyaseelan; Urs, Aadithya B

    2015-01-01

    Establishing the human dental identification process relies upon sufficient post-mortem data being recovered to allow for a meaningful comparison with ante-mortem records of the deceased person. Teeth are the most indestructible components of the human body and are structurally unique in their composition. They possess the highest resistance to most environmental effects like fire, desiccation, decomposition and prolonged immersion. In most natural as well as man-made disasters, teeth may provide the only means of positive identification of an otherwise unrecognizable body. It is imperative that dental evidence should not be destroyed through erroneous handling until appropriate radiographs, photographs, or impressions can be fabricated. Proper methods of physical stabilization of incinerated human dental remains should be followed. The maintenance of integrity of extremely fragile structures is crucial to the successful confirmation of identity. In such situations, the forensic dentist must stabilise these teeth before the fragile remains are transported to the mortuary to ensure preservation of possibly vital identification evidence. Thus, while dealing with any incinerated dental remains, a systematic approach must be followed through each stage of evaluation of incinerated dental remains to prevent the loss of potential dental evidence. This paper presents a composite review of various studies on incinerated human dental remains and discusses their impact on the process of human identification and suggests a step by step approach. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  4. The memory remains: Understanding collective memory in the digital age.

    Science.gov (United States)

    García-Gavilanes, Ruth; Mollgaard, Anders; Tsvetkova, Milena; Yasseri, Taha

    2017-04-01

    Recently developed information communication technologies, particularly the Internet, have affected how we, both as individuals and as a society, create, store, and recall information. The Internet also provides us with a great opportunity to study memory using transactional large-scale data in a quantitative framework similar to the practice in natural sciences. We make use of online data by analyzing viewership statistics of Wikipedia articles on aircraft crashes. We study the relation between recent events and past events and particularly focus on understanding memory-triggering patterns. We devise a quantitative model that explains the flow of viewership from a current event to past events based on similarity in time, geography, topic, and the hyperlink structure of Wikipedia articles. We show that, on average, the secondary flow of attention to past events generated by these remembering processes is larger than the primary attention flow to the current event. We report these previously unknown cascading effects.

  5. PHYLOGENOMICS - GUIDED VALIDATION OF FUNCTION FOR CONSERVED UNKNOWN GENES

    Energy Technology Data Exchange (ETDEWEB)

    V, DE CRECY-LAGARD; D, HANSON A

    2012-01-03

    Identifying functions for all gene products in all sequenced organisms is a central challenge of the post-genomic era. However, at least 30-50% of the proteins encoded by any given genome are of unknown function, or wrongly or vaguely annotated. Many of these 'unknown' proteins are common to prokaryotes and plants. We accordingly set out to predict and experimentally test the functions of such proteins. Our approach to functional prediction is integrative, coupling the extensive post-genomic resources available for plants with comparative genomics based on hundreds of microbial genomes, and functional genomic datasets from model microorganisms. The early phase is computer-assisted; later phases incorporate intellectual input from expert plant and microbial biochemists. The approach thus bridges the gap between automated homology-based annotations and the classical gene discovery efforts of experimentalists, and is much more powerful than purely computational approaches to identifying gene-function associations. Among Arabidopsis genes, we focused on those (2,325 in total) that (i) are unique or belong to families with no more than three members, (ii) are conserved between plants and prokaryotes, and (iii) have unknown or poorly known functions. Computer-assisted selection of promising targets for deeper analysis was based on homology .. independent characteristics associated in the SEED database with the prokaryotic members of each family, specifically gene clustering and phyletic spread, as well as availability of functional genomics data, and publications that could link candidate families to general metabolic areas, or to specific functions. In-depth comparative genomic analysis was then performed for about 500 top candidate families, which connected ~55 of them to general areas of metabolism and led to specific functional predictions for a subset of ~25 more. Twenty predicted functions were experimentally tested in at least one prokaryotic organism

  6. A note on the blind deconvolution of multiple sparse signals from unknown subspaces

    Science.gov (United States)

    Cosse, Augustin

    2017-08-01

    This note studies the recovery of multiple sparse signals, xn ∈ ℝL, n = 1, . . . , N, from the knowledge of their convolution with an unknown point spread function h ∈ ℝL. When the point spread function is known to be nonzero, |h[k]| > 0, this blind deconvolution problem can be relaxed into a linear, ill-posed inverse problem in the vector concatenating the unknown inputs xn together with the inverse of the filter, d ∈ ℝL where d[k] := 1/h[k]. When prior information is given on the input subspaces, the resulting overdetermined linear system can be solved efficiently via least squares (see Ling et al. 20161). When no information is given on those subspaces, and the inputs are only known to be sparse, it still remains possible to recover these inputs along with the filter by considering an additional l1 penalty. This note certifies exact recovery of both the unknown PSF and unknown sparse inputs, from the knowledge of their convolutions, as soon as the number of inputs N and the dimension of each input, L , satisfy L ≳ N and N ≳ T2max, up to log factors. Here Tmax = maxn{Tn} and Tn, n = 1, . . . , N denote the supports of the inputs xn. Our proof system combines the recent results on blind deconvolution via least squares to certify invertibility of the linear map encoding the convolutions, with the construction of a dual certificate following the structure first suggested in Candés et al. 2007.2 Unlike in these papers, however, it is not possible to rely on the norm ||(A*TAT)-1|| to certify recovery. We instead use a combination of the Schur Complement and Neumann series to compute an expression for the inverse (A*TAT)-1. Given this expression, it is possible to show that the poorly scaled blocks in (A*TAT)-1 are multiplied by the better scaled ones or vanish in the construction of the certificate. Recovery is certified with high probablility on the choice of the supports and distribution of the signs of each input xn on the support. The paper

  7. Distributed Multisensor Data Fusion under Unknown Correlation and Data Inconsistency

    Directory of Open Access Journals (Sweden)

    Muhammad Abu Bakr

    2017-10-01

    Full Text Available The paradigm of multisensor data fusion has been evolved from a centralized architecture to a decentralized or distributed architecture along with the advancement in sensor and communication technologies. These days, distributed state estimation and data fusion has been widely explored in diverse fields of engineering and control due to its superior performance over the centralized one in terms of flexibility, robustness to failure and cost effectiveness in infrastructure and communication. However, distributed multisensor data fusion is not without technical challenges to overcome: namely, dealing with cross-correlation and inconsistency among state estimates and sensor data. In this paper, we review the key theories and methodologies of distributed multisensor data fusion available to date with a specific focus on handling unknown correlation and data inconsistency. We aim at providing readers with a unifying view out of individual theories and methodologies by presenting a formal analysis of their implications. Finally, several directions of future research are highlighted.

  8. Distributed Multisensor Data Fusion under Unknown Correlation and Data Inconsistency.

    Science.gov (United States)

    Bakr, Muhammad Abu; Lee, Sukhan

    2017-10-27

    The paradigm of multisensor data fusion has been evolved from a centralized architecture to a decentralized or distributed architecture along with the advancement in sensor and communication technologies. These days, distributed state estimation and data fusion has been widely explored in diverse fields of engineering and control due to its superior performance over the centralized one in terms of flexibility, robustness to failure and cost effectiveness in infrastructure and communication. However, distributed multisensor data fusion is not without technical challenges to overcome: namely, dealing with cross-correlation and inconsistency among state estimates and sensor data. In this paper, we review the key theories and methodologies of distributed multisensor data fusion available to date with a specific focus on handling unknown correlation and data inconsistency. We aim at providing readers with a unifying view out of individual theories and methodologies by presenting a formal analysis of their implications. Finally, several directions of future research are highlighted.

  9. An Efficient Algorithm for Direction Finding against Unknown Mutual Coupling

    Directory of Open Access Journals (Sweden)

    Weijiang Wang

    2014-10-01

    Full Text Available In this paper, an algorithm of direction finding is proposed in the presence of unknown mutual coupling. The preliminary direction of arrival (DOA is estimated using the whole array for high resolution. Further refinement can then be conducted by estimating the angularly dependent coefficients (ADCs with the subspace theory. The mutual coupling coefficients are finally determined by solving the least squares problem with all of the ADCs utilized without discarding any. Simulation results show that the proposed method can achieve better performance at a low signal-to-noise ratio (SNR with a small-sized array and is more robust, compared with the similar processes employing the initial DOA estimation and further improvement iteratively.

  10. An efficient algorithm for direction finding against unknown mutual coupling.

    Science.gov (United States)

    Wang, Weijiang; Ren, Shiwei; Ding, Yingtao; Wang, Haoyu

    2014-10-24

    In this paper, an algorithm of direction finding is proposed in the presence of unknown mutual coupling. The preliminary direction of arrival (DOA) is estimated using the whole array for high resolution. Further refinement can then be conducted by estimating the angularly dependent coefficients (ADCs) with the subspace theory. The mutual coupling coefficients are finally determined by solving the least squares problem with all of the ADCs utilized without discarding any. Simulation results show that the proposed method can achieve better performance at a low signal-to-noise ratio (SNR) with a small-sized array and is more robust, compared with the similar processes employing the initial DOA estimation and further improvement iteratively.

  11. Alternate Location Method of a Robot Team in Unknown Environment

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-zhong; LIU Jing-jing

    2008-01-01

    The alternate location method of a robot team is proposed. Three of the robots are kept still as beacon robots, not always the same ones, while the others are regarded as mobile robots. The mobile robots alternatively measure the distance between one of them and three beacon robots with ultrasonic measurement module. The distance data are combined with its dead-reckoning information using iterated extended Kalman filter(IEKF) to realize the optimal estimate of its position. According to the condition the future beacon robots positions should be desired ones, the target function and the nonlinear constrain equations are set up which are used by nonlinear optimization algorithm to estimate the position of the future beacon robots. By alternately changing the robots roles as active beacon, the alternate location in unknown environment can be realized. Process and result of the simulation test are given and the position estimation error is within±10mm, which proves the validity of this method.

  12. Impact of CT in patients with sepsis of unknown origin

    Energy Technology Data Exchange (ETDEWEB)

    Barkhausen, J.; Stoeblen, F.; Mueller, R.D. [University Hospital Essen (Germany). Dept. of Radiology; Dominguez-Fernandez, E. [University Hospital Essen (Germany). Dept. of General Surgery; Henseke, P. [Nycomed-Amersham Arzneimittel GmbH, Muenchen (Germany)

    1999-09-01

    Purpose: To evaluate the diagnostic relevance of CT in patients with sepsis of unknown origin. Material and Methods: Sixty-three consecutive intensive care patients with suspicion of an abscess and negative or inconclusive previous radiological examinations were included. CT was performed using the helical technique. A total of 45 abdominal and 38 chest examinations were evaluated. Results: 5/38 examinations of the chest revealed the source of sepsis (pleural empyema 2, lung abscess 1, mediastinitis 1, retrosternal abscess 1). 7/45 abdominal CT examinations showed the source of sepsis (intraabdominal abscess 2, hepatic abscess 3, intestinal perforation 1, gangrenous colitis 1). Conclusion: CT is useful for the evaluation of patients with fever or sepsis without a known source. Due to the detection of a spetic focus by CT, 19% of the patients in our study could be immediately referred to causal therapy as percutaneous drainage or surgery. (orig.)

  13. Autonomous Underwater Navigation and Optical Mapping in Unknown Natural Environments

    Directory of Open Access Journals (Sweden)

    Juan David Hernández

    2016-07-01

    Full Text Available We present an approach for navigating in unknown environments while, simultaneously, gathering information for inspecting underwater structures using an autonomous underwater vehicle (AUV. To accomplish this, we first use our pipeline for mapping and planning collision-free paths online, which endows an AUV with the capability to autonomously acquire optical data in close proximity. With that information, we then propose a reconstruction pipeline to create a photo-realistic textured 3D model of the inspected area. These 3D models are also of particular interest to other fields of study in marine sciences, since they can serve as base maps for environmental monitoring, thus allowing change detection of biological communities and their environment over time. Finally, we evaluate our approach using the Sparus II, a torpedo-shaped AUV, conducting inspection missions in a challenging, real-world and natural scenario.

  14. Autonomous Underwater Navigation and Optical Mapping in Unknown Natural Environments.

    Science.gov (United States)

    Hernández, Juan David; Istenič, Klemen; Gracias, Nuno; Palomeras, Narcís; Campos, Ricard; Vidal, Eduard; García, Rafael; Carreras, Marc

    2016-07-26

    We present an approach for navigating in unknown environments while, simultaneously, gathering information for inspecting underwater structures using an autonomous underwater vehicle (AUV). To accomplish this, we first use our pipeline for mapping and planning collision-free paths online, which endows an AUV with the capability to autonomously acquire optical data in close proximity. With that information, we then propose a reconstruction pipeline to create a photo-realistic textured 3D model of the inspected area. These 3D models are also of particular interest to other fields of study in marine sciences, since they can serve as base maps for environmental monitoring, thus allowing change detection of biological communities and their environment over time. Finally, we evaluate our approach using the Sparus II, a torpedo-shaped AUV, conducting inspection missions in a challenging, real-world and natural scenario.

  15. Analysing Trust Transitivity and The Effects of Unknown Dependence

    Directory of Open Access Journals (Sweden)

    Touhid Bhuiyan

    2010-03-01

    Full Text Available Trust can be used to improve online automated recommendation within a given domain. Trust transitivity is used to make it successful. But trust transitivity has different interpretations. Trust and trust transitivity; both are the human mental phenomenon and for this reason, there is no such thing as objective transitivity. Trust transitivity and trust fusion both are important elements in computational trust. This paper analyses the parameter dependence problem in trust transitivity and proposes some definitions considering the effects of base rate. In addition, it also proposes belief functions based on subjective logic to analyse trust transitivity of three specified cases with sensitive and insensitive based rate. Then it presents a quantitative analysis of the effects of unknown dependence problem in an interconnected network environment; such Internet.

  16. An active damper to suppress multiple resonances with unknown frequencies

    DEFF Research Database (Denmark)

    Wang, Xiongfei; Blaabjerg, Frede; Liserre, Marco

    2014-01-01

    The increasing use of power electronics devices tends to aggravate high-frequency harmonics and trigger resonances across a wide frequency range into power systems. This paper presents an active damper to suppress multiple resonances with unknown frequencies. The active damper is realized by a high......-bandwidth power converter that can selectively dampen out the wideband resonances. A cascaded adaptive notch filter structure is proposed to detect the frequencies of resonances, which makes the active damper different from the resistive-active power filter for harmonic resonance suppression. The performance...... of the active damper is validated by implementing it to suppress the resonances in a grid-connected inverter with a long power cable. The results show that the active damper can become a promising approach to stabilizing the future power electronics based power systems....

  17. Villitis of unknown aetiology: correlation of recurrence with clinical outcome.

    LENUS (Irish Health Repository)

    Feeley, L

    2010-01-01

    Villitis of unknown aetiology (VUA) is associated with adverse pregnancy outcome. Consequently, an ability to predict recurrence could be clinically relevant. We examined placentas where villitis was diagnosed in a previous pregnancy to establish the risk of recurrence and outcome. A total of 304 cases of VUA were diagnosed in our laboratory over a 4-year period. Subsequently, 19 of this cohort had a second placenta examined histologically. Recurrence and clinical outcome were recorded. Villitis recurred in 7 of 19 cases (37%). There was a high level of adverse pregnancy outcome in this cohort overall, characterised by small for gestational age infants and stillbirth, particularly in cases with high-grade villitis. We identified recurrent villitis more frequently than previously reported. Our findings confirm an association between high-grade villitis and poor outcome. Adequately powered prospective studies are required to determine if enhanced surveillance of subsequent pregnancies is indicated following a diagnosis of villitis.

  18. A Brief Introduction on Mystery, the Unknown, Surprise

    Directory of Open Access Journals (Sweden)

    Sean Scanlan

    2012-03-01

    Full Text Available In this age of globalization, this age of so many ways to know—and so many ways to know things so quickly—it is both satisfying and deeply unnerving to come upon things and events that are really hard to understand, things and events so shocking or strange or mysterious, that they seem Unknown. Perhaps even unknowable. The first note of NANO Issue 2 focuses on an unsolved murder and reveals a mystery that is confounding, creepy, and yet oddly compelling. In “Karr’s Kill Cult: Virtual Cults and Pseudo-Killing in the Digital Age,” Jeremy Biles and Brian Collins explore the edges of where cyber-crime threatens to turn real—and vice versa. In the second note, Jennifer Ballengee compares Oedipus at Colonus with Don DeLillo’s Falling Man.

  19. Modal Parameter Identification from Responses of General Unknown Random Inputs

    DEFF Research Database (Denmark)

    Ibrahim, S. R.; Asmussen, J. C.; Brincker, Rune

    1996-01-01

    Modal parameter identification from ambient responses due to a general unknown random inputs is investigated. Existing identification techniques which are based on assumptions of white noise and or stationary random inputs are utilized even though the inputs conditions are not satisfied....... This is accomplished via adding. In cascade. A force cascade conversion to the structures system under consideration. The input to the force conversion system is white noise and the output of which is the actual force(s) applied to the structure. The white noise input(s) and the structures responses are then used...... to identify the compined system. Identification results are then sorted as either structural parameters or input force(s) characteristics....

  20. Angiotropic large cell lymphoma presenting as fever of unknown origin.

    Science.gov (United States)

    Kuvliev, E; Glamour, T; Shekar, R; West, B C

    1999-04-01

    Fever has never before been described as the chief complaint and major finding in angiotropic large cell lymphoma (ALCL). ALCL is a rare and usually fatal intravascular tumor characterized by a widespread proliferation of malignant mononuclear cells within vessels of small caliber, causing their blockage. The majority present as high-grade, B-cell lymphomas with a predilection for the central nervous system and the skin. We report a 61-year-old woman who presented with a fever of unknown origin (FUO) that lasted 9 weeks from onset to death. To our knowledge, this is the first case of ALCL to present solely as a FUO, and the second case of ALCL to be diagnosed by muscle biopsy. We suggest that this rare malignancy (ALCL) be considered in the differential diagnosis of FUO.

  1. Obstacle Avoidance for Unmanned Undersea Vehicle in Unknown Unstructured Environment

    Directory of Open Access Journals (Sweden)

    Zheping Yan

    2013-01-01

    Full Text Available To avoid obstacle in the unknown environment for unmanned undersea vehicle (UUV, an obstacle avoiding system based on improved vector field histogram (VFH is designed. Forward looking sonar is used to detect the environment, and the divisional sonar modal is applied to deal with the measure uncertainty. To adapt to the VFH, rolling occupancy grids are used for the map building, and high accuracy details of local environment are obtained. The threshold is adaptively adjusted by the statistic of obstacles to solve the problem that VFH is sensitive to threshold. To improve the environment adaptability, the hybrid-behaviors strategy is proposed, which selects the optimal avoidance command according to the motion status and environment character. The simulation shows that UUV could avoid the obstacles fast and escape from the U shape obstacles.

  2. Mobile robot navigation in unknown static environments using ANFIS controller

    Directory of Open Access Journals (Sweden)

    Anish Pandey

    2016-09-01

    Full Text Available Navigation and obstacle avoidance are the most important task for any mobile robots. This article presents the Adaptive Neuro-Fuzzy Inference System (ANFIS controller for mobile robot navigation and obstacle avoidance in the unknown static environments. The different sensors such as ultrasonic range finder sensor and sharp infrared range sensor are used to detect the forward obstacles in the environments. The inputs of the ANFIS controller are obstacle distances obtained from the sensors, and the controller output is a robot steering angle. The primary objective of the present work is to use ANFIS controller to guide the mobile robot in the given environments. Computer simulations are conducted through MATLAB software and implemented in real time by using C/C++ language running Arduino microcontroller based mobile robot. Moreover, the successful experimental results on the actual mobile robot demonstrate the effectiveness and efficiency of the proposed controller.

  3. Blind reconstruction of sparse images with unknown point spread function

    Science.gov (United States)

    Herrity, Kyle; Raich, Raviv; Hero, Alfred O., III

    2008-02-01

    We consider the image reconstruction problem when the original image is assumed to be sparse and when partial knowledge of the point spread function (PSF) is available. In particular, we are interested in recovering the magnetization density given magnetic resonance force microscopy (MRFM) data, and we present an iterative alternating minimization algorithm (AM) to solve this problem. A smoothing penalty is introduced on allowable PSFs to improve the reconstruction. Simulations demonstrate its performance in reconstructing both the image and unknown point spread function. In addition, we develop an optimization transfer approach to solving a total variation (TV) blind deconvolution algorithm presented in a paper by Chan and Wong. We compare the performance of the AM algorithm to the blind TV algorithm as well as to a TV based majorization-minimization algorithm developed by Figueiredo et al.

  4. Smooth extrapolation of unknown anatomy via statistical shape models

    Science.gov (United States)

    Grupp, R. B.; Chiang, H.; Otake, Y.; Murphy, R. J.; Gordon, C. R.; Armand, M.; Taylor, R. H.

    2015-03-01

    Several methods to perform extrapolation of unknown anatomy were evaluated. The primary application is to enhance surgical procedures that may use partial medical images or medical images of incomplete anatomy. Le Fort-based, face-jaw-teeth transplant is one such procedure. From CT data of 36 skulls and 21 mandibles separate Statistical Shape Models of the anatomical surfaces were created. Using the Statistical Shape Models, incomplete surfaces were projected to obtain complete surface estimates. The surface estimates exhibit non-zero error in regions where the true surface is known; it is desirable to keep the true surface and seamlessly merge the estimated unknown surface. Existing extrapolation techniques produce non-smooth transitions from the true surface to the estimated surface, resulting in additional error and a less aesthetically pleasing result. The three extrapolation techniques evaluated were: copying and pasting of the surface estimate (non-smooth baseline), a feathering between the patient surface and surface estimate, and an estimate generated via a Thin Plate Spline trained from displacements between the surface estimate and corresponding vertices of the known patient surface. Feathering and Thin Plate Spline approaches both yielded smooth transitions. However, feathering corrupted known vertex values. Leave-one-out analyses were conducted, with 5% to 50% of known anatomy removed from the left-out patient and estimated via the proposed approaches. The Thin Plate Spline approach yielded smaller errors than the other two approaches, with an average vertex error improvement of 1.46 mm and 1.38 mm for the skull and mandible respectively, over the baseline approach.

  5. Twelve previously unknown phage genera are ubiquitous in global oceans.

    Science.gov (United States)

    Holmfeldt, Karin; Solonenko, Natalie; Shah, Manesh; Corrier, Kristen; Riemann, Lasse; Verberkmoes, Nathan C; Sullivan, Matthew B

    2013-07-30

    Viruses are fundamental to ecosystems ranging from oceans to humans, yet our ability to study them is bottlenecked by the lack of ecologically relevant isolates, resulting in "unknowns" dominating culture-independent surveys. Here we present genomes from 31 phages infecting multiple strains of the aquatic bacterium Cellulophaga baltica (Bacteroidetes) to provide data for an underrepresented and environmentally abundant bacterial lineage. Comparative genomics delineated 12 phage groups that (i) each represent a new genus, and (ii) represent one novel and four well-known viral families. This diversity contrasts the few well-studied marine phage systems, but parallels the diversity of phages infecting human-associated bacteria. Although all 12 Cellulophaga phages represent new genera, the podoviruses and icosahedral, nontailed ssDNA phages were exceptional, with genomes up to twice as large as those previously observed for each phage type. Structural novelty was also substantial, requiring experimental phage proteomics to identify 83% of the structural proteins. The presence of uncommon nucleotide metabolism genes in four genera likely underscores the importance of scavenging nutrient-rich molecules as previously seen for phages in marine environments. Metagenomic recruitment analyses suggest that these particular Cellulophaga phages are rare and may represent a first glimpse into the phage side of the rare biosphere. However, these analyses also revealed that these phage genera are widespread, occurring in 94% of 137 investigated metagenomes. Together, this diverse and novel collection of phages identifies a small but ubiquitous fraction of unknown marine viral diversity and provides numerous environmentally relevant phage-host systems for experimental hypothesis testing.

  6. Altamira cave Paleolithic paintings harbor partly unknown bacterial communities.

    Science.gov (United States)

    Schabereiter-Gurtner, Claudia; Saiz-Jimenez, Cesareo; Piñar, Guadalupe; Lubitz, Werner; Rölleke, Sabine

    2002-05-21

    Since it has been reported that microorganisms can affect painting pigments, Paleolithic painting microbiology deserves attention. The present study is the first report on the bacterial colonization of the valuable Paleolithic paintings in the famous Altamira cave (Spain). One sample taken from a painting area in the Polychromes Hall was analyzed culture-independently. This was the first time microbiologists were allowed to take sample material directly from Altamira paintings. Identification methods included PCR amplification of 16S rRNA genes (16S rDNA) and community fingerprinting by denaturing gradient gel electrophoresis (DGGE). The applied approach gave insight into a great bacterial taxonomic diversity, and allowed the detection of unexpected and unknown bacteria with potential effects on the conservation of the painting. Regarding the number of 29 visible DGGE bands in the community fingerprint, the numbers of analyzed clones described about 72% of the phylogenetic diversity present in the sample. Thirty-eight percent of the sequences analyzed were phylogenetically most closely related to cultivated bacteria, while the majority (62%) were most closely related to environmental 16S rDNA clones. Bacteria identified in Altamira were related with sequence similarities between 84.8 and 99.4% to members of the cosmopolitan Proteobacteria (52.3%), to members of the Acidobacterium division (23.8%), Cytophaga/Flexibacter/Bacteroides phylum (9.5%), green non-sulfur bacteria (4.8%), Planctomycetales (4.8%) and Actinobacteria (4.8%). The high number of clones most closely related to environmental 16S rDNA clones showed the broad spectrum of unknown and yet to be cultivated bacteria in Altamira cave.

  7. Microbial Dark Matter Phase II: Stepping deeper into unknown territory

    Energy Technology Data Exchange (ETDEWEB)

    Jarett, Jessica; Dunfield, Peter; Peura, Sari; Wielen, Paul van der; Hedlund, Brian; Elshahed, Mostafa; Kormas, Konstantinos; Stott, Andreas Teske8, Matt; Birkeland, Nils-Kare; Zhang, Chuanlun; Rengefors, Karin; Lindemann, Stephen; Ravin, Nikolai V.; Spear, John; Hallam, Steven; Crowe, Sean; Steele, Jillian; Goudeau, Danielle; Malmstrom, Rex; Kyrpides, Nikos; Stepanauskas, Ramunas; Woyke, Tanja

    2014-10-27

    Currently available microbial genomes are of limited phylogenetic breadth due to our historical inability to cultivate most microorganisms in the laboratory. The first phase of the Microbial Dark Matter project used single-cell genomics to sequence 201 single cells from uncultivated lineages, and was able to resolve new superphyla and reveal novel metabolic features in bacteria and archaea. However, many fundamental questions about the evolution and function of microbes remain unanswered, and many candidate phyla remain uncharacterized. Phase II of the Microbial Dark Matter project will target candidate phyla with no sequenced representatives at a variety of new sites using a combination of single-cell sequencing and shotgun metagenomics approaches.

  8. On random age and remaining lifetime for populations of items

    DEFF Research Database (Denmark)

    Finkelstein, M.; Vaupel, J.

    2015-01-01

    We consider items that are incepted into operation having already a random (initial) age and define the corresponding remaining lifetime. We show that these lifetimes are identically distributed when the age distribution is equal to the equilibrium distribution of the renewal theory. Then we...

  9. Holocene insect remains from south-western Greenland

    DEFF Research Database (Denmark)

    Bøcher, Jens Jensenius; Bennike, Ole; Wagner, Bernd

    2012-01-01

    Remains of plants and invertebrates from Holocene deposits in south-western Greenland include a number of insect fragments from Heteroptera and Coleoptera. Some of the finds extend the known temporal range of the species considerably back in time, and one of the taxa has not previously been found...... of terrestrial insects complement the scarce fossil Greenland record of the species concerned....

  10. Remaining childless : Causes and consequences from a life course perspective

    NARCIS (Netherlands)

    Keizer, R.

    2010-01-01

    Little is know about childless individuals in the Netherlands, although currently one out of every five Dutch individuals remains childless. Who are they? How did they end up being childless? How and to what extent are their life outcomes influenced by their childlessness? By focusing on individual

  11. Predicting the Remaining Useful Life of Rolling Element Bearings

    DEFF Research Database (Denmark)

    Hooghoudt, Jan Otto; Jantunen, E; Yi, Yang

    2017-01-01

    Condition monitoring of rolling element bearings is of vital importance in order to keep the industrial wheels running. In wind industry this is especially important due to the challenges in practical maintenance. The paper presents an attempt to improve the capability of prediction of remaining...

  12. Remaining a Nonparticipant in a Cooperative Group Setting.

    Science.gov (United States)

    Deardoff, Richard

    1996-01-01

    A high school history teacher of gifted students examined difficulties in establishing cooperative groups when members changed frequently. Student interviews and surveys indicated that some students were happy to remain nonparticipants in any group. Participation was less a factor of group makeup than a factor of student opinion about grades.…

  13. Dinosaur remains from the type Maastrichtian: An update

    NARCIS (Netherlands)

    Weishampel, David B.; Mulder, Eric W A; Dortangs, Rudi W.; Jagt, John W M; Jianu, Coralia Maria; Kuypers, Marcel M M; Peeters, Hans H G; Schulp, Anne S.

    1999-01-01

    Isolated cranial and post-cranial remains of hadrosaurid dinosaurs have been collected from various outcrops in the type area of the Maastrichtian stage during the last few years. In the present contribution, dentary and maxillary teeth are recorded from the area for the first time. Post-cranial

  14. Ancient DNA in human bone remains from Pompeii archaeological site.

    Science.gov (United States)

    Cipollaro, M; Di Bernardo, G; Galano, G; Galderisi, U; Guarino, F; Angelini, F; Cascino, A

    1998-06-29

    aDNA extraction and amplification procedures have been optimized for Pompeian human bone remains whose diagenesis has been determined by histological analysis. Single copy genes amplification (X and Y amelogenin loci and Y specific alphoid repeat sequences) have been performed and compared with anthropometric data on sexing.

  15. The Workers' Value of the Remaining Employment Contract Duration

    NARCIS (Netherlands)

    Ommeren, van Jos; Hazans, Mihails

    2005-01-01

    This paper introduces and applies a method for estimating workers' marginal willingness to pay for job attributes employing data on job search activity. Worker's willingness to pay for the remaining duration of the employment contract is derived. We provide evidence that workers attach substantial

  16. Robotics to Enable Older Adults to Remain Living at Home

    Directory of Open Access Journals (Sweden)

    Alan J. Pearce

    2012-01-01

    Full Text Available Given the rapidly ageing population, interest is growing in robots to enable older people to remain living at home. We conducted a systematic review and critical evaluation of the scientific literature, from 1990 to the present, on the use of robots in aged care. The key research questions were as follows: (1 what is the range of robotic devices available to enable older people to remain mobile, independent, and safe? and, (2 what is the evidence demonstrating that robotic devices are effective in enabling independent living in community dwelling older people? Following database searches for relevant literature an initial yield of 161 articles was obtained. Titles and abstracts of articles were then reviewed by 2 independent people to determine suitability for inclusion. Forty-two articles met the criteria for question 1. Of these, 4 articles met the criteria for question 2. Results showed that robotics is currently available to assist older healthy people and people with disabilities to remain independent and to monitor their safety and social connectedness. Most studies were conducted in laboratories and hospital clinics. Currently limited evidence demonstrates that robots can be used to enable people to remain living at home, although this is an emerging smart technology that is rapidly evolving.

  17. Five reasons why South African librarianship remains untransformed ...

    African Journals Online (AJOL)

    ... librarianship remains untransformed. These reasons are the result of misunderstandings by librarians about the historical process, social change, political change, professional change and the intellectual roles of librarians. Suggestions for dealing with these misunderstandings are provided. (Innovation: 2002 25: 27-36) ...

  18. Molecular genetic identification of skeletal remains of apartheid ...

    African Journals Online (AJOL)

    The Truth and Reconciliation Commission made significant progress in examining abuses committed during the apartheid era in South Africa. Despite information revealed by the commission, a large number of individuals remained missing when the commission closed its proceedings. This provided the impetus for the ...

  19. The experiences of remaining nurse tutors during the transformation ...

    African Journals Online (AJOL)

    The transformation of public services and education in South Africa is part of the political and socioeconomic transition to democracy. Changes are occurring in every fi eld, including that of the health services. A qualitative study was undertaken to investigate the experiences of the remaining nurse tutors at a school of ...

  20. The treatment of human remains | Satyapal | South African Journal ...

    African Journals Online (AJOL)

    Concerns regarding treatment of the dead in scientific and public arenas, issues related to consent, respect for human dignity, scientific integrity, societal expectations, and why treatment of cadavers are ethically significant are highlighted. The display of human remains claimed as 'edutainment' or 'anatomy art' in Body ...

  1. Collegial Climate and Novice Teachers' Intent to Remain Teaching

    Science.gov (United States)

    Pogodzinski, Ben; Youngs, Peter; Frank, Kenneth A.

    2013-01-01

    Using survey data from novice teachers across 99 schools, we estimated multilevel regressions to identify the association between novices' intent to remain teaching within their schools and their perceptions of the collegial climate. The results suggest that novice teachers who perceive a more positive collegial climate marked by higher degrees…

  2. Performing colonic mast cell counts in patients with chronic diarrhea of unknown etiology has limited diagnostic use.

    Science.gov (United States)

    Sethi, Aisha; Jain, Dhanpat; Roland, Bani Chander; Kinzel, Jason; Gibson, Joanna; Schrader, Ronald; Hanson, Joshua Anspach

    2015-02-01

    Mastocytic enterocolitis is a recently described entity defined by chronic diarrhea of unknown etiology and normal colon biopsy results with increased mast cells (MCs) seen on special stains. These patients may benefit from mast cell stabilizers; however, the clinical utility of MC counts remains unknown. To determine the clinical utility of colonic MC counts on normal biopsies in patients with chronic diarrhea of unknown etiology. Blinded MC counts using a c-Kit stain were performed in 76 consecutive patients with chronic diarrhea of unknown etiology who had normal colon biopsy results and in 89 consecutive control patients presenting for screening colonoscopy. Mast cells were counted per single high-power field in the highest-density area. A t test was used to compare the counts, and receiver operating characteristic curves were generated to examine sensitive and specific cutoff values. Overall, MC counts averaged 31 MCs per high-power field in the study group versus 24 MCs per high-power field in the control group (P chronic diarrhea of unknown etiology, primarily in the left colon. However, receiver operating characteristic analysis demonstrates no discriminatory cutoff values. Quantitative MC stains yield little useful diagnostic information, and further studies are necessary to determine whether mastocytic enterocolitis truly represents a distinct entity.

  3. Current status and bioanalytical challenges in the detection of unknown anabolic androgenic steroids in doping control analysis.

    Science.gov (United States)

    Pozo, Oscar J; De Brabanter, Nik; Fabregat, Andreu; Segura, Jordi; Ventura, Rosa; Van Eenoo, Peter; Deventer, Koen

    2013-11-01

    Androgenic anabolic steroids (AAS) are prohibited in sports due to their anabolic effects. Doping control laboratories usually face the screening of AAS misuse by target methods based on MS detection. Although these methods allow for the sensitive and specific detection of targeted compounds and metabolites, the rest remain undetectable. This fact opens a door for cheaters, since different AAS can be synthesized in order to evade doping control tests. This situation was evidenced in 2003 with the discovery of the designer steroid tetrahydrogestrinone. One decade after this discovery, the detection of unknown AAS still remains one of the main analytical challenges in the doping control field. In this manuscript, the current situation in the detection of unknown AAS is reviewed. Although important steps have been made in order to minimize this analytical problem and different analytical strategies have been proposed, there are still some drawbacks related to each approach.

  4. Communication to within a fidelity criterion over unknown networks by reduction to reliable communication problems over unknown networks

    CERN Document Server

    Agarwal, Mukul

    2010-01-01

    Consider a scenerio where various users want to communicate with each other over an unknown network to within a fidelity criterion. Thus, there are various users. Each user has a source that it wants to send to another user to within some distortion level. We abstract this problem as that of universal communication of random sources over networks to within a distortion criterion. We compute ta universally reliably achievable region for a set of networks where networks in the set are defined in terms of end to end distortion that they achieve for transmission of independent signals between various nodes assuming that there is common randomness between sender and corresponding receiver. Using this, we provide results for when communication of independent signals to within particular fidelity criteria is possible in terms of when reliable communication is possible. Using this, we show that when the sources at the various nodes are independent of each other, it is sufficient to consider separation architectures: ...

  5. Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study.

    Science.gov (United States)

    Naito, Toshio; Mizooka, Masafumi; Mitsumoto, Fujiko; Kanazawa, Kenji; Torikai, Keito; Ohno, Shiro; Morita, Hiroyuki; Ukimura, Akira; Mishima, Nobuhiko; Otsuka, Fumio; Ohyama, Yoshio; Nara, Noriko; Murakami, Kazunari; Mashiba, Kouichi; Akazawa, Kenichiro; Yamamoto, Koji; Senda, Shoichi; Yamanouchi, Masashi; Tazuma, Susumu; Hayashi, Jun

    2013-12-20

    Fever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO. A nationwide retrospective study. 17 hospitals affiliated with the Japanese Society of Hospital General Medicine. This study included patients ≥18 years diagnosed with 'classical fever of unknown origin' (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011. A total of 121 patients with FUO were enrolled. The median age was 59 years (range 19-94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients. With the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO.

  6. Remaining teeth, cardiovascular morbidity and death among adult Danes

    DEFF Research Database (Denmark)

    Heitmann, B L; Gamborg, M

    2008-01-01

    OBJECTIVE: To examine if number of remaining teeth was associated with development of cardiovascular morbidity and mortality over 5-12 years. METHODS: Prospective observational study among 1474 men and 1458 women born 1922, 1932, 1942 or 1952 from The Danish MONICA follow up study (MONItoring......, incidence of cardiovascular disease and coronary heart disease, during averagely 7.5 years of follow-up. Compared to those with most teeth remaining, the edentulous suffered >3-fold increased Hazard (HR) of developing stroke (HR=3.25; 95% CI: 1.48-7.14), whereas the risk of developing any cardiovascular...... disease was increased by 50% (HR=1.50; 95% CI: 1.02-2.19). Risk for coronary heart disease was increased by 31%, but was not significant, after the adjustment for education, age, smoking, diabetes, alcohol intake, systolic blood pressure and body mass index (HR= 1.31; 95% CI: 0.74-2.31). Associations were...

  7. Mandibular remains support taxonomic validity of Australopithecus sediba.

    Science.gov (United States)

    de Ruiter, Darryl J; DeWitt, Thomas J; Carlson, Keely B; Brophy, Juliet K; Schroeder, Lauren; Ackermann, Rebecca R; Churchill, Steven E; Berger, Lee R

    2013-04-12

    Since the announcement of the species Australopithecus sediba, questions have been raised over whether the Malapa fossils represent a valid taxon or whether inadequate allowance was made for intraspecific variation, in particular with reference to the temporally and geographically proximate species Au. africanus. The morphology of mandibular remains of Au. sediba, including newly recovered material discussed here, shows that it is not merely a late-surviving morph of Au. africanus. Rather-as is seen elsewhere in the cranium, dentition, and postcranial skeleton-these mandibular remains share similarities with other australopiths but can be differentiated from the hypodigm of Au. africanus in both size and shape as well as in their ontogenetic growth trajectory.

  8. Suicidal terrorist bombings in Israel--identification of human remains.

    Science.gov (United States)

    Kahana, T; Freund, M; Hiss, J

    1997-03-01

    Positive identification of human remains is one of the most important tasks in mass disaster investigations. Religious and jurisdictional demands in Israel, require the identification process to be completed in the shortest possible time. In the 18 suicidal terrorist bombings that took place in Israel between the years 1993-1996, 127 victims and 19 perpetrators were killed, and their severely fragmented bodies were identified within 24 h. The efficient completion of the identification endeavor was enabled by the implementation of a variety of techniques and the close collaboration in the investigation between the different emergency and forensic agencies. This paper presents the mass disaster identification policy and techniques currently used in Israel. The importance of an interdisciplinary approach for the identification of extremely fragmented human remains from mass disasters and the creation of a central data bank of fingerprints and genetic markers is emphasized.

  9. The impact of downsizing on remaining workers' sickness absence.

    Science.gov (United States)

    Østhus, Ståle; Mastekaasa, Arne

    2010-10-01

    It is generally assumed that organizational downsizing has considerable negative consequences, not only for workers that are laid off, but also for those who remain employed. The empirical evidence with regard to effects on sickness absence is, however, inconsistent. This study employs register data covering a major part of the total workforce in Norway over the period 2000-2003. The number of sickness absence episodes and the number of sickness absence days are analysed by means of Poisson regression. To control for both observed and unobserved stable individual characteristics, we use conditional (fixed effects) estimation. The analyses provide some weak indications that downsizing may lead to slightly less sickness absence, but the overall impression is that downsizing has few if any effects on the sickness absence of the remaining employees. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Mineral remains of early life on Earth? On Mars?

    Science.gov (United States)

    Iberall, Robbins E.; Iberall, A.S.

    1991-01-01

    The oldest sedimentary rocks on Earth, the 3.8-Ga Isua Iron-Formation in southwestern Greenland, are metamorphosed past the point where organic-walled fossils would remain. Acid residues and thin sections of these rocks reveal ferric microstructures that have filamentous, hollow rod, and spherical shapes not characteristic of crystalline minerals. Instead, they resemble ferric-coated remains of bacteria. Because there are no earlier sedimentary rocks to study on Earth, it may be necessary to expand the search elsewhere in the solar system for clues to any biotic precursors or other types of early life. A study of morphologies of iron oxide minerals collected in the southern highlands during a Mars sample return mission may therefore help to fill in important gaps in the history of Earth's earliest biosphere. -from Authors

  11. Osteometric sex determination of burned human skeletal remains.

    Science.gov (United States)

    Gonçalves, D; Thompson, T J U; Cunha, E

    2013-10-01

    Sex determination of human burned skeletal remains is extremely hard to achieve because of heat-related fragmentation, warping and dimensional changes. In particular, the latter is impeditive of osteometric analyses that are based on references developed on unburned bones. New osteometric references were thus obtained which allow for more reliable sex determinations. The calcined remains of cremated Portuguese individuals were examined and specific standard measurements of the humerus, femur, talus and calcaneus were recorded. This allowed for the compilation of new sex discriminating osteometric references which were then tested on independent samples with good results. Both the use of simple section points and of logistic regression equations provided successful sex classification scores. These references may now be used for the sex determination of burned skeletons. Its reliability is highest for contemporary Portuguese remains but nonetheless these results have important repercussion for forensic research. More conservative use of these references may also prove valuable for other populations as well as for archaeological research. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  12. Field contamination of skeletonized human remains with exogenous DNA.

    Science.gov (United States)

    Edson, Suni M; Christensen, Alexander F

    2013-01-01

    The Armed Forces DNA Identification Laboratory reports the mitochondrial DNA (mtDNA) sequences of over 800 skeletal samples a year for the Joint POW/MIA Accounting Command-Central Identification Laboratory. These sequences are generated from degraded skeletal remains that are presumed to belong to U.S. service members missing from past military conflicts. In the laboratory, it is possible to control for contamination of remains; however, in the field, it can be difficult to prevent modern DNA from being transferred to skeletal elements and being carried forward through the analysis process. Four such cases are described here along with the controls in place in the laboratory to eliminate the possibility of the exogenous DNA being reported as authentic. In each case, the controls implemented by the laboratories prevented the false reporting of contaminant exogenous DNA from remains that were either faunal or human, but lacked endogenous DNA. © 2012 American Academy of Forensic Sciences Published 2012. This article is a U.S. Government work and is in the public domain in the U.S.A.

  13. Postmortem Scavenging of Human Remains by Domestic Cats

    Directory of Open Access Journals (Sweden)

    Ananya Suntirukpong, M.D.

    2017-11-01

    Full Text Available Objective: Crime scene investigators, forensic medicine doctors and pathologists, and forensic anthropologists frequently encounter postmortem scavenging of human remains by household pets. Case presentation: The authors present a case report of a partially skeletonized adult male found dead after more than three months in his apartment in Thailand. The body was in an advanced stage of decomposition with nearly complete skeletonization of the head, neck, hands, and feet. The presence of maggots and necrophagous (flesh eating beetles on the body confirmed that insects had consumed much of the soft tissues. Examination of the hand and foot bones revealed canine tooth puncture marks. Evidence of chewing indicated that one or more of the decedent’s three house cats had fed on the body after death. Recognizing and identifying carnivore and rodent activity on the soft flesh and bones of human remains is important in interpreting and reconstructing postmortem damage. Thorough analysis may help explain why skeletal elements are missing, damaged, or out of anatomical position. Conclusion: This report presents a multi-disciplinary approach combining forensic anthropology and forensic medicine in examining and interpreting human remains.

  14. Choosing and remaining in nursing: Iranian male nurses' perspectives.

    Science.gov (United States)

    Zamanzadeh, Vahid; Azadi, Arman; Valizadeh, Leila; Keogh, Brian; Monadi, Morteza; Negarandeh, Reza

    2013-10-01

    Iranian male nurses' career-choosing practices have not been well investigated. The aim of this study was to explore the reasons why Iranian male nurses choose nursing as a career. In addition it sought to understand the reasons why they remain in nursing. An exploratory descriptive design, employing a qualitative approach was used. Eighteen semi-structured interviews were conducted and analyzed using content analysis. The analysis culminated in the development of three themes which described the participants' motivations for choosing nursing as a career as well as the factors that influenced their decisions to remain in nursing following qualification. Practical motivations such as job security were important factors in choosing nursing. The most common reason for remaining in nursing was desire to care for others, for God's sake. Factors that influenced their decision to leave mainly centered on the public view to nursing as a feminine discipline. However, the nurses in this study believed that nursing was a profession appropriate for both men and women because of gendered nursing care and preferences of patient in Iran.

  15. Pigment Cell Progenitors in Zebrafish Remain Multipotent through Metamorphosis.

    Science.gov (United States)

    Singh, Ajeet Pratap; Dinwiddie, April; Mahalwar, Prateek; Schach, Ursula; Linker, Claudia; Irion, Uwe; Nüsslein-Volhard, Christiane

    2016-08-08

    The neural crest is a transient, multipotent embryonic cell population in vertebrates giving rise to diverse cell types in adults via intermediate progenitors. The in vivo cell-fate potential and lineage segregation of these postembryonic progenitors is poorly understood, and it is unknown if and when the progenitors become fate restricted. We investigate the fate restriction in the neural crest-derived stem cells and intermediate progenitors in zebrafish, which give rise to three distinct adult pigment cell types: melanophores, iridophores, and xanthophores. By inducing clones in sox10-expressing cells, we trace and quantitatively compare the pigment cell progenitors at four stages, from embryogenesis to metamorphosis. At all stages, a large fraction of the progenitors are multipotent. These multipotent progenitors have a high proliferation ability, which diminishes with fate restriction. We suggest that multipotency of the nerve-associated progenitors lasting into metamorphosis may have facilitated the evolution of adult-specific traits in vertebrates. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Kriging with Unknown Variance Components for Regional Ionospheric Reconstruction

    Directory of Open Access Journals (Sweden)

    Ling Huang

    2017-02-01

    Full Text Available Ionospheric delay effect is a critical issue that limits the accuracy of precise Global Navigation Satellite System (GNSS positioning and navigation for single-frequency users, especially in mid- and low-latitude regions where variations in the ionosphere are larger. Kriging spatial interpolation techniques have been recently introduced to model the spatial correlation and variability of ionosphere, which intrinsically assume that the ionosphere field is stochastically stationary but does not take the random observational errors into account. In this paper, by treating the spatial statistical information on ionosphere as prior knowledge and based on Total Electron Content (TEC semivariogram analysis, we use Kriging techniques to spatially interpolate TEC values. By assuming that the stochastic models of both the ionospheric signals and measurement errors are only known up to some unknown factors, we propose a new Kriging spatial interpolation method with unknown variance components for both the signals of ionosphere and TEC measurements. Variance component estimation has been integrated with Kriging to reconstruct regional ionospheric delays. The method has been applied to data from the Crustal Movement Observation Network of China (CMONOC and compared with the ordinary Kriging and polynomial interpolations with spherical cap harmonic functions, polynomial functions and low-degree spherical harmonic functions. The statistics of results indicate that the daily ionospheric variations during the experimental period characterized by the proposed approach have good agreement with the other methods, ranging from 10 to 80 TEC Unit (TECU, 1 TECU = 1 × 1016 electrons/m2 with an overall mean of 28.2 TECU. The proposed method can produce more appropriate estimations whose general TEC level is as smooth as the ordinary Kriging but with a smaller standard deviation around 3 TECU than others. The residual results show that the interpolation precision of the

  17. Effects of Memory Colour on Colour Constancy for Unknown Coloured Objects

    Directory of Open Access Journals (Sweden)

    Jeroen J M Granzier

    2012-04-01

    Full Text Available The perception of an object's colour remains constant despite large variations in the chromaticity of the illumination—colour constancy. Hering suggested that memory colours, the typical colours of objects, could help in estimating the illuminant's colour and therefore be an important factor in establishing colour constancy. Here we test whether the presence of objects with diagnostical colours (fruits, vegetables, etc within a scene influence colour constancy for unknown coloured objects in the scene. Subjects matched one of four Munsell papers placed in a scene illuminated under either a reddish or a greenish lamp with the Munsell book of colour illuminated by a neutral lamp. The Munsell papers were embedded in four different scenes—one scene containing diagnostically coloured objects, one scene containing incongruent coloured objects, a third scene with geometrical objects of the same colour as the diagnostically coloured objects, and one scene containing non-diagnostically coloured objects (eg, a yellow coffee mug. All objects were placed against a black background. Colour constancy was on average significantly higher for the scene containing the diagnostically coloured objects compared with the other scenes tested. We conclude that the colours of familiar objects help in obtaining colour constancy for unknown objects.

  18. Effects of memory colour on colour constancy for unknown coloured objects.

    Science.gov (United States)

    Granzier, Jeroen J M; Gegenfurtner, Karl R

    2012-01-01

    The perception of an object's colour remains constant despite large variations in the chromaticity of the illumination-colour constancy. Hering suggested that memory colours, the typical colours of objects, could help in estimating the illuminant's colour and therefore be an important factor in establishing colour constancy. Here we test whether the presence of objects with diagnostical colours (fruits, vegetables, etc) within a scene influence colour constancy for unknown coloured objects in the scene. Subjects matched one of four Munsell papers placed in a scene illuminated under either a reddish or a greenish lamp with the Munsell book of colour illuminated by a neutral lamp. The Munsell papers were embedded in four different scenes-one scene containing diagnostically coloured objects, one scene containing incongruent coloured objects, a third scene with geometrical objects of the same colour as the diagnostically coloured objects, and one scene containing non-diagnostically coloured objects (eg, a yellow coffee mug). All objects were placed against a black background. Colour constancy was on average significantly higher for the scene containing the diagnostically coloured objects compared with the other scenes tested. We conclude that the colours of familiar objects help in obtaining colour constancy for unknown objects.

  19. Effects of memory colour on colour constancy for unknown coloured objects

    Science.gov (United States)

    Granzier, Jeroen J M; Gegenfurtner, Karl R

    2012-01-01

    The perception of an object's colour remains constant despite large variations in the chromaticity of the illumination—colour constancy. Hering suggested that memory colours, the typical colours of objects, could help in estimating the illuminant's colour and therefore be an important factor in establishing colour constancy. Here we test whether the presence of objects with diagnostical colours (fruits, vegetables, etc) within a scene influence colour constancy for unknown coloured objects in the scene. Subjects matched one of four Munsell papers placed in a scene illuminated under either a reddish or a greenish lamp with the Munsell book of colour illuminated by a neutral lamp. The Munsell papers were embedded in four different scenes—one scene containing diagnostically coloured objects, one scene containing incongruent coloured objects, a third scene with geometrical objects of the same colour as the diagnostically coloured objects, and one scene containing non-diagnostically coloured objects (eg, a yellow coffee mug). All objects were placed against a black background. Colour constancy was on average significantly higher for the scene containing the diagnostically coloured objects compared with the other scenes tested. We conclude that the colours of familiar objects help in obtaining colour constancy for unknown objects. PMID:23145282

  20. Viral Encephalitis of Unknown Cause: Current Perspective and Recent Advances

    Directory of Open Access Journals (Sweden)

    Peter G. E. Kennedy

    2017-06-01

    Full Text Available Viral encephalitis causes acute inflammation of the brain parenchyma and is a significant cause of human morbidity and mortality. Although Herpes Simplex encephalitis is the most frequent known cause of fatal sporadic encephalitis in humans, an increasingly wide range of viruses and other microbial pathogens are implicated. Up to 60% of cases of presumed viral encephalitis remain unexplained due to the failure of conventional laboratory techniques to detect an infectious agent. High-throughput DNA sequencing technologies have the potential to detect any microbial nucleic acid present in a biological specimen without any prior knowledge of the target sequence. While there remain challenges intrinsic to these technologies, they have great promise in virus discovery in unexplained encephalitis.

  1. The Difficulty of Sexing Skeletons from Unknown Populations

    OpenAIRE

    Ingrid Sierp; Maciej Henneberg

    2015-01-01

    Determination of sex from skeletal remains is performed using a number of methods developed by biological anthropology. They must be evaluated for consistency and for their performance in a forensic setting. Twenty skeletons of varied provenance had their sex determined by 15 existing methods of forensic anthropology (7 metric and 8 morphological). The methods were evaluated for their consistency in determination of sex. No single individual was identified as belonging to one sex exclusively....

  2. Territory: An Unknown Quantity in Debates on Territorial Cohesion

    Directory of Open Access Journals (Sweden)

    Andreas Faludi

    2013-08-01

    Full Text Available There are complaints about territorial cohesion being a vague concept, but in relevant debates territory, too, figures as an unknown quantity. Thus, is it the fixed property of any state, region or local administrative unit, or is it a malleable social construct; rather than being filled with bounded territories, does space overall contain a dynamic network with fuzzy internal, as well as external boundaries, with implications for territorial cohesion? After all, if the former were to be true, territorial cohesion would refer to qualities of what is inside bounded territories. If it were to be the latter, then the meaning of territorial cohesion would include qualities of the relations within a complex network of socially constructed, sometimes ephemeral constructs. There are implications for the ways subsidiarity and multi-level governance are invoked in EU discourse where there is a similar failure to question the underlying notion of territory. What is relevant here is the distinction between a ‘territorial’ and ‘relational’ geography. Considered opinion suggests that these alternatives can and, in view of the persistence of the principle of territorial representation, must be reconciled. However, though firmly entrenched, some constitutional theorists question the very principle. The debate is far from conclusive but at least it shows that discussion, even of this apparently fundamental principle is possible.

  3. Physics at 13 TeV: CMS - scanning the unknown

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    CMS is getting ready to use its accurate detector to scan the many ripples of the unknown physics that may lie beyond the Standard Model. Foremost in everyone’s mind is the search for signs of the production of dark matter at a man-made machine.   Interestingly, the observation of dark matter or new weakly interacting particles implies detecting that some energy has escaped, i.e. it’s missing from the upcoming proton collisions at the LHC. This is why measuring and understanding “missing energy” will be a very important step in that direction. “A large amount of missing energy is the signature for many processes of physics beyond the Standard Model. However, it’s not the only interesting signature that we will be able to exploit when the new collision energy is available,” explains Luca Malgeri, CMS Physics Coordinator. Among the interesting things not associated with missing energy are high-mass resonanc...

  4. [Tilt test for the evaluation of syncope of unknown origin].

    Science.gov (United States)

    Muratore, C; Rabinovich, R; Valentino, M; Baranchuk, A; Liprandi, A S

    1997-01-01

    The aim of this study was to evaluate the usefulness of head up tilt testing in patients with syncope of unknown origin. Between January 1994 and September 1995, 93 patients were referred for tilt table assessment due to recurrent syncope of uncertain etiology. There were 42 men (mean age 59 years). Thirty healthy volunteers served as a control group. The specific protocol used involved an initial period of supine rest for 15'. Baseline blood pressure (BP) and heart rate (HR) were recorded. This was followed by a tilt to 80 degrees for 30', BP and HR were measured every minute during the procedure. The test was considered positive when symptoms appeared associated with one of the following responses: systolic BP decreased more than 30 mmHg (vasodepressor), bradicardia or asystolia for up to 3" (cardioinhibitory) or mixed. The tilt test was positive in 31 of 93 patients (33%). Seventeen patients (55%) had a vasodepressor response, 3 patients (9%) a cardioinhibitory response and 11 patients (36%) mixed responses. The clinical manifestations were 62% near syncope, 19% syncope and the other patients presented dypsnea or dizziness. The symptoms disappeared promptly after adopting the supine position. None of the 30 healthy volunteers developed symptoms. We conclude that head up tilt test is a safe and effective method for identifying a neurocardiogenic origin in a syncope of uncertain etiology.

  5. Gravity, strings and particles a journey into the unknown

    CERN Document Server

    Gasperini, Maurizio

    2014-01-01

    New fundamental forces of Nature? New forms of "dark'' energy? Signals from epochs preceding the Big Bang? Is our space-time unique? Only a joint study of the three topics examined in this book – gravity, strings and particles – may provide answers to these questions. Such a study may also provide the key to solving one of the most fascinating mysteries of modern science, namely: Besides time and the three spatial dimensions, how many other dimensions exist in our universe? The book is primarily addressed to readers who do not necessarily have a specific background in physics but are nevertheless interested in discovering the originality and the possible implications of some of the amazing ideas in modern theoretical physics. The emphasis is on conveying ideas rather than explaining formulas, focusing not on what is known but -- mainly -- on what is still unknown. Many parts of the book are devoted to fundamental theoretical models and results which are potentially highly relevant for a deeper understand...

  6. Adaptive stochastic resonance for unknown and variable input signals.

    Science.gov (United States)

    Krauss, Patrick; Metzner, Claus; Schilling, Achim; Schütz, Christian; Tziridis, Konstantin; Fabry, Ben; Schulze, Holger

    2017-05-26

    All sensors have a threshold, defined by the smallest signal amplitude that can be detected. The detection of sub-threshold signals, however, is possible by using the principle of stochastic resonance, where noise is added to the input signal so that it randomly exceeds the sensor threshold. The choice of an optimal noise level that maximizes the mutual information between sensor input and output, however, requires knowledge of the input signal, which is not available in most practical applications. Here we demonstrate that the autocorrelation of the sensor output alone is sufficient to find this optimal noise level. Furthermore, we demonstrate numerically and analytically the equivalence of the traditional mutual information approach and our autocorrelation approach for a range of model systems. We furthermore show how the level of added noise can be continuously adapted even to highly variable, unknown input signals via a feedback loop. Finally, we present evidence that adaptive stochastic resonance based on the autocorrelation of the sensor output may be a fundamental principle in neuronal systems.

  7. Fever of unknown origin: subacute thyroiditis versus typhoid fever.

    Science.gov (United States)

    Cunha, Burke A; Thermidor, Marjorie; Mohan, Sowjanya; Valsamis, Ageliki S; Johnson, Diane H

    2005-01-01

    Fever of unknown origin (FUO) is not infrequently a diagnostic dilemma for clinicians. Common infectious causes include endocarditis and abscesses in adults, and noninfectious causes include neoplasms and certain collagen vascular diseases, for example, polymyalgia rheumatica, various vasculitides, and juvenile rheumatoid arthritis (adult Still's disease). Subacute thyroiditis is a rare cause of FUO. Among the infectious causes of FUO, typhoid fever is relatively uncommon. We present a case of FUO in a traveler returning from India whose initial complaints were that of left-sided neck pain and angle of the jaw pain, which initially suggested the diagnosis of subacute thyroiditis. After an extensive FUO workup, when typhoid fever is a likely diagnostic possibility, an empiric trial of anti- Salmonella therapy has diagnostic and therapeutic significance. The presence of relative bradycardia, and response to quinolone therapy, was the basis of the clinical diagnosis of typhoid fever as the explanation for this patients FUO. This case illustrates the diagnostic difficulties in assessing patients with FUO with few diagnostic findings.

  8. Fever of unknown origin responding to steroid therapy.

    Science.gov (United States)

    Suzuki, A; Ohosone, Y; Mita, S; Obana, M; Matsuoka, Y; Irimajiri, S

    1997-02-01

    It is not uncommon to find cases of fever of unknown origin (FUO) in which no final diagnosis is made ever after various examinations. We investigated such cases of undiagnosed FUO, with fever persisting for a long periods and responding to steroid therapy. Among 4,596 patients who were hospitalized over 3-year period from September 1991, 25 met Petersdorf's definition of FUO. Among these 25 patient, six cases were steroid-responsive undiagnosed FUO (SR-FUO). Patients with SR-FUO had the following characteristics: marked inflammatory findings and severe illness; without a definite underlying disease being found despite various examinations; no findings which indicated any known diseases such as adult-onset Still's disease, polymyalgia rheumatica, or other collagen diseases; elderly onset, at 58 to 77 years of age (mean age: 67 years); no improvement with antibiotics, antituberculous agents, or antimycotic drugs; significant improvement of symptoms and signs with steroid therapy; and a relatively good prognosis. SR-FUO, which is not caused by any known disease and is highly responsive to steroids, is included among the FUO cases which we have difficulty in diagnosing and treating.

  9. Kidnapping Detection and Recognition in Previous Unknown Environment

    Directory of Open Access Journals (Sweden)

    Yang Tian

    2017-01-01

    Full Text Available An unaware event referred to as kidnapping makes the estimation result of localization incorrect. In a previous unknown environment, incorrect localization result causes incorrect mapping result in Simultaneous Localization and Mapping (SLAM by kidnapping. In this situation, the explored area and unexplored area are divided to make the kidnapping recovery difficult. To provide sufficient information on kidnapping, a framework to judge whether kidnapping has occurred and to identify the type of kidnapping with filter-based SLAM is proposed. The framework is called double kidnapping detection and recognition (DKDR by performing two checks before and after the “update” process with different metrics in real time. To explain one of the principles of DKDR, we describe a property of filter-based SLAM that corrects the mapping result of the environment using the current observations after the “update” process. Two classical filter-based SLAM algorithms, Extend Kalman Filter (EKF SLAM and Particle Filter (PF SLAM, are modified to show that DKDR can be simply and widely applied in existing filter-based SLAM algorithms. Furthermore, a technique to determine the adapted thresholds of metrics in real time without previous data is presented. Both simulated and experimental results demonstrate the validity and accuracy of the proposed method.

  10. Crowdsourcing the unknown: the satellite search for Genghis Khan.

    Directory of Open Access Journals (Sweden)

    A Y M Lin

    Full Text Available Massively parallel collaboration and emergent knowledge generation is described through a large scale survey for archaeological anomalies within ultra-high resolution earth-sensing satellite imagery. Over 10K online volunteers contributed 30K hours (3.4 years, examined 6,000 km², and generated 2.3 million feature categorizations. Motivated by the search for Genghis Khan's tomb, participants were tasked with finding an archaeological enigma that lacks any historical description of its potential visual appearance. Without a pre-existing reference for validation we turn towards consensus, defined by kernel density estimation, to pool human perception for "out of the ordinary" features across a vast landscape. This consensus served as the training mechanism within a self-evolving feedback loop between a participant and the crowd, essential driving a collective reasoning engine for anomaly detection. The resulting map led a National Geographic expedition to confirm 55 archaeological sites across a vast landscape. A increased ground-truthed accuracy was observed in those participants exposed to the peer feedback loop over those whom worked in isolation, suggesting collective reasoning can emerge within networked groups to outperform the aggregate independent ability of individuals to define the unknown.

  11. Validation of X-ray fluorescence spectrometry for determining osseous or dental origin of unknown material.

    Science.gov (United States)

    Christensen, Angi M; Smith, Michael A; Thomas, Richard M

    2012-01-01

    Forensic anthropological examinations typically involve the analysis of human skeletal remains, but in cases where samples are very small and/or physically compromised, it may first be necessary to determine whether the material is even osseous or dental in origin. X-ray fluorescence spectrometry (XRF) is a technique that reveals the elemental composition of materials and is hypothesized to have utility in such cases. XRF analysis was conducted on a variety of tissues and materials in unaltered and altered (damaged) states. With few exceptions, osseous and dental tissues in unaltered and altered conditions contained characteristic levels of calcium and phosphorus, while other materials did not. Materials could be accurately identified as osseous or dental in origin based on the calcium and phosphorus levels identified by XRF, and we therefore conclude that XRF analysis is a valid and effective means of determining osseous or dental origin of unknown material. © 2011 American Academy of Forensic Sciences.

  12. Pacific salmon extinctions: quantifying lost and remaining diversity.

    Science.gov (United States)

    Gustafson, Richard G; Waples, Robin S; Myers, James M; Weitkamp, Laurie A; Bryant, Gregory J; Johnson, Orlay W; Hard, Jeffrey J

    2007-08-01

    Widespread population extirpations and the consequent loss of ecological, genetic, and life-history diversity can lead to extinction of evolutionarily significant units (ESUs) and species. We attempted to systematically enumerate extinct Pacific salmon populations and characterize lost ecological, life history, and genetic diversity types among six species of Pacific salmon (Chinook [Oncorhynchus tshawytscha], sockeye [O. nerka], coho [O. kisutch], chum [O. keta], and pink salmon [O. gorbuscha] and steelhead trout [O. mykiss]) from the western contiguous United States. We estimated that, collectively, 29% of nearly 1400 historical populations of these six species have been lost from the Pacific Northwest and California since Euro-American contact. Across all species there was a highly significant difference in the proportion of population extinctions between coastal (0.14 extinct) and interior (0.55 extinct) regions. Sockeye salmon (which typically rely on lacustrine habitats for rearing) and stream-maturing Chinook salmon (which stay in freshwater for many months prior to spawning) had significantly higher proportional population losses than other species and maturation types. Aggregate losses of major ecological, life-history, and genetic biodiversity components across all species were estimated at 33%, 15%, and 27%, respectively. Collectively, we believe these population extirpations represent a loss of between 16% and 30% of all historical ESUs in the study area. On the other hand, over two-thirds of historical Pacific salmon populations in this area persist, and considerable diversity remains at all scales. Because over one-third of the remaining populations belong to threatened or endangered species listed under the U.S. Endangered Species Act, it is apparent that a critical juncture has been reached in efforts to preserve what remains of Pacific salmon diversity. It is also evident that persistence of existing, and evolution of future, diversity will depend

  13. Studies on protozoa in ancient remains - A Review

    Directory of Open Access Journals (Sweden)

    Liesbeth Frías

    2013-02-01

    Full Text Available Paleoparasitological research has made important contributions to the understanding of parasite evolution and ecology. Although parasitic protozoa exhibit a worldwide distribution, recovering these organisms from an archaeological context is still exceptional and relies on the availability and distribution of evidence, the ecology of infectious diseases and adequate detection techniques. Here, we present a review of the findings related to protozoa in ancient remains, with an emphasis on their geographical distribution in the past and the methodologies used for their retrieval. The development of more sensitive detection methods has increased the number of identified parasitic species, promising interesting insights from research in the future.

  14. Tuberculosis remains a challenge despite economic growth in Panama.

    Science.gov (United States)

    Tarajia, M; Goodridge, A

    2014-03-01

    Tuberculosis (TB) is a disease associated with inequality, and wise investment of economic resources is considered critical to its control. Panama has recently secured its status as an upper-middle-income country with robust economic growth. However, the prioritisation of resources for TB control remains a major challenge. In this article, we highlight areas that urgently require action to effectively reduce TB burden to minimal levels. Our conclusions suggest the need for fund allocation and a multidisciplinary approach to ensure prompt laboratory diagnosis, treatment assurance and workforce reinforcement, complemented by applied and operational research, development and innovation.

  15. "Recent" macrofossil remains from the Lomonosov Ridge, central Arctic Ocean

    Science.gov (United States)

    Le Duc, Cynthia; de Vernal, Anne; Archambault, Philippe; Brice, Camille; Roberge, Philippe

    2016-04-01

    The examination of surface sediment samples collected from 17 sites along the Lomonosov Ridge at water depths ranging from 737 to 3339 meters during Polarstern Expedition PS87 in 2014 (Stein, 2015), indicates a rich biogenic content almost exclusively dominated by calcareous remains. Amongst biogenic remains, microfossils (planktic and benthic foraminifers, pteropods, ostracods, etc.) dominate but millimetric to centrimetric macrofossils occurred frequently at the surface of the sediment. The macrofossil remains consist of a large variety of taxa, including gastropods, bivalvia, polychaete tubes, scaphopods, echinoderm plates and spines, and fish otoliths. Among the Bivalvia, the most abundant taxa are Portlandia arctica, Hyalopecten frigidus, Cuspidaria glacilis, Policordia densicostata, Bathyarca spp., and Yoldiella spp. Whereas a few specimens are well preserved and apparently pristine, most mollusk shells displayed extensive alteration features. Moreover, most shells were covered by millimeter scale tubes of the serpulid polychaete Spirorbis sp. suggesting transport from low intertidal or subtidal zone. Both the ecological affinity and known geographic distribution of identified bivalvia as named above support the hypothesis of transportation rather than local development. In addition to mollusk shells, more than a hundred fish otoliths were recovered in surface sediments. The otoliths mostly belong to the Gadidae family. Most of them are well preserved and without serpulid tubes attached to their surface, suggesting a local/regional origin, unlike the shell remains. Although recovered at the surface, the macrofaunal assemblages of the Lomonosov Ridge do not necessarily represent the "modern" environments as they may result from reworking and because their occurrence at the surface of the sediment may also be due to winnowing of finer particles. Although the shells were not dated, we suspect that their actual ages may range from modern to several thousands of

  16. The Artificial Leaf: Recent Progress and Remaining Challenges

    Directory of Open Access Journals (Sweden)

    Mark D Symes

    2016-12-01

    Full Text Available The prospect of a device that uses solar energy to split water into H2 and O2 is highly attractive in terms of producing hydrogen as a carbon-neutral fuel. In this mini review, key research milestones that have been reached in this field over the last two decades will be discussed, with special focus on devices that use earth-abundant materials. Finally, the remaining challenges in the development of such “artificial leaves” will be highlighted.

  17. Yellow Fever Remains a Potential Threat to Public Health.

    Science.gov (United States)

    Vasconcelos, Pedro F C; Monath, Thomas P

    2016-08-01

    Yellow fever (YF) remains a serious public health threat in endemic countries. The recent re-emergence in Africa, initiating in Angola and spreading to Democratic Republic of Congo and Uganda, with imported cases in China and Kenya is of concern. There is such a shortage of YF vaccine in the world that the World Health Organization has proposed the use of reduced doses (1/5) during emergencies. In this short communication, we discuss these and other problems including the risk of spread of YF to areas free of YF for decades or never before affected by this arbovirus disease.

  18. Bayesian Estimation of Remaining Useful Life for Wind Turbine Blades

    DEFF Research Database (Denmark)

    Nielsen, Jannie Sønderkær; Sørensen, John Dalsgaard

    2017-01-01

    To optimally plan maintenance of wind turbine blades, knowledge of the degradation processes and the remaining useful life is essential. In this paper, a method is proposed for calibration of a Markov deterioration model based on past inspection data for a range of blades, and updating of the model...... for a specific wind turbine blade, whenever information is available from inspections and/or condition monitoring. Dynamic Bayesian networks are used to obtain probabilities of inspection outcomes for a maximum likelihood estimation of the transition probabilities in the Markov model, and are used again when...

  19. Cancer of unknown primary origin: utility and futility in clinical practice

    Directory of Open Access Journals (Sweden)

    Gianluca Airoldi

    2012-12-01

    Full Text Available Introduction Metastatic cancer of unknown primary (CUP origin is one of the 10 most frequent cancers in humans; it accounts for approximately 3% to 5% of all solid malignancies. Patients with CUP present with metastatic disease whose site of origin cannot be identified at the time of diagnosis despite a thorough history, physical examination and appropriate laboratory testing, histopathology investigations and modern imaging technology (including computed tomography, magnetic resonance imaging, and positron emission tomography.Materials and methods A “state of the art” review was written reflecting all articles retrieved through a PubMed Medline search with the keywords “cancer of unknown primary”, “occult primary tumor”, and “metastases of unknown origin”, with no limits regarding date of publication, type of article, or field.Results CUP represents a heterogeneous group of malignancies that can be classified into distinct clinicopathological entities. Certain entities are included in favorable sub-sets that are responsive to systemic chemotherapy and/or locoregional treatment: these include poorly differentiated carcinomas involving the mediastinal–retroperitoneal nodes, peritoneal papillary serous adenocarcinomatosis in females, poorly differentiated neuroendocrine carcinomas, isolated axillary node adenocarcinomas in females, cervical and inguinal node involvement by squamous cell carcinoma, and any other single metastatic site of limited extension. In these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Therefore, invasive endoscopic and laparoscopic procedures are rarely warranted in the absence of symptoms. Patients who belong to the non-favorable sub-sets (mainly metastatic CUP involving the liver, lung/pleura, brain, bones, or multiple sites or have a poor performance status have a dismal

  20. REMAINED DENTAL PARTICLES IN THE JAWS OF EDENTULOUSPATIENTS (ISFAHAN. 1999

    Directory of Open Access Journals (Sweden)

    R MOSHARRAF

    2002-09-01

    Full Text Available Remained teeth and other lesions such as cysts, abcesses and tumors is one of the important problems in edentulous patients. In a cross-sectional study, 330 edentulous patients were evaluated radiographically. The radiographic evaluation of patients revealed the presence of 86 residual roots in 58 radiographs. 17.58% of patients had residual roots & 5.8% of patients had Impacted teeth. 58.1% of residual roots and 45% of impacted teeth were in the maxilla and others were in mandible. Maximum Percentage of residual roots (58.1% and impacted teeth (70% were found in molar region. In this study revealed 23.3% of examined patients had remaining dental fragments. From these patients, 5.76% had impacted teeth and 17.58% had residual roots, and maximum percentage of rooth fragments (58.1% were found in molar region. In similar study by spyropoulus, maximum percentage of root fragments (45.6% reported in molar region and maximum percentage of impacted teeth were found in molar and canine region (41.2% in molar and 41.2 in canine region. In this study, 58.1% of root fragments and 45% of impacted teeth were found in the maxilla but in spyropoulos" report, 71.9% of root fragments and 94.1% of impacted teeth were found in the maxilla.

  1. Prions and lymphoid organs: solved and remaining mysteries.

    Science.gov (United States)

    O'Connor, Tracy; Aguzzi, Adriano

    2013-01-01

    Prion colonization of secondary lymphoid organs (SLOs) is a critical step preceding neuroinvasion in prion pathogenesis. Follicular dendritic cells (FDCs), which depend on both tumor necrosis factor receptor 1 (TNFR1) and lymphotoxin β receptor (LTβR) signaling for maintenance, are thought to be the primary sites of prion accumulation in SLOs. However, prion titers in RML-infected TNFR1 (-/-) lymph nodes and rates of neuroinvasion in TNFR1 (-/-) mice remain high despite the absence of mature FDCs. Recently, we discovered that TNFR1-independent prion accumulation in lymph nodes relies on LTβR signaling. Loss of LTβR signaling in TNFR1 (-/-) lymph nodes coincided with the de-differentiation of high endothelial venules (HEVs)-the primary sites of lymphocyte entry into lymph nodes. These findings suggest that HEVs are the sites through which prions initially invade lymph nodes from the bloodstream. Identification of HEVs as entry portals for prions clarifies a number of previous observations concerning peripheral prion pathogenesis. However, a number of questions still remain: What is the mechanism by which prions are taken up by HEVs? Which cells are responsible for delivering prions to lymph nodes? Are HEVs the main entry site for prions into lymph nodes or do alternative routes also exist? These questions and others are considered in this article.

  2. Mechanical determinants of bone form: insights from skeletal remains.

    Science.gov (United States)

    Ruff, C B

    2005-01-01

    Analysis of skeletal remains from humans living in the past forms an important complement to observational and experimental studies of living humans and animal models. Including earlier humans in such analyses increases the range of variation in both behavior and body size and shape that are represented, and can provide insights into the adaptive potential of the modern human skeleton. I review here a variety of studies of archaeological and paleontological remains that have investigated differences in skeletal structure from a mechanical perspective, focusing in particular on diaphyseal strength of the limb bones. Several conclusions can be drawn from these studies: 1) there has been a decline in overall skeletal strength relative to body size over the course of human evolution that has become progressively steeper in recent millennia, probably due to increased sedentism and technological advancement; 2) differences in pelvic structure and hip mechanical loadings affect femoral shape; 3) activity patterns affect overall strength and shape of both the lower and upper limb bones; and 4) responsiveness to changes in mechanical loading varies between skeletal features (e.g., articulations versus diaphyses) and by age.

  3. Detection of Buried Human Remains Using Bioreporter Fluorescence

    Energy Technology Data Exchange (ETDEWEB)

    Vass, A. Dr.; Singleton, G. B.

    2001-10-01

    The search for buried human remains is a difficult, laborious and time-consuming task for law enforcement agencies. This study was conducted as a proof of principle demonstration to test the concept of using bioreporter microorganisms as a means to cover large areas in such a search. These bioreporter microorganisms are affected by a particular component of decaying organic matter that is distinct from decaying vegetation. The diamino compounds cadaverine and putrescine were selected as target compounds for the proof-of-principle investigation, and a search for microorganisms and genes that are responsive to either of these compounds was conducted. One recombinant clone was singled out for characterization based on its response to putrescine. The study results show that small concentrations of putrescine increased expression from this bioreporter construct. Although the level of increase was small (making it difficult to distinguish the signal from background), the results demonstrate the principle that bioreporters can be used to detect compounds resulting from decaying human remains and suggest that a wider search for target compounds should be conducted.

  4. Determination of Remaining Useful Life of Gas Turbine Blade

    Directory of Open Access Journals (Sweden)

    Meor Said Mior Azman

    2016-01-01

    Full Text Available The aim of this research is to determine the remaining useful life of gas turbine blade, using service-exposed turbine blades. This task is performed using Stress Rupture Test (SRT under accelerated test conditions where the applied stresses to the specimen is between 400 MPa to 600 MPa and the test temperature is 850°C. The study will focus on the creep behaviour of the 52000 hours service-exposed blades, complemented with creep-rupture modelling using JMatPro software and microstructure examination using optical microscope. The test specimens, made up of Ni-based superalloy of the first stage turbine blades, are machined based on International Standard (ISO 24. The results from the SRT will be analyzed using these two main equations – Larson-Miller Parameter and Life Fraction Rule. Based on the results of the remaining useful life analysis, the 52000h service-exposed blade has the condition to operate in the range of another 4751 hr to 18362 hr. The microstructure examinations shows traces of carbide precipitation that deteriorate the grain boundaries that occurs during creep process. Creep-rupture life modelling using JMatPro software has shown good agreement with the accelerated creep rupture test with minimal error.

  5. Duplex Alu Screening for Degraded DNA of Skeletal Human Remains

    Directory of Open Access Journals (Sweden)

    Fabian Haß

    2017-10-01

    Full Text Available The human-specific Alu elements, belonging to the class of Short INterspersed Elements (SINEs, have been shown to be a powerful tool for population genetic studies. An earlier study in this department showed that it was possible to analyze Alu presence/absence in 3000-year-old skeletal human remains from the Bronze Age Lichtenstein cave in Lower Saxony, Germany. We developed duplex Alu screening PCRs with flanking primers for two Alu elements, each combined with a single internal Alu primer. By adding an internal primer, the approximately 400–500 bp presence signals of Alu elements can be detected within a range of less than 200 bp. Thus, our PCR approach is suited for highly fragmented ancient DNA samples, whereas NGS analyses frequently are unable to handle repetitive elements. With this analysis system, we examined remains of 12 individuals from the Lichtenstein cave with different degrees of DNA degradation. The duplex PCRs showed fully informative amplification results for all of the chosen Alu loci in eight of the 12 samples. Our analysis system showed that Alu presence/absence analysis is possible in samples with different degrees of DNA degradation and it reduces the amount of valuable skeletal material needed by a factor of four, as compared with a singleplex approach.

  6. Double-shell tank remaining useful life estimates

    Energy Technology Data Exchange (ETDEWEB)

    Anantatmula, R.P., Westinghouse Hanford

    1996-12-02

    The existing 28 double-shell tanks (DSTS) at Hanford are currently planned to continue operation through the year 2028 when disposal schedules show removal of waste. This schedule will place the DSTs in a service life window of 4O to 60 years depending on tank construction date and actual retirement date. This paper examines corrosion- related life-limiting conditions of DSTs and reports the results of remaining useful life models developed for estimating remaining tank life. Three models based on controllable parameters such as temperature, chemistry, and relative humidity are presented for estimates to the year in which a particular DST may receive a breach in the primary tank due to pitting in the liquid or vapor region. Pitting is believed to be the life-limiting condition for DSTs,however, the region of the most aggressive pitting (vapor space or liquid) requires further investigation. The results of the models presented suggest none of the existing DSTs should fail by through-wall pitting until well beyond scheduled retrieval in 2028. The estimates of tank breach years (the year in which a tank may be expected to breach the primary tank wall) range from 2056 for pitting corrosion in the liquid region of tank 104-AW to beyond the next millennium for several tanks in the vapor region.

  7. Radiocarbon analysis of human remains: a review of forensic applications.

    Science.gov (United States)

    Ubelaker, Douglas H

    2014-11-01

    Radiocarbon analysis of organic materials, with the comparison of values with those of the post-1950 modern bomb curve, has proven useful in forensic science to help evaluate the antiquity of evidence. Applications are particularly helpful in the study of human remains, especially with those displaying advanced decomposition of soft tissues. Radiocarbon analysis can reveal if the remains relate to the modern, post-1950 era and if so, also provide information needed to evaluate the death and birth date. Sample selection and interpretation of results must be guided by knowledge of the formation and remodeling of different human tissues, as well as contextual information and the approximate age at death of the individual represented. Dental enamel does not remodel and thus captures dietary radiocarbon values at the time of juvenile formation. Most other human tissues do remodel but at differing rates and therefore collectively offer key information relative to the estimation of the death date. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  8. Epidemic renal disease of unknown etiology in the Zuni Indians

    Energy Technology Data Exchange (ETDEWEB)

    Hoy, W.E.; Megill, D.M.; Hughson, M.D.

    1987-06-01

    An epidemic of renal disease is occurring among the Zuni Indians in western New Mexico. In 1985, 1.6% of Zunis had clinically recognized renal disease and 1% had renal insufficiency. The incidence of end-stage renal disease (ESRD) in 1984 and 1985 was 14 times the rate for US whites, and three times the rates of other Indians in ESRD network 6. One third of the cases of renal disease and ESRD is due to type 2 diabetes, but the etiology of disease in most of the remainder is unknown. Affected subjects range from early childhood to old age. Early signs are hematuria, mild to moderate proteinuria, normal BP, and low total hemolytic complement, normal or low C3 and C4 levels, in about 40% of the cases. The clinical course varies from benign to rapidly progressive renal failure. Biopsies usually reflect an immune-complex mediated mesangiopathic glomerulonephritis, with IgA, IgG, IgM, and C3 variably present in the mesangium. In some cases, there is a very strong familial pattern suggesting autosomal dominant inheritance or a marked communal exposure effect. This may be a genetic disease educed by the consanguinity in the ethnically homogeneous Zuni population. Mesangiopathic renal disease is common in some Oriental populations, and this phenomenon may reflect the American Indians' Oriental ancestry. This disease may also be due to toxic exposures related to jewelry-making, potting, Zuni water, Zuni salt, or herbal or other products used for medicinal or religious purposes. This epidemic is causing much morbidity and generating huge costs for ESRD treatment. Further study is needed to better understand its etiology.

  9. Popular Music in Jia Zhangke’s Unknown Pleasures

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2011-04-01

    Full Text Available With his documentary-style films reflecting upon China’s unprecedented transformation from a state-controlled to a market-driven economy, Jia Zhangke has risen from within the movement of independent Chinese cinema that began to flourish in the late 1990s to become one of the most recognized filmmakers of contemporary China. Born in 1970 and raised in the underdeveloped Shanxi Province, Jia studied film theory at Beijing Film Academy and was first noticed for his controversial “Hometown Trilogy”—'Pickpocket '('Xiao Wu', 1997, 'Platform '('Zhantai', 1999, and 'Unknown Pleasures '('Ren xiao yao', 2002. These three films, shot with handheld video camera on the streets of his hometown province, focus on the reckless changes that China’s aggressive economic growth and globalization have brought to socially marginalized groups. Like other independently made films—films that are produced with capital from outside the state-sponsored avenues and without the approval of film censorship, and that are not allowed to be shown in China’s public theaters—Jia’s first three films reach domestic audiences only through unofficial DVD copies and small-scaled screenings at universities, film bars, and art salons. His limited domestic influence sharply contrasts with the critical acclaim that he receives from international film festival audiences, who are searching for alternative film culture from China after the Fifth Generation directors. By the late 1990s, Jia had become a spokesperson for an ever-increasing group of aspiring Chinese independent filmmakers, particularly through writings and interviews that theorize independent Chinese cinema’s practice.

  10. Identification of unknown waste sites using MIVIS hyperspectral images

    Energy Technology Data Exchange (ETDEWEB)

    Gomarasca, M.A.; Strobelt, S. [National Research Council, Milano (Italy)

    1996-11-01

    This paper presents the results on the individuation of known and unknown (illegal) waste sites using Landsat TM satellite imagery and airborne MIVIS (Multispectral Infrared and Visible Imaging Spectrometer) data for detailed analysis in Italy. Previous results with Landsat TM imagery were partially positive for large waste site identification and negative for small sites. Information acquired by the MIVIS hyperspectral system presents three main characteristics: local scale study, possibility to plan the proper period based on the objectives of the study, high number of spectral bands with high spectral and geometrical resolution. MIVIS airborne shootings were carried out on 7 July 1994 at noon with 4x4 m pixel resolution. The MIVIS 102 bands` sensors can distinguish even objects with similar spectral behavior, thanks to its high spectral resolution. Identification of degraded sites is obtained using traditional spectral and statistical operators (NDVI, Principal Component Analysis, Maximum Likelihood classifier) and innovative combination of filtered band ratios realized to extract specific waste elements (acid slimes or contaminated soils). One of the aims that concerns with this study is the definition of an operative program for the characterization, identification and classification of defined categories of waste disposal sites. The best schedule for the data collection by airborne MIVIS oriented to this target is defined. The planning of the proper flight, based on the waste sites features, is important to optimize this technology. One of the most efficient methods for detecting hidden waste sites is the thermal inertia so two images are necessary: one during low sun load and one with high sun load. The results obtained are operationally useful and winning. This instrument, supported by correct analysis techniques, may offer new interesting prospects in territorial management and environmental monitoring. 5 refs., 5 figs., 1 tab.

  11. Adaptive vison aided integrated navigation for dynamic unknown enviroments

    Science.gov (United States)

    Nematallah, Heba

    In this research, a novel method for visual odometry (VO) and the integration with multi-sensors navigation systems for vehicular platforms is proposed. The proposed method partitions the field of single camera view into regions of interests where each region likely contains different types of visual features. By applying computer vision processing techniques, ambiguous pose estimation is calculated up to a scale factor. The proposed method uses aiding measurements from vehicle's odometer to adaptively resolve the scale factor ambiguity problem in monocular camera systems. Unlike some state-of-art approaches, this work does not depend on offline pre-processing or predefined landmarks or visual maps. In addition, this work addresses unknown uncontrolled environments where moving objects likely exist. Innovative odometer-aided Local Bundle Adjustment (LBA) along with a fuzzy C-mean clustering mechanism is proposed to reject outliers corresponding to moving objects. A Gaussian Mixture approach is also applied to detect visual background regions during stationary periods which enables further rejection of moving objects. Finally, an empirical scoring method is applied to calculate a matching score of the different visual features and to use this score in a Kalman filter as measurement covariance noise to integrate VOestimated pose changes within a larger multi-sensors integrated navigation system. Experimental work was performed with a physical vehicular platform equipped by MEMS inertial sensors, GPS, speed measurements and GPS-enabled camera. The experimental work includes three testing vehicular trajectories in downtown Toronto and the surrounding areas. The experimental work showed significant navigation improvements during long GPS outages where only VO is fused with inertial sensors and the vehicle's speed measurements.

  12. Homo naledi pelvic remains from the Dinaledi Chamber, South Africa.

    Science.gov (United States)

    VanSickle, Caroline; Cofran, Zachary; García-Martínez, Daniel; Williams, Scott A; Churchill, Steven E; Berger, Lee R; Hawks, John

    2017-11-20

    In the hominin fossil record, pelvic remains are sparse and are difficult to attribute taxonomically when they are not directly associated with craniodental material. Here we describe the pelvic remains from the Dinaledi Chamber in the Rising Star cave system, Cradle of Humankind, South Africa, which has produced hominin fossils of a new species, Homo naledi. Though this species has been attributed to Homo based on cranial and lower limb morphology, the morphology of some of the fragmentary pelvic remains recovered align more closely with specimens attributed to the species Australopithecus afarensis and Australopithecus africanus than they do with those of most (but not all) known species of the genus Homo. As with A. afarensis and A. africanus, H. naledi appears to have had marked lateral iliac flare and either a weakly developed or non-existent acetabulocristal buttress or a distinct, albeit weakly developed, acetabulospinous buttress. At the same time, H. naledi has robust superior pubic and ischiopubic rami and a short ischium with a narrow tuberoacetabular sulcus, similar to those found in modern humans. The fragmentary nature of the Dinaledi pelvic assemblage makes the attribution of sex and developmental age to individual specimens difficult, which in turn diminishes our ability to identify the number of individuals represented in the assemblage. At present, we can only confidently say that the pelvic fossils from Rising Star represent at least four individuals based on the presence of four overlapping right ischial fossils (whereas a minimum of 15 individuals can be identified from the Dinaledi dental assemblage). A primitive, early Australopithecus-like false pelvis combined with a derived Homo-like true pelvis is morphologically consistent with evidence from the lower ribcage and proximal femur of H. naledi. The overall similarity of H. naledi ilia to those of australopiths supports the inference, drawn from the observation of primitive pelvic

  13. Psychotherapy for Borderline Personality Disorder: Progress and Remaining Challenges.

    Science.gov (United States)

    Links, Paul S; Shah, Ravi; Eynan, Rahel

    2017-03-01

    The main purpose of this review was to critically evaluate the literature on psychotherapies for borderline personality disorder (BPD) published over the past 5 years to identify the progress with remaining challenges and to determine priority areas for future research. A systematic review of the literature over the last 5 years was undertaken. The review yielded 184 relevant abstracts, and after applying inclusion criteria, 16 articles were fully reviewed based on the articles' implications for future research and/or clinical practice. Our review indicated that patients with various severities benefited from psychotherapy; more intensive therapies were not significantly superior to less intensive therapies; enhancing emotion regulation processes and fostering more coherent self-identity were important mechanisms of change; therapies had been extended to patients with BPD and posttraumatic stress disorder; and more research was needed to be directed at functional outcomes.

  14. Tactile display on the remaining hand for unilateral hand amputees

    Directory of Open Access Journals (Sweden)

    Li Tao

    2016-09-01

    Full Text Available Human rely profoundly on tactile feedback from fingertips to interact with the environment, whereas most hand prostheses used in clinics provide no tactile feedback. In this study we demonstrate the feasibility to use a tactile display glove that can be worn by a unilateral hand amputee on the remaining healthy hand to display tactile feedback from a hand prosthesis. The main benefit is that users could easily distinguish the feedback for each finger, even without training. The claimed advantage is supported by preliminary tests with healthy subjects. This approach may lead to the development of effective and affordable tactile display devices that provide tactile feedback for individual fingertip of hand prostheses.

  15. Reidentification of avian embryonic remains from the cretaceous of mongolia.

    Science.gov (United States)

    Varricchio, David J; Balanoff, Amy M; Norell, Mark A

    2015-01-01

    Embryonic remains within a small (4.75 by 2.23 cm) egg from the Late Cretaceous, Mongolia are here re-described. High-resolution X-ray computed tomography (HRCT) was used to digitally prepare and describe the enclosed embryonic bones. The egg, IGM (Mongolian Institute for Geology, Ulaanbaatar) 100/2010, with a three-part shell microstructure, was originally assigned to Neoceratopsia implying extensive homoplasy among eggshell characters across Dinosauria. Re-examination finds the forelimb significantly longer than the hindlimbs, proportions suggesting an avian identification. Additional, postcranial apomorphies (strut-like coracoid, cranially located humeral condyles, olecranon fossa, slender radius relative to the ulna, trochanteric crest on the femur, and ulna longer than the humerus) identify the embryo as avian. Presence of a dorsal coracoid fossa and a craniocaudally compressed distal humerus with a strongly angled distal margin support a diagnosis of IGM 100/2010 as an enantiornithine. Re-identification eliminates the implied homoplasy of this tri-laminate eggshell structure, and instead associates enantiornithine birds with eggshell microstructure composed of a mammillary, squamatic, and external zones. Posture of the embryo follows that of other theropods with fore- and hindlimbs folded parallel to the vertebral column and the elbow pointing caudally just dorsal to the knees. The size of the egg and embryo of IGM 100/2010 is similar to the two other Mongolian enantiornithine eggs. Well-ossified skeletons, as in this specimen, characterize all known enantiornithine embryos suggesting precocial hatchlings, comparing closely to late stage embryos of modern precocial birds that are both flight- and run-capable upon hatching. Extensive ossification in enantiornithine embryos may contribute to their relatively abundant representation in the fossil record. Neoceratopsian eggs remain unrecognized in the fossil record.

  16. Reidentification of avian embryonic remains from the cretaceous of mongolia.

    Directory of Open Access Journals (Sweden)

    David J Varricchio

    Full Text Available Embryonic remains within a small (4.75 by 2.23 cm egg from the Late Cretaceous, Mongolia are here re-described. High-resolution X-ray computed tomography (HRCT was used to digitally prepare and describe the enclosed embryonic bones. The egg, IGM (Mongolian Institute for Geology, Ulaanbaatar 100/2010, with a three-part shell microstructure, was originally assigned to Neoceratopsia implying extensive homoplasy among eggshell characters across Dinosauria. Re-examination finds the forelimb significantly longer than the hindlimbs, proportions suggesting an avian identification. Additional, postcranial apomorphies (strut-like coracoid, cranially located humeral condyles, olecranon fossa, slender radius relative to the ulna, trochanteric crest on the femur, and ulna longer than the humerus identify the embryo as avian. Presence of a dorsal coracoid fossa and a craniocaudally compressed distal humerus with a strongly angled distal margin support a diagnosis of IGM 100/2010 as an enantiornithine. Re-identification eliminates the implied homoplasy of this tri-laminate eggshell structure, and instead associates enantiornithine birds with eggshell microstructure composed of a mammillary, squamatic, and external zones. Posture of the embryo follows that of other theropods with fore- and hindlimbs folded parallel to the vertebral column and the elbow pointing caudally just dorsal to the knees. The size of the egg and embryo of IGM 100/2010 is similar to the two other Mongolian enantiornithine eggs. Well-ossified skeletons, as in this specimen, characterize all known enantiornithine embryos suggesting precocial hatchlings, comparing closely to late stage embryos of modern precocial birds that are both flight- and run-capable upon hatching. Extensive ossification in enantiornithine embryos may contribute to their relatively abundant representation in the fossil record. Neoceratopsian eggs remain unrecognized in the fossil record.

  17. Premortal data in the process of skeletal remains identification

    Directory of Open Access Journals (Sweden)

    Marinković Nadica

    2012-01-01

    Full Text Available Background/Aim. The basic task of a forensic examiner during the exhumation of mass graves or in mass accidents is to establish identity of a person. The results obtained through these procedures depend on the level of perceptibility of post mortal changes and they are compared with premortal data obtained from family members of those missing or killed. Experience with exhumations has shown significant differences between the results obtained through exhumation and the premortal data. The aim of the study was to suggest the existance of the difference between premortal data and the results obtained by exhumation regarding the some parameters, as well as to direct premortal data colection to the specific skeletal forms. Methods. We performed comparative analysis of the results of exhumation of skeletal remains in a mass grave and the premortal data concerning the identified persons. The least number of individuals in this mass grave was calculated according to the upper parts of the right femur and it helped in calculating the smallest number of individuals in mass graves to be 48. A total of 27 persons were identified. Sex was determined by metrics and morphology of the pelvis. Personal age in the moment of death was determined by morphology features of groin symphisis and morphology of sternal edge of ribs and other parts of scelets observations. The hight was calculated as average results of length of long bones and Rollet coefficients. Results. There was a complete match in terms of sex and age matched within an interval that could be established based on the skeletal remains. All the other parameters were different, however, which made identification significantly more difficult. Conclusion. The premortal data is an important element of identification process and it should be obtained by the forensic doctor and directed towards more detailed examination of the skeletal system.

  18. Embracing the unknown: disentangling the complexities of the soil microbiome.

    Science.gov (United States)

    Fierer, Noah

    2017-10-01

    Soil microorganisms are clearly a key component of both natural and managed ecosystems. Despite the challenges of surviving in soil, a gram of soil can contain thousands of individual microbial taxa, including viruses and members of all three domains of life. Recent advances in marker gene, genomic and metagenomic analyses have greatly expanded our ability to characterize the soil microbiome and identify the factors that shape soil microbial communities across space and time. However, although most soil microorganisms remain undescribed, we can begin to categorize soil microorganisms on the basis of their ecological strategies. This is an approach that should prove fruitful for leveraging genomic information to predict the functional attributes of individual taxa. The field is now poised to identify how we can manipulate and manage the soil microbiome to increase soil fertility, improve crop production and improve our understanding of how terrestrial ecosystems will respond to environmental change.

  19. Demographic window to aging in the wild: constructing life tables and estimating survival functions from marked individuals of unknown age.

    Science.gov (United States)

    Müller, Hans-Georg; Wang, Jane-Ling; Carey, James R; Caswell-Chen, Edward P; Chen, Carl; Papadopoulos, Nikos; Yao, Fang

    2004-06-01

    Summary We address the problem of establishing a survival schedule for wild populations. A demographic key identity is established, leading to a method whereby age-specific survival and mortality can be deduced from a marked cohort life table established for individuals that are randomly sampled at unknown age and marked, with subsequent recording of time-to-death. This identity permits the construction of life tables from data where the birth date of subjects is unknown. An analogous key identity is established for the continuous case in which the survival schedule of the wild population is related to the density of the survival distribution in the marked cohort. These identities are explored for both life tables and continuous lifetime data. For the continuous case, they are implemented with statistical methods using non-parametric density estimation methods to obtain flexible estimates for the unknown survival distribution of the wild population. The analytical model provided here serves as a starting point to develop more complex models for residual demography, i.e. models for estimating survival of wild populations in which age-at-entry is unknown and using remaining information in randomly encountered individuals. This is a first step towards a broad new concept of 'expressed demographic information content of marked or captured individuals'. Copyright 2004 Blackwell Publishing Ltd.

  20. Calculation note for an underground leak which remains underground

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, H.J.

    1997-05-20

    This calculation note supports the subsurface leak accident scenario which remains subsurface. It is assumed that a single walled pipe carrying waste from tank 106-C ruptures, releasing the liquid waste into the soil. In this scenario, the waste does not form a surface pool, but remains subsurface. However, above the pipe is a berm, 0.762 m (2.5 ft) high and 2.44 m (8 ft) wide, and the liquid released from the leak rises into the berm. The slurry line, which transports a source term of higher activity than the sluice line, leaks into the soil at a rate of 5% of the maximum flow rate of 28.4 L/s (450 gpm) for twelve hours. The dose recipient was placed a perpendicular distance of 100 m from the pipe. Two source terms were considered, mitigated and unmitigated release as described in section 3.4.1 of UANF-SD-WM-BIO-001, Addendum 1. The unmitigated consisted of two parts of AWF liquid and one part AWF solid. The mitigated release consisted of two parts SST liquid, eighteen parts AWF liquid, nine parts SST solid, and one part AWF solid. The isotopic breakdown of the release in these cases is presented. Two geometries were considered in preliminary investigations, disk source, and rectangular source. Since the rectangular source results from the assumption that the contamination is wicked up into the berm, only six inches of shielding from uncontaminated earth is present, while the disk source, which remains six inches below the level of the surface of the land is often shielded by a thick shield due to the slant path to the dose point. For this reason, only the rectangular source was considered in the final analysis. The source model was a rectangle 2.134 m (7 ft) thick, 0.6096 m (2 ft) high, and 130.899 m (131 ft) long. The top and sides of this rectangular source was covered with earth of density 1.6 g/cm{sup 3} to a thickness of 15.24 cm (6 in). This soil is modeled as 40% void space. The source consisted of earth of the same density with the void spaces filled with

  1. Mineralized Remains of Morphotypes of Filamentous Cyanobacteria in Carbonaceous Meteorites

    Science.gov (United States)

    Hoover, Richard B.

    2005-01-01

    ) investigations of freshly fractured interior surfaces of carbonaceous meteorites, terrestrial rocks, and recent microbial extremophiles and filamentous cyanobacteria. These studies have resulted in the detection in a several carbonaceous meteorites of the mineralized remains of a wide variety of complex filamentous trichomic microorganisms. These embedded forms are consistent in size and microstructure with well-preserved morphotypes of mat- forming filamentous trichomic cyanobacteria and the degraded remains of microfibrils of cyanobacterial sheaths. We present the results of comparative imaging studies and EDAX elemental analyses of recent cyanobacteria (e.g. Calothrix, Oscillatoria, and Lyngbya) that are similar in size, morphology and microstructure to morphotypes found embedded in meteorites. EDAX elemental studies reveal that forms found in carbonaceous meteorites often have highly carbonized sheaths in close association with permineralized filaments, trichomes and microbial cells. Ratios of critical bioelements (C:O, C:N, C:P, and C:S) reveal dramatic differences between microfossils in Earth rocks and meteorites and in filaments, trichomes, hormogonia, and cells of recent cyanobacteria.

  2. Future Remains: Industrial Heritage at the Hanford Plutonium Works

    Science.gov (United States)

    Freer, Brian

    This dissertation argues that U.S. environmental and historic preservation regulations, industrial heritage projects, history, and art only provide partial frameworks for successfully transmitting an informed story into the long range future about nuclear technology and its related environmental legacy. This argument is important because plutonium from nuclear weapons production is toxic to humans in very small amounts, threatens environmental health, has a half-life of 24, 110 years and because the industrial heritage project at Hanford is the first time an entire U.S. Department of Energy weapons production site has been designated a U.S. Historic District. This research is situated within anthropological interest in industrial heritage studies, environmental anthropology, applied visual anthropology, as well as wider discourses on nuclear studies. However, none of these disciplines is really designed or intended to be a completely satisfactory frame of reference for addressing this perplexing challenge of documenting and conveying an informed story about nuclear technology and its related environmental legacy into the long range future. Others have thought about this question and have made important contributions toward a potential solution. Examples here include: future generations movements concerning intergenerational equity as evidenced in scholarship, law, and amongst Native American groups; Nez Perce and Confederated Tribes of the Umatilla Indian Reservation responses to the Hanford End State Vision and Hanford's Canyon Disposition Initiative; as well as the findings of organizational scholars on the advantages realized by organizations that have a long term future perspective. While these ideas inform the main line inquiry of this dissertation, the principal approach put forth by the researcher of how to convey an informed story about nuclear technology and waste into the long range future is implementation of the proposed Future Remains clause, as

  3. Antenatal genetic testing and the right to remain in ignorance.

    Science.gov (United States)

    Bennett, R

    2001-09-01

    As knowledge increases about the human genome, prenatal genetic testing will become cheaper, safer and more comprehensive. It is likely that there will be a great deal of support for making prenatal testing for a wide range of genetic disorders a routine part of antenatal care. Such routine testing is necessarily coercive in nature and does not involve the same standard of consent as is required in other health care settings. This paper asks whether this level of coercion is ethically justifiable in this case, or whether pregnant women have a right to remain in ignorance of the genetic make-up of the fetus they are carrying. While information gained by genetic testing may be useful for pregnant women when making decisions about their pregnancy, it does not prevent harm to future children. It is argued that as this kind of testing provides information in the interests of the pregnant women and not in the interests of any future child, the same standards of consent that are normally required for genetic testing should be required in this instance.

  4. Factors influencing home care nurse intention to remain employed.

    Science.gov (United States)

    Tourangeau, Ann; Patterson, Erin; Rowe, Alissa; Saari, Margaret; Thomson, Heather; MacDonald, Geraldine; Cranley, Lisa; Squires, Mae

    2014-11-01

    To identify factors affecting Canadian home care nurse intention to remain employed (ITR). In developed nations, healthcare continues to shift into community settings. Although considerable research exists on examining nurse ITR in hospitals, similar research related to nurses employed in home care is limited. In the face of a global nursing shortage, it is important to understand the factors influencing nurse ITR across healthcare sectors. A qualitative exploratory descriptive design was used. Focus groups were conducted with home care nurses. Data were analysed using qualitative content analysis. Six categories of influencing factors were identified by home care nurses as affecting ITR: job characteristics; work structures; relationships/communication; work environment; nurse responses to work; and employment conditions. Findings suggest the following factors influence home care nurse ITR: having autonomy; flexible scheduling; reasonable and varied workloads; supportive work relationships; and receiving adequate pay and benefits. Home care nurses did not identify job satisfaction as a single concept influencing ITR. Home care nursing management should support nurse autonomy, allow flexible scheduling, promote reasonable workloads and create opportunities for team building that strengthen supportive relationships among home care nurses and other health team members. © 2013 John Wiley & Sons Ltd.

  5. [Bacterial vaginosis in 2011: a lot of questions remain].

    Science.gov (United States)

    Bohbot, J-M; Lepargneur, J-P

    2012-01-01

    Bacterial vaginosis is one of the most frequent vaginal affections. It results from a deep imbalance of the vaginal ecosystem whose mechanisms remain mysterious, even if recent progress were accomplished in their comprehension: if the flora implied in the bacterial vaginosis is recognized like polymorphic, it appears that Gardnerella vaginalis plays a major part with two genomically different forms: a commensal form (slightly adhesive to the epithelial cells), and a pathogenic one (strongly adhesive to the epithelial cells); the changes in lactobacilli are also to take into account: L. iners could be a marker of the vaginal flora imbalance whereas L. crispatus is generally met in the normal vaginal flora. These findings could influence the composition of coming probiotics; it is recognized that bacterial vaginosis is involved in the risk of prematurity but molecular quantification of G. vaginalis (and of Atopobium vaginae) is more sensitive for the diagnosis of BV what could improve the detection of high-risk pregnant women. The isolated antibiotic treatments are not very effective on the prevention of recurrences. The rebalancing of the vaginal flora is essential. In this field, the local estrogens showed some effectiveness. The use of probiotics is promising and can be recommended in complement of the antibiotic treatment even if the results of the clinical studies are still too heterogeneous to lead to precise indications. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  6. Anion exchange membrane fuel cells: Current status and remaining challenges

    Science.gov (United States)

    Gottesfeld, Shimshon; Dekel, Dario R.; Page, Miles; Bae, Chulsung; Yan, Yushan; Zelenay, Piotr; Kim, Yu Seung

    2018-01-01

    The anion exchange membrane fuel cell (AEMFC) is an attractive alternative to acidic proton exchange membrane fuel cells, which to date have required platinum-based catalysts, as well as acid-tolerant stack hardware. The AEMFC could use non-platinum-group metal catalysts and less expensive metal hardware thanks to the high pH of the electrolyte. Over the last decade, substantial progress has been made in improving the performance and durability of the AEMFC through the development of new materials and the optimization of system design and operation conditions. In this perspective article, we describe the current status of AEMFCs as having reached beginning of life performance very close to that of PEMFCs when using ultra-low loadings of Pt, while advancing towards operation on non-platinum-group metal catalysts alone. In the latter sections, we identify the remaining technical challenges, which require further research and development, focusing on the materials and operational factors that critically impact AEMFC performance and/or durability. These perspectives may provide useful insights for the development of next-generation of AEMFCs.

  7. Barrett's esophagus-related diseases remain uncommon in China.

    Science.gov (United States)

    Huang, Qin; Fang, Dian Chun; Yu, Cheng Gong; Zhang, Jun; Chen, Min Hu

    2011-12-01

    Barrett's esophagus (BE)-related esophageal adenocarcinoma (EAC) has shown the fastest rise in incidence in Western countries; however, research data on BE-related diseases from China are inconclusive. We aimed to review and analyze the published results on these diseases in China. We searched PubMed and Chinese medical literature for key words: BE, EAC, Chinese and China. Relevant research papers along with the study results from our own groups were reviewed and analyzed. Using standardized criteria, columnar-lined esophagus (CLE) was found in as many as 29% of resection specimens in Chinese patients with proximal gastric cancer. However, BE with intestinal metaplasia was rare, ranging from 0.06% in the general population to disease and tobacco or alcohol abuse, but not male gender or obesity. At endoscopy, most CLE/BE were diseases, except for CLE, are rare in China. The clinical significance and malignant potential of CLE in the Chinese population remain elusive. Further investigation on these diseases is in progress. © 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

  8. New Evidence Links Stellar Remains to Oldest Recorded Supernova

    Science.gov (United States)

    2006-09-01

    Recent observations have uncovered evidence that helps to confirm the identification of the remains of one of the earliest stellar explosions recorded by humans. The new study shows that the supernova remnant RCW 86 is much younger than previously thought. As such, the formation of the remnant appears to coincide with a supernova observed by Chinese astronomers in 185 A.D. The study used data from NASA's Chandra X-ray Observatory and the European Space Agency's XMM-Newton Observatory, "There have been previous suggestions that RCW 86 is the remains of the supernova from 185 A.D.," said Jacco Vink of University of Utrecht, the Netherlands, and lead author of the study. "These new X-ray data greatly strengthen the case." When a massive star runs out of fuel, it collapses on itself, creating a supernova that can outshine an entire galaxy. The intense explosion hurls the outer layers of the star into space and produces powerful shock waves. The remains of the star and the material it encounters are heated to millions of degrees and can emit intense X-ray radiation for thousands of years. Animation of a Massive Star Explosion Animation of a Massive Star Explosion In their stellar forensic work, Vink and colleagues studied the debris in RCW 86 to estimate when its progenitor star originally exploded. They calculated how quickly the shocked, or energized, shell is moving in RCW 86, by studying one part of the remnant. They combined this expansion velocity with the size of the remnant and a basic understanding of how supernovas expand to estimate the age of RCW 86. "Our new calculations tell us the remnant is about 2,000 years old," said Aya Bamba, a coauthor from the Institute of Physical and Chemical Research (RIKEN), Japan. "Previously astronomers had estimated an age of 10,000 years." The younger age for RCW 86 may explain an astronomical event observed almost 2000 years ago. In 185 AD, Chinese astronomers (and possibly the Romans) recorded the appearance of a new

  9. The remaining challenges of pneumococcal disease in adults

    Directory of Open Access Journals (Sweden)

    E. Ludwig

    2012-03-01

    Full Text Available Pneumococcal disease can be divided into invasive disease, i.e. when bacteria are detected in normally sterile body fluids, and noninvasive disease. Pneumococcal disease occurs more frequently in younger children and older adults. It is estimated that, in 2050, 30.3% of the European population will be ≥65 yrs old, compared with 15.7% in 2000. Preventive medicine, including vaccination, is essential for the promotion of healthy ageing. Uptake rates for influenza vaccination in the elderly are generally low, despite recommendations in many countries. In addition, it has been reported that influenza infections can make people more susceptible to pneumococcal infections. Despite pneumococcal vaccination, case fatality rates for patients hospitalised with invasive pneumococcal disease have remained at around 12% since the 1950s. Even when effective antibiotic therapy is administered, mortality can be high amongst immunocompetent patients in intensive care. Timely and accurate diagnosis of pneumococcal disease and identification of patients at high risk of poor outcome is essential to ensure that adequate treatment, including hospitalisation when necessary, is implemented as early as possible. Improved diagnostic techniques and more efficacious treatments may help to reduce the burden of pneumococcal disease, but preventive measures, such as influenza and pneumococcal vaccination, should be promoted in order to avoid preventable disease, particularly in the elderly.

  10. Cohesin Can Remain Associated with Chromosomes during DNA Replication

    Directory of Open Access Journals (Sweden)

    James D.P. Rhodes

    2017-09-01

    Full Text Available To ensure disjunction to opposite poles during anaphase, sister chromatids must be held together following DNA replication. This is mediated by cohesin, which is thought to entrap sister DNAs inside a tripartite ring composed of its Smc and kleisin (Scc1 subunits. How such structures are created during S phase is poorly understood, in particular whether they are derived from complexes that had entrapped DNAs prior to replication. To address this, we used selective photobleaching to determine whether cohesin associated with chromatin in G1 persists in situ after replication. We developed a non-fluorescent HaloTag ligand to discriminate the fluorescence recovery signal from labeling of newly synthesized Halo-tagged Scc1 protein (pulse-chase or pcFRAP. In cells where cohesin turnover is inactivated by deletion of WAPL, Scc1 can remain associated with chromatin throughout S phase. These findings suggest that cohesion might be generated by cohesin that is already bound to un-replicated DNA.

  11. Cohesin Can Remain Associated with Chromosomes during DNA Replication.

    Science.gov (United States)

    Rhodes, James D P; Haarhuis, Judith H I; Grimm, Jonathan B; Rowland, Benjamin D; Lavis, Luke D; Nasmyth, Kim A

    2017-09-19

    To ensure disjunction to opposite poles during anaphase, sister chromatids must be held together following DNA replication. This is mediated by cohesin, which is thought to entrap sister DNAs inside a tripartite ring composed of its Smc and kleisin (Scc1) subunits. How such structures are created during S phase is poorly understood, in particular whether they are derived from complexes that had entrapped DNAs prior to replication. To address this, we used selective photobleaching to determine whether cohesin associated with chromatin in G1 persists in situ after replication. We developed a non-fluorescent HaloTag ligand to discriminate the fluorescence recovery signal from labeling of newly synthesized Halo-tagged Scc1 protein (pulse-chase or pcFRAP). In cells where cohesin turnover is inactivated by deletion of WAPL, Scc1 can remain associated with chromatin throughout S phase. These findings suggest that cohesion might be generated by cohesin that is already bound to un-replicated DNA. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Skeletal remains of Dr. Eugenio Antonio Berríos Sagredo.

    Science.gov (United States)

    Solla, H E; Işcan, M Y

    2001-02-15

    It is often noted that even a well-designed osteological technique may not provide accurate results when applied to single forensic cases. Case studies are ideal to test if this concern is valid, and forensic anthropology is a testing ground for applying a population based standard to individual skeletal remains. Secondly, the increasing role anthropologists have played in forensic sciences has aided the medicolegal disciplines in a number of ways. For example, identification of skeletal remains is now more accurate than ever before. Many of these cases have brought perpetrators to court for justice. The purpose of this paper is to use osteological techniques to analyze skeletal remains and make a positive identification. The victim was found partially buried in the sand near El Pinar, Uruguay in 1995. The analysis indicated that the victim was a 45-year old, white, male who was about 170cm tall. Based on preliminary evidence that the victim might be Dr. Eugenio Antonio Berríos Sagredo, a digital superimposition was made using the victim's photograph and the unknown skull. This examination revealed that the skull corresponded consistently with the individual in the photograph. Results were supported by the fact that personal belongings, such as a medal and wrist watch, also pointed to the same individual. Dental records and radiographs when made available later also indicated the same identity. Dr. Berríos was accused of making nerve gas during the dictatorial regime of former Chilean President General Augusto Pinochet. It was also alleged that he made bombs that killed a Spanish diplomat in his laboratory and a Chilean diplomat in Washington, DC. Many complex techniques are often needed to make a positive identification and such was the case for this study. Because of the nature of anthropology as a holistic discipline, such complexity is an integral part of human biology and behavior and can be used successfully in the forensic sciences and medicolegal

  13. Organizational conditions for dealing with the unknown unknown : illustrated by how a Dutch water management authority is preparing for climate change

    NARCIS (Netherlands)

    Termeer, C.J.A.M.; Brink, van den M.A.

    2013-01-01

    The central question of this article is the extent to which organizations, governmental authorities in particular, are able to deal with the unknown unknown. Drawing on Weick’s work on sensemaking, we introduce seven organizational conditions that can facilitate organizations to be reliable under

  14. Organizational Conditions for Dealing with The Unknown Unknown Illustrated by how a Dutch water management authority is preparing for climate change

    NARCIS (Netherlands)

    Termeer, Catrien J. A. M.; van den Brink, Margo A.

    2013-01-01

    The central question of this article is the extent to which organizations, governmental authorities in particular, are able to deal with the unknown unknown. Drawing on Weick's work on sensemaking, we introduce seven organizational conditions that can facilitate organizations to be reliable under

  15. Remaining lifetime modeling using State-of-Health estimation

    Science.gov (United States)

    Beganovic, Nejra; Söffker, Dirk

    2017-08-01

    Technical systems and system's components undergo gradual degradation over time. Continuous degradation occurred in system is reflected in decreased system's reliability and unavoidably lead to a system failure. Therefore, continuous evaluation of State-of-Health (SoH) is inevitable to provide at least predefined lifetime of the system defined by manufacturer, or even better, to extend the lifetime given by manufacturer. However, precondition for lifetime extension is accurate estimation of SoH as well as the estimation and prediction of Remaining Useful Lifetime (RUL). For this purpose, lifetime models describing the relation between system/component degradation and consumed lifetime have to be established. In this contribution modeling and selection of suitable lifetime models from database based on current SoH conditions are discussed. Main contribution of this paper is the development of new modeling strategies capable to describe complex relations between measurable system variables, related system degradation, and RUL. Two approaches with accompanying advantages and disadvantages are introduced and compared. Both approaches are capable to model stochastic aging processes of a system by simultaneous adaption of RUL models to current SoH. The first approach requires a priori knowledge about aging processes in the system and accurate estimation of SoH. An estimation of SoH here is conditioned by tracking actual accumulated damage into the system, so that particular model parameters are defined according to a priori known assumptions about system's aging. Prediction accuracy in this case is highly dependent on accurate estimation of SoH but includes high number of degrees of freedom. The second approach in this contribution does not require a priori knowledge about system's aging as particular model parameters are defined in accordance to multi-objective optimization procedure. Prediction accuracy of this model does not highly depend on estimated SoH. This model

  16. Mineralized remains of morphotypes of filamentous cyanobacteria in carbonaceous meteorites

    Science.gov (United States)

    Hoover, Richard B.

    2005-09-01

    rocks, living, cryopreserved and fossilized extremophiles and cyanobacteria. These studies have resulted in the detection of mineralized remains of morphotypes of filamentous cyanobacteria, mats and consortia in many carbonaceous meteorites. These well-preserved and embedded microfossils are consistent with the size, morphology and ultra-microstructure of filamentous trichomic prokaryotes and degraded remains of microfibrils of cyanobacterial sheaths. EDAX elemental studies reveal that the forms in the meteorites often have highly carbonized sheaths in close association with permineralized filaments, trichomes, and microbial cells. The eextensive protocols and methodologies that have been developed to protect the samples from contamination and to distinguish recent contaminants from indigenous microfossils are described recent bio-contaminants. Ratios of critical bioelements (C:O, C:N, C:P, and C:S) reveal dramatic differences between microfossils in Earth rocks and meteorites and in the cells, filaments, trichomes, and hormogonia of recently living cyanobacteria. The results of comparative optical, ESEM and FESEM studies and EDAX elemental analyses of recent cyanobacteria (e.g. Calothrix, Oscillatoria, and Lyngbya) of similar size, morphology and microstructure to microfossils found embedded in the Murchison CM2 and the Orgueil CI1 carbonaceous meteorites are presented

  17. Oral inoculation of neonatal Suffolk sheep with the agent of classical scrapie results in PrP(Sc) accumulation in sheep with the PRNP ARQ/ARQ but not the ARQ/ARR genotype.

    Science.gov (United States)

    Greenlee, Justin J; Smith, Jodi D; Hamir, Amir N

    2016-04-01

    Scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent. This study reports the failure to detect PrP(Sc) in nervous or lymphoid tissues of Suffolk sheep of the PRNP ARQ/ARR genotype after oral inoculation with a U.S. scrapie isolate. Lambs were inoculated within the first 24 h of birth with 1 ml of a 10% (wt./vol.) brain homogenate derived from a clinically affected ARQ/ARQ sheep. The inoculated sheep were observed daily throughout the experiment for clinical signs suggestive of scrapie until they were necropsied at 86 months post inoculation. Tissues were collected for examination by immunohistochemistry and enzyme immunoassay, but all failed to demonstrate evidence of scrapie infection. Neonatal sheep of the ARQ/ARQ genotype receiving the same inoculum developed scrapie within 24 months. Lambs of the ARQ/ARR genotype that received the same inoculum by intracranial inoculation develop scrapie with a prolonged incubation period and with abnormal prion present within the central nervous system, but not peripheral lymphoid tissues. Results of this study suggest that ARQ/ARR sheep are resistant to oral infection with the scrapie isolate used even during the neonatal period. Published by Elsevier Ltd.

  18. Two similar cases of elderly women with moderate abdominal pain and pneumoperitoneum of unknown origin: a surgeon's successful conservative management.

    Science.gov (United States)

    Vinzens, Fabrizio; Zumstein, Valentin; Bieg, Christian; Ackermann, Christoph

    2016-05-26

    Patients presenting with abdominal pain and pneumoperitoneum in radiological examination usually require emergency explorative laparoscopy or laparotomy. Pneumoperitoneum mostly associates with gastrointestinal perforation. There are very few cases where surgery can be avoided. We present 2 cases of pneumoperitoneum with unknown origin and successful conservative treatment. Both patients were elderly women presenting to our emergency unit, with moderate abdominal pain. There was neither medical intervention nor trauma in their medical history. Physical examination revealed mild abdominal tenderness, but no clinical sign of peritonitis. Cardiopulmonary examination remained unremarkable. Blood studies showed only slight abnormalities, in particular, inflammation parameters were not significantly increased. Finally, obtained CTs showed free abdominal gas of unknown origin in both cases. We performed conservative management with nil per os, nasogastric tube, total parenteral nutrition and prophylactic antibiotics. After 2 weeks, both were discharged home. 2016 BMJ Publishing Group Ltd.

  19. The clandestine multiple graves in Malaysia: The first mass identification operation of human skeletal remains.

    Science.gov (United States)

    Mohd Noor, Mohd Suhani; Khoo, Lay See; Zamaliana Alias, Wan Zafirah; Hasmi, Ahmad Hafizam; Ibrahim, Mohamad Azaini; Mahmood, Mohd Shah

    2017-09-01

    The first ever mass identification operation of skeletal remains conducted for the clandestine graves in Malaysia consisted of 165 individuals unearthed from 28 human trafficking transit camps located in Wang Kelian, along the Thai-Malaysia border. A DVI response was triggered in which expert teams comprising of pathologists, anthropologists, odontologists, radiologists and DNA experts were gathered at the identified operation centre. The Department of Forensic Medicine, Hospital Sultanah Bahiyah, Alor Star, Kedah, located approximately 75km away from Wang Kelian, was temporarily converted into a victim identification centre (VIC) as it is the nearest available forensic facility to the mass grave site. The mortuary operation was conducted over a period of 3 months from June to September 2015, and was divided into two phases; phase 1 involving the postmortem examination of the remains of 116 suspected individuals and for phase 2 the remains of 49 suspected individuals. The fact that the graves were of unknown individuals afforded the mass identification operation a sufficient duration of 2 weeks as preparatory phase enabling procedurals and daily victim identification workflow to be established, and the setting up of a temporary body storage for the designated mortuary. The temporary body storage has proven to be a significant factor in enabling the successful conclusion of the VIC operation to the final phase of temporary controlled burials. Recognition from two international observers, Mr. Andréas Patiño Umaña, from the International Committee of Red Cross (ICRC) and Prof. Noel Woodford from Victoria Institute of Forensic Medicine (VIFM) had proven the mortuary operation was in compliance to the international quality and standards. The overall victim identification and mortuary operation identified a number of significant challenges, in particular the management of commingled human remains as well as the compilation of postmortem data in the absence of

  20. Extrapolation of urn models via poissonization: accurate measurements of the microbial unknown.

    Directory of Open Access Journals (Sweden)

    Manuel E Lladser

    Full Text Available The availability of high-throughput parallel methods for sequencing microbial communities is increasing our knowledge of the microbial world at an unprecedented rate. Though most attention has focused on determining lower-bounds on the α-diversity i.e. the total number of different species present in the environment, tight bounds on this quantity may be highly uncertain because a small fraction of the environment could be composed of a vast number of different species. To better assess what remains unknown, we propose instead to predict the fraction of the environment that belongs to unsampled classes. Modeling samples as draws with replacement of colored balls from an urn with an unknown composition, and under the sole assumption that there are still undiscovered species, we show that conditionally unbiased predictors and exact prediction intervals (of constant length in logarithmic scale are possible for the fraction of the environment that belongs to unsampled classes. Our predictions are based on a poissonization argument, which we have implemented in what we call the Embedding algorithm. In fixed i.e. non-randomized sample sizes, the algorithm leads to very accurate predictions on a sub-sample of the original sample. We quantify the effect of fixed sample sizes on our prediction intervals and test our methods and others found in the literature against simulated environments, which we devise taking into account datasets from a human-gut and -hand microbiota. Our methodology applies to any dataset that can be conceptualized as a sample with replacement from an urn. In particular, it could be applied, for example, to quantify the proportion of all the unseen solutions to a binding site problem in a random RNA pool, or to reassess the surveillance of a certain terrorist group, predicting the conditional probability that it deploys a new tactic in a next attack.

  1. File list: ALL.YSt.20.AllAg.Unknown [Chip-atlas[Archive

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  9. File list: InP.YSt.10.AllAg.Unknown [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.YSt.10.AllAg.Unknown sacCer3 Input control Yeast strain Unknown SRX423150,SRX38...1248,SRX390617,SRX390619 http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/InP.YSt.10.AllAg.Unknown.bed ...

  10. Sky-view factor visualization for detection of archaeological remains

    Science.gov (United States)

    Kokalj, Žiga; Oštir, Krištof; Zakšek, Klemen

    2013-04-01

    Many archaeological remains are covered by sand or vegetation but it still possible to detect them by remote sensing techniques. One of them is airborne laser scanning that enables production of digital elevation models (DEM) of very high resolution (better than 1 m) with high relative elevation accuracy (centimetre level), even under forest. Thus, it has become well established in archaeological applications. However, effective interpretation of digital elevation models requires appropriate data visualization. Analytical relief shading is used in most cases. Although widely accepted, this method has two major drawbacks: identifying details in deep shades and inability to properly represent linear features lying parallel to the light beam. Several authors have tried to overcome these limitations by changing the position of the light source or by filtering. This contribution addresses the DEM visualization problem by sky-view factor, a visualization technique based on diffuse light that overcomes the directional problems of hill-shading. Sky-view factor is a parameter that describes the portion of visible sky limited by relief. It can be used as a general relief visualization technique to show relief characteristics. In particular, we show that this visualization is a very useful tool in archaeology. Applying the sky-view factor for visualization purposes gives advantages over other techniques because it reveals small (or large, depending on the scale of the observed phenomenon and consequential algorithm settings) relief features while preserving the perception of general topography. In the case study (DEM visualization of a fortified enclosure of Tonovcov grad in Slovenia) we show that for the archaeological purposes the sky-view factor is the optimal DEM visualization method. Its ability to consider the neighborhood context makes it an outstanding tool when compared to other visualization techniques. One can choose a large search radius and the most important

  11. The Right to Remain Silent in Criminal Trial

    Directory of Open Access Journals (Sweden)

    Gianina Anemona Radu

    2013-05-01

    Full Text Available A person's right not to incriminate oneself or to remain silent and not contribute to their own incrimination is a basic requirement of due process, although the right not to testify against oneself is not expressly guaranteed. This legal right is intended to protect the accused/ the defendant against the authorities’ abusive coercion. The scope of the right not to incriminate oneself is related to criminal matter under the Convention, and thus susceptible or applicable to criminal proceedings concerning all types of crimes as a guarantee to a fair trial. The European Court of Justice ruled that despite the fact that art. 6 paragraph 2 of the Convention does not expressly mention the right not to incriminate oneself and the right not to contribute to their own incrimination (nemo tenetur are ipsum accusare these are generally recognized international rules that are in consistence with the notion of “fair trial” stipulated in art. 6. By virtue of the right to silence, the person charged with a crime is free to answer the questions or not, as he/she believes it is in his/her interest. Therefore, the right to silence involves not only the right not to testify against oneself, but also the right of the accused/ defendant not to incriminate oneself. Thus, the accused/defendant cannot be compelled to assist in the production of evidence and cannot be sanctioned for failing to provide certain documents or other evidence. Obligation to testify against personal will, under the constraint of a fine or any other form of coercion constitutes an interference with the negative aspect of the right to freedom of expression which must be necessary in a democratic society. It is essential to clarify certain issues as far as this right is concerned. First of all, the statutory provision in question is specific to adversarial systems, which are found mainly in Anglo-Saxon countries and are totally different from that underlying the current Romanian Criminal

  12. [RECONSTRUCTING THE LIFE OF AN UNKNOWN MAN--INTERDISCIPLINARY APPROACH].

    Science.gov (United States)

    Hincak, Z; Filipec, K; Iacumin, P; Cavalli, F; Mihelić, D; Jeleč, V; Korušić, A

    2016-09-01

    The remains of a tomb were discovered below the foundations of the Roman church of “Majka Bozja Gorska” in Lobor in 2002. It was a vaulted tomb carved from a single stone. The narthex of ancient Christian and pre-roman churches often served as the resting place of religious, secular and noble dignitaries, who were credited for founding the church at the time. By anthropological methods, the age, gender, height, pathological changes, tendon and ligament hinges and degree of development were able to be analysed. The stable isotopes of Carbon-13, Nitrogen-15 and Oxygen-18 were analysed and expressed as ��-values according to the PDB standard. Dental analysis showed a build-up of tartar on the buccal side, with 5 teeth missing from the dentition post-mortem and a partial lowering and accretion of the alveolar walls of the 2nd molar space secondary to tooth loss. The remains of the person from grave 107 show that the person was approximately 30-35 years of age, confirmed by microscopical analysis of the bone samples. Almost all of the cranial sutures were exposed with the exception of the saggital suture which was closed at the S3 position, while the transverse palatal suture was in the initial stages of closure on the lateral sides. Analysis of the iliac bone showed visible changes on the bone. The surface had retained its youthful appearance however with a microporous and pronounced granular structure and only a slight apical and marginal activity. The transverse striations are still apparent, but no longer along the entirety of the bone surface. Anthropometric analysis according to cranial cavity indexes, showed a cranium or relatively large volume (aristencephalic in type), long, narrow and medium in height. The index values were used in facial reconstruction. Analysis of the development of tendon and ligament hinges of the preserved anatomical elements, gave further information about the morphology and physical activity of the person. The hinge sites of the

  13. Biodiversity and global health—hubris, humility and the unknown

    Science.gov (United States)

    Stephens, Carolyn

    2012-03-01

    biodiversity and well-being; and the links of biodiversity to the green economy in the context of sustainable development and poverty alleviation. References [1] Schuiteman A et al 2011 Nocturne for an unknown pollinator: first description of a night-flowering orchid (Bulbophyllum nocturnum) Bot. J. Linean Soc. 167 344-50 [2] Kinver M and Gill V 2011 Botanists discover 'remarkable' night-flowering orchid BBC News Science and Environment (www.bbc.co.uk/news/science-environment-15818662) [3] Rudd M A 2011 Scientists' opinions on the global status and management of biological diversity Conserv. Biol. 25 1165-75 [4] Bottrill M C et al 2008 Is conservation triage just smart decision making? Trends Ecol. Evol. 23 649-54 [5] Parr M J et al 2009 Why we should aim for zero extinction Trends Ecol. Evol. 24 181 Bottrill M C et al 2009 Finite conservation funds mean triage is unavoidable Trends Ecol. Evol. 24 183-4 [6] Pushpangadan P and Behl H M 2005 Environment & Biodiversity: Agenda for Future (Lucknow: International Society of Environmental Botanists) (http://isebindia.com/icpep-3/icpep3-s-2.html) [7] Alves R and Rosa I 2007 Biodiversity, traditional medicine and public health: where do they meet? J. Ethnobiol. Ethnomed. 3 14 [8] Center for Biodiversity and Conservation 1997 Biodiversity and Human Health: A Guide for Policymakers (New York: American Museum of Natural History) [9] Chivian E 1997 Global environmental degradation and biodiversity loss: implications for human health Biodiversity and Human Health ed F Grifo and J Rosenthal (Washington, DC: Island) pp 7-38 [10] UNEP-WCMC 2011 Health and Well Being of Communities Directly Dependent on Ecosystem Goods and Services: An Indicator for the Convention on Biological Diversity (Cambridge: UNEP-World Conservation Monitoring Centre) [11] Nettleton C, Stephens C and Bristow F 2007 Utz Wachil: a study of indigenous perceptions of health and environment in five countries Ecohealth 4 461-772 [12] Jones G P et al 2004 Coral decline

  14. Fever of unknown origin − diagnostic methods in a European developing country

    Directory of Open Access Journals (Sweden)

    Bosilkovski Mile

    2016-01-01

    Full Text Available Background/Aim. Fewer of unknown origin (FUO remains amongst the most difficult diagnostic dilemmas in contemporary medicine. The aim of this study was to determine the causes of FUO and to identify the methods of diagnosis in patients with FUO in a tertiary care setting in the Republic of Macedonia. Methods. Retrospectively histories of 123 immunocompetent patients older than 14 years with classical FUO that had been examined at the University Hospital for Infectious Diseases and Febrile Conditions in the city of Skopje, during the period 2006−2012 were evaluated. FUO was defined as axillary fever of ≥ 37.5°C on several occasions, fever duration of more than 21 days and failure to reach the diagnosis after the initial diagnostic workup comprised of several defined basic investigations. Results. Infections were the cause of FUO in 51 (41.5% of the patients, followed by non-infective inflammatory disorders (NIID in 28 (22.8%, miscellaneous in 12 (9.7% and neoplasm in 11 (8.9% of the patients. Twenty one of the patients (17.1% remained undiagnosed. The most common causes for FUO were visceral leishmaniasis, abscesses, urinary tract infections, subacute endocarditis, polymyalgia rheumatica and adult onset of Still disease. The final diagnosis was reached with histology in 24 (23.5%, imaging and endoscopic procedures in 21 (20.6%, clinical course and empiric therapy response in 20 (19.6%, serology in 18 (17.6% and cultures in 16 (15.7% of the cases. Conclusion. In the Republic of Macedonia infections are the leading cause of FUO, predominately visceral leishmaniasis. In the future in patients with prolonged fever, physicians should think more often of this disease, as well as of the possibility of atypical presentation of the common classical causes of FUO.

  15. Fever of unknown origin--diagnostic methods in a European developing country.

    Science.gov (United States)

    Bosilkovski, Mile; Dimzova, Marija; Stevanović, Milena; Cvetkovska, Vesna Semenakova; Duganovska, Maja Vasileva

    2016-06-01

    Fewer of unknown origin (FUO) remains amongst the most difficult diagnostic dilemmas in contemporary medicine. The aim of this study was to determine the causes of FU and to identify the methods of diagnosis in patients with FUO in a tertiary care setting in the Republic of Macedonia. Retrospectively histories of 123 immunocompetent patients older than 14 years with classical FUO that had been examined at the University Hospital for Infectious Diseases and Febrile Conditions in the city of Skopje, during the period 2006-2012 were evaluated. FUO was defined as axillary fever of ≥ 37.5 °C on several occasions, fever duration of more than 21 days and failure to reach the diagnosis after the initial diagnostic workup comprised of several defined basic investigations. Infections were the cause of FUO in 51 (41.5%) of the patients, followed by non-infective inflammatory disorders (NIID) in 28 (22.8%), miscellaneous in 12 (9.7%) and neoplasm in 11 (8.9%) of the patients. Twenty one of the patients (17.1%) remained undiagnosed. The most common causes for FUO were visceral leishmaniasis, abscesses, urinary tract infections, subacute endocarditis, polymyalgia rheumatica and adult onset of Still disease. The final diagnosis was reached with histology in 24 (23.5%), imaging and endoscopic procedures in 21 (20.6%), clinical course and empiric therapy response in 20 (19.6%), serology in 18 (17.6%) and cultures in 16 (15.7%) of the cases. In the Republic of Macedonia infections are the leading cause of FUO, predominately visceral leishmaniasis. In the future in patients with prolonged fever, physicians should think more often of this disease, as well as of the possibility of atypical presentation of the common classical causes of FUO.

  16. Pedro Ferreira, um escultor baiano desconhecido Pedro Ferreira, an unknown sculptor from Bahia

    Directory of Open Access Journals (Sweden)

    Maria Helena Ochi Flexor

    2008-12-01

    Full Text Available Este trabalho é o resultado do início de um estudo sobre o escultor Pedro Ferreira. Embora seja autor de obras importantes, passa quase desapercebido na historiografia da arte baiana. Trata-se de artista que pertence ao tempo em que o neoclassicismo se impunha à cultura Ocidental, porém, ainda restavam, na Bahia, as práticas do período barroco, em especial a cópia dos grandes mestres renascentistas. Pedro Ferreira foi um desses artistas e teve como principal inspirador Murillo, da escola espanhola.This work is the result of a beginning study about a sculptor Pedro Ferreira. Although he was author of important workmanships, he passes almost unknown in the bahian history of art. He was an artist who lives belongs a time when the neoclassicismo was imposed to the Occidental culture, but, still remained in Bahia, the practical ones of the baroque period, in special the copy of the great Renaissance masters. Pedro Ferreira was one of these artists and has inspired, as main artist, Murillo, of the Spanish school.

  17. Key Concepts in Pregnancy of Unknown Location: Identifying Ectopic Pregnancy and Providing Patient-Centered Care.

    Science.gov (United States)

    Fields, Loren; Hathaway, Alison

    2017-03-01

    Pregnancy of unknown location (PUL) is a descriptive term for when a woman with a positive pregnancy test has a transvaginal ultrasound that cannot determine the site of the pregnancy. While the majority of women with PUL are subsequently diagnosed with a spontaneous abortion or viable intrauterine pregnancy, 7% to 20% of these women have an ectopic pregnancy. The potential for morbidity and mortality related to an ectopic pregnancy means that considerable care is necessary in the evaluation and management of women with PUL. In some cases, the location of the pregnancy is never determined and the PUL is categorized as resolving or persisting. Evidence suggests expectant management is a safe and effective approach for most women with PUL and should be the mainstay of care. However, in the case of persisting PUL, continued concern for ectopic pregnancy remains. Strategies for deciding when to intervene when a woman has a PUL are reviewed. A variety of clinical tools, including serum beta human chorionic gonadotropin (β-hCG), repeat ultrasonography, dilation and curettage (D&C), and empiric methotrexate therapy are discussed. Finally, a proposal is made that women with persisting PUL can be presented with the option of choosing expectant management, diagnostic D&C, or empiric methotrexate treatment. © 2016 by the American College of Nurse-Midwives.

  18. Fever of unknown origin: temporal arteritis presenting with persistent cough and elevated serum ferritin levels.

    Science.gov (United States)

    Cunha, Burke A; Parchuri, Suhba; Mohan, Sowjania

    2006-01-01

    Fever of unknown origin (FUO) at the present time is most frequently caused by neoplasm and less commonly by infection. Currently, collagen vascular diseases (CVDs) are an uncommon cause of FUO because most are readily diagnosable by serologic methods and do not remain undiagnosed for sufficient time to present as FUOs. CVDs presenting as FUOs not readily diagnosable with specific tests include late-onset rheumatoid arthritis, adult juvenile rheumatoid arthritis, and polymyalgia rheumatica/temporal arteritis (TA). TA, or giant cell arteritis, is an uncommon arteritis of the mid- and large-sized extracranial arteries of the head and neck and is a rare cause of FUO. TA is characterized by headache, scalp tenderness, jaw pain on chewing, and sudden loss of vision. Fever, anorexia, weight loss, and night sweats may also be present. With TA, respiratory symptoms occur in 9% and are the presenting feature in 4%. Laboratory abnormalities associated with TA include a highly elevated erythrocyte sedimentation rate, anemia, and thrombocytosis, and mildly increased alkaline phosphatase/serum transaminases. We present a patient with FUO caused by TA whose predominant presenting symptom was persistent cough that overshadowed head and neck symptoms of TA. To the best of our knowledge, this is the first case of TA presenting as an FUO, with a highly elevated serum ferritin level. We conclude that highly elevated serum ferritin levels in patients with FUO should alert the clinician to consider TA in the differential diagnosis.

  19. FROM THE UNKNOWN STUDENT TO THE FAMOUS GRADUATE OF NOVOROSSIYSK UNIVERSITY

    Directory of Open Access Journals (Sweden)

    Д. И. Бургеля

    2016-10-01

    Full Text Available The theme of the article is illumination of the biography of the graduate of Imperial Novorossiysk University Vasyl Petrovich Gutor. The main task of article – to expand and aggregate biographic information and highlight career of V. P. Gutor. On one concrete example to show how graduates of university proved and realized in various fields of activity, sometimes far from the education got at classical university. V. P. Gutor known as the musician-cellist, he has developed the basic principles of teaching music and has made the significant contribution to musical education of broad masses of the population, was the author methodical and critiques, one of the founders of classical music education. Gutor V. P. was a founder, the director of music schools in Chisinau and Elisavetgrad, and then the teacher and professor of the Odessa conservatory. In article is special attention paid to the Odessa period of his activity. However, unfortunately, it is not enough data on this period. The main finding of the work is that, having tracked a course of life of one specific person, it is possible to tell with confidence that else many destinies of the people carrying a  proud rank of graduates of Imperial Novorossiysk University remain unknown for modern scientists and researchers. The research findings have the practical value for all who are interested in music history, musical pedagogics and history of music in Odessa in the first half of the 20th century.

  20. Iterative MIMO Turbo Multiuser Detection and Equalization for STTrC-Coded Systems with Unknown Interference

    Directory of Open Access Journals (Sweden)

    Veselinovic Nenad

    2004-01-01

    Full Text Available Iterative multiuser detection in a single-carrier broadband multiple-input multiple-output (MIMO system is studied in this paper. A minimum mean squared error (MMSE low-complexity multiuser receiver is derived for space-division multiple-access (SDMA space-time trellis-coded (STTrC systems in frequency-selective fading channels. The receiver uses MMSE filtering to jointly detect several transmit antennas of the user of interest, while the interference from the undetected transmit antennas, cochannel interference (CCI, and intersymbol interference (ISI are all cancelled by the soft cancellation. The performances of two extreme receiver cases are evaluated. In the first case, only one transmit antenna of the user of interest is detected at a time and the remaining ones are cancelled by soft cancellation. In the second case, all the transmit antennas are detected jointly. The comparison of the two cases shows improvement with the latter one, both in single-user and multiuser communications and in the presence of unknown cochannel interference (UCCI. It is further shown that in the multiuser case, the proposed receivers approach the corresponding single-user bounds. The number of receive antenna elements required to achieve single-user bound is thereby equal to the number of users and not to the total number of transmit antennas.

  1. Previously unknown and highly divergent ssDNA viruses populate the oceans.

    Science.gov (United States)

    Labonté, Jessica M; Suttle, Curtis A

    2013-11-01

    Single-stranded DNA (ssDNA) viruses are economically important pathogens of plants and animals, and are widespread in oceans; yet, the diversity and evolutionary relationships among marine ssDNA viruses remain largely unknown. Here we present the results from a metagenomic study of composite samples from temperate (Saanich Inlet, 11 samples; Strait of Georgia, 85 samples) and subtropical (46 samples, Gulf of Mexico) seawater. Most sequences (84%) had no evident similarity to sequenced viruses. In total, 608 putative complete genomes of ssDNA viruses were assembled, almost doubling the number of ssDNA viral genomes in databases. These comprised 129 genetically distinct groups, each represented by at least one complete genome that had no recognizable similarity to each other or to other virus sequences. Given that the seven recognized families of ssDNA viruses have considerable sequence homology within them, this suggests that many of these genetic groups may represent new viral families. Moreover, nearly 70% of the sequences were similar to one of these genomes, indicating that most of the sequences could be assigned to a genetically distinct group. Most sequences fell within 11 well-defined gene groups, each sharing a common gene. Some of these encoded putative replication and coat proteins that had similarity to sequences from viruses infecting eukaryotes, suggesting that these were likely from viruses infecting eukaryotic phytoplankton and zooplankton.

  2. Febrile rhabdomyolysis of unknown origin in refugees coming from West Africa through the Mediterranean.

    Science.gov (United States)

    Odolini, Silvia; Gobbi, Federico; Zammarchi, Lorenzo; Migliore, Simona; Mencarini, Paola; Vecchia, Marco; di Lauria, Nicoletta; Schivazappa, Simona; Sabatini, Tony; Chianura, Leonardo; Vanino, Elisa; Piacentini, Daniela; Zanotti, Paola; Bussi, Anna; Bartoloni, Alessandro; Bisoffi, Zeno; Castelli, Francesco

    2017-09-01

    Cases of undiagnosed severe febrile rhabdomyolysis in refugees coming from West Africa, mainly from Nigeria, has been observed since May 2014. The aim of this study was to describe this phenomenon. This was a multicentre retrospective observational study of cases of febrile rhabdomyolysis reported from May 2014 to December 2016 in 12 Italian centres. A total of 48 cases were observed, mainly in young males. The mean time interval between the day of departure from Libya and symptom onset was 26.2 days. An average 8.3 further days elapsed before medical care was sought. All patients were hospitalized with fever and very intense muscle aches. Creatine phosphokinase, aspartate aminotransferase, and lactate dehydrogenase values were abnormal in all cases. The rhabdomyolysis was ascribed to an infective agent in 16 (33.3%) cases. In the remaining cases, the aetiology was undefined. Four out of seven patients tested had sickle cell trait. No alcohol abuse or drug intake was reported, apart from a single reported case of khat ingestion. The long incubation period does not support a mechanical cause of rhabdomyolysis. Furthermore, viral infections such as those caused by coxsackievirus are rarely associated with such a severe clinical presentation. It is hypothesized that other predisposing conditions like genetic factors, unknown infections, or unreported non-conventional remedies may be involved. Targeted surveillance of rhabdomyolysis cases is warranted. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Deep-sea biodiversity in the Mediterranean Sea: the known, the unknown, and the unknowable.

    Directory of Open Access Journals (Sweden)

    Roberto Danovaro

    investigated (Prokaryotes excluded, most of the unknown species are within the phylum Nematoda, followed by Foraminifera, but an important fraction of macrofaunal and megafaunal species also remains unknown. Data reported here provide new insights into the patterns of biodiversity in the deep-sea Mediterranean and new clues for future investigations aimed at identifying the factors controlling and threatening deep-sea biodiversity.

  4. Deep-sea biodiversity in the Mediterranean Sea: the known, the unknown, and the unknowable.

    Science.gov (United States)

    Danovaro, Roberto; Company, Joan Batista; Corinaldesi, Cinzia; D'Onghia, Gianfranco; Galil, Bella; Gambi, Cristina; Gooday, Andrew J; Lampadariou, Nikolaos; Luna, Gian Marco; Morigi, Caterina; Olu, Karine; Polymenakou, Paraskevi; Ramirez-Llodra, Eva; Sabbatini, Anna; Sardà, Francesc; Sibuet, Myriam; Tselepides, Anastasios

    2010-08-02

    (Prokaryotes excluded), most of the unknown species are within the phylum Nematoda, followed by Foraminifera, but an important fraction of macrofaunal and megafaunal species also remains unknown. Data reported here provide new insights into the patterns of biodiversity in the deep-sea Mediterranean and new clues for future investigations aimed at identifying the factors controlling and threatening deep-sea biodiversity.

  5. Hepatitis B immunisation in persons not previously exposed to hepatitis B or with unknown exposure status

    DEFF Research Database (Denmark)

    Mathew, Joseph L; El Dib, Regina; Mathew, Preethy J

    2008-01-01

    The benefits and harms of hepatitis B vaccination in persons not previously exposed to hepatitis B infection or with unknown exposure status have not been established.......The benefits and harms of hepatitis B vaccination in persons not previously exposed to hepatitis B infection or with unknown exposure status have not been established....

  6. 39 CFR 946.4 - Disposition of property of unknown owners.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Disposition of property of unknown owners. 946.4 Section 946.4 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PROCEDURE RELATING TO THE... § 946.4 Disposition of property of unknown owners. (a) Where no apparent owner of property subject to...

  7. Detection of unknown primary head and neck tumors by positron emission tomography

    NARCIS (Netherlands)

    Braams, JW; Pruim, J; Kole, AC; Nikkels, PGJ; Vaalburg, W; Vermey, A; Roodenburg, JLN

    The purpose of this study was to investigate the potential of using positron emission tomography (PET) with F-18-labeled fluoro-2-deoxy-D-glucose (FDG) to detect unknown primary tumors of cervical metastases. Thirteen patients with various histologic types of cervical metastases of unknown primary

  8. Fast grasping of unknown objects using cylinder searching on a single point cloud

    NARCIS (Netherlands)

    Lei, Q.; Wisse, M.; Verikas, Antanas; Radeva, Petia; Nikolaev, Dmitry P.; Zhang, Wei; Zhou, Jianhong

    2017-01-01

    Grasping of unknown objects with neither appearance data nor object models given in advance is very important for robots that work in an unfamiliar environment. The goal of this paper is to quickly synthesize an executable grasp for one unknown object by using cylinder searching on a single point

  9. Evaluation of the prognostic benefit of identifying the probable primary site in cancer of unknown primary

    Directory of Open Access Journals (Sweden)

    Das Joyutpal

    2015-09-01

    Full Text Available With the development of site-specific cancer therapy, identifying the primary origin allows the oncologist to personalise therapy for patients with the cancer of unknown primaries (CUPs. At present, immunohistochemistry (IHC screening is the standard method used to postulate the primary site in CUP. In this retrospective study, we evaluated the prognostic benefit of identifying the primary site in CUP. All 84 patients who presented with suspected CUP to the Royal Stoke University Hospital between 2011 and 2012 were included in our study. Forty-eight percent (40/84 of these patients were unable to undergo necessary investigations to identify primary sites because of poor performance status. IHC screening was able to postulate the primary site in 59% (26/44 of the remaining patients with confirmed CUP. Therefore, the primary site was not identified in a significant proportion of patients with CUP. The median survival of confirmed CUP with probable primary site was 2.0 months (95% confidence interval (CI: 1.2 to 2.9 months, whereas the median survival of confirmed CUP with no probable primary site was 4.1 months (95% CI: 1.5 to 9.7 months. This difference in survival time was statistically significant. In addition, using the Cox regression model, we found that patients with confirmed CUP with primary sites had prognostically unfavourable diseases with a shorter median survival, regardless of the age of disease onset, gender, sites of metastases or number of metastases. One approach to improve the survival would be to start systemic therapy at the earliest possible opportunity rather than waiting for all investigation results, such as IHC.

  10. Occlusal management for a patient with aural symptoms of unknown etiology: a case report

    Directory of Open Access Journals (Sweden)

    Torii Kengo

    2007-09-01

    Full Text Available Abstract Background Although the discrepancy between the habitual occlusal position (HOP and the flat bite plate-induced occlusal position (BPOP (regarded as the muscular physiological reference position has been recently reported to be related to symptoms of temporomandibular disorders (TMDs, it still remains unclear whether the occlusal equilibration in the reference position is effective to resolve TMD-related discrepancy and symptoms. Aural symptoms (otalgia, tinnitus, vertigo et cetera have been included under TMD symptoms. Methods To examine the effect of occlusal equilibration for the treatment of TMDs, occlusal equilibration was performed for a patient with aural symptoms (otalgia, tinnitus and vertigo of unknown etiology in the right ear. An occlusal analysis was performed on this patient with dental models mounted on an articulator after relieving painful symptoms by an appliance therapy and a discrepancy was identified (p Results At completion of treatment, the discrepancy was not significant (p > 0.25, and the patient's right condyle had shifted 2.8 mm posteromedially in the horizontal plane, and the left condyle had shifted 1.0 mm laterally in the voluntarily closed position from the previous HOP. The aural symptoms of the patient were resolved, and there has been no recurrence to date after a two-year follow-up period. Conclusion An occlusal analysis should be performed in patients exhibiting TMD symptoms to identify the presence or absence of any discrepancy between the HOP and the BPOP. If a discrepancy exists, occlusal equilibration should be attempted in the reference position.

  11. Prevalence of detecting unknown cerebral metastases in fluorodeoxyglucose positron emission tomography/computed tomography and its potential clinical impact.

    Science.gov (United States)

    Kung, Boom Ting; Auyong, T K; Tong, C M

    2014-05-01

    To determine the prevalence of incidental finding of unknown cerebral metastases and explore the clinical impact of detecting unknown brain metastases among individuals underwent whole body fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) with brain included in field of view. A retrospective review of 1876 patients who underwent whole body PET/CT examination in our clinical PET center for oncological evaluation from January 2009 to September 2009 was performed. The total number and prevalence of unknown brain metastases detected by PET/CT were calculated. Patients diagnosed with cerebral metastases by PET/CT were further analyzed via the electronic patient record system for relevant clinical and radiological findings. Positive predictive value of PET/CT for the diagnosis of cerebral metastases was calculated with reference to contrast enhanced magnetic resonance imaging (MRI) or contrast enhanced CT. Of the 1876 subjects, 71 patients (3.8%) were diagnosed with cerebral metastases by PET/CT. 31 patients were already diagnosed with brain metastases before PET/CT. Among the 40 patients with unknown brain metastasis, 24 (60.0%) underwent either MRI (n = 5) or CT (n = 19) after PET/CT, of which 17 patients were confirmed with cerebral metastases. The true positive rate was 70.8% (17/24), while the false positive rate of PET/CT was 29.2% (7/24). Nearly 94.1% (16/17) patients with confirmed cerebral metastases on MRI or CT had subsequent change in management. Among the remaining 16 patients with positive findings of cerebral metastases without further radiological correlation, 43.8% (7/16) patients had change in management after PET/CT. A total of 57.5% (23/40) patients had change in management after PET/CT. The point prevalence of detecting unknown cerebral metastases by PET/CT was 2.1% (40/1876). 94.1% patients with newly diagnosed brain metastases confirmed with either MRI or CT received immediate treatment for cerebral

  12. Designing an optimal, universal, programmable, and unambiguous discriminator for N unknown qubits

    Science.gov (United States)

    Jafarizadeh, M. A.; Mahmoudi, P.; Akhgar, D.; Faizi, E.

    2017-11-01

    The universal programmable discriminator is a device for discrimination between unknown quantum states. It has two kinds of registers: the program register and the data register. The states that are stored in registers are all unknown. It is assured that the data state is identical with one of the program states with the certain probability. The aim is to optimally identify the state stored in the data register with one of the program states that it is done by discriminating between unknown states of the combined system contains program and data registers. We design an optimal universal unambiguous programmable discriminator that has N qubit systems in the program register, to unambiguously identify the qubit state of data with one of N program qubit states. All unknown qubit states are pure and ND copies of the data state are available. We determine the optimal positive-operator valued measure (POVM) elements in two different ways. First, we find optimal POVMs that maximize the average of the overall success probability of discrimination between N unknown pure states of the combined system. In another way, the problem of discrimination between N unknown pure states of the combined system is reduced to discrimination between N known average mixed states. It is shown that theses two different ways lead to the same results. We show that at least N -1 copies of the data state are necessary for discriminating between N unknown states of the combined system.

  13. Impact of Accurate 30-Day Status on Operative Mortality: Wanted Dead or Alive, Not Unknown.

    Science.gov (United States)

    Ring, W Steves; Edgerton, James R; Herbert, Morley; Prince, Syma; Knoff, Cathy; Jenkins, Kristin M; Jessen, Michael E; Hamman, Baron L

    2017-12-01

    Risk-adjusted operative mortality is the most important quality metric in cardiac surgery for determining The Society of Thoracic Surgeons (STS) Composite Score for star ratings. Accurate 30-day status is required to determine STS operative mortality. The goal of this study was to determine the effect of unknown or missing 30-day status on risk-adjusted operative mortality in a regional STS Adult Cardiac Surgery Database cooperative and demonstrate the ability to correct these deficiencies by matching with an administrative database. STS Adult Cardiac Surgery Database data were submitted by 27 hospitals from five hospital systems to the Texas Quality Initiative (TQI), a regional quality collaborative. TQI data were matched with a regional hospital claims database to resolve unknown 30-day status. The risk-adjusted operative mortality observed-to-expected (O/E) ratio was determined before and after matching to determine the effect of unknown status on the operative mortality O/E. TQI found an excessive (22%) unknown 30-day status for STS isolated coronary artery bypass grafting cases. Matching the TQI data to the administrative claims database reduced the unknowns to 7%. The STS process of imputing unknown 30-day status as alive underestimates the true operative mortality O/E (1.27 before vs 1.30 after match), while excluding unknowns overestimates the operative mortality O/E (1.57 before vs 1.37 after match) for isolated coronary artery bypass grafting. The current STS algorithm of imputing unknown 30-day status as alive and a strategy of excluding cases with unknown 30-day status both result in erroneous calculation of operative mortality and operative mortality O/E. However, external validation by matching with an administrative database can improve the accuracy of clinical databases such as the STS Adult Cardiac Surgery Database. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Row Reduced Echelon Form for Solving Fully Fuzzy System with Unknown Coefficients

    Directory of Open Access Journals (Sweden)

    Ghassan Malkawi

    2014-08-01

    Full Text Available This study proposes a new method for finding a feasible fuzzy solution in positive Fully Fuzzy Linear System (FFLS, where the coefficients are unknown. The fully fuzzy system is transferred to linear system in order to obtain the solution using row reduced echelon form, thereafter; the crisp solution is restricted in obtaining the positive fuzzy solution. The fuzzy solution of FFLS is included crisp intervals, to assign alternative values of unknown entries of fuzzy numbers. To illustrate the proposed method, numerical examples are solved, where the entries of coefficients are unknown in right or left hand side, to demonstrate the contributions in this study.

  15. Learning Innovative Routes for Mobile Robots in Dynamic Partially Unknown Environments

    Directory of Open Access Journals (Sweden)

    Maarja Kruusmaa

    2008-11-01

    Full Text Available This paper examines path planning strategies in partially unknown dynamic environemnts and introduces an approach to learning innovative routes. The approach is verified against shortest path planning with a distance transform algorithm, local and global replanning and suboptimal route following in unknown, partially unknown, static and dynamic environments. We show that the learned routes are more reliable and when traversed repeatedly the robot?s behaviour becomes more predictable. The test results also suggest that the knowledge about the environemnt but not about the path planning strategy used.

  16. Seven and up: individual differences in male voice fundamental frequency emerge before puberty and remain stable throughout adulthood.

    Science.gov (United States)

    Fouquet, Meddy; Pisanski, Katarzyna; Mathevon, Nicolas; Reby, David

    2016-10-01

    Voice pitch (the perceptual correlate of fundamental frequency, F0) varies considerably even among individuals of the same sex and age, communicating a host of socially and evolutionarily relevant information. However, due to the almost exclusive utilization of cross-sectional designs in previous studies, it remains unknown whether these individual differences in voice pitch emerge before, during or after sexual maturation, and whether voice pitch remains stable into adulthood. Here, we measured the F0 parameters of men who were recorded once every 7 years from age 7 to 56 as they participated in the British television documentary Up Series. Linear mixed models revealed significant effects of age on all F0 parameters, wherein F0 mean, minimum, maximum and the standard deviation of F0 showed sharp pubertal decreases between age 7 and 21, yet remained remarkably stable after age 28. Critically, men's pre-pubertal F0 at age 7 strongly predicted their F0 at every subsequent adult age, explaining up to 64% of the variance in post-pubertal F0. This finding suggests that between-individual differences in voice pitch that are known to play an important role in men's reproductive success are in fact largely determined by age 7, and may therefore be linked to prenatal and/or pre-pubertal androgen exposure.

  17. Increased level of organochlorine pesticides in chronic kidney disease patients of unknown etiology: role of GSTM1/GSTT1 polymorphism.

    Science.gov (United States)

    Siddarth, Manushi; Datta, Sudip K; Mustafa, Md; Ahmed, Rafat S; Banerjee, Basu D; Kalra, Om P; Tripathi, Ashok K

    2014-02-01

    Chronic kidney disease (CKD) of unknown etiology represents about 16% of CKD patients in Indian subcontinents and 10% worldwide. The aetiology of CKD of unknown etiology remains unclear though epidemiological studies indicate the involvement of the environmental toxins. Organochlorine pesticides (OCPs) have been detected in general population in India. It is possible that polymorphism of xenobiotic metabolizing enzymes (XMEs) may play an important role in this process. In this we intend to find out blood levels of OCPs in CKD patients of unknown etiology and to evaluate the consequence of glutathione S-transferase (GST) gene polymorphism on the same. We have assessed 270 CKD patients and 270 age-sex-matched healthy controls for this study. The blood OCP levels were analyzed by gas chromatograph. GSTM1, GSTT1 genotyping were carried out by multiplex PCR. Blood levels of HCH, endosulfan and total pesticides were significantly higher in CKD patients and negatively correlated with eGFR. The combined frequency of GSTM1(-)/GSTT1(-) genotype increased the risk of CKD by 1.8-fold as compared to healthy controls. To find out the dependence of blood OCPs level on genotype, we carried out logistic regression analysis and results revealed that GSTM1(-)/GSTT1(-) genotype associated significantly with a number of OCPs namely γ-HCH, p,p'-DDT and total pesticides. Polymorphism of XMEs not only increased accumulation of pesticides but also aggravates kidney dysfunction as evident from significant decrease in eGFR. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. 76 FR 14058 - Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human Remains...

    Science.gov (United States)

    2011-03-15

    ... National Park Service Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human... University of Wyoming Anthropology Department, Human Remains Repository, Laramie, WY. The human remains were..., Anthropology Department, Human Remains Repository, professional staff in consultation with representatives of...

  19. A Rationale for the Use of F18-FDG PET/CT in Fever and Inflammation of Unknown Origin

    Directory of Open Access Journals (Sweden)

    H. Balink

    2012-01-01

    Full Text Available This review focuses on the diagnostic value of hybrid F18-FDG Positron Emission Tomography/Computerized tomography (PET/CT in fever of unknown origin (FUO and inflammation of unknown origin (IUO. Due to the wide range of possible causes both FUO and IUO remain a clinical challenge for both patients and physicians. In addition, the aetiology of IUO shows the same variation in diseases as the FUO spectrum and probably requires the same diagnostic approach as FUO. There are numerous historically used diagnostic approaches incorporating invasive and non-invasive, and imaging techniques, all with relative high specificity but limited sensitivity. This hampers the generalization of these diagnostic approaches. However, recently published reports show that F18-FDG PET/CT in FUO and IUO has a high sensitivity and a relative non-specificity for malignancy, infection and inflammation. This makes F18-FDG PET/CT an ideal diagnostic tool to start the diagnostic process and to guide subsequent focused diagnostic approaches with higher specificity. In addition, F18-FDG PET/CT has a relative high negative predictive value. Therefore F18 FDG PET/CT should be incorporated in the routine diagnostic work-up of patients with FUO and IUO, preferably at an early stage in the diagnostic process.

  20. Fever of unknown origin; Re-evaluation of sup 67 Ga scintigraphy in detecting causes of fever

    Energy Technology Data Exchange (ETDEWEB)

    Misaki, Takashi; Matsui, Akira; Tanaka, Fumiko; Okuno, Yoshishige; Mitsumori, Michihide; Torizuka, Tatsurou; Dokoh, Shigeharu; Hayakawa, Katsumi; Shimbo, Shin-ichirou (Kyoto City Hospital (Japan))

    1990-06-01

    Gallium-67 scintigraphy is a commonly performed imaging modality in deteting pyrogenic lesions in cases of long-standing inexplainable fever. To re-evaluate the significance of gallium imaging in such cases, a retrospective review was made of 56 scans performed in febrile patients in whom sufficient clinical and laboratory findings were obtained. Gallium scans were true positive in 30 patients, false positive in 3, true negative in 19, and false negative in 4. In the group of true positive, local inflammatory lesions were detected in 23 patients with a final diagnosis of lung tuberculosis, urinary tract infection, and inflammatory joint disease. Abnormal gallium accumulation, as shown in the other 7 patients, provided clues to the diagnosis of generalized disorders, such as hematological malignancies (n=3), systemic autoimmune diseases (n=3), and severe infectious mononucleosis (n=one). In the group of false positive, gallium imaging revealed intestinal excretion of gallium in 2 patients and physiological pulmonary hilar accumulation in one. In the true negative group of 19 patients, fever of unknown origin was resolved spontaneously in 12 patients, and with antibiotics and corticosteroids in 2 and 5 patients, respectively. Four patients having false negative scans were finally diagnosed as having urinary tract infection (n=2), bacterial meningitis (n=one), and polyarteritis (n=one). Gallium imaging would remain the technique of choice in searching for origin of unknown fever. It may also be useful for early diagnosis of systemic disease, as well as focal inflammation. (N.K.).

  1. Comprehensive tumor profiling identifies numerous biomarkers of drug response in cancers of unknown primary site: analysis of 1806 cases.

    Science.gov (United States)

    Gatalica, Zoran; Millis, Sherri Z; Vranic, Semir; Bender, Ryan; Basu, Gargi D; Voss, Andreas; Von Hoff, Daniel D

    2014-12-15

    Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Despite extensive laboratory and imaging efforts, the primary site usually cannot be unequivocally confirmed, and the treatment for the most part remains empirical. Recently, identification of common cancer pathway alterations in diverse cancer lineages has offered an opportunity to provide targeted therapies for patients with CUP, irrespective of the primary site. 1806 cancers of unknown primary were identified among more than 63,000 cases profiled at Caris Life Sciences. Multiplatform profiling of the tumor samples included immunohistochemistry, gene sequencing and in situ hybridization methods in an effort to identify changes in biomarkers that are predictive of drug responses. Biomarkers associated with a potential drug benefit were identified in 96% of cases. Biomarkers identified included those associated with potential benefit in nearly all classes of approved cancer drugs (cytotoxic, hormonal, targeted biological drugs). Additionally, biomarkers associated with a potential lack of benefit were identified in numerous cases, which could further refine the management of patients with CUP. Comprehensive biomarker profiling of CUP may provide additional choices in treatment of patients with these difficult to treat malignancies.

  2. Range-based underwater vehicle localization in the presence of unknown ocean currents: Theory and experiments

    Digital Repository Service at National Institute of Oceanography (India)

    Bayat, M.; Crasta, N.; Aguiar, A.P.; Pascoal, A.M.

    This paper addresses the problem of range-based autonomous underwater vehicle (AUV) localization in the presence of unknown ocean currents. In the setup adopted, the AUV is equipped with an attitude and heading reference system, a depth sensor...

  3. Identification of unknown corpses through odontological examination – two case reports

    National Research Council Canada - National Science Library

    Katarzyna Wochna; Anna K. Smędra; Jarosław Berent; Szymon Szustowski

    2017-01-01

    The presented paper illustrates the significance of dental documentation which played a key role in the process of identification of two unknown male cadavers by means of dental features examination...

  4. Design of a DNA chip for detection of unknown genetically modified organisms (GMOs).

    Science.gov (United States)

    Nesvold, Håvard; Kristoffersen, Anja Bråthen; Holst-Jensen, Arne; Berdal, Knut G

    2005-05-01

    Unknown genetically modified organisms (GMOs) have not undergone a risk evaluation, and hence might pose a danger to health and environment. There are, today, no methods for detecting unknown GMOs. In this paper we propose a novel method intended as a first step in an approach for detecting unknown genetically modified (GM) material in a single plant. A model is designed where biological and combinatorial reduction rules are applied to a set of DNA chip probes containing all possible sequences of uniform length n, creating probes capable of detecting unknown GMOs. The model is theoretically tested for Arabidopsis thaliana Columbia, and the probabilities for detecting inserts and receiving false positives are assessed for various parameters for this organism. From a theoretical standpoint, the model looks very promising but should be tested further in the laboratory. The model and algorithms will be available upon request to the corresponding author.

  5. Robust Control for the Segway with Unknown Control Coefficient and Model Uncertainties.

    Science.gov (United States)

    Kim, Byung Woo; Park, Bong Seok

    2016-06-29

    The Segway, which is a popular vehicle nowadays, is an uncertain nonlinear system and has an unknown time-varying control coefficient. Thus, we should consider the unknown time-varying control coefficient and model uncertainties to design the controller. Motivated by this observation, we propose a robust control for the Segway with unknown control coefficient and model uncertainties. To deal with the time-varying unknown control coefficient, we employ the Nussbaum gain technique. We introduce an auxiliary variable to solve the underactuated problem. Due to the prescribed performance control technique, the proposed controller does not require the adaptive technique, neural network, and fuzzy logic to compensate the uncertainties. Therefore, it can be simple. From the Lyapunov stability theory, we prove that all signals in the closed-loop system are bounded. Finally, we provide the simulation results to demonstrate the effectiveness of the proposed control scheme.

  6. Robust Control for the Segway with Unknown Control Coefficient and Model Uncertainties

    Directory of Open Access Journals (Sweden)

    Byung Woo Kim

    2016-06-01

    Full Text Available The Segway, which is a popular vehicle nowadays, is an uncertain nonlinear system and has an unknown time-varying control coefficient. Thus, we should consider the unknown time-varying control coefficient and model uncertainties to design the controller. Motivated by this observation, we propose a robust control for the Segway with unknown control coefficient and model uncertainties. To deal with the time-varying unknown control coefficient, we employ the Nussbaum gain technique. We introduce an auxiliary variable to solve the underactuated problem. Due to the prescribed performance control technique, the proposed controller does not require the adaptive technique, neural network, and fuzzy logic to compensate the uncertainties. Therefore, it can be simple. From the Lyapunov stability theory, we prove that all signals in the closed-loop system are bounded. Finally, we provide the simulation results to demonstrate the effectiveness of the proposed control scheme.

  7. Adaptive Projective Synchronization between Two Different Fractional-Order Chaotic Systems with Fully Unknown Parameters

    Directory of Open Access Journals (Sweden)

    Liping Chen

    2012-01-01

    between the fractional-order chaotic Chen system and the fractional-order chaotic Lü system with unknown parameters is achieved. Theoretical analysis and numerical simulations are presented to demonstrate the validity and feasibility of the proposed method.

  8. Realtime motion planning for a mobile robot in an unknown environment using a neurofuzzy based approach

    Science.gov (United States)

    Zheng, Taixiong

    2005-12-01

    A neuro-fuzzy network based approach for robot motion in an unknown environment was proposed. In order to control the robot motion in an unknown environment, the behavior of the robot was classified into moving to the goal and avoiding obstacles. Then, according to the dynamics of the robot and the behavior character of the robot in an unknown environment, fuzzy control rules were introduced to control the robot motion. At last, a 6-layer neuro-fuzzy network was designed to merge from what the robot sensed to robot motion control. After being trained, the network may be used for robot motion control. Simulation results show that the proposed approach is effective for robot motion control in unknown environment.

  9. WATER TEMPERATURE and Other Data from UNKNOWN from 19630301 to 19650331 (NODC Accession 9500033)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The chorophyll data set was collected from unknown platforms. Data was collected over two year period spanning from March 1, 1963 to March 31, 1965. The data...

  10. Application of the TTC concept to unknown substances found in analysis of foods

    NARCIS (Netherlands)

    Koster, S.; Boobis, A.R.; Cubberley, R.; Hollnagel, H.M.; Richling, E.; Wildemann, T.; Würtzen, G.; Galli, C.L.

    2011-01-01

    Unknown substances, not previously observed, are frequently detected in foods by quality control laboratories. In many cases, the assessment of these 'new' substances requires additional chemical analysis for their identification prior to assessing risk. This identification procedure can be

  11. Super-Resolution of Complex Exponentials from Modulations with Unknown Waveforms

    OpenAIRE

    Yang, Dehui; Tang, Gongguo; Wakin, Michael B.

    2016-01-01

    Super-resolution is generally referred to as the task of recovering fine details from coarse information. Motivated by applications such as single-molecule imaging, radar imaging, etc., we consider parameter estimation of complex exponentials from their modulations with unknown waveforms, allowing for non-stationary blind super-resolution. This problem, however, is ill-posed since both the parameters associated with the complex exponentials and the modulating waveforms are unknown. To allevia...

  12. Unknown sequence amplification: Application to in vitro genome walking in Chlamydia trachomatis L2

    Energy Technology Data Exchange (ETDEWEB)

    Copley, C.G.; Boot, C.; Bundell, K.; McPheat, W.L. (ICI Diagnostics, Cheshire (United Kingdom))

    1991-01-01

    A recently described technique, Chemical Genetics' unknown sequence amplification method, which requires only one specific oligonucleotide, has broadened the applicability of the polymerase chain reaction to DNA of unknown sequence. The authors have adapted this technique to the study of the genome of Chlamydia trachomatis, an obligate intracellular bacterium, and describe modifications that significantly improve the utility of this approach. These techniques allow for rapid genomic analysis entirely in vitro, using DNA of limited quantity of purity.

  13. Pattern Recognition Algorithm for High-Sensitivity Odorant Detection in Unknown Environments

    Science.gov (United States)

    Duong, Tuan A.

    2012-01-01

    In a realistic odorant detection application environment, the collected sensory data is a mix of unknown chemicals with unknown concentrations and noise. The identification of the odorants among these mixtures is a challenge in data recognition. In addition, deriving their individual concentrations in the mix is also a challenge. A deterministic analytical model was developed to accurately identify odorants and calculate their concentrations in a mixture with noisy data.

  14. Average Consensus Problems in Networks of Agents with Fixed and Switching Topology and Unknown Control Direction

    Directory of Open Access Journals (Sweden)

    Caixian Sun

    2014-01-01

    Full Text Available This paper is devoted to the average consensus problems in directed networks of agents with unknown control direction. In this paper, by using Nussbaum function techniques and Laplacian matrix, novel average consensus protocols are designed for multiagent systems with unknown control direction in the cases of directed networks with fixed and switching topology. In the case of switching topology, the disagreement vector is utilized. Finally, simulation is provided to demonstrate the effectiveness of our results.

  15. Adaptive Fault-Tolerant Control of Uncertain Nonlinear Large-Scale Systems With Unknown Dead Zone.

    Science.gov (United States)

    Chen, Mou; Tao, Gang

    2016-08-01

    In this paper, an adaptive neural fault-tolerant control scheme is proposed and analyzed for a class of uncertain nonlinear large-scale systems with unknown dead zone and external disturbances. To tackle the unknown nonlinear interaction functions in the large-scale system, the radial basis function neural network (RBFNN) is employed to approximate them. To further handle the unknown approximation errors and the effects of the unknown dead zone and external disturbances, integrated as the compounded disturbances, the corresponding disturbance observers are developed for their estimations. Based on the outputs of the RBFNN and the disturbance observer, the adaptive neural fault-tolerant control scheme is designed for uncertain nonlinear large-scale systems by using a decentralized backstepping technique. The closed-loop stability of the adaptive control system is rigorously proved via Lyapunov analysis and the satisfactory tracking performance is achieved under the integrated effects of unknown dead zone, actuator fault, and unknown external disturbances. Simulation results of a mass-spring-damper system are given to illustrate the effectiveness of the proposed adaptive neural fault-tolerant control scheme for uncertain nonlinear large-scale systems.

  16. Evaluation of the prevalence and clinical impact of toxocariasis in patients with eosinophilia of unknown origin.

    Science.gov (United States)

    Kim, Hong-Beum; Seo, Jun-Won; Lee, Jun-Hyung; Choi, Byung-Seok; Park, Sang-Gon

    2017-05-01

    Eosinophilia has numerous diverse causes, and in many patients, it is not possible to establish the cause of eosinophilia. Recently, toxocariasis was introduced as one cause of eosinophilia. The aims of this study were to evaluate the prevalence of toxocariasis and the clinical impact of albendazole treatment for toxocariasis in patients suspected of eosinophilia of unknown origin. We performed a retrospective chart review. After evaluation of cause of eosinophilia, the patients suspected of eosinophilia of unknown origin performed immunoglobulin G antibody specific assay for the Toxocara canis larval antigen by enzyme-linked immunosorbent assay. This study evaluated 113 patients, 69 patients (61%) were suspected of eosinophilia of unknown origin. Among these 69 patients, the frequency of T. canis infection was very high (45 patients, 65.2%), and albendazole treatment for 45 eosinophilia with toxocariasis was highly effective for a cure of eosinophilia than no albendazole group regardless of steroid (82.3%, p = 0.007). Furthermore, among the nonsteroid treated small group (19 patients), albendazole treatment for eosinophilia were more effective than no albendazole group, too (83.3% vs. 28.6 %, p = 0.045). The prevalence of toxocariasis was high among patients suspected of eosinophilia of unknown origin; therefore, evaluation for T. canis infection is recommended for patients with eosinophilia of unknown origin. Furthermore, for patients suspected of eosinophilia of unknown origin who have positive results for T. canis, albendazole treatment may be considered a valuable treatment option.

  17. Accounting for genetic differences among unknown parents in microevolutionary studies: how to include genetic groups in quantitative genetic animal models.

    Science.gov (United States)

    Wolak, Matthew E; Reid, Jane M

    2017-01-01

    Quantifying and predicting microevolutionary responses to environmental change requires unbiased estimation of quantitative genetic parameters in wild populations. 'Animal models', which utilize pedigree data to separate genetic and environmental effects on phenotypes, provide powerful means to estimate key parameters and have revolutionized quantitative genetic analyses of wild populations. However, pedigrees collected in wild populations commonly contain many individuals with unknown parents. When unknown parents are non-randomly associated with genetic values for focal traits, animal model parameter estimates can be severely biased. Yet, such bias has not previously been highlighted and statistical methods designed to minimize such biases have not been implemented in evolutionary ecology. We first illustrate how the occurrence of non-random unknown parents in population pedigrees can substantially bias animal model predictions of breeding values and estimates of additive genetic variance, and create spurious temporal trends in predicted breeding values in the absence of local selection. We then introduce 'genetic group' methods, which were developed in agricultural science, and explain how these methods can minimize bias in quantitative genetic parameter estimates stemming from genetic heterogeneity among individuals with unknown parents. We summarize the conceptual foundations of genetic group animal models and provide extensive, step-by-step tutorials that demonstrate how to fit such models in a variety of software programs. Furthermore, we provide new functions in r that extend current software capabilities and provide a standardized approach across software programs to implement genetic group methods. Beyond simply alleviating bias, genetic group animal models can directly estimate new parameters pertaining to key biological processes. We discuss one such example, where genetic group methods potentially allow the microevolutionary consequences of local

  18. Transcriptome Sequencing Reveals Wide Expression Reprogramming of Basal and Unknown Genes in Leptospira biflexa Biofilms.

    Science.gov (United States)

    Iraola, Gregorio; Spangenberg, Lucía; Lopes Bastos, Bruno; Graña, Martín; Vasconcelos, Larissa; Almeida, Áurea; Greif, Gonzalo; Robello, Carlos; Ristow, Paula; Naya, Hugo

    2016-01-01

    The genus Leptospira is composed of pathogenic and saprophytic spirochetes. Pathogenic Leptospira is the etiological agent of leptospirosis, a globally spread neglected disease. A key ecological feature of some pathogenic species is their ability to survive both within and outside the host. For most leptospires, the ability to persist outside the host is associated with biofilm formation, a most important bacterial strategy to face and overcome hostile environmental conditions. The architecture and biochemistry of leptospiral biofilms are rather well understood; however, the genetic program underpinning biofilm formation remains mostly unknown. In this work, we used the saprophyte Leptospira biflexa as a model organism to assess over- and underrepresented transcripts during the biofilm state, using transcriptome sequencing (RNA-seq) technology. Our results showed that some basal biological processes like DNA replication and cell division are downregulated in the mature biofilm. Additionally, we identified significant expression reprogramming for genes involved in motility, sugar/lipid metabolism, and iron scavenging, as well as for outer membrane-encoding genes. A careful manual annotation process allowed us to assign molecular functions to many previously uncharacterized genes that are probably involved in biofilm metabolism. We also provided evidence for the presence of small regulatory RNAs in this species. Finally, coexpression networks were reconstructed to pinpoint functionally related gene clusters that may explain how biofilm maintenance is regulated. Beyond elucidating some genetic aspects of biofilm formation, this work reveals a number of pathways whose functional dissection may impact our understanding of leptospiral biology, in particular how these organisms adapt to environmental changes. IMPORTANCE In this work, we describe the first transcriptome based on RNA-seq technology focused on studying transcriptional changes associated with biofilm growth

  19. Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?

    Energy Technology Data Exchange (ETDEWEB)

    Santhanam, Prasanna; Chandramahanti, Sangeeta [Marshall University, Section of Endocrinology, Department of Internal Medicine, Joan C Edwards School of Medicine, Huntington, WV (United States); Kroiss, Alexander [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Yu, Run [Cedars-Sinai Medical Center, Division of Endocrinology and Carcinoid and Neuroendocrine Tumor Center, Los Angeles, CA (United States); Ruszniewski, Philippe [Beaujon Hospital and Paris-Diderot University, Department of Gastroenterology-Pancreatology, Paris (France); Kumar, Rakesh [All India Institute of Medical Sciences, Diagnostic Nuclear Medicine Division, Department of Nuclear Medicine, New Delhi (India); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France)

    2015-03-13

    Neuroendocrine tumors (NETs) with unknown primary (CUP-NET) are associated with a poor prognosis (10-year survival 22 %), grade 1 and 2 NETs having a more favorable outcome than grade 3 (also called carcinoma). There is evidence that an effort should be made to localize the primary tumor even in the presence of metastasis because resection of the primary tumor(s) may improve disease-free and overall survival, and because the choice of chemotherapeutic agent depends on the location of the primary tumor. Localization of the tumors remains challenging and often relies on a combination of radiological, endoscopic and functional imaging. The functional imaging protocol for evaluation of these patients has historically relied on somatostatin receptor scintigraphy (SRS). However, the sensitivity and specificity of SRS may be unsatisfactory, especially for NETs of midgut origin. Newer PET radiotracers such as {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSTa) and {sup 18}F-DOPA have shown promise. In direct comparisons between {sup 68}Ga-DOTA-SSTa PET/CT and {sup 99m}Tc-HYNIC-octreotide/{sup 111}In-pentetreotide SPECT(/CT), {sup 68}Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. {sup 18}F-DOPA performs better than SRS and CT in well-differentiated NETs of the small intestine. For detecting pancreatic NETs, the high background uptake of {sup 18}F-DOPA by the normal exocrine pancreas can be somewhat overcome by pretreatment with carbidopa. We have suggested a protocol in which SRS is replaced by one of the two agents (preferably with {sup 68}Ga-DOTA-SSTa, alternatively {sup 18}F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and {sup 18}F-FDG PET/CT may be an additional diagnostic test for poorly differentiated tumors and for prognostication. In the near future, it is expected that patients with CUP-NET will benefit from newly

  20. Nuclear Imaging for Classic Fever of Unknown Origin: Meta-Analysis.

    Science.gov (United States)

    Takeuchi, Motoki; Dahabreh, Issa J; Nihashi, Takashi; Iwata, Mitsunaga; Varghese, George M; Terasawa, Teruhiko

    2016-12-01

    Several studies have assessed nuclear imaging tests for localizing the source of fever in patients with classic fever of unknown origin (FUO); however, the role of these tests in clinical practice remains unclear. We systematically reviewed the test performance, diagnostic yield, and management decision impact of nuclear imaging tests in patients with classic FUO. We searched PubMed, Scopus, and other databases through October 31, 2015, to identify studies reporting on the diagnostic accuracy or impact on diagnosis and management decisions of (18)F-FDG PET alone or integrated with CT ((18)F-FDG PET/CT), gallium scintigraphy, or leukocyte scintigraphy. Two reviewers extracted data. We quantitatively synthesized test performance and diagnostic yield and descriptively analyzed evidence about the impact on management decisions. We included 42 studies with 2,058 patients. Studies were heterogeneous and had methodologic limitations. Diagnostic yield was higher in studies with higher prevalence of neoplasms and infections. Nonneoplastic causes, such as adult-onset Still's disease and polymyalgia rheumatica, were less successfully localized. Indirect evidence suggested that (18)F-FDG PET/CT had the best test performance and diagnostic yield among the 4 imaging tests; summary sensitivity was 0.86 (95% confidence interval [CI], 0.81-0.90), specificity 0.52 (95% CI, 0.36-0.67), and diagnostic yield 0.58 (95% CI, 0.51-0.64). Evidence on direct comparisons of alternative imaging modalities or on the impact of tests on management decisions was limited. Nuclear imaging tests, particularly (18)F-FDG PET/CT, can be useful in identifying the source of fever in patients with classic FUO. The contribution of nuclear imaging may be limited in clinical settings in which infective and neoplastic causes are less common. Studies using standardized diagnostic algorithms are needed to determine the optimal timing for testing and to assess the impact of tests on management decisions and

  1. Classical Fever of Unknown Origin: Retrospective Study in Infectious Clinical Hospital №2

    Science.gov (United States)

    Lunchenkov, Nikolay; Filippov, Eugene; Prihodko, Olga; Volchkova, Elena

    2017-01-01

    Abstract Background Despite the recent advances in medicine, fever of unknown origin (FUO) remains a diagnostic and therapeutic challenge even to expert physicians. The etiological structure of FUO is determined by many factors, including the one where a person lived and where has been hospitalized. The aim of this study is to investigate the etiology and clinical characteristics of adult classical FUO with more diagnostics available and to analyze the factors for certain disease categories. Methods The clinical data were retrospectively analyzed from 80 patients with cFUO hospitalized at the Infectious Clinical Hospital №2 between October 2015 and October 2016 the patients who met the D.Durack criteria (1) An axillary temperature of >38.0 which corresponds oral temperature of >38.3; (2) illness duration is more than 3 weeks; (3) there is no definite diagnosis after three outpatient visits or 3 days in the hospital with intensive investigations; (4) the fever is not related to FUO of other groups: nosocomial FUO, FUO in patients with AIDS, neutropenia were included. Results Of the 80 FUO cases, 70 were positively diagnosed with a diagnosis rate of 87,5%. Infectious diseases were still the primary causes of FUO 63% (n = 50). Among them the most frequent diagnoses were bacterial infection of unspecified site 12.5%
(n = 10), infective endocarditis 11% (n = 9), as well as pneumonia 7.5% (n = 6) and viral infections of unspecified site 7.5% (n=6). Connective tissue diseases and other noninfectious inflammatory diseases accounted for 17.5% of the FUO cases among which SLE and autoimmune thyroiditis were the most common etiologies and made up 5% (n = 4) and 3,75% (n = 3), respectively. Neoplasms were 8% (n = 6) in our sample. Also ten patients (12,5%) could not be confirmed until they were discharged from hospital. Conclusion Infectious diseases are the major causes of FUO, and the most common cause is bacterial infection of unspecified site. To determine the

  2. The usage of fasting glucose and glycated hemoglobin for the identification of unknown type 2 diabetes in high risk patients with morbid obesity.

    Science.gov (United States)

    Valderhaug, Tone G; Sharma, Archana; Kravdal, Gunnhild; Rønningen, Reidun; Nermoen, Ingrid

    2017-11-01

    In spite of increased vigilance of undiagnosed type 2 diabetes (DM2), the prevalence of unknown DM2 in subjects with morbid obesity is not known. To assess the prevalence of undiagnosed DM2 and compare the performance of glycated A1c (HbA1c) and fasting glucose (FG) for the diagnosis of DM2 and prediabetes (preDM) in patients with morbid obesity. We measured fasting glucose and HbA1c in 537 consecutive patients with morbid obesity without previously known DM2. A total of 49 (9%) patients with morbid obesity had unknown DM2 out of which 16 (33%) fulfilled both the criteria for HbA1c and FG. Out of 284 (53%) subjects with preDM, 133 (47%) fulfilled both the criteria for HbA1c and FG. Measurements of agreement for FG and HbA1c were moderate for DM2 (κ = 0.461, p DM2 were 0.970 (95% CI 0.942, 0.998) and 0.894 (95% CI 0.837, 0.951) respectively. The optimal thresholds to identify unknown DM2 were FG ≥6.6 mmol/L and HbA1c ≥ 6.1% (43 mmol/mol). The prevalence of DM2 remains high and both FG and HbA1c identify patients with unknown DM2. FG was slightly superior to HbA1c in predicting and separating patients with unknown DM2 from patients without DM2. We suggest that an FG ≥6.6 mmol/L or an HbA1c ≥6.1% (43 mmol/mol) may be used as primary cut points for the identification of unknown DM2 among patients with morbid obesity.

  3. Detection of viral sequence fragments of HIV-1 subfamilies yet unknown.

    Science.gov (United States)

    Unterthiner, Thomas; Schultz, Anne-Kathrin; Bulla, Jan; Morgenstern, Burkhard; Stanke, Mario; Bulla, Ingo

    2011-04-11

    Methods of determining whether or not any particular HIV-1 sequence stems - completely or in part - from some unknown HIV-1 subtype are important for the design of vaccines and molecular detection systems, as well as for epidemiological monitoring. Nevertheless, a single algorithm only, the Branching Index (BI), has been developed for this task so far. Moving along the genome of a query sequence in a sliding window, the BI computes a ratio quantifying how closely the query sequence clusters with a subtype clade. In its current version, however, the BI does not provide predicted boundaries of unknown fragments. We have developed Unknown Subtype Finder (USF), an algorithm based on a probabilistic model, which automatically determines which parts of an input sequence originate from a subtype yet unknown. The underlying model is based on a simple profile hidden Markov model (pHMM) for each known subtype and an additional pHMM for an unknown subtype. The emission probabilities of the latter are estimated using the emission frequencies of the known subtypes by means of a (position-wise) probabilistic model for the emergence of new subtypes. We have applied USF to SIV and HIV-1 sequences formerly classified as having emerged from an unknown subtype. Moreover, we have evaluated its performance on artificial HIV-1 recombinants and non-recombinant HIV-1 sequences. The results have been compared with the corresponding results of the BI. Our results demonstrate that USF is suitable for detecting segments in HIV-1 sequences stemming from yet unknown subtypes. Comparing USF with the BI shows that our algorithm performs as good as the BI or better.

  4. Detection of viral sequence fragments of HIV-1 subfamilies yet unknown

    Directory of Open Access Journals (Sweden)

    Stanke Mario

    2011-04-01

    Full Text Available Abstract Background Methods of determining whether or not any particular HIV-1 sequence stems - completely or in part - from some unknown HIV-1 subtype are important for the design of vaccines and molecular detection systems, as well as for epidemiological monitoring. Nevertheless, a single algorithm only, the Branching Index (BI, has been developed for this task so far. Moving along the genome of a query sequence in a sliding window, the BI computes a ratio quantifying how closely the query sequence clusters with a subtype clade. In its current version, however, the BI does not provide predicted boundaries of unknown fragments. Results We have developed Unknown Subtype Finder (USF, an algorithm based on a probabilistic model, which automatically determines which parts of an input sequence originate from a subtype yet unknown. The underlying model is based on a simple profile hidden Markov model (pHMM for each known subtype and an additional pHMM for an unknown subtype. The emission probabilities of the latter are estimated using the emission frequencies of the known subtypes by means of a (position-wise probabilistic model for the emergence of new subtypes. We have applied USF to SIV and HIV-1 sequences formerly classified as having emerged from an unknown subtype. Moreover, we have evaluated its performance on artificial HIV-1 recombinants and non-recombinant HIV-1 sequences. The results have been compared with the corresponding results of the BI. Conclusions Our results demonstrate that USF is suitable for detecting segments in HIV-1 sequences stemming from yet unknown subtypes. Comparing USF with the BI shows that our algorithm performs as good as the BI or better.

  5. Estimation of stature by cephalometric facial dimensions in skeletonized bodies: study from a sample modern Colombians skeletal remains.

    Science.gov (United States)

    González-Colmenares, Gretel; Medina, César Sanabria; Báez, Liliana Carolina

    2016-01-01

    Estimation of stature is an important factor in the identification of the deceased from unknown fragmentary and dismembered remains. The skull sometimes is the only remain available for identification. The aim of the present study was to estimate the stature of an individual from cephalo-facial dimensions. The study was carried out on 54 males and 16 females from the bone collection of the contemporary Colombian population that belongs to the National Institute of Legal Medicine. Ten cephalo-facial measurements were also made on each subject. The stature of each individual in centimeters was taken from the registration and/or from the autopsy document. The results indicate that the measurements N-M (pstature for males. The correlation between these measures with stature for females was not significant. However, the formulae obtained from univariate linear regression analysis using cephalo-facial measurements showed a greater degree of reliability for estimation of stature in males and females. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. The optimal immunosuppressive protocol for the portal vein infusion of PGE1 and methylprednisolone in pediatric liver transplantation for fulminant hepatic failure of unknown etiology.

    Science.gov (United States)

    Yamada, Yohei; Hoshino, Ken; Irie, Rie; Tomita, Hirofumi; Kato, Mototoshi; Shimojima, Naoki; Fujino, Akihiro; Hibi, Taizo; Shinoda, Masahiro; Obara, Hideaki; Itano, Osamu; Kawachi, Shigeyuki; Tanabe, Minoru; Sakamoto, Michiie; Kitagawa, Yuko; Kuroda, Tatsuo

    2016-08-01

    The outcome of LTx in pediatric patients with FHF of unknown etiology remains inferior to that of LTx in pediatric patients with cholestatic diseases. A higher incidence of steroid-resistant severe rejection has been increasingly recognized among the responsible factors. We assessed the efficacy of the administration of steroids and PGE1 via PVI in the management of LTx for FHF in pediatric patients. In our early cohort (1995-2007), seven patients who underwent LTx for FHF of unknown etiology were treated with conventional immunosuppressive therapy (calcineurin inhibitor and a steroid). Seven of eight grafts (one patient underwent re-LTx) sustained CV and/or CPV associated with ACR, and four patients died of a graft failure or infectious complications that were associated with the treatment for rejection. Of note, the pathological incidence of CV/CPV was significantly higher in recipients with FHF of unknown etiology than in recipients with biliary cholestatic disease during the same study period (87.5% vs. 13.7%, p pediatric patients who undergo LTx for FHF of unknown etiology and that it does not increase the risk of fatal infectious complications. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Circuit realization, chaos synchronization and estimation of parameters of a hyperchaotic system with unknown parameters

    Directory of Open Access Journals (Sweden)

    A. Elsonbaty

    2014-10-01

    Full Text Available In this article, the adaptive chaos synchronization technique is implemented by an electronic circuit and applied to the hyperchaotic system proposed by Chen et al. We consider the more realistic and practical case where all the parameters of the master system are unknowns. We propose and implement an electronic circuit that performs the estimation of the unknown parameters and the updating of the parameters of the slave system automatically, and hence it achieves the synchronization. To the best of our knowledge, this is the first attempt to implement a circuit that estimates the values of the unknown parameters of chaotic system and achieves synchronization. The proposed circuit has a variety of suitable real applications related to chaos encryption and cryptography. The outputs of the implemented circuits and numerical simulation results are shown to view the performance of the synchronized system and the proposed circuit.

  8. Content-Based Multimedia Retrieval in the Presence of Unknown User Preferences

    DEFF Research Database (Denmark)

    Beecks, Christian; Assent, Ira; Seidl, Thomas

    2011-01-01

    address the problem of content-based multimedia retrieval in the presence of unknown user preferences. Our idea consists in performing content-based retrieval by considering all possibilities in a family of similarity models simultaneously. To this end, we propose a novel content-based retrieval approach......Content-based multimedia retrieval requires an appropriate similarity model which reflects user preferences. When these preferences are unknown or when the structure of the data collection is unclear, retrieving the most preferable objects the user has in mind is challenging, as the notion...... of similarity varies from data to data, from task to task, and ultimately from user to user. Based on a specific query object and unknown user preferences, retrieving the most similar objects according to some default similarity model does not necessarily include the most preferable ones. In this work, we...

  9. Identification of fractional-order systems with unknown initial values and structure

    Science.gov (United States)

    Du, Wei; Miao, Qingying; Tong, Le; Tang, Yang

    2017-06-01

    In this paper, the identification problem of fractional-order chaotic systems is proposed and investigated via an evolutionary optimization approach. Different with other studies to date, this research focuses on the identification of fractional-order chaotic systems with not only unknown orders and parameters, but also unknown initial values and structure. A group of fractional-order chaotic systems, i.e., Lorenz, Lü, Chen, Rössler, Arneodo and Volta chaotic systems, are set as the system candidate pool. The identification problem of fractional-order chaotic systems in this research belongs to mixed integer nonlinear optimization in essence. A powerful evolutionary algorithm called composite differential evolution (CoDE) is introduced for the identification problem presented in this paper. Extensive experiments are carried out to show that the fractional-order chaotic systems with unknown initial values and structure can be successfully identified by means of CoDE.

  10. Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Boiteau, Rene M.; Hoyt, David W.; Nicora, Carrie D.; Kinmonth-Schultz, Hannah A.; Ward, Joy K.; Bingol, Ahmet K.

    2018-01-17

    We introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS2), and NMR in a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS2 approach is well suited for discovery of new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases.

  11. Unknown Input Observer Design for Fuzzy Bilinear System: An LMI Approach

    Directory of Open Access Journals (Sweden)

    D. Saoudi

    2012-01-01

    Full Text Available A new method to design a fuzzy bilinear observer (FBO with unknown inputs is developed for a class of nonlinear systems. The nonlinear system is modeled as a fuzzy bilinear model (FBM. This kind of T-S fuzzy model is especially suitable for a nonlinear system with a bilinear term. The proposed fuzzy bilinear observer subject to unknown inputs is developed to ensure the asymptotic convergence of the error dynamic using the Lyapunov method. The proposed design conditions are given in linear matrix inequality (LMI formulation. The paper studies also the problem of fault detection and isolation. An unknown input fuzzy bilinear fault diagnosis observer design is proposed. This work is given for both continuous and discrete cases of fuzzy bilinear models. Illustrative examples are chosen to provide the effectiveness of the given methodology.

  12. Adaptive synchronization of T-S fuzzy chaotic systems with unknown parameters

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Hun [Department of Electrical and Electronic Engineering, Yonsei University, 134 Shinchon-dong, Sudaemoon-gu, Seoul 120-749 (Korea, Republic of)]. E-mail: jhkim@yeics.yonsei.ac.kr; Park, Chang-Woo [Precision Machinery Research Center, Korea Electronics Technology Institute, 203-103 B/D 192, Yakdae-dong, Wonmi-gu, Puchon-si, Kyunggi-do 420-140 (Korea, Republic of); Kim, Euntai [Department of Electrical and Electronic Engineering, Yonsei University, 134 Shinchon-dong, Sudaemoon-gu, Seoul 120-749 (Korea, Republic of); Park, Mignon [Department of Electrical and Electronic Engineering, Yonsei University, 134 Shinchon-dong, Sudaemoon-gu, Seoul 120-749 (Korea, Republic of)

    2005-06-01

    This paper presents a fuzzy model-based adaptive approach for synchronization of chaotic systems which consist of the drive and response systems. Takagi-Sugeno (T-S) fuzzy model is employed to represent the chaotic drive and response systems. Since the parameters of the drive system are assumed unknown, we design the response system that estimates the parameters of the drive system by adaptive strategy. The adaptive law is derived to estimate the unknown parameters and its stability is guaranteed by Lyapunov stability theory. In addition, the controller in the response system contains two parts: one part that can stabilize the synchronization error dynamics and the other part that estimates the unknown parameters. Numerical examples, including Duffing oscillator and Lorenz attractor, are given to demonstrate the validity of the proposed adaptive synchronization approach.

  13. Diagnostical value of arthroscopy of significance knee chronic monosynovitis of unknown origin

    Directory of Open Access Journals (Sweden)

    V V Lyalina

    2003-01-01

    Full Text Available Objective. To estimate arthroscopy diagnostic significance in knee chronic monosynovitis (CMS of unknown origin. Methods. 83 pts (41 female and 42 male aged 20 to 72 years with CMS were examined. Duration of the diseases varied from 2 months to 12 years. Origin of synovitis was unknown. Diseased knee joint arthroscopy was performed with synovial biopsy and microscopic examination of synovial tissue samples. Results. Early or atypical forms of at least 12 diseases were identified as reasons for CMS. Most often CMS reasons were rheumatoid arthritis, osteoarthritis, microcrystalline arthropathy. Presumable and final diagnosis coincidence was noted in 18,3%. Some CMS causes were not considered before the examination. Arthroscopy allowed to identify Knee joint CMS origin in 96,5%. Conclusion. Arthroscopy is a valuable diagnostic method and should be included in plan of obligatory examination of pts with knee joint CMS of unknown origin.

  14. Building a RAPPOR with the Unknown: Privacy-Preserving Learning of Associations and Data Dictionaries

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    Fanti Giulia

    2016-07-01

    Full Text Available Techniques based on randomized response enable the collection of potentially sensitive data from clients in a privacy-preserving manner with strong local differential privacy guarantees. A recent such technology, RAPPOR [12], enables estimation of the marginal frequencies of a set of strings via privacy-preserving crowdsourcing. However, this original estimation process relies on a known dictionary of possible strings; in practice, this dictionary can be extremely large and/or unknown. In this paper, we propose a novel decoding algorithm for the RAPPOR mechanism that enables the estimation of “unknown unknowns,” i.e., strings we do not know we should be estimating. To enable learning without explicit dictionary knowledge, we develop methodology for estimating the joint distribution of multiple variables collected with RAPPOR. Our contributions are not RAPPOR-specific, and can be generalized to other local differential privacy mechanisms for learning distributions of string-valued random variables.

  15. Adaptive Synchronization between Fractional-Order Chaotic Real and Complex Systems with Unknown Parameters

    Directory of Open Access Journals (Sweden)

    Xiaomin Tian

    2014-01-01

    Full Text Available The complex modified projective synchronization (CMPS between fractional-order chaotic real and complex systems is investigated for the first time. The parameters of both master and slave systems are assumed to be unknown in advance; moreover, the slave system is perturbed by unknown but bounded external disturbances. The master and slave systems that achieved CMPS can be synchronized up to a complex constant matrix. On the basis of frequency distributed model of fractional integrator and Lyapunov stability theory, a robust adaptive control law is designed to realize the CMPS for two different types of fractional-order chaotic systems. Meanwhile, to deal with these unknown parameters, some fractional-order type parametric update laws are provided. An example is given to demonstrate the effectiveness and feasibility of the proposed synchronization scheme.

  16. Adaptive Tracking and Obstacle Avoidance Control for Mobile Robots with Unknown Sliding

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    Mingyue Cui

    2012-11-01

    Full Text Available An adaptive control approach is proposed for trajectory tracking and obstacle avoidance for mobile robots with consideration given to unknown sliding. A kinematic model of mobile robots is established in this paper, in which both longitudinal and lateral sliding are considered and processed as three time-varying parameters. A sliding model observer is introduced to estimate the sliding parameters online. A stable tracking control law for this nonholonomic system is proposed to compensate the unknown sliding effect. From Lyapunov-stability analysis, it is proved, regardless of unknown sliding, that tracking errors of the controlled closed-loop system are asymptotically stable, the tracking errors converge to zero outside the obstacle detection region and obstacle avoidance is guaranteed inside the obstacle detection region. The efficiency and robustness of the proposed control system are verified by simulation results.

  17. High-order sliding mode observer for fractional commensurate linear systems with unknown input

    KAUST Repository

    Belkhatir, Zehor

    2017-05-20

    In this paper, a high-order sliding mode observer (HOSMO) is proposed for the joint estimation of the pseudo-state and the unknown input of fractional commensurate linear systems with single unknown input and a single output. The convergence of the proposed observer is proved using a Lyapunov-based approach. In addition, an enhanced variant of the proposed fractional-HOSMO is introduced to avoid the peaking phenomenon and thus to improve the estimation results in the transient phase. Simulation results are provided to illustrate the performance of the proposed fractional observer in both noise-free and noisy cases. The effect of the observer’s gains on the estimated pseudo-state and unknown input is also discussed.

  18. Adaptive Robust Actuator Fault Accommodation for a Class of Uncertain Nonlinear Systems with Unknown Control Gains

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    Yuefei Wu

    2014-01-01

    Full Text Available An adaptive robust fault tolerant control approach is proposed for a class of uncertain nonlinear systems with unknown signs of high-frequency gain and unmeasured states. In the recursive design, neural networks are employed to approximate the unknown nonlinear functions, K-filters are designed to estimate the unmeasured states, and a dynamical signal and Nussbaum gain functions are introduced to handle the unknown sign of the virtual control direction. By incorporating the switching function σ algorithm, the adaptive backstepping scheme developed in this paper does not require the real value of the actuator failure. It is mathematically proved that the proposed adaptive robust fault tolerant control approach can guarantee that all the signals of the closed-loop system are bounded, and the output converges to a small neighborhood of the origin. The effectiveness of the proposed approach is illustrated by the simulation examples.

  19. Renal Cancer Patients with Unknown Ethnicity in Cancer Registry Data: Comparisons to Patients with Known Ethnicity.

    Science.gov (United States)

    Lin, Jie; Butts, Elizabeth; Rockswold, Paul D; Shriver, Craig D; Zhu, Kangmin

    2015-01-01

    Information on ethnicity is important for health disparity research and health service planning. However, information on ethnicity is often incomplete in large routine databases such as cancer registries. This study aimed to compare survival status and other characteristics between cancer patients with and without information on Hispanic ethnicity in cancer registry data. The study included 2,426 patients with clear cell renal cell carcinoma (RCC) diagnosed between 1988 and 2004 and identified from the US Department of Defense (DoD)'s Automated Central Tumor Registry (ACTUR) database. There were 1,353 non-Hispanic patients, 134 Hispanic patients, and 939 patients with unknown ethnicity. Patients were followed through death, date of last contact, or censored on December 31, 2007. Patients with unknown ethnicity exhibited significantly shorter survival than non-Hispanic or Hispanic patients (Log Rank P ethnicity, patients with unknown ethnicity were more likely to have advanced tumor stage at diagnosis and more likely to have missing information on tumor grade, size, and some demographic characteristics. After adjustment for demographic, tumor and treatment variables, patients with unknown ethnicity still exhibited significantly higher mortality than non-Hispanic patients (hazard ratio [HR], 1.69; 95% CI, 1.48-1.92), while Hispanic patients were not different from non-Hispanic patients (HR, 0.95; 95% CI, 0.71-1.28). The shorter survival in the unknown ethnicity group was consistently observed in subgroups by age, race, stage, grade, and surgical treatment, suggesting factors other than those investigated in the current study may play a role in the survival differences between patients with and without information on Hispanic ethnicity. The poor survival of patients with unknown ethnicity in ACTUR warrants further research to elucidate missing mechanisms. Improvement in collection of data by reaching out for more engagement of patients, clinicians and registrars and

  20. Adaptive Fuzzy Synchronization of Fractional-Order Chaotic (Hyperchaotic Systems with Input Saturation and Unknown Parameters

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    Heng Liu

    2017-01-01

    Full Text Available We investigate the synchronization problem of fractional-order chaotic systems with input saturation and unknown external disturbance by means of adaptive fuzzy control. An adaptive controller, accompanied with fractional adaptation law, is established, fuzzy logic systems are used to approximate the unknown nonlinear functions, and the fractional Lyapunov stability theorem is used to analyze the stability. This control method can realize the synchronization of two fractional-order chaotic or hyperchaotic systems and the synchronization error tends to zero asymptotically. Finally, we show the effectiveness of the proposed method by two simulation examples.