WorldWideScience

Sample records for prpsc remains unknown

  1. Infectivity-associated PrP(Sc) and disease duration-associated PrP(Sc) of mouse BSE prions.

    Science.gov (United States)

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

    2015-01-01

    Disease-related prion protein (PrP(Sc)), 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 PrP(Sc) 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 PrP(Sc) in the brain. Centrifugation (20,000 ×g) of the brain homogenate showed that most of the PrP(Sc) was precipitated into the pellet, and the supernatant contained only a slight amount of PrP(Sc). 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 PrP(Sc) may be responsible for prion infectivity and that large, aggregated PrP(Sc) may contribute to determining prion disease duration.

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

    Science.gov (United States)

    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.

  3. Role of cell death in the propagation of PrP(Sc) in immune cells.

    Science.gov (United States)

    Takahashi, Kenichi; Inoshima, Yasuo; Ishiguro, Naotaka

    2015-03-01

    A number of studies have suggested that macrophages, dendritic cells, and follicular dendritic cells play an important role in the propagation of PrP(Sc). Both accumulation and proteolysis of PrP(Sc) have been demonstrated in peripheral macrophages. Macrophages may act as reservoirs for PrP(Sc) particles if the cells die during transient PrP(Sc) propagation. However, whether cell death plays a role in PrP(Sc) propagation in macrophages remains unclear. In this study, we investigated the possibility of propagation and transmission of PrP(Sc) between dead immune cells and living neural cells. We found that under specific conditions, transient PrP(Sc) propagation occurs in dead cells, indicating that interaction between PrP(C) and PrP(Sc) on plasma membrane lipid rafts might be important for PrP(Sc) propagation. Co-culturing of killed donor PrP(Sc)-infected macrophages with recipient N2a-3 neuroblastoma cells accelerated PrP(Sc) transmission. Our results suggest that cell death may play an important role in PrP(Sc) propagation, whereas transient PrP(Sc) propagation in macrophages has little effect on PrP(Sc) transmission.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. L-Arginine ethylester enhances in vitro amplification of PrP(Sc) in macaques with atypical L-type bovine spongiform encephalopathy and enables presymptomatic detection of PrP(Sc) in the bodily fluids.

    Science.gov (United States)

    Murayama, Y; Ono, F; Shimozaki, N; Shibata, H

    2016-02-12

    Protease-resistant, misfolded isoforms (PrP(Sc)) of a normal cellular prion protein (PrP(C)) in the bodily fluids, including blood, urine, and saliva, are expected to be useful diagnostic markers of prion diseases, and nonhuman primate models are suited for performing valid diagnostic tests for human Creutzfeldt-Jakob disease (CJD). We developed an effective amplification method for PrP(Sc) derived from macaques infected with the atypical L-type bovine spongiform encephalopathy (L-BSE) prion by using mouse brain homogenate as a substrate in the presence of polyanions and L-arginine ethylester. This method was highly sensitive and detected PrP(Sc) in infected brain homogenate diluted up to 10(10) by sequential amplification. This method in combination with PrP(Sc) precipitation by sodium phosphotungstic acid is capable of amplifying very small amounts of PrP(Sc) contained in the cerebrospinal fluid (CSF), saliva, urine, and plasma of macaques that have been intracerebrally inoculated with the L-BSE prion. Furthermore, PrP(Sc) was detectable in the saliva or urine samples as well as CSF samples obtained at the preclinical phases of the disease. Thus, our novel method may be useful for furthering the understanding of bodily fluid leakage of PrP(Sc) in nonhuman primate models. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. PrP expression, PrPSc accumulation and innervation of splenic compartments in sheep experimentally infected with scrapie.

    Directory of Open Access Journals (Sweden)

    Randi Sørby

    Full Text Available BACKGROUND: In prion disease, the peripheral expression of PrP(C is necessary for the transfer of infectivity to the central nervous system. The spleen is involved in neuroinvasion and neural dissemination in prion diseases but the nature of this involvement is not known. The present study undertook the investigation of the spatial relationship between sites of PrP(Sc accumulation, localisation of nerve fibres and PrP(C expression in the tissue compartments of the spleen of scrapie-inoculated and control sheep. METHODOLOGY/PRINCIPAL FINDINGS: Laser microdissection and quantitative PCR were used to determine PrP mRNA levels and results were compared with immunohistochemical protocols to distinguish PrP(C and PrP(Sc in tissue compartments of the spleen. In sheep experimentally infected with scrapie, the major sites of accumulation of PrP(Sc in the spleen, namely the lymphoid nodules and the marginal zone, expressed low levels of PrP mRNA. Double immunohistochemical labelling for PrP(Sc and the pan-nerve fibre marker, PGP, was used to evaluate the density of innervation of splenic tissue compartments and the intimacy of association between PrP(Sc and nerves. Some nerve fibres were observed to accompany blood vessels into the PrP(Sc-laden germinal centres. However, the close association between nerves and PrP(Sc was most apparent in the marginal zone. Other sites of close association were adjacent to the wall of the central artery of PALS and the outer rim of germinal centres. CONCLUSIONS/SIGNIFICANCE: The findings suggest that the degree of PrP(Sc accumulation does not depend on the expression level of PrP(C. Though several splenic compartments may contribute to neuroinvasion, the marginal zone may play a central role in being the compartment with most apparent association between nerves and PrP(Sc.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

  14. 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-infection. To ......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...

  15. Detection and Localization of PrPSc in the Skeletal Muscle of Patients with Variant, Iatrogenic, and Sporadic Forms of Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Peden, Alexander H.; Ritchie, Diane L.; Head, Mark W.; Ironside, James W.

    2006-01-01

    Variant Creutzfeldt-Jakob disease (vCJD) differs from other human prion diseases in that the pathogenic prion protein PrPSc can be detected to a greater extent at extraneuronal sites throughout the body, principally within lymphoid tissues. However, a recent study using a high-sensitivity Western blotting technique revealed low levels of PrPSc in skeletal muscle from a quarter of Swiss patients with sporadic CJD (sCJD). This posed the question of whether PrPSc in muscle could also be detected in vCJD, sCJD, and iatrogenic (iCJD) patients from other populations. Therefore, we have used the same high-sensitivity Western blotting technique, in combination with paraffin-embedded tissue blotting, to screen for PrPSc in muscle tissue specimens taken at autopsy from 49 CJD patients in the United Kingdom. These techniques identified muscle PrPSc in 8 of 17 vCJD, 7 of 26 sCJD, and 2 of 5 iCJD patients. Paraffin-embedded tissue blotting analysis showed PrPSc in skeletal muscle in localized anatomical structures that had the morphological and immunohistochemical characteristics of nerve fibers. The detection of PrPSc in muscle tissue from all forms of CJD indicates the possible presence of infectivity in these tissues, suggesting important implications for assessing the potential risk of iatrogenic spread via contaminated surgical instruments. PMID:16507908

  16. Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected CAD neuronal cells.

    Science.gov (United States)

    Dron, Michel; Dandoy-Dron, Françoise; Farooq Salamat, Muhammad Khalid; Laude, Hubert

    2009-08-01

    Dysfunction of the endoplasmic reticulum associated protein degradation/proteasome system is believed to contribute to the initiation or aggravation of neurodegenerative disorders associated with protein misfolding, and there is some evidence to suggest that proteasome dysfunctions might be implicated in prion disease. This study investigated the effect of proteasome inhibitors on the biogenesis of both the cellular (PrP(C)) and abnormal (PrP(Sc)) forms of prion protein in CAD neuronal cells, a newly introduced prion cell system. In uninfected cells, proteasome impairment altered the intracellular distribution of PrP(C), leading to a strong accumulation in the Golgi apparatus. Moreover, a detergent-insoluble and weakly protease-resistant PrP species of 26 kDa, termed PrP(26K), accumulated in the cells, whether they were prion-infected or not. However, no evidence was found that, in infected cells, this PrP(26K) species converts into the highly proteinase K-resistant PrP(Sc). In the infected cultures, proteasome inhibition caused an increased intracellular aggregation of PrP(Sc) that was deposited into large aggresomes. These findings strengthen the view that, in neuronal cells expressing wild-type PrP(C) from the natural promoter, proteasomal impairment may affect both the process of PrP(C) biosynthesis and the subcellular sites of PrP(Sc) accumulation, despite the fact that these two effects could essentially be disconnected.

  17. 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

  18. 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.

  19. 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...

  20. 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

  1. 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.

  2. No novel, high penetrant gene might remain to be found in Japanese patients with unknown MODY.

    Science.gov (United States)

    Horikawa, Yukio; Hosomichi, Kazuyoshi; Enya, Mayumi; Ishiura, Hiroyuki; Suzuki, Yutaka; Tsuji, Shoji; Sugano, Sumio; Inoue, Ituro; Takeda, Jun

    2018-07-01

    MODY 5 and 6 have been shown to be low-penetrant MODYs. As the genetic background of unknown MODY is assumed to be similar, a new analytical strategy is applied here to elucidate genetic predispositions to unknown MODY. We examined to find whether there are major MODY gene loci remaining to be identified using SNP linkage analysis in Japanese. Whole-exome sequencing was performed with seven families with typical MODY. Candidates for novel MODY genes were examined combined with in silico network analysis. Some peaks were found only in either parametric or non-parametric analysis; however, none of these peaks showed a LOD score greater than 3.7, which is approved to be the significance threshold of evidence for linkage. Exome sequencing revealed that three mutated genes were common among 3 families and 42 mutated genes were common in two families. Only one of these genes, MYO5A, having rare amino acid mutations p.R849Q and p.V1601G, was involved in the biological network of known MODY genes through the intermediary of the INS. Although only one promising candidate gene, MYO5A, was identified, no novel, high penetrant MODY genes might remain to be found in Japanese MODY.

  3. 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...

  4. Mechanistic prospective for human PrPC conversion to PrPSc: Molecular dynamic insights

    OpenAIRE

    Nooshin Azari; Mohammad Reza Dayer; Nematollah Razmi; Mohammad Saaid Dayer

    2013-01-01

    PrPC conversion to PrPSc isoform is the main known cause for prion diseases including Crutzfeldt-Jakob, Gerstmann-Sträussler-Sheinker syndrome and fatal familial insomnia in human. The precise mechanism underling this conversion is yet to be well understood. In the present work, using the coordinate file of PrPC (available on the Protein Data Bank) as a starting structure, separate molecular dynamic simulations were carried out at neutral and acidic pH in an explicit water box at 37°C and 1 ...

  5. Detection of PrP(Sc) in peripheral tissues of clinically affected cattle after oral challenge with bovine spongiform encephalopathy

    Science.gov (United States)

    Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that affects cattle and can be transmitted to human beings as new variant Creutzfeldt-Jakob disease (vCJD). A protease-resistant, disease-associated isoform of the prion protein (PrP**Sc) accumulates in the central ner...

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Yuichi Murayama

    Full Text Available 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

  8. 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

  9. Polo-like kinase 3 (PLK3) mediates the clearance of the accumulated PrP mutants transiently expressed in cultured cells and pathogenic PrP(Sc) in prion infected cell line via protein interaction.

    Science.gov (United States)

    Wang, Hui; Tian, Chan; Fan, Xue-Yu; Chen, Li-Na; Lv, Yan; Sun, Jing; Zhao, Yang-Jing; Zhang, Lu-bin; Wang, Jing; Shi, Qi; Gao, Chen; Chen, Cao; Shao, Qi-Xiang; Dong, Xiao-Ping

    2015-05-01

    Polo-like kinases (PLKs) family has long been known to be critical for cell cycle and recent studies have pointed to new dimensions of PLKs function in the nervous system. Our previous study has verified that the levels of PLK3 in the brain are severely downregulated in prion-related diseases. However, the associations of PLKs with prion protein remain unclear. In the present study, we confirmed that PrP protein constitutively interacts with PLK3 as determined by both in vitro and in vivo assays. Both the kinase domain and polo-box domain of PLK3 were proved to bind PrP proteins expressed in mammalian cell lines. Overexpression of PLK3 did not affect the level of wild-type PrP, but significantly decreased the levels of the mutated PrPs in cultured cells. The kinase domain appeared to be responsible for the clearance of abnormally aggregated PrPs, but this function seemed to be independent of its kinase activity. RNA-mediated knockdown of PLK3 obviously aggravated the accumulation of cytosolic PrPs. Moreover, PLK3 overexpression in a scrapie infected cell line caused notable reduce of PrP(Sc) level in a dose-dependent manner, but had minimal effect on the expression of PrP(C) in its normal partner cell line. Our findings here confirmed the molecular interaction between PLK3 and PrP and outlined the regulatory activity of PLK3 on the degradation of abnormal PrPs, even its pathogenic isoform PrP(Sc). We, therefore, assume that the recovery of PLK3 in the early stage of prion infection may be helpful to prevent the toxic accumulation of PrP(Sc) in the brain tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients.

    Science.gov (United States)

    Moore, Roger A; Head, Mark W; Ironside, James W; Ritchie, Diane L; Zanusso, Gianluigi; Choi, Young Pyo; Pyo Choi, Young; Priola, Suzette A

    2016-02-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C)) into infectious PrP(Sc). By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrP(Sc). In both forms of CJD, heterozygosity at residue 129 for methionine (M) or valine (V) in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrP(C) allotype to PrP(Sc) in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrP(Sc) with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrP(C) containing an M or V at residue 129 having a similar propensity to misfold into PrP(Sc) thus causing sCJD. By contrast, PrP(Sc) with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrP(Sc) containing V at residue 129. In both types of CJD, the PrP(Sc) allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrP(Sc) allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD.

  11. Mechanisms of action of brief alcohol interventions remain largely unknown - a narrative review.

    Science.gov (United States)

    Gaume, Jacques; McCambridge, Jim; Bertholet, Nicolas; Daeppen, Jean-Bernard

    2014-01-01

    A growing body of evidence has shown the 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 are disappointing. Indeed, BI comprises varying content; exploring BI content and mechanisms of action may be a promising way to enhance efficacy and effectiveness. Medline and PsychInfo, as well as references of retrieved publications were searched for original research or review on active ingredients (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 patients in the emergency room, 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Designing towards the unknown

    DEFF Research Database (Denmark)

    Wilde, Danielle; Underwood, Jenny

    2018-01-01

    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......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......, 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...

  14. Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification.

    Science.gov (United States)

    Moudjou, Mohammed; Chapuis, Jérôme; Mekrouti, Mériem; Reine, Fabienne; Herzog, Laetitia; Sibille, Pierre; Laude, Hubert; Vilette, Didier; Andréoletti, Olivier; Rezaei, Human; Dron, Michel; Béringue, Vincent

    2016-07-07

    Prions are formed of misfolded assemblies (PrP(Sc)) of the variably N-glycosylated cellular prion protein (PrP(C)). In infected species, prions replicate by seeding the conversion and polymerization of host PrP(C). Distinct prion strains can be recognized, exhibiting defined PrP(Sc) biochemical properties such as the glycotype and specific biological traits. While strain information is encoded within the conformation of PrP(Sc) assemblies, the storage of the structural information and the molecular requirements for self-perpetuation remain uncertain. Here, we investigated the specific role of PrP(C) glycosylation status. First, we developed an efficient protein misfolding cyclic amplification method using cells expressing the PrP(C) species of interest as substrate. Applying the technique to PrP(C) glycosylation mutants expressing cells revealed that neither PrP(C) nor PrP(Sc) glycoform stoichiometry was instrumental to PrP(Sc) formation and strainness perpetuation. Our study supports the view that strain properties, including PrP(Sc) glycotype are enciphered within PrP(Sc) structural backbone, not in the attached glycans.

  15. Quantum circuits cannot control unknown operations

    International Nuclear Information System (INIS)

    Araújo, Mateus; Feix, Adrien; Costa, Fabio; Brukner, Časlav

    2014-01-01

    One of the essential building blocks of classical computer programs is the ‘if’ clause, which executes a subroutine depending on the value of a control variable. Similarly, several quantum algorithms rely on applying a unitary operation conditioned on the state of a control system. Here we show that this control cannot be performed by a quantum circuit if the unitary is completely unknown. The task remains impossible even if we allow the control to be done modulo a global phase. However, this no-go theorem does not prevent implementing quantum control of unknown unitaries in practice, as any physical implementation of an unknown unitary provides additional information that makes the control possible. We then argue that one should extend the quantum circuit formalism to capture this possibility in a straightforward way. This is done by allowing unknown unitaries to be applied to subspaces and not only to subsystems. (paper)

  16. Known knowns, known unknowns and unknown unknowns in prokaryotic transposition.

    Science.gov (United States)

    Siguier, Patricia; Gourbeyre, Edith; Chandler, Michael

    2017-08-01

    Although the phenomenon of transposition has been known for over 60 years, its overarching importance in modifying and streamlining genomes took some time to recognize. In spite of a robust understanding of transposition of some TE, there remain a number of important TE groups with potential high genome impact and unknown transposition mechanisms and yet others, only recently identified by bioinformatics, yet to be formally confirmed as mobile. Here, we point to some areas of limited understanding concerning well established important TE groups with DDE Tpases, to address central gaps in our knowledge of characterised Tn with other types of Tpases and finally, to highlight new potentially mobile DNA species. It is not exhaustive. Examples have been chosen to provide encouragement in the continued exploration of the considerable prokaryotic mobilome especially in light of the current threat to public health posed by the spread of multiple Ab R . Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 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.

  18. Increased expression of p62/SQSTM1 in prion diseases and its association with pathogenic prion protein.

    Science.gov (United States)

    Homma, Takujiro; Ishibashi, Daisuke; Nakagaki, Takehiro; Satoh, Katsuya; Sano, Kazunori; Atarashi, Ryuichiro; Nishida, Noriyuki

    2014-03-28

    Prion diseases are neurodegenerative disorders characterized by the aggregation of abnormally folded prion protein (PrP(Sc)). In this study, we focused on the mechanism of clearance of PrP(Sc), which remains unclear. p62 is a cytosolic protein known to mediate both the formation and degradation of aggregates of abnormal proteins. The levels of p62 protein increased in prion-infected brains and persistently infected cell cultures. Upon proteasome inhibition, p62 co-localized with PrP(Sc), forming a large aggregate in the perinuclear region, hereafter referred to as PrP(Sc)-aggresome. These aggregates were surrounded with autophagosome marker LC3 and lysosomes in prion-infected cells. Moreover, transient expression of the phosphomimic form of p62, which has enhanced ubiquitin-binding activity, reduced the amount of PrP(Sc) in prion-infected cells, indicating that the activation of p62 could accelerate the clearance of PrP(Sc). Our findings would thus suggest that p62 could be a target for the therapeutic control of prion diseases.

  19. 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.

    Science.gov (United States)

    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.

  20. Protease-resistant prions selectively decrease Shadoo protein.

    Directory of Open Access Journals (Sweden)

    Joel C Watts

    2011-11-01

    Full Text Available The central event in prion diseases is the conformational conversion of the cellular prion protein (PrP(C into PrP(Sc, a partially protease-resistant and infectious conformer. However, the mechanism by which PrP(Sc causes neuronal dysfunction remains poorly understood. Levels of Shadoo (Sho, a protein that resembles the flexibly disordered N-terminal domain of PrP(C, were found to be reduced in the brains of mice infected with the RML strain of prions [1], implying that Sho levels may reflect the presence of PrP(Sc in the brain. To test this hypothesis, we examined levels of Sho during prion infection using a variety of experimental systems. Sho protein levels were decreased in the brains of mice, hamsters, voles, and sheep infected with different natural and experimental prion strains. Furthermore, Sho levels were decreased in the brains of prion-infected, transgenic mice overexpressing Sho and in infected neuroblastoma cells. Time-course experiments revealed that Sho levels were inversely proportional to levels of protease-resistant PrP(Sc. Membrane anchoring and the N-terminal domain of PrP both influenced the inverse relationship between Sho and PrP(Sc. Although increased Sho levels had no discernible effect on prion replication in mice, we conclude that Sho is the first non-PrP marker specific for prion disease. Additional studies using this paradigm may provide insight into the cellular pathways and systems subverted by PrP(Sc during prion disease.

  1. Emergence of two prion subtypes in ovine PrP transgenic mice infected with human MM2-cortical Creutzfeldt-Jakob disease prions.

    Science.gov (United States)

    Chapuis, Jérôme; Moudjou, Mohammed; Reine, Fabienne; Herzog, Laetitia; Jaumain, Emilie; Chapuis, Céline; Quadrio, Isabelle; Boulliat, Jacques; Perret-Liaudet, Armand; Dron, Michel; Laude, Hubert; Rezaei, Human; Béringue, Vincent

    2016-02-05

    Mammalian prions are proteinaceous pathogens responsible for a broad range of fatal neurodegenerative diseases in humans and animals. These diseases can occur spontaneously, such as Creutzfeldt-Jakob disease (CJD) in humans, or be acquired or inherited. Prions are primarily formed of macromolecular assemblies of the disease-associated prion protein PrP(Sc), a misfolded isoform of the host-encoded prion protein PrP(C). Within defined host-species, prions can exist as conformational variants or strains. Based on both the M/V polymorphism at codon 129 of PrP and the electrophoretic signature of PrP(Sc) in the brain, sporadic CJD is classified in different subtypes, which may encode different strains. A transmission barrier, the mechanism of which remains unknown, limits prion cross-species propagation. To adapt to the new host, prions have the capacity to 'mutate' conformationally, leading to the emergence of a variant with new biological properties. Here, we transmitted experimentally one rare subtype of human CJD, designated cortical MM2 (129 MM with type 2 PrP(Sc)), to transgenic mice overexpressing either human or the VRQ allele of ovine PrP(C). In marked contrast with the reported absence of transmission to knock-in mice expressing physiological levels of human PrP, this subtype transmitted faithfully to mice overexpressing human PrP, and exhibited unique strain features. Onto the ovine PrP sequence, the cortical MM2 subtype abruptly evolved on second passage, thereby allowing emergence of a pair of strain variants with distinct PrP(Sc) biochemical characteristics and differing tropism for the central and lymphoid tissues. These two strain components exhibited remarkably distinct replicative properties in cell-free amplification assay, allowing the 'physical' cloning of the minor, lymphotropic component, and subsequent isolation in ovine PrP mice and RK13 cells. Here, we provide in-depth assessment of the transmissibility and evolution of one rare subtype of

  2. Fever of unknown origin

    International Nuclear Information System (INIS)

    Misaki, Takashi; Matsui, Akira; Tanaka, Fumiko; Okuno, Yoshishige; Mitsumori, Michihide; Torizuka, Tatsurou; Dokoh, Shigeharu; Hayakawa, Katsumi; Shimbo, Shin-ichirou

    1990-01-01

    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.)

  3. 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

  4. Endogenous proteolytic cleavage of disease-associated prion protein to produce C2 fragments is strongly cell- and tissue-dependent.

    Science.gov (United States)

    Dron, Michel; Moudjou, Mohammed; Chapuis, Jérôme; Salamat, Muhammad Khalid Farooq; Bernard, Julie; Cronier, Sabrina; Langevin, Christelle; Laude, Hubert

    2010-04-02

    The abnormally folded form of the prion protein (PrP(Sc)) accumulating in nervous and lymphoid tissues of prion-infected individuals can be naturally cleaved to generate a N-terminal-truncated fragment called C2. Information about the identity of the cellular proteases involved in this process and its possible role in prion biology has remained limited and controversial. We investigated PrP(Sc) N-terminal trimming in different cell lines and primary cultured nerve cells, and in the brain and spleen tissue from transgenic mice infected by ovine and mouse prions. We found the following: (i) the full-length to C2 ratio varies considerably depending on the infected cell or tissue. Thus, in primary neurons and brain tissue, PrP(Sc) accumulated predominantly as untrimmed species, whereas efficient trimming occurred in Rov and MovS cells, and in spleen tissue. (ii) Although C2 is generally considered to be the counterpart of the PrP(Sc) proteinase K-resistant core, the N termini of the fragments cleaved in vivo and in vitro can actually differ, as evidenced by a different reactivity toward the Pc248 anti-octarepeat antibody. (iii) In lysosome-impaired cells, the ratio of full-length versus C2 species dramatically increased, yet efficient prion propagation could occur. Moreover, cathepsin but not calpain inhibitors markedly inhibited C2 formation, and in vitro cleavage by cathepsins B and L produced PrP(Sc) fragments lacking the Pc248 epitope, strongly arguing for the primary involvement of acidic hydrolases of the endolysosomal compartment. These findings have implications on the molecular analysis of PrP(Sc) and cell pathogenesis of prion infection.

  5. Endogenous Proteolytic Cleavage of Disease-associated Prion Protein to Produce C2 Fragments Is Strongly Cell- and Tissue-dependent*

    Science.gov (United States)

    Dron, Michel; Moudjou, Mohammed; Chapuis, Jérôme; Salamat, Muhammad Khalid Farooq; Bernard, Julie; Cronier, Sabrina; Langevin, Christelle; Laude, Hubert

    2010-01-01

    The abnormally folded form of the prion protein (PrPSc) accumulating in nervous and lymphoid tissues of prion-infected individuals can be naturally cleaved to generate a N-terminal-truncated fragment called C2. Information about the identity of the cellular proteases involved in this process and its possible role in prion biology has remained limited and controversial. We investigated PrPSc N-terminal trimming in different cell lines and primary cultured nerve cells, and in the brain and spleen tissue from transgenic mice infected by ovine and mouse prions. We found the following: (i) the full-length to C2 ratio varies considerably depending on the infected cell or tissue. Thus, in primary neurons and brain tissue, PrPSc accumulated predominantly as untrimmed species, whereas efficient trimming occurred in Rov and MovS cells, and in spleen tissue. (ii) Although C2 is generally considered to be the counterpart of the PrPSc proteinase K-resistant core, the N termini of the fragments cleaved in vivo and in vitro can actually differ, as evidenced by a different reactivity toward the Pc248 anti-octarepeat antibody. (iii) In lysosome-impaired cells, the ratio of full-length versus C2 species dramatically increased, yet efficient prion propagation could occur. Moreover, cathepsin but not calpain inhibitors markedly inhibited C2 formation, and in vitro cleavage by cathepsins B and L produced PrPSc fragments lacking the Pc248 epitope, strongly arguing for the primary involvement of acidic hydrolases of the endolysosomal compartment. These findings have implications on the molecular analysis of PrPSc and cell pathogenesis of prion infection. PMID:20154089

  6. Effects of solution chemistry and aging time on prion protein adsorption and replication of soil-bound prions.

    Directory of Open Access Journals (Sweden)

    Samuel E Saunders

    2011-04-01

    Full Text Available Prion interactions with soil may play an important role in the transmission of chronic wasting disease (CWD and scrapie. Prions are known to bind to a wide range of soil surfaces, but the effects of adsorption solution chemistry and long-term soil binding on prion fate and transmission risk are unknown. We investigated HY TME prion protein (PrP(Sc adsorption to soil minerals in aqueous solutions of phosphate buffered saline (PBS, sodium chloride, calcium chloride, and deionized water using western blotting. The replication efficiency of bound prions following adsorption in these solutions was also evaluated by protein misfolding cyclic amplification (PMCA. Aging studies investigated PrP(Sc desorption and replication efficiency up to one year following adsorption in PBS or DI water. Results indicate that adsorption solution chemistry can affect subsequent prion replication or desorption ability, especially after incubation periods of 30 d or longer. Observed effects were minor over the short-term (7 d or less. Results of long-term aging experiments demonstrate that unbound prions or prions bound to a diverse range of soil surfaces can readily replicate after one year. Our results suggest that while prion-soil interactions can vary with solution chemistry, prions bound to soil could remain a risk for transmitting prion diseases after months in the environment.

  7. Diagnosis of the cancer of unknown primary origin

    International Nuclear Information System (INIS)

    Jurisova, S.; Poersoek, S.

    2013-01-01

    Cancer of unknown primary origin (CUP) is one of the ten most frequent cancers worldwide. It constitutes of 3-5% of all human malignancies. At time of diagnosis patients with CUP present with disseminated metastases without established primary origin. CUP manifests as heterogenous group of mainly epithelial cancers recognised by distinct clinico pathological entities. The diagnostic work-up includes extensive histopathology investigations and modern imaging technology. Nevertheless, the primary tumour remains undetected most of the time. (author)

  8. 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.

  9. Intraabdominal abscessus of unknown etiology

    Directory of Open Access Journals (Sweden)

    Čolović Radoje

    2012-01-01

    Full Text Available Introduction. Intraabdominal abscesses are in 98-99% cases the result of secondary and only in 1-2% of primary peritonitis. They are easy and successfully diagnosed. Abdominal abscesses of unknown cause are extremely rare. Case Outline. The authors present a 68-year-old man, without significant data in past history, who suddenly developed epigastric pain, nausea, vomiting and leukocytosis which was treated with antibiotics resulting in the alleviation of complaints and reduction of white blood cells count. After five days ultrasonography showed incapsulated collection of dense fluid in the epigastrium confirmed by CT scan two days later. Upper endoscopy excluded ulcer and/or perforation of the stomach and duodenum. Under local anesthesia, through the upper part of the left rectal muscle, puncture followed by incision was done, and about 50 ml of dense pus was removed. Finger exploration of the cavity showed no foreign body within the cavity. Using drainage, the recovery was quick and uneventful. By preoperative and postoperative abdominal investigations no cause of the abscess was found. Two and a half years after surgery the patient remained symptom-free with normal clinical, laboratory and ultrasonographic findings. Conclusion. The authors presented an intraabdominal abscess of unknown cause that was successfully treated with antibiotics, percutaneous puncture and drainage under local anaesthesia. In spite of all diagnostic methods the cause of the abscess could not be found. Thus, such a possibility, although being rare, should be taken into account.

  10. 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.

  11. Intrathecal immunoglobulin synthesis in patients with symptomatic epilepsy and epilepsy of unknown etiology ('cryptogenic').

    Science.gov (United States)

    Fauser, S; Soellner, C; Bien, C G; Tumani, H

    2017-09-01

    To compare the frequency of intrathecal immunoglobulin (Ig) synthesis in patients with symptomatic epilepsy and epilepsy of unknown etiology ('cryptogenic'). Patients with epileptic (n = 301) and non-epileptic (n = 10) seizures were retrospectively screened for autochthonous intrathecal Ig synthesis and oligoclonal bands (OCBs) in the cerebrospinal fluid. Intrathecal IgG/OCBs were detected in 8% of patients with epilepsies of unknown etiology, 5% of patients with first seizures of unknown cause and 0-4% of patients with epilepsy due to brain tumors, cerebrovascular disease or other etiologies. Intrathecal IgG/OCBs were not seen in patients with psychogenic seizures. Identical OCBs in serum and cerebrospinal fluid were more common in all patient groups (10-40% depending on underlying etiology). Intrathecal IgG synthesis/OCBs were observed slightly more frequently in patients with 'cryptogenic' epilepsy and with first seizures of unknown etiology than in other patient groups. However, this remained an infrequent finding and thus we could not confirm humoral immunity as a leading disease mechanism in patients with epilepsy in general or with unknown etiology in particular. © 2017 EAN.

  12. Using mass spectrometry and small molecule reagents to detect distinctive structural features of different prion conformations (strains)

    Science.gov (United States)

    A prion (PrPSc) is a conformer of a normal cellular prion protein (PrPC). Although they are isosequential, PrPSc is an infectious protein able to convert PrPC into the prion conformation and thereby propagate an infection. PrPC is monomeric while PrPSc is a multimer. PrPSc can adopt more than one co...

  13. Allocating monitoring effort in the face of unknown unknowns

    Science.gov (United States)

    Wintle, B.A.; Runge, M.C.; Bekessy, S.A.

    2010-01-01

    There is a growing view that to make efficient use of resources, ecological monitoring should be hypothesis-driven and targeted to address specific management questions. 'Targeted' monitoring has been contrasted with other approaches in which a range of quantities are monitored in case they exhibit an alarming trend or provide ad hoc ecological insights. The second form of monitoring, described as surveillance, has been criticized because it does not usually aim to discern between competing hypotheses, and its benefits are harder to identify a priori. The alternative view is that the existence of surveillance data may enable rapid corroboration of emerging hypotheses or help to detect important 'unknown unknowns' that, if undetected, could lead to catastrophic outcomes or missed opportunities. We derive a model to evaluate and compare the efficiency of investments in surveillance and targeted monitoring. We find that a decision to invest in surveillance monitoring may be defensible if: (1) the surveillance design is more likely to discover or corroborate previously unknown phenomena than a targeted design and (2) the expected benefits (or avoided costs) arising from discovery are substantially higher than those arising from a well-planned targeted design. Our examination highlights the importance of being explicit about the objectives, costs and expected benefits of monitoring in a decision analytic framework. ?? 2010 Blackwell Publishing Ltd/CNRS.

  14. Financial Development and Economic Growth: Known Knowns, Known Unknowns, and Unknown Unknowns

    OpenAIRE

    Ugo Panizza

    2014-01-01

    This paper summarizes the main findings of the literature on the relationship between financial and economic development (the known knowns), points to directions for future research (the known unknowns), and then speculates on the third Rumsfeldian category. The known knowns section organizes the empirical literature on finance and growth into three strands: (i) the traditional literature which established the link between finance and growth; (ii) the new literature which qualified some of th...

  15. Implications of prion adaptation and evolution paradigm for human neurodegenerative diseases.

    Science.gov (United States)

    Kabir, M Enamul; Safar, Jiri G

    2014-01-01

    There is a growing body of evidence indicating that number of human neurodegenerative diseases, including Alzheimer disease, Parkinson disease, fronto-temporal dementias, and amyotrophic lateral sclerosis, propagate in the brain via prion-like intercellular induction of protein misfolding. Prions cause lethal neurodegenerative diseases in humans, the most prevalent being sporadic Creutzfeldt-Jakob disease (sCJD); they self-replicate and spread by converting the cellular form of prion protein (PrP(C)) to a misfolded pathogenic conformer (PrP(Sc)). The extensive phenotypic heterogeneity of human prion diseases is determined by polymorphisms in the prion protein gene, and by prion strain-specific conformation of PrP(Sc). Remarkably, even though informative nucleic acid is absent, prions may undergo rapid adaptation and evolution in cloned cells and upon crossing the species barrier. In the course of our investigation of this process, we isolated distinct populations of PrP(Sc) particles that frequently co-exist in sCJD. The human prion particles replicate independently and undergo competitive selection of those with lower initial conformational stability. Exposed to mutant substrate, the winning PrP(Sc) conformers are subject to further evolution by natural selection of the subpopulation with the highest replication rate due to the lowest stability. Thus, the evolution and adaptation of human prions is enabled by a dynamic collection of distinct populations of particles, whose evolution is governed by the selection of progressively less stable, faster replicating PrP(Sc) conformers. This fundamental biological mechanism may explain the drug resistance that some prions gained after exposure to compounds targeting PrP(Sc). Whether the phenotypic heterogeneity of other neurodegenerative diseases caused by protein misfolding is determined by the spectrum of misfolded conformers (strains) remains to be established. However, the prospect that these conformers may evolve and

  16. Generalized cerebral atrophy seen on MRI in a naturally exposed animal model for creutzfeldt-jakob disease

    Directory of Open Access Journals (Sweden)

    Dasanu Constantin A

    2010-11-01

    Full Text Available Abstract Background Magnetic resonance imaging has been used in the diagnosis of human prion diseases such as sCJD and vCJD, but patients are scanned only when clinical signs appear, often at the late stage of disease. This study attempts to answer the questions "Could MRI detect prion diseases before clinical symptoms appear?, and if so, with what confidence?" Methods Scrapie, the prion disease of sheep, was chosen for the study because sheep can fit into a human sized MRI scanner (and there were no large animal MRI scanners at the time of this study, and because the USDA had, at the time of the study, a sizeable sample of scrapie exposed sheep, which we were able to use for this purpose. 111 genetically susceptible sheep that were naturally exposed to scrapie were used in this study. Results Our MRI findings revealed no clear, consistent hyperintense or hypointense signal changes in the brain on either clinically affected or asymptomatic positive animals on any sequence. However, in all 37 PrPSc positive sheep (28 asymptomatic and 9 symptomatic, there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrPSc negative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC. Conclusions Our findings indicate that MRI imaging can detect diffuse cerebral atrophy in asymptomatic and symptomatic sheep infected with scrapie. Nine of these 37 positive sheep, including 2 one-year old animals, were PrPSc positive only in lymph tissues but PrPSc negative in the brain. This suggests either 1 that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrPSc within the brain or 2 that the amount of PrPSc in the brain is below the detectable limits of the utilized immunohistochemistry assay. The significance of these findings remains to be confirmed in human subjects with CJD.

  17. [Focal myositis: An unknown disease].

    Science.gov (United States)

    Gallay, L; Streichenberger, N; Benveniste, O; Allenbach, Y

    2017-10-01

    Focal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual. Copyright © 2017. Published by Elsevier SAS.

  18. Intraepithelial and interstitial deposition of pathological prion protein in kidneys of scrapie-affected sheep.

    Directory of Open Access Journals (Sweden)

    Ciriaco Ligios

    Full Text Available Prions have been documented in extra-neuronal and extra-lymphatic tissues of humans and various ruminants affected by Transmissible Spongiform Encephalopathy (TSE. The presence of prion infectivity detected in cervid and ovine blood tempted us to reason that kidney, the organ filtrating blood derived proteins, may accumulate disease associated PrP(Sc. We collected and screened kidneys of experimentally, naturally scrapie-affected and control sheep for renal deposition of PrP(Sc from distinct, geographically separated flocks. By performing Western blot, PET blot analysis and immunohistochemistry we found intraepithelial (cortex, medulla and papilla and occasional interstitial (papilla deposition of PrP(Sc in kidneys of scrapie-affected sheep. Interestingly, glomerula lacked detectable signals indicative of PrP(Sc. PrP(Sc was also detected in kidneys of subclinical sheep, but to significantly lower degree. Depending on the stage of the disease the incidence of PrP(Sc in kidney varied from approximately 27% (subclinical to 73.6% (clinical in naturally scrapie-affected sheep. Kidneys from flocks without scrapie outbreak were devoid of PrP(Sc. Here we demonstrate unexpectedly frequent deposition of high levels of PrP(Sc in ovine kidneys of various flocks. Renal deposition of PrP(Sc is likely to be a pre-requisite enabling prionuria, a possible co-factor of horizontal prion-transmission in sheep.

  19. The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy.

    Directory of Open Access Journals (Sweden)

    Ester Vázquez-Fernández

    2016-09-01

    Full Text Available The structure of the infectious prion protein (PrPSc, which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate. PrPSc replicates by converting the non-infectious, cellular prion protein (PrPC into the misfolded, infectious conformer through an unknown mechanism. PrPSc and its N-terminally truncated variant, PrP 27-30, aggregate into amorphous aggregates, 2D crystals, and amyloid fibrils. The structure of these infectious conformers is essential to understanding prion replication and the development of structure-based therapeutic interventions. Here we used the repetitive organization inherent to GPI-anchorless PrP 27-30 amyloid fibrils to analyze their structure via electron cryomicroscopy. Fourier-transform analyses of averaged fibril segments indicate a repeating unit of 19.1 Å. 3D reconstructions of these fibrils revealed two distinct protofilaments, and, together with a molecular volume of 18,990 Å3, predicted the height of each PrP 27-30 molecule as ~17.7 Å. Together, the data indicate a four-rung β-solenoid structure as a key feature for the architecture of infectious mammalian prions. Furthermore, they allow to formulate a molecular mechanism for the replication of prions. Knowledge of the prion structure will provide important insights into the self-propagation mechanisms of protein misfolding.

  20. Mitigation of Prion Infectivity and Conversion Capacity by a Simulated Natural Process—Repeated Cycles of Drying and Wetting

    Science.gov (United States)

    Yuan, Qi; Eckland, Thomas; Telling, Glenn; Bartz, Jason; Bartelt-Hunt, Shannon

    2015-01-01

    Prions enter the environment from infected hosts, bind to a wide range of soil and soil minerals, and remain highly infectious. Environmental sources of prions almost certainly contribute to the transmission of chronic wasting disease in cervids and scrapie in sheep and goats. While much is known about the introduction of prions into the environment and their interaction with soil, relatively little is known about prion degradation and inactivation by natural environmental processes. In this study, we examined the effect of repeated cycles of drying and wetting on prion fitness and determined that 10 cycles of repeated drying and wetting could reduce PrPSc abundance, PMCA amplification efficiency and extend the incubation period of disease. Importantly, prions bound to soil were more susceptible to inactivation by repeated cycles of drying and wetting compared to unbound prions, a result which may be due to conformational changes in soil-bound PrPSc or consolidation of the bonding between PrPSc and soil. This novel finding demonstrates that naturally-occurring environmental process can degrade prions. PMID:25665187

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

    OpenAIRE

    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...

  2. Recension: Mao - The Unknown Story

    DEFF Research Database (Denmark)

    Clausen, Søren

    2005-01-01

    Anmeldelse - kritisk! - til Sveriges førende Kinatidsskrift af Jung Chang & Jon Halliday's sensationelle "Mao - the Unknown Story".......Anmeldelse - kritisk! - til Sveriges førende Kinatidsskrift af Jung Chang & Jon Halliday's sensationelle "Mao - the Unknown Story"....

  3. Using small molecule reagents to help distinguish among prion structural models

    Science.gov (United States)

    The only demonstrated difference between infectious prions (PrPSc) and the isosequential normal cellular prion protein (PrPC) is conformation. The structure of PrPC has been determined by a variety of instrumental techniques. The structure of prions remains uncertain. Recent instrumental analysis h...

  4. Previously unknown species of Aspergillus.

    Science.gov (United States)

    Gautier, M; Normand, A-C; Ranque, S

    2016-08-01

    The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care. Copyright © 2016 European Society of Clinical Microbiology and

  5. Prion propagation and toxicity occur in vitro with two-phase kinetics specific to strain and neuronal type.

    Science.gov (United States)

    Hannaoui, Samia; Maatouk, Layal; Privat, Nicolas; Levavasseur, Etienne; Faucheux, Baptiste A; Haïk, Stéphane

    2013-03-01

    Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders that occur in humans and animals. The neuropathological hallmarks of TSEs are spongiosis, glial proliferation, and neuronal loss. The only known specific molecular marker of TSEs is the abnormal isoform (PrP(Sc)) of the host-encoded prion protein (PrP(C)), which accumulates in the brain of infected subjects and forms infectious prion particles. Although this transmissible agent lacks a specific nucleic acid component, several prion strains have been isolated. Prion strains are characterized by differences in disease outcome, PrP(Sc) distribution patterns, and brain lesion profiles at the terminal stage of the disease. The molecular factors and cellular mechanisms involved in strain-specific neuronal tropism and toxicity remain largely unknown. Currently, no cellular model exists to facilitate in vitro studies of these processes. A few cultured cell lines that maintain persistent scrapie infections have been developed, but only two of them have shown the cytotoxic effects associated with prion propagation. In this study, we have developed primary neuronal cultures to assess in vitro neuronal tropism and toxicity of different prion strains (scrapie strains 139A, ME7, and 22L). We have tested primary neuronal cultures enriched in cerebellar granular, striatal, or cortical neurons. Our results showed that (i) a strain-specific neuronal tropism operated in vitro; (ii) the cytotoxic effect varied among strains and neuronal cell types; (iii) prion propagation and toxicity occurred in two kinetic phases, a replicative phase followed by a toxic phase; and (iv) neurotoxicity peaked when abnormal PrP accumulation reached a plateau.

  6. PrPST, a Soluble, Protease Resistant and Truncated PrP Form Features in the Pathogenesis of a Genetic Prion Disease

    Science.gov (United States)

    Frid, Kati; Binyamin, Orli; Gabizon, Ruth

    2013-01-01

    While the conversion of PrPC into PrPSc in the transmissible form of prion disease requires a preexisting PrPSc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrPST), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrPST as in TgMHu2ME199K mice, and “classical” PrPSc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition. PMID:23922744

  7. Effects of heme-PrP complex on cell-free conversion and peroxidase-linked immunodetection of prions in blood-based assays.

    Science.gov (United States)

    Soutyrine, Andrei; Yogasingam, Nishandan; Huang, Hongsheng; Mitchell, Gordon

    2015-08-01

    Prion protein (PrP) binding to natural and synthetic porphyrins has been previously demonstrated but the effects of endogenous heme interactions with PrP remain uncertain. This study investigated implications of this interaction in blood-based peroxidase-linked prion immunodetection and seeded conversion of cellular prion (PrP(C)) into disease associated form (PrP(Sc)). Heme binding to recombinant PrP(C) enhanced intrinsic peroxidase activity (POD) by 2.5-fold and POD inherent to denatured blood accounted for over 84% of luminol-based substrate oxidation in a prion immunodetection assay. An immuno-capture assay showed that 75-98% of blood POD was attributable to binding of PrP(C) with endogenous heme. Additionally, 10 μM heme inhibited (PPrP(C) to PrP(Sc) through the protein misfolding cycling amplification assay. We conclude that the observed effects can interfere with cell-free conversion and peroxidase-linked immunodetection of prions in blood-based assays. These results indicate that heme-PrP interactions could modulate intrinsic POD and protect PrP(C) from conversion into PrP(Sc). Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  8. Membranoproliferative glomerulonephritis in a carcinoma with unknown primary: An autopsy study

    Directory of Open Access Journals (Sweden)

    Gupta Kirti

    2008-04-01

    Full Text Available Kidney disease frequently complicates malignancy and its treatment. Although many solid and hematologic cancers may involve the renal parenchyma, clinical sequelae are usually not prominent. Published reports cite membranous nephropathy as the most common malignancy-associated glomerulopathy, occurring with many carcinomas and occasionally with leukemia and lymphoma followed by minimal change disease. Rarely membranoproliferative glomerulonephritis (MPGN has been reported in patients with malignancy. The mechanism by which malignancy induces disease remains unproved, but may involve deposition of tumor antigen in the subepithelial space with in situ immune complex formation and subsequent complement activation. Treatment of the underlying malignancy may lead to resolution of nephrotic syndrome, lending indirect support to this theory. We report a rare autopsy case of a patient with metastatic carcinoma (with unknown primary associated with MPGN. The association between MPGN and metastatic carcinoma with unknown primary is uncommon and has not been previously reported in the literature.

  9. Investigation of the effects of experimental autolysis on the detection of abnormal prion protein in lymphoid and central nervous system tissues from elk and sheep using the Western blotting method.

    Science.gov (United States)

    Huang, Hongsheng; Soutyrine, Andrei; Rendulich, Jasmine; O'Rourke, Katherine; Balachandran, Aru

    2011-01-01

    Tissues unsuitable for standard immunohistochemical and histopathological examinations for chronic wasting disease (CWD) in cervids and for scrapie in sheep are frequently submitted for testing. This study investigated the effects of experimental autolysis on the detection of abnormal prion protein (PrPsc) in lymphoid and central nervous system (CNS) tissues from elk and sheep. The PrPsc was detected using a Western blotting (WB) test following PrPsc enrichment using sodium phosphotungstic acid (PTA) precipitation (PTA-WB). A commercial enzyme-linked immunosorbent assay (ELISA) was used as a reference test for quantitative measurement. This study showed that the amount of PrPsc in lymphoid and CNS tssues from elk and sheep decreased gradually as a result of autolysis, but PrPsc was still detectable after 5 and 15 d incubation at 37°C by PTA-WB for all lymphoid and CNS samples. The results of the ELISA supported those of PTA-WB, particularly for CNS tissues. In conclusion, autolysis at 37°C for 15 d would not significantly affect the detection of PrPsc in lymphoid and CNS tissues by WB and ELISA and, particularly, PTA-WB is a valuable and alternative confirmatory test to detect PrPsc in autolyzed lymphoid and CNS samples.

  10. Strain-dependent profile of misfolded prion protein aggregates.

    Science.gov (United States)

    Morales, Rodrigo; Hu, Ping Ping; Duran-Aniotz, Claudia; Moda, Fabio; Diaz-Espinoza, Rodrigo; Chen, Baian; Bravo-Alegria, Javiera; Makarava, Natallia; Baskakov, Ilia V; Soto, Claudio

    2016-02-15

    Prions are composed of the misfolded prion protein (PrP(Sc)) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP(Sc) aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP(Sc) aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal manipulations. We show that PrP(Sc) aggregates distribute in a wide range of arrangements and the relative proportion of each species depends on the prion strain. We observed a direct correlation between the density of the predominant PrP(Sc) aggregates and the incubation periods for the strains studied. The relative presence of PrP(Sc) in fractions of different sucrose densities was indicative of the protein deposits present in the brain as analyzed by histology. Interestingly, no association was found between sensitivity to proteolytic degradation and aggregation profiles. Therefore, the organization of PrP molecules in terms of the density of aggregates generated may determine some of the particular strain properties, whereas others are independent from it. Our findings may contribute to understand the mechanisms of strain variation and the role of PrP(Sc) aggregates in prion-induced neurodegeneration.

  11. Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Schreuder, B.E.C.; Meloen, R.H.; Mooij-Harkes, G.; Vromans, M.E.W.; Langeveld, J.P.M.

    1996-01-01

    The scrapie-associated form of the prion protein (PrP(Sc)) accumulates in the brain and lymphoid tissues of sheep with scrapie. In order to assess whether detecting PrP(Sc) in lymphoid tissue could he used as a diagnostic test for scrapie, we studied the localization and distribution of PrP(Sc) in

  12. 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.

  13. Relationship between magnetism and prion protein

    Directory of Open Access Journals (Sweden)

    F. Balzano

    2010-01-01

    Full Text Available The mechanism of conversion of the normal prion protein (PrPC into aggregates of its pathological conformer (PrPSc reamins unclear. The aim of this study was to evaluate the effects induced by exposure of biological samples containing PrPSC to a magnetic field induced prominent molecular changes of samples indicated by the IR spectra located in the region that contains contribution primarily from absorption of amides. This finding suggests the existence of a strong correlation between magnetism and PrPsc and supports a new hypothesis that explains the conversion of normal PrPc to abnormal isoform PrPsc.

  14. Pathogenesis of bovine spongiform encephalopathy in sheep.

    Science.gov (United States)

    van Keulen, L J M; Vromans, M E W; Dolstra, C H; Bossers, A; van Zijderveld, F G

    2008-01-01

    The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrP(Sc)) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrP(Sc) was detected after 6 months in the tonsil and the ileal Peyer's patches. At 9 months postinfection, PrP(Sc) accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. At this time point, PrP(Sc) accumulation in the peripheral neural tissues was first seen in the enteric nervous system of the caudal jejunum and ileum and in the coeliac-mesenteric ganglion. In the central nervous system, PrP(Sc) was first detected in the dorsal motor nucleus of the nervus Vagus in the medulla oblongata and in the intermediolateral column in the spinal cord segments T7-L1. At subsequent time points, PrP(Sc) was seen to spread within the lymphoid system to also involve all non-gut-associated lymphoid tissues. In the enteric nervous system, further spread of PrP(Sc) involved the neural plexi along the entire gastrointestinal tract and in the CNS the complete neuraxis. These findings indicate a spread of the BSE agent in sheep from the enteric nervous system through parasympathetic and sympathetic nerves to the medulla oblongata and the spinal cord.

  15. Genesis of mammalian prions: from non-infectious amyloid fibrils to a transmissible prion disease.

    Directory of Open Access Journals (Sweden)

    Natallia Makarava

    2011-12-01

    Full Text Available The transmissible agent of prion disease consists of a prion protein in its abnormal, β-sheet rich state (PrP(Sc, which is capable of replicating itself according to the template-assisted mechanism. This mechanism postulates that the folding pattern of a newly recruited polypeptide chain accurately reproduces that of a PrP(Sc template. Here we report that authentic PrP(Sc and transmissible prion disease can be generated de novo in wild type animals by recombinant PrP (rPrP amyloid fibrils, which are structurally different from PrP(Sc and lack any detectable PrP(Sc particles. When induced by rPrP fibrils, a long silent stage that involved two serial passages preceded development of the clinical disease. Once emerged, the prion disease was characterized by unique clinical, neuropathological, and biochemical features. The long silent stage to the disease was accompanied by significant transformation in neuropathological properties and biochemical features of the proteinase K-resistant PrP material (PrPres before authentic PrP(Sc evolved. The current work illustrates that transmissible prion diseases can be induced by PrP structures different from that of authentic PrP(Sc and suggests that a new mechanism different from the classical templating exists. This new mechanism designated as "deformed templating" postulates that a change in the PrP folding pattern from the one present in rPrP fibrils to an alternative specific for PrP(Sc can occur. The current work provides important new insight into the mechanisms underlying genesis of the transmissible protein states and has numerous implications for understanding the etiology of neurodegenerative diseases.

  16. PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

    Science.gov (United States)

    Friedman-Levi, Yael; Mizrahi, Michal; Frid, Kati; Binyamin, Orli; Gabizon, Ruth

    2013-01-01

    While the conversion of PrP(C) into PrP(Sc) in the transmissible form of prion disease requires a preexisting PrP(Sc) seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST)), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST) as in TgMHu2ME199K mice, and "classical" PrP(Sc) as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

  17. PrP(ST, a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

    Directory of Open Access Journals (Sweden)

    Yael Friedman-Levi

    Full Text Available While the conversion of PrP(C into PrP(Sc in the transmissible form of prion disease requires a preexisting PrP(Sc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST, a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST as in TgMHu2ME199K mice, and "classical" PrP(Sc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

  18. Mammalian prions

    Science.gov (United States)

    Salamat, Muhammad Khalid; Munoz-Montesino, Carola; Moudjou, Mohammed; Rezaei, Human; Laude, Hubert; Béringue, Vincent; Dron, Michel

    2013-01-01

    Upon prion infection, abnormal prion protein (PrPSc) self-perpetuate by conformational conversion of α-helix-rich PrPC into β sheet enriched form, leading to formation and deposition of PrPSc aggregates in affected brains. However the process remains poorly understood at the molecular level and the regions of PrP critical for conversion are still debated. Minimal amino acid substitutions can impair prion replication at many places in PrP. Conversely, we recently showed that bona fide prions could be generated after introduction of eight and up to 16 additional amino acids in the H2-H3 inter-helix loop of PrP. Prion replication also accommodated the insertions of an octapeptide at different places in the last turns of H2. This reverse genetic approach reveals an unexpected tolerance of prions to substantial sequence changes in the protease-resistant part which is associated with infectivity. It also demonstrates that conversion does not require the presence of a specific sequence in the middle of the H2-H3 area. We discuss the implications of our findings according to different structural models proposed for PrPSc and questioned the postulated existence of an N- or C-terminal prion domain in the protease-resistant region. PMID:23232499

  19. 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.

  20. 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.

  1. Oldest Directly Dated Remains of Sheep in China

    Science.gov (United States)

    Dodson, John; Dodson, Eoin; Banati, Richard; Li, Xiaoqiang; Atahan, Pia; Hu, Songmei; Middleton, Ryan J.; Zhou, Xinying; Nan, Sun

    2014-11-01

    The origins of domesticated sheep (Ovis sp.) in China remain unknown. Previous workers have speculated that sheep may have been present in China up to 7000 years ago, however many claims are based on associations with archaeological material rather than independent dates on sheep material. Here we present 7 radiocarbon dates on sheep bone from Inner Mongolia, Ningxia and Shaanxi provinces. DNA analysis on one of the bones confirms it is Ovis sp. The oldest ages are about 4700 to 4400 BCE and are thus the oldest objectively dated Ovis material in eastern Asia. The graphitisised bone collagen had δ13C values indicating some millet was represented in the diet. This probably indicates sheep were in a domestic setting where millet was grown. The younger samples had δ13C values indicating that even more millet was in the diet, and this was likely related to changes in foddering practices

  2. Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology.

    Science.gov (United States)

    Dubey, Divyanshu; Alqallaf, Abdulradha; Hays, Ryan; Freeman, Matthew; Chen, Kevin; Ding, Kan; Agostini, Mark; Vernino, Steven

    2017-04-01

    Autoimmune epilepsy is an underrecognized condition, and its true incidence is unknown. Identifying patients with an underlying autoimmune origin is critical because these patients' condition may remain refractory to conventional antiseizure medications but may respond to immunotherapy. To determine the prevalence of neurological autoantibodies (Abs) among adult patients with epilepsy of unknown etiology. Consecutive patients presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology were identified. Serum samples were tested for autoimmune encephalitis Abs as well as thyroperoxidase (TPO) and glutamic acid decarboxylase 65 (GAD65) Abs. An antibody prevalence in epilepsy (APE) score based on clinical characteristics was assigned prospectively. Data were collected from June 1, 2015, to June 1, 2016. Presence of neurological Abs. A score based on clinical characteristics was assigned to estimate the probability of seropositivity prior to antibody test results. Good seizure outcome was estimated on the basis of significant reduction of seizure frequency at the first follow-up or seizure freedom. Of the 127 patients (68 males and 59 females) enrolled in the study, 15 were subsequently excluded after identification of an alternative diagnosis. Serum Abs suggesting a potential autoimmune etiology were detected in 39 (34.8%) cases. More than 1 Ab was detected in 7 patients (6.3%): 3 (2.7%) had TPO-Ab and voltage-gated potassium channel complex (VGKCc) Ab, 2 (1.8%) had GAD65-Ab and VGKCc-Ab, 1 had TPO-Ab and GAD65-Ab, and 1 had anti-Hu Ab and GAD65-Ab. Thirty-two patients (28.6%) had a single Ab marker. Among 112 patients included in the study, 15 (13.4%) had TPO-Ab, 14 (12.5%) had GAD65-Ab, 12 (10.7%) had VGKCc (4 of whom were positive for leucine-rich glioma-inactivated protein 1 [LGI1] Ab), and 4 (3.6%) had N-methyl-D-aspartate receptor (NMDAR) Ab. Even after excluding TPO-Ab and low-titer GAD65-Ab, Abs strongly suggesting an

  3. Cryo-immunogold electron microscopy for prions: toward identification of a conversion site.

    Science.gov (United States)

    Godsave, Susan F; Wille, Holger; Kujala, Pekka; Latawiec, Diane; DeArmond, Stephen J; Serban, Ana; Prusiner, Stanley B; Peters, Peter J

    2008-11-19

    Prion diseases are caused by accumulation of an abnormally folded isoform (PrP(Sc)) of the cellular prion protein (PrP(C)). The subcellular distribution of PrP(Sc) and the site of its formation in brain are still unclear. We performed quantitative cryo-immunogold electron microscopy on hippocampal sections from mice infected with the Rocky Mountain Laboratory strain of prions. Two antibodies were used: R2, which recognizes both PrP(C) and PrP(Sc); and F4-31, which only detects PrP(C) in undenatured sections. At a late subclinical stage of prion infection, both PrP(C) and PrP(Sc) were detected principally on neuronal plasma membranes and on vesicles resembling early endocytic or recycling vesicles in the neuropil. The R2 labeling was approximately six times higher in the infected than the uninfected hippocampus and gold clusters were only evident in infected tissue. The biggest increase in labeling density (24-fold) was found on the early/recycling endosome-like vesicles of small-diameter neurites, suggesting these as possible sites of conversion. Trypsin digestion of infected hippocampal sections resulted in a reduction in R2 labeling of >85%, which suggests that a high proportion of PrP(Sc) may be oligomeric, protease-sensitive PrP(Sc).

  4. 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.

  5. Known Unknowns in Judgment and Choice

    OpenAIRE

    Walters, Daniel

    2017-01-01

    This dissertation investigates how people make inferences about missing information. Whereas most prior literature focuses on how people process known information, I show that the extent to which people make inferences about missing information impacts judgments and choices. Specifically, I investigate how (1) awareness of known unknowns affects overconfidence in judgment in Chapter 1, (2) beliefs about the knowability of unknowns impacts investment strategies in Chapter 2, and (3) inferences...

  6. 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.

  7. Detection of unknown primary tumours in patients with cerebral metastases using whole-body 18F-flouorodeoxyglucose positron emission tomography

    DEFF Research Database (Denmark)

    Klee, B; Law, I; Højgaard, L

    2002-01-01

    Identification of the unknown primary tumours in patients presenting with cerebral metastasis is a continued diagnostic challenge. Despite extensive and lengthy diagnostic work-up, the primary tumours will remain obscure in a significant proportion of the patients. The aim of this study was to ev...

  8. Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

    Science.gov (United States)

    Bishop, Matthew T.; Will, Robert G.; Manson, Jean C.

    2010-01-01

    The biological determinants of the phenotypic variation in sporadic Creutzfeldt-Jakob disease (sCJD) are unknown. To categorize sCJD cases, the prion protein (PrP) codon 129 genotype and the biochemical characteristics of the disease-associated form of PrP (PrPSc) can be combined to form six subgroups (MM1, MM2, MV1, MV2, VV1, and VV2). This classification largely correlates with the known variation in the clinical and pathological features of sCJD, with the MM1 and MV1 cases representing the “classic” phenotype of sCJD. To address how this classification relates to different strains of sCJD we have inoculated each subgroup of sCJD to a panel of mice expressing different forms of the human PRNP gene (129MM, 129VV, and 129MV). We have established that all subtypes are transmissible to at least one genotype of mouse, and both agent and host factors determine transmission efficiency and the form of PrPSc deposited in the brain. Moreover, we have identified four distinct strains of sCJD using our in vivo strain typing panel. PMID:20547859

  9. Fever of unknown origin (FUO): CMV infectious mononucleosis or lymphoma?

    Science.gov (United States)

    Cunha, Burke A; Chawla, Karishma

    2018-04-20

    Fever of unknown origin (FUO) refers to fevers of > 101 °F that persist for > 3 weeks and remain undiagnosed after a focused inpatient or outpatient workup. FUO may be due to infectious, malignant/neoplastic, rheumatic/inflammatory, or miscellaneous disorders. The FUO category determines the focus of the diagnostic workup. In the case presented of an FUO in a young woman, there were clinical findings of both CMV infectious mononucleosis or a lymphoma, e.g., highly elevated ESR, elevated ferritin levels, and elevated ACE level, β-2 microglobulins. The indium scan showed intense splenic uptake. Lymph node biopsy, PET scan, and flow cytometry were negative for lymphoma. CMV infectious mononucleosis was the diagnosis, and she made a slow recovery.

  10. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    National Research Council Canada - National Science Library

    Caughey, Byron

    2006-01-01

    .... One therapeutic approach is the inhibitors of PrPSc accumulation indeed many inhibitors of PrPSc accumulation in scrapie-infected cells also have anti-scrapie activity in rodents During This year...

  11. Mobile assistant for unknown caller identification

    OpenAIRE

    Hribernik, Andraž

    2012-01-01

    The main motivation of this diploma thesis is a development of Android application, which helps user of application to find out who is the owner of unknown phone number. Data source for finding unknown phone number are free available web sources. Through the development of prototype, data from different web sources were integrated. Result of this integration is shown in Android application. Data integration includes access to semi-structured data on web portal of Phone Directory of Slovenia, ...

  12. 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.

  13. Transmission of chronic wasting disease identifies a prion strain causing cachexia and heart infection in hamsters.

    Directory of Open Access Journals (Sweden)

    Richard A Bessen

    Full Text Available Chronic wasting disease (CWD is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrP(Sc, prion infection of the central and peripheral neuroendocrine system, and PrP(Sc deposition in cardiac muscle. There was also prominent PrP(Sc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the 'wasting' or WST strain of hamster CWD.

  14. Recombinant human prion protein inhibits prion propagation in vitro.

    Science.gov (United States)

    Yuan, Jue; Zhan, Yi-An; Abskharon, Romany; Xiao, Xiangzhu; Martinez, Manuel Camacho; Zhou, Xiaochen; Kneale, Geoff; Mikol, Jacqueline; Lehmann, Sylvain; Surewicz, Witold K; Castilla, Joaquín; Steyaert, Jan; Zhang, Shulin; Kong, Qingzhong; Petersen, Robert B; Wohlkonig, Alexandre; Zou, Wen-Quan

    2013-10-09

    Prion diseases are associated with the conformational conversion of the cellular prion protein (PrP(C)) into the pathological scrapie isoform (PrP(Sc)) in the brain. Both the in vivo and in vitro conversion of PrP(C) into PrP(Sc) is significantly inhibited by differences in amino acid sequence between the two molecules. Using protein misfolding cyclic amplification (PMCA), we now report that the recombinant full-length human PrP (rHuPrP23-231) (that is unglycosylated and lacks the glycophosphatidylinositol anchor) is a strong inhibitor of human prion propagation. Furthermore, rHuPrP23-231 also inhibits mouse prion propagation in a scrapie-infected mouse cell line. Notably, it binds to PrP(Sc), but not PrP(C), suggesting that the inhibitory effect of recombinant PrP results from blocking the interaction of brain PrP(C) with PrP(Sc). Our findings suggest a new avenue for treating prion diseases, in which a patient's own unglycosylated and anchorless PrP is used to inhibit PrP(Sc) propagation without inducing immune response side effects.

  15. Angiogenesis in cancer of unknown primary: clinicopathological study of CD34, VEGF and TSP-1

    International Nuclear Information System (INIS)

    Karavasilis, Vasilis; Malamou-Mitsi, Vasiliki; Briasoulis, Evangelos; Tsanou, Elena; Kitsou, Evangelia; Kalofonos, Haralambos; Fountzilas, George; Fotsis, Theodore; Pavlidis, Nicholas

    2005-01-01

    Cancer of unknown primary remains a mallignancy of elusive biology and grim prognosis that lacks effective therapeutic options. We investigated angiogenesis in cancer of unknown primary to expand our knowledge on the biology of these tumors and identify potential therapeutic targets. Paraffin embedded archival material from 81 patients diagnosed with CUP was used. Tumor histology was adenocarcinoma (77%), undifferentiated carcinoma (18%) and squamous cell carcinoma (5%). The tissue expression of CD34, VEGF and TSP-1 was assessed immunohistochemically by use of specific monoclonal antibodies and was analyzed against clinicopathological data. VEGF expression was detected in all cases and was strong in 83%. Stromal expression of TSP-1 was seen in 80% of cases and was strong in 20%. The expression of both proteins was not associated with any clinical or pathological parameters. Tumor MVD was higher in tumors classified as unfavorable compared to more favorable and was positively associated with VEGF and negatively with TSP-1. Angiogenesis is very active and expression of VEGF is almost universal in cancers of unknown primary. These findings support the clinical investigation of VEGF targeted therapy in this clinical setting

  16. Prions in the Urine of Patients with Variant Creutzfeldt–Jakob Disease

    Science.gov (United States)

    Moda, Fabio; Gambetti, Pierluigi; Notari, Silvio; Concha-Marambio, Luis; Catania, Marcella; Park, Kyung-Won; Maderna, Emanuela; Suardi, Silvia; Haïk, Stéphane; Brandel, Jean-Philippe; Ironside, James; Knight, Richard; Tagliavini, Fabrizio; Soto, Claudio

    2014-01-01

    BACKGROUND Prions, the infectious agents responsible for transmissible spongiform encephalopathies, consist mainly of the misfolded prion protein (PrPSc). The unique mechanism of transmission and the appearance of a variant form of Creutzfeldt–Jakob disease, which has been linked to consumption of prion-contaminated cattle meat, have raised concerns about public health. Evidence suggests that variant Creutzfeldt–Jakob disease prions circulate in body fluids from people in whom the disease is silently incubating. METHODS To investigate whether PrPSc can be detected in the urine of patients with variant Creutzfeldt–Jakob disease, we used the protein misfolding cyclic amplification (PMCA) technique to amplify minute quantities of PrPSc, enabling highly sensitive detection of the protein. We analyzed urine samples from several patients with various transmissible spongiform encephalopathies (variant and sporadic Creutzfeldt–Jakob disease and genetic forms of prion disease), patients with other degenerative or nondegenerative neurologic disorders, and healthy persons. RESULTS PrPSc was detectable only in the urine of patients with variant Creutzfeldt–Jakob disease and had the typical electrophoretic profile associated with this disease. PrPSc was detected in 13 of 14 urine samples obtained from patients with variant Creutzfeldt–Jakob disease and in none of the 224 urine samples obtained from patients with other neurologic diseases and from healthy controls, resulting in an estimated sensitivity of 92.9% (95% confidence interval [CI], 66.1 to 99.8) and a specificity of 100.0% (95% CI, 98.4 to 100.0). The PrPSc concentration in urine calculated by means of quantitative PMCA was estimated at 1×10−16 g per milliliter, or 3×10−21 mol per milliliter, which extrapolates to approximately 40 to 100 oligomeric particles of PrPSc per milliliter of urine. CONCLUSIONS Urine samples obtained from patients with variant Creutzfeldt–Jakob disease contained minute

  17. Prions in the urine of patients with variant Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Moda, Fabio; Gambetti, Pierluigi; Notari, Silvio; Concha-Marambio, Luis; Catania, Marcella; Park, Kyung-Won; Maderna, Emanuela; Suardi, Silvia; Haïk, Stéphane; Brandel, Jean-Philippe; Ironside, James; Knight, Richard; Tagliavini, Fabrizio; Soto, Claudio

    2014-08-07

    Prions, the infectious agents responsible for transmissible spongiform encephalopathies, consist mainly of the misfolded prion protein (PrP(Sc)). The unique mechanism of transmission and the appearance of a variant form of Creutzfeldt-Jakob disease, which has been linked to consumption of prion-contaminated cattle meat, have raised concerns about public health. Evidence suggests that variant Creutzfeldt-Jakob disease prions circulate in body fluids from people in whom the disease is silently incubating. To investigate whether PrP(Sc) can be detected in the urine of patients with variant Creutzfeldt-Jakob disease, we used the protein misfolding cyclic amplification (PMCA) technique to amplify minute quantities of PrP(Sc), enabling highly sensitive detection of the protein. We analyzed urine samples from several patients with various transmissible spongiform encephalopathies (variant and sporadic Creutzfeldt-Jakob disease and genetic forms of prion disease), patients with other degenerative or nondegenerative neurologic disorders, and healthy persons. PrP(Sc) was detectable only in the urine of patients with variant Creutzfeldt-Jakob disease and had the typical electrophoretic profile associated with this disease. PrP(Sc) was detected in 13 of 14 urine samples obtained from patients with variant Creutzfeldt-Jakob disease and in none of the 224 urine samples obtained from patients with other neurologic diseases and from healthy controls, resulting in an estimated sensitivity of 92.9% (95% confidence interval [CI], 66.1 to 99.8) and a specificity of 100.0% (95% CI, 98.4 to 100.0). The PrP(Sc) concentration in urine calculated by means of quantitative PMCA was estimated at 1×10(-16) g per milliliter, or 3×10(-21) mol per milliliter, which extrapolates to approximately 40 to 100 oligomeric particles of PrP(Sc) per milliliter of urine. Urine samples obtained from patients with variant Creutzfeldt-Jakob disease contained minute quantities of PrP(Sc). (Funded by the

  18. 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.

  19. MoCha: Molecular Characterization of Unknown Pathways.

    Science.gov (United States)

    Lobo, Daniel; Hammelman, Jennifer; Levin, Michael

    2016-04-01

    Automated methods for the reverse-engineering of complex regulatory networks are paving the way for the inference of mechanistic comprehensive models directly from experimental data. These novel methods can infer not only the relations and parameters of the known molecules defined in their input datasets, but also unknown components and pathways identified as necessary by the automated algorithms. Identifying the molecular nature of these unknown components is a crucial step for making testable predictions and experimentally validating the models, yet no specific and efficient tools exist to aid in this process. To this end, we present here MoCha (Molecular Characterization), a tool optimized for the search of unknown proteins and their pathways from a given set of known interacting proteins. MoCha uses the comprehensive dataset of protein-protein interactions provided by the STRING database, which currently includes more than a billion interactions from over 2,000 organisms. MoCha is highly optimized, performing typical searches within seconds. We demonstrate the use of MoCha with the characterization of unknown components from reverse-engineered models from the literature. MoCha is useful for working on network models by hand or as a downstream step of a model inference engine workflow and represents a valuable and efficient tool for the characterization of unknown pathways using known data from thousands of organisms. MoCha and its source code are freely available online under the GPLv3 license.

  20. 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.

  1. Thin-layer chromatography of polyphosphoinositides from platelet extracts: interference by an unknown phospholipid

    International Nuclear Information System (INIS)

    Tysnes, O.B.; Aarbakke, G.M.; Verhoeven, A.J.; Holmsen, H.

    1985-01-01

    Different ratios of radioactive polyphosphoinositides in platelets pulse-labelled with 32p-orthophosphate have been reported by various laboratories. We studied whether these differences originate from differences in methodology. Extracts of 32p-Pi labelled human platelets were prepared at various times after gel-filtration and phosphatidylinositol (PI)-, mono (PIP)- and bisphosphate (PIP2) were separated by thin-layer chromatography using four different solvent systems. The 32p-levels in PIP and PIP2 remained constant during one hour after gel-filtration, whereas 32p-PI increased continuously and more than doubled within the first h. In two of the systems PIP co-chromatographed with a radioactive compound which separated well from PIP in the two other systems. This unknown compound was also labelled with 3H-glycerol, 3H-inositol and 3H-arachidonic acid, but it was metabolically and functionally different from the polyphosphoinositides. Both the co-chromatography of this unknown phospholipid and the increase in 32p-PI in gel-filtered platelets can explain the difference in 32p-labelling in phosphoinositides reported in the literature

  2. Determination of the origin of unknown irradiated nuclear fuel.

    Science.gov (United States)

    Nicolaou, G

    2006-01-01

    An isotopic fingerprinting method is presented to determine the origin of unknown nuclear material with forensic importance. Spent nuclear fuel of known origin has been considered as the 'unknown' nuclear material in order to demonstrate the method and verify its prediction capabilities. The method compares, using factor analysis, the measured U, Pu isotopic compositions of the 'unknown' material with U, Pu isotopic compositions simulating well known spent fuels from a range of commercial nuclear power stations. Then, the 'unknown' fuel has the same origin as the commercial fuel with which it exhibits the highest similarity in U, Pu compositions.

  3. Determination of the origin of unknown irradiated nuclear fuel

    International Nuclear Information System (INIS)

    Nicolaou, G.

    2006-01-01

    An isotopic fingerprinting method is presented to determine the origin of unknown nuclear material with forensic importance. Spent nuclear fuel of known origin has been considered as the 'unknown' nuclear material in order to demonstrate the method and verify its prediction capabilities. The method compares, using factor analysis, the measured U, Pu isotopic compositions of the 'unknown' material with U, Pu isotopic compositions simulating well known spent fuels from a range of commercial nuclear power stations. Then, the 'unknown' fuel has the same origin as the commercial fuel with which it exhibits the highest similarity in U, Pu compositions

  4. 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...... to describe different aspects of molecular biology of the cell, to study changes that occur in the cell due to overexpression or deletion of a gene and to identify various protein modifications. The biological questions and the results of the described studies show the diversity of the information that can...... genes and proteins. It reports the first global proteome database collecting 36 yeast single gene deletion mutants and selecting over 650 differences between analysed mutants and the wild type strain. The obtained results show that two-dimensional gel electrophoresis and mass spectrometry based proteome...

  5. Discovery of a novel, monocationic, small-molecule inhibitor of scrapie prion accumulation in cultured sheep microglia and Rov cells.

    Directory of Open Access Journals (Sweden)

    James B Stanton

    Full Text Available Prion diseases, including sheep scrapie, are neurodegenerative diseases with the fundamental pathogenesis involving conversion of normal cellular prion protein (PrP(C to disease-associated prion protein (PrP(Sc. Chemical inhibition of prion accumulation is widely investigated, often using rodent-adapted prion cell culture models. Using a PrP(Sc-specific ELISA we discovered a monocationic phenyl-furan-benzimidazole (DB772, which has previously demonstrated anti-pestiviral activity and represents a chemical category previously untested for anti-prion activity, that inhibited PrP(Sc accumulation and prion infectivity in primary sheep microglial cell cultures (PRNP 136VV/154RR/171QQ and Rov9 cultures (VRQ-ovinized RK13 cells. We investigated potential mechanisms of this anti-prion activity by evaluating PrP(C expression with quantitative RT-PCR and PrP ELISA, comparing the concentration-dependent anti-prion and anti-pestiviral effects of DB772, and determining the selectivity index. Results demonstrate at least an approximate two-log inhibition of PrP(Sc accumulation in the two cell systems and confirmed that the inhibition of PrP(Sc accumulation correlates with inhibition of prion infectivity. PRNP transcripts and total PrP protein concentrations within cell lysates were not decreased; thus, decreased PrP(C expression is not the mechanism of PrP(Sc inhibition. PrP(Sc accumulation was multiple logs more resistant than pestivirus to DB772, suggesting that the anti-PrP(Sc activity was independent of anti-pestivirus activity. The anti-PrP(Sc selectivity index in cell culture was approximately 4.6 in microglia and 5.5 in Rov9 cells. The results describe a new chemical category that inhibits ovine PrP(Sc accumulation in primary sheep microglia and Rov9 cells, and can be used for future studies into the treatment and mechanism of prion diseases.

  6. Lack of prion accumulation in lymphoid tissues of PRNP ARQ/ARR sheep intracranially inoculated with the agent of scrapie.

    Science.gov (United States)

    Greenlee, Justin J; Kunkle, Robert A; Richt, Jürgen A; Nicholson, Eric M; Hamir, Amir N

    2014-01-01

    Sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted horizontally. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in affected sheep. The purpose of this study was to compare the survival time and PrPSc tissue distribution in sheep with highly resistant and highly susceptible PRNP genotypes after intracranial inoculation of the agent of scrapie. Five sheep each of genotype VRQ/VRQ, VRQ/ARR or ARQ/ARR were inoculated. Sheep were euthanized when clinical signs of scrapie became severe. Clinical signs, microscopic lesions, and western blot profiles were uniform across genotypes and consistent with manifestations of classical scrapie. Mean survival time differences were associated with the 171 polymorphic site with VRQ/VRQ sheep surviving 18 months, whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively. Labeling of PrPSc by immunohistochemistry revealed similar accumulations in central nervous system tissues regardless of host genotype. Immunoreactivity for PrPSc in lymphoid tissue was consistently abundant in VRQ/VRQ, present but confined to tonsil or retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep. The results of this study demonstrate the susceptibility of sheep with the ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrPSc accumulation in CNS tissues, but prolonged incubation times and lack of PrPSc in lymphoid tissue.

  7. 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

  8. Pathogenesis of bovine spongiform encephalopathy in sheep

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Vromans, M.E.W.; Dolstra, C.H.; Bossers, A.; Zijderveld, van F.G.

    2008-01-01

    The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was

  9. Unknown foundation determination for scour.

    Science.gov (United States)

    2012-04-01

    Unknown foundations affect about 9,000 bridges in Texas. For bridges over rivers, this creates a problem : regarding scour decisions as the calculated scour depth cannot be compared to the foundation depth, and a : very conservative costly approach m...

  10. 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

  11. Keratosis of unknown significance and leukoplakia: a preliminary study.

    Science.gov (United States)

    Woo, Sook-Bin; Grammer, Rebecca L; Lerman, Mark A

    2014-12-01

    The objectives were to (1) determine the frequency of specific diagnoses in a series of white lesions, and (2) describe the nature of keratotic lesions that are neither reactive nor dysplastic. White lesions were analyzed and diagnosed as reactive keratoses, dysplastic/malignant, or keratoses of unknown significance (KUS). Of the 1251 specimens that were evaluated, 703 met criteria for inclusion, and approximately 75% were reactive, 10% dysplastic/malignant, and 14% KUS. Excluding reactive keratoses, 43% were dysplastic/malignant and 57% were KUS. Reactive keratoses were the most common white lesions followed by lichen planus. Dysplastic/malignant lesions constituted almost 50% of all true leukoplakias. KUS constituted the remaining cases and do not show typical reactive histopathology as well as clear dysplasia. They may represent evolving or devolving reactive keratoses but may also represent the very earliest dysplasia phenotype. Clinical findings may be helpful in differentiating the two. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. 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.

  13. Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy.

    Science.gov (United States)

    Hoffmann, Christine; Ziegler, Ute; Buschmann, Anne; Weber, Artur; Kupfer, Leila; Oelschlegel, Anja; Hammerschmidt, Baerbel; Groschup, Martin H

    2007-03-01

    To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.

  14. Quantifying the relative amounts of PrP polymorphisms present in prions isolated from heterozygous prion-infected animals

    Science.gov (United States)

    Prions cause protein misfolding diseases, such as transmissible spongiform encephalopathy. They propagate infections by converting a normal cellular prion protein into a prion (PrPSc). PrPC and PrPSc are isosequential and differ only in their respective conformations. PrPC is monomeric and sensit...

  15. Piperazine derivatives inhibit PrP/PrP(res) propagation in vitro and in vivo.

    Science.gov (United States)

    Leidel, Fabienne; Eiden, Martin; Geissen, Markus; Hirschberger, Thomas; Tavan, Paul; Giese, Armin; Kretzschmar, Hans A; Schätzl, Hermann; Groschup, Martin H

    2014-02-28

    Prion diseases are fatal neurodegenerative disorders, which are not curable and no effective treatment exists so far. The major neuropathological change in diseased brains is the conversion of the normal cellular form of the prion protein PrPc(C) into a disease-associated isoform PrP(Sc). PrP(Sc) accumulates into multimeres and fibrillar aggregates, which leads to the formation of amyloid plaques. Increasing evidence indicates a fundamental role of PrP(Sc) species and its aggregation in the pathogenesis of prion diseases, which initiates the pathological cascade and leads to neurodegeneration accompanied by spongiform changes. In search of compounds that have the potential to interfere with PrP(Sc) formation and propagation, we used a cell based assay for the screening of potential aggregation inhibitors. The assay deals with a permanently prion infected cell line that was adapted for a high-throughput screening of a compound library composed of 10,000 compounds (DIVERset 2, ChemBridge). We could detect six different classes of highly potent inhibitors of PrP(Sc) propagation in vitro and identified piperazine derivatives as a new inhibitory lead structure, which increased incubation time of scrapie infected mice. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Lung Lesions During Fever of Unknown Origin.

    Science.gov (United States)

    Krupa, Renata; Zielonka, Tadeusz M; Hadzik-Blaszczyk, Malgorzata; Wardyn, Kazimierz A; Zycinska, Katarzyna

    2017-01-01

    Fever of unknown origin (FUO) remains one of the most difficult diagnostic challenges. The causes of FUO can be various diseases located in different organs. The aim of the study was to determine the prevalence and nature of pulmonary lesions during FUO. One hundred and sixty one patients with FUO participated in this prospective study. We performed a detailed comprehensive history, physical examination, and a wide spectrum of tests. The most common causes of FUO were infections (39%), autoimmune conditions (28%), and neoplasms (17%). Lung lesions were found in 30% of patients. In this group 35% were infections, 30% autoimmune diseases, and 4% cancer. Among patients with respiratory infections, there were cases of tuberculosis, atypical pneumonia, lung abscess, and bronchiectases. Autoimmune pulmonary lesions were observed during vasculitis and systemic lupus. The causes of FUO in the group of patients with lung lesions were also pulmonary embolism, sarcoidosis, and pulmonary fibrosis. Chest CT played an important role in the diagnosis of the causes of FUO with pulmonary manifestations. Pulmonary lesions are a common cause of FUO. Most FUO with pulmonary lesions are recognized during infections and autoimmune diseases. An important part of diagnosing FUO is a detailed evaluation of the respiratory system.

  17. 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

    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.......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...

  18. Preclinical deposition of pathological prion protein in muscle of experimentally infected primates.

    Directory of Open Access Journals (Sweden)

    Susanne Krasemann

    Full Text Available Prion diseases are transmissible fatal neurodegenerative disorders affecting humans and animals. A central step in disease progression is the accumulation of a misfolded form (PrP(Sc of the host encoded prion protein (PrP(C in neuronal and non-neuronal tissues. The involvement of peripheral tissues in preclinical states increases the risk of accidental transmission. On the other hand, detection of PrP(Sc in non-neuronal easy-accessible compartments such as muscle may offer a novel diagnostic tool. Primate models have proven invaluable to investigate prion diseases. We have studied the deposition of PrP(Sc in muscle and central nervous system of rhesus monkeys challenged with sporadic Creutzfeldt-Jakob disease (sCJD, variant CJD (vCJD and bovine spongiform encephalopathy (BSE in preclinical and clinical stage using biochemical and morphological methods. Here, we show the preclinical presence of PrP(Sc in muscle and central nervous system of rhesus monkeys experimentally infected with vCJD.

  19. A significant abiotic pathway for the formation of unknown nitrogen in nature

    Science.gov (United States)

    Jokic, A.; Schulten, H.-R.; Cutler, J. N.; Schnitzer, M.; Huang, P. M.

    2004-03-01

    The global nitrogen cycle is of prime importance in natural ecosystems. However, the origin and nature of up to one-half of total soil N remains obscure despite all attempts at elucidation. Our data provide, for the first time, unequivocal evidence that the promoting action of Mn (IV) oxide on the Maillard reaction (sugar-amino acid condensation) under ambient conditions results in the abiotic formation of heterocyclic N compounds, which are often referred to as unknown nitrogen, and of amides which are apparently the dominant N moieties in nature. The information presented is of fundamental significance in understanding the role of mineral colloids in abiotic transformations of organic N moieties, the incorporation of N in the organic matrix of fossil fuels, and the global N cycle.

  20. Glycoform-selective prion formation in sporadic and familial forms of prion disease

    NARCIS (Netherlands)

    Xiao, X.; Yuan, J.; Haïk, S.; Cali, I.; Zhan, Y.; Moudjou, M.; Li, B.; Laplanche, J.L.; Laude, H.; Langeveld, J.P.M.; Gambetti, P.

    2013-01-01

    The four glycoforms of the cellular prion protein (PrP(C)) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrP(Sc)) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrP(Sc) in the recently identified

  1. Classification of Unknown Thermocouple Types Using Similarity Factor Measurement

    Directory of Open Access Journals (Sweden)

    Seshu K. DAMARLA

    2011-01-01

    Full Text Available In contrast to classification using PCA method, a new methodology is proposed for type identification of unknown thermocouple. The new methodology is based on calculating the degree of similarity between two multivariate datasets using two types of similarity factors. One similarity factor is based on principle component analysis and the angles between the principle component subspaces while the other is based on the Mahalanobis distance between the datasets. Datasets containing thermo-emfs against given temperature ranges are formed for each type of thermocouple (e.g. J, K, S, T, R, E, B and N type by experimentation are considered as reference datasets. Datasets corresponding to unknown type are captured. Similarity factor between the datasets one of which being the unknown type and the other being each known type are compared. When maximum similarity factor occurs, then the class of unknown type is allocated to that of known type.

  2. [Assessment of the prognosis in patients who remain comatose after resuscitation from cardiac arrest].

    Science.gov (United States)

    Ramberg, Emilie; Fedder, Anette Marianne; Dyrskog, Stig Eric; Degn, Niels Sanderhoff; Hassager, Christian; Jensen, Reinhold; Kirkegaard, Hans; Weber, Sven; Hoffmann-Petersen, Joachim Torp; Larsen, Niels Heden; Strange, Ditte Gry; Sonne, Morten; Lippert, Freddy K

    2014-06-30

    In Denmark there are around 3,500 unexpected cardiac arrests (CA) out of hospital each year. There is an unknown number of CA in hospitals. The survival rate after CA outside a hospital in Denmark is 10% after 30 days. There are varying data for the neurological outcome in this group of patients. The purpose of this work is to disseminate new knowledge and to help standardizing the treatment in the group of patients who remain comatose after being resuscitated from CA. Assessment of the prognosis for a patient in this group can be made after 72 hours and a multi-modal approach to the patient is required.

  3. Magnetic resonance imaging (MRI) of liver and brain in haematologic-organic patients with fever of unknown origin

    International Nuclear Information System (INIS)

    Heussel, C.P.; Kauczor, H.U.; Poguntke, M.; Schadmand-Fischer, S.; Mildenberger, P.; Thelen, M.; Heussel, G.

    1998-01-01

    To examine the advantage of liver and brain MRI in clinically anomalous haematological patients with fever of unknown origin. Material and Methods: Twenty liver MRI (T 2 -TSE, T 2 -HASTE, T 1 -FLASH±Gd dynamic) and 16 brain MRI (T 2 -TSE, FLAIR, T 1 -TSE±Gd) were performed searching for a focus of fever with a suspected organ system. Comparison with clinical follow-up. Results: suspected organ system. Comparison with clinical follow-up. Results: A focus was detected in 11/20 liver MRI. Candidiasis (n=3), mycobacteriosis (n=2), relapse of haematological disease (n=3), graft versus host disease (n=1), non-clarified (n=2). The remaining 9 cases with normal MRI were not suspicious of infectious hepatic disease during follo-wup. In brain MRI, 3/16 showed a focus (toxoplasmosis, aspergillosis, mastoiditis). Clinical indication for an infectious involvement of the brain was found in 4/16 cases 2--5 months after initially normal brain MRI. No suspicion of an infectious involvement of brain was present in the remaining 9/16 cases. Conclusion: In case of fever of unknown origin and suspicion of liver involvement, MRI of the liver should be performed due to data given in literature and its sensitivity of 100%. Because of the delayed detectability of cerebral manifestations, in cases of persisting suspicion even a previously normal MRI of the brain should be repeated. (orig.) [de

  4. InSourcerer: a high-throughput method to search for unknown metabolite modifications by mass spectrometry.

    Science.gov (United States)

    Mrzic, Aida; Lermyte, Frederik; Vu, Trung Nghia; Valkenborg, Dirk; Laukens, Kris

    2017-09-15

    Using mass spectrometry, the analysis of known metabolite structures has become feasible in a systematic high-throughput fashion. Nevertheless, the identification of previously unknown structures remains challenging, partially because many unidentified variants originate from known molecules that underwent unexpected modifications. Here, we present a method for the discovery of unknown metabolite modifications and conjugate metabolite isoforms in a high-throughput fashion. The method is based on user-controlled in-source fragmentation which is used to induce loss of weakly bound modifications. This is followed by the comparison of product ions from in-source fragmentation and collision-induced dissociation (CID). Diagonal MS 2 -MS 3 matching allows the detection of unknown metabolite modifications, as well as substructure similarities. As the method relies heavily on the advantages of in-source fragmentation and its ability to 'magically' elucidate unknown modification, we have named it inSourcerer as a portmanteau of in-source and sorcerer. The method was evaluated using a set of 15 different cytokinin standards. Product ions from in-source fragmentation and CID were compared. Hierarchical clustering revealed that good matches are due to the presence of common substructures. Plant leaf extract, spiked with a mix of all 15 standards, was used to demonstrate the method's ability to detect these standards in a complex mixture, as well as confidently identify compounds already present in the plant material. Here we present a method that incorporates a classic liquid chromatography/mass spectrometry (LC/MS) workflow with fragmentation models and computational algorithms. The assumptions upon which the concept of the method was built were shown to be valid and the method showed that in-source fragmentation can be used to pinpoint structural similarities and indicate the occurrence of a modification. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Detection of type 1 prion protein in variant Creutzfeldt-Jakob disease

    NARCIS (Netherlands)

    Yull, H.M.; Ritchie, D.L.; Langeveld, J.P.M.; Zijderveld, van F.G.; Bruce, M.E.; Ironside, J.W.; Head, M.W.

    2006-01-01

    Molecular typing of the abnormal form of the prion protein (PrPSc) has come to be regarded as a powerful tool in the investigation of the prion diseases. All evidence thus far presented indicates a single PrPSc molecular type in variant Creutzfeldt-Jakob disease (termed type 2B), presumably

  6. Semi-purification procedures of prions from a prion-infected brain using sucrose has no influence on the nonenzymatic glycation of the disease-associated prion isoform.

    Science.gov (United States)

    Choi, Yeong-Gon; Kim, Jae-Il; Choi, Eun-Kyoung; Carp, Richard I; Kim, Yong-Sun

    2016-01-01

    Previous studies have shown that the Nε-carboxymethyl group is linked to not only one or more N-terminal Lys residues but also to one or more Lys residues of the protease-resistant core region of the pathogenic prion isoform (PrPSc) in prion-infected brains. Using an anti-advanced glycation end product (AGE) antibody, we detected nonenzymatically glycated PrPSc (AGE-PrPSc) in prion-infected brains following concentration by a series of ultracentrifugation steps with a sucrose cushion. In the present study, the levels of in vitro nonenzymatic glycation of PrPSc using sucrose were investigated to determine whether sucrose cushion can artificially and nonenzymatically induce in vitro glycation during ultracentrifugation. The first insoluble pellet fraction following the first ultracentrifugation (PU1st) collected from 263K scrapie-infected brains was incubated with sucrose, glucose or colloidal silica coated with polyvinylpyrrolidone (percoll). None of the compounds in vitro resulted in AGE-PrPSc. Nonetheless, glucose and percoll produced AGEs in vitro from other proteins within PU1st of the infected brains. This reaction could lead to the AGE-modified polymer(s) of nonenzymatic glycation-prone protein(s). This study showed that PrPSc is not nonenzymatically glycated in vitro with sucrose, glucose or percoll and that AGE-modified PrPSc can be isolated and enriched from prion-infected brains.

  7. Clinical applications of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in carcinoma of unknown primary

    Institute of Scientific and Technical Information of China (English)

    HU Man; YU Jin-ming; ZHAO Wei; ZHANG Pin-liang; JU Gui-fang; FU Zheng; ZHANG Guo-li; KONG Li; YANG Yan-qin; MA Yi-dong

    2011-01-01

    Background Carcinoma of unknown primary (CUP) encompasses a heterogeneous group of tumors with varying clinical features. The management of patients of CUP remains a clinical challenge. The purpose of this study was to evaluate the clinical applications of integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) information in patients with CUP,including detecting the occult primary tumor and effecting on disease therapy.Methods One hundred and forty-nine patients with histologically-proven metastases of CUP were included. For all patients,the conventional diagnostic work-up was unsuccessful in localizing the primary site. Whole-body PET/CT images were obtained approximately 60 minutes after intravenous injection of 350-425 MBq of 18F-FDG.Results In 24.8% of patients,FDG PET/CT detected primary tumors that were not apparent after conventional workup.In this group of patients,the overall sensitivity,specificity,and accuracy rates of FDG PET/CT in detecting unknown primary tumors were 86.0%,87.7%,and 87.2%,respectively. FDG PET/CT imaging also led to the detection of previously unrecognized metastases in 29.5% of patients. Forty-seven (31.5%,47 of 149) patients underwent a change in therapeutic management.Conclusions FDG PET/CT is a valuable tool in patients with CUP,because it assisted in detecting unknown primary tumors and previously unrecognized distant metastases,and optimized the mangement of these patients.

  8. Multifocal, chronic osteomyelitis of unknown etiology

    International Nuclear Information System (INIS)

    Kozlowski, K.; Beluffi, G.; Feltham, C.; James, M.; Nespoli, L.; Tamaela, L.; Pavia Univ.; Municipal Hospital, Nelson; Medical School, Jakarta

    1985-01-01

    Four cases of multifocal osteomyelitis of unknown origin in childhood are reported. The variable clinical and radiographic appearances of the disease are illustrated and the diagnostic difficulties in the early stages of the disease are stressed. (orig.) [de

  9. Covalent surface modification of prions: a mass spectrometry-based means of detecting distinctive structural features of prion strains

    Science.gov (United States)

    Prions (PrPSc) are molecular pathogens that are able to convert the isosequential normal cellular prion protein (PrPC) into a prion. The only demonstrated differences between PrPC and PrPSc is conformational, they are isoforms. A given host can be infected by more than one kind or strain of prion. F...

  10. A single footshock causes long-lasting hypoactivity in unknown environments that is dependent on the development of contextual fear conditioning.

    Science.gov (United States)

    Daviu, Núria; Fuentes, Silvia; Nadal, Roser; Armario, Antonio

    2010-09-01

    Exposure to a single session of footshocks induces long-lasting inhibition of activity in unknown environments that markedly differ from the shock context. Interestingly, these effects are not necessarily associated to an enhanced anxiety and interpretation of this hypoactivity remains unclear. In the present experiment we further studied this phenomenon in male Sprague-Dawley rats. In a first experiment, a session of three shocks resulted in hypoactivity during exposure, 6-12days later, to three different unknown environments. This altered behaviour was not accompanied by a greater hypothalamic-pituitary-adrenal (HPA) activation, although greater HPA activation paralleling higher levels of freezing was observed in the shock context. In a second experiment we used a single shock and two procedures, one with pre-exposure to the context before the shock and another with immediate shock that did not induce contextual fear conditioning. Hypoactivity and a certain level of generalization of fear (freezing) to the unknown environments only appeared in the group that developed fear conditioning, but no evidence for enhanced anxiety in the elevated plus-maze was found in any group. The results suggest that if animals are able to associate an aversive experience with a distinct unknown environment, they would display more cautious behaviour in any unknown environment and such strategy persists despite repeated experience with different environments. This long-lasting cautious behaviour was not associated to greater HPA response to the unknown environment that was however observed in the shock context. The present findings raised some concerns about interpretation of long-lasting behavioural changes caused by brief stressors. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Hyperprolactinemia after laparoscopic ovarian drilling: An unknown phenomenon

    Directory of Open Access Journals (Sweden)

    Omrani Gholamhossein R

    2005-08-01

    Full Text Available Abstract Background The effects of ovarian drilling on the serum levels of gonadotropins and androgens have been studied previously. The aim of this study is to evaluate the effects of ovarian drilling on the serum prolactin levels and its relation to ovulation in women with polycystic ovary syndrome. Methods This is a prospective controlled study. Thirty-six women with PCOS underwent ovarian electrocauterization in university hospitals. Control group consisted of 35 ovulatory women with unexplained infertility. Hormonal assessment performed in early follicular phase of spontaneous or induced cycle before operation in the two groups and repeated one week after operation. Hormonal assay was also performed in the early follicular phase of the first post-operative menstruation, folliculometry and progesterone assay were also performed in the same cycle. Data were analyzed by "repeated measurement design, discriminant analysis, correlation coefficient, and Fisher exact test". Results Six to ten weeks after operation the serum mean +/- SD prolactin levels increased from 284.41 +/- 114.32 mIU/ml to 354.06 +/- 204.42 mIU/ml (P = 0.011. The same values for the control group were 277.73 +/- 114.65 to 277.4 +/- 111.4 (P = 0.981 respectively. Approximately 45% of subjects in PCOS group remained anovulatory in spite of decreased level of LH and testosterone. Prolactin level remained elevated in 73.2% of women who did not ovulate 6–10 weeks after the procedure. Conclusion Hyperprolactinemia after ovarian cauterization may be considered as a possible cause of anovulation in women with polycystic ovaries and improved gonadotropin and androgen levels. The cause of hyperprolactinemia is unknown. Hormonal assay particularly PRL in anovulatory patients after ovarian cauterization is recommended.

  12. 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.

  13. Utilizing NMR and EPR spectroscopy to probe the role of copper in prion diseases

    KAUST Repository

    Emwas, Abdul-Hamid M.; Al-Talla, Zeyad; Guo, Xianrong; Al-Ghamdi, Suliman; Al-Masri, Harbi Tomah

    2013-01-01

    Copper is an essential nutrient for the normal development of the brain and nervous system, although the hallmark of several neurological diseases is a change in copper concentrations in the brain and central nervous system. Prion protein (PrP) is a copper-binding, cell-surface glycoprotein that exists in two alternatively folded conformations: a normal isoform (PrPC) and a disease-associated isoform (PrPSc). Prion diseases are a group of lethal neurodegenerative disorders that develop as a result of conformational conversion of PrPC into PrPSc. The pathogenic mechanism that triggers this conformational transformation with the subsequent development of prion diseases remains unclear. It has, however, been shown repeatedly that copper plays a significant functional role in the conformational conversion of prion proteins. In this review, we focus on current research that seeks to clarify the conformational changes associated with prion diseases and the role of copper in this mechanism, with emphasis on the latest applications of NMR and EPR spectroscopy to probe the interactions of copper with prion proteins. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Utilizing NMR and EPR spectroscopy to probe the role of copper in prion diseases

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2013-02-24

    Copper is an essential nutrient for the normal development of the brain and nervous system, although the hallmark of several neurological diseases is a change in copper concentrations in the brain and central nervous system. Prion protein (PrP) is a copper-binding, cell-surface glycoprotein that exists in two alternatively folded conformations: a normal isoform (PrPC) and a disease-associated isoform (PrPSc). Prion diseases are a group of lethal neurodegenerative disorders that develop as a result of conformational conversion of PrPC into PrPSc. The pathogenic mechanism that triggers this conformational transformation with the subsequent development of prion diseases remains unclear. It has, however, been shown repeatedly that copper plays a significant functional role in the conformational conversion of prion proteins. In this review, we focus on current research that seeks to clarify the conformational changes associated with prion diseases and the role of copper in this mechanism, with emphasis on the latest applications of NMR and EPR spectroscopy to probe the interactions of copper with prion proteins. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Comparing the Folds of Prions and Other Pathogenic Amyloids

    Directory of Open Access Journals (Sweden)

    José Miguel Flores-Fernández

    2018-05-01

    Full Text Available Pathogenic amyloids are the main feature of several neurodegenerative disorders, such as Creutzfeldt–Jakob disease, Alzheimer’s disease, and Parkinson’s disease. High resolution structures of tau paired helical filaments (PHFs, amyloid-β(1-42 (Aβ(1-42 fibrils, and α-synuclein fibrils were recently reported using cryo-electron microscopy. A high-resolution structure for the infectious prion protein, PrPSc, is not yet available due to its insolubility and its propensity to aggregate, but cryo-electron microscopy, X-ray fiber diffraction, and other approaches have defined the overall architecture of PrPSc as a 4-rung β-solenoid. Thus, the structure of PrPSc must have a high similarity to that of the fungal prion HET-s, which is part of the fungal heterokaryon incompatibility system and contains a 2-rung β-solenoid. This review compares the structures of tau PHFs, Aβ(1-42, and α-synuclein fibrils, where the β-strands of each molecule stack on top of each other in a parallel in-register arrangement, with the β-solenoid folds of HET-s and PrPSc.

  16. Ubiquitin Ligase gp78 Targets Unglycosylated Prion Protein PrP for Ubiquitylation and Degradation

    OpenAIRE

    Shao, Jia; Choe, Vitnary; Cheng, Haili; Tsai, Yien Che; Weissman, Allan M.; Luo, Shiwen; Rao, Hai

    2014-01-01

    Prion protein PrP is a central player in several devastating neurodegenerative disorders, including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels of PrP are regulated is poorly understood. Human PrP is known to be degraded by the proteasome, but the specific proteolytic pathway responsible for PrP destruction remains elusive. Here, we demonstrate that the ubiquitin ligas...

  17. Quantum jointly assisted cloning of an unknown three-dimensional equatorial state

    Science.gov (United States)

    Ma, Peng-Cheng; Chen, Gui-Bin; Li, Xiao-Wei; Zhan, You-Bang

    2018-02-01

    We present two schemes for perfectly cloning an unknown single-qutrit equatorial state with assistance from two and N state preparers, respectively. In the first scheme, the sender wishes to teleport an unknown single-qutrit equatorial state from two state preparers to a remote receiver, and then to create a perfect copy of the unknown state at her location. The scheme consists of two stages. The first stage of the scheme requires the usual teleportation. In the second stage, to help the sender realize the quantum cloning, two state preparers perform single-qutrit projective measurements on their own qutrits from the sender, then the sender can acquire a perfect copy of the unknown state. It is shown that, only if the two state preparers collaborate with each other, the sender can create a copy of the unknown state by means of some appropriate unitary operations. In the second scheme, we generalized the jointly assisted cloning in the first scheme to the case of N state prepares. In the present schemes, the total probability of success for assisted cloning of a perfect copy of the unknown state can reach 1.

  18. MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.

    Science.gov (United States)

    Moda, Fabio; Suardi, Silvia; Di Fede, Giuseppe; Indaco, Antonio; Limido, Lucia; Vimercati, Chiara; Ruggerone, Margherita; Campagnani, Ilaria; Langeveld, Jan; Terruzzi, Alessandro; Brambilla, Antonio; Zerbi, Pietro; Fociani, Paolo; Bishop, Matthew T; Will, Robert G; Manson, Jean C; Giaccone, Giorgio; Tagliavini, Fabrizio

    2012-09-01

    In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

  19. Iterative Selection of Unknown Weights in Direct Weight Optimization Identification

    Directory of Open Access Journals (Sweden)

    Xiao Xuan

    2014-01-01

    Full Text Available To the direct weight optimization identification of the nonlinear system, we add some linear terms about input sequences in the former linear affine function so as to approximate the nonlinear property. To choose the two classes of unknown weights in the more linear terms, this paper derives the detailed process on how to choose these unknown weights from theoretical analysis and engineering practice, respectively, and makes sure of their key roles between the unknown weights. From the theoretical analysis, the added unknown weights’ auxiliary role can be known in the whole process of approximating the nonlinear system. From the practical analysis, we learn how to transform one complex optimization problem to its corresponding common quadratic program problem. Then, the common quadratic program problem can be solved by the basic interior point method. Finally, the efficiency and possibility of the proposed strategies can be confirmed by the simulation results.

  20. 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.

  1. Remaining useful life prediction of degrading systems subjected to imperfect maintenance: Application to draught fans

    Science.gov (United States)

    Wang, Zhao-Qiang; Hu, Chang-Hua; Si, Xiao-Sheng; Zio, Enrico

    2018-02-01

    Current degradation modeling and remaining useful life prediction studies share a common assumption that the degrading systems are not maintained or maintained perfectly (i.e., to an as-good-as new state). This paper concerns the issues of how to model the degradation process and predict the remaining useful life of degrading systems subjected to imperfect maintenance activities, which can restore the health condition of a degrading system to any degradation level between as-good-as new and as-bad-as old. Toward this end, a nonlinear model driven by Wiener process is first proposed to characterize the degradation trajectory of the degrading system subjected to imperfect maintenance, where negative jumps are incorporated to quantify the influence of imperfect maintenance activities on the system's degradation. Then, the probability density function of the remaining useful life is derived analytically by a space-scale transformation, i.e., transforming the constructed degradation model with negative jumps crossing a constant threshold level to a Wiener process model crossing a random threshold level. To implement the proposed method, unknown parameters in the degradation model are estimated by the maximum likelihood estimation method. Finally, the proposed degradation modeling and remaining useful life prediction method are applied to a practical case of draught fans belonging to a kind of mechanical systems from steel mills. The results reveal that, for a degrading system subjected to imperfect maintenance, our proposed method can obtain more accurate remaining useful life predictions than those of the benchmark model in literature.

  2. Chaos Synchronization Based on Unknown Input Proportional Multiple-Integral Fuzzy Observer

    Directory of Open Access Journals (Sweden)

    T. Youssef

    2013-01-01

    Full Text Available This paper presents an unknown input Proportional Multiple-Integral Observer (PIO for synchronization of chaotic systems based on Takagi-Sugeno (TS fuzzy chaotic models subject to unmeasurable decision variables and unknown input. In a secure communication configuration, this unknown input is regarded as a message encoded in the chaotic system and recovered by the proposed PIO. Both states and outputs of the fuzzy chaotic models are subject to polynomial unknown input with kth derivative zero. Using Lyapunov stability theory, sufficient design conditions for synchronization are proposed. The PIO gains matrices are obtained by resolving linear matrix inequalities (LMIs constraints. Simulation results show through two TS fuzzy chaotic models the validity of the proposed method.

  3. Characterizing unknown systematics in large scale structure surveys

    International Nuclear Information System (INIS)

    Agarwal, Nishant; Ho, Shirley; Myers, Adam D.; Seo, Hee-Jong; Ross, Ashley J.; Bahcall, Neta; Brinkmann, Jonathan; Eisenstein, Daniel J.; Muna, Demitri; Palanque-Delabrouille, Nathalie; Yèche, Christophe; Pâris, Isabelle; Petitjean, Patrick; Schneider, Donald P.; Streblyanska, Alina; Weaver, Benjamin A.

    2014-01-01

    Photometric large scale structure (LSS) surveys probe the largest volumes in the Universe, but are inevitably limited by systematic uncertainties. Imperfect photometric calibration leads to biases in our measurements of the density fields of LSS tracers such as galaxies and quasars, and as a result in cosmological parameter estimation. Earlier studies have proposed using cross-correlations between different redshift slices or cross-correlations between different surveys to reduce the effects of such systematics. In this paper we develop a method to characterize unknown systematics. We demonstrate that while we do not have sufficient information to correct for unknown systematics in the data, we can obtain an estimate of their magnitude. We define a parameter to estimate contamination from unknown systematics using cross-correlations between different redshift slices and propose discarding bins in the angular power spectrum that lie outside a certain contamination tolerance level. We show that this method improves estimates of the bias using simulated data and further apply it to photometric luminous red galaxies in the Sloan Digital Sky Survey as a case study

  4. Characterizing unknown systematics in large scale structure surveys

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Nishant; Ho, Shirley [McWilliams Center for Cosmology, Department of Physics, Carnegie Mellon University, Pittsburgh, PA 15213 (United States); Myers, Adam D. [Department of Physics and Astronomy, University of Wyoming, Laramie, WY 82071 (United States); Seo, Hee-Jong [Berkeley Center for Cosmological Physics, LBL and Department of Physics, University of California, Berkeley, CA 94720 (United States); Ross, Ashley J. [Institute of Cosmology and Gravitation, University of Portsmouth, Portsmouth, PO1 3FX (United Kingdom); Bahcall, Neta [Princeton University Observatory, Peyton Hall, Princeton, NJ 08544 (United States); Brinkmann, Jonathan [Apache Point Observatory, P.O. Box 59, Sunspot, NM 88349 (United States); Eisenstein, Daniel J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States); Muna, Demitri [Department of Astronomy, Ohio State University, Columbus, OH 43210 (United States); Palanque-Delabrouille, Nathalie; Yèche, Christophe [CEA, Centre de Saclay, Irfu/SPP, F-91191 Gif-sur-Yvette (France); Pâris, Isabelle [Departamento de Astronomía, Universidad de Chile, Casilla 36-D, Santiago (Chile); Petitjean, Patrick [Université Paris 6 et CNRS, Institut d' Astrophysique de Paris, 98bis blvd. Arago, 75014 Paris (France); Schneider, Donald P. [Department of Astronomy and Astrophysics, Pennsylvania State University, University Park, PA 16802 (United States); Streblyanska, Alina [Instituto de Astrofisica de Canarias (IAC), E-38200 La Laguna, Tenerife (Spain); Weaver, Benjamin A., E-mail: nishanta@andrew.cmu.edu [Center for Cosmology and Particle Physics, New York University, New York, NY 10003 (United States)

    2014-04-01

    Photometric large scale structure (LSS) surveys probe the largest volumes in the Universe, but are inevitably limited by systematic uncertainties. Imperfect photometric calibration leads to biases in our measurements of the density fields of LSS tracers such as galaxies and quasars, and as a result in cosmological parameter estimation. Earlier studies have proposed using cross-correlations between different redshift slices or cross-correlations between different surveys to reduce the effects of such systematics. In this paper we develop a method to characterize unknown systematics. We demonstrate that while we do not have sufficient information to correct for unknown systematics in the data, we can obtain an estimate of their magnitude. We define a parameter to estimate contamination from unknown systematics using cross-correlations between different redshift slices and propose discarding bins in the angular power spectrum that lie outside a certain contamination tolerance level. We show that this method improves estimates of the bias using simulated data and further apply it to photometric luminous red galaxies in the Sloan Digital Sky Survey as a case study.

  5. A novel class of potential prion drugs: preliminary in vitro and in vivo data for multilayer coated gold nanoparticles.

    Science.gov (United States)

    Ai Tran, Hoang Ngoc; Sousa, Fernanda; Moda, Fabio; Mandal, Subhra; Chanana, Munish; Vimercati, Chiara; Morbin, Michela; Krol, Silke; Tagliavini, Fabrizio; Legname, Giuseppe

    2010-12-01

    Gold nanoparticles coated with oppositely charged polyelectrolytes, such as polyallylamine hydrochloride and polystyrenesulfonate, were examined for potential inhibition of prion protein aggregation and prion (PrPSc) conversion and replication. Different coatings, finishing with a positive or negative layer, were tested, and different numbers of layers were investigated for their ability to interact and reduce the accumulation of PrPSc in scrapie prion infected ScGT1 and ScN2a cells. The particles efficiently hampered the accumulation of PrPSc in ScN2a cells and showed curing effects on ScGT1 cells with a nanoparticle concentration in the picomolar range. Finally, incubation periods of prion-infected mice treated with nanomolar concentrations of gold nanoparticles were significantly longer compared to untreated controls.

  6. Robust Fault Detection for Switched Fuzzy Systems With Unknown Input.

    Science.gov (United States)

    Han, Jian; Zhang, Huaguang; Wang, Yingchun; Sun, Xun

    2017-10-03

    This paper investigates the fault detection problem for a class of switched nonlinear systems in the T-S fuzzy framework. The unknown input is considered in the systems. A novel fault detection unknown input observer design method is proposed. Based on the proposed observer, the unknown input can be removed from the fault detection residual. The weighted H∞ performance level is considered to ensure the robustness. In addition, the weighted H₋ performance level is introduced, which can increase the sensibility of the proposed detection method. To verify the proposed scheme, a numerical simulation example and an electromechanical system simulation example are provided at the end of this paper.

  7. 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.

  8. Off-Policy Actor-Critic Structure for Optimal Control of Unknown Systems With Disturbances.

    Science.gov (United States)

    Song, Ruizhuo; Lewis, Frank L; Wei, Qinglai; Zhang, Huaguang

    2016-05-01

    An optimal control method is developed for unknown continuous-time systems with unknown disturbances in this paper. The integral reinforcement learning (IRL) algorithm is presented to obtain the iterative control. Off-policy learning is used to allow the dynamics to be completely unknown. Neural networks are used to construct critic and action networks. It is shown that if there are unknown disturbances, off-policy IRL may not converge or may be biased. For reducing the influence of unknown disturbances, a disturbances compensation controller is added. It is proven that the weight errors are uniformly ultimately bounded based on Lyapunov techniques. Convergence of the Hamiltonian function is also proven. The simulation study demonstrates the effectiveness of the proposed optimal control method for unknown systems with disturbances.

  9. Treatment-related changes in serum lipids and inflammation: clinical relevance remains unclear. Analyses from the Women's Interagency HIV Study

    Science.gov (United States)

    Parrinello, Christina M; Landay, Alan L; Hodis, Howard N; Gange, Stephen J; Norris, Philip J; Young, Mary; Anastos, Kathryn; Tien, Phyllis C; Xue, Xiaonan; Lazar, Jason; Benning, Lorie; Tracy, Russell P; Kaplan, Robert C

    2014-01-01

    Summary Among 127 HIV-infected women, the magnitude of HDLc increases after HAART initiation predicted the magnitude of concurrent decreases in inflammation biomarkers. After HAART initiation, changes in LDLc and inflammation were unrelated. In the same population, predicted risk of coronary heart disease based upon levels of standard clinical risk factors was similar before and after HAART treatment. Thus, it remains unknown whether short-term treatment-related changes in standard risk factors may appreciably change risk of CVD. PMID:23435295

  10. [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.

  11. 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.

  12. Rapid and Quantitative Assay of Amyloid-Seeding Activity in Human Brains Affected with Prion Diseases.

    Directory of Open Access Journals (Sweden)

    Hanae Takatsuki

    Full Text Available The infectious agents of the transmissible spongiform encephalopathies are composed of amyloidogenic prion protein, PrPSc. Real-time quaking-induced conversion can amplify very small amounts of PrPSc seeds in tissues/body fluids of patients or animals. Using this in vitro PrP-amyloid amplification assay, we quantitated the seeding activity of affected human brains. End-point assay using serially diluted brain homogenates of sporadic Creutzfeldt-Jakob disease patients demonstrated that 50% seeding dose (SD50 is reached approximately 10(10/g brain (values varies 10(8.79-10.63/g. A genetic case (GSS-P102L yielded a similar level of seeding activity in an autopsy brain sample. The range of PrPSc concentrations in the samples, determined by dot-blot assay, was 0.6-5.4 μg/g brain; therefore, we estimated that 1 SD50 unit was equivalent to 0.06-0.27 fg of PrPSc. The SD50 values of the affected brains dropped more than three orders of magnitude after autoclaving at 121°C. This new method for quantitation of human prion activity provides a new way to reduce the risk of iatrogenic prion transmission.

  13. Psychological profile: the problem of modeling the unknown criminal personality

    Directory of Open Access Journals (Sweden)

    Г. М. Гетьман

    2013-10-01

    Full Text Available The article investigates the problem of modeling an unknown person in the preparation of criminal psychological profile. Some approaches to the concept of "psychological profile" and "psychological portrait", in particular the proposed delineation of these terms. We consider the system steps in the development of the psychological profile of an unknown perpetrator.

  14. Multifocal chronic osteomyelitis of unknown etiology

    International Nuclear Information System (INIS)

    Kozlowski, K.; Masel, J.; Harbison, S.; Yu, J.; Royal Brisbane Children Hospital; Regional Hospital Bowral

    1983-01-01

    Five cases of chronic, inflammatory, multifocal bone lesions of unknown etiology are reported. Although bone biopsy confirmed osteomyelitis in each case in none of them were organisms found inspite of an extensive work up. Different clinical course of the disease reflects different aetiology in respective cases. These cases present changing aspects of osteomyelitis emerging since introduction of antibiotics. (orig.)

  15. 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).

  16. Celiac Disease Presenting as Fever of Unknown Origin

    Directory of Open Access Journals (Sweden)

    Megan J. Cooney

    2013-01-01

    Full Text Available Celiac disease (CD is a common autoimmune enteropathy that occurs, in affected individuals, with exposure to gluten in the diet and improves with removal of dietary gluten. Although CD is readily considered in patients with classical presentations of the disease, atypical manifestations may be the only presenting symptoms. We present a case of CD in a 16-year-old female presenting as fever of unknown origin, which has not been reported previously. The postulated mechanism for fever in CD and the importance of clinicians having a low threshold for considering CD in the differential diagnosis of fever of unknown origin and other enigmatic clinical presentations is discussed.

  17. 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.

  18. Removal of transmissible spongiform encephalopathy prion from large volumes of cell culture media supplemented with fetal bovine serum by using hollow fiber anion-exchange membrane chromatography.

    Science.gov (United States)

    Chou, Ming Li; Bailey, Andy; Avory, Tiffany; Tanimoto, Junji; Burnouf, Thierry

    2015-01-01

    Cases of variant Creutzfeldt-Jakob disease in people who had consumed contaminated meat products from cattle with bovine spongiform encephalopathy emphasize the need for measures aimed at preventing the transmission of the pathogenic prion protein (PrPSc) from materials derived from cattle. Highly stringent scrutiny is required for fetal bovine serum (FBS), a growth-medium supplement used in the production of parenteral vaccines and therapeutic recombinant proteins and in the ex vivo expansion of stem cells for transplantation. One such approach is the implementation of manufacturing steps dedicated to removing PrPSc from materials containing FBS. We evaluated the use of the QyuSpeed D (QSD) adsorbent hollow-fiber anion-exchange chromatographic column (Asahi Kasei Medical, Tokyo, Japan) for the removal of PrPSc from cell culture media supplemented with FBS. We first established that QSD filtration had no adverse effect on the chemical composition of various types of culture media supplemented with 10% FBS or the growth and viability characteristics of human embryonic kidney (HEK293) cells, baby hamster kidney (BHK-21) cells, African green monkey kidney (Vero) cells, and Chinese hamster ovary (CHO-k1) cells propagated in the various culture-medium filtrates. We used a 0.6-mL QSD column for removing PrPSc from up to 1000 mL of Dulbecco's modified Eagle's medium containing 10% FBS previously spiked with the 263K strain of hamster-adapted scrapie. The Western blot analysis, validated alongside an infectivity assay, revealed that the level of PrPSc in the initial 200mL flow-through was reduced by 2.5 to > 3 log10, compared with that of the starting material. These results indicate that QSD filtration removes PrPSc from cell culture media containing 10% FBS, and demonstrate the ease with which QSD filtration can be implemented in at industrial-scale to improve the safety of vaccines, therapeutic recombinant proteins, and ex vivo expanded stem cells produced using growth

  19. Quantum key distribution with an unknown and untrusted source

    Science.gov (United States)

    Zhao, Yi; Qi, Bing; Lo, Hoi-Kwong

    2009-03-01

    The security of a standard bi-directional ``plug & play'' quantum key distribution (QKD) system has been an open question for a long time. This is mainly because its source is equivalently controlled by an eavesdropper, which means the source is unknown and untrusted. Qualitative discussion on this subject has been made previously. In this paper, we present the first quantitative security analysis on a general class of QKD protocols whose sources are unknown and untrusted. The securities of standard BB84 protocol, weak+vacuum decoy state protocol, and one-decoy decoy state protocol, with unknown and untrusted sources are rigorously proved. We derive rigorous lower bounds to the secure key generation rates of the above three protocols. Our numerical simulation results show that QKD with an untrusted source gives a key generation rate that is close to that with a trusted source. Our work is published in [1]. [4pt] [1] Y. Zhao, B. Qi, and H.-K. Lo, Phys. Rev. A, 77:052327 (2008).

  20. 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 ...... and comparing vision-based grasping methods, and the creation of algorithms for bootstrapping a process of acquiring world understanding for artificial cognitive agents....... 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...... of the thesis are: the extension of the Early Cognitive Vision representation with a new type of feature hierarchy in the texture domain, the definition and evaluation of contour based grasping methods, the definition and evaluation of surface based grasping methods, the definition of a benchmark for testing...

  1. 18F-FDG-PET/CT in fever of unknown origin

    DEFF Research Database (Denmark)

    Middelbo Buch-Olsen, Karen; Andersen, Rikke V; Hess, Søren

    2014-01-01

    OBJECTIVE: Fever of unknown origin continues to be a diagnostic challenge for clinicians. The aim of this study was to confirm whether (18)F-fluorodeoxyglucose ((18)F-FDG)-PET/computed tomography (CT) is a helpful tool in patients suffering from this condition. PATIENTS AND METHODS: Fifty......-seven patients with fever of unknown origin were examined with (18)F-FDG-PET/CT as part of their diagnostic workup at the clinicians' discretion. The medical records were read retrospectively to establish the final diagnosis and evaluate the degree to which PET/CT contributed to the diagnosis. RESULTS......-FDG-PET/CT is a useful tool in the investigation of fever of unknown origin; it can reduce patient inconvenience and possibly costs to society if used earlier in the diagnostic process....

  2. Scheme for teleportation of unknown states of trapped ion

    Institute of Scientific and Technical Information of China (English)

    Chen Mei-Feng; Ma Song-She

    2008-01-01

    A scheme is presented for teleporting an unknown state in a trapped ion system.The scheme only requires a single laser beam.It allows the trap to be in any state with a few phonons,e.g.a thermal motion.Furthermore,it works in the regime,where the Rabi frequency of the laser is on the order of the trap frequency.Thus,the teleportation speed is greatly increased,which is important for decreasing the decoherence effect.This idea can also be used to teleport an unknown ionic entangled state.

  3. Prevalence and Impact of Unknown Diabetes in the ICU.

    Science.gov (United States)

    Carpenter, David L; Gregg, Sara R; Xu, Kejun; Buchman, Timothy G; Coopersmith, Craig M

    2015-12-01

    Many patients with diabetes and their care providers are unaware of the presence of the disease. Dysglycemia encompassing hyperglycemia, hypoglycemia, and glucose variability is common in the ICU in patients with and without diabetes. The purpose of this study was to determine the impact of unknown diabetes on glycemic control in the ICU. Prospective observational study. Nine ICUs in an academic, tertiary hospital and a hybrid academic/community hospital. Hemoglobin A1c levels were ordered at all ICU admissions from March 1, 2011 to September 30, 2013. Electronic medical records were examined for a history of antihyperglycemic medications or International Classification of Diseases, 9th Edition diagnosis of diabetes. Patients were categorized as having unknown diabetes (hemoglobin A1c > 6.5%, without history of diabetes), no diabetes (hemoglobin A1c 6.5%, with documented history of diabetes). None. A total of 15,737 patients had an hemoglobin A1c and medical record evaluable for the history of diabetes, and 5,635 patients had diabetes diagnosed by either medical history or an elevated hemoglobin A1c in the ICU. Of these, 1,460 patients had unknown diabetes, accounting for 26.0% of all patients with diabetes. This represented 41.0% of patients with an hemoglobin A1c > 6.5% and 9.3% of all ICU patients. Compared with patients without diabetes, patients with unknown diabetes had a higher likelihood of requiring an insulin infusion (44.3% vs 29.3%; p 180 mg/dL; p < 0.0001) and hypoglycemia (8.9% vs 2.5%; blood glucose < 70 mg/dL; p < 0.0001), higher glycemic variability (55.6 vs 28.8, average of patient SD of glucose; p < 0.0001), and increased mortality (13.8% vs 11.4%; p = 0.01). Patients with unknown diabetes represent a significant percentage of ICU admissions. Measurement of hemoglobin A1c at admission can prospectively identify a population that are not known to have diabetes but have significant challenges in glycemic control in the ICU.

  4. Decentralised output feedback control of Markovian jump interconnected systems with unknown interconnections

    Science.gov (United States)

    Li, Li-Wei; Yang, Guang-Hong

    2017-07-01

    The problem of decentralised output feedback control is addressed for Markovian jump interconnected systems with unknown interconnections and general transition rates (TRs) allowed to be unknown or known with uncertainties. A class of decentralised dynamic output feedback controllers are constructed, and a cyclic-small-gain condition is exploited to dispose the unknown interconnections so that the resultant closed-loop system is stochastically stable and satisfies an H∞ performance. With slack matrices to cope with the nonlinearities incurred by unknown and uncertain TRs in control synthesis, a novel controller design condition is developed in linear matrix inequality formalism. Compared with the existing works, the proposed approach leads to less conservatism. Finally, two examples are used to illustrate the effectiveness of the new results.

  5. 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.

  6. Autonomous Flight in Unknown Indoor Environments

    OpenAIRE

    Bachrach, Abraham Galton; He, Ruijie; Roy, Nicholas

    2009-01-01

    This paper presents our solution for enabling a quadrotor helicopter, equipped with a laser rangefinder sensor, to autonomously explore and map unstructured and unknown indoor environments. While these capabilities are already commodities on ground vehicles, air vehicles seeking the same performance face unique challenges. In this paper, we describe the difficulties in achieving fully autonomous helicopter flight, highlighting the differences between ground and helicopter robots that make it ...

  7. The POM monoclonals: a comprehensive set of antibodies to non-overlapping prion protein epitopes.

    Directory of Open Access Journals (Sweden)

    Magdalini Polymenidou

    Full Text Available PrP(Sc, a misfolded and aggregated form of the cellular prion protein PrP(C, is the only defined constituent of the transmissible agent causing prion diseases. Expression of PrP(C in the host organism is necessary for prion replication and for prion neurotoxicity. Understanding prion diseases necessitates detailed structural insights into PrP(C and PrP(Sc. Towards this goal, we have developed a comprehensive collection of monoclonal antibodies denoted POM1 to POM19 and directed against many different epitopes of mouse PrP(C. Three epitopes are located within the N-terminal octarepeat region, one is situated within the central unstructured region, and four epitopes are discontinuous within the globular C-proximal domain of PrP(C. Some of these antibodies recognize epitopes that are resilient to protease digestion in PrP(Sc. Other antibodies immunoprecipitate PrP(C, but not PrP(Sc. A third group was found to immunoprecipitate both PrP isoforms. Some of the latter antibodies could be blocked with epitope-mimicking peptides, and incubation with an excess of these peptides allowed for immunochromatography of PrP(C and PrP(Sc. Amino-proximal antibodies were found to react with repetitive PrP(C epitopes, thereby vastly increasing their avidity. We have also created functional single-chain miniantibodies from selected POMs, which retained the binding characteristics despite their low molecular mass. The POM collection, thus, represents a unique set of reagents allowing for studies with a variety of techniques, including western blotting, ELISA, immunoprecipitation, conformation-dependent immunoassays, and plasmon surface plasmon resonance-based assays.

  8. Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Simon, Stéphanie; Lugan, Séverine; Bilheude, Jean-Marc; Perret-Liaudet, Armand; Ironside, James W.; Haik, Stéphane; Basset-Leobon, Christelle; Lacroux, Caroline; Peoch', Katell; Streichenberger, Nathalie; Langeveld, Jan; Head, Mark W.; Grassi, Jacques; Hauw, Jean-Jacques; Schelcher, Francois; Delisle, Marie Bernadette; Andréoletti, Olivier

    2008-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability. PMID:18389084

  9. Oxidation of Helix-3 methionines precedes the formation of PK resistant PrP.

    Directory of Open Access Journals (Sweden)

    Tamar Canello

    2010-07-01

    Full Text Available While elucidating the peculiar epitope of the alpha-PrP mAb IPC2, we found that PrPSc exhibits the sulfoxidation of residue M213 as a covalent signature. Subsequent computational analysis predicted that the presence of sulfoxide groups at both Met residues 206 and 213 destabilize the alpha-fold, suggesting oxidation may facilitate the conversion of PrPC into PrPSc. To further study the effect of oxidation on prion formation, we generated pAbs to linear PrP peptides encompassing the Helix-3 region, as opposed to the non-linear complexed epitope of IPC2. We now show that pAbs, whose epitopes comprise Met residues, readily detected PrPC, but could not recognize most PrPSc bands unless they were vigorously reduced. Next, we showed that the alpha-Met pAbs did not recognize newly formed PrPSc, as is the case for the PK resistant PrP present in lines of prion infected cells. In addition, these reagents did not detect intermediate forms such as PK sensitive and partially aggregated PrPs present in infected brains. Finally, we show that PrP molecules harboring the pathogenic mutation E200K, which is linked to the most common form of familial CJD, may be spontaneously oxidized. We conclude that the oxidation of methionine residues in Helix-3 represents an early and important event in the conversion of PrPC to PrPSc. We believe that further investigation into the mechanism and role of PrP oxidation will be central in finally elucidating the mechanism by which a normal cell protein converts into a pathogenic entity that causes fatal brain degeneration.

  10. Value of Bone marrow Examination in Pyrexia of unknown origin

    Directory of Open Access Journals (Sweden)

    A Jha

    2013-10-01

    Full Text Available Background: Pyrexia of unknown origin is a common diagnostic dilemma. Series of diagnostic modalities are required to arrive at diagnosis. Bone marrow examination is one of the common tests implicated in the diagnosis in combination with other diagnostic modalities. Present study has attempted to explore the causes of pyrexia of unknown origin based on bone marrow morphological study. Materials and Methods: In a one year prospective study conducted at Manipal Teaching Hospital, Pokhara, Nepal; bone marrow aspiration and biopsy was performed and evaluated morphologically, in 57 patients fulfilling the criteria of classic pyrexia of unknown origin. Results: In 42% cases; specific diagnosis could be made and hematological neoplasm was the most common finding followed by megaloblastic anemia, hypoplastic anemia and one case each of hemophagocytosis, malaria and tuberculosis. Acute leukemia was the most frequently encountered hematological malignancy followed by multiple myeloma, chronic myeloid leukemia, essential thrombocythemia and myelodysplastic syndrome. Conclusion: Morphological examination of bone marrow has important role in diagnosis of pyrexia of unknown origin. However, yield of diagnosis can be increased if it is combined with other diagnostic modalities including radiological, microbiological and serological tests. DOI: http://dx.doi.org/10.3126/jpn.v3i6.8991 Journal of Pathology of Nepal (2013 Vol. 3, 447-451

  11. Carnivoran remains from the Malapa hominin site, South Africa.

    Directory of Open Access Journals (Sweden)

    Brian F Kuhn

    Full Text Available Recent discoveries at the new hominin-bearing deposits of Malapa, South Africa, have yielded a rich faunal assemblage associated with the newly described hominin taxon Australopithecus sediba. Dating of this deposit using U-Pb and palaeomagnetic methods has provided an age of 1.977 Ma, being one of the most accurately dated, time constrained deposits in the Plio-Pleistocene of southern Africa. To date, 81 carnivoran specimens have been identified at this site including members of the families Canidae, Viverridae, Herpestidae, Hyaenidae and Felidae. Of note is the presence of the extinct taxon Dinofelis cf. D. barlowi that may represent the last appearance date for this species. Extant large carnivores are represented by specimens of leopard (Panthera pardus and brown hyaena (Parahyaena brunnea. Smaller carnivores are also represented, and include the genera Atilax and Genetta, as well as Vulpes cf. V. chama. Malapa may also represent the first appearance date for Felis nigripes (Black-footed cat. The geochronological age of Malapa and the associated hominin taxa and carnivoran remains provide a window of research into mammalian evolution during a relatively unknown period in South Africa and elsewhere. In particular, the fauna represented at Malapa has the potential to elucidate aspects of the evolution of Dinofelis and may help resolve competing hypotheses about faunal exchange between East and Southern Africa during the late Pliocene or early Pleistocene.

  12. 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.

  13. Elimination of some unknown parameters and its effect on outlier detection

    Directory of Open Access Journals (Sweden)

    Serif Hekimoglu

    Full Text Available Outliers in observation set badly affect all the estimated unknown parameters and residuals, that is because outlier detection has a great importance for reliable estimation results. Tests for outliers (e.g. Baarda's and Pope's tests are frequently used to detect outliers in geodetic applications. In order to reduce the computational time, sometimes elimination of some unknown parameters, which are not of interest, is performed. In this case, although the estimated unknown parameters and residuals do not change, the cofactor matrix of the residuals and the redundancies of the observations change. In this study, the effects of the elimination of the unknown parameters on tests for outliers have been investigated. We have proved that the redundancies in initial functional model (IFM are smaller than the ones in reduced functional model (RFM where elimination is performed. To show this situation, a horizontal control network was simulated and then many experiences were performed. According to simulation results, tests for outlier in IFM are more reliable than the ones in RFM.

  14. 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.

  15. Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein.

    Science.gov (United States)

    Asante, Emmanuel A; Linehan, Jacqueline M; Smidak, Michelle; Tomlinson, Andrew; Grimshaw, Andrew; Jeelani, Asif; Jakubcova, Tatiana; Hamdan, Shyma; Powell, Caroline; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

    2013-01-01

    Prions are infectious agents causing fatal neurodegenerative diseases of humans and animals. In humans, these have sporadic, acquired and inherited aetiologies. The inherited prion diseases are caused by one of over 30 coding mutations in the human prion protein (PrP) gene (PRNP) and many of these generate infectious prions as evidenced by their experimental transmissibility by inoculation to laboratory animals. However, some, and in particular an extensively studied type of Gerstmann-Sträussler-Scheinker syndrome (GSS) caused by a PRNP A117V mutation, are thought not to generate infectious prions and instead constitute prion proteinopathies with a quite distinct pathogenetic mechanism. Multiple attempts to transmit A117V GSS have been unsuccessful and typical protease-resistant PrP (PrP(Sc)), pathognomonic of prion disease, is not detected in brain. Pathogenesis is instead attributed to production of an aberrant topological form of PrP, C-terminal transmembrane PrP ((Ctm)PrP). Barriers to transmission of prion strains from one species to another appear to relate to structural compatibility of PrP in host and inoculum and we have therefore produced transgenic mice expressing human 117V PrP. We found that brain tissue from GSS A117V patients did transmit disease to these mice and both the neuropathological features of prion disease and presence of PrP(Sc) was demonstrated in the brains of recipient transgenic mice. This PrP(Sc) rapidly degraded during laboratory analysis, suggesting that the difficulty in its detection in patients with GSS A117V could relate to post-mortem proteolysis. We conclude that GSS A117V is indeed a prion disease although the relative contributions of (Ctm)PrP and prion propagation in neurodegeneration and their pathogenetic interaction remains to be established.

  16. Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein.

    Directory of Open Access Journals (Sweden)

    Emmanuel A Asante

    Full Text Available Prions are infectious agents causing fatal neurodegenerative diseases of humans and animals. In humans, these have sporadic, acquired and inherited aetiologies. The inherited prion diseases are caused by one of over 30 coding mutations in the human prion protein (PrP gene (PRNP and many of these generate infectious prions as evidenced by their experimental transmissibility by inoculation to laboratory animals. However, some, and in particular an extensively studied type of Gerstmann-Sträussler-Scheinker syndrome (GSS caused by a PRNP A117V mutation, are thought not to generate infectious prions and instead constitute prion proteinopathies with a quite distinct pathogenetic mechanism. Multiple attempts to transmit A117V GSS have been unsuccessful and typical protease-resistant PrP (PrP(Sc, pathognomonic of prion disease, is not detected in brain. Pathogenesis is instead attributed to production of an aberrant topological form of PrP, C-terminal transmembrane PrP ((CtmPrP. Barriers to transmission of prion strains from one species to another appear to relate to structural compatibility of PrP in host and inoculum and we have therefore produced transgenic mice expressing human 117V PrP. We found that brain tissue from GSS A117V patients did transmit disease to these mice and both the neuropathological features of prion disease and presence of PrP(Sc was demonstrated in the brains of recipient transgenic mice. This PrP(Sc rapidly degraded during laboratory analysis, suggesting that the difficulty in its detection in patients with GSS A117V could relate to post-mortem proteolysis. We conclude that GSS A117V is indeed a prion disease although the relative contributions of (CtmPrP and prion propagation in neurodegeneration and their pathogenetic interaction remains to be established.

  17. Rendezvous with connectivity preservation for multi-robot systems with an unknown leader

    Science.gov (United States)

    Dong, Yi

    2018-02-01

    This paper studies the leader-following rendezvous problem with connectivity preservation for multi-agent systems composed of uncertain multi-robot systems subject to external disturbances and an unknown leader, both of which are generated by a so-called exosystem with parametric uncertainty. By combining internal model design, potential function technique and adaptive control, two distributed control strategies are proposed to maintain the connectivity of the communication network, to achieve the asymptotic tracking of all the followers to the output of the unknown leader system, as well as to reject unknown external disturbances. It is also worth to mention that the uncertain parameters in the multi-robot systems and exosystem are further allowed to belong to unknown and unbounded sets when applying the second fully distributed control law containing a dynamic gain inspired by high-gain adaptive control or self-tuning regulator.

  18. Lod score curves for phase-unknown matings.

    Science.gov (United States)

    Hulbert-Shearon, T; Boehnke, M; Lange, K

    1996-01-01

    For a phase-unknown nuclear family, we show that the likelihood and lod score are unimodal, and we describe conditions under which the maximum occurs at recombination fraction theta = 0, theta = 1/2, and 0 < theta < 1/2. These simply stated necessary and sufficient conditions seem to have escaped the notice of previous statistical geneticists.

  19. Adaptive Incentive Controls for Stackelberg Games with Unknown Cost Functionals.

    Science.gov (United States)

    1984-01-01

    APR EZT:: F I AN 73S e OsL:-: UNCLASSI?:-- Q4~.’~- .A.., 6, *~*i i~~*~~*.- U ADAPTIVE INCENTIVE CONTROLS FOR STACKELBERG GAMES WITH UNKNOWN COST...AD-A161 885 ADAPTIVE INCENTIVE CONTROLS FOR STACKELBERG GAMES WITH i/1 UNKNOWN COST FUNCTIONALSCU) ILLINOIS UNIV AT URBANA DECISION AND CONTROL LAB T...ORGANIZATION 6b. OFFICE SYMBOL 7.. NAME OF MONITORING ORGANIZATION CoriaeLcenef~pda~ Joint Services Electronics Program Laboratory, Univ. of Illinois N/A

  20. M-MRAC Backstepping for Systems with Unknown Virtual Control Coefficients

    Science.gov (United States)

    Stepanyan, Vahram; Krishnakumar, Kalmanje

    2015-01-01

    The paper presents an over-parametrization free certainty equivalence state feedback backstepping adaptive control design method for systems of any relative degree with unmatched uncertainties and unknown virtual control coefficients. It uses a fast prediction model to estimate the unknown parameters, which is independent of the control design. It is shown that the system's input and output tracking errors can be systematically decreased by the proper choice of the design parameters. The benefits of the approach are demonstrated in numerical simulations.

  1. Speeding up transmissions of unknown quantum information along Ising-type quantum channels

    International Nuclear Information System (INIS)

    Guo W J; Wei L F

    2017-01-01

    Quantum teleportation with entanglement channels and a series of two-qubit SWAP gates between the nearest-neighbor qubits are usually utilized to achieve the transfers of unknown quantum state from the sender to the distant receiver. In this paper, by simplifying the usual SWAP gates we propose an approach to speed up the transmissions of unknown quantum information, specifically including the single-qubit unknown state and two-qubit unknown entangled ones, by a series of entangling and disentangling operations between the remote qubits with distant interactions. The generic proposal is demonstrated specifically with experimentally-existing Ising-type quantum channels without transverse interaction; liquid NMR-molecules driven by global radio frequency electromagnetic pulses and capacitively-coupled Josephson circuits driven by local microwave pulses. The proposal should be particularly useful to set up the connections between the distant qubits in a chip of quantum computing. (paper)

  2. 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.

  3. Identification of fractional-order systems with unknown initial values and structure

    Energy Technology Data Exchange (ETDEWEB)

    Du, Wei, E-mail: duwei0203@gmail.com [Key Laboratory of Advanced Control and Optimization for Chemical Processes, Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Miao, Qingying, E-mail: qymiao@sjtu.edu.cn [School of Continuing Education, Shanghai Jiao Tong University, Shanghai 200030 (China); Tong, Le, E-mail: tongle0328@gmail.com [Faculty of Applied Science and Textiles, The Hong Kong Polytechnic University, Hong Kong (China); Tang, Yang [Key Laboratory of Advanced Control and Optimization for Chemical Processes, Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China)

    2017-06-21

    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. - Highlights: • Unknown initial values and structure are introduced in the identification of fractional-order chaotic systems; • Only a series of output is utilized in the identification of fractional-order chaotic systems; • CoDE is used for the identification problem and the results are satisfactory when compared with other DE variants.

  4. Sialic Acid on the Glycosylphosphatidylinositol Anchor Regulates PrP-mediated Cell Signaling and Prion Formation.

    Science.gov (United States)

    Bate, Clive; Nolan, William; Williams, Alun

    2016-01-01

    The prion diseases occur following the conversion of the cellular prion protein (PrP(C)) into disease-related isoforms (PrP(Sc)). In this study, the role of the glycosylphosphatidylinositol (GPI) anchor attached to PrP(C) in prion formation was examined using a cell painting technique. PrP(Sc) formation in two prion-infected neuronal cell lines (ScGT1 and ScN2a cells) and in scrapie-infected primary cortical neurons was increased following the introduction of PrP(C). In contrast, PrP(C) containing a GPI anchor from which the sialic acid had been removed (desialylated PrP(C)) was not converted to PrP(Sc). Furthermore, the presence of desialylated PrP(C) inhibited the production of PrP(Sc) within prion-infected cortical neurons and ScGT1 and ScN2a cells. The membrane rafts surrounding desialylated PrP(C) contained greater amounts of sialylated gangliosides and cholesterol than membrane rafts surrounding PrP(C). Desialylated PrP(C) was less sensitive to cholesterol depletion than PrP(C) and was not released from cells by treatment with glimepiride. The presence of desialylated PrP(C) in neurons caused the dissociation of cytoplasmic phospholipase A2 from PrP-containing membrane rafts and reduced the activation of cytoplasmic phospholipase A2. These findings show that the sialic acid moiety of the GPI attached to PrP(C) modifies local membrane microenvironments that are important in PrP-mediated cell signaling and PrP(Sc) formation. These results suggest that pharmacological modification of GPI glycosylation might constitute a novel therapeutic approach to prion diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Protease resistance of infectious prions is suppressed by removal of a single atom in the cellular prion protein.

    Science.gov (United States)

    Leske, Henning; Hornemann, Simone; Herrmann, Uli Simon; Zhu, Caihong; Dametto, Paolo; Li, Bei; Laferriere, Florent; Polymenidou, Magdalini; Pelczar, Pawel; Reimann, Regina Rose; Schwarz, Petra; Rushing, Elisabeth Jane; Wüthrich, Kurt; Aguzzi, Adriano

    2017-01-01

    Resistance to proteolytic digestion has long been considered a defining trait of prions in tissues of organisms suffering from transmissible spongiform encephalopathies. Detection of proteinase K-resistant prion protein (PrPSc) still represents the diagnostic gold standard for prion diseases in humans, sheep and cattle. However, it has become increasingly apparent that the accumulation of PrPSc does not always accompany prion infections: high titers of prion infectivity can be reached also in the absence of protease resistant PrPSc. Here, we describe a structural basis for the phenomenon of protease-sensitive prion infectivity. We studied the effect on proteinase K (PK) resistance of the amino acid substitution Y169F, which removes a single oxygen atom from the β2-α2 loop of the cellular prion protein (PrPC). When infected with RML or the 263K strain of prions, transgenic mice lacking wild-type (wt) PrPC but expressing MoPrP169F generated prion infectivity at levels comparable to wt mice. The newly generated MoPrP169F prions were biologically indistinguishable from those recovered from prion-infected wt mice, and elicited similar pathologies in vivo. Surprisingly, MoPrP169F prions showed greatly reduced PK resistance and density gradient analyses showed a significant reduction in high-density aggregates. Passage of MoPrP169F prions into mice expressing wt MoPrP led to full recovery of protease resistance, indicating that no strain shift had taken place. We conclude that a subtle structural variation in the β2-α2 loop of PrPC affects the sensitivity of PrPSc to protease but does not impact prion replication and infectivity. With these findings a specific structural feature of PrPC can be linked to a physicochemical property of the corresponding PrPSc.

  6. Multidimensional procurement auctions with unknown weights

    DEFF Research Database (Denmark)

    Greve, Thomas

    This paper studies the consequences of holding a procurement auction when the principal chooses not to show its preferences. My paper extends the procurement auction model of Che (1993) to a situation where both the principal and the agents have private information. Thus, unknown parameters of bo...... 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....

  7. Clostridium difficile: A healthcare-associated infection of unknown ...

    African Journals Online (AJOL)

    Clostridium difficile: A healthcare-associated infection of unknown significance in adults in sub-Saharan Africa. ... Abstract. Background: Clostridium difficile infection (CDI) causes a high burden of disease in high-resource healthcare systems, with significant morbidity, mortality, and financial implications. CDI is a ...

  8. 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.

  9. 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.

  10. Vision-based autonomous grasping of unknown piled objects

    International Nuclear Information System (INIS)

    Johnson, R.K.

    1994-01-01

    Computer vision techniques have been used to develop a vision-based grasping capability for autonomously picking and placing unknown piled objects. This work is currently being applied to the problem of hazardous waste sorting in support of the Department of Energy's Mixed Waste Operations Program

  11. 48 CFR 52.222-49 - Service Contract Act-Place of Performance Unknown.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Service Contract Act-Place... Provisions and Clauses 52.222-49 Service Contract Act—Place of Performance Unknown. As prescribed in 22.1006(f), insert the following clause: Service Contract Act—Place of Performance Unknown (MAY 1989) (a...

  12. Carcinoma of Unknown Primary Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Carcinoma of unknown primary (CUP), treatment can include surgery, radiation therapy, chemotherapy, or hormone therapy. Get detailed information about the diagnosis and treatment of CUP in this expert-reviewed summary.

  13. 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).

  14. Atmospheric turbulence profiling with unknown power spectral density

    Science.gov (United States)

    Helin, Tapio; Kindermann, Stefan; Lehtonen, Jonatan; Ramlau, Ronny

    2018-04-01

    Adaptive optics (AO) is a technology in modern ground-based optical telescopes to compensate for the wavefront distortions caused by atmospheric turbulence. One method that allows to retrieve information about the atmosphere from telescope data is so-called SLODAR, where the atmospheric turbulence profile is estimated based on correlation data of Shack-Hartmann wavefront measurements. This approach relies on a layered Kolmogorov turbulence model. In this article, we propose a novel extension of the SLODAR concept by including a general non-Kolmogorov turbulence layer close to the ground with an unknown power spectral density. We prove that the joint estimation problem of the turbulence profile above ground simultaneously with the unknown power spectral density at the ground is ill-posed and propose three numerical reconstruction methods. We demonstrate by numerical simulations that our methods lead to substantial improvements in the turbulence profile reconstruction compared to the standard SLODAR-type approach. Also, our methods can accurately locate local perturbations in non-Kolmogorov power spectral densities.

  15. A Neuronal Culture System to Detect Prion Synaptotoxicity.

    Directory of Open Access Journals (Sweden)

    Cheng Fang

    2016-05-01

    Full Text Available Synaptic pathology is an early feature of prion as well as other neurodegenerative diseases. Although the self-templating process by which prions propagate is well established, the mechanisms by which prions cause synaptotoxicity are poorly understood, due largely to the absence of experimentally tractable cell culture models. Here, we report that exposure of cultured hippocampal neurons to PrPSc, the infectious isoform of the prion protein, results in rapid retraction of dendritic spines. This effect is entirely dependent on expression of the cellular prion protein, PrPC, by target neurons, and on the presence of a nine-amino acid, polybasic region at the N-terminus of the PrPC molecule. Both protease-resistant and protease-sensitive forms of PrPSc cause dendritic loss. This system provides new insights into the mechanisms responsible for prion neurotoxicity, and it provides a platform for characterizing different pathogenic forms of PrPSc and testing potential therapeutic agents.

  16. Grass Plants Bind, Retain, Uptake, and Transport Infectious Prions

    Directory of Open Access Journals (Sweden)

    Sandra Pritzkow

    2015-05-01

    Full Text Available Prions are the protein-based infectious agents responsible for prion diseases. Environmental prion contamination has been implicated in disease transmission. Here, we analyzed the binding and retention of infectious prion protein (PrPSc to plants. Small quantities of PrPSc contained in diluted brain homogenate or in excretory materials (urine and feces can bind to wheat grass roots and leaves. Wild-type hamsters were efficiently infected by ingestion of prion-contaminated plants. The prion-plant interaction occurs with prions from diverse origins, including chronic wasting disease. Furthermore, leaves contaminated by spraying with a prion-containing preparation retained PrPSc for several weeks in the living plant. Finally, plants can uptake prions from contaminated soil and transport them to aerial parts of the plant (stem and leaves. These findings demonstrate that plants can efficiently bind infectious prions and act as carriers of infectivity, suggesting a possible role of environmental prion contamination in the horizontal transmission of the disease.

  17. Bidirectional ventricular tachycardia of unknown etiology

    International Nuclear Information System (INIS)

    Ali, M.; Khan, J.A.; Masood, T.; Shamsi, F.; Dero, M.H.; Khan, S.

    2013-01-01

    A 45 years old male presented to the emergency department with palpitations, headache and apprehension. His electrocardiogram revealed bidirectional ventricular tachycardia. He remained vitally stable and responded to intravenous beta-blocker. Initially digitalis toxicity was suspected but history was negative for digitalis intake. The cause remained unidentified in patient despite detailed investigations. During a short follow-up (of 6 months) he remained asymptomatic and no cause was further identified during this period. Some other unseen causes of bidirectional ventricular tachycardia need to be explored. (author)

  18. [PALEOPATHOLOGY OF HUMAN REMAINS].

    Science.gov (United States)

    Minozzi, Simona; Fornaciari, Gino

    2015-01-01

    Many diseases induce alterations in the human skeleton, leaving traces of their presence in ancient remains. Paleopathological examination of human remains not only allows the study of the history and evolution of the disease, but also the reconstruction of health conditions in the past populations. This paper describes the most interesting diseases observed in skeletal samples from the Roman Imperial Age necropoles found in urban and suburban areas of Rome during archaeological excavations in the last decades. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumours, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, the palaeopathological study allowed to highlight the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.

  19. 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.

  20. The Effect of Known-and-Unknown Word Combinations on Intentional Vocabulary Learning

    Science.gov (United States)

    Kasahara, Kiwamu

    2011-01-01

    The purpose of this study is to examine whether learning a known-and-unknown word combination is superior in terms of retention and retrieval of meaning to learning a single unknown word. The term "combination" in this study means a two-word collocation of a familiar word and a word that is new to the participants. Following the results of…

  1. High Precision Fast Projective Synchronization for Chaotic Systems with Unknown Parameters

    Science.gov (United States)

    Nian, Fuzhong; Wang, Xingyuan; Lin, Da; Niu, Yujun

    2013-08-01

    A high precision fast projective synchronization method for chaotic systems with unknown parameters was proposed by introducing optimal matrix. Numerical simulations indicate that the precision be improved about three orders compared with other common methods under the same condition of software and hardware. Moreover, when average error is less than 10-3, the synchronization speed is 6500 times than common methods, the iteration needs only 4 times. The unknown parameters also were identified rapidly. The theoretical analysis and proof also were given.

  2. 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.

  3. Unknown quantum states: The quantum de Finetti representation

    International Nuclear Information System (INIS)

    Caves, Carlton M.; Fuchs, Christopher A.; Schack, Ruediger

    2002-01-01

    We present an elementary proof of the quantum de Finetti representation theorem, a quantum analog of de Finetti's classical theorem on exchangeable probability assignments. This contrasts with the original proof of Hudson and Moody [Z. Wahrschein. verw. Geb. 33, 343 (1976)], which relies on advanced mathematics and does not share the same potential for generalization. The classical de Finetti theorem provides an operational definition of the concept of an unknown probability in Bayesian probability theory, where probabilities are taken to be degrees of belief instead of objective states of nature. The quantum de Finetti theorem, in a closely analogous fashion, deals with exchangeable density-operator assignments and provides an operational definition of the concept of an ''unknown quantum state'' in quantum-state tomography. This result is especially important for information-based interpretations of quantum mechanics, where quantum states, like probabilities, are taken to be states of knowledge rather than states of nature. We further demonstrate that the theorem fails for real Hilbert spaces and discuss the significance of this point

  4. Plasminogen stimulates propagation of protease-resistant prion protein in vitro.

    Science.gov (United States)

    Mays, Charles E; Ryou, Chongsuk

    2010-12-01

    To clarify the role of plasminogen as a cofactor for prion propagation, we conducted functional assays using a cell-free prion protein (PrP) conversion assay termed protein misfolding cyclic amplification (PMCA) and prion-infected cell lines. Here, we report that plasminogen stimulates propagation of the protease-resistant scrapie PrP (PrP(Sc)). Compared to control PMCA conducted without plasminogen, addition of plasminogen in PMCA using wild-type brain material significantly increased PrP conversion, with an EC(50) = ∼56 nM. PrP conversion in PMCA was substantially less efficient with plasminogen-deficient brain material than with wild-type material. The activity stimulating PrP conversion was specific for plasminogen and conserved in its kringle domains. Such activity was abrogated by modification of plasminogen structure and interference of PrP-plasminogen interaction. Kinetic analysis of PrP(Sc) generation demonstrated that the presence of plasminogen in PMCA enhanced the PrP(Sc) production rate to ∼0.97 U/μl/h and reduced turnover time to ∼1 h compared to those (∼0.4 U/μl/h and ∼2.5 h) obtained without supplementation. Furthermore, as observed in PMCA, plasminogen and kringles promoted PrP(Sc) propagation in ScN2a and Elk 21(+) cells. Our results demonstrate that plasminogen functions in stimulating conversion processes and represents the first cellular protein cofactor that enhances the hypothetical mechanism of prion propagation.

  5. Enzymatic formulation capable of degrading scrapie prion under mild digestion conditions.

    Directory of Open Access Journals (Sweden)

    Emeka A Okoroma

    Full Text Available The prion agent is notoriously resistant to common proteases and conventional sterilisation procedures. The current methods known to destroy prion infectivity such as incineration, alkaline and thermal hydrolysis are harsh, destructive, environmentally polluting and potentially hazardous, thus limit their applications for decontamination of delicate medical and laboratory devices, remediation of prion contaminated environment and for processing animal by-products including specified risk materials and carcases. Therefore, an environmentally friendly, non-destructive enzymatic degradation approach is highly desirable. A feather-degrading Bacillus licheniformis N22 keratinase has been isolated which degraded scrapie prion to undetectable level of PrP(Sc signals as determined by Western Blot analysis. Prion infectivity was verified by ex vivo cell-based assay. An enzymatic formulation combining N22 keratinase and biosurfactant derived from Pseudomonas aeruginosa degraded PrP(Sc at 65 °C in 10 min to undetectable level -. A time-course degradation analysis carried out at 50 °C over 2 h revealed the progressive attenuation of PrP(Sc intensity. Test of residual infectivity by standard cell culture assay confirmed that the enzymatic formulation reduced PrP(Sc infectivity to undetectable levels as compared to cells challenged with untreated standard scrapie sheep prion (SSBP/1 (p-value = 0.008 at 95% confidence interval. This novel enzymatic formulation has significant potential application for prion decontamination in various environmentally friendly systems under mild treatment conditions.

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

    Indian Academy of Sciences (India)

    , 172 ... the effect of disturbance to an H∞ norm constraint. It is shown that ... unknown chaotic systems; linear matrix inequality (LMI); learning law. 1. Introduction .... (9) is RBFNN H∞ synchronized if the synchronization error e(t) satisfies. ∫ ∞.

  7. 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.).

  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...... would have provided an evolutionary advantage for modern humans, living in the far North of Europe, where little UV-B penetrates the atomosphere. In a recent article, it was concluded not only that the UVB-Vitamin D3 hypothesis is invalid, but also that FLG genetic variations, including loss...

  9. Content-Based Multimedia Retrieval in the Presence of Unknown User Preferences

    DEFF Research Database (Denmark)

    Beecks, Christian; Assent, Ira; Seidl, Thomas

    2011-01-01

    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...... 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...

  10. Liability for Unknown Risks: A Law and Economics Perspective

    NARCIS (Netherlands)

    M.G. Faure (Michael); L.T. Visscher (Louis); F. Weber (Franziska)

    2017-01-01

    textabstractIn the law and economics literature liability is generally regarded as an instrument which provides potential tortfeasors with incentives for optimal care taking. The question, however, arises whether liability can still provide those incentives when risks are unknown. That is the

  11. Teleportation of Unknown Superpositions of Collective Atomic Coherent States

    Institute of Scientific and Technical Information of China (English)

    ZHENG ShiBiao

    2001-01-01

    We propose a scheme to teleport an unknown superposition of two atomic coherent states with different phases. Our scheme is based on resonant and dispersive atom-field interaction. Our scheme provides a possibility of teleporting macroscopic superposition states of many atoms first time.``

  12. Cervical Lymph Node Metastases of Unknown Origin: Primary Tumor Detection with Whole-Body Positron Emission Tomography/Computed Tomography

    International Nuclear Information System (INIS)

    Nassenstein, K.; Veit-Haibach, P.; Stergar, H.; Gutzeit, A.; Freudenberg, L.; Kuehl, H.; Fischer, M.; Barkhausen, J.; Bockisch, A.; Antoch, G.

    2007-01-01

    Background: Identification of primary tumor in patients with cervical lymph node metastasis of unknown primary (MUO) has a great impact on therapy approach and potentially on patient prognosis. Purpose: To assess the diagnostic accuracy of combined positron emission tomography (PET)/computer tomography (CT) for primary tumor detection in cervical metastases of unknown origin compared to PET, CT, and PET+CT side-by-side evaluation. Material and Methods: 39 consecutive patients (eight women, 31 men; mean age 59.9±11.2 years) with MUO were enrolled in this study. PET/CT images were obtained 1 hour after injection of 350 MBq of fluorodeoxyglucose. Oral and intravenous contrast agents were administered in all patients to ensure diagnostic CT data. Fused PET/CT data were evaluated for primary tumor detection. Diagnostic accuracy was calculated and compared with CT alone, PET alone, and side-by-side PET+CT evaluation. Statistical analysis of differences in diagnostic performance between the different imaging procedures was based on the McNemar test. Results: Fused PET/CT depicted the primary tumor in 11 of 39 (28%) patients. In 28 (72%) patients, the primary tumor remained occult. CT revealed the primary in five (13%), PET alone in 10 (26%), and side-by-side evaluation of PET+CT in 10 (26%) of 39 patients. Statistical analysis showed no significant differences between the imaging modalities. Conclusion: PET, side-by-side PET+CT, and PET/CT revealed similar detection rates for primary tumors in cervical MUO patients. Therefore, cervical metastases of an unknown primary may be assessed with either of these imaging modalities. Detection rates with CT were substantially lower. Thus, inclusion of functional data for assessment of cervical MUO patients must be recommended

  13. Adresse inconnue / Address unknown / Suchwiin Bulmyeong

    OpenAIRE

    Serge Gruzinski

    2005-01-01

    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'...

  14. Adaptive Tracking and Obstacle Avoidance Control for Mobile Robots with Unknown Sliding

    Directory of Open Access Journals (Sweden)

    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.

  15. Multiple analysis of an unknown optical multilayer coating

    International Nuclear Information System (INIS)

    Dobrowolski, J.A.; Ho, F.C.; Waldorf, A.

    1985-01-01

    Results are given of the analysis at five different laboratories of an unknown optical multilayer coating. In all, eleven different analytical and laboratory techniques were applied to the problem. The multilayer nominally consisted of three dielectric and two metallic layers. It was demonstrated convincingly that with present day techniques it is possible to determine the basic structure of such a coating

  16. Distributed Optimization Design of Continuous-Time Multiagent Systems With Unknown-Frequency Disturbances.

    Science.gov (United States)

    Wang, Xinghu; Hong, Yiguang; Yi, Peng; Ji, Haibo; Kang, Yu

    2017-05-24

    In this paper, a distributed optimization problem is studied for continuous-time multiagent systems with unknown-frequency disturbances. A distributed gradient-based control is proposed for the agents to achieve the optimal consensus with estimating unknown frequencies and rejecting the bounded disturbance in the semi-global sense. Based on convex optimization analysis and adaptive internal model approach, the exact optimization solution can be obtained for the multiagent system disturbed by exogenous disturbances with uncertain parameters.

  17. Estimation of the false discovery proportion with unknown dependence.

    Science.gov (United States)

    Fan, Jianqing; Han, Xu

    2017-09-01

    Large-scale multiple testing with correlated test statistics arises frequently in many scientific research. Incorporating correlation information in approximating false discovery proportion has attracted increasing attention in recent years. When the covariance matrix of test statistics is known, Fan, Han & Gu (2012) provided an accurate approximation of False Discovery Proportion (FDP) under arbitrary dependence structure and some sparsity assumption. However, the covariance matrix is often unknown in many applications and such dependence information has to be estimated before approximating FDP. The estimation accuracy can greatly affect FDP approximation. In the current paper, we aim to theoretically study the impact of unknown dependence on the testing procedure and establish a general framework such that FDP can be well approximated. The impacts of unknown dependence on approximating FDP are in the following two major aspects: through estimating eigenvalues/eigenvectors and through estimating marginal variances. To address the challenges in these two aspects, we firstly develop general requirements on estimates of eigenvalues and eigenvectors for a good approximation of FDP. We then give conditions on the structures of covariance matrices that satisfy such requirements. Such dependence structures include banded/sparse covariance matrices and (conditional) sparse precision matrices. Within this framework, we also consider a special example to illustrate our method where data are sampled from an approximate factor model, which encompasses most practical situations. We provide a good approximation of FDP via exploiting this specific dependence structure. The results are further generalized to the situation where the multivariate normality assumption is relaxed. Our results are demonstrated by simulation studies and some real data applications.

  18. Numerical method of identification of an unknown source term in a heat equation

    Directory of Open Access Journals (Sweden)

    Fatullayev Afet Golayo?lu

    2002-01-01

    Full Text Available A numerical procedure for an inverse problem of identification of an unknown source in a heat equation is presented. Approach of proposed method is to approximate unknown function by polygons linear pieces which are determined consecutively from the solution of minimization problem based on the overspecified data. Numerical examples are presented.

  19. Cancer of unknown primitive metastatic. About two clinical cases

    International Nuclear Information System (INIS)

    Cawen, L; Cordoba, A.

    2010-01-01

    This work is about the two clinical cases about the unknown primitive metastatic cancer. The main techniques used for the diagnosis, treatment and monitoring of different s carcinomas are: Electronic microscope, molecular biology and genetics, especially histopathological study, topographic survey, ultrasound, radiography, chemotherapy, radiotherapy

  20. High-order sliding mode observer for fractional commensurate linear systems with unknown input

    KAUST Repository

    Belkhatir, Zehor; Laleg-Kirati, Taous-Meriem

    2017-01-01

    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.

  1. 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.

  2. On reconstruction of an unknown polygonal cavity in a linearized elasticity with one measurement

    International Nuclear Information System (INIS)

    Ikehata, M; Itou, H

    2011-01-01

    In this paper we consider a reconstruction problem of an unknown polygonal cavity in a linearized elastic body. For this problem, an extraction formula of the convex hull of the unknown polygonal cavity is established by means of the enclosure method introduced by Ikehata. The advantages of our method are that it needs only a single set of boundary data and we do not require any a priori assumptions for the unknown polygonal cavity and any constraints on boundary data. The theoretical formula may have possibility of application in nondestructive evaluation.

  3. 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.

  4. Insights into mechanisms of transmission and pathogenesis from transgenic mouse models of prion diseases

    Science.gov (United States)

    Moreno, Julie A.; Telling, Glenn C.

    2018-01-01

    Prions represent a new paradigm of protein-mediated information transfer. In the case of mammals, prions are the cause of fatal, transmissible neurodegenerative diseases, sometimes referred to as transmissible spongiform encephalopathies (TSE’s), which frequently occur as epidemics. An increasing body of evidence indicates that the canonical mechanism of conformational corruption of cellular prion protein (PrPC) by the pathogenic isoform (PrPSc) that is the basis of prion formation in TSE’s, is common to a spectrum of proteins associated with various additional human neurodegenerative disorders, including the more common Alzheimer’s and Parkinson’s diseases. The peerless infectious properties of TSE prions, and the unparalleled tools for their study, therefore enable elucidation of mechanisms of template-mediated conformational propagation that are generally applicable to these related disease states. Many unresolved issues remain including the exact molecular nature of the prion, the detailed cellular and molecular mechanisms of prion propagation, and the means by which prion diseases can be both genetic and infectious. In addition, we know little about the mechanism by which neurons degenerate during prion diseases. Tied to this, the physiological role of the normal form of the prion protein remains unclear and it is uncertain whether or not loss of this function contributes to prion pathogenesis. The factors governing the transmission of prions between species remain unclear, in particular the means by which prion strains and PrP primary structure interact to affect inter-species prion transmission. Despite all these unknowns, advances in our understanding of prions have occurred because of their transmissibility to experimental animals and the development of transgenic (Tg) mouse models has done much to further our understanding about various aspects of prion biology. In this review we will focus on advances in our understanding of prion biology that

  5. Extensive screening for primary tumor is redundant in melanoma of unknown primary

    DEFF Research Database (Denmark)

    Tos, Tina; Klyver, Helle; Drzewiecki, Krzysztof T

    2011-01-01

    For decades, patients in our institution with metastastic melanoma of unknown primary have been subjected to extensive examinations in search of the primary tumor. This retrospective study questions the results, and thus the feasibility of these examinations. Of 103 patients diagnosed with unknow......, for patients referred with metastastic melanoma of unknown primary, we recommend that a detailed history is obtained, and a standard physical examination performed, in addition to a histopathological review and CT/PET for staging....

  6. Teleportation of an Unknown Atomic State via Adiabatic Passage

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    We propose a scheme for teleporting an unknown atomic state via adiabatic passage. Taking advantage of adiabatic passage, the atom has no probability of being excited and thus the atomic spontaneous emission is suppressed.We also show that the fidelity can reach 1 under certain condition.

  7. Metastasis to neck from unknown primary tumor

    International Nuclear Information System (INIS)

    Jose, B.; Bosch, A.; Caldwell, W.L.; Frias, Z.

    1979-01-01

    The records of 54 consecutive patients who were irradiated for metastatic disease in the neck from an unknown primary tumor were reviewed. The overall survival results are comparable to those of other reported series. Patients with high or posterior cervical lymph node involvement were irradiated with fields including the nasopharynx and oropharynx. Patients with high neck nodes had a better survival rate than those with low neck nodes. The size of the neck tumors and the local control after treatment also have prognostic significance. (Auth.)

  8. 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.

  9. Matrix- and tensor-based recommender systems for the discovery of currently unknown inorganic compounds

    Science.gov (United States)

    Seko, Atsuto; Hayashi, Hiroyuki; Kashima, Hisashi; Tanaka, Isao

    2018-01-01

    Chemically relevant compositions (CRCs) and atomic arrangements of inorganic compounds have been collected as inorganic crystal structure databases. Machine learning is a unique approach to search for currently unknown CRCs from vast candidates. Herein we propose matrix- and tensor-based recommender system approaches to predict currently unknown CRCs from database entries of CRCs. Firstly, the performance of the recommender system approaches to discover currently unknown CRCs is examined. A Tucker decomposition recommender system shows the best discovery rate of CRCs as the majority of the top 100 recommended ternary and quaternary compositions correspond to CRCs. Secondly, systematic density functional theory (DFT) calculations are performed to investigate the phase stability of the recommended compositions. The phase stability of the 27 compositions reveals that 23 currently unknown compounds are newly found to be stable. These results indicate that the recommender system has great potential to accelerate the discovery of new compounds.

  10. A closer look at prion strains

    Science.gov (United States)

    Solforosi, Laura; Milani, Michela; Mancini, Nicasio; Clementi, Massimo; Burioni, Roberto

    2013-01-01

    Prions are infectious proteins that are responsible for transmissible spongiform encephalopathies (TSEs) and consist primarily of scrapie prion protein (PrPSc), a pathogenic isoform of the host-encoded cellular prion protein (PrPC). The absence of nucleic acids as essential components of the infectious prions is the most striking feature associated to these diseases. Additionally, different prion strains have been isolated from animal diseases despite the lack of DNA or RNA molecules. Mounting evidence suggests that prion-strain-specific features segregate with different PrPSc conformational and aggregation states. Strains are of practical relevance in prion diseases as they can drastically differ in many aspects, such as incubation period, PrPSc biochemical profile (e.g., electrophoretic mobility and glycoform ratio) and distribution of brain lesions. Importantly, such different features are maintained after inoculation of a prion strain into genetically identical hosts and are relatively stable across serial passages. This review focuses on the characterization of prion strains and on the wide range of important implications that the study of prion strains involves. PMID:23357828

  11. Grass plants bind, retain, uptake, and transport infectious prions.

    Science.gov (United States)

    Pritzkow, Sandra; Morales, Rodrigo; Moda, Fabio; Khan, Uffaf; Telling, Glenn C; Hoover, Edward; Soto, Claudio

    2015-05-26

    Prions are the protein-based infectious agents responsible for prion diseases. Environmental prion contamination has been implicated in disease transmission. Here, we analyzed the binding and retention of infectious prion protein (PrP(Sc)) to plants. Small quantities of PrP(Sc) contained in diluted brain homogenate or in excretory materials (urine and feces) can bind to wheat grass roots and leaves. Wild-type hamsters were efficiently infected by ingestion of prion-contaminated plants. The prion-plant interaction occurs with prions from diverse origins, including chronic wasting disease. Furthermore, leaves contaminated by spraying with a prion-containing preparation retained PrP(Sc) for several weeks in the living plant. Finally, plants can uptake prions from contaminated soil and transport them to aerial parts of the plant (stem and leaves). These findings demonstrate that plants can efficiently bind infectious prions and act as carriers of infectivity, suggesting a possible role of environmental prion contamination in the horizontal transmission of the disease. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. The unknown-unknowns: Revealing the hidden insights in massive biomedical data using combined artificial intelligence and knowledge networks

    Directory of Open Access Journals (Sweden)

    Chris Yoo

    2017-12-01

    Full Text Available Genomic data is estimated to be doubling every seven months with over 2 trillion bases from whole genome sequence studies deposited in Genbank in just the last 15 years alone. Recent advances in compute and storage have enabled the use of artificial intelligence techniques in areas such as feature recognition in digital pathology and chemical synthesis for drug development. To apply A.I. productively to multidimensional data such as cellular processes and their dysregulation, the data must be transformed into a structured format, using prior knowledge to create contextual relationships and hierarchies upon which computational analysis can be performed. Here we present the organization of complex data into hypergraphs that facilitate the application of A.I. We provide an example use case of a hypergraph containing hundreds of biological data values and the results of several classes of A.I. algorithms applied in a popular compute cloud. While multiple, biologically insightful correlations between disease states, behavior, and molecular features were identified, the insights of scientific import were revealed only when exploration of the data included visualization of subgraphs of represented knowledge. The results suggest that while machine learning can identify known correlations and suggest testable ones, the greater probability of discovering unexpected relationships between seemingly independent variables (unknown-unknowns requires a context-aware system – hypergraphs that impart biological meaning in nodes and edges. We discuss the implications of a combined hypergraph-A.I. analysis approach to multidimensional data and the pre-processing requirements for such a system.

  13. 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...

  14. 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.

  15. Optimal conclusive teleportation of a d-dimensional two-particle unknown quantum state

    Institute of Scientific and Technical Information of China (English)

    Yang Yu-Guang; Wen Qiao-Yan; Zhu Fu-Chen

    2006-01-01

    A conclusive teleportation protocol of a d-dimensional two-particle unknown quantum state using three ddimensional particles in an arbitrary pure state is proposed. A sender teleports the unknown state conclusively to a receiver by using the positive operator valued measure(POVM) and introducing an ancillary qudit to perform the generalized Bell basis measurement. We calculate the optimal teleportation fidelity. We also discuss and analyse the reason why the information on the teleported state is lost in the course of the protocol.

  16. Na+/K+-ATPase is present in scrapie-associated fibrils, modulates PrP misfolding in vitro and links PrP function and dysfunction.

    Directory of Open Access Journals (Sweden)

    James F Graham

    Full Text Available Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms of the prion protein. These aggregated forms are produced by misfolding of the normal prion protein, PrP(C, to the disease-associated form, PrP(Sc, through mechanisms that remain elusive but which require either direct or indirect interaction between PrP(C and PrP(Sc isoforms. A wealth of evidence implicates other non-PrP molecules as active participants in the misfolding process, to catalyse and direct the conformational conversion of PrP(C or to provide a scaffold ensuring correct alignment of PrP(C and PrP(Sc during conversion. Such molecules may be specific to different scrapie strains to facilitate differential prion protein misfolding. Since molecular cofactors may become integrated into the growing protein fibril during prion conversion, we have investigated the proteins contained in prion disease-specific deposits by shotgun proteomics of scrapie-associated fibrils (SAF from mice infected with 3 different strains of mouse-passaged scrapie. Concomitant use of negative control preparations allowed us to identify and discount proteins that are enriched non-specifically by the SAF isolation protocol. We found several proteins that co-purified specifically with SAF from infected brains but none of these were reproducibly and demonstrably specific for particular scrapie strains. The α-chain of Na(+/K(+-ATPase was common to SAF from all 3 strains and we tested the ability of this protein to modulate in vitro misfolding of recombinant PrP. Na(+/K(+-ATPase enhanced the efficiency of disease-specific conversion of recombinant PrP suggesting that it may act as a molecular cofactor. Consistent with previous results, the same protein inhibited fibrillisation kinetics of recombinant PrP. Since functional interactions between PrP(C and Na(+/K(+-ATPase have previously been reported in astrocytes, our data highlight this molecule as

  17. 18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumours (UPT)

    DEFF Research Database (Denmark)

    Lassen, U; Daugaard, G; Eigtved, A

    1999-01-01

    adenocarcinomas and 1 poorly differentiated carcinoma). The remaining patients had metastases located in bone (3), bone marrow (1), brain (1), pericardium (1), skin (1), pleura (1) and chest wall (1). All metastatic lesions were visible with PET. In 13 patients PET suggested the site for the primary tumour...... by the PET result. The rest received either radical radiotherapy to the head and neck region (7), palliative radiotherapy to the metastatic lesion (8), chemotherapy based on signet ring cell carcinoma in bone marrow (1) or no therapy (1). These results indicates that PET is useful in UPT preceding expensive......The management of patients with unknown primary tumours (UPT) often includes a large number of radiographical studies and invasive procedures, but the occult primary tumour is detected in less than 25%. In this prospective study we explored whether non-invasive whole body PET scans using FDG (18-F...

  18. Blind Identification of FIR Channels in the Presence of Unknown Noise

    Directory of Open Access Journals (Sweden)

    Kon Max Wong

    2007-01-01

    Full Text Available Blind channel identification techniques based on second-order statistics (SOS of the received data have been a topic of active research in recent years. Among the most popular is the subspace method (SS proposed by Moulines et al. (1995. It has good performance when the channel output is corrupted by white noise. However, when the channel noise is correlated and unknown as is often encountered in practice, the performance of the SS method degrades severely. In this paper, we address the problem of estimating FIR channels in the presence of arbitrarily correlated noise whose covariance matrix is unknown. We propose several algorithms according to the different available system resources: (1 when only one receiving antenna is available, by upsampling the output, we develop the maximum a posteriori (MAP algorithm for which a simple criterion is obtained and an efficient implementation algorithm is developed; (2 when two receiving antennae are available, by upsampling both the outputs and utilizing canonical correlation decomposition (CCD to obtain the subspaces, we present two algorithms (CCD-SS and CCD-ML to blindly estimate the channels. Our algorithms perform well in unknown noise environment and outperform existing methods proposed for similar scenarios.

  19. A novel algorithm for fast grasping of unknown objects using C-shape configuration

    Science.gov (United States)

    Lei, Qujiang; Chen, Guangming; Meijer, Jonathan; Wisse, Martijn

    2018-02-01

    Increasing grasping efficiency is very important for the robots to grasp unknown objects especially subjected to unfamiliar environments. To achieve this, a new algorithm is proposed based on the C-shape configuration. Specifically, the geometric model of the used under-actuated gripper is approximated as a C-shape. To obtain an appropriate graspable position, this C-shape configuration is applied to fit geometric model of an unknown object. The geometric model of unknown object is constructed by using a single-view partial point cloud. To examine the algorithm using simulations, a comparison of the commonly used motion planners is made. The motion planner with the highest number of solved runs, lowest computing time and the shortest path length is chosen to execute grasps found by this grasping algorithm. The simulation results demonstrate that excellent grasping efficiency is achieved by adopting our algorithm. To validate this algorithm, experiment tests are carried out using a UR5 robot arm and an under-actuated gripper. The experimental results show that steady grasping actions are obtained. Hence, this research provides a novel algorithm for fast grasping of unknown objects.

  20. 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.

  1. A sensitivity analysis approach to control of manipulators with unknown load

    International Nuclear Information System (INIS)

    Tzes, A.; Yurkovich, S.

    1987-01-01

    This paper presents a straightforward control strategy applied to an N-link manipulator holding an unknown load and driving its end effector along a prespecified trajectory. The control is constituted into two primary components. The non-adaptive component is derived from the inverse problem technique while the adaptive component is computed via the application of sensitivity analysis applied to the complete, centralized dynamic model of the manipulator. The result is a robust adaptive controller which tunes its parameters at specified time instants and can withstand all expected variations of the payload. The control synthesis is illustrated by simulations in a 2-link planar manipulator holding an unknown load

  2. Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect cattle transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-Type bovine spongiform encephalopathy.

    Science.gov (United States)

    Hwang, Soyoun; Greenlee, Justin J; Nicholson, Eric M

    2017-01-01

    Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from the normal cellular prion protein to the pathogenic misfolded conformation (PrPSc). This conversion has been used for in vitro assays including serial protein misfolding amplification and real-time quaking induced conversion (RT-QuIC). RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. Extensive work has been done to demonstrate that RT-QuIC is a rapid, specific, and highly sensitive prion detection assay. RT-QuIC uses recombinant prion protein to detect minute amounts of PrPSc. RT-QuIC has been successfully used to detect PrPSc from different prion diseases with a variety of substrates including hamster, human, sheep, bank vole, bovine and chimeric forms of prion protein. However, recombinant bovine prion protein has not been used to detect transmissible mink encephalopathy (TME) or to differentiate types of bovine spongiform encephalopathy (BSE) in samples from cattle. We evaluated whether PrPSc from TME and BSE infected cattle can be detected with RT-QuIC using recombinant bovine prion proteins, and optimized the reaction conditions to specifically detect cattle TME and to discriminate between classical and atypical BSE by conversion efficiency. We also found that substrate composed of the disease associated E211K mutant protein can be effective for the detection of TME in cattle and that wild type prion protein appears to be a practical substrate to discriminate between the different types of BSEs.

  3. PrP(Sc-specific antibodies with the ability to immunodetect prion oligomers.

    Directory of Open Access Journals (Sweden)

    Mourad Tayebi

    Full Text Available The development of antibodies with binding capacity towards soluble oligomeric forms of PrPSc recognised in the aggregation process in early stage of the disease would be of paramount importance in diagnosing prion diseases before extensive neuropathology has ensued. As blood transfusion appears to be efficient in the transmission of the infectious prion agent, there is an urgent need to develop reagents that would specifically recognize oligomeric forms of the abnormally folded prion protein, PrPSc.To that end, we show that anti-PrP monoclonal antibodies (called PRIOC mAbs derived from mice immunised with native PrP-coated microbeads are able to immunodetect oligomers/multimers of PrPSc. Oligomer-specific immunoreactivity displayed by these PRIOC mAbs was demonstrated as large aggregates of immunoreactive deposits in prion-permissive neuroblastoma cell lines but not in equivalent non-infected or prn-p(0/0 cell lines. In contrast, an anti-monomer PrP antibody displayed diffuse immunoreactivity restricted to the cell membrane. Furthermore, our PRIOC mAbs did not display any binding with monomeric recombinant and cellular prion proteins but strongly detected PrPSc oligomers as shown by a newly developed sensitive and specific ELISA. Finally, PrioC antibodies were also able to bind soluble oligomers formed of Aβ and α-synuclein. These findings demonstrate the potential use of anti-prion antibodies that bind PrPSc oligomers, recognised in early stage of the disease, for the diagnosis of prion diseases in blood and other body fluids.

  4. Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. The GRI Study Group.

    Science.gov (United States)

    Bellaïche, L; Laredo, J D; Lioté, F; Koeger, A C; Hamze, B; Ziza, J M; Pertuiset, E; Bardin, T; Tubiana, J M

    1997-11-01

    A prospective multicenter study. To evaluate the use of magnetic resonance imaging, in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. Although multiple myeloma has been studied extensively with magnetic resonance imaging, to the authors' knowledge, no study has evaluated the clinical interest of magnetic resonance imaging in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. The magnetic resonance examinations of the thoracolumbar spine in 24 patients with newly diagnosed monoclonal gammopathies of unknown significance were compared with those performed in 44 patients with newly diagnosed nontreated multiple myeloma. All findings on magnetic resonance examination performed in patients with monoclonal gammopathies of unknown significance were normal, whereas findings on 38 (86%) of the 44 magnetic resonance examinations performed in patients with multiple myeloma were abnormal. Magnetic resonance imaging can be considered as an additional diagnostic tool in differentiating between monoclonal gammopathies of unknown significance and multiple myeloma, which may be helpful when routine criteria are not sufficient. An abnormal finding on magnetic resonance examination in a patient with monoclonal gammopathies of unknown significance should suggest the diagnosis of multiple myeloma after other causes of marrow signal abnormalities are excluded. Magnetic resonance imaging also may be proposed in the long-term follow-up of monoclonal gammopathies of unknown significance when a new biologic or clinical event suggests the diagnosis of malignant monoclonal gammopathy.

  5. MUSIC-type imaging of small perfectly conducting cracks with an unknown frequency

    International Nuclear Information System (INIS)

    Park, Won-Kwang

    2015-01-01

    MUltiple SIgnal Classification (MUSIC) is a famous non-iterative detection algorithm in inverse scattering problems. However, when the applied frequency is unknown, inaccurate locations are identified via MUSIC. This fact has been confirmed through numerical simulations. However, the reason behind this phenomenon has not been investigated theoretically. Motivated by this fact, we identify the structure of MUSIC-type imaging functionals with unknown frequency, by establishing a relationship with Bessel functions of order zero of the first kind. Through this, we can explain why inaccurate results appear. (paper)

  6. MUSIC-type imaging of small perfectly conducting cracks with an unknown frequency

    Science.gov (United States)

    Park, Won-Kwang

    2015-09-01

    MUltiple SIgnal Classification (MUSIC) is a famous non-iterative detection algorithm in inverse scattering problems. However, when the applied frequency is unknown, inaccurate locations are identified via MUSIC. This fact has been confirmed through numerical simulations. However, the reason behind this phenomenon has not been investigated theoretically. Motivated by this fact, we identify the structure of MUSIC-type imaging functionals with unknown frequency, by establishing a relationship with Bessel functions of order zero of the first kind. Through this, we can explain why inaccurate results appear.

  7. Integrity of Helix 2-Helix 3 Domain of the PrP Protein Is Not Mandatory for Prion Replication*

    Science.gov (United States)

    Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

    2012-01-01

    The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrPSc. We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrPSc and elucidate the conformational changes underlying prions generation. PMID:22511770

  8. Integrity of helix 2-helix 3 domain of the PrP protein is not mandatory for prion replication.

    Science.gov (United States)

    Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

    2012-06-01

    The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrP(Sc). We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrP(Sc) and elucidate the conformational changes underlying prions generation.

  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. Automated pathway and reaction prediction facilitates in silico identification of unknown metabolites in human cohort studies.

    Science.gov (United States)

    Quell, Jan D; Römisch-Margl, Werner; Colombo, Marco; Krumsiek, Jan; Evans, Anne M; Mohney, Robert; Salomaa, Veikko; de Faire, Ulf; Groop, Leif C; Agakov, Felix; Looker, Helen C; McKeigue, Paul; Colhoun, Helen M; Kastenmüller, Gabi

    2017-12-15

    Identification of metabolites in non-targeted metabolomics continues to be a bottleneck in metabolomics studies in large human cohorts. Unidentified metabolites frequently emerge in the results of association studies linking metabolite levels to, for example, clinical phenotypes. For further analyses these unknown metabolites must be identified. Current approaches utilize chemical information, such as spectral details and fragmentation characteristics to determine components of unknown metabolites. Here, we propose a systems biology model exploiting the internal correlation structure of metabolite levels in combination with existing biochemical and genetic information to characterize properties of unknown molecules. Levels of 758 metabolites (439 known, 319 unknown) in human blood samples of 2279 subjects were measured using a non-targeted metabolomics platform (LC-MS and GC-MS). We reconstructed the structure of biochemical pathways that are imprinted in these metabolomics data by building an empirical network model based on 1040 significant partial correlations between metabolites. We further added associations of these metabolites to 134 genes from genome-wide association studies as well as reactions and functional relations to genes from the public database Recon 2 to the network model. From the local neighborhood in the network, we were able to predict the pathway annotation of 180 unknown metabolites. Furthermore, we classified 100 pairs of known and unknown and 45 pairs of unknown metabolites to 21 types of reactions based on their mass differences. As a proof of concept, we then looked further into the special case of predicted dehydrogenation reactions leading us to the selection of 39 candidate molecules for 5 unknown metabolites. Finally, we could verify 2 of those candidates by applying LC-MS analyses of commercially available candidate substances. The formerly unknown metabolites X-13891 and X-13069 were shown to be 2-dodecendioic acid and 9

  11. Molecular architecture of human prion protein amyloid: a parallel, in-register beta-structure.

    Science.gov (United States)

    Cobb, Nathan J; Sönnichsen, Frank D; McHaourab, Hassane; Surewicz, Witold K

    2007-11-27

    Transmissible spongiform encephalopathies (TSEs) represent a group of fatal neurodegenerative diseases that are associated with conformational conversion of the normally monomeric and alpha-helical prion protein, PrP(C), to the beta-sheet-rich PrP(Sc). This latter conformer is believed to constitute the main component of the infectious TSE agent. In contrast to high-resolution data for the PrP(C) monomer, structures of the pathogenic PrP(Sc) or synthetic PrP(Sc)-like aggregates remain elusive. Here we have used site-directed spin labeling and EPR spectroscopy to probe the molecular architecture of the recombinant PrP amyloid, a misfolded form recently reported to induce transmissible disease in mice overexpressing an N-terminally truncated form of PrP(C). Our data show that, in contrast to earlier, largely theoretical models, the con formational conversion of PrP(C) involves major refolding of the C-terminal alpha-helical region. The core of the amyloid maps to C-terminal residues from approximately 160-220, and these residues form single-molecule layers that stack on top of one another with parallel, in-register alignment of beta-strands. This structural insight has important implications for understanding the molecular basis of prion propagation, as well as hereditary prion diseases, most of which are associated with point mutations in the region found to undergo a refolding to beta-structure.

  12. Navigation through unknown and dynamic open spaces using topological notions

    Science.gov (United States)

    Miguel-Tomé, Sergio

    2018-04-01

    Until now, most algorithms used for navigation have had the purpose of directing system towards one point in space. However, humans communicate tasks by specifying spatial relations among elements or places. In addition, the environments in which humans develop their activities are extremely dynamic. The only option that allows for successful navigation in dynamic and unknown environments is making real-time decisions. Therefore, robots capable of collaborating closely with human beings must be able to make decisions based on the local information registered by the sensors and interpret and express spatial relations. Furthermore, when one person is asked to perform a task in an environment, this task is communicated given a category of goals so the person does not need to be supervised. Thus, two problems appear when one wants to create multifunctional robots: how to navigate in dynamic and unknown environments using spatial relations and how to accomplish this without supervision. In this article, a new architecture to address the two cited problems is presented, called the topological qualitative navigation architecture. In previous works, a qualitative heuristic called the heuristic of topological qualitative semantics (HTQS) has been developed to establish and identify spatial relations. However, that heuristic only allows for establishing one spatial relation with a specific object. In contrast, navigation requires a temporal sequence of goals with different objects. The new architecture attains continuous generation of goals and resolves them using HTQS. Thus, the new architecture achieves autonomous navigation in dynamic or unknown open environments.

  13. Neurological autoantibodies in drug-resistant epilepsy of unknown cause.

    Science.gov (United States)

    Tecellioglu, Mehmet; Kamisli, Ozden; Kamisli, Suat; Yucel, Fatma Ebru; Ozcan, Cemal

    2018-03-09

    Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were determined. Serum antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive patients. Autoimmune factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

  14. 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.

  15. Detection of unknown primary neuroendocrine tumours (CUP-NET) using 68Ga-DOTA-NOC receptor PET/CT

    International Nuclear Information System (INIS)

    Prasad, Vikas; Baum, Richard P.; Ambrosini, Valentina; Fanti, Stefano; Hommann, Merten; Hoersch, Dieter

    2010-01-01

    This bi-centric study aimed to determine the role of receptor PET/CT using 68 Ga-DOTA-NOC in the detection of undiagnosed primary sites of neuroendocrine tumours (NETs) and to understand the molecular behaviour of the primarily undiagnosed tumours. Overall 59 patients (33 men and 26 women, age: 65 ± 9 years) with documented NET and unknown primary were enrolled. PET/CT was performed after injection of approximately 100 MBq (46-260 MBq) of 68 Ga-DOTA-NOC. The maximum standardised uptake values (SUV max ) were calculated and compared with SUV max in known pancreatic NET (pNET) and ileum/jejunum/duodenum (SI-NET). The results of PET/CT were also correlated with CT alone. In 35 of 59 patients (59%), 68 Ga-DOTA-NOC PET/CT localised the site of the primary: ileum/jejunum (14), pancreas (16), rectum/colon (2), lungs (2) and paraganglioma (1). CT alone (on retrospective analyses) confirmed the findings in 12 of 59 patients (20%). The mean SUV max of identified previously unknown pNET and SI-NET were 18.6 ± 9.8 (range: 7.8-34.8) and 9.1 ± 6.0 (range: 4.2-27.8), respectively. SUV max in patients with previously known pNET and SI-NET were 26.1 ± 14.5 (range: 8.7-42.4) and 11.3 ± 3.7 (range: 5.6-17.9). The SUV max of the unknown pNET and SI-NET were significantly lower (p 68 Ga-DOTA-NOC receptor PET/CT, 6 of 59 patients were operated and the primary was removed (4 pancreatic, 1 ileal and 1 rectal tumour) resulting in a management change in approximately 10% of the patients. In the remaining 29 patients, because of the far advanced stage of the disease (due to distant metastases), the primary tumours were not operated. Additional histopathological sampling was available from one patient with bronchial carcinoid (through bronchoscopy). Our data indicate that 68 Ga-DOTA-NOC PET/CT is highly superior to 111 In-OctreoScan (39% detection rate for CUP according to the literature) and can play a major role in the management of patients with CUP-NET. (orig.)

  16. Unknown loads affect force production capacity in early phases of bench press throws.

    Science.gov (United States)

    Hernández Davó, J L; Sabido Solana, R; Sarabia Marínm, J M; Sánchez Martos, Á; Moya Ramón, M

    2015-10-01

    Explosive strength training aims to improve force generation in early phases of movement due to its importance in sport performance. The present study examined the influence of lack of knowledge about the load lifted in explosive parameters during bench press throws. Thirteen healthy young men (22.8±2.0 years) participated in the study. Participants performed bench press throws with three different loads (30, 50 and 70% of 1 repetition maximum) in two different conditions (known and unknown loads). In unknown condition, loads were changed within sets in each repetition and participants did not know the load, whereas in known condition the load did not change within sets and participants had knowledge about the load lifted. Results of repeated-measures ANOVA revealed that unknown conditions involves higher power in the first 30, 50, 100 and 150 ms with the three loads, higher values of ratio of force development in those first instants, and differences in time to reach maximal rate of force development with 50 and 70% of 1 repetition maximum. This study showed that unknown conditions elicit higher values of explosive parameters in early phases of bench press throws, thereby this kind of methodology could be considered in explosive strength training.

  17. 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

  18. Zero Distribution of System with Unknown Random Variables Case Study: Avoiding Collision Path

    Directory of Open Access Journals (Sweden)

    Parman Setyamartana

    2014-07-01

    Full Text Available This paper presents the stochastic analysis of finding the feasible trajectories of robotics arm motion at obstacle surrounding. Unknown variables are coefficients of polynomials joint angle so that the collision-free motion is achieved. ãk is matrix consisting of these unknown feasible polynomial coefficients. The pattern of feasible polynomial in the obstacle environment shows as random. This paper proposes to model the pattern of this randomness values using random polynomial with unknown variables as coefficients. The behavior of the system will be obtained from zero distribution as the characteristic of such random polynomial. Results show that the pattern of random polynomial of avoiding collision can be constructed from zero distribution. Zero distribution is like building block of the system with obstacles as uncertainty factor. By scale factor k, which has range, the random coefficient pattern can be predicted.

  19. Carcinoma of Unknown Primary Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Carcinoma of unknown primary (CUP) treatment depends on the best determination of the primary site, if possible. Treatment options may include surgery, radiation therapy, and systemic treatment. Get detailed information about diagnosis and treatment of CUP in this summary for clinicians.

  20. Running over unknown rough terrain with a one-legged planar robot

    International Nuclear Information System (INIS)

    Andrews, Ben; Miller, Bruce; Clark, Jonathan E; Schmitt, John

    2011-01-01

    The ability to traverse unknown, rough terrain is an advantage that legged locomoters have over their wheeled counterparts. However, due to the complexity of multi-legged systems, research in legged robotics has not yet been able to reproduce the agility found in the animal kingdom. In an effort to reduce the complexity of the problem, researchers have developed single-legged models to gain insight into the fundamental dynamics of legged running. Inspired by studies of animal locomotion, researchers have proposed numerous control strategies to achieve stable, one-legged running over unknown, rough terrain. One such control strategy incorporates energy variations into the system during the stance phase by changing the force-free leg length as a sinusoidal function of time. In this research, a one-legged planar robot capable of implementing this and other state-of-the-art control strategies was designed and built. Both simulated and experimental results were used to determine and compare the stability of the proposed controllers as the robot was subjected to unknown drop and raised step perturbations equal to 25% of the nominal leg length. This study illustrates the relative advantages of utilizing a minimal-sensing, active energy removal control scheme to stabilize running over rough terrain.

  1. Iron overload patients with unknown etiology from national survey in Japan.

    Science.gov (United States)

    Ikuta, Katsuya; Hatayama, Mayumi; Addo, Lynda; Toki, Yasumichi; Sasaki, Katsunori; Tatsumi, Yasuaki; Hattori, Ai; Kato, Ayako; Kato, Koichi; Hayashi, Hisao; Suzuki, Takahiro; Kobune, Masayoshi; Tsutsui, Miyuki; Gotoh, Akihiko; Aota, Yasuo; Matsuura, Motoo; Hamada, Yuzuru; Tokuda, Takahiro; Komatsu, Norio; Kohgo, Yutaka

    2017-03-01

    Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

  2. Approximate and Conditional Teleportation of an Unknown Atomic-Entangled State Without Bell-State Measurement

    Institute of Scientific and Technical Information of China (English)

    CHEN Chang-Yong; LI Shao-Hua

    2007-01-01

    A scheme for approximately and conditionally teleporting an unknown atomic-entangled state in cavity QED is proposed.It is the novel extension of the scheme of [Phys.Rev.A 69 (2004) 064302],where the state to be teleported is an unknown atomic state and where only a time point of system evolution and the corresponding fidelity implementing the teleportation are given.In fact,there exists multi-time points and the corresponding fidclities,which are shown in this paper and then are used to realize the approximate and conditional teleportation of the unknown atomic-entangled state.Naturally,our scheme does not involve the Bell-state measurement or an additional atom,which is required in the Bell-state measurement,only requiring one single-mode cavity.The scheme may be generalized to not only the teleportation of the cavity-mode-entangled-state by means of a single atom but also the teleportation of the unknown trapped-ion-entangled-state in a linear ion trap and the teleportation of the multi-atomic entangled states included in generalized GHZ states.

  3. Metastatic meningioma presenting as cancer of unknown primary

    Directory of Open Access Journals (Sweden)

    Vinay Gupta

    2013-12-01

    Full Text Available We describe a case of anaplastic meningioma presenting in an extracranial osseous location, initially diagnosed as cancer of unknown primary. Although anaplastic meningioma comprise 3% of all meningiomas, this subtype is more likely to be associated with metastases. The increased degree of dedifferentiation in anaplastic meningioma makes diagnosis difficult, especially if characteristic imaging findings of meningioma are not identified. Adequate tissue for diagnostic purposes and appropriate imaging studies may help in establishing a definitive diagnosis.

  4. 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

  5. Sliding Mode Observer-Based Current Sensor Fault Reconstruction and Unknown Load Disturbance Estimation for PMSM Driven System.

    Science.gov (United States)

    Zhao, Kaihui; Li, Peng; Zhang, Changfan; Li, Xiangfei; He, Jing; Lin, Yuliang

    2017-12-06

    This paper proposes a new scheme of reconstructing current sensor faults and estimating unknown load disturbance for a permanent magnet synchronous motor (PMSM)-driven system. First, the original PMSM system is transformed into two subsystems; the first subsystem has unknown system load disturbances, which are unrelated to sensor faults, and the second subsystem has sensor faults, but is free from unknown load disturbances. Introducing a new state variable, the augmented subsystem that has sensor faults can be transformed into having actuator faults. Second, two sliding mode observers (SMOs) are designed: the unknown load disturbance is estimated by the first SMO in the subsystem, which has unknown load disturbance, and the sensor faults can be reconstructed using the second SMO in the augmented subsystem, which has sensor faults. The gains of the proposed SMOs and their stability analysis are developed via the solution of linear matrix inequality (LMI). Finally, the effectiveness of the proposed scheme was verified by simulations and experiments. The results demonstrate that the proposed scheme can reconstruct current sensor faults and estimate unknown load disturbance for the PMSM-driven system.

  6. Accounting for unknown foster dams in the genetic evaluation of embryo transfer progeny.

    Science.gov (United States)

    Suárez, M J; Munilla, S; Cantet, R J C

    2015-02-01

    Animals born by embryo transfer (ET) are usually not included in the genetic evaluation of beef cattle for preweaning growth if the recipient dam is unknown. This is primarily to avoid potential bias in the estimation of the unknown age of dam. We present a method that allows including records of calves with unknown age of dam. Assumptions are as follows: (i) foster cows belong to the same breed being evaluated, (ii) there is no correlation between the breeding value (BV) of the calf and the maternal BV of the recipient cow, and (iii) cows of all ages are used as recipients. We examine the issue of bias for the fixed level of unknown age of dam (AOD) and propose an estimator of the effect based on classical measurement error theory (MEM) and a Bayesian approach. Using stochastic simulation under random mating or selection, the MEM estimating equations were compared with BLUP in two situations as follows: (i) full information (FI); (ii) missing AOD information on some dams. Predictions of breeding value (PBV) from the FI situation had the smallest empirical average bias followed by PBV obtained without taking measurement error into account. In turn, MEM displayed the highest bias, although the differences were small. On the other hand, MEM showed the smallest MSEP, for either random mating or selection, followed by FI, whereas ignoring measurement error produced the largest MSEP. As a consequence from the smallest MSEP with a relatively small bias, empirical accuracies of PBV were larger for MEM than those for full information, which in turn showed larger accuracies than the situation ignoring measurement error. It is concluded that MEM equations are a useful alternative for analysing weaning weight data when recipient cows are unknown, as it mitigates the effects of bias in AOD by decreasing MSEP. © 2014 Blackwell Verlag GmbH.

  7. 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

  8. Stochastic Online Learning in Dynamic Networks under Unknown Models

    Science.gov (United States)

    2016-08-02

    The key is to develop online learning strategies at each individual node. Specifically, through local information exchange with its neighbors, each...infinitely repeated game with incomplete information and developed a dynamic pricing strategy referred to as Competitive and Cooperative Demand Learning...Stochastic Online Learning in Dynamic Networks under Unknown Models This research aims to develop fundamental theories and practical algorithms for

  9. Optimal unambiguous comparison of two unknown squeezed vacua

    International Nuclear Information System (INIS)

    Olivares, Stefano; Paris, Matteo G. A.; Sedlak, Michal; Rapsan, Peter; Busek, Vladimir

    2011-01-01

    We propose a scheme for the unambiguous state comparison (USC) of two unknown squeezed vacuum states of the electromagnetic field. Our setup is based on linear optical elements and photon-number detectors, and it achieves optimal USC in an ideal case of unit quantum efficiency. In realistic conditions, i.e., for nonunit quantum efficiency of photodetectors, we evaluate the probability of getting an ambiguous result as well as the reliability of the scheme, thus showing its robustness in comparison to previous proposals.

  10. Critical significance of the region between Helix 1 and 2 for efficient dominant-negative inhibition by conversion-incompetent prion protein.

    Directory of Open Access Journals (Sweden)

    Yuzuru Taguchi

    Full Text Available Prion diseases are fatal infectious neurodegenerative disorders in man and animals associated with the accumulation of the pathogenic isoform PrP(Sc of the host-encoded prion protein (PrP(c. A profound conformational change of PrP(c underlies formation of PrP(Sc and prion propagation involves conversion of PrP(c substrate by direct interaction with PrP(Sc template. Identifying the interfaces and modalities of inter-molecular interactions of PrPs will highly advance our understanding of prion propagation in particular and of prion-like mechanisms in general. To identify the region critical for inter-molecular interactions of PrP, we exploited here dominant-negative inhibition (DNI effects of conversion-incompetent, internally-deleted PrP (ΔPrP on co-expressed conversion-competent PrP. We created a series of ΔPrPs with different lengths of deletions in the region between first and second α-helix (H1∼H2 which was recently postulated to be of importance in prion species barrier and PrP fibril formation. As previously reported, ΔPrPs uniformly exhibited aberrant properties including detergent insolubility, limited protease digestion resistance, high-mannose type N-linked glycans, and intracellular localization. Although formerly controversial, we demonstrate here that ΔPrPs have a GPI anchor attached. Surprisingly, despite very similar biochemical and cell-biological properties, DNI efficiencies of ΔPrPs varied significantly, dependant on location and inversely correlated with the size of deletion. This data demonstrates that H1∼H2 and the region C-terminal to it are critically important for efficient DNI. It also suggests that this region is involved in PrP-PrP interaction and conversion of PrP(C into PrP(Sc. To reconcile the paradox of how an intracellular PrP can exert DNI, we demonstrate that ΔPrPs are subject to both proteasomal and lysosomal/autophagic degradation pathways. Using autophagy pathways ΔPrPs obtain access to the locale

  11. Evidence of scrapie transmission to sheep via goat milk.

    Science.gov (United States)

    Konold, Timm; Thorne, Leigh; Simmons, Hugh A; Hawkins, Steve A C; Simmons, Marion M; González, Lorenzo

    2016-09-17

    Previous studies confirmed that classical scrapie can be transmitted via milk in sheep. The current study aimed to investigate whether scrapie can also be transmitted via goat milk using in vivo (new-born lambs fed milk from scrapie-affected goats due to the unavailability of goat kids from guaranteed scrapie-free herds) and in vitro methods (serial protein misfolding cyclic amplification [sPMCA] on milk samples). In an initial pilot study, new-born lambs of two different prion protein gene (PRNP) genotypes (six VRQ/VRQ and five ARQ/ARQ) were orally challenged with 5 g brain homogenate from two scrapie-affected goats to determine susceptibility of sheep to goat scrapie. All sheep challenged with goat scrapie brain became infected based on the immunohistochemical detection of disease-associated PrP (PrP(sc)) in lymphoid tissue, with an ARQ/ARQ sheep being the first to succumb. Subsequent feeding of milk to eight pairs of new-born ARQ/ARQ lambs, with each pair receiving milk from a different scrapie-affected goat, resulted in scrapie in the six pairs that received the largest volume of milk (38-87 litres per lamb), whereas two pairs fed 8-9 litres per lamb, and an environmental control group raised on sheep milk from healthy ewes, did not show evidence of infection when culled at up to 1882 days of age. Infection in those 12 milk recipients occurred regardless of the clinical status, PrP(sc) distribution, caprine arthritis-encephalitis virus infection status and PRNP polymorphisms at codon 142 (II or IM) of the donor goats, but survival time was influenced by PRNP polymorphisms at codon 141. Serial PMCA applied to a total of 32 milk samples (four each from the eight donor goats collected throughout lactation) detected PrP(sc) in one sample each from two goats. The scrapie agent was present in the milk from infected goats and was able to transmit to susceptible species even at early preclinical stage of infection, when PrP(sc) was undetectable in the brain of the

  12. 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.

  13. Prion Propagation in Cells Expressing PrP Glycosylation Mutants ▿

    Science.gov (United States)

    Salamat, Muhammad K.; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

    2011-01-01

    Infection by prions involves conversion of a host-encoded cell surface protein (PrPC) to a disease-related isoform (PrPSc). PrPC carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrPC glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrPSc and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrPSc, while PrPC with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrPC, were able to form infectious PrPSc. Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection. PMID:21248032

  14. Prion propagation in cells expressing PrP glycosylation mutants.

    Science.gov (United States)

    Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

    2011-04-01

    Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

  15. Glypican-1 mediates both prion protein lipid raft association and disease isoform formation.

    Directory of Open Access Journals (Sweden)

    David R Taylor

    2009-11-01

    Full Text Available In prion diseases, the cellular form of the prion protein, PrP(C, undergoes a conformational conversion to the infectious isoform, PrP(Sc. PrP(C associates with lipid rafts through its glycosyl-phosphatidylinositol (GPI anchor and a region in its N-terminal domain which also binds to heparan sulfate proteoglycans (HSPGs. We show that heparin displaces PrP(C from rafts and promotes its endocytosis, suggesting that heparin competes with an endogenous raft-resident HSPG for binding to PrP(C. We then utilised a transmembrane-anchored form of PrP (PrP-TM, which is targeted to rafts solely by its N-terminal domain, to show that both heparin and phosphatidylinositol-specific phospholipase C can inhibit its association with detergent-resistant rafts, implying that a GPI-anchored HSPG targets PrP(C to rafts. Depletion of the major neuronal GPI-anchored HSPG, glypican-1, significantly reduced the raft association of PrP-TM and displaced PrP(C from rafts, promoting its endocytosis. Glypican-1 and PrP(C colocalised on the cell surface and both PrP(C and PrP(Sc co-immunoprecipitated with glypican-1. Critically, treatment of scrapie-infected N2a cells with glypican-1 siRNA significantly reduced PrP(Sc formation. In contrast, depletion of glypican-1 did not alter the inhibitory effect of PrP(C on the beta-secretase cleavage of the Alzheimer's amyloid precursor protein. These data indicate that glypican-1 is a novel cellular cofactor for prion conversion and we propose that it acts as a scaffold facilitating the interaction of PrP(C and PrP(Sc in lipid rafts.

  16. 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.

  17. Fever of Unknown Origin: the Value of FDG-PET/CT

    NARCIS (Netherlands)

    Kouijzer, I.J.E.; Mulders-Manders, C.M.; Bleeker-Rovers, C.P.; Oyen, W.J.G.

    2018-01-01

    Fever of unknown origin (FUO) is commonly defined as fever higher than 38.3 degrees C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory investigations. The differential diagnosis of FUO can be subdivided in four categories: infections, malignancies,

  18. Unknown facets of Well-Known Scientists Series - Part II

    Directory of Open Access Journals (Sweden)

    V S Dixit

    2016-01-01

    Full Text Available 1st in the series of articles on “Unknown Facets of well-known Scientists” was about Sir Frederick Grant Banting, co-discoverer of Insulin, who also researched in Aviation and Diving Medicines, results of which brought extraordinary benefits for Flight crew during the World War II. The article was published in the previous issue of the Journal Unknown facets could be celebrated attributes, talents or otherwise, but it is necessary that we get to know fully about the “great mind". THIS ARTICLE IS ABOUT DR WERNER THEODOR OTTO FORSSMANN, A CARDIOLOGIST, WHO BECAME A UROLOGIST! Does the name Dr Forssmann ring a bell? He shared the 1956 Nobel Prize in Physiology or Medicine with “Andre Cournand and Dickinson Richards". The trio was awarded for their “discoveries concerning heart catheterization and pathological changes in the circulatory system". Dr Forssmann was nominated for performing an experiment in which he introduced a catheter into a vein of his arm, further passing it onward into his heart It was risky. This was in the year 1929. Subject of this article is the self-experimentation he carried out and what happened later.

  19. Parameter identification of chaos system based on unknown parameter observer

    International Nuclear Information System (INIS)

    Wang Shaoming; Luo Haigeng; Yue Chaoyuan; Liao Xiaoxin

    2008-01-01

    Parameter identification of chaos system based on unknown parameter observer is discussed generally. Based on the work of Guan et al. [X.P. Guan, H.P. Peng, L.X. Li, et al., Acta Phys. Sinica 50 (2001) 26], the design of unknown parameter observer is improved. The application of the improved approach is extended greatly. The works in some literatures [X.P. Guan, H.P. Peng, L.X. Li, et al., Acta Phys. Sinica 50 (2001) 26; J.H. Lue, S.C. Zhang, Phys. Lett. A 286 (2001) 148; X.Q. Wu, J.A. Lu, Chaos Solitons Fractals 18 (2003) 721; J. Liu, S.H. Chen, J. Xie, Chaos Solitons Fractals 19 (2004) 533] are only the special cases of our Corollaries 1 and 2. Some observers for Lue system and a new chaos system are designed to test our improved method, and simulations results demonstrate the effectiveness and feasibility of the improved approach

  20. Discovery of small molecules binding to the normal conformation of prion by combining virtual screening and multiple biological activity evaluation methods

    Science.gov (United States)

    Li, Lanlan; Wei, Wei; Jia, Wen-Juan; Zhu, Yongchang; Zhang, Yan; Chen, Jiang-Huai; Tian, Jiaqi; Liu, Huanxiang; He, Yong-Xing; Yao, Xiaojun

    2017-12-01

    Conformational conversion of the normal cellular prion protein, PrPC, into the misfolded isoform, PrPSc, is considered to be a central event in the development of fatal neurodegenerative diseases. Stabilization of prion protein at the normal cellular form (PrPC) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrPC to PrPSc conversion. Compound 3253-0207 that can bind to PrPC with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound 3253-0207 can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrPC to PrPSc.

  1. Peripheral Tissue Involvement in Sporadic, Iatrogenic, and Variant Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Head, Mark W.; Ritchie, Diane; Smith, Nadine; McLoughlin, Victoria; Nailon, William; Samad, Sazia; Masson, Stephen; Bishop, Matthew; McCardle, Linda; Ironside, James W.

    2004-01-01

    Human prion diseases are rare fatal neurodegenerative conditions that occur as acquired, familial, or idiopathic disorders. A key event in their pathogenesis is the accumulation of an altered form of the prion protein, termed PrPSc, in the central nervous system. A novel acquired human prion disease, variant Creutzfeldt-Jakob disease, is thought to result from oral exposure to the bovine spongiform encephalopathy agent. This disease differs from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. We have used immunohistochemistry and Western blot techniques to analyze the tissue distribution and biochemical properties of PrPSc in peripheral tissues in a unique series of nine cases of variant Creutzfeldt-Jakob disease. We have compared this with the distribution and biochemical forms found in all of the major subtypes of sporadic Creutzfeldt-Jakob disease and in a case of iatrogenic Creutzfeldt-Jakob disease associated with growth hormone therapy. The results show that involvement of the lymphoreticular system is a defining feature of variant Creutzfeldt-Jakob disease, but that the biochemical isoform of PrPSc found is influenced by the cell type in which it accumulates. PMID:14695328

  2. Reversible unfolding of infectious prion assemblies reveals the existence of an oligomeric elementary brick.

    Directory of Open Access Journals (Sweden)

    Angélique Igel-Egalon

    2017-09-01

    Full Text Available Mammalian prions, the pathogens that cause transmissible spongiform encephalopathies, propagate by self-perpetuating the structural information stored in the abnormally folded, aggregated conformer (PrPSc of the host-encoded prion protein (PrPC. To date, no structural model related to prion assembly organization satisfactorily describes how strain-specified structural information is encoded and by which mechanism this information is transferred to PrPC. To achieve progress on this issue, we correlated the PrPSc quaternary structural transition from three distinct prion strains during unfolding and refolding with their templating activity. We reveal the existence of a mesoscopic organization in PrPSc through the packing of a highly stable oligomeric elementary subunit (suPrP, in which the strain structural determinant (SSD is encoded. Once kinetically trapped, this elementary subunit reversibly loses all replicative information. We demonstrate that acquisition of the templating interface and infectivity requires structural rearrangement of suPrP, in concert with its condensation. The existence of such an elementary brick scales down the SSD support to a small oligomer and provide a basis of reflexion for prion templating process and propagation.

  3. Comparison of various structural damage tracking techniques with unknown excitations based on experimental data

    Science.gov (United States)

    Huang, Hongwei; Yang, Jann N.; Zhou, Li

    2009-03-01

    An early detection of structural damages is critical for the decision making of repair and replacement maintenance in order to guarantee a specified structural reliability. Consequently, the structural damage detection, based on vibration data measured from the structural health monitoring (SHM) system, has received considerable attention recently. The traditional time-domain analysis techniques, such as the least square estimation (LSE) method and the extended Kalman filter (EKF) approach, require that all the external excitations (inputs) be available, which may not be the case for some SHM systems. Recently, these two approaches have been extended to cover the general case where some of the external excitations (inputs) are not measured, referred to as the LSE with unknown inputs (LSE-UI) and the EKF with unknown inputs (EKF-UI). Also, new analysis methods, referred to as the sequential non-linear least-square estimation with unknown inputs and unknown outputs (SNLSE-UI-UO) and the quadratic sum-square error with unknown inputs (QSSE-UI), have been proposed for the damage tracking of structures when some of the acceleration responses are not measured and the external excitations are not available. In this paper, these newly proposed analysis methods will be compared in terms of accuracy, convergence and efficiency, for damage identification of structures based on experimental data obtained through a series of experimental tests using a small-scale 3-story building model with white noise excitation. The capability of the LSE-UI, EKF-UI, SNLSE-UI-UO and QSSE-UI approaches in tracking the structural damages will be demonstrated.

  4. <<Unknown>> earthquakes: a growing contribution to the Catalogue of Strong Italian Earthquakes

    Directory of Open Access Journals (Sweden)

    E. Guidoboni

    2000-06-01

    Full Text Available The particular structure of the research into historical seismology found in this catalogue has allowed a lot of information about unknown seismic events to be traced. This new contribution to seismologic knowledge mainly consists in: i the retrieval and organisation within a coherent framework of documentary evidence of earthquakes that took place between the Middle Ages and the sixteenth century; ii the improved knowledge of seismic events, even destructive events, which in the past had been "obscured" by large earthquakes; iii the identification of earthquakes in "silent" seismic areas. The complex elements to be taken into account when dealing with unknown seismic events have been outlined; much "new" information often falls into one of the following categories: simple chronological errors relative to other well-known events; descriptions of other natural phenomena, though defined in texts as "earthquakes" (landslides, hurricanes, tornadoes, etc.; unknown tremors belonging to known seismic periods; tremors that may be connected with events which have been catalogued under incorrect dates and with very approximate estimates of location and intensity. This proves that this was not a real seismic "silence" but a research vacuum.

  5. Compensating Unknown Time-Varying Delay in Opto-Electronic Platform Tracking Servo System

    Directory of Open Access Journals (Sweden)

    Ruihong Xie

    2017-05-01

    Full Text Available This paper investigates the problem of compensating miss-distance delay in opto-electronic platform tracking servo system. According to the characteristic of LOS (light-of-sight motion, we setup the Markovian process model and compensate this unknown time-varying delay by feed-forward forecasting controller based on robust H∞ control. Finally, simulation based on double closed-loop PI (Proportion Integration control system indicates that the proposed method is effective for compensating unknown time-varying delay. Tracking experiments on the opto-electronic platform indicate that RMS (root-mean-square error is 1.253 mrad when tracking 10° 0.2 Hz signal.

  6. 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...

  7. Solving differential equations with unknown constitutive relations as recurrent neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Hagge, Tobias J.; Stinis, Panagiotis; Yeung, Enoch H.; Tartakovsky, Alexandre M.

    2017-12-08

    We solve a system of ordinary differential equations with an unknown functional form of a sink (reaction rate) term. We assume that the measurements (time series) of state variables are partially available, and use a recurrent neural network to “learn” the reaction rate from this data. This is achieved by including discretized ordinary differential equations as part of a recurrent neural network training problem. We extend TensorFlow’s recurrent neural network architecture to create a simple but scalable and effective solver for the unknown functions, and apply it to a fedbatch bioreactor simulation problem. Use of techniques from recent deep learning literature enables training of functions with behavior manifesting over thousands of time steps. Our networks are structurally similar to recurrent neural networks, but differ in purpose, and require modified training strategies.

  8. Modeling of load lifting process with unknown center of gravity position

    Science.gov (United States)

    Kamanin, Y. N.; Zhukov, M. I.; Panichkin, A. V.; Redelin, R. A.

    2018-03-01

    The article proposes a new type of lifting beams that allows one to lift loads where the position of the center of gravity is unknown beforehand. The benefit of implementing this type of traverse is confirmed by the high demand for this product from the industrial enterprises and lack of their availability on the market. In conducted studies, the main kinematic and dynamic dependencies of the load lifting process with an unknown position of the center of gravity were described allowing for design and verification calculations of the traverse with flexible slings and an adjustable bail to be carried out. The obtained results can be useful to engineers and employees of enterprises engaged in the design and manufacturing of the lifting equipment and scientists doing research in “Carrying and lifting machines”.

  9. Stability of Nonlinear Systems with Unknown Time-varying Feedback Delay

    Science.gov (United States)

    Chunodkar, Apurva A.; Akella, Maruthi R.

    2013-12-01

    This paper considers the problem of stabilizing a class of nonlinear systems with unknown bounded delayed feedback wherein the time-varying delay is 1) piecewise constant 2) continuous with a bounded rate. We also consider application of these results to the stabilization of rigid-body attitude dynamics. In the first case, the time-delay in feedback is modeled specifically as a switch among an arbitrarily large set of unknown constant values with a known strict upper bound. The feedback is a linear function of the delayed states. In the case of linear systems with switched delay feedback, a new sufficiency condition for average dwell time result is presented using a complete type Lyapunov-Krasovskii (L-K) functional approach. Further, the corresponding switched system with nonlinear perturbations is proven to be exponentially stable inside a well characterized region of attraction for an appropriately chosen average dwell time. In the second case, the concept of the complete type L-K functional is extended to a class of nonlinear time-delay systems with unknown time-varying time-delay. This extension ensures stability robustness to time-delay in the control design for all values of time-delay less than the known upper bound. Model-transformation is used in order to partition the nonlinear system into a nominal linear part that is exponentially stable with a bounded perturbation. We obtain sufficient conditions which ensure exponential stability inside a region of attraction estimate. A constructive method to evaluate the sufficient conditions is presented together with comparison with the corresponding constant and piecewise constant delay. Numerical simulations are performed to illustrate the theoretical results of this paper.

  10. Remaining Sites Verification Package for the 600-233 Waste Site, Vertical Pipe Near 100-B Electrical Laydown Area. Attachment to Waste Site Reclassification Form 2005-041

    International Nuclear Information System (INIS)

    Carlson, R.A.

    2005-01-01

    The 600-233 waste site consisted of three small-diameter pipelines within the 600-232 waste site, including previously unknown diesel fuel supply lines discovered during site remediation. The 600-233 waste site has been remediated to achieve the remedial action objectives specified in the Remaining Sites ROD. The results of verification sampling show that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also demonstrate that residual contaminant concentrations are protective of groundwater and the Columbia River

  11. Eddy current analysis by BEM utilizing loop electric and surface magnetic currents as unknowns

    International Nuclear Information System (INIS)

    Ishibashi, Kazuhisa

    2002-01-01

    The surface integral equations whose unknowns are the surface electric and magnetic currents are widely used in eddy current analysis. However, when the skin depth is thick, computational error is increased especially in obtaining electromagnetic fields near the edge of the conductor. In order to obtain the electromagnetic field accurately, we propose an approach to solve surface integral equations utilizing loop electric and surface magnetic currents as unknowns. (Author)

  12. Approximate Teleportation of an Unknown Atomic-Entangled State with Dissipative Atom-Cavity Resonant Jaynes-Cummings Model

    Institute of Scientific and Technical Information of China (English)

    LIU Zong-Liang; LI Shao-Hua; CHEN Chang-Yong

    2008-01-01

    We propose a scheme for approximately and conditionally teleporting an unknown atomic-entangled state in dissipative cavity QED.It is the further development of the scheme of [Phys.Rev.A 69 (2004) 064302],where the cavity mode decay has not been considered and the state teleportated is an unknown atomic state.In this paper,we investigate the influence of the decay on the approximate and conditional teleportation of the unknown atomic-entangled state,which is different from that teleportated in [Phys.Rev.A 69 (2004) 064302] and then give the fidelity of the teleportation,which depends on the cavity mode decay.The scheme may be generalized to not only the teleportation of the cavity-mode-entangled-state by means of a single atom but also the teleportation of the unknown trapped-ion-entangled-state in a linear ion trap.

  13. Searching for unknown transfusion-transmitted hepatitis viruses

    DEFF Research Database (Denmark)

    Edgren, G.; Hjalgrim, H.; Rostgaard, K.

    2018-01-01

    Background: Both hepatitis B and C viruses were transmitted through blood transfusion before implementation of donor screening. The existence of additional, yet unknown transfusion transmittable agents causing liver disease could have important public health implications. Methods: Analyses were...... 1992 to account for the effect of screening for hepatitis C virus. Results: A total of 1 482 922 transfused patients were included in the analyses. Analyses showed evidence of transfusion transmission of liver diseases before, but not after the implementation of hepatitis C virus screening in 1992...... for transfusion transmission of agents causing liver disease after the implementation of screening for hepatitis B and C, and suggest that if such transmission does occur, it is rare....

  14. Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction.

    Science.gov (United States)

    Boiteau, Rene M; Hoyt, David W; Nicora, Carrie D; Kinmonth-Schultz, Hannah A; Ward, Joy K; Bingol, Kerem

    2018-01-17

    We introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS²), and NMR into 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 out 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 to the 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.

  15. Pragmatic application of the precautionary principle to deal with unknown safety challenges

    Energy Technology Data Exchange (ETDEWEB)

    Frappier, G.; Viktorov, A., E-mail: gerry.frappier@cnsc-ccsn.gc.ca, E-mail: alex.viktorov@cnsc-ccsn.gc.ca [Canadian Nuclear Safety Commission, Ottawa, Ontario (Canada)

    2011-07-01

    Nuclear power technology has matured over a number of decades to the point where our understanding of the technology under a wide variety of circumstances is quite high. Despite this high degree of maturity, discoveries of new challenges occasionally surface. These may arise from either unusual or unexpected operational conditions or new experimental findings from ongoing research. With the early realization that such discoveries could occur, a conscious effort was made to take precautions against their negative impacts. Principles such as defence-in-depth, designing for high reliability, incorporation of robust safety margins and use of justified conservatisms are key examples of established practices that are embedded in national regulatory regimes of most, if not all countries with nuclear programs. Because of these provisions the safety cases of the current generation of reactors proved to be quite resilient to discoveries of earlier unrecognized challenges. A fundamentally important element in the management of “unknown unknowns” is a healthy research programme. Such a programme is especially necessary as a precondition for understanding potential impacts from changes in operating conditions or implementation of novel design features. A research programme helps minimizing chances of stumbling on “unknown unknowns”, and allows resolution of emerging issues to by virtue of the accumulated understanding and capability to predict challenges to safety. In the few instances when discoveries occurred with recognized negative effects on safety, these spurred changes in operating conditions, maintenance or testing practices, design modifications, as well as required targeted research projects. This paper outlines several CANDU-specific “discoveries” in the field of thermalhydraulics, illustrating past “unknown unknowns” and the actions taken to address those. The main message, however, is to point out that both the industry and the regulator should

  16. Pragmatic application of the precautionary principle to deal with unknown safety challenges

    International Nuclear Information System (INIS)

    Frappier, G.; Viktorov, A.

    2011-01-01

    Nuclear power technology has matured over a number of decades to the point where our understanding of the technology under a wide variety of circumstances is quite high. Despite this high degree of maturity, discoveries of new challenges occasionally surface. These may arise from either unusual or unexpected operational conditions or new experimental findings from ongoing research. With the early realization that such discoveries could occur, a conscious effort was made to take precautions against their negative impacts. Principles such as defence-in-depth, designing for high reliability, incorporation of robust safety margins and use of justified conservatisms are key examples of established practices that are embedded in national regulatory regimes of most, if not all countries with nuclear programs. Because of these provisions the safety cases of the current generation of reactors proved to be quite resilient to discoveries of earlier unrecognized challenges. A fundamentally important element in the management of “unknown unknowns” is a healthy research programme. Such a programme is especially necessary as a precondition for understanding potential impacts from changes in operating conditions or implementation of novel design features. A research programme helps minimizing chances of stumbling on “unknown unknowns”, and allows resolution of emerging issues to by virtue of the accumulated understanding and capability to predict challenges to safety. In the few instances when discoveries occurred with recognized negative effects on safety, these spurred changes in operating conditions, maintenance or testing practices, design modifications, as well as required targeted research projects. This paper outlines several CANDU-specific “discoveries” in the field of thermalhydraulics, illustrating past “unknown unknowns” and the actions taken to address those. The main message, however, is to point out that both the industry and the regulator should

  17. 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…

  18. Elevation of CD16+CD56+ NK-cells and down-regulation of serum interleukin-21 (IL-21) and IL-1α after splenectomy in relapsed hemophagocytic lymphohistiocytosis of unknown cause.

    Science.gov (United States)

    Wang, Jingshi; Han, Wei; Gao, Zhuo; Wang, Yini; Wu, Lin; Zhang, Jia; Lai, Wenyuan; Wang, Zhao

    2017-09-01

    Encouraging progress has been made in application of splenectomy in the treatment of relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause. The aim was to determine the roles of lymphocyte subpopulations and inflammatory cytokines in splenectomy. We retrospectively analyzed changes in lymphocyte subpopulations and levels of inflammatory cytokines at different time-points before and after splenectomy in the patients with relapsed HLH of unknown cause, as well as the correlations between these changes and the disease prognosis. During the period from June 2006 to June 2016, we enrolled 107 patients with relapsed HLH of unknown cause, of whom 29 were treated with splenectomy. Among the 29 patients, 7 cases were non-Hodgkin lymphomas based on spleen pathology, 1 case withdrew and the remaining 21 non-lymphoma cases were available for analysis. Results showed a significant increase in both percentage of CD16 + CD56 + NK cells (P = 0.003) and NK cell activity (P = 0.028) at 24 wk after splenectomy compared to their baseline pre-surgery levels. We also examined seven patients for the changes in cytokine levels before and after splenectomy and found that IL-21 and IL-1α decreased at 4 wk after splenectomy (P splenectomy had significantly longer survival (P = 0.001) compared to the 24 patients with relapsed HLH of unknown cause who were also determined as NR but not treated by splenectomy. Splenectomy can improve clinical symptoms and survival of patients with relapsed HLH of unknown cause. The mechanism is likely related to the changes in percent NK cells and cytokines (IL-21 and IL-1α) after surgery.

  19. Fever of unknown origin: prospective comparison of diagnostic value of 18F-FDG PET and 111In-granulocyte scintigraphy

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Lebech, Anne-Mette; Eigtved, Annika

    2004-01-01

    The diagnostic work-up in patients with fever of unknown origin (FUO) is often challenging and frequently includes nuclear medicine procedures. Whereas a role for leucocyte or granulocyte scintigraphy in FUO is generally accepted, a possible role of fluorine-18 fluorodeoxyglucose (FDG) positron...... emission tomography (PET) in these patients remains to be established. To study this, we compared prospectively, on a head-to-head basis, the diagnostic value of FDG-PET and indium-111 granulocyte scintigraphy in patients with FUO. Nineteen patients with FUO underwent both FDG-PET and (111)In......-granulocyte scintigraphy within 1 week. FDG-PET scans and granulocyte scintigrams were reviewed by different doctors who were blinded to the result of the other investigation. The diagnostic values of FDG-PET and granulocyte scintigraphy were evaluated with regard to identification of a focal infectious...

  20. 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.

  1. Robust adaptive fuzzy neural tracking control for a class of unknown ...

    Indian Academy of Sciences (India)

    In this paper, an adaptive fuzzy neural controller (AFNC) for a class of unknown chaotic systems is ... The robust controller is used to guarantee the stability and to control the per- ..... From the above analysis we have the following theorem:.

  2. Adaptive control of Parkinson's state based on a nonlinear computational model with unknown parameters.

    Science.gov (United States)

    Su, Fei; Wang, Jiang; Deng, Bin; Wei, Xi-Le; Chen, Ying-Yuan; Liu, Chen; Li, Hui-Yan

    2015-02-01

    The objective here is to explore the use of adaptive input-output feedback linearization method to achieve an improved deep brain stimulation (DBS) algorithm for closed-loop control of Parkinson's state. The control law is based on a highly nonlinear computational model of Parkinson's disease (PD) with unknown parameters. The restoration of thalamic relay reliability is formulated as the desired outcome of the adaptive control methodology, and the DBS waveform is the control input. The control input is adjusted in real time according to estimates of unknown parameters as well as the feedback signal. Simulation results show that the proposed adaptive control algorithm succeeds in restoring the relay reliability of the thalamus, and at the same time achieves accurate estimation of unknown parameters. Our findings point to the potential value of adaptive control approach that could be used to regulate DBS waveform in more effective treatment of PD.

  3. Building a RAPPOR with the Unknown: Privacy-Preserving Learning of Associations and Data Dictionaries

    Directory of Open Access Journals (Sweden)

    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.

  4. Ratbot automatic navigation by electrical reward stimulation based on distance measurement in unknown environments.

    Science.gov (United States)

    Gao, Liqiang; Sun, Chao; Zhang, Chen; Zheng, Nenggan; Chen, Weidong; Zheng, Xiaoxiang

    2013-01-01

    Traditional automatic navigation methods for bio-robots are constrained to configured environments and thus can't be applied to tasks in unknown environments. With no consideration of bio-robot's own innate living ability and treating bio-robots in the same way as mechanical robots, those methods neglect the intelligence behavior of animals. This paper proposes a novel ratbot automatic navigation method in unknown environments using only reward stimulation and distance measurement. By utilizing rat's habit of thigmotaxis and its reward-seeking behavior, this method is able to incorporate rat's intrinsic intelligence of obstacle avoidance and path searching into navigation. Experiment results show that this method works robustly and can successfully navigate the ratbot to a target in the unknown environment. This work might put a solid base for application of ratbots and also has significant implication of automatic navigation for other bio-robots as well.

  5. Broadly reactive pan-paramyxovirus reverse transcription polymerase chain reaction and sequence analysis for the detection of Canine distemper virus in a case of canine meningoencephalitis of unknown etiology

    Science.gov (United States)

    Schatzberg, Scott J.; Li, Qiang; Porter, Brian F.; Barber, Renee M.; Claiborne, Mary Kate; Levine, Jonathan M.; Levine, Gwendolyn J.; Israel, Sarah K.; Young, Benjamin D.; Kiupel, Matti; Greene, Craig; Ruone, Susan; Anderson, Larry; Tong, Suxiang

    2016-01-01

    Despite the immunologic protection associated with routine vaccination protocols, Canine distemper virus (CDV) remains an important pathogen of dogs. Antemortem diagnosis of systemic CDV infection may be made by reverse transcription polymerase chain reaction (RT-PCR) and/or immunohistochemical testing for CDV antigen; central nervous system infection often requires postmortem confirmation via histopathology and immunohistochemistry. An 8-month-old intact male French Bulldog previously vaccinated for CDV presented with multifocal neurologic signs. Based on clinical and postmortem findings, the dog’s disease was categorized as a meningoencephalitis of unknown etiology. Broadly reactive, pan-paramyxovirus RT-PCR using consensus-degenerate hybrid oligonucleotide primers, combined with sequence analysis, identified CDV amplicons in the dog’s brain. Immunohistochemistry confirmed the presence of CDV antigens, and a specific CDV RT-PCR based on the phosphoprotein gene identified a wild-type versus vaccinal virus strain. This case illustrates the utility of broadly reactive PCR and sequence analysis for the identification of pathogens in diseases with unknown etiology. PMID:19901287

  6. Accessory papillary muscles and papillary muscle hypertrophy are associated with sudden cardiac arrest of unknown cause.

    Science.gov (United States)

    Uhm, Jae-Sun; Youn, Jong-Chan; Lee, Hye-Jeong; Park, Junbeom; Park, Jin-Kyu; Shim, Chi Young; Hong, Geu-Ru; Joung, Boyoung; Pak, Hui-Nam; Lee, Moon-Hyoung

    2015-10-15

    The present study was performed for elucidating the associations between the morphology of the papillary muscles (PMs) and sudden cardiac arrest (SCA). We retrospectively reviewed history, laboratory data, electrocardiography, echocardiography, coronary angiography, and cardiac CT/MRI for 190 patients with SCA. The prevalence of accessory PMs and PM hypertrophy in patients with SCA of unknown cause was compared with that in patients with SCA of known causes and 98 age- and sex-matched patients without SCA. An accessory PM was defined as a PM with origins separated from the anterolateral and posteromedial PMs, or a PM that branched into two or three bellies at the base of the anterolateral or posteromedial PM. PM hypertrophy was defined as at least one of the two PMs having a diameter of ≥1.1cm. In 49 patients (age 49.9±15.9years; 38 men) the cause of SCA was unknown, whereas 141 (age 54.2±16.6years; 121 men) had a known cause. The prevalence of accessory PMs was significantly higher in the unknown-cause group than in the known-cause group (24.5% and 7.8%, respectively; p=0.002) or the no-SCA group (7.1%, p=0.003). The same was true for PM hypertrophy (unknown-cause 12.2%, known-cause 2.1%, p=0.010; no SCA group 1.0%, p=0.006). By logistic regression, accessory PM and PM hypertrophy were independently associated with sudden cardiac arrest of unknown cause. An accessory PM and PM hypertrophy are associated with SCA of unknown cause. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Biomarkers for Ectopic Pregnancy and Pregnancy of Unknown Location

    OpenAIRE

    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...

  8. 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

  9. Scrapie prion liposomes and rods exhibit target sizes of 55,000 Da

    International Nuclear Information System (INIS)

    Bellinger-Kawahara, C.G.; Kempner, E.; Groth, D.; Gabizon, R.; Prusiner, S.B.

    1988-01-01

    Scrapie is a degenerative neurologic disease in sheep and goats which can be experimentally transmitted to laboratory rodents. Considerable evidence suggests that the scrapie agent is composed largely, if not entirely, of an abnormal isoform of the prion protein (PrPSc). Inactivation of scrapie prions by ionizing radiation exhibited single-hit kinetics and gave a target size of 55,000 +/- 9000 mol wt. The inactivation profile was independent of the form of the prion. Scrapie agent infectivity in brain homogenates, microsomal fractions, detergent-extracted microsomes, purified amyloid rods, and liposomes exhibited the same inactivation profile. Our data are consistent with the hypothesis that the infectious particle causing scrapie contains approximately 2 PrPSc molecules

  10. Long Valley Caldera-Mammoth Mountain unrest: The knowns and unknowns

    Science.gov (United States)

    Hill, David P.

    2017-01-01

    This perspective is based largely on my study of the Long Valley Caldera (California, USA) over the past 40 years. Here, I’ll examine the “knowns” and the “known unknowns” of the complex tectonic–magmatic system of the Long Valley Caldera volcanic complex. I will also offer a few brief thoughts on the “unknown unknowns” of this system.

  11. Metastatic Carcinoma of Unknown Primary Presenting as Jugular Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Prince Cheriyan Modayil

    2009-01-01

    Full Text Available Jugular venous thrombosis is unusual and is associated with central venous catheterisation, intravenous drug abuse and head and neck sepsis. It is rarely associated with malignancy. We report a case of metastatic carcinoma of unknown primary in a forty year old female which presented with jugular venous thrombosis. The discussion includes investigation and treatment options for this condition.

  12. Four Unknown Prison Poems by H. C. Bosman | MacKenzie ...

    African Journals Online (AJOL)

    Four Unknown Prison Poems by H. C. Bosman. C MacKenzie. Abstract. No Abstract. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/eia.v40i2.1 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

  13. Use of Medicines with Unknown Fetal Risk among Parturient Women from the 2004 Pelotas Birth Cohort (Brazil

    Directory of Open Access Journals (Sweden)

    Andréa Dâmaso Bertoldi

    2012-01-01

    Full Text Available Background. To estimate the exposure to medicines with unknown fetal risk during pregnancy and to analyze the maternal characteristics associated with it. Methods. A questionnaire was administered to 4,189 mothers of children belonging to the 2004 Pelotas (Brazil birth cohort study about use of any medicine during gestation. We evaluated the associations between use of medicines with unknown fetal risk and the independent variables through logistic regression models. Unknown fetal risk was defined as medicines in which studies in animals have revealed adverse effects on the fetus, and no controlled studies in women, or studies in women and animals, are available. Results. Out of the 4,189 women, 52.5% used at least one medicine from unknown fetal risk. Use of these medicines was associated with white skin color, high schooling, high income, six or more antenatal care consultations, hospital admission during pregnancy, and morbidity during gestation. Conclusion. The use of unknown fetal risk medicines is high, suggesting that their use must be addressed with caution with the aim of restricting their use to cases in which the benefits are greater than the potential risks.

  14. General methods for modified projective synchronization of hyperchaotic systems with known or unknown parameters

    Science.gov (United States)

    Tang, Yang; Fang, Jian-an

    2008-03-01

    This work is concerned with the general methods for modified projective synchronization of hyperchaotic systems. A systematic method of active control is developed to synchronize two hyperchaotic systems with known parameters. Moreover, by combining the adaptive control and linear feedback methods, general sufficient conditions for the modified projective synchronization of identical or different chaotic systems with fully unknown or partially unknown parameters are presented. Meanwhile, the speed of parameters identification can be regulated by adjusting adaptive gain matrix. Numerical simulations verify the effectiveness of the proposed methods.

  15. 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....

  16. Remaining Sites Verification Package for the 1607-B1 Septic System. Attachment to Waste Site Reclassification Form 2007-015

    International Nuclear Information System (INIS)

    Dittmer, L.M.

    2007-01-01

    The 1607-B1 Septic System includes a septic tank, drain field, and associated connecting pipelines and influent sanitary sewer lines. This septic system serviced the former 1701-B Badgehouse, 1720-B Patrol Building/Change Room, and the 1709-B Fire Headquarters. The 1607-B1 waste site received unknown amounts of nonhazardous, nonradioactive sanitary sewage from these facilities during its operational history from 1944 to approximately 1970. In accordance with this evaluation, the confirmatory sampling results support a reclassification of this site to No Action. The current site conditions achieve the remedial action objectives and the corresponding remedial action goals established in the Remaining Sites ROD. The results of confirmatory sampling show that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also demonstrate that residual contaminant concentrations are protective of groundwater and the Columbia River

  17. Saliency-Guided Detection of Unknown Objects in RGB-D Indoor Scenes.

    Science.gov (United States)

    Bao, Jiatong; Jia, Yunyi; Cheng, Yu; Xi, Ning

    2015-08-27

    This paper studies the problem of detecting unknown objects within indoor environments in an active and natural manner. The visual saliency scheme utilizing both color and depth cues is proposed to arouse the interests of the machine system for detecting unknown objects at salient positions in a 3D scene. The 3D points at the salient positions are selected as seed points for generating object hypotheses using the 3D shape. We perform multi-class labeling on a Markov random field (MRF) over the voxels of the 3D scene, combining cues from object hypotheses and 3D shape. The results from MRF are further refined by merging the labeled objects, which are spatially connected and have high correlation between color histograms. Quantitative and qualitative evaluations on two benchmark RGB-D datasets illustrate the advantages of the proposed method. The experiments of object detection and manipulation performed on a mobile manipulator validate its effectiveness and practicability in robotic applications.

  18. Performance study of LMS based adaptive algorithms for unknown system identification

    Energy Technology Data Exchange (ETDEWEB)

    Javed, Shazia; Ahmad, Noor Atinah [School of Mathematical Sciences, Universiti Sains Malaysia, 11800 Penang (Malaysia)

    2014-07-10

    Adaptive filtering techniques have gained much popularity in the modeling of unknown system identification problem. These techniques can be classified as either iterative or direct. Iterative techniques include stochastic descent method and its improved versions in affine space. In this paper we present a comparative study of the least mean square (LMS) algorithm and some improved versions of LMS, more precisely the normalized LMS (NLMS), LMS-Newton, transform domain LMS (TDLMS) and affine projection algorithm (APA). The performance evaluation of these algorithms is carried out using adaptive system identification (ASI) model with random input signals, in which the unknown (measured) signal is assumed to be contaminated by output noise. Simulation results are recorded to compare the performance in terms of convergence speed, robustness, misalignment, and their sensitivity to the spectral properties of input signals. Main objective of this comparative study is to observe the effects of fast convergence rate of improved versions of LMS algorithms on their robustness and misalignment.

  19. Performance study of LMS based adaptive algorithms for unknown system identification

    International Nuclear Information System (INIS)

    Javed, Shazia; Ahmad, Noor Atinah

    2014-01-01

    Adaptive filtering techniques have gained much popularity in the modeling of unknown system identification problem. These techniques can be classified as either iterative or direct. Iterative techniques include stochastic descent method and its improved versions in affine space. In this paper we present a comparative study of the least mean square (LMS) algorithm and some improved versions of LMS, more precisely the normalized LMS (NLMS), LMS-Newton, transform domain LMS (TDLMS) and affine projection algorithm (APA). The performance evaluation of these algorithms is carried out using adaptive system identification (ASI) model with random input signals, in which the unknown (measured) signal is assumed to be contaminated by output noise. Simulation results are recorded to compare the performance in terms of convergence speed, robustness, misalignment, and their sensitivity to the spectral properties of input signals. Main objective of this comparative study is to observe the effects of fast convergence rate of improved versions of LMS algorithms on their robustness and misalignment

  20. State, Parameter, and Unknown Input Estimation Problems in Active Automotive Safety Applications

    Science.gov (United States)

    Phanomchoeng, Gridsada

    A variety of driver assistance systems such as traction control, electronic stability control (ESC), rollover prevention and lane departure avoidance systems are being developed by automotive manufacturers to reduce driver burden, partially automate normal driving operations, and reduce accidents. The effectiveness of these driver assistance systems can be significant enhanced if the real-time values of several vehicle parameters and state variables, namely tire-road friction coefficient, slip angle, roll angle, and rollover index, can be known. Since there are no inexpensive sensors available to measure these variables, it is necessary to estimate them. However, due to the significant nonlinear dynamics in a vehicle, due to unknown and changing plant parameters, and due to the presence of unknown input disturbances, the design of estimation algorithms for this application is challenging. This dissertation develops a new approach to observer design for nonlinear systems in which the nonlinearity has a globally (or locally) bounded Jacobian. The developed approach utilizes a modified version of the mean value theorem to express the nonlinearity in the estimation error dynamics as a convex combination of known matrices with time varying coefficients. The observer gains are then obtained by solving linear matrix inequalities (LMIs). A number of illustrative examples are presented to show that the developed approach is less conservative and more useful than the standard Lipschitz assumption based nonlinear observer. The developed nonlinear observer is utilized for estimation of slip angle, longitudinal vehicle velocity, and vehicle roll angle. In order to predict and prevent vehicle rollovers in tripped situations, it is necessary to estimate the vertical tire forces in the presence of unknown road disturbance inputs. An approach to estimate unknown disturbance inputs in nonlinear systems using dynamic model inversion and a modified version of the mean value theorem is

  1. Group prioritisation with unknown expert weights in incomplete linguistic context

    Science.gov (United States)

    Cheng, Dong; Cheng, Faxin; Zhou, Zhili; Wang, Juan

    2017-09-01

    In this paper, we study a group prioritisation problem in situations when the expert weights are completely unknown and their judgement preferences are linguistic and incomplete. Starting from the theory of relative entropy (RE) and multiplicative consistency, an optimisation model is provided for deriving an individual priority vector without estimating the missing value(s) of an incomplete linguistic preference relation. In order to address the unknown expert weights in the group aggregating process, we define two new kinds of expert weight indicators based on RE: proximity entropy weight and similarity entropy weight. Furthermore, a dynamic-adjusting algorithm (DAA) is proposed to obtain an objective expert weight vector and capture the dynamic properties involved in it. Unlike the extant literature of group prioritisation, the proposed RE approach does not require pre-allocation of expert weights and can solve incomplete preference relations. An interesting finding is that once all the experts express their preference relations, the final expert weight vector derived from the DAA is fixed irrespective of the initial settings of expert weights. Finally, an application example is conducted to validate the effectiveness and robustness of the RE approach.

  2. 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.

  3. Hyperfamiliarity for unknown faces after left lateral temporo-occipital venous infarction: a double dissociation with prosopagnosia.

    Science.gov (United States)

    Vuilleumier, Patrik; Mohr, Christine; Valenza, Nathalie; Wetzel, Corinne; Landis, Theodor

    2003-04-01

    Right hemisphere dominance in face processing is well established and unilateral right inferior temporo-occipital damage can result in prosopagnosia. Here, we describe a 21-year-old right-handed woman with acute impairment in face recognition that selectively concerned unfamiliar faces, following a focal left lateral temporo-occipital venous infarct. She was severely impaired in discerning that unknown people seen in everyday life were unfamiliar, although she had no difficulty recognizing familiar people. Thus, she had no prosopagnosia, but abnormal 'hyperfamiliarity' for unknown faces. Her difficulty was not accompanied by delusions or deficits in discrimination, identification or memory for faces. Standard neuropsychological testing showed that her recognition of familiar faces was entirely normal. By contrast, her sense of personally knowing faces was severely impaired when unknown faces evoked weak signals of familiarity based on spurious cues, to the extent that she would misattribute fame to faces that were unknown but to which she had been incidentally exposed on a prior occasion. Priming experiments also revealed that, unlike normal subjects, she made familiarity judgements without accessing semantic identity representations. Moreover, in face recognition tests, she generally showed bias in that she relied more on right-hemisphere strategies to identify global traits and less on left-hemisphere processes compared with healthy subjects. This case provides novel evidence for a differential contribution of the two hemispheres to face recognition. Hyperfamiliarity for unknown faces might arise from an imbalance between reciprocal hemispheric functions in face recognition, with relative hypoactivation of left hemisphere processes but hyperactivation of right-hemisphere processes for retrieving stored associations about people, linking seen faces to representations of affective and personal relevance. Hence, abnormal bias in attributing some personal meaning to

  4. 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.

  5. Detection of unknown primary neuroendocrine tumours (CUP-NET) using {sup 68}Ga-DOTA-NOC receptor PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Vikas; Baum, Richard P. [Zentralklinik Bad Berka, Department of Nuclear Medicine and Centre for PET/CT, Bad Berka (Germany); Ambrosini, Valentina; Fanti, Stefano [University of Bologna, Nuclear Medicine Unit, Policlinico S. Orsola-Malpighi, Bologna (Italy); Hommann, Merten [Zentralklinik Bad Berka, Department of General and Visceral Surgery, Bad Berka (Germany); Hoersch, Dieter [Zentralklinik Bad Berka, Department of Internal Medicine/Gastroenterology, Oncology and Endocrinology, Bad Berka (Germany)

    2010-01-15

    This bi-centric study aimed to determine the role of receptor PET/CT using {sup 68}Ga-DOTA-NOC in the detection of undiagnosed primary sites of neuroendocrine tumours (NETs) and to understand the molecular behaviour of the primarily undiagnosed tumours. Overall 59 patients (33 men and 26 women, age: 65 {+-} 9 years) with documented NET and unknown primary were enrolled. PET/CT was performed after injection of approximately 100 MBq (46-260 MBq) of {sup 68}Ga-DOTA-NOC. The maximum standardised uptake values (SUV{sub max}) were calculated and compared with SUV{sub max} in known pancreatic NET (pNET) and ileum/jejunum/duodenum (SI-NET). The results of PET/CT were also correlated with CT alone. In 35 of 59 patients (59%), {sup 68}Ga-DOTA-NOC PET/CT localised the site of the primary: ileum/jejunum (14), pancreas (16), rectum/colon (2), lungs (2) and paraganglioma (1). CT alone (on retrospective analyses) confirmed the findings in 12 of 59 patients (20%). The mean SUV{sub max} of identified previously unknown pNET and SI-NET were 18.6 {+-} 9.8 (range: 7.8-34.8) and 9.1 {+-} 6.0 (range: 4.2-27.8), respectively. SUV{sub max} in patients with previously known pNET and SI-NET were 26.1 {+-} 14.5 (range: 8.7-42.4) and 11.3 {+-} 3.7 (range: 5.6-17.9). The SUV{sub max} of the unknown pNET and SI-NET were significantly lower (p < 0.05) as compared to the ones with known primary tumour sites; 19% of the patients had high-grade and 81% low-grade NET. Based on {sup 68}Ga-DOTA-NOC receptor PET/CT, 6 of 59 patients were operated and the primary was removed (4 pancreatic, 1 ileal and 1 rectal tumour) resulting in a management change in approximately 10% of the patients. In the remaining 29 patients, because of the far advanced stage of the disease (due to distant metastases), the primary tumours were not operated. Additional histopathological sampling was available from one patient with bronchial carcinoid (through bronchoscopy). Our data indicate that {sup 68}Ga-DOTA-NOC PET/CT is

  6. Active fault tolerance control of a wind turbine system using an unknown input observer with an actuator fault

    Directory of Open Access Journals (Sweden)

    Li Shanzhi

    2018-03-01

    Full Text Available This paper proposes a fault tolerant control scheme based on an unknown input observer for a wind turbine system subject to an actuator fault and disturbance. Firstly, an unknown input observer for state estimation and fault detection using a linear parameter varying model is developed. By solving linear matrix inequalities (LMIs and linear matrix equalities (LMEs, the gains of the unknown input observer are obtained. The convergence of the unknown input observer is also analysed with Lyapunov theory. Secondly, using fault estimation, an active fault tolerant controller is applied to a wind turbine system. Finally, a simulation of a wind turbine benchmark with an actuator fault is tested for the proposed method. The simulation results indicate that the proposed FTC scheme is efficient.

  7. 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.

  8. Algorithms for Rapidly Dispersing Robot Swarms in Unknown Environments

    OpenAIRE

    Hsiang, Tien-Ruey; Arkin, Esther M.; Bender, Michael; Fekete, Sandor P.; Mitchell, Joseph S. B.

    2002-01-01

    We develop and analyze algorithms for dispersing a swarm of primitive robots in an unknown environment, R. The primary objective is to minimize the makespan, that is, the time to fill the entire region. An environment is composed of pixels that form a connected subset of the integer grid. There is at most one robot per pixel and robots move horizontally or vertically at unit speed. Robots enter R by means of k>=1 door pixels Robots are primitive finite automata, only having local communicatio...

  9. Regulating the unknown: Managing the occupational health risks of nanomedical technologies and nanopharmaceuticals in the research laboratory

    Science.gov (United States)

    Ersin, Ozlem Hacer

    Novel technologies and their resultant products demand fresh ways of thinking about pre-market risk analysis and post-market surveillance. A regulatory framework that is responsive to emerging knowledge about the hazards of novel technologies offers repeatable and transparent processes and remains economically and socially feasible. Workers are an especially vulnerable population who are exposed to unknown hazards of novel technologies and serve often as unwitting sentinels of impending risks. This Grounded Theory-based case study identifies gaps in our current ability to regulate novel technologies so as to minimize occupational health risks and offers necessary modifications for an environment that is conducive to proper regulation. Nanopharmaceuticals and the nano-based technologies at their base are used by way of exemplar technologies that are currently taxing the ability of the regulatory system to provide adequate oversight. Ambiguities of definition, absence of a tracking system (of who is doing nanotechnology research), and the paucity of scientific evidence to support risk management efforts are among the findings of the study and need to be addressed as ameliorative steps toward an effective regulatory structure.

  10. The Annuity Puzzle Remains a Puzzle

    NARCIS (Netherlands)

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

    We examine incomplete annuity menus and background 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 irrespective of whether real or

  11. The energy equation with three unknowns

    International Nuclear Information System (INIS)

    Schifano, Fabio; Moriconi, Daniele

    2008-01-01

    This article discusses the alarming situation of energy in Italy as this country depends at 82 per cent on its imports (oil, natural gas and electricity), a dependence which could even increase. The authors first propose overviews of the situation regarding oil, natural gas and electric power (origins of imports, role of Italian companies, status of infrastructures), and also briefly of renewable energies. They recall the history of the use of nuclear energy: Italy has been one of the first country to use nuclear energy to produce electric power, but a referendum organised after Chernobyl resulted in phasing out nuclear. Then, the authors discuss perspectives associated with three main strategic unknowns: an increase of energy dependence with respect to hydrocarbons and to foreign nuclear power, a supply insecurity due to a dependence concentrated on a small number of countries (notably as far as natural gas is concerned), and an increasing interdependence between economic growth and sustainable development (the reduction of greenhouse emissions is a prevailing parameter for future energetic choices)

  12. RSS-based localization of isotropically decaying source with unknown power and pathloss factor

    International Nuclear Information System (INIS)

    Sun, Shunyuan; Sun, Li; Ding, Zhiguo

    2016-01-01

    This paper addresses the localization of an isotropically decaying source based on the received signal strength (RSS) measurements that are collected from nearby active sensors that are position-known and wirelessly connected, and it propose a novel iterative algorithm for RSS-based source localization in order to improve the location accuracy and realize real-time location and automatic monitoring for hospital patients and medical equipment in the smart hospital. In particular, we consider the general case where the source power and pathloss factor are both unknown. For such a source localization problem, we propose an iterative algorithm, in which the unknown source position and two other unknown parameters (i.e. the source power and pathloss factor) are estimated in an alternating way based on each other, with our proposed sub-optimum initial estimate on source position obtained based on the RSS measurements that are collected from a few (closest) active sensors with largest RSS values. Analysis and simulation study show that our proposed iterative algorithm guarantees globally convergence to the least-squares (LS) solution, where for our suitably assumed independent and identically distributed (i.i.d.) zero-mean Gaussian RSS measurement errors the converged localization performance achieves the optimum that corresponds to the Cramer–Rao lower bound (CRLB).

  13. Problems of determination of principle of psychological profile of unknown criminal person in investigational activity

    Directory of Open Access Journals (Sweden)

    Galina Getman

    2017-03-01

    By the author of the article of analysis different determinations of «psychological profile of unknown criminal person» were subjected. They are set positive lines and separate positions that in opinion of author are not expedient and important are subjected to criticism. That is why, the author points in conclusions the argued positions in relation to the necessity of the use of psychological profile of  unknown criminal person during investigation of criminal realizations in activity of investigator.

  14. 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.

  15. An Evidence-Based Review Literature About Risk Indicators and Management of Unknown-Origin Xerostomia

    Directory of Open Access Journals (Sweden)

    Farzaneh Agha-hosseini

    2013-01-01

    Full Text Available Objective: This evidence-based article reviews risk indicators and management of unknown-origin xerostomia. Xerostomia and hyposalivation refer to different aspects of dry mouth. Xerostomia is a subjective sensation of dry mouth, whilst hyposalivation is defined as an objective assessment of reduced salivary flow rate. About 30% of the elderly (65 years and older experience xerostomia and hyposalivation. Structural and functional factors, or both may lead to salivary gland dysfunction.Study Selection: The EBM literature search was conducted by using the medical literature database MEDLINE via PubMed and OvidMedline search engines. Results were limited to English language articles (1965 to present including clinical trials (CT, randomized controlled trials (RCT, systematic reviews and review articles. Case control or cohort studies were included for the etiology.Results: Neuropathic etiology such as localized oral alteration of thermal sensations, saliva composition change (for example higher levels of K, Cl, Ca, IgA, amylase, calcium, PTH and cortisol, lower levels of estrogen and progesterone, smaller salivary gland size, and illnesses such as lichen planus, are risk indicators for unknown-origin xerostomia. The management is palliative and preventative. Management of symptoms includes drug administration (systemic secretogogues, saliva substitutes and bile secretion-stimulator, night guard, diet and habit modifications. Other managements may be indicated to treat adverse effects.Conclusion: Neuropathic etiology, saliva composition change, smaller salivary gland size, and illnesses such as oral lichen planus can be suggestive causes for unknown-origin xerostomia. However, longitudinal studies will be important to elucidate the causes of unknown-origin xerostomia.

  16. Comparative study of methods for recognition of an unknown person's action from a video sequence

    Science.gov (United States)

    Hori, Takayuki; Ohya, Jun; Kurumisawa, Jun

    2009-02-01

    This paper proposes a Tensor Decomposition Based method that can recognize an unknown person's action from a video sequence, where the unknown person is not included in the database (tensor) used for the recognition. The tensor consists of persons, actions and time-series image features. For the observed unknown person's action, one of the actions stored in the tensor is assumed. Using the motion signature obtained from the assumption, the unknown person's actions are synthesized. The actions of one of the persons in the tensor are replaced by the synthesized actions. Then, the core tensor for the replaced tensor is computed. This process is repeated for the actions and persons. For each iteration, the difference between the replaced and original core tensors is computed. The assumption that gives the minimal difference is the action recognition result. For the time-series image features to be stored in the tensor and to be extracted from the observed video sequence, the human body silhouette's contour shape based feature is used. To show the validity of our proposed method, our proposed method is experimentally compared with Nearest Neighbor rule and Principal Component analysis based method. Experiments using 33 persons' seven kinds of action show that our proposed method achieves better recognition accuracies for the seven actions than the other methods.

  17. Robust adaptive fuzzy neural tracking control for a class of unknown ...

    Indian Academy of Sciences (India)

    In this paper, an adaptive fuzzy neural controller (AFNC) for a class of unknown chaotic systems is proposed. The proposed AFNC is comprised of a fuzzy neural controller and a robust controller. The fuzzy neural controller including a fuzzy neural network identifier (FNNI) is the principal controller. The FNNI is used for ...

  18. 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…

  19. Selective angiographic diagnosis of unknown reason gastrointestinal hemorrhage: correlation with pathology

    International Nuclear Information System (INIS)

    Xi Jiayuan; Lu Liang; Deng Gang

    2001-01-01

    Objective: To evaluate the diagnostic value of selective angiography for unknown reason gastrointestinal hemorrhage. Methods: 32 patients with acute or chronic gastrointestinal recurrent hemorrhage were examined. Among them, 26 patients had upper gastrointestinal hemorrhage and 6 with inferior gastrointestinal hemorrhage. All patients were under gone DSA and/or Puck angiography with Seldinger's technique. Results: The accuracy of localization was 84.38% (27/32) and the coincident rates with the operation or pathology was 78.95%(15/19). In all of patients, tumor of 9 case were shown and 15 cases of vascular diseases, namely, 9 with vascular malformation, 2 with small intestinal aneurysm, 3 with arteriosclerosis and 1 with broken gallbladder aneurysm; 3 cases of ulcer or nonspecific inflammation and 5 cases were negative. 23 cases (71.87%) showed the direct hemorrhagic sign, namely the contrast media extra vacation. Conclusions: Selective angiography is very helpful for determining the location and the character of unknown reasoned acute or chronic gastrointestinal hemorrhage, especially for the hemorrhage of the small intestine and biliary tracts

  20. Forensically Important Blow Flies Chrysomya pinguis, C. villeneuvi, and Lucilia porphyrina (Diptera: Calliphoridae) in a Case of Human Remains in Thailand

    Science.gov (United States)

    Monum, Tawatchai; Sukontason, Kabkaew L.; Sribanditmongkol, Pongruk; Sukontason, Kom; Samerjai, Chutharat; Limsopatham, Kwankamol; Suwannayod, Suttida; Klong-klaew, Tunwadee; Wannasan, Anchalee

    2017-01-01

    This is the first study to report Chrysomya pinguis (Walker) and Lucilia porphyrina (Walker) (Diptera: Calliphoridae) as forensically important blow fly species from human cadavers in Thailand, in addition to Chrysomya villeneuvi (Patton) already known in Thailand. In 2016, a fully decomposed body of an unknown adult male was discovered in a high mountainous forest during winter in Chiang Mai province. The remains were infested heavily with thousands of blow fly larvae feeding simultaneously on them. Morphological identification of adults reared from the larvae, and molecular analysis based on sequencing of 1,247 bp partial mitochondrial cytochrome c oxidase subunit 1 gene (CO1) of the larvae and puparia, confirmed the above mentioned 3 species. The approving forensic fly evidence by molecular approach was described for the first time in Thailand. Moreover, neighbor-joining phylogenetic analysis of the CO1 was performed to compare the relatedness of the species, thereby affirming the accuracy of identification. As species of entomofauna varies among cases in different geographic and climatic circumstances, C. pinguis and L. porphyrina were added to the list of Thai forensic entomology caseworks, including colonizers of human remains in open, high mountainous areas during winter. Further research should focus on these 3 species, for which no developmental data are currently available. PMID:28285509

  1. Dose uncertainties associated with a set density override of unknown hip prosthetic composition.

    Science.gov (United States)

    Rijken, James D; Colyer, Christopher J

    2017-09-01

    The dosimetric uncertainties associated with radiotherapy through hip prostheses while overriding the implant to a set density within the TPS has not yet been reported. In this study, the uncertainty in dose within a PTV resulting from this planning choice was investigated. A set of metallic hip prosthetics (stainless steel, titanium, and two different Co-Cr-Mo alloys) were CT scanned in a water bath. Within the TPS, the prosthetic pieces were overridden to densities between 3 and 10 g/cm 3 and irradiated on a linear accelerator. Measured dose maps were compared to the TPS to determine which density was most appropriate to override each metal. This was shown to be in disagreement with the reported literature values of density which was attributed to the TPS dose calculation algorithm and total mass attenuation coefficient differences in water and metal. The dose difference was then calculated for a set density override of 6 g/cm 3 in the TPS and used to estimate the dose uncertainty beyond the prosthesis. For beams passing through an implant, the dosimetric uncertainty in regions of the PTV may be as high as 10% if the implant composition remains unknown and a set density override is used. These results highlight limitations of such assumptions and the need for careful consideration by radiation oncologist, therapist, and physics staff. © 2017 Adelaide Radiotherapy Centre. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  2. Self-guided method to search maximal Bell violations for unknown quantum states

    Science.gov (United States)

    Yang, Li-Kai; Chen, Geng; Zhang, Wen-Hao; Peng, Xing-Xiang; Yu, Shang; Ye, Xiang-Jun; Li, Chuan-Feng; Guo, Guang-Can

    2017-11-01

    In recent decades, a great variety of research and applications concerning Bell nonlocality have been developed with the advent of quantum information science. Providing that Bell nonlocality can be revealed by the violation of a family of Bell inequalities, finding maximal Bell violation (MBV) for unknown quantum states becomes an important and inevitable task during Bell experiments. In this paper we introduce a self-guided method to find MBVs for unknown states using a stochastic gradient ascent algorithm (SGA), by parametrizing the corresponding Bell operators. For three investigated systems (two qubit, three qubit, and two qutrit), this method can ascertain the MBV of general two-setting inequalities within 100 iterations. Furthermore, we prove SGA is also feasible when facing more complex Bell scenarios, e.g., d -setting d -outcome Bell inequality. Moreover, compared to other possible methods, SGA exhibits significant superiority in efficiency, robustness, and versatility.

  3. Mean--variance portfolio optimization when means and covariances are unknown

    OpenAIRE

    Tze Leung Lai; Haipeng Xing; Zehao Chen

    2011-01-01

    Markowitz's celebrated mean--variance portfolio optimization theory assumes that the means and covariances of the underlying asset returns are known. In practice, they are unknown and have to be estimated from historical data. Plugging the estimates into the efficient frontier that assumes known parameters has led to portfolios that may perform poorly and have counter-intuitive asset allocation weights; this has been referred to as the "Markowitz optimization enigma." After reviewing differen...

  4. Anticipated Guilt as Behavioral Motivation: An Examination of Appeals to Help Unknown Others through Bone Marrow Donation

    Science.gov (United States)

    Lindsey, Lisa L. Massi

    2005-01-01

    The current study posits that messages used to elicit behaviors to help unknown others must present substantial perceptions of a threat and efficacy to be successful. Given that many prosocial helping messages depict a threat to unknown others, the current investigation proposed that anticipated guilt is a motivating force behind individuals'…

  5. 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.

  6. 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.

  7. Children with hypercholesterolemia of unknown cause: Value of genetic risk scores.

    Science.gov (United States)

    Sjouke, Barbara; Tanck, Michael W T; Fouchier, Sigrid W; Defesche, Joep C; Hutten, Barbara A; Wiegman, Albert; Kastelein, John J P; Hovingh, G Kees

    2016-01-01

    Familial hypercholesterolemia (FH) is caused by mutations in LDLR, APOB, or PCSK9, and in a previous study, we identified a causative mutation in these FH genes in 95% (255 of 269) of children with the FH phenotype. It has been hypothesized that a polygenic form of hypercholesterolemia is present in FH patients in whom no mutation is identified in the 3 FH genes. To address whether a polygenic form of hypercholesterolemia, defined as high-weighted effect of low-density lipoprotein cholesterol (LDL-C) raising SNPs expressed as the genetic risk score (GRS), is present in the remaining 14 children. On reassessment of the molecular diagnosis and clinical phenotype, 8 FH kindreds met the criteria for hypercholesterolemia of unknown cause and were included in this study. We calculated a weighted GRS comprising 10 established LDL-C-associated SNPs and the APOE genotype in these index cases and evaluated whether the index cases were characterized by an increased GRS compared to 26 first-degree relatives. Phenotypically affected and unaffected individuals could not be distinguished based on any of the risk scores. In this and our previous study, we show that a causal mutation in LDLR, APOB, and PCSK9 can be identified in almost all children with a definite clinical diagnosis of FH. In the small group of patients without a mutation, we did not observe a higher GRS compared with unaffected relatives, which suggests that the FH phenotype is not caused by the aggregate of LDL-C increasing SNPs. Our data imply that application of the GRS is not instrumental as a diagnostic tool to individually define clinically diagnosed FH patients with polygenic hypercholesterolemia in our study population. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Identification of unknown sample using NAA, EDXRF, XRD techniques

    International Nuclear Information System (INIS)

    Dalvi, Aditi A.; Swain, K.K.; Chavan, Trupti; Remya Devi, P.S.; Wagh, D.N.; Verma, R.

    2015-01-01

    Analytical Chemistry Division (ACD), Bhabha Atomic Research Centre (BARC) receives samples from law enforcement agencies such as Directorate of Revenue Intelligence, Customs for analysis. Five unknown grey powdered samples were received for identification and were suspected to be Iridium (Ir). Identification of unknown sample is always a challenging task and suitable analytical techniques have to be judiciously utilized for arriving at the conclusion. Qualitative analysis was carried out using Jordan Valley, EX-3600 M Energy dispersive X-ray fluorescence (EDXRF) spectrometer at ACD, BARC. A SLP series LEO Si (Li) detector (active area: 30 mm 2 ; thickness: 3.5 mm; resolution: 140 eV at 5.9 keV of Mn K X-ray) was used during the measurement and only characteristic X-rays of Ir (Lα: 9.17 keV and Lβ: 10.70 keV) was seen in the X-ray spectrum. X-ray diffraction (XRD) measurement results indicated that the Ir was in the form of metal. To confirm the XRD data, neutron activation analysis (NAA) was carried out by irradiating samples and elemental standards (as comparator) in graphite reflector position of Advanced Heavy Water Reactor Critical Facility (AHWR CF) reactor, BARC, Mumbai. After suitable decay period, gamma activity measurements were carried out using 45% HPGe detector coupled to 8 k multi channel analyzer. Characteristic gamma line at 328.4 keV of the activation product 194 Ir was used for quantification of iridium and relative method of NAA was used for concentration calculations. NAA results confirmed that all the samples were Iridium metal. (author)

  10. A Retrospective Review of Forensic Odontology Reports Written by the Joint POW/MIA Accounting Command Central Identification Laboratory for Remains Identified from the Korean War.

    Science.gov (United States)

    Shiroma, Calvin Y

    2016-01-01

    As of August 2014, the Joint POW/MIA Accounting Command has identified the remains of 1980 previously unknown U.S. service members; 280 were from the Korean War. To determine the accuracy and completeness of the available antemortem (AM) dental records, a review of the AM/postmortem (AM/PM) dental record comparisons from 233 Forensic Odontology Reports written in support of remains identified from the Korean War was performed. Seventy-two AM/PM comparisons resulted in exact dental chartings while 161 contained discrepancies which were explainable. Explainable discrepancies include undocumented treatment (103), incorrectly charted third molars as missing (82), differing opinions of specific molars present/missing (20), and erroneous treatment documentation and/or misidentification of teeth present/missing (22, other than molars). Reassessment has revealed varying levels of completeness for our available AM dental records, the need to thoroughly review our computerized comparisons, adjust our comparisons to include molar pattern variations/third molars, and updating our database comparison program. Published 2015. This article is a U.S. Government work and is in the public domain in the U.S.A.

  11. SEM-EDX analysis of an unknown "known" white powder found in a shipping container from Peru

    Science.gov (United States)

    Albright, Douglas C.

    2009-05-01

    In 2008, an unknown white powder was discovered spilled inside of a shipping container of whole kernel corn during an inspection by federal inspectors in the port of Baltimore, Maryland. The container was detained and quarantined while a sample of the powder was collected and sent to a federal laboratory where it was screened using chromatography for the presence of specific poisons and pesticides with negative results. Samples of the corn kernels and the white powder were forwarded to the Food and Drug Administration, Forensic Chemistry Center for further analysis. Stereoscopic Light Microscopy (SLM), Scanning Electron Microscopy/Energy Dispersive X-ray Spectrometry (SEM/EDX), and Polarized Light Microscopy/Infrared Spectroscopy (PLM-IR) were used in the analysis of the kernels and the unknown powder. Based on the unique particle analysis by SLM and SEM as well as the detection of the presence of aluminum and phosphorous by EDX, the unknown was determined to be consistent with reacted aluminum phosphide (AlP). While commonly known in the agricultural industry, aluminum phosphide is relatively unknown in the forensic community. A history of the use and acute toxicity of this compound along with some very unique SEM/EDX analysis characteristics of aluminum phosphide will be discussed.

  12. A dynamical approach in exploring the unknown mass in the Solar system using pulsar timing arrays

    Science.gov (United States)

    Guo, Y. J.; Lee, K. J.; Caballero, R. N.

    2018-04-01

    The error in the Solar system ephemeris will lead to dipolar correlations in the residuals of pulsar timing array for widely separated pulsars. In this paper, we utilize such correlated signals, and construct a Bayesian data-analysis framework to detect the unknown mass in the Solar system and to measure the orbital parameters. The algorithm is designed to calculate the waveform of the induced pulsar-timing residuals due to the unmodelled objects following the Keplerian orbits in the Solar system. The algorithm incorporates a Bayesian-analysis suit used to simultaneously analyse the pulsar-timing data of multiple pulsars to search for coherent waveforms, evaluate the detection significance of unknown objects, and to measure their parameters. When the object is not detectable, our algorithm can be used to place upper limits on the mass. The algorithm is verified using simulated data sets, and cross-checked with analytical calculations. We also investigate the capability of future pulsar-timing-array experiments in detecting the unknown objects. We expect that the future pulsar-timing data can limit the unknown massive objects in the Solar system to be lighter than 10-11-10-12 M⊙, or measure the mass of Jovian system to a fractional precision of 10-8-10-9.

  13. Transfer of an unknown quantum state, quantum networks, and memory

    International Nuclear Information System (INIS)

    Biswas, Asoka; Agarwal, G.S.

    2004-01-01

    We present a protocol for transfer of an unknown quantum state. The protocol is based on a two-mode cavity interacting dispersively in a sequential manner with three-level atoms in the Λ configuration. We propose a scheme for quantum networking using an atomic channel. We investigate the effect of cavity decoherence in the entire process. Further, we demonstrate the possibility of an efficient quantum memory for arbitrary superposition of two modes of a cavity containing one photon

  14. Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy

    Science.gov (United States)

    Cortes, Constanza J.; Qin, Kefeng; Norstrom, Eric M.; Green, William N.; Bindokas, Vytautas P.; Mastrianni, James A.

    2013-01-01

    Prion diseases are linked to the accumulation of a misfolded isoform (PrPSc) of prion protein (PrP). Evidence suggests that lysosomes are degradation endpoints and sites of the accumulation of PrPSc. We questioned whether lysosomes participate in the early quality control of newly generated misfolded PrP. We found PrP carrying the disease-associated T182A mutation (Mut-PrP) was delivered to lysosomes in a Golgi-independent manner. Time-lapse live cell imaging revealed early formation and uptake of GFP-tagged Mut-PrP aggregates into LysoTracker labeled vesicles. Compared with Wt-PrP, Mut-PrP expression was associated with an elevation in several markers of the autophagy-lysosomal pathway, and it extensively colocalized with the autophagosome-specific marker, LC3B. In autophagy deficient (ATG5−/−) mouse embryonic fibroblasts, or in normal cells treated with the autophagy-inhibitor 3-MA, Mut-PrP colocalization with lysosomes was reduced to a similar extent. Additionally, 3-MA selectively impaired the degradation of insoluble Mut-PrP, resulting in an increase in protease-resistant PrP, whereas the induction of autophagy by rapamycin reduced it. These findings suggest that autophagy might function as a quality control mechanism to limit the accumulation of misfolded PrP that normally leads to the generation of PrPSc. PMID:24454378

  15. Comparative Study of Prions in Iatrogenic and Sporadic Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Xiao, Xiangzhu; Yuan, Jue; Qing, Liuting; Cali, Ignazio; Mikol, Jacqueline; Delisle, Marie-Bernadette; Uro-Coste, Emmanuelle; Zeng, Liang; Abouelsaad, Mai; Gazgalis, Dimitris; Martinez, Manuel Camacho; Wang, Gong-Xian; Brown, Paul; Ironside, James W.; Gambetti, Pierluigi; Kong, Qingzhong; Zou, Wen-Quan

    2014-01-01

    Differentiating iatrogenic Creutzfeldt-Jakob disease (iCJD) from sporadic CJD (sCJD) would be useful for the identification and prevention of human-to-human prion transmission. Currently, the diagnosis of iCJD depends on identification of a recognized source of contamination to which patients have been exposed, in addition to fulfilling basic requirements for the establishment of diagnosis of CJD. Attempts to identify differences in clinical manifestations, neuropathological changes and pathological prion protein (PrPSc) between iCJD and sCJD have been unsuccessful. In the present study, using a variety of more sophisticated methods including sucrose step gradient sedimentation, conformational stability immunoassay, protein misfolding cyclic amplification (PMCA), fragment-mapping, and transmission study, we show no significant differences in gel profiles, oligomeric state, conformational stability and infectivity of PrPSc between iCJD and sCJD. However, using PMCA, we find that convertibility and amplification efficiency of PrPSc is greater in iCJD than in sCJD in a polymorphism-dependent manner. Moreover, two protease-resistant PrP C-terminal fragments (termed PrP-CTF12/13) were detected in all 9 cases of sCJD but not in 6 of 8 cases of iCJD tested in this study. The use of fragment mapping- and PMCA-based assays thus provides a means to distinguish most cases of iCJD from sCJD. PMID:25419482

  16. Calculation of Unknown Preoperative K Readings in Postrefractive Surgery Patients

    Directory of Open Access Journals (Sweden)

    Nicola Rosa

    2018-01-01

    Full Text Available Purpose. To determine the unknown preoperative K readings (Kpre to be used in history-based methods, for intraocular lens (IOL power calculation in patients who have undergone myopic photorefractive keratectomy (PRK. Methods. A regression formula generated from the left eyes of 174 patients who had undergone PRK for myopia or for myopic astigmatism was compared with other methods in 168 right eyes. The Pearson index and paired t-test were utilized for statistical analysis. Results. The differences between Kpre and those obtained with the other methods were as follows: 0.61 ± 0.94 D (range: −3.94 to 2.05 D, p<0.01 subtracting the effective treatment, 0.01 ± 0.86 D (range: −2.61 to 2.34 D, p=0.82 with Rosa’s formula, −0.02 ± 1.31 D (range: −3.43 to 3.68 D, p=0.82 with the current study formula, and −0.43 ± 1.40 D (range: −3.98 to 3.12 D, p<0.01 utilizing a mean K (Km of 43.5 D. Conclusions. These formulas may permit the utilization of history-based methods, that is, the double-K method in calculating the IOL power following PRK when Kpre are unknown.

  17. Unknown grapevine genetic resources in Asturias (Spain on the edge of extinction

    Directory of Open Access Journals (Sweden)

    Paula Moreno-Sanz

    2013-12-01

    Significance and impact of the study: Considering the limited number of accessions of the unknown cultivars and the replanting of old vineyards with vines approved by Cangas Quality Wine regulations, their conservation and study is vital to provide genetic resources for potential breeding or technological purposes in the future.

  18. Robust Adaptive Neurocontrol of SISO Nonlinear Systems Preceded by Unknown Deadzone

    Directory of Open Access Journals (Sweden)

    J. Humberto Pérez-Cruz

    2012-01-01

    Full Text Available In this study, the problem of controlling an unknown SISO nonlinear system in Brunovsky canonical form with unknown deadzone input in such a way that the system output follows a specified bounded reference trajectory is considered. Based on universal approximation property of the neural networks, two schemes are proposed to handle this problem. The first scheme utilizes a smooth adaptive inverse of the deadzone. By means of Lyapunov analyses, the exponential convergence of the tracking error to a bounded zone is proven. The second scheme considers the deadzone as a combination of a linear term and a disturbance-like term. Thus, the estimation of the deadzone inverse is not required. By using a Lyapunov-like analyses, the asymptotic converge of the tracking error to a bounded zone is demonstrated. Since this control strategy requires the knowledge of a bound for an uncertainty/disturbance term, a procedure to find such bound is provided. In both schemes, the boundedness of all closed-loop signals is guaranteed. A numerical experiment shows that a satisfactory performance can be obtained by using any of the two proposed controllers.

  19. THE ANALYSIS OF PHYSICO-CHEMICAL PROPERTIES OF TWO UNKNOWN FILTER MATERIALS

    Directory of Open Access Journals (Sweden)

    Iwona Skoczko

    2016-07-01

    Full Text Available One of the most important technological processes of water treatment is the process of filtration. Scientists and producers keep on searching new filtration materials which allow for better water purification, are simple in exploitation and do not add chemical substances to the treated water. Therefore, the aim of the present study was to analyze physical and chemical parameters of two unknown porous masses X1 and X2. Such physical parameters as color, granulation, bulk density, the equivalent diameter, the coefficient of uniformity and the porosity of the material were measured and determined. Additionally, the possibility of water treatment was studied during the filtration process in the laboratory tests. Chemical parameters were examined in the water flowing through the mass, such as pH, conductivity and COD-Mn as a general indicator of the content of organic substances in the water. Both studied porous masses were characterized by uniform size of particles. But they were not efficient enough in satisfactory reduction of oxygen consumption. Mass X2 slightly better adsorbed organic substances. It was found that the tested unknown mass filter slightly increase the pH of the filtered water.

  20. Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy of unknown location.

    Science.gov (United States)

    Insogna, Iris G; Farland, Leslie V; Missmer, Stacey A; Ginsburg, Elizabeth S; Brady, Paula C

    2017-08-01

    Pregnancies of unknown location with abnormal beta-human chorionic gonadotropin trends are frequently treated as presumed ectopic pregnancies with methotrexate. Preliminary data suggest that outpatient endometrial aspiration may be an effective tool to diagnose pregnancy location, while also sparing women exposure to methotrexate. The purpose of this study was to evaluate the utility of an endometrial sampling protocol for the diagnosis of pregnancies of unknown location after in vitro fertilization. A retrospective cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles from October 2007 to September 2015 was performed; 110 patients were diagnosed with pregnancy of unknown location, defined as a positive beta-human chorionic gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and an abnormal beta-human chorionic gonadotropin trend (location, failed intrauterine pregnancy was diagnosed in 46 patients (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical variables that included fresh or frozen embryo transfer, day of embryo transfer, serum beta-human chorionic gonadotropin at the time of sampling, endometrial thickness, and presence of an adnexal mass were not significantly different between patients with failed intrauterine pregnancy or ectopic pregnancy. In patients with failed intrauterine pregnancy, 100% demonstrated adequate postsampling beta-human chorionic gonadotropin declines; villi were identified in just 46% (n=21 patients). Patients with failed intrauterine pregnancy had significantly shorter time to resolution (negative serum beta-human chorionic gonadotropin) after sampling compared with patients with ectopic pregnancy (12.6 vs 26.3 days; Plocation are spared methotrexate, with a shorter time to pregnancy resolution than those who receive methotrexate. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. From Intensity Profile to Surface Normal: Photometric Stereo for Unknown Light Sources and Isotropic Reflectances.

    Science.gov (United States)

    Lu, Feng; Matsushita, Yasuyuki; Sato, Imari; Okabe, Takahiro; Sato, Yoichi

    2015-10-01

    We propose an uncalibrated photometric stereo method that works with general and unknown isotropic reflectances. Our method uses a pixel intensity profile, which is a sequence of radiance intensities recorded at a pixel under unknown varying directional illumination. We show that for general isotropic materials and uniformly distributed light directions, the geodesic distance between intensity profiles is linearly related to the angular difference of their corresponding surface normals, and that the intensity distribution of the intensity profile reveals reflectance properties. Based on these observations, we develop two methods for surface normal estimation; one for a general setting that uses only the recorded intensity profiles, the other for the case where a BRDF database is available while the exact BRDF of the target scene is still unknown. Quantitative and qualitative evaluations are conducted using both synthetic and real-world scenes, which show the state-of-the-art accuracy of smaller than 10 degree without using reference data and 5 degree with reference data for all 100 materials in MERL database.

  2. Transmissibility of H-Type Bovine Spongiform Encephalopathy to Hamster PrP Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Okada

    Full Text Available Two distinct forms of atypical bovine spongiform encephalopathies (H-BSE and L-BSE can be distinguished from classical (C- BSE found in cattle based on biochemical signatures of disease-associated prion protein (PrPSc. H-BSE is transmissible to wild-type mice-with infected mice showing a long survival period that is close to their normal lifespan-but not to hamsters. Therefore, rodent-adapted H-BSE with a short survival period would be useful for analyzing H-BSE characteristics. In this study, we investigated the transmissibility of H-BSE to hamster prion protein transgenic (TgHaNSE mice with long survival periods. Although none of the TgHaNSE mice manifested the disease during their lifespan, PrPSc accumulation was observed in some areas of the brain after the first passage. With subsequent passages, TgHaNSE mice developed the disease with a mean survival period of 220 days. The molecular characteristics of proteinase K-resistant PrPSc (PrPres in the brain were identical to those observed in first-passage mice. The distribution of immunolabeled PrPSc in the brains of TgHaNSE mice differed between those infected with H-BSE as compared to C-BSE or L-BSE, and the molecular properties of PrPres in TgHaNSE mice infected with H-BSE differed from those of the original isolate. The strain-specific electromobility, glycoform profiles, and proteolytic cleavage sites of H-BSE in TgHaNSE mice were indistinguishable from those of C-BSE, in which the diglycosylated form was predominant. These findings indicate that strain-specific pathogenic characteristics and molecular features of PrPres in the brain are altered during cross-species transmission. Typical H-BSE features were restored after back passage from TgHaNSE to bovinized transgenic mice, indicating that the H-BSE strain was propagated in TgHaNSE mice. This could result from the overexpression of the hamster prion protein.

  3. Scrapie infectivity is quickly cleared in tissues of orally-infected farmed fish

    Directory of Open Access Journals (Sweden)

    Faoro Franco

    2006-06-01

    Full Text Available Abstract Background Scrapie and bovine spongiform encephalopathy (BSE belongs to the group of animal transmissible spongiform encephalopathy (TSE. BSE epidemic in the UK and elsewhere in Europe has been linked to the use of bovine meat and bone meals (MBM in the feeding of cattle. There is concern that pigs, poultry and fish bred for human consumption and fed with infected MBM would eventually develop BSE or carry residual infectivity without disease. Although there has been no evidence of infection in these species, experimental data on the susceptibility to the BSE agent of farm animals other than sheep and cow are limited only to pigs and domestic chicken. In the framework of a EU-granted project we have challenged two species of fish largely used in human food consumption, rainbow trout (Oncorhynchus mykiss and turbot (Scophthalmus maximus, with a mouse-adapted TSE strain (scrapie 139A, to assess the risk related to oral consumption of TSE contaminated food. In trout, we also checked the "in vitro" ability of the pathological isoform of the mouse prion protein (PrPSc to cross the intestinal epithelium when added to the mucosal side of everted intestine. Results Fish challenged with a large amount of scrapie mouse brain homogenate by either oral or parenteral routes, showed the ability to clear the majority of infectivity load. None of the fish tissues taken at different time points after oral or parenteral inoculation was able to provoke scrapie disease after intracerebral inoculation in recipient mice. However, a few recipient mice were positive for PrPSc and spongiform lesions in the brain. We also showed a specific binding of PrPSc to the mucosal side of fish intestine in the absence of an active uptake of the prion protein through the intestinal wall. Conclusion These results indicate that scrapie 139A, and possibly BSE, is quickly removed from fish tissues despite evidence of a prion like protein in fish and of a specific binding of PrPSc

  4. Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone.

    Science.gov (United States)

    Cali, Ignazio; Miller, Cathleen J; Parisi, Joseph E; Geschwind, Michael D; Gambetti, Pierluigi; Schonberger, Lawrence B

    2015-06-25

    The present study compares the clinical, pathological and molecular features of a United States (US) case of growth hormone (GH)-associated Creutzfeldt-Jakob disease (GH-CJD) (index case) to those of two earlier referred US cases of GH-CJD and one case of dura mater (d)-associated CJD (dCJD). All iatrogenic CJD (iCJD) subjects were methionine (M) homozygous at codon 129 (129MM) of the prion protein (PrP) gene and had scrapie prion protein (PrP(Sc)) type 1 (iCJDMM1). The index subject presented with ataxia, weight loss and changes in the sleep pattern about 38 years after the midpoint of GH treatment. Autopsy examination revealed a neuropathological phenotype reminiscent of both sCJDMV2-K (a sporadic CJD subtype in subjects methionine/valine heterozygous at codon 129 with PrP(Sc) type 2 and the presence of kuru plaques) and variant CJD (vCJD). The two earlier cases of GH-CJDMM1 and the one of dCJDMM1 were associated with neuropathological phenotypes that differed from that of the index case mainly because they lacked PrP plaques. The phenotype of the earlier GH-CJDMM1 cases shared several, but not all, characteristics with sCJDMM1, whereas dCJDMM1 was phenotypically indistinguishable from sCJDMM1. Two distinct groups of dCJDMM1 have also been described in Japan based on clinical features, the presence or absence of PrP plaques and distinct PK-resistant PrP(Sc) (resPrP(Sc)) electrophoretic mobilities. The resPrP(Sc) electrophoretic mobility was, however, identical in our GH-CJDMM1 and dCJDMM1 cases, and matched that of sCJDMM1. Our study shows that receipt of prion-contaminated GH can lead to a prion disease with molecular features (129MM and PrP(Sc) type 2) and phenotypic characteristics that differ from those of sporadic prion disease (sCJDMM1), a difference that may reflect adaptation of "heterologous" prion strains to the 129MM background.

  5. Solving the Unknown with Algebra: Poster/Teaching Guide for Pre-Algebra Students. Expect the Unexpected with Math[R

    Science.gov (United States)

    Actuarial Foundation, 2013

    2013-01-01

    "Solving the Unknown with Algebra" is a new math program aligned with the National Council of Teachers of Mathematics (NCTM) standards and designed to help students practice pre-algebra skills including using formulas, solving for unknowns, and manipulating equations. Developed by The Actuarial Foundation with Scholastic, this program provides…

  6. Neuroendocrine Merkel cell nodal carcinoma of unknown primary site: management and outcomes of a rare entity.

    Science.gov (United States)

    Kotteas, E A; Pavlidis, N

    2015-04-01

    Merkel cell nodal carcinoma of unknown primary (MCCUP) is a rare neuroendocrine tumour with distinct clinical and biological behaviour. We conducted a review of retrospective data extracted from 90 patients focusing on the management and outcome of this disease. We also compared life expectancy of these patients with the outcome of patients with known Merkel primaries and with neuroendocrine cancers of unidentifiable primary. There is a limited body of data for this type of malignancy, however, patients with Merkel cell nodal carcinoma of unknown primary site, seem to have better survival when treated aggressively than patients with cutaneous Merkel tumours of the same stage and equal survival with patients with low-grade neuroendocrine tumour of unknown origin. The lack of prospective trials, and the inadequate data, hamper the management of these tumours. Establishment of treatment guidelines is urgently needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Virtue-Epistemology and the Chagos Unknown: Questioning the Indictment of Knowledge Transmission

    Science.gov (United States)

    Papastephanou, Marianna

    2015-01-01

    Though concerned with knowledge, this article begins with unknown political events that are ignored by the culture and educational practices of the societies in whose name the events took place. The questions that these events raise indicate a relation of epistemology with ethics and education that complicates some theoretical and managerial…

  8. Learning from the patient: the East, synchronicity and transference in the history of an unknown case of C.G. Jung.

    Science.gov (United States)

    de Moura, Vicente

    2014-06-01

    This article presents the history of one until now unknown case of C.G. Jung: Maggy Reichstein. Born in Indonesia in 1894 in a very aristocratic family, she brought her sister to Zurich to be treated by Jung in 1919, and later she herself was in analysis with him. Jung used her case as example in his lecture in 1937 on the realities of practical psychotherapy, relating it to the process of transference and countertransference. Jung deepened his studies in Eastern psychology after a series of dreams she had, which culminated in the Yoga Kundalini Seminars. She was also the case presented in his article of 1951 on the concept of synchronicity. Jung wrote that her case, concerning synchronicity, remained unique in his experience. Jung also published some of her mandalas. He considered her able to understand his ideas in depth. Reichstein was for Jung an important case, which challenged and triggered his interests in different subjects. © 2014, The Society of Analytical Psychology.

  9. A NEW METHOD OF CHANNEL FRICTION INVERSION BASED ON KALMAN FILTER WITH UNKNOWN PARAMETER VECTOR

    Institute of Scientific and Technical Information of China (English)

    CHENG Wei-ping; MAO Gen-hai; LIU Guo-hua

    2005-01-01

    Channel friction is an important parameter in hydraulic analysis.A channel friction parameter inversion method based on Kalman Filter with unknown parameter vector is proposed.Numerical simulations indicate that when the number of monitoring stations exceeds a critical value, the solution is hardly affected.In addition, Kalman Filter with unknown parameter vector is effective only at unsteady state.For the nonlinear equations, computations of sensitivity matrices are time-costly.Two simplified measures can reduce computing time, but not influence the results.One is to reduce sensitivity matrix analysis time, the other is to substitute for sensitivity matrix.

  10. Projective and hybrid projective synchronization for the Lorenz-Stenflo system with estimation of unknown parameters

    International Nuclear Information System (INIS)

    Mukherjee, Payel; Banerjee, Santo

    2010-01-01

    In this work, in the first phase, we study the phenomenon of projective synchronization in the Lorenz-Stenflo system. Synchronization is then investigated for the same system with unknown parameters. We show analytically that synchronization is possible for some proper choice of the nonlinear controller by using a suitable Lyapunov function. With the help of this result, it is also possible to estimate the values of the unknown system parameters. In the second phase as an extension of our analysis, we investigate the new hybrid projective synchronization for the same system. All our analyses are well supported with numerical evidence.

  11. Structure-based inference of molecular functions of proteins of unknown function from Berkeley Structural Genomics Center

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Hou; Shin, Dong Hae; Hou, Jingtong; Chandonia, John-Marc; Das, Debanu; Choi, In-Geol; Kim, Rosalind; Kim, Sung-Hou

    2007-09-02

    Advances in sequence genomics have resulted in an accumulation of a huge number of protein sequences derived from genome sequences. However, the functions of a large portion of them cannot be inferred based on the current methods of sequence homology detection to proteins of known functions. Three-dimensional structure can have an important impact in providing inference of molecular function (physical and chemical function) of a protein of unknown function. Structural genomics centers worldwide have been determining many 3-D structures of the proteins of unknown functions, and possible molecular functions of them have been inferred based on their structures. Combined with bioinformatics and enzymatic assay tools, the successful acceleration of the process of protein structure determination through high throughput pipelines enables the rapid functional annotation of a large fraction of hypothetical proteins. We present a brief summary of the process we used at the Berkeley Structural Genomics Center to infer molecular functions of proteins of unknown function.

  12. 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.

  13. Acute Pulmonary Oedema after Removal of Sand Bag at the End of Open Cholecystectomy due to Unknown Cause

    Directory of Open Access Journals (Sweden)

    Pramod Gupta

    2008-01-01

    Full Text Available Pulmonary oedema developes acutely during perioperative period and is usually due to unknown cause,but this life threatening complication if managed on time ,leads to rapid and full recovery. Here a case of 70 year old man is reported who developed acute pulmonary oedema after conclusion of surgery due to unknown cause.

  14. Impulsive synchronization of Markovian jumping randomly coupled neural networks with partly unknown transition probabilities via multiple integral approach.

    Science.gov (United States)

    Chandrasekar, A; Rakkiyappan, R; Cao, Jinde

    2015-10-01

    This paper studies the impulsive synchronization of Markovian jumping randomly coupled neural networks with partly unknown transition probabilities via multiple integral approach. The array of neural networks are coupled in a random fashion which is governed by Bernoulli random variable. The aim of this paper is to obtain the synchronization criteria, which is suitable for both exactly known and partly unknown transition probabilities such that the coupled neural network is synchronized with mixed time-delay. The considered impulsive effects can be synchronized at partly unknown transition probabilities. Besides, a multiple integral approach is also proposed to strengthen the Markovian jumping randomly coupled neural networks with partly unknown transition probabilities. By making use of Kronecker product and some useful integral inequalities, a novel Lyapunov-Krasovskii functional was designed for handling the coupled neural network with mixed delay and then impulsive synchronization criteria are solvable in a set of linear matrix inequalities. Finally, numerical examples are presented to illustrate the effectiveness and advantages of the theoretical results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Gemcitabine and irinotecan as first-line therapy for carcinoma of unknown primary: results of a multicenter phase II trial.

    Directory of Open Access Journals (Sweden)

    Shernan G Holtan

    Full Text Available Metastatic carcinoma of unknown primary (CUP has a very poor prognosis, and no standard first-line therapy currently exists. Here, we report the results of a phase II study utilizing a combination of gemcitabine and irinotecan as first-line therapy. Treatment was with gemcitabine 1000 mg/m(2 and irinotecan 75 mg/m(2 weekly times four on a six week cycle (Cohort I. Due to excessive toxicity, the dose and schedule were modified as follows: gemcitabine 750 mg/m(2 and irinotecan 75 mg/m(2 given weekly times three on a four week cycle (Cohort II. The primary endpoint was the confirmed response rate (CR + PR. Secondary endpoints consisted of adverse events based upon the presence or absence of the UDP glucuronosyltransferase 1 family, polypeptide A1*28 (UGT1A1*28 polymorphism, time to progression, and overall survival. Thirty-one patients were enrolled with a median age of 63 (range: 38-94, and 26 patients were evaluable for efficacy. Significant toxicity was observed in Cohort 1, characterized by 50% (7/14 patients experiencing a grade 4+ adverse event, but not in cohort II. The confirmed response rate including patients from both cohorts was 12% (95% CI: 2-30%, which did not meet the criteria for continued enrollment. Overall median survival was 7.2 months (95% CI: 4.0 to 11.6 for the entire cohort but notably longer in cohort II than in cohort I (9.3 months (95% CI: 4.1 to 12.1 versus 4.0 months (95% CI: 2.2 to 15.6. Gemcitabine and irinotecan is not an active combination when used as first line therapy in patients with metastatic carcinoma of unknown primary. Efforts into developing novel diagnostic and therapeutic approaches remain important for improving the outlook for this heterogeneous group of patients.ClinicalTrials.gov NCT00066781.

  16. 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.

  17. Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction

    Directory of Open Access Journals (Sweden)

    Butenko Melinka A

    2009-10-01

    Full Text Available Abstract Background When generating a genetically modified organism (GMO, the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown. Results We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of Arabidopsis thaliana and published EST datasets from commercially relevant species (rice and papaya. Conclusion We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs.

  18. Development of a remaining lifetime management system for NPPS

    International Nuclear Information System (INIS)

    Galvan, J.C.; Regano, M.; Hevia Ruperez, F.

    1994-01-01

    The interest evinced by Spain nuclear power plants in providing a tool to support remaining lifetime management led to UNESA's application to OCIDE in 1992, and the latter's approval, for financing the project to develop a Remaining Lifetime Evaluation System for LWR nuclear power plants. This project is currently being developed under UNESA leadership, and the collaboration of three Spanish engineering companies and a research centre. The paper will describe its objectives, activities, current status and prospects. The project is defined in two phases, the first consisting of the identification and analysis of the main ageing phenomena and their significant parameters and specification of the Remaining Lifetime Evaluation System (RLES), and the second implementation of a pilot application of the RLES to verify its effectiveness. (Author)

  19. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes

    NARCIS (Netherlands)

    Dutilh, Bas E; Cassman, Noriko; McNair, Katelyn; Sanchez, Savannah E; Silva, Genivaldo G Z; Boling, Lance; Barr, Jeremy J; Speth, Daan R; Seguritan, Victor; Aziz, Ramy K; Felts, Ben; Dinsdale, Elizabeth A; Mokili, John L; Edwards, Robert A

    2014-01-01

    Metagenomics, or sequencing of the genetic material from a complete microbial community, is a promising tool to discover novel microbes and viruses. Viral metagenomes typically contain many unknown sequences. Here we describe the discovery of a previously unidentified bacteriophage present in the

  20. Study on search of unknown materials. 1; Michi busshitsu no tansaku ni kansuru kenkyu. 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-11-28

    This is No.92 report of National Institute for Research in Inorganic Materials, concerning search of unknown materials. Purposes of this study are to construct new chemical bond and reaction theory, to systematize the existing compounds, and to search and create the unknown materials, systematically. Structure prediction of electronic state was investigated by means of molecular dynamic method, to determine the electronic state and structure of multi-systems. For the magnetic semiconductors, interactions were investigated between the magnetic spin and electron or hole which is a carrier. The in-solid bond theory aims at clarifying the bond state of materials in which transition metal compounds and inter-electronic interactions are significant. Prediction of the electronic structure of unknown materials can suggest the design of new materials. In the fields of synthesis, design and synthesis of new inorganic ion exchanger and ionic conductor are investigated using Bi oxides and its related materials. There are a lot of compounds having various crystal forms for rare earth element oxides and transition metal oxides. To establish the system of material design, thermodynamics, phase equilibrium diagram, crystal structure, and physical properties of new materials were discussed. 168 refs., 127 figs., 44 tabs.

  1. Iterative Adaptive Dynamic Programming for Solving Unknown Nonlinear Zero-Sum Game Based on Online Data.

    Science.gov (United States)

    Zhu, Yuanheng; Zhao, Dongbin; Li, Xiangjun

    2017-03-01

    H ∞ control is a powerful method to solve the disturbance attenuation problems that occur in some control systems. The design of such controllers relies on solving the zero-sum game (ZSG). But in practical applications, the exact dynamics is mostly unknown. Identification of dynamics also produces errors that are detrimental to the control performance. To overcome this problem, an iterative adaptive dynamic programming algorithm is proposed in this paper to solve the continuous-time, unknown nonlinear ZSG with only online data. A model-free approach to the Hamilton-Jacobi-Isaacs equation is developed based on the policy iteration method. Control and disturbance policies and value are approximated by neural networks (NNs) under the critic-actor-disturber structure. The NN weights are solved by the least-squares method. According to the theoretical analysis, our algorithm is equivalent to a Gauss-Newton method solving an optimization problem, and it converges uniformly to the optimal solution. The online data can also be used repeatedly, which is highly efficient. Simulation results demonstrate its feasibility to solve the unknown nonlinear ZSG. When compared with other algorithms, it saves a significant amount of online measurement time.

  2. 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...

  3. Splenectomy as a treatment for adults with relapsed hemophagocytic lymphohistiocytosis of unknown cause.

    Science.gov (United States)

    Jing-Shi, Wang; Yi-Ni, Wang; Lin, Wu; Zhao, Wang

    2015-05-01

    Our aim was to evaluate the clinical value of splenectomy as a treatment for relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause in adults. We retrospectively reviewed the clinical data from medical records of 19 adults with relapsed HLH of unknown cause treated with splenectomy in our institution from June 2007 to March 2014. To rule out possible underlying diseases, including infection, autoimmune disease, neoplasms, and primary HLH, the patients had undergone examinations including F18 fluoro-2-deoxyglucose positron emission tomography/computed tomography, HLH-associated gene defects, and lymph node biopsies. Twelve patients (63.2%) achieved partial responses (PR), whereas seven patients (36.8%) had no response (NR) prior to splenectomy. Infection and hemorrhage were the main complications of splenectomy. Eighteen cases were evaluable after follow-up. Seven cases with histopathologic diagnoses of lymphoma had received chemotherapy, four of whom had achieved complete responses (CR), one PR, and two NR. Maintenance treatment was ceased 2 or 3 months after splenectomy in the other 11 cases, five of whom had CR, four PR, and two NR. Eleven of 18 cases (61.1%) survived with a median follow-up of 25 months (range 3-79 months) for survivors. Twelve- and 36-month progression-free survival rates were 48 and 24%, respectively; 12- and 36-month overall survival rates were 57 and 25%, respectively. Median survival time was 22 months. Our results indicate splenectomy may be an effective means of diagnosis and treatment of relapsed HLH of unknown cause. Further study is required to establish the mechanism and value of splenectomy in this disease.

  4. STUDY OF SPECTRUM OF PYREXIA OF UNKNOWN ORIGIN PATIENTS IN A TERTIARY CARE HOSPITAL IN COASTAL ANDHRA PRADESH

    Directory of Open Access Journals (Sweden)

    Suryaprakasa Rao Salla

    2017-09-01

    Full Text Available BACKGROUND Pyrexia of Unknown Origin (PUO/Fever of Unknown Origin (FUO was defined in 1961 by Petersdorf RG and Beeson PB2 as the following- A temperature greater than 38.3°C (101°F on several occasions; more than 3 weeks' duration of illness; and failure to reach a diagnosis despite 1 week of inpatient investigation. The aim of the study is to study the spectrum of cases of Pyrexia of Unknown Origin (PUO/Fever of Unknown Origin (FUO in a tertiary care hospital in coastal Andhra Pradesh. MATERIALS AND METHODS All patients with PUO admitted under the Department of General Medicine in the NRI Institute of Medical Sciences (Anil Neerukonda Hospital Sangivalasa, Visakhapatnam, during the period from 1st September, 2016, to 31st August, 2017, and who fulfil inclusion and exclusion criteria of classic PUO defined by Durrack and AC street1 were selected for the study. RESULTS The present study included 34 patients with pyrexia of unknown origin in which the patients’ age ranged from 15 years to 77 years. Most of the cases, 41.2% were in the age group 21 to 40 years and 35.3% in the age group 41 to 60 yrs. This indicates PUO is common in middle age group in our study. CONCLUSION Noninfectious causes like collagen vascular disease and neoplasms are becoming important differential diagnosis. But, in India, infections like tuberculosis, enteric fever are still the most common cause of FUO.

  5. Non-predictor control of a class of feedforward nonlinear systems with unknown time-varying delays

    Science.gov (United States)

    Koo, Min-Sung; Choi, Ho-Lim

    2016-08-01

    This paper generalises the several recent results on the control of feedforward time-delay nonlinear systems. First, in view of system formulation, there are unknown time-varying delays in both states and main control input. Also, the considered nonlinear system has extended feedforward nonlinearities. Second, in view of control solution, our proposed controller is a non-predictor feedback controller whereas smith-predictor type controllers are used in the several existing results. Moreover, our controller does not need any information on the unknown delays except their upper bounds. Thus, our result has certain merits in both system formulation and control solution perspective. The analysis and example are given for clear illustration.

  6. 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.

  7. High Valence, Normal Valence and Unknown Valence

    DEFF Research Database (Denmark)

    Morsing, Thorbjørn Juul

    the serendipitous synthesis of the nitrido-bridged [Rh(en)3]2- [(CN)5MnNMn(CN)5]. The complex anion have previously been studied in the form of the mixed Rb4Na2-salt. In this earlier study, the nitrido-bridge was found to be asymmetrical with the axial ligands in an eclipsed formation. The complex was described...... the [Rh(en)3]2-salt is best described as Mn3.5/Mn3.5. This means that the [(CN)5MnNMn(CN)5]6􀀀 ion displays crystal packing induced oxidation state isomerism, a rare phenomenon. Chapter 4 details the synthesis and characterisation of group 9 dithiolene complexes with focus on the hitherto unknown...... homoleptic iridium dithiolene complexes. When the complexes [M(mnt)3]3􀀀, M = Rh and Co are chemically oxidized, they decompose to yield dinuclear complexes with the metal still in oxidation state III. This is not the case for the corresponding Ir complex which can be oxidized and the oxidation...

  8. Remaining life assessment of a high pressure turbine rotor

    International Nuclear Information System (INIS)

    Nguyen, Ninh; Little, Alfie

    2012-01-01

    This paper describes finite element and fracture mechanics based modelling work that provides a useful tool for evaluation of the remaining life of a high pressure (HP) steam turbine rotor that had experienced thermal fatigue cracking. An axis-symmetrical model of a HP rotor was constructed. Steam temperature, pressure and rotor speed data from start ups and shut downs were used for the thermal and stress analysis. Operating history and inspection records were used to benchmark the damage experienced by the rotor. Fracture mechanics crack growth analysis was carried out to evaluate the remaining life of the rotor under themal cyclic loading conditions. The work confirmed that the fracture mechanics approach in conjunction with finite element modelling provides a useful tool for assessing the remaining life of high temperature components in power plants.

  9. Reachable set estimation for Takagi-Sugeno fuzzy systems against unknown output delays with application to tracking control of AUVs.

    Science.gov (United States)

    Zhong, Zhixiong; Zhu, Yanzheng; Ahn, Choon Ki

    2018-03-20

    In this paper, we address the problem of reachable set estimation for continuous-time Takagi-Sugeno (T-S) fuzzy systems subject to unknown output delays. Based on the reachable set concept, a new controller design method is also discussed for such systems. An effective method is developed to attenuate the negative impact from the unknown output delays, which likely degrade the performance/stability of systems. First, an augmented fuzzy observer is proposed to capacitate a synchronous estimation for the system state and the disturbance term owing to the unknown output delays, which ensures that the reachable set of the estimation error is limited via the intersection operation of ellipsoids. Then, a compensation technique is employed to eliminate the influence on the system performance stemmed from the unknown output delays. Finally, the effectiveness and correctness of the obtained theories are verified by the tracking control of autonomous underwater vehicles. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  10. 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.

  11. A collation of recently published Western European formulae for age estimation of subadult skeletal remains: recommendations for forensic anthropology and osteoarchaeology.

    Science.gov (United States)

    Rissech, Carme; Márquez-Grant, Nicholas; Turbón, Daniel

    2013-01-01

    The aim of this study is to provide an effective and quick reference guide based on the most useful European formulae recently published for subadult age estimation. All of these formulae derive from studies on postnatal growth of the scapula, innominate, femur, and tibia, based on modern skeletal data (173 ♂, 173 ♀) from five documented collections from Spain, Portugal, and Britain. The formulae were calculated from Inverse Regression. For this reason, these formulae are especially useful for modern samples from Western Europe and in particular on 20th century human remains from the Iberian Peninsula. Eleven formulae were selected as the most useful because they can be applied to individuals from within a wide age range and in individuals of unknown sex. Due to their high reliability and because they derive from documented European skeletal samples, we recommend these formulae be used on individuals of Caucasoid ancestry from Western Europe. © 2012 American Academy of Forensic Sciences.

  12. Can healthy, young adults uncover personal details of unknown target individuals in their dreams?

    Science.gov (United States)

    Smith, Carlyle

    2013-01-01

    We investigated the possibility that undergraduate college students could incubate dreams containing information about unknown target individuals with significant life problems. In Experiment 1, students provided two baseline dreams. They were then exposed to a photo of an individual and invited to dream about a health problem (unknown to them and the experimenter) of that individual and asked to provide two more dreams. From a class of 65 students, 12 dreamers volunteered dreams about the unknown target. In Experiment 2, 66 students were asked to dream about the life problems of a second individual, simply by looking at the photo (experimental group). Another 56 students were exposed to this same paradigm, but the photo that they examined was computer generated and the target individual was fictitious (control group). The dream elements were objectively scored with categories devised using the Hall-Van de Castle system as a model. Data were ordinal, and the nonparametric Wilcoxon signed rank test was used to examine preincubation (baseline) versus postincubation (photo examination and incubation) dream content in Experiment 1. In Experiment 2, a Z score for proportions was used to compare differences in frequency of devised categories between experimental and control groups. In Experiment 1, the comparison of postincubation dreams (all categories combined) was significant compared with the preincubation dreams (Z = 2.09, P = .036). The postincubation dreams reflected the health problem of the target. In Experiment 2, the proportion of scored categories in experimental and control groups were compared at the preincubation and postincubation conditions. The proportions of "Combined" (all categories) was very significantly larger at the postincubation condition (Z = 6.27, P dreams of the experimental group were related to the problems of the target individual. Young, healthy adults are capable of dreaming details about the personal problems of an unknown individual

  13. Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.

    Science.gov (United States)

    Uchiyama, Keiji; Miyata, Hironori; Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

    2014-01-01

    Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc.

  14. The value of digital subtraction angiography in diagnosing small intestinal hemorrhage with unknown reasons

    International Nuclear Information System (INIS)

    Luo Guanghua; Xiao Wenlian; Tang Deqiu; Chan Hong

    2006-01-01

    Objective: To discuss the diagnostic value of DSA for unknown reason hemorrhage of small intestine. Methods: 25 patients with hemorrhage of small intestine were performed angiography with Seldinger's technique through superior mesenteric artery. Results: Eleven cases demonstrated direct signs of hemorrhage, 12 cases of indirect signs of hemorrhage and 5 with both of the signs. The positive rate of hemorrhage was 72% including 10 cases of tumor (6 leiomyomas, 2 leiomyosarcomas, 1 interstitial tumor, 1 small intestinal cancer), 4 cases of Meckel's diverticulum, 3 cases of vascular malformation and 1 case of inflammation. The coincidence rate of positive cases with pathology was 75% and the diagnostic accuracy of localization was 100%. Conclusions: DSA angiography is very helpful for determining the location and character of unknown reason hemorrhage of small intestine. (authors)

  15. A Real-Time Reaction Obstacle Avoidance Algorithm for Autonomous Underwater Vehicles in Unknown Environments.

    Science.gov (United States)

    Yan, Zheping; Li, Jiyun; Zhang, Gengshi; Wu, Yi

    2018-02-02

    A novel real-time reaction obstacle avoidance algorithm (RRA) is proposed for autonomous underwater vehicles (AUVs) that must adapt to unknown complex terrains, based on forward looking sonar (FLS). To accomplish this algorithm, obstacle avoidance rules are planned, and the RRA processes are split into five steps Introduction only lists 4 so AUVs can rapidly respond to various environment obstacles. The largest polar angle algorithm (LPAA) is designed to change detected obstacle's irregular outline into a convex polygon, which simplifies the obstacle avoidance process. A solution is designed to solve the trapping problem existing in U-shape obstacle avoidance by an outline memory algorithm. Finally, simulations in three unknown obstacle scenes are carried out to demonstrate the performance of this algorithm, where the obtained obstacle avoidance trajectories are safety, smooth and near-optimal.

  16. Explosives remain preferred methods for platform abandonment

    International Nuclear Information System (INIS)

    Pulsipher, A.; Daniel, W. IV; Kiesler, J.E.; Mackey, V. III

    1996-01-01

    Economics and safety concerns indicate that methods involving explosives remain the most practical and cost-effective means for abandoning oil and gas structures in the Gulf of Mexico. A decade has passed since 51 dead sea turtles, many endangered Kemp's Ridleys, washed ashore on the Texas coast shortly after explosives helped remove several offshore platforms. Although no relationship between the explosions and the dead turtles was ever established, in response to widespread public concern, the US Minerals Management Service (MMS) and National Marine Fisheries Service (NMFS) implemented regulations limiting the size and timing of explosive charges. Also, more importantly, they required that operators pay for observers to survey waters surrounding platforms scheduled for removal for 48 hr before any detonations. If observers spot sea turtles or marine mammals within the danger zone, the platform abandonment is delayed until the turtles leave or are removed. However, concern about the effects of explosives on marine life remains

  17. Decomposition Technique for Remaining Useful Life Prediction

    Science.gov (United States)

    Saha, Bhaskar (Inventor); Goebel, Kai F. (Inventor); Saxena, Abhinav (Inventor); Celaya, Jose R. (Inventor)

    2014-01-01

    The prognostic tool disclosed here decomposes the problem of estimating the remaining useful life (RUL) of a component or sub-system into two separate regression problems: the feature-to-damage mapping and the operational conditions-to-damage-rate mapping. These maps are initially generated in off-line mode. One or more regression algorithms are used to generate each of these maps from measurements (and features derived from these), operational conditions, and ground truth information. This decomposition technique allows for the explicit quantification and management of different sources of uncertainty present in the process. Next, the maps are used in an on-line mode where run-time data (sensor measurements and operational conditions) are used in conjunction with the maps generated in off-line mode to estimate both current damage state as well as future damage accumulation. Remaining life is computed by subtracting the instance when the extrapolated damage reaches the failure threshold from the instance when the prediction is made.

  18. Gene variants of unknown clinical significance in Lynch syndrome. An introduction for clinicians

    NARCIS (Netherlands)

    Sijmons, Rolf H.; Greenblatt, Marc S.; Genuardi, Maurizio

    Clinicians referring patients for genetic testing for Lynch syndrome will sooner or later receive results for DNA Mismatch Repair (MMR) genes reporting DNA changes that are unclear from a clinical point of view. These changes are referred to as variants of unknown, or unclear, clinical significance

  19. The role of nuclear medicine in the diagnosis of cancer of unknown origin

    DEFF Research Database (Denmark)

    Demir, H; Berk, F; Raderer, M

    2004-01-01

    Cancer of unknown origin (CUO) is defined by the absence of any primary tumour in biopsy-proved metastatic cancer. CUO accounts for a 5-10% of all malignancies. These tumors have a specific biology with clinical characteristics of rapid progression and atypical metastases. Diagnostic evaluation i...

  20. Nonlinear unbiased minimum-variance filter for Mars entry autonomous navigation under large uncertainties and unknown measurement bias.

    Science.gov (United States)

    Xiao, Mengli; Zhang, Yongbo; Fu, Huimin; Wang, Zhihua

    2018-05-01

    High-precision navigation algorithm is essential for the future Mars pinpoint landing mission. The unknown inputs caused by large uncertainties of atmospheric density and aerodynamic coefficients as well as unknown measurement biases may cause large estimation errors of conventional Kalman filters. This paper proposes a derivative-free version of nonlinear unbiased minimum variance filter for Mars entry navigation. This filter has been designed to solve this problem by estimating the state and unknown measurement biases simultaneously with derivative-free character, leading to a high-precision algorithm for the Mars entry navigation. IMU/radio beacons integrated navigation is introduced in the simulation, and the result shows that with or without radio blackout, our proposed filter could achieve an accurate state estimation, much better than the conventional unscented Kalman filter, showing the ability of high-precision Mars entry navigation algorithm. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  1. Discrete-time online learning control for a class of unknown nonaffine nonlinear systems using reinforcement learning.

    Science.gov (United States)

    Yang, Xiong; Liu, Derong; Wang, Ding; Wei, Qinglai

    2014-07-01

    In this paper, a reinforcement-learning-based direct adaptive control is developed to deliver a desired tracking performance for a class of discrete-time (DT) nonlinear systems with unknown bounded disturbances. We investigate multi-input-multi-output unknown nonaffine nonlinear DT systems and employ two neural networks (NNs). By using Implicit Function Theorem, an action NN is used to generate the control signal and it is also designed to cancel the nonlinearity of unknown DT systems, for purpose of utilizing feedback linearization methods. On the other hand, a critic NN is applied to estimate the cost function, which satisfies the recursive equations derived from heuristic dynamic programming. The weights of both the action NN and the critic NN are directly updated online instead of offline training. By utilizing Lyapunov's direct method, the closed-loop tracking errors and the NN estimated weights are demonstrated to be uniformly ultimately bounded. Two numerical examples are provided to show the effectiveness of the present approach. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Inactivation of Template-Directed Misfolding of Infectious Prion Protein by Ozone

    Science.gov (United States)

    Ding, Ning; Price, Luke M.; Braithwaite, Shannon L.; Balachandran, Aru; Belosevic, Miodrag

    2012-01-01

    Misfolded prions (PrPSc) are well known for their resistance to conventional decontamination processes. The potential risk of contamination of the water environment, as a result of disposal of specified risk materials (SRM), has raised public concerns. Ozone is commonly utilized in the water industry for inactivation of microbial contaminants and was tested in this study for its ability to inactivate prions (263K hamster scrapie = PrPSc). Treatment variables included initial ozone dose (7.6 to 25.7 mg/liter), contact time (5 s and 5 min), temperature (4°C and 20°C), and pH (pH 4.4, 6.0, and 8.0). Exposure of dilute suspensions of the infected 263K hamster brain homogenates (IBH) (0.01%) to ozone resulted in the in vitro destruction of the templating properties of PrPSc, as measured by the protein misfolding cyclic amplification (PMCA) assay. The highest levels of prion inactivation (≥4 log10) were observed with ozone doses of 13.0 mg/liter, at pH 4.4 and 20°C, resulting in a CT (the product of residual ozone concentration and contact time) value as low as 0.59 mg · liter−1 min. A comparison of ozone CT requirements among various pathogens suggests that prions are more susceptible to ozone degradation than some model bacteria and protozoa and that ozone treatment may be an effective solution for inactivating prions in water and wastewater. PMID:22138993

  3. Infectious prion diseases in humans: cannibalism, iatrogenicity and zoonoses.

    Science.gov (United States)

    Haïk, Stéphane; Brandel, Jean-Philippe

    2014-08-01

    In contrast with other neurodegenerative disorders associated to protein misfolding, human prion diseases include infectious forms (also called transmitted forms) such as kuru, iatrogenic Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease. The transmissible agent is thought to be solely composed of the abnormal isoform (PrP(Sc)) of the host-encoded prion protein that accumulated in the central nervous system of affected individuals. Compared to its normal counterpart, PrP(Sc) is β-sheet enriched and aggregated and its propagation is based on an autocatalytic conversion process. Increasing evidence supports the view that conformational variations of PrP(Sc) encoded the biological properties of the various prion strains that have been isolated by transmission studies in experimental models. Infectious forms of human prion diseases played a pivotal role in the emergence of the prion concept and in the characterization of the very unconventional properties of prions. They provide a unique model to understand how prion strains are selected and propagate in humans. Here, we review and discuss how genetic factors interplay with strain properties and route of transmission to influence disease susceptibility, incubation period and phenotypic expression in the light of the kuru epidemics due to ritual endocannibalism, the various series iatrogenic diseases secondary to extractive growth hormone treatment or dura mater graft and the epidemics of variant Creutzfeldt-Jakob disease linked to dietary exposure to the agent of bovine spongiform encephalopathy. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Effect of Q211 and K222 PRNP Polymorphic Variants in the Susceptibility of Goats to Oral Infection With Goat Bovine Spongiform Encephalopathy.

    Science.gov (United States)

    Aguilar-Calvo, Patricia; Fast, Christine; Tauscher, Kerstin; Espinosa, Juan-Carlos; Groschup, Martin H; Nadeem, Muhammad; Goldmann, Wilfred; Langeveld, Jan; Bossers, Alex; Andreoletti, Olivier; Torres, Juan-María

    2015-08-15

    The prion protein-encoding gene (PRNP) is one of the major determinants for scrapie occurrence in sheep and goats. However, its effect on bovine spongiform encephalopathy (BSE) transmission to goats is not clear. Goats harboring wild-type, R/Q211 or Q/K222 PRNP genotypes were orally inoculated with a goat-BSE isolate to assess their relative susceptibility to BSE infection. Goats were killed at different time points during the incubation period and after the onset of clinical signs, and their brains as well as several peripheral tissues were analyzed for the accumulation of pathological prion protein (PrP(Sc)) and prion infectivity by mouse bioassay. R/Q211 goats displayed delayed clinical signs compared with wild-type goats. Deposits of PrP(Sc) were detected only in brain, whereas infectivity was present in peripheral tissues too. In contrast, none of the Q/K222 goats showed any evidence of clinical prion disease. No PrP(Sc) accumulation was observed in their brains or peripheral tissues, but very low infectivity was detected in some tissues very long after inoculation (44-45 months). These results demonstrate that transmission of goat BSE is genotype dependent, and they highlight the pivotal protective effect of the K222 PRNP variant in the oral susceptibility of goats to BSE. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. 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...

  6. 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.

  7. Adaptive fuzzy wavelet network control of second order multi-agent systems with unknown nonlinear dynamics.

    Science.gov (United States)

    Taheri, Mehdi; Sheikholeslam, Farid; Najafi, Majddedin; Zekri, Maryam

    2017-07-01

    In this paper, consensus problem is considered for second order multi-agent systems with unknown nonlinear dynamics under undirected graphs. A novel distributed control strategy is suggested for leaderless systems based on adaptive fuzzy wavelet networks. Adaptive fuzzy wavelet networks are employed to compensate for the effect of unknown nonlinear dynamics. Moreover, the proposed method is developed for leader following systems and leader following systems with state time delays. Lyapunov functions are applied to prove uniformly ultimately bounded stability of closed loop systems and to obtain adaptive laws. Three simulation examples are presented to illustrate the effectiveness of the proposed control algorithms. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  8. Why Agricultural Educators Remain in the Classroom

    Science.gov (United States)

    Crutchfield, Nina; Ritz, Rudy; Burris, Scott

    2013-01-01

    The purpose of this study was to identify and describe factors that are related to agricultural educator career retention and to explore the relationships between work engagement, work-life balance, occupational commitment, and personal and career factors as related to the decision to remain in the teaching profession. The target population for…

  9. A Next-Generation Sequencing Data Analysis Pipeline for Detecting Unknown Pathogens from Mixed Clinical Samples and Revealing Their Genetic Diversity.

    Directory of Open Access Journals (Sweden)

    Yu-Nong Gong

    Full Text Available Forty-two cytopathic effect (CPE-positive isolates were collected from 2008 to 2012. All isolates could not be identified for known viral pathogens by routine diagnostic assays. They were pooled into 8 groups of 5-6 isolates to reduce the sequencing cost. Next-generation sequencing (NGS was conducted for each group of mixed samples, and the proposed data analysis pipeline was used to identify viral pathogens in these mixed samples. Polymerase chain reaction (PCR or enzyme-linked immunosorbent assay (ELISA was individually conducted for each of these 42 isolates depending on the predicted viral types in each group. Two isolates remained unknown after these tests. Moreover, iteration mapping was implemented for each of these 2 isolates, and predicted human parechovirus (HPeV in both. In summary, our NGS pipeline detected the following viruses among the 42 isolates: 29 human rhinoviruses (HRVs, 10 HPeVs, 1 human adenovirus (HAdV, 1 echovirus and 1 rotavirus. We then focused on the 10 identified Taiwanese HPeVs because of their reported clinical significance over HRVs. Their genomes were assembled and their genetic diversity was explored. One novel 6-bp deletion was found in one HPeV-1 virus. In terms of nucleotide heterogeneity, 64 genetic variants were detected from these HPeVs using the mapped NGS reads. Most importantly, a recombination event was found between our HPeV-3 and a known HPeV-4 strain in the database. Similar event was detected in the other HPeV-3 strains in the same clade of the phylogenetic tree. These findings demonstrated that the proposed NGS data analysis pipeline identified unknown viruses from the mixed clinical samples, revealed their genetic identity and variants, and characterized their genetic features in terms of viral evolution.

  10. Testing the Granger noncausality hypothesis in stationary nonlinear models of unknown functional form

    DEFF Research Database (Denmark)

    Péguin-Feissolle, Anne; Strikholm, Birgit; Teräsvirta, Timo

    In this paper we propose a general method for testing the Granger noncausality hypothesis in stationary nonlinear models of unknown functional form. These tests are based on a Taylor expansion of the nonlinear model around a given point in the sample space. We study the performance of our tests b...

  11. Chronic kidney disease of unknown etiology in agricultural communities.

    Science.gov (United States)

    Almaguer, Miguel; Herrera, Raúl; Orantes, Carlos M

    2014-04-01

    In recent years, Central America, Egypt, India and Sri Lanka have reported a high prevalence of chronic kidney disease of unknown etiology in agricultural communities, predominantly among male farmworkers. This essay examines the disease's case definitions, epidemiology (disease burden, demographics, associated risk factors) and causal hypotheses, by reviewing published findings from El Salvador, Nicaragua, Costa Rica, Sri Lanka, Egypt and India. The range of confirmed chronic kidney disease prevalence was 17.9%-21.1%. Prevalence of reduced glomerular filtration (homemade alcohol use and family history of chronic kidney disease. There is no strong evidence for a single cause, and multiple environmental, occupational and social factors are probably involved. Further etiological research is needed, plus interventions to reduce preventable risk factors.

  12. Mysteries and unknowns of single bubble sonoluminescence from viewpoint of plasma spectroscopy

    International Nuclear Information System (INIS)

    Lavrov, B.P.

    2001-01-01

    The main goal of the present work is to propose and consider electronically excited H 2 * (a 3 Σ g + ) molecules (and possibly hydrides of rare gases like ArH*(A 2 Σ)) as light emitters responsible for continua observed in both MBSL and SBSL experiments with hydrogen-containing liquids. This provides new sight on the well known ''mysteries and unknowns'' of the SBSL phenomenon

  13. 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.

  14. Sheep scrapie susceptibility-linked polymorphisms do not modulate the initial binding of cellular to disease-associated prion protein prior to conversion

    NARCIS (Netherlands)

    Rigter, A.; Bossers, A.

    2005-01-01

    Conversion of the host-encoded protease-sensitive cellular prion protein (PrPC) into the scrapie-associated protease-resistant isoform (PrPSc) of prion protein (PrP) is the central event in transmissible spongiform encephalopathies or prion diseases. Differences in transmissibility and

  15. Localization of disease-related PrP in Danish patients with different subtypes of prion disease

    DEFF Research Database (Denmark)

    Bergström, A. L.; Heegaard, Peter M. H.; Dyrbye, H.

    2009-01-01

    Objective: The transmissible spongiform encephalopaties are characterized by vacuolization, neuronal loss, gliosis and deposition of a misfilded and Proteinase K resistant isoform of the prion protein (PrPSc) in the central nervous system. Methods, materials and patients: Paraffin-embedded tissue...

  16. Gene expression profiling of mesenteric lymph nodes from sheep with natural scrapie

    NARCIS (Netherlands)

    Filali, H.; Martin-Burriel, I.; Harders, F.; Varona, L.; Hedman, C.; Mediano, D.R.; Monzón, M.; Bossers, A.; Badiola, J.J.

    2014-01-01

    Background - Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect

  17. Coding ill-defined and unknown cause of death is 13 times more frequent in Denmark than in Finland

    DEFF Research Database (Denmark)

    Ylijoki-Sørensen, Seija; Sajantila, Antti; Lalu, Kaisa

    2014-01-01

    Exact cause and manner of death determination improves legislative safety for the individual and for society and guides aspects of national public health. In the International Classification of Diseases, codes R00-R99 are used for "symptoms, signs and abnormal clinical and laboratory findings......, not elsewhere classified" designated as "ill-defined" or "with unknown etiology". The World Health Organisation recommends avoiding the use of ill-defined and unknown causes of death in the death certificate as this terminology does not give any information concerning the possible conditions that led...... autopsy. Our study suggests that if all deaths in all age groups with unclear cause of death were systematically investigated with a forensic autopsy, only 2-3/1000 deaths per year would be coded as an ill-defined and unknown cause of death in national mortality statistics. At the same time the risk...

  18. Systemic treatment of cancer of unknown primary origin

    International Nuclear Information System (INIS)

    Reckova, M.

    2013-01-01

    Cancer of unknown primary origin (CUP) comprises a heterogenous group of cancers with distinct biology and prognosis. There is, however, a specific group of patients with curable diseases, or incurable diseases with good prognosis. The main aim of treatment in the group of patients with CUP is timely initiation of therapy in the cases of curable disease. There is no known standard of care in the cases of CUP with poor prognosis, but most frequently, platinum-based regimens are used. In the cases of specific immunohistochemistry (IHC) or molecular gene expression profile, there are used the treatment regimens similar to those used in the patients with known primary tumor and similar IHC or molecular profile. Currently, most of data in patients with CUP are from phase II clinical trials. Thus proficiently designed phase III randomized clinical trials with translation research is priority, with aim to improve our knowledge and personalize treatment of such heterogenous group of patients as is a group of patients with CUP. (author)

  19. Efficacy of Gefitinib for Young Patients with Unknown EGFR Gene Mutation 
in Advanced Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Yutao LIU

    2014-05-01

    Full Text Available Background and objective Lung cancer in young patients (less or equal to 45 years is relatively rare. We explored the efficacy and survival of Gefitinib for young patients with unknown epidermal growth factor receptor (EGFR gene mutation of advanced lung adenocarcinoma. Methods The clinical data of 55 young patients with unknown EGFR gene mutation in advanced lung adenocarcinoma referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from Jan 2006 through Dec 2010 were analyzed retrospectively. Results Of 55 young patients enrolled, the median age was 41 years. The objective response rate and disease control rate were 43.6% and 90.9%, respectively.. The median progression-free survival (PFS was 9.0 months. Among the factors analyzed, brain metastasis had significant effect on PFS (P=0.017. The median overall survival (OS was 24.0 months. The independent prognostic factors to significantly improve OS included non-smoking history (P=0.028 and receiving other anti-cancer treatment after Gefitinib therapy (P<0.001. Conclusion The median PFS and OS of the young patients with Unknown EGFR gene mutation in advanced lung adenocarcinoma were similar with general population.

  20. Global Learning Spectral Archive- A new Way to deal with Unknown Urban Spectra -

    Science.gov (United States)

    Jilge, M.; Heiden, U.; Habermeyer, M.; Jürgens, C.

    2015-12-01

    Rapid urbanization processes and the need of identifying urban materials demand urban planners and the remote sensing community since years. Urban planners cannot overcome the issue of up-to-date information of urban materials due to time-intensive fieldwork. Hyperspectral remote sensing can facilitate this issue by interpreting spectral signals to provide information of occurring materials. However, the complexity of urban areas and the occurrence of diverse urban materials vary due to regional and cultural aspects as well as the size of a city, which makes identification of surface materials a challenging analysis task. For the various surface material identification approaches, spectral libraries containing pure material spectra are commonly used, which are derived from field, laboratory or the hyperspectral image itself. One of the requirements for successful image analysis is that all spectrally different surface materials are represented by the library. Currently, a universal library, applicable in every urban area worldwide and taking each spectral variability into account, is and will not be existent. In this study, the issue of unknown surface material spectra and the demand of an urban site-specific spectral library is tackled by the development of a learning spectral archive tool. Starting with an incomplete library of labelled image spectra from several German cities, surface materials of pure image pixels will be identified in a hyperspectral image based on a similarity measure (e.g. SID-SAM). Additionally, unknown image spectra of urban objects are identified based on an object- and spectral-based-rule set. The detected unknown surface material spectra are entered with additional metadata, such as regional occurrence into the existing spectral library and thus, are reusable for further studies. Our approach is suitable for pure surface material detection of urban hyperspectral images that is globally applicable by taking incompleteness into account

  1. Reconstruction of signals with unknown spectra in information field theory with parameter uncertainty

    International Nuclear Information System (INIS)

    Ensslin, Torsten A.; Frommert, Mona

    2011-01-01

    The optimal reconstruction of cosmic metric perturbations and other signals requires knowledge of their power spectra and other parameters. If these are not known a priori, they have to be measured simultaneously from the same data used for the signal reconstruction. We formulate the general problem of signal inference in the presence of unknown parameters within the framework of information field theory. To solve this, we develop a generic parameter-uncertainty renormalized estimation (PURE) technique. As a concrete application, we address the problem of reconstructing Gaussian signals with unknown power-spectrum with five different approaches: (i) separate maximum-a-posteriori power-spectrum measurement and subsequent reconstruction, (ii) maximum-a-posteriori reconstruction with marginalized power-spectrum, (iii) maximizing the joint posterior of signal and spectrum, (iv) guessing the spectrum from the variance in the Wiener-filter map, and (v) renormalization flow analysis of the field-theoretical problem providing the PURE filter. In all cases, the reconstruction can be described or approximated as Wiener-filter operations with assumed signal spectra derived from the data according to the same recipe, but with differing coefficients. All of these filters, except the renormalized one, exhibit a perception threshold in case of a Jeffreys prior for the unknown spectrum. Data modes with variance below this threshold do not affect the signal reconstruction at all. Filter (iv) seems to be similar to the so-called Karhune-Loeve and Feldman-Kaiser-Peacock estimators for galaxy power spectra used in cosmology, which therefore should also exhibit a marginal perception threshold if correctly implemented. We present statistical performance tests and show that the PURE filter is superior to the others, especially if the post-Wiener-filter corrections are included or in case an additional scale-independent spectral smoothness prior can be adopted.

  2. [Reconstructive investigations and identification measures in unknown soldiers of the Second World War].

    Science.gov (United States)

    Jopp-van Well, Eilin; Gehl, Axel; Säring, Dennis; Amling, Michael; Hahn, Michael; Sperhake, Jan; Augustin, Christa; Krebs, Oliver; Püschel, Klaus

    2016-01-01

    The article reports on the exhumation and identification of unknown soldiers from the Second World War. With the help of medicolegal investigation and reconstruction methods an American pilot presumably murdered by a shot to the head (lynch law) and an interned Italian soldier could be identified after about 70 years and brought back home.

  3. Inverse estimation for the unknown frost geometry on the external wall of a forced-convection pipe

    International Nuclear Information System (INIS)

    Chen, W.-L.; Yang, Y.-C.

    2009-01-01

    In this study, a conjugate gradient method based inverse algorithm is applied to estimate the unknown frost-layer boundary profile on the external wall of a pipe system using temperature measurements. It is assumed that no prior information is available on the functional form of the unknown profile; hence the procedure is classified as the function estimation in inverse calculation. The temperature data obtained from the direct problem are used to simulate the temperature measurements. The accuracy of the inverse analysis is examined by using simulated exact and inexact temperature measurements. Results show that an excellent estimation on boundary profile can be obtained for the test case considered in this study.

  4. Quantum Logic Networks for Probabilistic and Controlled Teleportation of Unknown Quantum States

    Institute of Scientific and Technical Information of China (English)

    GAO Ting

    2004-01-01

    We present simplification schemes for probabilistic and controlled teleportation of the unknown quantum states of both one particle and two particles and construct efficient quantum logic networks for implementing the new schemes by means of the primitive operations consisting of single-qubit gates, two-qubit controlled-not gates, Von Neumann measurement, and classically controlled operations. In these schemes the teleportation are not always successful but with certain probability.

  5. Recognition of internal structure of unknown objects with simultaneous neutron and gamma radiography

    International Nuclear Information System (INIS)

    Moghadam, K.K.; Nasseri, M.M.

    2004-01-01

    Generally speaking in customary industrial and medical radiography, there is no tendency to reveal the nature of the samples. Ordinarily, the main objective of taking a radiograph is to show the position and dimension of unknown parts, inside the test object and to determine cracks, defects, etc. Whereas in radiography many important factors such as material cross-sections and build-up factors are also involved. In this paper, by using both neutron and gamma radiography techniques, some mathematical relations were successfully generated, in order to calculate the neutron and gamma total macroscopic cross-sections of some unknown elements in the presence of the other elements. For this work, some test pieces were defined and made of lead, silver, copper, Nickel, tin, graphite and polyethylene. The neutron radiography facility at Tehran Research Reactor (TRR) was used as mixed neutron and gamma radiography source (Proceedings of the Second World Conference on Neutron Radiography, Paris, France, pp. 25-32). On testing of a correction of the above-mentioned generated relations, a new technique of simultaneous neutron and gamma radiography was also investigated

  6. 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...

  7. Fast entanglement detection for unknown states of two spatial qutrits

    International Nuclear Information System (INIS)

    Lima, G.; Gomez, E. S.; Saavedra, C.; Vargas, A.; Vianna, R. O.

    2010-01-01

    We investigate the practicality of the method proposed by Maciel et al. [Phys. Rev. A. 80, 032325 (2009).] for detecting the entanglement of two spatial qutrits (three-dimensional quantum systems), which are encoded in the discrete transverse momentum of single photons transmitted through a multislit aperture. The method is based on the acquisition of partial information of the quantum state through projective measurements, and a data processing analysis done with semidefinite programs. This analysis relies on generating gradually an optimal entanglement witness operator, and numerical investigations have shown that it allows for the entanglement detection of unknown states with a cost much lower than full state tomography.

  8. Heuristic method for searching global maximum of multimodal unknown function

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, K; Araki, Y; Inoue, K

    1983-06-01

    The method is composed of three kinds of searches. They are called g (grasping)-mode search, f (finding)-mode search and c (confirming)-mode search. In the g-mode search and the c-mode search, a heuristic method is used which was extracted from search behaviors of human subjects. In f-mode search, the simplex method is used which is well known as a search method for unimodal unknown function. Each mode search and its transitions are shown in the form of flowchart. The numerical results for one-dimensional through six-dimensional multimodal functions prove the proposed search method to be an effective one. 11 references.

  9. Fault diagnosis of an intelligent hydraulic pump based on a nonlinear unknown input observer

    Directory of Open Access Journals (Sweden)

    Zhonghai MA

    2018-02-01

    Full Text Available Hydraulic piston pumps are commonly used in aircraft. In order to improve the viability of aircraft and energy efficiency, intelligent variable pressure pump systems have been used in aircraft hydraulic systems more and more widely. Efficient fault diagnosis plays an important role in improving the reliability and performance of hydraulic systems. In this paper, a fault diagnosis method of an intelligent hydraulic pump system (IHPS based on a nonlinear unknown input observer (NUIO is proposed. Different from factors of a full-order Luenberger-type unknown input observer, nonlinear factors of the IHPS are considered in the NUIO. Firstly, a new type of intelligent pump is presented, the mathematical model of which is established to describe the IHPS. Taking into account the real-time requirements of the IHPS and the special structure of the pump, the mechanism of the intelligent pump and failure modes are analyzed and two typical failure modes are obtained. Furthermore, a NUIO of the IHPS is performed based on the output pressure and swashplate angle signals. With the residual error signals produced by the NUIO, online intelligent pump failure occurring in real-time can be detected. Lastly, through analysis and simulation, it is confirmed that this diagnostic method could accurately diagnose and isolate those typical failure modes of the nonlinear IHPS. The method proposed in this paper is of great significance in improving the reliability of the IHPS. Keywords: Fault diagnosis, Hydraulic piston pump, Model-based, Nonlinear unknown input observer (NUIO, Residual error

  10. A novel KFCM based fault diagnosis method for unknown faults in satellite reaction wheels.

    Science.gov (United States)

    Hu, Di; Sarosh, Ali; Dong, Yun-Feng

    2012-03-01

    Reaction wheels are one of the most critical components of the satellite attitude control system, therefore correct diagnosis of their faults is quintessential for efficient operation of these spacecraft. The known faults in any of the subsystems are often diagnosed by supervised learning algorithms, however, this method fails to work correctly when a new or unknown fault occurs. In such cases an unsupervised learning algorithm becomes essential for obtaining the correct diagnosis. Kernel Fuzzy C-Means (KFCM) is one of the unsupervised algorithms, although it has its own limitations; however in this paper a novel method has been proposed for conditioning of KFCM method (C-KFCM) so that it can be effectively used for fault diagnosis of both known and unknown faults as in satellite reaction wheels. The C-KFCM approach involves determination of exact class centers from the data of known faults, in this way discrete number of fault classes are determined at the start. Similarity parameters are derived and determined for each of the fault data point. Thereafter depending on the similarity threshold each data point is issued with a class label. The high similarity points fall into one of the 'known-fault' classes while the low similarity points are labeled as 'unknown-faults'. Simulation results show that as compared to the supervised algorithm such as neural network, the C-KFCM method can effectively cluster historical fault data (as in reaction wheels) and diagnose the faults to an accuracy of more than 91%. Copyright © 2011 ISA. Published by Elsevier Ltd. All rights reserved.

  11. Review of the Dinosaur Remains from the Middle Jurassic of Scotland, UK

    Directory of Open Access Journals (Sweden)

    Neil D. L. Clark

    2018-02-01

    Full Text Available Dinosaurs are rare from the Middle Jurassic worldwide. The Isle of Skye, is the only place in Scotland thus far to have produced dinosaur remains. These remains consist mainly of footprints, but also several bones and teeth. These Bajocian and Bathonian remains represent an important collection of a basal eusauropod, early examples of non-neosauropod and possible basal titanosauriform eusauropods, and theropod remains that may belong to an early coelurosaur and a possible megalosaurid, basal tyrannosauroid, or dromaeosaurid. The footprints from here also suggest a rich and diverse dinosaur fauna for which further better diagnosable remains are likely to be found.

  12. Distributed Synchronization Control of Multiagent Systems With Unknown Nonlinearities.

    Science.gov (United States)

    Su, Shize; Lin, Zongli; Garcia, Alfredo

    2016-01-01

    This paper revisits the distributed adaptive control problem for synchronization of multiagent systems where the dynamics of the agents are nonlinear, nonidentical, unknown, and subject to external disturbances. Two communication topologies, represented, respectively, by a fixed strongly-connected directed graph and by a switching connected undirected graph, are considered. Under both of these communication topologies, we use distributed neural networks to approximate the uncertain dynamics. Decentralized adaptive control protocols are then constructed to solve the cooperative tracker problem, the problem of synchronization of all follower agents to a leader agent. In particular, we show that, under the proposed decentralized control protocols, the synchronization errors are ultimately bounded, and their ultimate bounds can be reduced arbitrarily by choosing the control parameter appropriately. Simulation study verifies the effectiveness of our proposed protocols.

  13. 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.

  14. Marginalized adaptive particle filtering for nonlinear models with unknown time-varying noise parameters

    Czech Academy of Sciences Publication Activity Database

    Ökzan, E.; Šmídl, Václav; Saha, S.; Lundquist, C.; Gustafsson, F.

    2013-01-01

    Roč. 49, č. 6 (2013), s. 1566-1575 ISSN 0005-1098 R&D Projects: GA ČR(CZ) GAP102/11/0437 Keywords : Unknown Noise Statistics * Adaptive Filtering * Marginalized Particle Filter * Bayesian Conjugate prior Subject RIV: BC - Control Systems Theory Impact factor: 3.132, year: 2013 http://library.utia.cas.cz/separaty/2013/AS/smidl-0393047.pdf

  15. Venturing into unknown territory: the preparation and formulation of the Second Benelux Structural Outline

    NARCIS (Netherlands)

    de Vries, J.

    2008-01-01

    Inherent in transnational planning are obstacles which cause spatial planners to venture into unknown territory. The scale, the issues and the institutional context are significantly different from planning at the national level or below. What does this mean for the role of spatial plan-making,

  16. Protecting unknown two-qubit entangled states by nesting Uhrig's dynamical decoupling sequences

    International Nuclear Information System (INIS)

    Mukhtar, Musawwadah; Soh, Wee Tee; Saw, Thuan Beng; Gong, Jiangbin

    2010-01-01

    Future quantum technologies rely heavily on good protection of quantum entanglement against environment-induced decoherence. A recent study showed that an extension of Uhrig's dynamical decoupling (UDD) sequence can (in theory) lock an arbitrary but known two-qubit entangled state to the Nth order using a sequence of N control pulses [Mukhtar et al., Phys. Rev. A 81, 012331 (2010)]. By nesting three layers of explicitly constructed UDD sequences, here we first consider the protection of unknown two-qubit states as superposition of two known basis states, without making assumptions of the system-environment coupling. It is found that the obtained decoherence suppression can be highly sensitive to the ordering of the three UDD layers and can be remarkably effective with the correct ordering. The detailed theoretical results are useful for general understanding of the nature of controlled quantum dynamics under nested UDD. As an extension of our three-layer UDD, it is finally pointed out that a completely unknown two-qubit state can be protected by nesting four layers of UDD sequences. This work indicates that when UDD is applicable (e.g., when the environment has a sharp frequency cutoff and when control pulses can be taken as instantaneous pulses), dynamical decoupling using nested UDD sequences is a powerful approach for entanglement protection.

  17. Use of implantable and external loop recorders in syncope with unknown causes

    Directory of Open Access Journals (Sweden)

    Kaoru Tanno

    2017-12-01

    Full Text Available The gold standard for diagnosing syncope is to elucidate the symptom-electrocardiogram (ECG correlation. The ECG recordings during syncope allow physicians to either confirm or exclude an arrhythmia as the mechanism of syncope. Many studies have investigated the use of internal loop recorder (ILR, while few studies have used external loop recorder (ELR for patients with unexplained syncope. The aim of this review is to clarify the clinical usefulness of ILR and ELR in the diagnosis and management of patients with unexplained syncope. Many observational and four randomized control studies have shown that ILR for patients with unknown syncope is a useful tool for early diagnosis and improving diagnosis rate. ILR also provides important information on the mechanism of syncope and treatment strategy. However, there is no evidence of total mortality or quality of life improvements with ILR. The diagnostic yield of ELR in patients with syncope was similar to that with ILR within the same timeframe. Therefore, ELR could be considered for long-term ECG monitoring before a patient switches to using ILR. A systematic approach and selection of ECG monitoring tools reduces health care costs and improves the selection of patients for optimal treatment possibilities. Keywords: Internal loop recorder, External loop recorder, Unknown Syncope

  18. Remaining life diagnosis method and device for nuclear reactor

    International Nuclear Information System (INIS)

    Yamamoto, Michiyoshi.

    1996-01-01

    A neutron flux measuring means is inserted from the outside of a reactor pressure vessel during reactor operation to forecast neutron-degradation of materials of incore structural components in the vicinity of portions to be measured based on the measured values, and the remaining life of the reactor is diagnosed by the forecast degraded state. In this case, the neutron fluxes to be measured are desirably fast and/or medium neutron fluxes. As the positions where the measuring means is to be inserted, for example, the vicinity of the structural components at the periphery of the fuel assembly is selected. Aging degradation characteristics of the structural components are determined by using the aging degradation data for the structural materials. The remaining life is analyzed based on obtained aging degradation characteristics and stress evaluation data of the incore structural components at portions to be measured. Neutron irradiation amount of structural components at predetermined positions can be recognized accurately, and appropriate countermeasures can be taken depending on the forecast remaining life thereby enabling to improve the reliability of the reactor. (N.H.)

  19. Industry remains stuck in a transitional mode

    International Nuclear Information System (INIS)

    Garb, F.A.

    1991-01-01

    The near future for industry remains foggy for several obvious reasons. The shake-up of the Soviet Union and how the pieces will reform remains unclear. How successful efforts are to privatize government oil company operations around the world has yet to be determined. A long sought peace in the Middle East seems to be inching closer, but will this continue? If it does continue, what impact will it have on world energy policy? Will American companies, which are now transferring their attention to foreign E and P, also maintain an interest in domestic activities? Is the U.S. economy really on the upswing? We are told that the worst of the recession is over, but try telling this to thousands of workers in the oil patch who are being released monthly by the big players in domestic operations. This paper reports that 1992 should be a better year than 1991, if measured in opportunity. There are more exploration and acquisition options available, both domestically and internationally, than there have been in years. Probably more opportunities exist than there are players-certainly more than can be funded with current financial resources

  20. Data-driven remaining useful life prognosis techniques stochastic models, methods and applications

    CERN Document Server

    Si, Xiao-Sheng; Hu, Chang-Hua

    2017-01-01

    This book introduces data-driven remaining useful life prognosis techniques, and shows how to utilize the condition monitoring data to predict the remaining useful life of stochastic degrading systems and to schedule maintenance and logistics plans. It is also the first book that describes the basic data-driven remaining useful life prognosis theory systematically and in detail. The emphasis of the book is on the stochastic models, methods and applications employed in remaining useful life prognosis. It includes a wealth of degradation monitoring experiment data, practical prognosis methods for remaining useful life in various cases, and a series of applications incorporated into prognostic information in decision-making, such as maintenance-related decisions and ordering spare parts. It also highlights the latest advances in data-driven remaining useful life prognosis techniques, especially in the contexts of adaptive prognosis for linear stochastic degrading systems, nonlinear degradation modeling based pro...

  1. A learning-based semi-autonomous controller for robotic exploration of unknown disaster scenes while searching for victims.

    Science.gov (United States)

    Doroodgar, Barzin; Liu, Yugang; Nejat, Goldie

    2014-12-01

    Semi-autonomous control schemes can address the limitations of both teleoperation and fully autonomous robotic control of rescue robots in disaster environments by allowing a human operator to cooperate and share such tasks with a rescue robot as navigation, exploration, and victim identification. In this paper, we present a unique hierarchical reinforcement learning-based semi-autonomous control architecture for rescue robots operating in cluttered and unknown urban search and rescue (USAR) environments. The aim of the controller is to enable a rescue robot to continuously learn from its own experiences in an environment in order to improve its overall performance in exploration of unknown disaster scenes. A direction-based exploration technique is integrated in the controller to expand the search area of the robot via the classification of regions and the rubble piles within these regions. Both simulations and physical experiments in USAR-like environments verify the robustness of the proposed HRL-based semi-autonomous controller to unknown cluttered scenes with different sizes and varying types of configurations.

  2. Adaptive neural network output feedback control for stochastic nonlinear systems with unknown dead-zone and unmodeled dynamics.

    Science.gov (United States)

    Tong, Shaocheng; Wang, Tong; Li, Yongming; Zhang, Huaguang

    2014-06-01

    This paper discusses the problem of adaptive neural network output feedback control for a class of stochastic nonlinear strict-feedback systems. The concerned systems have certain characteristics, such as unknown nonlinear uncertainties, unknown dead-zones, unmodeled dynamics and without the direct measurements of state variables. In this paper, the neural networks (NNs) are employed to approximate the unknown nonlinear uncertainties, and then by representing the dead-zone as a time-varying system with a bounded disturbance. An NN state observer is designed to estimate the unmeasured states. Based on both backstepping design technique and a stochastic small-gain theorem, a robust adaptive NN output feedback control scheme is developed. It is proved that all the variables involved in the closed-loop system are input-state-practically stable in probability, and also have robustness to the unmodeled dynamics. Meanwhile, the observer errors and the output of the system can be regulated to a small neighborhood of the origin by selecting appropriate design parameters. Simulation examples are also provided to illustrate the effectiveness of the proposed approach.

  3. Mapping of possible prion protein self interaction domains using peptide arrays

    NARCIS (Netherlands)

    Rigter, A.; Langeveld, J.P.M.; Timmers-Parohi, D.; Jacobs, J.G.; Moonen, P.L.J.M.; Bossers, A.

    2007-01-01

    Background The common event in transmissible spongiform encephalopathies (TSEs) or prion diseases is the conversion of host-encoded protease sensitive cellular prion protein (PrPC) into strain dependent isoforms of scrapie associated protease resistant isoform (PrPSc) of prion protein (PrP). These

  4. Scrapie susceptibility-linked polymorphisms modulate the in vitro conversion of sheep prion protein to protease-resistant forms

    NARCIS (Netherlands)

    Bossers, A.; Belt, P.B.G.M.; Raymond, G.J.; Caughey, B.; Vries, de R.; Smits, M.

    1997-01-01

    Prion diseases are natural transmissible neurodegenerative disorders in humans and animals. They are characterized by the accumulation of a protease-resistant scrapie-associated prion protein (PrPSc) of the host-encoded cellular prion protein (PrPC) mainly in the central nervous system.

  5. Adult human microglia secrete cytokines when exposed to neurotoxic prion protein peptide: no intermediary role for prostaglandin E2

    NARCIS (Netherlands)

    Veerhuis, Robert; Hoozemans, Jeroen J. M.; Janssen, Ingrid; Boshuizen, Ronald S.; Langeveld, Jan P. M.; Eikelenboom, Piet

    2002-01-01

    Prion diseases are characterized by accumulation of protease resistant isoforms of prion protein (termed PrP(SC)), glial activation and neurodegeneration. The time course of PrP deposition, appearance of activated microglia, and of neuronal apoptosis in experimentally-induced prion disease suggests

  6. A novel seven-octapeptide repeat insertion in the prion protein gene (PRNP) in a Dutch pedigree with Gerstmann-Sträussler-Scheinker disease phenotype: comparison with similar cases from the literature

    NARCIS (Netherlands)

    Jansen, Casper; Voet, Willem; Head, Mark W.; Parchi, Piero; Yull, Helen; Verrips, Aad; Wesseling, Pieter; Meulstee, Jan; Baas, Frank; van Gool, Willem A.; Ironside, James W.; Rozemuller, Annemieke J. M.

    2011-01-01

    Human prion diseases can be sporadic, inherited or acquired by infection and show considerable phenotypic heterogeneity. We describe the clinical, histopathological and pathological prion protein (PrP(Sc)) characteristics of a Dutch family with a novel 7-octapeptide repeat insertion (7-OPRI) in

  7. “Speaking in the Unknown Tongue, Holiness Church, Jackson, 1939”

    Directory of Open Access Journals (Sweden)

    Diana Almeida

    2010-02-01

    Full Text Available “Speaking in the Unknown Tongue, Holiness Church, Jackson, 1939, ” Photographs, p. 104, with the gracious permission of the Eudora Welty FoundationDear Welty,Writing by the fireplace, I see you standing with the camerathe eye of the eye of the eyein awe and wonder,a guest in Holiness Churchwatching: the painted horse “The Lord on the Cloud” in the centera white mass moving through mountainslines upon valleys, there goes the Lord ridingoh yes, rise your heart to God in praise, sisterspeaking i...

  8. Work-related factors influencing home care nurse intent to remain employed.

    Science.gov (United States)

    Tourangeau, Ann E; Patterson, Erin; Saari, Margaret; Thomson, Heather; Cranley, Lisa

    Health care is shifting out of hospitals into community settings. In Ontario, Canada, home care organizations continue to experience challenges recruiting and retaining nurses. However, factors influencing home care nurse retention that can be modified remain largely unexplored. Several groups of factors have been identified as influencing home care nurse intent to remain employed including job characteristics, work structures, relationships and communication, work environment, responses to work, and conditions of employment. The aim of this study was to test and refine a model that identifies which factors are related to home care nurse intentions to remain employed for the next 5 years with their current home care employer organization. A cross-sectional survey design was implemented to test and refine a hypothesized model of home care nurse intent to remain employed. Logistic regression was used to determine which factors influence home care nurse intent to remain employed. Home care nurse intent to remain employed for the next 5 years was associated with increasing age, higher nurse-evaluated quality of care, having greater variety of patients, experiencing greater meaningfulness of work, having greater income stability, having greater continuity of client care, experiencing more positive relationships with supervisors, experiencing higher work-life balance, and being more satisfied with salary and benefits. Home care organizations can promote home care nurse intent to remain employed by (a) ensuring nurses have adequate training and resources to provide quality client care, (b) improving employment conditions to increase income stability and satisfaction with pay and benefits, (c) ensuring manageable workloads to facilitate improved work-life balance, and (d) ensuring leaders are accessible and competent.

  9. Red Assembly: the work remains

    Directory of Open Access Journals (Sweden)

    Leslie Witz

    installed. What to do at this limit, at the transgressive encounter between saying yes and no to history, remains the challenge. It is the very challenge of what insistently remains.

  10. Detection of prions in the faeces of sheep naturally infected with classical scrapie

    Directory of Open Access Journals (Sweden)

    Terry Linda A

    2011-05-01

    Full Text Available Abstract Classical scrapie is a naturally transmitted prion disease of sheep and goats. Contaminated environments may contribute to the spread of disease and evidence from animal models has implicated urine, blood, saliva, placenta and faeces as possible sources of the infection. Here we sought to determine whether sheep naturally infected with classical scrapie shed prions in their faeces. We used serial protein misfolding cyclic amplification (sPMCA along with two extraction methods to examine faeces from sheep during both the clinical and preclinical phases of the disease and showed amplification of PrPSc in 7 of 15 and 14 of 14 sheep respectively. However PrPSc was not amplified from the faeces of 25 sheep not exposed to scrapie. These data represent the first demonstration of prion shedding in faeces from a naturally infected host and thus a likely source of prion contamination in the environment.

  11. Neuroendocrine Cell Carcinoma of Unknown Primary Arising in Long Standing History of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stergios Boussios

    2015-01-01

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune disease that targets myelinated axons in the central nervous system (CNS. Cancer of unknown primary site (CUP is a well-recognised clinical disorder, accounting for 3–5% of all malignant epithelial tumors. CUP is clinically characterised as an aggressive disease with early dissemination. Studies of cancer risk in MS patients have shown inconsistent findings. An increased risk of malignancy in patients with MS has been suggested, but recently serious questions have been raised regarding this association. Use of disease-modifying therapies might contribute to an increased cancer risk in selected MS patients. The concurrence of MS and CUP is exceptionally rare. Here we describe the case of a neuroendocrine carcinoma of unknown primary diagnosed in a male patient with a nine-year history of MS. The discussion includes data from all available population-based register studies with estimates of certain malignancies in patients with MS.

  12. Taming the unknown a history of algebra from antiquity to the early twentieth century

    CERN Document Server

    Katz, Victor J

    2014-01-01

    What is algebra? For some, it is an abstract language of x's and y's. For mathematics majors and professional mathematicians, it is a world of axiomatically defined constructs like groups, rings, and fields. Taming the Unknown considers how these two seemingly different types of algebra evolved and how they relate. Victor Katz and Karen Parshall explore the history of algebra, from its roots in the ancient civilizations of Egypt, Mesopotamia, Greece, China, and India, through its development in the medieval Islamic world and medieval and early modern Europe, to its modern form in the early twentieth century. Defining algebra originally as a collection of techniques for determining unknowns, the authors trace the development of these techniques from geometric beginnings in ancient Egypt and Mesopotamia and classical Greece. They show how similar problems were tackled in Alexandrian Greece, in China, and in India, then look at how medieval Islamic scholars shifted to an algorithmic stage, which was further dev...

  13. Biological characterization of two xenografts derived from human CUPs (carcinomas of unknown primary

    Directory of Open Access Journals (Sweden)

    Bernheim Alain

    2007-12-01

    Full Text Available Abstract Background Carcinomas of unknown primary site (CUP are epithelial malignancies revealed by metastatic lesions in the absence of any detectable primary tumor. Although they often adopt an aggressive clinical pattern, their basic biology remains poorly understood. Laboratory research on their biology have been hampered so far by the absence of cell lines representative of CUPs. Methods We attempted xenografts of CUP clinical specimens in immunodeficient mice and subsequent in vitro culture of transplanted malignant cells. Whenever possible, malignant xenografted or cultured cells were characterized by microsatellite genotyping, immunohistology, electron microscopy, multifish chromosome analysis and search of TP 53 gene mutations. Results Successful xenografts were achieved in 2 cases out of 4. One of them (Capi1 was lost after 3 passages whereas the other one (Capi3 has been adapted to in vitro culture and is currently available to the scientific community with reliable identification based on microsatellite genotyping. Both Capi1 and Capi3 have histological characteristics of adenocarcinomas and display intense expression of EMA, CEA and cytokeratin 7. Multifish chromosome analysis demonstrated a translocation involving chromosomes 4 and 21 in both specimens. Distinct rare missense mutations of the TP53 gene were detected in Capi1 (codon 312 and Capi3 (codon 181; the codon 181 mutation is consistent with a previously reported similar finding in a small series of CUP specimens. Finally, intense membrane expression of c-kit was recorded in Capi3. Conclusion Our data suggest that xenografted tumors can be obtained from a substantial fraction of CUP clinical specimens. The hypothesis of a preferential association of CUPs with TP 53 mutations of codon 181 deserves further investigations. The Capi3 cell line will be a useful tool for assessment of novel c-kit inhibitors.

  14. A 'range test' for determining scatterers with unknown physical properties

    Science.gov (United States)

    Potthast, Roland; Sylvester, John; Kusiak, Steven

    2003-06-01

    We describe a new scheme for determining the convex scattering support of an unknown scatterer when the physical properties of the scatterers are not known. The convex scattering support is a subset of the scatterer and provides information about its location and estimates for its shape. For convex polygonal scatterers the scattering support coincides with the scatterer and we obtain full shape reconstructions. The method will be formulated for the reconstruction of the scatterers from the far field pattern for one or a few incident waves. The method is non-iterative in nature and belongs to the type of recently derived generalized sampling schemes such as the 'no response test' of Luke-Potthast. The range test operates by testing whether it is possible to analytically continue a far field to the exterior of any test domain Omegatest. By intersecting the convex hulls of various test domains we can produce a minimal convex set, the convex scattering support of which must be contained in the convex hull of the support of any scatterer which produces that far field. The convex scattering support is calculated by testing the range of special integral operators for a sampling set of test domains. The numerical results can be used as an approximation for the support of the unknown scatterer. We prove convergence and regularity of the scheme and show numerical examples for sound-soft, sound-hard and medium scatterers. We can apply the range test to non-convex scatterers as well. We can conclude that an Omegatest which passes the range test has a non-empty intersection with the infinity-support (the complement of the unbounded component of the complement of the support) of the true scatterer, but cannot find a minimal set which must be contained therein.

  15. Uric Acid: The Unknown Uremic Toxin.

    Science.gov (United States)

    Treviño-Becerra, Alejandro

    2018-01-01

    This review brings together concepts of uric acid metabolism affecting renal parenchyma and its function and the current therapies to reduce hyperuricemia (HyU) and avoid renal disease progression. High uric acid plays an important role in several chronic diseases including kidney diseases such as lithiasis, gout nephropathy, and preeclampsia. In the last 30 years, it has been shown that reducing HyU with low protein and low purine diets in addition to allopurinol creates physiopathological conditions that produce a slight increase in the glomerular filtration rate (GFR). In recent years, in a new era of research in clinical, genetics, pharmacological, and epidemiologic fields, they have been moving forward to support the idea that reduction in HyU could benefit the chronic renal failure (CRF) patients (stage III-IV), thereby avoiding the drop of GFR for undefined mechanisms. There are several clinical trials in progress that show the HyU reducing to very low values and an increased GFR. In a young population, when treating HyU there is a reduction in high blood pressure. There are some reports showing that HyU could play a role in the diabetic nephropathy. Therefore, there have been some speculations that HyU treatment could stop the progression of CRF modifying the natural history of the diseases. So there will be new clinical trials with old and new medication and metabolic procedure to maintain a very low blood levels in the unknown uremic toxin know as uric acid which seems to be the toxin to the damage kidney. © 2018 S. Karger AG, Basel.

  16. Putting prions into focus: application of single molecule detection to the diagnosis of prion diseases.

    Science.gov (United States)

    Giese, A; Bieschke, J; Eigen, M; Kretzschmar, H A

    2000-01-01

    Prion diseases are characterized by the cerebral deposition of an aggregated pathological isoform of the prion protein (PrP(Sc)) which constitutes the principal component of the transmissible agent termed prion. In order to develop a highly sensitive method for the detection of PrP(Sc) aggregates in biological samples such as cerebrospinal fluid (CSF), we used a method based on Fluorescence Correlation Spectroscopy (FCS), a technique which allows detection of single fluorescently labeled molecules in solution. Within the FCS setup, fluorescent photons emitted by molecules passing an open volume element defined by the beam of an excitation laser focussed into a diffraction-limited spot are imaged confocally onto a single photon counting detector. Aggregates of PrP(Sc) could be labeled by co-aggregation of probe molecules such as monomeric recombinant PrP or PrP-specific antibodies tagged with a fluorescent dye. In addition to slow diffusion, labeled aggregates are characterized by high fluorescence intensity, which allows detection and quantification by analysis of fluorescence intensity distribution. To improve detection of rare target particles, the accessible volume element was increased by scanning for intensely fluorescent targets (SIFT). To further improve sensitivity and specificity, two different probes were used simultaneously in a two-color setup. In a diagnostic model system of CSF spiked with purified prion rods, dual-color SIFT was more sensitive than Western blot analysis. In addition, a PrP(Sc)-specific signal was also detected in a number of CSF samples derived from CJD patients but not in controls.

  17. PrP mRNA and protein expression in brain and PrP(c) in CSF in Creutzfeldt-Jakob disease MM1 and VV2.

    Science.gov (United States)

    Llorens, Franc; Ansoleaga, Belén; Garcia-Esparcia, Paula; Zafar, Saima; Grau-Rivera, Oriol; López-González, Irene; Blanco, Rosi; Carmona, Margarita; Yagüe, Jordi; Nos, Carlos; Del Río, José Antonio; Gelpí, Ellen; Zerr, Inga; Ferrer, Isidre

    2013-01-01

    Creutzfeldt-Jakob disease (CJD) is a heterogenic neurodegenerative disorder associated with abnormal post-translational processing of cellular prion protein (PrP(c)). CJD displays distinctive clinical and pathological features which correlate with the genotype at the codon 129 (methionine or valine: M or V respectively) in the prion protein gene and with size of the protease-resistant core of the abnormal prion protein PrP(sc) (type 1: 20/21 kDa and type 2: 19 kDa). MM1 and VV2 are the most common sporadic CJD (sCJD) subtypes. PrP mRNA expression levels in the frontal cortex and cerebellum are reduced in sCJD in a form subtype-dependent. Total PrP protein levels and PrP(sc) levels in the frontal cortex and cerebellum accumulate differentially in sCJD MM1 and sCJD VV2 with no relation between PrP(sc) deposition and spongiform degeneration and neuron loss, but with microgliosis, and IL6 and TNF-α response. In the CSF, reduced PrP(c), the only form present in this compartment, occurs in sCJD MM1 and VV2. PrP mRNA expression is also reduced in the frontal cortex in advanced stages of Alzheimer disease, Lewy body disease, progressive supranuclear palsy, and frontotemporal lobe degeneration, but PrP(c) levels in brain varies from one disease to another. Reduced PrP(c) levels in CSF correlate with PrP mRNA expression in brain, which in turn reflects severity of degeneration in sCJD.

  18. Performance and Difficulties of Students in Formulating and Solving Quadratic Equations with One Unknown

    Science.gov (United States)

    Didis, Makbule Gozde; Erbas, Ayhan Kursat

    2015-01-01

    This study attempts to investigate the performance of tenth-grade students in solving quadratic equations with one unknown, using symbolic equation and word-problem representations. The participants were 217 tenth-grade students, from three different public high schools. Data was collected through an open-ended questionnaire comprising eight…

  19. [Pilot study of domain-specific terminology adaptation for morphological analysis: research on unknown terms in national examination documents of radiological technologists].

    Science.gov (United States)

    Tsuji, Shintarou; Nishimoto, Naoki; Ogasawara, Katsuhiko

    2008-07-20

    Although large medical texts are stored in electronic format, they are seldom reused because of the difficulty of processing narrative texts by computer. Morphological analysis is a key technology for extracting medical terms correctly and automatically. This process parses a sentence into its smallest unit, the morpheme. Phrases consisting of two or more technical terms, however, cause morphological analysis software to fail in parsing the sentence and output unprocessed terms as "unknown words." The purpose of this study was to reduce the number of unknown words in medical narrative text processing. The results of parsing the text with additional dictionaries were compared with the analysis of the number of unknown words in the national examination for radiologists. The ratio of unknown words was reduced 1.0% to 0.36% by adding terminologies of radiological technology, MeSH, and ICD-10 labels. The terminology of radiological technology was the most effective resource, being reduced by 0.62%. This result clearly showed the necessity of additional dictionary selection and trends in unknown words. The potential for this investigation is to make available a large body of clinical information that would otherwise be inaccessible for applications other than manual health care review by personnel.

  20. An analysis of the alleged skeletal remains of Carin Göring.

    Directory of Open Access Journals (Sweden)

    Anna Kjellström

    Full Text Available In 1991, treasure hunters found skeletal remains in an area close to the destroyed country residence of former Nazi leader Hermann Göring in northeastern Berlin. The remains, which were believed to belong to Carin Göring, who was buried at the site, were examined to determine whether it was possible to make a positive identification. The anthropological analysis showed that the remains come from an adult woman. The DNA analysis of several bone elements showed female sex, and a reference sample from Carin's son revealed mtDNA sequences identical to the remains. The profile has one nucleotide difference from the Cambridge reference sequence (rCRS, the common variant 263G. A database search resulted in a frequency of this mtDNA sequence of about 10% out of more than 7,000 European haplotypes. The mtDNA sequence found in the ulna, the cranium and the reference sample is, thus, very common among Europeans. Therefore, nuclear DNA analysis was attempted. The remains as well as a sample from Carin's son were successfully analysed for the three nuclear markers TH01, D7S820 and D8S1179. The nuclear DNA analysis of the two samples revealed one shared allele for each of the three markers, supporting a mother and son relationship. This genetic information together with anthropological and historical files provides an additional piece of circumstantial evidence in our efforts to identify the remains of Carin Göring.

  1. A Nonlinear Unit Root Test in the Presence of an Unknown Break

    OpenAIRE

    Popp, Stephan

    2008-01-01

    The Perron test is the most commonly applied procedure to test for a unit root in the presence of a structural break of unknown timing in the trend function. Deriving the Perron-type test regression from an unobserved component model, it is shown that the test regression in fact is nonlinear in coefficient. Taking account of the nonlinearity leads to a test with properties that are exclusively assigned to Schmidt-Phillips LM-type unit root tests.

  2. Robust exponential stabilization of nonholonomic wheeled mobile robots with unknown visual parameters

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The visual servoing stabilization of nonholonomic mobile robot with unknown camera parameters is investigated.A new kind of uncertain chained model of nonholonomic kinemetic system is obtained based on the visual feedback and the standard chained form of type (1,2) mobile robot.Then,a novel time-varying feedback controller is proposed for exponentially stabilizing the position and orientation of the robot using visual feedback and switching strategy when the camera parameters are not known.The exponential s...

  3. Estimating unknown input parameters when implementing the NGA ground-motion prediction equations in engineering practice

    Science.gov (United States)

    Kaklamanos, James; Baise, Laurie G.; Boore, David M.

    2011-01-01

    The ground-motion prediction equations (GMPEs) developed as part of the Next Generation Attenuation of Ground Motions (NGA-West) project in 2008 are becoming widely used in seismic hazard analyses. However, these new models are considerably more complicated than previous GMPEs, and they require several more input parameters. When employing the NGA models, users routinely face situations in which some of the required input parameters are unknown. In this paper, we present a framework for estimating the unknown source, path, and site parameters when implementing the NGA models in engineering practice, and we derive geometrically-based equations relating the three distance measures found in the NGA models. Our intent is for the content of this paper not only to make the NGA models more accessible, but also to help with the implementation of other present or future GMPEs.

  4. The role of PET in initial work-up and evaluation after therapy in patients with carcinoma of unknown primary

    Energy Technology Data Exchange (ETDEWEB)

    Ryoo, Baek Yeol; Kang, Yoon Koo

    1998-12-01

    The carcinoma of unknown primary occupied 5 - 10 % of all malignancies. It is heterogenous in origin and has poor prognosis. The indentification of primary site and definition of involved area are more helpful in the management. The efficacy of positron emission tomography (PET) with fluorine-18- fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (F18-FDG) was evaluated in several tumors such as breast, pancreas and head and neck cancers. In carcinoma of unknown primary, it was reported that the concentration of FDG was increased in tumor tissues, and that PET with F18-FDG may be much helpful in identifying primary site and defining involved area. The authors evaluated the usefulness of PET with F18-FDG in initial work-up and in evaluation after radical therapy for the patients with carcinoma of unknown primary. The visual analysis of FDG-PET would be helpful in identifying primary site and defining involved area. In detecting recurrent of residual lesions, FDG-PET seemed to be less helpful than conventional diagnostic work-up. But more studies with larger number of cases and longer follow-up were required. The results of this study can be bases for the direction of future studies for the usefulness of PET in carcinoma of unknown primary.

  5. The role of PET in initial work-up and evaluation after therapy in patients with carcinoma of unknown primary

    International Nuclear Information System (INIS)

    Ryoo, Baek Yeol; Kang, Yoon Koo

    1998-12-01

    The carcinoma of unknown primary occupied 5 - 10 % of all malignancies. It is heterogenous in origin and has poor prognosis. The indentification of primary site and definition of involved area are more helpful in the management. The efficacy of positron emission tomography (PET) with fluorine-18- fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (F18-FDG) was evaluated in several tumors such as breast, pancreas and head and neck cancers. In carcinoma of unknown primary, it was reported that the concentration of FDG was increased in tumor tissues, and that PET with F18-FDG may be much helpful in identifying primary site and defining involved area. The authors evaluated the usefulness of PET with F18-FDG in initial work-up and in evaluation after radical therapy for the patients with carcinoma of unknown primary. The visual analysis of FDG-PET would be helpful in identifying primary site and defining involved area. In detecting recurrent of residual lesions, FDG-PET seemed to be less helpful than conventional diagnostic work-up. But more studies with larger number of cases and longer follow-up were required. The results of this study can be bases for the direction of future studies for the usefulness of PET in carcinoma of unknown primary

  6. Radiotherapeutic concepts in cancer of unknown primary site

    International Nuclear Information System (INIS)

    Krug, D.; Debus, J.; Sterzing, F.

    2014-01-01

    The term cancer of unknown primary (CUP) encompasses a group of entities which differ to a great extent regarding etiology, prognosis and therapeutic management. The aim of the study was an elaboration of the role of radiotherapy in CUP syndrome. Systematic literature search and specification of the available treatment options. Radiotherapy is an integral part of interdisciplinary management approaches for patients with CUP in both curative and palliative situations. Radio-oncological techniques, such as intensity-modulated radiotherapy and stereotactic body radiotherapy increase the therapeutic window. Modern diagnostic modalities from radiology and nuclear medicine are the cornerstone of radiotherapeutic interventions, especially in terms of target volume definition and pretherapeutic staging. In the interdisciplinary setting radiation oncology offers the possibility of curative and often organ preserving approaches in patients with axillary and cervical CUP. In addition, improvement and preservation of quality of life can be achieved in patients with metastatic disease. Radiation oncology is a crucial component of the interdisciplinary management of patients with CUP. Therapeutic decisions in patients with CUP should be made in an interdisciplinary setting. (orig.) [de

  7. And the Dead Remain Behind

    Directory of Open Access Journals (Sweden)

    Peter Read

    2013-08-01

    Full Text Available In most cultures the dead and their living relatives are held in a dialogic relationship. The dead have made it clear, while living, what they expect from their descendants. The living, for their part, wish to honour the tombs of their ancestors; at the least, to keep the graves of the recent dead from disrepair. Despite the strictures, the living can fail their responsibilities, for example, by migration to foreign countries. The peripatetic Chinese are one of the few cultures able to overcome the dilemma of the wanderer or the exile. With the help of a priest, an Australian Chinese migrant may summon the soul of an ancestor from an Asian grave to a Melbourne temple, where the spirit, though removed from its earthly vessel, will rest and remain at peace. Amongst cultures in which such practices are not culturally appropriate, to fail to honour the family dead can be exquisitely painful. Violence is the cause of most failure.

  8. 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 ...

  9. Palmar, Patellar, and Pedal Human Remains from Pavlov

    Czech Academy of Sciences Publication Activity Database

    Trinkaus, E.; Wojtal, P.; Wilczyński, J.; Sázelová, Sandra; Svoboda, Jiří

    2017-01-01

    Roč. 2017, June (2017), s. 73-101 ISSN 1545-0031 Institutional support: RVO:68081758 Keywords : Gravettian * human remains * isolated bones * anatomically modern humans * Upper Paleolithic Subject RIV: AC - Archeology, Anthropology, Ethnology OBOR OECD: Archaeology http://paleoanthro.org/media/journal/content/PA20170073.pdf

  10. Experience Replay for Optimal Control of Nonzero-Sum Game Systems With Unknown Dynamics.

    Science.gov (United States)

    Zhao, Dongbin; Zhang, Qichao; Wang, Ding; Zhu, Yuanheng

    2016-03-01

    In this paper, an approximate online equilibrium solution is developed for an N -player nonzero-sum (NZS) game systems with completely unknown dynamics. First, a model identifier based on a three-layer neural network (NN) is established to reconstruct the unknown NZS games systems. Moreover, the identifier weight vector is updated based on experience replay technique which can relax the traditional persistence of excitation condition to a simplified condition on recorded data. Then, the single-network adaptive dynamic programming (ADP) with experience replay algorithm is proposed for each player to solve the coupled nonlinear Hamilton- (HJ) equations, where only the critic NN weight vectors are required to tune for each player. The feedback Nash equilibrium is provided by the solution of the coupled HJ equations. Based on the experience replay technique, a novel critic NN weights tuning law is proposed to guarantee the stability of the closed-loop system and the convergence of the value functions. Furthermore, a Lyapunov-based stability analysis shows that the uniform ultimate boundedness of the closed-loop system is achieved. Finally, two simulation examples are given to verify the effectiveness of the proposed control scheme.

  11. Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease

    Science.gov (United States)

    Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study,...

  12. Amidation and structure relaxation abolish the neurotoxicity of the prion peptide PrP106-126 in vivo and in vitro

    DEFF Research Database (Denmark)

    Bergstrøm, Linda Alice; Hvass, Henriette Cordes; Zsurger, N.

    2005-01-01

    One of the major pathological hallmarks of transmissible spongiform encephalopathies (TSEs) is the accumulation of a pathogenic (scrapie) isoform (PrPSc) of the cellular prion protein (PrPC) primarily in the central nervous system. The synthetic prion peptide PrP106-126 shares many characteristics...

  13. Characterisation of new monoclonal antibodies reacting with prions from both human and animal brain tissues

    DEFF Research Database (Denmark)

    Hvass, Henriette Cordes; Bergström, Ann-Louise; Ohm, Jakob

    2008-01-01

    spongiform encephalopathy (bovine brain), scrapie (ovine brain) and experimental scrapie in hamster and in mice. The antibodies were also used for PET-blotting in which PrPSc blotted from brain tissue sections onto a nitrocellulose membrane is visualized with antibodies after protease and denaturant...

  14. Prions in Variably Protease-Sensitive Prionopathy: An Update

    NARCIS (Netherlands)

    Zou, W.Q.; Gambetti, P.; Xiao, X.; Yuan, J.; Langeveld, J.P.M.; Pirisinu, L.

    2013-01-01

    Human prion diseases, including sporadic, familial, and acquired forms such as Creutzfeldt-Jakob disease (CJD), are caused by prions in which an abnormal prion protein (PrPSc) derived from its normal cellular isoform (PrPC) is the only known component. The recently-identified variably

  15. Robotics to enable older adults to remain living at home.

    Science.gov (United States)

    Pearce, Alan J; Adair, Brooke; Miller, Kimberly; Ozanne, Elizabeth; Said, Catherine; Santamaria, Nick; Morris, Meg E

    2012-01-01

    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.

  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. The three unknown data of climate

    International Nuclear Information System (INIS)

    Noblet-Ducoudre, N.; Dupouey, J.L.; Levy, M.; Bopp, L.; Boucher, O.; Dahan Dalmedico, A.; Baruch, J.O.

    2007-01-01

    Even if the relation between global warming and the increase of greenhouse gases of anthropic origin in the atmosphere is now well established, several questions remain unanswered. The climate machine is so complex that the multiple actions and retroactions can hardly be modelled and the uncertainties of carbon and water cycles are numerous. This press-kit presents in five parts the complex problem of the understanding of climatic change: 1 - the ambiguous role of forests: making a status of the effects of forests on climate is a difficult task involving the biosphere, the leaf respiration, the migration of vegetable species and their reaction with respect to climate change. 2 - the turbulences in the ocean: according to measurements performed since 15 years, the ocean traps more than a quarter of anthropic carbon emissions. But, will the oceanic CO 2 pump be capable of following up the permanent increase of emissions? 3 - the double game of aerosols: some aerosols contribute to the cooling down of the Earth's surface while others influence the formation of clouds and contribute to the greenhouse effect. The role of aerosols remains a puzzling problem for climatologists. 4 - a world of uncertainties: according to the last estimates of the Intergovernmental Panel on Climatic Change, the average world temperature should rise from 1.1 to 6.4 deg. C from now to the end of the century. This wide range reflects the uncertainties in the modelling of the Earth system. 5 - the necessary blend of economics and climate or the impact of climate models and of their uncertainties on political-economical decisions and on international negotiations. (J.S.)

  18. 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

  19. Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?

    International Nuclear Information System (INIS)

    Santhanam, Prasanna; Chandramahanti, Sangeeta; Kroiss, Alexander; Yu, Run; Ruszniewski, Philippe; Kumar, Rakesh; Taieb, David

    2015-01-01

    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 68 Ga-labeled somatostatin analogs ( 68 Ga-DOTA-SSTa) and 18 F-DOPA have shown promise. In direct comparisons between 68 Ga-DOTA-SSTa PET/CT and 99m Tc-HYNIC-octreotide/ 111 In-pentetreotide SPECT(/CT), 68 Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. 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 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 68 Ga-DOTA-SSTa, alternatively 18 F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and 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 developed PET approaches (radiopharmaceuticals) and

  20. Frequency of different causes of pyrexia of unknown origin on bone marrow examination in a tertiary care hospital

    Energy Technology Data Exchange (ETDEWEB)

    Noor, A.; Ayyub, M.; Shafiq, M. [National Univ. of Science and Technology, Islamabad (Pakistan)

    2014-09-15

    To determine the frequency of underlying causes of pyrexia of unknown origin on bone marrow examination. Study Design: Descriptive study. Place and Duration of Study: The study was carried out at Hematology department (pathology) of Army Medical College, National University of Sciences and Technology (NUST) and Military Hospital Rawalpindi (during the period of one year) from Jan 2012-Dec 2012. Material and Methods: Total of 94 patients reporting with pyrexia of unknown origin at MH Rawalpindi underwent bone marrow examination. Bone marrow aspiration procedure was done from posterior superioriliac spine in patients older than one year while tibial tuberosity was used in patients less than one year of age. Lumbar puncture needle of 16 Gwas used for bone narrow aspiration and trephine biopsy was done by using 11 Gtrephine biopsy needle. Results: In children, commonest causes observed were acute lymphoblastic leukaemia in 7 (23.3%), marked haemophagocytosis in 4 (13.3%) and visceral leishmaniasis in 4 (13.3%) patients. In adults, commonest causes included megaloblastic anaemia in 13 (20.3%), lymphoproliferative disorders in 8 (12.5%) and hypersplenism in 5(7.8%) patients. Conclusion: This study concludes that causes of pyrexia of unknown origin vary with age of the patient. The most frequent causes of pyrexia of unknown origin observed in children were acute lymphoblastic leukaemia, marked haemophagocytosis, and visceral leishmaniasis where in adults main causes were megaloblastic anaemia, lymphoproliferative disorders and hypersplenism. (author)

  1. Unintentional drinking-water contamination events of unknown origin: surrogate for terrorism preparedness.

    Science.gov (United States)

    Winston, Gary; Leventhal, Alex

    2008-01-01

    Drinking-water is a direct conduit to many human receptors. An intentional attack (e.g. terrorism) on drinking-water systems can shock and disrupt elements of national infrastructures. We report on an unintentional drinking-water contamination event that occurred in Tel Aviv, Israel in July, 2001. Initially of unknown origin, this event involved risk management strategies used by the Ministry of Health for abating a potential public health crisis as might be envisaged of water contamination due to terrorism. In an abrupt event of unknown origin, public health officials need to be responsible for the same level of preparedness and risk communication. This is emphasized by comparison of management strategies between the Tel Aviv event and one of dire consequences that occurred in Camelford, England in 1988. From the onset of the Tel Aviv incident, the public health strategy was to employ the precautionary principle by warning residents of the affected region to not drink tap water, even if boiled. This strategy was in contrast to an earlier crisis that occurred in Camelford, England in 1988. An outcome of this event was heightened awareness that a water crisis can occur in peacetime and not only in association with terrorism. No matter how minor the contamination event or short-term the disruption of delivery of safe drinking-water, psychological, medical and public health impact could be significant.

  2. Prediction of unknown deep foundation lengths using the Hilbert Huang Transform (HHT

    Directory of Open Access Journals (Sweden)

    Ahmed T.M. Farid

    2012-08-01

    Full Text Available Prediction of unknown deep foundation embedment depth is a great deal nowadays, especially in case of upgrading or rehabilitation of old structures. Many old bridges and marine or pier structures in the United States are established using deep foundations system of timber piles and their foundation records do not exist. Non-Destructive Testing (NDT or Non-Destructive Evaluation (NDE method for a great variety of materials and structures has become an integral part of many tests. However, the process of testing long piles, deeply embedded in the ground, is more complex than (NDT of the other structural materials. This paper summarizes some of the most common non-destructive test methods for deep foundations and presents a new method called the Hilbert Huang Transform (HHT. This Hilbert Huang Transform (HHT method is used now by a wide range in a different health monitoring of many systems. In this paper, some field tests on the timber Piles of one bridge at North Carolina was performed to verify the using the (HHT method for predicting the embedded depth of the unknown piles. Percentage of the accuracy achieved using HHT method for pile length compared to the actual pile length data was performed. Finally, a recommendation is presented for the limitation of using this new method as a new non-destructive method for deep foundations.

  3. 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

  4. Diagnostic and prognostic yield of tumor markers in cancer of unknown primary site

    International Nuclear Information System (INIS)

    Pervez, T.; Ibraheim, M.I.

    2006-01-01

    A case of metastatic carcinoma of unknown primary is reported that had widely disseminated disease from the very outset. Every effort was made to find out the primary by integrating all results and specially tumor markers. It was assumed that lung was the most possible site for primary. Tumor markers did not show their diagnostic value even in combined panel, they only showed their prognostic value. (author)

  5. Unknown Regulations in Ladino from Salonika (ca. 1740: Ethos, Ideal, Reality

    Directory of Open Access Journals (Sweden)

    Yaron Ben-Naeh

    2016-12-01

    Full Text Available

    In the mid-1930s, Viennese bookseller David Fränkel described a booklet containing regulations in Ladino. Its whereabouts were unknown until it recently appeared in a public auction in Jerusalem. Though Fränkel attributed it to Istanbul, his description leaves no room for doubt that this is the same text, but internal evidence points to Salonika. The four-page booklet is unsigned and undated; one can only conjecture that it was printed in the mid-1740s upon the initiative of the rabbinical and communal leadership in Salonika. It contains two groups of regulations…

  6. Adaptive control of chaotic systems with stochastic time varying unknown parameters

    Energy Technology Data Exchange (ETDEWEB)

    Salarieh, Hassan [Center of Excellence in Design, Robotics and Automation, Department of Mechanical Engineering, Sharif University of Technology, P.O. Box 11365-9567, Azadi Avenue, Tehran (Iran, Islamic Republic of)], E-mail: salarieh@mech.sharif.edu; Alasty, Aria [Center of Excellence in Design, Robotics and Automation, Department of Mechanical Engineering, Sharif University of Technology, P.O. Box 11365-9567, Azadi Avenue, Tehran (Iran, Islamic Republic of)], E-mail: aalasti@sharif.edu

    2008-10-15

    In this paper based on the Lyapunov stability theorem, an adaptive control scheme is proposed for stabilizing the unstable periodic orbits (UPO) of chaotic systems. It is assumed that the chaotic system has some linearly dependent unknown parameters which are stochastically time varying. The stochastic parameters are modeled through the Weiner process derivative. To demonstrate the effectiveness of the proposed technique it has been applied to the Lorenz, Chen and Rossler dynamical systems, as some case studies. Simulation results indicate that the proposed adaptive controller has a high performance in stabilizing the UPO of chaotic systems in noisy environment.

  7. Decontamination and management of human remains following incidents of hazardous chemical release.

    Science.gov (United States)

    Hauschild, Veronique D; Watson, Annetta; Bock, Robert

    2012-01-01

    To provide specific guidance and resources for systematic and orderly decontamination of human remains resulting from a chemical terrorist attack or accidental chemical release. A detailed review and health-based decision criteria protocol is summarized. Protocol basis and logic are derived from analyses of compound-specific toxicological data and chemical/physical characteristics. Guidance is suitable for civilian or military settings where human remains potentially contaminated with hazardous chemicals may be present, such as sites of transportation accidents, terrorist operations, or medical examiner processing points. Guidance is developed from data-characterizing controlled experiments with laboratory animals, fabrics, and materiel. Logic and specific procedures for decontamination and management of remains, protection of mortuary affairs personnel, and decision criteria to determine when remains are sufficiently decontaminated are presented. Established procedures as well as existing materiel and available equipment for decontamination and verification provide reasonable means to mitigate chemical hazards from chemically exposed remains. Unique scenarios such as those involving supralethal concentrations of certain liquid chemical warfare agents may prove difficult to decontaminate but can be resolved in a timely manner by application of the characterized systematic approaches. Decision criteria and protocols to "clear" decontaminated remains for transport and processing are also provided. Once appropriate decontamination and verification have been accomplished, normal procedures for management of remains and release can be followed.

  8. 76 FR 14057 - Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human Remains...

    Science.gov (United States)

    2011-03-15

    ...: University of Wyoming, Anthropology Department, Human Remains Repository, Laramie, WY AGENCY: National Park... Anthropology Department, Human Remains Repository, Laramie, WY. The human remains and associated funerary... the human remains was made by University of Wyoming, Anthropology Department, Human Remains Repository...

  9. Metastatic cancer of unknown primary in 21 dogs.

    Science.gov (United States)

    Rossi, F; Aresu, L; Vignoli, M; Buracco, P; Bettini, G; Ferro, S; Gattino, F; Ghiani, F; Costantino, R; Ressel, L; Bellei, E; Marconato, L

    2015-03-01

    The aim of this retrospective study was to describe clinical features, treatment and outcome of 21 dogs with metastatic cancer of unknown primary (MCUP), a biopsy-proven malignancy being diagnosed at a metastatic stage, in which the anatomical origin of the primary tumour cannot be detected. All dogs underwent total-body computed tomography. Signalment, type and duration of clinical signs, metastasis site, pathology results, treatment and outcome were recorded. Carcinoma was the most common diagnosis (57.1%), followed by sarcoma, melanoma and mast cell tumour. The median number of disease sites per dog was 2, with bones, lymph nodes, lungs and spleen being the most frequent metastatic locations. The median survival for all dogs was 30 days. Overall, a primary site was not identified in 20 (95.2%) dogs. MCUP encompasses a variety of different pathologic entities and harbours a poor prognosis. © 2013 Blackwell Publishing Ltd.

  10. Dynamic modelling and adaptive robust tracking control of a space robot with two-link flexible manipulators under unknown disturbances

    Science.gov (United States)

    Yang, Xinxin; Ge, Shuzhi Sam; He, Wei

    2018-04-01

    In this paper, both the closed-form dynamics and adaptive robust tracking control of a space robot with two-link flexible manipulators under unknown disturbances are developed. The dynamic model of the system is described with assumed modes approach and Lagrangian method. The flexible manipulators are represented as Euler-Bernoulli beams. Based on singular perturbation technique, the displacements/joint angles and flexible modes are modelled as slow and fast variables, respectively. A sliding mode control is designed for trajectories tracking of the slow subsystem under unknown but bounded disturbances, and an adaptive sliding mode control is derived for slow subsystem under unknown slowly time-varying disturbances. An optimal linear quadratic regulator method is proposed for the fast subsystem to damp out the vibrations of the flexible manipulators. Theoretical analysis validates the stability of the proposed composite controller. Numerical simulation results demonstrate the performance of the closed-loop flexible space robot system.

  11. Residual generation with unknown input observer for linear systems in the presence of unmatched uncertainties

    International Nuclear Information System (INIS)

    Bagherpour, Esmaeel A.; HairiTazdi, Mohammad Reza; Mahjoob, Mohammad

    2014-01-01

    In this paper, we deal with residual vector generation for fault detection problems in linear systems via unknown input observer (UIO) when the so-called observer matching condition is not satisfied. Based on the relative degree between unknown input and output, a vector of the auxiliary output is introduced so that the observer matching condition is satisfied with respect to the vector. Auxiliary outputs are related to the derivatives of measured signals. However, differentiation leads to excessive amplification of measurement noise. A dynamically equivalent configuration of linear systems is developed using successive integrations to avoid differentiation. As such, auxiliary outputs are constructed without differentiation. Then, the equivalent dynamic system and its corresponding auxiliary outputs are used to generate the residual vector via an exponentially converging UIO. Fault detection in the generated residual vector is also investigated. Finally, the effectiveness of the proposed method is shown via numerical simulation.

  12. Reinforcement learning for adaptive optimal control of unknown continuous-time nonlinear systems with input constraints

    Science.gov (United States)

    Yang, Xiong; Liu, Derong; Wang, Ding

    2014-03-01

    In this paper, an adaptive reinforcement learning-based solution is developed for the infinite-horizon optimal control problem of constrained-input continuous-time nonlinear systems in the presence of nonlinearities with unknown structures. Two different types of neural networks (NNs) are employed to approximate the Hamilton-Jacobi-Bellman equation. That is, an recurrent NN is constructed to identify the unknown dynamical system, and two feedforward NNs are used as the actor and the critic to approximate the optimal control and the optimal cost, respectively. Based on this framework, the action NN and the critic NN are tuned simultaneously, without the requirement for the knowledge of system drift dynamics. Moreover, by using Lyapunov's direct method, the weights of the action NN and the critic NN are guaranteed to be uniformly ultimately bounded, while keeping the closed-loop system stable. To demonstrate the effectiveness of the present approach, simulation results are illustrated.

  13. Distributed Containment Control for Multiple Unknown Second-Order Nonlinear Systems With Application to Networked Lagrangian Systems.

    Science.gov (United States)

    Mei, Jie; Ren, Wei; Li, Bing; Ma, Guangfu

    2015-09-01

    In this paper, we consider the distributed containment control problem for multiagent systems with unknown nonlinear dynamics. More specifically, we focus on multiple second-order nonlinear systems and networked Lagrangian systems. We first study the distributed containment control problem for multiple second-order nonlinear systems with multiple dynamic leaders in the presence of unknown nonlinearities and external disturbances under a general directed graph that characterizes the interaction among the leaders and the followers. A distributed adaptive control algorithm with an adaptive gain design based on the approximation capability of neural networks is proposed. We present a necessary and sufficient condition on the directed graph such that the containment error can be reduced as small as desired. As a byproduct, the leaderless consensus problem is solved with asymptotical convergence. Because relative velocity measurements between neighbors are generally more difficult to obtain than relative position measurements, we then propose a distributed containment control algorithm without using neighbors' velocity information. A two-step Lyapunov-based method is used to study the convergence of the closed-loop system. Next, we apply the ideas to deal with the containment control problem for networked unknown Lagrangian systems under a general directed graph. All the proposed algorithms are distributed and can be implemented using only local measurements in the absence of communication. Finally, simulation examples are provided to show the effectiveness of the proposed control algorithms.

  14. Methodology for Extraction of Remaining Sodium of Used Sodium Containers

    International Nuclear Information System (INIS)

    Jung, Minhwan; Kim, Jongman; Cho, Youngil; Jeong, Jiyoung

    2014-01-01

    Sodium used as a coolant in the SFR (Sodium-cooled Fast Reactor) reacts easily with most elements due to its high reactivity. If sodium at high temperature leaks outside of a system boundary and makes contact with oxygen, it starts to burn and toxic aerosols are produced. In addition, it generates flammable hydrogen gas through a reaction with water. Hydrogen gas can be explosive within the range of 4.75 vol%. Therefore, the sodium should be handled carefully in accordance with standard procedures even though there is a small amount of target sodium remainings inside the containers and drums used for experiment. After the experiment, all sodium experimental apparatuses should be dismantled carefully through a series of draining, residual sodium extraction, and cleaning if they are no longer reused. In this work, a system for the extraction of the remaining sodium of used sodium drums has been developed and an operation procedure for the system has been established. In this work, a methodology for the extraction of remaining sodium out of the used sodium container has been developed as one of the sodium facility maintenance works. The sodium extraction system for remaining sodium of the used drums was designed and tested successfully. This work will contribute to an establishment of sodium handling technology for PGSFR. (Prototype Gen-IV Sodium-cooled Fast Reactor)

  15. Organic Spectroscopy Laboratory: Utilizing IR and NMR in the Identification of an Unknown Substance

    Science.gov (United States)

    Glagovich, Neil M.; Shine, Timothy D.

    2005-01-01

    A laboratory experiment that emphasizes the interpretation of both infrared (IR) and nuclear magnetic resonance (NMR) spectra in the elucidation of the structure of an unknown compound was developed. The method helps students determine [to the first power]H- and [to the thirteenth power]C-NMR spectra from the structures of compounds and to…

  16. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation.

    Science.gov (United States)

    Henninge, John; Pepaj, Milaim; Hullstein, Ingunn; Hemmersbach, Peter

    2010-01-01

    Several peptide drugs are being manufactured illicitly, and in some cases they are being made available to the public before entering or completing clinical trials. At the request of Norwegian police and customs authorities, unknown pharmaceutical preparations suspected to contain peptide drugs are regularly subjected to analysis. In 2009, an unknown pharmaceutical preparation was submitted for analysis by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). The preparation was found to contain a 29 amino acid peptide with a C-terminal amide function. Based on the interpretation of mass spectrometric data, an amino acid sequence was proposed. The sequence is consistent with a peptide currently marketed under the name CJC-1295. CJC-1295 is a releasing factor for growth hormone and is therefore considered a Prohibited Substance under Section S2 of the WADA Prohibited List. This substance has potential performance-enhancing effects, it is readily available, and there is reason to believe that it is being used within the bodybuilding community. Copyright © 2010 John Wiley & Sons, Ltd.

  17. Determining the relative susceptibility of four prion protein genotypes to atypical scrapie

    Science.gov (United States)

    Atypical scrapie is a sheep prion (PrPSc) disease whose epidemiology is consistent with a sporadic origin and is associated with specific polymorphisms of the normal cellular prion protein (PrPC). We describe a mass spectrometry-based method of detecting and quantifying the polymorphisms of sheep P...

  18. Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP

    NARCIS (Netherlands)

    Jansen, Casper; Parchi, Piero; Capellari, Sabina; Vermeij, Ad J.; Corrado, Patrizia; Baas, Frank; Strammiello, Rosaria; van Gool, Willem A.; van Swieten, John C.; Rozemuller, Annemieke J. M.

    2010-01-01

    Stop codon mutations in the gene encoding the prion protein (PRNP) are very rare and have thus far only been described in two patients with prion protein cerebral amyloid angiopathy (PrP-CAA). In this report, we describe the clinical, histopathological and pathological prion protein (PrPSc)

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

    OpenAIRE

    Pearce, Alan J.; Adair, Brooke; Miller, Kimberly; Ozanne, Elizabeth; Said, Catherine; Santamaria, Nick; Morris, Meg E.

    2012-01-01

    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 effec...

  20. Mummified remains from the Archaeological Museum in Zagreb, Croatia - Reviewing peculiarities and limitations of human and non-human radiological identification and analysis in mummified remains.

    Science.gov (United States)

    Petaros, Anja; Janković, Ivor; Cavalli, Fabio; Ivanac, Gordana; Brkljačić, Boris; Čavka, Mislav

    2015-10-01

    Forensic protocols and medico-legal techniques are increasingly being employed in investigations of museological material. The final findings of such investigations may reveal interesting facts on historical figures, customs and habits, as well as provide meaningful data for forensic use. Herein we present a case review where forensic experts were requested to identify taxonomic affinities, stage of preservation and provide skeletal analysis of mummified non-human archaeological remains, and verify whether two mummified hands are human or not. The manuscript offers a short review on the process and particularities of radiological species identification, the impact of post-mortem changes in the analysis and imaging of mummified remains as well as the macroscopical interpretation of trauma, pathology and authenticity in mummified remains, which can all turn useful when dealing with forensic cases. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.