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Sample records for halotag protein-mediated specific

  1. HaloTag protein-mediated specific labeling of living cells with quantum dots

    International Nuclear Information System (INIS)

    So, Min-kyung; Yao Hequan; Rao Jianghong

    2008-01-01

    Quantum dots emerge as an attractive alternative to small molecule fluorophores as fluorescent tags for in vivo cell labeling and imaging. This communication presents a method for specific labeling of live cells using quantum dots. The labeling is mediated by HaloTag protein expressed at the cell surface which forms a stable covalent adduct with its ligand (HaloTag ligand). The labeling can be performed in one single step with quantum dot conjugates that are functionalized with HaloTag ligand, or in two steps with biotinylated HaloTag ligand first and followed by streptavidin coated quantum dots. Live cell fluorescence imaging indicates that the labeling is specific and takes place at the cell surface. This HaloTag protein-mediated cell labeling method should facilitate the application of quantum dots for live cell imaging

  2. Sorting of a HaloTag protein that has only a signal peptide sequence into exocrine secretory granules without protein aggregation.

    Science.gov (United States)

    Fujita-Yoshigaki, Junko; Matsuki-Fukushima, Miwako; Yokoyama, Megumi; Katsumata-Kato, Osamu

    2013-11-15

    The mechanism involved in the sorting and accumulation of secretory cargo proteins, such as amylase, into secretory granules of exocrine cells remains to be solved. To clarify that sorting mechanism, we expressed a reporter protein HaloTag fused with partial sequences of salivary amylase protein in primary cultured parotid acinar cells. We found that a HaloTag protein fused with only the signal peptide sequence (Met(1)-Ala(25)) of amylase, termed SS25H, colocalized well with endogenous amylase, which was confirmed by immunofluorescence microscopy. Percoll-density gradient centrifugation of secretory granule fractions shows that the distributions of amylase and SS25H were similar. These results suggest that SS25H is transported to secretory granules and is not discriminated from endogenous amylase by the machinery that functions to remove proteins other than granule cargo from immature granules. Another reporter protein, DsRed2, that has the same signal peptide sequence also colocalized with amylase, suggesting that the sorting to secretory granules is not dependent on a characteristic of the HaloTag protein. Whereas Blue Native PAGE demonstrates that endogenous amylase forms a high-molecular-weight complex, SS25H does not participate in the complex and does not form self-aggregates. Nevertheless, SS25H was released from cells by the addition of a β-adrenergic agonist, isoproterenol, which also induces amylase secretion. These results indicate that addition of the signal peptide sequence, which is necessary for the translocation in the endoplasmic reticulum, is sufficient for the transportation and storage of cargo proteins in secretory granules of exocrine cells.

  3. ABC-F Proteins Mediate Antibiotic Resistance through Ribosomal Protection.

    Science.gov (United States)

    Sharkey, Liam K R; Edwards, Thomas A; O'Neill, Alex J

    2016-03-22

    Members of the ABC-F subfamily of ATP-binding cassette proteins mediate resistance to a broad array of clinically important antibiotic classes that target the ribosome of Gram-positive pathogens. The mechanism by which these proteins act has been a subject of long-standing controversy, with two competing hypotheses each having gained considerable support: antibiotic efflux versus ribosomal protection. Here, we report on studies employing a combination of bacteriological and biochemical techniques to unravel the mechanism of resistance of these proteins, and provide several lines of evidence that together offer clear support to the ribosomal protection hypothesis. Of particular note, we show that addition of purified ABC-F proteins to anin vitrotranslation assay prompts dose-dependent rescue of translation, and demonstrate that such proteins are capable of displacing antibiotic from the ribosomein vitro To our knowledge, these experiments constitute the first direct evidence that ABC-F proteins mediate antibiotic resistance through ribosomal protection.IMPORTANCEAntimicrobial resistance ranks among the greatest threats currently facing human health. Elucidation of the mechanisms by which microorganisms resist the effect of antibiotics is central to understanding the biology of this phenomenon and has the potential to inform the development of new drugs capable of blocking or circumventing resistance. Members of the ABC-F family, which includelsa(A),msr(A),optr(A), andvga(A), collectively yield resistance to a broader range of clinically significant antibiotic classes than any other family of resistance determinants, although their mechanism of action has been controversial since their discovery 25 years ago. Here we present the first direct evidence that proteins of the ABC-F family act to protect the bacterial ribosome from antibiotic-mediated inhibition. Copyright © 2016 Sharkey et al.

  4. Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins

    NARCIS (Netherlands)

    Neumann, S.

    2008-01-01

    Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins In this thesis, I studied the intra- and intercellular transport of lipidic molecules, in particular glycosphingolipids and lipid-modified proteins. The first part focuses on the intracellular transport of

  5. Recombination Proteins Mediate Meiotic Spatial Chromosome Organization and Pairing

    Science.gov (United States)

    Storlazzi, Aurora; Gargano, Silvana; Ruprich-Robert, Gwenael; Falque, Matthieu; David, Michelle; Kleckner, Nancy; Zickler, Denise

    2010-01-01

    SUMMARY Meiotic chromosome pairing involves not only recognition of homology but also juxtaposition of entire chromosomes in a topologically regular way. Analysis of filamentous fungus Sordaria macrospora reveals that recombination proteins Mer3, Msh4 and Mlh1 play direct roles in all of these aspects, in advance of their known roles in recombination. Absence of Mer3 helicase results in interwoven chromosomes, thereby revealing the existence of features that specifically ensure “entanglement avoidance”. Entanglements that remain at zygotene, i.e. “interlockings”, require Mlh1 for resolution, likely to eliminate constraining recombinational connections. Patterns of Mer3 and Msh4 foci along aligned chromosomes show that the double-strand breaks mediating homologous alignment have spatially separated ends, one localized to each partner axis, and that pairing involves interference among developing interhomolog interactions. We propose that Mer3, Msh4 and Mlh1 execute all of these roles during pairing by modulating the state of nascent double-strand break/partner DNA contacts within axis-associated recombination complexes. PMID:20371348

  6. Protein mediated synthesis of fluorescent Au-nanoclusters for metal sensory coatings

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, Manja; Raff, Johannes [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biogeochemistry

    2017-06-01

    Fluorescent Au-nanocluster were successfully synthesized and used for the selective detection of Cu{sup 2} {sup +}. The synthesized Au-BSA-nanoclusters remain functional also after immobilization and show high thermal stability. Additionally, the transfer of the protein mediated Au-nanocluster synthesis route to S-layer proteins was achieved. (The presented work is part of the project BIONEWS dealing with long-term stable cells for the set-up and regeneration of sensor and actor materials for strategic relevant metals, in particular rare earth elements).

  7. Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection.

    Science.gov (United States)

    Yun, Bing-Ling; Guan, Xiao-Lu; Liu, Yong-Zhen; Zhang, Yao; Wang, Yong-Qiang; Qi, Xiao-Le; Cui, Hong-Yu; Liu, Chang-Jun; Zhang, Yan-Ping; Gao, Hong-Lei; Gao, Li; Li, Kai; Gao, Yu-Long; Wang, Xiao-Mei

    2016-07-08

    Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection*

    Science.gov (United States)

    Yun, Bing-Ling; Guan, Xiao-Lu; Liu, Yong-Zhen; Zhang, Yao; Wang, Yong-Qiang; Qi, Xiao-Le; Cui, Hong-Yu; Liu, Chang-Jun; Zhang, Yan-Ping; Gao, Hong-Lei; Gao, Li; Li, Kai; Gao, Yu-Long; Wang, Xiao-Mei

    2016-01-01

    Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. PMID:27226547

  9. Protein-mediated efficient synergistic "antenna effect" in a ternary system in D₂O medium.

    Science.gov (United States)

    Ghorai, Shyamal Kr; Samanta, Swarna Kamal; Mukherjee, Manini; Ghosh, Sanjib

    2012-08-16

    A ternary system consisting of a protein, catechin (either + or - epimer), and Tb(III) in suitable aqueous buffer medium at physiological pH (= 6.8) has been shown to exhibit highly efficient "antenna effect". Steady state and time-resolved emission studies of each component in the binary complexes (protein with Tb(III) and (+)- or (-)-catechin with Tb(III)) and the ternary systems along with the molecular docking studies reveal that the efficient sensitization could be ascribed to the effective shielding of microenvironment of Tb(III) from O-H oscillator and increased Tb-C (+/-) interaction in the ternary systems in aqueous medium. The ternary system exhibits protein-mediated efficient antenna effect in D(2)O medium due to synergistic ET from both the lowest ππ* triplet state of Trp residue in protein and that of catechin apart from protection of the Tb(III) environment from matrix vibration. The simple system consisting of (+)- or (-)-catechin and Tb(III) in D(2)O buffer at pH 6.8 has been prescribed to be a useful biosensor.

  10. Refractive-index-based screening of membrane-protein-mediated transfer across biological membranes.

    Science.gov (United States)

    Brändén, Magnus; Tabaei, Seyed R; Fischer, Gerhard; Neutze, Richard; Höök, Fredrik

    2010-07-07

    Numerous membrane-transport proteins are major drug targets, and therefore a key ingredient in pharmaceutical development is the availability of reliable, efficient tools for membrane transport characterization and inhibition. Here, we present the use of evanescent-wave sensing for screening of membrane-protein-mediated transport across lipid bilayer membranes. This method is based on a direct recording of the temporal variations in the refractive index that occur upon a transfer-dependent change in the solute concentration inside liposomes associated to a surface plasmon resonance (SPR) active sensor surface. The applicability of the method is demonstrated by a functional study of the aquaglyceroporin PfAQP from the malaria parasite Plasmodium falciparum. Assays of the temperature dependence of facilitated diffusion of sugar alcohols on a single set of PfAQP-reconstituted liposomes reveal that the activation energies for facilitated diffusion of xylitol and sorbitol are the same as that previously measured for glycerol transport in the aquaglyceroporin of Escherichia coli (5 kcal/mole). These findings indicate that the aquaglyceroporin selectivity filter does not discriminate sugar alcohols based on their length, and that the extra energy cost of dehydration of larger sugar alcohols, upon entering the pore, is compensated for by additional hydrogen-bond interactions within the aquaglyceroporin pore. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors.

    Directory of Open Access Journals (Sweden)

    Patrick Vancura

    Full Text Available The mammalian retina harbors a circadian clockwork that regulates vision and promotes healthiness of retinal neurons, mainly through directing the rhythmic release of the neurohormones dopamine-acting on dopamine D4 receptors-and melatonin-acting on MT1 and MT2 receptors. The gene Gnaz-a unique Gi/o subfamily member-was seen in the present study to be expressed in photoreceptors where its protein product Gαz shows a daily rhythm in its subcellular localization. Apart from subcellular localization, Gnaz displays a daily rhythm in expression-with peak values at night-in preparations of the whole retina, microdissected photoreceptors and photoreceptor-related pinealocytes. In retina, Gnaz rhythmicity was observed to persist under constant darkness and to be abolished in retina deficient for Clock or dopamine D4 receptors. Furthermore, circadian regulation of Gnaz was disturbed in the db/db mouse, a model of diabetic retinopathy. The data of the present study suggest that Gnaz links the circadian clockwork-via dopamine acting on D4 receptors-to G protein-mediated signaling in intact but not diabetic retina.

  12. The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.

    Science.gov (United States)

    Goldman, Aaron David; Beatty, Joshua T; Landweber, Laura F

    2016-01-01

    The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10% of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.

  13. Cooxidation of styrene by horseradish peroxidase and phenols. A biochemical model for protein-mediated cooxidation

    International Nuclear Information System (INIS)

    Ortiz de Montellano, P.R.; Grab, L.A.

    1987-01-01

    Styrene is oxidized to styrene oxide and benzaldehyde when incubated with horseradish peroxidase, H 2 O 2 , and 4-methylphenol. Styrene oxide is not formed in the absence of any of these reaction components or of molecular oxygen. The coupling products 2-(4-methylphenoxy)-1-phenylethane, 2-(4-methylphenoxy)-1-phenylethan-1-ol, and 2-(4-methylphenoxy)-2-phenylethan-1-ol are not formed, but the ortho-linked dimer of 4-methylphenol is a major product. The epoxide oxygen is labeled in the presence of 18 O 2 but not H 2 18 O 2 . Styrene oxide formation is not inhibited by mannitol or superoxide dismutase. The stereochemistry of trans-[1- 2 H]styrene is partially scrambled in the epoxide product. EPR signals attributable to the 2,4-dihydroxyl-5-methylphenoxy radical, a product of the oxidation of 4-methylcatechol, are observed if Zn 2+ is added to stabilize the radical. This radical is only detected in the presence of styrene. The results imply that styrene is epoxidized by the hydroperoxy radical generated by addition of molecular oxygen to the 4-methylphenoxy radical. The epoxidation mimics the chemistry proposed to occur in the protein-mediated cooxidation of styrene by hemoglobin and myoglobin

  14. Natural products induce a G protein-mediated calcium pathway activating p53 in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ginkel, Paul R. van; Yan, Michael B. [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Bhattacharya, Saswati [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Department of Pediatrics, University of Wisconsin, Madison, WI 53792 (United States); Polans, Arthur S., E-mail: aspolans@wisc.edu [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Kenealey, Jason D. [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, UT 84602 (United States)

    2015-11-01

    Paclitaxel, etoposide, vincristine and doxorubicin are examples of natural products being used as chemotherapeutics but with adverse side effects that limit their therapeutic window. Natural products derived from plants and having low toxicity, such as quercetin, resveratrol, epigallocatechin gallate and piceatannol, have been shown to inhibit tumor cell growth both in vitro and in pre-clinical models of cancer, but their mechanisms of action have not been fully elucidated, thus restricting their use as prototypes for developing synthetic analogs with improved anti-cancer properties. We and others have demonstrated that one of the earliest and consistent events upon exposure of tumor cells to these less toxic natural products is a rise in cytoplasmic calcium, activating several pro-apoptotic pathways. We describe here a G protein/inositol 1,4,5-trisphosphate pathway (InsP3) in MDA-MB-231 human breast cancer cells that mediates between these less toxic natural products and the release of calcium from the endoplasmic reticulum. Further, we demonstrate that this elevation of intracellular calcium modulates p53 activity and the subsequent transcription of several pro-apoptotic genes encoding PIG8, CD95, PIDD, TP53INP, RRM2B, Noxa, p21 and PUMA. We conclude from our findings that less toxic natural products likely bind to a G protein coupled receptor that activates a G protein-mediated and calcium-dependent pathway resulting selectively in tumor cell death. - Highlights: • Natural products having low toxicity increase cytoplasmic calcium in cancer cells. • A G-protein/IP{sub 3} pathway mediates the release of calcium from the ER. • The elevation of intracellular calcium modulates p53 activity. • p53 and other Ca{sup 2+}-dependent pro-apoptotic pathways inhibit cancer cell growth.

  15. Natural products induce a G protein-mediated calcium pathway activating p53 in cancer cells

    International Nuclear Information System (INIS)

    Ginkel, Paul R. van; Yan, Michael B.; Bhattacharya, Saswati; Polans, Arthur S.; Kenealey, Jason D.

    2015-01-01

    Paclitaxel, etoposide, vincristine and doxorubicin are examples of natural products being used as chemotherapeutics but with adverse side effects that limit their therapeutic window. Natural products derived from plants and having low toxicity, such as quercetin, resveratrol, epigallocatechin gallate and piceatannol, have been shown to inhibit tumor cell growth both in vitro and in pre-clinical models of cancer, but their mechanisms of action have not been fully elucidated, thus restricting their use as prototypes for developing synthetic analogs with improved anti-cancer properties. We and others have demonstrated that one of the earliest and consistent events upon exposure of tumor cells to these less toxic natural products is a rise in cytoplasmic calcium, activating several pro-apoptotic pathways. We describe here a G protein/inositol 1,4,5-trisphosphate pathway (InsP3) in MDA-MB-231 human breast cancer cells that mediates between these less toxic natural products and the release of calcium from the endoplasmic reticulum. Further, we demonstrate that this elevation of intracellular calcium modulates p53 activity and the subsequent transcription of several pro-apoptotic genes encoding PIG8, CD95, PIDD, TP53INP, RRM2B, Noxa, p21 and PUMA. We conclude from our findings that less toxic natural products likely bind to a G protein coupled receptor that activates a G protein-mediated and calcium-dependent pathway resulting selectively in tumor cell death. - Highlights: • Natural products having low toxicity increase cytoplasmic calcium in cancer cells. • A G-protein/IP 3 pathway mediates the release of calcium from the ER. • The elevation of intracellular calcium modulates p53 activity. • p53 and other Ca 2+ -dependent pro-apoptotic pathways inhibit cancer cell growth.

  16. Protein-mediated antagonism between HIV reverse transcriptase ligands nevirapine and MgATP.

    Science.gov (United States)

    Zheng, Xunhai; Mueller, Geoffrey A; DeRose, Eugene F; London, Robert E

    2013-06-18

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) play a central role in the treatment of AIDS, but their mechanisms of action are incompletely understood. The interaction of the NNRTI nevirapine (NVP) with HIV-1 reverse transcriptase (RT) is characterized by a preference for the open conformation of the fingers/thumb subdomains, and a reported variation of three orders of magnitude between the binding affinity of NVP for RT in the presence or absence of primer/template DNA. To investigate the relationship between conformation and ligand binding, we evaluated the use of methionine NMR probes positioned near the tip of the fingers or thumb subdomains. Such probes would be expected to be sensitive to changes in the local environment depending on the fractions of open and closed RT. Comparisons of the NMR spectra of three conservative mutations, I63M, L74M, and L289M, indicated that M63 showed the greatest shift sensitivity to the addition of NVP. The exchange kinetics of the M63 resonance are fast on the chemical shift timescale, but become slow in the presence of NVP due to the slow binding of RT with the inhibitor. The simplest model consistent with this behavior involves a rapid open/closed equilibrium coupled with a slow interaction of the inhibitor with the open conformation. Studies of RT in the presence of both NVP and MgATP indicate a strong negative cooperativity. Binding of MgATP reduces the fraction of RT bound to NVP, as indicated by the intensity of the NVP-perturbed M230 resonance, and enhances the dissociation rate constant of the NVP, resulting in an increase of the open/closed interconversion rate, so that the M63 resonance moves into the fast/intermediate-exchange regime. Protein-mediated interactions appear to explain most of the affinity variation of NVP for RT. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Light-induced, GTP-binding protein mediated membrane currents of Xenopus oocytes injected with rhodopsin of cephalopods.

    Science.gov (United States)

    Ando, H; Seidou, M; Kito, Y

    1991-01-01

    Xenopus oocytes that were injected with rhabdomeric membranes of squid and octopus photoreceptors acquired light sensitivity. The injected oocytes showed a light-induced current having characteristics similar to other G-protein-mediated Cl- currents induced by the activation of other membrane receptors. Pretreatment of the oocytes with pertussis toxin before the injection suppressed the generation of the light-induced current, indicating an ability of cephalopod rhodopsin to cross-react with an endogenous G-protein of Xenopus oocytes.

  18. Long-range neural and gap junction protein-mediated cues control polarity during planarian regeneration

    NARCIS (Netherlands)

    Morokuma, Junji; Oviedo, Nestor J.; Walentek, Peter; Kema, Ido P.; Gu, Man Bock; Ahn, Joo-Myung; Hwang, Jung Shan; Gojobori, Takashi; Levin, Michael

    2010-01-01

    Having the ability to coordinate the behavior of stem cells to induce regeneration of specific large-scale structures would have far-reaching consequences in the treatment of degenerative diseases, acute injury, and aging. Thus, identifying and learning to manipulate the sequential steps that

  19. Ultramild protein-mediated click chemistry creates efficient oligonucleotide probes for targeting and detecting nucleic acids

    DEFF Research Database (Denmark)

    Nåbo, Lina J.; Madsen, Charlotte S.; Jensen, Knud J.

    2015-01-01

    Functionalized synthetic oligonucleotides are finding growing applications in research, clinical studies, and therapy. However, it is not easy to prepare them in a biocompatible and highly efficient manner. We report a new strategy to synthesize oligonucleotides with promising nucleic acid...... targeting and detection properties. We focus in particular on the pH sensitivity of these new probes and their high target specificity. For the first time, human copper(I)-binding chaperon Cox17 was applied to effectively catalyze click labeling of oligonucleotides. This was performed under ultramild...... conditions with fluorophore, peptide, and carbohydrate azide derivatives. In thermal denaturation studies, the modified probes showed specific binding to complementary DNA and RNA targets. Finally, we demonstrated the pH sensitivity of the new rhodamine-based fluorescent probes in vitro and rationalize our...

  20. Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design.

    Science.gov (United States)

    Cai, Lifeng; Gochin, Miriam; Liu, Keliang

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors.

  1. Solitary BioY Proteins Mediate Biotin Transport into Recombinant Escherichia coli

    Science.gov (United States)

    Finkenwirth, Friedrich; Kirsch, Franziska

    2013-01-01

    Energy-coupling factor (ECF) transporters form a large group of vitamin uptake systems in prokaryotes. They are composed of highly diverse, substrate-specific, transmembrane proteins (S units), a ubiquitous transmembrane protein (T unit), and homo- or hetero-oligomeric ABC ATPases. Biotin transporters represent a special case of ECF-type systems. The majority of the biotin-specific S units (BioY) is known or predicted to interact with T units and ABC ATPases. About one-third of BioY proteins, however, are encoded in organisms lacking any recognizable T unit. This finding raises the question of whether these BioYs function as transporters in a solitary state, a feature ascribed to certain BioYs in the past. To address this question in living cells, an Escherichia coli K-12 derivative deficient in biotin synthesis and devoid of its endogenous high-affinity biotin transporter was constructed as a reference strain. This organism is particularly suited for this purpose because components of ECF transporters do not naturally occur in E. coli K-12. The double mutant was viable in media containing either high levels of biotin or a precursor of the downstream biosynthetic path. Importantly, it was nonviable on trace levels of biotin. Eight solitary bioY genes of proteobacterial origin were individually expressed in the reference strain. Each of the BioYs conferred biotin uptake activity on the recombinants, which was inferred from uptake assays with [3H]biotin and growth of the cells on trace levels of biotin. The results underscore that solitary BioY transports biotin across the cytoplasmic membrane. PMID:23836870

  2. Enhanced plastic deformations of nanofibrillated cellulose film by adsorbed moisture and protein-mediated interactions.

    Science.gov (United States)

    Malho, Jani-Markus; Ouellet-Plamondon, Claudiane; Rüggeberg, Markus; Laaksonen, Päivi; Ikkala, Olli; Burgert, Ingo; Linder, Markus B

    2015-01-12

    Biological composites are typically based on an adhesive matrix that interlocks rigid reinforcing elements in fiber composite or brick-and-mortar assemblies. In nature, the adhesive matrix is often made up of proteins, which are also interesting model systems, as they are unique among polymers in that we know how to engineer their structures with atomic detail and to select protein elements for specific interactions with other components. Here we studied how fusion proteins that consist of cellulose binding proteins linked to proteins that show a natural tendency to form multimer complexes act as an adhesive matrix in combination with nanofibrillated cellulose. We found that the fusion proteins are retained with the cellulose and that the proteins mainly affect the plastic yield behavior of the cellulose material as a function of water content. Interestingly, the proteins increased the moisture absorption of the composite, but the well-known plastifying effect of water was clearly decreased. The work helps to understand the functional basis of nanocellulose composites as materials and aims toward building model systems for molecular biomimetic materials.

  3. Insig proteins mediate feedback inhibition of cholesterol synthesis in the intestine.

    Science.gov (United States)

    McFarlane, Matthew R; Liang, Guosheng; Engelking, Luke J

    2014-01-24

    Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes.

  4. Insig Proteins Mediate Feedback Inhibition of Cholesterol Synthesis in the Intestine*

    Science.gov (United States)

    McFarlane, Matthew R.; Liang, Guosheng; Engelking, Luke J.

    2014-01-01

    Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes. PMID:24337570

  5. Cth2 Protein Mediates Early Adaptation of Yeast Cells to Oxidative Stress Conditions.

    Directory of Open Access Journals (Sweden)

    Laia Castells-Roca

    Full Text Available Cth2 is an mRNA-binding protein that participates in remodeling yeast cell metabolism in iron starvation conditions by promoting decay of the targeted molecules, in order to avoid excess iron consumption. This study shows that in the absence of Cth2 immediate upregulation of expression of several of the iron regulon genes (involved in high affinity iron uptake and intracellular iron redistribution upon oxidative stress by hydroperoxide is more intense than in wild type conditions where Cth2 is present. The oxidative stress provokes a temporary increase in the levels of Cth2 (itself a member of the iron regulon. In such conditions Cth2 molecules accumulate at P bodies-like structures when the constitutive mRNA decay machinery is compromised. In addition, a null Δcth2 mutant shows defects, in comparison to CTH2 wild type cells, in exit from α factor-induced arrest at the G1 stage of the cell cycle when hydroperoxide treatment is applied. The cell cycle defects are rescued in conditions that compromise uptake of external iron into the cytosol. The observations support a role of Cth2 in modulating expression of diverse iron regulon genes, excluding those specifically involved in the reductive branch of the high-affinity transport. This would result in immediate adaptation of the yeast cells to an oxidative stress, by controlling uptake of oxidant-promoting iron cations.

  6. The Impact of "Coat Protein-Mediated Virus Resistance" in Applied Plant Pathology and Basic Research.

    Science.gov (United States)

    Lindbo, John A; Falk, Bryce W

    2017-06-01

    Worldwide, plant viruses cause serious reductions in marketable crop yield and in some cases even plant death. In most cases, the most effective way to control virus diseases is through genetically controlled resistance. However, developing virus-resistant (VR) crops through traditional breeding can take many years, and in some cases is not even possible. Because of this, the demonstration of the first VR transgenic plants in 1985 generated much attention. This seminal report served as an inflection point for research in both basic and applied plant pathology, the results of which have dramatically changed both basic research and in a few cases, commercial crop production. The typical review article on this topic has focused on only basic or only applied research results stemming from this seminal discovery. This can make it difficult for the reader to appreciate the full impact of research on transgenic virus resistance, and the contributions from fundamental research that led to translational applications of this technology. In this review, we take a global view of this topic highlighting the significant changes to both basic and applied plant pathology research and commercial food production that have accumulated in the last 30 plus years. We present these milestones in the historical context of some of the scientific, economic, and environmental drivers for developing specific VR crops. The intent of this review is to provide a single document that adequately records the significant accomplishments of researchers in both basic and applied plant pathology research on this topic and how they relate to each other. We hope this review therefore serves as both an instructional tool for students new to the topic, as well as a source of conversation and discussion for how the technology of engineered virus resistance could be applied in the future.

  7. Sme4 coiled-coil protein mediates synaptonemal complex assembly, recombinosome relocalization, and spindle pole body morphogenesis.

    Science.gov (United States)

    Espagne, Eric; Vasnier, Christelle; Storlazzi, Aurora; Kleckner, Nancy E; Silar, Philippe; Zickler, Denise; Malagnac, Fabienne

    2011-06-28

    We identify a large coiled-coil protein, Sme4/PaMe4, that is highly conserved among the large group of Sordariales and plays central roles in two temporally and functionally distinct aspects of the fungal sexual cycle: first as a component of the meiotic synaptonemal complex (SC) and then, after disappearing and reappearing, as a component of the spindle pole body (SPB). In both cases, the protein mediates spatial juxtaposition of two major structures: linkage of homolog axes through the SC and a change in the SPB from a planar to a bent conformation. Corresponding mutants exhibit defects, respectively, in SC and SPB morphogenesis, with downstream consequences for recombination and astral-microtubule nucleation plus postmeiotic nuclear migration. Sme4 is also required for reorganization of recombination complexes in which Rad51, Mer3, and Msh4 foci relocalize from an on-axis position to a between-axis (on-SC) position concomitant with SC installation. Because involved recombinosome foci represent total recombinational interactions, these dynamics are irrespective of their designation for maturation into cross-overs or noncross-overs. The defined dual roles for Sme4 in two different structures that function at distinct phases of the sexual cycle also provide more functional links and evolutionary dynamics among the nuclear envelope, SPB, and SC.

  8. Protein- mediated enamel mineralization

    Science.gov (United States)

    Moradian-Oldak, Janet

    2012-01-01

    Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable mechanical properties of enamel are associated with its hierarchical structural organization and its thorough connection with underlying dentin. This dynamic mineralizing system offers scientists a wealth of information that allows the study of basic principals of organic matrix-mediated biomineralization and can potentially be utilized in the fields of material science and engineering for development and design of biomimetic materials. This chapter will provide a brief overview of enamel hierarchical structure and properties as well as the process and stages of amelogenesis. Particular emphasis is given to current knowledge of extracellular matrix protein and proteinases, and the structural chemistry of the matrix components and their putative functions. The chapter will conclude by discussing the potential of enamel for regrowth. PMID:22652761

  9. On the mechanism of aluminum ion-induced neurotoxicity: The effects of aluminum species on G-protein-mediated processes and on drug interactions with the N-methyl-D-aspartate modulated ionophore

    International Nuclear Information System (INIS)

    Hubbard, C.M.

    1989-01-01

    To establish what effects Al 3+ may have on G-protein mediate signal transduction, the effects of Al 3+ on the signal-coupling G-protein from retinal rod outer segments (G t or transducin) have been investigated as a model for the effects of Al 3+ on signal transduction by G-proteins in general. In this investigation, we have studied the effects of Al 3+ on the isolated, light-dependent rhodopsin catalyzed GTP-GDP exchange on G t ; the light-dependent GTPase activity of G t ; the light-independent cGMP hydrolysis by PDE; and the light activated, rhodopsin catalyzed, cGMP hydrolysis by PDE in vitro. To determine the effects of two defined species of aluminum on N-methyl-D-aspartic acid (NMDA) receptor-channel modulation we utilized a specific radioligand binding assay. This allowed us to compare the effects of aluminum to other metal ions on specific [ 3 H]MK-801 binding to the NMDA receptor-channel complex. This complex is involved in long-term potentiation, which is currently being investigated as the mechanism by which learning and memory occur and has been implicated in the pathology of Alzheimer's disease. We have investigated the effects of two different species of aluminum, as well as Ca 2+ , Zn 2+ , Mg 2+ , and Li + on the specific binding of [ 3 H]MK-801 to the NMDA receptor-channel complex under depolarized conditions

  10. Tomato Cf resistance proteins mediate recognition of cognate homologous effectors from fungi pathogenic on diots and monocots

    NARCIS (Netherlands)

    Stergiopoulos, I.; Burg, van den H.A.; Ökmen, B.; Beenen, H.G.; Liere, van S.; Kema, G.H.J.; Wit, de P.J.G.M.

    2010-01-01

    Most fungal effectors characterized so far are species-specific and facilitate virulence on a particular host plant. During infection of its host tomato, Cladosporium fulvum secretes effectors that function as virulence factors in the absence of cognate Cf resistance proteins and induce

  11. Neuronal Orphan G-Protein Coupled Receptor Proteins Mediate Plasmalogens-Induced Activation of ERK and Akt Signaling.

    Directory of Open Access Journals (Sweden)

    Md Shamim Hossain

    Full Text Available The special glycerophospholipids plasmalogens (Pls are enriched in the brain and reported to prevent neuronal cell death by enhancing phosphorylation of Akt and ERK signaling in neuronal cells. Though the activation of Akt and ERK was found to be necessary for the neuronal cells survival, it was not known how Pls enhanced cellular signaling. To answer this question, we searched for neuronal specific orphan GPCR (G-protein coupled receptor proteins, since these proteins were believed to play a role in cellular signal transduction through the lipid rafts, where both Pls and some GPCRs were found to be enriched. In the present study, pan GPCR inhibitor significantly reduced Pls-induced ERK signaling in neuronal cells, suggesting that Pls could activate GPCRs to induce signaling. We then checked mRNA expression of 19 orphan GPCRs and 10 of them were found to be highly expressed in neuronal cells. The knockdown of these 10 neuronal specific GPCRs by short hairpin (sh-RNA lentiviral particles revealed that the Pls-mediated phosphorylation of ERK was inhibited in GPR1, GPR19, GPR21, GPR27 and GPR61 knockdown cells. We further found that the overexpression of these GPCRs enhanced Pls-mediated phosphorylation of ERK and Akt in cells. Most interestingly, the GPCRs-mediated cellular signaling was reduced significantly when the endogenous Pls were reduced. Our cumulative data, for the first time, suggest a possible mechanism for Pls-induced cellular signaling in the nervous system.

  12. The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle.

    Science.gov (United States)

    Arredondo, Silvia A; Kappe, Stefan H I

    2017-06-01

    During their life cycle Plasmodium parasites rely upon an arsenal of proteins that establish key interactions with the host and vector, and between the parasite sexual stages, with the purpose of ensuring infection, reproduction and proliferation. Among these is a group of secreted or membrane-anchored proteins known as the six-cysteine (6-cys) family. This is a small but important family with only 14 members thus far identified, each stage-specifically expressed during the parasite life cycle. 6-cys proteins often localise at the parasite surface or interface with the host and vector, and are conserved in different Plasmodium species. The unifying feature of the family is the s48/45 domain, presumably involved in adhesion and structurally related to Ephrins, the ligands of Eph receptors. The most prominent s48/45 members are currently under functional investigation and are being pursued as vaccine candidates. In this review, we examine what is known about the 6-cys family, their structure and function, and discuss future research directions. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  13. The Hem protein mediates neuronal migration by inhibiting WAVE degradation and functions opposite of Abelson tyrosine kinase

    Science.gov (United States)

    Zhu, Zengrong; Bhat, Krishna Moorthi

    2011-01-01

    In the nervous system, neurons form in different regions, then they migrate and occupy specific positions. We have previously shown that RP2/sib, a well-studied neuronal pair in the Drosophila ventral nerve cord (VNC), has a complex migration route. Here, we show that the Hem protein, via the WAVE complex, regulates migration of GMC-1 and its progeny RP2 neuron. In Hem or WAVE mutants, RP2 neuron either abnormally migrates, crossing the midline from one hemisegment to the contralateral hemisegment, or does not migrate at al and fail to send out its axon projection. We report that Hem regulates neuronal migration through stabilizing WAVE. Since Hem and WAVE normally form a complex, our data argues that in the absence of Hem, WAVE, which is presumably no longer in a complex, becomes susceptible to degradation. We also find that Abelson Tyrosine kinase affects RP2 migration in a similar manner as Hem and WAVE, and appears to operate via WAVE. However, while Abl negatively regulates the levels of WAVE, it regulates migration via regulating the activity of WAVE. Our results also show that during the degradation of WAVE, Hem function is opposite to that of and downstream of Abl. PMID:21726548

  14. Tomato Cf resistance proteins mediate recognition of cognate homologous effectors from fungi pathogenic on dicots and monocots.

    Science.gov (United States)

    Stergiopoulos, Ioannis; van den Burg, Harrold A; Okmen, Bilal; Beenen, Henriek G; van Liere, Sabine; Kema, Gert H J; de Wit, Pierre J G M

    2010-04-20

    Most fungal effectors characterized so far are species-specific and facilitate virulence on a particular host plant. During infection of its host tomato, Cladosporium fulvum secretes effectors that function as virulence factors in the absence of cognate Cf resistance proteins and induce effector-triggered immunity in their presence. Here we show that homologs of the C. fulvum Avr4 and Ecp2 effectors are present in other pathogenic fungi of the Dothideomycete class, including Mycosphaerella fijiensis, the causal agent of black Sigatoka disease of banana. We demonstrate that the Avr4 homolog of M. fijiensis is a functional ortholog of C. fulvum Avr4 that protects fungal cell walls against hydrolysis by plant chitinases through binding to chitin and, despite the low overall sequence homology, triggers a Cf-4-mediated hypersensitive response (HR) in tomato. Furthermore, three homologs of C. fulvum Ecp2 are found in M. fijiensis, one of which induces different levels of necrosis or HR in tomato lines that lack or contain a putative cognate Cf-Ecp2 protein, respectively. In contrast to Avr4, which acts as a defensive virulence factor, M. fijiensis Ecp2 likely promotes virulence by interacting with a putative host target causing host cell necrosis, whereas Cf-Ecp2 could possibly guard the virulence target of Ecp2 and trigger a Cf-Ecp2-mediated HR. Overall our data suggest that Avr4 and Ecp2 represent core effectors that are collectively recognized by single cognate Cf-proteins. Transfer of these Cf genes to plant species that are attacked by fungi containing these cognate core effectors provides unique ways for breeding disease-resistant crops.

  15. Effects of SIRT1 gene knock-out via activation of SREBP2 protein-mediated PI3K/AKT signaling on osteoarthritis in mice.

    Science.gov (United States)

    Yu, Fei; Zeng, Hui; Lei, Ming; Xiao, De-Ming; Li, Wei; Yuan, Hao; Lin, Jian-Jing

    2016-10-01

    This study investigated the effects of SIRT1 gene knock-out on osteoarthritis in mice, and the possible roles of SREBP2 protein and the PI3K/AKT signaling pathway in the effects. Mice were randomly divided into a normal group and a SIRT1 gene knock-out group (6 mice in each group). In these groups, one side of the knee anterior cruciate ligament was traversed, and the ipsilateral medial meniscus was cut to establish an osteoarthritis model of knee joint. The countralateral synovial bursa was cut out, serving as controls. The knee joint specimens were then divided into four groups: SIRT1 +/+ control group (group A, n=6); SIRT1 +/+ osteoarthritis group (group B, n=6); SIRT1 -/- control group (group C, n=6); SIRT1 -/- osteoarthritis group (group D, n=6). HE staining, Masson staining, Safranin O-Fast Green staining and Van Gieson staining were used to observe the morphological changes in the articular cartilage of the knee. Immunohistochemical staining was employed to detect the expression of SIRT1, SREBP2, VEGF, AKT, HMGCR and type II collagen proteins. SA-β-gal staining was utilized to evaluate chondrocyte aging. The results showed clear knee joint cartilage destruction and degeneration in the SIRT1 -/- osteoarthritis group. The tidal line was twisted and displaced anteriorly. Type II collagen was destroyed and distributed unevenly. Compared with the SIRT1 +/+ osteoarthritis group and SIRT1 -/- control group, SIRT1 protein expression was not obviously changed in the SIRT1 -/- osteoarthritis group (P>0.05), while the expression levels of the SREBP2, VEGF and HMGCR proteins were significantly increased (Pknock-out may aggravate cartilage degeneration in osteoarthritis by activating the SREBP2 protein-mediated PI3K/AKT signalling pathway, suggesting that SIRT1 gene may play a protective role against osteoarthritis.

  16. Evaluation of the P-glycoprotein- and breast cancer resistance protein-mediated brain penetration of 11C-labeled topotecan using small-animal positron emission tomography

    International Nuclear Information System (INIS)

    Yamasaki, Tomoteru; Fujinaga, Masayuki; Kawamura, Kazunori; Hatori, Akiko; Yui, Joji; Nengaki, Nobuki; Ogawa, Masanao; Yoshida, Yuichiro; Wakizaka, Hidekatsu; Yanamoto, Kazuhiko; Fukumura, Toshimitsu; Zhang Mingrong

    2011-01-01

    Introduction: Topotecan (TPT) is a camptothecin derivative and is an anticancer drug working as a topoisomerase-I-specific inhibitor. But TPT cannot penetrate through the blood-brain barrier. In this study, we synthesized a new positron emission tomography (PET) probe, [ 11 C]TPT, to evaluate the P-glycoprotein (Pgp)- and breast cancer resistance protein (BCRP)-mediated brain penetration of [ 11 C]TPT using small-animal PET. Methods: [ 11 C]TPT was synthesized by the reaction of a desmethyl precursor with [ 11 C]CH 3 I. In vitro study using [ 11 C]TPT was carried out in MES-SA and doxorubicin-resistant MES-SA/Dx5 cells in the presence or absence of elacridar, a specific inhibitor for Pgp and BCRP. The biodistribution of [ 11 C]TPT was determined using small-animal PET and the dissection method in mice. Results: The transport of [ 11 C]TPT to the extracellular side was determined in MES-SA/Dx5 cells exhibiting the expressions of Pgp and BCRP at high levels. This transport was inhibited by coincubation with elacridar. In Mdr1a/b -/- Bcrp1 -/- mice, PET results indicated that the brain uptake of [ 11 C]TPT was about two times higher than that in wild-type mice. Similarly, the brain penetration of [ 11 C]TPT in wild-type mice was increased by treatment with elacridar. The radioactivity in the brain of elacridar-treated mice was maintained at a certain level after the injection of [ 11 C]TPT, although the radioactivity in the blood decreased with time. Conclusions: We demonstrated the increase of brain penetration of [ 11 C]TPT by deficiency and inhibition of Pgp and BCRP functions using small-animal PET in mice.

  17. Small heat shock proteins mediate cell-autonomous and -nonautonomous protection in a Drosophila model for environmental-stress-induced degeneration.

    Science.gov (United States)

    Kawasaki, Fumiko; Koonce, Noelle L; Guo, Linda; Fatima, Shahroz; Qiu, Catherine; Moon, Mackenzie T; Zheng, Yunzhen; Ordway, Richard W

    2016-09-01

    Cell and tissue degeneration, and the development of degenerative diseases, are influenced by genetic and environmental factors that affect protein misfolding and proteotoxicity. To better understand the role of the environment in degeneration, we developed a genetic model for heat shock (HS)-stress-induced degeneration in Drosophila This model exhibits a unique combination of features that enhance genetic analysis of degeneration and protection mechanisms involving environmental stress. These include cell-type-specific failure of proteostasis and degeneration in response to global stress, cell-nonautonomous interactions within a simple and accessible network of susceptible cell types, and precise temporal control over the induction of degeneration. In wild-type flies, HS stress causes selective loss of the flight ability and degeneration of three susceptible cell types comprising the flight motor: muscle, motor neurons and associated glia. Other motor behaviors persist and, accordingly, the corresponding cell types controlling leg motor function are resistant to degeneration. Flight motor degeneration was preceded by a failure of muscle proteostasis characterized by diffuse ubiquitinated protein aggregates. Moreover, muscle-specific overexpression of a small heat shock protein (HSP), HSP23, promoted proteostasis and protected muscle from HS stress. Notably, neurons and glia were protected as well, indicating that a small HSP can mediate cell-nonautonomous protection. Cell-autonomous protection of muscle was characterized by a distinct distribution of ubiquitinated proteins, including perinuclear localization and clearance of protein aggregates associated with the perinuclear microtubule network. This network was severely disrupted in wild-type preparations prior to degeneration, suggesting that it serves an important role in muscle proteostasis and protection. Finally, studies of resistant leg muscles revealed that they sustain proteostasis and the microtubule

  18. Gene expression profiling of low-grade endometrial stromal sarcoma indicates fusion protein-mediated activation of the Wnt signaling pathway.

    Science.gov (United States)

    Przybyl, Joanna; Kidzinski, Lukasz; Hastie, Trevor; Debiec-Rychter, Maria; Nusse, Roel; van de Rijn, Matt

    2018-05-01

    Low-grade endometrial stromal sarcomas (LGESS) harbor chromosomal translocations that affect proteins associated with chromatin remodeling Polycomb Repressive Complex 2 (PRC2), including SUZ12, PHF1 and EPC1. Roughly half of LGESS also demonstrate nuclear accumulation of β-catenin, which is a hallmark of Wnt signaling activation. However, the targets affected by the fusion proteins and the role of Wnt signaling in the pathogenesis of these tumors remain largely unknown. Here we report the results of a meta-analysis of three independent gene expression profiling studies on LGESS and immunohistochemical evaluation of nuclear expression of β-catenin and Lef1 in 112 uterine sarcoma specimens obtained from 20 LGESS and 89 LMS patients. Our results demonstrate that 143 out of 310 genes overexpressed in LGESS are known to be directly regulated by SUZ12. In addition, our gene expression meta-analysis shows activation of multiple genes implicated in Wnt signaling. We further emphasize the role of the Wnt signaling pathway by demonstrating concordant nuclear expression of β-catenin and Lef1 in 7/16 LGESS. Based on our findings, we suggest that LGESS-specific fusion proteins disrupt the repressive function of the PRC2 complex similar to the mechanism seen in synovial sarcoma, where the SS18-SSX fusion proteins disrupt the mSWI/SNF (BAF) chromatin remodeling complex. We propose that these fusion proteins in LGESS contribute to overexpression of Wnt ligands with subsequent activation of Wnt signaling pathway and formation of an active β-catenin/Lef1 transcriptional complex. These observations could lead to novel therapeutic approaches that focus on the Wnt pathway in LGESS. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Cold-inducible RNA-binding protein mediates cold air inducible airway mucin production through TLR4/NF-κB signaling pathway.

    Science.gov (United States)

    Chen, Lingxiu; Ran, Danhua; Xie, Wenyue; Xu, Qing; Zhou, Xiangdong

    2016-10-01

    Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases and cold air stimulation has been shown to be associated with the severity of these diseases. However, the regulatory mechanisms that mediate excessive mucin production under cold stress remain elusive. Recently, the cold-inducible RNA-binding protein (CIRP) has been shown to be markedly induced after exposure to cold air. In this study, we sought to explore the expression of CIRP within bronchial biopsy specimens, the effect on mucin5AC (MUC5AC) production in chronic inflammatory airway diseases and the potential signaling pathways involved in cold air stimulation process. We found that CIRP protein expression was significantly increased in patients with COPD and in mice treated with cold air. Moreover, cold air stimulation induced MUC5AC expression in wild-type mice but not in CIRP(-/-) mice. In vitro, cold air stress significantly elevated the transcriptional and protein expression levels of MUC5AC in human bronchial epithelial cells. CIRP, toll-like receptor 4 (TLR4) and phosphorylated NF-κB p65 (p-p65) increased significantly in response to cold stress and CIRP siRNA, TLR4 - neutralizing Ab and a specific inhibitor of NF-κB could attenuated cold stress inducible MUC5AC expression. In addition, CIRP siRNA could hindered the expression levels of TLR4 and p-p65 both induced by cold stress. Taken together, these results suggest that airway epithelial cells constitutively express CIRP in vitro and in vivo. CIRP is responsible for cold-inducible MUC5AC expression by activating TLR4/NF-κB signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Induction of the unfolded protein response by cigarette smoke is primarily an activating transcription factor 4-C/EBP homologous protein mediated process

    Directory of Open Access Journals (Sweden)

    Geraghty P

    2011-06-01

    Full Text Available Patrick Geraghty, Alison Wallace, Jeanine M D'ArmientoDepartment of Medicine, Divisions of Molecular and Pulmonary Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USAPurpose: Cigarette smoke is the major risk factor associated with the development of chronic obstructive pulmonary disease (COPD. Recent studies propose a link between endoplasmic reticulum (ER stress and emphysema, demonstrated by increased ER stress markers under smoking conditions. Here, we investigate whether cigarette smoke-induced ER stress is cell specific and correlates with acute and chronic cigarette smoke exposure.Methods: Gene and protein expression changes in human primary lung cell cultures following cigarette smoke extract (CSE exposure were monitored by qPCR and Western blot analysis. Mice and guinea pigs were exposed to cigarette smoke and ER stress markers examined in whole lung homogenates. Inflammatory cells from the bronchoalveolar lavage fluid of 10 days smoke exposed mice were also examined.Results: Cigarette smoke induced a trend increase in the ER stress response through an activating transcription factor 4 (ATF4 mediated induction of C/EBP homologous protein (CHOP in primary small airway epithelial cells. Bronchial epithelial cells and macrophages responded similarly to CSE. Wild-type mice and guinea pigs exposed to acute levels of cigarette smoke exhibited increased levels of CHOP but not at significant levels. However, after long-term chronic cigarette smoke exposure, CHOP expression was reduced. Interestingly, inflammatory cells from smoke exposed mice had a significant increase in CHOP/ATF4 expression.Conclusion: A trend increase in CHOP levels appear in multiple human lung cell types following acute cigarette smoke exposure in vitro. In vivo, inflammatory cells, predominately macrophages, demonstrate significant cigarette smoke-induced ER stress. Early induction of CHOP in cigarette smoke may play a pivotal role in early

  1. E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection.

    Directory of Open Access Journals (Sweden)

    Yueting Zheng

    2016-01-01

    Full Text Available Interferons (IFNs are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate that both IFNα and IFNγ blocked wild-type Ad5 replication in primary human bronchial epithelial cells (NHBEC and TERT-immortalized normal human diploid fibroblasts (HDF-TERT. IFNs inhibited the replication of divergent adenoviruses. The inhibition of Ad5 replication by IFNα and IFNγ is the consequence of repression of transcription of the E1A immediate early gene product. Both IFNα and IFNγ impede the association of the transactivator GABP with the E1A enhancer region during the early phase of infection. The repression of E1A expression by IFNs requires a conserved E2F binding site in the E1A enhancer, and IFNs increased the enrichment of the E2F-associated pocket proteins, Rb and p107, at the E1A enhancer in vivo. PD0332991 (Pabociclib, a specific CDK4/6 inhibitor, dephosphoryles pocket proteins to promote their interaction with E2Fs and inhibited wild-type Ad5 replication dependent on the conserved E2F binding site. Consistent with this result, expression of the small E1A oncoprotein, which abrogates E2F/pocket protein interactions, rescued Ad replication in the presence of IFNα or IFNγ. Finally, we established a persistent Ad infection model in vitro and demonstrated that IFNγ suppresses productive Ad replication in a manner dependent on the E2F binding site in the E1A enhancer. This is the first study that probes the molecular basis of persistent adenovirus infection and reveals a novel mechanism by which adenoviruses utilize IFN signaling to suppress lytic virus replication and to promote persistent infection.

  2. Protein-mediated surface structuring in biomembranes

    Directory of Open Access Journals (Sweden)

    Maggio B.

    2005-01-01

    Full Text Available The lipids and proteins of biomembranes exhibit highly dissimilar conformations, geometrical shapes, amphipathicity, and thermodynamic properties which constrain their two-dimensional molecular packing, electrostatics, and interaction preferences. This causes inevitable development of large local tensions that frequently relax into phase or compositional immiscibility along lateral and transverse planes of the membrane. On the other hand, these effects constitute the very codes that mediate molecular and structural changes determining and controlling the possibilities for enzymatic activity, apposition and recombination in biomembranes. The presence of proteins constitutes a major perturbing factor for the membrane sculpturing both in terms of its surface topography and dynamics. We will focus on some results from our group within this context and summarize some recent evidence for the active involvement of extrinsic (myelin basic protein, integral (Folch-Lees proteolipid protein and amphitropic (c-Fos and c-Jun proteins, as well as a membrane-active amphitropic phosphohydrolytic enzyme (neutral sphingomyelinase, in the process of lateral segregation and dynamics of phase domains, sculpturing of the surface topography, and the bi-directional modulation of the membrane biochemical reactivity.

  3. Proteins mediating DNA loops effectively block transcription.

    Science.gov (United States)

    Vörös, Zsuzsanna; Yan, Yan; Kovari, Daniel T; Finzi, Laura; Dunlap, David

    2017-07-01

    Loops are ubiquitous topological elements formed when proteins simultaneously bind to two noncontiguous DNA sites. While a loop-mediating protein may regulate initiation at a promoter, the presence of the protein at the other site may be an obstacle for RNA polymerases (RNAP) transcribing a different gene. To test whether a DNA loop alters the extent to which a protein blocks transcription, the lac repressor (LacI) was used. The outcome of in vitro transcription along templates containing two LacI operators separated by 400 bp in the presence of LacI concentrations that produced both looped and unlooped molecules was visualized with scanning force microscopy (SFM). An analysis of transcription elongation complexes, moving for 60 s at an average of 10 nt/s on unlooped DNA templates, revealed that they more often surpassed LacI bound to the lower affinity O2 operator than to the highest affinity Os operator. However, this difference was abrogated in looped DNA molecules where LacI became a strong roadblock independently of the affinity of the operator. Recordings of transcription elongation complexes, using magnetic tweezers, confirmed that they halted for several minutes upon encountering a LacI bound to a single operator. The average pause lifetime is compatible with RNAP waiting for LacI dissociation, however, the LacI open conformation visualized in the SFM images also suggests that LacI could straddle RNAP to let it pass. Independently of the mechanism by which RNAP bypasses the LacI roadblock, the data indicate that an obstacle with looped topology more effectively interferes with transcription. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  4. Orm family proteins mediate sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Breslow, David K; Collins, Sean R; Bodenmiller, Bernd

    2010-01-01

    a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression...... or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma....

  5. Quantitative Measurement of GPCR Endocytosis via Pulse-Chase Covalent Labeling.

    Directory of Open Access Journals (Sweden)

    Hidetoshi Kumagai

    Full Text Available G protein-coupled receptors (GPCRs play a critical role in many physiological systems and represent one of the largest families of signal-transducing receptors. The number of GPCRs at the cell surface regulates cellular responsiveness to their cognate ligands, and the number of GPCRs, in turn, is dynamically controlled by receptor endocytosis. Recent studies have demonstrated that GPCR endocytosis, in addition to affecting receptor desensitization and resensitization, contributes to acute G protein-mediated signaling. Thus, endocytic GPCR behavior has a significant impact on various aspects of physiology. In this study, we developed a novel GPCR internalization assay to facilitate characterization of endocytic GPCR behavior. We genetically engineered chimeric GPCRs by fusing HaloTag (a catalytically inactive derivative of a bacterial hydrolase to the N-terminal end of the receptor (HT-GPCR. HaloTag has the ability to form a stable covalent bond with synthetic HaloTag ligands that contain fluorophores or a high-affinity handle (such as biotin and the HaloTag reactive linker. We selectively labeled HT-GPCRs at the cell surface with a HaloTag PEG ligand, and this pulse-chase covalent labeling allowed us to directly monitor the relative number of internalized GPCRs after agonist stimulation. Because the endocytic activities of GPCR ligands are not necessarily correlated with their agonistic activities, applying this novel methodology to orphan GPCRs, or even to already characterized GPCRs, will increase the likelihood of identifying currently unknown ligands that have been missed by conventional pharmacological assays.

  6. Specifying Specification.

    Science.gov (United States)

    Paulo, Norbert

    2016-03-01

    This paper tackles the accusation that applied ethics is no serious academic enterprise because it lacks theoretical bracing. It does so in two steps. In the first step I introduce and discuss a highly acclaimed method to guarantee stability in ethical theories: Henry Richardson's specification. The discussion shows how seriously ethicists take the stability of the connection between the foundational parts of their theories and their further development as well as their "application" to particular problems or cases. A detailed scrutiny of specification leads to the second step, where I use insights from legal theory to inform the debate around stability from that point of view. This view reveals some of specification's limitations. I suggest that, once specification is sufficiently specified, it appears astonishingly similar to deduction as used in legal theory. Legal theory also provides valuable insight into the functional range of deduction and its relation to other forms of reasoning. This leads to a richer understanding of stability in normative theories and to a smart division of labor between deduction and other forms of reasoning. The comparison to legal theory thereby provides a framework for how different methods such as specification, deduction, balancing, and analogy relate to one another.

  7. Probe specificity

    International Nuclear Information System (INIS)

    Laget, J.M.

    1986-11-01

    Specificity and complementarity of hadron and electron probes must be systematically developed to answer three questions currently asked in intermediate energy nuclear physics: what is nucleus structure at short distances, what is nature of short range correlations, what is three body force nature [fr

  8. HRT Specification

    CERN Document Server

    Möller, M

    1996-01-01

    In the context of the AIS Project (Advanced Informatics Systems for administration and management) a study has been conducted that resulted in the definition of a high level information systems model. Thirteen proposed systems were defined for detailed analysis. The Finance, Foundation, Human Resources, Logistics and Purchasing areas have been studied in detail. These studies have lead to the purchase and implementation of the ORIAC and SIRIAC packages, the Foundation database, the Oracle HR package, the Triton package and EDH and BHT. This specification describes the Human Resources Toolkit (HRT) intended to be used for accessing data in the HR and Foundation systems. This toolkit should help the divisions carry out their Human Resource management, planning and follow-up. It will have extensive report generation capabilities and offer a variety of standard graphs. It should have an easy-to-use graphical user interface and run on the CERN standard desktop platforms.

  9. Evaluation of the P-glycoprotein- and breast cancer resistance protein-mediated brain penetration of {sup 11}C-labeled topotecan using small-animal positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, Tomoteru; Fujinaga, Masayuki; Kawamura, Kazunori; Hatori, Akiko; Yui, Joji [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Nengaki, Nobuki; Ogawa, Masanao; Yoshida, Yuichiro [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); SHI Accelerator Service, Ltd., Tokyo 141-8686 (Japan); Wakizaka, Hidekatsu [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Yanamoto, Kazuhiko [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka 565-0871 (Japan); Fukumura, Toshimitsu [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Zhang Mingrong, E-mail: zhang@nirs.go.jp [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2011-07-15

    Introduction: Topotecan (TPT) is a camptothecin derivative and is an anticancer drug working as a topoisomerase-I-specific inhibitor. But TPT cannot penetrate through the blood-brain barrier. In this study, we synthesized a new positron emission tomography (PET) probe, [{sup 11}C]TPT, to evaluate the P-glycoprotein (Pgp)- and breast cancer resistance protein (BCRP)-mediated brain penetration of [{sup 11}C]TPT using small-animal PET. Methods: [{sup 11}C]TPT was synthesized by the reaction of a desmethyl precursor with [{sup 11}C]CH{sub 3}I. In vitro study using [{sup 11}C]TPT was carried out in MES-SA and doxorubicin-resistant MES-SA/Dx5 cells in the presence or absence of elacridar, a specific inhibitor for Pgp and BCRP. The biodistribution of [{sup 11}C]TPT was determined using small-animal PET and the dissection method in mice. Results: The transport of [{sup 11}C]TPT to the extracellular side was determined in MES-SA/Dx5 cells exhibiting the expressions of Pgp and BCRP at high levels. This transport was inhibited by coincubation with elacridar. In Mdr1a/b{sup -/-}Bcrp1{sup -/-} mice, PET results indicated that the brain uptake of [{sup 11}C]TPT was about two times higher than that in wild-type mice. Similarly, the brain penetration of [{sup 11}C]TPT in wild-type mice was increased by treatment with elacridar. The radioactivity in the brain of elacridar-treated mice was maintained at a certain level after the injection of [{sup 11}C]TPT, although the radioactivity in the blood decreased with time. Conclusions: We demonstrated the increase of brain penetration of [{sup 11}C]TPT by deficiency and inhibition of Pgp and BCRP functions using small-animal PET in mice.

  10. Species differences in ligand specificity of auxin-controlled elongation and auxin transport: comparing Zea and Vigna

    Science.gov (United States)

    Zhao, Hu; Hertel, Rainer; Ishikawa, Hideo; Evans, Michael L.

    2002-01-01

    The plant hormone auxin affects cell elongation in both roots and shoots. In roots, the predominant action of auxin is to inhibit cell elongation while in shoots auxin, at normal physiological levels, stimulates elongation. The question of whether the primary receptor for auxin is the same in roots and shoots has not been resolved. In addition to its action on cell elongation in roots and shoots, auxin is transported in a polar fashion in both organs. Although auxin transport is well characterized in both roots and shoots, there is relatively little information on the connection, if any, between auxin transport and its action on elongation. In particular, it is not clear whether the protein mediating polar auxin movement is separate from the protein mediating auxin action on cell elongation or whether these two processes might be mediated by one and the same receptor. We examined the identity of the auxin growth receptor in roots and shoots by comparing the response of roots and shoots of the grass Zea mays L. and the legume Vigna mungo L. to indole-3-acetic acid, 2-naphthoxyacetic acid, 4,6-dichloroindoleacetic acid, and 4,7-dichloroindoleacetic acid. We also studied whether or not a single protein might mediate both auxin transport and auxin action by comparing the polar transport of indole-3-acetic acid and 2-naphthoxyacetic acid through segments from Vigna hypocotyls and maize coleoptiles. For all of the assays performed (root elongation, shoot elongation, and polar transport) the action and transport of the auxin derivatives was much greater in the dicots than in the grass species. The preservation of ligand specificity between roots and shoots and the parallels in ligand specificity between auxin transport and auxin action on growth are consistent with the hypothesis that the auxin receptor is the same in roots and shoots and that this protein may mediate auxin efflux as well as auxin action in both organ types.

  11. Myositis specific autoantibodies; specificity and clinical applications.

    NARCIS (Netherlands)

    Hengstman, G.J.D.

    2005-01-01

    The sera of about half of the patients with myositis contain autoantibodies that are specific for this group of diseases compared to other inflammatory connective tissue disorders. In a recent study we showed that these myositis specific autoantibodies (MSAs) are also specific for myositis as

  12. Polycomb group protein-mediated repression of transcription

    DEFF Research Database (Denmark)

    Morey, Lluís; Helin, Kristian

    2010-01-01

    The polycomb group (PcG) proteins are essential for the normal development of multicellular organisms. They form multi-protein complexes that work as transcriptional repressors of several thousand genes controlling differentiation pathways during development. How the PcG proteins work as transcri......The polycomb group (PcG) proteins are essential for the normal development of multicellular organisms. They form multi-protein complexes that work as transcriptional repressors of several thousand genes controlling differentiation pathways during development. How the PcG proteins work...... as transcriptional repressors is incompletely understood, but involves post-translational modifications of histones by two major PcG protein complexes: polycomb repressive complex 1 and polycomb repressive complex 2....

  13. Multidrug and toxin extrusion proteins mediate cellular transport of cadmium

    International Nuclear Information System (INIS)

    Yang, Hong; Guo, Dong; Obianom, Obinna N.; Su, Tong; Polli, James E.; Shu, Yan

    2017-01-01

    Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. As compared to the extensive research in Cd tissue accumulation, little was known about the elimination of Cd, particularly its toxic form, Cd ion (Cd 2+ ). In this study, we aimed to examine whether Cd 2+ is a substrate of multidrug and toxin extrusion proteins (MATEs) that are important in renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK-hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to study the cellular transport and toxicity of Cd 2+ . The cells overexpressing MATEs showed a 2–4 fold increase of Cd 2+ uptake that could be blocked by the MATE inhibitor cimetidine. A saturable transport profile was observed with the Michaelis-Menten constant (K m ) of 130 ± 15.8 μM for HEK-hMATE1; 139 ± 21.3 μM for HEK-hMATE2-K; and 88.7 ± 13.5 μM for HEK-mMate1, respectively. Cd 2+ could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC 50 ) of 97.5 ± 6.0 μM, 20.2 ± 2.6 μM, and 49.9 ± 6.9 μM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively. In addition, hMATE1 could transport preloaded Cd 2+ out of the HEK-hMATE1 cells, thus resulting in a significant decrease of Cd 2+ -induced cytotoxicity. The present study has provided the first evidence supporting that MATEs transport Cd 2+ and may function as cellular elimination machinery in Cd intoxication. - Highlights: • Cadmium is an environmentally prevalent toxicant. • Little was known regarding the elimination and detoxification of cadmium. • Cadmium ion is here demonstrated as a substrate of MATE transporters. • MATEs may function as cellular elimination machinery in cadmium detoxification.

  14. Protein-Mediated Interactions of Pancreatic Islet Cells

    Directory of Open Access Journals (Sweden)

    Paolo Meda

    2013-01-01

    Full Text Available The islets of Langerhans collectively form the endocrine pancreas, the organ that is soley responsible for insulin secretion in mammals, and which plays a prominent role in the control of circulating glucose and metabolism. Normal function of these islets implies the coordination of different types of endocrine cells, noticeably of the beta cells which produce insulin. Given that an appropriate secretion of this hormone is vital to the organism, a number of mechanisms have been selected during evolution, which now converge to coordinate beta cell functions. Among these, several mechanisms depend on different families of integral membrane proteins, which ensure direct (cadherins, N-CAM, occludin, and claudins and paracrine communications (pannexins between beta cells, and between these cells and the other islet cell types. Also, other proteins (integrins provide communication of the different islet cell types with the materials that form the islet basal laminae and extracellular matrix. Here, we review what is known about these proteins and their signaling in pancreatic β-cells, with particular emphasis on the signaling provided by Cx36, given that this is the integral membrane protein involved in cell-to-cell communication, which has so far been mostly investigated for effects on beta cell functions.

  15. Signaling via G proteins mediates tumorigenic effects of GPR87

    DEFF Research Database (Denmark)

    Arfelt, Kristine Niss; Fares, Suzan; Sparre-Ulrich, Alexander H.

    2017-01-01

    G protein-coupled receptors (GPCRs) constitute a large protein family of seven transmembrane (7TM) spanning proteins that regulate multiple physiological functions. GPR87 is overexpressed in several cancers and plays a role in tumor cell survival. Here, the basal activity of GPR87 was investigated...

  16. Multidrug and toxin extrusion proteins mediate cellular transport of cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hong; Guo, Dong; Obianom, Obinna N. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Su, Tong [Department of Oral Maxillofacial Surgery, the First Affiliated Hospital, Xiangya Medical School, Central South University, Hunan 410007 (China); Polli, James E. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Shu, Yan, E-mail: yshu@rx.umaryland.edu [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States)

    2017-01-01

    Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. As compared to the extensive research in Cd tissue accumulation, little was known about the elimination of Cd, particularly its toxic form, Cd ion (Cd{sup 2+}). In this study, we aimed to examine whether Cd{sup 2+} is a substrate of multidrug and toxin extrusion proteins (MATEs) that are important in renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK-hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to study the cellular transport and toxicity of Cd{sup 2+}. The cells overexpressing MATEs showed a 2–4 fold increase of Cd{sup 2+} uptake that could be blocked by the MATE inhibitor cimetidine. A saturable transport profile was observed with the Michaelis-Menten constant (K{sub m}) of 130 ± 15.8 μM for HEK-hMATE1; 139 ± 21.3 μM for HEK-hMATE2-K; and 88.7 ± 13.5 μM for HEK-mMate1, respectively. Cd{sup 2+} could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC{sub 50}) of 97.5 ± 6.0 μM, 20.2 ± 2.6 μM, and 49.9 ± 6.9 μM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively. In addition, hMATE1 could transport preloaded Cd{sup 2+} out of the HEK-hMATE1 cells, thus resulting in a significant decrease of Cd{sup 2+}-induced cytotoxicity. The present study has provided the first evidence supporting that MATEs transport Cd{sup 2+} and may function as cellular elimination machinery in Cd intoxication. - Highlights: • Cadmium is an environmentally prevalent toxicant. • Little was known regarding the elimination and detoxification of cadmium. • Cadmium ion is here demonstrated as a substrate of MATE transporters. • MATEs may function as cellular elimination machinery in cadmium detoxification.

  17. Structure and Sequence Analyses of Clustered Protocadherins Reveal Antiparallel Interactions that Mediate Homophilic Specificity.

    Science.gov (United States)

    Nicoludis, John M; Lau, Sze-Yi; Schärfe, Charlotta P I; Marks, Debora S; Weihofen, Wilhelm A; Gaudet, Rachelle

    2015-11-03

    Clustered protocadherin (Pcdh) proteins mediate dendritic self-avoidance in neurons via specific homophilic interactions in their extracellular cadherin (EC) domains. We determined crystal structures of EC1-EC3, containing the homophilic specificity-determining region, of two mouse clustered Pcdh isoforms (PcdhγA1 and PcdhγC3) to investigate the nature of the homophilic interaction. Within the crystal lattices, we observe antiparallel interfaces consistent with a role in trans cell-cell contact. Antiparallel dimerization is supported by evolutionary correlations. Two interfaces, located primarily on EC2-EC3, involve distinctive clustered Pcdh structure and sequence motifs, lack predicted glycosylation sites, and contain residues highly conserved in orthologs but not paralogs, pointing toward their biological significance as homophilic interaction interfaces. These two interfaces are similar yet distinct, reflecting a possible difference in interaction architecture between clustered Pcdh subfamilies. These structures initiate a molecular understanding of clustered Pcdh assemblies that are required to produce functional neuronal networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. How specific is specific self-efficacy?

    DEFF Research Database (Denmark)

    Nielsen, Tine; Makransky, Guido; Vang, Maria Louison

    2017-01-01

    academic learning self-efficacy (SAL-SE) and specific academic exam self-efficacy (SAE-SE), each scale being measurement invariant relative to age, Gender, admission method and specific course targeted. Furthermore, significant and relevant differences between the SAL-SE and SAE-SE scores dependent......Self-efficacy is an important and much used construct in psychology and social science studies. The validity of the measurements used is not always sufficiently evaluated. The aim was to evaluate the psychometric properties of the Danish translation of the self-efficacy subscale of The Motivated...... Strategies for Learning Questionnaire (MSLQ-SE) within a higher education context. Rasch measurement models were employed focusing on measurement invariance and dimensionality. Results with one students sample showed the MSLQ-SE to be not one, but two separate unidimensional subscales, measuring specific...

  19. Urine specific gravity test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003587.htm Urine specific gravity test To use the sharing features on this page, please enable JavaScript. Urine specific gravity is a laboratory test that shows the concentration ...

  20. Real-time specifications

    DEFF Research Database (Denmark)

    David, A.; Larsen, K.G.; Legay, A.

    2015-01-01

    A specification theory combines notions of specifications and implementations with a satisfaction relation, a refinement relation, and a set of operators supporting stepwise design. We develop a specification framework for real-time systems using Timed I/O Automata as the specification formalism......, with the semantics expressed in terms of Timed I/O Transition Systems. We provide constructs for refinement, consistency checking, logical and structural composition, and quotient of specifications-all indispensable ingredients of a compositional design methodology. The theory is implemented in the new tool Ecdar...

  1. The Escherichia coli Tus-Ter replication fork barrier causes site-specific DNA replication perturbation in yeast.

    Science.gov (United States)

    Larsen, Nicolai B; Sass, Ehud; Suski, Catherine; Mankouri, Hocine W; Hickson, Ian D

    2014-04-07

    Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus, to specific DNA sequences called Ter. Here, we demonstrate that Tus-Ter modules also induce polar RF pausing when engineered into the Saccharomyces cerevisiae genome. This heterologous RF barrier is distinct from a number of previously characterized, protein-mediated, RF pause sites in yeast, as it is neither Tof1-dependent nor counteracted by the Rrm3 helicase. Although the yeast replisome can overcome RF pausing at Tus-Ter modules, this event triggers site-specific homologous recombination that requires the RecQ helicase, Sgs1, for its timely resolution. We propose that Tus-Ter can be utilized as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications.

  2. Understanding transporter specificity and the discrete appearance of channel-like gating domains in transporters

    Directory of Open Access Journals (Sweden)

    GEORGE eDIALLINAS

    2014-09-01

    Full Text Available Transporters are ubiquitous proteins mediating the translocation of solutes across cell membranes, a biological process involved in nutrition, signaling, neurotransmission, cell communication and drug uptake or efflux. Similarly to enzymes, most transporters have a single substrate binding-site and thus their activity follows Michaelis-Menten kinetics. Substrate binding elicits a series of structural changes, which produce a transporter conformer open towards the side opposite to the one from where the substrate was originally bound. This mechanism, involving alternate outward- and inward-facing transporter conformers, has gained significant support from structural, genetic, biochemical and biophysical approaches. Most transporters are specific for a given substrate or a group of substrates with similar chemical structure, but substrate specificity and/or affinity can vary dramatically, even among members of a transporter family that show high overall amino acid sequence and structural similarity. The current view is that transporter substrate affinity or specificity is determined by a small number of interactions a given solute can make within a specific binding site. However, genetic, biochemical and in silico modeling studies with the purine transporter UapA of the filamentous ascomycete Aspergillus nidulans have challenged this dogma. This review highlights results leading to a novel concept, stating that substrate specificity, but also transport kinetics and transporter turnover, are determined by subtle intramolecular interactions between a major substrate binding site and independent outward- or cytoplasmically-facing gating domains, analogous to those present in channels. This concept is supported by recent structural evidence from several, phylogenetically and functionally distinct transporter families. The significance of this concept is discussed in relationship to the role and potential exploitation of transporters in drug action.

  3. Experiences with effects specifications

    DEFF Research Database (Denmark)

    Simonsen, Jesper; Hertzum, Morten; Barlach, Anders

    2011-01-01

    We describe the effects-specification process from a project that was conducted during the fall 2010 and spring of 2011 in this chapter. The project configured and implemented an electronic patient record system at a maternity ward at a hospital located in a European region. The process comprised...... workshops with effects specification with management and end-users and an agile development process including prototypes configured from the effects specifications. We describe the project and the effects-specification process through which effects were related to the system design and instruments...... for measuring effects were designed. The project is analyzed and lessons learned are discussed....

  4. Review of technical specifications

    International Nuclear Information System (INIS)

    Bedrich, M.; Scholz, D.

    1980-01-01

    The present paper deals with position and function of technical specifications before and during the manufacturing of reactor components, their structure and reasons for specific regulations due to safety philosophy and explains the cooperation of supplier, manufacturer, utilities and supervisory organizations. (RW)

  5. Point specificity in acupuncture

    Directory of Open Access Journals (Sweden)

    Choi Emma M

    2012-02-01

    Full Text Available Abstract The existence of point specificity in acupuncture is controversial, because many acupuncture studies using this principle to select control points have found that sham acupoints have similar effects to those of verum acupoints. Furthermore, the results of pain-related studies based on visual analogue scales have not supported the concept of point specificity. In contrast, hemodynamic, functional magnetic resonance imaging and neurophysiological studies evaluating the responses to stimulation of multiple points on the body surface have shown that point-specific actions are present. This review article focuses on clinical and laboratory studies supporting the existence of point specificity in acupuncture and also addresses studies that do not support this concept. Further research is needed to elucidate the point-specific actions of acupuncture.

  6. FOXP3-specific immunity

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2013-01-01

    Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3 and regulat...... and regulatory T cells, but also to kill FOXP3(+) malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network of immune regulation....

  7. Place-Specific Computing

    DEFF Research Database (Denmark)

    Messeter, Jörn; Johansson, Michael

    project place- specific computing is explored through design oriented research. This article reports six pilot studies where design students have designed concepts for place-specific computing in Berlin (Germany), Cape Town (South Africa), Rome (Italy) and Malmö (Sweden). Background and arguments...... for place-specific computing as a genre of interaction design are described. A total number of 36 design concepts designed for 16 designated zones in the four cities are presented. An analysis of the design concepts is presented indicating potentials, possibilities and problems as directions for future......An increased interest in the notion of place has evolved in interaction design. Proliferation of wireless infrastructure, developments in digital media, and a ‘spatial turn’ in computing provides the base for place-specific computing as a suggested new genre of interaction design. In the REcult...

  8. TWRSview system requirements specification

    International Nuclear Information System (INIS)

    Caldwell, J.A.; Lee, A.K.

    1995-12-01

    This document provides the system requirements specification for the TWRSview software system. The TWRSview software system is being developed to integrate electronic data supporting the development of the TWRS technical baseline

  9. specific low back pain

    African Journals Online (AJOL)

    2015-09-01

    Sep 1, 2015 ... SPECIFIC LOW BACK PAIN: IMPLICATION FOR DIRECT HEALTH. CARE COST ... abundant evidence suggesting the benefits of therapeu- tic exercise on pain and ... Exercise and behavioural therapies in chronic pain. 174.

  10. Site Specific Vendor's License

    Data.gov (United States)

    Montgomery County of Maryland — This dataset contains information of a site-specific vendor's license which is required if an individual sells or offers to sell goods or services from a stationary...

  11. Construction and material specification

    Science.gov (United States)

    2002-01-01

    These Construction and Material Specifications are written to the Bidder before award of the : Contract and to the Contractor after award of the Contract. The sentences that direct the Contractor to perform Work are written as commands. For example, ...

  12. Specific radiography technique

    International Nuclear Information System (INIS)

    Abdul Nassir Ibrahim; Azali Muhammad; Ab. Razak Hamzah; Abd. Aziz Mohamed; Mohamad Pauzi Ismail

    2008-01-01

    Beside radiography testing using x-ray machine and gamma source, there are several technique that developed specifically to complete the testing that cannot be done with the two earlier. This technique was specific based on several factor, for the example, the advantages of neutron and electron using to show the image was unique compare to x-ray and gamma. Besides that, these special radiography techniques maybe differ in how to detect the radiation get through the object. These technique can used to inspect thin or specimen that contained radioactive material. There are several technique will discussed in this chapter such as neutron radiography, electron radiography, fluoroscopy and also autoradiography.

  13. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

     This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....... This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....

  14. IDC System Specification Document.

    Energy Technology Data Exchange (ETDEWEB)

    Clifford, David J.

    2014-12-01

    This document contains the system specifications derived to satisfy the system requirements found in the IDC System Requirements Document for the IDC Reengineering Phase 2 project. Revisions Version Date Author/Team Revision Description Authorized by V1.0 12/2014 IDC Reengineering Project Team Initial delivery M. Harris

  15. Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    relation over two objects and an event. In the model, objects can be composed by parallel composition, encapsulation, and hiding of operations. Refinement between objects is defined as fair trace inclusion.A specification language is presented where objects can be specified operationally by abstract...

  16. Place-Specific Computing

    DEFF Research Database (Denmark)

    Messeter, Jörn

    2009-01-01

    An increased interest in the notion of place has evolved in interaction design based on the proliferation of wireless infrastructures, developments in digital media, and a ‘spatial turn’ in computing. In this article, place-specific computing is suggested as a genre of interaction design that add......An increased interest in the notion of place has evolved in interaction design based on the proliferation of wireless infrastructures, developments in digital media, and a ‘spatial turn’ in computing. In this article, place-specific computing is suggested as a genre of interaction design...... that addresses the shaping of interactions among people, place-specific resources and global socio-technical networks, mediated by digital technology, and influenced by the structuring conditions of place. The theoretical grounding for place-specific computing is located in the meeting between conceptions...... of place in human geography and recent research in interaction design focusing on embodied interaction. Central themes in this grounding revolve around place and its relation to embodiment and practice, as well as the social, cultural and material aspects conditioning the enactment of place. Selected...

  17. Sports-specific injuries.

    Science.gov (United States)

    Plancher, K D; Minnich, J M

    1996-04-01

    Injuries to the upper extremities can happen in any sport. Injury patterns are common to specific sports. Understanding which injuries occur with these sports allows the examiner to diagnose and treat the athlete easily. This article reviews some of the injuries common in sports such as bicycling, golf, gymnastics, martial arts, racquet sports, and weightlifting.

  18. Site-Specific Innovation

    DEFF Research Database (Denmark)

    Reeh, Henrik; Hemmersam, Peter

    2015-01-01

    Currently, cities across the Northern European region are actively redeveloping their former industrial harbours. Indeed, harbours areas are essential in the long-term transition from industrial to information and experience societies; harbours are becoming sites for new businesses and residences...... question is how innovation may contribute to urban life and site-specific qualities....

  19. Specification of Nonmonotonic Reasoning.

    NARCIS (Netherlands)

    Engelfriet, J.; Treur, J.

    2000-01-01

    Two levels of description of nonmonotonic reasoning are distinguished. For these levels semantical formalizations are given. The first Level is defined semantically by the notion of belief state frame, the second Level by the notion of reasoning frame. We introduce two specification languages to

  20. Specification of Nonmonotonic Reasoning

    NARCIS (Netherlands)

    Engelfriet, J.; Treur, J.

    1996-01-01

    Two levels of description of nonmonotonic reasoning are distinguished. For these levels semantical formalizations are given. The first level is defined semantically by the notion of belief state frame, the second level by the notion of reasoning frame. We introduce two specification languages to

  1. Domain-Specific Multimodeling

    DEFF Research Database (Denmark)

    Hessellund, Anders

    the overall level of abstraction. It does, however, also introduce a new problem of coordinating multiple different languages in a single system. We call this problem the coordination problem. In this thesis, we present the coordination method for domain-specific multimodeling that explicitly targets...

  2. Specific Language Impairment

    Science.gov (United States)

    ... Some of the tests use interactions between the child and puppets and other toys to focus on specific rules of grammar, especially ... is not treated early, it can affect a child’s performance in school. ... language development. This kind of classroom program might enlist normally ...

  3. Specifications in software prototyping

    OpenAIRE

    Luqi; Chang, Carl K.; Zhu, Hong

    1998-01-01

    We explore the use of software speci®cations for software prototyping. This paper describes a process model for software prototyping, and shows how specifications can be used to support such a process via a cellular mobile phone switch example.

  4. New usable technical specifications

    International Nuclear Information System (INIS)

    Webster, S.A.; Tomasi, L.T.; Bernier, R.A.

    1989-01-01

    After 2 yr of preparation, 1988 finally saw the nuclear industry writing operator-oriented technical specifications. This effort is a continuation of previous efforts to develop improved and usable standard technical specifications (STSs), and is being conducted by the four nuclear steam supply system vendor owners' groups under the auspices of the Nuclear Management Resources Council. Each participant is currently preparing a set of improved STSs based on a writer's guide that was developed through a combined industry effort. In May of 1987, a Human Factors Improvements to Technical Specifications (HFITS) task group was formed to prepare a writer's guide for improved, industrywide STSs. This task group was composed of two representatives from each owners' group, one with a human factors background and one with some operations background. Two documents were prepared in 6 months, a human factors report laying the groundwork for the considerations to go into technical specifications and a writer's guide for their preparation. This paper reports on the application of this writer's guide to the writing of improved STS

  5. Spatial separation and bidirectional trafficking of proteins using a multi-functional reporter

    Directory of Open Access Journals (Sweden)

    Klaubert Dieter H

    2008-04-01

    Full Text Available Abstract Background The ability to specifically label proteins within living cells can provide information about their dynamics and function. To study a membrane protein, we fused a multi-functional reporter protein, HaloTag®, to the extracellular domain of a truncated integrin. Results Using the HaloTag technology, we could study the localization, trafficking and processing of an integrin-HaloTag fusion, which we showed had cellular dynamics consistent with native integrins. By labeling live cells with different fluorescent impermeable and permeable ligands, we showed spatial separation of plasma membrane and internal pools of the integrin-HaloTag fusion, and followed these protein pools over time to study bi-directional trafficking. In addition to combining the HaloTag reporter protein with different fluorophores, we also employed an affinity tag to achieve cell capture. Conclusion The HaloTag technology was used successfully to study expression, trafficking, spatial separation and real-time translocation of an integrin-HaloTag fusion, thereby demonstrating that this technology can be a powerful tool to investigate membrane protein biology in live cells.

  6. Sport-specific balance.

    Science.gov (United States)

    Zemková, Erika

    2014-05-01

    This review includes the latest findings based on experimental studies addressing sport-specific balance, an area of research that has grown dramatically in recent years. The main objectives of this work were to investigate the postural sway response to different forms of exercise under laboratory and sport-specific conditions, to examine how this effect can vary with expertise, and to provide examples of the association of impaired balance with sport performance and/or increasing risk of injury. In doing so, sports where body balance is one of the limiting factors of performance were analyzed. While there are no significant differences in postural stability between athletes of different specializations and physically active individuals during standing in a standard upright position (e.g., bipedal stance), they have a better ability to maintain balance in specific conditions (e.g., while standing on a narrow area of support). Differences in magnitude of balance impairment after specific exercises (rebound jumps, repeated rotations, etc.) and mainly in speed of its readjustment to baseline are also observed. Besides some evidence on an association of greater postural sway with the increasing risk of injuries, there are many myths related to the negative influence of impaired balance on sport performance. Though this may be true for shooting or archery, findings have shown that in many other sports, highly skilled athletes are able to perform successfully in spite of increased postural sway. These findings may contribute to better understanding of the postural control system under various performance requirements. It may provide useful knowledge for designing training programs for specific sports.

  7. ENVIRONMENTAL SPECIFICATION REQUIREMENTS

    International Nuclear Information System (INIS)

    TIFFT, S.R.

    2003-01-01

    Through regulations, permitting or binding negotiations, Regulators establish requirements, limits, permit conditions and Notice of Construction (NOC) conditions with which the Office of River Protection (ORP) and the Tank Farm Contractor (TFC) must comply. Operating Specifications are technical limits which are set on a process to prevent injury to personnel, or damage to the facility or environment. The main purpose of this document is to provide specification limits and recovery actions for the TFC Environmental Surveillance Program at the Hanford Site. Specification limits are given for monitoring frequencies and permissible variation of readings from an established baseline or previous reading. The requirements in this document are driven by environmental considerations and data analysis issues, rather than facility design or personnel safety issues. This document is applicable to all single-shell tank (SST) and double-shell tank (DST) waste tanks, and the associated catch tanks and receiver tanks, and transfer systems. This Tank Farm Environmental Specifications Document (ESD) implements environmental-regulatory limits on the configuration and operation of the Hanford Tank Farms facility that have been established by Regulators. This ESD contains specific field operational limits and recovery actions for compliance with airborne effluent regulations and agreements, liquid effluents regulations and agreements, and environmental tank system requirements. The scope of this ESD is limited to conditions that have direct impact on Operations Projects or that Operations/Projects have direct impact upon. This document does not supercede or replace any DOE Orders, regulatory permits, notices of construction, or Regulatory agency agreements binding on the ORP or the TFC. Refer to the appropriate regulation, permit, or NOC for an inclusive listing of requirements

  8. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. In the comp....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases. The comparative test cases include: ventilation, shading and geometry....

  9. Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. I....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases....

  10. ENVIRONMENTAL SPECIFICATION REQUIREMENTS

    International Nuclear Information System (INIS)

    TIFFT, S.R.

    2003-01-01

    Through regulations, permitting or binding negotiations, Regulators establish requirements, limits, permit conditions and Notice of Construction (NOC) conditions with which the Office of River Protection (ORP) and the Tank Farm Contractor (TFC) must comply. Operating Specifications are technical limits which are set on a process to prevent injury to personnel, or damage to the facility or environment. The main purpose of this document is to provide specification limits and recovery actions for the TFC Environmental Surveillance Program at the Hanford Site. Specification limits are given for monitoring frequencies and permissible variation of readings from an established baseline or previous reading. The requirements in this document are driven by environmental considerations and data analysis issues, rather than facility design or personnel safety issues. This document is applicable to all SST and DST waste tanks, and the associated catch tanks and receiver tanks, and transfer systems. This Tank Farm ESD implements environmental-regulatory limits on the configuration and operation of the Hanford Tank Farms facility that have been established by Regulators. This ESD contains specific field operational limits and recovery actions for compliance with airborne effluent regulations and agreements, liquid effluents regulations and agreements, and environmental tank system requirements. The scope of this ESD is limited to conditions that have direct impact on Operations/Projects or that Operations/Projects have direct impact upon. This document does not supercede or replace any DOE Orders, regulatory permits, notices of construction, or Regulatory agency agreements binding on the ORP or the TFC. Refer to the appropriate regulation, permit, or NOC for an inclusive listing of requirements

  11. Allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Moote William

    2011-11-01

    Full Text Available Abstract Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity. However, despite its proven efficacy in these conditions, it is frequently underutilized in Canada. The decision to proceed with allergen-specific immunotherapy should be made on a case-by-case basis, taking into account individual patient factors such as the degree to which symptoms can be reduced by avoidance measures and pharmacological therapy, the amount and type of medication required to control symptoms, the adverse effects of pharmacological treatment, and patient preferences. Since this form of therapy carries the risk of anaphylactic reactions, it should only be prescribed by physicians who are adequately trained in the treatment of allergy. Furthermore, injections must be given under medical supervision in clinics that are equipped to manage anaphylaxis. In this article, the authors review the indications and contraindications, patient selection criteria, and the administration, safety and efficacy of allergen-specific immunotherapy.

  12. Data specifications for INSPIRE

    Science.gov (United States)

    Portele, Clemens; Woolf, Andrew; Cox, Simon

    2010-05-01

    In Europe a major recent development has been the entering in force of the INSPIRE Directive in May 2007, establishing an infrastructure for spatial information in Europe to support Community environmental policies, and policies or activities which may have an impact on the environment. INSPIRE is based on the infrastructures for spatial information established and operated by the 27 Member States of the European Union. The Directive addresses 34 spatial data themes needed for environmental applications, with key components specified through technical implementing rules. This makes INSPIRE a unique example of a legislative "regional" approach. One of the requirements of the INSPIRE Directive is to make existing spatial data sets with relevance for one of the spatial data themes available in an interoperable way, i.e. where the spatial data from different sources in Europe can be combined to a coherent result. Since INSPIRE covers a wide range of spatial data themes, the first step has been the development of a modelling framework that provides a common foundation for all themes. This framework is largely based on the ISO 19100 series of standards. The use of common generic spatial modelling concepts across all themes is an important enabler for interoperability. As a second step, data specifications for the first set of themes has been developed based on the modelling framework. The themes include addresses, transport networks, protected sites, hydrography, administrative areas and others. The data specifications were developed by selected experts nominated by stakeholders from all over Europe. For each theme a working group was established in early 2008 working on their specific theme and collaborating with the other working groups on cross-theme issues. After a public review of the draft specifications starting in December 2008, an open testing process and thorough comment resolution process, the draft technical implementing rules for these themes have been

  13. Substructural Logical Specifications

    Science.gov (United States)

    2012-11-14

    and independently in the context of CLF by Schack-Nielsen [SN07] and by Cruz and Hou [CH12]; Schack-Nielsen proves the equivalence of the two specifi...cations, whereas Cruz and Hou used the connection informally. The contribution of this section is to describe a general transformation (of which...Functional Programming (LFP’86), pages 13–27. ACM, 1986. 5.1 [CDE+11] Manuel Clavel, Francisco Durán, Steven Eker, Patrick Lincoln, Narciso Martı́- 290 Oliet

  14. Tendering specification and contracting

    International Nuclear Information System (INIS)

    Koch, E. von

    1975-01-01

    The lecture tendering, specification and contracting is prepared in two parts: This first part deals with technical aspects while part two features the commercial and legal situation in the partnership of two: the supplier of the fuel bundles and the utility. In this lecture a look is given on the way how a supplier can offer its fuel and some certain points are mentioned which are important to compare the bid of one competitor to the other. The major points are summarized which are or at least should be in an offer so as to find out which offer is the best. (orig./FW) [de

  15. Disease specific protein corona

    Science.gov (United States)

    Rahman, M.; Mahmoudi, M.

    2015-03-01

    It is now well accepted that upon their entrance into the biological environments, the surface of nanomaterials would be covered by various biomacromolecules (e.g., proteins and lipids). The absorption of these biomolecules, so called `protein corona', onto the surface of (nano)biomaterials confers them a new `biological identity'. Although the formation of protein coronas on the surface of nanoparticles has been widely investigated, there are few reports on the effect of various diseases on the biological identity of nanoparticles. As the type of diseases may tremendously changes the composition of the protein source (e.g., human plasma/serum), one can expect that amount and composition of associated proteins in the corona composition may be varied, in disease type manner. Here, we show that corona coated silica and polystyrene nanoparticles (after interaction with in the plasma of the healthy individuals) could induce unfolding of fibrinogen, which promotes release of the inflammatory cytokines. However, no considerable releases of inflammatory cytokines were observed for corona coated graphene sheets. In contrast, the obtained corona coated silica and polystyrene nanoparticles from the hypofibrinogenemia patients could not induce inflammatory cytokine release where graphene sheets do. Therefore, one can expect that disease-specific protein coronas can provide a novel approach for applying nanomedicine to personalized medicine, improving diagnosis and treatment of different diseases tailored to the specific conditions and circumstances.

  16. Code, standard and specifications

    International Nuclear Information System (INIS)

    Abdul Nassir Ibrahim; Azali Muhammad; Ab. Razak Hamzah; Abd. Aziz Mohamed; Mohamad Pauzi Ismail

    2008-01-01

    Radiography also same as the other technique, it need standard. This standard was used widely and method of used it also regular. With that, radiography testing only practical based on regulations as mentioned and documented. These regulation or guideline documented in code, standard and specifications. In Malaysia, level one and basic radiographer can do radiography work based on instruction give by level two or three radiographer. This instruction was produced based on guideline that mention in document. Level two must follow the specifications mentioned in standard when write the instruction. From this scenario, it makes clearly that this radiography work is a type of work that everything must follow the rule. For the code, the radiography follow the code of American Society for Mechanical Engineer (ASME) and the only code that have in Malaysia for this time is rule that published by Atomic Energy Licensing Board (AELB) known as Practical code for radiation Protection in Industrial radiography. With the existence of this code, all the radiography must follow the rule or standard regulated automatically.

  17. Specification of brachytherapy sources

    Energy Technology Data Exchange (ETDEWEB)

    1984-10-01

    BCRU recommends that the following specification of gamma-ray brachytherapy sources be adopted. Unless otherwise stated, the output of a cylindrical source should be specified in air kerma rate at a point in free space at a distance of 1 m from the source on the radial plane of symmetry, i.e. the plane bisecting the active length and perpendicular to the cylindrical axis of the source. For a wire source the output should be specified for a 1 cm length. For any other construction of source, the point at which the output is specified should be stated. It is also recommended that the units in which the air kerma rate is expressed should be micrograys per hour (..mu..Gy/h).

  18. Site specific plan

    International Nuclear Information System (INIS)

    Hutchison, J.; Jernigan, G.

    1989-12-01

    The Environmental Restoration and Waste Management Five-Year Plan (FYP) covers the period for FY 1989 through FY 1995. The plan establishes a Department of Energy -- Headquarters (DOE-HQ) agenda for cleanup and compliance against which overall progress can be measured. The FYP covers three areas: Corrective Activities, Environmental Restoration, and Waste Management Operations. Corrective Activities are those activities necessary to bring active or standby facilities into compliance with local, state, and federal environmental regulations. Environmental restoration activities include the assessment and cleanup of surplus facilities and inactive waste sites. Waste management operations includes the treatment, storage, and disposal of wastes which are generated as a result of ongoing operations. This Site Specific Plan (SSP) has been prepared by the Savannah River Site (SRS) in order to show how environmental restoration and waste management activities that were identified during the preparation of the FYP will be implemented, tracked, and reported. The SSP describes DOE Savannah River (DOE-SR) and operating contractor, Westinghouse Savannah River Company (WSRC), organizations that are responsible, for undertaking the activities identified in this plan. The SSP has been prepared in accordance with guidance received from DOE-HQ. DOE-SR is accountable to DOE-HQ for the implementation of this plan. 8 refs., 46 figs., 23 tabs

  19. ADANS database specification

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-01-16

    The purpose of the Air Mobility Command (AMC) Deployment Analysis System (ADANS) Database Specification (DS) is to describe the database organization and storage allocation and to provide the detailed data model of the physical design and information necessary for the construction of the parts of the database (e.g., tables, indexes, rules, defaults). The DS includes entity relationship diagrams, table and field definitions, reports on other database objects, and a description of the ADANS data dictionary. ADANS is the automated system used by Headquarters AMC and the Tanker Airlift Control Center (TACC) for airlift planning and scheduling of peacetime and contingency operations as well as for deliberate planning. ADANS also supports planning and scheduling of Air Refueling Events by the TACC and the unit-level tanker schedulers. ADANS receives input in the form of movement requirements and air refueling requests. It provides a suite of tools for planners to manipulate these requirements/requests against mobility assets and to develop, analyze, and distribute schedules. Analysis tools are provided for assessing the products of the scheduling subsystems, and editing capabilities support the refinement of schedules. A reporting capability provides formatted screen, print, and/or file outputs of various standard reports. An interface subsystem handles message traffic to and from external systems. The database is an integral part of the functionality summarized above.

  20. Adequate procedures for specific exams

    International Nuclear Information System (INIS)

    Staevie, G.L.G.; Gattringer, D.K.; Dal Mas, C.R.; Tessman, M.

    1996-01-01

    Some ideal procedures for specific radiographic exams are briefly presented. The aim is to improve the quality standard, establishing a specific method for each exam in order to decrease films waste and reduce the patient dose exposure

  1. Teaching English for Specific Purposes

    Directory of Open Access Journals (Sweden)

    Nijolė Netikšienė

    2011-04-01

    Full Text Available Teaching English for Specific Purposes and General English is analysed in the article. The scientific approach of a scientist M. Rosenberg is presented. The experience of teaching English for Specific Purposesat VGTU is alsopresented. The ideas and teaching methods from the classes of general English can be transferred to the classes of English for Specific Purposes.

  2. Flip-flop of phospholipids in proteoliposomes reconstituted from detergent extract of chloroplast membranes: kinetics and phospholipid specificity.

    Directory of Open Access Journals (Sweden)

    Archita Rajasekharan

    Full Text Available Eukaryotic cells are compartmentalized into distinct sub-cellular organelles by lipid bilayers, which are known to be involved in numerous cellular processes. The wide repertoire of lipids, synthesized in the biogenic membranes like the endoplasmic reticulum and bacterial cytoplasmic membranes are initially localized in the cytosolic leaflet and some of these lipids have to be translocated to the exoplasmic leaflet for membrane biogenesis and uniform growth. It is known that phospholipid (PL translocation in biogenic membranes is mediated by specific membrane proteins which occur in a rapid, bi-directional fashion without metabolic energy requirement and with no specificity to PL head group. A recent study reported the existence of biogenic membrane flippases in plants and that the mechanism of plant membrane biogenesis was similar to that found in animals. In this study, we demonstrate for the first time ATP independent and ATP dependent flippase activity in chloroplast membranes of plants. For this, we generated proteoliposomes from Triton X-100 extract of intact chloroplast, envelope membrane and thylakoid isolated from spinach leaves and assayed for flippase activity using fluorescent labeled phospholipids. Half-life time of flipping was found to be 6 ± 1 min. We also show that: (a intact chloroplast and envelope membrane reconstituted proteoliposomes can flip fluorescent labeled analogs of phosphatidylcholine in ATP independent manner, (b envelope membrane and thylakoid reconstituted proteoliposomes can flip phosphatidylglycerol in ATP dependent manner, (c Biogenic membrane ATP independent PC flipping activity is protein mediated and (d the kinetics of PC translocation gets affected differently upon treatment with protease and protein modifying reagents.

  3. Technical specification use and application

    International Nuclear Information System (INIS)

    Williamson, D.; Hoffman, D.R.

    1991-01-01

    Since early 1988 intensive efforts have been under way to produce a new and improved Standard Technical Specification. The program involves a coordinated effort between utility personnel representing each of the four nuclear steam supply system (NSSS) product lines, the NSSS vendors, and the US Nuclear Regulatory Commission (NRC). This intensive work period is actually the culmination of a decade of rhetoric about shortcomings of the existing technical specifications. Work on the improved technical specifications provided a unique forum for intense philosophical discussions between the users and enforcers of technical specifications, the outcome of which could have an impact on all licensees. Some of the more intriguing difficulties in the use and application of existing technical specifications, as well as discussions of the resolutions being applied in the improved technical specifications and the dilemmas remaining to be resolved are discussed in the paper

  4. [Multilingualism and specific language impairment].

    Science.gov (United States)

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja

    2013-01-01

    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  5. Trojan technical specification verification project

    International Nuclear Information System (INIS)

    Bates, L.; Rickenback, M.

    1991-01-01

    The Trojan Technical Specification Verification (TTSV) project at the Trojan plant of Portland General Electric Company was motivated by the recognition that many numbers in the Trojan technical specifications (TTS) potentially lacked the consideration of instrument- and/or process-related errors. The plant setpoints were known to consider such errors, but many of the values associated with the limiting conditions for operation (LCO) did not. In addition, the existing plant instrument error analyses were based on industry values that do not reflect the Trojan plant-specific experience. The purpose of this project is to ensure that the Trojan plant setpoint and LCO values include plant-specific instrument error

  6. Hanford Site environmental management specification

    International Nuclear Information System (INIS)

    Grygiel, M.L.

    1998-01-01

    The US Department of Energy, Richland Operations Office (RL) uses this Hanford Site Environmental Management Specification (Specification) to document top-level mission requirements and planning assumptions for the prime contractors involved in Hanford Site cleanup and infrastructure activities under the responsibility of the US Department of Energy, Office of Environmental Management. This Specification describes at a top level the activities, facilities, and infrastructure necessary to accomplish the cleanup of the Hanford Site and assigns this scope to Site contractors and their respective projects. This Specification also references the key National Environmental Policy Act of 1969 (NEPA), Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), and safety documentation necessary to accurately describe the cleanup at a summary level. The information contained in this document reflects RL's application of values, priorities, and critical success factors expressed by those involved with and affected by the Hanford Site project. The prime contractors and their projects develop complete baselines and work plans to implement this Specification. These lower-level documents and the data that support them, together with this Specification, represent the full set of requirements applicable to the contractors and their projects. Figure 1-1 shows the relationship of this Specification to the other basic Site documents. Similarly, the documents, orders, and laws referenced in this specification represent only the most salient sources of requirements. Current and contractual reference data contain a complete set of source documents

  7. Hanford Site environmental management specification

    Energy Technology Data Exchange (ETDEWEB)

    Grygiel, M.L.

    1998-06-10

    The US Department of Energy, Richland Operations Office (RL) uses this Hanford Site Environmental Management Specification (Specification) to document top-level mission requirements and planning assumptions for the prime contractors involved in Hanford Site cleanup and infrastructure activities under the responsibility of the US Department of Energy, Office of Environmental Management. This Specification describes at a top level the activities, facilities, and infrastructure necessary to accomplish the cleanup of the Hanford Site and assigns this scope to Site contractors and their respective projects. This Specification also references the key National Environmental Policy Act of 1969 (NEPA), Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), and safety documentation necessary to accurately describe the cleanup at a summary level. The information contained in this document reflects RL`s application of values, priorities, and critical success factors expressed by those involved with and affected by the Hanford Site project. The prime contractors and their projects develop complete baselines and work plans to implement this Specification. These lower-level documents and the data that support them, together with this Specification, represent the full set of requirements applicable to the contractors and their projects. Figure 1-1 shows the relationship of this Specification to the other basic Site documents. Similarly, the documents, orders, and laws referenced in this specification represent only the most salient sources of requirements. Current and contractual reference data contain a complete set of source documents.

  8. Measuring wood specific gravity, correctly

    Science.gov (United States)

    G. Bruce Williamson; Michael C. Wiemann

    2010-01-01

    The specific gravity (SG) of wood is a measure of the amount of structural material a tree species allocates to support and strength. In recent years, wood specific gravity, traditionally a forester’s variable, has become the domain of ecologists exploring the universality of plant functional traits and conservationists estimating global carbon stocks. While these...

  9. SPECIFIC RESISTANCE AND SPECIFIC INTENSITY OF BELT SANDING OF WOOD

    Directory of Open Access Journals (Sweden)

    Boleslaw Porankiewicz

    2010-06-01

    Full Text Available This paper examines and discusses the specific belt sanding resistance K (N·cm-2 and specific belt sanding intensity SI (g·cm-2·min-1, for wood of Pinus sylvestris L., Picea abies L., Quercus robra L., Acer pseudoplatanus L., Alnus glutinosa Gaertn., and Populus Nigra L., by different sanding pressure pS, different sanding grit NG number, and different wood grain angles Phi(v.

  10. Specificity of immunoassays. Pt. 2

    International Nuclear Information System (INIS)

    Pratt, J.J.; Woldring, M.G.; Boonman, R.; Kittikool, J.

    1979-01-01

    Practical aspects of the measurement of the specificity of immunoassay are reviewed. Antibody heterogeneity in an antiserum makes a pragmatic rather than a theoretical approach necessary. A new method for the measurement of immunoassay specificity is described. This method is based on the errors caused by the cross-reacting antigens and is directly relevant to the validity of results obtained by immunoassay methods. The effect of selectively blocking the least specific antibodies in antisera raised against steroid haptens is tested. The practical consequences of these considerations are tested using steroid radioimmunoassay and enzyme-immunoassay. (orig.) [de

  11. Patient-Specific Computational Modeling

    CERN Document Server

    Peña, Estefanía

    2012-01-01

    This book addresses patient-specific modeling. It integrates computational modeling, experimental procedures, imagine clinical segmentation and mesh generation with the finite element method (FEM) to solve problems in computational biomedicine and bioengineering. Specific areas of interest include cardiovascular problems, ocular and muscular systems and soft tissue modeling. Patient-specific modeling has been the subject of serious research over the last seven years and interest in the area is continually growing and this area is expected to further develop in the near future.

  12. Bid specifications and bid evaluations

    International Nuclear Information System (INIS)

    Zijl, N.A. van

    1977-01-01

    Bid specifications are in view of the size of these projects important and comprehensive documents. The basic content and set up of the specifications are discussed such as: 1) Bid invitation letter, 2) instruction to bidders, 3) draft contract (terms and conditions), 4) technical specifications, 5) side data and information. - The evaluations of bids for nuclear power stations is due to the complexity of such bids a difficult undertaking. Evaluation methods and approaches which can be applied for such bid evaluations are discussed as well as the preparations which are required for carrying out such evaluations. (orig.) [de

  13. Synergy of Technical Specification, functional specifications and scenarios in requirements specifications

    NARCIS (Netherlands)

    Miedema, J.; van der Voort, Mascha C.; Lutters, Diederick; van Houten, Frederikus J.A.M.; Krause, Frank-Lothar

    2007-01-01

    In the (mechanical) design process, the requirements specification is a formal registration of the conditions that are imposed on a new or altered product design, both preceding as well as during the corresponding product development cycle. For a long time, the use of technical specifications has

  14. Youth job market specific features

    Directory of Open Access Journals (Sweden)

    Evgeniya Yu. Zhuravleva

    2011-05-01

    Full Text Available The article considers youth job market peculiarities, its specific features and regulation means, determines theoretical and application tasks of qualitative and quantitative comparison of vocations, which are highly in demand at the job market.

  15. GPS Civil Monitoring Performance Specification

    Science.gov (United States)

    2009-02-10

    This Civil Monitoring Performance Specification (CMPS) is published and maintained at : the direction of the Program Manager for Civil Applications, Global Positioning Systems : Wing (GPSW). The purpose of this document is to provide a comprehensive ...

  16. The role of formal specifications

    International Nuclear Information System (INIS)

    McHugh, J.

    1994-01-01

    The role of formal requirements specification is discussed under the premise that the primary purpose of such specifications is to facilitate clear and unambiguous communications among the communities of interest for a given project. An example is presented in which the failure to reach such an understanding resulted in an accident at a chemical plant. Following the example, specification languages based on logical formalisms and notations are considered. These are rejected as failing to serve the communications needs of diverse communities. The notion of a specification as a surrogate for a program is also considered and rejected. The paper ends with a discussion of the type of formal notation that will serve the communications role and several encouraging developments are noted

  17. CCL22-specific T Cells

    DEFF Research Database (Denmark)

    Martinenaite, Evelina; Munir Ahmad, Shamaila; Hansen, Morten

    2016-01-01

    Tumor cells and tumor-infiltrating macrophages produce the chemokine CCL22, which attracts regulatory T cells (Tregs) into the tumor microenvironment, decreasing anticancer immunity. Here, we investigated the possibility of targeting CCL22-expressing cells by activating specific T cells. We...... analyzed the CCL22 protein signal sequence, identifying a human leukocyte antigen A2- (HLA-A2-) restricted peptide epitope, which we then used to stimulate peripheral blood mononuclear cells (PMBCs) to expand populations of CCL22-specific T cells in vitro. T cells recognizing an epitope derived from...... the signal-peptide of CCL22 will recognize CCL22-expressing cells even though CCL22 is secreted out of the cell. CCL22-specific T cells recognized and killed CCL22-expressing cancer cells. Furthermore, CCL22-specific T cells lysed acute monocytic leukemia cells in a CCL22 expression-dependent manner. Using...

  18. Eternity Variables to Simulate Specifications

    NARCIS (Netherlands)

    Hesselink, WH; Boiten, EA; Moller, B

    2002-01-01

    Simulation of specifications is introduced as a unification and generalization of refinement mappings, history variables, forward simulations, prophecy variables, and backward simulations. Eternity variables are introduced as a more powerful alternative for prophecy variables and backward

  19. Autonomic Fuselet Specification and Composition

    National Research Council Canada - National Science Library

    Mills, Peter H

    2006-01-01

    ... model for its business logic, and to perform workflow composition from a goal and specifications to executable model in a manner that enables feedback mechanisms that can assess and adapt the process...

  20. ATR Technical Specification Upgrade Program

    International Nuclear Information System (INIS)

    McCracken, R.T.; Durney, J.L.; Freund, G.A.

    1990-01-01

    The Advanced Test Reactor (ATR) is a 250 MW, uranium-aluminum fueled test reactor which began full power operation in 1969. The initial operation was controlled by an Operating Limits document based on the original Safety Analysis Report. Additional safety bases were later developed to support Technical Specifications which were approved and implemented in 1977. The Technical Specifications which were initially developed with content and format specified in ANSI/ANS--15.1, ''The Development of Technical Specifications for Research Reactors.'' The safety basis documentation and the Technical Specifications have been updated as required to maintain them current with the ATR facility configuration. All revisions have been made with a content, format and style consistent with the original. A major, two-phase program to upgrade the content, format and style is in progress. This paper describes the first phase of this program

  1. Specific immunotherapy ameliorates ulcerative colitis.

    Science.gov (United States)

    Cai, Min; Zeng, Lu; Li, Lin-Jing; Mo, Li-Hua; Xie, Rui-Di; Feng, Bai-Sui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Liu, Zhan-Ju; Yang, Ping-Chang

    2016-01-01

    Hypersensitivity reaction to certain allergens plays a role in the pathogenesis of inflammatory bowel disease (IBD). This study aims to observe the effect of specific immunotherapy in a group of IBD patients. Patients with both ulcerative colitis (UC) and food allergy were recruited into this study. Food allergy was diagnosed by skin prick test and serum specific IgE. The patients were treated with specific immunotherapy (SIT) and Clostridium butyricum (CB) capsules. After treating with SIT and CB, the clinical symptoms of UC were markedly suppressed as shown by reduced truncated Mayo scores and medication scores. The serum levels of specific IgE, interleukin (IL)-4 and tumor necrosis factor (TNF)-α were also suppressed. Treating with SIT alone or CB alone did not show appreciable improvement of the clinical symptoms of UC. UC with food allergy can be ameliorated by administration with SIT and butyrate-production probiotics.

  2. SPECIFIC EMISSIONS FROM BIOMASS COMBUSTION

    Directory of Open Access Journals (Sweden)

    Pavel Skopec

    2014-02-01

    Full Text Available This paper deals with determining the specific emissions from the combustion of two kinds of biomass fuels in a small-scale boiler. The tested fuels were pellets made of wood and pellets made of rape plant straw. In order to evaluate the specific emissions, several combustion experiments were carried out using a commercial 25 kW pellet-fired boiler. The specific emissions of CO, SO2 and NOx were evaluated in relation to a unit of burned fuel, a unit of calorific value and a unit of produced heat. The specific emissions were compared with some data acquired from the reference literature, with relatively different results. The differences depend mainly on the procedure used for determining the values, and references provide no information about this. Although some of our experimental results may fit with one of the reference sources, they do not fit with the other. The reliability of the references is therefore disputable.

  3. Grade 6 Science Curriculum Specifications.

    Science.gov (United States)

    Alberta Dept. of Education, Edmonton. Curriculum Branch.

    This material describes curriculum specifications for grade 6 science in Alberta. Emphases recommended are: (1) process skills (50%); (2) psychomotor skills (10%); (3) attitudes (10%); and (4) subject matter (30%). Priorities within each category are identified. (YP)

  4. Patient-specific surgical simulation.

    Science.gov (United States)

    Soler, Luc; Marescaux, Jacques

    2008-02-01

    Technological innovations of the twentieth century have provided medicine and surgery with new tools for education and therapy definition. Thus, by combining Medical Imaging and Virtual Reality, patient-specific applications providing preoperative surgical simulation have become possible.

  5. Base compaction specification feasibility analysis.

    Science.gov (United States)

    2012-12-01

    The objective of this research is to establish the technical engineering and cost : analysis concepts that will enable WisDOT management to objectively evaluate the : feasibility of switching construction specification philosophies for aggregate base...

  6. [Tissue-specific nucleoprotein complexes].

    Science.gov (United States)

    Riadnova, I Iu; Shataeva, L K; Khavinson, V Kh

    2000-01-01

    A method of isolation of native nucleorprotein complexes from cattle cerebral cortex, thymus, and liver was developed. Compositions of these complexes were studied by means of gel-chromatography and ion-exchange chromatography. These preparations were shown to consist of several fractions of proteins and their complexes differ by molecular mass and electro-chemical properties. Native nucleoprotein complexes revealed high tissue specific activity, which was not species-specific.

  7. XML specifications DanRIS

    DEFF Research Database (Denmark)

    2009-01-01

    XML specifications for DanRIS (Danish Registration- og InformationsSystem), where the the aim is: Improved exchange of data Improved data processing Ensuring future access to all gathered data from the year 1999 until now......XML specifications for DanRIS (Danish Registration- og InformationsSystem), where the the aim is: Improved exchange of data Improved data processing Ensuring future access to all gathered data from the year 1999 until now...

  8. Niche-specific cognitive strategies

    DEFF Research Database (Denmark)

    Hulgard, K.; Ratcliffe, J. M.

    2014-01-01

    Related species with different diets are predicted to rely on different cognitive strategies: those best suited for locating available and appropriate foods. Here we tested two predictions of the niche-specific cognitive strategies hypothesis in bats, which suggests that predatory species should...... the niche-specific cognitive strategies hypothesis and suggest that for gleaning and clutter-resistant aerial hawking bats, learning to associate shape with food interferes with subsequent spatial memory learning....

  9. NIF optical specifications - the importance of the RMS gradient specification

    International Nuclear Information System (INIS)

    Auerbach, J. M.; Cotton, C. T.; English, R. E.; Henesian, M. A.; Hunt, J. T.; Kelly, J. H.; Lawson, J. K.; Sacks, J. B.; Shoup, M. J.; Trenholme, W. H.

    1998-01-01

    The performance of the National Ignition Facility (NIF), especially in terms of laser focusability, will be determined by several key factors. One of these key factors is the optical specification for the thousands of large aperture optics that will comprise the 192 beamlines. We have previously reported on the importance of the specification of the power spectral density (PSD) on NIF performance. Recently, we have been studying the importance of long spatial wavelength (>33 mm) phase errors on focusability. We have concluded that the preferred metric for determining the impact of these long spatial wavelength phase errors is the rms phase gradient. In this paper, we outline the overall approach to NIF optical specifications, detail the impact of the rms phase gradient on NIF focusability, discuss its trade-off with the PSD in determining the spot size and review measurements of optics similar to those to be manufactured for NIF

  10. CASL, the Common Algebraic Specification Language

    DEFF Research Database (Denmark)

    Mossakowski, Till; Haxthausen, Anne Elisabeth; Sannella, Donald

    2008-01-01

    CASL is an expressive specification language that has been designed to supersede many existing algebraic specification languages and provide a standard. CASL consists of several layers, including basic (unstructured) specifications, structured specifications and architectural specifications...

  11. Standard Technical Specifications, Westinghouse plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Westinghouse Plants and documents the positions of the Nuclear Regulatory Commission based on the Westinghouse Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council (NUMARC). The improved STS were developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume 1 contains the Specifications for all chapters and sections of the improved STS. Volume 2 contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the improved STS. This document, Volume 3, contains the Bases for Sections 3.4--3.9 of the improved STS

  12. Standard Technical Specifications, Westinghouse Plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Westinghouse Plants and documents the positions of the Nuclear Regulatory Commission based on the Westinghouse Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council (NUMARC). The improved STS were developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume 1 contains the Specifications for all chapters and sections of the improved STS. Volume 2 contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the unproved STS. Volume 3 contains the Bases for Sections 3.4--3.9 of the improved STS which contain information on safety limits, reactivity control systems, power distribution limits, and instrumentation

  13. Industry specific financial distress modeling

    Directory of Open Access Journals (Sweden)

    Naz Sayari

    2017-01-01

    Full Text Available This study investigates uncertainty levels of various industries and tries to determine financial ratios having the greatest information content in determining the set of industry characteristics. It then uses these ratios to develop industry specific financial distress models. First, we employ factor analysis to determine the set of ratios that are most informative in specified industries. Second, we use a method based on the concept of entropy to measure the level of uncertainty in industries and also to single out the ratios that best reflect the uncertainty levels in specific industries. Finally, we conduct a logistic regression analysis and derive industry specific financial distress models which can be used to judge the predictive ability of selected financial ratios for each industry. The results show that financial ratios do indeed echo industry characteristics and that information content of specific ratios varies among different industries. Our findings show diverging impact of industry characteristics on companies; and thus the necessity of constructing industry specific financial distress models.

  14. Technical specification for vacuum systems

    International Nuclear Information System (INIS)

    Khaw, J.

    1987-01-01

    The vacuum systems at the Stanford Linear Accelerator Center (SLAC) are primarily of all-metal construction and operate at pressures from 10 -5 to 10 -11 Torr. The primary gas loads during operation result from thermal desorption and beam-induced desorption from the vacuum chamber walls. These desorption rates can be extremely high in the case of hydrocarbons and other contaminants. These specifications place a major emphasis on eliminating contamination sources. The specifications and procedures have been written to insure the cleanliness and vacuum integrity of all SLAC vacuum systems, and to assist personnel involved with SLAC vacuum systems in choosing and designing components that are compatible with existing systems and meet the quality and reliability of SLAC vacuum standards. The specification includes requirements on design, procurement, fabrication, chemical cleaning, clean room practices, welding and brazing, helium leak testing, residual gas analyzer testing, bakeout, venting, and pumpdown. Also appended are specifications regarding acceptable vendors, isopropyl alcohol, bakeable valve cleaning procedure, mechanical engineering safety inspection, notes on synchrotron radiation, and specifications of numerous individual components

  15. Standard Technical Specifications, Westinghouse plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Westinghouse Plants and documents the positions of the Nuclear Regulatory Commission based on the Westinghouse Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council (NUMARC). The improved STS were developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. This document, Volume 1, contains the Specifications for all chapters and sections of the improved STS. Volume 2 contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the improved STS. Volume 3 contains the Bases for Sections 3.4--3.9 of the improved STS

  16. Age‑specific Serum Prostate Specific Antigen Ranges Among ...

    African Journals Online (AJOL)

    ethnic differences.[16] Although similar studies have been presented for a number of different groups of men and few studies have looked at the pattern of serum PSA among Nigerians[17‑20] but no such studies on normal serum PSA ranges and the age‑specific pattern have been carried out among healthy Nigerian men.

  17. ROS signalling - specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian M; Sweetlove, Lee J

    2010-01-01

    Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression...

  18. Methylation-Specific PCR Unraveled

    Directory of Open Access Journals (Sweden)

    Sarah Derks

    2004-01-01

    Full Text Available Methylation‐specific PCR (MSP is a simple, quick and cost‐effective method to analyze the DNA methylation status of virtually any group of CpG sites within a CpG island. The technique comprises two parts: (1 sodium bisulfite conversion of unmethylated cytosine's to uracil under conditions whereby methylated cytosines remains unchanged and (2 detection of the bisulfite induced sequence differences by PCR using specific primer sets for both unmethylated and methylated DNA. This review discusses the critical parameters of MSP and presents an overview of the available MSP variants and the (clinical applications.

  19. Fluorescent Rhodamines and Fluorogenic Carbopyronines for Super‐Resolution STED Microscopy in Living Cells

    Science.gov (United States)

    Mitronova, Gyuzel Yu.; Sidenstein, Sven C.; Klocke, Jessica L.; Kamin, Dirk; Meineke, Dirk N. H.; D'Este, Elisa; Kraemer, Philip‐Tobias; Danzl, Johann G.

    2016-01-01

    Abstract A range of bright and photostable rhodamines and carbopyronines with absorption maxima in the range of λ=500–630 nm were prepared, and enabled the specific labeling of cytoskeletal filaments using HaloTag technology followed by staining with 1 μm solutions of the dye–ligand conjugates. The synthesis, photophysical parameters, fluorogenic behavior, and structure–property relationships of the new dyes are discussed. Light microscopy with stimulated emission depletion (STED) provided one‐ and two‐color images of living cells with an optical resolution of 40–60 nm. PMID:26844929

  20. An Intramolecular Chaperone Inserted in Bacteriophage P22 Coat Protein Mediates Its Chaperonin-independent Folding*

    Science.gov (United States)

    Suhanovsky, Margaret M.; Teschke, Carolyn M.

    2013-01-01

    The bacteriophage P22 coat protein has the common HK97-like fold but with a genetically inserted domain (I-domain). The role of the I-domain, positioned at the outermost surface of the capsid, is unknown. We hypothesize that the I-domain may act as an intramolecular chaperone because the coat protein folds independently, and many folding mutants are localized to the I-domain. The function of the I-domain was investigated by generating the coat protein core without its I-domain and the isolated I-domain. The core coat protein shows a pronounced folding defect. The isolated I-domain folds autonomously and has a high thermodynamic stability and fast folding kinetics in the presence of a peptidyl prolyl isomerase. Thus, the I-domain provides thermodynamic stability to the full-length coat protein so that it can fold reasonably efficiently while still allowing the HK97-like core to retain the flexibility required for conformational switching during procapsid assembly and maturation. PMID:24126914

  1. Coat protein-mediated resistance against an Indian isolate of the ...

    Indian Academy of Sciences (India)

    Coat protein (CP)-mediated resistance against an Indian isolate of the Cucumber mosaic virus (CMV) subgroup IB was demonstrated in transgenic lines of Nicotiana benthamiana through Agrobacterium tumefaciens-mediated transformation. Out of the fourteen independently transformed lines developed, two lines were ...

  2. Modulation of Wound Healing and Scar Formation by MG53 Protein-mediated Cell Membrane Repair*

    Science.gov (United States)

    Li, Haichang; Duann, Pu; Lin, Pei-Hui; Zhao, Li; Fan, Zhaobo; Tan, Tao; Zhou, Xinyu; Sun, Mingzhai; Fu, Minghuan; Orange, Matthew; Sermersheim, Matthew; Ma, Hanley; He, Duofen; Steinberg, Steven M.; Higgins, Robert; Zhu, Hua; John, Elizabeth; Zeng, Chunyu; Guan, Jianjun; Ma, Jianjie

    2015-01-01

    Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53−/− mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing. PMID:26306047

  3. Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair.

    Science.gov (United States)

    Li, Haichang; Duann, Pu; Lin, Pei-Hui; Zhao, Li; Fan, Zhaobo; Tan, Tao; Zhou, Xinyu; Sun, Mingzhai; Fu, Minghuan; Orange, Matthew; Sermersheim, Matthew; Ma, Hanley; He, Duofen; Steinberg, Steven M; Higgins, Robert; Zhu, Hua; John, Elizabeth; Zeng, Chunyu; Guan, Jianjun; Ma, Jianjie

    2015-10-02

    Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53(-/-) mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Negative Regulation of STAT3 Protein-mediated Cellular Respiration by SIRT1 Protein

    DEFF Research Database (Denmark)

    Bernier, Michel; Paul, Rajib K; Martin-Montalvo, Alejandro

    2011-01-01

    those of wild-type controls. Comparison of profiles of phospho-antibody array data indicated that the deletion of SirT1 was accompanied by constitutive activation of the pro-inflammatory NF-¿B pathway, which is key for STAT3 induction and increased cellular respiration in Sirt1-KO cells. Thus, SIRT1...... cells exhibited higher mitochondrial respiration as compared with wild-type MEFs. Two independent approaches, including ectopic expression of SIRT1 and siRNA-mediated knockdown of STAT3, led to reduction in intracellular ATP levels and increased lactate production in Sirt1-KO cells that were approaching...

  5. Rho GTPase activity modulates paramyxovirus fusion protein-mediated cell-cell fusion

    International Nuclear Information System (INIS)

    Schowalter, Rachel M.; Wurth, Mark A.; Aguilar, Hector C.; Lee, Benhur; Moncman, Carole L.; McCann, Richard O.; Dutch, Rebecca Ellis

    2006-01-01

    The paramyxovirus fusion protein (F) promotes fusion of the viral envelope with the plasma membrane of target cells as well as cell-cell fusion. The plasma membrane is closely associated with the actin cytoskeleton, but the role of actin dynamics in paramyxovirus F-mediated membrane fusion is unclear. We examined cell-cell fusion promoted by two different paramyxovirus F proteins in three cell types in the presence of constitutively active Rho family GTPases, major cellular coordinators of actin dynamics. Reporter gene and syncytia assays demonstrated that expression of either Rac1 V12 or Cdc42 V12 could increase cell-cell fusion promoted by the Hendra or SV5 glycoproteins, though the effect was dependent on the cell type expressing the viral glycoproteins. In contrast, RhoA L63 decreased cell-cell fusion promoted by Hendra glycoproteins but had little affect on SV5 F-mediated fusion. Also, data suggested that GTPase activation in the viral glycoprotein-containing cell was primarily responsible for changes in fusion. Additionally, we found that activated Cdc42 promoted nuclear rearrangement in syncytia

  6. Arrestin-related proteins mediate pH signaling in fungi

    OpenAIRE

    Herranz, Silvia; Rodríguez, José M.; Bussink, Henk-Jan; Sánchez-Ferrero, Juan C.; Arst, Herbert N.; Peñalva, Miguel A.; Vincent, Olivier

    2005-01-01

    Metazoan arrestins bind to seven-transmembrane (7TM) receptors to regulate function. Aspergillus nidulans PalF, a protein involved in the fungal ambient pH signaling pathway, contains arrestin N-terminal and C-terminal domains and binds strongly to two different regions within the C-terminal cytoplasmic tail of the 7TM, putative pH sensor PalH. Upon exposure to alkaline ambient pH, PalF is phosphorylated and, like mammalian β-arrestins, ubiquitinated in a signal-dependent and 7TM protein-depe...

  7. The cytoplasmic tails of infectious bronchitis virus E and M proteins mediate their interaction

    International Nuclear Information System (INIS)

    Corse, Emily; Machamer, Carolyn E.

    2003-01-01

    Virus-like particle (VLP) formation by the coronavirus E and M proteins suggests that interactions between these proteins play a critical role in coronavirus assembly. We studied interactions between the infectious bronchitis virus (IBV) E and M proteins using in vivo crosslinking and VLP assembly assays. We show that IBV E and M can be crosslinked to each other in IBV-infected and transfected cells, indicating that they interact. The cytoplasmic tails of both proteins are important for this interaction. We also examined the ability of the mutant and chimeric E and M proteins to form VLPs. IBV M proteins that are missing portions of their cytoplasmic tails or transmembrane regions were not able to support VLP formation, regardless of their ability to be crosslinked to IBV E. Interactions between the E and M proteins and the membrane bilayer are likely to play an important role in VLP formation and virus budding

  8. G-protein mediated signaling pathways in myogenic responsiveness of mouse mesenteric artery

    DEFF Research Database (Denmark)

    Jensen, Lars Jørn; Joseph, Philomeena Daphne; Haanes, Kristian Agmund

    2015-01-01

    of PLA2 (AACOCF3, 5 µM), DAG lipase (RHC80267, 20 µM), PI3-kinase (wortmannin, 0.03 µM), CYP4A (HET0016, 10 µM), and TRPC channels (SKF96365, 10 µM) had no effects. Gq/11 and G12 mRNA and protein were expressed in MA. The Gα/q inhibitor YM-254890 (0.1 µM) and the AT1-R blocker valsartan (0.3 µ...

  9. Quantitative Proteomics Reveals Membrane Protein-Mediated Hypersaline Sensitivity and Adaptation in Halophilic Nocardiopsis xinjiangensis.

    Science.gov (United States)

    Zhang, Yao; Li, Yanchang; Zhang, Yongguang; Wang, Zhiqiang; Zhao, Mingzhi; Su, Na; Zhang, Tao; Chen, Lingsheng; Wei, Wei; Luo, Jing; Zhou, Yanxia; Xu, Yongru; Xu, Ping; Li, Wenjun; Tao, Yong

    2016-01-04

    The genus Nocardiopsis is one of the most dominant Actinobacteria that survives in hypersaline environments. However, the adaptation mechanisms for halophilism are still unclear. Here, we performed isobaric tags for relative and absolute quantification based quantitative proteomics to investigate the functions of the membrane proteome after salt stress. A total of 683 membrane proteins were identified and quantified, of which 126 membrane proteins displayed salt-induced changes in abundance. Intriguingly, bioinformatics analyses indicated that these differential proteins showed two expression patterns, which were further validated by phenotypic changes and functional differences. The majority of ABC transporters, secondary active transporters, cell motility proteins, and signal transduction kinases were up-regulated with increasing salt concentration, whereas cell differentiation, small molecular transporter (ions and amino acids), and secondary metabolism proteins were significantly up-regulated at optimum salinity, but down-regulated or unchanged at higher salinity. The small molecule transporters and cell differentiation-related proteins acted as sensing proteins that played a more important biological role at optimum salinity. However, the ABC transporters for compatible solutes, Na(+)-dependent transporters, and cell motility proteins acted as adaptive proteins that actively counteracted higher salinity stress. Overall, regulation of membrane proteins may provide a major protection strategy against hyperosmotic stress.

  10. The Legionella pneumophila Collagen-Like Protein Mediates Sedimentation, Autoaggregation, and Pathogen-Phagocyte Interactions

    Science.gov (United States)

    Abdel-Nour, Mena; Duncan, Carla; Prashar, Akriti; Rao, Chitong; Ginevra, Christophe; Jarraud, Sophie; Low, Donald E.; Ensminger, Alexander W.; Terebiznik, Mauricio R.

    2014-01-01

    Although only partially understood, multicellular behavior is relatively common in bacterial pathogens. Bacterial aggregates can resist various host defenses and colonize their environment more efficiently than planktonic cells. For the waterborne pathogen Legionella pneumophila, little is known about the roles of autoaggregation or the parameters which allow cell-cell interactions to occur. Here, we determined the endogenous and exogenous factors sufficient to allow autoaggregation to take place in L. pneumophila. We show that isolates from Legionella species which do not produce the Legionella collagen-like protein (Lcl) are deficient in autoaggregation. Targeted deletion of the Lcl-encoding gene (lpg2644) and the addition of Lcl ligands impair the autoaggregation of L. pneumophila. In addition, Lcl-induced autoaggregation requires divalent cations. Escherichia coli producing surface-exposed Lcl is able to autoaggregate and shows increased biofilm production. We also demonstrate that L. pneumophila infection of Acanthamoeba castellanii and Hartmanella vermiformis is potentiated under conditions which promote Lcl dependent autoaggregation. Overall, this study shows that L. pneumophila is capable of autoaggregating in a process that is mediated by Lcl in a divalent-cation-dependent manner. It also reveals that Lcl potentiates the ability of L. pneumophila to come in contact, attach, and infect amoebae. PMID:24334670

  11. Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression.

    Science.gov (United States)

    Lomniczi, Alejandro; Wright, Hollis; Castellano, Juan Manuel; Matagne, Valerie; Toro, Carlos A; Ramaswamy, Suresh; Plant, Tony M; Ojeda, Sergio R

    2015-12-16

    In primates, puberty is unleashed by increased GnRH release from the hypothalamus following an interval of juvenile quiescence. GWAS implicates Zinc finger (ZNF) genes in timing human puberty. Here we show that hypothalamic expression of several ZNFs decreased in agonadal male monkeys in association with the pubertal reactivation of gonadotropin secretion. Expression of two of these ZNFs, GATAD1 and ZNF573, also decreases in peripubertal female monkeys. However, only GATAD1 abundance increases when gonadotropin secretion is suppressed during late infancy. Targeted delivery of GATAD1 or ZNF573 to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation. GATAD1 represses transcription of two key puberty-related genes, KISS1 and TAC3, directly, and reduces the activating histone mark H3K4me2 at each promoter via recruitment of histone demethylase KDM1A. We conclude that GATAD1 epitomizes a subset of ZNFs involved in epigenetic repression of primate puberty.

  12. Arabidopsis COBRA-LIKE 10, a GPI-anchored protein, mediates directional growth of pollen tubes

    NARCIS (Netherlands)

    Li, S.; Ge, F.R.; Xu, M.; Zhao, X.Y.; Huang, G.Q.; Zhou, L.Z.; Wang, J.G.; Kombrink, A.; McCormick, S.; Zhang, X.S.; Zhang, Y.

    2013-01-01

    Successful reproduction of flowering plants requires constant communication between female tissues and growing pollen tubes. Female cells secrete molecules and peptides as nutrients or guidance cues for fast and directional tube growth, which is executed by dynamic changes of intracellular

  13. Different effects of guanine nucleotides (GDP and GTP) on protein-mediated mitochondrial proton leak.

    Science.gov (United States)

    Woyda-Ploszczyca, Andrzej M; Jarmuszkiewicz, Wieslawa

    2014-01-01

    In this study, we compared the influence of GDP and GTP on isolated mitochondria respiring under conditions favoring oxidative phosphorylation (OXPHOS) and under conditions excluding this process, i.e., in the presence of carboxyatractyloside, an adenine nucleotide translocase inhibitor, and/or oligomycin, an FOF1-ATP synthase inhibitor. Using mitochondria isolated from rat kidney and human endothelial cells, we found that the action of GDP and GTP can differ diametrically depending on the conditions. Namely, under conditions favoring OXPHOS, both in the absence and presence of linoleic acid, an activator of uncoupling proteins (UCPs), the addition of 1 mM GDP resulted in the state 4 (non-phosphorylating respiration)-state 3 (phosphorylating respiration) transition, which is characteristic of ADP oxidative phosphorylation. In contrast, the addition of 1 mM GTP resulted in a decrease in the respiratory rate and an increase in the membrane potential, which is characteristic of UCP inhibition. The stimulatory effect of GDP, but not GTP, was also observed in inside-out submitochondrial particles prepared from rat kidney mitochondria. However, the effects of GDP and GTP were more similar in the presence of OXPHOS inhibitors. The importance of these observations in connection with the action of UCPs, adenine nucleotide translocase (or other carboxyatractyloside-sensitive carriers), carboxyatractyloside- and purine nucleotide-insensitive carriers, as well as nucleoside-diphosphate kinase (NDPK) are considered. Because the measurements favoring oxidative phosphorylation better reflect in vivo conditions, our study strongly supports the idea that GDP cannot be considered a significant physiological inhibitor of UCP. Moreover, it appears that, under native conditions, GTP functions as a more efficient UCP inhibitor than GDP and ATP.

  14. Mycobacterial laminin-binding histone-like protein mediates collagen-dependent cytoadherence

    Directory of Open Access Journals (Sweden)

    André Alves Dias

    2012-12-01

    Full Text Available When grown in the presence of exogenous collagen I, Mycobacterium bovis BCG was shown to form clumps. Scanning electron microscopy examination of these clumps revealed the presence of collagen fibres cross-linking the bacilli. Since collagen is a major constituent of the eukaryotic extracellular matrices, we assayed BCG cytoadherence in the presence of exogenous collagen I. Collagen increased the interaction of the bacilli with A549 type II pneumocytes or U937 macrophages, suggesting that BCG is able to recruit collagen to facilitate its attachment to host cells. Using an affinity chromatography approach, we have isolated a BCG collagen-binding protein corresponding to the previously described mycobacterial laminin-binding histone-like protein (LBP/Hlp, a highly conserved protein associated with the mycobacterial cell wall. Moreover, Mycobacterium leprae LBP/Hlp, a well-characterized adhesin, was also able to bind collagen I. Finally, using recombinant fragments of M. leprae LBP/Hlp, we mapped the collagen-binding activity within the C-terminal domain of the adhesin. Since this protein was already shown to be involved in the recognition of laminin and heparan sulphate-containing proteoglycans, the present observations reinforce the adhesive activities of LBP/Hlp, which can be therefore considered as a multifaceted mycobacterial adhesin, playing an important role in both leprosy and tuberculosis pathogenesis.

  15. An intracellular threonine of amyloid-β precursor protein mediates synaptic plasticity deficits and memory loss.

    Directory of Open Access Journals (Sweden)

    Franco Lombino

    Full Text Available Mutations in Amyloid-ß Precursor Protein (APP and BRI2/ITM2b genes cause Familial Alzheimer and Danish Dementias (FAD/FDD, respectively. APP processing by BACE1, which is inhibited by BRI2, yields sAPPß and ß-CTF. ß-CTF is cleaved by gamma-secretase to produce Aß. A knock-in mouse model of FDD, called FDDKI, shows deficits in memory and synaptic plasticity, which can be attributed to sAPPß/ß-CTF but not Aß. We have investigated further the pathogenic function of ß-CTF focusing on Thr(668 of ß-CTF because phosphorylation of Thr(668 is increased in AD cases. We created a knock-in mouse bearing a Thr(668Ala mutation (APP(TA mice that prevents phosphorylation at this site. This mutation prevents the development of memory and synaptic plasticity deficits in FDDKI mice. These data are consistent with a role for the carboxyl-terminal APP domain in the pathogenesis of dementia and suggest that averting the noxious role of Thr(668 is a viable therapeutic strategy for human dementias.

  16. Nuclear pore complex protein mediated nuclear localization of dicer protein in human cells.

    Directory of Open Access Journals (Sweden)

    Yoshinari Ando

    Full Text Available Human DICER1 protein cleaves double-stranded RNA into small sizes, a crucial step in production of single-stranded RNAs which are mediating factors of cytoplasmic RNA interference. Here, we clearly demonstrate that human DICER1 protein localizes not only to the cytoplasm but also to the nucleoplasm. We also find that human DICER1 protein associates with the NUP153 protein, one component of the nuclear pore complex. This association is detected predominantly in the cytoplasm but is also clearly distinguishable at the nuclear periphery. Additional characterization of the NUP153-DICER1 association suggests NUP153 plays a crucial role in the nuclear localization of the DICER1 protein.

  17. MicroProtein-mediated recruitment of CONSTANS into a TOPLESS trimeric complex represses flowering in Arabidopsis

    DEFF Research Database (Denmark)

    Graeff, Moritz; Straub, Daniel; Eguen, Tenai E.

    2016-01-01

    MicroProteins are short, single domain proteins that act by sequestering larger, multi-domain proteins into non-functional complexes. MicroProteins have been identified in plants and animals, where they are mostly involved in the regulation of developmental processes. Here we show that two...

  18. Coat protein-mediated resistance against an Indian isolate of the ...

    Indian Academy of Sciences (India)

    Madhu urs

    Molecular Virology Lab, National Botanical Research Institute, Lucknow 226 001, India. *Corresponding .... days for the development of symptoms and compared with the control ... low or no seed setting was observed, probably because of.

  19. Enterococcus faecalis zinc-responsive proteins mediate bacterial defence against zinc overload, lysozyme and oxidative stress

    NARCIS (Netherlands)

    C. Abrantes, Marta; Kok, Jan; de Fatima Silva Lopes, Maria

    2014-01-01

    Two Enterococcus faecalis genes encoding the P-type ATPase EF1400 and the putative SapB protein EF0759 were previously shown to be strongly upregulated in the presence of high concentrations of zinc. In the present work, we showed that a Zn(2+)-responsive DNA-binding motif (zim) is present in the

  20. RNA- and protein-mediated control of Listeria monocytogenes virulence gene expression

    Science.gov (United States)

    Lebreton, Alice; Cossart, Pascale

    2017-01-01

    ABSTRACT The model opportunistic pathogen Listeria monocytogenes has been the object of extensive research, aiming at understanding its ability to colonize diverse environmental niches and animal hosts. Bacterial transcriptomes in various conditions reflect this efficient adaptability. We review here our current knowledge of the mechanisms allowing L. monocytogenes to respond to environmental changes and trigger pathogenicity, with a special focus on RNA-mediated control of gene expression. We highlight how these studies have brought novel concepts in prokaryotic gene regulation, such as the ‘excludon’ where the 5′-UTR of a messenger also acts as an antisense regulator of an operon transcribed in opposite orientation, or the notion that riboswitches can regulate non-coding RNAs to integrate complex metabolic stimuli into regulatory networks. Overall, the Listeria model exemplifies that fine RNA tuners act together with master regulatory proteins to orchestrate appropriate transcriptional programmes. PMID:27217337

  1. Olfactory proteins mediating chemical communication in the navel orangeworm moth, Amyelois transitella.

    Directory of Open Access Journals (Sweden)

    Walter S Leal

    2009-09-01

    Full Text Available The navel orangeworm, Amyelois transitella Walker (Lepidoptera: Pyralidae, is the most serious insect pest of almonds and pistachios in California for which environmentally friendly alternative methods of control--like pheromone-based approaches--are highly desirable. Some constituents of the sex pheromone are unstable and could be replaced with parapheromones, which may be designed on the basis of molecular interaction of pheromones and pheromone-detecting olfactory proteins.By analyzing extracts from olfactory and non-olfactory tissues, we identified putative olfactory proteins, obtained their N-terminal amino acid sequences by Edman degradation, and used degenerate primers to clone the corresponding cDNAs by SMART RACE. Additionally, we used degenerate primers based on conserved sequences of known proteins to fish out other candidate olfactory genes. We expressed the gene encoding a newly identified pheromone-binding protein, which was analyzed by circular dichroism, fluorescence, and nuclear magnetic resonance, and used in a binding assay to assess affinity to pheromone components.We have cloned nine cDNAs encoding olfactory proteins from the navel orangeworm, including two pheromone-binding proteins, two general odorant-binding proteins, one chemosensory protein, one glutathione S-transferase, one antennal binding protein X, one sensory neuron membrane protein, and one odorant receptor. Of these, AtraPBP1 is highly enriched in male antennae. Fluorescence, CD and NMR studies suggest a dramatic pH-dependent conformational change, with high affinity to pheromone constituents at neutral pH and no binding at low pH.

  2. Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery.

    Science.gov (United States)

    Yang, Qi; Parker, Christina L; McCallen, Justin D; Lai, Samuel K

    2015-12-28

    Tumors are frequently characterized by genomically and phenotypically distinct cancer cell subpopulations within the same tumor or between tumor lesions, a phenomenon termed tumor heterogeneity. These diverse cancer cell populations pose a major challenge to targeted delivery of diagnostic and/or therapeutic agents, as the conventional approach of conjugating individual ligands to nanoparticles is often unable to facilitate intracellular delivery to the full spectrum of cancer cells present in a given tumor lesion or patient. As a result, many cancers are only partially suppressed, leading to eventual tumor regrowth and/or the development of drug-resistant tumors. Pretargeting (multistep targeting) approaches involving the administration of 1) a cocktail of bispecific proteins that can collectively bind to the entirety of a mixed tumor population followed by 2) nanoparticles containing therapeutic and/or diagnostic agents that can bind to the bispecific proteins accumulated on the surface of target cells offer the potential to overcome many of the challenges associated with drug delivery to heterogeneous tumors. Despite its considerable success in improving the efficacy of radioimmunotherapy, the pretargeting strategy remains underexplored for a majority of nanoparticle therapeutic applications, especially for targeted delivery to heterogeneous tumors. In this review, we will present concepts in tumor heterogeneity, the shortcomings of conventional targeted systems, lessons learned from pretargeted radioimmunotherapy, and important considerations for harnessing the pretargeting strategy to improve nanoparticle delivery to heterogeneous tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: mediators of age-related macular degeneration.

    Science.gov (United States)

    Lu, Liang; Gu, Xiaorong; Hong, Li; Laird, James; Jaffe, Keeve; Choi, Jaewoo; Crabb, John; Salomon, Robert G

    2009-11-01

    Protein modifications in which the epsilon-amino group of lysyl residues is incorporated into a 2-(omega-carboxyethyl)pyrrole (CEP) are mediators of age-related macular degeneration (AMD). They promote both angiogenesis into the retina ('wet AMD') and geographic retinal atrophy ('dry AMD'). Blood levels of CEPs are biomarkers for clinical prognosis of the disease. To enable mechanistic studies of their role in promoting AMD, for example, through the activation of B- and T-cells, interaction with receptors, or binding with complement proteins, we developed an efficient synthesis of CEP derivatives, that is especially effective for proteins. The structures of tryptic peptides derived from CEP-modified proteins were also determined. A key finding is that 4,7-dioxoheptanoic acid 9-fluorenylmethyl ester reacts with primary amines to provide 9-fluorenylmethyl esters of CEP-modified proteins that can be deprotected in situ with 1,8-diazabicyclo[5.4.0]undec-7-ene without causing protein denaturation. The introduction of multiple CEP-modifications with a wide variety of CEP:protein ratios is readily achieved using this strategy.

  4. Portable File Format (PFF) specifications

    Energy Technology Data Exchange (ETDEWEB)

    Dolan, Daniel H. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-02-01

    Created at Sandia National Laboratories, the Portable File Format (PFF) allows binary data transfer across computer platforms. Although this capability is supported by many other formats, PFF files are still in use at Sandia, particularly in pulsed power research. This report provides detailed PFF specifications for accessing data without relying on legacy code.

  5. Human-Specific Endogenous Retroviruses

    Directory of Open Access Journals (Sweden)

    Anton Buzdin

    2007-01-01

    Full Text Available This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

  6. Manufacturer Usage Description Specification Implementation

    OpenAIRE

    Srinivasan, Kaushik

    2017-01-01

    Manufacturer Usage Description Specification (MUDS) is aframework under RFC development that aims to automate Internet access control rules for IoT devices . These access controls prevent malicious IoT devices from attacking other devices and also protect the IoT devices from being attacked by other devices.We are implementing this framework and trying to improve its security.

  7. Competitive Procurement and Asset Specificity

    NARCIS (Netherlands)

    Sorana, V.

    2003-01-01

    This paper studies the effects of asset specificity on the performance of procurement auctions with subcontracting and asset sales.The analysis highlights the role of several asset features like transfer costs, type of alternative uses and maintenance requirements.It is argued that, if bargaining

  8. Final Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one....

  9. LOTOS specification style for OSI

    NARCIS (Netherlands)

    Turner, K.J.; van Sinderen, Marten J.; Bolognesi, T.; van de Lagemaat, J.; Vissers, C.A.

    1995-01-01

    The architecture of OSI is used to derive guidelines for writing LOTOS specifications of distributed systems. In particular, the architectural concepts that underlie service and protocol designs are examined in detail. For each of these concepts a representation in LOTOS is given. Examples are

  10. LOTOS specification style for OSI

    NARCIS (Netherlands)

    Brinksma, Hendrik; Turner, K.J.; Bolognesi, T.; van Sinderen, Marten J.; Vissers, C.A.

    1992-01-01

    The architecture of OSI is used to derive guidelines for writing LOTOS specifications of distributed systems. In particular, the architectural concepts that underlie service and protocol designs are examined in detail. For each of these concepts a representation in LOTOS is given. Examples are

  11. THE SPECIFICITY OF INTRACOMMUNITY TRANSACTIONS

    Directory of Open Access Journals (Sweden)

    PALIU-POPA LUCIA

    2011-09-01

    Full Text Available Considered from the perspective of Romania's accession to the European Union, we can say that starting with 1 January 2007, foreign trade transactions were delimited in relation to the customs borders in intra-Community transactions and international transactions. In this context, the way of conducting these operations is influenced by both the economic and financial features specific to both categories of transactions, that relate to the economic character of the activity, the diversity and specificity of the foreign trade activity, transport of goods, the complexity and regulation of intra-Community and international commercial transactions, and by the specific features of each category of transaction. Starting from the consideration that the economic and financial characteristics of foreign trade activity, specific to intra-Community commercial transactions, have a significant influence in the organization and management of accounting of the entities involved in such transactions, determining in a greater or lesser extent, the way of capitalization of the financial and accounting information in the processes of analysis, decision and control, in this paper we proposed to address the features of intra-Community trade.

  12. Microbeams, microdosimetry and specific dose

    International Nuclear Information System (INIS)

    Randers-Pehrson, H.

    2002-01-01

    Dose and its usefulness as a single parameter to describe the amount of radiation absorbed are well established for most situations. The conditions where the concept of dose starts to break down are well known, mostly from the study of microdosimetry. For low doses of high LET radiation it is noted that the process of taking the limiting value of the energy absorbed within a test volume divided by the mass within that volume yields either zero or a relatively large value. The problem is further exacerbated with microbeam irradiations where the uniformity of the energy deposition is experimentally manipulated on the spatial scale of cells being irradiated. Booz introduced a quantity to deal with these problems: the unfortunately named 'mean specific energy in affected volumes'. This quantity multiplied by the probability that a test volume has received an energy deposit is equal to dose (in situations where dose can be defined). I propose that Booz's quantity be renamed 'specific dose', that is the mean energy deposited divided by the mass within a specified volume. If we believe for instance that the nucleus of a cell is the critical volume for biological effects, we can refer to the nuclear specific dose. A microbeam experiment wherein 10 per cent of the cell nuclei were targeted with 10 alpha particles would be described as delivering a nuclear specific dose of 1.6 Gy to 10 per cent of the population. (author)

  13. [Specificities in children wound healing].

    Science.gov (United States)

    Sanchez, J; Antonicelli, F; Tuton, D; Mazouz Dorval, S; François, C

    2016-10-01

    Children have specific characteristics of wound healing. The aim of this study was to describe the specific clinical characteristics of wounds healing in children and to present the current knowledge on the specific mechanisms with regard to infant age. The tissue insult or injury in fetus can heal without scar, mainly due to reduced granulation tissue associated to diminished or even no inflammatory phase, modified extracellular matrix such as the concentration of hyaluronic acid in amniotic liquid, expression and arrangement of collagen and tenascin. Thickness of children skin is a serious negative factor in case of trauma, whereas poor co-morbidities and efficient growth tissue mechanisms are beneficial to good evolution, even in cases of extensive damage and loss of tissue. The subsequent tissue mechanical forces, wound healing during childhood, spanning from the age of 2 until the end of puberty, is associated with more hypertrophic scars, both in duration and in intensity. Consequently, unnecessary surgery has to be avoided during this period when possible, and children with abnormal or pathologic wound healing should benefit from complementary treatments (hydration, massage, brace, silicone, hydrotherapy…), which represent efficient factors to minimize tissue scarring. After wound healing, the growth body rate can be responsible for specific complications, such as contractures, alopecia, and scar intussusceptions. Its evolutionary character implies the need of an attentive follow-up until adult age. Psychologic repercussions, as a consequence of pathologic scars, must be prevented and investigated by the surgeon. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Specific and non-specific match effects in negative priming.

    Science.gov (United States)

    Labossière, Danielle I; Leboe-McGowan, Jason P

    2018-01-01

    The negative priming effect occurs when withholding a response to a stimulus impairs generation of subsequent responding to a same or a related stimulus. Our goal was to use the negative priming procedure to obtain insights about the memory representations generated by ignoring vs. attending/responding to a prime stimulus. Across three experiments we observed that ignoring a prime stimulus tends to generate higher identity-independent, non-specific repetition effects, owing to an overlap in the coarse perceptual form of a prime distractor and a probe target. By contrast, attended repetition effects generate predominantly identity-specific sources of facilitation. We use these findings to advocate for using laboratory phenomena to illustrate general principles that can be of practical use to non-specialists. In the case of the negative priming procedure, we propose that the procedure provides a useful means for investigating attention/memory interactions, even if the specific cause (or causes) of negative priming effects remain unresolved. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. [Specific immunotherapy with depigmented allergoids].

    Science.gov (United States)

    Klimek, L; Thorn, C; Pfaar, O

    2010-01-01

    Specific immunotherapy is the only available causative treatment for IgE-mediated allergic conditions. The state of the art is treatment via the subcutaneous route with crude extracts in a water solution, with physically linked (semidepot) extracts or chemically modified semidepot extracts (allergoids). A relatively new purification method combines depigmentation followed by polymerization with glutaraldehyde. This modification results in increased tolerance with a reduction in both local and systemic adverse effects. As controlled clinical trials have shown, the effectiveness is comparable to that of specific immunotherapy with crude allergen extracts. Recent data suggest that the modified polymerized allergoids allow a safe rush titration in a few days or even in 1 day (ultra-rush titration).

  16. UNBIASED ESTIMATORS OF SPECIFIC CONNECTIVITY

    Directory of Open Access Journals (Sweden)

    Jean-Paul Jernot

    2011-05-01

    Full Text Available This paper deals with the estimation of the specific connectivity of a stationary random set in IRd. It turns out that the "natural" estimator is only asymptotically unbiased. The example of a boolean model of hypercubes illustrates the amplitude of the bias produced when the measurement field is relatively small with respect to the range of the random set. For that reason unbiased estimators are desired. Such an estimator can be found in the literature in the case where the measurement field is a right parallelotope. In this paper, this estimator is extended to apply to measurement fields of various shapes, and to possess a smaller variance. Finally an example from quantitative metallography (specific connectivity of a population of sintered bronze particles is given.

  17. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David

    2014-01-01

    We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...... chromosomes, we find a core set of 1269 encoded protein families for chromosome 1, and a core of 252 encoded protein families for chromosome 2. Many of these core proteins are also found in the draft genomes (although which chromosome they are located on is unknown.) Of the chromosome specific core protein...... families, 1169 and 153 are uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO) terms for each of the protein families were determined, and the different sets for each chromosome were compared. A total of 363 different "Molecular Function" GO categories were found for chromosome 1...

  18. Specific bibliography on Anastrepha fraterculus

    International Nuclear Information System (INIS)

    Salles, L.A.; Jaldo, H.

    1999-01-01

    Most publications on Anastrepha fraterculus are in the literature sources from South America, and papers were published in Spanish or Portuguese. Many literature sources mentioned in this list are not indexed in entomological abstracts and, consequently, are not easily available outside their home state or country. Due to this fact, the inclusion of a list of specific bibliography on A. fraterculus could be a help for researchers and students interested in fruit flies. In this list are included only references directly dealing with Anastrepha fraterculus. Obviously, many more references exist that consider this species, but general or non-specific work or data concerning A. fraterculus were not included in the present list. (author)

  19. Multilingualism and Specific Language Impairment

    OpenAIRE

    Engel de Abreu, Pascale

    2014-01-01

    Is a multilingual education beneficial for children? What are the optimal conditions under which a child can become perfectly multilingual? When should we be concerned about a multilingual child's language skills? What are the signs of Specific Language Impairment in a child who speaks more than one language? Developmental psychologist and Associate Professor in multilingual cognitive development at the University of Luxembourg Pascale Engel de Abreu will address these questions based on what...

  20. Nanobody Based Dual Specific CARs

    Directory of Open Access Journals (Sweden)

    Stijn De Munter

    2018-01-01

    Full Text Available Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR. High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.

  1. Nanobody Based Dual Specific CARs.

    Science.gov (United States)

    De Munter, Stijn; Ingels, Joline; Goetgeluk, Glenn; Bonte, Sarah; Pille, Melissa; Weening, Karin; Kerre, Tessa; Abken, Hinrich; Vandekerckhove, Bart

    2018-01-30

    Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.

  2. Mutational specificity of SOS mutagenesis

    International Nuclear Information System (INIS)

    Kato, Takeshi

    1986-01-01

    In an approach to the isolation of mutants of E. coli unable to produce mutations by ultraviolet light, the author has found new umuC-mutants. Their properties could be explained by ''SOS hypothesis of Radman and Witkin'', which has now been justified by many investigators. Analysis of the umuC region of E. coli chromosome cloned in pSK 100 has led to the conclusion that two genes, umuD and umuC, having the capacity of mutation induction express in the same mechanism as that of SOS genes, which is known to be inhibited by LexA protein bonding to ''SOS box'' found at promotor region. Suppressor analysis for mutational specificity has revealed: (i) umuDC-independent mutagens, such as EMS and (oh) 4 Cy, induce selected base substitution alone; and (ii) umuDC-dependent mutagens, such as X-rays and gamma-rays, induce various types of base substitution simultaneously, although they have mutational specificity. In the umuDC-dependent processes of basechange mutagenesis, the spectra of base substitution were a mixture of base substitution reflecting the specific base damages induced by individual mutagens and nonspecific base substitution. In conclusion, base substitution plays the most important role in umuDC-dependent mutagenesis, although mutagenesis of umuDC proteins remains uncertain. (Namekawa, K.)

  3. Conversion of NEK standard technical specifications into improved technical specifications

    International Nuclear Information System (INIS)

    Glaser, B.

    2003-01-01

    Neck is currently using a standard format of operation's Technical Specifications - STS (based on NUREG-0452), which are planned to be converted into Improved Technical Specifications - ITS (based on NUREG-1431). To facilitate the development of individual ITS, each reactor vendor owners group (OG) and the NRC staff developed improved standard TS (ISTS). For Westinghouse plants, the ISTS are published as NUREG-1431, and this document is going to be the basis for the new NEK ITS. It has been recognized that nuclear safety in all plants would benefit from improvement and standardization of ITS, so this was also addressed and recognized by the NRC. There are several plants around Europe and US, which have replaced the format into ITS which brings a lot of improvements and practical value in operations. The main objective of conversion is to completely rewrite, reformat, and streamline the existing STS. Emphasis is placed on human factors principles to improve clarity and understanding. The Bases section will be significantly expanded to clarify and better explain the purpose and foundation of each specification. There might be some proposed changes to the existing STS that deviated from the ITS in NUREG-1431 and constitute a relaxation of the existing STS. Each of these additional proposed changes will be described and evaluated in amendment application and justified on a case-by-case basis. Since the NEK is going to operate for more than 20 year without considering life extension, such conversion will be beneficial for operation personnel as well as regulation, surveillance and focus on operation's safety. At the present, only preliminary plan of STS conversion exists, showing the time frame of approximately 2 years of conversion process and numerous tasks that need to be performed. The plan is to begin with process in year 2004 and finish project in 2006, which means use of new ITS in main control room in year 2007. Beside the main process of conversion, there are

  4. JBK-75 microstructure specification recommendation

    International Nuclear Information System (INIS)

    Brewer, A.W.

    1977-01-01

    Since the ASTM-E-45 standard for microcleanliness is not applicable to superalloys like JBK-75 stainless steel (Modified A-286), Rocky Flats should adopt the Ladish microcleanliness standard (APML Cleanliness Classification of High Temperature Alloys Chart, 1971), as a guide for setting material acceptance specifications for JBK-75. Inclusion ratings of S-2, N-2, C-2, and M-2 should be acceptable. The microstructure should have a grain size of 5 or finer, but not smaller than 9, and microsegregation (banding) should be kept to a minimum

  5. Gender specific determinants of goitre

    International Nuclear Information System (INIS)

    Jamshid, F.; Kerstin, C.; Elena, G.; Wilhelm, O.; Karl, W.; Hwe, M.

    2004-01-01

    Despite the strong implications of differences between females and males in the risk of goitre, gender-specific issues have not been extensively addressed in investigations of goitre prevalence. The Objective of our analysis was to investigate the gender-specific determinants of goitre. Methods: A total of 853 healthy employees from 4 institutions in western part of Germany aged between 18 and 68 years were examined by ultrasound of the neck to determine the thyroid volume between April 2001 and April 2002. Information on sex, age, daily use of iodised salt, the history of goitre in the first degree relatives, type and amount of' smoking, oral contraceptives and number of pregnancies were assessed by standardised questionnaires. Gender-specific predictors of goitre prevalence were assessed by multivariate logistic regression. Results: The overall prevalence of goitre among study subjects was (204/853) 23.9%. Goitre was present in 80 out of 370 females (21.6%) vs. 124/483 (25.7%) in males.In general smoking (<0.0001), increasing age (p<0.0001) and lack of daily intake of iodised salt (p=0.004) associated with goitre prevalence, but not sex (0.4) and family history of goitre (p=0.2). In 370 females, parity (p=0.004) and lack of daily intake of iodised salt (p=0.01) were the major determinants for goitre, whereas, age (p=0.2), oral contraceptives (p=0.8), family history of goitre (p=0.3), and smoking (p=0.1) did not affect the goitre prevalence. In 483 males, smoking (p<0.0001) and age (p<0.001) affected the goitre prevalence, but not family history of goitre (p=0.4) and the iodine status failed just to reach the significant level (p=0.08) in this analysis. Conclusions: Gender specific determinants of goitre are parity and iodine status in females and smoking and increasing age in males. (authors)

  6. Specification for personal photographic dosemeters

    International Nuclear Information System (INIS)

    1981-01-01

    The 1981 British/International Standard Specification, prepared under the direction of the Nuclear Engineering Standards Committee and TC85 of the International Organization for Standardization, is described for personal photographic dosemeters. The Standard specifies classification, characteristics and test procedures to determine absorbed doses due to X or gamma radiations (energy less than 3 MeV) and absorbed doses due to beta radiation (max. energy 0.6 to 3 MeV), whether or not accompanied by X, gamma or bremsstrahlung photon radiation. The Standard is particularly applicable to dosemeters intended to be carried on the chest or wrist. (U.K.)

  7. Domain specific MT in use

    DEFF Research Database (Denmark)

    Offersgaard, Lene; Povlsen, Claus; Almsten, Lisbeth Kjeldgaard

    2008-01-01

    point scale evaluate the sentence from the point of view of the post-editor. The post-editor profile defined by the LSP is based on the experiences of introducing MT in the LSP workflow. The relation between the Translation Edit Rate (TER) scores and “Usability” scores is tested. We find TER a candidate......The paper focuses on domain specific use of MT with a special focus on SMT in the workflow of a Language Service Provider (LSP). We report on the feedback of post-editors using fluency/adequacy evaluation and the evaluation metric ’Usability’, understood in this context as where users on a three...

  8. Central Solenoid Insert Technical Specification

    Energy Technology Data Exchange (ETDEWEB)

    Martovetsky, Nicolai N [ORNL; Smirnov, Alexandre [ORNL

    2011-09-01

    The US ITER Project Office (USIPO) is responsible for the ITER central solenoid (CS) contribution to the ITER project. The Central Solenoid Insert (CSI) project will allow ITER validation the appropriate lengths of the conductors to be used in the full-scale CS coils under relevant conditions. The ITER Program plans to build and test a CSI to verify the performance of the CS conductor. The CSI is a one-layer solenoid with an inner diameter of 1.48 m and a height of 4.45 m between electric terminal ends. The coil weight with the terminals is approximately 820 kg without insulation. The major goal of the CSI is to measure the temperature margin of the CS under the ITER direct current (DC) operating conditions, including determining sensitivity to load cycles. Performance of the joints, ramp rate sensitivity, and stability against thermal or electromagnetic disturbances, electrical insulation, losses, and instrumentation are addressed separately and therefore are not major goals in this project. However, losses and joint performance will be tested during the CSI testing campaign. The USIPO will build the CSI that will be tested at the Central Solenoid Model Coil (CSMC) Test Facility at the Japan Atomic Energy Agency (JAEA), Naka, Japan. The industrial vendors (the Suppliers) will report to the USIPO (the Company). All approvals to proceed will be issued by the Company, which in some cases, as specified in this document, will also require the approval of the ITER Organization. Responsibilities and obligations will be covered by respective contracts between the USIPO, called Company interchangeably, and the industrial Prime Contractors, called Suppliers. Different stages of work may be performed by more than one Prime Contractor, as described in this specification. Technical requirements of the contract between the Company and the Prime Contractor will be covered by the Fabrication Specifications developed by the Prime Contractor based on this document and approved by

  9. The Specificity of Human Aesthetics

    DEFF Research Database (Denmark)

    Bouchet, Dominique

    2015-01-01

    Today, humankind is being reintroduced within nature. Humankind is no longer presented as supernatural to nature. There is no longer a clear divide between animal and human. What makes us human is neither culture, nor language nor labor, nor art, but the degree of complexity those products and ca...... creativity. Art is fundamentally about shaping visions and very closely related to this specific human ability to make projects. Especially in times of crisis, when the old sources of meaning hardly can make sense in a new context, imagination must be used in order to survive....

  10. Advances in bacterial specific imaging

    International Nuclear Information System (INIS)

    Wareham, David; Das, Satya; London Univ.

    2005-01-01

    Nuclear medicine is a powerful diagnostic technique able to detect inflammatory foci in human disease. A wide range of agents have been evaluated for their ability to distinguish lesions due to microbial infection from those due to sterile inflammation. Advances continue to be made on the use of radiolabelled antibiotics which as well as being highly specific in the diagnosis of infection may be useful in monitoring the treatment and course of disease. Here we provide an update on in-vitro and clinical studies with a number of established and novel radiopharmaceuticals. (author)

  11. Logic programming and metadata specifications

    Science.gov (United States)

    Lopez, Antonio M., Jr.; Saacks, Marguerite E.

    1992-01-01

    Artificial intelligence (AI) ideas and techniques are critical to the development of intelligent information systems that will be used to collect, manipulate, and retrieve the vast amounts of space data produced by 'Missions to Planet Earth.' Natural language processing, inference, and expert systems are at the core of this space application of AI. This paper presents logic programming as an AI tool that can support inference (the ability to draw conclusions from a set of complicated and interrelated facts). It reports on the use of logic programming in the study of metadata specifications for a small problem domain of airborne sensors, and the dataset characteristics and pointers that are needed for data access.

  12. Food Odours Direct Specific Appetite

    Directory of Open Access Journals (Sweden)

    Harriët F. A. Zoon

    2016-02-01

    Full Text Available Olfactory food cues were found to increase appetite for products similar in taste. We aimed to replicate this phenomenon for taste (sweet/savoury, determine whether it extends to energy density (high/low as well, and uncover whether this effect is modulated by hunger state. Twenty-nine healthy-weight females smelled four odours differing in the energy density and taste they signalled, one non-food odour, and one odourless solution (control, in random order, for three minutes each. Appetite for 15 food products was rated in the following two minutes. Mixed model analyses revealed that exposure to an odour signalling a specific taste (respectively sweet, savoury led to a greater appetite for congruent food products (sweet/savoury compared to incongruent food products (savoury p < 0.001; sweet p < 0.001 or neutral food products (p = 0.02; p = 0.003. A similar pattern was present for the energy-density category (respectively high-energy dense, low-energy dense signalled by the odours (low-energy products p < 0.001; high-energy products p = 0.008. Hunger state did not have a significant impact on sensory-specific appetite. These results suggest that exposure to food odours increases appetite for congruent products, in terms of both taste and energy density, irrespective of hunger state. We speculate that food odours steer towards intake of products with a congruent macronutrient composition.

  13. Hanford Site Environmental Management Specification

    International Nuclear Information System (INIS)

    DAILY, J.L.

    2001-01-01

    The US Department of Energy, Richland Operations Office (RL) has established a document hierarchy as part of its integrated management system. The Strategic Plan defines the vision, values, missions, strategic goals, high-level outcomes, and the basic strategies in achieving those outcomes. As shown in Figure 1-1, the Site Specification derives requirements from the Strategic Plan and documents the top-level mission technical requirements for the work involved in the RL Hanford Site cleanup and infrastructure activities under the responsibility of the U.S. Department of Energy, Office of Environmental Management (EM). It also provides the basis for all contract technical requirements. Since this is limited to the EM work, neither the Fast Flux Test Facility (FFTF) nor the Pacific Northwest National Laboratory (PNNL) non-EM science activities are included. Figure 1-1 also shows the relationship between this Site Specification and the other Site management and planning documents. Similarly, the documents, orders, and laws referenced in this document represent only the most salient sources of requirements. Current and contractual reference data contain a complete set of source documents

  14. [Specific immunotherapy. Hyposensitization with allergens].

    Science.gov (United States)

    Wedi, B; Kapp, A

    2004-04-01

    Successful allergen-specific immunotherapy (SIT) induces complex immunologic chan-ges resulting in reduced allergic inflammatory reactions. SIT has long-term effects in mild forms of inhalant allergies and is effective even when standard pharmacotherapy fails. Moreover, the risk to develop additional allergic sensitizations and the development of asthma is significantly reduced in children with allergic rhinitis. SIT is the treatment of choice in patients with systemic reactions to hymenoptera venoms. Although the exact effector mechanisms of SIT still have to be clarified, the most probable effect is a modulation of regulatory T cells associated with a switch of allergen-specific B-cells towards IgG4 production. The critical point to insure efficacy and safety is the selection of patients and allergens, task best performed by a specialist trained in allergology. Further details are available in the position papers of the German allergy societies - DGAI(Deutsche Gesellschaft fiir Allergologie und Klinische Immunologie) and ADA (Arzte-verband Deutscher Allergologen) - which can be found at www.dgaki.de.

  15. Is sexual victimization gender specific?

    DEFF Research Database (Denmark)

    Sundaram, Vanita; Laursen, Bjarne; Helweg-Larsen, Karin

    2008-01-01

    The present study investigates the prevalence of sexual victimization and correlations between sexual victimization and indicators of poor health in two representative samples of men and women in Denmark. Specifically, the authors explore the prevalence of self-reported victimization among...... adolescents (N = 5,829) and adults (N = 3,932) and analyze differences in self-reported health outcomes between male and female victims and corresponding controls. Gender differences are found in the reported prevalence of sexual victimization. Significantly more females than males reported forced sexual...... experiences in both samples. Associations between sexual victimization and poor health outcomes are found for both genders. Comparable patterns of association for men and women are found on a number of variables, particularly those pertaining to risk behavior....

  16. Compositional specification of commercial contracts

    DEFF Research Database (Denmark)

    Andersen, Jesper; Elsborg, Ebbe; Henglein, Fritz

    2006-01-01

    -definable analysis of their state before, during and after execution. We provide several realistic examples of commercial contracts and their analyses. A variety of (real) contracts can be expressed in such a fashion as to support their integration, management and analysis in an operational environment......We present a declarative language for compositional specification of contracts governing the exchange of resources. It extends Eber and Peyton Jones’s declarative language for specifying financial contracts (Jones et al. in The Fun of Programming. 2003) to the exchange of money, goods and services...... amongst multiple parties and complements McCarthy’s Resources, Events and Agents (REA) accounting model (McCarthy in Account Rev. LVII(3), 554–578, 1982) with a view- independent formal contract model that supports definition of user-defined contracts, automatic monitoring under execution and user...

  17. Specificity of discoveries in radiochemistry

    International Nuclear Information System (INIS)

    Krivomazov, A.N.

    1977-01-01

    The development of radiochemistry as a science is elucidated. On the basis of original papers and archives materials which have become available only recently, specific features of opening the law of radioactive displacements and isotopy of radioactive elements are presented in detail. A contribution of Hevesy, Russel, Fajans, and Soddy into the solution of this problem is considered; an important role of Rutherford in putting down the priority conflict is shown. Two stages of scientific generalization are singled out in the history of opening the law of radioactive displacements: the stage of the rules and the stage of the laws. On this basis the solutions of the priority problems have been reconsidered. It is shown that the history of radiochemistry is rich in discoveries which have undergone a relatively long evolution

  18. Genetic specificity of face recognition.

    Science.gov (United States)

    Shakeshaft, Nicholas G; Plomin, Robert

    2015-10-13

    Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities.

  19. Testing of badminton specific endurance

    DEFF Research Database (Denmark)

    Madsen, Christian Møller; Højlyng, Mads; Nybo, Lars

    2016-01-01

    In the present study, a novel intermittent badminton endurance test (B-ENDURANCE) was developed and tested in elite (n=17) and skilled (n=9) badminton players as well as in age-matched physically active men (non-badminton players; n=8). In addition, B-ENDURANCE test-retest reproducibility...... was evaluated in nine badminton players.B-ENDURANCE is an incremental test where each level consists of repeated sequences of badminton specific actions towards the four corners on the court. The subject starts in the center of the court in front of a computer screen and within each sequence he must...... decreases until the subjects cannot follow the dictated tempo.B-ENDURANCE performance for elite players was better (Pbadminton players. In addition, B-ENDURANCE performance correlated (r=0.8; P

  20. An RNA Domain Imparts Specificity and Selectivity to a Viral DNA Packaging Motor

    Science.gov (United States)

    Zhao, Wei; Jardine, Paul J.

    2015-01-01

    molecular motor that translocates the viral DNA into a preformed viral shell. A key event in DNA packaging is recognition of the viral DNA among other nucleic acids in the host cell. Commonly, a DNA-binding protein mediates the interaction of viral DNA with the motor/head shell. Here we show that for the bacteriophage ϕ29, this essential step of genome recognition is mediated by a viral genome-encoded RNA rather than a protein. A domain of the prohead RNA (pRNA) imparts specificity and stringency to the motor by ensuring the correct orientation of DNA packaging and restricting initiation to a single event. Since this assembly step is unique to the virus, DNA packaging is a novel target for the development of antiviral drugs. PMID:26423956

  1. An RNA Domain Imparts Specificity and Selectivity to a Viral DNA Packaging Motor.

    Science.gov (United States)

    Zhao, Wei; Jardine, Paul J; Grimes, Shelley

    2015-12-01

    that translocates the viral DNA into a preformed viral shell. A key event in DNA packaging is recognition of the viral DNA among other nucleic acids in the host cell. Commonly, a DNA-binding protein mediates the interaction of viral DNA with the motor/head shell. Here we show that for the bacteriophage ϕ29, this essential step of genome recognition is mediated by a viral genome-encoded RNA rather than a protein. A domain of the prohead RNA (pRNA) imparts specificity and stringency to the motor by ensuring the correct orientation of DNA packaging and restricting initiation to a single event. Since this assembly step is unique to the virus, DNA packaging is a novel target for the development of antiviral drugs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. The complex becomes more complex: protein-protein interactions of SnRK1 with DUF581 family proteins provide a framework for cell- and stimulus type-specific SnRK1 signaling in plants

    Directory of Open Access Journals (Sweden)

    Madlen eNietzsche

    2014-02-01

    Full Text Available In plants, SNF1-related kinase (SnRK1 responds to the availability of carbohydrates as well as to environmental stresses by down-regulating ATP consuming biosynthetic processes, while stimulating energy-generating catabolic reactions through gene expression and post-transcriptional regulation. The functional SnRK1 complex is a heterotrimer where the catalytic alpha subunit associates with a regulatory beta subunit and an activating gamma subunit. Several different metabolites as well as the hormone abscisic acid (ABA have been shown to modulate SnRK1 activity in a cell- and stimulus-type specific manner. It has been proposed that tissue- or stimulus-specific expression of adapter proteins mediating SnRK1 regulation can at least partly explain the differences observed in SnRK1 signaling. By using yeast two-hybrid and in planta bi-molecular fluorescence complementation assays we were able to demonstrate that proteins containing the domain of unknown function (DUF 581 could interact with both isoforms of the SnRK1 alpha subunit (AKIN10/11 of Arabidopsis. A structure/function analysis suggests that the DUF581 is a generic SnRK1 interaction module and co-expression with DUF581 proteins in plant cells leads to reallocation of the kinase to specific regions within the nucleus. Yeast two-hybrid analyses suggest that SnRK1 and DUF581 proteins can share common interaction partners inside the nucleus. The analysis of available microarray data implies that expression of the 19 members of the DUF581 encoding gene family in Arabidopsis is differentially regulated by hormones and environmental cues, indicating specialized functions of individual family members. We hypothesize that DUF581 proteins could act as mediators conferring tissue- and stimulus-type specific differences in SnRK1 regulation.

  3. FY97 ICCS prototype specification

    International Nuclear Information System (INIS)

    Woodruff, J.

    1997-01-01

    The ICCS software team will implement and test two iterations of their software product during FY97. This document specifies the products to be delivered in that first prototype and projects the direction that the second prototype will take. Detailed specification of the later iteration will be written when the results of the first iteration are complete. The selection of frameworks to be implemented early is made on a basis of risk analysis from the point of view of future development in the ICCS project. The prototype will address risks in integration of object- oriented components, in refining our development process, and in emulation testing for FEP devices. This document is a specification that identifies products and processes to undertake for resolving these risks. The goals of this activity are to exercise our development process at a modest scale and to probe our architecture plan for fundamental limits and failure modes. The product of the iterations will be the framework software which will be useful in future ICCS code. Thus the FY97 products are intended for internal usage by the ICCS team and for demonstration to the FEP software developers of the strategy for integrating supervisory software with FEP computers. This will be the first of several expected iterations of the software development process and the performance measurements that ICCS will demonstrate, intended to support confidence in our ability to meet project RAM goals. The design of the application software is being carried out in a separate WBS 1.5.2 activity. The design activity has as its FY97 product a series of Software Design Documents that will specify the functionality of the controls software of ICCS. During the testing of this year''s prototypes, the application functionality needed for test will be provided by sample maintenance controls. These are early precursors of controls that can be used for low level device control. Since the devices under test will be represented by

  4. Eternity Variables to Prove Simulation of Specifications

    NARCIS (Netherlands)

    Hesselink, Wim H.

    2005-01-01

    Simulations of specifications are introduced as a unification and generalization of refinement mappings, history variables, forward simulations, prophecy variables, and backward simulations. A specification implements another specification if and only if there is a simulation from the first one to

  5. Are specific emotions narrated differently?

    Science.gov (United States)

    Habermas, Tilmann; Meier, Michaela; Mukhtar, Barbara

    2009-12-01

    Two studies test the assertion that anger, sadness, fear, pride, and happiness are typically narrated in different ways. Everyday events eliciting these 5 emotions were narrated by young women (Study 1) and 5- and 8-year-old girls (Study 2). Negative narratives were expected to engender more effort to process the event, be longer, more grammatically complex, more often have a complication section, and use more specific emotion labels than global evaluations. Narratives of Hogan's (2003) juncture emotions anger and fear were expected to focus more on action and to contain more core narrative sections of orientation, complication, and resolution than narratives of the outcome emotions sadness and happiness. Hypotheses were confirmed for adults except for syntactic complexity, whereas children showed only some of these differences. Hogan's theory that juncture emotions are restricted to the complication section was not confirmed. Finally, in adults, indirect speech was more frequent in anger narratives and internal monologue in fear narratives. It is concluded that different emotions should be studied in how they are narrated, and that narratives should be analyzed according to qualitatively different emotions.

  6. [Amusia and its topic specification].

    Science.gov (United States)

    Buklina, S B; Skvortsova, V B

    2007-01-01

    A historical development of views on amusia and its clinical phenomenology is reviewed. The authors present a case of atypical amusia in a patient aged 32 years with glioma of the right temporal lobe including the upper temporal gyrus. Amusia was combined with euphoria and disturbances of evaluation of speech intonation. It has been assumed that different mechanisms implicated with different regions of both brain hemispheres may underlie amusia. Sometimes these mechanisms appear to be universal, e.g. disorders of symbolic gnosis in posterior hemisphere lesions, being comorbid with amusia as disturbances in reading music and letter agnosia. In our case, the right temporal lobe lesion, especially with involvement of the upper temporal gyrus, caused specific music agnosia with disturbances of perception of some notes and duration of their phonation or a musical contour of the whole melody. Motor amusia is developed due to additional disturbances of motor and premotor brain functions, with significant contribution of the Broca's speech area. Music may be a model for investigation into processes of multimodal integration and hemisphere interaction.

  7. Advances in bacterial specific imaging

    Directory of Open Access Journals (Sweden)

    David Wareham

    2005-10-01

    Full Text Available Nuclear medicine is a powerful diagnostic technique able to detect inflammatory foci in human disease. A wide range of agents have been evaluated for their ability to distinguish lesions due to microbial infection from those due to sterile inflammation. Advances continue to be made on the use of radiolabelled antibiotics which as well as being highly specific in the diagnosis of infection may be useful in monitoring the treatment and course of disease. Here we provide an update on in-vitro and clinical studies with a number of established and novel radiopharmaceuticalsA medicina nuclear é uma técnica poderosa de diagnóstico capaz de detectar focos inflamatórios em doenças humanas. Uma ampla gama de agentes tem sido avaliada em sua capacidade de distinguir lesões, devidas a infecções microbianas daquelas causadas por inflamações estéreis. Avanços continuam sendo realizados no uso de antibióticos radiomarcados que, da mesma forma que têm sido usados no diagnóstico altamente específico de infecções, podem ser úteis na monitoração do tratamento e do curso da doença. Neste estudo, nós apresentamos uma atualização sobre estudos in vitro e clínicos, com alguns novos radiofármacos e outros já consagrados.

  8. Specificities of sustainable tourism planning

    Directory of Open Access Journals (Sweden)

    Jegdić Vaso

    2013-01-01

    Full Text Available In the past two decades, companies have been mentioning achievement of sustainability in their activities as a target of companies, governments and non-profit organizations, although measuring the degree to which an organization conducts its activities in a sustainable manner, can be very difficult. Sustainable tourism development requires a process of planning and management that will unite the interests of various stakeholders in a sustainable and strategic way. It requires an understanding of the meaning of sustainable development and guiding values for promoting sustainable tourism. The paper points to the importance of cross-sector partnerships and the roles of different stakeholders in the planning of sustainable tourism projects. Special importance is given to the community of which a willingness to understand the impacts of tourism industry is expected, as well as various procedures of engagement in participatory planning, consensus building and conflict resolution among all stakeholders. The aim of this research is to find an optimal model of planning of sustainable tourism projects that would take into consideration the interests of all stakeholders and reflect the specificities imposed by the acceptance of the concept of sustainable development by all participants in the project.

  9. 31 CFR 596.309 - Specific license.

    Science.gov (United States)

    2010-07-01

    ... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM LIST GOVERNMENTS SANCTIONS REGULATIONS General Definitions § 596.309 Specific license. The term specific license means any license or...

  10. The Specificity Principle in Acculturation Science

    Science.gov (United States)

    Bornstein, Marc H.

    2016-01-01

    The Specificity Principle in Acculturation Science asserts that specific setting conditions of specific people at specific times moderate specific domains in acculturation by specific processes. Our understanding of acculturation depends critically on what is studied where, in whom, how, and when. This article defines, explains, and illustrates the Specificity Principle in Acculturation Science. Research hypotheses about acculturation can be more adequately tested, inconsistencies and discrepancies in the acculturation literature can be satisfactorily resolved, acculturation interventions can be tailored to be more successful, and acculturation policies can be brought to new levels of effectiveness if the specificity principle that governs acculturation science is more widely recognized. PMID:28073331

  11. Specific CT findings of eclampsia

    International Nuclear Information System (INIS)

    Takahashi, Hiroshi; Nakazawa, Shozo; Imaya, Hisatoshi

    1985-01-01

    Two cases of specific computed tomographic (CT) findings of eclampsia were reported. Case 1 was a 25-year-old primipara in the 10th month of pregnancy, and Case 2 was a 36-year-old primipara in the 9th month of pregnancy. Both were brought to our hospital because of attacks of preeclampsia and eclampsia. On admission, they were in a comatose state. Computed tomography (CT) on admission showed low- and high-density areas in the basal ganglia regions in Case 1 and low-density areas in the same regions in Case 2. In Case 1, cerebral angiograms obtained two days after the attack showed diffuse cerebral vasospasms in the anterior and middle cerebral arteries of both sides and the basilar artery. In Case 2, however, cerebral angiograms obtained three days after the attack showed no abnormal findings. The patients were saved by crisis-overcoming emergency treatment and care. The neurological condition gradually improved. Repeated CT three weeks after the onset showed only a slight low-density area and a small high-density area in the left basal ganglia region in Case 1, while the low-density areas in the bilateral basal ganglia regions disappeared in Case 2. Seven weeks after the attack, cerebral angiography was again performed, but the diffuse vasospasms had disappeared. The clinical courses were good, and the patients were discharged about eight weeks after the onset, by which time their consciousness had become clear and the neurological deficits had been well overcome. Cerebrovascular disorders caused by toxemia of pregnancy is rare; when they do occur, the main lesions of the brain are edema, focal ischemia, thrombosis, and hemorrhage. They may be related to cerebral vasospasm, and subsequent ischemic changes are observed at times with eclampsia. (author)

  12. Gender-Specific Health Challenges Facing Women

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Gender-Specific Health Challenges Facing Women Global Research Global ... adverse reactions to the drugs. Women also suffer gender-specific consequences of HIV, including recurrent vaginal yeast ...

  13. Model Commissioning Plan and Guide Specifications

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The objectives of Model Commissioning Plan and Guide Specifications are to ensure that the design team applies commissioning concepts to the design and prepares commissioning specifications and a commission plan for inclusion in the bid construction documents.

  14. Technical specification improvement through safety margin considerations

    International Nuclear Information System (INIS)

    Howard, R.C.; Jansen, R.L.

    1986-01-01

    Westinghouse has developed an approach for utilizing safety analysis margin considerations to improve plant operability through technical specification revision. This approach relies on the identification and use of parameter interrelations and sensitivities to identify acceptable operating envelopes. This paper summarizes technical specification activities to date and presents the use of safety margin considerations as another viable method to obtain technical specification improvement

  15. Genre-Specific Semantic Video Indexing

    NARCIS (Netherlands)

    Wu, J.; Worring, M.

    2010-01-01

    In many applications, we find large video collections from different genres where the user is often only interested in one or two specific video genres. So, when users are querying the system with a specific semantic concept, they are likely aiming a genre specific instantiation of this concept.

  16. 42 CFR 37.203 - Autopsy specifications.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Autopsy specifications. 37.203 Section 37.203... EXAMINATIONS SPECIFICATIONS FOR MEDICAL EXAMINATIONS OF UNDERGROUND COAL MINERS Autopsies § 37.203 Autopsy specifications. (a) Every autopsy for which a claim for payment is submitted pursuant to this part: (1) Shall be...

  17. Specific cooling capacity of liquid nitrogen

    Science.gov (United States)

    Kilgore, R. A.; Adcock, J. B.

    1977-01-01

    The assumed cooling process and the method used to calculate the specific cooling capacity of liquid nitrogen are described, and the simple equation fitted to the calculated specific cooling capacity data, together with the graphical form calculated values of the specific cooling capacity of nitrogen for stagnation temperatures from saturation to 350 K and stagnation pressures from 1 to 10 atmospheres, are given.

  18. Isothermal Gravitational Segregation: Algorithms and Specifications

    DEFF Research Database (Denmark)

    Halldórsson, Snorri; Stenby, Erling Halfdan

    2000-01-01

    New algorithms for calculating the isothermal equilibrium state of reservoir fluids under the influence of gravity are presented. Two types of specifications are considered: the specification of pressure and composition at a reference depth; and the specification of the total overall content of t...

  19. Information Concerning Preparation of Specifications for Carpeting.

    Science.gov (United States)

    Gilliland, John W.

    This paper argues for detailed, written carpeting specifications to assure that schools obtain quality products at competitive prices. The advantages of and specifications for school carpeting are given. A sample written specification contains items on: scope, general features, materials, acoustic characteristics, identification and acoustic…

  20. 14 CFR 91.1015 - Management specifications.

    Science.gov (United States)

    2010-01-01

    ... complete and separate set of its management specifications at its principal base of operations, or at a... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Management specifications. 91.1015 Section... Operations Program Management § 91.1015 Management specifications. (a) Each person conducting operations...

  1. Towards a theory of product design specifications

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Andreasen, Mogens Myrup

    2004-01-01

    , which express the customers¿ need and perception of value. In this paper we will scrutinize this assumption. We outline the roles and tasks of the product design specification in order to identify the requirements on a theory of product design specifications and we identify existing theory elements....... In the design methodology literature we find guidelines and methods to compile a product design specification. The contributions are based on the common underlying assumption that it is meaningful and the only feasible approach to interpret the result of a need analysis into a set of technical specifications...... to build such a theory of product design specifications upon....

  2. Standard technical specifications combustion engineering plants

    International Nuclear Information System (INIS)

    1992-09-01

    This report documents the results of the combined effort of the NRC and the industry to produce improved Standard Technical Specifications (STS) for Combustion Engineering Plants. The improved STS wee developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. This document, Volume 1, contains the Specifications for all chapters and sections of the improved STS. Volume 2 contains the Bases for Sections 3.4--3.9 of the improved STS

  3. Technical specifications and performance of CANDU fuel

    International Nuclear Information System (INIS)

    Sejnoha, R.

    1997-01-01

    The relations between Technical Specifications and fuel performance are discussed in terms of design limits and margins. The excellent performance record of CANDU reactor fuel demonstrates that the fuel design defined in the Technical Specifications (and with it other components of the procurement cycle, such as fuel manufacturing), satisfy the requirements. New requirements, changing conditions of fuel application and accumulating experience make periodic updates of the Technical Specifications necessary. Under the CANDU Owners Group (COG) Working Party 9, a Work Package has been conducted to support the review of the Specifications and the documentation of the rationales for their requirements. So far, the review has been completed for 4 Specifications: 1 for Zircaloy tubing, and 3 for uranium dioxide powder. It is planned to complete the review of all 11 currently used specifications by 1999. The paper summarizes the results achieved to mid 1997. (author)

  4. An Algebraic Specification of the Semantic Web

    OpenAIRE

    Ksystra, Katerina; Triantafyllou, Nikolaos; Stefaneas, Petros; Frangos, Panayiotis

    2011-01-01

    We present a formal specification of the Semantic Web, as an extension of the World Wide Web using the well known algebraic specification language CafeOBJ. Our approach allows the description of the key elements of the Semantic Web technologies, in order to give a better understanding of the system, without getting involved with their implementation details that might not yet be standardized. This specification is part of our work in progress concerning the modeling the Social Semantic Web.

  5. Map Specifications and Exchange of Geographical Information

    DEFF Research Database (Denmark)

    Frederiksen, Poul

    1999-01-01

    Specifications for Technical Maps 1993 – 99 are described giving an overview of the specification structure including the object description of the latest version: TK99.The technical map specifications are related to the standards for topographical maps - especially the TOP10DK standard. Common...... object definitions are essential for the standards. Technical as well as topographical map information is exchangeable through the Danish developed “Standard for Exchange of Digital Map Information”, known as the DSFL-format....

  6. Cervical cancer: intracavitary dose specification and prescription

    International Nuclear Information System (INIS)

    Potish, R.A.; Gerbi, B.J.

    1987-01-01

    Dose and volume specifications for reporting intracavitary therapy were analyzed according to criteria recommended by the International Commission on Radiation Units and Measurements (ICRU). Ninety Fletcher-Suit radium applications were studied to examine the validity of the assumptions of the ICRU and the merit of their routine reporting. It was demonstrated that the reporting recommendations were inconsistent with clinical prescription systems and added little to dose specification. The distinction between dose specification and dose prescription was stressed

  7. Product specifications for the end use

    International Nuclear Information System (INIS)

    Navaretta, G.

    1992-01-01

    This paper reports on the concept of total quality which provides a foundation upon which NGL specifications could be built. Total quality has been embraced by a large constituency within the Refining and Petrochemical business, so, the NGL industry can not afford to discount it. As a concept, total quality certainly includes a specific management approach, but the roots of the quality movement lie with traditional product quality values. Naturally, the subject of product quality leads directly to product specifications, thus proving the intimate relationship between the total quality concept and NGL specifications

  8. Steps in Modular Specifications for Concurrent Modules

    DEFF Research Database (Denmark)

    Da Rocha Pinto, Pedro; Dinsdale-Young, Thomas; Gardner, Philippa

    2015-01-01

    The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent module......, in particular highlighting four key concepts: auxiliary state, interference abstraction, resource ownership and atomicity. We show how these concepts combine to provide powerful approaches to specifying concurrent modules.......The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent modules...

  9. Technical specifications for the Bulk Shielding Reactor

    International Nuclear Information System (INIS)

    1982-04-01

    Technical specifications are presented concerning the safety limits and limiting safety system settings; limiting conditions for operation; surveillance requirements; design features; and administrative controls

  10. AOV Facility Tool/Facility Safety Specifications -

    Data.gov (United States)

    Department of Transportation — Develop and maintain authorizing documents that are standards that facilities must follow. These standards are references of FAA regulations and are specific to the...

  11. User Interface Technology for Formal Specification Development

    Science.gov (United States)

    Lowry, Michael; Philpot, Andrew; Pressburger, Thomas; Underwood, Ian; Lum, Henry, Jr. (Technical Monitor)

    1994-01-01

    Formal specification development and modification are an essential component of the knowledge-based software life cycle. User interface technology is needed to empower end-users to create their own formal specifications. This paper describes the advanced user interface for AMPHION1 a knowledge-based software engineering system that targets scientific subroutine libraries. AMPHION is a generic, domain-independent architecture that is specialized to an application domain through a declarative domain theory. Formal specification development and reuse is made accessible to end-users through an intuitive graphical interface that provides semantic guidance in creating diagrams denoting formal specifications in an application domain. The diagrams also serve to document the specifications. Automatic deductive program synthesis ensures that end-user specifications are correctly implemented. The tables that drive AMPHION's user interface are automatically compiled from a domain theory; portions of the interface can be customized by the end-user. The user interface facilitates formal specification development by hiding syntactic details, such as logical notation. It also turns some of the barriers for end-user specification development associated with strongly typed formal languages into active sources of guidance, without restricting advanced users. The interface is especially suited for specification modification. AMPHION has been applied to the domain of solar system kinematics through the development of a declarative domain theory. Testing over six months with planetary scientists indicates that AMPHION's interactive specification acquisition paradigm enables users to develop, modify, and reuse specifications at least an order of magnitude more rapidly than manual program development.

  12. Motorcycle Education Curriculum Specifications. Final Report.

    Science.gov (United States)

    McKnight, A. James; And Others

    This report contains specifications for a motorcycle safety education curriculum designed to reduce the incidence and severity of motorcycle accidents. The specifications prescribe objectives, prerequisites, methods, materials, equipment, facilities, and proficiency measures for six units of instruction: (1) basic riding skills, (2) street riding…

  13. Domain-specific languages in perspective

    NARCIS (Netherlands)

    J. Heering (Jan); M. Mernik (Marjan)

    2007-01-01

    textabstractDomain-specific languages (DSLs) are languages tailored to a specific application domain. They offer substantial gains in expressiveness and ease of use compared with general-purpose languages in their domain of application. Although the use of DSLs is by no means new, it is receiving

  14. The Logic of the RAISE Specification Language

    DEFF Research Database (Denmark)

    George, Chris; Haxthausen, Anne Elisabeth

    2003-01-01

    This paper describes the logic of the RAISE Specification Language, RSL. It explains the particular logic chosen for RAISE, and motivates this choice as suitable for a wide spectrum language to be used for designs as well as initial specifications, and supporting imperative and concurrent...

  15. Specific and social phobias in ICD-11

    NARCIS (Netherlands)

    Emmelkamp, P.M.G.

    2012-01-01

    The purpose of this article is to discuss the current status of research with respect to specific phobias and social phobia as defined in the ICD-10 and DSM-IV, and to provide op- tions for their classification in the ICD-11. Both ICD-10 and DSM-IV identify three main classes of phobias: specific

  16. Technical specifications: Health Physics Research Reactor

    International Nuclear Information System (INIS)

    1979-02-01

    The technical specifications define the key limitations that must be observed for safe operation of the Health Physics Research Reactor (HPRR) and an envelope of operation within which there is assurance that these limits will not be exceeded. The specifications were written to satisfy the requirements of the Department of Energy (DOE) Manual Chapter 0540, September 1, 1972

  17. Guidelines for writing user friendly technical specifications

    International Nuclear Information System (INIS)

    Webster, S.A.; Braun, J.C.; Pearce, R.T.

    1986-01-01

    This study investigates some of the ergonomic considerations of writer's guides for the preparation of instructions. It is a precedent for the preparation of such a writer's guide for technical specifications for nuclear power plants. This writer's guide will be part of a revision to the industry's standard ANSI/ANS 58.4, Criteria for Technical Specifications for Nuclear Power Stations

  18. Specific skills and social competence in schizophrenia

    NARCIS (Netherlands)

    Appelo, M.T.; van Nieuwenhuizen, C.J.; Emmelkamp, P.M.G.; Slooff, C.J.; Louwerens, J.W.

    1992-01-01

    Generalization of skills is a major problem in social skills training for schizophrenic patients. Assessment of skills is mostly not based on objective indices of specific skill deficits. The results of this study show that global competence of schizophrenics can be differentiated from specific

  19. The Logic of the RAISE Specification Language

    DEFF Research Database (Denmark)

    George, Chris; Haxthausen, Anne Elisabeth

    2008-01-01

    This chapter describes the logic of the RAISE Specification Language, RSL. It explains the particular logic chosen for RAISE, and motivates this choice as suitable for a wide spectrum language to be used for designs as well as initial specifications, and supporting imperative and concurrent...

  20. Specific heats of degenerate ideal gases

    OpenAIRE

    Caruso, Francisco; Oguri, Vitor; Silveira, Felipe

    2017-01-01

    From arguments based on Heisenberg's uncertainty principle and Pauli's exclusion principle, the molar specific heats of degenerate ideal gases at low temperatures are estimated, giving rise to values consistent with the Nerst-Planck Principle (third law of Thermodynamics). The Bose-Einstein condensation phenomenon based on the behavior of specific heat of massive and non-relativistic boson gases is also presented.

  1. Shape configuration and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, Ian; Paulson, Olaf B.

    2006-01-01

    a recent account of category-specificity and lends support to the notion that category-specific impairments can occur for both natural objects and artefacts following damage to pre-semantic stages in visual object recognition. The implications of the present findings are discussed in relation to theories...

  2. Fundamental Characteristics of Industrial Variant Specification Systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars

    2004-01-01

    fundamental concepts related to this task, which are relevant to understand for academia and practitioners working with the subject. This is done through a description of variant specification tasks and typical aspects of system solutions. To support the description of variant specification tasks and systems...

  3. SPECIFIC SKILLS AND SOCIAL COMPETENCE IN SCHIZOPHRENIA

    NARCIS (Netherlands)

    APPELO, MT; WOONINGS, FMJ; VANNIEUWENHUIZEN, CJ; EMMELKAMP, PMG; SLOOFF, CJ; LOUWERENS, JW

    Generalization of skills is a major problem in social skills training for schizophrenic patients. Assessment of skills is mostly not based on objective indices of specific skill deficits. The results of this study show that global competence of schizophrenics can be differentiated from specific

  4. Building finite automata from DI specifications

    NARCIS (Netherlands)

    Udding, J.T

    1998-01-01

    Numerous formalisms exist to specify delay-insensitive computations and their implementations. It is not always straightforward to compare specifications in the different formalisms. One way of comparing specifications is transforming them to automata in which nodes are annotated with progress

  5. The Specificity of Creativity: Figurative and Scientific

    Science.gov (United States)

    Bernal, Ana; Esparza, Javier; Ruiz, María-José; Ferrando, Mercedes; Sainz, Marta

    2017-01-01

    Introduction: This work tackles the question about the nature of creativity as a general vs. domain-specific ability. First we deal with the concept of creativity and then, the main approaches to the debate of generality vs. specificity are exposed. Method: A total of 133 students attending 3rd grade of secondary education in Murcia Region took…

  6. Efficient genre-specific semantic video indexing

    NARCIS (Netherlands)

    Wu, J.; Worring, M.

    2012-01-01

    Large video collections such as YouTube contain many different video genres, while in many applications the user might be interested in one or two specific video genres only. Thus, when users are querying the system with a specific semantic concept like AnchorPerson, and MovieStars, they are likely

  7. Autonomy Level Specification for Intelligent Autonomous Vehicles

    Science.gov (United States)

    2003-09-01

    Autonomy Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report Hui-Min Huang, Elena Messina, James Albus...Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

  8. 324 and 327 Facilities Environmental Effluent Specifications

    International Nuclear Information System (INIS)

    JOHNSON, D.L.

    1999-01-01

    These effluent specifications address requirements for the 324/321 Facilities, which are undergoing stabilization activities. Effluent specifications are imposed to protect personnel, the environment and the public, by ensuring adequate implementation and compliance with federal and state regulatory requirements and Hanford programs

  9. PCR specific for Actinobacillus pleuropneumoniae serotype 3

    DEFF Research Database (Denmark)

    Zhou, L.; Jones, S.C.P.; Angen, Øystein

    2008-01-01

    , but the method has liminations, for example, cross-reactions between serotypes 3, 6, and 8. This study describes the development of a serotype 3-specific PCR, based on the capsule locus, which can be used in a multiplex format with the organism's specific gene apxIV. The PCR test was evaluated on 266 strains...

  10. ITER ISS system alternative specification study

    International Nuclear Information System (INIS)

    Kveton, O.K.

    1990-08-01

    Recent comments suggested that the fuel systems, in particular the ISS, could be simplified if the ITER specifications were relaxed from the data specified for ITER. This interim report addresses the first part of the analysis, which considers the impact of design specifications on fuel systems design

  11. Plutonium Immobilization Can Loading Preliminary Specifications

    Energy Technology Data Exchange (ETDEWEB)

    Kriikku, E.

    1998-11-25

    This report discusses the Plutonium Immobilization can loading preliminary equipment specifications and includes a process block diagram, process description, equipment list, preliminary equipment specifications, plan and elevation sketches, and some commercial catalogs. This report identifies loading pucks into cans and backfilling cans with helium as the top priority can loading development areas.

  12. Technical specifications: Tower Shielding Reactor II

    International Nuclear Information System (INIS)

    1979-02-01

    The technical specifications define the key limitations that must be observed for safe operation of the Tower Shielding Reactor II (TSR-II) and an envelope of operation within which there is reasonable assurance that these limits cannot be exceeded. The specifications were written to satisfy the requirements of the Department of Energy (DOE) Manual Chapter 0540, September 1, 1972

  13. Development of technical specifications for research reactors

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    This standard identifies and establishes the content of technical specifications for research reactors. Areas addressed are: definitions, safety limits, limiting safety system settings, limiting conditions for operation, surveillance requirements, design features and administrative controls. Sufficient detail is incorporated so that applicable specifications can be derived or extracted

  14. 11 CFR 1.14 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... to refer apparent violations of the Act to the Attorney General or other law enforcement authorities... 11 Federal Elections 1 2010-01-01 2010-01-01 false Specific exemptions. 1.14 Section 1.14 Federal Elections FEDERAL ELECTION COMMISSION PRIVACY ACT § 1.14 Specific exemptions. (a) No individual, under the...

  15. Determining the specific electric resistance of rock

    Energy Technology Data Exchange (ETDEWEB)

    Persad' ko, V.Ia.

    1982-01-01

    Data are presented on perfecting the method of laboratory determination of the specific electric resistance of a rock formation. The average error in determining the specific electric resistance of the core at various locations is no more than two percent with low resistance values (2-5 ohms).

  16. Specific phobia predicts psychopathology in young women

    NARCIS (Netherlands)

    Trumpf, J.; Margraf, J.; Vriends, N.; Meyer, A.H.; Becker, E.S.

    2010-01-01

    Although specific phobia is characterized by an early age at onset and by high rates of comorbidity, few studies have examined comorbid relationships prospectively. The present study investigated the association between specific phobia and the risk of a broad range of psychopathology among young

  17. Screening specifications for Gulf Coast salt domes

    International Nuclear Information System (INIS)

    Brunton, G.D.; Laughon, R.B.; McClain, W.C.

    1978-01-01

    A reconnaissance survey of the salt domes of Mississippi, Louisiana, and east Texas is being planned to identify study areas for potential sites for radioactive waste disposal. Preliminary screening specifications were derived for each of the geological evaluation criteria by application of the significant factors that will have an impact on the reconnaissance survey. The procedure for the derivation of each screening specification is discussed. The screening specifications are the official OWI values to be used for the first-cut acceptance for salt dome study areas along the Gulf Coast. The derivation of the screening specifications is illustrated by (1) a statement of the geological evaluation criterion, (2) a discussion of the pertinent factors affecting the criterion, and (3) the evaluation of the value of the specification

  18. Tissue Specific Promoters in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    A. R. Rama

    2015-01-01

    Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

  19. Specifications in early conceptual design work

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Andreasen, Mogens Myrup

    2007-01-01

    In early conceptual design the design team is working in an uncertain situation, where the understanding of a need is limited and not much is known about the solution space. In this situation the design team has to both analyse need and explore solution space. Thus, the team has to formulate design...... specifications, which express attractive product goals, and has to synthesise the product idea. The authors of this paper see a challenge to enhance and improve our understanding of the nature of design specifications as a means to support the synthesis of a product idea. In this empirical study we analyse...... the structure and content of design specifications during early ideation activities, where initial design specifications are formulated and a product idea is synthesised. We have analysed specification documents of 19 teams of novice designers. Our analysis indicates that a productive product design...

  20. Improvements to Technical Specifications surveillance requirements

    International Nuclear Information System (INIS)

    Lobel, R.; Tjader, T.R.

    1992-12-01

    In August 1983 an NRC task group was formed to investigate problems with surveillance testing required by Technical Specifications, and to recommend approaches to effect improvements. NUREG-1024 (''Technical Specifications-Enhancing Safety Impact'') resulted, and it contained recommendations to review the basis for test frequencies; to ensure that the tests promote safety and do not degrade equipment; and to review surveillance tests so that they do not unnecessarily burden personnel. The Technical Specifications Improvement Program (TSIP) was established in December 1984 to provide the framework for rewriting and improving the Technical Specifications. As an element of the TSIP, all Technical Specifications surveillance requirements were comprehensively examined as recommended in NUREG-1024. The results of that effort are presented in this report. The study found that while some testing at power is essential to verify equipment and system operability, safety can be improved, equipment degradation decreased, and unnecessary personnel burden relaxed by reducing the amount of testing at power

  1. Standard Technical Specifications, Babcock and Wilcox plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Babcock and Wilcox (B ampersand W) Plants and documents the positions of the Nuclear Regulatory Commission based on the B ampersand W Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council (NUMARC). The unproved STS were developed based on the, criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop proved plant-specific technical specifications. This report contains three volumes. This document, Volume 1 contains the Specifications for all chapters and sections of the improved STS

  2. Rf system specifications for a linear accelerator

    International Nuclear Information System (INIS)

    Young, A.; Eaton, L.E.

    1992-01-01

    A linear accelerator contains many systems; however, the most complex and costly is the RF system. The goal of an RF system is usually simply stated as maintaining the phase and amplitude of the RF signal within a given tolerance to accelerate the charged particle beam. An RF system that drives a linear accelerator needs a complete system specification, which should contain specifications for all the subsystems (i.e., high-power RF, low-level RF, RF generation/distribution, and automation control). This paper defines a format for the specifications of these subsystems and discusses each RF subsystem independently to provide a comprehensive understanding of the function of each subsystem. This paper concludes with an example of a specification spreadsheet allowing one to input the specifications of a subsystem. Thus, some fundamental parameters (i.e., the cost and size) of the RF system can be determined

  3. Specificity of transmembrane protein palmitoylation in yeast.

    Directory of Open Access Journals (Sweden)

    Ayelén González Montoro

    Full Text Available Many proteins are modified after their synthesis, by the addition of a lipid molecule to one or more cysteine residues, through a thioester bond. This modification is called S-acylation, and more commonly palmitoylation. This reaction is carried out by a family of enzymes, called palmitoyltransferases (PATs, characterized by the presence of a conserved 50- aminoacids domain called "Asp-His-His-Cys- Cysteine Rich Domain" (DHHC-CRD. There are 7 members of this family in the yeast Saccharomyces cerevisiae, and each of these proteins is thought to be responsible for the palmitoylation of a subset of substrates. Substrate specificity of PATs, however, is not yet fully understood. Several yeast PATs seem to have overlapping specificity, and it has been proposed that the machinery responsible for palmitoylating peripheral membrane proteins in mammalian cells, lacks specificity altogether.Here we investigate the specificity of transmembrane protein palmitoylation in S. cerevisiae, which is carried out predominantly by two PATs, Swf1 and Pfa4. We show that palmitoylation of transmembrane substrates requires dedicated PATs, since other yeast PATs are mostly unable to perform Swf1 or Pfa4 functions, even when overexpressed. Furthermore, we find that Swf1 is highly specific for its substrates, as it is unable to substitute for other PATs. To identify where Swf1 specificity lies, we carried out a bioinformatics survey to identify amino acids responsible for the determination of specificity or Specificity Determination Positions (SDPs and showed experimentally, that mutation of the two best SDP candidates, A145 and K148, results in complete and partial loss of function, respectively. These residues are located within the conserved catalytic DHHC domain suggesting that it could also be involved in the determination of specificity. Finally, we show that modifying the position of the cysteines in Tlg1, a Swf1 substrate, results in lack of palmitoylation, as

  4. Validating Avionics Conceptual Architectures with Executable Specifications

    Directory of Open Access Journals (Sweden)

    Nils Fischer

    2012-08-01

    Full Text Available Current avionics systems specifications, developed after conceptual design, have a high degree of uncertainty. Since specifications are not sufficiently validated in the early development process and no executable specification exists at aircraft level, system designers cannot evaluate the impact of their design decisions at aircraft or aircraft application level. At the end of the development process of complex systems, e. g. aircraft, an average of about 65 per cent of all specifications have to be changed because they are incorrect, incomplete or too vaguely described. In this paper, a model-based design methodology together with a virtual test environment is described that makes complex high level system specifications executable and testable during the very early levels of system design. An aircraft communication system and its system context is developed to demonstrate the proposed early validation methodology. Executable specifications for early conceptual system architectures enable system designers to couple functions, architecture elements, resources and performance parameters, often called non-functional parameters. An integrated executable specification at Early Conceptual Architecture Level is developed and used to determine the impact of different system architecture decisions on system behavior and overall performance.

  5. Position paper: the science of deep specification.

    Science.gov (United States)

    Appel, Andrew W; Beringer, Lennart; Chlipala, Adam; Pierce, Benjamin C; Shao, Zhong; Weirich, Stephanie; Zdancewic, Steve

    2017-10-13

    We introduce our efforts within the project 'The science of deep specification' to work out the key formal underpinnings of industrial-scale formal specifications of software and hardware components, anticipating a world where large verified systems are routinely built out of smaller verified components that are also used by many other projects. We identify an important class of specification that has already been used in a few experiments that connect strong component-correctness theorems across the work of different teams. To help popularize the unique advantages of that style, we dub it deep specification , and we say that it encompasses specifications that are rich , two-sided , formal and live (terms that we define in the article). Our core team is developing a proof-of-concept system (based on the Coq proof assistant) whose specification and verification work is divided across largely decoupled subteams at our four institutions, encompassing hardware microarchitecture, compilers, operating systems and applications, along with cross-cutting principles and tools for effective specification. We also aim to catalyse interest in the approach, not just by basic researchers but also by users in industry.This article is part of the themed issue 'Verified trustworthy software systems'. © 2017 The Author(s).

  6. Cell-cycle phase specificity of chloroethylnitrosoureas

    International Nuclear Information System (INIS)

    Linfoot, P.A.

    1986-01-01

    Although the cancer chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is considered a non-cell cycle phase specific drug, it has been shown to produce differential cell killing in G 1 , S, and G 2 /M phase cells, with S phase cells appearing relatively resistant. Studies of cell cycle phase specific cell killing produced by nitrosoureas with different chemical reactivities, clearly indicated that the ability of compounds to cross-link DNA was important in determining their phase specificity. Cells that lacked guanine O 6 -alkytransferase activity showed similar patterns of BCNU phase specificity regardless of their intrinsic sensitivity to BCNU. DNA inter-strand cross-linking, as measured by alkaline elution, was similar in cells exposed to BCNU in G 1 or S phase. 3 H [1-chloroethyl-1nitrosourea] binding to DNA was the same in G 1 , S and G 2 /M phase cells indicating that phase-specific differences in drug uptake and intracellular drug dose were not responsible for phase specific cell kill. These studies suggest that cross-link lesions, other than DNA inter-strand cross-links, and/or effects on DNA repair, other than guanine O 6 -alkyltransferase, are additional important determinants of BCNU phase specific cell killing

  7. Formal specifications for safety grade systems

    International Nuclear Information System (INIS)

    Chisholm, G.H.; Smith, B.T.; Wojcik, A.S.

    1992-01-01

    The authors describe the findings of a study into the application of formal methods to the specification of a safety system for an operating nuclear reactor. They developed a formal specification that is used to verify and validate that no unsafe condition will result from action or inaction of the system. For this reason, the specification must facilitate thinking about, talking about, and implementing the system. In fact, the specification must provide a bridge between people (designers, engineers, policy makers) and diverse implementations (hardware, software, sensors, power supplies) at all levels. For a specification to serve as an effective linkage, it must have the following properties: (1) completeness, (2) conciseness, (3) unambiguity, and (4) communicativeness. In this paper they describe the development of a specification that has three properties. This development is based on the use of formal methods, i.e., methods that add mathematical rigor to the development, analysis and operation of computer systems and to applications based thereon (Neumann). They demonstrate that a specification derived from a formal basis facilitates development of the design and its subsequent verification

  8. Non-specific immunization against babesiosis

    International Nuclear Information System (INIS)

    Cox, F.E.G.

    1980-01-01

    The rodent babesias, Babesia rodhaini and the less virulent B. microti, are useful models with which to study immunity to and immunization against babesiosis. In contrast with the difficulty in inducing specific immunity to these parasites it is comparatively easy to induce non-specific immunity by prior exposure to related and unrelated intra-erythrocytic protozoa, micro-organisms such as Mycobacterium bovis (BCG) and Corynebacterium parvum, microbial extracts and muramyl dipeptide. This non-specific immunity is long lasting and extremely effective. It is characterized by the facts that (a) it occurs early in the infection at the height of the first peak of parasitaemia, and (b) it involves the intra-erythrocytic death of the parasites. After the primary parasitaemia has resolved, some parasites continue to persist at a low level and when introduced into clean mice produce only low-level 'attenuated' infections in these. Non-specific immunity is not equally effective in all strains of mice. It is suggested that immunity to babesiosis, and infections caused by other intra-erythrocytic protozoa, involves two mechanisms, the first non-specific and the second specific. The actual balance between these two mechanisms varies from parasite to parasite and from host to host. An effective vaccine would have to be based on an understanding of the roles of non-specific immunity in the actual disease under consideration, and would ideally combine an adjuvant that would also stimulate non-specific immunity and an attenuated strain of parasite that would induce a specific response. (author)

  9. Assessment of the specificity of norethisterone radioimmunoassays

    Energy Technology Data Exchange (ETDEWEB)

    Bedolla-Tovar, N; Rahman, S A; Cekan, S Z; Diczfalusy, E [Swedish Medical Research Council, Karolinska Hospital, Stockholm

    1978-06-01

    It is concluded that (1) the significance of cross- reaction studies as well as that of the parallelism test for the assessment of the over-all specificity of the assay is limited, (2) a single chromatography prior to the radioimmunoassay proper improves the assay specificity, but may not be sufficient to remove all interfering compounds, (3) a comparison of the direct and chromatographic assay procedures using several antisera is useful for the selection of the relatively most specific radioimmunoassay procedure. In the present study, this is the technique employing either antiserum C or antiserum D, the latter, however, only after chromatography.

  10. PD-L1-specific T cells

    DEFF Research Database (Denmark)

    Ahmad, Shamaila Munir; Borch, Troels Holz; Hansen, Morten

    2016-01-01

    -specific T cells that recognize both PD-L1-expressing immune cells and malignant cells. Thus, PD-L1-specific T cells have the ability to modulate adaptive immune reactions by reacting to regulatory cells. Thus, utilization of PD-L1-derived T cell epitopes may represent an attractive vaccination strategy...... for targeting the tumor microenvironment and for boosting the clinical effects of additional anticancer immunotherapy. This review summarizes present information about PD-L1 as a T cell antigen, depicts the initial findings about the function of PD-L1-specific T cells in the adjustment of immune responses...

  11. Quality Assurance for Iraqi Bottled Water Specifications

    Directory of Open Access Journals (Sweden)

    May George Kassir

    2015-10-01

    Full Text Available In this research the specifications of Iraqi drinking bottled water brands are investigated throughout the comparison between local brands, Saudi Arabia and the World Health Organization (WHO for bottled water standard specifications. These specifications were also compared to that of Iraqi Tap Water standards. To reveal variations in the specifications for Iraqi bottled water, and above mentioned standards some quality control tools are conducted for more than 33% of different bottled water brands (of different origins such as spring, purified,..etc in Iraq by investigating the selected quality parameters registered on their marketing labels. Results employing Minitab software (ver. 16 to generate X bar, and Pareto chart. It was found from X bar charts that the quality parameters of some drinking bottled water brands are not within Iraqi standards set by the “Central Agency for Standardization and Quality Control” such as pH values, Fe, Na, and Mg concentrations. While the comparison of previously mentioned standard specifications through radar chart many important issues are detected such as the absence of lower limits the whole bottled water quality parameters such as for Na and Mg also the radar chart shows that Iraqi bottled and tap water specifications are almost equal in their quality values. Also the same chart pictured the limited range of Iraqi specifications compared to that of Saudi Arabia, and WHO and the need to introduce other water specifications such as K, Na, etc. This confirms the need to improve Iraqi bottled water specifications since it was introduced on 2000. These results also highlighted the weakness of quality assurance activities since only 33 % of the investigated companies registered the whole water quality specifications as shown in Pareto chart. Other companies do not register any quality characteristics. Also certain companies should be stopped due to non-conforming specifications, yet these companies are

  12. Technical specification optimization program - engineered safety features

    International Nuclear Information System (INIS)

    Andre, G.R.; Jansen, R.L.

    1986-01-01

    The Westinghouse Technical Specification Program (TOP) was designed to evaluate on a quantitative basis revisions to Nuclear Power Plant Technical Specifications. The revisions are directed at simplifying plant operation, and reducing unnecessary transients, shutdowns, and manpower requirements. In conjunction with the Westinghouse Owners Group, Westinghouse initiated a program to develop a methodology to justify Technical Specification revisions; particularly revisions related to testing and maintenance requirements on plant operation for instrumentation systems. The methodology was originally developed and applied to the reactor trip features of the reactor protection system (RPS). The current study further refined the methodology and applied it to the engineered safety features of the RPS

  13. Table of specific activities of selected isotopes

    International Nuclear Information System (INIS)

    Shipley, G.

    The bulk of this publication consists of a table of the half-lives, decay modes, and specific activities of isotopes selected for their particular interest to the Environmental Health and Safety Department, LBL. The specific activities were calculated with a PDP 9/15 computer. Also included in the report is a table of stable isotopes, the Th and U decay chains, a chart of the nuclides for elements 101 through 106, the heavy element region of the periodic table, and a specific activity monograph. 5 figures, 2 tables

  14. Mining software specifications methodologies and applications

    CERN Document Server

    Lo, David

    2011-01-01

    An emerging topic in software engineering and data mining, specification mining tackles software maintenance and reliability issues that cost economies billions of dollars each year. The first unified reference on the subject, Mining Software Specifications: Methodologies and Applications describes recent approaches for mining specifications of software systems. Experts in the field illustrate how to apply state-of-the-art data mining and machine learning techniques to address software engineering concerns. In the first set of chapters, the book introduces a number of studies on mining finite

  15. Breckinridge Project, initial effort. Report III, Volume 2. Specifications

    Energy Technology Data Exchange (ETDEWEB)

    None

    1982-01-01

    Report III, Volume 2 contains those specifications numbered K through Y, as follows: Specifications for Compressors (K); Specifications for Piping (L); Specifications for Structures (M); Specifications for Insulation (N); Specifications for Electrical (P); Specifications for Concrete (Q); Specifications for Civil (S); Specifications for Welding (W); Specifications for Painting (X); and Specifications for Special (Y). The standard specifications of Bechtel Petroleum Incorporated have been amended as necessary to reflect the specific requirements of the Breckinridge Project and the more stringent specifications of Ashland Synthetic Fuels, Inc. These standard specifications are available for the Initial Effort (Phase Zero) work performed by all contractors and subcontractors.

  16. Interior Design's Role in Educational Specifications.

    Science.gov (United States)

    Keller, Mary Ann

    1986-01-01

    An experienced interior designer, equipped with a well-written educational specification, will specify the best materials and coordinate colors, materials, and furnishings in line with the district's budget. (MLF)

  17. Cockpit management and Specific Behavioral Objectives (SBOs)

    Science.gov (United States)

    Mudge, R. W.

    1987-01-01

    One of the primary tools used to accomplish the task of effective training is the specific behavioral objective (SBO). An SBO is simply a statement which specifically identifies a small segment of the final behavior sought, and a little more. The key word is specific. The company pinpoints exactly what it is it wants the pilot to do after completing training, and what it should evaluate from the point of view of both the program and the pilot. It tells the junior crewmember exactly, specifically, what he should monitor and support insofar as the management function is concerned. It gives greater meaning to the term second in command. And finally, it tells the supervisory pilot exactly what he should observe, evaluate, and instruct, insofar as the management function is concerned.

  18. 14 CFR 211.10 - Filing specifications.

    Science.gov (United States)

    2010-01-01

    ...) ECONOMIC REGULATIONS APPLICATIONS FOR PERMITS TO FOREIGN AIR CARRIERS General Requirements § 211.10 Filing... in § 302.3 of this chapter as to execution, number of copies, and formal specifications of papers. (b...

  19. Non-specific immunization against parasites

    International Nuclear Information System (INIS)

    Cox, F.E.G.

    1981-01-01

    Non-specific resistance to tumours can be induced by pretreating animals with micro-organisms, microbial extracts or various synthetic substances. Mycobacterium bovis, Corynebacterium parvum and a number of other micro-organisms also protect mice against rodent piroplasms and there is evidence that they are also protective against other parasites including Schistosoma mansoni. The actual mechanisms of non-specific immunity are still unclear but it is influenced by both the genetic make-up of the host and the nature of the parasite. Non-specific immunization may be a possible alternative to specific immunization and may avoid many of the potential immunopathological changes induced during parasite infections. Irradiated vaccines (Dictyocaulus viviparus, schistomiasis) are mentioned marginally only

  20. Standard specification for silvered flat glass mirror

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2008-01-01

    1.1 This specification covers the requirements for silvered flat glass mirrors of rectangular shape supplied as cut sizes, stock sheets or as lehr ends and to which no further processing (such as edgework or other fabrication) has been done. 1.2 This specification covers the quality requirements of silvered annealed monolithic clear and tinted flat glass mirrors up to 6 mm (¼ in.) thick. The mirrors are intended to be used indoors for mirror glazing, for components of decorative accessories or for similar uses. 1.3 This specification does not address safety glazing materials nor requirements for mirror applications. Consult model building codes and other applicable standards for safety glazing applications. 1.4 Mirrors covered in this specification are not intended for use in environments where high humidity or airborne corrosion promoters, or both, are consistently present (such as swimming pool areas, ocean-going vessels, chemical laboratories and other corrosive environments). 1.5 The dimensional val...

  1. Chemical cleaning specification: few tube test model

    International Nuclear Information System (INIS)

    Hampton, L.V.; Simpson, J.L.

    1979-09-01

    The specification is for the waterside chemical cleaning of the 2 1/4 Cr - 1 Mo steel steam generator tubes. It describes the reagents and conditions for post-chemical cleaning passivation of the evaporator tubes

  2. Performance evaluation and specification of trackless tack.

    Science.gov (United States)

    2016-09-01

    Several trackless tack products have come to market in Texas; however, there are currently no specifications to : ensure the products have trackless properties and adequate bond strength. The objectives of this project were to : (1) evaluate the trac...

  3. ROS signalling – Specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian Max; Sweetlove, Lee J

    2011-01-01

    The production of reactive oxygen species (ROS) increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 may induce a general stress response, but it does...... messengers and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. (This is a new project funded by FNU) References: Møller, I.M. & Sweetlove, L.J. 2010. ROS signalling – Specificity is required. Trends Plant Sci. 15: 370-374...... not have the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g., in chloroplasts or mitochondria. We here argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS...

  4. Technical specifications: Health Physics Research Reactor

    International Nuclear Information System (INIS)

    1986-03-01

    These technical specifications define the key limitations that must be observed for safe operation of the Health Physics Research Reactor (HPRR) and an envelope of operation within which there is assurance that these limits will not be exceeded

  5. Iteration and Prototyping in Creating Technical Specifications.

    Science.gov (United States)

    Flynt, John P.

    1994-01-01

    Claims that the development process for computer software can be greatly aided by the writers of specifications if they employ basic iteration and prototyping techniques. Asserts that computer software configuration management practices provide ready models for iteration and prototyping. (HB)

  6. Computational network design from functional specifications

    KAUST Repository

    Peng, Chi Han; Yang, Yong Liang; Bao, Fan; Fink, Daniel; Yan, Dongming; Wonka, Peter; Mitra, Niloy J.

    2016-01-01

    of people in a workspace. Designing such networks from scratch is challenging as even local network changes can have large global effects. We investigate how to computationally create networks starting from only high-level functional specifications

  7. Double-Shell Tank (DST) Utilities Specification

    International Nuclear Information System (INIS)

    SUSIENE, W.T.

    2000-01-01

    This specification establishes the performance requirements and provides the references to the requisite codes and standards to he applied during the design of the Double-Shell Tank (DST) Utilities Subsystems that support the first phase of waste feed delivery (WFD). The DST Utilities Subsystems provide electrical power, raw/potable water, and service/instrument air to the equipment and structures used to transfer low-activity waste (LAW) and high-level waste (HLW) to designated DST staging tanks. The DST Utilities Subsystems also support the equipment and structures used to deliver blended LAW and HLW feed from these staging tanks to the River Protection Project (RPP) Privatization Contractor facility where the waste will be immobilized. This specification is intended to be the basis for new projects/installations. This specification is not intended to retroactively affect previously established project design criteria without specific direction by the program

  8. Specific energy released in power reactors

    International Nuclear Information System (INIS)

    Zaritskaya, T.S.; Kiselev, G.V.; Rudik, A.P.; Tsenter, Eh.M.

    1986-01-01

    Technique of determination are described and analysis of specific energy for different methods of critically maintance of RBMK and WWER-440 reactors are conducted. Characteristics of the optimal mode of critically maintanance are determined

  9. Finding Specification Pages from the Web

    Science.gov (United States)

    Yoshinaga, Naoki; Torisawa, Kentaro

    This paper presents a method of finding a specification page on the Web for a given object (e.g., ``Ch. d'Yquem'') and its class label (e.g., ``wine''). A specification page for an object is a Web page which gives concise attribute-value information about the object (e.g., ``county''-``Sauternes'') in well formatted structures. A simple unsupervised method using layout and symbolic decoration cues was applied to a large number of the Web pages to acquire candidate attributes for each class (e.g., ``county'' for a class ``wine''). We then filter out irrelevant words from the putative attributes through an author-aware scoring function that we called site frequency. We used the acquired attributes to select a representative specification page for a given object from the Web pages retrieved by a normal search engine. Experimental results revealed that our system greatly outperformed the normal search engine in terms of this specification retrieval.

  10. High Flux Isotope Reactor technical specifications

    International Nuclear Information System (INIS)

    1985-11-01

    This report gives technical specifications for the High Flux Isotope Reactor (HFIR) on the following: safety limits and limiting safety system settings; limiting conditions for operation; surveillance requirements; design features; and administrative controls

  11. Cdc42-mediated tubulogenesis controls cell specification

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe

    2009-01-01

    Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and later...... for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the Supplemental Data...

  12. Site-specific weed control technologies

    DEFF Research Database (Denmark)

    Christensen, Svend; Søgaard, Henning Tangen; Kudsk, Per

    2009-01-01

    Site-specific weed control technologies are defined as machinery or equipment embedded with technologies that detect weeds growing in a crop and, taking into account predefined factors such as economics, takes action to maximise the chances of successfully controlling them. In the article, we...... describe the basic parts of site specific weed control technologies, comprising of weed sensing systems, weed management models and precision weed control implements. A review of state-of-the-art technologies shows that several weed sensing systems and precision implements have been developed over the last...... of knowledge about the economic and environmental potential for increasing the resolution of weed control. The integration of site-specific information on weed distribution, weed species composition and density, and the effect on crop yield, is decisive for successful site-specific weed management.   Keywords...

  13. Cancer Chemotherapy Specific to Acidic Nests.

    Science.gov (United States)

    Kobayashi, Hiroshi

    2017-04-20

    The realization of cancer therapeutics specific to cancer cells with less of an effect on normal tissues is our goal. Many trials have been carried out for this purpose, but this goal is still far from being realized. It was found more than 80 years ago that solid cancer nests are acidified, but in vitro studies under acidic conditions have not been extensively studied. Recently, in vitro experiments under acidic conditions were started and anti-cancer drugs specific to acidic areas have been identified. Many genes have been reported to be expressed at a high level under acidic conditions, and such genes may be potent targets for anti-cancer drugs specific to acidic nests. In this review article, recent in vitro, in vivo, and clinical achievements in anti-cancer drugs with marked efficacy under acidic conditions are summarized, and the clinical use of anti-cancer drugs specific to acidic nests is discussed.

  14. Specification for symbol for ionizing radiation

    International Nuclear Information System (INIS)

    1974-01-01

    This Malaysia Standard specification specifies a symbol recommended for use only to signify the actual or potential presence of ionizing radiation (#betta#, α, #betta# only) and to identify objects, devices, materials or combinations of materials which emit such radiation. (author)

  15. Standard Technical Specifications, Babcock and Wilcox Plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Babcock and Wilcox (B ampersand W) plants and documents the positions of the Nuclear Regulatory Commission (NRC) based on the B ampersand W Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council. The improved STS were developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for developing improved plant-specific technical specifications by individual nuclear power plant licensees. This volume contains sections 3.4--3.9 which cover: Reactor coolant systems, emergency core cooling systems, containment systems, plant systems, electrical power systems, refueling operations

  16. Factors influencing women's decisions to purchase specific ...

    African Journals Online (AJOL)

    aimed at identifying the factors that influence women's decisions to purchase specific .... influence of all the factors influencing their decision to purchase a selected .... one free” promotions seemed to have had the greatest influence on this ...

  17. Disease specific therapies in leukodystrophies and leukoencephalopathies

    NARCIS (Netherlands)

    Helman, Guy; van Haren, Keith; Bonkowsky, Joshua L.; Bernard, Genevieve; Pizzino, Amy; Braverman, Nancy; Suhr, Dean; Patterson, Marc C.; Ali Fatemi, S.; Leonard, Jeff; van der Knaap, Marjo S.; Back, Stephen A.; Damiani, Stephen; Goldman, Steven A.; Takanohashi, Asako; Petryniak, Magdalena; Rowitch, David; Messing, Albee; Wrabetz, Lawrence; Schiffmann, Raphael; Eichler, Florian; Escolar, Maria L.; Vanderver, Adeline

    2015-01-01

    Leukodystrophies are a heterogeneous, often progressive group of disorders manifesting a wide range of symptoms and complications. Most of these disorders have historically had no etiologic or disease specific therapeutic approaches. Recently, a greater understanding of the pathologic mechanisms

  18. Peptide binding specificity of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Sandhu, N.; Duus, K.; Jorgensen, C.S.

    2007-01-01

    Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composit......Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length...... than 5 amino acids showed binding and a clear correlation with hydrophobicity was demonstrated for oligomers of different hydrophobic amino acids. Insertion of hydrophilic amino acids in a hydrophobic sequence diminished or abolished binding. In conclusion our results show that calreticulin has...

  19. Prostate-Specific Antigen (PSA) Test

    Science.gov (United States)

    ... Cancer Prostate Cancer Screening Research Prostate-Specific Antigen (PSA) Test On This Page What is the PSA ... parts of the body before being detected. The PSA test may give false-positive or false-negative ...

  20. Bottomland Hardwood Planting: Example Contract Specifications

    National Research Council Canada - National Science Library

    Humprey, Monica

    2002-01-01

    This technical note provides an example of contract specifications that can be used as a template by USACE biologists, engineers, or contracting officers for contracting the planting of bottomland hardwood (BLH) seedlings...

  1. Specific detection of proteins using Nanomechanical resonators

    DEFF Research Database (Denmark)

    Fischer, Lee MacKenzie; Wright, V.A.; Guthy, C.

    2008-01-01

    of probes onto their surfaces in order to enable the specificity of the detection. Such nanoresonator-based specific detection of proteins is here reported using streptavidin as target system, and immobilized biotin as probe. Nanomechanical resonators resistant to stiction were first realized from silicon...... carbonitride using a novel fabrication method. Vapor-phase deposition of mercaptopropyl trimethoxysilane was performed, and an added mass of 2.22 +/- 0.07 fg/mu m(2) was measured. This linker molecule was used to attach biotin onto the devices, enabling the specific detection of streptavidin. A mass of 3.6 fg....../mu m(2) was attributed to the added streptavidin, corresponding to one molecule per 27 nm(2). The specificity of this recognition was confirmed by exposing the devices to a solution of streptavidin that was already saturated with biotin. An additional negative control was also performed by also...

  2. Analyzing Security-Enhanced Linux Policy Specifications

    National Research Council Canada - National Science Library

    Archer, Myla

    2003-01-01

    NSA's Security-Enhanced (SE) Linux enhances Linux by providing a specification language for security policies and a Flask-like architecture with a security server for enforcing policies defined in the language...

  3. Technical specifications for the bulk shielding reactor

    International Nuclear Information System (INIS)

    1986-05-01

    This report provides information concerning the technical specifications for the Bulk Shielding Reactor. Areas covered include: safety limits and limiting safety settings; limiting conditions for operation; surveillance requirements; design features; administrative controls; and monitoring of airborne effluents. 10 refs

  4. Technical specifications for the pool critical assembly

    International Nuclear Information System (INIS)

    1978-07-01

    Technical specifications for the ORNL-PCA Reactor are presented concerning safety limits and limiting safety system settings, limiting conditions for operation, surveillance requirements, design features, and administrative controls

  5. Index to Drug-Specific Information

    Science.gov (United States)

    ... Postmarket Drug Safety Information for Patients and Providers Index to Drug-Specific Information Share Tweet Linkedin Pin ... options Linkedin Pin it Email Print Note: This Index does not include all FDA approved drugs. It ...

  6. Project NEO Specific Impulse Testing Solutions

    Science.gov (United States)

    Baffa, Bill

    2018-01-01

    The Neo test stand is currently configured to fire a horizontally mounted rocket motor with up to 6500 lbf thrust. Currently, the Neo test stand can measure flow of liquid propellant and oxidizer, pressures residing in the closed system up to the combustion chamber. The current configuration does not have the ability to provide all data needed to compute specific impulse. This presents three methods to outfit the NEO test fixture with instrumentation allowing for calculation of specific impulse.

  7. Affect and person specificity in mood regulation

    OpenAIRE

    Corby, Emma Kate

    2007-01-01

    489 university students in three countries completed questionnaires in a study investigating affect and person specificity in the use of mood regulation strategies. The major aims of the study were to (1) describe the relationship between specific affective states and the strategies utilised, (2) explore the role that individual differences variables played in the tendency to use particular strategies, and (3) measure the impact that the use of different strategies had upon subjective well-b...

  8. Production of Monoclonal Antibodies specific for Progesterone

    OpenAIRE

    YÜCEL, Fatıma

    2014-01-01

    Progesterone levels in milk and serum are indicators of pregnancy in cattle. The progesterone level reaches a peak on the 21 st and 22 nd days of pregnancy. Monoclonal antibodies specific to progesterone could be used for the immunodetection of milk and serum progesterone levels. We report here the development of hybrid cells prdoducing monoclonal antibodies specific for progesterone using hybridoma technology. Hybridoma cells secreting monoclonal antibodies against progesterone (MAM 2H1...

  9. Chemical and radiochemical specifications - PWR power plants

    International Nuclear Information System (INIS)

    Stutzmann, A.

    1997-01-01

    Published by EDF this document gives the chemical specifications of the PWR (Pressurized Water Reactor) nuclear power plants. Among the chemical parameters, some have to be respected for the safety. These parameters are listed in the STE (Technical Specifications of Exploitation). The values to respect, the analysis frequencies and the time states of possible drops are noticed in this document with the motion STE under the concerned parameter. (A.L.B.)

  10. [Psychological specificities of living donor kidney transplantation].

    Science.gov (United States)

    Papeloux-Heitzmann, Élodie

    2016-12-01

    For people with end-stage kidney disease, a transplant is the promise of a future without dialysis. Living donor kidney transplantation comprises many specificities and is distinct from cadaveric donor transplantation. Some psychological aspects explain these specificities. They may be subconscious and difficult to access, but it is essential to decipher them in order to adapt the support provided to these people. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Patient-Specific Modeling in Tomorrow's Medicine

    CERN Document Server

    2012-01-01

    This book reviews the frontier of research and clinical applications of Patient Specific Modeling, and provides a state-of-the-art update as well as perspectives on future directions in this exciting field. The book is useful for medical physicists, biomedical engineers and other engineers who are interested in the science and technology aspects of Patient Specific Modeling, as well as for radiologists and other medical specialists who wish to be updated about the state of implementation.

  12. Task-Specific Training and Job Design

    OpenAIRE

    Felipe Balmaceda

    2006-01-01

    This paper provides a simple theoretical framework based on a new type of human capital introduced by Gibbons and Waldman (2004), called task-specific training, to understand job design. Mainly, in the presence of task-specific training, promotions might result ex-post in the underutilization of human capital and thus firms at the time of designing jobs should attempt to diversify this risk.

  13. Specific phobia predicts psychopathology in young women

    OpenAIRE

    Trumpf, Julia; Margraf, Jürgen; Vriends, Noortje; Meyer, Andrea Hans; Becker, Eni S.

    2010-01-01

    Background Although specific phobia is characterized by an early age at onset and by high rates of comorbidity, few studies have examined comorbid relationships prospectively. Objectives The present study investigated the association between specific phobia and the risk of a broad range of psychopathology among young women in the community. Method Data came from the Dresden Predictor Study in which 1,538 German women (18?25?years) completed a diagnostic interview at two time points. Results W...

  14. Enzyme specific activity in functionalized nanoporous supports

    International Nuclear Information System (INIS)

    Lei Chenghong; Soares, Thereza A; Shin, Yongsoon; Liu Jun; Ackerman, Eric J

    2008-01-01

    Here we reveal that enzyme specific activity can be increased substantially by changing the protein loading density (P LD ) in functionalized nanoporous supports so that the enzyme immobilization efficiency (I e , defined as the ratio of the specific activity of the immobilized enzyme to the specific activity of the free enzyme in solution) can be much higher than 100%. A net negatively charged glucose oxidase (GOX) and a net positively charged organophosphorus hydrolase (OPH) were entrapped spontaneously in NH 2 - and HOOC-functionalized mesoporous silica (300 A, FMS) respectively. The specific activity of GOX entrapped in FMS increased with decreasing P LD . With decreasing P LD , I e of GOX in FMS increased from 150%. Unlike GOX, OPH in HOOC-FMS showed increased specific activity with increasing P LD . With increasing P LD , the corresponding I e of OPH in FMS increased from 100% to>200%. A protein structure-based analysis of the protein surface charges directing the electrostatic interaction-based orientation of the protein molecules in FMS demonstrates that substrate access to GOX molecules in FMS is limited at high P LD , consequently lowering the GOX specific activity. In contrast, substrate access to OPH molecules in FMS remains open at high P LD and may promote a more favorable confinement environment that enhances the OPH activity

  15. Autobiographical memory specificity in dissociative identity disorder.

    Science.gov (United States)

    Huntjens, Rafaële J C; Wessel, Ineke; Hermans, Dirk; van Minnen, Agnes

    2014-05-01

    A lack of adequate access to autobiographical knowledge has been related to psychopathology. More specifically, patients suffering from depression or a history of trauma have been found to be characterized by overgeneral memory, in other words, they show a relative difficulty in retrieving a specific event from memory located in time and place. Previous studies of overgeneral memory have not included patients with dissociative disorders. These patients are interesting to consider, as they are hypothesized to have the ability to selectively compartmentalize information linked to negative emotions. This study examined avoidance and overgeneral memory in patients with dissociative identity disorder (DID; n = 12). The patients completed the autobiographical memory test (AMT). Their performance was compared with control groups of posttraumatic stress disorder (PTSD) patients (n = 26), healthy controls (n = 29), and DID simulators (n = 26). Specifically, we compared the performance of separate identity states in DID hypothesized to diverge in the use of avoidance as a coping strategy to deal with negative affect. No significant differences in memory specificity were found between the separate identities in DID. Irrespective of identity state, DID patients were characterized by a lack of memory specificity, which was similar to the lack of memory specificity found in PTSD patients. The converging results for DID and PTSD patients add empirical evidence for the role of overgeneral memory involved in the maintenance of posttraumatic psychopathology.

  16. Standardized Technical Specifications for Westinghouse PWRs

    International Nuclear Information System (INIS)

    1978-01-01

    This Standard Technical Specification (STS) has been structured for the broadest possible use on Westinghouse plants currently being reviewed for an Operating License. Accordingly, the document contains specifications applicable to plants (1) with either 3 or 4 loops and (2) with and without loop stop valves. In addition, four separate and discrete containment specification sections are provided for each of the following containment types: Atmospheric, Ice Condenser, Sub-Atmospheric, and Dual. Optional specifications are provided for those features and systems which may be included in individual plant designs but are not generic in their scope of application. Alternate specifications are provided in a limited number of cases to cover situations where alternate specification requirements are necessary on a generic basis because of design differences. The format of the STS addresses the categories required by 10 CFR 50 and consists of six sections covering the areas of: Definitions, Safety Limits and Limiting Safety System Settings, Limiting Conditions for Operation, Surveillance Requirements, Design Features, and Administrative Controls

  17. Age-specific reference ranges of serum prostate-specific antigen in Iranian men

    Directory of Open Access Journals (Sweden)

    Gholamreza Pourmand

    2015-08-01

    Conclusion: Findings of the present study showed that PSA levels are correlated with age. It was also revealed that the PSA age-specific reference range obtained in this study is different from other races and is specific to Iranian men. Therefore, age-specific reference ranges of PSA obtained in the present study can increase PSA test sensitivity and specificity by reducing unnecessary diagnostic procedures and early detection of prostate cancer in Iranian men.

  18. Domain Specific Language Support for Exascale

    Energy Technology Data Exchange (ETDEWEB)

    Mellor-Crummey, John [Rice Univ., Houston, TX (United States)

    2017-10-20

    A multi-institutional project known as D-TEC (short for “Domain- specific Technology for Exascale Computing”) set out to explore technologies to support the construction of Domain Specific Languages (DSLs) to map application programs to exascale architectures. DSLs employ automated code transformation to shift the burden of delivering portable performance from application programmers to compilers. Two chief properties contribute: DSLs permit expression at a high level of abstraction so that a programmer’s intent is clear to a compiler and DSL implementations encapsulate human domain-specific optimization knowledge so that a compiler can be smart enough to achieve good results on specific hardware. Domain specificity is what makes these properties possible in a programming language. If leveraging domain specificity is the key to keep exascale software tractable, a corollary is that many different DSLs will be needed to encompass the full range of exascale computing applications; moreover, a single application may well need to use several different DSLs in conjunction. As a result, developing a general toolkit for building domain-specific languages was a key goal for the D-TEC project. Different aspects of the D-TEC research portfolio were the focus of work at each of the partner institutions in the multi-institutional project. D-TEC research and development work at Rice University focused on on three principal topics: understanding how to automate the tuning of code for complex architectures, research and development of the Rosebud DSL engine, and compiler technology to support complex execution platforms. This report provides a summary of the research and development work on the D-TEC project at Rice University.

  19. Formal specification level concepts, methods, and algorithms

    CERN Document Server

    Soeken, Mathias

    2015-01-01

    This book introduces a new level of abstraction that closes the gap between the textual specification of embedded systems and the executable model at the Electronic System Level (ESL). Readers will be enabled to operate at this new, Formal Specification Level (FSL), using models which not only allow significant verification tasks in this early stage of the design flow, but also can be extracted semi-automatically from the textual specification in an interactive manner.  The authors explain how to use these verification tasks to check conceptual properties, e.g. whether requirements are in conflict, as well as dynamic behavior, in terms of execution traces. • Serves as a single-source reference to a new level of abstraction for embedded systems, known as the Formal Specification Level (FSL); • Provides a variety of use cases which can be adapted to readers’ specific design flows; • Includes a comprehensive illustration of Natural Language Processing (NLP) techniques, along with examples of how to i...

  20. Standard Technical Specifications, Babcock and Wilcox plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Babcock and Wilcox (B ampersand W) Plants and documents the positions of the Nuclear Regulatory Commission based on the B ampersand W Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council (NUMARC). The improved STS were developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume 1 contains the Specifications for all chapters and sections of the improved STS. This document Volume 2, contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the improved STS. Volume 3 contains the Bases for Sections 3.4--3.10 of the improved STS

  1. Standard Technical Specifications, Combustion Engineering plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (M) for Combustion Engineering (CE) Plants and documents the positions of the Nuclear Regulatory Commission based on the CE Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council (NUMARC). The improved STS were developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume 1 contains the Specifications for all chapters and sections of the improved STS. This document Volume 2 contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the improved STS. Volume 3 contains the Bases for Sections 3.4--3.9 of the improved STS

  2. Chromosome-specific DNA Repeat Probes

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

    2006-03-16

    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  3. Standard Technical Specifications, Combustion Engineering plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Combustion Engineering (CE) Plants and documents the positions of the Nuclear Regulatory Commission based on the CE Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council (NUMARC). The improved STS were developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume 1 contains the Specifications for all chapters and sections of the improved SM. Volume 2 contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the improved STS. This document Volume 3 contains the Bases for Sections 3.4--3.9 of the improved M

  4. The specificity and organisation of autobiographical memories.

    Science.gov (United States)

    Schulkind, Matthew D; Rahhal, Tamara A; Klein, Megan R; Lacher, Samantha R

    2012-01-01

    Previous research suggests that autobiographical memories are over-general and are organised according to life periods. One experiment assessed the specificity and organisation of autobiographical memory by manipulating two variables. The retrieval cues were either a set of three words (a theme, a time period, and an emotional valence) or a short narrative that included a specific theme, time period, and emotional valence. The instructions either encouraged the participants to respond as though they were conversing with a friend (social instructions) or did not specify a target audience (standard instructions). Narrative cues and standard instructions elicited more specific responses than word cues and social instructions, respectively. Whereas word cues elicited memories that were most likely to match the cues in terms of time period, narrative cues elicited memories that were most likely to match the cues in terms of theme. These data suggest that previous research underestimated the specificity of the autobiographical knowledge base and overestimated the importance of temporally defined life periods for organising autobiographical memory. Previous conclusions regarding the specificity and organisation of autobiographical memory may reflect the structure of autobiographical narratives and the methodologies used to collect such narratives rather than the content of autobiographical memory itself.

  5. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  6. Arabidopsis cryptochrome 1 is a soluble protein mediating blue light-dependent regulation of plant growth and development

    International Nuclear Information System (INIS)

    Lin ChenTao; Ahmad, M.; Cashmore, A.R.

    1996-01-01

    Cryptochrome 1 (CRY1) is a flavin-type blue type receptor of Arabidopsis thaliana which mediates inhibition of hypocotyl elongation. In the work described in this report it is demonstrated that CRY1 is a soluble protein expressed in both young seedlings grown either in the dark or under light, and in different organs of adult plants. The functional role of CRY1 was further investigated using transgenic Arabidopsis plants overexpressing CRY1. It is demonstrated that overexpression of CRY1 resulted in hypersensitivity to blue, UV-A, and green light for the inhibition of hypocotyl elongation response. Transgenic plants overexpressing CRY1 also exhibited a dwarf phenotype with reduced size in almost every organ. This was in keeping with the previous observation of reciprocal alterations found in hy4 mutant plants and is consistent with a hypothesis that CRY1 mediates a light-dependent process resulting in a general inhibitory effect on plant growth. In addition, transgenic plants overexpressing CRY1 showed increased anthocyanin accumulation in response to blue, UV-A, and green light in a fluence rate-dependent manner. This increase in anthocyanin accumulation in transgenic plants was shown to be concomitant with increased blue light-induction of CHS gene expression. It is concluded that CRY1 is a photoreceptor mediating blue light-dependent regulation of gene expression in addition to its affect on plant growth. (author)

  7. Amyloid protein-mediated differential DNA methylation status regulates gene expression in Alzheimer’s disease model cell line

    International Nuclear Information System (INIS)

    Sung, Hye Youn; Choi, Eun Nam; Ahn Jo, Sangmee; Oh, Seikwan; Ahn, Jung-Hyuck

    2011-01-01

    Highlights: ► Genome-wide DNA methylation pattern in Alzheimer’s disease model cell line. ► Integrated analysis of CpG methylation and mRNA expression profiles. ► Identify three Swedish mutant target genes; CTIF, NXT2 and DDR2 gene. ► The effect of Swedish mutation on alteration of DNA methylation and gene expression. -- Abstract: The Swedish mutation of amyloid precursor protein (APP-sw) has been reported to dramatically increase beta amyloid production through aberrant cleavage at the beta secretase site, causing early-onset Alzheimer’s disease (AD). DNA methylation has been reported to be associated with AD pathogenesis, but the underlying molecular mechanism of APP-sw-mediated epigenetic alterations in AD pathogenesis remains largely unknown. We analyzed genome-wide interplay between promoter CpG DNA methylation and gene expression in an APP-sw-expressing AD model cell line. To identify genes whose expression was regulated by DNA methylation status, we performed integrated analysis of CpG methylation and mRNA expression profiles, and identified three target genes of the APP-sw mutant; hypomethylated CTIF (CBP80/CBP20-dependent translation initiation factor) and NXT2 (nuclear exporting factor 2), and hypermethylated DDR2 (discoidin domain receptor 2). Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored mRNA expression of these three genes, implying methylation-dependent transcriptional regulation. The profound alteration in the methylation status was detected at the −435, −295, and −271 CpG sites of CTIF, and at the −505 to −341 region in the promoter of DDR2. In the promoter region of NXT2, only one CpG site located at −432 was differentially unmethylated in APP-sw cells. Thus, we demonstrated the effect of the APP-sw mutation on alteration of DNA methylation and subsequent gene expression. This epigenetic regulatory mechanism may contribute to the pathogenesis of AD.

  8. Role of protein disulfide isomerase and other thiol-reactive proteins in HIV-1 envelope protein-mediated fusion

    International Nuclear Information System (INIS)

    Ou Wu; Silver, Jonathan

    2006-01-01

    Cell-surface protein disulfide isomerase (PDI) has been proposed to promote disulfide bond rearrangements in HIV-1 envelope protein (Env) that accompany Env-mediated fusion. We evaluated the role of PDI in ways that have not been previously tested by downregulating PDI with siRNA and by overexpressing wild-type or variant forms of PDI in transiently and stably transfected cells. These manipulations, as well as treatment with anti-PDI antibodies, had only small effects on infection or cell fusion mediated by NL4-3 or AD8 strains of HIV-1. However, the cell-surface thiol-reactive reagent 5, 5'-dithiobis(2-nitrobenzoic acid) (DTNB) had a much stronger inhibitory effect in our system, suggesting that cell-surface thiol-containing molecules other than PDI, acting alone or in concert, have a greater effect than PDI on HIV-1 Env-mediated fusion. We evaluated one such candidate, thioredoxin, a PDI family member reported to reduce a labile disulfide bond in CD4. We found that the ability of thioredoxin to reduce the disulfide bond in CD4 is enhanced in the presence of HIV-1 Env gp120 and that thioredoxin also reduces disulfide bonds in gp120 directly in the absence of CD4. We discuss the implications of these observations for identification of molecules involved in disulfide rearrangements in Env during fusion

  9. Mechanisms of photosensitization by drugs: Involvement of tyrosines in the photomodification of proteins mediated by tiaprofenic acid in vitro.

    Science.gov (United States)

    Miranda, M A; Castell, J V; Sarabia, Z; Hernández, D; Puertes, I; Morera, I M; Gómez-Lechón, M J

    1997-10-01

    The photosensitizing potential of drugs must be related to their photoreactivity towards the target biomolecules. In this context, a representative photosensitizing drug (tiaprofenic acid) was co-irradiated with a model protein, bovine serum albumin (BSA). This led to a significant degree of protein crosslinking and to the formation of trace amounts of drug-BSA photoadducts. Amino acid analysis of the hydrolysed (HC1) protein showed that His and Tyr undergo a dramatic decrease (approx. 90%) as a consequence of drug-mediated photodynamic processes. When the drug was irradiated in the presence of the pure amino acids, extensive phototransformation of the latter was observed. Other photosensitizing drugs gave rise to similar processes when irradiated in the presence of BSA or the isolated amino acids. In conclusion, histidine and tyrosine appear to be key sites for the photosensitized damage to proteins. Photodegradation of the isolated amino acids in vitro may be an indicator of the photosensitizing potential of drugs.

  10. Isonicotinamide Enhances Sir2 Protein-mediated Silencing and Longevity in Yeast by Raising Intracellular NAD+ Concentration*

    Science.gov (United States)

    McClure, Julie M.; Wierman, Margaret B.; Maqani, Nazif; Smith, Jeffrey S.

    2012-01-01

    Sirtuins are an evolutionarily conserved family of NAD+-dependent protein deacetylases that function in the regulation of gene transcription, cellular metabolism, and aging. Their activity requires the maintenance of an adequate intracellular NAD+ concentration through the combined action of NAD+ biosynthesis and salvage pathways. Nicotinamide (NAM) is a key NAD+ precursor that is also a byproduct and feedback inhibitor of the deacetylation reaction. In Saccharomyces cerevisiae, the nicotinamidase Pnc1 converts NAM to nicotinic acid (NA), which is then used as a substrate by the NAD+ salvage pathway enzyme NA phosphoribosyltransferase (Npt1). Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition. In this study, we determined that INAM stimulates Sir2 through an additional mechanism in vivo, which involves elevation of the intracellular NAD+ concentration. INAM enhanced normal silencing at the rDNA locus but only partially suppressed the silencing defects of an npt1Δ mutant. Yeast cells grown in media lacking NA had a short replicative life span, which was extended by INAM in a SIR2-dependent manner and correlated with increased NAD+. The INAM-induced increase in NAD+ was strongly dependent on Pnc1 and Npt1, suggesting that INAM increases flux through the NAD+ salvage pathway. Part of this effect was mediated by the NR salvage pathways, which generate NAM as a product and require Pnc1 to produce NAD+. We also provide evidence suggesting that INAM influences the expression of multiple NAD+ biosynthesis and salvage pathways to promote homeostasis during stationary phase. PMID:22539348

  11. Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration.

    Science.gov (United States)

    McClure, Julie M; Wierman, Margaret B; Maqani, Nazif; Smith, Jeffrey S

    2012-06-15

    Sirtuins are an evolutionarily conserved family of NAD(+)-dependent protein deacetylases that function in the regulation of gene transcription, cellular metabolism, and aging. Their activity requires the maintenance of an adequate intracellular NAD(+) concentration through the combined action of NAD(+) biosynthesis and salvage pathways. Nicotinamide (NAM) is a key NAD(+) precursor that is also a byproduct and feedback inhibitor of the deacetylation reaction. In Saccharomyces cerevisiae, the nicotinamidase Pnc1 converts NAM to nicotinic acid (NA), which is then used as a substrate by the NAD(+) salvage pathway enzyme NA phosphoribosyltransferase (Npt1). Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition. In this study, we determined that INAM stimulates Sir2 through an additional mechanism in vivo, which involves elevation of the intracellular NAD(+) concentration. INAM enhanced normal silencing at the rDNA locus but only partially suppressed the silencing defects of an npt1Δ mutant. Yeast cells grown in media lacking NA had a short replicative life span, which was extended by INAM in a SIR2-dependent manner and correlated with increased NAD(+). The INAM-induced increase in NAD(+) was strongly dependent on Pnc1 and Npt1, suggesting that INAM increases flux through the NAD(+) salvage pathway. Part of this effect was mediated by the NR salvage pathways, which generate NAM as a product and require Pnc1 to produce NAD(+). We also provide evidence suggesting that INAM influences the expression of multiple NAD(+) biosynthesis and salvage pathways to promote homeostasis during stationary phase.

  12. Yeast G-proteins mediate directional sensing and polarization behaviors in response to changes in pheromone gradient direction

    Science.gov (United States)

    Moore, Travis I.; Tanaka, Hiromasa; Kim, Hyung Joon; Jeon, Noo Li; Yi, Tau-Mu

    2013-01-01

    Yeast cells polarize by projecting up mating pheromone gradients, a classic cell polarity behavior. However, these chemical gradients may shift direction. We examine how yeast cells sense and respond to a 180o switch in the direction of microfluidically generated pheromone gradients. We identify two behaviors: at low concentrations of α-factor, the initial projection grows by bending, whereas at high concentrations, cells form a second projection toward the new source. Mutations that increase heterotrimeric G-protein activity expand the bending-growth morphology to high concentrations; mutations that increase Cdc42 activity result in second projections at low concentrations. Gradient-sensing projection bending requires interaction between Gβγ and Cdc24, whereas gradient-nonsensing projection extension is stimulated by Bem1 and hyperactivated Cdc42. Of interest, a mutation in Gα affects both bending and extension. Finally, we find a genetic perturbation that exhibits both behaviors. Overexpression of the formin Bni1, a component of the polarisome, makes both bending-growth projections and second projections at low and high α-factor concentrations, suggesting a role for Bni1 downstream of the heterotrimeric G-protein and Cdc42 during gradient sensing and response. Thus we demonstrate that G-proteins modulate in a ligand-dependent manner two fundamental cell-polarity behaviors in response to gradient directional change. PMID:23242998

  13. Role of hypoxia-inducible factor-α in hepatitis-B-virus X protein-mediated MDR1 activation

    International Nuclear Information System (INIS)

    Han, Hyo-Kyung; Han, Chang Yeob; Cheon, Eun-Pa; Lee, Jaewon; Kang, Keon Wook

    2007-01-01

    The transition from chemotherapy-responsive cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multi-drug resistance 1 (MDR1). We found that hepatitis-B-virus X protein (HBx) increases the transcriptional activity and protein level of MDR1 in a hepatoma cell line, H4IIE. In addition, HBx overexpression made H4IIE cells more resistant to verapamil-uptake. HBx stabilized hypoxia-inducible factor-1α (HIF-1α) and induced the nuclear translocation of C/EBPβ. Reporter gene analyses showed that HBx increased the reporter activity in the cells transfected with the reporter containing MDR1 gene promoter. Moreover, the luciferase reporter gene activity was significantly inhibited by HIF-1α siRNA but not by overexpression of C/EBP dominant negative mutant. These results imply that HBx increases the MDR1 transporter activity through the transcriptional activation of the MDR1 gene with HIF-1α activation, and suggest HIF-1α for the therapeutic target of HBV-mediated chemoresistance

  14. Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs.

    Science.gov (United States)

    Gagnon, James A; Valen, Eivind; Thyme, Summer B; Huang, Peng; Akhmetova, Laila; Ahkmetova, Laila; Pauli, Andrea; Montague, Tessa G; Zimmerman, Steven; Richter, Constance; Schier, Alexander F

    2014-01-01

    The CRISPR/Cas9 system has been implemented in a variety of model organisms to mediate site-directed mutagenesis. A wide range of mutation rates has been reported, but at a limited number of genomic target sites. To uncover the rules that govern effective Cas9-mediated mutagenesis in zebrafish, we targeted over a hundred genomic loci for mutagenesis using a streamlined and cloning-free method. We generated mutations in 85% of target genes with mutation rates varying across several orders of magnitude, and identified sequence composition rules that influence mutagenesis. We increased rates of mutagenesis by implementing several novel approaches. The activities of poor or unsuccessful single-guide RNAs (sgRNAs) initiating with a 5' adenine were improved by rescuing 5' end homogeneity of the sgRNA. In some cases, direct injection of Cas9 protein/sgRNA complex further increased mutagenic activity. We also observed that low diversity of mutant alleles led to repeated failure to obtain frame-shift mutations. This limitation was overcome by knock-in of a stop codon cassette that ensured coding frame truncation. Our improved methods and detailed protocols make Cas9-mediated mutagenesis an attractive approach for labs of all sizes.

  15. SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

    Energy Technology Data Exchange (ETDEWEB)

    Verbakel, Werner, E-mail: werner.verbakel@chem.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium); Carmeliet, Geert, E-mail: geert.carmeliet@med.kuleuven.be [Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Herestraat 49, Bus 902, 3000 Leuven (Belgium); Engelborghs, Yves, E-mail: yves.engelborghs@fys.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)

    2011-08-12

    Highlights: {yields} The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. {yields} This SAP-like domain is essential for chromosome loading during early mitosis. {yields} NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. {yields} The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase NuSAP-chromatin interaction suggests additional functions for NuSAP, as recently identified for other nuclear spindle assembly factors with a role in gene expression or DNA damage response.

  16. Modification of the Campylobacter jejuni N-linked glycan by EptC protein-mediated addition of phosphoethanolamine

    DEFF Research Database (Denmark)

    Scott, Nichollas E; Nothaft, Harald; Edwards, Alistair V G

    2012-01-01

    . Interrogation of these data allowed the identification of a phosphoethanolamine (pEtN)-modified variant of the N-glycan that was attached to multiple proteins. The pEtN moiety was attached to the terminal GalNAc of the canonical N-glycan. Deletion of the pEtN transferase eptC removed all evidence of the p......, yet above background levels of pEtN-glycan were also observed in E. coli not expressing eptC, suggesting that endogenous E. coli pEtN transferases can mediate the addition of pEtN to N-glycans. The addition of pEtN must be considered in the context of glycoengineering and may alter C. jejuni glycan...

  17. IGF-binding proteins mediate TGF-beta 1-induced apoptosis in bovine mammary epithelial BME-UV1 cells.

    Science.gov (United States)

    Gajewska, Małgorzata; Motyl, Tomasz

    2004-10-01

    TGF-beta 1 is an antiproliferative and apoptogenic factor for mammary epithelial cells (MEC) acting in an auto/paracrine manner and thus considered an important local regulator of mammary tissue involution. However, the apoptogenic signaling pathway induced by this cytokine in bovine MEC remains obscure. The present study was focused on identification of molecules involved in apoptogenic signaling of transforming growth factor-beta 1 (TGF-beta 1) in the model of bovine mammary epithelial cell line (BME-UV1). Laser scanning cytometry (LSC), Western blot and electrophoretic mobility shift assay (EMSA) were used for analysis of expression and activity of TGF-beta 1-related signaling molecules. The earliest response occurring within 1-2 h after TGF-beta 1 administration was an induction and activation of R-Smads (Smad2 and Smad3) and Co-Smad (Smad4). An evident formation of Smad-DNA complexes began from 2nd hour after MEC exposure to TGF-beta 1. Similarly to Smads, proteins of AP1 complex: phosphorylated c-Jun and JunD appeared to be early reactive molecules; however, an increase in their expression was detected only in cytosolic fraction. In the next step, an increase of IGF binding protein-3 (IGFBP-3) and IGFBP-4 expression was observed from 6th hour followed by a decrease in the activity of protein kinase B (PKB/Akt), which occurred after 24 h of MEC exposure to TGF-beta 1. The decrease in PKB/Akt activity coincided in time with the decline of phosphorylated Bad expression (inactive form). Present study supported additional evidence that stimulation of insulin-like growth factor I (IGF-I) was associated with complete abrogation of TGF-beta 1-induced activation of Bad and Bax and in the consequence protection against apoptosis. In conclusion, apoptotic effect of TGF-beta 1 in bovine MEC is mediated by IGFBPs and occurs through IGF-I sequestration, resulting in inhibition of PKB/Akt-dependent survival pathway.

  18. G-protein mediates voltage regulation of agonist binding to muscarinic receptors: effects on receptor-Na+ channel interaction

    International Nuclear Information System (INIS)

    Cohen-Armon, M.; Garty, H.; Sokolovsky, M.

    1988-01-01

    The authors previous experiments in membranes prepared from rat heart and brain led them to suggest that the binding of agonist to the muscarinic receptors and to the Na + channels is a coupled event mediated by guanine nucleotide binding protein(s) [G-protein(s)]. These in vitro findings prompted us to employ synaptoneurosomes from brain stem tissue to examine (i) the binding properties of [ 3 H] acetylcholine at resting potential and under depolarization conditions in the absence and presence of pertussis toxin; (ii) the binding of [ 3 H]batrachotoxin to Na + channel(s) in the presence of the muscarinic agonists; and (iii) muscarinically induced 22 Na + uptake in the presence and absence of tetrodotoxin, which blocks Na + channels. The findings indicate that agonist binding to muscarinic receptors is voltage dependent, that this process is mediated by G-protein(s), and that muscarinic agonists induce opening of Na + channels. The latter process persists even after pertussis toxin treatment, indicating that it is not likely to be mediated by pertussis toxin sensitive G-protein(s). The system with its three interacting components-receptor, G-protein, and Na + channel-is such that at resting potential the muscarinic receptor induces opening of Na + channels; this property may provide a possible physiological mechanism for the depolarization stimulus necessary for autoexcitation or repetitive firing in heart or brain tissues

  19. SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

    International Nuclear Information System (INIS)

    Verbakel, Werner; Carmeliet, Geert; Engelborghs, Yves

    2011-01-01

    Highlights: → The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. → This SAP-like domain is essential for chromosome loading during early mitosis. → NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. → The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase NuSAP-chromatin interaction suggests additional functions for NuSAP, as recently identified for other nuclear spindle assembly factors with a role in gene expression or DNA damage response.

  20. Different integration site structures between L1 protein-mediated retrotransposition in cis and retrotransposition in trans

    Directory of Open Access Journals (Sweden)

    Kojima Kenji K

    2010-07-01

    Full Text Available Abstract Background Long interspersed nuclear element-1 (LINE-1 or L1 is a dominant repetitive sequence in the human genome. Besides mediating its own retrotransposition, L1 can mobilize Alu and messenger RNA (mRNA in trans, and probably also SVA and non-coding RNA. The structures of L1 copies and trans-mobilized retrocopies are variable and can be classified into three categories: full-length; 5'-truncated; and 5'-inverted insertions. These structures may be generated by different 5' integration mechanisms. Results In this study, a method to correctly characterize insertions with short target site duplications (TSDs is developed and extranucleotides, TSDs and microhomologies (MHs at junctions were analysed for the three types of insertions. Only 5'-truncated L1 insertions were found to be associated with short TSDs. Both full-length and 5'-truncated retrotransposed sequences in trans, including Alu, SVA and mRNA retrocopies and also full-length and 5'-inverted L1, were not associated with short TSDs, indicating the difference of 5' attachment between retrotransposition in cis and retrotransposition in trans. Target sequence analysis suggested that short TSDs were generated in an L1 endonuclease-dependent manner. The MHs were longer for 5'-inverted L1 than for 5'-truncated L1, indicating less dependence on annealing in 5'-truncated L1 insertions. Conclusions The results suggest that insertions flanked by short TSDs occur more often coupled with the insertion of 5'-truncated L1 than with those of other types of insertions in vivo. The method used in this study can be used to characterize elements without any apparent boundary structures.

  1. The flexible C-terminal arm of the Lassa arenavirus Z-protein mediates interactions with multiple binding partners.

    Science.gov (United States)

    May, Eric R; Armen, Roger S; Mannan, Aristotle M; Brooks, Charles L

    2010-08-01

    The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation, and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics (MD) was used to refine the structures, which were then subsequently clustered. Population-weighted ensembles of low-energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was identified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during MD trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein-binding recognition motifs for Tsg101 and eIF4E and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. (c) 2010 Wiley-Liss, Inc.

  2. G protein-mediated signaling in the myogenic response – role of Rho-kinase and aging

    DEFF Research Database (Denmark)

    Björling, Karl; Joseph, Philomeena Daphne; Egebjerg, Kristian

    2017-01-01

    . Aim: 1) to investigate the signaling events from Gq/11 and/or G12 activation to MT development; 2) to elucidate the impact of aging. We used pressure myography, calcium imaging, Q-PCR and immunofluorescence to study small (lumen D ...M) suppressed MT development. The Phosholipase C inhibitors U73122 (0.5 µM) and ET18-OCH3 (10 µM) robustly inhibited MT, and the TRPC channel blocker SKF 96365 (10 µM) slightly reduced MT. There was a significant effect of age (P

  3. G protein-mediated signaling in the myogenic response – role of Rho-kinase and aging

    DEFF Research Database (Denmark)

    Björling, Karl; Joseph, Philomeena Daphne; Egebjerg, Kristian

    . Aim: 1) to investigate the signaling events from Gq/11 and/or G12 activation to MT development; 2) to elucidate the impact of aging. We used pressure myography, calcium imaging, Q-PCR and immunofluorescence to study small (lumen D ...M) suppressed MT development. The Phosholipase C inhibitors U73122 (0.5 µM) and ET18-OCH3 (10 µM) robustly inhibited MT, and the TRPC channel blocker SKF 96365 (10 µM) slightly reduced MT. There was a significant effect of age (P

  4. Electron microscopic visualization of the RecA protein-mediated pairing and branch migration phases of DNA strand exchange

    DEFF Research Database (Denmark)

    Register, JC; Christiansen, Gunna; Griffith, J

    1987-01-01

    examined by electron microscopy: supertwisted double-stranded (ds) DNA and linear single-stranded (ss) DNA, linear dsDNA and circular ssDNA, and linear dsDNA and colinear ssDNA. Several major observations were: (i) with RecA protein bound to the DNA, plectonemic joints were ultrastructurally...

  5. MDM2 Antagonist Nutlin-3a Reverses Mitoxantrone Resistance by Inhibiting Breast Cancer Resistance Protein Mediated Drug Transport

    Science.gov (United States)

    Zhang, Fan; Throm, Stacy L.; Murley, Laura L.; Miller, Laura A.; Zatechka, D. Steven; Guy, R. Kiplin; Kennedy, Rachel; Stewart, Clinton F.

    2011-01-01

    Breast cancer resistance protein (BCRP; ABCG2), a clinical marker for identifying the side population (SP) cancer stem cell subgroup, affects intestinal absorption, brain penetration, hepatobiliary excretion, and multidrug resistance of many anti-cancer drugs. Nutlin-3a is currently under pre-clinical investigation in a variety of solid tumor and leukemia models as a p53 reactivation agent, and has been recently demonstrated to also have p53 independent actions in cancer cells. In the present study, we first report that nutlin-3a can inhibit the efflux function of BCRP. We observed that although the nutlin-3a IC50 did not differ between BCRP over-expressing and vector control cells, nutlin-3a treatment significantly potentiated the cells to treatment with the BCRP substrate mitoxantrone. Combination index calculations suggested synergism between nutlin-3a and mitoxantrone in cell lines over-expressing BCRP. Upon further investigation, it was confirmed that nutlin-3a increased the intracellular accumulation of BCRP substrates such as mitoxantrone and Hoechst 33342 in cells expressing functional BCRP without altering the expression level or localization of BCRP. Interestingly, nutlin-3b, considered virtually “inactive” in disrupting the MDM2/p53 interaction, reversed Hoechst 33342 efflux with the same potency as nutlin-3a. Intracellular accumulation and bi-directional transport studies using MDCKII cells suggested that nutlin-3a is not a substrate of BCRP. Additionally, an ATPase assay using Sf9 insect cell membranes over-expressing wild-type BCRP indicated that nutlin-3a inhibits BCRP ATPase activity in a dose-dependent fashion. In conclusion, our studies demonstrate that nutlin-3a inhibits BCRP efflux function, which consequently reverses BCRP-related drug resistance. PMID:21459080

  6. Non-essential MCM-related proteins mediate a response to DNA damage in the archaeon Methanococcus maripaludis.

    Science.gov (United States)

    Walters, Alison D; Chong, James P J

    2017-05-01

    The single minichromosome maintenance (MCM) protein found in most archaea has been widely studied as a simplified model for the MCM complex that forms the catalytic core of the eukaryotic replicative helicase. Organisms of the order Methanococcales are unusual in possessing multiple MCM homologues. The Methanococcus maripaludis S2 genome encodes four MCM homologues, McmA-McmD. DNA helicase assays reveal that the unwinding activity of the three MCM-like proteins is highly variable despite sequence similarities and suggests additional motifs that influence MCM function are yet to be identified. While the gene encoding McmA could not be deleted, strains harbouring individual deletions of genes encoding each of the other MCMs display phenotypes consistent with these proteins modulating DNA damage responses. M. maripaludis S2 is the first archaeon in which MCM proteins have been shown to influence the DNA damage response.

  7. Destabilization of Heterologous Proteins Mediated by the GSK3β Phosphorylation Domain of the β-Catenin Protein

    Directory of Open Access Journals (Sweden)

    Yuhan Kong

    2013-11-01

    Full Text Available Background and Aims: Wnt/β-catenin signaling plays important roles in development and cellular processes. The hallmark of canonical Wnt signaling activation is the stabilization of β-catenin protein in cytoplasm and/or nucleus. The stability of β-catenin is the key to its biological functions and is controlled by the phosphorylation of its amino-terminal degradation domain. Aberrant activation of β-catenin signaling has been implicated in the development of human cancers. It has been recently suggested that GSK3βmay play an essential role in regulating global protein turnover. Here, we investigate if the GSK3β phosphorylation site-containing degradation domain of β-catenin is sufficient to destabilize heterologous proteins. Methods and Results: We engineer chimeric proteins by fusing β-catenin degradation domain at the N- and/or C-termini of the enhanced green fluorescent protein (eGFP. In both transient and stable expression experiments, the chimeric GFP proteins exhibit a significantly decreased stability, which can be effectively antagonized by lithium and Wnt1. An activating mutation in the destruction domain significantly stabilizes the fusion protein. Furthermore, GSK3 inhibitor SB-216763 effectively increases the GFP signal of the fusion protein. Conversely, the inhibition of Wnt signaling with tankyrase inhibitor XAV939 results in a decrease in GFP signal of the fusion proteins, while these small molecules have no significant effects on the mutant destruction domain-GFP fusion protein. Conclusion: Our findings strongly suggest that the β-catenin degradation domain may be sufficient to destabilize heterologous proteins in Wnt signaling-dependent manner. It is conceivable that the chimeric GFP proteins may be used as a functional reporter to measure the dynamic status of β-catenin signaling, and to identify potential anticancer drugs that target β-catenin signaling.

  8. Fem1b, a proapoptotic protein, mediates proteasome inhibitor-induced apoptosis of human colon cancer cells.

    Science.gov (United States)

    Subauste, M Cecilia; Sansom, Owen J; Porecha, Nehal; Raich, Natacha; Du, Liqin; Maher, Joseph F

    2010-02-01

    In the treatment of colon cancer, the development of resistance to apoptosis is a major factor in resistance to therapy. New molecular approaches to overcome apoptosis resistance, such as selectively upregulating proapoptotic proteins, are needed in colon cancer therapy. In a mouse model with inactivation of the adenomatous polyposis coli (Apc) tumor suppressor gene, reflecting the pathogenesis of most human colon cancers, the gene encoding feminization-1 homolog b (Fem1b) is upregulated in intestinal epithelium following Apc inactivation. Fem1b is a proapoptotic protein that interacts with apoptosis-inducing proteins Fas, tumor necrosis factor receptor-1 (TNFR1), and apoptotic protease activating factor-1 (Apaf-1). Increasing Fem1b expression induces apoptosis of cancer cells, but effects on colon cancer cells have not been reported. Fem1b is a homolog of feminization-1 (FEM-1), a protein in Caenorhabditis elegans that is regulated by proteasomal degradation, but whether Fem1b is likewise regulated by proteasomal degradation is unknown. Herein, we found that Fem1b protein is expressed in primary human colon cancer specimens, and in malignant SW620, HCT-116, and DLD-1 colon cancer cells. Increasing Fem1b expression, by transfection of a Fem1b expression construct, induced apoptosis of these cells. We found that proteasome inhibitor treatment of SW620, HCT-116, and DLD-1 cells caused upregulation of Fem1b protein levels, associated with induction of apoptosis. Blockade of Fem1b upregulation with morpholino antisense oligonucleotide suppressed the proteasome inhibitor-induced apoptosis of these cells. In conclusion, the proapoptotic protein Fem1b is downregulated by the proteasome in malignant colon cancer cells and mediates proteasome inhibitor-induced apoptosis of these cells. Therefore, Fem1b could represent a novel molecular target to overcome apoptosis resistance in therapy of colon cancer.

  9. Multiscale approaches to protein-mediated interactions between membranes—relating microscopic and macroscopic dynamics in radially growing adhesions

    International Nuclear Information System (INIS)

    Bihr, Timo; Smith, Ana-Suncana; Seifert, Udo

    2015-01-01

    Macromolecular complexation leading to coupling of two or more cellular membranes is a crucial step in a number of biological functions of the cell. While other mechanisms may also play a role, adhesion always involves the fluctuations of deformable membranes, the diffusion of proteins and the molecular binding and unbinding. Because these stochastic processes couple over a multitude of time and length scales, theoretical modeling of membrane adhesion has been a major challenge. Here we present an effective Monte Carlo scheme within which the effects of the membrane are integrated into local rates for molecular recognition. The latter step in the Monte Carlo approach enables us to simulate the nucleation and growth of adhesion domains within a system of the size of a cell for tens of seconds without loss of accuracy, as shown by comparison to 10 6 times more expensive Langevin simulations. To perform this validation, the Langevin approach was augmented to simulate diffusion of proteins explicitly, together with reaction kinetics and membrane dynamics. We use the Monte Carlo scheme to gain deeper insight to the experimentally observed radial growth of micron sized adhesion domains, and connect the effective rate with which the domain is growing to the underlying microscopic events. We thus demonstrate that our technique yields detailed information about protein transport and complexation in membranes, which is a fundamental step toward understanding even more complex membrane interactions in the cellular context. (paper)

  10. Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells

    DEFF Research Database (Denmark)

    Zheng, Lin; Terman, Alexei; Hallbeck, Martin

    2011-01-01

    and accumulation of Aβ within lysosomes, induced apoptosis in differentiated SH-SY5Y neuroblastoma cells. Cells under hyperoxia showed: (1) increased numbers of autophagic vacuoles that contained amyloid precursor protein (APP) as well as Aβ monomers and oligomers, (2) increased reactive oxygen species production...... and resulting lysosomal Aβ accumulation are essential for oxidant-induced apoptosis in cultured neuroblastoma cells and provide additional support for the interactive role of oxidative stress and the lysosomal system in AD-related neurodegeneration....

  11. Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.

    Science.gov (United States)

    Zhang, Juan; Yong, Yue; Li, Xing; Hu, Yu; Wang, Jian; Wang, Yong-qiang; Song, Wei; Chen, Wen-ting; Xie, Jian; Chen, Xue-mei; Lv, Xin; Hou, Li-li; Wang, Ke; Zhou, Jia; Wang, Xiang-rui; Song, Jian-gang

    2015-10-26

    Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion.

  12. Staurosporine and extracellular matrix proteins mediate the conversion of small cell lung carcinoma cells into a neuron-like phenotype.

    Directory of Open Access Journals (Sweden)

    Tamara Murmann

    Full Text Available Small cell lung carcinomas (SCLCs represent highly aggressive tumors with an overall five-year survival rate in the range of 5 to 10%. Here, we show that four out of five SCLC cell lines reversibly develop a neuron-like phenotype on extracellular matrix constituents such as fibronectin, laminin or thrombospondin upon staurosporine treatment in an RGD/integrin-mediated manner. Neurite-like processes extend rapidly with an average speed of 10 µm per hour. Depending on the cell line, staurosporine treatment affects either cell cycle arrest in G2/M phase or induction of polyploidy. Neuron-like conversion, although not accompanied by alterations in the expression pattern of a panel of neuroendocrine genes, leads to changes in protein expression as determined by two-dimensional gel electrophoresis. It is likely that SCLC cells already harbour the complete molecular repertoire to convert into a neuron-like phenotype. More extensive studies are needed to evaluate whether the conversion potential of SCLC cells is suitable for therapeutic interventions.

  13. A NIN-LIKE PROTEIN mediates nitrate-induced control of root nodule symbiosis in Lotus japonicus.

    Science.gov (United States)

    Nishida, Hanna; Tanaka, Sachiko; Handa, Yoshihiro; Ito, Momoyo; Sakamoto, Yuki; Matsunaga, Sachihiro; Betsuyaku, Shigeyuki; Miura, Kenji; Soyano, Takashi; Kawaguchi, Masayoshi; Suzaki, Takuya

    2018-02-05

    Legumes and rhizobia establish symbiosis in root nodules. To balance the gains and costs associated with the symbiosis, plants have developed two strategies for adapting to nitrogen availability in the soil: plants can regulate nodule number and/or stop the development or function of nodules. Although the former is accounted for by autoregulation of nodulation, a form of systemic long-range signaling, the latter strategy remains largely enigmatic. Here, we show that the Lotus japonicus NITRATE UNRESPONSIVE SYMBIOSIS 1 (NRSYM1) gene encoding a NIN-LIKE PROTEIN transcription factor acts as a key regulator in the nitrate-induced pleiotropic control of root nodule symbiosis. NRSYM1 accumulates in the nucleus in response to nitrate and directly regulates the production of CLE-RS2, a root-derived mobile peptide that acts as a negative regulator of nodule number. Our data provide the genetic basis for how plants respond to the nitrogen environment and control symbiosis to achieve proper plant growth.

  14. Forum on specification and Design Languages

    CERN Document Server

    Maehne, Torsten

    2015-01-01

    This book brings together a selection of the best papers from the sixteenth edition of the Forum on specification and Design Languages Conference (FDL), which was held in September 2013 in Paris, France. FDL is a well-established international forum devoted to dissemination of research results, practical experiences and new ideas in the application of specification, design and verification languages to the design, modeling and verification of integrated circuits, complex hardware/software embedded systems, and mixed-technology systems. • Covers applications of formal methods for specification, verification and debug; • Includes embedded analog and mixed-signal system design; • Enables model-driven engineering for embedded systems design and development.

  15. Safety of MR liver specific contrast media

    Energy Technology Data Exchange (ETDEWEB)

    Bellin, Marie-France [Hopital Paul Brousse, Universite Paris 11, Villejuif Cedex (France); Webb, Judith A.W. [St. Bartholomew' s Hospital, Department of Diagnostic Imaging, London (United Kingdom); Molen, Aart J. van der [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands); Thomsen, Henrik S. [Copenhagen University Hospital at Herlev, Department of Diagnostic Radiology 54E2, Herlev (Denmark); Morcos, Sameh K. [Northern General Hospital, Sheffield Teaching Hospitals NHS Trust, Department of Diagnostic Imaging, Sheffield (United Kingdom)

    2005-08-01

    Over the past few years a number of magnetic resonance (MR) liver specific contrast agents have been introduced. In this report the safety issues of these agents are addressed. A literature search was carried out. Based on the available information, simple guidelines on the safety issue of liver specific contrast agents have been produced by the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The report and guidelines were discussed at the 11th European Symposium on Urogenital Radiology in Santiago de Compostela. Liver specific contrast agents appear in general to be safe and well tolerated. However, the incidence of adverse reactions with iron oxides and the intravenous manganese based agent seems to be slightly higher than with gadolinium based agents. However, no safety information from comparative clinical trials has been published. Guidelines on the safety aspects are presented. (orig.)

  16. Safety of MR liver specific contrast media

    International Nuclear Information System (INIS)

    Bellin, Marie-France; Webb, Judith A.W.; Molen, Aart J. van der; Thomsen, Henrik S.; Morcos, Sameh K.

    2005-01-01

    Over the past few years a number of magnetic resonance (MR) liver specific contrast agents have been introduced. In this report the safety issues of these agents are addressed. A literature search was carried out. Based on the available information, simple guidelines on the safety issue of liver specific contrast agents have been produced by the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The report and guidelines were discussed at the 11th European Symposium on Urogenital Radiology in Santiago de Compostela. Liver specific contrast agents appear in general to be safe and well tolerated. However, the incidence of adverse reactions with iron oxides and the intravenous manganese based agent seems to be slightly higher than with gadolinium based agents. However, no safety information from comparative clinical trials has been published. Guidelines on the safety aspects are presented. (orig.)

  17. Procedures for evaluating technical specifications (PETS)

    International Nuclear Information System (INIS)

    Samanta, P.K.; Boccio, J.L.; Vesely, W.E.

    1987-01-01

    In this paper, aspects of technical specifications relating to Generic Issues B-56 and B-61 are discussed from a risk-standpoint. These primarily deal with the risk issues associated with (1) adaptive diesel test requirements/surveillance test intervals, and (2) the effectiveness of cumulative outage time requirements for controlling downtime risk. Risk and reliability approaches are presented which (1) allow risk-acceptable test intervals to be determined for any diesel and (2) show the potential risk-control capability of prescribed allowed cumulative outage times. This work was conducted through NRC's Procedures for Evaluating Technical Specifications (PETS) Program. The overall objective of this program is to develop and demonstrate methodologies that utilize risk insights and reliability techniques for evaluating the scope, detailed requirements, and safety impact of plant technical specifications

  18. Technical specifications requirements: Automated reasoning applications

    International Nuclear Information System (INIS)

    Lidsky, L.M.; Dobrzeniecki, A.B.

    1990-03-01

    Several software systems were developed and tested to determine what advantages could be gained from explicitly translating complicated regulatory requirements into computerized relationships. The Technical Specifications for US nuclear power plants were chosen as the test-bed application domain, and two analysis systems were developed to monitor plant compliance with operational limits, and track and schedule equipment test and maintenance activities mandated by Technical Specifications. Choosing PROLOG as the computer language to represent these regulatory requirements resulted in a natural match between the semantic structure of the written specifications and the corollary coded rules. Additional research results affirmed the utility of declarative programming styles, explicit management of problem complexity, and attention to the robustness and flexibility of the overall software systems. 5 refs., 2 figs

  19. Specifications for human factors guiding documents

    Energy Technology Data Exchange (ETDEWEB)

    Rhodes, W; Szlapetis, I; MacGregor, C [Rhodes and Associates Inc., Toronto, ON (Canada)

    1995-04-01

    This report specifies the content, function and appearance of three proposed human factors guiding documents to be used by the Atomic Energy Control board and its licensees. These three guiding documents, to be developed at a later date, are: (a) Human Factors Process Guide; (b) Human Factors Activities Guide; and (c) Human Factors Design Integration Guide. The specifications were developed by examining the best documents as identified in a previous contract with the AECB (Review of Human Factors Guidelines and Methods by W. Rhodes, I. Szlapetis et al. 1992), and a brief literature review. The best features and content were selected from existing documents and used to develop specifications for the guiding documents. The developer of the actual guides would use these specifications to produce comprehensive and consolidated documents at a later date. (author). 128 ref., 7 figs.

  20. Specifications for human factors guiding documents

    International Nuclear Information System (INIS)

    Rhodes, W.; Szlapetis, I.; MacGregor, C.

    1995-04-01

    This report specifies the content, function and appearance of three proposed human factors guiding documents to be used by the Atomic Energy Control board and its licensees. These three guiding documents, to be developed at a later date, are: (a) Human Factors Process Guide; (b) Human Factors Activities Guide; and (c) Human Factors Design Integration Guide. The specifications were developed by examining the best documents as identified in a previous contract with the AECB (Review of Human Factors Guidelines and Methods by W. Rhodes, I. Szlapetis et al. 1992), and a brief literature review. The best features and content were selected from existing documents and used to develop specifications for the guiding documents. The developer of the actual guides would use these specifications to produce comprehensive and consolidated documents at a later date. (author). 128 ref., 7 figs

  1. Property Specification Patterns for intelligence building software

    Science.gov (United States)

    Chun, Seungsu

    2018-03-01

    In this paper, through the property specification pattern research for Modal MU(μ) logical aspects present a single framework based on the pattern of intelligence building software. In this study, broken down by state property specification pattern classification of Dwyer (S) and action (A) and was subdivided into it again strong (A) and weaknesses (E). Through these means based on a hierarchical pattern classification of the property specification pattern analysis of logical aspects Mu(μ) was applied to the pattern classification of the examples used in the actual model checker. As a result, not only can a more accurate classification than the existing classification systems were easy to create and understand the attributes specified.

  2. Emergency Medicine Gender-specific Education.

    Science.gov (United States)

    Ashurst, John V; McGregor, Alyson J; Safdar, Basmah; Weaver, Kevin R; Quinn, Shawn M; Rosenau, Alex M; Goyke, Terrence E; Roth, Kevin R; Greenberg, Marna R

    2014-12-01

    The 2014 Academic Emergency Medicine consensus conference has taken the first step in identifying gender-specific care as an area of importance to both emergency medicine (EM) and research. To improve patient care, we need to address educational gaps in this area concurrent with research gaps. In this article, the authors highlight the need for sex- and gender-specific education in EM and propose guidelines for medical student, resident, and faculty education. Specific examples of incorporating this content into grand rounds, simulation, bedside teaching, and journal club sessions are reviewed. Future challenges and strategies to fill the gaps in the current education model are also described. © 2014 by the Society for Academic Emergency Medicine.

  3. Computational network design from functional specifications

    KAUST Repository

    Peng, Chi Han

    2016-07-11

    Connectivity and layout of underlying networks largely determine agent behavior and usage in many environments. For example, transportation networks determine the flow of traffic in a neighborhood, whereas building floorplans determine the flow of people in a workspace. Designing such networks from scratch is challenging as even local network changes can have large global effects. We investigate how to computationally create networks starting from only high-level functional specifications. Such specifications can be in the form of network density, travel time versus network length, traffic type, destination location, etc. We propose an integer programming-based approach that guarantees that the resultant networks are valid by fulfilling all the specified hard constraints and that they score favorably in terms of the objective function. We evaluate our algorithm in two different design settings, street layout and floorplans to demonstrate that diverse networks can emerge purely from high-level functional specifications.

  4. Transactions in domain-specific information systems

    Science.gov (United States)

    Zacek, Jaroslav

    2017-07-01

    Substantial number of the current information system (IS) implementations is based on transaction approach. In addition, most of the implementations are domain-specific (e.g. accounting IS, resource planning IS). Therefore, we have to have a generic transaction model to build and verify domain-specific IS. The paper proposes a new transaction model for domain-specific ontologies. This model is based on value oriented business process modelling technique. The transaction model is formalized by the Petri Net theory. First part of the paper presents common business processes and analyses related to business process modeling. Second part defines the transactional model delimited by REA enterprise ontology paradigm and introduces states of the generic transaction model. The generic model proposal is defined and visualized by the Petri Net modelling tool. Third part shows application of the generic transaction model. Last part of the paper concludes results and discusses a practical usability of the generic transaction model.

  5. Spent nuclear fuel project product specification

    International Nuclear Information System (INIS)

    Pajunen, A.L.

    1998-01-01

    Product specifications are limits and controls established for each significant parameter that potentially affects safety and/or quality of the Spent Nuclear Fuel (SNF) packaged for transport to dry storage. The product specifications in this document cover the spent fuel packaged in MultiCanister Overpacks (MCOs) to be transported throughout the SNF Project. The SNF includes N Reactor fuel and single-pass reactor fuel. The FRS removes the SNF from the storage canisters, cleans it, and places it into baskets. The MCO loading system places the baskets into MCO/Cask assembly packages. These packages are then transferred to the Cold Vacuum Drying (CVD) Facility. After drying at the CVD Facility, the MCO cask packages are transferred to the Canister Storage Building (CSB), where the MCOs are removed from the casks, staged, inspected, sealed (by welding), and stored until a suitable permanent disposal option is implemented. The key criteria necessary to achieve these goals are documented in this specification

  6. Naturally occurring, tumor-specific, therapeutic proteins.

    Science.gov (United States)

    Argiris, Konstantinos; Panethymitaki, Chrysoula; Tavassoli, Mahvash

    2011-05-01

    The emerging approach to cancer treatment known as targeted therapies offers hope in improving the treatment of therapy-resistant cancers. Recent understanding of the molecular pathogenesis of cancer has led to the development of targeted novel drugs such as monoclonal antibodies, small molecule inhibitors, mimetics, antisense and small interference RNA-based strategies, among others. These compounds act on specific targets that are believed to contribute to the development and progression of cancers and resistance of tumors to conventional therapies. Delivered individually or combined with chemo- and/or radiotherapy, such novel drugs have produced significant responses in certain types of cancer. Among the most successful novel compounds are those which target tyrosine kinases (imatinib, trastuzumab, sinutinib, cetuximab). However, these compounds can cause severe side-effects as they inhibit pathways such as epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor, which are also important for normal functions in non-transformed cells. Recently, a number of proteins have been identified which show a remarkable tumor-specific cytotoxic activity. This toxicity is independent of tumor type or specific genetic changes such as p53, pRB or EGFR aberrations. These tumor-specific killer proteins are either derived from common human and animal viruses such as E1A, E4ORF4 and VP3 (apoptin) or of cellular origin, such as TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and MDA-7 (melanoma differentiation associated-7). This review aims to present a current overview of a selection of these proteins with preferential toxicity among cancer cells and will provide an insight into the possible mechanism of action, tumor specificity and their potential as novel tumor-specific cancer therapeutics.

  7. Engineered waste-package-system design specification

    International Nuclear Information System (INIS)

    1983-05-01

    This report documents the waste package performance requirements and geologic and waste form data bases used in developing the conceptual designs for waste packages for salt, tuff, and basalt geologies. The data base reflects the latest geotechnical information on the geologic media of interest. The parameters or characteristics specified primarily cover spent fuel, defense high-level waste, and commercial high-level waste forms. The specification documents the direction taken during the conceptual design activity. A separate design specification will be developed prior to the start of the preliminary design activity

  8. Automated effect-specific mammographic pattern measures

    DEFF Research Database (Denmark)

    Raundahl, Jakob; Loog, Marco; Pettersen, Paola

    2008-01-01

    We investigate the possibility to develop methodologies for assessing effect specific structural changes of the breast tissue using a general statistical machine learning framework. We present an approach of obtaining objective mammographic pattern measures quantifying a specific biological effect......, such as hormone replacement therapy (HRT). We compare results using this approach to using standard density measures. We show that the proposed method can quantify both age related effects and effects caused by HRT. Age effects are significantly detected by our method where standard methodologies fail...

  9. System specifications for the NDS EXFOR System

    International Nuclear Information System (INIS)

    Attree, P.M.; Smith, P.M.

    1979-07-01

    EXFOR is the agreed exchange format for the magnetic-tape exchange of nuclear reaction data between national and international nuclear data centres for the benefit of nuclear data users in all countries. The NDS EXFOR System is a computerized system for the storage and retrieval of EXFOR information compiled or received by the IAEA. This document is an internal manual for the system specifications of the NDS EXFOR System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. The manual is updated from time to time when system modifications are made

  10. Technical specifications for PWR secondary water chemistry

    International Nuclear Information System (INIS)

    Weeks, J.R.; van Rooyen, D.

    1977-08-01

    The bases for establishing Technical Specifications for PWR secondary water chemistry are reviewed. Whereas extremely stringent control of secondary water needs to be maintained to prevent denting in some units, sound bases for establishing limits that will prevent stress corrosion, wastage, and denting do not exist at the present time. This area is being examined very thoroughly by industry-sponsored research programs. Based on the evidence available to date, short term control limits are suggested; establishment of these or other limits as Technical Specifications is not recommended until the results of the research programs have been obtained and evaluated

  11. Asian product specifications to tighten by 2000

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    The Asia/Pacific region is characterized by much diversity in environmental standards for petroleum products. Specifications in Japan, for example, are quite stringent, while, in India, kerosene--even that used for cooking or lighting--may contain as much as 0.2% sulfur. Widhyawan Prawiraatmadja and Fereidun Fesharaki of the East-West Center in Honolulu outlined regional product quality in a report titled, ''Trends in Petroleum Product Specifications in the Asia-Pacific Region: A Supply/Demand Analysis and Government Policy Responses.'' This paper summarizes the findings of this report with emphasis on gasoline, diesel fuels, and fuel oil demand, fuel consumption, and quality

  12. Site-Specific Infrared Probes of Proteins

    Science.gov (United States)

    Ma, Jianqiang; Pazos, Ileana M.; Zhang, Wenkai; Culik, Robert M.; Gai, Feng

    2015-01-01

    Infrared spectroscopy has played an instrumental role in studying a wide variety of biological questions. However, in many cases it is impossible or difficult to rely on the intrinsic vibrational modes of biological molecules of interest, such as proteins, to reveal structural and/or environmental information in a site-specific manner. To overcome this limitation, many recent efforts have been dedicated to the development and application of various extrinsic vibrational probes that can be incorporated into biological molecules and used to site-specifically interrogate their structural and/or environmental properties. In this Review, we highlight some recent advancements of this rapidly growing research area. PMID:25580624

  13. Clojure for domain-specific languages

    CERN Document Server

    Kelker, Ryan D

    2013-01-01

    An example-oriented approach to develop custom domain-specific languages.If you've already developed a few Clojure applications and wish to expand your knowledge on Clojure or domain-specific languages in general, then this book is for you. If you're an absolute Clojure beginner, then you may only find the detailed examples of the core Clojure components of value. If you've developed DSLs in other languages, this Lisp and Java-based book might surprise you with the power of Clojure.

  14. Photomask specifications for high energy physics detectors

    CERN Document Server

    Pindo, M

    2002-01-01

    Planar technologies used for radiation detector fabrication imply an extensive use of photomasks whose characteristics are critical in determining final detector performance. Compatibly with their manufacturing process, photomasks must satisfy the application-specific requirements dictated both by wafer manufacturers and detector final users. The design and realization of microstrip and pixel detectors, widely used in high energy physics experiments, ask for intensive scientific effort, advanced technology and important economical investments. Photomask specification definition is one of the fundamental steps to optimize detector fabrication processes and fulfill experimental requirements at the most appropriate cost.

  15. System specifications for the NDS EXFOR System

    Energy Technology Data Exchange (ETDEWEB)

    Attree, P M; Smith, P M

    1982-06-01

    EXFOR is the agreed exchange format for the magnetic-tape exchange of nuclear reaction data between national and international nuclear data centers for the benefit of nuclear data users in all countries. The NDS EXFOR System is a computerized system for the storage and retrieval of EXFOR information compiled or received of the IAEA. This document is an internal manual for the system specifications of the NDS EXFOR System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. The manual is updated from time to time when system modifications are made; the first version was issued in July 1979. (author)

  16. Immunotherapy with GD2 specific monoclonal antibodies

    International Nuclear Information System (INIS)

    Cheung, N.K.V.; Medof, E.M.; Munn, D.

    1988-01-01

    Targeted immunotherapy focuses anti-tumor activity of antibodies and effector cells, which are actively developed by the host or adoptively transferred, onto tumor cells and into tumor sites. Such tumor selective therapy can be more specific and efficient. The value of such an approach is evident in the classical interaction of antibodies. This paper reports that the ganglioside G D2 is an ideal antigen for specific tumor targeting because of its relative lack of heterogeneity among human neuroblastoma, its high density on tumor cells, its lack of antigen modulation upon binding to antibody, and its restricted distribution in normal tissues

  17. A Class-Specific Optimizing Compiler

    Directory of Open Access Journals (Sweden)

    Michael D. Sharp

    1993-01-01

    Full Text Available Class-specific optimizations are compiler optimizations specified by the class implementor to the compiler. They allow the compiler to take advantage of the semantics of the particular class so as to produce better code. Optimizations of interest include the strength reduction of class:: array address calculations, elimination of large temporaries, and the placement of asynchronous send/recv calls so as to achieve computation/communication overlap. We will outline our progress towards the implementation of a C++ compiler capable of incorporating class-specific optimizations.

  18. DOE site-specific threat assessment

    International Nuclear Information System (INIS)

    West, D.J.; Al-Ayat, R.A.; Judd, B.R.

    1985-01-01

    A facility manager faced with the challenges of protecting a nuclear facility against potential threats must consider the likelihood and consequences of such threats, know the capabilities of the facility safeguards and security systems, and make informed decisions about the cost-effectivness of safeguards and security upgrades. To help meet these challenges, the San Francisco Operations Office of the Department of Energy, in conjunction with the Lawrence Livermore Laboratory, has developed a site-specific threat assessment approach and a quantitative model to improve the quality and consistency of site-specific threat assessment and resultant security upgrade decisions at sensitive Department of Energy facilities. 5 figs

  19. Software engineering with application-specific languages

    Science.gov (United States)

    Campbell, David J.; Barker, Linda; Mitchell, Deborah; Pollack, Robert H.

    1993-01-01

    Application-Specific Languages (ASL's) are small, special-purpose languages that are targeted to solve a specific class of problems. Using ASL's on software development projects can provide considerable cost savings, reduce risk, and enhance quality and reliability. ASL's provide a platform for reuse within a project or across many projects and enable less-experienced programmers to tap into the expertise of application-area experts. ASL's have been used on several software development projects for the Space Shuttle Program. On these projects, the use of ASL's resulted in considerable cost savings over conventional development techniques. Two of these projects are described.

  20. System specifications for the NDS Dictionary System

    International Nuclear Information System (INIS)

    Attree, P.M.; Smith, P.M.

    1979-09-01

    The NDS Dictionary System is a computerized system for maintaining and distributing the EXFOR dictionaries and for preparing internal versions of these dictionaries for use in the NDS EXFOR System and other NDS systems. This document is an internal manual for the system specifications of the NDS Dictionary System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. This manual is updated from time to time when system modifications are made; this is the version of January 1979

  1. [Development of domain specific search engines].

    Science.gov (United States)

    Takai, T; Tokunaga, M; Maeda, K; Kaminuma, T

    2000-01-01

    As cyber space exploding in a pace that nobody has ever imagined, it becomes very important to search cyber space efficiently and effectively. One solution to this problem is search engines. Already a lot of commercial search engines have been put on the market. However these search engines respond with such cumbersome results that domain specific experts can not tolerate. Using a dedicate hardware and a commercial software called OpenText, we have tried to develop several domain specific search engines. These engines are for our institute's Web contents, drugs, chemical safety, endocrine disruptors, and emergent response for chemical hazard. These engines have been on our Web site for testing.

  2. Specifications from a biotechnology industry perspective.

    Science.gov (United States)

    Garnick, R L

    1997-01-01

    The emergence of new analytical technology and the production of pharmaceuticals for a global market in a cost-effective manner necessitate the establishment of worldwide specifications that are appropriate for the product and the manufacturing process. This requires a thorough knowledge of the protein and control of the systems that produce it as well as an understanding of the accuracy and precision of the assays used for testing. Harmonization of specifications among the worldwide regulatory authorities is critical for the future development of new pharmaceuticals. A continuing dialogue between industry and regulators to achieve this goal needs to be encouraged and supported.

  3. From UML Specification into FPGA Implementation

    Directory of Open Access Journals (Sweden)

    Grzegorz Bazydlo

    2014-01-01

    Full Text Available In the paper a method of using the Unified Modeling Language for specification of digital systems, especially logic controllers, is presented. The proposed method is based mainly on the UML state machine diagrams and uses Hierarchical Concurrent Finite State Machines (HCFSMs as a temporary model. The paper shows a way to transform the UML diagrams, expressed in XML language, to the form that is acceptable by reconfigurable FPGAs (Field Programmable Gate Arrays. The UML specification is used to generate an effective program in Hardware Description Languages (HDLs, especially Verilog.

  4. Domain Specific Language Support for Exascale

    Energy Technology Data Exchange (ETDEWEB)

    Sadayappan, Ponnuswamy [The Ohio State Univ., Columbus, OH (United States)

    2017-02-24

    Domain-Specific Languages (DSLs) offer an attractive path to Exascale software since they provide expressive power through appropriate abstractions and enable domain-specific optimizations. But the advantages of a DSL compete with the difficulties of implementing a DSL, even for a narrowly defined domain. The DTEC project addresses how a variety of DSLs can be easily implemented to leverage existing compiler analysis and transformation capabilities within the ROSE open source compiler as part of a research program focusing on Exascale challenges. The OSU contributions to the DTEC project are in the area of code generation from high-level DSL descriptions, as well as verification of the automatically-generated code.

  5. NEEDS ANALYSIS IN ENGLISH FOR SPECIFIC PURPOSES

    Directory of Open Access Journals (Sweden)

    SIMION MINODORA OTILIA

    2015-03-01

    Full Text Available Needs analysis is considered to be the cornerstone of English for Specific Purposes(ESP. The concept of Needs analysis has been different along the decades. At the initial stages of ESP( the 1960s and early 1970s, needs analysis consisted in assessing the communicative needs of the learners and the techniques of achieving specific teaching objectives. Nowadays, the tasks of needs analysis is much more complex: it aims at collecting information about the learners and at defining the target situation and environment of studying ESP.

  6. Spent Nuclear Fuel (SNF) Project Product Specification

    International Nuclear Information System (INIS)

    PAJUNEN, A.L.

    2000-01-01

    The process for removal of Spent Nuclear Fuel (SNF) from the K Basins has been divided into major sub-systems. The Fuel Retrieval System (FRS) removes fuel from the existing storage canisters, cleans it, and places it into baskets. The multi-canister overpack (MCO) loading system places the baskets into an MCO that has been pre-loaded in a cask. The cask, containing a loaded MCO, is then transferred to the Cold Vacuum Drying (CVD) Facility. After drying at the CVD Facility, the cask, and MCO, are transferred to the Canister Storage Building (CSB), where the MCO is removed from the cask, staged, inspected, sealed (by welding), and stored until a suitable permanent disposal option is implemented. The purpose of this document is to specify the process related characteristics of an MCO at the interface between major process systems. The characteristics are derived from the primary technical documents that form the basis for safety analysis and design calculations. This document translates the calculation assumptions into implementation requirements and describes the method of verifying that the requirement is achieved. These requirements are used to define validation test requirements and describe requirements that influence multiple sub-project safety analysis reports. This product specification establishes limits and controls for each significant process parameter at interfaces between major sub-systems that potentially affect the overall safety and/or quality of the SNF packaged for processing, transport, and interim dry storage. The product specifications in this document cover the SNF packaged in MCOs to be transported throughout the SNF Project. The description of the product specifications are organized in the document as follows: Section 2.0--Summary listing of product specifications at each major sub-system interface. Section 3.0--Summary description providing guidance as to how specifications are complied with by equipment design or processing within a major

  7. Spent Nuclear Fuel (SNF) Project Product Specification

    Energy Technology Data Exchange (ETDEWEB)

    PAJUNEN, A.L.

    2000-12-07

    The process for removal of Spent Nuclear Fuel (SNF) from the K Basins has been divided into major sub-systems. The Fuel Retrieval System (FRS) removes fuel from the existing storage canisters, cleans it, and places it into baskets. The multi-canister overpack (MCO) loading system places the baskets into an MCO that has been pre-loaded in a cask. The cask, containing a loaded MCO, is then transferred to the Cold Vacuum Drying (CVD) Facility. After drying at the CVD Facility, the cask, and MCO, are transferred to the Canister Storage Building (CSB), where the MCO is removed from the cask, staged, inspected, sealed (by welding), and stored until a suitable permanent disposal option is implemented. The purpose of this document is to specify the process related characteristics of an MCO at the interface between major process systems. The characteristics are derived from the primary technical documents that form the basis for safety analysis and design calculations. This document translates the calculation assumptions into implementation requirements and describes the method of verifying that the requirement is achieved. These requirements are used to define validation test requirements and describe requirements that influence multiple sub-project safety analysis reports. This product specification establishes limits and controls for each significant process parameter at interfaces between major sub-systems that potentially affect the overall safety and/or quality of the SNF packaged for processing, transport, and interim dry storage. The product specifications in this document cover the SNF packaged in MCOs to be transported throughout the SNF Project. The description of the product specifications are organized in the document as follows: Section 2.0--Summary listing of product specifications at each major sub-system interface. Section 3.0--Summary description providing guidance as to how specifications are complied with by equipment design or processing within a major

  8. Ultrahigh Specific Impulse Nuclear Thermal Propulsion

    Energy Technology Data Exchange (ETDEWEB)

    Anne Charmeau; Brandon Cunningham; Samim Anghaie

    2009-02-09

    Research on nuclear thermal propulsion systems (NTP) have been in forefront of the space nuclear power and propulsion due to their design simplicity and their promise for providing very high thrust at reasonably high specific impulse. During NERVA-ROVER program in late 1950's till early 1970's, the United States developed and ground tested about 18 NTP systems without ever deploying them into space. The NERVA-ROVER program included development and testing of NTP systems with very high thrust (~250,000 lbf) and relatively high specific impulse (~850 s). High thrust to weight ratio in NTP systems is an indicator of high acceleration that could be achieved with these systems. The specific impulse in the lowest mass propellant, hydrogen, is a function of square root of absolute temperature in the NTP thrust chamber. Therefor optimizing design performance of NTP systems would require achieving the highest possible hydrogen temperature at reasonably high thrust to weight ratio. High hydrogen exit temperature produces high specific impulse that is a diret measure of propellant usage efficiency.

  9. Language specific bootstraps for UG categories

    NARCIS (Netherlands)

    van Kampen, N.J.

    2005-01-01

    This paper argues that the universal categories N/V are not applied to content words before the grammatical markings for reference D(eterminers) and predication I(nflection) have been acquired (van Kampen, 1997, contra Pinker, 1984). Child grammar starts as proto-grammar with language-specific

  10. DETERMINATION OF THE SPECIFIC GROWTH RATE ON ...

    African Journals Online (AJOL)

    Sewage generation is one of the dense problems Nigerians encounter on daily bases, mostly at the urbanized area where factories and industries are located. This paper is aimed at determining the specific growth rate “K” of biological activities on cassava wastewater during degradation using Michaelis-Menten Equation.

  11. Side-Specific Reward Memories in Honeybees

    Science.gov (United States)

    Gil, Mariana; Menzel, Randolf; De Marco, Rodrigo J.

    2009-01-01

    We report a hitherto unknown form of side-specific learning in honeybees. We trained bees individually by coupling gustatory and mechanical stimulation of each antenna with either increasing or decreasing volumes of sucrose solution offered to the animal's proboscis along successive learning trials. Next, we examined their proboscis extension…

  12. Autobiographical Memory Specificity in Dissociative Identity Disorder

    NARCIS (Netherlands)

    Huntjens, R.J.C.; Wessel, I.; Hermans, D.; Minnen, A. van

    2014-01-01

    A lack of adequate access to autobiographical knowledge has been related to psychopathology. More specifically, patients suffering from depression or a history of trauma have been found to be characterized by overgeneral memory, in other words, they show a relative difficulty in retrieving a

  13. Autobiographical memory specificity in dissociative identity disorder

    NARCIS (Netherlands)

    Huntjens, Rafaële J. C.; Wessel, Ineke; Hermans, Dirk; van Minnen, Agnes

    A lack of adequate access to autobiographical knowledge has been related to psychopathology. More specifically, patients suffering from depression or a history of trauma have been found to be characterized by overgeneral memory, in other words, they show a relative difficulty in retrieving a

  14. Patient-specific models of cardiac biomechanics

    Science.gov (United States)

    Krishnamurthy, Adarsh; Villongco, Christopher T.; Chuang, Joyce; Frank, Lawrence R.; Nigam, Vishal; Belezzuoli, Ernest; Stark, Paul; Krummen, David E.; Narayan, Sanjiv; Omens, Jeffrey H.; McCulloch, Andrew D.; Kerckhoffs, Roy C. P.

    2013-07-01

    Patient-specific models of cardiac function have the potential to improve diagnosis and management of heart disease by integrating medical images with heterogeneous clinical measurements subject to constraints imposed by physical first principles and prior experimental knowledge. We describe new methods for creating three-dimensional patient-specific models of ventricular biomechanics in the failing heart. Three-dimensional bi-ventricular geometry is segmented from cardiac CT images at end-diastole from patients with heart failure. Human myofiber and sheet architecture is modeled using eigenvectors computed from diffusion tensor MR images from an isolated, fixed human organ-donor heart and transformed to the patient-specific geometric model using large deformation diffeomorphic mapping. Semi-automated methods were developed for optimizing the passive material properties while simultaneously computing the unloaded reference geometry of the ventricles for stress analysis. Material properties of active cardiac muscle contraction were optimized to match ventricular pressures measured by cardiac catheterization, and parameters of a lumped-parameter closed-loop model of the circulation were estimated with a circulatory adaptation algorithm making use of information derived from echocardiography. These components were then integrated to create a multi-scale model of the patient-specific heart. These methods were tested in five heart failure patients from the San Diego Veteran's Affairs Medical Center who gave informed consent. The simulation results showed good agreement with measured echocardiographic and global functional parameters such as ejection fraction and peak cavity pressures.

  15. Community-Specific Strategies of Intergenerational Language ...

    African Journals Online (AJOL)

    This study concerns minority language maintenance, specifically it explores local practices that make it possible for a community to sustain its traditional language. Two variables were the focus of the research; speakers' attitudes and language use patterns. These were examined to determine their influence in facilitating ...

  16. SPECIFICITY IN DEVELOPMENT OF CONSTRUCTION INDUSTRY

    Directory of Open Access Journals (Sweden)

    O. S. Golubova

    2012-01-01

    Full Text Available Specificity in development of construction industry of the Republic of Belarus determines  character of competition on the construction market, forms a pricing, marketing and product policy of building companies. Construction represents itself as a highly developed complex where interaction of business entities is of rather complicated multilateral character.

  17. Essential Specification Elements for Heat Exchanger Replacement

    Energy Technology Data Exchange (ETDEWEB)

    Bower, L.

    2015-07-01

    Performance upgrade and equipment degradation are the primary impetuses for a nuclear power plant to engage in the large capital cost project of heat exchanger replacement. Along with attention to these issues, consideration of heat exchanger Codes and Standards, material improvements, thermal redesign, and configuration are essential for developing User’s Design Specifications for successful replacement projects. The User’s Design Specification is the central document in procuring ASME heat exchangers. Properly stated objectives for the heat exchanger replacement are essential for obtaining the materials, configurations and thermal designs best suited for the nuclear power plant. Additionally, the code of construction required and the applied manufacturing standard (TEMA or HEI) affects how the heat exchanger may be designed or configured to meet the replacement goals. Knowledge of how Codes and Standards affect design and configuration details will aid in writing the User’s Design Specification. Joseph Oat Corporation has designed and fabricated many replacement heat exchangers for the nuclear power industry. These heat exchangers have been constructed per ASME Section III to various Code-Years or ASME Section VIII-1 to the current Code-Year also in accordance with TEMA and HEI. These heat exchangers have been a range of like-for-like replacement to complete thermal, material and configuration redesigns. Several examples of these heat exchangers with their Code, Standard and specification implications are presented. (Author.

  18. Research overview : design specifications for hybrid vehicles

    NARCIS (Netherlands)

    Hofman, T.; Druten, van R.M.

    2004-01-01

    In this paper a method is proposed for determination of the design specifications regarding the energy exchange systems for different chargesustaining hybrid vehicles of different vehicle classes. Hybrid drivetrains for vehicles combine multiple power sources in order to increase the driving

  19. Isotope specific arbitrary material flow meter

    Science.gov (United States)

    Barty, Christopher P. J.; Post, John C.; Jones, Edwin

    2016-10-25

    A laser-based mono-energetic gamma-ray source is used to provide non-destructive and non-intrusive, quantitative determination of the absolute amount of a specific isotope contained within pipe as part of a moving fluid or quasi-fluid material stream.

  20. Composing a Tumor Specific Bacterial Promoter.

    Directory of Open Access Journals (Sweden)

    Igor V Deyneko

    Full Text Available Systemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules. Specificity of such delivery is solely depending on promoter sequences that control the production of a target molecule. We have established the functional structure of bacterial promoters that are transcriptionally active exclusively in tumor tissues after systemic application. We observed that the specific transcriptional activation is accomplished by a combination of a weak basal promoter and a strong FNR binding site. This represents a minimal set of control elements required for such activation. In natural promoters, additional DNA remodeling elements are found that alter the level of transcription quantitatively. Inefficiency of the basal promoter ensures the absence of transcription outside tumors. As a proof of concept, we compiled an artificial promoter sequence from individual motifs representing FNR and basal promoter and showed specific activation in a tumor microenvironment. Our results open possibilities for the generation of promoters with an adjusted level of expression of target proteins in particular for applications in bacterial tumor therapy.

  1. Specific Ion Effects in Cholesterol Monolayers

    Directory of Open Access Journals (Sweden)

    Teresa Del Castillo-Santaella

    2016-05-01

    Full Text Available The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl2 and MgCl2 on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance and theoretically (molecular dynamics (MD all-atomic simulations. We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces.

  2. Measurement of low-temperature specific heat

    International Nuclear Information System (INIS)

    Stewart, G.R.

    1983-01-01

    The measurement of low-temperature specific heat (LTSH) (0.1 K< T<60 K) has seen a number of breakthroughs both in design concepts and instrumentation in the last 15 years: particularly in small sample calorimetry. This review attempts to provide an overview of both large and small sample calorimetry techniques at temperatures below 60 K, with sufficient references to enable more detailed study. A comprehensive review is made of the most reliable measurements of the LTSH of 84 of the elements to illustrate briefly some of the problems of measurements and analysis, as well as to provide additional references. More detail is devoted to three special areas of low-temperature calorimetry that have seen rapid development recently: (1) measurement of the specific heat of highly radioactive samples, (2) measurement of the specific heat of materials in high magnetic fields (18 T), and (3) measurement of the specific heat of very small (100 μg) samples. The review ends with a brief discussion of the frontier research currently underway on microcalorimetry for nanogram sample weights

  3. Specificity, Transfer, and the Development of Expertise

    Science.gov (United States)

    Brookes, David T.; Ross, Brian H.; Mestre, Jose P.

    2011-01-01

    In this paper we present the results of two experiments designed to understand how physics students' learning of the concept of refraction is influenced by the cognitive phenomenon of "specificity." In both experiments participants learned why light bends as it travels from one optical medium to another with an analogy made to a car…

  4. 21 CFR 107.100 - Nutrient specifications.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Nutrient specifications. 107.100 Section 107.100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Maximum level Protein Grams 1.8 4.5 Fat do 3.3 6.0 Percent calories 30 54 Linoleic acid Milligrams 300...

  5. Population specific analysis of Yakut exomes

    NARCIS (Netherlands)

    Zlobin, A. S.; Sharapov, S. Sh.; Guryev, V. P.; Bevova, M. R.; Tsepilov, Y. A.; Sivtseva, T. M.; Boyarskih, U. A.; Sokolova, E. A.; Aulchenko, Y. S.; Filipenko, M. L.; Osakovsky, V. L.

    We studied the genetic diversity of the Yakut population using exome sequencing. We performed comparative analysis of the Yakut population and the populations that are included in the "1000 Genomes" project and we identified the alleles specific to the Yakut population. We showed, that the Yakuts

  6. Brayton Isotope Power System (BIPS) facility specification

    International Nuclear Information System (INIS)

    1976-01-01

    General requirements for the Brayton Isotope Power System (BIPS)/Ground Demonstration System (GDS) assembly and test facility are defined. The facility will include provisions for a complete test laboratory for GDS checkout, performance, and endurance testing, and a contamination-controlled area for assembly, fabrication, storage, and storage preparation of GDS components. Specifications, schedules, and drawings are included

  7. Prospects for site specific weed management

    DEFF Research Database (Denmark)

    Christensen, Svend; Rasmussen, Jesper; Pedersen, Søren Marcus

    2014-01-01

    Research on Site Specific Weed Management (SSWM) started in the late 80's. Since that moment, considerable research has been conducted on different aspects of SSWM, from fundamental studies on the spatial ecology of weeds to the applied development and testing of new technologies for weed detection...

  8. Social-psychological specific of individual adaptation

    OpenAIRE

    Ovsyanik, Olga

    2012-01-01

    There is analyzing of specific of social-psychological adaptation person by model of adaptation. Structure model of adaptation of women of our age group, which was named “adaptation complex” was made by theoretic analyzes of problem of adaptation adult.

  9. Structural similarity and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, Ian; Paulson, Olaf B

    2004-01-01

    It has been suggested that category-specific recognition disorders for natural objects may reflect that natural objects are more structurally (visually) similar than artefacts and therefore more difficult to recognize following brain damage. On this account one might expect a positive relationshi...

  10. Methodes for identification of specific language impairment

    Directory of Open Access Journals (Sweden)

    Toktam Maleki Shahmahmood

    2014-06-01

    Full Text Available Background and Aim: Specific language impiarment (SLI is one of the most prevalent developmental language disorders its diagnosis is a problematic issue among researchers and clinicians because of the heterogeneity of language profiles in the affected population and overlapping with other developmental language disorders. The aim of this study was to review the suggested diagnostic criteria for this disorder, controversies about these criteria and identify the most accurate diagnostic methods.Methods: Published article from 1980 to 2012 in bibliographic and publisher databases including Pubmed, Google scholar, Cochran library, Web of Science, ProQuest, Springer, Oxford, Science direct, Ovid, Iran Medex and Magiran about the diagnostic methods for discriminating preschoool children with specific language impiarment from normal developing children were reviewd in this article. These keywords were used for research: “specific language impairment”, “SLI”, “diagnosis or identification”, “standardized tests”, and “tests for language development”.Conclusion: The results of this study show inspite of agreement of researchers and clinicians about exclusionary criteria as one basic part of the diagnosis of specific language impiarment , there is no consensus about the other part, inclusionary criteria. Different studies used different inclusionary criteria which can be divided to categories of clincal judgment, discrepancy-based criteria, standardized testing, clinical markers and markers from spontaneous speech samples. Advantages, disadvantages, and clinical applicability of each diagnostic method are discussed in this article.

  11. IPv6-specific misconfigurations in the DNS

    NARCIS (Netherlands)

    Hendriks, Luuk; de Boer, Pieter-Tjerk; Pras, Aiko

    2017-01-01

    With the Internet transitioning from IPv4 to IPv6, the number of IPv6-specific DNS records (AAAA) increases. Misconfigurations in these records often go unnoticed, as most systems are provided with connectivity over both IPv4 and IPv6, and automatically fall back to IPv4 in case of connection

  12. 31 CFR 595.312 - Specific license.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 595.312 Section 595.312 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS General Definitions...

  13. Ultrasonic hydrometer. [Specific gravity of electrolyte

    Science.gov (United States)

    Swoboda, C.A.

    1982-03-09

    The disclosed ultrasonic hydrometer determines the specific gravity (density) of the electrolyte of a wet battery, such as a lead-acid battery. The hydrometer utilizes a transducer that when excited emits an ultrasonic impulse that traverses through the electrolyte back and forth between spaced sonic surfaces. The transducer detects the returning impulse, and means measures the time t between the initial and returning impulses. Considering the distance d between the spaced sonic surfaces and the measured time t, the sonic velocity V is calculated with the equation V = 2d/t. The hydrometer also utilizes a thermocouple to measure the electrolyte temperature. A hydrometer database correlates three variable parameters including sonic velocity in and temperature and specific gravity of the electrolyte, for temperature values between 0 and 40/sup 0/C and for specific gravity values between 1.05 and 1.30. Upon knowing two parameters (the calculated sonic velocity and the measured temperature), the third parameter (specific gravity) can be uniquely found in the database. The hydrometer utilizes a microprocessor for data storage and manipulation.

  14. COMPARATIVE STUDY ON SPECIFIC AND EARLY DETECTION ...

    African Journals Online (AJOL)

    The objective of this study was to compare the sensitivity and specificity of smear and culture methods with rapid serological EIA myco kits manufactured by Omega diagnostics, for the early detection of Mycobacterium tuberculosis (MTB) complex. Sera from various categories of smear and culture results were compared ...

  15. 32 CFR 292.4 - Specific policy.

    Science.gov (United States)

    2010-07-01

    ... INFORMATION ACT PROGRAM DEFENSE INTELLIGENCE AGENCY (DIA) FREEDOM OF INFORMATION ACT § 292.4 Specific policy... of source and object codes, regardless of medium are not agency records. (This does not include the... existing computer program or printout for retrieval of the requested information. (c) The prior application...

  16. Radioimmunoassay for a human prostate specific antigen

    International Nuclear Information System (INIS)

    Machida, T.; Miki, M.; Ohishi, Y.; Kido, A.; Morikawa, J.; Ogawa, Y.

    1983-01-01

    As a marker for prostatic cancer, a prostate-specific antigen was purified from human prostatic tissues. Double antibody radioimmunoassay utilizing immune reaction was developed on the basis of the purified prostatic antigen (PA). Measurement results have revealed that PA radioimmunoassay is much better than prostatic acid phosphatase (PAP) radioimmunoassay in the diagnosis of prostatic cancer

  17. Justifying group-specific common morality.

    Science.gov (United States)

    Strong, Carson

    2008-01-01

    Some defenders of the view that there is a common morality have conceived such morality as being universal, in the sense of extending across all cultures and times. Those who deny the existence of such a common morality often argue that the universality claim is implausible. Defense of common morality must take account of the distinction between descriptive and normative claims that there is a common morality. This essay considers these claims separately and identifies the nature of the arguments for each claim. It argues that the claim that there is a universal common morality in the descriptive sense has not been successfully defended to date. It maintains that the claim that there is a common morality in the normative sense need not be understood as universalist. This paper advocates the concept of group specific common morality, including country-specific versions. It suggests that both the descriptive and the normative claims that there are country-specific common moralities are plausible, and that a country-specific normative common morality could provide the basis for a country's bioethics.

  18. Modular specification of real-time systems

    DEFF Research Database (Denmark)

    Inal, Recep

    1994-01-01

    Duration Calculus, a real-time interval logic, has been embedded in the Z specification language to provide a notation for real-time systems that combines the modularisation and abstraction facilities of Z with a logic suitable for reasoning about real-time properties. In this article the notation...

  19. Canine specific ELISA for coagulation factor VII

    DEFF Research Database (Denmark)

    Knudsen, Tom; Kjelgaard-Hansen, Mads; Tranholm, Mikael

    2011-01-01

    available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable...

  20. Specificity of Structural Assessment of Knowledge

    Science.gov (United States)

    Trumpower, David L.; Sharara, Harold; Goldsmith, Timothy E.

    2010-01-01

    This study examines the specificity of information provided by structural assessment of knowledge (SAK). SAK is a technique which uses the Pathfinder scaling algorithm to transform ratings of concept relatedness into network representations (PFnets) of individuals' knowledge. Inferences about individuals' overall domain knowledge based on the…

  1. Parallel object-oriented specification language

    NARCIS (Netherlands)

    Florescu, O.; Voeten, J.P.M.; Theelen, B.D.; Geilen, M.C.W.; Corporaal, H.; Burns, Alan

    2008-01-01

    The Parallel Object-Oriented Specification Language (POOSL) is an expressive modelling language for hardware/software systems [10]. It was originally defined in [7] as an object-oriented extension of process algebra CCS [6], supporting (conditional) synchronous message passing between

  2. Primary Auditory Cortex Regulates Threat Memory Specificity

    Science.gov (United States)

    Wigestrand, Mattis B.; Schiff, Hillary C.; Fyhn, Marianne; LeDoux, Joseph E.; Sears, Robert M.

    2017-01-01

    Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used…

  3. 48 CFR 836.202 - Specifications.

    Science.gov (United States)

    2010-10-01

    ... specifications. (b) During the design stage, contract architect-engineers must not use “brand name or equal” or... phase, prior to award of a contract for design. (c) If VA has determined that only one product will meet.... This clause places bidders on notice that the “brand name or equal” provisions of the clause found at...

  4. Specificity in liquid metal induced embrittlement

    CSIR Research Space (South Africa)

    Fernandes, PJL

    1996-12-01

    Full Text Available One of the most intriguing features of liquid metal induced embrittlement (LMIE) is the observation that some liquid metal-solid metal couples are susceptible to embrittlement, while others appear to be immune. This is referred to as the specificity...

  5. Age-Specific Correlates of Child Growth

    NARCIS (Netherlands)

    M. Rieger (Matthias); S.K. Trommlerová (Sofia Karina)

    2016-01-01

    textabstractGrowth faltering describes a widespread phenomenon that height- and weight-for-age of children in developing countries collapse rapidly in the first two years of life. We study age-specific correlates of child nutrition using Demographic and Health Surveys from 56 developing countries to

  6. Brayton Isotope Power System (BIPS) facility specification

    Energy Technology Data Exchange (ETDEWEB)

    1976-05-31

    General requirements for the Brayton Isotope Power System (BIPS)/Ground Demonstration System (GDS) assembly and test facility are defined. The facility will include provisions for a complete test laboratory for GDS checkout, performance, and endurance testing, and a contamination-controlled area for assembly, fabrication, storage, and storage preparation of GDS components. Specifications, schedules, and drawings are included.

  7. 12 CFR 347.119 - Specific consent.

    Science.gov (United States)

    2010-01-01

    ... processing procedure. (d) Specific consent. Direct or indirect investments in or activities of foreign... control such organization as a result of a foreign investment; or (ii) A bank would be establishing a... foreign country. (1) Applicable law or practice in the foreign country where the foreign organization or...

  8. TAL effectors specificity stems from negative discrimination.

    Directory of Open Access Journals (Sweden)

    Basile I M Wicky

    Full Text Available Transcription Activator-Like (TAL effectors are DNA-binding proteins secreted by phytopathogenic bacteria that interfere with native cellular functions by binding to plant DNA promoters. The key element of their architecture is a domain of tandem-repeats with almost identical sequences. Most of the polymorphism is located at two consecutive amino acids termed Repeat Variable Diresidue (RVD. The discovery of a direct link between the RVD composition and the targeted nucleotide allowed the design of TAL-derived DNA-binding tools with programmable specificities that revolutionized the field of genome engineering. Despite structural data, the molecular origins of this specificity as well as the recognition mechanism have remained unclear. Molecular simulations of the recent crystal structures suggest that most of the protein-DNA binding energy originates from non-specific interactions between the DNA backbone and non-variable residues, while RVDs contributions are negligible. Based on dynamical and energetic considerations we postulate that, while the first RVD residue promotes helix breaks--allowing folding of TAL as a DNA-wrapping super-helix--the second provides specificity through a negative discrimination of matches. Furthermore, we propose a simple pharmacophore-like model for the rationalization of RVD-DNA interactions and the interpretation of experimental findings concerning shared affinities and binding efficiencies. The explanatory paradigm presented herein provides a better comprehension of this elegant architecture and we hope will allow for improved designs of TAL-derived biotechnological tools.

  9. Accounting valuation development of specific assets

    Directory of Open Access Journals (Sweden)

    I.V. Zhigley

    2017-12-01

    Full Text Available The current issues of accounting estimate development are considered. The necessity of the development of accounting estimate in the context of the non-institutional theory principles based on the selection of a number of reasons is grounded. The reasons for deterioration of accounting reputation as a separate socio-economic institute in the context of developing the methodology for specific assets accounting are discovered. The system of normative regulation of accounting estimate of enterprise non-current assets in the case of diminishing their usefulness is analyzed. The procedure for determining and accounting for the depreciation of assets in accordance with IFRS 36 «Depreciation of Assets» is developed. The features of the joint use of the concept of «value in use» and «fair value» in the accounting system are disclosed. The procedure for determining the value of compensation depending on the degree of specificity of assets is developed. The necessity to clarify the features that indicate the possibility of diminishing the usefulness of specific assets (termination or pre-term termination of the contract for the use of a specific asset is grounded.

  10. Iron addition to soil specifically stabilized lignin

    Science.gov (United States)

    Steven J. Hall; Whendee L. Silver; Vitaliy I. Timokhin; Kenneth E. Hammel

    2016-01-01

    The importance of lignin as a recalcitrant constituent of soil organic matter (SOM) remains contested. Associations with iron (Fe) oxides have been proposed to specifically protect lignin from decomposition, but impacts of Fe-lignin interactions on mineralization rates remain unclear. Oxygen (O2) fluctuations characteristic of humid tropical...

  11. Chapter 9: Questions from CNEN specific exams

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2018-04-01

    The following are real questions from CNEN specific exams for obtaining the certification of RSO for gamma irradiators. These are questions that require essay answers, that are interpretative ones and therefore that may accept more than one interpretation, therefore more than one answer. For this reason, suggestions of answers will be presented in the second part of this chapter.

  12. 14 CFR 29.1397 - Color specifications.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Color specifications. 29.1397 Section 29.1397 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT...) Aviation green— x is not greater than 0.440−0.320y; x is not greater than y−0.170; and y is not less than 0...

  13. 14 CFR 23.1397 - Color specifications.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Color specifications. 23.1397 Section 23.1397 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... greater than 0.002. (b) Aviation green— x is not greater than 0.440−0.320y; x is not greater than y−0.170...

  14. 14 CFR 25.1397 - Color specifications.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Color specifications. 25.1397 Section 25.1397 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT...) Aviation green— x is not greater than 0.440−0.320y ; x is not greater than y−0.170; and y is not less than...

  15. 14 CFR 27.1397 - Color specifications.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Color specifications. 27.1397 Section 27.1397 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT...) Aviation green— x is not greater than 0.440−0.320y; x is not greater than y−0.170; and y is not less than 0...

  16. MODEL OF TEACHING PROFESSION SPECIFIC BILATERAL TRANSLATION

    Directory of Open Access Journals (Sweden)

    Yana Fabrychna

    2017-03-01

    Full Text Available The article deals with the author’s interpretation of the process of teaching profession specific bilateral translation to student teacher of English in the Master’s program. The goal of the model of teaching profession specific bilateral translation development is to determine the logical sequence of educational activities of the teacher as the organizer of the educational process and students as its members. English and Ukrainian texts on methods of foreign languages and cultures teaching are defined as the object of study. Learning activities aimed at the development of student teachers of English profession specific competence in bilateral translation and Translation Proficiency Language Portfolio for Student Teachers of English are suggested as teaching tools. The realization of the model of teaching profession specific bilateral translation to student teachers of English in the Master’s program is suggested within the module topics of the academic discipline «Practice of English as the first foreign language»: Globalization; Localization; Education; Work; The role of new communication technologies in personal and professional development. We believe that the amount of time needed for efficient functioning of the model is 48 academic hours, which was determined by calculating the total number of academic hours allotted for the academic discipline «Practice of English as the first foreign language» in Ukrainian universities. Peculiarities of the model realization as well as learning goals and content of class activities and home self-study work of students are outlined.

  17. Slicing AADL specifications for model checking

    NARCIS (Netherlands)

    Odenbrett, M.R.; Nguyen, V.Y.; Noll, T.

    2010-01-01

    To combat the state-space explosion problem in model checking larger systems, abstraction techniques can be employed. Here, methods that operate on the system specification before constructing its state space are preferable to those that try to minimize the resulting transition system as they

  18. [The "specific" liability regime for blood products].

    Science.gov (United States)

    Byk, Christian

    2017-10-13

    Based on the system of liability for defective products as organized by the European Directive of 25 July 1985, responsibility for blood products does not therefore constitute a genuine specific regime. However, European law leaves States a margin of discretion in the implementation of the Directive with regard to health products. This is the case in particular with the exemption for development risk.

  19. Digital PET compliance to EARL accreditation specifications

    NARCIS (Netherlands)

    Koopman, Daniëlle; Groot Koerkamp, Maureen; Jager, Pieter L.; Arkies, Hester; Knollema, Siert; Slump, Cornelis H.; Sanches, Pedro G.; van Dalen, Jorn A.

    2017-01-01

    Background: Our aim was to evaluate if a recently introduced TOF PET system with digital photon counting technology (Philips Healthcare), potentially providing an improved image quality over analogue systems, can fulfil EANM research Ltd (EARL) accreditation specifications for tumour imaging with

  20. Chapter 9: Questions from CNEN specific exams

    International Nuclear Information System (INIS)

    2018-01-01

    The following are real questions from CNEN specific exams for obtaining the certification of RSO for gamma irradiators. These are questions that require essay answers, that are interpretative ones and therefore that may accept more than one interpretation, therefore more than one answer. For this reason, suggestions of answers will be presented in the second part of this chapter

  1. Standard specification for agencies performing nondestructive testing

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2009-01-01

    1.1 This specification covers minimum requirements for agencies performing nondestructive testing (NDT). 1.2 When using this specification to assess the capability of, or to accredit NDT agencies, Guide E 1359 shall be used as a basis for the survey. It can be supplemented as necessary with more detail in order to meet the auditor's specific needs. 1.3 This specification can be used as a basis to evaluate testing or inspection agencies, or both, and is intended for use for the qualifying or accrediting, or both, of testing or inspection agencies, public or private. 1.4 The use of SI or inch-pound units, or combination thereof, will be the responsibility of the technical committee whose standards are referred to in this standard. 1.5 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to...

  2. NIF small optics laser damage test specifications

    International Nuclear Information System (INIS)

    Sheehan, L

    1999-01-01

    The Laser Damage Group is currently conducting tests on small optics samples supplied for initial evaluation of potential NIF suppliers. This document is meant to define the specification of laser-induced damage for small optics and the test methods used to collect the data. A rating system which will be applied for vendor selection is presented

  3. Spent nuclear fuel project product specification

    International Nuclear Information System (INIS)

    PAJUNEN, A.L.

    1999-01-01

    This document establishes the limits and controls for the significant parameters that could potentially affect the safety and/or quality of the Spent Nuclear Fuel (SNF) packaged for processing, transport, and storage. The product specifications in this document cover the SNF packaged in Multi-Canister Overpacks to be transported throughout the SNF Project

  4. A camera specification for tendering purposes

    International Nuclear Information System (INIS)

    Lunt, M.J.; Davies, M.D.; Kenyon, N.G.

    1985-01-01

    A standardized document is described which is suitable for sending to companies which are being invited to tender for the supply of a gamma camera. The document refers to various features of the camera, the performance specification of the camera, maintenance details, price quotations for various options and delivery, installation and warranty details. (U.K.)

  5. Teaching Case: Enterprise Architecture Specification Case Study

    Science.gov (United States)

    Steenkamp, Annette Lerine; Alawdah, Amal; Almasri, Osama; Gai, Keke; Khattab, Nidal; Swaby, Carval; Abaas, Ramy

    2013-01-01

    A graduate course in enterprise architecture had a team project component in which a real-world business case, provided by an industry sponsor, formed the basis of the project charter and the architecture statement of work. The paper aims to share the team project experience on developing the architecture specifications based on the business case…

  6. Ontology Assisted Formal Specification Extraction from Text

    Directory of Open Access Journals (Sweden)

    Andreea Mihis

    2010-12-01

    Full Text Available In the field of knowledge processing, the ontologies are the most important mean. They make possible for the computer to understand better the natural language and to make judgments. In this paper, a method which use ontologies in the semi-automatic extraction of formal specifications from a natural language text is proposed.

  7. Cell-specific targeting by heterobivalent ligands.

    Science.gov (United States)

    Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

    2011-07-20

    Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

  8. microRNA expression during trophectoderm specification.

    Directory of Open Access Journals (Sweden)

    Srinivas R Viswanathan

    2009-07-01

    Full Text Available Segregation of the trophectoderm from the inner cell mass of the embryo represents the first cell-fate decision of mammalian development. Transcription factors essential for specifying trophectoderm have been identified, but the role of microRNAs (miRNAs in modulating this fate-choice has been largely unexplored. We have compared miRNA expression in embryonic stem cell (ESC-derived trophectoderm and in staged murine embryos to identify a set of candidate miRNAs likely to be involved in trophectoderm specification.We profiled embryonic stem cells (ESCs as they were induced to differentiate into trophectodermal cells by ectopic expression of HRas/Q61L. We also profiled murine embryos at progressive stages of preimplantation development (zygote, 2-cell, 4-cell, 8-cell, morula, and blastocyst, which includes the time window in which the trophectoderm is specified in vivo Q61L/H.We describe miRNA expression changes that occur during trophectoderm specification and validate that our in vitro system faithfully recapitulates trophectoderm specification in vivo. By comparing our in vitro and in vivo datasets, we have identified a minimal set of candidate miRNAs likely to play a role in trophectoderm specification. These miRNAs are predicted to regulate a host of development-associated target genes, and many of these miRNAs have previously reported roles in development and differentiation. Additionally, we highlight a number of miRNAs whose tight developmental regulation may reflect a functional role in other stages of embryogenesis. Our embryo profiling data may be useful to investigators studying trophectoderm specification and other stages of preimplantation development.

  9. Hepatocyte specific expression of human cloned genes

    Energy Technology Data Exchange (ETDEWEB)

    Cortese, R

    1986-01-01

    A large number of proteins are specifically synthesized in the hepatocyte. Only the adult liver expresses the complete repertoire of functions which are required at various stages during development. There is therefore a complex series of regulatory mechanisms responsible for the maintenance of the differentiated state and for the developmental and physiological variations in the pattern of gene expression. Human hepatoma cell lines HepG2 and Hep3B display a pattern of gene expression similar to adult and fetal liver, respectively; in contrast, cultured fibroblasts or HeLa cells do not express most of the liver specific genes. They have used these cell lines for transfection experiments with cloned human liver specific genes. DNA segments coding for alpha1-antitrypsin and retinol binding protein (two proteins synthesized both in fetal and adult liver) are expressed in the hepatoma cell lines HepG2 and Hep3B, but not in HeLa cells or fibroblasts. A DNA segment coding for haptoglobin (a protein synthesized only after birth) is only expressed in the hepatoma cell line HepG2 but not in Hep3B nor in non hepatic cell lines. The information for tissue specific expression is located in the 5' flanking region of all three genes. In vivo competition experiments show that these DNA segments bind to a common, apparently limiting, transacting factor. Conventional techniques (Bal deletions, site directed mutagenesis, etc.) have been used to precisely identify the DNA sequences responsible for these effects. The emerging picture is complex: they have identified multiple, separate transcriptional signals, essential for maximal promoter activation and tissue specific expression. Some of these signals show a negative effect on transcription in fibroblast cell lines.

  10. Hand Specific Representations in Language Comprehension

    Directory of Open Access Journals (Sweden)

    Claire eMoody-Triantis

    2014-06-01

    Full Text Available Theories of embodied cognition argue that language comprehension involves sensory-motor re-enactments of the actions described. However, the degree of specificity of these re-enactments as well as the relationship between action and language remains a matter of debate. Here we investigate these issues by examining how hand-specific information (left or right hand is recruited in language comprehension and action execution. An fMRI study tested right-handed participants in two separate tasks that were designed to be as similar as possible to increase sensitivity of the comparison across task: an action execution go/no-go task where participants performed right or left hand actions, and a language task where participants read sentences describing the same left or right handed actions as in the execution task. We found that language-induced activity did not match the hand-specific patterns of activity found for action execution in primary somatosensory and motor cortex, but it overlapped with pre-motor and parietal regions associated with action planning. Within these pre-motor regions, both right hand actions and sentences elicited stronger activity than left hand actions and sentences - a dominant hand effect -. Importantly, both dorsal and ventral sections of the left pre-central gyrus were recruited by both tasks, suggesting different action features being recruited. These results suggest that (a language comprehension elicits motor representations that are hand-specific and akin to multimodal action plans, rather than full action re-enactments; and (b language comprehension and action execution share schematic hand-specific representations that are richer for the dominant hand, and thus linked to previous motor experience.

  11. Are videogame training gains specific or general?

    Science.gov (United States)

    Oei, Adam C; Patterson, Michael D

    2014-01-01

    Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the "common demands" hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements.

  12. Are videogame training gains specific or general?

    Directory of Open Access Journals (Sweden)

    Adam C. Oei

    2014-04-01

    Full Text Available Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames. Playing action games (e.g., Call of Duty, Medal of Honor is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the action videogames because the action videogames and laboratory tasks contain similar demands. We review studies of action and non-action videogames to show support for the latter proposal. To explain transfer in action videogames, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking, rapid attentional switches, and peripheral vision. In non-action videogames, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g, Tetris. In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning. Thus, the common demands hypothesis of transfer not only characterizes transfer effects in action videogames, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements.

  13. Are videogame training gains specific or general?

    Science.gov (United States)

    Patterson, Michael D.

    2014-01-01

    Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the “common demands” hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements. PMID:24782722

  14. Hand specific representations in language comprehension.

    Science.gov (United States)

    Moody-Triantis, Claire; Humphreys, Gina F; Gennari, Silvia P

    2014-01-01

    Theories of embodied cognition argue that language comprehension involves sensory-motor re-enactments of the actions described. However, the degree of specificity of these re-enactments as well as the relationship between action and language remains a matter of debate. Here we investigate these issues by examining how hand-specific information (left or right hand) is recruited in language comprehension and action execution. An fMRI study tested self-reported right-handed participants in two separate tasks that were designed to be as similar as possible to increase sensitivity of the comparison across task: an action execution go/no-go task where participants performed right or left hand actions, and a language task where participants read sentences describing the same left or right handed actions as in the execution task. We found that language-induced activity did not match the hand-specific patterns of activity found for action execution in primary somatosensory and motor cortex, but it overlapped with pre-motor and parietal regions associated with action planning. Within these pre-motor regions, both right hand actions and sentences elicited stronger activity than left hand actions and sentences-a dominant hand effect. Importantly, both dorsal and ventral sections of the left pre-central gyrus were recruited by both tasks, suggesting different action features being recruited. These results suggest that (a) language comprehension elicits motor representations that are hand-specific and akin to multimodal action plans, rather than full action re-enactments; and (b) language comprehension and action execution share schematic hand-specific representations that are richer for the dominant hand, and thus linked to previous motor experience.

  15. Adolescents with specific learning disabilities - perceptions of specific learning disabilities in the environment of secondary schools

    OpenAIRE

    Pospíšilová, Zuzana

    2012-01-01

    The thesis focuses on adolescents with specific learning disabilities in the milieu of secondary schools. It is divided into a theoretical part and an empirical part. The first part introduces a topic of specific learning disabilities in the developmental stage of adolescence. It first describes the most relevant aspects of adolescent development. The attention is then paid to typical manifestations of specific learning disabilities in adolescence, and also to secondary symptoms usually conne...

  16. Specific developmental pathways underlie host specificity in the parasitic plant Orobanche

    Science.gov (United States)

    Hiscock, Simon

    2010-01-01

    Parasitic angiosperms are an ecologically and economically important group of plants. However our understanding of the basis for host specificity in these plants is embryonic. Recently we investigated host specificity in the parasitic angiosperm Orobanche minor, and demonstrated that this host generalist parasite comprises genetically defined races that are physiologically adapted to specific hosts. Populations occurring naturally on red clover (Trifolium pratense) and sea carrot (Daucus carota subsp. gummifer) respectively, showed distinct patterns of host specificity at various developmental stages, and a higher fitness on their natural hosts, suggesting these races are locally adapted. Here we discuss the implications of our findings from a broader perspective. We suggest that differences in signal responsiveness and perception by the parasite, as well as qualitative differences in signal production by the host, may elicit host specificity in this parasitic plant. Together with our earlier demonstration that these O. minor races are genetically distinct based on molecular markers, our recent data provide a snapshot of speciation in action, driven by host specificity. Indeed, host specificity may be an underestimated catalyst for speciation in parasitic plants generally. We propose that identifying host specific races using physiological techniques will complement conventional molecular marker-based approaches to provide a framework for delineating evolutionary relationships among cryptic host-specific parasitic plants. PMID:20081361

  17. Risk management through dynamic technical specifications

    International Nuclear Information System (INIS)

    Klopp, George T.; Petersen, Thomas A.

    2004-01-01

    The wide deployment of plant specific probabilistic risk assessments for nuclear power plants has provided the means to effect a fresh risk management perspective and a fresh, risk based, regulatory outlook on nuclear power. There has been a great deal of conversation on risk based regulation within the U. S. nuclear power industry but, curiously, very little on effective risk management. This paper proposes a means to link the two subjects through the plant Technical Specifications. A revised concept for Technical Specifications is suggested which is based on deterministic analyses and probabilistic risk assessments for each plant. The revised Technical Specifications would consider, on a real-time basis, the exact state of the plant in terms of the status of key components and systems. It would depict current plant risk levels and compare those levels to the desired and limiting (alert/action) levels. It would advise the plant operator on the risk impact of proposed actions through a simple query system and illustrate the impact of such actions on plant status relative to designated risk values. The basis for the proposed approach lies in realistic deterministic plant analyses and probabilistic risk assessment (PRA) deployment tools being developed, in parallel, by a number of parties in the U.S. today. These PRAs are based primarily on the existing plant responses to Generic Letter 88-20, 'Individual Plant Examinations' (IPEs). Each of these tools allows the plant operator to input, on a real-time basis, the status of key equipment and systems. The tools then provide explicit illustrations of dependency effects; updated, 'real-time' risk status indications such as core damage frequency; and, in some cases, allow the operator to assess the risk impact of removing from service selected components for maintenance or testing. These systems generally operate on personal computers and provide nearly instantaneous responses to plant queries. Moving from these tools to

  18. Nanoparticles for Site Specific Genome Editing

    Science.gov (United States)

    McNeer, Nicole Ali

    Triplex-forming peptide nucleic acids (PNAs) can be used to coordinate the recombination of short 50-60 by "donor DNA" fragments into genomic DNA, resulting in site-specific correction of genetic mutations or the introduction of advantageous genetic modifications. Site-specific gene editing in hematopoietic stem and progenitor cells (HSPCs) could result in treatment or cure of inherited disorders of the blood such as beta-thalassemia. Gene editing in HSPCs and differentiated T cells could help combat HIV/AIDs by modifying receptors, such as CCR5, necessary for R5-tropic HIV entry. However, translation of genome modification technologies to clinical practice is limited by challenges in intracellular delivery, especially in difficult-to-transfect hematolymphoid cells. In vivo gene editing could also provide novel treatment for systemic monogenic disorders such as cystic fibrosis, an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor. Here, we have engineered biodegradable nanoparticles to deliver oligonucleotides for site-specific genome editing of disease-relevant genes in human cells, with high efficiency, low toxicity, and editing of clinically relevant cell types. We designed nanoparticles to edit the human beta-globin and CCR5 genes in hematopoietic cells. We show that poly(lactic-co-glycolic acid) (PLGA) nanoparticles can delivery PNA and donor DNA for site-specific gene modification in human hematopoietic cells in vitro and in vivo in NOD-scid IL2rgammanull mice. Nanoparticles delivered by tail vein localized to hematopoietic compartments in the spleen and bone marrow of humanized mice, resulting in modification of the beta-globin and CCR5 genes. Modification frequencies ranged from 0.005 to 20% of cells depending on the organ and cell type, without detectable toxicity. This project developed highly versatile methods for delivery of therapeutics to hematolymphoid cells and hematopoietic stem cells, and will help to

  19. Development of industrial variant specification systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer

    be developed from a holistic and strategically anchored point of view. Another assumption is that this is a challenge for many industrial companies. Even though the literature presents many considerations on general issues covering new information technology, little work is found on the business perspectives...... are discussed. A list of structural variables and solution components has been created. These are related to four design aspects in the holistic system design covering the aspects of process design, selection of resources (such as hardware, software and humans), the design of information structures...... solution elements and structural variables to be used in the design of variant specification systems. The thesis presents a “top-down” procedure to be used to develop variant specification systems from a strategically anchored and holistic point of view. A methodology and related task variables...

  20. Risk based technique for improving technical specifications

    International Nuclear Information System (INIS)

    Kim, I. S.; Jae, M. S.; Kim, B. S.; Hwang, S. W.; Kang, K. M.; Park, S. S.; Yu, Y. S.

    2001-03-01

    The objective of this study is to develop the systematic guidance for reviewing the documents associated with the changes of technical specifications. The work done in this fiscal year is the following : surveys in TS requirements, TS improvements and TS regulations in foreign countries as well as Korea, surveys on the state-of-the-art of RITSs and their use in Korea, development of a decision-making framework for both the licensee and the regulation agency, description of risk measures, assessment methodology on STI/AOT, and adverse effects caused by periodic maintenance, which are explained in appendix. The results of this study might contribute to enhancing the quality of the current technical specifications and contribute to preparing the risk informed regulation program using the decision-making framework developed in this study

  1. Duration and specificity of olfactory nonassociative memory.

    Science.gov (United States)

    Freedman, Kaitlin G; Radhakrishna, Sreya; Escanilla, Olga; Linster, Christiane

    2013-05-01

    Olfactory habituation is a simple form of nonassociative memory in which responsiveness to stable but behaviorally nonsignificant stimuli is decreased. Olfactory habituation has recently become a paradigm widely used to probe the neural substrate underlying olfactory perception and memory. This simple behavioral paradigm has been used successfully used to probe many aspects of olfactory processing, and it has recently become clear that the neural processes underlying olfactory habituation can depend on the task parameters used. We here further investigate memory specificity and duration using 2 variations in task parameters: the number of habituation trials and the time delay between habituation and cross-habituation testing. We find that memory specificity increases with the number of habituation trials but decreases with time after the last habituation trial.

  2. Reversal of target-specific oral anticoagulants

    Science.gov (United States)

    Siegal, D.M.; Cuker, Adam

    2014-01-01

    Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed. PMID:24880102

  3. The Econometric Procedures of Specific Transaction Identification

    Directory of Open Access Journals (Sweden)

    Doszyń Mariusz

    2017-06-01

    Full Text Available The paper presents the econometric procedures of identifying specific transactions, in which atypical conditions or attributes may occur. These procedures are based on studentized and predictive residuals of the accordingly specified econometric models. The dependent variable is a unit transactional price, and explanatory variables are both the real properties’ attributes and accordingly defined artificial binary variables. The utility of the proposed method has been verified by means of a real market data base. The proposed procedures can be helpful during the property valuation process, making it possible to reject real properties that are specific (both from the point of view of the transaction conditions and the properties’ attributes and, consequently, to select an appropriate set of similar attributes that are essential for the valuation process.

  4. Wp specific methylation of highly proliferated LCLs

    International Nuclear Information System (INIS)

    Park, Jung-Hoon; Jeon, Jae-Pil; Shim, Sung-Mi; Nam, Hye-Young; Kim, Joon-Woo; Han, Bok-Ghee; Lee, Suman

    2007-01-01

    The epigenetic regulation of viral genes may be important for the life cycle of EBV. We determined the methylation status of three viral promoters (Wp, Cp, Qp) from EBV B-lymphoblastoid cell lines (LCLs) by pyrosequencing. Our pyrosequencing data showed that the CpG region of Wp was methylated, but the others were not. Interestingly, Wp methylation was increased with proliferation of LCLs. Wp methylation was as high as 74.9% in late-passage LCLs, but 25.6% in early-passage LCLs. From two Burkitt's lymphoma cell lines, Wp specific hypermethylation was also found (>80%). Interestingly, the expression of EBNA2 gene which located directly next to Wp was associated with its methylation. Our data suggested that Wp specific methylation may be important for the indicator of the proliferation status of LCLs, and the epigenetic viral gene regulation of EBNA2 gene by Wp should be further defined possibly with other biological processes

  5. Beta-endorphin radioimmunoassay: specificity studies

    Energy Technology Data Exchange (ETDEWEB)

    Colas-Linhart, N.; Perdrisot, R.; Petiet, A.; Bok, B.

    1986-01-01

    This note describes the technical details of a cerebrospinal fluid (CSF) B-Endorphin (B-End) radioimmunoassay (RIA). We used an antiserum raised in rabbits against human B-End which cross-reacs 100% with B-Lipotrophin (B-Lph). Thus, filtration chromatography is used to separate both peptides. The assay is sensitive (limit detection=14 pmoles/l), reproducible (the intra and inter assay coefficients of variation are 5 and 6% respectively). Specificity studies are performed to verify the cross-reactions with other opioid peptides and the non specific reactions with the biological fluid (CSF). In order to evaluate the effects of iodine-containing contrast media on the RIA, additional standard curves were analyzed in the presence of varying concentrations of two contrast materials.

  6. Psoralen photomutagenic specificity in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Koch, W.H.

    1986-01-01

    The cytotoxic and mutagenic specificity of two therapeutically employed psoralens was examined in several Ames Salmonella typhimurium strains with near ultraviolet light activation. Photomutagenic activity of 8-methoxypsoralen (8MOP) and 4,5',8-trimethylpsoralen (TMP) was found to be sequence-specific, and additionally was dependent on the level of DNA-repair proficiency. Phototoxicity was essentially identical in hisC3076, hisD3052 and hisG46 strains; uvrB - excision-repair-deficient bacteria were considerably more susceptible to lethal effects than wild-type parental strains. Finally, the data show that psoralens are potent frameshift photomutagens in Salmonella hisC3076 strains and demonstrate the potential utility of these strains in evaluating photomutagenic and phototoxic activity of new furocoumarin derivatives. (Auth.)

  7. Production of high specific activity silicon-32

    International Nuclear Information System (INIS)

    Phillips, D.R.; Brzezinski, M.A.

    1998-01-01

    This is the final report of a three-year, Laboratory Directed Research and Development Project (LDRD) at Los Alamos National Laboratory (LANL). There were two primary objectives for the work performed under this project. The first was to take advantage of capabilities and facilities at Los Alamos to produce the radionuclide 32 Si in unusually high specific activity. The second was to combine the radioanalytical expertise at Los Alamos with the expertise at the University of California to develop methods for the application of 32 Si in biological oceanographic research related to global climate modeling. The first objective was met by developing targetry for proton spallation production of 32 Si in KCl targets and chemistry for its recovery in very high specific activity. The second objective was met by developing a validated field-useable, radioanalytical technique, based upon gas-flow proportional counting, to measure the dynamics of silicon uptake by naturally occurring diatoms

  8. Specificity and robustness in transcription control networks.

    Science.gov (United States)

    Sengupta, Anirvan M; Djordjevic, Marko; Shraiman, Boris I

    2002-02-19

    Recognition by transcription factors of the regulatory DNA elements upstream of genes is the fundamental step in controlling gene expression. How does the necessity to provide stability with respect to mutation constrain the organization of transcription control networks? We examine the mutation load of a transcription factor interacting with a set of n regulatory response elements as a function of the factor/DNA binding specificity and conclude on theoretical grounds that the optimal specificity decreases with n. The predicted correlation between variability of binding sites (for a given transcription factor) and their number is supported by the genomic data for Escherichia coli. The analysis of E. coli genomic data was carried out using an algorithm suggested by the biophysical model of transcription factor/DNA binding. Complete results of the search for candidate transcription factor binding sites are available at http://www.physics.rockefeller.edu/~boris/public/search_ecoli.

  9. Specificity of economic and social nature tourism

    Directory of Open Access Journals (Sweden)

    Chabanjuk Oleg Vasil'evich

    2015-11-01

    Full Text Available The article considers a number of factors specific to the tourism industry: a multiplier effect, a kind of method of generating working capital, specific "invisible exports", the factor most risky activities, the principle of direct and inverse transformation, and others. The data of experts of the World Tourism Organization (UNWTO on tourism as an indicator of welfare. It is emphasized along with the economic function of tourism on the social dimension of tourism in its mass phenomenon. The paper highlights the main problems and shortcomings of tourism as a complex socio-economic system; analysis of theoretical approaches to periodization of tourism that reflects the genesis of approaches regarding the nature of tourism; The factors of external and internal tourism development, made their ranking to measure the relationship between the measurement periods allocated for tourism development using the Spearman rank correlation coefficient.

  10. Cell-Specific Aptamers as Emerging Therapeutics

    Directory of Open Access Journals (Sweden)

    Cindy Meyer

    2011-01-01

    Full Text Available Aptamers are short nucleic acids that bind to defined targets with high affinity and specificity. The first aptamers have been selected about two decades ago by an in vitro process named SELEX (systematic evolution of ligands by exponential enrichment. Since then, numerous aptamers with specificities for a variety of targets from small molecules to proteins or even whole cells have been selected. Their applications range from biosensing and diagnostics to therapy and target-oriented drug delivery. More recently, selections using complex targets such as live cells have become feasible. This paper summarizes progress in cell-SELEX techniques and highlights recent developments, particularly in the field of medically relevant aptamers with a focus on therapeutic and drug-delivery applications.

  11. Shape configuration and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, I; Paulson, Olaf B.

    2006-01-01

    and fragmented drawings. We also examined whether fragmentation had different impact on the recognition of natural objects and artefacts and found that recognition of artefacts was more affected by fragmentation than recognition of natural objects. Thus, the usual finding of an advantage for artefacts...... in difficult object decision tasks, which is also found in the present experiments with outlines, is reversed when the stimuli are fragmented. This interaction between category (natural versus artefacts) and stimulus type (outlines versus fragmented forms) is in accordance with predictions derived from...... a recent account of category-specificity and lends support to the notion that category-specific impairments can occur for both natural objects and artefacts following damage to pre-semantic stages in visual object recognition. The implications of the present findings are discussed in relation to theories...

  12. A beta-endorphin radioimmunoassay: specificity studies

    International Nuclear Information System (INIS)

    Colas-Linhart, N.; Perdrisot, R.; Petiet, A.; Bok, B.

    1986-01-01

    This note describes the technical details of a cerebrospinal fluid (CSF) B-Endorphin (B-End) radioimmunoassay (RIA). We used an antiserum raised in rabbits against human B-End which cross-reacs 100% with B-Lipotrophin (B-Lph). Thus, filtration chromatography is used to separate both peptides. The assay is sensitive (limit detection=14 pmoles/l), reproducible (the intra and inter assay coefficients of variation are 5 and 6% respectively). Specificity studies are performed to verify the cross-reactions with other opioid peptides and the non specific reactions with the biological fluid (CSF). In order to evaluate the effects of iodine-containing contrast media on the RIA, additional standard curves were analyzed in the presence of varying concentrations of two contrast materials [fr

  13. Phase-II Associative Memory ASIC Specifications

    CERN Document Server

    Stabile, Alberto; Warren, Matthew; Green, Barry; Konstantinidis, Nikolaos; Motuk, Halil Erdem; Frontini, Luca; Liberali, Valentino; Crescioli, Francesco; Fedi, Giacomo; Sotiropoulou, Calliope-louisa; De Canio, Francesco; Traversi, Gianluca; Shojaii, Seyed Ruhollah; Kubota, Takashi; Calderini, Giovanni; Palla, Fabrizio; Checcucci, Bruno; Spiller, Laurence Anthony; Mcnamara, Peter Charles

    2018-01-01

    This documents defines the specifications for the Associative Memory ASIC for Phase-II. The work-flow toward the final ASIC is organized in the following three steps • AM08 prototype: small area MPW prototype to test all the full custom features, the VHDL logic and the I/O. This chip must be fully functional with smaller memory area than the final ASIC; • AM09pre pre-production: full area ASIC to be fabricated with a full-mask set pilot run. Production corner wafers will be created; • AM09 production: full area ASIC with refinements for the mass production. The AM09 will be developed built on the AM08 extending the memory area, therefore the specification of both versions must be compatible.

  14. Accessing Specific Peptide Recognition by Combinatorial Chemistry

    DEFF Research Database (Denmark)

    Li, Ming

    Molecular recognition is at the basis of all processes for life, and plays a central role in many biological processes, such as protein folding, the structural organization of cells and organelles, signal transduction, and the immune response. Hence, my PhD project is entitled “Accessing Specific...... Peptide Recognition by Combinatorial Chemistry”. Molecular recognition is a specific interaction between two or more molecules through noncovalent bonding, such as hydrogen bonding, metal coordination, van der Waals forces, π−π, hydrophobic, or electrostatic interactions. The association involves kinetic....... Combinatorial chemistry was invented in 1980s based on observation of functional aspects of the adaptive immune system. It was employed for drug development and optimization in conjunction with high-throughput synthesis and screening. (chapter 2) Combinatorial chemistry is able to rapidly produce many thousands...

  15. Atmospheric pollution and specific tolerance of lichens

    Energy Technology Data Exchange (ETDEWEB)

    De Sloover, J

    1968-01-01

    An ecological method has been designed which allows a quantitative estimation of specific sensitivity of lichens to atmospheric pollution. That method is based on a comparison of the ''cortege moyen specifique'' i.e. the mean number of lichens growing with each species in a given area. Four of the obtained sequences are compared (The Dender valley and the area surrounding Gand, Belgium: the Oslo and the Helsinki areas); they show the order to toxiphoby of the related epiphytic lichens.

  16. Extinction Generates Outcome-Specific Conditioned Inhibition.

    Science.gov (United States)

    Laurent, Vincent; Chieng, Billy; Balleine, Bernard W

    2016-12-05

    Extinction involves altering a previously established predictive relationship between a cue and its outcome by repeatedly presenting that cue alone. Although it is widely accepted that extinction generates some form of inhibitory learning [1-4], direct evidence for this claim has been lacking, and the nature of the associative changes induced by extinction have, therefore, remained a matter of debate [5-8]. In the current experiments, we used a novel behavioral approach that we recently developed and that provides a direct measure of conditioned inhibition [9] to compare the influence of extinguished and non-extinguished cues on choice between goal-directed actions. Using this approach, we provide direct evidence that extinction generates outcome-specific conditioned inhibition. Furthermore, we demonstrate that this inhibitory learning is controlled by the infralimbic cortex (IL); inactivation of the IL using M4 DREADDs abolished outcome-specific inhibition and rendered the cue excitatory. Importantly, we found that context modulated this inhibition. Outside its extinction context, the cue was excitatory and functioned as a specific predictor of its previously associated outcome, biasing choice toward actions earning the same outcome. In its extinction context, however, the cue acted as a specific inhibitor and biased choice toward actions earning different outcomes. Context modulation of these excitatory and inhibitory memories was mediated by the dorsal hippocampus (HPC), suggesting that the HPC and IL act in concert to control the influence of conditioned inhibitors on choice. These findings demonstrate for the first time that extinction turns a cue into a net inhibitor that can influence choice via counterfactual action-outcome associations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. HAL/S-FC compiler system specifications

    Science.gov (United States)

    1976-01-01

    This document specifies the informational interfaces within the HAL/S-FC compiler, and between the compiler and the external environment. This Compiler System Specification is for the HAL/S-FC compiler and its associated run time facilities which implement the full HAL/S language. The HAL/S-FC compiler is designed to operate stand-alone on any compatible IBM 360/370 computer and within the Software Development Laboratory (SDL) at NASA/JSC, Houston, Texas.

  18. Performance specifications for proton medical facility

    Energy Technology Data Exchange (ETDEWEB)

    Chu, W.T.; Staples, J.W.; Ludewigt, B.A.; Renner, T.R.; Singh, R.P.; Nyman, M.A.; Collier, J.M.; Daftari, I.K.; Petti, P.L.; Alonso, J.R. [Lawrence Berkeley Lab., CA (United States); Kubo, H.; Verhey, L.J. [University of California Davis Medical Center, Sacramento, CA (United States). Cancer Center]|[California Univ., San Francisco, CA (United States). School of Medicine; Castro, J.R. [Lawrence Berkeley Lab., CA (United States)]|[University of California Davis Medical Center, Sacramento, CA (United States). Cancer Center]|[California Univ., San Francisco, CA (United States). School of Medicine

    1993-03-01

    Performance specifications of technical components of a modern proton radiotherapy facility are presented. The technical items specified include: the accelerator; the beam transport system including rotating gantry; the treatment beamline systems including beam scattering, beam scanning, and dosimetric instrumentation; and an integrated treatment and accelerator control system. Also included are treatment ancillary facilities such as diagnostic tools, patient positioning and alignment devices, and treatment planning systems. The facility specified will accommodate beam scanning enabling the three-dimensional conformal therapy deliver .

  19. Gender-specific information search behavior

    OpenAIRE

    Parinaz Maghferat; Wolfgang G. Stock

    2010-01-01

    This paper presents an empirical gender study in the context of information science. It discusses an exploratory investigation, which provides empirical data about differences of information seeking activities by female and male students. The research focus was on whether there are gender-specific differences when people perform searches with the aid of general search engines and specialized Deep Web information services. It has been observed how the participants behaved in getting informatio...

  20. A Requirement Specification Language for AADL

    Science.gov (United States)

    2016-06-01

    models. The objective of ReqSpec is to support the elicitation , definition, and modeling of requirements for real-time embedded systems in an iterative...A Requirement Specification Language for AADL Peter H. Feiler Julien Delange Lutz Wrage June 2016 TECHNICAL REPORT CMU/SEI-2016-TR-008...is required for any other external and/or commercial use. Requests for permission should be directed to the Software En- gineering Institute at

  1. 50 CFR 648.200 - Specifications.

    Science.gov (United States)

    2010-10-01

    ..., unless an OY that exceeds MSY in a specific year is consistent with a control rule that ensures the... northerly along the Hague Line to the U.S.-Canadian border, to include state and Federal waters adjacent to...., northeasterly to the Hague Line at 42°53′14″ N. lat., 67°44′35″ W. long. [72 FR 11277, Mar. 12, 2007, as amended...

  2. EFFECTS OF MACRONUTRIENT COMPOSITION ON SPECIFIC ...

    African Journals Online (AJOL)

    Admin

    (6.1%) and lastly high and medium fat-fed mice (3.9% and 4.5%). KEY WORDS: ..... Sucrose. 147. 350. 172.8. 68.8. Cellulose. 50. 50. 50. 50. Soya oil. 25. 25. 25. 25. Lard. 20 .... J. Clin. Invest. 4, 353-387. McCue, M. D., 2006. Specific dynamic action: A century ... between certain amino acids and proteins with reference to ...

  3. Specific heat of praseodymium and neodymium

    International Nuclear Information System (INIS)

    Narayana Murthy, J.V.S.S.; Ramji Rao, R.

    1983-01-01

    The elements of the dynamical matrix of an ideal deep lattice, with nearest neighbour central interactions, have been obtained in a homogeneously strained state. The dispersion relations along the [0001] direction, on this model, have been presented for Pr and Nd. The frequency distribution function g(ω) is obtained and the lattice specific heat is calculated for Pr and Nd and the temperature variation of the equivalent Debye temperature is presented. (author)

  4. Domain-Specific Control of Selective Attention

    Science.gov (United States)

    Lin, Szu-Hung; Yeh, Yei-Yu

    2014-01-01

    Previous research has shown that loading information on working memory affects selective attention. However, whether the load effect on selective attention is domain-general or domain-specific remains unresolved. The domain-general effect refers to the findings that load in one content (e.g. phonological) domain in working memory influences processing in another content (e.g., visuospatial) domain. Attentional control supervises selection regardless of information domain. The domain-specific effect refers to the constraint of influence only when maintenance and processing operate in the same domain. Selective attention operates in a specific content domain. This study is designed to resolve this controversy. Across three experiments, we manipulated the type of representation maintained in working memory and the type of representation upon which the participants must exert control to resolve conflict and select a target into the focus of attention. In Experiments 1a and 1b, participants maintained digits and nonverbalized objects, respectively, in working memory while selecting a target in a letter array. In Experiment 2, we presented auditory digits with a letter flanker task to exclude the involvement of resource competition within the same input modality. In Experiments 3a and 3b, we replaced the letter flanker task with an object flanker task while manipulating the memory load on object and digit representation, respectively. The results consistently showed that memory load modulated distractibility only when the stimuli of the two tasks were represented in the same domain. The magnitude of distractor interference was larger under high load than under low load, reflecting a lower efficacy of information prioritization. When the stimuli of the two tasks were represented in different domains, memory load did not modulate distractibility. Control of processing priority in selective attention demands domain-specific resources. PMID:24866977

  5. Domain Specific Languages for Interactive Web Services

    DEFF Research Database (Denmark)

    Brabrand, Claus

    This dissertation shows how domain specific languages may be applied to the domain of interactive Web services to obtain flexible, safe, and efficient solutions. We show how each of four key aspects of interactive Web services involving sessions, dynamic creation of HTML/XML documents, form field......, , that supports virtually all aspects of the development of interactive Web services and provides flexible, safe, and efficient solutions....

  6. Reasoning About Higher-Order Relational Specifications

    OpenAIRE

    Wang , Yuting; Chaudhuri , Kaustuv; Gacek , Andrew; Nadathur , Gopalan

    2013-01-01

    International audience; The logic of hereditary Harrop formulas (HH) has proven useful for specifying a wide range of formal systems. This logic includes a form of hypothetical judgment that leads to dynamically changing sets of assumptions and that is key to encoding side conditions and contexts that occur frequently in structural operational semantics (SOS) style presentations. Specifications are often useful in reasoning about the systems they describe. The Abella theorem prover supports s...

  7. Cultural Specifics of Management in Multinational Companies

    OpenAIRE

    Křečková Kroupová, Zuzana

    2002-01-01

    Nowadays the world is becoming increasingly economically connected, and cultural diversity of employees is gaining importance as a crucial competitive advantage. Cross-cultural communication ability is becoming a key management skill in multinational firms and is equally important for other employees who are exposed to other cultures in the workplace. This work mainly focuses on cultural specifics of management in multinational firms. The goal of this thesis is to discover how different natio...

  8. Learning LM Specificity for Ganglion Cells

    Science.gov (United States)

    Ahumada, Albert J.

    2015-01-01

    Unsupervised learning models have been proposed based on experience (Ahumada and Mulligan, 1990;Wachtler, Doi, Lee and Sejnowski, 2007) that allow the cortex to develop units with LM specific color opponent receptive fields like the blob cells reported by Hubel and Wiesel on the basis of visual experience. These models used ganglion cells with LM indiscriminate wiring as inputs to the learning mechanism, which was presumed to occur at the cortical level.

  9. On emotion specificity in decision making

    OpenAIRE

    Marcel Zeelenberg; Rob M. A. Nelissen; Seger M. Breugelmans; Rik Pieters

    2008-01-01

    We present a motivational account of the impact of emotion on decision making, termed the feeling-is-for-doing approach. We first describe the psychology of emotion and argue for a need to be specific when studying emotion's impact on decision making. Next we describe what our approach entails and how it relates emotion, via motivation to behavior. Then we offer two illustrations of our own research that provide support for two important elements in our reasoning. We end with specifying four ...

  10. Sedentary behavior and residual-specific mortality

    OpenAIRE

    Paul D. Loprinzi; Meghan K. Edwards; Eveleen Sng; Ovuokerie Addoh

    2016-01-01

    Background: The purpose of this study was to examine the association of accelerometer-assessed sedentary behavior and residual-specific mortality. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used (N = 5536), with follow-up through 2011. Sedentary behavior was objectively measured over 7 days via accelerometry. Results: When expressing sedentary behavior as a 60 min/day increase, the hazard ratio across the models ranged from 1.07-1.40 (P < 0...

  11. Specific methods on in-pile gammametry

    International Nuclear Information System (INIS)

    Pointud, M.-L.; Michel, Francois.

    1979-01-01

    The gammametry technique in nuclear research reactors has evolved by the adequation of its means and the quality of its results since its beginnings in 1972. We do not propose here to make a detailed presentation, nor describe the kinds of well known results that can henceforth be attained with it in a conventional manner; our intention, on the other hand, is to describe a few specific methods developed for using it in the SILOE reactor of the CEN/G [fr

  12. RD53A Integrated Circuit Specifications

    OpenAIRE

    Garcia-Sciveres, Mauricio

    2015-01-01

    Specifications for the RD53 collaboration’s first engineering wafer run of an integrated circuit (IC) for hybrid pixel detector readout, called RD53A. RD53A is intended to demonstrate in a large format IC the suitability of the technology (including radiation tolerance), the stable low threshold operation, and the high hit and trigger rate capabilities, required for HL-LHC upgrades of ATLAS and CMS. The wafer scale production will permit the experiments to prototype bump bonding assembly with...

  13. Modality-specificity of Selective Attention Networks

    OpenAIRE

    Stewart, Hannah J.; Amitay, Sygal

    2015-01-01

    Objective: To establish the modality specificity and generality of selective attention networks. Method: Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT), the Test of Everyday Attention (TEA), and the Test of Attention in Listening (TAiL). These provided independent measures for auditory and visual alerting, orienting, and conflict resoluti...

  14. Diagrammatic Representations in Domain-Specific Languages

    OpenAIRE

    Tourlas, Konstantinos

    2002-01-01

    One emerging approach to reducing the labour and costs of software development favours the specialisation of techniques to particular application domains. The rationale is that programs within a given domain often share enough common features and assumptions to enable the incorporation of substantial support mechanisms into domain-specific programming languages and associated tools. Instead of being machine-oriented, algorithmic implementations, programs in many domain-speci...

  15. Specifications development for "Karbatril" codenamed tablets

    Directory of Open Access Journals (Sweden)

    L. I. Kucherenko

    2017-08-01

    Full Text Available Introduction. According to current legislation of Ukraine the specifications of tablets include the following indicators: description, identification, average weight, disintegration and assay. The aim of the study. The development of specifications and project of quality control methods for "Karbatril" codenamed tablets. Materials and methods. During the study we analyzed 6 series of tablets "Karbatril." For the description, identification, determination of the average mass, disintegration, active ingredients quantify of "Karbatril" codenamed tablets we used appropriate methods and instruments. Results and discussion. Tablets "Karbatril" were analyzed for the following parameters: - Overview - Tablets white or nearly white; - Average weight - during the study the average weight of 6 series of obtained tablets ranged from 339,0 mg to 369,9 mg according to SPU from 337,0 mg to 373,0 mg; - Disintegration – according to SPU the disintegration for tablet without shell shall not exceed 15 min. Analyzed tablets disintegrated in the period from 5 to 10 minutes; - Identification and quantification of the active ingredients of tablets were conducted using modified HPLC methods. During the identification obtained chromatograms show compliance with SPU. In quantitative determination of the active ingredients content in "Karbatril" codenamed tablets we found carbamazepine from 148.18 mg to 150.19 mg, thiotriazoline - from 98.93 mg to 99.71 mg. This data is consistent to SPU which regulates content of carbamazepine - 150 mg ± 7,5%, thiotriazoline - 100 mg ± 10%. Conclusions. This study has developed specification for "Karbatril" codenamed tablets and also methods of HPLC qualitative and quantitative determination of active ingredients. In the specification the following parameters are included: description, identification, average weight, disintegration and assay. The study drafted quality control methods which are planned to be later offered to the

  16. Salt bridges: geometrically specific, designable interactions.

    Science.gov (United States)

    Donald, Jason E; Kulp, Daniel W; DeGrado, William F

    2011-03-01

    Salt bridges occur frequently in proteins, providing conformational specificity and contributing to molecular recognition and catalysis. We present a comprehensive analysis of these interactions in protein structures by surveying a large database of protein structures. Salt bridges between Asp or Glu and His, Arg, or Lys display extremely well-defined geometric preferences. Several previously observed preferences are confirmed, and others that were previously unrecognized are discovered. Salt bridges are explored for their preferences for different separations in sequence and in space, geometric preferences within proteins and at protein-protein interfaces, co-operativity in networked salt bridges, inclusion within metal-binding sites, preference for acidic electrons, apparent conformational side chain entropy reduction on formation, and degree of burial. Salt bridges occur far more frequently between residues at close than distant sequence separations, but, at close distances, there remain strong preferences for salt bridges at specific separations. Specific types of complex salt bridges, involving three or more members, are also discovered. As we observe a strong relationship between the propensity to form a salt bridge and the placement of salt-bridging residues in protein sequences, we discuss the role that salt bridges might play in kinetically influencing protein folding and thermodynamically stabilizing the native conformation. We also develop a quantitative method to select appropriate crystal structure resolution and B-factor cutoffs. Detailed knowledge of these geometric and sequence dependences should aid de novo design and prediction algorithms. Copyright © 2010 Wiley-Liss, Inc.

  17. One step processing for future diesel specifications

    International Nuclear Information System (INIS)

    Brierley, G.R.

    1997-01-01

    The trend in diesel fuel specifications is to limit the sulfur level to less than 0.05 wt- per cent. Many regions have also specified that diesel fuels must have lower aromatic levels, higher cetane numbers, and lower distillation end points. These changes will require significant refinery investment to meet the new diesel fuel specifications. The changes may also significantly affect the value of synthetic crude stocks. UOP has developed a new hydroprocessing catalyst which makes it possible to meet the new diesel specifications in one single processing step and at minimal cost. The catalyst saturates aromatics while opening ring structures at the same time. By selectively cracking heavy components into the diesel range with minimal cracking to gas or naphtha, heavier feedstocks can be upgraded to diesel, and refinery diesel yield can be augmented. Synthetic crude distillate is often high in aromatics and low in cetane number. This new UOP hydroprocessing system will allow synthetic crude producers and refiners to produce diesel fuels with higher cetane numbers, high-quality distillate blendstocks and distillate fuels. 26 figs

  18. Trait-specific dependence in romantic relationships.

    Science.gov (United States)

    Ellis, Bruce J; Simpson, Jeffry A; Campbell, Lorne

    2002-10-01

    Informed by three theoretical frameworks--trait psychology, evolutionary psychology, and interdependence theory--we report four investigations designed to develop and test the reliability and validity of a new construct and accompanying multiscale inventory, the Trait-Specific Dependence Inventory (TSDI). The TSDI assesses comparisons between present and alternative romantic partners on major dimensions of mate value. In Study 1, principal components analyses revealed that the provisional pool of theory-generated TSDI items were represented by six factors: Agreeable/Committed, Resource Accruing Potential, Physical Prowess, Emotional Stability, Surgency, and Physical Attractiveness. In Study 2, confirmatory factor analysis replicated these results on a different sample and tested how well different structural models fit the data. Study 3 provided evidence for the convergent and discriminant validity of the six TSDI scales by correlating each one with a matched personality trait scale that did not explicitly incorporate comparisons between partners. Study 4 provided further validation evidence, revealing that the six TSDI scales successfully predicted three relationship outcome measures--love, time investment, and anger/upset--above and beyond matched sets of traditional personality trait measures. These results suggest that the TSDI is a reliable, valid, and unique construct that represents a new trait-specific method of assessing dependence in romantic relationships. The construct of trait-specific dependence is introduced and linked with other theories of mate value.

  19. Development of Specifications for Radioactive Waste Packages

    International Nuclear Information System (INIS)

    2006-10-01

    The main objective of this publication is to provide guidelines for the development of waste package specifications that comply with waste acceptance requirements for storage and disposal of radioactive waste. It will assist waste generators and waste package producers in selecting the most significant parameters and in developing and implementing specifications for each individual type of waste and waste package. This publication also identifies and reviews the activities and technical provisions that are necessary to meet safety requirements; in particular, selection of the significant safety parameters and preparation of specifications for waste forms, waste containers and waste packages using proven approaches, methods and technologies. This report provides guidance using a systematic, stepwise approach, integrating the technical, organizational and administrative factors that need to be considered at each step of planning and implementing waste package design, fabrication, approval, quality assurance and control. The report reflects the considerable experience and knowledge that has been accumulated in the IAEA Member States and is consistent with the current international requirements, principles, standards and guidance for the safe management of radioactive waste

  20. Development of Specifications for Radioactive Waste Packages

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-10-15

    The main objective of this publication is to provide guidelines for the development of waste package specifications that comply with waste acceptance requirements for storage and disposal of radioactive waste. It will assist waste generators and waste package producers in selecting the most significant parameters and in developing and implementing specifications for each individual type of waste and waste package. This publication also identifies and reviews the activities and technical provisions that are necessary to meet safety requirements; in particular, selection of the significant safety parameters and preparation of specifications for waste forms, waste containers and waste packages using proven approaches, methods and technologies. This report provides guidance using a systematic, stepwise approach, integrating the technical, organizational and administrative factors that need to be considered at each step of planning and implementing waste package design, fabrication, approval, quality assurance and control. The report reflects the considerable experience and knowledge that has been accumulated in the IAEA Member States and is consistent with the current international requirements, principles, standards and guidance for the safe management of radioactive waste.