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Sample records for direct cdc48 activity

  1. Dsc E3 ligase localization to the Golgi requires the ATPase Cdc48 and cofactor Ufd1 for activation of sterol regulatory element-binding protein in fission yeast.

    Science.gov (United States)

    Burr, Risa; Ribbens, Diedre; Raychaudhuri, Sumana; Stewart, Emerson V; Ho, Jason; Espenshade, Peter J

    2017-09-29

    Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases associated with diverse cellular activities (AAA + ) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released into the cytosol to enter the nucleus and regulate gene expression. Previously, we reported that Cdc48 binding to Rbd2 is required for Rbd2-mediated SREBP cleavage. Here, using affinity chromatography and mass spectrometry experiments, we identified Cdc48-binding proteins in S. pombe , generating a list of many previously unknown potential Cdc48-binding partners. We show that the established Cdc48 cofactor Ufd1 is required for SREBP cleavage but does not interact with the Cdc48-Rbd2 complex. Cdc48-Ufd1 is instead required at a step prior to Rbd2 function, during Golgi localization of the Dsc E3 ligase complex. Together, these findings demonstrate that two distinct Cdc48 complexes, Cdc48-Ufd1 and Cdc48-Rbd2, are required for SREBP activation and low-oxygen adaptation in S. pombe . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Cdc48: A Swiss Army Knife of Cell Biology

    Directory of Open Access Journals (Sweden)

    Guem Hee Baek

    2013-01-01

    Full Text Available Cdc48 (also called VCP and p97 is an abundant protein that plays essential regulatory functions in a broad array of cellular processes. Working with various cofactors, Cdc48 utilizes its ATPase activity to promote the assembly and disassembly of protein complexes. Here, we review key biological functions and regulation of Cdc48 in ubiquitin-related events. Given the broad employment of Cdc48 in cell biology and its intimate ties to human diseases (e.g., amyotrophic lateral sclerosis, studies of Cdc48 will bring significant insights into the mechanism and function of ubiquitin in health and diseases.

  3. Role of AtCDC48 & the AtCDC48 Regulatory Protein Family, PUX, in Plant Cell Morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bednarek, Sebastian, Y.

    2009-11-08

    The long-term objective of this work is to understand the molecular events and mechanisms involved in secretory membrane trafficking and organelle biogenesis, which are crucial for normal plant growth and development. Our studies have suggested a vital role for the cytosolic chaperone Cdc48p/p97 during cytokinesis and cell expansion which are highly dependent upon secretory membrane trafficking. Localization studies have shown that the plant Cdc48p/p97, AtCDC48, and the Arabidopsis ortholog of the ER- and Golgi-associated SNARE, syntaxin 5, (referred to as SYP31) are targeted to the division plane during cytokinesis. In addition, AtCDC48 and SYP31 were shown to interact in vitro and in vivo. To characterize further the function of AtCDC48 and SYP31 we have utilized affinity chromatography and MALDI-MS to identify several plant-specific proteins that interact with SYP31 and/or modulate the activity of AtCDC48 including two UBX (i.e. ubiquitin-like) domain containing proteins, PUX1 and PUX2 (Proteins containing UBX domain). These proteins define a plant protein family consisting of 15 uncharacterized members that we postulate interact with AtCDC48. Biochemical studies have demonstrated that PUX2 is a novel membrane adapter for AtCDC48 that mediates AtCDC48/SYP31 interaction and is likely to control AtCDC48-dependent membrane fusion. In contrast, PUX1 negatively regulates AtCDC48 by inhibiting its ATPase activity and by promoting the disassembly of the active hexamer. These findings provide the first evidence that the assembly and disassembly of the CDC48/p97complex is actually a dynamic process. This new unexpected level of regulation for CDC48/p97 was demonstrated to be critical in vivo as pux1 loss-of-function mutants grow faster than wild-type plants. These studies suggest a role for AtCDC48 in plant cell cycle progression including cytokinesis and/or cell expansion. The proposed studies are designed to: 1) characterize further the localization and function of AtCDC

  4. Shedding light on the expansion and diversification of the Cdc48 protein family during the rise of the eukaryotic cell.

    Science.gov (United States)

    Kienle, Nickias; Kloepper, Tobias H; Fasshauer, Dirk

    2016-10-18

    A defining feature of eukaryotic cells is the presence of various distinct membrane-bound compartments with different metabolic roles. Material exchange between most compartments occurs via a sophisticated vesicle trafficking system. This intricate cellular architecture of eukaryotes appears to have emerged suddenly, about 2 billion years ago, from much less complex ancestors. How the eukaryotic cell acquired its internal complexity is poorly understood, partly because no prokaryotic precursors have been found for many key factors involved in compartmentalization. One exception is the Cdc48 protein family, which consists of several distinct classical ATPases associated with various cellular activities (AAA+) proteins with two consecutive AAA domains. Here, we have classified the Cdc48 family through iterative use of hidden Markov models and tree building. We found only one type, Cdc48, in prokaryotes, although a set of eight diverged members that function at distinct subcellular compartments were retrieved from eukaryotes and were probably present in the last eukaryotic common ancestor (LECA). Pronounced changes in sequence and domain structure during the radiation into the LECA set are delineated. Moreover, our analysis brings to light lineage-specific losses and duplications that often reflect important biological changes. Remarkably, we also found evidence for internal duplications within the LECA set that probably occurred during the rise of the eukaryotic cell. Our analysis corroborates the idea that the diversification of the Cdc48 family is closely intertwined with the development of the compartments of the eukaryotic cell.

  5. ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans.

    Science.gov (United States)

    Rodrigues, Ana-João; Neves-Carvalho, Andreia; Ferro, Anabela; Rokka, Anne; Corthals, Garry; Logarinho, Elsa; Maciel, Patrícia

    2009-09-04

    Ataxin-3 is the protein involved in Machado-Joseph disease, a neurodegenerative disorder caused by a polyglutamine expansion. Ataxin-3 binds ubiquitylated proteins and acts as a deubiquitylating enzyme in vitro. It was previously proposed that ataxin-3, along with the VCP/p97 protein, escorts ubiquitylated substrates for proteasomal degradation, although other players of this escort complex were not identified yet. In this work, we show that the Caenorhabditis elegans ataxin-3 protein (ATX-3) interacts with both VCP/p97 worm homologs, CDC-48.1 and CDC-48.2 and we map the interaction domains. We describe a motility defect in both ATX-3 and CDC-48.1 mutants and, in addition, we identify a new protein interactor, UBXN-5, potentially an adaptor of the CDC-48-ATX-3 escort complex. CDC-48 binds to both ATX-3 and UBXN-5 in a non-competitive manner, suggesting the formation of a trimolecular complex. Both CDC-48 and ATX-3, but not UBXN-5, were able to bind K-48 polyubiquitin chains, the standard signal for proteasomal degradation. Additionally, we describe several common interactors of ATX-3 and UBXN-5, some of which can be in vivo targets of this complex.

  6. Molecular Mechanism of Substrate Processing by the Cdc48 ATPase Complex.

    Science.gov (United States)

    Bodnar, Nicholas O; Rapoport, Tom A

    2017-05-04

    The Cdc48 ATPase and its cofactors Ufd1/Npl4 (UN) extract polyubiquitinated proteins from membranes or macromolecular complexes, but how they perform these functions is unclear. Cdc48 consists of an N-terminal domain that binds UN and two stacked hexameric ATPase rings (D1 and D2) surrounding a central pore. Here, we use purified components to elucidate how the Cdc48 complex processes substrates. After interaction of the polyubiquitin chain with UN, ATP hydrolysis by the D2 ring moves the polypeptide completely through the double ring, generating a pulling force on the substrate and causing its unfolding. ATP hydrolysis by the D1 ring is important for subsequent substrate release from the Cdc48 complex. This release requires cooperation of Cdc48 with a deubiquitinase, which trims polyubiquitin to an oligoubiquitin chain that is then also translocated through the pore. Together, these results lead to a new paradigm for the function of Cdc48 and its mammalian ortholog p97/VCP. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Structure and function of the AAA+ ATPase p97/Cdc48p.

    Science.gov (United States)

    Xia, Di; Tang, Wai Kwan; Ye, Yihong

    2016-05-25

    p97 (also known as valosin-containing protein (VCP) in mammals or Cdc48p in Saccharomyces cerevisiae) is an evolutionarily conserved ATPase present in all eukaryotes and archaebacteria. In conjunction with a collection of cofactors and adaptors, p97/Cdc48p performs an array of biological functions mostly through modulating the stability of 'client' proteins. Using energy from ATP hydrolysis, p97/Cdc48p segregates these molecules from immobile cellular structures such as protein assemblies, membrane organelles, and chromatin. Consequently, the released polypeptides can be efficiently degraded by the ubiquitin proteasome system or recycled. This review summarizes our current understanding of the structure and function of this essential cellular chaperoning system. Published by Elsevier B.V.

  8. Electron cryo-microscopy of VAT, the archaeal p97/CDC48 homologue from Thermoplasma acidophilum.

    Science.gov (United States)

    Rockel, Beate; Jakana, Joanita; Chiu, Wah; Baumeister, Wolfgang

    2002-04-12

    VAT (valosine containing protein-like ATPase from Thermoplasma acidophilum), an archaeal member of the AAA-family (ATPases associated with a variety of cellular activities) that possesses foldase as well as unfoldase-activity, forms homo-hexameric rings like its eukaryotic homologues p97 and CDC48. The VAT-monomer exhibits the tripartite domain architecture typical for type II AAA-ATPases: N-D1-D2, whereby N is the substrate binding N-terminal domain preceding domains D1 and D2, both containing AAA-modules. Recent 3-D reconstructions of VAT and p97 as obtained by electron microscopy suffer from weakly represented N-domains, probably a consequence of their flexible linkage to the hexameric core. Here we used electron cryo-microscopy and 3-D reconstruction of single particles in order to generate a 3-D model of VAT at 2.3 nm resolution. The hexameric core of the VAT-complex (diameter 13.2 nm, height 8.4 nm) encloses a central cavity and the substrate-binding N-domains are clearly arranged in the upper periphery. Comparison with the p97 3-D reconstruction and the recently determined crystal structure of p97-N-D1 suggests a tail-to-tail arrangement of D1 and D2 in VAT. Copyright 2002 Elsevier Science Ltd.

  9. A Mighty “Protein Extractor” of the Cell: Structure and Function of the p97/CDC48 ATPase

    Directory of Open Access Journals (Sweden)

    Yihong Ye

    2017-06-01

    Full Text Available p97/VCP (known as Cdc48 in S. cerevisiae or TER94 in Drosophila is one of the most abundant cytosolic ATPases. It is highly conserved from archaebacteria to eukaryotes. In conjunction with a large number of cofactors and adaptors, it couples ATP hydrolysis to segregation of polypeptides from immobile cellular structures such as protein assemblies, membranes, ribosome, and chromatin. This often results in proteasomal degradation of extracted polypeptides. Given the diversity of p97 substrates, this “segregase” activity has profound influence on cellular physiology ranging from protein homeostasis to DNA lesion sensing, and mutations in p97 have been linked to several human diseases. Here we summarize our current understanding of the structure and function of this important cellular machinery and discuss the relevant clinical implications.

  10. Suppressor Analysis of CRL4Cdt2 Defective and cdc48-353 Temperature Sensitive Mutants in Fission Yeast

    DEFF Research Database (Denmark)

    Marinova, Irina Nikolaeva

    between Spd1 and PCNA. Our results provide evidence that excess Spd1 causes replication stress and genome instability by inhibiting PCNA. Furthermore, we examined the potential regulation of Spd1 function by Gad8-mediated phosphorylation of residue S43.Part 2Cdc48/p97 is a ring-shaped homohexameric...

  11. Direct Activation Of Methane

    KAUST Repository

    Basset, Jean-Marie

    2013-07-15

    Heteropolyacids (HPAs) can activate methane at ambient temperature (e.g., 20.degree. C.) and atmospheric pressure, and transform methane to acetic acid, in the absence of any noble metal such as Pd). The HPAs can be, for example, those with Keggin structure: H.sub.4SiW.sub.12O.sub.40, H.sub.3PW.sub.12O.sub.40, H.sub.4SiMo.sub.12O.sub.40, or H.sub.3PMo.sub.12O.sub.40, can be when supported on silica.

  12. Direct activation of microcrystalline zeolites

    NARCIS (Netherlands)

    Ortiz-Iniesta, Maria Jesus; Heeres, Hero Jan; Melian-Cabrera, Ignacio

    2013-01-01

    In this work a direct activation route of zeolites is assessed. It consists of NH4-exchanging the as-synthesized solids before removing the organic template. Calcination afterwards serves to combust the organic template and creates the Bronsted sites directly; thus applying merely a single thermal

  13. Direction of Nuclear Energy. Activity report 2010

    International Nuclear Information System (INIS)

    2011-11-01

    This report proposes an overview of the research activities performed by the French DEN (Direction de l'Energie Nucleaire, Direction of Nuclear Energy) within the CEA. These activities address the future nuclear industrial systems (4. generation reactors, back-end of the future fuel cycle, basic scientific and technological research), the optimization of the industrial nuclear power (fuel cycle front end, second and third generation reactors, back-end of the present fuel cycle), major tools for the development of nuclear energy (simulation tools, Jules Horowitz reactor, value creation), clean up and dismantling of nuclear facilities (present status, the Passage project in Grenoble, the Aladin project in Fontenay-aux-Roses, projects at Marcoule, flow management of radioactive wastes, materials and disused fuels, transport). Three research centres are presented: Marcoule, Cadarache and Saclay

  14. ETF design activities: status and future direction

    International Nuclear Information System (INIS)

    Steiner, D.

    1980-01-01

    The nature of the device to follow TFTR has been evolving over the past six years. The most recent design activities have been directed to the Engineering Test Facility (ETF) concept. In order to address the design of the ETF a centralized laboratory/industry design team was established and hosted at ORNL. This Design Center began ETF Preconceptual design in October, 1979. The ETF design effort has been judged to be sound. However, the ETF mission has been judged to be overly ambitious. It has been recommended that the device to follow TFTR be dedicated to the investigation of engineering feasibility and that device has been designated the Fusion Engineering Device (FED). The ETF design activities provide a basis for developing the FED design. This will be accomplished under the direction of the newly formed FED Technical Management Board

  15. Antioxidant activity directed isolations form punica granatum

    International Nuclear Information System (INIS)

    Siddiqi, R.; Saeed, M.G.; Sayeed, S.A.

    2012-01-01

    The extracts derived from pomegranate juice following antioxidant activity directed isolation were screened for their antioxidant activity through their ability to scavenge 2,2- diphenyl-l-picrylhydrazyl (DPPH) radicals. Only fractions which exhibited >50 / 0 DPPH scavenging effect at each step of isolation were selected for further purification and their ability to reduce peroxide formation (peroxide value) in heated com oil. Phytochemical analysis of the pure compounds finally obtained, revealed the presence of pelargonidin-3- galactose (Pg-3-galactose), cyanidin-3-glucose (Cy-3-Glucose), gallic acid, quercetin and myricetin in the fractions exhibiting >50% DPPH scavenging potential. The order of antioxidant activity of these pure compounds by DPPH method was found to be gallic acid> quercetin> myricetin> Cy-3-galactose> Pg-3-Glucose while order with respect to reduction in peroxide value (PV) was the reverse of DPPH. (author)

  16. A gradient activation method for direct methanol fuel cells

    International Nuclear Information System (INIS)

    Liu, Guicheng; Yang, Zhaoyi; Halim, Martin; Li, Xinyang; Wang, Manxiang; Kim, Ji Young; Mei, Qiwen; Wang, Xindong; Lee, Joong Kee

    2017-01-01

    Highlights: • A gradient activation method was reported firstly for direct methanol fuel cells. • The activity recovery of Pt-based catalyst was introduced into the novel activation process. • The new activation method led to prominent enhancement of DMFC performance. • DMFC performance was improved with the novel activation step by step within 7.5 h. - Abstract: To realize gradient activation effect and recover catalytic activity of catalyst in a short time, a gradient activation method has firstly been proposed for enhancing discharge performance and perfecting activation mechanism of the direct methanol fuel cell (DMFC). This method includes four steps, i.e. proton activation, activity recovery activation, H 2 -O 2 mode activation and forced discharging activation. The results prove that the proposed method has gradually realized replenishment of water and protons, recovery of catalytic activity of catalyst, establishment of transfer channels for electrons, protons, and oxygen, and optimization of anode catalyst layer for methanol transfer in turn. Along with the novel activation process going on, the DMFC discharge performance has been improved, step by step, to more than 1.9 times higher than that of the original one within 7.5 h. This method provides a practicable activation way for the real application of single DMFCs and stacks.

  17. Operationalising active involvement in the EU water framework directive

    DEFF Research Database (Denmark)

    Wright, Stuart Anthony Lewis; Fritsch, Oliver

    2011-01-01

    We identify two key stages in the river basin planning process under the Water Framework Directive: the selection of instruments for a programme of measures to achieve the environmental targets, and disproportionate cost analysis to determine whether selected measures involve high costs. Some EU...... member states such as Denmark are operationalising these two key stages using cost effectiveness analysis and cost–benefit analysis. However, implementation guidelines encourage the active involvement of all interested parties in the implementation of the Directive. We discuss the potential benefits...... to comply with the statutory requirements of the Directive, but should strive for active involvement due to the potential for increasing the effectiveness of the Water Framework Directive and improving its implementation...

  18. Direct Microbicidal Activity of Cytotoxic T-Lymphocytes

    Directory of Open Access Journals (Sweden)

    Paul Oykhman

    2010-01-01

    Full Text Available Cytotoxic T-lymphocytes (CTL are famous for their ability to kill tumor, allogeneic and virus-infected cells. However, an emerging literature has now demonstrated that CTL also possess the ability to directly recognize and kill bacteria, parasites, and fungi. Here, we review past and recent findings demonstrating the direct microbicidal activity of both CD4+ and CD8+ CTL against various microbial pathogens. Further, this review will outline what is known regarding the mechanisms of direct killing and their underlying signalling pathways.

  19. phytochemical screening of activity directed extracts of vernonia ...

    African Journals Online (AJOL)

    Admin

    Fractionation of the crude ethanolic extract of vernonia amygdalina using organic solvents of increasing polarities yielded activity directed fractions of benzene, chloroform, ethyl acetate, butanol, methanol and residue E. Phytochemical screening of the fractions show that there were significant differences (p≤0.05) ...

  20. Activating PER repressor through a DBT-directed phosphorylation switch.

    Directory of Open Access Journals (Sweden)

    Saul Kivimäe

    2008-07-01

    Full Text Available Protein phosphorylation plays an essential role in the generation of circadian rhythms, regulating the stability, activity, and subcellular localization of certain proteins that constitute the biological clock. This study examines the role of the protein kinase Doubletime (DBT, a Drosophila ortholog of human casein kinase I (CKIepsilon/delta. An enzymatically active DBT protein is shown to directly phosphorylate the Drosophila clock protein Period (PER. DBT-dependent phosphorylation sites are identified within PER, and their functional significance is assessed in a cultured cell system and in vivo. The per(S mutation, which is associated with short-period (19-h circadian rhythms, alters a key phosphorylation target within PER. Inspection of this and neighboring sequence variants indicates that several DBT-directed phosphorylations regulate PER activity in an integrated fashion: Alternative phosphorylations of two adjoining sequence motifs appear to be associated with switch-like changes in PER stability and repressor function.

  1. Parent-child relationship of directly measured physical activity

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    Mâsse Louise C

    2011-03-01

    Full Text Available Abstract Background Studies on parent-child correlations of physical activity have been mixed. Few studies have examined concurrent temporal patterns of physical activity and sedentary behaviors in parents and children using direct measures. The purpose of this study was to examine parent-child activity correlations by gender, day of week, and time of day, using accelerometers - a method for direct assessment of physical activity. Methods Accelerometers were used to assess physical activity and sedentary time in 45 fathers, 45 mothers and their children (23 boys, 22 girls, mean age 9.9 years over the course of 4 days (Thursday - Sunday. Participants were instructed to wear accelerometers for 24 hours per day. Data from accelerometers were aggregated into waking hours on weekdays and weekends (6:00 am to midnight and weekday after-school hours (3:00 - 7:00 pm. Results Across the 4 days, the mean minutes per day of moderate-to-vigorous physical activity (MVPA for fathers was 30.0 (s.d. = 17.3, for mothers was 30.1 (s.d. = 20.1 and for children was 145.47 (s.d. = 51.64. Mothers' and fathers' minutes of MVPA and minutes of sedentary time were positively correlated with child physical activity and sedentary time (all ps Conclusions Greater parental MVPA was associated with increased child MVPA. In addition, having two parents with higher levels of MVPA was associated with greater levels of activity in children. Sedentary time in children was not as strongly correlated with that of their parents. Findings lend support to the notion that to increase childhood activity levels it may be fruitful to improve physical activity among parents.

  2. Inflammatory aetiology of human myometrial activation tested using directed graphs.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available THERE ARE THREE MAIN HYPOTHESES FOR THE ACTIVATION OF THE HUMAN UTERUS AT LABOUR: functional progesterone withdrawal, inflammatory stimulation, and oxytocin receptor activation. To test these alternatives we have taken information and data from the literature to develop causal pathway models for the activation of human myometrium. The data provided quantitative RT-PCR results on key genes from samples taken before and during labour. Principal component analysis showed that pre-labour samples form a homogenous group compared to those during labour. We therefore modelled the alternative causal pathways in non-labouring samples using directed graphs and statistically compared the likelihood of the different models using structural equations and D-separation approaches. Using the computer program LISREL, inflammatory activation as a primary event was highly consistent with the data (p = 0.925, progesterone withdrawal, as a primary event, is plausible (p = 0.499, yet comparatively unlikely, oxytocin receptor mediated initiation is less compatible with the data (p = 0.091. DGraph, a software program that creates directed graphs, produced similar results (p= 0.684, p= 0.280, and p = 0.04, respectively. This outcome supports an inflammatory aetiology for human labour. Our results demonstrate the value of directed graphs in determining the likelihood of causal relationships in biology in situations where experiments are not possible.

  3. Head direction cell activity in mice: robust directional signal depends on intact otolith organs

    Science.gov (United States)

    Yoder, Ryan M.; Taube, Jeffrey S.

    2009-01-01

    The head direction (HD) cell signal is a representation of an animal's perceived directional heading with respect to its environment. This signal appears to originate in the vestibular system, which includes the semicircular canals and otolith organs. Preliminary studies indicate the semicircular canals provide a necessary component of the HD signal, but involvement of otolithic information in the HD signal has not been tested. The present study was designed to determine the otolithic contribution to the HD signal, as well as to compare HD cell activity of mice to that of rats. HD cell activity in the anterodorsal thalamus was assessed in wild-type C57BL/6J and otoconia-deficient tilted mice during locomotion within a cylinder containing a prominent visual landmark. HD cell firing properties in C57BL/6J mice were generally similar to those in rats. However, in C57BL/6J mice, landmark rotation failed to demonstrate dominant control of the HD signal in 36% of the sessions. In darkness, directional firing became unstable during 42% of the sessions, but landmark control was not associated with HD signal stability in darkness. HD cells were identified in tilted mice, but directional firing properties were not as robust as those of C57BL/6J mice. Most HD cells in tilted mice were controlled by landmark rotation, but showed substantial signal degradation across trials. These results support current models that suggest otolithic information is involved in the perception of directional heading. Furthermore, compared to rats, the HD signal in mice appears to be less reliably anchored to prominent environmental cues. PMID:19176815

  4. Direct instrumental identification of catalytically active surface sites

    Science.gov (United States)

    Pfisterer, Jonas H. K.; Liang, Yunchang; Schneider, Oliver; Bandarenka, Aliaksandr S.

    2017-09-01

    The activity of heterogeneous catalysts—which are involved in some 80 per cent of processes in the chemical and energy industries—is determined by the electronic structure of specific surface sites that offer optimal binding of reaction intermediates. Directly identifying and monitoring these sites during a reaction should therefore provide insight that might aid the targeted development of heterogeneous catalysts and electrocatalysts (those that participate in electrochemical reactions) for practical applications. The invention of the scanning tunnelling microscope (STM) and the electrochemical STM promised to deliver such imaging capabilities, and both have indeed contributed greatly to our atomistic understanding of heterogeneous catalysis. But although the STM has been used to probe and initiate surface reactions, and has even enabled local measurements of reactivity in some systems, it is not generally thought to be suited to the direct identification of catalytically active surface sites under reaction conditions. Here we demonstrate, however, that common STMs can readily map the catalytic activity of surfaces with high spatial resolution: we show that by monitoring relative changes in the tunnelling current noise, active sites can be distinguished in an almost quantitative fashion according to their ability to catalyse the hydrogen-evolution reaction or the oxygen-reduction reaction. These data allow us to evaluate directly the importance and relative contribution to overall catalyst activity of different defects and sites at the boundaries between two materials. With its ability to deliver such information and its ready applicability to different systems, we anticipate that our method will aid the rational design of heterogeneous catalysts.

  5. Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.

    Science.gov (United States)

    White, Mark A; Li, Sheng; Tsalkova, Tamara; Mei, Fang C; Liu, Tong; Woods, Virgil L; Cheng, Xiaodong

    2012-01-01

    Exchange proteins directly activated by cAMP (EPACs) are important allosteric regulators of cAMP-mediated signal transduction pathways. To understand the molecular mechanism of EPAC activation, we have combined site-directed mutagenesis, X-ray crystallography, and peptide amide hydrogen/deuterium exchange mass spectrometry (DXMS) to probe the structural and conformational dynamics of EPAC2-F435G, a constitutively active EPAC2 mutant. Our study demonstrates that conformational dynamics plays a critical role in cAMP-induced EPAC activation. A glycine mutation at 435 position shifts the equilibrium of conformational dynamics towards the extended active conformation.

  6. Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.

    Directory of Open Access Journals (Sweden)

    Mark A White

    Full Text Available Exchange proteins directly activated by cAMP (EPACs are important allosteric regulators of cAMP-mediated signal transduction pathways. To understand the molecular mechanism of EPAC activation, we have combined site-directed mutagenesis, X-ray crystallography, and peptide amide hydrogen/deuterium exchange mass spectrometry (DXMS to probe the structural and conformational dynamics of EPAC2-F435G, a constitutively active EPAC2 mutant. Our study demonstrates that conformational dynamics plays a critical role in cAMP-induced EPAC activation. A glycine mutation at 435 position shifts the equilibrium of conformational dynamics towards the extended active conformation.

  7. Direct determination of phosphatase activity from physiological substrates in cells.

    Directory of Open Access Journals (Sweden)

    Zhongyuan Ren

    Full Text Available A direct and continuous approach to determine simultaneously protein and phosphate concentrations in cells and kinetics of phosphate release from physiological substrates by cells without any labeling has been developed. Among the enzymes having a phosphatase activity, tissue non-specific alkaline phosphatase (TNAP performs indispensable, multiple functions in humans. It is expressed in numerous tissues with high levels detected in bones, liver and neurons. It is absolutely required for bone mineralization and also necessary for neurotransmitter synthesis. We provided the proof of concept that infrared spectroscopy is a reliable assay to determine a phosphatase activity in the osteoblasts. For the first time, an overall specific phosphatase activity in cells was determined in a single step by measuring simultaneously protein and substrate concentrations. We found specific activities in osteoblast like cells amounting to 116 ± 13 nmol min(-1 mg(-1 for PPi, to 56 ± 11 nmol min(-1 mg(-1 for AMP, to 79 ± 23 nmol min(-1 mg(-1 for beta-glycerophosphate and to 73 ± 15 nmol min(-1 mg(-1 for 1-alpha-D glucose phosphate. The assay was also effective to monitor phosphatase activity in primary osteoblasts and in matrix vesicles. The use of levamisole--a TNAP inhibitor--served to demonstrate that a part of the phosphatase activity originated from this enzyme. An IC50 value of 1.16 ± 0.03 mM was obtained for the inhibition of phosphatase activity of levamisole in osteoblast like cells. The infrared assay could be extended to determine any type of phosphatase activity in other cells. It may serve as a metabolomic tool to monitor an overall phosphatase activity including acid phosphatases or other related enzymes.

  8. Direct detection of relic active and sterile neutrinos

    Science.gov (United States)

    Li, Yu-Feng

    2016-05-01

    Both active and sterile sub-eV neutrinos can form the cosmic neutrino background in the early Universe. We consider the beta-decaying (e.g., 3H) and EC-decaying (e.g., 163Ho) nuclei as the promising targets to capture relic neutrinos in the laboratory. We calculate the capture rates of relic electron neutrinos and antineutrinos against the corresponding beta decay or electron capture (EC) decay backgrounds in the (3+Ns) flavor mixing scheme, and discuss the future prospect in terms of the PTOLEMY project. We stress that such direct measurements of hot DM might not be hopeless in the long term.

  9. Experimental study of anti-tumor activity of direct current

    International Nuclear Information System (INIS)

    Ito, Hisao; Hashimoto, Shozo

    1989-01-01

    The anti-tumor activity of direct current combined with radiation was studied. The experiments were performed with fibrosarcomas (FSA, NFSA) syngenetic to C3H mice. Direct current (0.6mA, 120min) alone was effective to reduce the tumor sizes, but could not cure the tumors. When the direct current therapy (DC therapy) was combined with radiation the DC therapy following radiation was more effective than that before radiation. Using TCD 50 assay, the DC therapy enhanced the effect of a single dose of radiation with the dose-modifying factor of 1.2. However, tumor control rates by the combination therapy were more improved at the smaller doses of radiation than at the larger ones. When the single DC therapy (0.6mA, 120min) was applied immediately after the first radiation of fractionated one the combination therapy still showed the enhanced effect. However, both DC therapy and the radiation therapy were divided in three fractions, and the DC therapy (0.6mA, 40min) was applied after each radiation. Tumor growth retardation by the combination therapy was no different from that by radiation alone. This result suggests that there might be a minimum required dose of coulombs to show the effect of the combination therapy. (author)

  10. Metabolic activity of bacterial cell enumerated by direct viable count

    International Nuclear Information System (INIS)

    Roszak, D.B.; Colwell, R.R.

    1987-01-01

    The direct viable count (DVC) method was modified by incorporation radiolabeled substrates in microautoradiographic analyses to assess bacterial survival in controlled laboratory microcosms. The DVC method, which permits enumeration of culturable and nonculturable cells, discriminates those cells that are responsive to added nutrients but in which division is inhibited by the addition of nalidixic acid. The resulting elongated cells represent all viable cells; this includes those that are culturable on routine media and those that are not. Escherichia coli and Salmonella enteritidis were employed in the microcosm studies, and radiolabeled substrates included [methyl- 3 H] thymidine or [U- 14 C] glutamic acid. Samples taken at selected intervals during the survival experiments were examined by epifluorescence microscopy to enumerate cells by the DVC and acridine orange direct count methods, as well as by culture methods. Good correlation was obtained for cell-associated metabolic activity, measured by microautoradiography and substrate responsiveness (by the DVC method) at various stages of survival. Of the cells responsive to nutrients by the DVC method, ca. 90% were metabolically active by the microautoradiographic method. No significant difference was observed between DVC enumerations with or without added radiolabeled substrate

  11. Automated Ecological Assessment of Physical Activity: Advancing Direct Observation

    Directory of Open Access Journals (Sweden)

    Jordan A. Carlson

    2017-12-01

    Full Text Available Technological advances provide opportunities for automating direct observations of physical activity, which allow for continuous monitoring and feedback. This pilot study evaluated the initial validity of computer vision algorithms for ecological assessment of physical activity. The sample comprised 6630 seconds per camera (three cameras in total of video capturing up to nine participants engaged in sitting, standing, walking, and jogging in an open outdoor space while wearing accelerometers. Computer vision algorithms were developed to assess the number and proportion of people in sedentary, light, moderate, and vigorous activity, and group-based metabolic equivalents of tasks (MET-minutes. Means and standard deviations (SD of bias/difference values, and intraclass correlation coefficients (ICC assessed the criterion validity compared to accelerometry separately for each camera. The number and proportion of participants sedentary and in moderate-to-vigorous physical activity (MVPA had small biases (within 20% of the criterion mean and the ICCs were excellent (0.82–0.98. Total MET-minutes were slightly underestimated by 9.3–17.1% and the ICCs were good (0.68–0.79. The standard deviations of the bias estimates were moderate-to-large relative to the means. The computer vision algorithms appeared to have acceptable sample-level validity (i.e., across a sample of time intervals and are promising for automated ecological assessment of activity in open outdoor settings, but further development and testing is needed before such tools can be used in a diverse range of settings.

  12. Discoveries from Revisiting Apollo Direct Active Measurements of Lunar Dust

    Science.gov (United States)

    O'Brien, Brian

    2010-05-01

    New missions to the moon being developed by China, Japan, India, USA, Russia and Europe and possibilities of human missions about 2020 face the reality that 6 Apollo expeditions did not totally manage or mitigate effects of easily-mobilised and very "sticky" lunar dust on humans and hardware. Laboratory and theoretical modelling cannot reliably simulate the complex lunar environments that affect dynamical movements of lunar dust. The only direct active measurements of lunar dust during Apollo were made by matchbox-sized minimalist Dust Detector Experiments (DDEs) deployed to transmit some 30 million digital measurements from Apollo 11, 12, 14 and 15. These were misplaced or relatively ignored until 2009, when a self-funded suite of discoveries (O'Brien Geophys. Research Letters FIX 6 May 2099) revealed unexpected properties of lunar dust, such as the adhesive force being stronger as illumination increased. We give the first reports of contrasting effects, contamination or cleansing, from rocket exhausts of Apollo 11, 12, 14 and 15 Lunar Modules leaving the moon. We further strengthen the importance of collateral dust inadvertently splashed on Apollo hardware by human activities. Dust management designs and mission plans require optimum use of such in situ measurements, extended by laboratory simulations and theoretical modelling.

  13. Active Learning for Directed Exploration of Complex Systems

    Science.gov (United States)

    Burl, Michael C.; Wang, Esther

    2009-01-01

    Physics-based simulation codes are widely used in science and engineering to model complex systems that would be infeasible to study otherwise. Such codes provide the highest-fidelity representation of system behavior, but are often so slow to run that insight into the system is limited. For example, conducting an exhaustive sweep over a d-dimensional input parameter space with k-steps along each dimension requires k(sup d) simulation trials (translating into k(sup d) CPU-days for one of our current simulations). An alternative is directed exploration in which the next simulation trials are cleverly chosen at each step. Given the results of previous trials, supervised learning techniques (SVM, KDE, GP) are applied to build up simplified predictive models of system behavior. These models are then used within an active learning framework to identify the most valuable trials to run next. Several active learning strategies are examined including a recently-proposed information-theoretic approach. Performance is evaluated on a set of thirteen synthetic oracles, which serve as surrogates for the more expensive simulations and enable the experiments to be replicated by other researchers.

  14. Fat cells directly sense temperature to activate thermogenesis.

    Science.gov (United States)

    Ye, Li; Wu, Jun; Cohen, Paul; Kazak, Lawrence; Khandekar, Melin J; Jedrychowski, Mark P; Zeng, Xing; Gygi, Steven P; Spiegelman, Bruce M

    2013-07-23

    Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1. This nonshivering thermogenesis is crucial for mammals as a defense against cold and obesity/diabetes. Cold is known to act indirectly through the sympathetic nervous systems and β-adrenergic signaling, but here we report that cool temperature (27-33 °C) can directly activate a thermogenic gene program in adipocytes in a cell-autonomous manner. White and beige fat cells respond to cool temperatures, but classic brown fat cells do not. Importantly, this activation in isolated cells is independent of the canonical cAMP/Protein Kinase A/cAMP response element-binding protein pathway downstream of the β-adrenergic receptors. These findings provide an unusual insight into the role of adipose tissues in thermoregulation, as well as an alternative way to target nonshivering thermogenesis for treatment of obesity and metabolic diseases.

  15. Incorporating direct marketing activity into latent attrition models

    NARCIS (Netherlands)

    Schweidel, David A.; Knox, George

    2013-01-01

    When defection is unobserved, latent attrition models provide useful insights about customer behavior and accurate forecasts of customer value. Yet extant models ignore direct marketing efforts. Response models incorporate the effects of direct marketing, but because they ignore latent attrition,

  16. LABORATORY DIRECTED RESEARCH AND DEVELOPMENT PROGRAM ACTIVITIES FOR FY2002.

    Energy Technology Data Exchange (ETDEWEB)

    FOX,K.J.

    2002-12-31

    Brookhaven National (BNL) Laboratory is a multidisciplinary laboratory that carries out basic and applied research in the physical, biomedical, and environmental sciences, and in selected energy technologies. It is managed by Brookhaven Science Associates, LLC, under contract with the U. S. Department of Energy. BNL's total annual budget has averaged about $450 million. There are about 3,000 employees, and another 4,500 guest scientists and students who come each year to use the Laboratory's facilities and work with the staff. The BNL Laboratory Directed Research and Development (LDRD) Program reports its status to the U.S. Department of Energy (DOE) annually in March, as required by DOE Order 4 1 3.2A, ''Laboratory Directed Research and Development,'' January 8, 2001, and the LDRD Annual Report guidance, updated February 12, 1999. The LDRD Program obtains its funds through the Laboratory overhead pool and operates under the authority of DOE Order 413.2A. The goals and objectives of BNL's LDRD Program can be inferred from the Program's stated purposes. These are to (1) encourage and support the development of new ideas and technology, (2) promote the early exploration and exploitation of creative and innovative concepts, and (3) develop new ''fundable'' R&D projects and programs. The emphasis is clearly articulated by BNL to be on supporting exploratory research ''which could lead to new programs, projects, and directions'' for the Laboratory. As one of the premier scientific laboratories of the DOE, BNL must continuously foster groundbreaking scientific research. At Brookhaven National Laboratory one such method is through its LDRD Program. This discretionary research and development tool is critical in maintaining the scientific excellence and long-term vitality of the Laboratory. Additionally, it is a means to stimulate the scientific community and foster new science and technology

  17. Laboratory Directed Research and Development Program Activities for FY 2008.

    Energy Technology Data Exchange (ETDEWEB)

    Looney,J.P.; Fox, K.

    2009-04-01

    with limited management filtering to encourage the creativity of individual researchers. The competition is open to all BNL staff in programmatic, scientific, engineering, and technical support areas. Researchers submit their project proposals to the Assistant Laboratory Director for Policy and Strategic Planning. A portion of the LDRD budget is held for the Strategic LDRD (S-LDRD) category. Projects in this category focus on innovative R&D activities that support the strategic agenda of the Laboratory. The Laboratory Director entertains requests or articulates the need for S-LDRD funds at any time. Strategic LDRD Proposals also undergo rigorous peer review; the approach to review is tailored to the size and scope of the proposal. These Projects are driven by special opportunities, including: (1) Research project(s) in support of Laboratory strategic initiatives as defined and articulated by the Director; (2) Research project(s) in support of a Laboratory strategic hire; (3) Evolution of Program Development activities into research and development activities; and (4) ALD proposal(s) to the Director to support unique research opportunities. The goals and objectives of BNL's LDRD Program can be inferred fronl the Program's stated purposes. These are to (1) encourage and support the development of new ideas and technology, (2) promote the early exploration and exploitation of creative and innovative concepts, and (3) develop new 'fundable' R&D projects and programs. The emphasis is clearly articulated by BNL to be on supporting exploratory research 'which could lead to new programs, projects, and directions' for the Laboratory. We explicitly indicate that research conducted under the LDRD Program should be highly innovative, and an element of high risk as to success is acceptable. To be one of the premier DOE National Laboratories, BNL must continuously foster groundbreaking scientific research. At Brookhaven National Laboratory one such method is through its LDRD Program

  18. Science and technology of plasma activated direct wafer bonding

    Science.gov (United States)

    Roberds, Brian Edward

    This dissertation studied the kinetics of silicon direct wafer bonding with emphasis on low temperature bonding mechanisms. The project goals were to understand the topological requirements for initial bonding, develop a tensile test to measure the bond strength as a function of time and temperature and, using the kinetic information obtained, develop lower temperature methods of bonding. A reproducible surface metrology metric for bonding was best described by power spectral density derived from atomic force microscopy measurements. From the tensile strength kinetics study it was found that low annealing temperatures could be used to obtain strong bonds, but at the expense of longer annealing times. Three models were developed to describe the kinetics. A diffusion controlled model and a reaction rate controlled model were developed for the higher temperature regimes (T > 600sp°C), and an electric field assisted oxidation model was proposed for the low temperature range. An in situ oxygen plasma treatment was used to further enhance the field-controlled mechanism which resulted in dramatic increases in the low temperature bonding kinetics. Multiple internal transmission Fourier transform infrared spectroscopy (MIT-FTIR) was used to monitor species evolution at the bonded interface and a capacitance-voltage (CV) study was undertaken to investigate charge distribution and surface states resulting from plasma activation. A short, less than a minute, plasma exposure prior to contacting the wafers was found to obtain very strong bonds for hydrophobic silicon wafers at very low temperatures (100sp°C). This novel bonding method may enable new technologies involving heterogeneous material systems or bonding partially fabricated devices to become realities.

  19. Lateral Directional Active Flow Control on a Hybrid ICE 101/Saccon UCAV

    Science.gov (United States)

    2015-10-08

    Lateral-Directional Active Flow Control on a Hybrid ICE-101/Saccon UCAV Lateral-Directional Active Flow Control on a Hybrid ICE-101/Saccon UCAV ...Jürgen Seidel October 8, 2015 Lateral-Directional Active Flow Control on a Hybrid ICE-101/Saccon UCAV Table of contents 1 Simulations Setup Results...Lateral-Directional Active Flow Control on a Hybrid ICE-101/Saccon UCAV Simulations Setup CFD description CFD code HPCMP CREATE-AVTM/Kestrel Cell-centered

  20. Directive properties of active coated nano-particles

    DEFF Research Database (Denmark)

    Arslanagic, Samel; Ziolkowski, W.

    2012-01-01

    and optical gain constant on the directivities. While significant variations in the directivities are realized in the cylindrical cases for different source locations within and slightly outside the nano-particles and values of the optical gain constant, the corresponding spherical cases exhibit negligible...

  1. Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Pengxiang; Nedelcu, Daniel; Watanabe, Miyako; Jao, Cindy; Kim, Youngchang; Liu, Jing; Salic, Adrian

    2016-08-01

    In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed with sterols and alone, revealing that sterols induce a dramatic conformational change of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing receptors. We demonstrate that Hedgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognition and activity. We also show that cholesterol itself binds and activates Smoothened. Furthermore, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol and Hedgehog. We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol.

  2. Diffusion properties of active particles with directional reversal

    International Nuclear Information System (INIS)

    Großmann, R; Bär, M; Peruani, F

    2016-01-01

    The diffusion properties of self-propelled particles which move at constant speed and, in addition, reverse their direction of motion repeatedly are investigated. The internal dynamics of particles triggering these reversal processes is modeled by a stochastic clock. The velocity correlation function as well as the mean squared displacement is investigated and, furthermore, a general expression for the diffusion coefficient for self-propelled particles with directional reversal is derived. Our analysis reveals the existence of an optimal, finite rotational noise amplitude which maximizes the diffusion coefficient. We comment on the relevance of these results with regard to biological systems and suggest further experiments in this context. (paper)

  3. The dopamine D2 receptor can directly recruit and activate GRK2 without G protein activation.

    Science.gov (United States)

    Pack, Thomas F; Orlen, Margo I; Ray, Caroline; Peterson, Sean M; Caron, Marc G

    2018-02-27

    The dopamine D2 receptor (D2R) is a G protein-coupled receptor (GPCR) that is critical for many central nervous system functions. The D2R carries out these functions by signaling through two transducers: G proteins and β-arrestins (βarrs). Selectively engaging either the G protein or βarr pathway may be a way to improve drugs targeting GPCRs. The current model of GPCR signal transduction posits a chain of events where G protein activation ultimately leads to βarr recruitment. GPCR kinases (GRKs), which are regulated by G proteins and whose kinase action facilitates βarr recruitment, bridge these pathways. Therefore βarr recruitment appears to be intimately tied to G protein activation via GRKs. Here, we sought to understand how GRK2 action at the D2R would be disrupted when G protein activation is eliminated and the effect of this on βarr recruitment. We used two recently developed biased D2R mutants that can preferentially interact either with G proteins or βarrs as well as a βarr-biased D2R ligand, UNC9994. With these functionally selective tools, we investigated the mechanism whereby the βarr-preferring D2R achieves βarr pathway activation in the complete absence of G protein activation. We describe how direct, G protein-independent recruitment of GRK2 drives interactions at the βarr-preferring D2R and also contributes to βarr recruitment at the WT D2R. Additionally, we found an additive interaction between the βarr-preferring D2R mutant and UNC9994. These results reveal that the D2R can directly recruit GRK2 without G protein activation and that this mechanism may have relevance to achieving βarr-biased signaling. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Directed enzymatic activation of 1-D DNA tiles.

    Science.gov (United States)

    Garg, Sudhanshu; Chandran, Harish; Gopalkrishnan, Nikhil; LaBean, Thomas H; Reif, John

    2015-02-24

    The tile assembly model is a Turing universal model of self-assembly where a set of square shaped tiles with programmable sticky sides undergo coordinated self-assembly to form arbitrary shapes, thereby computing arbitrary functions. Activatable tiles are a theoretical extension to the Tile assembly model that enhances its robustness by protecting the sticky sides of tiles until a tile is partially incorporated into a growing assembly. In this article, we experimentally demonstrate a simplified version of the Activatable tile assembly model. In particular, we demonstrate the simultaneous assembly of protected DNA tiles where a set of inert tiles are activated via a DNA polymerase to undergo linear assembly. We then demonstrate stepwise activated assembly where a set of inert tiles are activated sequentially one after another as a result of attachment to a growing 1-D assembly. We hope that these results will pave the way for more sophisticated demonstrations of activated assemblies.

  5. Food Activism in Italy as an Anthropology of Direct Democracy

    NARCIS (Netherlands)

    Grasseni, Cristina

    This article presents qualitative and quantitative findings on provisioning activism in Italy, focusing on Solidarity Purchase Groups (Gruppi di Acquisto Solidale, GAS). By using quantitative data about GAS growth, numerical consistence and economic impact and through ethnographic insights based on

  6. Fast and direct detection of neuronal activation with diffusion MRI

    International Nuclear Information System (INIS)

    Le Bihan, D.; Urayama, S.; Aso, T.; Hanakawa, T.; Fukuyama, H.

    2006-01-01

    Over the last 30 years functional neuroimaging has emerged as a revolutionary path to study the brain and the mind. This has been possible because of significant advances mainly in two imaging modalities, namely Positron Emission Tomograph y (PET) and Magnetic Resonance Imaging (MRI). Amazingly, although those two modalities are based on radically different physical approaches (detection of 1 3 radioactivity for the first one and nuclear magnetization for the second), both allo w brain activation images to be obtained through measurements involving water molecules. So far, PET and MRI functional imaging have relied on the same principle that neuronal activation and blood flow are coupled through metabolism: Blood flow increases locally in activated brain regions. In the case of PET one uses H 2 O radioactive water which is produced by using a cyclotron and injected to the subject vasculature. In activated brain regions the increase in blood flow leads to a local increase in the tissue radioactive water content detected and localized by the PE T camera. With MRI the hydrogen nuclei of brain endogenous water molecules are magnetized by a strong external magnetic field. In activated regions the increase in blood flow results in an increase of blood oxygenation which induces a slight perturbation of the magnetization relaxation properties of the water molecules around blood vessels detected by the MRI scanner (so called 'BOLD' effect). I n both approaches water is, thus, merely an indirect means to look at changes in cerebral blood flow which accompany brain activation, and although PET and BOLD f MRI have been extremely successful for the functional neuroimaging community, present well known limitations. While the coupling between neuronal activation, metabolism and blood flow has been verified in most instances including BOLD f MRI, the degree and the mechanism of coupling remains largely debated (Magistratt, Pellerin, Mangia) and may fail in some pathological

  7. Perceived Direction of Self-Motion from Orthogonally Directed Visual and Vestibular Stimulation in Passive and Active Observation

    Directory of Open Access Journals (Sweden)

    Kenzo Sakurai

    2011-10-01

    Full Text Available Perceiving the direction of self-motion is typically a multisensory process. The most effective cue to detect the observer's heading direction is the visual optic-flow pattern. In the initial period of body movement, however, the vestibular sense is another effective cue to detect the direction in which one's body started to move. Here I report our recent research on the perception of self-motion, 1 when observers are passively experiencing their real somatic motion in different body posture, and 2 when observers are actively moving their bodies forward and backward. Previously, we reported that when upright observers passively experience real linear oscillatory somatic motion (leftward/rightward or forward/backward while viewing orthogonal visual optic flow patterns (translating or expanding/contracting, their perceived body motion direction is intermediate to those specified by visual and vestibular information individually (Sakurai et al., 2002, ACV; 2003, ECVP; Sakurai et al., 2010, VSS; Kubodera et al., 2010, APCV. We then generalized those findings exploring other visual/vestibular combinations, investigating when the vertical axis of body coordinates is orthogonal to the gravity axis. Observers lay supinely and reported their perceived direction of self-motion, experiencing real upward/downward or leftward/rightward motion in body coordinates, while viewing orthogonal optic-flow patterns that were phase-locked to the swing motion. The results are very similar to our previous reports, but for combinations of body motion with visual expanding/contracting optic-flow, some observers' judgments were vision-only or vestibular-only, suggesting that multimodal integration in this context is an either-or process for these observers. Compared to our previous reports, one possible reason for this weighted combination failure is the discrepancy between body coordinates and gravity coordinates (Sakurai et al., 2011, ECVP. We recently extended those

  8. Diversification as the strategic direction of foreign economic activity

    Directory of Open Access Journals (Sweden)

    Yu.I. Dozorova

    2015-12-01

    Full Text Available The issue of diversification, diversification of exports and imports, diversification of foreign trade. Determined the importance of diversification strategy to improve economic performance and proved that diversification allows the flexibility to respond to changing market opportunities and reduce the risks that may occur during production specialization. With the diversification of the company reinforce its competitive position in the market. The concept of diversification is used in the formulation of portfolio strategy as one of the four components, namely a vector or direction of future growth areas of the company. The proposed provisions, by which we can achieve a positive result. Proved that by diversifying, the company improves its economic performance.

  9. Directed transport of active magnetotactic bacteria in porous media flow

    Science.gov (United States)

    Waisbord, Nicolas; Dehkharghani, Amin; Coons, Thomas; Guasto, Jeffrey S.

    2017-11-01

    Swimming cell migration through porous media is a topic of ecological and technical relevance for understanding sediment ecosystems and bioremediation of soil for decontamination. We focus on magnetotactic bacteria - which align passively with Earth's magnetic field and migrate in such sediment environments - as a model system. The transport properties of magnetotactic bacteria are measured in a 2D microfluidic porous medium as a function of the porous microstructure geometry and under a variety of environmental conditions. In a quiescent fluid and in the absence of an external, guiding magnetic field, the effective diffusion of cells' random walk is unsurprisingly hindered with decreasing porosity due to cell-surface interactions. When guided by a magnetic field, cell trajectories acquire a net direction and form lanes, a behavior that is enhanced with increasing magnetic field. When the directed motility is coupled with an opposing fluid flow through the porous medium, convective cells form and locally trap the swimming bacteria. These results, which are corroborated by Langevin Simulations are an important step toward understanding magnetotactic bacterial ecology as well as for the magnetic guidance of microrobots in complex environments. Supported by NSF Grant CBET-1511340.

  10. Direct estimate of active bacteria: CTC use and limitations

    NARCIS (Netherlands)

    Creach, V.; Baudoux, A.C.; Bertru, G.; Le Rouzic, B.

    2003-01-01

    During the last 10 years, the dye 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) has been used to determine the in situ number of "active" bacteria in different ecosystems. A part of this success is due to a simple protocol, which does not require sophisticated equipment. However, it has not been

  11. Rocket Fuel R and D at AFRL: Recent Activities and Future Direction

    Science.gov (United States)

    2017-04-12

    Charts 14 March 2017 - 12 April 2017 Rocket Fuel R&D at AFRL: Recent Activities & Future Direction Matt Billingsley Air Force Research Laboratory (AFMC...Fuel R&D at AFRL: Recent Activities & Future Direction 12 April, 2017 DLA Worldwide Energy Conference National Harbor, MD Matt Billingsley Air Force...PA Clearance Number 17163 Future Direction • Gov’t/Commercial relationships will clarify R&D activities • Air Force buys launches from commercial

  12. Fast and direct detection of neuronal activation with diffusion MRI

    Energy Technology Data Exchange (ETDEWEB)

    Le Bihan, D. [Service Hospitalier Frederic Joliot (CEA/DSV/DRM), Lab. Anatomical and Functional Neuroimaging, 91 - Orsay (France); Urayama, S.; Aso, T.; Hanakawa, T.; Fukuyama, H. [Kyoto Univ. Graduate School of Medicine, Human Brain Research Center, Kyoto (Japan)

    2006-07-01

    Over the last 30 years functional neuroimaging has emerged as a revolutionary path to study the brain and the mind. This has been possible because of significant advances mainly in two imaging modalities, namely Positron Emission Tomograph y (PET) and Magnetic Resonance Imaging (MRI). Amazingly, although those two modalities are based on radically different physical approaches (detection of 1 3 radioactivity for the first one and nuclear magnetization for the second), both allo w brain activation images to be obtained through measurements involving water molecules. So far, PET and MRI functional imaging have relied on the same principle that neuronal activation and blood flow are coupled through metabolism: Blood flow increases locally in activated brain regions. In the case of PET one uses H{sub 2}O radioactive water which is produced by using a cyclotron and injected to the subject vasculature. In activated brain regions the increase in blood flow leads to a local increase in the tissue radioactive water content detected and localized by the PE T camera. With MRI the hydrogen nuclei of brain endogenous water molecules are magnetized by a strong external magnetic field. In activated regions the increase in blood flow results in an increase of blood oxygenation which induces a slight perturbation of the magnetization relaxation properties of the water molecules around blood vessels detected by the MRI scanner (so called 'BOLD' effect). I n both approaches water is, thus, merely an indirect means to look at changes in cerebral blood flow which accompany brain activation, and although PET and BOLD f MRI have been extremely successful for the functional neuroimaging community, present well known limitations. While the coupling between neuronal activation, metabolism and blood flow has been verified in most instances including BOLD f MRI, the degree and the mechanism of coupling remains largely debated (Magistratt, Pellerin, Mangia) and may fail in some

  13. Laboratory Directed Research and Development Program Activities for FY 2007.

    Energy Technology Data Exchange (ETDEWEB)

    Newman,L.

    2007-12-31

    Brookhaven National Laboratory (BNL) is a multidisciplinary laboratory that carries out basic and applied research in the physical, biomedical, and environmental sciences, and in selected energy technologies. It is managed by Brookhaven Science Associates, LLC, (BSA) under contract with the U. S. Department of Energy (DOE). BNL's Fiscal year 2007 budget was $515 million. There are about 2,600 employees, and another 4,500 guest scientists and students who come each year to use the Laboratory's facilities and work with the staff. The BNL Laboratory Directed Research and Development (LDRD) Program reports its status to the U.S. Department of Energy (DOE) annually in March, as required by DOE Order 413.2B, 'Laboratory Directed Research and Development', April 19, 2006, and the Roles, Responsibilities, and Guidelines for Laboratory Directed Research and Development at the Department of Energy/National Nuclear Security Administration Laboratories dated June 13, 2006. In accordance this is our Annual Report in which we describe the Purpose, Approach, Technical Progress and Results, and Specific Accomplishments of all LDRD projects that received funding during Fiscal Year 2007. The goals and objectives of BNL's LDRD Program can be inferred from the Program's stated purposes. These are to (1) encourage and support the development of new ideas and technology, (2) promote the early exploration and exploitation of creative and innovative concepts, and (3) develop new 'fundable' R&D projects and programs. The emphasis is clearly articulated by BNL to be on supporting exploratory research 'which could lead to new programs, projects, and directions' for the Laboratory. We explicitly indicate that research conducted under the LDRD Program should be highly innovative, and an element of high risk as to success is acceptable. In the solicitation for new proposals for Fiscal Year 2007 we especially requested innovative new projects in

  14. Direct harmonic voltage control strategy for shunt active power filter

    DEFF Research Database (Denmark)

    Munir, Hafiz Mudassir; Zou, JianXiao; Xie, Chuan

    2017-01-01

    voltage control strategy for the S-APF is proposed with local point of common coupling (PCC) voltage detection only. The control strategy design procedure is given in detail. Simulation is conducted in Matlab/Simulink to compare the performance between the R-APF and the proposed method. The results......Shunt active power filters (S-APF) are highly popular ways for harmonic compensation due to the high performance and simplicity of installation. S-APF is commonly controlled in current control mode with load harmonic current detection, which is not quite suitable for the distributed power...

  15. Lepidium meyenii (Maca) does not exert direct androgenic activities.

    Science.gov (United States)

    Bogani, P; Simonini, F; Iriti, M; Rossoni, M; Faoro, F; Poletti, A; Visioli, F

    2006-04-06

    Maca is the edible root of the Peruvian plant Lepidum meyenii, traditionally employed for its purported aphrodisiac and fertility-enhancing properties. This study aimed at testing the hypothesis that Maca contains testosterone-like compounds, able to bind the human androgen receptor and promote transcription pathways regulated by steroid hormone signaling. Maca extracts (obtained with different solvents: methanol, ethanol, hexane and chloroform) are not able to regulate GRE (glucocorticoid response element) activation. Further experiments are needed to assess which compound, of the several Maca's components, is responsible of the observed in vivo effects.

  16. Chitinase producing bacteria with direct algicidal activity on marine diatoms.

    Science.gov (United States)

    Li, Yi; Lei, Xueqian; Zhu, Hong; Zhang, Huajun; Guan, Chengwei; Chen, Zhangran; Zheng, Wei; Fu, Lijun; Zheng, Tianling

    2016-02-23

    Chitinase producing bacteria can involve extensively in nutrient cycling and energy flow in the aquatic environment through degradation and utilization of chitin. It is well known that diatoms cells are encased by box-like frustules composed of chitin. Thus the chitin containing of diatoms shall be a natural target of chitinase producing bacteria, however, the interaction between these two organismic groups has not been studied thus far. Therefore, in this study, the algicidal mechanism of one chitinase producing bacterium (strain LY03) on Thalassiosira pseudonana was investigated. The algicidal range and algicidal mode of strain LY03 were first studied, and then bacterial viability, chemotactic ability and direct interaction characteristic between bacteria and diatom were also confirmed. Finally, the characteristic of the intracellular algicidal substance was identified and the algicidal mechanism was determined whereby algicidal bacterial cells showed chemotaxis to algal cells, fastened themselves on algal cells with their flagella, and then produced chitinase to degrade algal cell walls, and eventually caused algal lysis and death. It is the first time to investigate the interaction between chitinase producing bacteria and diatoms, and this novel special interaction mode was confirmed in this study, which will be helpful in protection and utilization of diatoms resources.

  17. Direct 4D printing via active composite materials

    Science.gov (United States)

    Ding, Zhen; Yuan, Chao; Peng, Xirui; Wang, Tiejun; Qi, H. Jerry; Dunn, Martin L.

    2017-01-01

    We describe an approach to print composite polymers in high-resolution three-dimensional (3D) architectures that can be rapidly transformed to a new permanent configuration directly by heating. The permanent shape of a component results from the programmed time evolution of the printed shape upon heating via the design of the architecture and process parameters of a composite consisting of a glassy shape memory polymer and an elastomer that is programmed with a built-in compressive strain during photopolymerization. Upon heating, the shape memory polymer softens, releases the constraint on the strained elastomer, and allows the object to transform into a new permanent shape, which can then be reprogrammed into multiple subsequent shapes. Our key advance, the markedly simplified creation of high-resolution complex 3D reprogrammable structures, promises to enable myriad applications across domains, including medical technology, aerospace, and consumer products, and even suggests a new paradigm in product design, where components are simultaneously designed to inhabit multiple configurations during service. PMID:28439560

  18. Heterogeneous Effects of Direct Hypoxia Pathway Activation in Kidney Cancer.

    Directory of Open Access Journals (Sweden)

    Rafik Salama

    Full Text Available General activation of hypoxia-inducible factor (HIF pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumor suppressor. However HIF-1α and HIF-2α have contrasting effects on experimental tumor progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1α and HIF-2α and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of canonical and non-canonical HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1α-specific binding, and genes associated with favorable prognosis and between HIF-2α-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-α isoform contributes a highly complex mix of pro- and anti-tumorigenic effects.

  19. 78 FR 77665 - Agency Information Collection Activities; Comment Request; Federal Direct Consolidation Loan...

    Science.gov (United States)

    2013-12-24

    ... existing Federal Direct Consolidation Loan within a specified time period. The LVC serves as the means by... Agency Information Collection Activities; Comment Request; Federal Direct Consolidation Loan Program... to this notice will be considered public records. Title of Collection: Federal Direct Consolidation...

  20. Dual gene activation and knockout screen reveals directional dependencies in genetic networks. | Office of Cancer Genomics

    Science.gov (United States)

    Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.

  1. Direct care staff perspectives related to physical activity in mental health group homes.

    Science.gov (United States)

    Harding, Shari L

    2013-12-01

    Sedentary lifestyle is a modifiable risk factor that contributes to health disparities in individuals with serious mental illness. Direct care staff in mental health group homes were surveyed to determine barriers and resource needs related to conducting physical activity interventions with individuals. An investigator-designed survey was used. The most significant barriers cited by staff were individuals did not want to engage in physical activity and staff needed more information about how to conduct physical activity interventions. Resource needs cited by staff included engagement strategies to gain and maintain individual interest as well as resource acquisition. Direct care staff are well positioned to deliver physical activity interventions but need support and direction to engage individuals in safe and effective exercise. Mental health nurses are well placed to provide support and direction to staff for these interventions. Copyright 2013, SLACK Incorporated.

  2. 29 CFR 1620.4 - “Closely related” and “directly essential” activities.

    Science.gov (United States)

    2010-07-01

    ....4 Section 1620.4 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION THE EQUAL PAY ACT § 1620.4 “Closely related” and “directly essential” activities. An employee is... if the employees's work is not an actual and direct part of such production, so long as the employee...

  3. Directional preference of activation of abdominal and paraspinal muscles during position-control tasks in sitting.

    Science.gov (United States)

    Eriksson Crommert, Martin; Tucker, Kylie; Holford, Christopher; Wight, Alexander; McCook, Donna; Hodges, Paul

    2017-08-01

    Controversy exists in the literature regarding antagonist activity of trunk muscles during different types of trunk loading, and the direction-specificity of activation of trunk muscles, particularly the deeper trunk muscles. This study aimed to systematically compare activation of a range of trunk muscles between directions of statically applied loads, and to consider the impact of breathing in this activation. In a semi-seated position, 13 healthy male participants resisted moderate inertial loads applied to the trunk in eight different directions. Intramuscular electromyography was recorded from eight abdominal and back muscles on the right side during 1s prior to peak inspiration/expiration. All muscles demonstrated a directional preference of activation. No muscle displayed antagonistic activation during loading conditions of an intensity that exceded that recorded in upright sitting without a load. During these moderate intensity sustained efforts, trunk muscle activation varied little between respiratory phases. Antagonistic muscle activation of amplitude equivalent to the activation recorded in upright sitting without load is sufficient to maintain control of the spine during predictable and sustained low load tasks. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Correlation of fingertip shear force direction with somatosensory cortical activity in monkey

    Science.gov (United States)

    Fortier-Poisson, Pascal; Langlais, Jean-Sébastien

    2015-01-01

    To examine the activity of somatosensory cortex (S1) neurons to self-generated shear forces on the index and thumb, two monkeys were trained to grasp a stationary metal tab with a key grip and exert forces without the fingers slipping in one of four orthogonal directions for 1 s. A majority (∼85%) of slowly adapting and rapidly adapting (RA) S1 neurons had activity modulated with shear force direction. The cells were recorded mainly in areas 1 and 2 of the S1, although some area 3b neurons also responded to shear direction or magnitude. The preferred shear vectors were distributed in every direction, with tuning arcs varying from 50° to 170°. Some RA neurons sensitive to dynamic shear force direction also responded to static shear force but within a narrower range, suggesting that the direction of the shear force may influence the adaptation rate. Other neurons were modulated with shear forces in diametrically opposite directions. The directional sensitivity of S1 cortical neurons is consistent with recordings from cutaneous afferents showing that shear direction, even without slip, is a powerful stimulus to S1 neurons. PMID:26467520

  5. Is directly measured physical activity related to adiposity in preschool children?

    NARCIS (Netherlands)

    Sijtsma, Anna; Sauer, Pieter J. J.; Stolk, Ronald P.; Corpeleijn, Eva

    2011-01-01

    This review summarizes the association between directly assessed physical activity and adiposity in preschool children (age 1.5-6 years). It includes 17 cross-sectional and longitudinal studies that were published between January 1999 and February 2010. The association between physical activity and

  6. The Effect of Creative Drama Activities on Candidate Teachers' Self- Directed Skills

    Science.gov (United States)

    Kosucu, Emine; Hursen, Cigdem

    2017-01-01

    This research aimed to specify the effect of creative drama activities on candidate teachers' self-directed skills. 35 candidate teachers participated in this study in which a mixture of a qualitative and quantitative method was used. The results obtained from the research showed that creative drama activities are effective on candidate teachers'…

  7. Iranian Clinical Nurses' Activities for Self-Directed Learning: A Qualitative Study.

    Science.gov (United States)

    Ghiyasvandian, Shahrzad; Malekian, Morteza; Cheraghi, Mohammad Ali

    2015-09-01

    Clinical nurses need lifelong learning skills for responding to the rapid changes of clinical settings. One of the best strategies for lifelong learning is self-directed learning. The aim of this study was to explore Iranian clinical nurses' activities for self-directed learning. In this qualitative study, 23 semi-structured personal interviews were conducted with nineteen clinical nurses working in all four hospitals affiliated to Isfahan Social Security Organization, Isfahan, Iran. Study data were analyzed by using the content analysis approach. The study was conducted from June 2013 to October 2014. Study participants' activities for self-directed learning fell into two main categories of striving for knowledge acquisition and striving for skill development. The main theme of the study was 'Revising personal performance based on intellectual-experiential activities'. Study findings suggest that Iranian clinical nurses continually revise their personal performance by performing self-directed intellectual and experiential activities to acquire expertise. The process of acquiring expertise is a linear process which includes two key steps of knowledge acquisition and knowledge development. In order to acquire and advance their knowledge, nurses perform mental learning activities such as sensory perception, self-evaluation, and suspended judgment step-by-step. Moreover, they develop their skills through doing activities like apprenticeship, masterly performance, and self-regulation. The absolute prerequisite to expertise acquisition is that a nurse needs to follow these two steps in a sequential manner.

  8. Asymmetric active nano-particles for directive near-field radiation

    DEFF Research Database (Denmark)

    Arslanagic, Samel; Thorsen, Rasmus O.

    2016-01-01

    In this work, we demonstrate the potential of cylindrical active coated nano-particles with certain geometrical asymmetries for the creation of directive near-field radiation. The particles are excited by a near-by magnetic line source, and their performance characteristics are reported in terms...... of radiated power, near-field and power flow distributions as well as the far-field directivity....

  9. Translational Optic Flow Induces Shifts in Direction of Active Forward and Backward Self-Motion

    Directory of Open Access Journals (Sweden)

    Kenzo Sakurai

    2011-05-01

    Full Text Available Previously, we reported that when observers passively experience real linear oscillatory somatic motion while viewing orthogonal visual optic flow patterns, their perceived motion direction is intermediate to those specified by visual and vestibular information individually (Sakurai et al., 2002, ACV; 2003, ECVP; 2010, VSS; Kubodera et al., 2010, APCV. Here, we extend those studies to active somatic motion, measuring the angular shift in body direction after active body motion while viewing synchronized orthogonal optic flow. Experimental visual stimuli consisted of 1 second of translating leftward (rightward random-dots and 1 second of random noise. Control stimuli consisted of two 1-second intervals of random noise separated by a static interval. Observers viewed the stimulus for 30 seconds through a face-mounted display while actively stepping forward and backward such that their forward body movement was synchronized with the random-dot translational motion. Observers' body direction was measured before and after each trial. Translational optic flow induced shifts in body direction that were opposite to shifts in perceived direction with passive viewing in our previous reports. Observers may have compensated their body motion in response to perceived direction shifts similar to those we reported for passive viewing.

  10. Direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp

    Energy Technology Data Exchange (ETDEWEB)

    Ljusev, P.; Andersen, Michael A.E.

    2005-07-01

    This paper discusses the advantages and problems when implementing direct energy conversion switching-mode audio power amplifiers. It is shown that the total integration of the power supply and Class D audio power amplifier into one compact direct converter can simplify design, increase efficiency and integration level, reduce product volume and lower its cost. As an example, the principle of operation and the measurements made on a direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp are presented. (au)

  11. Direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    This paper discusses the advantages and problems when implementing direct energy conversion switching-mode audio power amplifiers. It is shown that the total integration of the power supply and Class D audio power amplifier into one compact direct converter can simplify the design, increase effic...... efficiency, reduce the product volume and lower its cost. As an example, the principle of operation and the measurements made on a direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp are presented....

  12. Highly porous activated carbons prepared from carbon rich Mongolian anthracite by direct NaOH activation

    Energy Technology Data Exchange (ETDEWEB)

    Byamba-Ochir, Narandalai [School of Chemical Engineering, Chonnam National University, 77 Yongbong-Ro, Gwangju 61186 (Korea, Republic of); Shim, Wang Geun [Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-Ro, Suncheon, Jeollanam-Do 57922 (Korea, Republic of); Balathanigaimani, M.S., E-mail: msbala@rgipt.ac.in [Department of Chemical Engineering, Rajiv Gandhi Institute of Petroleum Technology, Ratapur Chowk, Rae Bareli, 229316 Uttar Pradesh (India); Moon, Hee, E-mail: hmoon@jnu.ac.kr [School of Chemical Engineering, Chonnam National University, 77 Yongbong-Ro, Gwangju 61186 (Korea, Republic of)

    2016-08-30

    Highlights: • Highly porous carbon materials from Mongolian anthracite by chemical activation. • Cheaper and eco-friendly activation process has been employed. • Activated carbons with graphitic structure and energetically heterogeneous surface. • Surface hydrophobicity and porosity of the activated carbons can be controlled. - Abstract: Highly porous activated carbons (ACs) were prepared from Mongolian raw anthracite (MRA) using sodium hydroxide as an activation agent by varying the mass ratio (powdered MRA/NaOH) as well as the mixing method of chemical agent and powdered MRA. The specific BET surface area and total pore volume of the prepared MRA-based activated carbons (MACs) are in the range of 816–2063 m{sup 2}/g and of 0.55–1.61 cm{sup 3}/g, respectively. The pore size distribution of MACs show that most of the pores are in the range from large micropores to small mesopores and their distribution can be controlled by the mass ratio and mixing method of the activating agent. As expected from the intrinsic property of the MRA, the highly graphitic surface morphology of prepared carbons was confirmed from Raman spectra and transmission electron microscopy (TEM) studies. Furthermore the FTIR and XPS results reveal that the preparation of MACs with hydrophobic in nature is highly possible by controlling the mixing conditions of activating agent and powdered MRA. Based on all the results, it is suggested that the prepared MACs could be used for many specific applications, requiring high surface area, optimal pore size distribution, proper surface hydrophobicity as well as strong physical strength.

  13. Modulation of cortical activity by transcranial direct current stimulation in patients with affective disorder.

    Directory of Open Access Journals (Sweden)

    Tamara Y Powell

    Full Text Available Transcranial direct current stimulation (tDCS has been shown to have antidepressant efficacy in patients experiencing a major depressive episode, but little is known about the underlying neurophysiology. The purpose of our study was to investigate the acute effects of tDCS on cortical activity using electroencephalography (EEG in patients with an affective disorder. Eighteen patients diagnosed with an affective disorder and experiencing a depressive episode participated in a sham-controlled study of tDCS, each receiving a session of active (2 mA for 20 minutes and sham tDCS to the left dorsolateral prefrontal cortex (DLPFC. The effects of tDCS on EEG activity were assessed after each session using event-related potentials (ERP and measurement of spectral activity during a visual working memory (VWM task. We observed task and intervention dependent effects on both ERPs and task-related alpha and theta activity, where active compared to sham stimulation resulted in a significant reduction in the N2 amplitude and reduced theta activity over frontal areas during memory retrieval. In summary a single session of anodal tDCS stimulation to the left DLPFC during a major depressive episode resulted in modulated brain activity evident in task-related EEG. Effects on the N2 and frontal theta activity likely reflect modulated activity in the medial frontal cortex and hence indicate that the after-effects of tDCS extend beyond the direct focal effects to the left DLPFC.

  14. Head Direction Cell Activity Is Absent in Mice without the Horizontal Semicircular Canals.

    Science.gov (United States)

    Valerio, Stephane; Taube, Jeffrey S

    2016-01-20

    Head direction (HD) cells fire when an animal faces a particular direction in its environment, and they are thought to represent the neural correlate of the animal's perceived spatial orientation. Previous studies have shown that vestibular information is critical for generating the HD signal but have not delineated whether information from all three semicircular canals or just the horizontal canals, which are primarily sensitive to angular head rotation in the horizontal (yaw) plane, are critical for the signal. Here, we monitored cell activity in the anterodorsal thalamus (ADN), an area known to contain HD cells, in epstatic circler (Ecl) mice, which have a bilateral malformation of the horizontal (lateral) semicircular canals. Ecl mice and their littermates that did not express the mutation (controls) were implanted with recording electrodes in the ADN. Results confirm the important role the horizontal canals play in forming the HD signal. Although normal HD cell activity (Raleigh's r > 0.4) was recorded in control mice, no such activity was found in Ecl mice, although some cells had activity that was mildly modulated by HD (0.4 > r > 0.2). Importantly, we also observed activity in Ecl mice that was best characterized as bursty--a pattern of activity similar to an HD signal but without any preferred firing direction. These results suggest that the neural structure for the HD network remains intact in Ecl mice, but the absence of normal horizontal canals results in an inability to control the network properly and brings about an unstable HD signal. Significance statement: Cells in the anterior dorsal thalamic nucleus normally fire in relation to the animal's directional heading with respect to the environment--so-called head direction cells. To understand how these head direction cells generate their activity, we recorded single-unit activity from the anterior dorsal thalamus in transgenic mice that lack functional horizontal semicircular canals. We show that the

  15. Recent and past musical activity predicts cognitive aging variability: direct comparison with general lifestyle activities.

    Science.gov (United States)

    Hanna-Pladdy, Brenda; Gajewski, Byron

    2012-01-01

    Studies evaluating the impact of modifiable lifestyle factors on cognition offer potential insights into sources of cognitive aging variability. Recently, we reported an association between extent of musical instrumental practice throughout the life span (greater than 10 years) on preserved cognitive functioning in advanced age. These findings raise the question of whether there are training-induced brain changes in musicians that can transfer to non-musical cognitive abilities to allow for compensation of age-related cognitive declines. However, because of the relationship between engagement in general lifestyle activities and preserved cognition, it remains unclear whether these findings are specifically driven by musical training or the types of individuals likely to engage in greater activities in general. The current study controlled for general activity level in evaluating cognition between musicians and nomusicians. Also, the timing of engagement (age of acquisition, past versus recent) was assessed in predictive models of successful cognitive aging. Seventy age and education matched older musicians (>10 years) and non-musicians (ages 59-80) were evaluated on neuropsychological tests and general lifestyle activities. Musicians scored higher on tests of phonemic fluency, verbal working memory, verbal immediate recall, visuospatial judgment, and motor dexterity, but did not differ in other general leisure activities. Partition analyses were conducted on significant cognitive measures to determine aspects of musical training predictive of enhanced cognition. The first partition analysis revealed education best predicted visuospatial functions in musicians, followed by recent musical engagement which offset low education. In the second partition analysis, early age of musical acquisition (memory in musicians, while analyses for other measures were not predictive. Recent and past musical activity, but not general lifestyle activities, predicted variability

  16. Direct electrical stimulation of human cortex evokes high gamma activity that predicts conscious somatosensory perception

    Science.gov (United States)

    Muller, Leah; Rolston, John D.; Fox, Neal P.; Knowlton, Robert; Rao, Vikram R.; Chang, Edward F.

    2018-04-01

    Objective. Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. Approach. To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. Main results. We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. Significance. Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.

  17. Recent and Past Musical Activity Predicts Cognitive Aging Variability: Direct Comparison with Leisure Activities

    Directory of Open Access Journals (Sweden)

    Brenda eHanna-Pladdy

    2012-07-01

    Full Text Available Studies evaluating the impact of modifiable lifestyle factors on cognition offer potential insights into sources of cognitive aging variability. Recently, we reported an association between extent of musical instrumental practice throughout the life span (greater than 10 years on preserved cognitive functioning in advanced age . These findings raise the question of whether there are training-induced brain changes in musicians that can transfer to nonmusical cognitive abilities to allow for compensation of age-related cognitive declines. However, because of the relationship between engagement in lifestyle activities and preserved cognition, it remains unclear whether these findings are specifically driven by musical training or the types of individuals likely to engage in greater activities in general. The current study examined the type of leisure activity (musical versus other as well as the timing of engagement (age of acquisition, past versus recent in predictive models of successful cognitive aging. Seventy age and education matched older musicians (> 10 years and nonmusicians (ages 59-80 were evaluated on neuropsychological tests and life-style activities (AAP. Partition analyses were conducted on significant cognitive measures to explain performance variance in musicians. Musicians scored higher on tests of phonemic fluency, verbal immediate recall, judgment of line orientation (JLO, and Letter Number Sequencing (LNS, but not the AAP. The first partition analysis revealed education best predicted JLO in musicians, followed by recent musical engagement which offset low education. In the second partition analysis, early age of musical acquisition (< 9 years predicted enhanced LNS in musicians, while analyses for AAP, verbal recall and fluency were not predictive. Recent and past musical activity, but not leisure activity, predicted variability across verbal and visuospatial domains in aging. Early musical acquisition predicted auditory

  18. Main Aspects and Directions of an Increase in the Innovative Activity of Logistics Operators

    OpenAIRE

    Dudin, Mihail N.; Voykova, Natalia A.; Frolova, Evgenia E.; Artemieva, Julia A.; Grebennikov, Valeriy V.

    2016-01-01

    In this article, the authors have considered some aspects and perspectives that have both direct and indirect impact on the innovation activity of companies and firms that operate in the logistics market. The main tasks that have been solved in this article include the following: a study of trends and dynamics of development of the global logistics market; a review of transformations in external environment defining the need to strengthen the innovative activity of logistics operators; system...

  19. Choosing the Direction of Development of Foreign Economic Activity for Enterprises in the Aviation Industry

    Directory of Open Access Journals (Sweden)

    Shtal Tetyana V.

    2017-11-01

    Full Text Available The article is aimed at studying the existing approaches to the development of foreign economic activity (FEA of enterprise, elaborating the procedure of its management in order to determine the direction of development of FEA of enterprises in the aviation industry of Ukraine. The authors have developed, formalized and visualized a phased mechanism of choosing the direction of development of FEA for enterprise, according to the method of functional modeling. The obtained instrument was used to determine the direction of FEA development for a typical enterprise in the aviation industry. Features of the aforementioned enterprise have been allocated, a suitable set of development directions has been selected, a reasoned procedure of implementation of activities on development of foreign economic activity at the enterprise has been analyzed and determined. Prospect for further research in this direction can be implementation of the mechanism at the enterprises of other industries, refinement of the instrumentarium for each stage of the process according to their features and needs.

  20. Trunk muscle activation. The effects of torso flexion, moment direction, and moment magnitude.

    Science.gov (United States)

    Lavender, S; Trafimow, J; Andersson, G B; Mayer, R S; Chen, I H

    1994-04-01

    This study was performed to quantify the electromyographic trunk muscle activities in response to variations in moment magnitude and direction while in forward-flexed postures. Recordings were made over eight trunk muscles in 19 subjects who maintained forward-flexed postures of 30 degrees and 60 degrees. In each of the two flexed postures, external moments of 20 Nm and 40 Nm were applied via a chest harness. The moment directions were varied in seven 30 degrees increments to a subject's right side, such that the direction of the applied load ranged from the upper body's anterior midsagittal plane (0 degree) to the posterior midsagittal plane (180 degrees). Statistical analyses yielded significant moment magnitude by moment-direction interaction effects for the EMG output from six of the eight muscles. Trunk flexion by moment-direction interactions were observed in the responses from three muscles. In general, the primary muscle supporting the torso and the applied load was the contralateral (left) erector spinae. The level of electromyographic activity in the anterior muscles was quite low, even with the posterior moment directions.

  1. Field trials using a digital hearing aid with active noise reduction and dual-microphone directionality

    NARCIS (Netherlands)

    Boymans, M.; Dreschler, W. A.

    2000-01-01

    In this study, we measured the effects of a digital hearing aid on speech recognition or reception in noise for two noise reduction concepts: active noise reduction by speech-sensitive processing (SSP) and improved directionality by a dual- or so-called twin-microphone system (TMS). This was

  2. Modulation of cortical activity by transcranial direct current stimulation in patients with affective disorder

    NARCIS (Netherlands)

    Powell, T.Y.; Boonstra, T.W.; Martin, D.M.; Loo, C.K.; Breakspear, M.

    2014-01-01

    Transcranial direct current stimulation (tDCS) has been shown to have antidepressant efficacy in patients experiencing a major depressive episode, but little is known about the underlying neurophysiology. The purpose of our study was to investigate the acute effects of tDCS on cortical activity

  3. Hedge Fund Activism and the Revision of the Shareholder Rights Directive

    NARCIS (Netherlands)

    A.M. Passes (Alessio)

    2017-01-01

    markdownabstractThis paper looks at shareholder activism from the perspective of the revision of the EU Shareholder Rights Directive, which was approved by the European Parliament on 14 March 2017. The main findings are as follows. First, the effective engagement of institutional investors in

  4. Feature-based attention modulates direction-selective hemodynamic activity within human MT.

    Science.gov (United States)

    Stoppel, Christian Michael; Boehler, Carsten Nicolas; Strumpf, Hendrik; Heinze, Hans-Jochen; Noesselt, Toemme; Hopf, Jens-Max; Schoenfeld, Mircea Ariel

    2011-12-01

    Attending to the spatial location or to nonspatial features of a stimulus modulates neural activity in cortical areas that process its perceptual attributes. The feature-based attentional selection of the direction of a moving stimulus is associated with increased firing of individual neurons tuned to the direction of the movement in area V5/MT, while responses of neurons tuned to opposite directions are suppressed. However, it is not known how these multiplicatively scaled responses of individual neurons tuned to different motion-directions are integrated at the population level, in order to facilitate the processing of stimuli that match the perceptual goals. Using functional magnetic resonance imaging (fMRI) the present study revealed that attending to the movement direction of a dot field enhances the response in a number of areas including the human MT region (hMT) as a function of the coherence of the stimulus. Attending the opposite direction, however, lead to a suppressed response in hMT that was inversely correlated with stimulus-coherence. These findings demonstrate that the multiplicative scaling of single-neuron responses by feature-based attention results in an enhanced direction-selective population response within those cortical modules that processes the physical attributes of the attended stimuli. Our results provide strong support for the validity of the "feature similarity gain model" on the integrated population response as quantified by parametric fMRI in humans. Copyright © 2011 Wiley Periodicals, Inc.

  5. Innovative Activity in the Industry of Ukraine: Problems, Risks, Activization Directions

    Directory of Open Access Journals (Sweden)

    Pidorycheva, I.

    2014-09-01

    Full Text Available The general characteristic of a condition of innovative activity of the industrial enterprises in Ukraine and positive tendencies of the last years in this plane are shined. The key problems and demotivating factors of increase of interest of the industry in innovations are analyzed. Risks of preservation of available tendencies in the sphere of innovative and technological development of the industry, which can lead to preservation of outdated structure of national production are defined. Priorities and medium-term measures for overcoming of available restrictions in realization of new model of economic development, at the heart of which — investments into the innovative activity, new industrialization and industrial updating of the country are offered.

  6. The Implementation of ‘Comic Life’ Through Directed Reading Activities to Increase Students’ Reading Comprehension

    Directory of Open Access Journals (Sweden)

    Suardi

    2014-08-01

    Full Text Available The research was conducted to know the effectiveness of the use of Comic Life through Directed Reading Activities to increase students’ reading comprehension. It covered students’ literal comprehension, interpretive comprehension and applied comprehension. And to find out the students’ interest in teaching reading comprehension toward the application of Comic Life through Directed Reading Activities to increase students’ reading comprehension. The research method employed was quasi experimental. This research was designed into two groups, namely experimental group and control group. Each group consisted of 32 students. The sample was chosen by applying cluster sampling technique. The researcher used multiple choice of reading test both in experimental and control groups. The data obtained through the test were analyzed by using inferential statistic through SPSS 16.0 program. The research findings showed that Comic Life through Directed Reading Activities gave higher contribution to the students’ reading comprehension. The mean score of pre- test of the experimental and control group was not significantly different. The mean score of post- test of the experimental group was higher than the control group (75.62 > 56.87. Besides, all the three level of comprehension improved after the treatment, the literal level got the highest improvement with 9.69 point. It was followed by interpretive level which got 21.25 point and applied level which got 42.19 point improvement. This led to the conclusion that the application of Comic Life through Directed Reading Activities increased the students’ reading comprehension. It means that the use of Comic Life through Directed Reading Activities in teaching reading is very effective to increase the students’ reading comprehension.

  7. Corporate Secretarial Bilingual Activity: An English Teaching Proposal Based on Corpora Directed to the Secretaries

    Directory of Open Access Journals (Sweden)

    José Roberto Lourenço

    2015-07-01

    Full Text Available This article presents part of research conducted in the field of Corpus Linguistics about the use of corpora in English Language Teaching specifically directed to corporate secretarial activities. The study developed at the doctoral level had FATEC-SP students as voluntary respondents to a questionnaire on corporate secretarial activities; the responses presented as one of the most important and frequent secretarial activities, "Reading, Preparation and Presentation of Administrative Report". We present a model of practice in English Teaching with an initial focus on "Company History, Strategies and Structure".

  8. Modification of Purine and Pyrimidine Nucleosides by Direct C-H Bond Activation

    Directory of Open Access Journals (Sweden)

    Yong Liang

    2015-03-01

    Full Text Available Transition metal-catalyzed modifications of the activated heterocyclic bases of nucleosides as well as DNA or RNA fragments employing traditional cross-coupling methods have been well-established in nucleic acid chemistry. This review covers advances in the area of cross-coupling reactions in which nucleosides are functionalized via direct activation of the C8-H bond in purine and the C5-H or C6-H bond in uracil bases. The review focuses on Pd/Cu-catalyzed couplings between unactivated nucleoside bases with aryl halides. It also discusses cross-dehydrogenative arylations and alkenylations as well as other reactions used for modification of nucleoside bases that avoid the use of organometallic precursors and involve direct C-H bond activation in at least one substrate. The scope and efficiency of these coupling reactions along with some mechanistic considerations are discussed.

  9. Active Flow Control of Lifting Surface With Flap-Current Activities and Future Directions

    Science.gov (United States)

    Ahmadi, G.; Marzocca, P.; Jha, R.; Alstorm, B.; Obied, S.; Kabir, P.; Shahrabi, A.

    2010-01-01

    The main objective is to develop effective control strategies for separation control of an airfoil with a single hinge flap. The specific objectives are: Develop an active control architecture for flow control around an airfoil with flap. Design, fabricate, a wind tunnel test of a high lift wing (with flap) with integrated actuators and sensors. Design, development and fabrication of synthetic jet actuators. Develop appropriate control strategy for application to the airfoil. Wind tunnel testing of the high lift wing at various angles of attack and flap positions with closed loop control.

  10. Direct observation is a valid criterion for estimating physical activity and sedentary behavior.

    Science.gov (United States)

    Lyden, Kate; Petruski, Natalia; Staudenmayer, John; Freedson, Patty

    2014-05-01

    Physical activity and sedentary behavior measurement tools need to be validated in free-living settings. Direct observation (DO) may be an appropriate criterion for these studies. However, it is not known if trained observers can correctly judge the absolute intensity of free-living activities. To compare DO estimates of total MET-hours and time in activity intensity categories to a criterion measure from indirect calorimetry (IC). Fifteen participants were directly observed on three separate days for two hours each day. During this time participants wore an Oxycon Mobile indirect calorimeter and performed any activity of their choice within the reception area of the wireless metabolic equipment. Participants were provided with a desk for sedentary activities (writing, reading, computer use) and had access to exercise equipment (treadmill, bike). DO accurately and precisely estimated MET-hours [% bias (95% CI) = -12.7% (-16.4, -7.3), ICC = 0.98], time in low intensity activity [% bias (95% CI) = 2.1% (1.1, 3.2), ICC = 1.00] and time in moderate to vigorous intensity activity [% bias (95% CI) -4.9% (-7.4, -2.5), ICC = 1.00]. This study provides evidence that DO can be used as a criterion measure of absolute intensity in free-living validation studies.

  11. Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

    Science.gov (United States)

    Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

    2017-10-13

    The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

  12. Brain activation during direct and indirect processing of positive and negative words.

    Science.gov (United States)

    Straube, Thomas; Sauer, Andreas; Miltner, Wolfgang H R

    2011-09-12

    The effects of task conditions on brain activation to emotional stimuli are poorly understood. In this event-related fMRI study, brain activation to negative and positive words (matched for arousal) and neutral words was investigated under two task conditions. Subjects either had to attend to the emotional meaning (direct task) or to non-emotional features of the words (indirect task). Regardless of task, positive vs. negative words led to increased activation in the ventral medial prefrontal cortex, while negative vs. positive words induced increased activation of the insula. Compared to neutral words, all emotional words were associated with increased activation of the amygdala. Finally, the direct condition, as compared to the indirect condition, led to enhanced activation to emotional vs. neutral words in the dorsomedial prefrontal cortex and the anterior cingulate cortex. These results suggest valence and arousal dependent brain activation patterns that are partially modulated by participants' processing mode of the emotional stimuli. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Participant observation of time allocation, direct patient contact and simultaneous activities in hospital physicians

    Directory of Open Access Journals (Sweden)

    Zupanc Andrea

    2009-06-01

    Full Text Available Abstract Background Hospital physicians' time is a critical resource in medical care. Two aspects are of interest. First, the time spent in direct patient contact – a key principle of effective medical care. Second, simultaneous task performance ('multitasking' which may contribute to medical error, impaired safety behaviour, and stress. There is a call for instruments to assess these aspects. A preliminary study to gain insight into activity patterns, time allocation and simultaneous activities of hospital physicians was carried out. Therefore an observation instrument for time-motion-studies in hospital settings was developed and tested. Methods 35 participant observations of internists and surgeons of a German municipal 300-bed hospital were conducted. Complete day shifts of hospital physicians on wards, emergency ward, intensive care unit, and operating room were continuously observed. Assessed variables of interest were time allocation, share of direct patient contact, and simultaneous activities. Inter-rater agreement of Kappa = .71 points to good reliability of the instrument. Results Hospital physicians spent 25.5% of their time at work in direct contact with patients. Most time was allocated to documentation and conversation with colleagues and nursing staff. Physicians performed parallel simultaneous activities for 17–20% of their work time. Communication with patients, documentation, and conversation with colleagues and nursing staff were the most frequently observed simultaneous activities. Applying logit-linear analyses, specific primary activities increase the probability of particular simultaneous activities. Conclusion Patient-related working time in hospitals is limited. The potential detrimental effects of frequently observed simultaneous activities on performance outcomes need further consideration.

  14. Balance Control Mediated by Vestibular Circuits Directing Limb Extension or Antagonist Muscle Co-activation

    Directory of Open Access Journals (Sweden)

    Andrew J. Murray

    2018-01-01

    Full Text Available Maintaining balance after an external perturbation requires modification of ongoing motor plans and the selection of contextually appropriate muscle activation patterns that respect body and limb position. We have used the vestibular system to generate sensory-evoked transitions in motor programming. In the face of a rapid balance perturbation, the lateral vestibular nucleus (LVN generates exclusive extensor muscle activation and selective early extension of the hindlimb, followed by the co-activation of extensor and flexor muscle groups. The temporal separation in EMG response to balance perturbation reflects two distinct cell types within the LVN that generate different phases of this motor program. Initially, an LVNextensor population directs an extension movement that reflects connections with extensor, but not flexor, motor neurons. A distinct LVNco-activation population initiates muscle co-activation via the pontine reticular nucleus. Thus, distinct circuits within the LVN generate different elements of a motor program involved in the maintenance of balance.

  15. Annulation of aromatic imines via directed C-H bond activation.

    Science.gov (United States)

    Thalji, Reema K; Ahrendt, Kateri A; Bergman, Robert G; Ellman, Jonathan A

    2005-08-19

    A directed C-H bond activation approach to the synthesis of indans, tetralins, dihydrofurans, dihydroindoles, and other polycyclic aromatic compounds is presented. Cyclization of aromatic ketimines and aldimines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using (PPh3)3RhCl (Wilkinson's catalyst). The cyclization of a range of aromatic ketimines and aldimines provides bi- and tricyclic ring systems with good regioselectivity. Different ring sizes and substitution patterns can be accessed through the coupling of monosubstituted, 1,1- or 1,2-disubstituted, and trisubstituted alkenes bearing both electron-rich and electron-deficient functionality.

  16. Direct impacts of outer continental shelf activities on wetland loss in the central Gulf of Mexico

    International Nuclear Information System (INIS)

    Baumann, R.H.; Turner, R.E.

    1990-01-01

    The direct impacts of outer continental shelf (OCS) development on recent wetland loss in the northern Gulf of Mexico were quantified using aerial imagery, field surveys, and literature review. The total direct impacts accounted for an estimated 25.6 percent of total net wetland loss within the Louisiana portion of the study area from 1955/56 to 1978. Of the total direct impacts of 73,905 ha, OCS-related activities accounted for 11,589-13,631 ha of the wetland loss during the same time interval. Although this is a substantial areal loss, it represents only 4.0-4.7 percent of the total Louisiana wetland loss from 1955/56 to 1978, and 15.7-18.4 percent of direct impacts. Direct impacts from OCS pipelines averages 2.49 ha/km, lower than published guidelines, and totaled 12,012 ha. Lowest impacts are for backfilled pipelines in the Chenier Plain of western Louisiana and for small young pipeline canals does not appear to be an important factor for total new wetland loss in the coastal zone because few pipelines are open to navigation and, for the examples found, the impact width was not significantly different than for open pipelines closed to navigation. Navigation channels account for a minimum of 16,902 ha of habitat change. Direct impacts per unit length of navigation channel average 20 times greater than pipelines

  17. Novel direct AMPK activator suppresses non-small cell lung cancer through inhibition of lipid metabolism

    Science.gov (United States)

    Chen, Xi; Xie, Chun; Fan, Xing-Xing; Jiang, Ze-Bo; Wong, Vincent Kam-Wai; Xu, Jia-Hui; Yao, Xiao-Jun; Liu, Liang; Leung, Elaine Lai-Han

    2017-01-01

    Drug resistance is becoming an obstacle in anti-cancer therapies. For target-based therapy of lung cancer, gefitinib, as the first generation of tyrosine kinase inhibitors (TKIs), demonstrated good initial response to the non-small cell lung cancer (NSCLC) patients whom harbors epidermal growth factor receptor (EGFR) mutation. However, within one year, additional EGFR mutation occurred, leading to eventual gefitinib-resistance. Therefore, it is urgently to discover novel effective small molecule inhibitors for those patients. Abnormal energy metabolism is accepted as new cancer hallmark. Recently, a metabolism rate-limiting enzyme 5’-adenosine menophosphate-activated protein kinase (AMPK) has become a promising anti-cancer target. In this study, we have identified a novel direct AMPK agonist, D561-0775 from a compound library by using molecular docking screening technique. We demonstrated that D561-0775 exhibited significant inhibitory effect on gefitinib-resistant NSCLC cell lines but less cytotoxicity on normal cells. Furthermore, D561-0775 demonstrated a remarkable in vitro AMPK enzyme activation effect. Taken together, D561-0775 showed potential anti-cancer activity via inducing apoptosis, cell cycle arrest, suppressing glycolysis and cholesterol synthesis after activation of AMPK in gefitinib-resistant H1975 cells. D561-0775 has provided a new chemical structure that could be developed as cancer drug for gefitinib-resistant NSCLC patients through inhibition lipid metabolism by directly targeting at AMPK directly. PMID:29221189

  18. Direct measurement of catalase activity in living cells and tissue biopsies

    Energy Technology Data Exchange (ETDEWEB)

    Scaglione, Christine N.; Xu, Qijin; Ramanujan, V. Krishnan, E-mail: Ramanujanv@csmc.edu

    2016-01-29

    Spatiotemporal regulation of enzyme-substrate interactions governs the decision-making steps in biological systems. Enzymes, being functional units of every living cell, contribute to the macromolecular stability of cell survival, proliferation and hence are vital windows to unraveling the biological complexity. Experimental measurements capturing this dynamics of enzyme-substrate interactions in real time add value to this understanding. Furthermore these measurements, upon validation in realistic biological specimens such as clinical biopsies – can further improve our capability in disease diagnostics and treatment monitoring. Towards this direction, we describe here a novel, high-sensitive measurement system for measuring diffusion-limited enzyme-substrate kinetics in real time. Using catalase (enzyme) and hydrogen peroxide (substrate) as the example pair, we demonstrate that this system is capable of direct measurement of catalase activity in vitro and the measured kinetics follows the classical Michaelis-Menten reaction kinetics. We further demonstrate the system performance by measuring catalase activity in living cells and in very small amounts of liver biopsies (down to 1 μg total protein). Catalase-specific enzyme activity is demonstrated by genetic and pharmacological tools. Finally we show the clinically-relevant diagnostic capability of our system by comparing the catalase activities in liver biopsies from young and old mouse (liver and serum) samples. We discuss the potential applicability of this system in clinical diagnostics as well as in intraoperative surgical settings. - Highlights: • A novel, direct measurement of Catalase enzyme activity via, oxygen sensing method. • Steady-stateprofiles of Catalase activity follow the Michaelis-Menten Kinetics. • Catalase-specific activity demonstrated using genetic and pharmacological tools. • Overcomes limitations of spectroscopic methods and indirect calorimetric approaches. • Clear

  19. Direct measurement of catalase activity in living cells and tissue biopsies

    International Nuclear Information System (INIS)

    Scaglione, Christine N.; Xu, Qijin; Ramanujan, V. Krishnan

    2016-01-01

    Spatiotemporal regulation of enzyme-substrate interactions governs the decision-making steps in biological systems. Enzymes, being functional units of every living cell, contribute to the macromolecular stability of cell survival, proliferation and hence are vital windows to unraveling the biological complexity. Experimental measurements capturing this dynamics of enzyme-substrate interactions in real time add value to this understanding. Furthermore these measurements, upon validation in realistic biological specimens such as clinical biopsies – can further improve our capability in disease diagnostics and treatment monitoring. Towards this direction, we describe here a novel, high-sensitive measurement system for measuring diffusion-limited enzyme-substrate kinetics in real time. Using catalase (enzyme) and hydrogen peroxide (substrate) as the example pair, we demonstrate that this system is capable of direct measurement of catalase activity in vitro and the measured kinetics follows the classical Michaelis-Menten reaction kinetics. We further demonstrate the system performance by measuring catalase activity in living cells and in very small amounts of liver biopsies (down to 1 μg total protein). Catalase-specific enzyme activity is demonstrated by genetic and pharmacological tools. Finally we show the clinically-relevant diagnostic capability of our system by comparing the catalase activities in liver biopsies from young and old mouse (liver and serum) samples. We discuss the potential applicability of this system in clinical diagnostics as well as in intraoperative surgical settings. - Highlights: • A novel, direct measurement of Catalase enzyme activity via, oxygen sensing method. • Steady-stateprofiles of Catalase activity follow the Michaelis-Menten Kinetics. • Catalase-specific activity demonstrated using genetic and pharmacological tools. • Overcomes limitations of spectroscopic methods and indirect calorimetric approaches. • Clear

  20. PCNA function in the activation and strand direction of MutLα endonuclease in mismatch repair

    Science.gov (United States)

    Pluciennik, Anna; Dzantiev, Leonid; Iyer, Ravi R.; Constantin, Nicoleta; Kadyrov, Farid A.; Modrich, Paul

    2010-01-01

    MutLα (MLH1–PMS2) is a latent endonuclease that is activated in a mismatch-, MutSα-, proliferating cell nuclear antigen (PCNA)-, replication factor C (RFC)-, and ATP-dependent manner, with nuclease action directed to the heteroduplex strand that contains a preexisting break. RFC depletion experiments and use of linear DNAs indicate that RFC function in endonuclease activation is limited to PCNA loading. Whereas nicked circular heteroduplex DNA is a good substrate for PCNA loading and for endonuclease activation on the incised strand, covalently closed, relaxed circular DNA is a poor substrate for both reactions. However, covalently closed supercoiled or bubble-containing relaxed heteroduplexes, which do support PCNA loading, also support MutLα activation, but in this case cleavage strand bias is largely abolished. Based on these findings we suggest that PCNA has two roles in MutLα function: The clamp is required for endonuclease activation, an effect that apparently involves interaction of the two proteins, and by virtue of its loading orientation, PCNA determines the strand direction of MutLα incision. These results also provide a potential mechanism for activation of mismatch repair on nonreplicating DNA, an effect that may have implications for the somatic phase of triplet repeat expansion. PMID:20713735

  1. A multiple-fan active control wind tunnel for outdoor wind speed and direction simulation

    Science.gov (United States)

    Wang, Jia-Ying; Meng, Qing-Hao; Luo, Bing; Zeng, Ming

    2018-03-01

    This article presents a new type of active controlled multiple-fan wind tunnel. The wind tunnel consists of swivel plates and arrays of direct current fans, and the rotation speed of each fan and the shaft angle of each swivel plate can be controlled independently for simulating different kinds of outdoor wind fields. To measure the similarity between the simulated wind field and the outdoor wind field, wind speed and direction time series of two kinds of wind fields are recorded by nine two-dimensional ultrasonic anemometers, and then statistical properties of the wind signals in different time scales are analyzed based on the empirical mode decomposition. In addition, the complexity of wind speed and direction time series is also investigated using multiscale entropy and multivariate multiscale entropy. Results suggest that the simulated wind field in the multiple-fan wind tunnel has a high degree of similarity with the outdoor wind field.

  2. Eccentrically-Layered Active Coated Nano-Particles for Directive Near- and Far-Field Radiation

    Directory of Open Access Journals (Sweden)

    Rasmus Ø. Thorsen

    2015-06-01

    Full Text Available The present work shows how the eccentricity in active nano-particles may lead to very interesting and rather directive near- and far-field radiation patterns. The nano-particle is of a three-layer type and consists of a silica core, a free-space middle layer and an outer silver shell and is excited by a magnetic line source. The constant frequency gain model is included in the silica core, and the eccentricity is introduced through appropriate displacements of the core. It is shown that the eccentricity in a nano-particle, which was initially designed to excite a strong dipole mode, causes a progressively larger excitation of several other (including higher order modes, this being more so the larger the core displacement. Specifically, eccentric nano-particles are identified with comparable simultaneous excitations of dipole and quadrupole modes, with associated large values of the radiated power and, even more notably, enhanced and directive near- and far-field radiation patterns. The main beam of these patterns is shown to be effectively tailored (enhanced, reshaped and steered by the direction and amount of the core displacement. The eccentric nano-particles can be additionally gain optimized to boost their near-field response and the radiated power, while retaining the directivity of the gain unoptimized eccentric cases. Owing to their very directive nearand far-field patterns, the proposed eccentric, active three-layer nano-particles may provide alternative strategies towards the design of directive nano-antennas relative to several of the existing solutions.

  3. The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration

    Directory of Open Access Journals (Sweden)

    Lena Collenburg

    2017-08-01

    Full Text Available Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization. Because these are important parameters in directional T cell migration and motility in tissues, we analyzed the role of the NSM in these processes. Pharmacological inhibition of NSM interfered with early lymph node homing of T cells in vivo indicating that the enzyme impacts on endothelial adhesion, transendothelial migration, sensing of chemokine gradients or, at a cellular level, acquisition of a polarized phenotype. NSM inhibition reduced adhesion of T cells to TNF-α/IFN-γ activated, but not resting endothelial cells, most likely via inhibiting high-affinity LFA-1 clustering. NSM activity proved to be highly important in directional T cell motility in response to SDF1-α, indicating that their ability to sense and translate chemokine gradients might be NSM dependent. In fact, pharmacological or genetic NSM ablation interfered with T cell polarization both at an overall morphological level and redistribution of CXCR4 and pERM proteins on endothelial cells or fibronectin, as well as with F-actin polymerization in response to SDF1-α stimulation, indicating that efficient directional perception and signaling relay depend on NSM activity. Altogether, these data support a central role of the NSM in T cell recruitment and migration both under homeostatic and inflamed conditions by regulating polarized redistribution of receptors and their coupling to the cytoskeleton.

  4. Improving Glyphosate Oxidation Activity of Glycine Oxidase from Bacillus cereus by Directed Evolution

    Science.gov (United States)

    Zhan, Tao; Zhang, Kai; Chen, Yangyan; Lin, Yongjun; Wu, Gaobing; Zhang, Lili; Yao, Pei; Shao, Zongze; Liu, Ziduo

    2013-01-01

    Glyphosate, a broad spectrum herbicide widely used in agriculture all over the world, inhibits 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, and glycine oxidase (GO) has been reported to be able to catalyze the oxidative deamination of various amines and cleave the C-N bond in glyphosate. Here, in an effort to improve the catalytic activity of the glycine oxidase that was cloned from a glyphosate-degrading marine strain of Bacillus cereus (BceGO), we used a bacteriophage T7 lysis-based method for high-throughput screening of oxidase activity and engineered the gene encoding BceGO by directed evolution. Six mutants exhibiting enhanced activity toward glyphosate were screened from two rounds of error-prone PCR combined with site directed mutagenesis, and the beneficial mutations of the six evolved variants were recombined by DNA shuffling. Four recombinants were generated and, when compared with the wild-type BceGO, the most active mutant B3S1 showed the highest activity, exhibiting a 160-fold increase in substrate affinity, a 326-fold enhancement in catalytic efficiency against glyphosate, with little difference between their pH and temperature stabilities. The role of these mutations was explored through structure modeling and molecular docking, revealing that the Arg51 mutation is near the active site and could be an important residue contributing to the stabilization of glyphosate binding, while the role of the remaining mutations is unclear. These results provide insight into the application of directed evolution in optimizing glycine oxidase function and have laid a foundation for the development of glyphosate-tolerant crops. PMID:24223901

  5. The Explicit Instruction of Reading Strategies: Directed Reading Thinking Activity vs. Guided Reading Strategies

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi Yazdani

    2015-05-01

    Full Text Available Investigating the efficiencies and deficiencies of reading strategies is one of the noticeable issues in the related theory and research in reading comprehension instruction. This study was to examine the impact of Directed Reading Thinking Activity (DRTA and Guided Reading (GR on reading comprehension. Sixty three Iranian students of grade one in Shahed high school in the city of Bojnourd took part in the study. They were assigned in three groups, one control and two experimental groups. The instruction lasted for ten weeks. This study utilized a pretest posttest control group in quantitative quasi- experimental design. The same reading comprehension test was administered as pre-test and post-test. The results were twofold: First, the instruction of learning strategies could foster reading comprehension skill. Second, while the explicit instruction of both strategies could improve the students' reading comprehension skill, Directed Reading Thinking Activity had a more significant positive effect than Guided Reading.

  6. Probenecid directly impairs activation of the canine P2X7 receptor.

    Science.gov (United States)

    Bartlett, Rachael; Stokes, Leanne; Curtis, Stephen J; Curtis, Belinda L; Sluyter, Ronald

    2017-12-02

    The current study aimed to determine if probenecid could directly impair the canine P2X7 receptor, a ligand-gated cation channel activated by extracellular adenosine 5'-triphosphate (ATP). Patch clamp measurements demonstrated that probenecid impairs ATP-induced inward currents in HEK-293 cells expressing canine P2X7. Flow cytometric measurements of ethidium + uptake into HEK-293 cells expressing canine P2X7 showed that probenecid impairs ATP-induced pore formation in a concentration-dependent manner, with a half maximal inhibitory concentration of 158 µM. Finally, ELISA measurements revealed that probenecid impairs ATP-induced interleukin-1β release in dog blood. In conclusion, this study reveals that probenecid can directly impair canine P2X7 activation.

  7. Improvement of silicon direct bonding using surfaces activated by hydrogen plasma treatment

    CERN Document Server

    Choi, W B; Lee Jae Sik; Sung, M Y

    2000-01-01

    The plasma surface treatment, using hydrogen gas, of silicon wafers was studied as a pretreatment for silicon direct bonding. Chemical reactions of the hydrogen plasma with the surfaces were used for both surface activation and removal of surface contaminants. Exposure of the silicon wafers to the plasma formed an active oxide layer on the surface. This layer was hydrophilic. The surface roughness and morphology were examined as functions of the plasma exposure time and power. The surface became smoother with shorter plasma exposure time and lower power. In addition, the plasma surface treatment was very efficient in removing the carbon contaminants on the silicon surface. The value of the initial surface energy, as estimated by using the crack propagation method, was 506 mJ/M sup 2 , which was up to about three times higher than the value for the conventional direct bonding method using wet chemical treatments.

  8. Direct Synthesis of Phenol from Benzene on an Activated Carbon Catalyst Treated with Nitric Acid

    Science.gov (United States)

    Chen, Cui-hong; Xu, Jia-quan; Jin, Ming-ming; Li, Gui-ying; Hu, Chang-wei

    2011-06-01

    Commercially available coal-based activated carbon was treated by nitric acid with different concentrations and the resultant samples were used as catalysts for the direct hydroxylation of benzene to phenol in acetonitrile. Boehm titration, X-ray photoelectron spectroscopy, scanning electron microscope coupled with an energy dispersive X-ray microanalyzer, and Brunauer-Emmett-Teller method were used to characterize the samples. The number of carboxyl groups on the surface was found to be the main factor affecting the catalytic activity. An optimum catalytic performance with a yield of 15.7% and a selectivity of 87.2% to phenol was obtained.

  9. Lozenge directly activates argos and klumpfuss to regulate programmed cell death.

    Science.gov (United States)

    Wildonger, Jill; Sosinsky, Alona; Honig, Barry; Mann, Richard S

    2005-05-01

    We show that reducing the activity of the Drosophila Runx protein Lozenge (Lz) during pupal development causes a decrease in cell death in the eye. We identified Lz-binding sites in introns of argos (aos) and klumpfuss (klu) and demonstrate that these genes are directly activated targets of Lz. Loss of either aos or klu reduces cell death, suggesting that Lz promotes apoptosis at least in part by regulating aos and klu. These results provide novel insights into the control of programmed cell death (PCD) by Lz during Drosophila eye development.

  10. MEK1 inhibits cardiac PPARα activity by direct interaction and prevents its nuclear localization.

    Directory of Open Access Journals (Sweden)

    Hamid el Azzouzi

    Full Text Available BACKGROUND: The response of the postnatal heart to growth and stress stimuli includes activation of a network of signal transduction cascades, including the stress activated protein kinases such as p38 mitogen-activated protein kinase (MAPK, c-Jun NH2-terminal kinase (JNK and the extracellular signal-regulated kinase (ERK1/2 pathways. In response to increased workload, the mitogen-activated protein kinase kinase (MAPKK MEK1 has been shown to be active. Studies embarking on mitogen-activated protein kinase (MAPK signaling cascades in the heart have indicated peroxisome-proliferators activated-receptors (PPARs as downstream effectors that can be regulated by this signaling cascade. Despite the importance of PPARα in controlling cardiac metabolism, little is known about the relationship between MAPK signaling and cardiac PPARα signaling. METHODOLOGY/PRINCIPAL FINDING: Using co-immunoprecipitation and immunofluorescence approaches we show a complex formation of PPARα with MEK1 and not with ERK1/2. Binding of PPARα to MEK1 is mediated via a LXXLL motif and results in translocation from the nucleus towards the cytoplasm, hereby disabling the transcriptional activity of PPARα. Mice subjected to voluntary running-wheel exercise showed increased cardiac MEK1 activation and complex formation with PPARα, subsequently resulting in reduced PPARα activity. Inhibition of MEK1, using U0126, blunted this effect. CONCLUSION: Here we show that activation of the MEK1-ERK1/2 pathway leads to specific inhibition of PPARα transcriptional activity. Furthermore we show that this inhibitory effect is mediated by MEK1, and not by its downstream effector kinase ERK1/2, through a mechanism involving direct binding to PPARα and subsequent stimulation of PPARα export from the nucleus.

  11. Central Venous Catheter-directed Tissue Plasminogen Activator in Massive Pulmonary Embolism

    OpenAIRE

    Vishal Gulati

    2018-01-01

    We present the case of an 88-year-old female who presented to the emergency department (ED) with suspected massive pulmonary embolism (PE) causing respiratory failure, right heart strain, and shock, who despite early and aggressive resuscitation with vasopressors and continuous peripheral infusion of tissue plasminogen activator (tPA), suffered a cardiac arrest in the ED. We describe the approach of a tPA bolus directed through a central venous catheter, resulting in return of spontaneous cir...

  12. Evaluation of the BH3-only protein Puma as a direct Bak activator.

    Science.gov (United States)

    Dai, Haiming; Pang, Yuan-Ping; Ramirez-Alvarado, Marina; Kaufmann, Scott H

    2014-01-03

    Interactions among Bcl-2 family proteins play critical roles in cellular life and death decisions. Previous studies have established the BH3-only proteins Bim, tBid, and Noxa as "direct activators" that are able to directly initiate the oligomerization and activation of Bak and/or Bax. Earlier studies of Puma have yielded equivocal results, with some concluding that it also acts as a direct activator and other studies suggesting that it acts solely as a sensitizer BH3-only protein. In the present study we examined the interaction of Puma BH3 domain or full-length protein with Bak by surface plasmon resonance, assessed Bak oligomerization status by cross-linking followed by immunoblotting, evaluated the ability of the Puma BH3 domain to induce Bak-mediated permeabilization of liposomes and mitochondria, and determined the effect of wild type and mutant Puma on cell viability in a variety of cellular contexts. Results of this analysis demonstrate high affinity (KD = 26 ± 5 nM) binding of the Puma BH3 domain to purified Bak ex vivo, leading to Bak homo-oligomerization and membrane permeabilization. Mutations in Puma that inhibit (L141E/M144E/L148E) or enhance (M144I/A145G) Puma BH3 binding to Bak also produce corresponding alterations in Bak oligomerization, Bak-mediated membrane permeabilization and, in a cellular context, Bak-mediated killing. Collectively, these results provide strong evidence that Puma, like Bim, Noxa, and tBid, is able to act as a direct Bak activator.

  13. The strategic use of lecture recordings to facilitate an active and self-directed learning approach

    OpenAIRE

    Topale, Luminica

    2016-01-01

    Background New learning technologies have the capacity to dramatically impact how students go about learning and to facilitate an active, self-directed learning approach. In U. S. medical education, students encounter a large volume of content, which must be mastered at an accelerated pace. The added pressure to excel on the USMLE Step 1 licensing exam and competition for residency placements, require that students adopt an informed approach to the use of learning technologies so as to enhanc...

  14. Direct activation of sleep-promoting VLPO neurons by volatile anesthetics contributes to anesthetic hypnosis.

    Science.gov (United States)

    Moore, Jason T; Chen, Jingqiu; Han, Bo; Meng, Qing Cheng; Veasey, Sigrid C; Beck, Sheryl G; Kelz, Max B

    2012-11-06

    Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep. Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, whereas neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance. Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Work group IV: Future directions for measures of the food and physical activity environments.

    Science.gov (United States)

    Story, Mary; Giles-Corti, Billie; Yaroch, Amy Lazarus; Cummins, Steven; Frank, Lawrence Douglas; Huang, Terry T-K; Lewis, LaVonna Blair

    2009-04-01

    Much progress has been made in the past 5 to 10 years in measuring and understanding the impact of the food and physical activity environments on behavioral outcomes. Nevertheless, this research is in its infancy. A work group was convened to identify current evidence gaps and barriers in food and physical activity environments and policy research measures, and develop recommendations to guide future directions for measurement and methodologic research efforts. A nominal group process was used to determine six priority areas for food and physical activity environments and policy measures to move the field forward by 2015, including: (1) identify relevant factors in the food and physical activity environments to measure, including those most amenable to change; (2) improve understanding of mechanisms for relationships between the environment and physical activity, diet, and obesity; (3) develop simplified measures that are sensitive to change, valid for different population groups and settings, and responsive to changing trends; (4) evaluate natural experiments to improve understanding of food and physical activity environments and their impact on behaviors and weight; (5) establish surveillance systems to predict and track change over time; and (6) develop standards for adopting effective health-promoting changes to the food and physical activity environments. The recommendations emanating from the work group highlight actions required to advance policy-relevant research related to food and physical activity environments.

  16. THE RESEARCH ACTIVITY OF THE UNIVERSITY TEACHERS: DIRECTIONS, RESULTS, AND PROSPECTS. SOCIOLOGICAL CONTENT

    Directory of Open Access Journals (Sweden)

    I. A. Vasilyev

    2016-01-01

    Full Text Available The main purpose of an integrated monitoring research is the analysis of the main directions of research activity of faculty, staff and young scientists of the university.Methods. Scientific and theoretical analysis of publications on the researched topic are used as basic methods; sociological and diagnostic data collection methods; the method of statistical processing and classification of documentary and empirical data; the methods of content analysis and quantification of documentary and sociological information.Scientific novelty. The research is characterized by an integrated approach to the study of the problem: the basic provisions are analyzed; conclusions and recommendations of reports on research projects made by members of temporary research teams (or, university scientists and teaching staff. The classification (depending on the translation vectors results of dissertation works of graduate students, doctoral candidates is carried out in the course of the present study. Documentary information about the publication and presentation of scientific and pedagogical staff of the university is systematized; the report and information cards on the activities of innovative platforms are analyzed. The research team, with the direct participation of the author, after studying a few scientific publications on the subject, has developed an original method of complex research of the main directions of research activity of university scientists.Results. The presented research has allowed to note publication and innovative activity of the research and educational personnel, along with other its types, can act as the indicators characterizing the main directions of research activity both of higher education institution in general, and its concrete educational and scientific divisions. At the same, time the author emphasizes that efficiency of research process is caused not so much by quantitative as qualitative characteristics of concrete research

  17. Direct activation of protein kinase C by 1 alpha,25-dihydroxyvitamin D3.

    Science.gov (United States)

    Slater, S J; Kelly, M B; Taddeo, F J; Larkin, J D; Yeager, M D; McLane, J A; Ho, C; Stubbs, C D

    1995-03-24

    The key metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3 (1,25-D3), induces rapid cellular responses that constitute a so-called "non-genomic" response. This effect is distinguished from its "classic" genomic role in calcium homeostasis involving the nuclear 1,25-D3 receptor. Evidence is presented that protein kinase C (PKC) is directly activated by 1,25-D3 at physiological concentrations (EC50 = 16 +/- 1 nM). The effect was demonstrable with single PKC-alpha, -gamma, and -epsilon isoform preparations, assayed in a system containing only purified enzyme, substrate, co-factors, and lipid vesicles, from which it is inferred that a direct interaction with the enzyme is involved. The finding that calcium-independent isoform PKC-epsilon was also activated by 1,25-D3 shows that the calcium binding C2 domain is not required. The level of 1,25-D3-induced activation, paired with either diacylglycerol or 4 beta-12-O-tetradecanoylphorbol-13-acetate, was greater than that achievable by any individual activator alone, each at a saturating concentration, a result that implies two distinct activator sites on the PKC molecule. Phosphatidylethanolamine present in the lipid vesicles potentiated 4 beta-12-O-tetradecanoylphorbol-13-acetate- and diacylglycerol-induced PKC activities, whereas 1,25-D3-induced activity decreased, consistent with 1,25-D3-activated PKC possessing a distinct conformation. The results suggest that PKC is a "membrane-bound receptor" for 1,25-D3 and that it could be important in the control of non-genomic cellular responses to the hormone.

  18. Silent reading of direct versus indirect speech activates voice-selective areas in the auditory cortex.

    Science.gov (United States)

    Yao, Bo; Belin, Pascal; Scheepers, Christoph

    2011-10-01

    In human communication, direct speech (e.g., Mary said: "I'm hungry") is perceived to be more vivid than indirect speech (e.g., Mary said [that] she was hungry). However, for silent reading, the representational consequences of this distinction are still unclear. Although many of us share the intuition of an "inner voice," particularly during silent reading of direct speech statements in text, there has been little direct empirical confirmation of this experience so far. Combining fMRI with eye tracking in human volunteers, we show that silent reading of direct versus indirect speech engenders differential brain activation in voice-selective areas of the auditory cortex. This suggests that readers are indeed more likely to engage in perceptual simulations (or spontaneous imagery) of the reported speaker's voice when reading direct speech as opposed to meaning-equivalent indirect speech statements as part of a more vivid representation of the former. Our results may be interpreted in line with embodied cognition and form a starting point for more sophisticated interdisciplinary research on the nature of auditory mental simulation during reading.

  19. Direct interaction of natural and synthetic catechins with signal transducer activator of transcription 1 affects both its phosphorylation and activity

    KAUST Repository

    Menegazzi, Marta

    2013-12-10

    Our previous studies showed that (-)-epigallocatechin-3-gallate (EGCG) inhibits signal transducer activator of transcription 1 (STAT1) activation. Since EGCG may be a promising lead compound for new anti-STAT1 drug design, 15 synthetic catechins, characterized by the (-)-gallocatechin-3-gallate stereochemistry, were studied in the human mammary MDA-MB-231 cell line to identify the minimal structural features that preserve the anti-STAT1 activity. We demonstrate that the presence of three hydroxyl groups of B ring and one hydroxyl group in D ring is essential to preserve their inhibitory action. Moreover, a possible molecular target of these compounds in the STAT1 pathway was investigated. Our results demonstrate a direct interaction between STAT1 protein and catechins displaying anti-STAT1 activity. In particular, surface plasmon resonance (SPR) analysis and molecular modeling indicate the presence of two putative binding sites (a and b) with different affinity. Based on docking data, site-directed mutagenesis was performed, and interaction of the most active catechins with STAT1 was studied with SPR to test whether Gln518 on site a and His568 on site b could be important for the catechin-STAT1 interaction. Data indicate that site b has higher affinity for catechins than site a as the highest affinity constant disappears in the H568ASTAT1 mutant. Furthermore, Janus kinase 2 (JAK2) kinase assay data suggest that the contemporary presence in vitro of STAT1 and catechins inhibits JAK2-elicited STAT1 phosphorylation. The very tight catechin-STAT1 interaction prevents STAT1 phosphorylation and represents a novel, specific and efficient molecular mechanism for the inhibition of STAT1 activation. © Copyright 2014 Federation of European Biochemical Societies. All rights reserved.

  20. CINPA1 binds directly to constitutive androstane receptor and inhibits its activity.

    Science.gov (United States)

    Cherian, Milu T; Chai, Sergio C; Wright, William C; Singh, Aman; Alexandra Casal, Morgan; Zheng, Jie; Wu, Jing; Lee, Richard E; Griffin, Patrick R; Chen, Taosheng

    2018-03-31

    The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic sensors that regulate the expression of drug-metabolizing enzymes and efflux transporters. CAR activation promotes drug elimination, thereby reducing therapeutic effectiveness, or causes adverse drug effects via toxic metabolites. CAR inhibitors could be used to attenuate these adverse drug effects. CAR and PXR share ligands and target genes, confounding the understanding of the regulation of receptor-specific activity. We previously identified a small-molecule inhibitor, CINPA1, that inhibits CAR (without activating PXR at lower concentrations) by altering CAR-coregulator interactions and reducing CAR recruitment to DNA response elements of regulated genes. However, solid evidence was not presented for the direct binding of CINPA1 to CAR. In this study, we demonstrate direct interaction of CINPA1 with the CAR ligand-binding domain (CAR-LBD) and identify key residues involved in such interactions through a combination of biophysical and computational methods. We found that CINPA1 resides in the ligand-binding pocket to stabilize the CAR-LBD in a more rigid, less fluid state. Molecular dynamics simulations, together with our previously reported docking model, enabled us to predict which CAR residues were critical for interactions with CINPA1. The importance of these residues for CINPA1 binding were then validated by directed mutations and testing the mutant CAR proteins in transcription reporter and coregulatory interaction assays. We demonstrated strong hydrogen bonding of CINPA1 with N165 and H203 and identified other residues involved in hydrophobic contacts with CINPA1. Overall, our data confirm that CINPA1 directly binds to CAR. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Evaluation of the BH3-only Protein Puma as a Direct Bak Activator*

    Science.gov (United States)

    Dai, Haiming; Pang, Yuan-Ping; Ramirez-Alvarado, Marina; Kaufmann, Scott H.

    2014-01-01

    Interactions among Bcl-2 family proteins play critical roles in cellular life and death decisions. Previous studies have established the BH3-only proteins Bim, tBid, and Noxa as “direct activators” that are able to directly initiate the oligomerization and activation of Bak and/or Bax. Earlier studies of Puma have yielded equivocal results, with some concluding that it also acts as a direct activator and other studies suggesting that it acts solely as a sensitizer BH3-only protein. In the present study we examined the interaction of Puma BH3 domain or full-length protein with Bak by surface plasmon resonance, assessed Bak oligomerization status by cross-linking followed by immunoblotting, evaluated the ability of the Puma BH3 domain to induce Bak-mediated permeabilization of liposomes and mitochondria, and determined the effect of wild type and mutant Puma on cell viability in a variety of cellular contexts. Results of this analysis demonstrate high affinity (KD = 26 ± 5 nm) binding of the Puma BH3 domain to purified Bak ex vivo, leading to Bak homo-oligomerization and membrane permeabilization. Mutations in Puma that inhibit (L141E/M144E/L148E) or enhance (M144I/A145G) Puma BH3 binding to Bak also produce corresponding alterations in Bak oligomerization, Bak-mediated membrane permeabilization and, in a cellular context, Bak-mediated killing. Collectively, these results provide strong evidence that Puma, like Bim, Noxa, and tBid, is able to act as a direct Bak activator. PMID:24265320

  2. Performance of an Active Micro Direct Methanol Fuel Cell Using Reduced Catalyst Loading MEAs

    Directory of Open Access Journals (Sweden)

    D.S. Falcão

    2017-10-01

    Full Text Available The micro direct methanol fuel cell (MicroDMFC is an emergent technology due to its special interest for portable applications. This work presents the results of a set of experiments conducted at room temperature using an active metallic MicroDMFC with an active area of 2.25 cm2. The MicroDMFC uses available commercial materials with low platinum content in order to reduce the overall fuel cell cost. The main goal of this work is to provide useful information to easily design an active MicroDMFC with a good performance recurring to cheaper commercial Membrane Electrode Assemblies MEAs. A performance/cost analysis for each MEA tested is provided. The maximum power output obtained was 18.1 mW/cm2 for a hot-pressed MEA with materials purchased from Quintech with very low catalyst loading (3 mg/cm2 Pt–Ru at anode side and 0.5 mg/cm2 PtB at the cathode side costing around 15 euros. Similar power values are reported in literature for the same type of micro fuel cells working at higher operating temperatures and substantially higher cathode catalyst loadings. Experimental studies using metallic active micro direct methanol fuel cells operating at room temperature are very scarce. The results presented in this work are, therefore, very useful for the scientific community.

  3. Direct measurement of catalase activity in living cells and tissue biopsies.

    Science.gov (United States)

    Scaglione, Christine N; Xu, Qijin; Ramanujan, V Krishnan

    2016-01-29

    Spatiotemporal regulation of enzyme-substrate interactions governs the decision-making steps in biological systems. Enzymes, being functional units of every living cell, contribute to the macromolecular stability of cell survival, proliferation and hence are vital windows to unraveling the biological complexity. Experimental measurements capturing this dynamics of enzyme-substrate interactions in real time add value to this understanding. Furthermore these measurements, upon validation in realistic biological specimens such as clinical biopsies - can further improve our capability in disease diagnostics and treatment monitoring. Towards this direction, we describe here a novel, high-sensitive measurement system for measuring diffusion-limited enzyme-substrate kinetics in real time. Using catalase (enzyme) and hydrogen peroxide (substrate) as the example pair, we demonstrate that this system is capable of direct measurement of catalase activity in vitro and the measured kinetics follows the classical Michaelis-Menten reaction kinetics. We further demonstrate the system performance by measuring catalase activity in living cells and in very small amounts of liver biopsies (down to 1 μg total protein). Catalase-specific enzyme activity is demonstrated by genetic and pharmacological tools. Finally we show the clinically-relevant diagnostic capability of our system by comparing the catalase activities in liver biopsies from young and old mouse (liver and serum) samples. We discuss the potential applicability of this system in clinical diagnostics as well as in intraoperative surgical settings. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Estimating Am-241 activity in the body: comparison of direct measurements and radiochemical analyses

    International Nuclear Information System (INIS)

    Lynch, Timothy P.; Tolmachev, Sergei Y.; James, Anthony C.

    2009-01-01

    The assessment of dose and ultimately the health risk from intakes of radioactive materials begins with estimating the amount actually taken into the body. An accurate estimate provides the basis to best assess the distribution in the body, the resulting dose, and ultimately the health risk. This study continues the time-honored practice of evaluating the accuracy of results obtained using in vivo measurement methods and techniques. Results from the radiochemical analyses of the 241Am activity content of tissues and organs from four donors to the United States Transuranium and Uranium Registries were compared to the results from direct measurements of radioactive material in the body performed in vivo and post mortem. Two were whole body donations and two were partial body donations The skeleton was the organ with the highest deposition of 241Am activity in all four cases. The activities ranged from 30 Bq to 300 Bq. The skeletal estimates obtained from measurements over the forehead were within 20% of the radiochemistry results in three cases and differed by 78% in one case. The 241Am lung activity estimates ranged from 1 Bq to 30 Bq in the four cases. The results from the direct measurements were within 40% of the radiochemistry results in 3 cases and within a factor of 3 for the other case. The direct measurement estimates of liver activity ranged from 2 Bq to 60 Bq and were generally lower than the radiochemistry results. The results from this study suggest that the measurement methods and calibration techniques used at the In Vivo Radiobioassay and Research Facility to quantify the activity in the lungs, skeleton and liver are reasonable under the most challenging conditions where there is 241Am activity in multiple organs. These methods and techniques are comparable to those used at other Department of Energy sites. This suggests that the current in vivo methods and calibration techniques provide reasonable estimates of radioactive material in the body. Not

  5. Fencing direct memory access data transfers in a parallel active messaging interface of a parallel computer

    Science.gov (United States)

    Blocksome, Michael A.; Mamidala, Amith R.

    2013-09-03

    Fencing direct memory access (`DMA`) data transfers in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI including data communications endpoints, each endpoint including specifications of a client, a context, and a task, the endpoints coupled for data communications through the PAMI and through DMA controllers operatively coupled to segments of shared random access memory through which the DMA controllers deliver data communications deterministically, including initiating execution through the PAMI of an ordered sequence of active DMA instructions for DMA data transfers between two endpoints, effecting deterministic DMA data transfers through a DMA controller and a segment of shared memory; and executing through the PAMI, with no FENCE accounting for DMA data transfers, an active FENCE instruction, the FENCE instruction completing execution only after completion of all DMA instructions initiated prior to execution of the FENCE instruction for DMA data transfers between the two endpoints.

  6. Direct binding and activation of protein kinase C isoforms by steroid hormones.

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2008-10-01

    The non-genomic action of steroid hormones regulates a wide variety of cellular responses including regulation of ion transport, cell proliferation, migration, death and differentiation. In order to achieve such plethora of effects steroid hormones utilize nearly all known signal transduction pathways. One of the key signalling molecules regulating the non-genomic action of steroid hormones is protein kinase C (PKC). It is thought that rapid action of steroids hormones results from the activation of plasma membrane receptors; however, their molecular identity remains elusive. In recent years, an increasing number of studies have pointed at the selective binding and activation of specific PKC isoforms by steroid hormones. This has led to the hypothesis that PKC could act as a receptor as well as a transducer of the non-genomic effects of these hormones. In this review we summarize the current knowledge of the direct binding and activation of PKC by steroid hormones.

  7. Clustering of children's activity behaviour: the use of self-report versus direct measures

    Directory of Open Access Journals (Sweden)

    Tremblay Mark S

    2011-05-01

    Full Text Available Abstract While we concur with the objectives of the recent International Journal of Behavioural Nutrition and Physical Activity paper published by Jago and colleagues titled "Physical activity and sedentary behaviour typologies of 10-11 year olds", we feel that the results as currently presented do not support their conclusions. Though the authors created groups of children with dramatically different patterns of self-reported physical activity and sedentary behaviour, an inspection of the objectively measured accelerometry data shows little difference between the groups. Further, in at least one instance the difference between groups was of the opposite direction when using objective measures, as opposed to the self-report measures used in the published analysis. Thus, we caution the authors from making conclusions based on their self-report data, and propose that they re-analyze their data using their objectively measured data instead.

  8. Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.

    Science.gov (United States)

    Shabalina, Irina G; Kalinovich, Anastasia V; Cannon, Barbara; Nedergaard, Jan

    2016-05-01

    The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged.

  9. A novel method for direct measurement of complement convertases activity in human serum.

    Science.gov (United States)

    Blom, A M; Volokhina, E B; Fransson, V; Strömberg, P; Berghard, L; Viktorelius, M; Mollnes, T E; López-Trascasa, M; van den Heuvel, L P; Goodship, T H; Marchbank, K J; Okroj, M

    2014-10-01

    Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function leads directly or indirectly to pathological conditions, including higher infection rate, kidney diseases, autoimmune- or neurodegenerative diseases and ischaemia-reperfusion injury. An assay for direct measurement of activity of the convertases in patient sera is not available. Existing assays testing convertase function are based on purified complement components and, thus, convertase formation occurs under non-physiological conditions. We designed a new assay, in which C5 blocking compounds enabled separation of the complement cascade into two phases: the first ending at the stage of C5 convertases and the second ending with membrane attack complex formation. The use of rabbit erythrocytes or antibody-sensitized sheep erythrocytes as the platforms for convertase formation enabled easy readout based on measurement of haemolysis. Thus, properties of patient sera could be studied directly regarding convertase activity and membrane attack complex formation. Another advantage of this assay was the possibility to screen for host factors such as C3 nephritic factor and other anti-complement autoantibodies, or gain-of-function mutations, which prolong the half-life of complement convertases. Herein, we present proof of concept, detailed description and validation of this novel assay. © 2014 British Society for Immunology.

  10. New ATPase regulators-p97 goes to the PUB

    DEFF Research Database (Denmark)

    Madsen, Louise; Seeger, Michael; Semple, Colin A

    2009-01-01

    The conserved eukaryotic AAA-type ATPase complex, known as p97 or VCP in mammals and Cdc48 in yeast, is involved in a number of cellular pathways, including fusion of homotypic membranes, protein degradation, and activation of membrane-bound transcription factors. Most likely, p97 is directed...

  11. Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

    Directory of Open Access Journals (Sweden)

    Le Sun

    Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

  12. Annulation of Aromatic Imines via Directed C-H BondActivation

    Energy Technology Data Exchange (ETDEWEB)

    Thalji, Reema K.; Ahrendt, Kateri A.; Bergman, Robert G.; Ellman,Jonathan A.

    2005-04-14

    A directed C-H bond activation approach to the synthesis of indans, tetralins, dihydrofurans, dihydroindoles, and other polycyclic aromatic compounds is presented. Cyclization of aromatic ketimines and aldimines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using (PPh{sub 3}){sub 3}RhCl (Wilkinson's catalyst). The cyclization of a range of aromatic ketimines and aldimines provides bi- and tricyclic ring systems with good regioselectivity. Different ring sizes and substitution patterns can be accessed through the coupling of monosubstituted, 1,1- or 1,2-disubstituted, and trisubstituted alkenes bearing both electron-rich and electron-deficient functionality.

  13. Humanin directly protects cardiac mitochondria against dysfunction initiated by oxidative stress by decreasing complex I activity.

    Science.gov (United States)

    Thummasorn, Savitree; Shinlapawittayatorn, Krekwit; Khamseekaew, Juthamas; Jaiwongkam, Thidarat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2018-01-01

    Humanin (HN) is an endogenous peptide that exerts cytoprotection against oxidative stress and apoptosis. We recently reported that Humanin analogue (HNG) pretreatment can reduce reactive oxygen species production in the heart subjected to ischemia/reperfusion (I/R) injury via attenuating mitochondrial dysfunction. However, it is unclear if HNG has direct effects on mitochondrial function against oxidative stress. Thus, we sought to determine the effects of HNG on mitochondrial function under hydrogen peroxide (H 2 O 2 ) induced oxidative stress in isolated cardiac mitochondria. We found that HNG has direct protective effects on cardiac mitochondrial function against H 2 O 2 induced oxidative stress through decreasing complex I activity. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  14. Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury.

    Science.gov (United States)

    Li, Tuoyi; Yu, Bing; Liu, Zhixin; Li, Jingyuan; Ma, Mingliang; Wang, Yingbao; Zhu, Mingjiang; Yin, Huiyong; Wang, Xiaofeng; Fu, Yi; Yu, Fang; Wang, Xian; Fang, Xiaohong; Sun, Jinpeng; Kong, Wei

    2018-01-02

    Hyperhomocysteinemia (HHcy) is a risk factor for various cardiovascular diseases. However, the mechanism underlying HHcy-aggravated vascular injury remains unclear. Here we show that the aggravation of abdominal aortic aneurysm by HHcy is abolished in mice with genetic deletion of the angiotensin II type 1 (AT1) receptor and in mice treated with an AT1 blocker. We find that homocysteine directly activates AT1 receptor signalling. Homocysteine displaces angiotensin II and limits its binding to AT1 receptor. Bioluminescence resonance energy transfer analysis reveals distinct conformational changes of AT1 receptor upon binding to angiotensin II and homocysteine. Molecular dynamics and site-directed mutagenesis experiments suggest that homocysteine regulates the conformation of the AT1 receptor both orthosterically and allosterically by forming a salt bridge and a disulfide bond with its Arg 167 and Cys 289 residues, respectively. Together, these findings suggest that strategies aimed at blocking the AT1 receptor may mitigate HHcy-associated aneurysmal vascular injuries.

  15. High-activity PtRuPd/C catalyst for direct dimethyl ether fuel cells.

    Science.gov (United States)

    Li, Qing; Wen, Xiaodong; Wu, Gang; Chung, Hoon T; Gao, Rui; Zelenay, Piotr

    2015-06-22

    Dimethyl ether (DME) has been considered as a promising alternative fuel for direct-feed fuel cells but lack of an efficient DME oxidation electrocatalyst has remained the challenge for the commercialization of the direct DME fuel cell. The commonly studied binary PtRu catalyst shows much lower activity in DME than methanol oxidation. In this work, guided by density functional theory (DFT) calculation, a ternary carbon-supported PtRuPd catalyst was designed and synthesized for DME electrooxidation. DFT calculations indicated that Pd in the ternary PtRuPd catalyst is capable of significantly decreasing the activation energy of the CO and CH bond scission during the oxidation process. As evidenced by both electrochemical measurements in an aqueous electrolyte and polymer-electrolyte fuel cell testing, the ternary catalyst shows much higher activity (two-fold enhancement at 0.5 V in fuel cells) than the state-of-the-art binary Pt50 Ru50 /C catalyst (HiSPEC 12100). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Nallani Vijay; Yang, Jianbo; Pillai, Jitesh K.; Rawat, Swati; Solano, Carlos; Kumar, Abhay; Grøtli, Morten; Stemmler, Timothy L.; Rosen, Barry P.; Tamás, Markus J.

    2015-12-28

    The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeastSaccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)]in vitroandin vivoand that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation.

  17. A directly patternable click-active polymer film via initiated chemical vapor deposition (iCVD)

    International Nuclear Information System (INIS)

    Im, Sung Gap; Kim, Byeong-Su; Tenhaeff, Wyatt E.; Hammond, Paula T.; Gleason, Karen K.

    2009-01-01

    A new 'click chemistry' active functional polymer film was directly obtained from a commercially available monomer of propargyl acrylate (PA) via easy, one-step process of initiated chemical vapor deposition (iCVD). Fourier transform infrared (FTIR) spectra confirmed that significant amount of the click-active acetylene functional group was retained after the iCVD process. The degree of crosslinking could be controlled by intentionally adding crosslinker, such as ethylene glycol diacrylate (EGDA) that was polymerized with PA to form click-active, completely insoluble copolymer. The formed iCVD polymers could also be grafted on various inorganic substrates with silane coupling agents. These crosslinking and grafting techniques give iCVD polymers chemical and mechanical stability, which allows iCVD polymers applicable to various click chemistry without any modification of reaction conditions. Pre-patterned iCVD polymer could be obtained via photolithography and an azido-functionalized dye molecule was also successfully attached on iCVD polymer via click chemistry. Moreover, pPA film demonstrated sensitivity to e-beam irradiation, which enabled clickable substrates having nanometer scale patterns without requiring the use of an additional e-beam resist. Direct e-beam exposure of this multifunctional iCVD layer, a 200 nm pattern, and QD particles were selectively conjugated on the substrates via click chemistry. Thus, iCVD pPA has shown dual functionality as of 'clickable' e-beam sensitive material.

  18. Removal of direct blue-86 from aqueous solution by new activated carbon developed from orange peel.

    Science.gov (United States)

    Nemr, Ahmed El; Abdelwahab, Ola; El-Sikaily, Amany; Khaled, Azza

    2009-01-15

    The use of low-cost, easy obtained, high efficiency and eco-friendly adsorbents has been investigated as an ideal alternative to the current expensive methods of removing dyes from wastewater. This study investigates the potential use of activated carbon prepared from orange peel for the removal of direct blue-86 (DB-86) (Direct Fast Turquoise Blue GL) dye from simulated wastewater. The effects of different system variables, adsorbent dosage, initial dye concentration, pH and contact time were studied. The results showed that as the amount of the adsorbent increased, the percentage of dye removal increased accordingly. Optimum pH value for dye adsorption was determined as approximately 2.0. Maximum dye was sequestered within 30min after the beginning for every experiment. The adsorption of direct blue-86 followed a pseudo-second-order rate equation and fit well Langmuir, Tempkin and Dubinin-Radushkevich (D-R) equations better than Freundlich and Redlich-Peterson equations. The maximum removal of direct blue-86 was obtained at pH 2 as 92% for adsorbent dose of 6gL(-1) and 100mgL(-1) initial dye concentration at room temperature. The maximum adsorption capacity obtained from Langmuir equation was 33.78mgg(-1). Furthermore, adsorption kinetics of DB-86 was studied and the rate of adsorption was found to conform to pseudo-second-order kinetics with a good correlation (R2>0.99) with intraparticle diffusion as one of the rate determining steps. Activated carbon developed from orange peel can be attractive options for dye removal from diluted industrial effluents since test reaction made on simulated dyeing wastewater show better removal percentage of DB-86.

  19. Multi-criteria optimization of heating directly squeezed apple juice with the maximum antioxidant activity

    Directory of Open Access Journals (Sweden)

    N. V. Makarova

    2016-01-01

    Full Text Available Fruit production is an important source of essential nutrients. Currently, consumers are becoming increasingly aware of the importance of healthy eating and the consumption of fruit with high nutritional value. In this regard, the processing technology of fruit raw materials should be directed to the preservation of its taste, color, flavor and nutritional value. Heat treatment is the most common way of food preservation and is carried out under specific temperature-time regimes which can be categorized by intensity of a thermal effect on the product. In this connection, it is proposed to examine the questions of influence of the thermal treatment of directly squeezed apple juice on the properties of the product: antiradical, antioxidant activity, restoring force. Directly squeezed apple juice "Zhiguli" growing in Samara region was taken as the object of the study. We used experimental design method with the processing of the planning matrix. This article gives the description and study of the impact which heating directly squeezed apple juice makes on product properties: antiradical, antioxidant activities, and restoring force. It is shown that the juice heating regime at 115–120 ° C at 120 seconds is the most optimum. A mathematical model describing the influence of these parameters on the properties of ice cream. In this paper we propose a special method of processing databases in the form of tables, which uses methods of interpolation and approximation, choosing the appropriate algebraic polynomials, as well as other analytical dependences are widely used in engineering and technology research practice. This method of analytic extension of tabular data allows to transform the original (primary table of experimental data in the summary (final data table, which enables to solve certain problems of statistical and extreme content. This study was financially supported by the Ministry of Education and Science of the Russian Federation within

  20. The mast cell degranulator compound 48/80 directly activates neurons.

    Directory of Open Access Journals (Sweden)

    Michael Schemann

    Full Text Available BACKGROUND: Compound 48/80 is widely used in animal and tissue models as a "selective" mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. METHODOLOGY/PRINCIPAL FINDINGS: We used in vivo recordings from extrinsic intestinal afferents together with Ca(++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca(++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca(++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H(1 and H(2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca(++ transients in mast cell-free enteric neuron cultures. CONCLUSIONS/SIGNIFICANCE: The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn.

  1. Balance Control Mediated by Vestibular Circuits Directing Limb Extension or Antagonist Muscle Co-activation.

    Science.gov (United States)

    Murray, Andrew J; Croce, Katherine; Belton, Timothy; Akay, Turgay; Jessell, Thomas M

    2018-01-30

    Maintaining balance after an external perturbation requires modification of ongoing motor plans and the selection of contextually appropriate muscle activation patterns that respect body and limb position. We have used the vestibular system to generate sensory-evoked transitions in motor programming. In the face of a rapid balance perturbation, the lateral vestibular nucleus (LVN) generates exclusive extensor muscle activation and selective early extension of the hindlimb, followed by the co-activation of extensor and flexor muscle groups. The temporal separation in EMG response to balance perturbation reflects two distinct cell types within the LVN that generate different phases of this motor program. Initially, an LVN extensor population directs an extension movement that reflects connections with extensor, but not flexor, motor neurons. A distinct LVN co-activation population initiates muscle co-activation via the pontine reticular nucleus. Thus, distinct circuits within the LVN generate different elements of a motor program involved in the maintenance of balance. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  2. LDRD 2012 Annual Report: Laboratory Directed Research and Development Program Activities

    Energy Technology Data Exchange (ETDEWEB)

    Bookless, William [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2012-12-31

    Each year, Brookhaven National Laboratory (BNL) is required to provide a program description and overview of its Laboratory Directed Research and Development Program (LDRD) to the Department of Energy in accordance with DOE Order 413.2B dated April 19, 2006. This report provides a detailed look at the scientific and technical activities for each of the LDRD projects funded by BNL in FY2012, as required. In FY2012, the BNL LDRD Program funded 52 projects, 14 of which were new starts, at a total cost of $10,061,292.

  3. LDRD 2014 Annual Report: Laboratory Directed Research and Development Program Activities

    Energy Technology Data Exchange (ETDEWEB)

    Hatton, Diane [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-03-01

    Each year, Brookhaven National Laboratory (BNL) is required to provide a program description and overview of its Laboratory Directed Research and Development Program (LDRD) to the Department of Energy (DOE) in accordance with DOE Order 413.2B dated April 19, 2006. This report provides a detailed look at the scientific and technical activities for each of the LDRD projects funded by BNL in FY 2014, as required. In FY 2014, the BNL LDRD Program funded 40 projects, 8 of which were new starts, at a total cost of $9.6M.

  4. Highly efficient and enantioselective cyclization of aromatic imines via directed C-H bond activation.

    Science.gov (United States)

    Thalji, Reema K; Ellman, Jonathan A; Bergman, Robert G

    2004-06-16

    The first highly enantioselective catalytic reaction involving aromatic C-H bond activation is communicated. Enantioselective cyclization of aromatic ketimines containing alkenyl groups tethered at the meta position of an imine directing group has been achieved using 5 mol % [RhCl(coe)2]2 and 15 mol % of an (S)-binol-derived phosphoramidite ligand. Selectivities of up to 96% ee and up to quantitative yields were obtained. Moreover, the identified catalyst system enables the intramolecular alkylation reaction to be performed at temperatures 75 degrees C lower than our previously reported achiral system. The reaction can even be performed at room temperature for one of the optimal substrates.

  5. LDRD 2015 Annual Report: Laboratory Directed Research and Development Program Activities

    Energy Technology Data Exchange (ETDEWEB)

    Hatton, D. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-12-31

    Each year, Brookhaven National Laboratory (BNL) is required to provide a program description and overview of its Laboratory Directed Research and Development Program (LDRD) to the Department of Energy (DOE) in accordance with DOE Order 413.2B dated April 19, 2006. This report provides a detailed look at the scientific and technical activities for each of the LDRD projects funded by BNL in FY 2015, as required. In FY 2015, the BNL LDRD Program funded 43 projects, 12 of which were new starts, at a total cost of $9.5M.

  6. Sequential plasma activation methods for hydrophilic direct bonding at sub-200 °C

    Science.gov (United States)

    He, Ran; Yamauchi, Akira; Suga, Tadatomo

    2018-02-01

    We present our newly developed sequential plasma activation methods for hydrophilic direct bonding of silica glasses and thermally grown SiO2 films. N2 plasma was employed to introduce a metastable oxynitride layer on wafer surfaces for the improvement of bond energy. By using either O2-plasma/N2-plasma/N-radical or N2-plasma/N-radical sequential activation, the quartz-quartz bond energy was increased from 2.7 J/m2 to close to the quartz bulk fracture energy that was estimated to be around 9.0 J/m2 after post-bonding annealing at 200 °C. The silicon bulklike bond energy between thermal SiO2 films was also obtained. We suggest that the improvement is attributable to surface modification such as N-related defect formation and asperity softening by the N2 plasma surface treatment.

  7. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...

  8. Direct Ionic Regulation of the Activity of Myo-Inositol Biosynthesis Enzymes in Mozambique Tilapia.

    Directory of Open Access Journals (Sweden)

    Fernando D Villarreal

    Full Text Available Myo-inositol (Ins is a major compatible osmolyte in many cells, including those of Mozambique tilapia (Oreochromis mossambicus. Ins biosynthesis is highly up-regulated in tilapia and other euryhaline fish exposed to hyperosmotic stress. In this study, enzymatic regulation of two enzymes of Ins biosynthesis, Ins phosphate synthase (MIPS and inositol monophosphatase (IMPase, by direct ionic effects is analyzed. Specific MIPS and IMPase isoforms from Mozambique tilapia (MIPS-160 and IMPase 1 were selected based on experimental, phylogenetic, and structural evidence supporting their role for Ins biosynthesis during hyperosmotic stress. Recombinant tilapia IMPase 1 and MIPS-160 activity was assayed in vitro at ionic conditions that mimic changes in the intracellular milieu during hyperosmotic stress. The in vitro activities of MIPS-160 and IMPase 1 are highest at alkaline pH of 8.8. IMPase 1 catalytic efficiency is strongly increased during hyperosmolality (particularly for the substrate D-Ins-3-phosphate, Ins-3P, mainly as a result of [Na+] elevation. Furthermore, the substrate-specificity of IMPase 1 towards D-Ins-1-phosphate (Ins-1P is lower than towards Ins-3P. Because MIPS catalysis results in Ins-3P this results represents additional evidence for IMPase 1 being the isoform that mediates Ins biosynthesis in tilapia. Our data collectively demonstrate that the Ins biosynthesis enzymes are activated under ionic conditions that cells are exposed to during hypertonicity, resulting in Ins accumulation, which, in turn, results in restoration of intracellular ion homeostasis. We propose that the unique and direct ionic regulation of the activities of Ins biosynthesis enzymes represents an efficient biochemical feedback loop for regulation of intracellular physiological ion homeostasis during hyperosmotic stress.

  9. Rapid Detection of Thrombin and Other Protease Activity Directly in Whole Blood

    Science.gov (United States)

    Yu, Johnson Chung Sing

    Thrombin is a serine protease that plays a key role in the clotting cascade to promote hemostasis following injury to the endothelium. From a clinical diagnostic perspective, in-vivo thrombin activity is linked to various blood clotting disorders, as well as cardiovascular disease (DVT, arteriosclerosis, etc). Thus, the ability to rapidly measure protease activity directly in whole blood will provide important new diagnostics, and clinical researchers with a powerful tool to further elucidate the relationship between circulating protease levels and disease. The ultimate goal is to design novel point of care (POC) diagnostic devices that are capable of monitoring protease activities directly in whole blood and biological sample. A charge-changing substrate specific to the thrombin enzyme was engineered and its functionality was confirmed by a series of experiments. This led to the preliminary design, construction, and testing of two device platforms deemed fully functional for the electrophoretic separation and focusing of charged peptide fragments. The concept of using the existing charge-changing substrate platform for bacterial protease detection was also investigated. Certain strains of E coli are associated with severe symptoms such as abdominal cramps, bloody diarrhea, and vomiting. The OmpT protease is expressed on the outer membrane of E coli and plays a role in the cleavage of antimicrobial peptides, the degradation of recombinant heterologous proteins, and the activation of plasminogen in the host. Thus, a synthetic peptide substrate specific to the OmpT protease was designed and modeled for the purpose of detecting E coli in biological sample.

  10. Direct Ionic Regulation of the Activity of Myo-Inositol Biosynthesis Enzymes in Mozambique Tilapia.

    Science.gov (United States)

    Villarreal, Fernando D; Kültz, Dietmar

    2015-01-01

    Myo-inositol (Ins) is a major compatible osmolyte in many cells, including those of Mozambique tilapia (Oreochromis mossambicus). Ins biosynthesis is highly up-regulated in tilapia and other euryhaline fish exposed to hyperosmotic stress. In this study, enzymatic regulation of two enzymes of Ins biosynthesis, Ins phosphate synthase (MIPS) and inositol monophosphatase (IMPase), by direct ionic effects is analyzed. Specific MIPS and IMPase isoforms from Mozambique tilapia (MIPS-160 and IMPase 1) were selected based on experimental, phylogenetic, and structural evidence supporting their role for Ins biosynthesis during hyperosmotic stress. Recombinant tilapia IMPase 1 and MIPS-160 activity was assayed in vitro at ionic conditions that mimic changes in the intracellular milieu during hyperosmotic stress. The in vitro activities of MIPS-160 and IMPase 1 are highest at alkaline pH of 8.8. IMPase 1 catalytic efficiency is strongly increased during hyperosmolality (particularly for the substrate D-Ins-3-phosphate, Ins-3P), mainly as a result of [Na+] elevation. Furthermore, the substrate-specificity of IMPase 1 towards D-Ins-1-phosphate (Ins-1P) is lower than towards Ins-3P. Because MIPS catalysis results in Ins-3P this results represents additional evidence for IMPase 1 being the isoform that mediates Ins biosynthesis in tilapia. Our data collectively demonstrate that the Ins biosynthesis enzymes are activated under ionic conditions that cells are exposed to during hypertonicity, resulting in Ins accumulation, which, in turn, results in restoration of intracellular ion homeostasis. We propose that the unique and direct ionic regulation of the activities of Ins biosynthesis enzymes represents an efficient biochemical feedback loop for regulation of intracellular physiological ion homeostasis during hyperosmotic stress.

  11. The strategic use of lecture recordings to facilitate an active and self-directed learning approach.

    Science.gov (United States)

    Topale, Luminica

    2016-08-12

    New learning technologies have the capacity to dramatically impact how students go about learning and to facilitate an active, self-directed learning approach. In U. S. medical education, students encounter a large volume of content, which must be mastered at an accelerated pace. The added pressure to excel on the USMLE Step 1 licensing exam and competition for residency placements, require that students adopt an informed approach to the use of learning technologies so as to enhance rather than to detract from the learning process. The primary aim of this study was to gain a better understanding of how students were using recorded lectures in their learning and how their study habits have been influenced by the technology. Survey research was undertaken using a convenience sample. Students were asked to voluntarily participate in an electronic survey comprised of 27 closed ended, multiple choice questions, and one open ended item. The survey was designed to explore students' perceptions of how recorded lectures affected their choices regarding class participation and impacted their learning and to gain an understanding of how recorded lectures facilitated a strategic, active learning process. Findings revealed that recorded lectures had little influence on students' choices to participate, and that the perceived benefits of integrating recorded lectures into study practices were related to their facilitation of and impact on efficient, active, and self-directed learning. This study was a useful investigation into how the availability of lecture capture technology influenced medical students' study behaviors and how students were making valuable use of the technology as an active learning tool.

  12. Lack of direct mitogenic activity of dichloroacetate and trichloroacetate in cultured rat hepatocytes

    International Nuclear Information System (INIS)

    Walgren, Jennie L.; Kurtz, David T.; McMillan, JoEllyn M.

    2005-01-01

    Dichloroacetate (DCA) and trichloroacetate (TCA) are hepatocarcinogenic metabolites of the common groundwater contaminant, 1,1,2-trichloroethylene. DCA and TCA have been shown to induce hepatocyte proliferation in vivo, but it is not known if this response is the result of direct mitogenic activity or whether cell replication occurs indirectly in response to tissue injury or inflammation. In this study we used primary cultures of rat hepatocytes, a species susceptible to DCA- but not TCA-induced hepatocarcinogenesis, to determine whether DCA and TCA are direct hepatocyte mitogens. Rat hepatocytes, cultured in growth factor-free medium, were treated with 0.01-1.0 mM DCA or TCA for 10-40 h; cell replication was then assessed by measuring incorporation of 3 H-thymidine into DNA and by cell counts. DCA or TCA treatment did not alter 3 H-thymidine incorporation in the cultured hepatocytes. Although an increase in cell number was not observed, DCA treatment significantly abrogated the normal background cell loss, suggesting an ability to inhibit apoptotic cell death in primary hepatocyte cultures. Furthermore, treatment with DCA synergistically enhanced the mitogenic response to epidermal growth factor. The data indicate that DCA and TCA are not direct mitogens in hepatocyte cultures, which is of interest in view of their ability to stimulate hepatocyte replication in vivo. Nevertheless, the synergistic enhancement of epidermal growth factor-induced hepatocyte replication by DCA is of particular interest and warrants further study

  13. A Self-Sensing Active Magnetic Bearing Based on a Direct Current Measurement Approach

    Directory of Open Access Journals (Sweden)

    Carel P. du Rand

    2013-09-01

    Full Text Available Active magnetic bearings (AMBs have become a key technology in various industrial applications. Self-sensing AMBs provide an integrated sensorless solution for position estimation, consolidating the sensing and actuating functions into a single electromagnetic transducer. The approach aims to reduce possible hardware failure points, production costs, and system complexity. Despite these advantages, self-sensing methods must address various technical challenges to maximize the performance thereof. This paper presents the direct current measurement (DCM approach for self-sensing AMBs, denoting the direct measurement of the current ripple component. In AMB systems, switching power amplifiers (PAs modulate the rotor position information onto the current waveform. Demodulation self-sensing techniques then use bandpass and lowpass filters to estimate the rotor position from the voltage and current signals. However, the additional phase-shift introduced by these filters results in lower stability margins. The DCM approach utilizes a novel PA switching method that directly measures the current ripple to obtain duty-cycle invariant position estimates. Demodulation filters are largely excluded to minimize additional phase-shift in the position estimates. Basic functionality and performance of the proposed self-sensing approach are demonstrated via a transient simulation model as well as a high current (10 A experimental system. A digital implementation of amplitude modulation self-sensing serves as a comparative estimator.

  14. A self-sensing active magnetic bearing based on a direct current measurement approach.

    Science.gov (United States)

    Niemann, Andries C; van Schoor, George; du Rand, Carel P

    2013-09-11

    Active magnetic bearings (AMBs) have become a key technology in various industrial applications. Self-sensing AMBs provide an integrated sensorless solution for position estimation, consolidating the sensing and actuating functions into a single electromagnetic transducer. The approach aims to reduce possible hardware failure points, production costs, and system complexity. Despite these advantages, self-sensing methods must address various technical challenges to maximize the performance thereof. This paper presents the direct current measurement (DCM) approach for self-sensing AMBs, denoting the direct measurement of the current ripple component. In AMB systems, switching power amplifiers (PAs) modulate the rotor position information onto the current waveform. Demodulation self-sensing techniques then use bandpass and lowpass filters to estimate the rotor position from the voltage and current signals. However, the additional phase-shift introduced by these filters results in lower stability margins. The DCM approach utilizes a novel PA switching method that directly measures the current ripple to obtain duty-cycle invariant position estimates. Demodulation filters are largely excluded to minimize additional phase-shift in the position estimates. Basic functionality and performance of the proposed self-sensing approach are demonstrated via a transient simulation model as well as a high current (10 A) experimental system. A digital implementation of amplitude modulation self-sensing serves as a comparative estimator.

  15. Photogenerating Silver Nanoparticles and Polymer Nanocomposites by Direct Activation in the Near Infrared

    Directory of Open Access Journals (Sweden)

    Lavinia Balan

    2012-01-01

    Full Text Available This work reports on an improvement of the photochemically assisted synthesis of silver nanoparticles by direct photoreduction of AgNO3 with a laser source emitting in the near infrared range (NIR. For this, polymethine dyes were used as the photoactive agents. Both the effects of central chain structure and activation intensity were investigated. The reduction kinetics was followed up by UV-Vis spectroscopy, and the particles size was evaluated by transmission electron microscopy. The results showed that light intensity affects both the average size and size distribution of Ag nanoparticles generated through this process. The particles can also be generated in situ in a photopolymerizable formulation so that metal/polymer nanocomposites become available through a one-step photoassisted process on the basis of NIR activation. The process described herein is very fast (seconds to a few minutes, and it readily lends itself to automatization for mass production of micro-optical elements implemented directly onto integrated NIR sources.

  16. Direct and indirect antioxidant activity of polyphenol- and isothiocyanate-enriched fractions from Moringa oleifera.

    Science.gov (United States)

    Tumer, Tugba Boyunegmez; Rojas-Silva, Patricio; Poulev, Alexander; Raskin, Ilya; Waterman, Carrie

    2015-02-11

    Moringa oleifera Lam. is a fast-growing, tropical tree with various edible parts used as nutritious food and traditional medicine. This study describes an efficient preparatory strategy to extract and fractionate moringa leaves by fast centrifugal partition chromatography (FCPC) to produce polyphenol and isothiocyanate (ITC) rich fractions. Characterization and further purification of these fractions showed that moringa polyphenols were potent direct antioxidants assayed by oxygen radical absorbance capacity (ORAC), whereas moringa ITCs were effective indirect antioxidants assayed by induction of NAD(P)H quinone oxidoreductase 1 (NQO1) activity in Hepa1c1c7 cells. In addition, purified 4-[(α-l-rhamnosyloxy)benzyl]isothiocyanate and 4-[(4'-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate were further evaluated for their ORAC and NQO1 inducer potency in comparison with sulforaphane (SF). Both ITCs were as potent as SF in inducing NQO1 activity. These findings suggest that moringa leaves contain a potent mixture of direct and indirect antioxidants that can explain its various health-promoting effects.

  17. Effective degradation of primary color direct azo dyes using Fe0aggregates-activated persulfate process.

    Science.gov (United States)

    Liu, Na; Ding, Feng; Weng, Chih-Huang; Hwang, Chi-Chin; Lin, Yao-Tung

    2018-01-15

    The present study examined the oxidation power of a Fe 0 aggregates/persulfate (PS/Fe 0 ) system for the degradation of the wastewater containing mixed primary direct dyes (i.e., Sirius ® Gelb S-2G, Sirius ® Red F3B, and Sirius ® Turkis GL01). Results indicated that decolorization efficiency was determined by operating parameters of the PS/Fe 0 system and the structural complexity of dye molecules. System efficiency increased with increasing persulfate and Fe 0 dosages. Faster decolorization was observed in experiments conducted at pH 10.5) and low PS concentration (dye containing ADMI (the American Dye Manufacture Institute) 15105 was achieved within10 min in the PS/Fe 0 /55 °C system with an initial pH of 6.0 and dosages of 5 × 10 -3  M Na 2 S 2 O 8 and 0.5 g/L Fe 0 . Low molecular weight intermediates including organic acids were identified. Due to a relatively low activation energy (4.68 kcaL/mol), the PS/Fe 0 system exhibited higher efficiency at higher temperature. This study demonstrated that Fe 0 -activated PS is a promising process for the treatment of textile wastewaters containing mixed azo direct dyes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Carbamazepine directly inhibits adipocyte differentiation through activation of the ERK 1/2 pathway

    Science.gov (United States)

    Turpin, E; Muscat, A; Vatier, C; Chetrite, G; Corruble, E; Moldes, M; Fève, B

    2013-01-01

    Background and Purpose Carbamazepine (CBZ), known for its anti-epileptic, analgesic and mood-stabilizing properties, is also known to induce weight gain but the pathophysiology of this adverse effect is still largely unknown. We tested the hypothesis that CBZ could have a direct effect on adipocyte development and metabolism. Experimental Research We studied the effects of CBZ on morphological biochemical and molecular markers of adipogenesis, using several pre-adipocyte murine cell lines (3T3-L1, 3T3-F442A and T37i cells) and primary cultures of human pre-adipocytes. To delineate the mechanisms underlying the effect of CBZ, clonal expansion of pre-adipocytes, pro-adipogenic transcription factors, glucose uptake and lipolysis were also examined. Key Results CBZ strongly inhibited pre-adipocyte differentiation and triglyceride accumulation in a time- and dose-dependent manner in all models. Pleiotropic mechanisms were at the basis of the inhibitory effects of CBZ on adipogenesis and cell lipid accumulation. They included suppression of both clonal expansion and major adipogenic transcription factors such as PPAR-γ and CCAAT/enhancer binding protein-α, activation of basal lipolysis and decrease in insulin-stimulated glucose transport. Conclusions and Implications The effect of CBZ on adipogenesis involves activation of the ERK1/2 pathway. Our results show that CBZ acts directly on pre-adipocytes and adipocytes to alter adipose tissue development and metabolism. PMID:22889231

  19. A Study on Ukraine’s Exports Activities, Determining the Directions of its Intensification

    Directory of Open Access Journals (Sweden)

    Syhyda Liubov O.

    2017-09-01

    Full Text Available The article is aimed at determining Ukraine’s level of involvement in the world trade and globalization processes along with identifying the destructive factors of influence on Ukraine’s exports activity. The main indicators of Ukraine’s foreign trade activities for 2006-2016 were analyzed, in particular the exports and imports of goods and services, the export-import coverage ratio, the share of exports in GDP, and the share of imports in GDP. The foreign trade of Ukraine is determined to be dominated by imports, i.e. Ukrainian exporters are gradually losing their positions in foreign markets. It has been determined that the main factors that constrain Ukraine’s exports activity are the untenable structure of exports of goods and services, unreliable partner countries, and the unsuitable system of distribution of products in most enterprises engaged in foreign economic activities. Prospects for further research will be directed towards determining the best structure for marketing channels, thus facilitating the growth of exports.

  20. Study of removal of Direct Yellow 12 by cadmium oxide nanowires loaded on activated carbon

    Energy Technology Data Exchange (ETDEWEB)

    Ghaedi, Mehrorang, E-mail: m_ghaedi@mail.yu.ac.ir [Chemistry Department, Yasouj University Yasouj 75914-35 (Iran, Islamic Republic of); Sadeghian, Batuol [Chemistry Department, Yasouj University Yasouj 75914-35 (Iran, Islamic Republic of); Kokhdan, Syamak Nasiri, E-mail: syamak.nasiri@yahoo.com [Chemistry Department, Yasouj University Yasouj 75914-35 (Iran, Islamic Republic of); Pebdani, Arezou Amiri [Chemistry Department, Yasouj University Yasouj 75914-35 (Iran, Islamic Republic of); Sahraei, Reza; Daneshfar, Ali; Mihandoost, Asma [Department of Chemistry, University of Ilam, P.O. Box: 65315-516, Ilam (Iran, Islamic Republic of)

    2013-05-01

    In this research, cadmium oxide nanowires loaded on activated carbon (CdO-NW-AC) has been synthesized by a simple procedure and characterized by different techniques such as XRD, SEM and UV–vis spectrometry. This new adsorbent has been efficiently utilized for the removal of the Direct Yellow 12 (DY-12) from wastewater. To obtain maximum DY-12 removal efficiency, the influences of variables such as pH, DY-12 concentration, amount of CdO-NW-AC, contact time, and temperature have been examined and optimized in a batch method. Following the variable optimization, the experimental equilibrium data (at different concentration of DY-12) was fitted to conventional isotherm models such as Langmuir, Freundlich and Tempkin. The applicability of each method is based on the R{sup 2} and error analysis for each model. It was found that the experimental equilibrium data well fitted to the Langmuir isotherm model. The dependency of removal process to time and the experimental data follow second order kinetic model with involvement of intraparticle diffusion model. The negative value of Gibbs's free energy and positive value of adsorption enthalpy show the spontaneous and endothermic nature of adsorption process. - Graphical abstract: Typical FE-SEM image of the CdO nanowires. Highlights: ► Cadmium oxide nanowires loaded on activated carbon was utilized as an adsorbent. ► It was used for the removal of Direct Yellow 12 from aqueous solutions. ► The adsorption of Direct Yellow 12 on this adsorbent is endothermic in nature. ► The adsorption equilibrium data was well described by the Langmuir isotherm model.

  1. Using a simple apparatus to measure direct and diffuse photosynthetically active radiation at remote locations.

    Directory of Open Access Journals (Sweden)

    Michael J Cruse

    Full Text Available Plant canopy interception of photosynthetically active radiation (PAR drives carbon dioxide (CO2, water and energy cycling in the soil-plant-atmosphere system. Quantifying intercepted PAR requires accurate measurements of total incident PAR above canopies and direct beam and diffuse PAR components. While some regional data sets include these data, e.g. from Atmospheric Radiation Measurement (ARM Program sites, they are not often applicable to local research sites because of the variable nature (spatial and temporal of environmental variables that influence incoming PAR. Currently available instrumentation that measures diffuse and direct beam radiation separately can be cost prohibitive and require frequent adjustments. Alternatively, generalized empirical relationships that relate atmospheric variables and radiation components can be used but require assumptions that increase the potential for error. Our goal here was to construct and test a cheaper, highly portable instrument alternative that could be used at remote field sites to measure total, diffuse and direct beam PAR for extended time periods without supervision. The apparatus tested here uses a fabricated, solar powered rotating shadowband and other commercially available parts to collect continuous hourly PAR data. Measurements of total incident PAR had nearly a one-to-one relationship with total incident radiation measurements taken at the same research site by an unobstructed point quantum sensor. Additionally, measurements of diffuse PAR compared favorably with modeled estimates from previously published data, but displayed significant differences that were attributed to the important influence of rapidly changing local environmental conditions. The cost of the system is about 50% less than comparable commercially available systems that require periodic, but not continual adjustments. Overall, the data produced using this apparatus indicates that this instrumentation has the

  2. Direct Anandamide Activation of TRPV1 Produces Divergent Calcium and Current Responses

    Directory of Open Access Journals (Sweden)

    Axel J. Fenwick

    2017-06-01

    Full Text Available In the brainstem nucleus of the solitary tract (NTS, primary vagal afferent neurons express the transient receptor potential vanilloid subfamily member 1 (TRPV1 at their central terminals where it contributes to quantal forms of glutamate release. The endogenous membrane lipid anandamide (AEA is a putative TRPV1 agonist in the brain, yet the extent to which AEA activation of TRPV1 has a neurophysiological consequence is not well established. We investigated the ability of AEA to activate TRPV1 in vagal afferent neurons in comparison to capsaicin (CAP. Using ratiometric calcium imaging and whole-cell patch clamp recordings we confirmed that AEA excitatory activity requires TRPV1, binds competitively at the CAP binding site, and has low relative affinity. While AEA-induced increases in peak cytosolic calcium were similar to CAP, AEA-induced membrane currents were significantly smaller. Removal of bath calcium increased the AEA current with no change in peak CAP currents revealing a calcium sensitive difference in specific ligand activation of TRPV1. Both CAP- and AEA-activated TRPV1 currents maintained identical reversal potentials, arguing against a major difference in ion selectivity to resolve the AEA differences in signaling. In contrast with CAP, AEA did not alter spontaneous glutamate release at NTS synapses. We conclude: (1 AEA activation of TRPV1 is markedly different from CAP and produces different magnitudes of calcium influx from whole-cell current; and (2 exogenous AEA does not alter spontaneous glutamate release onto NTS neurons. As such, AEA may convey modulatory changes to calcium-dependent processes, but does not directly facilitate glutamate release.

  3. Topographic distribution of direct and hippocampus- mediated entorhinal cortex activity evoked by olfactory tract stimulation.

    Science.gov (United States)

    Gnatkovsky, Vadym; Uva, Laura; de Curtis, Marco

    2004-10-01

    Olfactory information is central for memory-related functions, such as recognition and spatial orientation. To understand the role of olfaction in learning and memory, the distribution and propagation of olfactory tract-driven activity in the parahippocampal region needs to be characterized. We recently demonstrated that repetitive stimulation of the olfactory tract in the isolated guinea pig brain preparation induces an early direct activation of the rostrolateral entorhinal region followed by a delayed response in the medial entorhinal cortex (EC), preceded by the interposed activation of the hippocampus. In the present study we performed a detailed topographic analysis of both the early and the delayed entorhinal responses induced by patterned stimulation of the lateral olfactory tract in the isolated guinea pig brain. Bi-dimensional maps of EC activity recorded at 128 recording sites with 4 x 4 matrix electrodes (410 microm interlead separation) sequentially placed in eight different positions, showed (i) an early (onset at 16.09 +/- 1.2 ms) low amplitude potential mediated by the monosynaptic LOT input, followed by (ii) an associative potential in the rostral EC which originates from the piriform cortex (onset at 33.2 +/- 2.3 ms), and (iii) a delayed potential dependent on the previous activation of the hippocampus. The sharp component of the delayed response had an onset latency between 52 and 63 ms and was followed by a slow wave. Laminar profile analysis demonstrated that in the caudomedial EC the delayed response was associated with two distinct current sinks located in deep and in superficial layers, whereas in the rostrolateral EC a small-amplitude sink could be detected in the superficial layers exclusively. The present report demonstrates that the output generated by the hippocampal activation is unevenly distributed across different EC subregions and indicates that exclusively the medial and caudal divisions receive a deep-layer input from the

  4. Direct measurement of tritium production rate in LiPb with removed parasitic activities: Preliminary experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kuc, Tadeusz, E-mail: kuc@agh.edu.pl; Pohorecki, Władysław; Ostachowicz, Beata

    2014-10-15

    Liquid scintillation (LS) technique applied to direct measurement of tritium activity produced in LiPb eutectic in Frascati HCLL TBM mock-up neutronic experiment has been tested so far in the case of LS measurement after long period since irradiation. LiPb samples irradiated in neutron filed show, except of tritium, meaningful activity of other radioisotopes (parasitic). Parasitic activity, mainly from isotopes of lead ({sup 209}Pb, {sup 204m}Pb, {sup 203}Pb) calculated with the use of FISPACT, exceeds ca 5 times tritium activity 1.4 h after irradiation. We propose to remove disturbing radioisotopes in a chemical way to avoid long “cooling” of the irradiated samples before tritium measurement. Samples (1 g of LiPb) irradiated in reactor fast neutron flux were diluted and metallic cations removed by chemical precipitation. For this purpose we used: potassium iodide (KJ), strontium chloride (SrCl{sub 2}), APDC (C{sub 5}H{sub 8}NS{sub 2}·NH{sub 4}), NaDDTC (C{sub 5}H{sub 10}NNaS{sub 2}·3H{sub 2}O), and PAN (C{sub 15}H{sub 11}N{sub 3}O). Precipitation procedure in each case lasted ca 5–25 min, and the following filtration next 10–20 min. In each filtrate (ca 120 ml) we measured Pb concentration in total reflection X-ray fluorescence (TXRF) analyzer and parasitic activity (left after 21-day “cooling”) applying HPGe gamma spectrometer. Pb cations precipitated by SrCl{sub 2} and than by PAN lowered activity of Pb isotopes to less than 1% of the initial tritium activity. Another combination of reagents: NaDDTC followed by SrCl{sub 2} in a single and double step filtration reduced Pb concentration 10{sup 2} and 10{sup 4} times, respectively. Reduction of this order allows tritium radiometric measurement ca 3 h after irradiation with acceptable accuracy. This time can be shortened by applying correction for decay of known parasitic activity. Input of {sup 76}As and other less abundant radioisotopes can be eliminated using high purity LiPb. Tritium activity of

  5. Increased expression of cathelicidin by direct activation of protease-activated receptor 2: possible implications on the pathogenesis of rosacea.

    Science.gov (United States)

    Kim, Ji Young; Kim, Yoon Jee; Lim, Beom Jin; Sohn, Hyo Jung; Shin, Dongyun; Oh, Sang Ho

    2014-11-01

    Recent findings of increased cathelicidin protein and its proteolytic fragments in rosacea suggest a pathogenic role for cathelicidin in this disease. The relationship between cathelicidin and protease-activated receptor 2 (PAR-2) is therefore of interest, as PAR-2, expressed principally in keratinocytes, regulates pro-inflammatory cytokine expression in the skin. The purpose of this study was to determine the relationship between expression of PAR-2 and cathelicidin in rosacea and to test the effect of direct PAR-2 activation on cathelicidin expression in keratinocytes. Samples from 40 patients with clinicopathologic diagnosis of rosacea and facial skin tissue samples from 20 patients with no specific findings or milium without inflammation were retrieved. Intensities of immunohistochemical staining for PAR-2 and cathelicidin were compared between normal and rosacea-affected skin tissues. Additionally, correlations between PAR-2 and cathelicidin staining intensities within rosacea patients were analyzed. In cultured keratinocytes, changes in PAR-2, cathelicidin, and vascular endothelial growth factor (VEGF) mRNA and protein were analyzed after treatment with PAR-2 activating peptide (AP). Cathelicidin expression was significantly higher in rosacea skin tissues than in normal tissues (prosacea tissues than in normal skin tissues. A positive correlation between PAR-2 and cathelicidin within rosacea samples was observed (R=0.330, p=0.037). After treatment of PAR-2 AP, both mRNA and protein levels for PAR-2, cathelicidin, and VEGF significantly increased in cultured keratinocytes, compared with PAR-2 control peptide treatment. PAR-2 may participate in the pathogenesis of rosacea through activation of cathelicidin LL-37, a mediator of innate immune responses in the skin.

  6. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Ibrahim M Salman

    2015-08-01

    Full Text Available Chronic kidney disease (CKD is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n=16 were instrumented for telemetric recording of RSNA and MAP. At 12–13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2 and central chemoreflex (hypercapnia: 7% CO2 activation and acute stress (open-field exposure, were measured. As indicators of renal function, urinary protein (UPro and creatinine (Ucr levels were assessed. LPK rats had higher resting RSNA (1.2±0.1 vs. 0.6±0.1 µV, p<0.05 and MAP (151±8 vs. 97±2 mmHg, p<0.05 compared to Lewis. MAP was negatively correlated with Ucr (r=-0.80, p=0.002 and positively correlated with RSNA (r=0.66, p=0.014, with multiple linear regression modeling indicating the strongest correlation was with Ucr. RSNA and MAP responses to activation of the central chemoreflex and open-field stress were reduced in the LPK relative to the Lewis (all p<0.05. This is the first description of dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways.

  7. Directed evolution of an LBP/CD14 inhibitory peptide and its anti-endotoxin activity.

    Directory of Open Access Journals (Sweden)

    Li Fang

    Full Text Available BACKGROUND: LPS-binding protein (LBP and its ligand CD14 are located upstream of the signaling pathway for LPS-induced inflammation. Blocking LBP and CD14 binding might prevent LPS-induced inflammation. In previous studies, we obtained a peptide analog (MP12 for the LBP/CD14 binding site and showed that this peptide analog had anti-endotoxin activity. In this study, we used in vitro directed evolution for this peptide analog to improve its in vivo and in vitro anti-endotoxin activity. METHODS: We used error-prone PCR (ep-PCR and induced mutations in the C-terminus of LBP and attached the PCR products to T7 phages to establish a mutant phage display library. The positive clones that competed with LBP for CD14 binding was obtained by screening. We used both in vivo and in vitro experiments to compare the anti-endotoxin activities of a polypeptide designated P1 contained in a positive clone and MP12. RESULTS: 11 positive clones were obtained from among target phages. Sequencing showed that 9 positive clones had a threonine (T to methionine (M mutation in amino acid 287 of LBP. Compared to polypeptide MP12, polypeptide P1 significantly inhibited LPS-induced TNF-α expression and NF-κB activity in U937 cells (P<0.05. Compared to MP12, P1 significantly improved arterial oxygen pressure, an oxygenation index, and lung pathology scores in LPS-induced ARDS rats (P<0.05. CONCLUSION: By in vitro directed evolution of peptide analogs for the LBP/CD14 binding site, we established a new polypeptide (P1 with a threonine (T-to-methionine (M mutation in amino acid 287 of LBP. This polypeptide had high anti-endotoxin activity in vitro and in vivo, which suggested that amino acid 287 in the C-terminus of LBP may play an important role in LBP binding with CD14.

  8. Explicit consideration of spatial hydrogen bonding direction for activity coefficient prediction based on implicit solvation calculations.

    Science.gov (United States)

    Chen, Wei-Lin; Lin, Shiang-Tai

    2017-08-09

    The activity coefficient of a chemical in a mixture is important in understanding the thermodynamic properties and non-ideality of the mixture. The COSMO-SAC model based on the result of quantum mechanical implicit solvation calculations has been shown to provide reliable predictions of activity coefficients for mixed fluids. However, it is found that the prediction accuracy is in general inferior for associating fluids. Existing methods for describing the hydrogen-bonding interaction consider the strength of the interaction based only on the polarity of the screening charges, neglecting the fact that the formation of hydrogen bonds requires a specific orientation between the donor and acceptor pairs. In this work, we propose a new approach that takes into account the spatial orientational constraints in hydrogen bonds. Based on the Valence Shell Electron Pair Repulsion (VSEPR) theory, the molecular surfaces associated with the formation of hydrogen bonds are limited to those in the projection of the lone pair electrons of hydrogen bond acceptors, in addition to the polarity of the surface screening charges. Our results show that this new directional hydrogen bond approach, denoted as the COSMO-SAC(DHB) model, requires fewer universal parameters and is significantly more accurate and reliable compared to previous models for a variety of properties, including vapor-liquid equilibria (VLE), infinite dilution activity coefficient (IDAC) and water-octanol partition coefficient (K ow ).

  9. Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6.

    Science.gov (United States)

    Chen, P L; Riley, D J; Chen-Kiang, S; Lee, W H

    1996-01-09

    The biological function of the retinoblastoma protein (RB) in the cell division cycle has been extensively documented, but its apparent role in differentiation remains largely unexplored. To investigate how RB is involved in differentiation, the U937 large-cell lymphoma line was induced to differentiate along a monocyte/macrophage lineage. During differentiation RB was found to interact directly through its simian virus 40 large tumor antigen (T antigen)-binding domain with NF-IL6, a member of the CAAT/enhancer-binding protein (C/EBP) family of transcription factors. NF-IL6 utilizes two distinct regions to bind to the hypophosphorylated form of RB in vitro and in cells. Wild-type but not mutant RB enhanced both binding activity of NF-IL6 to its cognate DNA sequences in vitro and promoter transactivation by NF-IL6 in cells. These findings indicate a novel biochemical function of RB: it activates, by an apparent chaperone-like activity, specific transcription factors important for differentiation. This contrasts with its sequestration and inactivation of other transcription factors, such as E2F-1, which promote progression of the cell cycle. Such disparate mechanisms may help to explain the dual role of RB in cell differentiation and the cell division cycle.

  10. Direct regulation of topoisomerase activity by a nucleoid-associated protein.

    Science.gov (United States)

    Ghosh, Soumitra; Mallick, Bratati; Nagaraja, Valakunja

    2014-01-01

    The topological homeostasis of bacterial chromosomes is maintained by the balance between compaction and the topological organization of genomes. Two classes of proteins play major roles in chromosome organization: the nucleoid-associated proteins (NAPs) and topoisomerases. The NAPs bind DNA to compact the chromosome, whereas topoisomerases catalytically remove or introduce supercoils into the genome. We demonstrate that HU, a major NAP of Mycobacterium tuberculosis specifically stimulates the DNA relaxation ability of mycobacterial topoisomerase I (TopoI) at lower concentrations but interferes at higher concentrations. A direct physical interaction between M. tuberculosis HU (MtHU) and TopoI is necessary for enhancing enzyme activity both in vitro and in vivo. The interaction is between the amino terminal domain of MtHU and the carboxyl terminal domain of TopoI. Binding of MtHU did not affect the two catalytic trans-esterification steps but enhanced the DNA strand passage, requisite for the completion of DNA relaxation, a new mechanism for the regulation of topoisomerase activity. An interaction-deficient mutant of MtHU was compromised in enhancing the strand passage activity. The species-specific physical and functional cooperation between MtHU and TopoI may be the key to achieve the DNA relaxation levels needed to maintain the optimal superhelical density of mycobacterial genomes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Enhanced electrocatalytic activity and stability of monodisperse Pt nanocomposites for direct methanol fuel cells.

    Science.gov (United States)

    Eris, Sinan; Daşdelen, Zeynep; Sen, Fatih

    2018-03-01

    Direct methanol fuel cells (DMFCs) are one of the most important fuel cells operating at low temperature using methanol as fuel and they need very efficient catalysts to activate the methanol. Generally, the most efficient fuel cell catalysts are platinum-based nanoparticles that can be used by different supporting materials such as different as prepared and functionalized carbon derivatives. For this purpose, herein, the carbon black has been mainly functionalized with an acidification process in order to increase the electrical conductivity and heterogeneous electron transfer rate of supporting materials. After functionalization of carbon black (f-CB), platinum salt (PtCl 4 ) was stabilized with propylamine (PA) in the presence of ethylene glycol (EG) and f-CB by microwave synthesis method. XPS, XRD, TEM and Raman Spectroscopy techniques were used to determine the morphology of the prepared catalyst. The results showed that the prepared nanocatalyst has face-centered cubic (fcc) structure and uniformly distribution on supporting material. Besides, chronoamperometry (CA) and cyclic voltammetry (CV) techniques were used to determine the electrochemical activity of functionalized carbon black supported Pt NPs (Pt/f-CB) towards methanol. From the results obtained from the CV and CA, it was found that the activity of the Pt/f-CB NPs (50 mA/cm 2 ) was almost 4-5 times higher than that of the Pt/CB NPs and commercial available Pt/C catalyst (ETEK). Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Oligosaccharide biosensor for direct monitoring of enzymatic activities using QCM-D.

    Science.gov (United States)

    Bouchet-Spinelli, Aurélie; Reuillard, Bertrand; Coche-Guérente, Liliane; Armand, Sylvie; Labbé, Pierre; Fort, Sébastien

    2013-11-15

    Enzymatic modification of saccharidic biomass is a subject of intensive research with potential applications in plant or human health, design of biomaterials and biofuel production. Bioengineering and metagenomics provide access to libraries of glycoside hydrolases but the biochemical characterization of these enzymes remains challenging, requiring fastidious colorimetric tests in discontinuous assays. Here, we describe a highly sensitive carbohydrate biosensor for the detection and characterization of glycoside hydrolases. Immobilization of oligosaccharides was achieved using copper-catalyzed azide-alkyne cycloaddition of maltoheptaose-modified probes onto self-assembled monolayers bearing azide reactive groups. This biosensor allowed detection of glycoside hydrolase activities at the picomolar level using quartz-crystal microbalance with dissipation monitoring (QCM-D). To our knowledge, this protocol provides the best performance to date for the detection of glycoside hydrolase activities. For each enzyme tested, we could determine the kinetic constant from the QCM-D data, and derive conclusions that correlated well with those of standard colorimetric tests. This opens the way to a new generation of rapid and direct tests characterizing functionally carbohydrate-active enzymes. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Direct electron imaging in electron microscopy with monolithic active pixel sensors

    Energy Technology Data Exchange (ETDEWEB)

    Deptuch, G. [Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: deptuch@ieee.org; Besson, A. [IPHC, CNRS-IN2P3/ULP, 23 rue du Loess, BP 28, 67037 Strasbourg Cedex 02 (France); Rehak, P. [Brookhaven National Laboratory, Upton, NY 11973 (United States); Szelezniak, M. [IPHC, CNRS-IN2P3/ULP, 23 rue du Loess, BP 28, 67037 Strasbourg Cedex 02 (France); Wall, J. [Brookhaven National Laboratory, Upton, NY 11973 (United States); Winter, M. [IPHC, CNRS-IN2P3/ULP, 23 rue du Loess, BP 28, 67037 Strasbourg Cedex 02 (France); Zhu, Y. [Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2007-08-15

    A new imaging device for dynamic electron microscopy is in great demand. The detector should provide the experimenter with images having sufficient spatial resolution at high speed. Immunity to radiation damage, accumulated during exposures, is critical. Photographic film, a traditional medium, is not adequate for studies that require large volumes of data or rapid recording and charge coupled device (CCD) cameras have limited resolution, due to phosphor screen coupling. CCD chips are not suitable for direct recording due to their extreme sensitivity to radiation damage. This paper discusses characterization of monolithic active pixel sensors (MAPS) in a scanning electron microscope (SEM) as well as in a transmission electron microscope (TEM). The tested devices were two versions of the MIMOSA V (MV) chip. This 1 M pixel device features pixel size of 17x17 {mu}m{sup 2} and was designed in a 0.6 {mu}m CMOS process. The active layer for detection is a thin (less than 20 {mu}m) epitaxial layer, limiting the broadening of the electron beam. The first version of the detector was a standard imager with electronics, passivation and interconnection layers on top of the active region; the second one was bottom-thinned, reaching the epitaxial layer from the bottom. The electron energies used range from a few keV to 30 keV for SEM and from 40 to 400 keV for TEM. Deterioration of the image resolution due to backscattering was quantified for different energies and both detector versions.

  14. The Influence of Prior Knowledge on the Retrieval-Directed Function of Note Taking in Prior Knowledge Activation

    Science.gov (United States)

    Wetzels, Sandra A. J.; Kester, Liesbeth; van Merrienboer, Jeroen J. G.; Broers, Nick J.

    2011-01-01

    Background: Prior knowledge activation facilitates learning. Note taking during prior knowledge activation (i.e., note taking directed at retrieving information from memory) might facilitate the activation process by enabling learners to build an external representation of their prior knowledge. However, taking notes might be less effective in…

  15. The concordance of directly and indirectly measured built environment attributes and physical activity adoption

    Directory of Open Access Journals (Sweden)

    O'Connor Daniel P

    2011-07-01

    Full Text Available Background Physical activity (PA adoption is essential for obesity prevention and control, yet ethnic minority women report lower levels of PA and are at higher risk for obesity and its comorbidities compared to Caucasians. Epidemiological studies and ecologic models of health behavior suggest that built environmental factors are associated with health behaviors like PA, but few studies have examined the association between built environment attribute concordance and PA, and no known studies have examined attribute concordance and PA adoption. Purpose The purpose of this study was to associate the degree of concordance between directly and indirectly measured built environment attributes with changes in PA over time among African American and Hispanic Latina women participating in a PA intervention. Method Women (N = 410 completed measures of PA at Time 1 (T1 and Time 2 (T2; environmental data collected at T1 were used to compute concordance between directly and indirectly measured built environment attributes. The association between changes in PA and the degree of concordance between each directly and indirectly measured environmental attribute was assessed using repeated measures analyses. Results There were no significant associations between built environment attribute concordance values and change in self-reported or objectively measured PA. Self-reported PA significantly increased over time (F(1,184 = 7.82, p = .006, but this increase did not vary by ethnicity or any built environment attribute concordance variable. Conclusions Built environment attribute concordance may not be associated with PA changes over time among minority women. In an effort to promote PA, investigators should clarify specific built environment attributes that are important for PA adoption and whether accurate perceptions of these attributes are necessary, particularly among the vulnerable population of minority women.

  16. Using complexity theory to develop a student-directed interprofessional learning activity for 1220 healthcare students.

    Science.gov (United States)

    Jorm, Christine; Nisbet, Gillian; Roberts, Chris; Gordon, Christopher; Gentilcore, Stacey; Chen, Timothy F

    2016-08-08

    More and better interprofessional practice is predicated to be necessary to deliver good care to the patients of the future. However, universities struggle to create authentic learning activities that enable students to experience the dynamic interprofessional interactions common in healthcare and that can accommodate large interprofessional student cohorts. We investigated a large-scale mandatory interprofessional learning (IPL) activity for health professional students designed to promote social learning. A mixed methods research approach determined feasibility, acceptability and the extent to which student IPL outcomes were met. We developed an IPL activity founded in complexity theory to prepare students for future practice by engaging them in a self-directed (self-organised) learning activity with a diverse team, whose assessable products would be emergent creations. Complicated but authentic clinical cases (n = 12) were developed to challenge student teams (n = 5 or 6). Assessment consisted of a written management plan (academically marked) and a five-minute video (peer marked) designed to assess creative collaboration as well as provide evidence of integrated collective knowledge; the cohesive patient-centred management plan. All students (including the disciplines of diagnostic radiology, exercise physiology, medicine, nursing, occupational therapy, pharmacy, physiotherapy and speech pathology), completed all tasks successfully. Of the 26 % of students who completed the evaluation survey, 70 % agreed or strongly agreed that the IPL activity was worthwhile, and 87 % agreed or strongly agreed that their case study was relevant. Thematic analysis found overarching themes of engagement and collaboration-in-action suggesting that the IPL activity enabled students to achieve the intended learning objectives. Students recognised the contribution of others and described negotiation, collaboration and creation of new collective knowledge after working

  17. Direct Hysteresis Heating of Catalytically Active Ni–Co Nanoparticles as Steam Reforming Catalyst

    DEFF Research Database (Denmark)

    Mortensen, Peter Mølgaard; Engbæk, Jakob Soland; Vendelbo, Søren Bastholm

    2017-01-01

    We demonstrated a proof-of-concept catalytic steam reforming flow reactor system heated only by supported magnetic nickel–cobalt nanoparticles in an oscillating magnetic field. The heat transfer was facilitated by the hysteresis heating in the nickel–cobalt nanoparticles alone. This produced...... a sufficient power input to equilibrate the reaction at above 780 °C with more than 98% conversion of methane. The high conversion of methane indicated that Co-rich nanoparticles with a high Curie temperature provide sufficient heat to enable the endothermic reaction, with the catalytic activity facilitated...... by the Ni content in the nanoparticles. The magnetic hysteresis losses obtained from temperature-dependent hysteresis measurements were found to correlate well with the heat generation in the system. The direct heating of the catalytic system provides a fast heat transfer and thereby overcomes the heat...

  18. LDRD 2016 Annual Report: Laboratory Directed Research and Development Program Activities

    Energy Technology Data Exchange (ETDEWEB)

    Hatton, D. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2017-03-31

    Each year, Brookhaven National Laboratory (BNL) is required to provide a program description and overview of its Laboratory Directed Research and Development Program (LDRD) to the Department of Energy (DOE) in accordance with DOE Order 413.2C dated October 22, 2015. This report provides a detailed look at the scientific and technical activities for each of the LDRD projects funded by BNL in FY 2016, as required. In FY 2016, the BNL LDRD Program funded 48 projects, 21 of which were new starts, at a total cost of $11.5M. The investments that BNL makes in its LDRD program support the Laboratory’s strategic goals. BNL has identified four Critical Outcomes that define the Laboratory’s scientific future and that will enable it to realize its overall vision. Two operational Critical Outcomes address essential operational support for that future: renewal of the BNL campus; and safe, efficient laboratory operations.

  19. Innate Reverse Transcriptase Activity of DNA Polymerase for Isothermal RNA Direct Detection.

    Science.gov (United States)

    Shi, Chao; Shen, Xiaotong; Niu, Shuyan; Ma, Cuiping

    2015-11-04

    RNA detection has become one of the most robust parts in molecular biology, medical diagnostics and drug discovery. Conventional RNA detection methods involve an extra reverse transcription step, which limits their further application for RNA rapid detection. We herein report a novel finding that Bst and Klenow DNA polymerases possess innate reverse transcriptase activities, so that the reverse transcription step and next amplification reaction can be combined to one step in isothermal RNA detection. We have demonstrated that Bst and Klenow DNA polymerases could be successfully used to reverse transcribe RNA within 125-nt length by real time RT-PCR and polyacrylamide gel electrophoresis (PAGE). Our findings will spur the development of a myriad of simple and easy to use RNA detection technologies for isothermal RNA direct detection. This will just meet the future needs of bioanalysis and clinical diagnosis to RNA rapid detection in POC settings and inspection and quarantine.

  20. Annealing effects on recombinative activity of nickel at direct silicon bonded interface

    International Nuclear Information System (INIS)

    Kojima, Takuto; Ohshita, Yoshio; Yamaguchi, Masafumi

    2015-01-01

    By performing capacitance transient analyses, the recombination activity at a (110)/(100) direct silicon bonded (DSB) interface contaminated with nickel diffused at different temperatures, as a model of grain boundaries in multicrystalline silicon, was studied. The trap level depth from the valence band, trap density of states, and hole capture cross section peaked at an annealing temperature of 300 °C. At temperatures ⩾400 °C, the hole capture cross section increased with temperature, but the density of states remained unchanged. Further, synchrotron-based X-ray analyses, microprobe X-ray fluorescence (μ-XRF), and X-ray absorption near edge structure (XANES) analyses were performed. The analysis results indicated that the chemical phase after the sample was annealed at 200 °C was a mixture of NiO and NiSi 2

  1. Maternal celiac disease autoantibodies bind directly to syncytiotrophoblast and inhibit placental tissue transglutaminase activity

    Directory of Open Access Journals (Sweden)

    Robinson Nicola J

    2009-02-01

    Full Text Available Abstract Background Celiac disease (CD occurs in as many as 1 in 80 pregnant women and is associated with poor pregnancy outcome, but it is not known if this is an effect on maternal nutrient absorption or, alternatively, if the placenta is an autoimmune target. The major autoantigen, tissue transglutaminase (tTG, has previously been shown to be present in the maternal-facing syncytiotrophoblast plasma membrane of the placenta. Methods ELISA was used to demonstrate the presence of antibodies to tissue transglutaminase in a panel of CD sera. Immunohistochemistry was used to evaluate the binding of IgA autoantibodies from CD serum to term placenta. In addition, novel direct binding and activity assays were developed to mimic the in vivo exposure of the villous placenta to maternal autoantibody. Results and Discussion CD IgA autoantibodies located to the syncytial surface of the placenta significantly more than IgA antibodies in control sera (P Conclusion These data indicate that direct immune effects in untreated CD women may compromise placental function.

  2. Direct Electrochemistry of Horseradish Peroxidase on NiO Nanoflower Modified Electrode and Its Electrocatalytic Activity

    Directory of Open Access Journals (Sweden)

    Lijun Yan

    2016-09-01

    Full Text Available In this paper nickel oxide (NiO nanoflower was synthesized and used for the realization of direct electrochemistry of horseradish peroxidase (HRP. By using carbon ionic liquid electrode (CILE as the substrate electrode, NiO-HRP composite was casted on the surface of CILE with chitosan (CTS as the film forming material and the modified electrode was denoted as CTS/NiO-HRP/CILE. UV-Vis absorption and FT-IR spectra confirmed that HRP retained its native structure after mixed with NiO nanoflower. Direct electron transfer of HRP on the modified electrode was investigated by cyclic voltammetry with a pair of quasi-reversible redox waves appeared, indicating that the presence of NiO nanoflower on the electrode surface could accelerate the electron transfer rate between the electroactive center of HRP and the substrate electrode. Electrochemical behaviors of HRP on the modified electrode were carefully investigated. The HRP modified electrode showed excellent electrocatalytic activity to the reduction of trichloroacetic acid with wider linear range and lower detection limit. Therefore the presence of NiO nanoflower could provide a friendly biocompatible interface for immobilizing biomolecules and keeping their native structure. The fabricated electrochemical biosensor displayed the advantages such as high sensitivity, good reproducibility and long-term stability. This work is licensed under a Creative Commons Attribution 4.0 International License.

  3. Direction in charge of the management of wastes. 1998 activity report

    International Nuclear Information System (INIS)

    1998-01-01

    This document is the 1998 activity report of the direction in charge of the management of radioactive wastes (DGD) of the French atomic energy commission (CEA). The role of the DGD is the elimination of radioactive wastes, the management of spent fuels, the cleansing and dismantling of shut-down and decommissioned installations at the CEA. This report summarizes the highlights of the 1998 year: the cleansing plan of the CEA (current policy, plan scheme, quality assurance, financing, public relation); the radioactive wastes (general considerations, management of liquid and solid effluents, management of sealed sources, modernization of equipments and new projects, relations with the Andra, studies in progress); the spent fuels (general considerations, solutions, long-term storage); the dismantling of shut-down installations (general considerations about decommissioning, dismantling actions at the CEA, main works performed, dismantling actions in progress); the management of wastes at the CEA-direction for military applications (DAM); the cleansing of the CEA-Marcoule site; 1998 status of the management of wastes (appendix). (J.S.)

  4. Understanding the direct involvement of parents in policy development and school activities in a primary school

    Directory of Open Access Journals (Sweden)

    Tobin Bernie

    2017-12-01

    Full Text Available It is acknowledged that parental engagement with children’s learning and education is of vital importance. But, there is a tendency to confuse engagement with learning with engagement with the school. While all types of parents’ involvement can have a positive effect, it is actually what parents do with their child at home that has the greatest impact. However, unless parental involvement in learning is embedded in whole-school processes it is unlikely to as effective as possible. This paper documents an action research study that explores the inclusion of parents and home values in the construction of the teaching and learning environment. This was a small step towards positive parent-teacher collaboration, which allowed an exchange of knowledge, values and cultural background experiences. In acknowledging the ways in which the parents already engaged with their children’s learning, it began to enhance self-efficacy in their ability to directly affect this learning. This work has also provoked reflexive engagement of my influence and understanding of involving parents of children with additional and diverse learning needs. But, it also details the transformative journey that influenced my thinking about how we as a school could begin to develop whole-school processes to directly involve parents in policy development and school activities.

  5. Prophylactic and therapeutic activity of fully human monoclonal antibodies directed against Influenza A M2 protein

    Directory of Open Access Journals (Sweden)

    Gwerder Myriam

    2009-12-01

    Full Text Available Abstract Influenza virus infection is a prevalent disease in humans. Antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. Antibodies directed against the highly conserved extracellular domain of M2 have also been shown to mediate protection against Influenza A infection in various animal models. Active vaccination is generally considered the best approach to combat viral diseases. However, passive immunization is an attractive alternative, particularly in acutely exposed or immune compromized individuals, young children and the elderly. We recently described a novel method for the rapid isolation of natural human antibodies by mammalian cell display. Here we used this approach to isolate human monoclonal antibodies directed against the highly conserved extracellular domain of the Influenza A M2 protein. The identified antibodies bound M2 peptide with high affinities, recognized native cell-surface expressed M2 and protected mice from a lethal influenza virus challenge. Moreover, therapeutic treatment up to 2 days after infection was effective, suggesting that M2-specific monoclonals have a great potential as immunotherapeutic agents against Influenza infection.

  6. Developing model-making and model-breaking skills using direct measurement video-based activities

    Science.gov (United States)

    Vonk, Matthew; Bohacek, Peter; Militello, Cheryl; Iverson, Ellen

    2017-12-01

    This study focuses on student development of two important laboratory skills in the context of introductory college-level physics. The first skill, which we call model making, is the ability to analyze a phenomenon in a way that produces a quantitative multimodal model. The second skill, which we call model breaking, is the ability to critically evaluate if the behavior of a system is consistent with a given model. This study involved 116 introductory physics students in four different sections, each taught by a different instructor. All of the students within a given class section participated in the same instruction (including labs) with the exception of five activities performed throughout the semester. For those five activities, each class section was split into two groups; one group was scaffolded to focus on model-making skills and the other was scaffolded to focus on model-breaking skills. Both conditions involved direct measurement videos. In some cases, students could vary important experimental parameters within the video like mass, frequency, and tension. Data collected at the end of the semester indicate that students in the model-making treatment group significantly outperformed the other group on the model-making skill despite the fact that both groups shared a common physical lab experience. Likewise, the model-breaking treatment group significantly outperformed the other group on the model-breaking skill. This is important because it shows that direct measurement video-based instruction can help students acquire science-process skills, which are critical for scientists, and which are a key part of current science education approaches such as the Next Generation Science Standards and the Advanced Placement Physics 1 course.

  7. Developing model-making and model-breaking skills using direct measurement video-based activities

    Directory of Open Access Journals (Sweden)

    Matthew Vonk

    2017-08-01

    Full Text Available This study focuses on student development of two important laboratory skills in the context of introductory college-level physics. The first skill, which we call model making, is the ability to analyze a phenomenon in a way that produces a quantitative multimodal model. The second skill, which we call model breaking, is the ability to critically evaluate if the behavior of a system is consistent with a given model. This study involved 116 introductory physics students in four different sections, each taught by a different instructor. All of the students within a given class section participated in the same instruction (including labs with the exception of five activities performed throughout the semester. For those five activities, each class section was split into two groups; one group was scaffolded to focus on model-making skills and the other was scaffolded to focus on model-breaking skills. Both conditions involved direct measurement videos. In some cases, students could vary important experimental parameters within the video like mass, frequency, and tension. Data collected at the end of the semester indicate that students in the model-making treatment group significantly outperformed the other group on the model-making skill despite the fact that both groups shared a common physical lab experience. Likewise, the model-breaking treatment group significantly outperformed the other group on the model-breaking skill. This is important because it shows that direct measurement video-based instruction can help students acquire science-process skills, which are critical for scientists, and which are a key part of current science education approaches such as the Next Generation Science Standards and the Advanced Placement Physics 1 course.

  8. Electroejaculation functions primarily by direct activation of pelvic musculature: Perspectives from a porcine model

    Directory of Open Access Journals (Sweden)

    Adam M.R. Groh

    2018-03-01

    Full Text Available Ejaculatory dysfunction is a significant cause of infertility in men that have incurred spinal cord injury or iatrogenic lesions to the sympathetic nerves in the retroperitoneum. For such patients, electroejaculation – whereby a voltage is applied transrectally under general anesthesia – is a highly-effective procedure to obtain ejaculate. At present, however, there remains uncertainty as to the physiological mechanism by which electroejaculation prompts seminal emission in males with neurogenic anejaculation. Thus, in the present study, we aimed to determine, for the first time, whether electroejaculation functions by mimicking a neurophysiological response, or by directly activating local pelvic musculature. Using electroejaculation in a novel porcine model, we monitored the strength of contraction of the internal urethral sphincter (a smooth muscle involved in ejaculation before and after lesioning its sympathetic innervation with a combination of progressively-worsening surgical and pharmacological insults in three anesthetized boars (46.1 ± 7.4 kg. Importantly, prior to this investigation, we confirmed the comparative structural anatomy of the porcine model to humans through gross dissection and histological analysis of the infrarenal retroperitoneal sympathetic nerves and ganglia in 18 unembalmed boars. Prior to sacrifice, three of these boars underwent functional testing to confirm control of the internal urethral sphincter by the hypogastric nerves. Our results demonstrate that electroejaculation-induced contraction of the internal urethral sphincter was preserved following each progressive neural insult compared to the control state (p > 0.05. In contrast, these same insults resulted in paralysis/paresis of the internal urethral sphincter when its sympathetic innervation was directly stimulated with bipolar electrodes (p < 0.05. Taken together, our results provide the first empirical evidence to suggest that

  9. Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels.

    Science.gov (United States)

    Zhao, T; Zhang, H; Jin, C; Qiu, F; Wu, Y; Shi, L

    2017-10-01

    Melatonin, synthesized primarily by the pineal gland, is a neuroendocrine hormone with high membrane permeability. The vascular effects of melatonin, including vasoconstriction and vasodilation, have been demonstrated in numerous studies. However, the mechanisms underlying these effects are not fully understood. Large-conductance Ca 2+ -activated K + (BK Ca ) channels are expressed broadly on smooth muscle cells and play an important role in vascular tone regulation. This study explored the mechanisms of myocyte BK Ca channels and endothelial factors underlying the action of melatonin on the mesenteric arteries (MAs). Vascular contractility and patch-clamp studies were performed on myocytes of MAs from Wistar rats. Melatonin induced significant vasodilation on MAs. In the presence of N ω -nitro-l-arginine methyl ester (l-NAME), a potent endothelial oxide synthase (eNOS) inhibitor, melatonin elicited concentration-dependent relaxation, with lowered pIC 50 The effect of melatonin was significantly attenuated in the presence of BK Ca channel blocker iberiotoxin or MT1/MT2 receptor antagonist luzindole in both (+) l-NAME and (-) l-NAME groups. In the (+) l-NAME group, iberiotoxin caused a parallel rightward shift of the melatonin concentration-relaxation curve, with pIC 50 lower than that of luzindole. Both inside-out and cell-attached patch-clamp recordings showed that melatonin significantly increased the open probability, mean open time and voltage sensitivity of BK Ca channels. In a cell-attached patch-clamp configuration, the melatonin-induced enhancement of BK Ca channel activity was significantly suppressed by luzindole. These findings indicate that in addition to the activation of eNOS, melatonin-induced vasorelaxation of MAs is partially attributable to its direct (passing through the cell membrane) and indirect (via MT1/MT2 receptors) activation of the BK Ca channels on mesenteric arterial myocytes. © 2017 Society for Endocrinology.

  10. Direct bursoscopic ossicle resection in young and active patients with unresolved Osgood-Schlatter disease.

    Science.gov (United States)

    Eun, Sang Soo; Lee, Seung Ah; Kumar, Ramakant; Sul, Eun Jin; Lee, Sang Ho; Ahn, Jin Hwan; Chang, Moon Jong

    2015-03-01

    The aim of this study was to determine the outcomes of bursoscopic ossicle excision in young and active patients with unresolved Osgood-Schlatter disease. This retrospective study included 18 male military recruits. A direct bursoscopic ossicle excision was performed using low anterolateral and low anteromedial portals. Outcomes were evaluated using the Lysholm knee score, pain score on a visual analog scale (VAS) (from 0 to 10), and Tegner activity scale score. In addition, patients were asked whether they could kneel or squat and whether they were able to return to their duty after surgery. Patient satisfaction was evaluated using the VAS and by asking whether patients thought that the prominence of the tibial tuberosity was reduced and whether they would recommend the same surgical treatment to others. Complications after surgery were also evaluated. The mean Lysholm knee score was 71 preoperatively and improved to 99 after surgery. The mean VAS pain score was 6.5 in the preoperative period and decreased to 0.9 after surgery. In addition, the mean Tegner activity scale score improved from 2.7 preoperatively to 6.2 at final follow-up. However, 4 patients were not able to return to their duty, and 4 patients still had difficulties with kneeling after surgery. A superficial infection occurred in 1 patient, and a recurrent ossicle formation was found in 1 patient. Of 18 patients, 17 were satisfied with their surgical outcomes, and the mean VAS score for patient satisfaction was 8.8. Furthermore, all but 1 patient would recommend the same surgical treatment to others. However, 6 patients did not believe that the prominence of the tibial tuberosity was reduced. Bursoscopic ossicle excision showed satisfactory outcomes in selective young and active patients with persistent symptoms. However, bursoscopic surgery showed limitation in reducing the prominence of the tibial tuberosity. Level IV, therapeutic case series. Copyright © 2015 Arthroscopy Association of North

  11. Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C-H Bond Activation

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Jared; Bergman, Robert; Ellman, Jonathan

    2008-02-04

    Nitrogen heterocycles are present in many compounds of enormous practical importance, ranging from pharmaceutical agents and biological probes to electroactive materials. Direct funtionalization of nitrogen heterocycles through C-H bond activation constitutes a powerful means of regioselectively introducing a variety of substituents with diverse functional groups onto the heterocycle scaffold. Working together, our two groups have developed a family of Rh-catalyzed heterocycle alkylation and arylation reactions that are notable for their high level of functional-group compatibility. This Account describes their work in this area, emphasizing the relevant mechanistic insights that enabled synthetic advances and distinguished the resulting transformations from other methods. They initially discovered an intramolecular Rh-catalyzed C-2-alkylation of azoles by alkenyl groups. That reaction provided access to a number of di-, tri-, and tetracyclic azole derivatives. They then developed conditions that exploited microwave heating to expedite these reactions. While investigating the mechanism of this transformation, they discovered that a novel substrate-derived Rh-N-heterocyclic carbene (NHC) complex was involved as an intermediate. They then synthesized analogous Rh-NHC complexes directly by treating precursors to the intermediate [RhCl(PCy{sub 3}){sub 2}] with N-methylbenzimidazole, 3-methyl-3,4-dihydroquinazolein, and 1-methyl-1,4-benzodiazepine-2-one. Extensive kinetic analysis and DFT calculations supported a mechanism for carbene formation in which the catalytically active RhCl(PCy{sub 3}){sub 2} fragment coordinates to the heterocycle before intramolecular activation of the C-H bond occurs. The resulting Rh-H intermediate ultimately tautomerizes to the observed carbene complex. With this mechanistic information and the discovery that acid co-catalysts accelerate the alkylation, they developed conditions that efficiently and intermolecularly alkylate a variety of

  12. Remifentanil has a minimal direct effect on sinoatrial node pacemaker activity in the Guinea pig heart.

    Science.gov (United States)

    Kojima, Akiko; Ito, Yuki; Kitagawa, Hirotoshi; Matsuura, Hiroshi; Nosaka, Shuichi

    2013-11-01

    Whereas remifentanil administration is associated with severe bradycardia, it has yet to be fully investigated whether the negative chronotropic action of remifentanil is mediated by its direct action on sinoatrial (SA) node pacemaker activity in the heart versus indirect results of enhanced vagal activity. We examined the effects of remifentanil and fentanyl on the spontaneous action potentials of guinea pig SA node cells at concentrations of 5, 10, 100, and 1000 nM using the amphotericin B-perforated whole-cell patch-clamp technique. Isolated guinea pig hearts were perfused in a Langendorff mode with 5, 10, 100, and 1000 nM remifentanil. The spontaneous firing rate and diastolic depolarization rate (DDR) of the SA node action potentials were 189.1 ± 14.8 /min and 74.1 ± 2.9 mV/s (n = 8), respectively, under control conditions, and were not significantly affected by exposure to 5 nM (P = 1.0 for both spontaneous firing rate and DDR; n = 6), 10 nM (P = 0.62 for spontaneous firing rate, P = 0.99 for DDR; n = 6), or 100 nM (P = 0.23 for spontaneous firing rate, P = 0.38 for DDR; n = 6) remifentanil. However, 1000 nM remifentanil modestly but significantly decreased the spontaneous firing rate (P = 0.0087) and DDR (P = 0.0072, n = 6). Remifentanil did not affect the heart rate of isolated Langendorff-perfused guinea pig hearts at concentrations of 5 nM (P = 0.98), 10 nM (P = 0.35), or 100 nM (P = 0.24) but significantly reduced the heart rate at 1000 nM (P DDR at concentrations of 5 nM (P = 1.0 for both spontaneous firing rate and DDR) and 10 nM (P = 0.62 for spontaneous firing rate, P = 0.79 for DDR), but it significantly reduced both at 100 nM (P = 0.00038 for spontaneous firing rate, P = 0.0080 for DDR) and 1000 nM (P DDR). Clinically relevant concentrations (nanomolar order concentrations) of remifentanil do not produce significant direct effects on intrinsic cardiac automaticity; thus, suggesting that remifentanil-induced bradycardia in the clinical setting is

  13. Segmentation-free direct tumor volume and metabolic activity estimation from PET scans.

    Science.gov (United States)

    Taghanaki, Saeid Asgari; Duggan, Noirin; Ma, Hillgan; Hou, Xinchi; Celler, Anna; Benard, Francois; Hamarneh, Ghassan

    2018-01-01

    Tumor volume and metabolic activity are two robust imaging biomarkers for predicting early therapy response in F-fluorodeoxyglucose (FDG) positron emission tomography (PET), which is a modality to image the distribution of radiotracers and thereby observe functional processes in the body. To date, estimation of these two biomarkers requires a lesion segmentation step. While the segmentation methods requiring extensive user interaction have obvious limitations in terms of time and reproducibility, automatically estimating activity from segmentation, which involves integrating intensity values over the volume is also suboptimal, since PET is an inherently noisy modality. Although many semi-automatic segmentation based methods have been developed, in this paper, we introduce a method which completely eliminates the segmentation step and directly estimates the volume and activity of the lesions. We trained two parallel ensemble models using locally extracted 3D patches from phantom images to estimate the activity and volume, which are derivatives of other important quantification metrics such as standardized uptake value (SUV) and total lesion glycolysis (TLG). For validation, we used 54 clinical images from the QIN Head and Neck collection on The Cancer Imaging Archive, as well as a set of 55 PET scans of the Elliptical Lung-Spine Body Phantom™with different levels of noise, four different reconstruction methods, and three different background activities, namely; air, water, and hot background. In the validation on phantom images, we achieved relative absolute error (RAE) of 5.11 % ±3.5% and 5.7 % ±5.25% for volume and activity estimation, respectively, which represents improvements of over 20% and 6% respectively, compared with the best competing methods. From the validation performed using clinical images, we found that the proposed method is capable of obtaining almost the same level of agreement with a group of trained experts, as a single trained

  14. Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity

    Directory of Open Access Journals (Sweden)

    Matthews Paul

    2004-11-01

    Full Text Available Abstract Background Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. The most extensively studied forms of synaptic plasticity are long-term potentiation (LTP and its counterpart long-term depression (LTD of AMPA receptor-mediated synaptic transmission. In the CA1 region of the hippocampus, it has been shown that LTP often involves a rapid increase in the unitary conductance of AMPA receptor channels. However, LTP can also occur in the absence of any alteration in AMPA receptor unitary conductance. In the present study we have used whole-cell dendritic recording, failures analysis and non-stationary fluctuation analysis to investigate the mechanism of depotentiation of LTP. Results We find that when LTP involves an increase in unitary conductance, subsequent depotentiation invariably involves the return of unitary conductance to pre-LTP values. In contrast, when LTP does not involve a change in unitary conductance then depotentiation also occurs in the absence of any change in unitary conductance, indicating a reduction in the number of activated receptors as the most likely mechanism. Conclusions These data show that unitary conductance can be bi-directionally modified by synaptic activity. Furthermore, there are at least two distinct mechanisms to restore synaptic strength from a potentiated state, which depend upon the mechanism of the previous potentiation.

  15. Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor.

    Science.gov (United States)

    Muzzi, Mirko; Coppi, Elisabetta; Pugliese, Anna Maria; Chiarugi, Alberto

    2013-12-01

    Purinergic neurotransmission mediated by adenosine (Ado) type 1 receptors (A1Rs) plays pivotal roles in negative modulation of epileptic seizures, and Ado is thought to be a key endogenous anticonvulsant. Recent evidence, however, indicates that AMP, the metabolic precursor of Ado, also activate A1Rs. Here, we evaluated the antiepileptic effects of AMP adopting in vitro and in vivo models of epilepsy. We report that AMP reversed the increase in population spike (PS) amplitude and the decrease in PS latency induced by a Mg(2+)-free extracellular solution in CA1 neurons of mouse hippocampal slices. The AMP effects were inhibited by the A1R antagonist DPCPX, but not prevented by inhibiting conversion of AMP into Ado, indicating that AMP inhibited per se sustained hippocampal excitatory neurotransmission by directly activating A1Rs. AMP also reduced seizure severity and mortality in a model of audiogenic convulsion. Of note, the anticonvulsant effects of AMP were potentiated by preventing its conversion into Ado and inhibited by DPCPX. When tested in a model of kainate-induced seizure, AMP prolonged latency of convulsions but had no effects on seizure severity and mortality. Data provide the first evidence that AMP is an endogenous anticonvulsant acting at A1Rs. © 2013.

  16. Active Speed Compensation Method of Direct Torque Control System and Stability Analysis

    Directory of Open Access Journals (Sweden)

    Rui Li

    2015-02-01

    Full Text Available By analyzing characteristics of the DTC (direct torque control system in electrical driving system, a shortcoming of the classical DTC method is to point out that it is unable to decouple the mutual interference between torque and speed, so that when a running asynchronous motor subjected to an instantaneous impact load, rotor speed and its deviation appears excessive fluctuations that can not be quickly restored to the initial set value. In this research, under conditions that without sensors for measuring load torque and rotor speed, to an electrical drive systems contains DTC devices, a novel ASCC (active speed compensation control method is proposed based on ADRC (active disturbance rejection control theory, on account of DTC model of asynchronous motor, a multiobjective observer is designed to regulate both the speed and the torque, and a proof of asymptotic stability that related this new control systems with the observer is made by theoretical deduction. Finally stimulating results show that this method can overcome the shortcomings of classical DTC system and greatly enhance the ability of the high-speed driving system to deal with unexpected impact loads.

  17. Anodal transcranial direct current stimulation of the motor cortex increases cortical voluntary activation and neural plasticity.

    Science.gov (United States)

    Frazer, Ashlyn; Williams, Jacqueline; Spittles, Michael; Rantalainen, Timo; Kidgell, Dawson

    2016-11-01

    We examined the cumulative effect of 4 consecutive bouts of noninvasive brain stimulation on corticospinal plasticity and motor performance, and whether these responses were influenced by the brain-derived neurotrophic factor (BDNF) polymorphism. In a randomized double-blinded cross-over design, changes in strength and indices of corticospinal plasticity were analyzed in 14 adults who were exposed to 4 consecutive sessions of anodal and sham transcranial direct current stimulation (tDCS). Participants also undertook a blood sample for BDNF genotyping (N = 13). We observed a significant increase in isometric wrist flexor strength with transcranial magnetic stimulation revealing increased corticospinal excitability, decreased silent period duration, and increased cortical voluntary activation compared with sham tDCS. The results show that 4 consecutive sessions of anodal tDCS increased cortical voluntary activation manifested as an improvement in strength. Induction of corticospinal plasticity appears to be influenced by the BDNF polymorphism. Muscle Nerve 54: 903-913, 2016. © 2016 Wiley Periodicals, Inc.

  18. Impacts of direct human activity and climate change on north Ethiopian mountain landscapes over 140 Years

    Science.gov (United States)

    Nyssen, Jan; Frankl, Amaury; Haile, Mitiku; Hurni, Hans; Descheemaeker, Katrien; Ritler, Alfons; Crummey, Donald; Nievergelt, Bernhard; Moeyersons, Jan; Munro, Neil

    2010-05-01

    Studies on recent environmental change in tropical areas are generally conducted over limited time scales. This study makes a multi-scale assessment over a time span of 140 years, in one of the world's most degraded areas: the highlands of Northern Ethiopia. 300 landscapes, pictured on historical photographs, starting 1868, were re-photographed and environmental changes apparent on the paired photographs were analysed through expert rating. General tendencies appearing include an improved vegetation cover nowadays as compared to any period of the last 140 years, with a second optimum in the early 20th century. In the uppermost areas (above 3500 m a.s.l.) an upward shift of the upper tree line (Erica arborea) is observed, demonstrating that global warming takes also place in this region. At lower elevations, increased vegetation cover is the result of 25 years of intense rehabilitation activities. Physical soil and water conservation follows the same trend. Regional variations occurring in these trends are observed and discussed. The findings are substantiated by field investigations. The positive changes that result from these conservation activities in the north Ethiopian highlands are an issue of global concern as they show that (1) in our study area direct human impact on the environment is overriding and (2) severe land degradation should not always be irreversible.

  19. Physical activity and self-esteem: testing direct and indirect relationships associated with psychological and physical mechanisms

    Science.gov (United States)

    Zamani Sani, Seyed Hojjat; Fathirezaie, Zahra; Brand, Serge; Pühse, Uwe; Holsboer-Trachsler, Edith; Gerber, Markus; Talepasand, Siavash

    2016-01-01

    In the present study, we investigated the relationship between physical activity (PA) and self-esteem (SE), while introducing body mass index (BMI), perceived physical fitness (PPF), and body image (BI) in adults (N =264, M =38.10 years). The findings indicated that PA was directly and indirectly associated with SE. BMI predicted SE neither directly nor indirectly, but was directly associated with PPF and both directly and indirectly with BI. Furthermore, PPF was directly related to BI and SE, and a direct association was found between BI and SE. The pattern of results suggests that among a sample of adults, PA is directly and indirectly associated with SE, PPF, and BI, but not with BMI. PA, PPF, and BI appear to play an important role in SE. Accordingly, regular PA should be promoted, in particular, among adults reporting lower SE. PMID:27789950

  20. Self-Directed Weight Loss Strategies: Energy Expenditure Due to Physical Activity Is Not Increased to Achieve Intended Weight Loss

    OpenAIRE

    Elbelt, Ulf; Schuetz, Tatjana; Knoll, Nina; Burkert, Silke

    2015-01-01

    Reduced physical activity and almost unlimited availability of food are major contributors to the development of obesity. With the decline of strenuous work, energy expenditure due to spontaneous physical activity has attracted increasing attention. Our aim was to assess changes in energy expenditure, physical activity patterns and nutritional habits in obese subjects aiming at self-directed weight loss. Methods: Energy expenditure and physical activity patterns were measured with a portable ...

  1. TGFβ produced by IL-10 re-directed Astrocytes Attenuates Microglial Activation

    Science.gov (United States)

    Norden, Diana M.; Fenn, Ashley M.; Dugan, Allison; Godbout, Jonathan P.

    2014-01-01

    While there clearly is an intimate relationship between astrocytes and microglia, few studies have examined these potentially dynamic interactions. In this study, cytokine-mediated communication between microglia and astrocytes under inflammatory conditions was investigated. We have previously shown that activated microglia produce Interleukin (IL)-10, a regulatory cytokine that plays an important role in resolving neuroinflammation. Nonetheless, the mechanism by which IL-10 attenuates pro-inflammatory cytokine expression in the brain is unclear. Here we show that IL-10 re-directed astrocytes regulate the activation of microglia in a Transforming growth factor (TGF)-β dependent manner. In support of this concept, astrocytes in the brain maintained higher IL-10 receptor (IL-10R1) expression and primary astrocytes in culture were markedly more sensitive to the anti-inflammatory effects of IL-10 compared to microglia. Moreover, studies using primary cultures and an astrocyte-microglia co-culture system revealed that astrocytes mediated the anti-inflammatory effects of IL-10 on microglia through the production of TGFβ. For instance, only when astrocytes were present did IL-10 stimulation reduce the expression of IL-1β and increase expression of anti-inflammatory mediators fractalkine receptor (CX3CR1) and interleukin 4 receptor-α (IL-4Rα) in microglia. Importantly, these IL-10-astrocyte dependent effects on microglia were blocked by a TGFβ inhibitor. Furthermore, inhibition of TGFβ signaling in the brain resulted in prolonged sickness behavior and amplified pro-inflammatory cytokine expression in mice challenged with lipopolysaccharide (LPS). Taken together, IL-10 stimulated the production of TGFβ by astrocytes, which in turn, attenuated microglial activation. Overall, these findings provide novel insight into the mechanisms by which astrocytes modulate microglia under inflammatory conditions. PMID:24616125

  2. Enhancing activity and thermostability of lipase A from Serratia marcescens by site-directed mutagenesis.

    Science.gov (United States)

    Mohammadi, Mohsen; Sepehrizadeh, Zargham; Ebrahim-Habibi, Azadeh; Shahverdi, Ahmad Reza; Faramarzi, Mohammad Ali; Setayesh, Neda

    2016-11-01

    Lipases as significant biocatalysts had been widely employed to catalyze various chemical reactions such as ester hydrolysis, ester synthesis, and transesterification. Improving the activity and thermostability of enzymes is desirable for industrial applications. The lipase of Serratia marcescens belonging to family I.3 lipase has a very important pharmaceutical application in production of chiral precursors. In the present study, to achieve improved lipase activity and thermostability, using computational predictions of protein, four mutant lipases of SML (MutG2P, MutG59P, Mut H279K and MutL613WA614P) were constructed by site-directed mutagenesis. The recombinant mutant proteins were over-expressed in E. coli and purified by affinity chromatography on the Ni-NTA system. Circular dichroism spectroscopy, differential scanning calorimetry and kinetic parameters (Km and kcat) were determined. Our results have shown that the secondary structure of all lipases was approximately similar to one another. The MutG2P and MutG59P were more stable than wild type by approximately 2.3 and 2.9 in T 1/2 , respectively. The catalytic efficiency (kcat/Km) of MutH279K was enhanced by 2-fold as compared with the wild type (p<0.05). These results indicate that using protein modeling program and creating mutation, can enhance lipase activity and/or thermostability of SML and it also could be used for improving other properties of enzyme to the desired requirements as well as further mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Tuning of acyl-ACP thioesterase activity directed for tailored fatty acid synthesis.

    Science.gov (United States)

    Feng, Yanbin; Zhang, Yunxiu; Wang, Yayue; Liu, Jiao; Liu, Yinghui; Cao, Xupeng; Xue, Song

    2018-04-01

    Medium-chain fatty acids have attracted significant attention as sources of biofuels in recent years. Acyl-ACP thioesterase, which is considered as the key enzyme to determine the carbon chain length, catalyzes the termination of de novo fatty acid synthesis. Although recombinant medium-chain acyl-ACP thioesterase (TE) affects the fatty acid profile in heterologous cells, tailoring of the fatty acid composition merely by engineering a specific TE is still intractable. In this study, the activity of a C8-C10-specific thioesterase FatB2 from Cuphea hookeriana on C10-ACP was quantified twice as high as that on C8-ACP based on a synthetic C8-C16 acyl-ACP pool in vitro. Whereas in vivo, it was demonstrated that ChFatB2 preferred to accumulate C8 fatty acids with 84.9% composition in the ChFatB2-engineered E. coli strain. To achieve C10 fatty acid production, ChFatB2 was rationally tuned based on structural investigation and enzymatic analysis. An I198E mutant was identified to redistribute the C8-ACP flow, resulting in C10 fatty acid being produced as the principal component at 57.6% of total fatty acids in vivo. It was demonstrated that the activity of TE relative to β-ketoacyl-ACP synthases (KAS) directly determined the fatty acid composition. Our results provide a prospective strategy in tailoring fatty acid synthesis by tuning of TE activities based on TE-ACP interaction.

  4. Electrocatalytic activity of carbon-supported catalysts for direct ethanol fuel cell applications

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Varela, F.J. [CINVESTAV-Unidad Saltillo, Coahuila, (Mexico). Grupo de Investigacion en Energia; Savadogo, O. [Ecole Polytechnique de Montreal, Montreal, PQ (Canada). Laboratoire de nouveaux materiaux pour l' energie et l' electrochimie

    2008-07-01

    Proton exchange membrane fuel cells (PEMFCs) can be fueled with hydrogen, alcohols, hydrocarbons and acetals. Ethanol is an important fuel candidate because it can be electro-oxidized to carbon dioxide on platinum (Pt)-based electrocatalysts in a direct ethanol fuel cell (DEFC) at relatively low temperatures. This study investigated the electrocatalytic activity of some carbon-supported electrocatalysts towards the ethanol oxidation (EOR) and the oxygen reduction reaction (ORR) in the presence of ethanol. Compared to other anode catalysts such as Pt, PtRu and Pt oxide, anodes based on PtSn alloys have a higher catalytic activity for the EOR. When tested in a DEFC, the current density at 0.4V and 90 degrees C based on a PtSn/C anode and a Pt/C cathode was 2 times higher than that of a cell based on a PtRu/C-Pt/C membrane electrode assembly (MEA) configuration. In addition, cathode catalysts based on Ru/C had good catalytic activity for the ORR and exhibited high selectivity for this reaction in the presence of ethanol. The results showed that in the presence of 0.125, 0.25 or 0.5 M ethanol concentrations, a decrease in onset potential of about 60, 62 and 68 mV emerged, respectively. These values were about 10 times lower than those measured for some Pt-based cathode catalysts tested in this study in the presence of 0.125 M EtOH. 20 refs., 5 figs.

  5. Direct observations of active school transportation and stroller use in kindergarten children

    Directory of Open Access Journals (Sweden)

    Linda Rothman

    2016-12-01

    Full Text Available Little is known about kindergarten students' active school transportation (AST and stroller/wagon use as sedentary travel devices. The primary objective of this cross-sectional study was to determine the prevalence of kindergarten children arriving to school by active and sedentary modes, including strollers, in Toronto elementary schools and compare to students in kindergarten to grade 6 (K–6. The secondary objective was to examine factors associated with AST in kindergarten and K–6 students. School travel mode was counted using direct observations at elementary schools in the City of Toronto in 2015. Two samples were observed: 1 Kindergarten sample: a random sample of schools with separate kindergarten entrances (n = 26 schools, 1069 children; 2 Kindergarten to grade 6 sample: observations were conducted at arrival locations at 50% of eligible elementary schools for students of all ages (n = 88 schools, 17,224 children. Proportions arriving by different travel modes were compared using Chi-square analysis. Negative binomial regression was conducted to examine the association between school characteristics and AST. AST was lower in the kindergarten compared to the K–6 sample (60% versus 74%, χ2 = 91.37, p < 0.001. The predominant sedentary mode for kindergarten students was by vehicle (38%, with <2% using strollers/wagons. Recent immigrant status was related to higher AST in kindergarten students; higher social disadvantage, crossing guards, school population and collision rates were related to higher AST in the K–6 sample. Factors influencing AST in young students require further investigation to influence the development of healthy active lifestyles at an early age.

  6. Impediments to Enhancement of CPT-11 Anticancer Activity by E. coli Directed Beta-Glucuronidase Therapy

    Science.gov (United States)

    Hsieh, Yuan-Ting; Chen, Kai-Chuan; Cheng, Chiu-Min; Cheng, Tian-Lu; Tao, Mi-Hua; Roffler, Steve R.

    2015-01-01

    CPT-11 is a camptothecin analog used for the clinical treatment of colorectal adenocarcinoma. CPT-11 is converted into the therapeutic anti-cancer agent SN-38 by liver enzymes and can be further metabolized to a non-toxic glucuronide SN-38G, resulting in low SN-38 but high SN-38G concentrations in the circulation. We previously demonstrated that adenoviral expression of membrane-anchored beta-glucuronidase could promote conversion of SN-38G to SN-38 in tumors and increase the anticancer activity of CPT-11. Here, we identified impediments to effective tumor therapy with E. coli that were engineered to constitutively express highly active E. coli beta-glucuronidase intracellularly to enhance the anticancer activity of CPT-11. The engineered bacteria, E. coli (lux/βG), could hydrolyze SN-38G to SN-38, increased the sensitivity of cultured tumor cells to SN-38G by about 100 fold and selectively accumulated in tumors. However, E. coli (lux/βG) did not more effectively increase CPT-11 anticancer activity in human tumor xenografts as compared to non-engineered E. coli. SN-38G conversion to SN-38 by E. coli (lux/βG) appeared to be limited by slow uptake into bacteria as well as by segregation of E. coli in necrotic regions of tumors that may be relatively inaccessible to systemically-administered drug molecules. Studies using a fluorescent glucuronide probe showed that significantly greater glucuronide hydrolysis could be achieved in mice pretreated with E. coli (lux/βG) by direct intratumoral injection of the glucuronide probe or by intratumoral lysis of bacteria to release intracellular beta-glucuronidase. Our study suggests that the distribution of beta-glucuronidase, and possibly other therapeutic proteins, in the tumor microenvironment might be an important barrier for effective bacterial-based tumor therapy. Expression of secreted therapeutic proteins or induction of therapeutic protein release from bacteria might therefore be a promising strategy to enhance anti

  7. Effects of Isoflurane Anesthesia on Ensemble Patterns of Ca2+ Activity in Mouse V1: Reduced Direction Selectivity Independent of Increased Correlations in Cellular Activity

    Science.gov (United States)

    Goltstein, Pieter M.; Montijn, Jorrit S.; Pennartz, Cyriel M. A.

    2015-01-01

    Anesthesia affects brain activity at the molecular, neuronal and network level, but it is not well-understood how tuning properties of sensory neurons and network connectivity change under its influence. Using in vivo two-photon calcium imaging we matched neuron identity across episodes of wakefulness and anesthesia in the same mouse and recorded spontaneous and visually evoked activity patterns of neuronal ensembles in these two states. Correlations in spontaneous patterns of calcium activity between pairs of neurons were increased under anesthesia. While orientation selectivity remained unaffected by anesthesia, this treatment reduced direction selectivity, which was attributable to an increased response to the null-direction. As compared to anesthesia, populations of V1 neurons coded more mutual information on opposite stimulus directions during wakefulness, whereas information on stimulus orientation differences was lower. Increases in correlations of calcium activity during visual stimulation were correlated with poorer population coding, which raised the hypothesis that the anesthesia-induced increase in correlations may be causal to degrading directional coding. Visual stimulation under anesthesia, however, decorrelated ongoing activity patterns to a level comparable to wakefulness. Because visual stimulation thus appears to ‘break’ the strength of pairwise correlations normally found in spontaneous activity under anesthesia, the changes in correlational structure cannot explain the awake-anesthesia difference in direction coding. The population-wide decrease in coding for stimulus direction thus occurs independently of anesthesia-induced increments in correlations of spontaneous activity. PMID:25706867

  8. An Evaluation of Semiempirical Models for Partitioning Photosynthetically Active Radiation Into Diffuse and Direct Beam Components

    Science.gov (United States)

    Oliphant, Andrew J.; Stoy, Paul C.

    2018-03-01

    Photosynthesis is more efficient under diffuse than direct beam photosynthetically active radiation (PAR) per unit PAR, but diffuse PAR is infrequently measured at research sites. We examine four commonly used semiempirical models (Erbs et al., 1982, https://doi.org/10.1016/0038-092X(82)90302-4; Gu et al., 1999, https://doi.org/10.1029/1999JD901068; Roderick, 1999, https://doi.org/10.1016/S0168-1923(99)00028-3; Weiss & Norman, 1985, https://doi.org/10.1016/0168-1923(85)90020-6) that partition PAR into diffuse and direct beam components based on the negative relationship between atmospheric transparency and scattering of PAR. Radiation observations at 58 sites (140 site years) from the La Thuille FLUXNET data set were used for model validation and coefficient testing. All four models did a reasonable job of predicting the diffuse fraction of PAR (ϕ) at the 30 min timescale, with site median r2 values ranging between 0.85 and 0.87, model efficiency coefficients (MECs) between 0.62 and 0.69, and regression slopes within 10% of unity. Model residuals were not strongly correlated with astronomical or standard meteorological variables. We conclude that the Roderick (1999, https://doi.org/10.1016/S0168-1923(99)00028-3) and Gu et al. (1999, https://doi.org/10.1029/1999JD901068) models performed better overall than the two older models. Using the basic form of these models, the data set was used to find both individual site and universal model coefficients that optimized predictive accuracy. A new universal form of the model is presented in section 5 that increased site median MEC to 0.73. Site-specific model coefficients increased median MEC further to 0.78, indicating usefulness of local/regional training of coefficients to capture the local distributions of aerosols and cloud types.

  9. Direct non-cell autonomous Pax6 activity regulates eye development in the zebrafish

    Directory of Open Access Journals (Sweden)

    Prochiantz Alain

    2007-01-01

    Full Text Available Abstract Background Modifications in Pax6 homeogene expression produce strong eye phenotypes. This suggested to us that eye development might be an appropriate model to verify if homeoprotein intercellular passage has important functions in early development. Similar to other homeoproteins, Pax6 has two domains that enable secretion and internalization by live cells and, thus, intercellular passage. In principle, a straightforward way to test the hypothesis would be to mutate one of the two sequences to produce a 'cell autonomous only' Pax6. However, this was not possible because these sequences are in the homeodomain and their modification would affect Pax6 transcriptional properties. We have thus developed an approach aimed at blocking Pax6 only in the extracellular milieu of developing zebrafish embryos. Results A first strategy was to inject a one-cell embryo with a mRNA encoding a secreted single-chain anti-Pax6 antibody. A second, complementary, strategy was to inject a Pax6 antibody in the blastula extracellular milieu. In both cases, 'dissymmetric eyes', 'one eye only' and 'no eye' phenotypes were produced. In most cases, lens phenotypes paralleled retina malformations. Although eye phenotypes were analyzed 30 hours post-fertilization, there was a strong correlation between early eye field asymmetry, early asymmetry in Pax6 expression and later-occurring eye malformations. Several controls were introduced, demonstrating that the effect is specific to Pax6 and cannot be explained by intracellular antibody activities. Conclusion This study supports the hypothesis that the Pax6 transcription factor is also a signaling molecule with direct non-cell autonomous activity.

  10. Transcranial direct current stimulation modulates neuronal activity and learning in pilot training

    Directory of Open Access Journals (Sweden)

    Jaehoon eChoe

    2016-02-01

    Full Text Available Skill acquisition requires distributed learning both within (online and across (offline days to consolidate experiences into newly learned abilities. In particular, piloting an aircraft requires skills developed from extensive training and practice. Here, we tested the hypothesis that transcranial direct current stimulation (tDCS can modulate neuronal function to improve skill learning and performance during flight simulator training of aircraft landing procedures. Thirty-two right-handed participants consented to participate in four consecutive daily sessions of flight simulation training and received sham or anodal high-definition-tDCS to the right dorsolateral prefrontal cortex (DLPFC or left motor cortex (M1 in a randomized, double-blind experiment. Continuous electroencephalography (EEG and functional near infrared spectroscopy (fNIRS were collected during flight simulation, n-back working memory, and resting-state assessments. tDCS of the right DLPFC increased midline-frontal theta-band activity in flight and n-back working memory training, confirming tDCS-related modulation of brain processes involved in executive function. This modulation corresponded to a significantly different online and offline learning rates for working memory accuracy and decreased inter-subject behavioral variability in flight and n-back tasks in the DLPFC stimulation group. Additionally, tDCS of left M1 increased parietal alpha power during flight tasks and tDCS to the right DLPFC increased midline frontal theta-band power during n-back and flight tasks. These results demonstrate a modulation of group variance in skill acquisition through an increasing in learned skill consistency in cognitive and real-world tasks with tDCS. Further, tDCS performance improvements corresponded to changes in electrophysiological and blood-oxygenation activity of the DLPFC and motor cortices, providing a stronger link between modulated neuronal function and behavior.

  11. Quantifying surface albedo and other direct biogeophysical climate forcings of forestry activities.

    Science.gov (United States)

    Bright, Ryan M; Zhao, Kaiguang; Jackson, Robert B; Cherubini, Francesco

    2015-09-01

    By altering fluxes of heat, momentum, and moisture exchanges between the land surface and atmosphere, forestry and other land-use activities affect climate. Although long recognized scientifically as being important, these so-called biogeophysical forcings are rarely included in climate policies for forestry and other land management projects due to the many challenges associated with their quantification. Here, we review the scientific literature in the fields of atmospheric science and terrestrial ecology in light of three main objectives: (i) to elucidate the challenges associated with quantifying biogeophysical climate forcings connected to land use and land management, with a focus on the forestry sector; (ii) to identify and describe scientific approaches and/or metrics facilitating the quantification and interpretation of direct biogeophysical climate forcings; and (iii) to identify and recommend research priorities that can help overcome the challenges of their attribution to specific land-use activities, bridging the knowledge gap between the climate modeling, forest ecology, and resource management communities. We find that ignoring surface biogeophysics may mislead climate mitigation policies, yet existing metrics are unlikely to be sufficient. Successful metrics ought to (i) include both radiative and nonradiative climate forcings; (ii) reconcile disparities between biogeophysical and biogeochemical forcings, and (iii) acknowledge trade-offs between global and local climate benefits. We call for more coordinated research among terrestrial ecologists, resource managers, and coupled climate modelers to harmonize datasets, refine analytical techniques, and corroborate and validate metrics that are more amenable to analyses at the scale of an individual site or region. © 2015 John Wiley & Sons Ltd.

  12. Direct Ring Fission of Salicylate by a Salicylate 1,2-Dioxygenase Activity from Pseudaminobacter salicylatoxidans

    Science.gov (United States)

    Hintner, Jan-Peter; Lechner, Christa; Riegert, Ulrich; Kuhm, Andrea Elisabeth; Storm, Thomas; Reemtsma, Thorsten; Stolz, Andreas

    2001-01-01

    In cell extracts of Pseudaminobacter salicylatoxidans strain BN12, an enzymatic activity was detected which converted salicylate in an oxygen-dependent but NAD(P)H-independent reaction to a product with an absorbance maximum at 283 nm. This metabolite was isolated, purified, and identified by mass spectrometry and 1H and 13C nuclear magnetic resonance spectroscopy as 2-oxohepta-3,5-dienedioic acid. This metabolite could be formed only by direct ring fission of salicylate by a 1,2-dioxygenase reaction. Cell extracts from P. salicylatoxidans also oxidized 5-aminosalicylate, 3-, 4-, and 5-chlorosalicylate, 3-, 4-, and 5-methylsalicylate, 3- and 5-hydroxysalicylate (gentisate), and 1-hydroxy-2-naphthoate. The dioxygenase was purified and shown to consist of four identical subunits with a molecular weight of about 45,000. The purified enzyme showed higher catalytic constants with gentisate or 1-hydroxy-2-naphthoate than with salicylate. It was therefore concluded that P. salicylatoxidans synthesized a gentisate 1,2-dioxygenase with an extraordinary substrate range, which also allowed the oxidation of salicylate. PMID:11698383

  13. A Design Methodology for Rapid Implementation of Active Control Systems Across Lean Direct Injection Combustor Platforms

    Science.gov (United States)

    Baumann, William T.; Saunders, William R.; Vandsburger, Uri; Saus, Joseph (Technical Monitor)

    2003-01-01

    The VACCG team is comprised of engineers at Virginia Tech who specialize in the subject areas of combustion physics, chemical kinetics, dynamics and controls, and signal processing. Currently, the team's work on this NRA research grant is designed to determine key factors that influence combustion control performance through a blend of theoretical and experimental investigations targeting design and demonstration of active control for three different combustors. To validiate the accuracy of conclusions about control effectiveness, a sequence of experimental verifications on increasingly complex lean, direct injection combustors is underway. During the work period January 1, 2002 through October 15, 2002, work has focused on two different laboratory-scale combustors that allow access for a wide variety of measurements. As the grant work proceeds, one key goal will be to obtain certain knowledge about a particular combustor process using a minimum of sophisticated measurements, due to the practical limitations of measurements on full-scale combustors. In the second year, results obtained in the first year will be validated on test combustors to be identified in the first quarter of that year. In the third year, it is proposed to validate the results at more realistic pressure and power levels by utilizing the facilities at the Glenn Research Center.

  14. Cytotoxicity, Bactericidal, and Antioxidant Activity of Sodium Alginate Hydrosols Treated with Direct Electric Current.

    Science.gov (United States)

    Król, Żaneta; Marycz, Krzysztof; Kulig, Dominika; Marędziak, Monika; Jarmoluk, Andrzej

    2017-03-22

    The aim of the study was to investigate the effect of using direct electric current (DC) of 0, 200, and 400 mA for five minutes on the physiochemical properties, cytotoxicity, antibacterial, and antioxidant activity of sodium alginate hydrosols with different sodium chloride concentrations. The pH, oxidation-reduction potential (ORP), electrical conductivity (EC), and available chlorine concentration (ACC) were measured. The effect of sodium alginate hydrosols treated with DC on Staphylococcus aureus , Listeria monocytogenes , Bacillus cereus , Micrococcus luteus , Escherichia coli , Salmonella enteritidis , Yersinia enterocolitica , Pseudomonas fluorescence , and RAW 264.7 and L929 cells was investigated. Subsequently, the antioxidant properties of hydrosols were evaluated by determining the scavenging ability of 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH) and ferric reducing antioxidant power (FRAP). The results have shown that after applying 400 mA in hydrosol samples with 0.1% and 0.2% NaCl all tested bacteria were inactivated. The ACC concentration of C400 samples with NaCl was equal to 13.95 and 19.71 mg/L, respectively. The cytotoxicity analysis revealed that optimized electric field conditions and the addition of sodium chloride allow for the avoidance of toxicity effects on normal cells without disturbing the antibacterial effects. Due to the presence of oxidizing substances, the DPPH of variants treated with DC was lower than the DPPH of control samples.

  15. Control of plasma properties in a short direct-current glow discharge with active boundaries

    Energy Technology Data Exchange (ETDEWEB)

    Adams, S. F. [Air Force Research Laboratory, WPAFB, Ohio 45433 (United States); Demidov, V. I., E-mail: vladimir.demidov@mail.wvu.edu [Air Force Research Laboratory, WPAFB, Ohio 45433 (United States); West Virginia University, Morgantown, West Virginia 26506 (United States); Bogdanov, E. A.; Kudryavtsev, A. A. [St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Koepke, M. E. [West Virginia University, Morgantown, West Virginia 26506 (United States); Kurlyandskaya, I. P. [St. Petersburg University of State Fire Service of EMERCOM RF, Murmansk Branch, Murmansk 183040 (Russian Federation)

    2016-02-15

    To demonstrate controlling electron/metastable density ratio and electron temperature by applying negative voltages to the active (conducting) discharge wall in a low-pressure plasma with nonlocal electron energy distribution function, modeling has been performed in a short (lacking the positive-column region) direct-current glow discharge with a cold cathode. The applied negative voltage can modify the trapping of the low-energy part of the energetic electrons that are emitted from the cathode sheath and that arise from the atomic and molecular processes in the plasma within the device volume. These electrons are responsible for heating the slow, thermal electrons, while production of slow electrons (ions) and metastable atoms is mostly due to the energetic electrons with higher energies. Increasing electron temperature results in increasing decay rate of slow, thermal electrons (ions), while decay rate of metastable atoms and production rates of slow electrons (ions) and metastable atoms practically are unchanged. The result is in the variation of electron/metastable density ratio and electron temperature with the variation of the wall negative voltage.

  16. Analysis of an active tubular liquid-feed direct methanol fuel cell

    Science.gov (United States)

    Xu, Chao; Faghri, Amir

    2011-08-01

    A two-dimensional, two-phase, non-isothermal model was developed for an active, tubular, liquid-feed direct methanol fuel cell (DMFC). The liquid-gas, two-phase mass transport in the porous anode and cathode was formulated based on the multi-fluid approach in the porous media. The two-phase mass transport in the anode and cathode channels was modeled using the drift-flux and the homogeneous mist-flow models, respectively. Water and methanol crossovers through the membrane were considered due to the effects of diffusion, electro-osmotic drag, and convection. The model enabled a numerical investigation of the effects of various operating parameters, such as current density, methanol flow rate, and oxygen flow rate, on the mass and heat transport characteristics in the tubular DMFC. It was shown that by choosing a proper tube radius and distance between the adjacent cells, a tubular DMFC stack can achieve a much higher energy density compared to its planar counterpart. The results also showed that a large anode flow rate is needed in order to avoid severe blockage of liquid methanol to the anode electrode due to the gas accumulation in the channel. Besides, lowering the flow rate of either the methanol solution or air can lead to a temperature increase along the flow channel. The methanol and water crossovers are nearly independent of the methanol flow rate and the air flow rate.

  17. First direct measurements of behavioural responses by Cuvier's beaked whales to mid-frequency active sonar.

    Science.gov (United States)

    DeRuiter, Stacy L; Southall, Brandon L; Calambokidis, John; Zimmer, Walter M X; Sadykova, Dinara; Falcone, Erin A; Friedlaender, Ari S; Joseph, John E; Moretti, David; Schorr, Gregory S; Thomas, Len; Tyack, Peter L

    2013-08-23

    Most marine mammal- strandings coincident with naval sonar exercises have involved Cuvier's beaked whales (Ziphius cavirostris). We recorded animal movement and acoustic data on two tagged Ziphius and obtained the first direct measurements of behavioural responses of this species to mid-frequency active (MFA) sonar signals. Each recording included a 30-min playback (one 1.6-s simulated MFA sonar signal repeated every 25 s); one whale was also incidentally exposed to MFA sonar from distant naval exercises. Whales responded strongly to playbacks at low received levels (RLs; 89-127 dB re 1 µPa): after ceasing normal fluking and echolocation, they swam rapidly, silently away, extending both dive duration and subsequent non-foraging interval. Distant sonar exercises (78-106 dB re 1 µPa) did not elicit such responses, suggesting that context may moderate reactions. The observed responses to playback occurred at RLs well below current regulatory thresholds; equivalent responses to operational sonars could elevate stranding risk and reduce foraging efficiency.

  18. Direct energy balance based active disturbance rejection control for coal-fired power plant.

    Science.gov (United States)

    Sun, Li; Hua, Qingsong; Li, Donghai; Pan, Lei; Xue, Yali; Lee, Kwang Y

    2017-09-01

    The conventional direct energy balance (DEB) based PI control can fulfill the fundamental tracking requirements of the coal-fired power plant. However, it is challenging to deal with the cases when the coal quality variation is present. To this end, this paper introduces the active disturbance rejection control (ADRC) to the DEB structure, where the coal quality variation is deemed as a kind of unknown disturbance that can be estimated and mitigated promptly. Firstly, the nonlinearity of a recent power plant model is analyzed based on the gap metric, which provides guidance on how to set the pressure set-point in line with the power demand. Secondly, the approximate decoupling effect of the DEB structure is analyzed based on the relative gain analysis in frequency domain. Finally, the synthesis of the DEB based ADRC control system is carried out based on multi-objective optimization. The optimized ADRC results show that the integrated absolute error (IAE) indices of the tracking performances in both loops can be simultaneously improved, in comparison with the DEB based PI control and H ∞ control system. The regulation performance in the presence of the coal quality variation is significantly improved under the ADRC control scheme. Moreover, the robustness of the proposed strategy is shown comparable with the H ∞ control. Copyright © 2017. Published by Elsevier Ltd.

  19. Anti-tumor activities of direct current (DC) therapy combined with fractionated radiation or chemotherapy

    International Nuclear Information System (INIS)

    Nakayama, Toshitake; Ito, Hisao; Hashimoto, Shozo

    1988-01-01

    Anti-tumor activities of direct current (DC) therapy combined with fractionated radiation or cyclophosphamide were studied in mice which were transplanted with murine fibrosarcoma (FSa) in the right thighs. Using TCD 50 assay, DC therapy, given in a single fraction, enhanced the effect of a single dose of radiation with the dose-modifying factor of 1.3. Tumor control rates were more improved by the combination therapy with the smaller doses of radiation than the larger ones. When DC therapy was applied one time immediately after the first radiation of fractionated ones, the combination therapy still showed the enhanced effect. However, both of DC therapy and radiation were divided in three fractions and DC therapy was applied everytime after radiation, tumor growth retardation were not different between the combination therapy and radiation alone. This result suggests that there is a minimum amount of Coulombs to improve the effect of radiation alone. On the other hand, DC therapy combined with cyclophosphamide given in one fraction showed the same enhancement effect as those divided in three fractions. These results suggest that DC therapy combined with radiation or cyclophosphamide is effective to improve tumor control, but the mechanisms to enhance the effect of radiation or cyclophosphamide are different. (author)

  20. Direct Ex Vivo Analysis of Activated, Fas-sensitive Autoreactive T Cells in Human Autoimmune Disease

    Science.gov (United States)

    Bieganowska, Katarzyna D.; Ausubel, Lara J.; Modabber, Yalda; Slovik, Elissa; Messersmith, Wells; Hafler, David A.

    1997-01-01

    The frequency of clonally expanded and persistent T cells recognizing the immunodominant autoantigenic peptide of myelin basic protein (MBP)p85-99 was directly measured ex vivo in subjects with typical relapsing remitting multiple sclerosis (MS). T cells expressing mRNA transcripts encoding T cell receptor (TCR)-α and -β chains found in T cell clones previously isolated from these subjects recognizing the MBPp85-99 epitope were examined. In contrast to frequencies of 1 in 105–106 as measured by limiting dilution analysis, estimates of the T cell frequencies expressing MBPp85-99–associated TCR chain transcripts were as high as 1 in 300. These high frequencies were confirmed by performing PCR on single T cells isolated by flow cytometry. MBPp85-99 TCR transcripts were present in IL-2 receptor α–positive T cells which were induced to undergo Fas-mediated cell death upon antigen stimulation. These data demonstrate that at least a subpopulation of patients with MS can have a very high frequency of activated autoreactive T cells. PMID:9151896

  1. Cytotoxicity, Bactericidal, and Antioxidant Activity of Sodium Alginate Hydrosols Treated with Direct Electric Current

    Directory of Open Access Journals (Sweden)

    Żaneta Król

    2017-03-01

    Full Text Available The aim of the study was to investigate the effect of using direct electric current (DC of 0, 200, and 400 mA for five minutes on the physiochemical properties, cytotoxicity, antibacterial, and antioxidant activity of sodium alginate hydrosols with different sodium chloride concentrations. The pH, oxidation-reduction potential (ORP, electrical conductivity (EC, and available chlorine concentration (ACC were measured. The effect of sodium alginate hydrosols treated with DC on Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Micrococcus luteus, Escherichia coli, Salmonella enteritidis, Yersinia enterocolitica, Pseudomonas fluorescence, and RAW 264.7 and L929 cells was investigated. Subsequently, the antioxidant properties of hydrosols were evaluated by determining the scavenging ability of 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH and ferric reducing antioxidant power (FRAP. The results have shown that after applying 400 mA in hydrosol samples with 0.1% and 0.2% NaCl all tested bacteria were inactivated. The ACC concentration of C400 samples with NaCl was equal to 13.95 and 19.71 mg/L, respectively. The cytotoxicity analysis revealed that optimized electric field conditions and the addition of sodium chloride allow for the avoidance of toxicity effects on normal cells without disturbing the antibacterial effects. Due to the presence of oxidizing substances, the DPPH of variants treated with DC was lower than the DPPH of control samples.

  2. Content Analysis of a Participant-Directed Intervention to Optimize Activity Engagement of Older Adult Cancer Survivors.

    Science.gov (United States)

    Lyons, Kathleen Doyle; Newman, Robin; Adachi-Mejia, Anna M; Whipple, Jessica; Hegel, Mark T

    2018-01-01

    Many older adult cancer survivors reduce their activity level during and after cancer treatment. Occupational therapy interventions need to flexibly address various obstacles to occupational engagement that survivors may face. The aim of this analysis was to describe the content of a participant-directed occupational therapy intervention for older adults with cancer. Content analysis was used to describe the treatment session data from the experimental arm of a pilot randomized controlled trial in terms of activities addressed, obstacles reported, and treatment strategies utilized. Participants predominantly used the intervention to increase exercise engagement or address instrumental activities of daily living. The most common obstacles to occupational engagement included fatigue, finding time, weather, and pain. Regarding treatment strategies, 77% of participants chose to practice the activity with the occupational therapist, 42% requested a piece of equipment, and 11% modified the environment to increase activity engagement. Overall, the participant-directed intervention appears flexible enough to address various activities and obstacles to occupational engagement.

  3. Argonne National Laboratory annual report of Laboratory Directed Research and Development Program Activities FY 2009

    International Nuclear Information System (INIS)

    2010-01-01

    I am pleased to submit Argonne National Laboratory's Annual Report on its Laboratory Directed Research and Development (LDRD) activities for fiscal year 2009. Fiscal year 2009 saw a heightened focus by DOE and the nation on the need to develop new sources of energy. Argonne scientists are investigating many different sources of energy, including nuclear, solar, and biofuels, as well as ways to store, use, and transmit energy more safely, cleanly, and efficiently. DOE selected Argonne as the site for two new Energy Frontier Research Centers (EFRCs) - the Institute for Atom-Efficient Chemical Transformations and the Center for Electrical Energy Storage - and funded two other EFRCs to which Argonne is a major partner. The award of at least two of the EFRCs can be directly linked to early LDRD-funded efforts. LDRD has historically seeded important programs and facilities at the lab. Two of these facilities, the Advanced Photon Source and the Center for Nanoscale Materials, are now vital contributors to today's LDRD Program. New and enhanced capabilities, many of which relied on LDRD in their early stages, now help the laboratory pursue its evolving strategic goals. LDRD has, since its inception, been an invaluable resource for positioning the Laboratory to anticipate, and thus be prepared to contribute to, the future science and technology needs of DOE and the nation. During times of change, LDRD becomes all the more vital for facilitating the necessary adjustments while maintaining and enhancing the capabilities of our staff and facilities. Although I am new to the role of Laboratory Director, my immediate prior service as Deputy Laboratory Director for Programs afforded me continuous involvement in the LDRD program and its management. Therefore, I can attest that Argonne's program adhered closely to the requirements of DOE Order 413.2b and associated guidelines governing LDRD. Our LDRD program management continually strives to be more efficient. In addition to

  4. Argonne National Laboratory annual report of Laboratory Directed Research and Development Program Activities FY 2009.

    Energy Technology Data Exchange (ETDEWEB)

    Office of the Director

    2010-04-09

    I am pleased to submit Argonne National Laboratory's Annual Report on its Laboratory Directed Research and Development (LDRD) activities for fiscal year 2009. Fiscal year 2009 saw a heightened focus by DOE and the nation on the need to develop new sources of energy. Argonne scientists are investigating many different sources of energy, including nuclear, solar, and biofuels, as well as ways to store, use, and transmit energy more safely, cleanly, and efficiently. DOE selected Argonne as the site for two new Energy Frontier Research Centers (EFRCs) - the Institute for Atom-Efficient Chemical Transformations and the Center for Electrical Energy Storage - and funded two other EFRCs to which Argonne is a major partner. The award of at least two of the EFRCs can be directly linked to early LDRD-funded efforts. LDRD has historically seeded important programs and facilities at the lab. Two of these facilities, the Advanced Photon Source and the Center for Nanoscale Materials, are now vital contributors to today's LDRD Program. New and enhanced capabilities, many of which relied on LDRD in their early stages, now help the laboratory pursue its evolving strategic goals. LDRD has, since its inception, been an invaluable resource for positioning the Laboratory to anticipate, and thus be prepared to contribute to, the future science and technology needs of DOE and the nation. During times of change, LDRD becomes all the more vital for facilitating the necessary adjustments while maintaining and enhancing the capabilities of our staff and facilities. Although I am new to the role of Laboratory Director, my immediate prior service as Deputy Laboratory Director for Programs afforded me continuous involvement in the LDRD program and its management. Therefore, I can attest that Argonne's program adhered closely to the requirements of DOE Order 413.2b and associated guidelines governing LDRD. Our LDRD program management continually strives to be more efficient. In

  5. Prothrombotic skeletal muscle myosin directly enhances prothrombin activation by binding factors Xa and Va

    Science.gov (United States)

    Deguchi, Hiroshi; Sinha, Ranjeet K.; Marchese, Patrizia; Ruggeri, Zaverio M.; Zilberman-Rudenko, Jevgenia; McCarty, Owen J. T.; Cohen, Mitchell J.

    2016-01-01

    To test the hypothesis that skeletal muscle myosins can directly influence blood coagulation and thrombosis, ex vivo studies of the effects of myosin on thrombogenesis in fresh human blood were conducted. Addition of myosin to blood augmented the thrombotic responses of human blood flowing over collagen-coated surfaces (300 s−1 shear rate). Perfusion of human blood over myosin-coated surfaces also caused fibrin and platelet deposition, evidencing myosin’s thrombogenicity. Myosin markedly enhanced thrombin generation in both platelet-rich plasma and platelet-poor plasma, indicating that myosin promoted thrombin generation in plasma primarily independent of platelets. In purified reaction mixtures composed only of factor Xa, factor Va, prothrombin, and calcium ions, myosin greatly enhanced prothrombinase activity. The Gla domain of factor Xa was not required for myosin’s prothrombinase enhancement. When binding of purified clotting factors to immobilized myosin was monitored using biolayer interferometry, factors Xa and Va each showed favorable binding interactions. Factor Va reduced by 100-fold the apparent Kd of myosin for factor Xa (Kd ∼0.48 nM), primarily by reducing koff, indicating formation of a stable ternary complex of myosin:Xa:Va. In studies to assess possible clinical relevance for this discovery, we found that antimyosin antibodies inhibited thrombin generation in acute trauma patient plasmas more than in control plasmas (P = .0004), implying myosin might contribute to acute trauma coagulopathy. We posit that myosin enhancement of thrombin generation could contribute either to promote hemostasis or to augment thrombosis risk with consequent implications for myosin’s possible contributions to pathophysiology in the setting of acute injuries. PMID:27421960

  6. 78 FR 52169 - Agency Information Collection Activities; Comment Request; William D. Ford Federal Direct Loan...

    Science.gov (United States)

    2013-08-22

    ... PLUS Loan borrower must not have an adverse credit history. If an applicant for a Direct PLUS Loan is determined to have an adverse credit history, the applicant may qualify for a Direct PLUS Loan by obtaining an endorser who does not have an adverse credit history. The Endorser Addendum serves as the means by...

  7. Assessment of Animated Self-Directed Learning Activities Modules for Children's Number Sense Development

    Science.gov (United States)

    Yang, Der-Ching; Li, Mao-Neng

    2013-01-01

    The purpose of this study was to examine the relative effectiveness of two different learning modes; namely, a computer animation self-directed learning approach and a paper version of the self-directed learning approach, to 5th-graders' number sense development. Two 5th-grade classes, 30 students each, were selected from a public elementary…

  8. Direct-to-consumer advertisements for prescription drugs as an argumentative activity type

    NARCIS (Netherlands)

    Wierda, R.; Visser, J.

    2012-01-01

    With direct-to-consumer advertisements (DTCA), pharmaceutical companies can market their prescription drugs directly to consumers. In order to properly study the argumentative aspect of these advertisements from a pragma-dialectical perspective, it is necessary to characterize DTCA as an

  9. Direct-to-consumer advertisements for prescription drugs as an argumentative activity type

    NARCIS (Netherlands)

    Wierda, R.; Visser, J.; Rubinelli, S.; Snoeck Henkemans, A.F.

    2014-01-01

    With direct-to-consumer advertisements (DTCA), pharmaceutical companies can market their prescription drugs directly to consumers. In order to properly study the argumentative aspects of these advertisements from a pragma-dialectical perspective, it is necessary to characterize DTCA as an

  10. Physical activity and self-esteem: testing direct and indirect relationships associated with psychological and physical mechanisms

    Directory of Open Access Journals (Sweden)

    Zamani Sani SH

    2016-10-01

    Full Text Available Seyed Hojjat Zamani Sani,1 Zahra Fathirezaie,1 Serge Brand,2 Uwe Pühse,3 Edith Holsboer-Trachsler,2 Markus Gerber,3 Siavash Talepasand4 1Department of Motor Behavior, Faculty of Physical Education and Sport Science, University of Tabriz, Tabriz, Iran; 2Psychiatric Clinics of the University of Basel, Center for Affective, Stress and Sleep Disorders (ZASS, 3Department of Sport, Exercise and Health, Sport Science Section, University of Basel, Basel, Switzerland; 4Department of Psychology and Educational Sciences, Semnan University, Semnan, Iran Abstract: In the present study, we investigated the relationship between physical activity (PA and self-esteem (SE, while introducing body mass index (BMI, perceived physical fitness (PPF, and body image (BI in adults (N =264, M =38.10 years. The findings indicated that PA was directly and indirectly associated with SE. BMI predicted SE neither directly nor indirectly, but was directly associated with PPF and both directly and indirectly with BI. Furthermore, PPF was directly related to BI and SE, and a direct association was found between BI and SE. The pattern of results suggests that among a sample of adults, PA is directly and indirectly associated with SE, PPF, and BI, but not with BMI. PA, PPF, and BI appear to play an important role in SE. Accordingly, regular PA should be promoted, in particular, among adults reporting lower SE. Keywords: physical activity, self-esteem, physical fitness, body image, adults

  11. Tablet formulation of an active pharmaceutical ingredient with a sticking and filming problem: direct compression and dry granulation evaluations.

    Science.gov (United States)

    Bejugam, Naveen K; Mutyam, Shravan K; Shankar, Gita N

    2015-02-01

    To develop a tablet formulation for an active pharmaceutical ingredient for which sticking and filming problems occurred during tablet punching. Direct compression and dry granulation tableting techniques were evaluated using factorial experimental design. The effects of chrome-coated punch tips, filler types and active percent in the tablet formulation by direct compression were evaluated. Similarly, for dry granulation using the roller compaction technique, three formulation factors - roller compaction pressure, intragranular filler percent and filler type - were studied. Tablets prepared by both techniques were characterized in regard to their compressibility index, tablet hardness, disintegration time, friability index and stickiness-filming index (an arbitrary index). Ten formulations were prepared by each technique. Using multiple response optimizations and estimated response surface plots, the data were analyzed to identify optimum levels for the formulation factors. Compressibility index values for all the formulations prepared by direct compression exceeded 25%, unlike the blends prepared by dry granulation. Both tablet hardness and disintegration time for direct compression formulations were significantly lower than for dry granulation formulations. The friability index values were significantly higher for direct compression formulations than for dry granulation formulations. All the direct compression formulations, unlike the dry granulation formulations, had a high stickiness-filming index. Statistical analysis helped in identifying the optimum levels of formulation factors, as well as the method for eliminating sticking and filming. Unlike the direct compression technique, dry granulation yielded tablets for which sticking and filming were completely eliminated.

  12. Improved thermostability and enzyme activity of a recombinant phyA mutant phytase from Aspergillus niger N25 by directed evolution and site-directed mutagenesis.

    Science.gov (United States)

    Tang, Zizhong; Jin, Weiqiong; Sun, Rong; Liao, Yan; Zhen, Tianrun; Chen, Hui; Wu, Qi; Gou, Lin; Li, Chenlei

    2018-01-01

    We previously constructed three recombinant phyA mutant strains (PP-NP m -8, PP-NP ep -6A and I44E/T252R-PhyA), showing improved catalytic efficiency or thermostability of Aspergillus niger N25 phytase, by error-prone PCR or site-directed mutagenesis. In this study, directed evolution and site-directed mutagenesis were further applied to improve the modified phytase properties. After one-round error-prone PCR for phytase gene of PP-NP ep -6A, a single transformant, T195L/Q368E/F376Y, was obtained with the significant improvements in catalytic efficiency and thermostability. The phytase gene of T195L/Q368E/F376Y, combined with the previous mutant phytase genes of PP-NP ep -6A, PP-NP m -8 and I44E/T252R-PhyA, was then sequentially modified by DNA shuffling. Three genetically engineered strains with desirable properties were then obtained, namedQ172R, Q172R/K432R andQ368E/K432R. Among them, Q172R/K432R showed the highest thermostability with the longest half-life and the greatest remaining phytase activity after heat treatment, while Q368E/K432R showed the highest catalytic activity. Five substitutions (Q172R, T195L, Q368E, F376Y, K432R) identified from random mutagenesis were added sequentially to the phytase gene of PP-NP ep -6A to investigate how the mutant sites influence the properties of phytase. Characterization and structural analysis demonstrated that these mutations could produce cumulative or synergistic improvements in thermostability or catalytic efficiency of phytase. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. New Gateways to the Platinum Group Metal-Catalyzed Direct Deuterium-Labeling Method Utilizing Hydrogen as a Catalyst Activator.

    Science.gov (United States)

    Sawama, Yoshinari; Park, Kwihwan; Yamada, Tsuyoshi; Sajiki, Hironao

    2018-01-01

    Deuterium-labeled compounds are widely utilized in various scientific fields. We summarize the recent advances in the direct deuteration of sugar, saturated fatty acid, and arene derivatives using heterogeneous platinum group metal on carbon catalysts by our research group. Hydrogen gas is a key catalyst-activator to facilitate the present H-D exchange reactions. In this review, the direct activation method of catalysts using in situ-generated hydrogen based on the dehydrogenation of alcohols is introduced. The obtained multiple deuterium-labeled products, including bioactive compounds, are expected to contribute to the development of many scientific investigations.

  14. Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor.

    Directory of Open Access Journals (Sweden)

    Joseph Chavarría-Smith

    Full Text Available Inflammasomes are multimeric protein complexes that respond to infection by recruitment and activation of the Caspase-1 (CASP1 protease. Activated CASP1 initiates immune defense by processing inflammatory cytokines and by causing a rapid and lytic cell death called pyroptosis. Inflammasome formation is orchestrated by members of the nucleotide-binding domain and leucine-rich repeat (NLR or AIM2-like receptor (ALR protein families. Certain NLRs and ALRs have been shown to function as direct receptors for specific microbial ligands, such as flagellin or DNA, but the molecular mechanism responsible for activation of most NLRs is still poorly understood. Here we determine the mechanism of activation of the NLRP1B inflammasome in mice. NLRP1B, and its ortholog in rats, is activated by the lethal factor (LF protease that is a key virulence factor secreted by Bacillus anthracis, the causative agent of anthrax. LF was recently shown to cleave mouse and rat NLRP1 directly. However, it is unclear if cleavage is sufficient for NLRP1 activation. Indeed, other LF-induced cellular events have been suggested to play a role in NLRP1B activation. Surprisingly, we show that direct cleavage of NLRP1B is sufficient to induce inflammasome activation in the absence of LF. Our results therefore rule out the need for other LF-dependent cellular effects in activation of NLRP1B. We therefore propose that NLRP1 functions primarily as a sensor of protease activity and thus could conceivably detect a broader spectrum of pathogens than just B. anthracis. By adding proteolytic cleavage to the previously established ligand-receptor mechanism of NLR activation, our results illustrate the remarkable flexibility with which the NLR architecture can be deployed for the purpose of pathogen-detection and host defense.

  15. Direct configuration interaction and multiconfigurational self-consistent-field method for multiple active spaces with variable occupations. I. Method

    Science.gov (United States)

    Ivanic, Joseph

    2003-11-01

    In order to reduce the number of ineffective configurations in a priori generated configuration spaces, a direct configuration interaction method has been developed which limits the electron occupations of orbital groups making up a total active space. A wave function is specified by first partitioning an active space into an unrestricted number of orbital groups and second by providing limiting values, in the form of minima and maxima, for the electron occupancies of each group. The configuration interaction problem corresponding to all possible determinants satisfying these conditions is solved in a fully direct manner by the use of Slater-Condon expressions in conjunction with single and double replacements. This configuration interaction approach, termed occupation restricted multiple active space-configuration interaction, has also been linked with orbital optimization programs to produce the occupation restricted multiple active space-self consistent field method.

  16. Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

    Science.gov (United States)

    Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

    2017-01-29

    Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A novel method for direct measurement of complement convertases activity in human serum

    NARCIS (Netherlands)

    Blom, A.M.; Volokhina, E.B.; Fransson, V.; Stromberg, P.; Berghard, L.; Viktorelius, M.; Mollnes, T.E.; Lopez-Trascasa, M.; Heuvel, B. van den; Goodship, T.H.; Marchbank, K.J.; Okroj, M.

    2014-01-01

    Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function leads directly or indirectly to pathological conditions, including higher infection rate, kidney diseases, autoimmune- or

  18. Index of Effort: An Analytical Model for Evaluating and Re-Directing Student Recruitment Activities for a Local Community College.

    Science.gov (United States)

    Landini, Albert J.

    This index of effort is proposed as a means by which those in charge of student recruitment activities at community colleges can be sure that their efforts are being directed toward all of the appropriate population. The index is an analytical model based on the concept of socio-economic profiles, using small area 1970 census data, and is the…

  19. The influence of prior knowledge on the retrieval-directed function of note taking in prior knowledge activation

    NARCIS (Netherlands)

    Wetzels, Sandra; Kester, Liesbeth; Van Merriënboer, Jeroen; Broers, Nick

    2010-01-01

    Wetzels, S. A. J., Kester, L., Van Merriënboer, J. J. G., & Broers, N. J. (2011). The influence of prior knowledge on the retrieval-directed function of note taking in prior knowledge activation. British Journal of Educational Psychology, 81(2), 274-291. doi: 10.1348/000709910X517425

  20. Characterization of novel anthracycline prodrugs activated by human beta-glucuronidase for use in antibody-directed enzyme prodrug therapy

    NARCIS (Netherlands)

    Houba, PHJ; Leenders, RGG; Boven, E; Scheeren, JW; Pinedo, HM; Haisma, HJ

    1996-01-01

    Antibody-directed enzyme prodrug therapy (ADEPT) alms at the specific activation of a prodrug by an enzyme-immuoconjugate localized in tumor tissue. The use of an enzyme of human origin is preferable in ADEPT because it might not be immunogenic when administered to patients. In the case of human

  1. Direct Angiotensin II Type 2 Receptor Stimulation Ameliorates Insulin Resistance in Type 2 Diabetes Mice with PPARγ Activation

    DEFF Research Database (Denmark)

    Ohshima, Kousei; Mogi, Masaki; Jing, Fei

    2012-01-01

    The role of angiotensin II type 2 (AT(2)) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT(2) receptor stimulation by compound 21 (C21) might contribute to possible insulin-sensitizing/anti-diabetic effects in type...... 2 diabetes (T2DM) with PPARγ activation, mainly focusing on adipose tissue....

  2. Direction in charge of the management of wastes. 1998 activity report; Direction chargee de la gestion des dechets. Rapport d'activite 1998

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-07-01

    This document is the 1998 activity report of the direction in charge of the management of radioactive wastes (DGD) of the French atomic energy commission (CEA). The role of the DGD is the elimination of radioactive wastes, the management of spent fuels, the cleansing and dismantling of shut-down and decommissioned installations at the CEA. This report summarizes the highlights of the 1998 year: the cleansing plan of the CEA (current policy, plan scheme, quality assurance, financing, public relation); the radioactive wastes (general considerations, management of liquid and solid effluents, management of sealed sources, modernization of equipments and new projects, relations with the Andra, studies in progress); the spent fuels (general considerations, solutions, long-term storage); the dismantling of shut-down installations (general considerations about decommissioning, dismantling actions at the CEA, main works performed, dismantling actions in progress); the management of wastes at the CEA-direction for military applications (DAM); the cleansing of the CEA-Marcoule site; 1998 status of the management of wastes (appendix). (J.S.)

  3. Leftward spatial bias in children's drawing placement: hemispheric activation versus directional hypotheses.

    Science.gov (United States)

    Picard, Delphine; Zarhbouch, Benaissa

    2014-01-01

    A leftward spatial bias in drawing placement was demonstrated by Heller (1991) using the draw-a-person test with right-handed American children. No such bias was observed in left-handed children who are assumed to be less lateralised than their right-handed peers. According to Heller the leftward spatial bias is primarily a reflection of the right hemisphere specialisation for spatial processing. However, an alternative explanation in terms of directional trends may be put forward. In the present study we first confirm Heller's findings of a handedness effect on drawing placement using the draw-a-tree task with a large sample of right- and left-handed French children aged 5-15 years (Exp. 1). We then provide evidence that a similar leftward bias occurs in right-handed Moroccan children aged 7-11 years with opposite script directionality and opposite preferred drawing movement directions (i.e., right-to-left directional trends) to the those of right-handed French children (Exp. 2). Taken together these findings suggest that directionality trends arising from learned cultural habits and motor preferences play little role in determining spatial bias in the centring of a single object drawn on a page. Rather there may be a cerebral origin for drawing single objects slightly on the left side of the graphic space.

  4. Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase

    DEFF Research Database (Denmark)

    Sayed, M; Kim, S O; Salh, B S

    2000-01-01

    Protein kinase CK2 has been implicated in the regulation of a wide range of proteins that are important in cell proliferation and differentiation. Here we demonstrate that the stress signaling agents anisomycin, arsenite, and tumor necrosis factor-alpha stimulate the specific enzyme activity of CK2...... to be an allosteric mechanism. Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities....

  5. Evaporation Of Hanford Waste Treatment Plant Direct Feed Low Activity Waste Effluent Management Facility Core Simulant

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Nash, C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Mcclane, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); McCabe, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-09-01

    The Hanford Waste Treatment and Immobilization Plant (WTP) Low Activity Waste (LAW) vitrification facility will generate an aqueous condensate recycle stream (LAW Melter Off-Gas Condensate, LMOGC) from the off-gas system. The baseline plan for disposition of this stream during full WTP operations is to send it to the WTP Pretreatment Facility, where it will be blended with LAW, concentrated by evaporation, and recycled to the LAW vitrification facility. However, during the Direct Feed LAW (DFLAW) scenario, planned disposition of this stream is to evaporate it in a new evaporator, in the Effluent Management Facility (EMF), and then return it to the LAW melter. It is important to understand the composition of the effluents from the melter and new evaporator, so that the disposition of these streams can be accurately planned and accommodated. Furthermore, alternate disposition of the LMOGC stream would eliminate recycling of problematic components, and would reduce the need for closely integrated operation of the LAW melter and the Pretreatment Facilities. Long-term implementation of this option after WTP start-up would decrease the LAW vitrification mission duration and quantity of glass waste, amongst the other operational complexities such a recycle stream presents. In order to accurately plan for the disposition path, it is key to experimentally determine the fate of contaminants. To do this, testing is needed to accurately account for the buffering chemistry of the components, determine the achievable evaporation end point, identify insoluble solids that form, and determine the distribution of key regulatory-impacting constituents. The LAW Melter Off-Gas Condensate stream will contain components that are volatile at melter temperatures, have limited solubility in the glass waste form, and represent a materials corrosion concern, such as halides and sulfate. Because this stream will recycle within WTP, these components will accumulate in the Melter Condensate

  6. Methods of Improving Active Listening Skills with Relation to Following Directions.

    Science.gov (United States)

    Enger, Tracy; Russell, Nancy; Setzer, Jill; Walkanoff, Jeanette

    A program was developed for improving listening skills so as not to interfere with the cognitive processing of directions. The targeted population consisted of third, fourth, fifth, and eighth grade students in a growing middle class community located in the Midwest United States. Problems of decreased listening ability were documented through…

  7. Design of the Dual Offset Active Caster Wheel for Holonomic Omni-directional Mobile Robots

    Directory of Open Access Journals (Sweden)

    Woojin Chung

    2011-01-01

    Full Text Available It is shown how a holonomic and omni-directional mobile robot is designed towards indoor public services. Dual offset steerable wheels with orthogonal velocity components are proposed. The proposed wheel provides precise positioning and reliable navigation performance as well as durability. A fabricated prototype is introduced, then, an experiment is carried out.

  8. Patient-derived monoclonal antibodies directed towards beta2 glycoprotein-1 display lupus anticoagulant activity

    NARCIS (Netherlands)

    Dienava-Verdoold, I.; Boon-Spijker, M. G.; de Groot, P. G.; Brinkman, H. J. M.; Voorberg, J.; Mertens, K.; Derksen, R. H. W. M.; de Laat, B.

    2011-01-01

    Patients with antiphospholipid syndrome (APS) display a heterogeneous population of antibodies with beta(2) glycoprotein-1 (β(2)GP1) as the major antigen. We isolated and characterized human mAbs directed against β(2)GP1 from the immune repertoire of APS patients. Variable heavy chain repertoires

  9. Design of the Dual Offset Active Caster Wheel for Holonomic Omni-Directional Mobile Robots

    Directory of Open Access Journals (Sweden)

    Woojin Chung

    2010-12-01

    Full Text Available It is shown how a holonomic and omni-directional mobile robot is designed towards indoor public services. Dual offset steerable wheels with orthogonal velocity components are proposed. The proposed wheel provides precise positioning and reliable navigation performance as well as durability. A fabricated prototype is introduced, then, an experiment is carried out.

  10. Design of the Dual Offset Active Caster Wheel for Holonomic Omni-directional Mobile Robots

    OpenAIRE

    Woojin Chung; Chang-bae Moon; Changbae Jung; Jiyong Jin

    2011-01-01

    It is shown how a holonomic and omni-directional mobile robot is designed towards indoor public services. Dual offset steerable wheels with orthogonal velocity components are proposed. The proposed wheel provides precise positioning and reliable navigation performance as well as durability. A fabricated prototype is introduced, then, an experiment is carried out.

  11. Higher efficacy of direct hemoperfusion using coated activated-charcoal column for disopyramide poisoning: A case report.

    Science.gov (United States)

    Iguchi, Shigekazu; Yamaguchi, Naotaka; Takami, Hiroki; Komatsu, Takayuki; Ookubo, Hirokazu; Sekii, Hajime; Inoue, Kenji; Okazaki, Shinya; Okai, Iwao; Maruyama, Sonomi; Nomura, Tomohisa; Sugita, Manabu

    2017-12-01

    Cases of severe disopyramide poisoning are rare and few have been reported. We report a case in which activated-charcoal column hemoperfusion was dramatically effective for life-threatening disopyramide poisoning. A teenage girl who had overdosed on disopyramide (total dose, 4950 mg) was brought to our hospital. She was resuscitated from short period cardiopulmonary arrest and subsequently showed severe cardiogenic shock and ventricular arrhythmia. Disopyramide poisoning (self-evident). As hemodynamics remained unstable after providing percutaneous cardiopulmonary support and intra-aortic balloon pumping, we attempted direct hemoperfusion using a coated activated-charcoal hemoperfusion column. Hemodynamics including electrocardiography and serum disopyramide concentration were dramatically improved, and the patient was ambulatory by hospital day 14. Because disopyramide has low molecular weight and a small distribution volume, blood purification is considered to be the most effective therapy. We selected direct hemoperfusion for relatively high protein-binding rate. In fact, clinical status was dramatically improved, and the calculated half-life of the direct hemoperfusion phase was the shortest of all phases. In cases of severe or life-threatening disopyramide poisoning, blood purification therapy including direct hemoperfusion using a coated activated-charcoal column should be performed.

  12. [Direct questioning of serially studied 8th grade students on their leisure time activities].

    Science.gov (United States)

    Bächlin, A; Mühlemann, R

    1979-08-01

    8th degree students were asked by questionnaire on their leisure-time activities. Home work was shown to interfere with time spent in front of the television screen, whereas sports did not. Girls spent more time at homework than boys, and less time at television. Also they were less active in sports, especially in the lower grade schools.

  13. AMP-Activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Yen-Hsing Li

    2015-07-01

    Full Text Available The Hedgehog (Hh pathway regulates cell differentiation and proliferation during development by controlling the Gli transcription factors. Cell fate decisions and progression toward organ and tissue maturity must be coordinated, and how an energy sensor regulates the Hh pathway is not clear. AMP-activated protein kinase (AMPK is an important sensor of energy stores and controls protein synthesis and other energy-intensive processes. AMPK is directly responsive to intracellular AMP levels, inhibiting a wide range of cell activities if ATP is low and AMP is high. Thus, AMPK can affect development by influencing protein synthesis and other processes needed for growth and differentiation. Activation of AMPK reduces GLI1 protein levels and stability, thus blocking Sonic-hedgehog-induced transcriptional activity. AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

  14. Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts

    International Nuclear Information System (INIS)

    Samoszuk, Michael; Tan, Jenny; Chorn, Guillaume

    2005-01-01

    Accumulating evidence suggests that fibroblasts play a pivotal role in promoting the growth of breast cancer cells. The objective of the present study was to characterize and validate an in vitro model of the interaction between small numbers of human breast cancer cells and human fibroblasts. We measured the clonogenic growth of small numbers of human breast cancer cells co-cultured in direct contact with serum-activated, normal human fibroblasts. Using DNA microarrays, we also characterized the gene expression profile of the serum-activated fibroblasts. In order to validate the in vivo relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing α-smooth muscle actin. Clonogenic growth of human breast cancer cells obtained directly from in situ and invasive tumors was dramatically and consistently enhanced when the tumor cells were co-cultured in direct contact with serum-activated fibroblasts. This effect was abolished when the cells were co-cultured in transwells separated by permeable inserts. The fibroblasts in our experimental model exhibited a gene expression signature characteristic of 'serum response' (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast cancer tissue confirmed that myofibroblasts are in direct contact with breast cancer cells. Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells in vitro through a mechanism that involves direct physical contact between the cells. This model shares many important molecular and phenotypic similarities with the fibroblasts that are naturally found in breast cancers

  15. Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C

    Science.gov (United States)

    Cooper, D.; Pellis, N. R.; McIntire, L. V. (Principal Investigator)

    1998-01-01

    Utilizing clinostatic rotating wall vessel (RWV) bioreactors that simulate aspects of microgravity, we found phytohemagglutinin (PHA) responsiveness to be almost completely diminished. Activation marker expression was significantly reduced in RWV cultures. Furthermore, cytokine secretion profiles suggested that monocytes are not as adversely affected by simulated microgravity as T cells. Reduced cell-cell and cell-substratum interactions may play a role in the loss of PHA responsiveness because placing peripheral blood mononuclear cells (PBMC) within small collagen beads did partially restore PHA responsiveness. However, activation of purified T cells with cross-linked CD2/CD28 and CD3/CD28 antibody pairs was completely suppressed in the RWV, suggesting a defect in signal transduction. Activation of purified T cells with PMA and ionomycin was unaffected by RWV culture. Furthermore, sub-mitogenic doses of PMA alone but not ionomycin alone restored PHA responsiveness of PBMC in RWV culture. Thus our data indicate that during polyclonal activation the signaling pathways upstream of PKC activation are sensitive to simulated microgravity.

  16. Peak-valley-peak pattern of histone modifications delineates active regulatory elements and their directionality

    DEFF Research Database (Denmark)

    Pundhir, Sachin; Bagger, Frederik Otzen; Lauridsen, Felicia Kathrine Bratt

    2016-01-01

    Formation of nucleosome free region (NFR) accompanied by specific histone modifications at flanking nucleosomes is an important prerequisite for enhancer and promoter activity. Due to this process, active regulatory elements often exhibit a distinct shape of histone signal in the form of a peak......-valley-peak (PVP) pattern. However, different features of PVP patterns and their robustness in predicting active regulatory elements have never been systematically analyzed. Here, we present PARE, a novel computational method that systematically analyzes the H3K4me1 or H3K4me3 PVP patterns to predict NFRs. We show...

  17. Enhanced Neural Processing of Goal-directed Actions After Active Training in 4-Month-Old Infants.

    Science.gov (United States)

    Bakker, Marta; Sommerville, Jessica A; Gredebäck, Gustaf

    2016-03-01

    The current study explores the neural correlates of action perception and its relation to infants' active experience performing goal-directed actions. Study 1 provided active training with sticky mittens that enables grasping and object manipulation in prereaching 4-month-olds. After training, EEG was recorded while infants observed images of hands grasping toward (congruent) or away from (incongruent) objects. We demonstrate that brief active training facilitates social perception as indexed by larger amplitude of the P400 ERP component to congruent compared with incongruent trials. Study 2 presented 4-month-old infants with passive training in which they observed an experimenter perform goal-directed reaching actions, followed by an identical ERP session to that used in Study 1. The second study did not demonstrate any differentiation between congruent and incongruent trials. These results suggest that (1) active experience alters the brains' response to goal-directed actions performed by others and (2) visual exposure alone is not sufficient in developing the neural networks subserving goal processing during action observation in infancy.

  18. Directional patterns of muscle activation at the lower limb in subjects with hemiparesis and in healthy subjects: A comparative study.

    Science.gov (United States)

    Filiatrault, J; Bourbonnais, D; Gauthier, J; Gravel, D; Arsenault, A B

    1992-01-01

    This article reports the results of a comparative study on directional patterns of muscle activation at the lower limb in 15 subjects with hemiparesis and 18 healthy subjects. Subjects were required to exert static hip and knee torques using multidirectional and biarticular dynamometers designed for the lower limbs. Hip torques were performed in abduction, adduction, flexion, extension, and in combined directions (e.g., hip flexion and abduction) and knee torques were exerted in flexion and extension. The required torque levels corresponded to approximately 5% of the maximal voluntary contraction of healthy subjects. Electromyographic (EMG) activities of the rectus femoris, biceps femoris, gracilis, gluteus medius, gluteus maximus, vastus lateralis, tibialis anterior, and soleus were recorded during these torques. The descriptive analysis involved comparison between either the polar plots (for hip tasks) or the histograms (for knee tasks) representing the mean muscle activity obtained across subjects during torques exerted in each direction for the three groups of muscles analyzed (normal, paretic, and nonparetic muscles). Ciucular statistics were also used to characterize directional patterns of activation in each muscle during hip tasks while linear statistics permitted one to analyze these patterns during knee tasks. In general, the results of both the descriptive and inferential statistical analyses indicated that directional patterns of muscle activation during hip and knee torques are not altered in subjects with hemiparesis. These results are in contrast to the disturbances observed previously in a study of directional patterns of muscle activation at the upper extremity in this population. It is suggested that the contrast between the present results and those obtained at the upper limb in subjects with hemiparesis may reflect the difference in the motor recovery of upper and lower paretic limbs or in the severity of spasticity in the muscles involved at

  19. Quercetin enhances hypoxia-mediated apoptosis via direct inhibition of AMPK activity in HCT116 colon cancer.

    Science.gov (United States)

    Kim, Hak-Su; Wannatung, Tirawat; Lee, Sooho; Yang, Woo Kyeom; Chung, Sung Hyun; Lim, Jong-Seok; Choe, Wonchae; Kang, Insug; Kim, Sung-Soo; Ha, Joohun

    2012-09-01

    Tumor hypoxia is considered the best validated target in clinical oncology because of its significant contribution to chemotherapy failure and drug resistance. As an approach to target hypoxia, we assessed the potential of quercetin, a flavonoid widely distributed in plants, as a anticancer agent under hypoxic conditions and examined its pharmacological mechanisms by primarily focusing on the role of AMP-activated protein kinase (AMPK). Quercetin significantly attenuated tumor growth in an HCT116 cancer xenograft in vivo model with a substantial reduction of AMPK activity. In a cell culture system, quercetin more dramatically induced apoptosis of HCT116 cancer cells under hypoxic conditions than normoxic conditions, and this was tightly associated with inhibition of hypoxia-induced AMPK activity. An in vitro kinase assay demonstrated that quercetin directly inhibits AMPK activity. Inhibition of AMPK by expressing a dominant-negative form resulted in an increase of apoptosis under hypoxia, and a constitutively active form of AMPK effectively blocked quercetin-induced apoptosis under hypoxia. Collectively, our data suggest that quercetin directly inhibits hypoxia-induced AMPK, which plays a protective role against hypoxia. Quercetin also reduced the activity of hypoxia-inducible factor-1 (HIF-1), a major transcription factor for adaptive cellular response to hypoxia. Moreover, quercetin sensitized HCT116 cancer cells to the anticancer drugs cisplatin and etoposide under hypoxic conditions. Our findings suggest that AMPK may serve as a novel target for overcoming tumor hypoxia-associated negative aspects.

  20. Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6.

    OpenAIRE

    Chen, P L; Riley, D J; Chen-Kiang, S; Lee, W H

    1996-01-01

    The biological function of the retinoblastoma protein (RB) in the cell division cycle has been extensively documented, but its apparent role in differentiation remains largely unexplored. To investigate how RB is involved in differentiation, the U937 large-cell lymphoma line was induced to differentiate along a monocyte/macrophage lineage. During differentiation RB was found to interact directly through its simian virus 40 large tumor antigen (T antigen)-binding domain with NF-IL6, a member o...

  1. In vitro fertilization and artificial activation of eggs of the direct-developing anuran Eleutherodactylus coqui

    Directory of Open Access Journals (Sweden)

    Toro Esteban

    2004-08-01

    Full Text Available Abstract Although much is known about the reproductive biology of pond-breeding frogs, there is comparatively little information about terrestrial-breeding anurans, a highly successful and diverse group. This study investigates the activation and in vitro fertilization of eggs of the Puerto Rican coqui frog obtained by hormonally induced ovulation. We report that spontaneous activation occurs in 34% of eggs, probably in response to mechanical stress during oviposition. Artificial activation, as evidenced by the slow block to polyspermy and the onset of zygote division, was elicited both by mechanical stimulation and calcium ionophore exposure in 64% and 83% of the cases, respectively. Finally, one in vitro fertilization protocol showed a 27% success rate, despite the fact that about one third of all unfertilized eggs obtained by hormone injection auto-activate. We expect these findings to aid in the conservation effort of Eleutherodactylus frogs, the largest vertebrate genus.

  2. Self-Directed Weight Loss Strategies: Energy Expenditure Due to Physical Activity Is Not Increased to Achieve Intended Weight Loss.

    Science.gov (United States)

    Elbelt, Ulf; Schuetz, Tatjana; Knoll, Nina; Burkert, Silke

    2015-07-16

    Reduced physical activity and almost unlimited availability of food are major contributors to the development of obesity. With the decline of strenuous work, energy expenditure due to spontaneous physical activity has attracted increasing attention. Our aim was to assess changes in energy expenditure, physical activity patterns and nutritional habits in obese subjects aiming at self-directed weight loss. Energy expenditure and physical activity patterns were measured with a portable armband device. Nutritional habits were assessed with a food frequency questionnaire. Data on weight development, energy expenditure, physical activity patterns and nutritional habits were obtained for 105 patients over a six-month period from an initial cohort of 160 outpatients aiming at weight loss. Mean weight loss was -1.5 ± 7.0 kg (p = 0.028). Patients with weight maintenance (n = 75), with substantial weight loss (>5% body weight, n = 20) and with substantial weight gain (>5% body weight, n = 10) did not differ in regard to changes of body weight adjusted energy expenditure components (total energy expenditure: -0.2 kcal/kg/day; non-exercise activity thermogenesis: -0.3 kcal/kg/day; exercise-related activity thermogenesis (EAT): -0.2 kcal/kg/day) or patterns of physical activity (duration of EAT: -2 min/day; steps/day: -156; metabolic equivalent unchanged) measured objectively with a portable armband device. Self-reported consumption frequency of unfavorable food decreased significantly (p = 0.019) over the six-month period. An increase in energy expenditure or changes of physical activity patterns (objectively assessed with a portable armband device) are not employed by obese subjects to achieve self-directed weight loss. However, modified nutritional habits could be detected with the use of a food frequency questionnaire.

  3. Self-Directed Weight Loss Strategies: Energy Expenditure Due to Physical Activity Is Not Increased to Achieve Intended Weight Loss

    Directory of Open Access Journals (Sweden)

    Ulf Elbelt

    2015-07-01

    Full Text Available Reduced physical activity and almost unlimited availability of food are major contributors to the development of obesity. With the decline of strenuous work, energy expenditure due to spontaneous physical activity has attracted increasing attention. Our aim was to assess changes in energy expenditure, physical activity patterns and nutritional habits in obese subjects aiming at self-directed weight loss. Methods: Energy expenditure and physical activity patterns were measured with a portable armband device. Nutritional habits were assessed with a food frequency questionnaire. Results: Data on weight development, energy expenditure, physical activity patterns and nutritional habits were obtained for 105 patients over a six-month period from an initial cohort of 160 outpatients aiming at weight loss. Mean weight loss was −1.5 ± 7.0 kg (p = 0.028. Patients with weight maintenance (n = 75, with substantial weight loss (>5% body weight, n = 20 and with substantial weight gain (>5% body weight, n = 10 did not differ in regard to changes of body weight adjusted energy expenditure components (total energy expenditure: −0.2 kcal/kg/day; non-exercise activity thermogenesis: −0.3 kcal/kg/day; exercise-related activity thermogenesis (EAT: −0.2 kcal/kg/day or patterns of physical activity (duration of EAT: −2 min/day; steps/day: −156; metabolic equivalent unchanged measured objectively with a portable armband device. Self-reported consumption frequency of unfavorable food decreased significantly (p = 0.019 over the six-month period. Conclusions: An increase in energy expenditure or changes of physical activity patterns (objectively assessed with a portable armband device are not employed by obese subjects to achieve self-directed weight loss. However, modified nutritional habits could be detected with the use of a food frequency questionnaire.

  4. Direct Activation of Innate and Antigen-Presenting Functions of Microglia following Infection with Theiler's Virus

    Science.gov (United States)

    Olson, Julie K.; Girvin, Ann M.; Miller, Stephen D.

    2001-01-01

    Microglia are resident central nervous system (CNS) macrophages. Theiler's murine encephalomyelitis virus (TMEV) infection of SJL/J mice causes persistent infection of CNS microglia, leading to the development of a chronic-progressive CD4+ T-cell-mediated autoimmune demyelinating disease. We asked if TMEV infection of microglia activates their innate immune functions and/or activates their ability to serve as antigen-presenting cells for activation of T-cell responses to virus and endogenous myelin epitopes. The results indicate that microglia lines can be persistently infected with TMEV and that infection significantly upregulates the expression of cytokines involved in innate immunity (tumor necrosis factor alpha, interleukin-6 [IL-6], IL-18, and, most importantly, type I interferons) along with upregulation of major histocompatibility complex class II, IL-12, and various costimulatory molecules (B7-1, B7-2, CD40, and ICAM-1). Most significantly, TMEV-infected microglia were able to efficiently process and present both endogenous virus epitopes and exogenous myelin epitopes to inflammatory CD4+ Th1 cells. Thus, TMEV infection of microglia activates these cells to initiate an innate immune response which may lead to the activation of naive and memory virus- and myelin-specific adaptive immune responses within the CNS. PMID:11559811

  5. Bi-directional astrocytic regulation of neuronal activity within a network

    Directory of Open Access Journals (Sweden)

    Susan Yu Gordleeva

    2012-11-01

    Full Text Available The concept of a tripartite synapse holds that astrocytes can affect both the pre- and postsynaptic compartments through the Ca2+-dependent release of gliotransmitters. Because astrocytic Ca2+ transients usually last for a few seconds, we assumed that astrocytic regulation of synaptic transmission may also occur on the scale of seconds. Here, we considered the basic physiological functions of tripartite synapses and investigated astrocytic regulation at the level of neural network activity. The firing dynamics of individual neurons in a spontaneous firing network was described by the Hodgkin-Huxley model. The neurons received excitatory synaptic input driven by the Poisson spike train with variable frequency. The mean field concentration of the released neurotransmitter was used to describe the presynaptic dynamics. The amplitudes of the excitatory postsynaptic currents (PSCs obeyed the gamma distribution law. In our model, astrocytes depressed the presynaptic release and enhanced the postsynaptic currents. As a result, low frequency synaptic input was suppressed while high frequency input was amplified. The analysis of the neuron spiking frequency as an indicator of network activity revealed that tripartite synaptic transmission dramatically changed the local network operation compared to bipartite synapses. Specifically, the astrocytes supported homeostatic regulation of the network activity by increasing or decreasing firing of the neurons. Thus, the astrocyte activation may modulate a transition of neural network into bistable regime of activity with two stable firing levels and spontaneous transitions between them.

  6. Bi-directional astrocytic regulation of neuronal activity within a network.

    Science.gov (United States)

    Gordleeva, S Yu; Stasenko, S V; Semyanov, A V; Dityatev, A E; Kazantsev, V B

    2012-01-01

    The concept of a tripartite synapse holds that astrocytes can affect both the pre- and post-synaptic compartments through the Ca(2+)-dependent release of gliotransmitters. Because astrocytic Ca(2+) transients usually last for a few seconds, we assumed that astrocytic regulation of synaptic transmission may also occur on the scale of seconds. Here, we considered the basic physiological functions of tripartite synapses and investigated astrocytic regulation at the level of neural network activity. The firing dynamics of individual neurons in a spontaneous firing network was described by the Hodgkin-Huxley model. The neurons received excitatory synaptic input driven by the Poisson spike train with variable frequency. The mean field concentration of the released neurotransmitter was used to describe the presynaptic dynamics. The amplitudes of the excitatory postsynaptic currents (PSCs) obeyed the gamma distribution law. In our model, astrocytes depressed the presynaptic release and enhanced the PSCs. As a result, low frequency synaptic input was suppressed while high frequency input was amplified. The analysis of the neuron spiking frequency as an indicator of network activity revealed that tripartite synaptic transmission dramatically changed the local network operation compared to bipartite synapses. Specifically, the astrocytes supported homeostatic regulation of the network activity by increasing or decreasing firing of the neurons. Thus, the astrocyte activation may modulate a transition of neural network into bistable regime of activity with two stable firing levels and spontaneous transitions between them.

  7. Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Vaught, Arthur J; Gavriilaki, Eleni; Hueppchen, Nancy; Blakemore, Karin; Yuan, Xuan; Seifert, Sara M; York, Sarah; Brodsky, Robert A

    2016-05-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  8. Ghrelin is produced by and directly activates corticotrope cells from adrenocorticotropin-secreting adenomas.

    Science.gov (United States)

    Martínez-Fuentes, Antonio J; Moreno-Fernández, Jesús; Vázquez-Martínez, Rafael; Durán-Prado, Mario; de la Riva, Andrés; Tena-Sempere, Manuel; Diéguez, Carlos; Jiménez-Reina, Luis; Webb, Susan M; Pumar, Alfonso; Leal-Cerro, Alfonso; Benito-López, Pedro; Malagón, María M; Castaño, Justo P

    2006-06-01

    In Cushing's disease, ACTH hypersecretion by pituitary corticotrope adenoma cells and resulting hypercortisolism is accompanied by a severely blunted GH secretory response. Interestingly, in Cushing's disease, ghrelin markedly increases plasma ACTH, whereas its stimulatory action on GH secretion is reduced. Although the reported expression of ghrelin receptors (GHS-R) in corticotrope tumors offers a potential mechanism for ghrelin-induced ACTH hypersecretion, studies on the direct effects of synthetic GH secretagogues on corticotropinoma cells offered contradictory results. To evaluate the direct action of ghrelin on corticotropinoma cells from two patients with Cushing's disease, we measured its effect on free cytosolic calcium concentration ([Ca(2+)](i)). Additionally, expression of GHS-R and its ligand ghrelin was examined in these cells and in five additional corticotropinomas. Ghrelin (10(-6) m) induced a marked [Ca(2+)](i) increase in 89.5% (case 1; n = 19 cells) and 85% (case 2; n = 13 cells) of corticotropinoma cells. Moreover, RT-PCR showed that expression of GHS-R isoforms is accompanied by that of ghrelin in all seven corticotrope adenomas examined. Importantly, double immunogold electron microscopy revealed that ghrelin is costored within ACTH secretory vesicles in densely granulated adenomatous corticotropes. These results constitute the first demonstration that ghrelin acts directly on corticotrope tumor cells derived from patients with Cushing's disease. The presence of ghrelin and GHS-R suggests that pituitary ghrelin may play an autocrine/paracrine role in regulating ACTH release in Cushing's disease. Our findings provide a plausible cellular basis for the exaggerated ACTH response to ghrelin in Cushing's disease and suggest novel research strategies to develop medical treatments for this disease.

  9. Symbol Grounding Without Direct Experience: Do Words Inherit Sensorimotor Activation From Purely Linguistic Context?

    Science.gov (United States)

    Günther, Fritz; Dudschig, Carolin; Kaup, Barbara

    2017-10-19

    Theories of embodied cognition assume that concepts are grounded in non-linguistic, sensorimotor experience. In support of this assumption, previous studies have shown that upwards response movements are faster than downwards movements after participants have been presented with words whose referents are typically located in the upper vertical space (and vice versa for downwards responses). This is taken as evidence that processing these words reactivates sensorimotor experiential traces. This congruency effect was also found for novel words, after participants learned these words as labels for novel objects that they encountered either in their upper or lower visual field. While this indicates that direct experience with a word's referent is sufficient to evoke said congruency effects, the present study investigates whether this direct experience is also a necessary condition. To this end, we conducted five experiments in which participants learned novel words from purely linguistic input: Novel words were presented in pairs with real up- or down-words (Experiment 1); they were presented in natural sentences where they replaced these real words (Experiment 2); they were presented as new labels for these real words (Experiment 3); and they were presented as labels for novel combined concepts based on these real words (Experiment 4 and 5). In all five experiments, we did not find any congruency effects elicited by the novel words; however, participants were always able to make correct explicit judgements about the vertical dimension associated to the novel words. These results suggest that direct experience is necessary for reactivating experiential traces, but this reactivation is not a necessary condition for understanding (in the sense of storing and accessing) the corresponding aspects of word meaning. © 2017 Cognitive Science Society, Inc.

  10. Interaction of cadmium(2) trifluoroacetate with activated aromatic compounds: a new reaction of direct metallation

    International Nuclear Information System (INIS)

    Boev, V.I.; Denisov, S.P.; Moskalenko, A.I.; Stamova, L.G.; Gulin, A.V.

    2000-01-01

    Interaction of cadmium trifluoroacetate with aniline, 4-bromo-aniline, indole and benzimidazole was studied to develop a simple method for synthesizing cadmium organic compounds by direct electrophilic metallation of aromatic compounds. It is shown that heating of the reagents in anhydrous ethanol for several hours or without a solvent at 100-120 deg C for 5-10 min with subsequent treatment of the reacting mass by sodium chloride involves formation of the relevant cadmium organic compounds. The substances prepared were characterized by the methods of element analysis, IR and 1 H NMR spectroscopy [ru

  11. Alpha 4 integrin directs virus-activated CD8+ T cells to sites of infection

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Andersson, E C; Scheynius, A

    1995-01-01

    This article examines the role of VLA-4 in directing lymphocytes to sites of viral infection using the murine lymphocytic choriomeningitis virus infection (LCMV) as the model system. This virus by itself induces little or no inflammation, but in most mouse/virus strain combinations a potent T cell...... response is induced, which is associated with marked CD8+ cell-mediated inflammation. Two expressions of LCMV-induced inflammation were studied: meningitis induced by intracerebral infection and adoptive transfer of virus-specific delayed-type hypersensitivity. Our previous studies have shown that LCMV...

  12. Direct current (DC) resistivity and induced polarization (IP) monitoring of active layer dynamics at high temporal resolution

    DEFF Research Database (Denmark)

    Doetsch, Joseph; Ingeman-Nielsen, Thomas; Christiansen, Anders V.

    2015-01-01

    With permafrost thawing and changes in active layer dynamics induced by climate change, interactions between biogeochemical and thermal processes in the ground are of great importance. Here, active layer dynamics have been monitored using direct current (DC) resistivity and induced polarization (IP...... and subsurface temperatures supplemented the DC-IP measurements. A time-lapse DC-IP monitoring system has been acquiring at least six datasets per day on a 42-electrode profile with 0.5. m electrode spacing since July 2013. Remote control of the data acquisition system enables interactive adaptation...

  13. The use of an active coded aperture for improved directional measurements in high energy gamma-ray astronomy

    Science.gov (United States)

    Johansson, A.; Beron, B. L.; Campbell, L.; Eichler, R.; Hofstadter, R.; Hughes, E. B.; Wilson, S.; Gorodetsky, P.

    1980-01-01

    The coded aperture, a refinement of the scatter-hole camera, offers a method for the improved measurement of gamma-ray direction in gamma-ray astronomy. Two prototype coded apertures have been built and tested. The more recent of these has 128 active elements of the heavy scintillator BGO. Results of tests for gamma-rays in the range 50-500 MeV are reported and future application in space discussed.

  14. Effects of observing normal and abnormal goal-directed hand movements on somatosensory cortical activation.

    Science.gov (United States)

    Cheng, Chia-Hsiung

    2018-01-01

    Existing evidence indicates the importance of observing correct, normal actions on the motor cortical activities. However, the exact neurophysiological mechanisms, particularly in the somatosensory system, remain unclear. This study aimed to elucidate the effects of observing normal and abnormal hand movements on the contralateral primary somatosensory (cSI), contralateral (cSII) and ipsilateral (iSII) secondary somatosensory activities. Experiment I was designed to investigate the effects of motor outputs on the somatosensory processing, in which subjects were instructed to relax or manipulate a small cube. Experiment II was tailored to examine the somatosensory responses to the observation of normal (Normal) and abnormal (Abnormal) hand movements. The subjects received electrical stimulation to right median nerve and magnetoencephalography (MEG) recordings during the whole experimental period. Regional cortical activation and functional connectivity were analyzed. Compared to the resting condition, a reduction in cSI and an enhancement of SII activation was found when subjects manipulated a cube, suggesting the motor outputs have an influence on the somatosensory responses. Further investigation of the effects of observing different hand movements showed that cSII activity was significantly stronger in the Normal than Abnormal condition. Moreover, compared with Abnormal condition, a higher cortical coherence of cSI-iSII at theta bands and cSII-iSII at beta bands was found in Normal condition. Conclusively, the present results suggest stronger activation and enhanced functional connectivity within the somatosensory system during the observation of normal than abnormal hand movements. These findings also highlight the importance of viewing normal, correct hands movements in the stroke rehabilitation. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. A Study on Ukraine’s Exports Activities, Determining the Directions of its Intensification

    OpenAIRE

    Syhyda Liubov O.

    2017-01-01

    The article is aimed at determining Ukraine’s level of involvement in the world trade and globalization processes along with identifying the destructive factors of influence on Ukraine’s exports activity. The main indicators of Ukraine’s foreign trade activities for 2006-2016 were analyzed, in particular the exports and imports of goods and services, the export-import coverage ratio, the share of exports in GDP, and the share of imports in GDP. The foreign trade of Ukraine is determined to be...

  16. Improving escape panel selectivity in Nephrops directed fisheries by actively stimulating fish behaviour

    DEFF Research Database (Denmark)

    Krag, Ludvig Ahm; Herrmann, Bent; Feekings, Jordan P.

    2017-01-01

    with it. To increase the efficiency of such panels, the contact probability needs to be improved. In this study, we investigate to what extent the efficiency of escape panels can be improved by actively stimulating the escape behaviour of fish. The performance of two identical panel sections was compared...... in a twin-trawl system, one with and one without a stimulation device. A new coupled analysis method was used to explicitly quantify the improvements in contact probability and release efficiency for the escape panel. The results demonstrate that by actively stimulating escape behaviour, the contact...

  17. Antifreeze activity enhancement by site directed mutagenesis on an antifreeze protein from the beetle Rhagium mordax

    DEFF Research Database (Denmark)

    Friis, Dennis Steven; Kristiansen, Erlend; von Solms, Nicolas

    2014-01-01

    The ice binding motifs of insect antifreeze proteins (AFPs) mainly consist of repetitive TxT motifs aligned on a flat face of the protein. However, these motifs often contain non-threonines that disrupt the TxT pattern. We substituted two such disruptive amino acids located in the ice binding face...... of an AFP from Rhagium mordax with threonine. Furthermore, a mutant with an extra ice facing TxT motif was constructed. These mutants showed enhanced antifreeze activity compared to the wild type at low concentrations. However, extrapolating the data indicates that the wild type will become the most active...

  18. Site-directed mutagenesis under the direction of in silico protein docking modeling reveals the active site residues of 3-ketosteroid-Δ1-dehydrogenase from Mycobacterium neoaurum.

    Science.gov (United States)

    Qin, Ning; Shen, Yanbing; Yang, Xu; Su, Liqiu; Tang, Rui; Li, Wei; Wang, Min

    2017-07-01

    3-Ketosteroid-Δ 1 -dehydrogenases (KsdD) from Mycobacterium neoaurum could transform androst-4-ene-3,17-dione (AD) to androst-1,4-diene-3,17-dione. This reaction has a significant effect on the product of pharmaceutical steroid. The crystal structure and active site residues information of KsdD from Mycobacterium is not yet available, which result in the engineering of KsdD is tedious. In this study, by the way of protein modeling and site-directed mutagenesis, we find that, Y122, Y125, S138, E140 and Y541 from the FAD-binding domain and Y365 from the catalytic domain play a key role in this transformation. Compared with the wild type, the decline in AD conversion for mutants illustrated that Y125, Y365, and Y541 were essential to the function of KsdD. Y122, S138 and E140 contributed to the catalysis of KsdD. The following analysis revealed the catalysis mechanism of these mutations in KsdD of Mycobacterium. These information presented here facilitate the manipulation of the catalytic properties of the enzyme to improve its application in the pharmaceutical steroid industry.

  19. Explosive percolation on directed networks due to monotonic flow of activity

    Science.gov (United States)

    Waagen, Alex; D'Souza, Raissa M.; Lu, Tsai-Ching

    2017-07-01

    An important class of real-world networks has directed edges, and in addition, some rank ordering on the nodes, for instance the popularity of users in online social networks. Yet, nearly all research related to explosive percolation has been restricted to undirected networks. Furthermore, information on such rank-ordered networks typically flows from higher-ranked to lower-ranked individuals, such as follower relations, replies, and retweets on Twitter. Here we introduce a simple percolation process on an ordered, directed network where edges are added monotonically with respect to the rank ordering. We show with a numerical approach that the emergence of a dominant strongly connected component appears to be discontinuous. Large-scale connectivity occurs at very high density compared with most percolation processes, and this holds not just for the strongly connected component structure but for the weakly connected component structure as well. We present analysis with branching processes, which explains this unusual behavior and gives basic intuition for the underlying mechanisms. We also show that before the emergence of a dominant strongly connected component, multiple giant strongly connected components may exist simultaneously. By adding a competitive percolation rule with a small bias to link uses of similar rank, we show this leads to formation of two distinct components, one of high-ranked users, and one of low-ranked users, with little flow between the two components.

  20. Anaerobic removal of the brl direct blue dye in Upflow Anaerobic Sludge Blanket (UASB with activated carbon

    Directory of Open Access Journals (Sweden)

    Christian Zavala-Rivera

    2015-07-01

    Full Text Available In this research the brl direct blue dye was used for anaerobic removal with a bacterial consortium of industrial effluents from Industrial Park Río Seco (IPRS, Arequipa, Peru; in an anaerobic reactor of UASB Upflow with activated carbon. The reactor had a capacity of 14.4 L with sludge and activated carbon of 40% of volume, with an organic load of 6 Kg COD/m3•dia and a hydraulic retention time of 1 day with an upward flow. The objective was to measure the efficiency of the anaerobic removal of coloring in a time of 28 days. The results showed an increase of 41% of the solids suspended volatile (SSV 12894 mg•L-1 up to 21546 mg•L-1 under the conditions of the experiment, with a removal of 57% of the chemical demand of oxygen (COD from 484 mg•L-1 to 122 mg•L-1 and a removal of 87% of the dye Blue direct the 69.61 brl mg•L-1 to 9 mg•L-1. Results with activated charcoal granular only, they showed a removal of 61% of the dye Blue direct 70.67 brl mg•L-1 to 27.83 mg•L-1 at 28 days.

  1. Increasing community capacity for participatory evaluation of healthy eating and active living strategies through direct observations and environmental audits.

    Science.gov (United States)

    Kemner, Allison L; Stachecki, Jessica R; Bildner, Michele E; Brennan, Laura K

    2015-01-01

    Local partnerships from the Healthy Kids, Healthy Communities initiative elected to participate in enhanced evaluation trainings to collect data through environmental audits and direct observations as well as to build their evaluation capacity. Environmental audit and direct observation tools and protocols were adapted for the relevant healthy eating and active living policy and environmental change approaches being conducted by the Healthy Kids, Healthy Communities partnerships. Customized trainings were conducted by the evaluation team to increase capacity and understanding for evaluation activities. A total of 87 trainings were conducted by the evaluation team in 31 Healthy Kids, Healthy Communities community partnerships. Data were collected for a total of 41 environmental audits and 17 direct observations. Community case examples illustrate how these trainings developed evaluation capacity. For instance, youth from one community presented environmental audit findings to local elected officials. The 31 partnerships participating in the community-based evaluation efforts resulted in 164 individuals trained in collecting context-specific data to assess the impact of healthy eating and active living policy and environmental strategies designed to create community change.

  2. Interventions directed at eating habits and physical activity using the Transtheoretical Model: a systematic review.

    Science.gov (United States)

    Carvalho de Menezes, Mariana; Bedeschi, Lydiane Bragunci; Santos, Luana Caroline Dos; Lopes, Aline Cristine Souza

    2016-09-20

    The multi-behavioral Transtheoretical Model (TTM) addresses multiple behaviors and it is a promising strategy to control multifactorial morbidities, such as chronic diseases. The results obtained using the TTM are positive, but are not consistently methodical. The aim of this study was to systematically review the effectiveness of the Transtheoretical Model in multi-behavioral interventions for changing eating habits and levels of physical activity. A search on PubMed and SciELO databases was performed with inclusion criteria set for intervention studies before 2016 using the Transtheoretical Model for more than one behavior, including eating habits and/or engaging in physical activity. Eighteen studies were identified; there was a predominance of randomized clinical trials, studies conducted in the United States, and the use of the Internet and/or telephone. The selected studies were aimed at changing eating behaviors; five of the studies did not address physical activity. The main results were reduction of fat consumption, an increase in the consumption of fruit and vegetables, and increases in physical activity, which are progressions in the stages of change and weight loss identified by the Transtheoretical Model. However, the studies showed methodological weaknesses, including high participant loss and the omission of information about randomization and blinding.

  3. Show Me the Way: Future Faculty Prefer Directive Feedback When Trying Active Learning Approaches

    Science.gov (United States)

    Stephens, Jessica D.; Battle, David C.; Gormally, Cara L.; Brickman, Peggy

    2017-01-01

    Early training opportunities for future faculty, namely graduate students and postdoctoral researchers, can better prepare them to use active learning approaches. We know that instructional feedback supports sustained change and motivates instructors to improve teaching practices. Here, we incorporate feedback as a key component of a pedagogical…

  4. Directed surfaces structures and interfaces for enhanced electrocatalyst activity, selectivity, and stability for energy conversion reactions

    Energy Technology Data Exchange (ETDEWEB)

    Jaramillo, Thomas F. [Stanford Univ., CA (United States). Dept. of Chemical Engineering. Shriram Center

    2016-04-20

    In this project, we have employed a systematic approach to develop active, selective, and stable catalyst materials for important electrochemical reactions involving energy conversion. In particular, we have focused our attention on developing active catalyst materials for the hydrogen evolution reaction (HER), oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). HER: We have synthesized and investigated several highly active and acid stable non-precious metal HER catalysts, including: [Mo3S13]2- nanoclusters (Nature Chemistry, 2014) and molybdenum phosphosulfide (MoP|S) (Angewandte Chemie, 2014). We have also aimed to engineer these catalyst formulations in a membrane electrode assembly (MEA) for fundamental studies of water electrolysis at high current densities, approximately 1 A/cm2 (ChemSusChem, 2015). We furthermore investigated transition metal phosphide (TMP) catalysts for HER by a combined experimental–theoretical approach (Energy & Environmental Science, 2015). By synthesizing different TMPs and comparing experimentally determined HER activities with the hydrogen adsorption free energies, ΔGH, calculated by density functional theory, we showed that the TMPs follow a volcano relationship for the HER. Using our combined experimental–theoretical model, we predicted that the mixed metal TMP, Fe0.5Co0.5P, should have a near-optimal ΔGH. We synthesized several mixtures of Co and Fe phosphides alloys and confirmed that Fe0.5Co0.5P exhibits the highest HER activity of the investigated TMPs (Energy & Environmental Science, 2015). The understanding gained as to how to improve catalytic activity for the HER, particularly for non-precious metal materials, is important to DOE targets for sustainable H2 production. OER: We have developed a SrIrO3/IrOx catalyst for acidic conditions (submitted, 2016). The Sr

  5. Direct photochemical activation of non-heme Fe(IV)=O complexes

    NARCIS (Netherlands)

    Chen, Juan; Draksharapu, Apparao; Harvey, Emma; Rasheed, Waqas; Que, Lawrence; Browne, Wesley R.

    2017-01-01

    Near-UV excitation of non-heme Fe-IV=O complexes results in light intensity dependent increase in reaction rates for the oxidation of C-H bonds even at low temperature (-30 degrees C). The enhancement of activity is ascribed to the ligand-to-[Fe-IV=O] charge transfer character of the near-UV bands

  6. Assessing the mutagenic activities of smoke from different cigarettes in direct exposure experiments using the modified Ames Salmonella assay.

    Science.gov (United States)

    Ishikawa, Shinkichi; Kanemaru, Yuki; Nara, Hidenori; Erami, Kazuo; Nagata, Yasufumi

    2016-06-01

    The Ames assay is useful for evaluating the mutagenic potentials of chemicals, and it has been used to evaluate the mutagenic potential of cigarette smoke (CS). In vitro direct exposure systems have been developed to mimic CS exposure in the human respiratory tract, and the Ames assay has been used with such systems. Ames tests were performed using the Vitrocell(®) direct exposure system in this study. The mutagenic potentials of whole mainstream CS and gas/vapor phase fractions produced by conventional combustible cigarettes under two smoking regimens were compared. Salmonella Typhimurium TA98 and TA100 were used with and without metabolic activation, and the number of revertants induced by exposure to each CS was determined. The amount of smoke particles to which cells were exposed were also determined, and dose-response curves describing the relationships between exposure to smoke particles and the number of revertants induced were plotted. The slopes of linear regressions of the dose-response curves were determined, and the slope for each CS was used as a mutagenic activity index for that CS. A new heated cigarette was also tested and smoke from the heated cigarette had a lower mutagenic activity in TA98 and TA100 with metabolic activation than did the conventional CS. The results indicate that the direct exposure system and the Ames test can be used to determine the mutagenic potentials of CS produced by different cigarettes under different conditions (i.e., using different Salmonella Typhimurium strains with and without metabolic activation, and using different smoking conditions). Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Direct measurement and characterization of active photosynthesis zones inside biofuel producing and wastewater remediating microalgal biofilms

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, Hans C.; Kesaano, Maureen; Moll, Karen; Smith, Terence; Gerlach, Robin; Carlson, Ross; Miller, Charles D.; Peyton, Brent; Cooksey, Keith; Gardner, Robert D.; Sims, Ronald C.

    2014-03-01

    Abstract: Microalgal biofilm based technologies are of keen interest due to their high biomass concentrations and ability to utilize renewable resources, such as light and CO2. While photoautotrophic biofilms have long been used for wastewater remediation applications, biofuel production represents a relatively new and under-represented focus area. However, the direct measurement and characterization of fundamental parameters required for physiological analyses are challenging due to biofilm heterogeneity. This study evaluated oxygenic photosynthesis and biofuel precursor molecule production using a novel rotating algal biofilm reactor (RABR) operated at field- and laboratory-scales for wastewater remediation and biofuel production, respectively. Clear differences in oxygenic-photosynthesis, respiration and biofuel-precursor capacities were observed between the two systems and different conditions based on light and nitrogen availability. Nitrogen depletion was not found to have the same effect on lipid accumulation compared to prior planktonic studies. Physiological characterizations of these microalgal biofilms identify potential areas for future process optimization.

  8. Enantioselective Intramolecular Hydroarylation of Alkenes via Directed C-H Bond Activation

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Hitoshi; Thalji, Reema; Bergman, Robert; Ellman, Jonathan

    2008-05-22

    Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe){sub 2}]{sub 2} and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer.

  9. Enantioselective intramolecular hydroarylation of alkenes via directed C-H bond activation.

    Science.gov (United States)

    Harada, Hitoshi; Thalji, Reema K; Bergman, Robert G; Ellman, Jonathan A

    2008-09-05

    Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe)2]2 and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer.

  10. Enantioselective Intramolecular Hydroarylation of Alkenes via Directed C–H Bond Activation

    Science.gov (United States)

    Harada, Hitoshi; Thalji, Reema K.; Bergman, Robert G.; Ellman, Jonathan A.

    2008-01-01

    Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe)2]2 and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer. PMID:18681407

  11. Ginkgo biloba Responds to Herbivory by Activating Early Signaling and Direct Defenses

    Science.gov (United States)

    Atsbaha Zebelo, Simon; Foti, Maria; Fliegmann, Judith; Bossi, Simone; Maffei, Massimo E.; Bertea, Cinzia M.

    2012-01-01

    Background Ginkgo biloba (Ginkgoaceae) is one of the most ancient living seed plants and is regarded as a living fossil. G. biloba has a broad spectrum of resistance or tolerance to many pathogens and herbivores because of the presence of toxic leaf compounds. Little is known about early and late events occurring in G. biloba upon herbivory. The aim of this study was to assess whether herbivory by the generalist Spodoptera littoralis was able to induce early signaling and direct defense in G. biloba by evaluating early and late responses. Methodology/Principal Findings Early and late responses in mechanically wounded leaves and in leaves damaged by S. littoralis included plasma transmembrane potential (Vm) variations, time-course changes in both cytosolic calcium concentration ([Ca2+]cyt) and H2O2 production, the regulation of genes correlated to terpenoid and flavonoid biosynthesis, the induction of direct defense compounds, and the release of volatile organic compounds (VOCs). The results show that G. biloba responded to hebivory with a significant Vm depolarization which was associated to significant increases in both [Ca2+]cyt and H2O2. Several defense genes were regulated by herbivory, including those coding for ROS scavenging enzymes and the synthesis of terpenoids and flavonoids. Metabolomic analyses revealed the herbivore-induced production of several flavonoids and VOCs. Surprisingly, no significant induction by herbivory was found for two of the most characteristic G. biloba classes of bioactive compounds; ginkgolides and bilobalides. Conclusions/Significance By studying early and late responses of G. biloba to herbivory, we provided the first evidence that this “living fossil” plant responds to herbivory with the same defense mechanisms adopted by the most recent angiosperms. PMID:22448229

  12. Ginkgo biloba responds to herbivory by activating early signaling and direct defenses.

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Mohanta

    Full Text Available BACKGROUND: Ginkgo biloba (Ginkgoaceae is one of the most ancient living seed plants and is regarded as a living fossil. G. biloba has a broad spectrum of resistance or tolerance to many pathogens and herbivores because of the presence of toxic leaf compounds. Little is known about early and late events occurring in G. biloba upon herbivory. The aim of this study was to assess whether herbivory by the generalist Spodoptera littoralis was able to induce early signaling and direct defense in G. biloba by evaluating early and late responses. METHODOLOGY/PRINCIPAL FINDINGS: Early and late responses in mechanically wounded leaves and in leaves damaged by S. littoralis included plasma transmembrane potential (Vm variations, time-course changes in both cytosolic calcium concentration ([Ca(2+](cyt and H(2O(2 production, the regulation of genes correlated to terpenoid and flavonoid biosynthesis, the induction of direct defense compounds, and the release of volatile organic compounds (VOCs. The results show that G. biloba responded to hebivory with a significant Vm depolarization which was associated to significant increases in both [Ca(2+](cyt and H(2O(2. Several defense genes were regulated by herbivory, including those coding for ROS scavenging enzymes and the synthesis of terpenoids and flavonoids. Metabolomic analyses revealed the herbivore-induced production of several flavonoids and VOCs. Surprisingly, no significant induction by herbivory was found for two of the most characteristic G. biloba classes of bioactive compounds; ginkgolides and bilobalides. CONCLUSIONS/SIGNIFICANCE: By studying early and late responses of G. biloba to herbivory, we provided the first evidence that this "living fossil" plant responds to herbivory with the same defense mechanisms adopted by the most recent angiosperms.

  13. Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

    Science.gov (United States)

    Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

    2017-01-01

    Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier

  14. Improvement of the directional stability of passenger car trailer couplings with actively controlled steering

    Science.gov (United States)

    Desens, Jens

    The stabilization of pendulum oscillations of passenger car trailer couplings, using active steering, was examined. A linear model of the couplings was presented. Each axle was provided with a controller. The controllers were optimized, with regard to necessary sensors, in order to minimize costs. The rear and the front axles were provided with a control unit in order to compute the potential prevailing in the active steering of several axles. It was shown that the passenger car rear axle was the most suitable for coupling stabilization. The experiment was simulated, using a complex coupling model. The developed controller allowed the passenger car trailer to be driven at a speed higher than 150 km per hour.

  15. Optogenetic activation of axon guidance receptors controls direction of neurite outgrowth

    Science.gov (United States)

    Endo, M.; Hattori, M.; Toriyabe, H.; Ohno, H.; Kamiguchi, H.; Iino, Y.; Ozawa, T.

    2016-01-01

    Growth cones of extending axons navigate to correct targets by sensing a guidance cue gradient via membrane protein receptors. Although most signaling mechanisms have been clarified using an in vitro approach, it is still difficult to investigate the growth cone behavior in complicated extracellular environment of living animals due to the lack of tools. We develop a system for the light-dependent activation of a guidance receptor, Deleted in Colorectal Cancer (DCC), using Arabidopsis thaliana Cryptochrome 2, which oligomerizes upon blue-light absorption. Blue-light illumination transiently activates DCC via its oligomerization, which initiates downstream signaling in the illuminated subcellular region. The extending axons are attracted by illumination in cultured chick dorsal root ganglion neurons. Moreover, light-mediated navigation of the growth cones is achieved in living Caenorhabditis elegans. The photo-manipulation system is applicable to investigate the relationship between the growth cone behavior and its surrounding environment in living tissue. PMID:27052670

  16. MMP-9 directed shRNAs as relevant inhibitors of matrix metalloproteinase 9 activity and signaling

    Directory of Open Access Journals (Sweden)

    Ewa Nowak

    2013-08-01

    Full Text Available Introduction: The main function of matrix metalloproteinases is the degradation of extracellular matrix components, which is related to changes in the proliferation of cells, their differentiation, motility, and death. MMPs play an important role in physiological processes such as embryogenesis, angiogenesis and tissue remodeling. The increase of MMPs activity is also observed in pathological conditions including tumorigenesis where MMP-2 (gelatinase A and MMP-9 (gelatinase B show the ability to degrade the basement membrane of vessels and they are involved in metastasis. The aim of our study was to verify the changes of MMP-9 enzymatic activity and the mobility of cells after inhibition of MMP-9 gene expression.Material and Methods: The oligonucleotide shRNA insert had been designed to silence MMP-9 gene expression and was cloned into the pSUPER.neo expression vector. The construct was introduced into the HeLa (CCL-2 cervical cancer cells by lipotransfection. Simultaneously in control cells MMP-9 were inhibited by doxycycline. Changes in activity of MMP-9 were analyzed by gelatin zymography and wound-healing assay.Results/Conclusions: Gelatin zymography allowed us to confirm that activity of MMP-9 in cells transfected by shRNA-MMP-9 and treated by doxycycline were similar and significantly lower in comparison with control cells. Phenotypic tests of migration in vitro confirm statistically significant (P<0.05 changes in cell migration – control cells healed 3 to 5 times faster in comparison with transfected or doxycycline treated cells. Our studies show the significant role of MMP-9 in mobility and invasiveness of tumor cells, thus indicating a potential target point of interest for gene therapy.

  17. Direct evidence of plant-pathogenic activity of fungal metabolites of Trichothecium roseum on apple

    Czech Academy of Sciences Publication Activity Database

    Žabka, Martin; Drastichová, K.; Jegorov, A.; Soukupová, Julie; Nedbal, Ladislav

    2006-01-01

    Roč. 162, č. 1 (2006), s. 65-68 ISSN 0301-486X R&D Projects: GA ČR GA203/04/0799; GA MŠk LN00A141; GA MŠk LC545 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z60870520 Keywords : fluorescence * plant-pathogenic activity * fungal metabolites Subject RIV: EE - Microbiology, Virology Impact factor: 0.915, year: 2006

  18. Directed evolution of DNA polymerase, RNA polymerase and reverse transcriptase activity in a single polypeptide.

    Science.gov (United States)

    Ong, Jennifer L; Loakes, David; Jaroslawski, Szymon; Too, Kathleen; Holliger, Philipp

    2006-08-18

    DNA polymerases enable key technologies in modern biology but for many applications, native polymerases are limited by their stringent substrate recognition. Here we describe short-patch compartmentalized self-replication (spCSR), a novel strategy to expand the substrate spectrum of polymerases in a targeted way. spCSR is based on the previously described CSR, but unlike CSR only a short region (a "patch") of the gene under investigation is diversified and replicated. This allows the selection of polymerases under conditions where catalytic activity and processivity are compromised to the extent that full self-replication is inefficient. We targeted two specific motifs involved in substrate recognition in the active site of DNA polymerase I from Thermus aquaticus (Taq) and selected for incorporation of both ribonucleotide- (NTP) and deoxyribonucleotide-triphosphates (dNTPs) using spCSR. This allowed the isolation of multiple variants of Taq with apparent dual substrate specificity. They were able to synthesize RNA, while still retaining essentially wild-type (wt) DNA polymerase activity as judged by PCR. One such mutant (AA40: E602V, A608V, I614M, E615G) was able to incorporate both NTPs and dNTPs with the same catalytic efficiency as the wt enzyme incorporates dNTPs. AA40 allowed the generation of mixed RNA-DNA amplification products in PCR demonstrating DNA polymerase, RNA polymerase as well as reverse transcriptase activity within the same polypeptide. Furthermore, AA40 displayed an expanded substrate spectrum towards other 2'-substituted nucleotides and was able to synthesize nucleic acid polymers in which each base bore a different 2'-substituent. Our results suggest that spCSR will be a powerful strategy for the generation of polymerases with altered substrate specificity for applications in nano- and biotechnology and in the enzymatic synthesis of antisense and RNAi probes.

  19. Direct evidence of complement activation in HELLP syndrome: a link to atypical hemolytic uremic syndrome

    OpenAIRE

    Vaught, Arthur J.; Gavriilaki, Eleni; Hueppchen, Nancy; Blakemore, Karin; Yuan, Xuan; Seifert, Sara M.; York, Sarah; Brodsky, Robert A.

    2016-01-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of preeclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome (aHUS), a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we utilized a functional complement assay, the modified Ham test, to test sera of women with ...

  20. Direct observation of children's preferences and activity levels during interactive and online electronic games.

    Science.gov (United States)

    Sit, Cindy H P; Lam, Jessica W K; McKenzie, Thomas L

    2010-07-01

    Interactive electronic games have recently been popularized and are believed to help promote children's physical activity (PA). The purpose of the study was to examine preferences and PA levels during interactive and online electronic games among overweight and nonoverweight boys and girls. Using a modification of the SOFIT, we systematically observed 70 Hong Kong Chinese children (35 boys, 35 girls; 50 nonoverweight, 20 overweight), age 9 to 12 years, during 2 60-minute recreation sessions and recorded their game mode choices and PA levels. During Session One children could play either an interactive or an online electronic bowling game and during Session Two they could play an interactive or an online electronic running game. Children chose to play the games during 94% of session time and split this time between interactive (52%) and online (48%) versions. They engaged in significantly more moderate-to-vigorous physical activity (MVPA) during interactive games than their online electronic versions (70% vs. 2% of game time). Boys and nonoverweight children expended relatively more energy during the interactive games than girls and overweight children, respectively. New-generation interactive games can facilitate physical activity in children, and given the opportunity children may select them over sedentary versions.

  1. Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity.

    Science.gov (United States)

    Lee, Wonhwa; Kim, Mi-Ae; Park, InWha; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

    2017-11-01

    Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo( L -Pro- L -Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619. They inhibited ADP- and U46619-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) and the expression of P-selectin and PAC-1 in platelets. They also improved the production of nitric oxide and inhibited the oversecretion of endothelin-1 compared to that of the ADP- or U46619-treated group. In an animal model of arterial and pulmonary thrombosis, the isolated compounds showed enhanced antithrombotic effects. They also elicited anticoagulant effects in mice. Compounds 1-2 inhibited ADP-, collagen-, or U46619-induced platelet aggregation and showed similar anti-thrombotic efficacy to rivaroxaban, a positive control. Therefore, 1-2 could serve as candidates and provide scaffolds for the development of new anti-FXa and anti-platelet drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. RIM proteins tether Ca2+-channels to presynaptic active zones via a direct PDZ-domain interaction

    Science.gov (United States)

    Kaeser, Pascal S.; Deng, Lunbin; Wang, Yun; Dulubova, Irina; Liu, Xinran; Rizo, Josep; Südhof, Thomas C.

    2011-01-01

    SUMMARY At a synapse, fast synchronous neurotransmitter release requires localization of Ca2+-channels to presynaptic active zones. How Ca2+-channels are recruited to active zones, however, remains unknown. Using unbiased yeast two-hybrid screens, we here identify a direct interaction of the central PDZ-domain of the active-zone protein RIM with the C-termini of presynaptic N- and P/Q-type Ca2+-channels, but not L-type Ca2+-channels. To test the physiological significance of this interaction, we generated conditional knockout mice lacking all presynaptic RIM isoforms. Deletion of all RIMs ablated most neurotransmitter release by simultaneously impairing the priming of synaptic vesicles and by decreasing the presynaptic localization of Ca2+-channels. Strikingly, rescue of the decreased Ca2+-channel localization required the RIM PDZ-domain, whereas rescue of vesicle priming required the RIM N-terminus. We propose that RIMs tether N- and P/Q-type Ca2+-channels to presynaptic active zones via a direct PDZ-domain mediated interaction, thereby enabling fast, synchronous triggering of neurotransmitter release at a synapse. PMID:21241895

  3. Fencing network direct memory access data transfers in a parallel active messaging interface of a parallel computer

    Science.gov (United States)

    Blocksome, Michael A.; Mamidala, Amith R.

    2015-07-07

    Fencing direct memory access (`DMA`) data transfers in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI including data communications endpoints, each endpoint including specifications of a client, a context, and a task, the endpoints coupled for data communications through the PAMI and through DMA controllers operatively coupled to a deterministic data communications network through which the DMA controllers deliver data communications deterministically, including initiating execution through the PAMI of an ordered sequence of active DMA instructions for DMA data transfers between two endpoints, effecting deterministic DMA data transfers through a DMA controller and the deterministic data communications network; and executing through the PAMI, with no FENCE accounting for DMA data transfers, an active FENCE instruction, the FENCE instruction completing execution only after completion of all DMA instructions initiated prior to execution of the FENCE instruction for DMA data transfers between the two endpoints.

  4. Deciphering the Neural Control of Sympathetic Nerve Activity: Status Report and Directions for Future Research

    Directory of Open Access Journals (Sweden)

    Susan M. Barman

    2017-12-01

    Full Text Available Sympathetic nerve activity (SNA contributes appreciably to the control of physiological function, such that pathological alterations in SNA can lead to a variety of diseases. The goal of this review is to discuss the characteristics of SNA, briefly review the methodology that has been used to assess SNA and its control, and to describe the essential role of neurophysiological studies in conscious animals to provide additional insights into the regulation of SNA. Studies in both humans and animals have shown that SNA is rhythmic or organized into bursts whose frequency varies depending on experimental conditions and the species. These rhythms are generated by brainstem neurons, and conveyed to sympathetic preganglionic neurons through several pathways, including those emanating from the rostral ventrolateral medulla. Although rhythmic SNA is present in decerebrate animals (indicating that neurons in the brainstem and spinal cord are adequate to generate this activity, there is considerable evidence that a variety of supratentorial structures including the insular and prefrontal cortices, amygdala, and hypothalamic subnuclei provide inputs to the brainstem regions that regulate SNA. It is also known that the characteristics of SNA are altered during stress and particular behaviors such as the defense response and exercise. While it is a certainty that supratentorial structures contribute to changes in SNA during these behaviors, the neural underpinnings of the responses are yet to be established. Understanding how SNA is modified during affective responses and particular behaviors will require neurophysiological studies in awake, behaving animals, including those that entail recording activity from neurons that generate SNA. Recent studies have shown that responses of neurons in the central nervous system to most sensory inputs are context-specific. Future neurophysiological studies in conscious animals should also ascertain whether this general

  5. TLC-bioautography directed isolation of antibacterial compounds from active fractionation of Ferula ferulioides.

    Science.gov (United States)

    Sun, Zhong-Lin; Liu, Tao; Wang, Shuang-Ying; Ji, Xiao-Yue; Mu, Qing

    2018-01-30

    A novel optimised isolation method, TLC-bioautography, was evaluated and utilised in this research. Antibacterial compounds which were isolated from the dichloromethane extract of Ferula ferulioides (Steud.) Korovin were detected by means of the method. Their structures were elucidated by extensive spectral and chemical methods. Their antibacterial activities against drug-resistant Staphylococcus aureus (S. aureus) strains were evaluated with broth microdilution method, and the results proved that TLC-bioautography was an effective and highly efficient way to screen natural compounds from plant extracts against drug-resistant strains.

  6. Transcriptomic-Wide Discovery of Direct and Indirect HuR RNA Targets in Activated CD4+ T Cells.

    Directory of Open Access Journals (Sweden)

    Patsharaporn Techasintana

    Full Text Available Due to poor correlation between steady state mRNA levels and protein product, purely transcriptomic profiling methods may miss genes posttranscriptionally regulated by RNA binding proteins (RBPs and microRNAs (miRNAs. RNA immunoprecipitation (RIP methods developed to identify in vivo targets of RBPs have greatly elucidated those mRNAs which may be regulated via transcript stability and translation. The RBP HuR (ELAVL1 and family members are major stabilizers of mRNA. Many labs have identified HuR mRNA targets; however, many of these analyses have been performed in cell lines and oftentimes are not independent biological replicates. Little is known about how HuR target mRNAs behave in conditional knock-out models. In the present work, we performed HuR RIP-Seq and RNA-Seq to investigate HuR direct and indirect targets using a novel conditional knock-out model of HuR genetic ablation during CD4+ T activation and Th2 differentiation. Using independent biological replicates, we generated a high coverage RIP-Seq data set (>160 million reads that was analyzed using bioinformatics methods specifically designed to find direct mRNA targets in RIP-Seq data. Simultaneously, another set of independent biological replicates were sequenced by RNA-Seq (>425 million reads to identify indirect HuR targets. These direct and indirect targets were combined to determine canonical pathways in CD4+ T cell activation and differentiation for which HuR plays an important role. We show that HuR may regulate genes in multiple canonical pathways involved in T cell activation especially the CD28 family signaling pathway. These data provide insights into potential HuR-regulated genes during T cell activation and immune mechanisms.

  7. GPS scintillation effects associated with polar cap patches and substorm auroral activity: direct comparison

    Directory of Open Access Journals (Sweden)

    Jin Yaqi

    2014-01-01

    Full Text Available We directly compare the relative GPS scintillation levels associated with regions of enhanced plasma irregularities called auroral arcs, polar cap patches, and auroral blobs that frequently occur in the polar ionosphere. On January 13, 2013 from Ny-Ålesund, several polar cap patches were observed to exit the polar cap into the auroral oval, and were then termed auroral blobs. This gave us an unprecedented opportunity to compare the relative scintillation levels associated with these three phenomena. The blobs were associated with the strongest phase scintillation (σϕ, followed by patches and arcs, with σϕ up to 0.6, 0.5, and 0.1 rad, respectively. Our observations indicate that most patches in the nightside polar cap have produced significant scintillations, but not all of them. Since the blobs are formed after patches merged into auroral regions, in space weather predictions of GPS scintillations, it will be important to enable predictions of patches exiting the polar cap.

  8. Laboratory directed research and development. FY 1991 program activities: Summary report

    Energy Technology Data Exchange (ETDEWEB)

    1991-11-15

    The purposes of Argonne`s Laboratory Directed Research and Development (LDRD) Program are to encourage the development of novel concepts, enhance the Laboratory`s R&D capabilities, and further the development of its strategic initiatives. Among the aims of the projects supported by the Program are establishment of engineering ``proof-of-principle``; development of an instrumental prototype, method, or system; or discovery in fundamental science. Several of these project are closely associated with major strategic thrusts of the Laboratory as described in Argonne`s Five Year Institutional Plan, although the scientific implications of the achieved results extend well beyond Laboratory plans and objectives. The projects supported by the Program are distributed across the major programmatic areas at Argonne. Areas of emphasis are (1) advanced accelerator and detector technology, (2) x-ray techniques in biological and physical sciences, (3) advanced reactor technology, (4) materials science, computational science, biological sciences and environmental sciences. Individual reports summarizing the purpose, approach, and results of projects are presented.

  9. Argonne National Laboratory: Laboratory Directed Research and Development FY 1993 program activities. Annual report

    Energy Technology Data Exchange (ETDEWEB)

    None

    1993-12-23

    The purposes of Argonne`s Laboratory Directed Research and Development (LDRD) Program are to encourage the development of novel concepts, enhance the Laboratory`s R&D capabilities, and further the development of its strategic initiatives. Projects are selected from proposals for creative and innovative R&D studies which are not yet eligible for timely support through normal programmatic channels. Among the aims of the projects supported by the Program are establishment of engineering ``proof-of-principle`` assessment of design feasibility for prospective facilities; development of an instrumental prototype, method, or system; or discovery in fundamental science. Several of these projects are closely associated with major strategic thrusts of the Laboratory as described in Argonne`s Five Year Institutional Plan, although the scientific implications of the achieved results extend well beyond Laboratory plans and objectives. The projects supported by the Program are distributed across the major programmatic areas at Argonne as indicated in the Laboratory LDRD Plan for FY 1993.

  10. Argonne National Laboratory Annual Report of Laboratory Directed Research and Development Program Activities for FY 1994

    Energy Technology Data Exchange (ETDEWEB)

    None

    1995-02-25

    The purposes of Argonne's Laboratory Directed Research and Development (LDRD) Program are to encourage the development of novel concepts, enhance the Laboratory's R and D capabilities, and further the development of its strategic initiatives. Projects are selected from proposals for creative and innovative R and D studies which are not yet eligible for timely support through normal programmatic channels. Among the aims of the projects supported by the Program are establishment of engineering proof-of-principle; assessment of design feasibility for prospective facilities; development of an instrumental prototype, method, or system; or discovery in fundamental science. Several of these projects are closely associated with major strategic thrusts of the Laboratory as described in Argonne's Five-Year Institutional Plan, although the scientific implications of the achieved results extend well beyond Laboratory plans and objectives. The projects supported by the Program are distributed across the major programmatic areas at Argonne as indicated in the Laboratory's LDRD Plan for FY 1994. Project summaries of research in the following areas are included: (1) Advanced Accelerator and Detector Technology; (2) X-ray Techniques for Research in Biological and Physical Science; (3) Nuclear Technology; (4) Materials Science and Technology; (5) Computational Science and Technology; (6) Biological Sciences; (7) Environmental Sciences: (8) Environmental Control and Waste Management Technology; and (9) Novel Concepts in Other Areas.

  11. Argonne National Laboratory Annual Report of Laboratory Directed Research and Development program activities FY 2010.

    Energy Technology Data Exchange (ETDEWEB)

    (Office of The Director)

    2012-04-25

    As a national laboratory Argonne concentrates on scientific and technological challenges that can only be addressed through a sustained, interdisciplinary focus at a national scale. Argonne's eight major initiatives, as enumerated in its strategic plan, are Hard X-ray Sciences, Leadership Computing, Materials and Molecular Design and Discovery, Energy Storage, Alternative Energy and Efficiency, Nuclear Energy, Biological and Environmental Systems, and National Security. The purposes of Argonne's Laboratory Directed Research and Development (LDRD) Program are to encourage the development of novel technical concepts, enhance the Laboratory's research and development (R and D) capabilities, and pursue its strategic goals. projects are selected from proposals for creative and innovative R and D studies that require advance exploration before they are considered to be sufficiently developed to obtain support through normal programmatic channels. Among the aims of the projects supported by the LDRD Program are the following: establishment of engineering proof of principle, assessment of design feasibility for prospective facilities, development of instrumentation or computational methods or systems, and discoveries in fundamental science and exploratory development.

  12. Argonne National Laboratory Annual Report of Laboratory Directed Research and Development program activities FY 2011.

    Energy Technology Data Exchange (ETDEWEB)

    (Office of The Director)

    2012-04-25

    As a national laboratory Argonne concentrates on scientific and technological challenges that can only be addressed through a sustained, interdisciplinary focus at a national scale. Argonne's eight major initiatives, as enumerated in its strategic plan, are Hard X-ray Sciences, Leadership Computing, Materials and Molecular Design and Discovery, Energy Storage, Alternative Energy and Efficiency, Nuclear Energy, Biological and Environmental Systems, and National Security. The purposes of Argonne's Laboratory Directed Research and Development (LDRD) Program are to encourage the development of novel technical concepts, enhance the Laboratory's research and development (R and D) capabilities, and pursue its strategic goals. projects are selected from proposals for creative and innovative R and D studies that require advance exploration before they are considered to be sufficiently developed to obtain support through normal programmatic channels. Among the aims of the projects supported by the LDRD Program are the following: establishment of engineering proof of principle, assessment of design feasibility for prospective facilities, development of instrumentation or computational methods or systems, and discoveries in fundamental science and exploratory development.

  13. Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering.

    Science.gov (United States)

    Gelmi, Amy; Cieslar-Pobuda, Artur; de Muinck, Ebo; Los, Marek; Rafat, Mehrdad; Jager, Edwin W H

    2016-06-01

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Improved Direct Deadbeat Voltage Control with an Actively Damped Inductor-Capacitor Plant Model in an Islanded AC Microgrid

    Directory of Open Access Journals (Sweden)

    Jaehong Kim

    2016-11-01

    Full Text Available A direct deadbeat voltage control design method for inverter-based microgrid applications is proposed in this paper. When the inductor-capacitor (LC filter output voltage is directly controlled using voltage source inverters (VSIs, the plant dynamics exhibit second-order resonant characteristics with a load current disturbance. To effectively damp the resonance caused by the output LC filter, an active damping strategy that does not cause additional energy loss is utilized. The proposed direct deadbeat voltage control law is devised from a detailed, actively damped LC plant model. The proposed deadbeat control method enhances voltage control performance owing to its better disturbance rejection capability than the conventional deadbeat or proportional-integral-based control methods. The most important advantage of the proposed deadbeat control method is that it makes the deadbeat control more robust by bringing discrete closed-loop poles closer to the origin. Simulation and experimental results are shown to verify the enhanced voltage control performance and stability of the proposed voltage control method.

  15. Herpes Simplex Virus 1 DNA Polymerase RNase H Activity Acts in a 3'-to-5' Direction and Is Dependent on the 3'-to-5' Exonuclease Active Site.

    Science.gov (United States)

    Lawler, Jessica L; Mukherjee, Purba; Coen, Donald M

    2018-03-01

    The catalytic subunit (Pol) of herpes simplex virus 1 (HSV-1) DNA polymerase has been extensively studied both as a model for other family B DNA polymerases and for its differences from these enzymes as an antiviral target. Among the activities of HSV-1 Pol is an intrinsic RNase H activity that cleaves RNA from RNA-DNA hybrids. There has long been a controversy regarding whether this activity is due to the 3'-to-5' exonuclease of Pol or whether it is a separate activity, possibly acting on 5' RNA termini. To investigate this issue, we compared wild-type HSV-1 Pol and a 3'-to-5' exonuclease-deficient mutant, D368A Pol, for DNA polymerase activity, 3'-to-5' exonuclease activity, and RNase H activity in vitro Additionally, we assessed the RNase H activity using differentially end-labeled templates with 5' or 3' RNA termini. The mutant enzyme was at most modestly impaired for DNA polymerase activity but was drastically impaired for 3'-to-5' exonuclease activity, with no activity detected even at high enzyme-to-DNA substrate ratios. Importantly, the mutant showed no detectable ability to excise RNA with either a 3' or 5' terminus, while the wild-type HSV-1 Pol was able to cleave RNA from the annealed RNA-DNA hairpin template, but only detectably with a 3' RNA terminus in a 3'-to-5' direction and at a rate lower than that of the exonuclease activity. These results suggest that HSV-1 Pol does not have an RNase H separable from its 3'-to-5' exonuclease activity and that this activity prefers DNA degradation over degradation of RNA from RNA-DNA hybrids. IMPORTANCE Herpes simplex virus 1 (HSV-1) is a member of the Herpesviridae family of DNA viruses, several of which cause morbidity and mortality in humans. Although the HSV-1 DNA polymerase has been studied for decades and is a crucial target for antivirals against HSV-1 infection, several of its functions remain to be elucidated. A hypothesis suggesting the existence of a 5'-to-3' RNase H activity intrinsic to this enzyme

  16. Alteration of Spinach Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Activase Activities by Site-Directed Mutagenesis

    Science.gov (United States)

    Shen, Jennie B.; Ogren, William L.

    1992-01-01

    Site-directed mutagenesis was performed on the 1.6 and 1.9 kilobase spinach (Spinacea oleracea) ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activase cDNAs, encoding the 41 and 45 kilodalton (kD) isoforms of the enzyme, to create single amino acid changes in the putative ATP-binding site of Rubisco activase (Lys-107, Gln-109, and Ser-112) and in an unrelated cysteine residue (Cys-256). Replacement of Lys-107 with Met produced soluble protein with reduced Rubisco activase and ATPase activities in both isoforms. Substituting Ala or Arg for Lys-107 produced insoluble proteins. Rubisco activase activity increased in the 41-kD isoform when Gln-109 was changed to Glu, but activity in the 45-kD isoform was similar to the wild-type enzyme. ATPase activity in the Glu-109 mutations did not parallel the changes in Rubisco activase activity. Rather, a higher ratio of Rubisco activase to ATPase activity occurred in both isoforms. The mutation of Gln-109 to Lys inactivated Rubisco activase activity. Replacement of Ser-112 with Pro created an inactive protein, whereas attempts to replace Ser-112 with Thr were not successful. The mutation of Cys-256 to Ser in the 45-kD isoform reduced both Rubisco activase and ATPase activities. The results indicate that the two activities of Rubisco activase are not tightly coupled and that variations in photosynthetic efficiency may occur in vivo by replacing the wild-type enzyme with mutant enzymes. ImagesFigure 3 PMID:16668989

  17. Characterization of Viscoelastic Materials Through an Active Mixer by Direct-Ink Writing

    Science.gov (United States)

    Drake, Eric

    The goal of this thesis is two-fold: First, to determine mixing effectiveness of an active mixer attachment to a three-dimensional (3D) printer by characterizing actively-mixed, three-dimensionally printed silicone elastomers. Second, to understand mechanical properties of a printed lattice structure with varying geometry and composition. Ober et al defines mixing effectiveness as a measureable quantity characterized by two key variables: (i) a dimensionless impeller parameter (O ) that depends on mixer geometry as well as Peclet number (Pe) and (ii) a coefficient of variation (COV) that describes the mixer effectiveness based upon image intensity. The first objective utilizes tungsten tracer particles distributed throughout a batch of Dow Corning SE1700 (two parts silicone) - ink "A". Ink "B" is made from pure SE1700. Using the in-site active mixer, both ink "A" and "B" coalesce to form a hybrid ink just before extrusion. Two samples of varying mixer speeds and composition ratios are printed and analyzed by microcomputed tomography (MicroCT). A continuous stirred tank reactor (CSTR) model is applied to better understand mixing behavior. Results are then compared with computer models to verify the hypothesis. Data suggests good mixing for the sample with higher impeller speed. A Radial Distrubtion Function (RDF) macro is used to provide further qualitative analysis of mixing efficiency. The second objective of this thesis utilized three-dimensionally printed samples of varying geometry and composition to ascertain mechanical properties. Samples were printed using SE1700 provided by Lawrence Livermore National Laboratory with a face-centered tetragonal (FCT) structure. Hardness testing is conducted using a Shore OO durometer guided by a computer-controlled, three-axis translation stage to provide precise movements. Data is collected across an 'x-y' plane of the specimen. To explain the data, a simply supported beam model is applied to a single unit cell which yields

  18. Direct nucleophilic difluoromethylation of aromatic isoxazoles activated by electron-withdrawing groups using (difluoromethyltrimethylsilane

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2014-12-01

    Full Text Available The activation of aromatic diaryl isoxazoles with strong electron-withdrawing groups, such as the nitro, triflyl, and the phenylsulfonyl groups, at the 4-position has enabled the first regio- and diastereoselective difluoromethylation at the 5-position of isoxazoles by nucleophilic addition using (difluoromethyl trimethylsilane, Me3SiCF2H, to provide difluoromethylated isoxazolines in good yields. Conjugated styryl-4-nitroisoxazoles were also nicely converted into the corresponding CF2H adducts with high regio- and excellent diastereoselectivities. Since the trifluoromethylated analogs of the corresponding diaryl-isoxazolines are effective ectoparasiticides, represented by fluralaner, should a series of difluoromethylated isoxazolines be obtained, they would be of great importance as promising drug candidates in this field.

  19. Japan Environment and Children's Study: backgrounds, activities, and future directions in global perspectives.

    Science.gov (United States)

    Ishitsuka, Kazue; Nakayama, Shoji F; Kishi, Reiko; Mori, Chisato; Yamagata, Zentaro; Ohya, Yukihiro; Kawamoto, Toshihiro; Kamijima, Michihiro

    2017-07-14

    There is worldwide concern about the effects of environmental factors on children's health and development. The Miami Declaration was signed at the G8 Environment Ministers Meeting in 1997 to promote children's environmental health research. The following ministerial meetings continued to emphasize the need to foster children's research. In response to such a worldwide movement, the Ministry of the Environment, Japan (MOE), launched a nationwide birth cohort study with 100,000 pairs of mothers and children, namely, the Japan Environment and Children's Study (JECS), in 2010. Other countries have also started or planned large-scale studies focusing on children's environmental health issues. The MOE initiated dialogue among those countries and groups to discuss and share the various processes, protocols, knowledge, and techniques for future harmonization and data pooling among such studies. The MOE formed the JECS International Liaison Committee in 2011, which plays a primary role in promoting the international collaboration between JECS and the other children's environmental health research projects and partnership with other countries. This review article aims to present activities that JECS has developed. As one of the committee's activities, a workshop and four international symposia were held between 2011 and 2015 in Japan. In these conferences, international researchers and government officials, including those from the World Health Organization, have made presentations on their own birth cohort studies and health policies. In 2015, the MOE hosted the International Advisory Board meeting and received constructive comments and recommendations from the board. JECS is a founding member of the Environment and Child Health International Birth Cohort Group, and has discussed harmonization of exposure and outcome measurements with member parties, which will make it possible to compare and further combine data from different studies, considering the diversity in the

  20. Global analysis of transcription in castration-resistant prostate cancer cells uncovers active enhancers and direct androgen receptor targets.

    Science.gov (United States)

    Toropainen, Sari; Niskanen, Einari A; Malinen, Marjo; Sutinen, Päivi; Kaikkonen, Minna U; Palvimo, Jorma J

    2016-09-19

    Androgen receptor (AR) is a male sex steroid-activated transcription factor (TF) that plays a critical role in prostate cancers, including castration-resistant prostate cancers (CRPC) that typically express amplified levels of the AR. CRPC-derived VCaP cells display an excessive number of chromatin AR-binding sites (ARBs) most of which localize to distal inter- or intragenic regions. Here, we analyzed direct transcription programs of the AR in VCaP cells using global nuclear run-on sequencing (GRO-seq) and integrated the GRO-seq data with the ARB and VCaP cell-specific TF-binding data. Androgen immediately activated transcription of hundreds of protein-coding genes, including IGF-1 receptor and EGF receptor. Androgen also simultaneously repressed transcription of a large number of genes, including MYC. As functional enhancers have been postulated to produce enhancer-templated non-coding RNAs (eRNAs), we also analyzed the eRNAs, which revealed that only a fraction of the ARBs reside at functional enhancers. Activation of these enhancers was most pronounced at the sites that also bound PIAS1, ERG and HDAC3, whereas binding of HDAC3 and PIAS1 decreased at androgen-repressed enhancers. In summary, our genome-wide data of androgen-regulated enhancers and primary target genes provide new insights how the AR can directly regulate cellular growth and control signaling pathways in CPRC cells.

  1. Combustion synthesized TiO2 for enhanced photocatalytic activity under the direct sunlight-optimization of titanylnitrate synthesis

    International Nuclear Information System (INIS)

    Daya Mani, A.; Laporte, V.; Ghosal, P.; Subrahmanyam, Ch.

    2012-01-01

    Graphical abstract: Effect of oxidant on the combustion synthesis of TiO 2 has been studied by preparing titanylnitrate in four different ways from Ti(IV) iso-propoxide. It is observed that oxidant preparation method has a significant effect on physico-chemical as well as photocatalytic properties of TiO 2 . All the catalysts showed excellent photocatalytic activity than Degussa P-25 under direct sunlight for the degradation of a textile dye (methylene blue), without the need of external light sources, oxygen supply and reactor systems. Highlights: ► Optimized synthesis of titanylnitrate. ► Influence of titanylnitrate synthesis on the physico-chemical properties of TiO 2 prepared by combustion synthesis. ► Development of highly efficient TiO 2 photocatalysts those are active under the direct sunlight in open atmosphere. ► Degradation of the textile dye (methylene blue) under direct sunlight. -- Abstract: Optimized synthesis of Ti-precursor ‘titanylnitrate’ for one step combustion synthesis of N- and C-doped TiO 2 catalysts were reported and characterized by using powder X-ray diffraction (XRD), transmission electron microscopy (TEM), diffused reflectance UV–vis spectroscopy, N 2 adsorption and X-ray photoelectron spectroscopy (XPS). XRD confirmed the formation of TiO 2 anatase and nano-crystallite size which was further confirmed by TEM. UV-DRS confirmed the decrease in the band gap to less than 3.0 eV, which was assigned due to the presence of C and N in the framework of TiO 2 as confirmed by X-ray photoelectron spectroscopy. Degradation of methylene blue in aqueous solution under the direct sunlight was carried out and typical results indicated the better performance of the synthesized catalysts than Degussa P-25.

  2. Influence of anodal transcranial direct current stimulation (tDCS over the right angular gyrus on brain activity during rest.

    Directory of Open Access Journals (Sweden)

    Benjamin Clemens

    Full Text Available Although numerous studies examined resting-state networks (RSN in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG. We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI. Significant differences between two fMRI sessions (pre-tDCS and post-tDCS were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site.

  3. Protein-directed gold nanoparticles with excellent catalytic activity for 4-nitrophenol reduction.

    Science.gov (United States)

    Liu, Kewei; Han, Lei; Zhuang, Junyang; Yang, Da-Peng

    2017-09-01

    To explore high-performance noble metal nanomaterials for the reduction of the biotoxin 4-nitrophenol (4-NP) in medicine, we developed a green synthesis strategy of bovine serum albumin-stabilized Au nanoparticles (Au@BSA NPs). The as-synthesized Au@BSA NPs were characterized by ultraviolet-visible absorption spectrum, fourier transformed infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The functional bio-nanocomposites showed Au-protein core-shell structure and uniform distribution, and their sizes were dependent on the additive amount of HAuCl 4 . Interestingly, Au@BSA NPs showed remarkable catalytic activity for the reduction of 4-NP into 4-aminophenol in the presence of sodium borohydride. Due to the introduction of Au@BSA NPs, the reduction reaction could be conducted at ambient temperature and pressure without any additional conditions. Moreover, the reduction rate was closely related to the sizes of NPs and reaction temperature, and the catalytic mechanism was verified to follow the pseudo-first-order kinetics. Due to the environmentally friendly synthesis process and green reduction strategy of 4-NP, Au@BSA NPs would show great potential in governance of the biotoxin in medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Pharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation.

    Science.gov (United States)

    Zhang, Mingliang; Lin, Yuan-Hung; Sun, Yujiao Jennifer; Zhu, Saiyong; Zheng, Jiashun; Liu, Kai; Cao, Nan; Li, Ke; Huang, Yadong; Ding, Sheng

    2016-05-05

    Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small-molecule approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine components (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts toward a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study provides an effective chemical approach for generating neural stem cells from mouse fibroblasts and reveals mechanistic insights into underlying reprogramming processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease.

    Science.gov (United States)

    Peng, Ruoqi; Sridhar, Sriram; Tyagi, Gaurav; Phillips, Jonathan E; Garrido, Rosario; Harris, Paul; Burns, Lisa; Renteria, Lorena; Woods, John; Chen, Leena; Allard, John; Ravindran, Palanikumar; Bitter, Hans; Liang, Zhenmin; Hogaboam, Cory M; Kitson, Chris; Budd, David C; Fine, Jay S; Bauer, Carla M T; Stevenson, Christopher S

    2013-01-01

    The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGFβ was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease.

  6. Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease.

    Directory of Open Access Journals (Sweden)

    Ruoqi Peng

    Full Text Available The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF, has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGFβ was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease.

  7. The standard model and some new directions. [for scientific theory of Active Galactic Nuclei

    Science.gov (United States)

    Blandford, R. D.; Rees, M. J.

    1992-01-01

    A 'standard' model of Active Galactic Nuclei (AGN), based upon a massive black hole surrounded by a thin accretion disk, is defined. It is argued that, although there is good evidence for the presence of black holes and orbiting gas, most of the details of this model are either inadequate or controversial. Magnetic field may be responsible for the confinement of continuum and line-emitting gas, for the dynamical evolution of accretion disks and for the formation of jets. It is further argued that gaseous fuel is supplied in molecular form and that this is responsible for thermal re-radiation, equatorial obscuration and, perhaps, the broad line gas clouds. Stars may also supply gas close to the black hole, especially in low power AGN and they may be observable in discrete orbits as probes of the gravitational field. Recent observations suggest that magnetic field, stars, dusty molecular gas and orientation effects must be essential components of a complete description of AGN. The discovery of quasars with redshifts approaching 5 is an important clue to the mechanism of galaxy formation.

  8. Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.

    Directory of Open Access Journals (Sweden)

    Laura M J Ylinen

    2010-08-01

    Full Text Available TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.

  9. Hippocampal neural activity reflects the economy of choices during goal-directed navigation.

    Science.gov (United States)

    Tryon, Valerie L; Penner, Marsha R; Heide, Shawn W; King, Hunter O; Larkin, Joshua; Mizumori, Sheri J Y

    2017-07-01

    Distinguishing spatial contexts is likely essential for the well-known role of the hippocampus in episodic memory. We studied whether types of hippocampal neural organization thought to underlie context discrimination are impacted by learned economic considerations of choice behavior. Hippocampal place cells and theta activity were recorded as rats performed a maze-based probability discounting task that involved choosing between a small certain reward or a large probabilistic reward. Different spatial distributions of place fields were observed in response to changes in probability, the outcome of the rats' choice, and whether or not rats were free to make that choice. The degree to which the reward location was represented by place cells scaled with the expected probability of rewards. Theta power increased around the goal location also in proportion to the expected probability of signaled rewards. Furthermore, theta power dynamically varied as specific econometric information was obtained "on the fly" during task performance. Such an economic perspective of memory processing by hippocampal place cells expands our view of the nature of context memories retrieved by hippocampus during adaptive navigation. © 2017 Wiley Periodicals, Inc.

  10. Silver nanoparticles directly formed on natural macroporous matrix and their anti-microbial activities

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Fang [Research Institute of Materials Science, South China University of Technology, Guangzhou 510640 (China); Hou Chao [Research Institute of Materials Science, South China University of Technology, Guangzhou 510640 (China); Wu Shuizhu [Research Institute of Materials Science, South China University of Technology, Guangzhou 510640 (China); Liu Xinxing [Research Institute of Materials Science, South China University of Technology, Guangzhou 510640 (China); Tong Zhen [Research Institute of Materials Science, South China University of Technology, Guangzhou 510640 (China); Yu Shuning [Guangdong Detection Center for Microbiology, Guangzhou 510070 (China)

    2007-02-07

    In this study, silver nanoparticles were formed on a natural macroporous matrix, the stem of rice-paper plant, by reducing Ag{sup +} in aqueous solution through in situ processing without using any other stabilizers. The pores of the matrix, with their size of about 100 {mu}m, were thought to act as reaction compartments for the nucleation and growth of silver nanoparticles, and the control of nucleation of silver crystal during the reduction reaction was found to be important to the successful formation of nanosized silver particles onto the matrix. The diameter and amount of resultant silver particles can be controlled by changing the reaction conditions. Under optimized conditions, the content of silver particles in the matrix can reach as high as 1.8 wt% with the particle diameters being kept below 100 nm. The anti-microbial activities in terms of minimum inhibitory concentration (MIC) for the silver nanoparticle composites against Escherichia coli and Candida albicans were assayed in agar gel, and the results show that MIC values for silver nanoparticle composites are 14.1 mg(Ag) l{sup -1} and 28.1 mg(Ag) l{sup -1} for Escherichia coli and Candida albicans respectively, which are comparable to the value for colloidal nanosilver.

  11. Silver nanoparticles directly formed on natural macroporous matrix and their anti-microbial activities

    Science.gov (United States)

    Zeng, Fang; Hou, Chao; Wu, Shuizhu; Liu, Xinxing; Tong, Zhen; Yu, Shuning

    2007-02-01

    In this study, silver nanoparticles were formed on a natural macroporous matrix, the stem of rice-paper plant, by reducing Ag+ in aqueous solution through in situ processing without using any other stabilizers. The pores of the matrix, with their size of about 100 µm, were thought to act as reaction compartments for the nucleation and growth of silver nanoparticles, and the control of nucleation of silver crystal during the reduction reaction was found to be important to the successful formation of nanosized silver particles onto the matrix. The diameter and amount of resultant silver particles can be controlled by changing the reaction conditions. Under optimized conditions, the content of silver particles in the matrix can reach as high as 1.8 wt% with the particle diameters being kept below 100 nm. The anti-microbial activities in terms of minimum inhibitory concentration (MIC) for the silver nanoparticle composites against Escherichia coli and Candida albicans were assayed in agar gel, and the results show that MIC values for silver nanoparticle composites are 14.1 mg(Ag) l-1 and 28.1 mg(Ag) l-1 for Escherichia coli and Candida albicans respectively, which are comparable to the value for colloidal nanosilver.

  12. Direct control of type IIA topoisomerase activity by a chromosomally encoded regulatory protein.

    Science.gov (United States)

    Vos, Seychelle M; Lyubimov, Artem Y; Hershey, David M; Schoeffler, Allyn J; Sengupta, Sugopa; Nagaraja, Valakunja; Berger, James M

    2014-07-01

    Precise control of supercoiling homeostasis is critical to DNA-dependent processes such as gene expression, replication, and damage response. Topoisomerases are central regulators of DNA supercoiling commonly thought to act independently in the recognition and modulation of chromosome superstructure; however, recent evidence has indicated that cells tightly regulate topoisomerase activity to support chromosome dynamics, transcriptional response, and replicative events. How topoisomerase control is executed and linked to the internal status of a cell is poorly understood. To investigate these connections, we determined the structure of Escherichia coli gyrase, a type IIA topoisomerase bound to YacG, a recently identified chromosomally encoded inhibitor protein. Phylogenetic analyses indicate that YacG is frequently associated with coenzyme A (CoA) production enzymes, linking the protein to metabolism and stress. The structure, along with supporting solution studies, shows that YacG represses gyrase by sterically occluding the principal DNA-binding site of the enzyme. Unexpectedly, YacG acts by both engaging two spatially segregated regions associated with small-molecule inhibitor interactions (fluoroquinolone antibiotics and the newly reported antagonist GSK299423) and remodeling the gyrase holoenzyme into an inactive, ATP-trapped configuration. This study establishes a new mechanism for the protein-based control of topoisomerases, an approach that may be used to alter supercoiling levels for responding to changes in cellular state. © 2014 Vos et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Direct observation of transcription activator-like effector (TALE) protein dynamics

    Science.gov (United States)

    Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M.

    2014-03-01

    In this work, we describe a single molecule assay to probe the site-search dynamics of transcription activator-like effector (TALE) proteins along DNA. In modern genetics, the ability to selectively edit the human genome is an unprecedented development, driven by recent advances in targeted nuclease proteins. Specific gene editing can be accomplished using TALE proteins, which are programmable DNA-binding proteins that can be fused to a nuclease domain. In this way, TALENs are a leading technology that has shown great success in the genomic editing of pluripotent stem cells. A major hurdle facing clinical implementation, however, is the potential for deleterious off-target binding events. For these reasons, a molecular-level understanding of TALE binding and target sequence search on DNA is essential. To this end, we developed a single-molecule fluorescence imaging assay that provides a first-of-its-kind view of the 1-D diffusion of TALE proteins along stretched DNA. Taken together with co-crystal structures of DNA-bound TALEs, our results suggest a rotationally-coupled, major groove tracking model for diffusion. We further report diffusion constants for TALE proteins as a function of salt concentration, consistent with previously described models of 1-D protein diffusion.

  14. Assessing direct paths of intracortical causal information flow of oscillatory activity with the isolated effective coherence (iCoh

    Directory of Open Access Journals (Sweden)

    Roberto D Pascual-Marqui

    2014-06-01

    Full Text Available Functional connectivity is of central importance in understanding brain function. For this purpose, multiple time series of electric cortical activity can be used for assessing the properties of a network: the strength, directionality, and spectral characteristics (i.e. which oscillations are preferentially transmitted of the connections. The partial directed coherence (PDC of Baccala and Sameshima (2001 is a widely used method for this problem. The three aims of this study are: (1 To show that the PDC can misrepresent the frequency response under plausible realistic conditions, thus defeating the main purpose for which the measure was developed; (2 To provide a solution to this problem, namely the isolated effective coherence (iCoh, which consists of estimating the partial coherence under a multivariate autoregressive model, followed by setting all irrelevant associations to zero, other than the particular directional association of interest; and (3 To show that adequate iCoh estimators can be obtained from non-invasively computed cortical signals based on exact low resolution electromagnetic tomography (eLORETA applied to scalp EEG recordings. To illustrate the severity of the problem with the PDC, and the solution achieved by the iCoh, three examples are given, based on: (1 Simulated time series with known dynamics; (2 Simulated cortical sources with known dynamics, used for generating EEG recordings, which are then used for estimating (with eLORETA the source signals for the final connectivity assessment; and (3 EEG recordings in rats. Lastly, real human recordings are analyzed, where the iCoh between six cortical regions of interest are calculated and compared under eyes open and closed conditions, using 61-channel EEG recordings from 109 subjects. During eyes closed, the posterior cingulate sends alpha activity to all other regions. During eyes open, the anterior cingulate sends theta-alpha activity to other frontal regions.

  15. Hoxa9 transduction induces hematopoietic stem and progenitor cell activity through direct down-regulation of geminin protein.

    Science.gov (United States)

    Ohno, Yoshinori; Yasunaga, Shin'ichiro; Janmohamed, Salima; Ohtsubo, Motoaki; Saeki, Keita; Kurogi, Toshiaki; Mihara, Keichiro; Iscove, Norman N; Takihara, Yoshihiro

    2013-01-01

    Hoxb4, a 3'-located Hox gene, enhances hematopoietic stem cell (HSC) activity, while a subset of 5'-located Hox genes is involved in hematopoiesis and leukemogenesis, and some of them are common translocation partners for Nucleoporin 98 (Nup98) in patients with leukemia. Although these Hox gene derivatives are believed to act as transcription regulators, the molecular involvement of the Hox gene derivatives in hematopoiesis and leukemogenesis remains largely elusive. Since we previously showed that Hoxb4 forms a complex with a Roc1-Ddb1-Cul4a ubiquitin ligase core component and functions as an E3 ubiquitin ligase activator for Geminin, we here examined the E3 ubiquitin ligase activities of the 5'-located Hox genes, Hoxa9 and Hoxc13, and Nup98-Hoxa9. Hoxa9 formed a similar complex with the Roc1-Ddb1-Cul4a component to induce ubiquitination of Geminin, but the others did not. Retroviral transduction-mediated overexpression or siRNA-mediated knock-down of Hoxa9 respectively down-regulated or up-regulated Geminin in hematopoietic cells. And Hoxa9 transduction-induced repopulating and clonogenic activities were suppressed by Geminin supertransduction. These findings suggest that Hoxa9 and Hoxb4 differ from Hoxc13 and Nup98-Hoxa9 in their molecular role in hematopoiesis, and that Hoxa9 induces the activity of HSCs and hematopoietic progenitors at least in part through direct down-regulation of Geminin.

  16. Hoxa9 transduction induces hematopoietic stem and progenitor cell activity through direct down-regulation of geminin protein.

    Directory of Open Access Journals (Sweden)

    Yoshinori Ohno

    Full Text Available Hoxb4, a 3'-located Hox gene, enhances hematopoietic stem cell (HSC activity, while a subset of 5'-located Hox genes is involved in hematopoiesis and leukemogenesis, and some of them are common translocation partners for Nucleoporin 98 (Nup98 in patients with leukemia. Although these Hox gene derivatives are believed to act as transcription regulators, the molecular involvement of the Hox gene derivatives in hematopoiesis and leukemogenesis remains largely elusive. Since we previously showed that Hoxb4 forms a complex with a Roc1-Ddb1-Cul4a ubiquitin ligase core component and functions as an E3 ubiquitin ligase activator for Geminin, we here examined the E3 ubiquitin ligase activities of the 5'-located Hox genes, Hoxa9 and Hoxc13, and Nup98-Hoxa9. Hoxa9 formed a similar complex with the Roc1-Ddb1-Cul4a component to induce ubiquitination of Geminin, but the others did not. Retroviral transduction-mediated overexpression or siRNA-mediated knock-down of Hoxa9 respectively down-regulated or up-regulated Geminin in hematopoietic cells. And Hoxa9 transduction-induced repopulating and clonogenic activities were suppressed by Geminin supertransduction. These findings suggest that Hoxa9 and Hoxb4 differ from Hoxc13 and Nup98-Hoxa9 in their molecular role in hematopoiesis, and that Hoxa9 induces the activity of HSCs and hematopoietic progenitors at least in part through direct down-regulation of Geminin.

  17. Hoxa9 Transduction Induces Hematopoietic Stem and Progenitor Cell Activity through Direct Down-Regulation of Geminin Protein

    Science.gov (United States)

    Ohno, Yoshinori; Yasunaga, Shin'ichiro; Janmohamed, Salima; Ohtsubo, Motoaki; Saeki, Keita; Kurogi, Toshiaki; Mihara, Keichiro; Iscove, Norman N.; Takihara, Yoshihiro

    2013-01-01

    Hoxb4, a 3′-located Hox gene, enhances hematopoietic stem cell (HSC) activity, while a subset of 5′-located Hox genes is involved in hematopoiesis and leukemogenesis, and some of them are common translocation partners for Nucleoporin 98 (Nup98) in patients with leukemia. Although these Hox gene derivatives are believed to act as transcription regulators, the molecular involvement of the Hox gene derivatives in hematopoiesis and leukemogenesis remains largely elusive. Since we previously showed that Hoxb4 forms a complex with a Roc1-Ddb1-Cul4a ubiquitin ligase core component and functions as an E3 ubiquitin ligase activator for Geminin, we here examined the E3 ubiquitin ligase activities of the 5′-located Hox genes, Hoxa9 and Hoxc13, and Nup98-Hoxa9. Hoxa9 formed a similar complex with the Roc1-Ddb1-Cul4a component to induce ubiquitination of Geminin, but the others did not. Retroviral transduction-mediated overexpression or siRNA-mediated knock-down of Hoxa9 respectively down-regulated or up-regulated Geminin in hematopoietic cells. And Hoxa9 transduction-induced repopulating and clonogenic activities were suppressed by Geminin supertransduction. These findings suggest that Hoxa9 and Hoxb4 differ from Hoxc13 and Nup98-Hoxa9 in their molecular role in hematopoiesis, and that Hoxa9 induces the activity of HSCs and hematopoietic progenitors at least in part through direct down-regulation of Geminin. PMID:23326393

  18. Shallow vent architecture of Puyehue Cordón-Caulle, as revealed by direct observation of explosive activity

    Science.gov (United States)

    Schipper, C. I.; Tuffen, H.; Castro, J. M.

    2012-04-01

    On June 4, 2011, an explosive eruption of rhyodacitic magma began at the Puyehue Cordón-Caulle volcanic complex (PCCVC), southern Chile. Initial Plinian phases of the eruption produced tephra plumes reaching > 14 km high, the ash from which quickly circumnavigated the globe to cause widespread disruption to air traffic in the Southern Hemisphere. Within two weeks, the continuing explosive eruption was joined by synchronous effusion of lava. We present observations of complex vent activity made 7 months after the eruption onset, on January 4th and 10th, 2012, when explosive activity from PCCVC continued at a lower level of intensity. Fortuitous climatic conditions permitted direct, ground-based observation and video recording of transient vent dynamics within the asymmetrical tephra cone around the main eruptive vent complex and site of lava effusion, as well as real-time collection of juvenile ash as it rained out directly from the active plume. On Jan. 4, explosive activity was semi-continuous ash jetting punctuated by Vulcanian-like blasts. In the ~50m-diameter sub-circular base of the ~400 m-wide, asymmetrical tephra cone, near-continuous ash jetting was observed from two primary point sources. The northerly source was clearly visible, with time-averaged diameter of ~10 m, and the apparently larger southerly source was mostly obscured from view by the ash plume. Activity was at all times somewhat erratic, but followed a rough cyclicity on 30-45 s timescales, consisting of: (1) restriction of the point source into a focused ash jet up to ~50 m high, producing coarse ash dominated by tube pumice (with minor free pyroxene crystals); followed by (2) Vulcanian-like failure of the region around the point source, producing incandescent ballistic bombs thrown up to 100-200 m from the vent. Jetting from the two main point sources combined in the crater to produce a low gas-thrust region and sustained buoyant plume. Directed ash plumes that climbed and breached the inner

  19. Structural and Functional Studies Indicate That the EPEC Effector, EspG, Directly Binds p21-Activated Kinase

    Energy Technology Data Exchange (ETDEWEB)

    Germane, Katherine L.; Spiller, Benjamin W. (Vanderbilt)

    2011-09-20

    Bacterial pathogens secrete effectors into their hosts that subvert host defenses and redirect host processes. EspG is a type three secretion effector with a disputed function that is found in enteropathogenic Escherichia coli. Here we show that EspG is structurally similar to VirA, a Shigella virulence factor; EspG has a large, conserved pocket on its surface; EspG binds directly to the amino-terminal inhibitory domain of human p21-activated kinase (PAK); and mutations to conserved residues in the surface pocket disrupt the interaction with PAK.

  20. Active site-directed alkylation of Na+-K+-ATPase by digitalis sulphonate derivatives of different lipophilicity.

    Science.gov (United States)

    Fricke, U.; Klaus, W.; Rogatti, M.

    1981-01-01

    1 Sulphonate derivatives of k-strophanthidin and digitoxigenin were tested as active site-directed labels of Na+-K+-adenosine triphosphatase (Na+-ATPase) from guinea-pig heart. 2 Lipophilicity ranged between P = 93 for strophanthidin-3-tosyloxy-acetate (STA) and P = 3028 for digitoxigenin-3-tosyloxy-acetate (DTA). 3 Although the alkylating moiety of STA and DTA was identical, the reversibility of Na+-K+-ATPase inhibition varied appreciably (82% and 35% respectively). 4 It is concluded that lipophilicity contributes considerably to the irreversible binding of alkylating cardiotonic steroids to myocardial Na+-K+-ATPase. PMID:6261865

  1. Thrombolysis by intravenous tissue plasminogen activator (t-PA). Current status and future direction

    International Nuclear Information System (INIS)

    Tanahashi, Norio

    2009-01-01

    In Japan, the intravenous tissue plasminogen activator (t-PA) Alteplase (0.6 mg/kg) administration of the within 3 h of the onset of acute ischemic stroke was approved for therapeutic use in the year 2006. t-PA induces thrombolysis in patients with acute ischemic stroke, and this method has gradually gained recognition among physicians and the general population. However, the number of patients who were treated using Alteplase is low (4,000-5,000 patients/year), and this figure accounts for only 2-3% of the annual number of cases of ischemic stroke. There is little doubt that Alteplase treatment is a potentially effective modality for some patients with acute ischemic stroke. The post-marketing surveillance of 4,749 Japanese patients treated using Alteplase showed that 33% of the patients had modified Rankin scale (mRS) scores of 0-1, 17% of patients died and 4.5% presented with symptomatic intracerebral hemorrhage (ICH); these results were comparable to those from other countries. The expansion of the therapeutic time window has been a matter of concern. The investigators of the European Cooperative Acute Stroke Study (ECASS) have reported that there was significant improvement in the clinical outcomes of patients with acute ischemie stroke when Alteplase was administered 3-4.5 h after the onset of the symptoms. Mismatches in perfusion- and diffusion-weighted (DW) magnetic resonance imaging (MRI) images have been used for selecting patients 3 h after the onset of symptoms, and the findings from MRI, dwimages (DWI) and MR angiography are practical predictors of t-PA therapy within 3 h of onset. The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan study showed that local intra-arterial fibrinolysis is effective in patients with embolic MCA occlusion within 6 h of the onset of symptoms. Combining the initiation of intravenous t-PA administration with further intra-arterial fibrinolysis or mechanical thrombolectomy may improve the

  2. Evaluation of 210Pb air activity concentration by direct gamma-ray spectrometry of air particulate samplings

    International Nuclear Information System (INIS)

    Rizzo, S.; Tomarchio, E.

    2007-01-01

    Main measurement techniques adopted to evaluate 210 PB air activity concentration differ in analysis and sample preparation methods. Some of them involved complex chemical processes or decay product detection (for example 210 Po), with a long decay time period between sampling and experimental measurement. The availability of a low-background gamma-ray spectrometric system, suitable to measure low-energy gamma radiations, allows the evaluation of 210 PB air activity concentration by direct gamma countings of particulate samplings after a short time period from the end of the sampling. The measurement procedure described in this work consists in the following steps: o Sampling of air particulate and recording of sampling data; o Fast reduction of the sample to measurement geometry; o Gamma-ray spectrometric measurement (or a series of measurements) after a minimum decay time period from the end of sampling; o A new gamma-ray spectrometric measurement, with reference to 46.5 keV gamma emission of 210 PB, after a few days from the sampling; o Comparison with a model to evaluate the 210 PB activity percentage produced by decay of short-lived radon daughters on the filter matrix during and after the sampling; o Determination of 210 PB net activity and derived air concentration. Experimental tests have allowed obtaining a range of 2†10 per cent for 210 PB activity percentage on a filter due to decay of short-lived radon daughters, with higher values when 210 PB air activity concentration is very low. All the measurements resulted above detection limit, even in the case of a short sampling time period. A statistical improvement on 210 PB activity can be obtained with a longer sampling time period, without any modification on the procedure and results. (Author)

  3. Project of the borehole neutron generator for the direct determination of oxygen and carbon by activation method

    Science.gov (United States)

    Bogdanovich, B. Yu; Vovchenko, E. D.; Iliinskiy, A. V.; Isaev, A. A.; Kozlovskiy, K. I.; Nesterovich, A. V.; Senyukov, V. A.; Shikanov, A. E.

    2016-09-01

    The paper deals with application features of borehole neutron generator (BNG) based on the vacuum accelerating tube (AT) with laser-plasma ion source for determination of oxygen isotope 16O and carbon isotope 12C by direct activation. The project of pulsed BNG for realization of an activation method in the conditions of natural presence of productive hydrocarbons is offered. The diode system with radial acceleration, magnetic electron insulation and laser-plasma source of deuterons at the anode in a sealed-off vacuum accelerating tube is applied. The permanent NdFeB magnet with induction about 0.5 T for produce the insulating magnetic field in the diode gap is proposed. In the experiments on the model of BNG with the accelerating voltage source (≈350 kV), performed by the scheme of Arkadiev-Marx generator, the output of (d, d) neutrons was ∼107 pulse-1.

  4. Direct current (DC) resistivity and Induced Polarization (IP) monitoring of active layer dynamics at high temporal resolution

    DEFF Research Database (Denmark)

    Doetsch, J.; Fiandaca, G.; Ingeman-Nielsen, Thomas

    2015-01-01

    With permafrost thawing and changes in active layer dynamics induced by climate change, interactions between biogeochemical and thermal processes in the ground are of great importance. Here, active layer dynamics have been monitored using direct current (DC) resistivity and induced polarization (...... non-intrusively and reliably image freezing patterns and their lateral variation on a 10-100 m scale that is difficult to sample by point measurements.......) measurements at high temporal resolution at a heath tundra site on Disko Island on the west coast of Greenland (69°N). Borehole sediment characteristics and subsurface temperatures supplemented the DC-IP measurements. Data acquired during the freezing period of October 2013 – February 2014 clearly image...... the soil freezing as a strong increase in resistivity. While the freezing horizon generally moves deeper with time, some variations in the freezing depth are observed along the profile. Comparison with depth-specific soil temperature indicates an exponential relationship between resistivity and below-freezing...

  5. Direct Imaging by Cryo-TEM Shows Membrane Break-up by Phospholipase A2 Enzymatic Activity

    DEFF Research Database (Denmark)

    Callisen, Thomas Hønger; Talmon, Y.

    1998-01-01

    increase our insight into the function of PLA2 under physiological conditions as well as into general interfacial catalysis. In the present study we apply for the first time cryo-transmission electron microscopy (cryo-TEM) and high-performance liquid chromatography (HPLC) to characterize the PLA2...... hydrolysis of phospholipid vesicles with respect to changes in lipid composition and morphology. Our direct experimental results show that the initial reaction conditions are strongly perturbed during the course of hydrolysis, Most strikingly, cryo-TEM reveals that starting in the lag phase, vesicles become...... perforated and degrade into open vesicles, bilayer fragments, and micelles, This structural instability extends throughout the system in the activity burst regime. In agreement with earlier reported correlations between initial phospholipase activity and substrate morphology, our results suggest that the lag...

  6. Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity

    Directory of Open Access Journals (Sweden)

    Leticia Corrales

    2015-05-01

    Full Text Available Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. On the basis of recent observations indicating that IFN-β expression was dependent upon activation of the host STING pathway, we hypothesized that direct engagement of STING through intratumoral (IT administration of specific agonists would result in effective anti-tumor therapy. After proof-of-principle studies using the mouse STING agonist DMXAA showed a potent therapeutic effect, we generated synthetic cyclic dinucleotide (CDN derivatives that activated all human STING alleles as well as murine STING. IT injection of STING agonists induced profound regression of established tumors in mice and generated substantial systemic immune responses capable of rejecting distant metastases and providing long-lived immunologic memory. Synthetic CDNs have high translational potential as a cancer therapeutic.

  7. New insights into the aquatic photochemistry of fluoroquinolone antibiotics: Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Linke; Na, Guangshui [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Siyu [Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016 (China); Li, Kai [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Peng, E-mail: pzhang@nmemc.org.cn [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Ren, Honglei; Yao, Ziwei [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China)

    2015-09-15

    The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface waters urge new insights into their aqueous photochemical behavior. This study concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate their solar direct photodegradation half-lives (t{sub d,E}) and hydroxyl-radical oxidation half-lives (t{sub ·OH,E}) in sunlit surface waters. The t{sub d,E} values range from 0.56 min to 28.8 min at 45° N latitude, whereas t{sub ·OH,E} ranges from 3.24 h to 33.6 h, suggesting that most FQs tend to undergo fast direct photolysis rather than hydroxyl-radical oxidation in surface waters. However, a case study for levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation induced risky photochlorination and resulted in multi-degradation pathways, such as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity of FQs caused by photodegradation in various waters were further examined using Escherichia coli, and it was found that the activity evolution depended on primary photodegradation pathways and products. Primary intermediates with intact FQ nuclei retained significant antibacterial activity. These results are important for assessing the fate and risk of FQs in surface waters. - Highlights: • It is first reported on hydroxyl-radical oxidation of 6 fluoroquinolone antibiotics. • Methods were developed to assess photolysis and oxidation fate in surface waters. • The neutral form reacted faster with hydroxyl radical than protonated forms. • The main oxidation intermediates and transformation pathways were clarified. • The antibacterial activity changes depend on dominant photolysis pathways.

  8. Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels

    Science.gov (United States)

    Hristov, Kiril L.; Parajuli, Shankar P.; Provence, Aaron

    2016-01-01

    In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability. Testosterone (100 nM) significantly increased the depolarization-induced whole cell outward currents in DSM cells. The selective pharmacological inhibition of the large-conductance voltage- and Ca2+-activated K+ (BK) channels with paxilline (1 μM) completely abolished this stimulatory effect of testosterone, suggesting a mechanism involving BK channels. At a holding potential of −20 mV, DSM cells exhibited transient BK currents (TBKCs). Testosterone (100 nM) significantly increased TBKC activity in DSM cells. In current-clamp mode, testosterone (100 nM) significantly hyperpolarized the DSM cell resting membrane potential and increased spontaneous transient hyperpolarizations. Testosterone (100 nM) rapidly increased the single BK channel open probability in inside-out excised membrane patches from DSM cells, clearly suggesting a direct BK channel activation via a nongenomic mechanism. Live-cell Ca2+ imaging showed that testosterone (100 nM) caused a decrease in global intracellular Ca2+ concentration, consistent with testosterone-induced membrane hyperpolarization. In conclusion, the data provide compelling mechanistic evidence that under physiological conditions, testosterone at nanomolar concentrations directly activates BK channels in DSM cells, independent from genomic testosterone receptors, and thus regulates DSM excitability. PMID:27605581

  9. New insights into the aquatic photochemistry of fluoroquinolone antibiotics: Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes

    International Nuclear Information System (INIS)

    Ge, Linke; Na, Guangshui; Zhang, Siyu; Li, Kai; Zhang, Peng; Ren, Honglei; Yao, Ziwei

    2015-01-01

    The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface waters urge new insights into their aqueous photochemical behavior. This study concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate their solar direct photodegradation half-lives (t d,E ) and hydroxyl-radical oxidation half-lives (t ·OH,E ) in sunlit surface waters. The t d,E values range from 0.56 min to 28.8 min at 45° N latitude, whereas t ·OH,E ranges from 3.24 h to 33.6 h, suggesting that most FQs tend to undergo fast direct photolysis rather than hydroxyl-radical oxidation in surface waters. However, a case study for levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation induced risky photochlorination and resulted in multi-degradation pathways, such as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity of FQs caused by photodegradation in various waters were further examined using Escherichia coli, and it was found that the activity evolution depended on primary photodegradation pathways and products. Primary intermediates with intact FQ nuclei retained significant antibacterial activity. These results are important for assessing the fate and risk of FQs in surface waters. - Highlights: • It is first reported on hydroxyl-radical oxidation of 6 fluoroquinolone antibiotics. • Methods were developed to assess photolysis and oxidation fate in surface waters. • The neutral form reacted faster with hydroxyl radical than protonated forms. • The main oxidation intermediates and transformation pathways were clarified. • The antibacterial activity changes depend on dominant photolysis pathways

  10. Features and amenities of school playgrounds: A direct observation study of utilization and physical activity levels outside of school time

    Directory of Open Access Journals (Sweden)

    Swayampakala Kamala

    2011-04-01

    Full Text Available Abstract Background A significant amount of research has examined whether park or playground availability is associated with physical activity. However, little research has examined whether specific features or amenities of parks or playgrounds, such as the number of unique types of playground equipment or the safety of the equipment is associated with utilization of the facility or physical activity levels while at the facility. There are no studies that use direct observation and a detailed park assessment to examine these associations. Methods Twenty urban schoolyards in the Midwest, ten of which were renovated, were included in this study. Using a detailed environmental assessment tool (i.e., Environmental Assessment of Public Recreation Spaces, information on a variety of playground attributes was collected. Using direct observation (i.e., System for Observing Play and Leisure Activity in Youth, the number of adults, girls and boys attending each schoolyard and their physical activity levels were recorded. Each schoolyard was observed ten times for 90 minutes each time outside of school hours. Clustered multivariable negative binomial regressions and linear regressions were completed to examine the association between playground attributes and utilization of the schoolyard and the proportion active on the playground, respectively. Effect modification by renovation status was also examined. Results At renovated schoolyards, the total number of play features was significantly associated with greater utilization in adults and girls; overall cleanliness was significantly associated with less utilization in girls and boys; and coverage/shade for resting features was significantly associated with greater utilization in adults and boys. At unrenovated schoolyards, overall safety was significantly associated with greater utilization in boys. No playground attribute was associated with the proportion active on the playground after adjusting for all

  11. Features and amenities of school playgrounds: a direct observation study of utilization and physical activity levels outside of school time.

    Science.gov (United States)

    Colabianchi, Natalie; Maslow, Andréa L; Swayampakala, Kamala

    2011-04-14

    A significant amount of research has examined whether park or playground availability is associated with physical activity. However, little research has examined whether specific features or amenities of parks or playgrounds, such as the number of unique types of playground equipment or the safety of the equipment is associated with utilization of the facility or physical activity levels while at the facility. There are no studies that use direct observation and a detailed park assessment to examine these associations. Twenty urban schoolyards in the Midwest, ten of which were renovated, were included in this study. Using a detailed environmental assessment tool (i.e., Environmental Assessment of Public Recreation Spaces), information on a variety of playground attributes was collected. Using direct observation (i.e., System for Observing Play and Leisure Activity in Youth), the number of adults, girls and boys attending each schoolyard and their physical activity levels were recorded. Each schoolyard was observed ten times for 90 minutes each time outside of school hours. Clustered multivariable negative binomial regressions and linear regressions were completed to examine the association between playground attributes and utilization of the schoolyard and the proportion active on the playground, respectively. Effect modification by renovation status was also examined. At renovated schoolyards, the total number of play features was significantly associated with greater utilization in adults and girls; overall cleanliness was significantly associated with less utilization in girls and boys; and coverage/shade for resting features was significantly associated with greater utilization in adults and boys. At unrenovated schoolyards, overall safety was significantly associated with greater utilization in boys. No playground attribute was associated with the proportion active on the playground after adjusting for all other significant playground attributes. Having a

  12. Activity of platinum/carbon and palladium/carbon catalysts promoted by Ni2 P in direct ethanol fuel cells.

    Science.gov (United States)

    Li, Guoqiang; Feng, Ligang; Chang, Jinfa; Wickman, Björn; Grönbeck, Henrik; Liu, Changpeng; Xing, Wei

    2014-12-01

    Ethanol is an alternative fuel for direct alcohol fuel cells, in which the electrode materials are commonly based on Pt or Pd. Owing to the excellent promotion effect of Ni2 P that was found in methanol oxidation, we extended the catalyst system of Pt or Pd modified by Ni2 P in direct ethanol fuel cells. The Ni2 P-promoted catalysts were compared to commercial catalysts as well as to reference catalysts promoted with only Ni or only P. Among the studied catalysts, Pt/C and Pd/C modified by Ni2 P (30 wt %) showed both the highest activity and stability. Upon integration into the anode of a homemade direct ethanol fuel cell, the Pt-Ni2 P/C-30 % catalyst showed a maximum power density of 21 mW cm(-2) , which is approximately two times higher than that of a commercial Pt/C catalyst. The Pd-Ni2 P/C-30 % catalyst exhibited a maximum power density of 90 mW cm(-2) . This is approximately 1.5 times higher than that of a commercial Pd/C catalyst. The discharge stability on both two catalysts was also greatly improved over a 12 h discharge operation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Direct and Sensitive Detection of CWA Simulants by Active Capillary Plasma Ionization Coupled to a Handheld Ion Trap Mass Spectrometer

    Science.gov (United States)

    Wolf, Jan-Christoph; Etter, Raphael; Schaer, Martin; Siegenthaler, Peter; Zenobi, Renato

    2016-07-01

    An active capillary plasma ionization (ACI) source was coupled to a handheld mass spectrometer (Mini 10.5; Aston Labs, West Lafayette, IN, USA) and applied to the direct gas-phase detection and quantification of chemical warfare agent (CWA) related chemicals. Complementing the discontinuous atmospheric pressure interface (DAPI) of the Mini 10.5 mass spectrometer with an additional membrane pump, a quasi-continuous sample introduction through the ACI source was achieved. Nerve agent simulants (three dialkyl alkylphosphonates, a dialkyl phosporamidate, and the pesticide dichlorvos) were detected at low gas-phase concentrations with limits of detection ranging from 1.0 μg/m3 to 6.3 μg/m3. Our results demonstrate a sensitivity enhancement for portable MS-instrumentation by using an ACI source, enabling direct, quantitative measurements of volatile organic compounds. Due to its high sensitivity, selectivity, low power consumption (<80 W) and weight (<13 kg), this instrumentation has the potential for direct on-site CWA detection as required by military or civil protection.

  14. Direct determination of thermodynamic activities of gold in the systems gold-palladium and gold-silver-palladium

    International Nuclear Information System (INIS)

    Hoehn, R.; Herzig, C.

    1986-01-01

    The thermodynamic activity of the gold component was directly measured in Au-Pd alloys in the concentration range between X Au =0.048 and 0.850 and in the temperature range 1070 and 1300 K. The ratio of the vapour pressures of pure gold and of the gold component of the alloys was determined - after effusion from a Knudsen twin cell and condensation on a collecting plate - by analysing the decay rate of the radioisotopes 195 Au and 198 Au in an intrinsic germanium well-type detector. The partial mixing enthalpy and the partial mixing entropy of Au were directly obtained from these results. By Gibbs-Duhem integration the integral mixing functions were deduced. Similar measurements were performed in several ternary Au-Ag-Pd alloys of fixed mole fraction X Ag /X Pd =1/9. A comparison of the directly measured partial free excess enthalpy of Au in these ternary alloys with data obtained by the approximate models of Kohler, Toop and Bonnier using data of the corresponding three binary systems yields satisfactory agreement. (orig.) [de

  15. Adsorption behavior of direct red 80 and congo red onto activated carbon/surfactant: Process optimization, kinetics and equilibrium

    Science.gov (United States)

    Cheng, Zhengjun; Zhang, Lei; Guo, Xiao; Jiang, Xiaohui; Li, Tian

    2015-02-01

    Adsorptions of congo red and direct red 80 onto activated carbon/surfactant from aqueous solution were optimized. The Box-Behnken design (BBD) has been employed to analyze the effects of concentration of surfactant, temperature, pH, and initial concentration of the dye in the adsorption capacity. Their corresponding experimental data could be evaluated excellently by second order polynomial regression models and the two models were also examined based on the analysis of variance and t test statistics, respectively. The optimum conditions were obtained as follows: Cs = 34.10 μM, T = 50 °C, pH = 3.5, and CCR = 160 mg/L for the congo red system, and Cs = 34.10 μM, T = 50 °C, pH = 6.1, and CDR80 = 110 mg/L for the direct red 80 system. And in these conditions, the measured experimental maximum adsorption capacities for the congo red and direct red 80 removals were 769.48 mg/g and 519.90 mg/g, which were consistent with their corresponding predicted values, with small relative errors of -2.81% and -0.67%, respectively. The adsorption equilibrium and kinetics for the two dye adsorptions onto AC/DDAC were also investigated. The experimental data were fitted by four isotherm models, and Langmuir model presented the best fit. The kinetic studies indicated that the kinetic data followed the pseudo-second-order model.

  16. Direct effect of chronic hypoxia in suppressing large conductance Ca(2+)-activated K(+) channel activity in ovine uterine arteries via increasing oxidative stress.

    Science.gov (United States)

    Hu, Xiang-Qun; Huang, Xiaohui; Xiao, Daliao; Zhang, Lubo

    2016-01-15

    Chronic hypoxia has a direct effect in down-regulating the BKCa channel β1 subunit and inhibiting the BKCa channel activity in uterine arteries of pregnant sheep. Oxidative stress plays a causal role in hypoxia-mediated suppression of BKCa channel function. The steroid hormone-induced effect on BKCa channels is a target of hypoxia-mediated oxidative stress. Inhibition of oxidative stress ameliorates the adverse effect of hypoxia both ex vivo and in vivo in pregnant sheep exposed to long-term high-altitude hypoxia. Our findings provide novel evidence of a causative role of oxidative stress in hypoxia-mediated inhibition of the BKCa channel activity in uterine arteries and new insights in understanding and alleviating pregnancy complications associated with gestational hypoxia such as pre-eclampsia and fetal growth restriction. Uterine arteries of pregnant sheep acclimatized to long-term high-altitude hypoxia were associated with a decrease in large-conductance Ca(2+)-activated K(+) (BKCa) channel activity. The present study tested the hypothesis that prolonged hypoxia has a direct effect in suppressing BKCa channel activity by increasing oxidative stress. Uterine arteries were isolated from non-pregnant and near-term (∼142 days) pregnant sheep, and were treated ex vivo with 21.0 or 10.5% O2 for 48 h. The hypoxia treatment significantly increased the production of reactive oxygen species in uterine arteries, which was blocked by N-acetylcysteine. In uterine arteries of pregnant sheep, hypoxia significantly inhibited BKCa channel current density, decreased NS1619-induced relaxations and increased pressure-dependent tone, which were annulled by N-acetylcysteine. In accordance, hypoxia resulted in down-regulation of BKCa channel β1 subunit, which was restored in the presence of N-acetylcysteine. In addition, the N-acetylcysteine treatment significantly increased BKCa channel β1 subunit abundance and BKCa channel current density in uterine arteries from pregnant

  17. DIRECTIONS OF PREPARATION OF FUTURE TEACHERS TO THE USE OF DISTANCE LEARNING TECHNOLOGIES IN PROFESSIONAL ACTIVITY (PRAXIOLOGICAL ASPECT OF THE ACTIVITY APPROACH

    Directory of Open Access Journals (Sweden)

    Tatyana A. Boronenko

    2015-01-01

    Full Text Available The aim of the article is to demonstrate the need of preparing future teachers to use distance learning technologies in the professional activities. Introduction in educational process of distance learning technologies contributes to improving the quality of education. Methods. The authors’ technique of preparation of students of pedagogical specialities to work in the information-educational environment is designed on the basis of the analysis and generalisation of numerous scientific publications. Results. The system of training to implementation of the distance learning technologies in the teaching activity is developed and described, consisting of the following directions: realisation within the program of the principal educational program of specialised training courses in variable-based curriculum parts; the organisation of educational and research activity of students with the use of distance learning technologies; classroom-based and extracurricular independent work of students directed to designing of teaching and learning aids and materials on the basis of distance learning technologies; application of elements of distance learning technologies for students’ teaching; attraction of students to formation of corpus of multimedia educational resources of university. The purposes, the content and expected results of each direction are specified. Scientific novelty. The authors point out that concrete scientifically wellfounded methodical recommendations for the future teachers on implementation of distance learning technologies haven’t been presented in the Russian literature till now; despite an abundance of scientifically-information sources of distance learning technologies and sufficiently high-leveled degree knowledge of the issues of its efficiency in educational activity, conditions of introduction of such technologies in high school, construction of models of distance training. Authors of article have tried to close this

  18. Directed divergent evolution of a thermostable D-tagatose epimerase towards improved activity for two hexose substrates.

    Science.gov (United States)

    Bosshart, Andreas; Hee, Chee Seng; Bechtold, Matthias; Schirmer, Tilman; Panke, Sven

    2015-03-02

    Functional promiscuity of enzymes can often be harnessed as the starting point for the directed evolution of novel biocatalysts. Here we describe the divergent morphing of an engineered thermostable variant (Var8) of a promiscuous D-tagatose epimerase (DTE) into two efficient catalysts for the C3 epimerization of D-fructose to D-psicose and of L-sorbose to L-tagatose. Iterative single-site randomization and screening of 48 residues in the first and second shells around the substrate-binding site of Var8 yielded the eight-site mutant IDF8 (ninefold improved kcat for the epimerization of D-fructose) and the six-site mutant ILS6 (14-fold improved epimerization of L-sorbose), compared to Var8. Structure analysis of IDF8 revealed a charged patch at the entrance of its active site; this presumably facilitates entry of the polar substrate. The improvement in catalytic activity of variant ILS6 is thought to relate to subtle changes in the hydration of the bound substrate. The structures can now be used to select additional sites for further directed evolution of the ketohexose epimerase. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Polyhydroxybutyrate production by direct use of waste activated sludge in phosphorus-limited fed-batch culture.

    Science.gov (United States)

    Cavaillé, Laëtitia; Grousseau, Estelle; Pocquet, Mathieu; Lepeuple, Anne-Sophie; Uribelarrea, Jean-Louis; Hernandez-Raquet, Guillermina; Paul, Etienne

    2013-12-01

    Polyhydroxybutyrate (PHB) production directly by waste activated sludge (WAS) was investigated in aerobic fed-batch conditions using acetic acid as substrate. PHB production was induced by phosphorus limitation. WAS of different origin were tested with various degrees of phosphorus limitation and PHB contents of up to 70% (gCOD PHB/gCOD particulate) were obtained. This strategy showed the importance of maintaining cell growth for PHB production in order to increase PHB concentration and that the degree of phosphorus limitation has a direct impact on the quantity of PHB produced. Pyrosequencing of 16S rRNA transcripts showed changes in the active bacteria of the WAS microbial community as well as the acclimation of populations depending on sludge origin. The monitoring of the process appeared as the key factor for optimal PHB production by WAS. Different strategies are discussed and compared in terms of carbon yield and PHB content with the feast and famine selection process. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Short term changes in methanol emission and pectin methylesterase activity are not directly affected by light in Lycopersicon esculentum

    Directory of Open Access Journals (Sweden)

    M. T. Lerdau

    2011-04-01

    Full Text Available Plants are an important source of atmospheric methanol (MeOH, the second most abundant organic gas after methane. Factors regulating phytogenic MeOH production are not well constrained in current MeOH emission models. Previous studies have indicated that light may have a direct influence on MeOH production. As light is known to regulate cell wall expansion, it was predicted that light would stimulate MeOH production through the pectin methylesterase (PME pathway. MeOH emissions normalized for stomatal conductance (gs did not, however, increase with light over short time scales (20–30 min. After experimentally controlling for gs and temperature, no light activation of PME activity or MeOH emission was observed. The results clearly demonstrate that light does not directly influence short-term changes in MeOH production and emission. Our data suggest that substrate limitation may be important in regulating MeOH production over short time scales. Future investigation of the long-term impacts of light on MeOH production may increase understanding of MeOH emission dynamics at the seasonal time scale.

  1. The effect of blood collection procedure on plasma renin activity (PRA) and concentrations of direct renin (DRC) and aldosterone.

    Science.gov (United States)

    Glinicki, Piotr; Jeske, Wojciech; Gietka-Czernel, Małgorzata; Bednarek-Papierska, Lucyna; Kruszyńska, Aleksandra; Słowińska-Srzednicka, Jadwiga; Zgliczyński, Wojciech

    2015-06-01

    Performing measurements of plasma renin activity (PRA) or direct renin concentration (DRC) and aldosterone concentration, we should be well informed about requirements concerning blood sample processing. Forty-seven patients had blood collected in the supine and upright positions. Blood was withdrawn into two EDTA2K tubes and one with clot activator. One EDTA2K tube was cooled at +4 °C and centrifuged at +4 °C whereas the other was prepared at room temperature. PRA and DRC were measured by radioimmunoassay (RIA) and radioimmunometry (IRMA), respectively, in both cooled and not cooled plasma samples, and aldosterone was measured by RIA in not cooled plasma and in serum. In all the groups, with low, medium, and high values of PRA and direct renin, the temperature of sample processing within 30 minutes had no marked influence on the final result (correlation coefficient for renin was 0.9994, and for PRA, 0.8297). The measured concentrations of aldosterone also showed high correlation (r = 0.9790) but were markedly higher in plasma. The measurements of DRC, and to a lesser extent PRA, were similar regardless of temperature condition during the 20-30 minutes necessary for blood sample processing. Aldosterone concentrations in plasma vs serum samples appeared to be markedly higher. © The Author(s) 2013.

  2. Alkali pH directly activates ATP-sensitive K+ channels and inhibits insulin secretion in beta-cells.

    Science.gov (United States)

    Manning Fox, Jocelyn E; Karaman, Gunce; Wheeler, Michael B

    2006-11-17

    Glucose stimulation of pancreatic beta-cells is reported to lead to sustained alkalization, while extracellular application of weak bases is reported to inhibit electrical activity and decrease insulin secretion. We hypothesize that beta-cell K(ATP) channel activity is modulated by alkaline pH. Using the excised patch-clamp technique, we demonstrate a direct stimulatory action of alkali pH on recombinant SUR1/Kir6.2 channels due to increased open probability. Bath application of alkali pH similarly activates native islet beta-cell K(ATP) channels, leading to an inhibition of action potentials, and hyperpolarization of membrane potential. In situ pancreatic perfusion confirms that these cellular effects of alkali pH are observable at a functional level, resulting in decreases in both phase 1 and phase 2 glucose-stimulated insulin secretion. Our data are the first to report a stimulatory effect of a range of alkali pH on K(ATP) channel activity and link this to downstream effects on islet beta-cell function.

  3. Discovered acetylcholinesterase inhibition and antibacterial activity of polyacetylenes in tansy root extract via effect-directed chromatographic fingerprints.

    Science.gov (United States)

    Móricz, Ágnes M; Ott, Péter G; Morlock, Gertrud E

    2018-03-30

    The knowledge about the activity of polyacetylenes was extended by their new acetylcholinesterase inhibition and antibacterial activity against plant pathogenic bacteria. For this discovery, an utmost streamlined workflow, which we consider to be of high potential in the field of natural product or superfood search was developed. It demonstrates the combined power of biological, biochemical and chemical fingerprints. Bioactive components of tansy (Tanacetum vulgare L.) root extract were profiled and identified by high-performance thin-layer chromatography hyphenated with in situ effect-directed analysis, chemical derivatizations and high-resolution mass spectrometry (HPTLC-UV/Vis/FLD-EDA-HRMS). The effect-directed profiling was performed using four bacterial bioassays including two plant pathogens, an antioxidant assay and acetyl- and butyrylcholinesterase inhibitory assays. The chromatographic, spectral and powerful mass spectrometric study of zones that exerted substantial antibacterial and/or antioxidant and/or acetylcholinesterase inhibitory effects allowed these multi-potent zones to be identified as polyacetylenes. Five polyacetylene compounds were assigned to be 2-non-1-ene-3,5,7-triynyl-3-vinyl-oxirane, 2-(2,4-hexadiynylidene)-3,4-epoxy-1,6-dioxaspiro[4.5]decane, trans- and cis-2-(2,4-hexadiynylidene)-1,6-dioxaspiro[4.5]dec-3-ene and tetradeca-2,4,6-triine-8-en-12-one. This study clearly showed the advantage of the combined use of different ionization sources, i.e. electrospray ionization via an elution-head based interface and also the Direct Analysis in Real Time interface, for HRMS analysis of compounds from the same class with very similar chromatographic behavior and polarity. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Enhancement in catalytic activity of Aspergillus niger XynB by selective site-directed mutagenesis of active site amino acids.

    Science.gov (United States)

    Wu, Xiuyun; Tian, Zhennan; Jiang, Xukai; Zhang, Qun; Wang, Lushan

    2018-01-01

    XynB from Aspergillus niger ATCC1015 (AnXynB) is a mesophilic glycoside hydrolase (GH) family 11 xylanase which holds great potentials in a wide variety of industrial applications. In the present study, the catalytic activity and stability of AnXynB were improved by a combination of computational and experimental approaches. Virtual mutation and molecular dynamics simulations indicated that the introduction of Glu and Asn altered the interaction network at the - 3 subsite. Interestingly, the double mutant S41N/T43E displayed 72% increase in catalytic activity when compared to the wild type (WT). In addition, it also showed a better thermostability than the WT enzyme. Kinetic determination of the T43E and S41N/T43E mutants suggested that the higher xylanase activity is probably due to the increasing binding affinity of enzyme and substrate. Consequently, the enzyme activity and thermostability of AnXynB was both increased by selective site-directed mutagenesis at the - 3 subsite of its active site architecture which provides a good example for a successfully engineered enzyme for potential industrial application. Moreover, the molecular evolution approach adopted in this study led to the design of a library of sequences that captures a meaningful functional diversity in a limited number of protein variants.

  5. Direct marketing

    Directory of Open Access Journals (Sweden)

    Čičić Muris

    2002-01-01

    Full Text Available Direct Marketing (DM is usually treated as unworthy activity, with actions at the edge of legality and activities minded cheating. Despite obvious problems regarding ethics and privacy threat, DM with its size, importance and role in a concept of integrated marketing communication deserves respect and sufficient analysis and review

  6. Activation of protein kinase A and exchange protein directly activated by cAMP promotes adipocyte differentiation of human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Jia, Bingbing; Madsen, Lise; Petersen, Rasmus Koefoed

    2012-01-01

    ) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence......Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA...... results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells....

  7. NTL8 Regulates Trichome Formation in Arabidopsis by Directly Activating R3 MYB Genes TRY and TCL1.

    Science.gov (United States)

    Tian, Hainan; Wang, Xianling; Guo, Hongyan; Cheng, Yuxin; Hou, Chunjiang; Chen, Jin-Gui; Wang, Shucai

    2017-08-01

    The NAM, ATAF1/2, and CUC (NAC) are plant-specific transcription factors that regulate multiple aspects of plant growth and development and plant response to environmental stimuli. We report here the identification of NTM1-LIKE8 (NTL8), a membrane-associated NAC transcription factor, as a novel regulator of trichome formation in Arabidopsis ( Arabidopsis thaliana ). From an activation-tagged Arabidopsis population, we identified a dominant, gain-of-function mutant with glabrous inflorescence stem. By using plasmid rescue and RT-PCR analyses, we found that NTL8 was tagged; thus, the mutant was named ntl8-1 Dominant ( ntl8-1D ). Recapitulation experiment further confirmed that the phenotype observed in the ntl8-1D mutant was caused by elevated expression of NTL8 Quantitative RT-PCR results showed that the expression level of the single-repeat R3 MYB genes TRIPTYCHON ( TRY ) and TRICHOMELESS1 ( TCL1 ) was elevated in the ntl8-1D mutant. Genetic analyses demonstrated that NTL8 acts upstream of TRY and TCL1 in the regulation of trichome formation. When recruited to the promoter region of the reporter gene Gal4:GUS by a fused GAL4 DNA-binding domain, NTL8 activated the expression of the reporter gene. Chromatin immunoprecipitation results indicated that TRY and TCL1 are direct targets of NTL8. However, NTL8 did not interact with SQUAMOSA PROMOTER BINDING PROTEIN LIKE9, another transcription factor that regulates the expression of TRY and TCL1 , in yeast and plant cells. Taken together, our results suggest that NTL8 negatively regulates trichome formation in Arabidopsis by directly activating the expression of TRY and TCL1 . © 2017 American Society of Plant Biologists. All Rights Reserved.

  8. Fuzzy-predictive direct power control implementation of a grid connected photovoltaic system, associated with an active power filter

    International Nuclear Information System (INIS)

    Ouchen, Sabir; Betka, Achour; Abdeddaim, Sabrina; Menadi, Abdelkrim

    2016-01-01

    Highlights: • An implementation on dSPACE 1104 of a double stage grid connected photovoltaic system, associated with an active power filter. • A fuzzy logic controller for maximum power point tracking of photovoltaic generator using a boost converter. • Predictive direct power control almost eliminates the effect of harmonics under a unite power factor. • The robustness of control strategies was examined in different irradiance level conditions. - Abstract: The present paper proposes a real time implementation of an optimal operation of a double stage grid connected photovoltaic system, associated with a shunt active power filter. On the photovoltaic side, a fuzzy logic based maximum power point taking control is proposed to track permanently the optimum point through an adequate tuning of a boost converter regardless the solar irradiance variations; whereas, on the grid side, a model predictive direct power control is applied, to ensure both supplying a part of the load demand with the extracted photovoltaic power, and a compensation of undesirable harmonic contents of the grid current, under a unity power factor operation. The implementation of the control strategies is conducted on a small scale photovoltaic system, controlled via a dSPACE 1104 single card. The obtained experimental results show on one hand, that the proposed Fuzzy logic based maximum power taking point technique provides fast and high performances under different irradiance levels while compared with a sliding mode control, and ensures 1.57% more in efficiency. On the other hand, the predictive power control ensures a flexible settlement of active power amounts exchanges with the grid, under a unity power functioning. Furthermore, the grid current presents a sinusoidal shape with a tolerable total harmonic distortion coefficient 4.71%.

  9. Brain oscillatory activity during motor preparation: Effect of directional uncertainty on beta, but not alpha, frequency band

    Directory of Open Access Journals (Sweden)

    Charidimos eTzagarakis

    2015-07-01

    Full Text Available In time-constraint activities, such as sports, it is advantageous to be prepared to act even before knowing precisely what action will be needed. Here, we studied the relation between neural oscillations during motor preparation and amount of uncertainty about the direction of the upcoming target. Ten right-handed volunteers participated in a cued center-out task. A brief visual cue identified the region of space in which the target would appear. Three cue sizes were used to vary the amount of information about the direction of the upcoming target. The target appeared at a random location within the region indicated by the cue, and the participants moved a joystick-controlled cursor towards it. Time-frequency analyses showed phasic increases of power in low (delta/theta: 30 Hz frequency-bands in relation to the onset of visual stimuli and of the motor response. More importantly in regard to motor preparation, there was a tonic reduction of power in the alpha (8-12 Hz and beta (14-30 Hz bands during the period between cue presentation and target onset. During motor preparation, the main source of change of power of the alpha band was localized over the contralateral sensorimotor region and both parietal cortices, whereas for the beta-band the main source was the contralateral sensorimotor region. During cue presentation, the reduction of power of the alpha-band in the occipital lobe showed a brief differentiation of condition: the wider the visual cue, the more the power of the alpha-band decreased. However during motor preparation, only the power of the beta-band was dependent on directional uncertainty: the less the directional uncertainty, the more the power of the beta-band decreased. In conclusion, the results indicate that the power in the alpha-band is associated briefly with cue size, but is otherwise an undifferentiated indication of neural activation, whereas the power of the beta-band reflects the level of motor preparation.

  10. The nucleoid occlusion protein SlmA is a direct transcriptional activator of chitobiose utilization in Vibrio cholerae.

    Science.gov (United States)

    Klancher, Catherine A; Hayes, Chelsea A; Dalia, Ankur B

    2017-07-01

    Chitin utilization by the cholera pathogen Vibrio cholerae is required for its persistence and evolution via horizontal gene transfer in the marine environment. Genes involved in the uptake and catabolism of the chitin disaccharide chitobiose are encoded by the chb operon. The orphan sensor kinase ChiS is critical for regulation of this locus, however, the mechanisms downstream of ChiS activation that result in expression of the chb operon are poorly understood. Using an unbiased transposon mutant screen, we uncover that the nucleoid occlusion protein SlmA is a regulator of the chb operon. SlmA has not previously been implicated in gene regulation. Also, SlmA is a member of the TetR family of proteins, which are generally transcriptional repressors. In vitro, we find that SlmA binds directly to the chb operon promoter, and in vivo, we show that this interaction is required for transcriptional activation of this locus and for chitobiose utilization. Using point mutations that disrupt distinct functions of SlmA, we find that DNA-binding, but not nucleoid occlusion, is critical for transcriptional activation. This study identifies a novel role for SlmA as a transcriptional regulator in V. cholerae in addition to its established role as a cell division licensing factor.

  11. Site directed mutagenesis of amino acid residues at the active site of mouse aldehyde oxidase AOX1.

    Directory of Open Access Journals (Sweden)

    Silvia Schumann

    Full Text Available Mouse aldehyde oxidase (mAOX1 forms a homodimer and belongs to the xanthine oxidase family of molybdoenzymes which are characterized by an essential equatorial sulfur ligand coordinated to the molybdenum atom. In general, mammalian AOs are characterized by broad substrate specificity and an yet obscure physiological function. To define the physiological substrates and the enzymatic characteristics of mAOX1, we established a system for the heterologous expression of the enzyme in Escherichia coli. The recombinant protein showed spectral features and a range of substrate specificity similar to the native protein purified from mouse liver. The EPR data of recombinant mAOX1 were similar to those of AO from rabbit liver, but differed from the homologous xanthine oxidoreductase enzymes. Site-directed mutagenesis of amino acids Val806, Met884 and Glu1265 at the active site resulted in a drastic decrease in the oxidation of aldehydes with no increase in the oxidation of purine substrates. The double mutant V806E/M884R and the single mutant E1265Q were catalytically inactive enzymes regardless of the aldehyde or purine substrates tested. Our results show that only Glu1265 is essential for the catalytic activity by initiating the base-catalyzed mechanism of substrate oxidation. In addition, it is concluded that the substrate specificity of molybdo-flavoenzymes is more complex and not only defined by the three characterized amino acids in the active site.

  12. Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle.

    Science.gov (United States)

    Patel, Anant B; Lai, James C K; Chowdhury, Golam M I; Hyder, Fahmeed; Rothman, Douglas L; Shulman, Robert G; Behar, Kevin L

    2014-04-08

    Previous (13)C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-D-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions.

  13. Adsorption behavior of direct red 80 and congo red onto activated carbon/surfactant: process optimization, kinetics and equilibrium.

    Science.gov (United States)

    Cheng, Zhengjun; Zhang, Lei; Guo, Xiao; Jiang, Xiaohui; Li, Tian

    2015-02-25

    Adsorptions of congo red and direct red 80 onto activated carbon/surfactant from aqueous solution were optimized. The Box-Behnken design (BBD) has been employed to analyze the effects of concentration of surfactant, temperature, pH, and initial concentration of the dye in the adsorption capacity. Their corresponding experimental data could be evaluated excellently by second order polynomial regression models and the two models were also examined based on the analysis of variance and t test statistics, respectively. The optimum conditions were obtained as follows: Cs=34.10 μM, T=50°C, pH=3.5, and CCR=160 mg/L for the congo red system, and Cs=34.10 μM, T=50°C, pH=6.1, and CDR80=110 mg/L for the direct red 80 system. And in these conditions, the measured experimental maximum adsorption capacities for the congo red and direct red 80 removals were 769.48 mg/g and 519.90 mg/g, which were consistent with their corresponding predicted values, with small relative errors of -2.81% and -0.67%, respectively. The adsorption equilibrium and kinetics for the two dye adsorptions onto AC/DDAC were also investigated. The experimental data were fitted by four isotherm models, and Langmuir model presented the best fit. The kinetic studies indicated that the kinetic data followed the pseudo-second-order model. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. C/ebpα controls osteoclast terminal differentiation, activation, function, and postnatal bone homeostasis through direct regulation of Nfatc1.

    Science.gov (United States)

    Chen, Wei; Zhu, Guochun; Tang, Jun; Zhou, Hou-De; Li, Yi-Ping

    2018-03-01

    Osteoclast lineage commitment and differentiation have been studied extensively, although the mechanism by which transcription factor(s) control osteoclast terminal differentiation, activation, and function remains unclear. CCAAT/enhancer-binding protein α (C/ebpα) has been reported to be a key regulator of osteoclast cell lineage commitment, yet C/ebpα's roles in osteoclast terminal differentiation, activation and function, and bone homeostasis, under physiological or pathological conditions, have not been studied because newborn C/ebpα-null mice die within several hours after birth. Furthermore, the function of C/ebpα in osteoclast terminal differentiation, activation, and function is largely unknown. Herein, we generated and analyzed an osteoclast-specific C/ebpα conditional knockout (CKO) mouse model via Ctsk-Cre mice and found that C/ebpα-deficient mice exhibited a severe osteopetrosis phenotype due to impaired osteoclast terminal differentiation, activation, and function, including mildly reduced osteoclast number, impaired osteoclast polarization, actin formation, and bone resorption, which demonstrated the novel function of C/ebpα in cell function and terminal differentiation. Interestingly, C/ebpα deficiency did not affect bone formation or monocyte/macrophage development. Our results further demonstrated that C/ebpα deficiency suppressed the expression of osteoclast functional genes, e.g. encoding cathepsin K (Ctsk), Atp6i (Tcirg1), and osteoclast regulator genes, e.g. encoding c-fos (Fos), and nuclear factor of activated T-cells 1 (Nfatc1), while having no effect on Pu.1 (Spi1) expression. Promoter activity mapping and ChIP assay defined the critical cis-regulatory element (CCRE) in the promoter region of Nfatc1, and also showed that the CCREs were directly associated with C/ebpα, which enhanced the promoter's activity. The deficiency of C/ebpα in osteoclasts completely blocked ovariectomy-induced bone loss, indicating that C/ebpα is a

  15. Direct and indirect relationships between physical activity and happiness levels among older adults: a cross-sectional study.

    Science.gov (United States)

    de Souto Barreto, Philipe

    2014-09-01

    The purposes of this study were to examine if physical activity (PA) is associated to happiness and to investigate if social functioning and health status mediate this association. Participants of this cross-sectional study were 323 men and women, age 60 or over, who were covered by the medical insurance of the French National Education System, France. They received by mail a self-report questionnaire that asked for information about general health, PA, and happiness. In multinomial logistic regressions, the total volume of PA was associated to higher levels of happiness, but this association disappeared in the presence of social functioning. A structural equation modelling (SEM) showed an indirect association between PA and happiness, which was mediated by participants' health status and social functioning; in this SEM model, social functioning was the only variable directly associated to happiness. Complex associations among PA, health status, and social functioning appear to determine happiness levels in older adults.

  16. Direct observation of enhanced plasmon-driven catalytic reaction activity of Au nanoparticles supported on reduced graphene oxides by SERS.

    Science.gov (United States)

    Liang, Xiu; You, Tingting; Liu, Dapeng; Lang, Xiufeng; Tan, Enzhong; Shi, Jihua; Yin, Penggang; Guo, Lin

    2015-04-21

    Graphene-based nanocomposites have recently attracted tremendous research interest in the field of catalysis due to their unique optical and electronic properties. However, direct observation of enhanced plasmon-driven catalytic activity of Au nanoparticles (NPs) supported on reduced graphene oxides (Au/rGO) has rarely been reported. Herein, based on the reduction from 4-nitrobenzenethiol (4-NBT) to p,p'-dimercaptoazobenzene (DMAB), the catalytic property of Au/rGO nanocomposites was investigated and compared with corresponding Au NP samples with similar size distribution. Our results show that Au/rGO nanocomposites could serve as a good catalytic and analytic platform for plasmon-driven chemical reactions. In addition, systematic comparisons were conducted during power- and time-dependent surface-enhanced Raman scattering (SERS) experiments, which exhibited a lower power threshold and higher catalytic efficiency for Au/rGO as compared to Au NPs toward the reaction.

  17. [Legal issues of physician-assisted euthanasia. Part II--Help in the dying process, direct and indirect active euthanasia].

    Science.gov (United States)

    Laux, Johannes; Röbel, Andreas; Parzeller, Markus

    2013-01-01

    In Germany, physician-assisted euthanasia involves numerous risks for the attending physician under criminal and professional law. In the absence of clear legal provisions, four different categories of euthanasia have been developed in legal practice and the relevant literature: help in the dying process, direct active euthanasia, indirect active euthanasia and passive euthanasia. The so-called "help during the dying process" by administering medically indicated analgesic drugs without a life-shortening effect is exempt from punishment if it corresponds to the will of the patient. If the physician omits to give such analgesic drugs although the patient demands them, this is deemed a punishable act of bodily injury. The same applies if the physician administers analgesics against the will of the patient. Medically indicated pain treatment which has a potential or certain life-shortening effect (indirect active euthanasia) is permitted under certain conditions: if there are no alternative and equally suitable treatment options without the risk of shortening the patient's life, if the patient has given his consent to the treatment and if the physician does not act with the intention to kill. The deliberate killing of a dying or terminally ill patient for the purpose of ending his suffering (direct active euthanasia) is prohibited. This includes both deliberately killing a patient against or without his will (by so-called "angels of death") and the killing of a patient who expressly and earnestly demands such an act from his physician (killing on request/on demand). Physician-assisted suicide is generally not liable to punishment in Germany. Nevertheless, the action may be subject to punishment if the physician omits to rescue the life of an unconscious suicide victim. "Palliative sedation" is regarded as a special case. It may become necessary if certain symptoms in the terminal stage of a fatal disease unbearable for the patient cannot be controlled by any other

  18. Bacille Calmette-Guerin can induce cellular apoptosis of urothelial cancer directly through toll-like receptor 7 activation

    Directory of Open Access Journals (Sweden)

    Dah-Shyong Yu

    2015-08-01

    Full Text Available Immunotherapy using bacille Calmette-Guerin (BCG instillation is the mainstay treatment modality for superficial urothelial cancer (UC through toll-like receptor (TLR activation of cognitive immune response. We investigated the roles of TLR7 in the activation of apoptosis in UC cells after BCG treatment. The in vitro cytotoxicity effect of BCG on UC cells was measured by a modified 3-(4,5-dimethylthiazo-2-yl-2,5-diphenyl tetrazolium assay. Expressions of TLR7 mRNA and protein in native UC cells prior to and after BCG treatment were analyzed using real-time quantitative polymerase chain reaction and western blot methods. Phagocytotic processes after BCG treatment in UC cells were observed microscopically using a specific immunostain, subsequent cellular apoptosis-related signals induced by TLR7 were analyzed by western blot. Low-grade UC cells, TSGH8301, showed significant cellular death (4.23-fold higher than the high-grade UC cells T24 and J82 when treated with BCG and the BCG cytotoxicity was displayed in a dose–time-dependent manner. TSGH8301 cells had the highest content of TLR7 mRNA, 7.2- and 4.5-fold higher than that of T24 and J82 cells, respectively. TLR7 protein expression was also significantly increased in TSGH8301 cells. Phagocytosis-related markers, including beclin 1, ATG2, and LC3, were increased when TSGH8301 cells were treated by BCG. Interleukin-1 receptor-associated kinases 2 and 4 were also increased markedly in TSGH8301 cells. On the contrary, cellular apoptosis of TSGH8301 cells decreased by 34% when TLR7 activation was suppressed by the TLR antagonist IRS661 after BCG treatment. Our findings suggest that well differentiated TCC cells have higher expression of TLR7 and BCG can drive cellular death of TCC cells directly via TLR7 activation and related apoptotic pathway.

  19. Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an activity-based artemisinin probe

    Directory of Open Access Journals (Sweden)

    Jigang Wang

    2016-04-01

    Full Text Available Artemisinin and its analogues are currently the most effective anti-malarial drugs. The activation of artemisinin requires the cleavage of the endoperoxide bridge in the presence of iron sources. Once activated, artemisinins attack macromolecules through alkylation and propagate a series of damages, leading to parasite death. Even though several parasite proteins have been reported as artemisinin targets, the exact mechanism of action (MOA of artemisinin is still controversial and its high potency and specificity against the malaria parasite could not be fully accounted for. Recently, we have developed an unbiased chemical proteomics approach to directly probe the MOA of artemisinin in P. falciparum. We synthesized an activity-based artemisinin probe with an alkyne tag, which can be coupled with biotin through click chemistry. This enabled selective purification and identification of 124 protein targets of artemisinin. Many of these targets are critical for the parasite survival. In vitro assays confirmed the specific artemisinin binding and inhibition of selected targets. We thus postulated that artemisinin kills the parasite through disrupting its biochemical landscape. In addition, we showed that artemisinin activation requires heme, rather than free ferrous iron, by monitoring the extent of protein binding using a fluorescent dye coupled with the alkyne-tagged artemisinin. The extremely high level of heme released from the hemoglobin digestion by the parasite makes artemisinin exceptionally potent against late-stage parasites (trophozoite and schizont stages compared to parasites at early ring stage, which have low level of heme, possibly derived from endogenous synthesis. Such a unique activation mechanism also confers artemisinin with extremely high specificity against the parasites, while the healthy red blood cells are unaffected. Our results provide a sound explanation of the MOA of artemisinin and its specificity against malaria

  20. The rapid and direct determination of ATPase activity by ion exchange chromatography and the application to the activity of heat shock protein-90.

    Science.gov (United States)

    Bartolini, Manuela; Wainer, Irving W; Bertucci, Carlo; Andrisano, Vincenza

    2013-01-25

    Adenosine nucleotides are involved as substrates or co-factors in several biochemical reactions, catalyzed by enzymes, which modulate energy production, signal transduction and cell proliferation. We here report the development and optimization of an ion exchange liquid chromatography (LC) method for the determination of ATP, ADP and AMP. This method is specifically aimed at the determination of the ATP-ase activity of human heat shock protein 90 (Hsp90), a molecular chaperone that has emerged as target enzyme in cancer therapy. Separation of the three nucleotides was achieved in a 15-min run by using a disk shaped monolithic ethylene diamine stationary phase of small dimensions (2mm×6mm i.d.), under a three-solvent gradient elution mode and UV detection at 256nm. The described direct LC method resulted highly specific as a consequence of the baseline separation of the three adenosine nucleotides and could be applied to the determination of the enzymatic activity of ADP/ATP generating or consuming enzymes (such as kinases). Furthermore, comparison of the LOD and LOQ values of the LC method with those obtained with the malachite green assay, which is one of the most used indirect screening methodologies for ATP-ase activity, showed that the LC method has a similar range of application without presenting the drawbacks related to contamination by inorganic phosphate ions and glycerol, which are present in Hsp90 commercial samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. A Comparison of Students' Outcomes in Two Classes: Business Administration Students vs Communication Arts Students Based on Self-Directed Learning Activities

    Science.gov (United States)

    Orawiwatnakul, Wiwat; Wichadee, Saovapa

    2011-01-01

    With research showing the benefits of self-directed learning, more activities are needed to provide learners opportunities for self-directed practice (Khomson, 1997; Lee, 1998; Phongnapharuk, 2007). A 12-week experimental study was performed with 80 EFL learners; one group contained 40 Communication Arts students and the other one consisted of 40…

  2. Acetylcholine stimulation of human neutrophil chemotactic activity is directly inhibited by tiotropium involving Gq and ERK-1/2 regulation

    Directory of Open Access Journals (Sweden)

    Kurai M

    2012-01-01

    Full Text Available Tiotropium, a long-acting anticholinergic, may improve chronic obstructive pulmonary disease (COPD by mechanisms beyond bronchodilatation. We tested the hypothesis that tiotropium may act as an anti-inflammatory mediator by directly acting on and inhibiting human neutrophil chemotactic activity (NCA that is promoted by acetylcholine (ACh exposure. ACh treatment increased NCA in a dose dependent manner (p < 0.001 and tiotropium pretreatment reduced ACh stimulation (dose effect; 0 to 1000 nM; p < 0.001. Selective muscarinic receptor inhibitors demonstrated that subtype-3 (M3 receptor plays a role in NCA regulation. In addition, NCA that was stimulated by cevimeline (M3 agonist and pasteurella multocida toxin (PMT, M3 coupled Gq agonist. However, the increased NCA to cevimeline and PMT was reduced by tiotropium pretreatment (p < 0.001. ACh treatment stimulated ERK-1/2 activation by promoting protein phosphorylation and tiotropium reduced this effect (p < 0.01. In addition, pretreatment of the cells with a specific MEK-1/2 kinase inhibitor reduced ACh stimulated NCA (p < 0.01. Together these results demonstrated that cholinergic stimulation of NCA is effectively inhibited by tiotropium and is governed by a mechanism involving M3 coupled Gq signaling and downstream ERK signaling. This study further demonstrates that tiotropium may act as an anti-inflammatory agent in lung disease.

  3. The BCL11A transcription factor directly activates RAG gene expression and V(D)J recombination.

    Science.gov (United States)

    Lee, Baeck-seung; Dekker, Joseph D; Lee, Bum-kyu; Iyer, Vishwanath R; Sleckman, Barry P; Shaffer, Arthur L; Ippolito, Gregory C; Tucker, Philip W

    2013-05-01

    Recombination-activating gene 1 protein (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The transcription factor BCL11A is required for B cell development, but its molecular function(s) in B cell fate specification and commitment is unknown. We show here that the major B cell isoform, BCL11A-XL, binds the RAG1 promoter and Erag enhancer to activate RAG1 and RAG2 transcription in pre-B cells. We employed BCL11A overexpression with recombination substrates in a cultured pre-B cell line as well as Cre recombinase-mediated Bcl11a(lox/lox) deletion in explanted murine pre-B cells to demonstrate direct consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that BCL11A is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination.

  4. Antibody-directed targeting of lysostaphin adsorbed onto polylactide nanoparticles increases its antimicrobial activity against S. aureus in vitro

    International Nuclear Information System (INIS)

    Satishkumar, R; Vertegel, A A

    2011-01-01

    The objective of this paper was to study the effect of antibody-directed targeting of S. aureus by comparing the activities of lysostaphin conjugated to biodegradable polylactide nanoparticles (NPs) in the presence and in the absence of co-immobilized anti-S. aureus antibody. Lysostaphin–antibody–NP conjugates were synthesized through physical adsorption at different enzyme:antibody:NP ratios. The synthesized enzyme–NP conjugates were characterized by means of dynamic light scattering and zeta potential analysis, and the total protein binding yield on the NPs was characterized using Alexa Fluor 350 and 594 dyes for the S. aureus antibody and lysostaphin respectively. We observed enhanced antimicrobial activity for both enzyme-coated and enzyme–antibody-coated NPs for lysostaphin coatings corresponding to ∼ 40% of the initial monolayer and higher compared to the free enzyme case (p < 0.05). At the highest antibody coating concentration, bacterial lysis rates for antibody-coated samples were significantly higher than for lysostaphin-coated samples lacking the antibody (p < 0.05). Such enzyme–NP conjugates thus have the potential for becoming novel therapeutic agents for treating antibiotic-resistant S. aureus infections.

  5. Glucocorticoids downregulate TLR4 signaling activity via its direct targeting by miR-511-5p.

    Science.gov (United States)

    Curtale, Graziella; Renzi, Tiziana A; Drufuca, Lorenzo; Rubino, Marcello; Locati, Massimo

    2017-12-01

    Endotoxin tolerance assures proper regulation of the TLR4 signaling pathway and avoids uncontrolled inflammation, limiting tissue damage and endotoxin shock development. Though underlying molecular mechanisms are still undefined, evidence indicates the involvement of microRNAs, which represent a new layer of regulation of inflammatory pathways. Here, we report that LPS and other inflammatory stimuli repress miR-511-5p expression in human monocytes, while anti-inflammatory stimuli, such as TGF-β and glucocorticoids, have the opposite effect. MiR-511-5p levels selectively influenced cell activation when endotoxin was used, while biological activity of other TLR agonists was unaffected. Consistent with this, TLR4 was validated as the miR-511-5p direct target responsible for glucocorticoids- and TGF-β-mediated inhibition of pro-inflammatory cytokines production observed in endotoxin tolerant monocytes. MiR-511-5p thus acts as an intracellular mediator of glucocorticoids and TGF-β for the induction of endotoxin tolerance in human monocytes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Analysis and experimental evaluation of shunt active power filter for power quality improvement based on predictive direct power control.

    Science.gov (United States)

    Aissa, Oualid; Moulahoum, Samir; Colak, Ilhami; Babes, Badreddine; Kabache, Nadir

    2017-10-12

    This paper discusses the use of the concept of classical and predictive direct power control for shunt active power filter function. These strategies are used to improve the active power filter performance by compensation of the reactive power and the elimination of the harmonic currents drawn by non-linear loads. A theoretical analysis followed by a simulation using MATLAB/Simulink software for the studied techniques has been established. Moreover, two test benches have been carried out using the dSPACE card 1104 for the classic and predictive DPC control to evaluate the studied methods in real time. Obtained results are presented and compared in this paper to confirm the superiority of the predictive technique. To overcome the pollution problems caused by the consumption of fossil fuels, renewable energies are the alternatives recommended to ensure green energy. In the same context, the tested predictive filter can easily be supplied by a renewable energy source that will give its impact to enhance the power quality.

  7. Standard Test Method for Oxygen Content Using a 14-MeV Neutron Activation and Direct-Counting Technique

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2007-01-01

    1.1 This test method covers the measurement of oxygen concentration in almost any matrix by using a 14-MeV neutron activation and direct-counting technique. Essentially, the same system may be used to determine oxygen concentrations ranging from over 50 % to about 10 g/g, or less, depending on the sample size and available 14-MeV neutron fluence rates. Note 1 - The range of analysis may be extended by using higher neutron fluence rates, larger samples, and higher counting efficiency detectors. 1.2 This test method may be used on either solid or liquid samples, provided that they can be made to conform in size, shape, and macroscopic density during irradiation and counting to a standard sample of known oxygen content. Several variants of this method have been described in the technical literature. A monograph is available which provides a comprehensive description of the principles of activation analysis using a neutron generator (1). 1.3 The values stated in either SI or inch-pound units are to be regarded...

  8. Direct and self-reported measures of physical activity and sedentary behaviours by weight status in school-aged children: results from ISCOLE-Kenya.

    Science.gov (United States)

    Muthuri, Stella K; Wachira, Lucy-Joy M; Onywera, Vincent O; Tremblay, Mark S

    2015-01-01

    Previous work has shown little association between self-report and directly measured physical activity. The objective of this study was to investigate the relationships between self-reported and directly assessed measures of physical activity and sedentary time by weight status in Kenyan children. Direct assessment of body weight, physical activity and sedentary time of 563 children was collected through anthropometry and accelerometry, while self-reported assessment was achieved by administering a questionnaire. Under/healthy weight children had significantly higher directly measured mean daily minutes of moderate-to-vigorous physical activity (MVPA) compared to overweight/obese children (39 vs 20 minutes); had lower mean weekend-day minutes of sedentary time (346 vs 365 minutes); had a higher proportion who met accepted physical activity guidelines (15.3% vs 2.6%); and a higher number reported using active transportation to/from school (49.2% vs 32.4%). Self-reported time spent outside before and after school and active transport to/from school were significantly associated with mean weekday minutes of MVPA (r-value range = 0.12-0.36), but only for the under/healthy weight children. The results of this study found a number of differences in the accumulation of MVPA and sedentary time by weight status and weak-to-moderate correlations between self-report and direct measures of weekday and weekend-day physical activity among the under/healthy weight children.

  9. Direct Quantification of Ice Nucleation Active Bacteria in Aerosols and Precipitation: Their Potential Contribution as Ice Nuclei

    Science.gov (United States)

    Hill, T. C.; DeMott, P. J.; Garcia, E.; Moffett, B. F.; Prenni, A. J.; Kreidenweis, S. M.; Franc, G. D.

    2013-12-01

    Ice nucleation active (INA) bacteria are a potentially prodigious source of highly active (≥-12°C) atmospheric ice nuclei, especially from agricultural land. However, we know little about the conditions that promote their release (eg, daily or seasonal cycles, precipitation, harvesting or post-harvest decay of litter) or their typical contribution to the pool of boundary layer ice nucleating particles (INP). To initiate these investigations we developed a quantitative Polymerase Chain Reaction (qPCR) test of the ina gene, the gene that codes for the ice nucleating protein, to directly count INA bacteria in environmental samples. The qPCR test amplifies most forms of the gene and is highly sensitive, able to detect perhaps a single gene copy (ie, a single bacterium) in DNA extracted from precipitation. Direct measurement of the INA bacteria is essential because environmental populations will be a mixture of living, viable-but-not culturable, moribund and dead cells, all of which may retain ice nucleating proteins. Using the qPCR test on leaf washings of plants from three farms in Wyoming, Colorado and Nebraska we found INA bacteria to be abundant on crops, especially on cereals. Mid-summer populations on wheat and barley were ~108/g fresh weigh of foliage. Broadleaf crops, such as corn, alfalfa, sugar beet and potato supported 105-107/g. Unexpectedly, however, in the absence of a significant physical disturbance, such as harvesting, we were unable to detect the ina gene in aerosols sampled above the crops. Likewise, in fresh snow samples taken over two winters, ina genes from a range of INA bacteria were detected in about half the samples but at abundances that equated to INA bacterial numbers that accounted for only a minor proportion of INP active at -10°C. By contrast, in a hail sample from a summer thunderstorm we found 0.3 INA bacteria per INP at -10°C and ~0.5 per hail stone. Although the role of the INA bacteria as warm-temperature INP in these samples

  10. Direct observation of solid-phase adsorbate concentration profile in powdered activated carbon particle to elucidate mechanism of high adsorption capacity on super-powdered activated carbon.

    Science.gov (United States)

    Ando, Naoya; Matsui, Yoshihiko; Matsushita, Taku; Ohno, Koichi

    2011-01-01

    Decreasing the particle size of powdered activated carbon (PAC) by pulverization increases its adsorption capacities for natural organic matter (NOM) and polystyrene sulfonate (PSS, which is used as a model adsorbate). A shell adsorption mechanism in which NOM and PSS molecules do not completely penetrate the adsorbent particle and instead preferentially adsorb near the outer surface of the particle has been proposed as an explanation for this adsorption capacity increase. In this report, we present direct evidence to support the shell adsorption mechanism. PAC particles containing adsorbed PSS were sectioned with a focused ion beam, and the solid-phase PSS concentration profiles of the particle cross-sections were directly observed by means of field emission-scanning electron microscopy/energy-dispersive X-ray spectrometry (FE-SEM/EDXS). X-ray emission from sulfur, an index of PSS concentration, was higher in the shell region than in the inner region of the particles. The X-ray emission profile observed by EDXS did not agree completely with the solid-phase PSS concentration profile predicted by shell adsorption model analysis of the PSS isotherm data, but the observed and predicted profiles were not inconsistent when the analytical errors were considered. These EDXS results provide the first direct evidence that PSS is adsorbed mainly in the vicinity of the external surface of the PAC particles, and thus the results support the proposition that the increase in NOM and PSS adsorption capacity with decreasing particle size is due to the increase in external surface area on which the molecules can be adsorbed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Bacillus Calmette Guerin induces fibroblast activation both directly and through macrophages in a mouse bladder cancer model.

    Directory of Open Access Journals (Sweden)

    Catalina Lodillinsky

    Full Text Available BACKGROUND: Bacillus Calmette-Guerin (BCG is the most effective treatment for non-muscle invasive bladder cancer. However, a failure in the initial response or relapse within the first five years of treatment has been observed in 20% of patients. We have previously observed that in vivo administration of an inhibitor of nitric oxide improved the response to BCG of bladder tumor bearing mice. It was described that this effect was due to a replacement of tumor tissue by collagen depots. The aim of the present work was to clarify the mechanism involved in this process. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that BCG induces NIH-3T3 fibroblast proliferation by activating the MAPK and PI3K signaling pathways and also differentiation determined by alpha-smooth muscle actin (alpha-SMA expression. In vivo, intratumoral inoculation of BCG also increased alpha-SMA and collagen expression. Oral administration of L-NAME enhanced the pro-fibrotic effect of BCG. Peritoneal macrophages obtained from MB49 tumor-bearing mice treated in vivo with combined treatment of BCG with L-NAME also enhanced fibroblast proliferation. We observed that FGF-2 is one of the factors released by BCG-activated macrophages that is able to induce fibroblast proliferation. The involvement of FGF-2 was evidenced using an anti-FGF2 antibody. At the same time, this macrophage population improved wound healing rate in normal mice and FGF-2 expression was also increased in these wounds. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that fibroblasts are targeted by BCG both directly and through activated macrophages in an immunotherapy context of a bladder murine model. We also described, for the first time, that FGF-2 is involved in a dialog between fibroblasts and macrophages induced after BCG treatment. The fact that L-NAME administration improves the BCG effect on fibroblasts, NO inhibition, might represent a new approach to add to the conventional BCG therapy.

  12. Catalytic Activities of Fe3+- and Zn2+-Natural Zeolite on the Direct Cyclisation-Acetylation of (R-(+-Citronellal

    Directory of Open Access Journals (Sweden)

    Edy Cahyono

    2014-07-01

    Full Text Available Characterisation and catalytic ativities investigation of modified natural zeolite on cyclisation acetylation reaction of (R-(+-citronellal was performed. The experimental work involved isolation of (R-(+-citronellal from Java Citronella oil (Cymbopogon winterianus by vacuum fractional distillation, determination of its enantiomer, preparation and characterisation of different catalysts i.e. H-natural zeolite (H-Za, Fe3+-natural zeolite (Fe3+-Za, and Zn2+-natural zeolite (Zn2+-Za, followed by examination of catalytic activity and selectivity. Isolated citronellal contained 88.21% ee of (R-(+-citronellal. The main products of cyclisation-acetylation of (R-(+-citronellal was IPA (isopulegyl acetate and NIPA (neo-isopulegyl acetate. Although the highest yield of IPA and NIPA was obtained by Fe3+-Za catalyst (78.69% at 80oC and 120 min, the stereoselectivity of Fe3+-Za slightly lower than that of Zn2+-Za. Structure elucidation of citronellal and products was carried out by means of GC and GC-MS. Lewis acidity plays the role of acetyl ionic formation from acetic anhydride. The Activity and stereoselectivity of catalysts depended on Lewis acidity and cation distribution on the catalyst surface. © 2014 BCREC UNDIP. All rights reservedReceived: 18th December 2013; Revised: 9th April 2014; Accepted: 17th April 2014[ How to Cite: Cahyono, E., Muchalal, M., Triyono, T., Pranowo, H.D. (2014. Catalytic Activities of Fe3+- and Zn2+-Natural Zeolite on the Direct Cyclisation-Acetylation of (R-(+-Citronellal. Bulletin of Chemical Reaction Engineering & Catalysis, 9 (2: 128-135. (doi:10.9767/bcrec.9.2.5936.128-135 ][ Permalink/DOI: http://dx.doi.org/10.9767/bcrec.9.2.5936.128-135 ] 

  13. Re-examining the automaticity and directionality of the activation of the spatial-valence "good is up" metaphoric association.

    Directory of Open Access Journals (Sweden)

    Yanli Huang

    Full Text Available According to the Conceptual Metaphor Theory, people understand abstract concepts depending on the activation of more concrete concepts, but not vice versa. The present research aims to investigate the role of directionality and automaticity regarding the activation of the conceptual metaphor "good is up". Experiment 1 tested the automaticity of the spatial-to-valence metaphoric congruency effect by having participants judge the valence of a positive or negative word that appeared either at the top or at the bottom of the screen. They performed the task concurrently with a 6-digit verbal rehearsal task in the working-memory-load (WML blocks and without this task in the non-WML blocks. The spatial-to-valence metaphoric congruency effect occurred for the positive words in the non-WML blocks (i.e., positive words are judged more quickly when they appeared at the top than at the bottom of the screen, but not in the WML blocks, suggesting that this metaphoric association might not be activated automatically. Experiments 2-6 investigated the valence-to-spatial metaphoric association and its automaticity. Participants processed a positive or negative prime, which appeared at the center of the screen, and then identified a letter (p/q that subsequently appeared at the top or bottom of the screen. The valence-to-spatial metaphoric congruency effect did not occur in the WML (6-digit verbal rehearsal or non-WML blocks, whether response modality to the prime was key-press or vocal, or whether the prime was a word or a picture. The effect only unexpectedly occurred when the task was simultaneously performed with a 4-dot-position visuospatial rehearsal task. Nevertheless, the data collapsed across multiple experiments showed a null valence-to-spatial metaphoric congruency effect, suggesting the absence of the valence-to-spatial metaphoric association in general. The implications of the current findings for the Conceptual Metaphor Theory and its alternatives

  14. Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway.

    Directory of Open Access Journals (Sweden)

    Jianhua Sui

    2008-11-01

    information in combination of chain-shuffling as well as hot-spot CDR mutagenesis, can be exploited to broaden neutralization activity, to improve anti-viral nAb therapies, and directly manipulate virus evolution.

  15. Direct in situ activation of Ag0 nanoparticles in synthesis of Ag/TiO2 and its photoactivity

    International Nuclear Information System (INIS)

    Jaafar, N.F.; Jalil, A.A.; Triwahyono, S.; Efendi, J.; Mukti, R.R.; Jusoh, R.; Jusoh, N.W.C.; Karim, A.H.; Salleh, N.F.M.; Suendo, V.

    2015-01-01

    Graphical abstract: - Highlights: • Ag 0 loaded on TiO 2 was prepared by a direct in situ electrochemical method. • 5 wt% Ag–TiO 2 demonstrated the best photocatalytic degradation of 2-CP. • Isomorphous substitution of Ag with Ti occurred to form Ti−O−Ag bonds. • Ag 0 and oxygen vacancies trapped electrons to enhance e–H + separation. • Substitution of Ag in the TiO 2 structure decreased the number of oxygen vacancies. - Abstract: Metallic Ag nanoparticles (Ag 0 ) were successfully activated using a direct in situ electrochemical method before being supported on TiO 2 . Catalytic testing showed that 5 wt% Ag–TiO 2 gave the highest photodegradation (94%) of 50 mg L −1 2-chlorophenol (2-CP) at pH 5 using 0.375 g L −1 catalyst within 6 h, while under similar conditions, 1 wt% and 10 wt% Ag–TiO 2 only gave 75% and 78% degradation, respectively. Characterization results illustrated that the photoactivity was affected by the amount of Ag 0 and oxygen vacancies which act as an electrons trap to enhance the electron–hole separation. While, the Ag−O−Ti bonds formation reduced the photoactivity. The degradation followed a pseudo-first order Langmuir–Hinshelwood model where adsorption was the controlling step. Study on the effect of scavengers showed that the hole (H + ) and hydroxyl radical (OH·) play important roles in the photodegradation. The regenerated photocatalyst was still stable after five cycling runs

  16. Rhodium-Catalyzed C-C Bond Formation via Heteroatom-Directed C-H Bond Activation

    Energy Technology Data Exchange (ETDEWEB)

    Colby, Denise; Bergman, Robert; Ellman, Jonathan

    2010-05-13

    Once considered the 'holy grail' of organometallic chemistry, synthetically useful reactions employing C-H bond activation have increasingly been developed and applied to natural product and drug synthesis over the past decade. The ubiquity and relative low cost of hydrocarbons makes C-H bond functionalization an attractive alternative to classical C-C bond forming reactions such as cross-coupling, which require organohalides and organometallic reagents. In addition to providing an atom economical alternative to standard cross - coupling strategies, C-H bond functionalization also reduces the production of toxic by-products, thereby contributing to the growing field of reactions with decreased environmental impact. In the area of C-C bond forming reactions that proceed via a C-H activation mechanism, rhodium catalysts stand out for their functional group tolerance and wide range of synthetic utility. Over the course of the last decade, many Rh-catalyzed methods for heteroatom-directed C-H bond functionalization have been reported and will be the focus of this review. Material appearing in the literature prior to 2001 has been reviewed previously and will only be introduced as background when necessary. The synthesis of complex molecules from relatively simple precursors has long been a goal for many organic chemists. The ability to selectively functionalize a molecule with minimal pre-activation can streamline syntheses and expand the opportunities to explore the utility of complex molecules in areas ranging from the pharmaceutical industry to materials science. Indeed, the issue of selectivity is paramount in the development of all C-H bond functionalization methods. Several groups have developed elegant approaches towards achieving selectivity in molecules that possess many sterically and electronically similar C-H bonds. Many of these approaches are discussed in detail in the accompanying articles in this special issue of Chemical Reviews. One approach

  17. Activation of protein kinase A and exchange protein directly activated by cAMP promotes adipocyte differentiation of human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Bingbing Jia

    Full Text Available Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA and exchange protein directly activated by cAMP (Epac in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS. We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence of the strong adipogenic inducers insulin, dexamethasone, and rosiglitazone, thereby clearly distinguishing the hMADS cells from murine preadipocytes cell lines, where rosiglitazone together with dexamethasone and insulin strongly promotes adipocyte differentiation. We further show that prostaglandin I(2 (PGI(2 may fully substitute for the cAMP-elevating agent isobutylmethylxanthine (IBMX. Moreover, selective activation of Epac-dependent signaling promoted adipocyte differentiation when the Rho-associated kinase (ROCK was inhibited. Unlike the case for murine preadipocytes cell lines, long-chain fatty acids, like arachidonic acid, did not promote adipocyte differentiation of hMADS cells in the absence of a PPARγ agonist. However, prolonged treatment with the synthetic PPARδ agonist L165041 promoted adipocyte differentiation of hMADS cells in the presence of IBMX. Taken together our results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells.

  18. Key directions of the Russian economy innovative development with the innovative activity practice of the integrated corporate structures

    Directory of Open Access Journals (Sweden)

    F. I. Shamhalov

    2016-01-01

    Full Text Available The article deals with the problems and the key directions of The article deals with the problems and key directions of innovative development of the Russian industry in connection with the need to reduce the dependence of the national economy on the situation on world commodity markets, as well as to create the conditions and incentives for the introduction and modern technologies development, improving energy and environmental efficiency of the economy and productivity for the development of economic sectors and industries, producing goods with high added value for the implementation of innovative projects and in general - to upgrade the socio-economic system of the country.The following statement is given: the development of innovative high-tech and knowledge-intensive industries must ensure import substitution products at the first stage, primarily in the militaryindustrial complex, and in the future - export-oriented competitive product.The article analyzes the experience of innovative activity of the integrated corporate structures with the participation of the state in the following areas: the integration of the industrial and financial capital; the concentration of capital (through the merger and acquisition of enterprises, strategic alliances; diversification of forms and fields of activity; globalization of activities (creation of subsidiaries in the most attractive countries and working on promising markets; capital internationalization (through the creation of transnational companies.On the basis of generalization of global corporate management experience in the state corporations the article analyzes key conditions and factors that determine the efficiency of the state-owned companies as a whole: a clear statement of goals and objectives of the state as the owner, whose interests go beyond the usual business purposes; fixing of these goals and objectives in the regulations, in the concepts and programs of long-term socioeconomic

  19. Metal-free oxidative olefination of primary amines with benzylic C-H bonds through direct deamination and C-H bond activation.

    Science.gov (United States)

    Gong, Liang; Xing, Li-Juan; Xu, Tong; Zhu, Xue-Ping; Zhou, Wen; Kang, Ning; Wang, Bin

    2014-09-14

    An oxidative olefination reaction between aliphatic primary amines and benzylic sp(3) C-H bonds has been achieved using N-bromosuccinimide as catalyst and tert-butyl hydroperoxide as oxidant. The olefination proceeds under mild metal-free conditions through direct deamination and benzylic C-H bond activation, and provides easy access to biologically active 2-styrylquinolines with (E)-configuration.

  20. Direct activation of EXPANSIN14 by LBD18 in the gene regulatory network of lateral root formation in Arabidopsis.

    Science.gov (United States)

    Kim, Jungmook; Lee, Han Woo

    2013-02-01

    Root system architecture is important for plants to adapt to a changing environment. The major determinant of the root system is lateral roots originating from the primary root. The developmental process of lateral root formation can be divided into priming, initiation, primordium development and the emergence of lateral roots, and is well characterized in Arabidopsis. The hormone auxin plays a critical role in lateral root development, and several auxin response modules involving AUXIN RESPONSE FACTORS (ARFs), transcriptional regulators of auxin-regulated genes and Aux/IAA, negative regulators of ARFs, regulate lateral root formation. The LATERAL ORGAN BOUNDARIES DOMAIN/ASYMMETRIC LEAVES2-LIKE (LBD/ASL) gene family encodes a unique class of transcription factors harbouring a conserved plant-specific lateral organ boundary domain and plays a role in lateral organ development of plants including lateral root formation. In our previous study, we showed that LBD18 stimulates lateral root formation in combination with LBD16 downstream of ARF7 and ARF19 during the auxin response. We have recently demonstrated that LBD18 activates expression of EXP14, a gene encoding the cell-wall loosening factor, by directly binding to the EXP14 promoter to promote lateral root emergence. Here we present the molecular function of LBD18 and its gene regulatory network during lateral root formation.

  1. Directed assembly of optoelectronically active alkyl-π-conjugated molecules by adding n-alkanes or π-conjugated species

    Science.gov (United States)

    Hollamby, Martin J.; Karny, Maciej; Bomans, Paul H. H.; Sommerdjik, Nico A. J. M.; Saeki, Akinori; Seki, Shu; Minamikawa, Hiroyuki; Grillo, Isabelle; Pauw, Brian R.; Brown, Paul; Eastoe, Julian; Möhwald, Helmuth; Nakanishi, Takashi

    2014-08-01

    Supramolecular assembly can yield ordered structures by taking advantage of the cumulative effect of multiple non-covalent interactions between adjacent molecules. The thermodynamic origin of many self-assembled structures in water is the balance between the hydrophilic and hydrophobic segments of the molecule. Here, we show that this approach can be generalized to use solvophobic and solvophilic segments of fully hydrophobic alkylated fullerene molecules. Addition of n-alkanes results in their assembly—due to the antipathy of C60 towards n-alkanes—into micelles and hexagonally packed gel-fibres containing insulated C60 nanowires. The addition of pristine C60 instead directs the assembly into lamellar mesophases by increasing the proportion of π-conjugated material in the mixture. The assembled structures contain a large fraction of optoelectronically active material and exhibit comparably high photoconductivities. This method is shown to be applicable to several alkyl-π-conjugated molecules, and can be used to construct organized functional materials with π-conjugated sections.

  2. Automatic media-adventitia IVUS image segmentation based on sparse representation framework and dynamic directional active contour model.

    Science.gov (United States)

    Zakeri, Fahimeh Sadat; Setarehdan, Seyed Kamaledin; Norouzi, Somayye

    2017-10-01

    Segmentation of the arterial wall boundaries from intravascular ultrasound images is an important image processing task in order to quantify arterial wall characteristics such as shape, area, thickness and eccentricity. Since manual segmentation of these boundaries is a laborious and time consuming procedure, many researchers attempted to develop (semi-) automatic segmentation techniques as a powerful tool for educational and clinical purposes in the past but as yet there is no any clinically approved method in the market. This paper presents a deterministic-statistical strategy for automatic media-adventitia border detection by a fourfold algorithm. First, a smoothed initial contour is extracted based on the classification in the sparse representation framework which is combined with the dynamic directional convolution vector field. Next, an active contour model is utilized for the propagation of the initial contour toward the interested borders. Finally, the extracted contour is refined in the leakage, side branch openings and calcification regions based on the image texture patterns. The performance of the proposed algorithm is evaluated by comparing the results to those manually traced borders by an expert on 312 different IVUS images obtained from four different patients. The statistical analysis of the results demonstrates the efficiency of the proposed method in the media-adventitia border detection with enough consistency in the leakage and calcification regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation.

    Directory of Open Access Journals (Sweden)

    Katsuya Kobayashi

    Full Text Available Physiological high frequency activities (HFA are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections, or different terminal layers (layer IV vs. layer II/III affect its frequency, we, in the primary somatosensory cortex (SI, compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response and N80 (late response of somatosensory evoked potentials (HFA(SEP(N20 and HFA(SEP(N80 and compared those overriding N1 and N2 (first and second responses of cortico-cortical evoked potentials (HFA(CCEP(N1 and HFA(CCEP(N2. HFA(SEP(N20 showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1 had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1 and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

  4. The contribution of organised sports to physical activity in Australia: Results and directions from the Active Healthy Kids Australia 2014 Report Card on physical activity for children and young people.

    Science.gov (United States)

    Vella, Stewart A; Schranz, Natasha K; Davern, Melanie; Hardy, Louise L; Hills, Andrew P; Morgan, Philip J; Plotnikoff, Ronald C; Tomkinson, Grant

    2016-05-01

    Youth participation in organised sport and physical activity is important for healthy development, growth and wellbeing. In 2014, Active Healthy Kids Australia released its inaugural Report Card on Physical Activity for Children and Young People, which synthesised the best available national- and state-level data for children and young people (Sport from the 2014 Report Card, compares Australia's Organised Sport grade with other countries, identifies future directions for research and surveillance, and explores possible beneficial strategies. The Report Card highlighted that between 64% and 85% of Australians aged 5-17 years participate in organised sports, a rate higher than alternate forms of physical activity such as active transportation, active play and school based physical activity. This finding reflects Australia's position as one of the global leaders for participating in organised sport. Future research and surveillance methodologies however, need to incorporate standardised metrics that aim to capture more detailed data regarding organised sport participation. Facilitating access for all children and preventing dropout from organised sports are important initiatives to improve current levels of sport participation. However, given that 80% of Australians aged 5-17 years are not sufficiently physically active to achieve the daily recommendation, participation in sport alone is not enough to ensure that children can accrue the health benefits associated with being physically active. As such, there is a pressing need to develop strategies that engage children in other forms of physical activity such as active transportation and active play. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  5. Preparation and evaporation of Hanford Waste treatment plant direct feed low activity waste effluent management facility simulant

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Nash, C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Howe, A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); McCabe, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-09-07

    The Hanford Waste Treatment and Immobilization Plant (WTP) Low Activity Waste (LAW) vitrification facility will generate an aqueous condensate recycle stream (LAW Melter Off-Gas Condensate, LMOGC) from the off-gas system. The baseline plan for disposition of this stream during full WTP operations is to send it to the WTP Pretreatment Facility, where it will be blended with LAW, concentrated by evaporation, and recycled to the LAW vitrification facility. However, during the Direct Feed LAW (DFLAW) scenario, planned disposition of this stream involves concentrating the condensate in a new evaporator at the Effluent Management Facility (EMF) and returning it to the LAW melter. The LMOGC stream will contain components, e.g. halides and sulfates, that are volatile at melter temperatures, have limited solubility in glass waste forms, and present a material corrosion concern. Because this stream will recycle within WTP, these components are expected to accumulate in the LMOGC stream, exacerbating their impact on the number of LAW glass containers that must be produced. Diverting the stream reduces the halides and sulfates in the glass and is a key objective of this program. In order to determine the disposition path, it is key to experimentally determine the fate of contaminants. To do this, testing is needed to account for the buffering chemistry of the components, determine the achievable evaporation end point, identify insoluble solids that form, determine the formation and distribution of key regulatoryimpacting constituents, and generate an aqueous stream that can be used in testing of the subsequent immobilization step. This overall program examines the potential treatment and immobilization of the LMOGC stream to enable alternative disposal. The objective of this task was to (1) prepare a simulant of the LAW Melter Off-gas Condensate expected during DFLAW operations, (2) demonstrate evaporation in order to predict the final composition of the effluents from the EMF

  6. The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group: past activities, current status and future direction.

    Science.gov (United States)

    Nakagawa, Kazuo; Watanabe, Shun-Ichi; Kunitoh, Hideo; Asamura, Hisao

    2017-03-01

    The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group was organized in 1986. Initially, 26 collaborative institutions participated. In the early period, the Lung Cancer Surgical Study Group focused on combined modality therapies and conducted nine trials, including JCOG9101: adjuvant chemotherapy for resected small-cell lung cancer, and JCOG9806: induction chemoradiotherapy followed by surgery for superior sulcus tumor, which greatly impacted the treatment strategies for some special kinds of lung cancer. Since the 2000s, the Lung Cancer Surgical Study Group has defined radiologically noninvasive adenocarcinoma: JCOG0201 and investigated adequate modes of surgical resection for small-sized non-small cell lung cancer: JCOG0802, JCOG0804 and JCOG1211. The accrual of these trials is now complete and we are waiting for the maturation of follow-up data. In addition, two adjuvant trials have been conducted: JCOG0707; a Phase III study of adjuvant chemotherapy for resected pathological stage I (T1 > 2 cm) non-small cell lung cancer, and JCOG1205; a Phase III study of adjuvant chemotherapy for completely resected pulmonary high-grade neuroendocrine tumor. The accrual of JCOG0707 is complete and we are waiting for the maturation of follow-up data. At present, 44 institutions are active members of the Lung Cancer Surgical Study Group. In addition to thoracic surgeons, medical oncologists, pathologists and radiotherapists are participating in the Lung Cancer Surgical Study Group. The Lung Cancer Surgical Study Group continues to conduct various clinical trials in an effort to improve survival in patients with lung cancer. In this review, we provide an overview of the past 30 years, as well as the present status and future direction of the Lung Cancer Surgical Study Group. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. P-I snake venom metalloproteinase is able to activate the complement system by direct cleavage of central components of the cascade.

    Directory of Open Access Journals (Sweden)

    Giselle Pidde-Queiroz

    Full Text Available BACKGROUND: Snake Venom Metalloproteinases (SVMPs are amongst the key enzymes that contribute to the high toxicity of snake venom. We have recently shown that snake venoms from the Bothrops genus activate the Complement system (C by promoting direct cleavage of C-components and generating anaphylatoxins, thereby contributing to the pathology and spread of the venom. The aim of the present study was to isolate and characterize the C-activating protease from Bothrops pirajai venom. RESULTS: Using two gel-filtration chromatography steps, a metalloproteinase of 23 kDa that activates Complement was isolated from Bothrops pirajai venom. The mass spectrometric identification of this protein, named here as C-SVMP, revealed peptides that matched sequences from the P-I class of SVMPs. C-SVMP activated the alternative, classical and lectin C-pathways by cleaving the α-chain of C3, C4 and C5, thereby generating anaphylatoxins C3a, C4a and C5a. In vivo, C-SVMP induced consumption of murine complement components, most likely by activation of the pathways and/or by direct cleavage of C3, leading to a reduction of serum lytic activity. CONCLUSION: We show here that a P-I metalloproteinase from Bothrops pirajai snake venom activated the Complement system by direct cleavage of the central C-components, i.e., C3, C4 and C5, thereby generating biologically active fragments, such as anaphylatoxins, and by cleaving the C1-Inhibitor, which may affect Complement activation control. These results suggest that direct complement activation by SVMPs may play a role in the progression of symptoms that follow envenomation.

  8. P-I Snake Venom Metalloproteinase Is Able to Activate the Complement System by Direct Cleavage of Central Components of the Cascade

    Science.gov (United States)

    Pidde-Queiroz, Giselle; Magnoli, Fábio Carlos; Portaro, Fernanda C. V.; Serrano, Solange M. T.; Lopes, Aline Soriano; Paes Leme, Adriana Franco; van den Berg, Carmen W.; Tambourgi, Denise V.

    2013-01-01

    Background Snake Venom Metalloproteinases (SVMPs) are amongst the key enzymes that contribute to the high toxicity of snake venom. We have recently shown that snake venoms from the Bothrops genus activate the Complement system (C) by promoting direct cleavage of C-components and generating anaphylatoxins, thereby contributing to the pathology and spread of the venom. The aim of the present study was to isolate and characterize the C-activating protease from Bothrops pirajai venom. Results Using two gel-filtration chromatography steps, a metalloproteinase of 23 kDa that activates Complement was isolated from Bothrops pirajai venom. The mass spectrometric identification of this protein, named here as C-SVMP, revealed peptides that matched sequences from the P-I class of SVMPs. C-SVMP activated the alternative, classical and lectin C-pathways by cleaving the α-chain of C3, C4 and C5, thereby generating anaphylatoxins C3a, C4a and C5a. In vivo, C-SVMP induced consumption of murine complement components, most likely by activation of the pathways and/or by direct cleavage of C3, leading to a reduction of serum lytic activity. Conclusion We show here that a P-I metalloproteinase from Bothrops pirajai snake venom activated the Complement system by direct cleavage of the central C-components, i.e., C3, C4 and C5, thereby generating biologically active fragments, such as anaphylatoxins, and by cleaving the C1-Inhibitor, which may affect Complement activation control. These results suggest that direct complement activation by SVMPs may play a role in the progression of symptoms that follow envenomation. PMID:24205428

  9. Do cardinal directions in different Acacia tree species affect biological activities of bruchid beetle, Bruchidius buettikeri Decelle (Bruchidae: Coleoptera), in Riyadh Region, Saudi Arabia.

    Science.gov (United States)

    Aldawood, A S

    2009-12-15

    Biological activities of bruchid beetle: Bruchidius buettikeri Decelle (Bruchidae: Coleoptera) were studied in four cardinal directions of Acacia tree species in Huraimila and Salbouk. In Huraimila, two species of Acacia; A. grrrardii, subspecies A. g. negevensis (Iraqi) and A. g. nagednsis (Najdi); and A. ehrenbergiana (Salam) were sampled. In Salbouk, A. tortilis radiana (Samar) was sampled. No significant differences were observed for entrance and exit holes per pod and beetles emergence until 45 days on four cardinal directions of different Acacia tree species, except for entrance holes at Dam and Farm locations on Najdi in Huraimila. However, greater activities were observed in south and east direction in farm locations whereas, in the valley (Abu Gatada, Alyata and Dam locations) more bruchid activities were observed in north and south on Najdi and samar while east and west on Iraqi. Moreover, activities were greater on Acacia trees with greater number of seed per pod. Greater bruchid infestation per pod was found on East direction in the farm locations but in the valley locations no distinct trend was observed. Results showed a significant, positive correlation between bruchid activities and temperature but similar strength negative correlation was observed for rest of various abiotic factors. Moreover, a strong positive correlation was recorded between neonate entrance and number of beetle emergence.

  10. A single gene directs synthesis of a precursor protein with beta- and alpha-amylase activities in Bacillus polymyxa.

    OpenAIRE

    Uozumi, N; Sakurai, K; Sasaki, T; Takekawa, S; Yamagata, H; Tsukagoshi, N; Udaka, S

    1989-01-01

    The Bacillus polymyxa amylase gene comprises 3,588 nucleotides. The mature amylase comprises 1,161 amino acids with a molecular weight of 127,314. The gene appeared to be divided into two portions by the direct-repeat sequence located at almost the middle of the gene. The 5' region upstream of the direct-repeat sequence was shown to be responsible for the synthesis of beta-amylase. The 3' region downstream of the direct-repeat sequence contained four sequences homologous with those in other a...

  11. Formulation and preparation of Hanford Waste Treatment Plant direct feed low activity waste Effluent Management Facility core simulant

    Energy Technology Data Exchange (ETDEWEB)

    McCabe, Daniel J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Nash, Charles A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL; Adamson, Duane J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL

    2016-05-01

    The Hanford Waste Treatment and Immobilization Plant (WTP) Low Activity Waste (LAW) vitrification facility will generate an aqueous condensate recycle stream (LAW Melter Off-Gas Condensate, LMOGC) from the off-gas system. The baseline plan for disposition of this stream during full WTP operations is to send it to the WTP Pretreatment Facility, where it will be blended with LAW, concentrated by evaporation and recycled to the LAW vitrification facility. However, during the Direct Feed LAW (DFLAW) scenario, planned disposition of this stream is to evaporate it in a new evaporator in the Effluent Management Facility (EMF) and then return it to the LAW melter. It is important to understand the composition of the effluents from the melter and new evaporator so that the disposition of these streams can be accurately planned and accommodated. Furthermore, alternate disposition of the LMOGC stream would eliminate recycling of problematic components, and would enable less integrated operation of the LAW melter and the Pretreatment Facilities. Alternate disposition would also eliminate this stream from recycling within WTP when it begins operations and would decrease the LAW vitrification mission duration and quantity of glass waste, amongst the other problems such a recycle stream present. This LAW Melter Off-Gas Condensate stream will contain components that are volatile at melter temperatures and are problematic for the glass waste form, such as halides and sulfate. Because this stream will recycle within WTP, these components accumulate in the Melter Condensate stream, exacerbating their impact on the number of LAW glass containers that must be produced. Diverting the stream reduces the halides and sulfate in the recycled Condensate and is a key outcome of this work. This overall program examines the potential treatment and immobilization of this stream to enable alternative disposal. The objective of this task was to formulate and prepare a simulant of the LAW Melter

  12. Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes

    DEFF Research Database (Denmark)

    Sondergaard, B C; Wulf, H; Henriksen, K

    2006-01-01

    OBJECTIVE: Calcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes...

  13. 78 FR 60816 - Proposed Directive for Additional Seasonal or Year-Round Recreation Activities at Ski Areas

    Science.gov (United States)

    2013-10-02

    ... appreciation for nature that could lead to further exploration of NFS lands beyond ski areas. Further guidance... determined that these proposed directives would not pose the risk of a taking of private property. Civil...

  14. Formation of the scientific activities direction at the department of medicinal and pharmaceutical chemistry (dedicated to 105th birthday anniversary of A. V. Dombrovsky)

    OpenAIRE

    Stadniychuk, Raisa; Bratenko, Mykhaylo; Perepelytsya, Olesya

    2017-01-01

    The article highlights the historical period of activity of the Department of General Chemistry from 1951 to 1953, and the importance of the influence of the personality of Andrei Vladimirovich Dombrovsky on the development of the new scientific direction of the department in the field of organic chemistry-the purposeful organic synthesis of biologically active substances-is revealed. In the course of an insignificant period of time, the head of the department was able to create favorable con...

  15. A Model for Direction Sensing in Dictyostelium discoideum: Ras Activity and Symmetry Breaking Driven by a Gβγ-Mediated, Gα2-Ric8 -- Dependent Signal Transduction Network.

    Science.gov (United States)

    Cheng, Yougan; Othmer, Hans

    2016-05-01

    Chemotaxis is a dynamic cellular process, comprised of direction sensing, polarization and locomotion, that leads to the directed movement of eukaryotic cells along extracellular gradients. As a primary step in the response of an individual cell to a spatial stimulus, direction sensing has attracted numerous theoretical treatments aimed at explaining experimental observations in a variety of cell types. Here we propose a new model of direction sensing based on experiments using Dictyostelium discoideum (Dicty). The model is built around a reaction-diffusion-translocation system that involves three main component processes: a signal detection step based on G-protein-coupled receptors (GPCR) for cyclic AMP (cAMP), a transduction step based on a heterotrimetic G protein Gα2βγ, and an activation step of a monomeric G-protein Ras. The model can predict the experimentally-observed response of cells treated with latrunculin A, which removes feedback from downstream processes, under a variety of stimulus protocols. We show that [Formula: see text] cycling modulated by Ric8, a nonreceptor guanine exchange factor for [Formula: see text] in Dicty, drives multiple phases of Ras activation and leads to direction sensing and signal amplification in cAMP gradients. The model predicts that both [Formula: see text] and Gβγ are essential for direction sensing, in that membrane-localized [Formula: see text], the activated GTP-bearing form of [Formula: see text], leads to asymmetrical recruitment of RasGEF and Ric8, while globally-diffusing Gβγ mediates their activation. We show that the predicted response at the level of Ras activation encodes sufficient 'memory' to eliminate the 'back-of-the wave' problem, and the effects of diffusion and cell shape on direction sensing are also investigated. In contrast with existing LEGI models of chemotaxis, the results do not require a disparity between the diffusion coefficients of the Ras activator GEF and the Ras inhibitor GAP. Since

  16. Monocytes and the 38kDa-antigen of mycobacterium tuberculosis modulate natural killer cell activity and their cytolysis directed against ovarian cancer cell lines

    Directory of Open Access Journals (Sweden)

    Gottschalk Nina

    2012-10-01

    Full Text Available Abstract Background Despite strong efforts to improve clinical outcome of ovarian cancer patients by conventional and targeted immuno-based therapies, the prognosis of advanced ovarian cancer is still poor. Natural killer (NK cells mediate antibody-dependent cellular cytotoxicity (ADCC, release immunostimulatory cytokines and thus function as potent anti-tumour effector cells. However, tumour cells developed mechanisms to escape from an effective immune response. So highly immunogenic substances, like the 38 kDa-preparation of M. tuberculosis, PstS-1, are explored for their potential to enhance cancer-targeted immune responses. In this study we examined the modulation of different NK cell functions by accessory monocytes and PstS-1. We focussed on NK cell activation as well as natural and antibody-dependent cellular cytotoxicity directed against epidermal-growth-factor-receptor (EGFR-positive ovarian cancer cell lines. Methods Activation, cytokine release and cytotoxicity of NK cells stimulated by monocytes and PstS-1 were determined by FACS-analysis, ELISA, Bioplex assay and quantitative polymerase-chain reaction (qPCR. Transwell assays were used to discriminate cell-cell contact-dependent from contact-independent mechanisms. Five ovarian cancer cell lines (A2780, IGROV-1, OVCAR-3, OVCAR-4 and SKOV-3 with different EGFR-expression were used as target cells for natural and antibody-dependent cellular cytotoxicity assays. Cetuximab (anti-EGFR-antibody was used for ADCC studies. Results Our data show that monocytes effectively enhance activation as well natural and antibody-dependent cytolytic activity of NK cells. PstS-1 directly stimulated monocytes and further activated monocyte-NK-co-cultures. However, PstS-1 did not directly influence purified NK cells and did also not affect natural and antibody-dependent cellular cytotoxicity directed against EGFR-positive ovarian cancer cells, even in presence of monocytes. Direct cell-cell contact between

  17. Site-Directed Mutagenesis Analysis of Amino Acids Critical for Activity of the Type I Signal Peptidase of the Archaeon Methanococcus voltae

    Science.gov (United States)

    Bardy, Sonia L.; Ng, Sandy Y. M.; Carnegie, David S.; Jarrell, Ken F.

    2005-01-01

    Site-directed mutagenesis studies of the signal peptidase of the methanogenic archaeon Methanococcus voltae identified three conserved residues (Ser52, His122, and Asp148) critical for activity. The requirement for one conserved aspartic acid residue distinguishes the archaeal enzyme from both the Escherichia coli and yeast Sec11 enzymes. PMID:15659694

  18. Pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism

    NARCIS (Netherlands)

    van Straten, E. M. E.; Huijkman, N. C. A.; Baller, J. F. W.; Kuipers, F.; Plosch, T.

    2008-01-01

    van Straten EM, Huijkman NC, Baller JF, Kuipers F, Plosch T. Pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism. Am J Physiol Endocrinol Metab 295: E1341-E1348, 2008. First published October

  19. Study of hydrogenases activity inhibition by O{sub 2} and direct electrochemistry; Etude de l'inhibition par O{sub 2} de l'activite d'hydrogenases par electrochimie directe

    Energy Technology Data Exchange (ETDEWEB)

    Baffert, C.; Leger, Ch.; Leroux, F.; Bertrand, P.; Guigliarelli, B. [Laboratoire de Bioenergetique et d' Ingenierie des proteines, BIP-CNRS, 13 - Marseille (France)

    2007-07-01

    At the present time, a great effort of research is made on the identification and the design of enzymes insensitive or low sensitive to O{sub 2}. In parallel, it seems important to understand the inhibition mechanisms in order to propose mutations able to limit this inhibition. The Protein Film Voltametry allows to obtain data which can not be observed or quantitatively obtained by other techniques. The enzyme is immobilized directly on the electrode and the electronic transfer is direct. The redox state of the enzyme depends on the potential of the electrode and the catalytic current is proportional to the enzyme activity. The data obtained for the Ni-Fe hydrogenase (Desulfovibrio fructosovorans) and for the Fe hydrogenase (Clostridium Acetobutylicum) will be compared to the data obtained for hydrogenases of other organisms, by Protein Film Voltametry as well as by other techniques. (O.M.)

  20. Neuronal activity in primate prefrontal cortex related to goal-directed behavior during auditory working memory tasks.

    Science.gov (United States)

    Huang, Ying; Brosch, Michael

    2016-06-01

    Prefrontal cortex (PFC) has been documented to play critical roles in goal-directed behaviors, like representing goal-relevant events and working memory (WM). However, neurophysiological evidence for such roles of PFC has been obtained mainly with visual tasks but rarely with auditory tasks. In the present study, we tested roles of PFC in auditory goal-directed behaviors by recording local field potentials in the auditory region of left ventrolateral PFC while a monkey performed auditory WM tasks. The tasks consisted of multiple events and required the monkey to change its mental states to achieve the reward. The events were auditory and visual stimuli, as well as specific actions. Mental states were engaging in the tasks and holding task-relevant information in auditory WM. We found that, although based on recordings from one hemisphere in one monkey only, PFC represented multiple events that were important for achieving reward, including auditory and visual stimuli like turning on and off an LED, as well as bar touch. The responses to auditory events depended on the tasks and on the context of the tasks. This provides support for the idea that neuronal representations in PFC are flexible and can be related to the behavioral meaning of stimuli. We also found that engaging in the tasks and holding information in auditory WM were associated with persistent changes of slow potentials, both of which are essential for auditory goal-directed behaviors. Our study, on a single hemisphere in a single monkey, reveals roles of PFC in auditory goal-directed behaviors similar to those in visual goal-directed behaviors, suggesting that functions of PFC in goal-directed behaviors are probably common across the auditory and visual modality. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Microwave-assisted synthesis of palladium nanoparticles intercalated nitrogen doped reduced graphene oxide and their electrocatalytic activity for direct-ethanol fuel cells.

    Science.gov (United States)

    Kumar, Rajesh; da Silva, Everson T S G; Singh, Rajesh K; Savu, Raluca; Alaferdov, Andrei V; Fonseca, Leandro C; Carossi, Lory C; Singh, Arvind; Khandka, Sarita; Kar, Kamal K; Alves, Oswaldo L; Kubota, Lauro T; Moshkalev, Stanislav A

    2018-04-01

    Palladium nanoparticles decorated reduced graphene oxide (Pd-rGO) and palladium nanoparticles intercalated inside nitrogen doped reduced graphene oxide (Pd-NrGO) hybrids have been synthesized by applying a very simple, fast and economic route using microwave-assisted in-situ reduction and exfoliation method. The Pd-NrGO hybrids materials show good activity as catalyst for ethanol electro oxidation for direct ethanol fuel cells (DEFCs) as compared to Pd-rGO hybrids. The enhanced direct ethanol fuel cell can serve as alternative to fossil fuels because it is renewable and environmentally-friendly with a high energy conversion efficiency and low pollutant emission. As proof of concept, the electrocatalytic activity of Pd-NrGO hybrid material was accessed by cyclic voltammetry in presence of ethanol to evaluate its applicability in direct-ethanol fuel cells (DEFCs). The Pd-NrGO catalyst presented higher electro active surface area (∼6.3 m 2  g -1 ) for ethanol electro-oxidation when compared to Pd-rGO hybrids (∼3.7 m 2  g -1 ). Despite the smaller catalytic activity of Pd-NrGO, which was attributed to the lower exfoliation rate of this material in relation to the Pd-rGO, Pd-NrGO showed to be very promising and its catalytic activity can be further improved by tuning the synthesis parameters to increase the exfoliation rate. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Gynecologic Cancer Prevention and Control in the National Comprehensive Cancer Control Program: Progress, Current Activities, and Future Directions

    OpenAIRE

    Stewart, Sherri L.; Lakhani, Naheed; Brown, Phaeydra M.; Larkin, O. Ann; Moore, Angela R.; Hayes, Nikki S.

    2013-01-01

    Gynecologic cancer confers a large burden among women in the United States. Several evidence-based interventions are available to reduce the incidence, morbidity, and mortality from these cancers. The National Comprehensive Cancer Control Program (NCCCP) is uniquely positioned to implement these interventions in the US population. This review discusses progress and future directions for the NCCCP in preventing and controlling gynecologic cancer.

  3. Gynecologic cancer prevention and control in the National Comprehensive Cancer Control Program: progress, current activities, and future directions.

    Science.gov (United States)

    Stewart, Sherri L; Lakhani, Naheed; Brown, Phaeydra M; Larkin, O Ann; Moore, Angela R; Hayes, Nikki S

    2013-08-01

    Gynecologic cancer confers a large burden among women in the United States. Several evidence-based interventions are available to reduce the incidence, morbidity, and mortality from these cancers. The National Comprehensive Cancer Control Program (NCCCP) is uniquely positioned to implement these interventions in the US population. This review discusses progress and future directions for the NCCCP in preventing and controlling gynecologic cancer.

  4. Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity

    DEFF Research Database (Denmark)

    Danovi, Davide; Meulmeester, Erik; Pasini, Diego

    2004-01-01

    Human tumors are believed to harbor a disabled p53 tumor suppressor pathway, either through direct mutation of the p53 gene or through aberrant expression of proteins acting in the p53 pathway, such as p14(ARF) or Mdm2. A role for Mdmx (or Mdm4) as a key negative regulator of p53 function in vivo...

  5. Gravitational and Dynamic Components of Muscle Torque Underlie Tonic and Phasic Muscle Activity during Goal-Directed Reaching

    Directory of Open Access Journals (Sweden)

    Erienne V. Olesh

    2017-09-01

    Full Text Available Human reaching movements require complex muscle activations to produce the forces necessary to move the limb in a controlled manner. How gravity and the complex kinetic properties of the limb contribute to the generation of the muscle activation pattern by the central nervous system (CNS is a long-standing and controversial question in neuroscience. To tackle this issue, muscle activity is often subdivided into static and phasic components. The former corresponds to posture maintenance and transitions between postures. The latter corresponds to active movement production and the compensation for the kinetic properties of the limb. In the present study, we improved the methodology for this subdivision of muscle activity into static and phasic components by relating them to joint torques. Ten healthy subjects pointed in virtual reality to visual targets arranged to create a standard center-out reaching task in three dimensions. Muscle activity and motion capture data were synchronously collected during the movements. The motion capture data were used to calculate postural and dynamic components of active muscle torques using a dynamic model of the arm with 5 degrees of freedom. Principal Component Analysis (PCA was then applied to muscle activity and the torque components, separately, to reduce the dimensionality of the data. Muscle activity was also reconstructed from gravitational and dynamic torque components. Results show that the postural and dynamic components of muscle torque represent a significant amount of variance in muscle activity. This method could be used to define static and phasic components of muscle activity using muscle torques.

  6. Increasing the transglycosylation activity of alpha-galactosidase from Bifidobacterium adolescentis DSM 20083 by site-directed mutagenesis

    NARCIS (Netherlands)

    Hinz, S.W.A.; Doeswijk-Voragen, C.H.L.; Schipperus, R.; Broek, van den L.A.M.; Vincken, J.P.; Voragen, A.G.J.

    2006-01-01

    The ¿-galactosidase (AGA) from Bifidobacterium adolescentis DSM 20083 has a high transglycosylation activity. The optimal conditions for this activity are pH 8, and 37°C. At high melibiose concentration (600 mM), approximately 64% of the enzyme-substrate encounters resulted in transglycosylation.

  7. HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains.

    Science.gov (United States)

    Wang, Chong; Long, Wenying; Peng, Chao; Hu, Lin; Zhang, Qiong; Wu, Ailing; Zhang, Xiaoqing; Duan, Xiaotao; Wong, Catherine C L; Tanaka, Yuetsu; Xia, Zongping

    2016-04-01

    The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation.

  8. Re-directed T cells for the treatment of fibroblast activation protein (FAP-positive malignant pleural mesothelioma (FAPME-1

    Directory of Open Access Journals (Sweden)

    Petrausch Ulf

    2012-12-01

    Full Text Available Abstract Background Asbestos is the main cause of MPM in industrialized countries. Even since asbestos is banned in most developed countries, the peak wave of MPM incidence is anticipated for the next years due to the long latency of asbestos induced MPM. MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomie have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. Methods/design This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x106 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor recognizing FAP which serves as target structure in MPM. At day 0 of the protocol, re-directed T cells will be injected in the pleural effusion and patients will be monitored for 48h under intermediate care conditions. AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT. No further patient can be treated before the previous patient passed day 14 after T cell transfer. The protocol will be judged as save when no DLT occurred in the first 3 patients, or 1 DLT in 6 patients. Secondary objectives are feasibility and immune monitoring. Discussion Adoptive T cell transfer is a new and rapidly expanding branch of immunotherapies focusing on cancer treatment. Recently, objective responses could be observed in patients with chronic lymphatic leukemia treated with adoptively transferred CD19-specific re-directed T cells. The choice of the target antigen determines the possible on-target off-tissue toxicity of such approaches. There are reports of

  9. Ongoing brain activity fluctuations directly account for intertrial and indirectly for intersubject variability in Stroop task performance.

    Science.gov (United States)

    Coste, Clio P; Sadaghiani, Sepideh; Friston, Karl J; Kleinschmidt, Andreas

    2011-11-01

    Recent studies have established a relation between ongoing brain activity fluctuations and intertrial variability in evoked neural responses, perception, and motor performance. Here, we extended these investigations into the domain of cognitive control. Using functional neuroimaging and a sparse event-related design (with long and unpredictable intervals), we measured ongoing activity fluctuations and evoked responses in volunteers performing a Stroop task with color-word interference. Across trials, prestimulus activity of several regions predicted subsequent response speed and across subjects this effect scaled with the Stroop effect size, being significant only in subjects manifesting behavioral interference. These effects occurred only in task relevant as the dorsal anterior cingulate and dorsolateral prefrontal cortex as well as ventral visual areas sensitive to color and visual words. Crucially, in subjects showing a Stroop effect, reaction times were faster when prestimulus activity was higher in task-relevant (color) regions and slower when activity was higher in irrelevant (word form) regions. These findings suggest that intrinsic brain activity fluctuations modulate neural mechanisms underpinning selective voluntary attention and cognitive control. Rephrased in terms of predictive coding models, ongoing activity can hence be considered a proxy of the precision (gain) with which prediction error signals are transmitted upon sensory stimulation.

  10. The alkylating prodrug J1 can be activated by aminopeptidase N, leading to a possible target directed release of melphalan

    DEFF Research Database (Denmark)

    Wickström, Malin; Viktorsson, Kristina; Lundholm, Lovisa

    2010-01-01

    The alkylating prodrug of melphalan, J1 (melphalanyl-l-p-fluorophenylalanyl ethyl ester) is currently in early clinical trials. Preclinical studies have shown that J1-mediated cytotoxicity is dependent on hydrolytic activity of tumor cells. In this report we have analyzed potential peptidases...... and apoptotic signaling. In conclusion, this study demonstrates a role of APN in the activation of the melphalan prodrug J1 and subsequently, its cytotoxicity. Given that APN is shown to be overexpressed in several solid tumors our data suggest that J1 may be activated in a tumor selective manner....

  11. Modulation of Brain Activity with Noninvasive Transcranial Direct Current Stimulation (tDCS: Clinical Applications and Safety Concerns

    Directory of Open Access Journals (Sweden)

    Haichao Zhao

    2017-05-01

    Full Text Available Transcranial direct current stimulation (tDCS is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children. This review covers the typical characteristics and the underlying neural mechanisms of tDCS treatment in such studies. This is followed by a discussion of safety, especially when the current intensity is increased or the stimulation duration is prolonged. Given such concerns, we provide detailed suggestions regarding safety procedures for tDCS operation. Lastly, future research directions are discussed. They include foci on the development of multi-tech combination with tDCS such as with TMS and fMRI; long-term behavioral and morphological changes; possible applications in other research domains, and more animal research to deepen the understanding of the biological and physiological mechanisms of tDCS stimulation.

  12. Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

    LENUS (Irish Health Repository)

    McCarron, Mark

    2012-02-01

    In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate\\'s natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.

  13. Direct activity determination of Mn-54 and Zn-65 by a non-extrapolation liquid scintillation method

    CSIR Research Space (South Africa)

    Simpson, BRS

    2004-02-01

    Full Text Available The measurement of Mn-54 and Zn-65 by liquid scintillation coincidence counting results in low detection efficiencies. The activity obtained from the extrapolation of efficiency data can therefore become problematic if curvature is present...

  14. Direct application of UNIFAC activity coefficient computer programs to the calculation of solvent activities and .chi.-parameters for polymer solutions

    NARCIS (Netherlands)

    van den Berg, J.W.A.

    1984-01-01

    Application of UNIFAC computer calculations to polymer solutions does not seem to make sense because of the value of the solvent activity: close to 1.000 over a considerable range of concentrations (up to 90% of polymer). A simple procedure is proposed to calculate solvent activity coefficients, and

  15. Phytol directly activates peroxisome proliferator-activated receptor α (PPARα) and regulates gene expression involved in lipid metabolism in PPARα-expressing HepG2 hepatocytes

    International Nuclear Information System (INIS)

    Goto, Tsuyoshi; Takahashi, Nobuyuki; Kato, Sota; Egawa, Kahori; Ebisu, Shogo; Moriyama, Tatsuya; Fushiki, Tohru; Kawada, Teruo

    2005-01-01

    The peroxisome proliferator-activated receptor (PPAR) is one of the indispensable transcription factors for regulating lipid metabolism in various tissues. In our screening for natural compounds that activate PPAR using luciferase assays, a branched-carbon-chain alcohol (a component of chlorophylls), phytol, has been identified as a PPARα-specific activator. Phytol induced the increase in PPARα-dependent luciferase activity and the degree of in vitro binding of a coactivator, SRC-1, to GST-PPARα. Moreover, the addition of phytol upregulated the expression of PPARα-target genes at both mRNA and protein levels in PPARα-expressing HepG2 hepatocytes. These findings indicate that phytol is functional as a PPARα ligand and that it stimulates the expression of PPARα-target genes in intact cells. Because PPARα activation enhances circulating lipid clearance, phytol may be important in managing abnormalities in lipid metabolism

  16. Divergent selection on home pen locomotor activity in a chicken model: Selection program, genetic parameters and direct response on activity and body weight.

    Directory of Open Access Journals (Sweden)

    Joergen B Kjaer

    Full Text Available General locomotor activity (GLA in poultry has attracted attention, as it negatively influences production costs (energy expenditure and feed consumption and welfare parameters (bone strength, litter quality, feather pecking and cannibalism. Laying hen lines diverging in the average level of spontaneous locomotor activity in the home pen were developed by genetic selection using the founder New Hampshire line. Activity was recorded using RFID technology at around five weeks of age during four to five days in the home pen. After initial phenotyping, the least active birds were selected for the low activity line and the most active for the high activity line, with no gene transfer between lines. In each of six generations, approximately ten sires were mated to twenty dams producing 158 to 334 offspring per line per generation. The response to selection was rapid and of a considerable magnitude. In sixth generation, the level of GLA was approximately halved in the low and doubled in the high line compared to the control (7.2, 14.9 and 28.7 recordings/h. Estimated heritability of locomotor activity in the low and high line was 0.38 and 0.33, respectively. Males, in general, were more active than females. High line birds were significantly heavier than low line birds. In fourth, fifth, and sixth generation, low as well as high line birds were lighter than control line birds. This selection experiment demonstrates variation in heritability for GLA and, as a result, genetically diverged lines have been developed. These lines can be used as models for further studies of underlying physiological, neural and molecular genetic mechanisms of spontaneous locomotor activity.

  17. Effects of Preventative Ankle Taping on Planned Change-of-Direction and Reactive Agility Performance and Ankle Muscle Activity in Basketballers

    Directory of Open Access Journals (Sweden)

    Matthew D. Jeffriess, Adrian B. Schultz, Tye S. McGann, Samuel J. Callaghan, Robert G. Lockie

    2015-12-01

    Full Text Available This study investigated the effects of preventative ankle taping on planned change-of-direction and reactive agility performance and peak ankle muscle activity in basketballers. Twenty male basketballers (age = 22.30 ± 3.97 years; height = 1.84 ± 0.09 meters; body mass = 85.96 ± 11.88 kilograms with no ankle pathologies attended two testing sessions. Within each session, subjects completed six planned and six reactive randomized trials (three to the left and three to the right for each condition of the Y-shaped agility test, which was recorded by timing lights. In one session, subjects had both ankles un-taped. In the other, both ankles were taped using a modified subtalar sling. Peak tibialis anterior, peroneus longus (PL, peroneus brevis (PB, and soleus muscle activity was recorded for both the inside and outside legs across stance phase during the directional change, which was normalized against 10-meter sprint muscle activity (nEMG. Both the inside and outside cut legs during the change-of-direction step were investigated. Repeated measures ANOVA determined performance time and nEMG differences between un-taped and taped conditions. There were no differences in planned change-of-direction or reactive agility times between the conditions. Inside cut leg PL nEMG decreased when taped for the planned left, reactive left, and reactive right cuts (p = 0.01. Outside leg PB and soleus nEMG increased during the taped planned left cut (p = 0.02. There were no other nEMG changes during the cuts with taping. Taping did not affect change-of-direction or agility performance. Inside leg PL activity was decreased, possibly due to the tape following the line of muscle action. This may reduce the kinetic demand for the PL during cuts. In conclusion, ankle taping did not significantly affect planned change-of-direction or reactive agility performance, and did not demonstrate large changes in activity of the muscle complex in healthy basketballers.

  18. ATP synthase in slow- and fast-growing mycobacteria is active in ATP synthesis and blocked in ATP hydrolysis direction.

    Science.gov (United States)

    Haagsma, Anna C; Driessen, Nicole N; Hahn, Marc-Manuel; Lill, Holger; Bald, Dirk

    2010-12-01

    ATP synthase is a validated drug target for the treatment of tuberculosis, and ATP synthase inhibitors are promising candidate drugs for the treatment of infections caused by other slow-growing mycobacteria, such as Mycobacterium leprae and Mycobacterium ulcerans. ATP synthase is an essential enzyme in the energy metabolism of Mycobacterium tuberculosis; however, no biochemical data are available to characterize the role of ATP synthase in slow-growing mycobacterial strains. Here, we show that inverted membrane vesicles from the slow-growing model strain Mycobacterium bovis BCG are active in ATP synthesis, but ATP synthase displays no detectable ATP hydrolysis activity and does not set up a proton-motive force (PMF) using ATP as a substrate. Treatment with methanol as well as PMF activation unmasked the ATP hydrolysis activity, indicating that the intrinsic subunit ɛ and inhibitory ADP are responsible for the suppression of hydrolytic activity. These results suggest that the enzyme is needed for the synthesis of ATP, not for the maintenance of the PMF. For the development of new antimycobacterial drugs acting on ATP synthase, screening for ATP synthesis inhibitors, but not for ATP hydrolysis blockers, can be regarded as a promising strategy. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  19. BART Inhibits Pancreatic Cancer Cell Invasion by Rac1 Inactivation through Direct Binding to Active Rac1

    Directory of Open Access Journals (Sweden)

    Keisuke Taniuchi

    2012-05-01

    Full Text Available We report that Binder of Arl Two (BART plays a role in inhibiting cell invasion by regulating the activity of the Rho small guanosine triphosphatase protein Rac1 in pancreatic cancer cells. BART was originally identified as a binding partner of ADP-ribosylation factor-like 2, a small G protein implicated as a regulator of microtubule dynamics and folding. BART interacts with active forms of Rac1, and the BART-Rac1 complex localizes at the leading edges of migrating cancer cells. Suppression of BART increases active Rac1, thereby increasing cell invasion. Treatment of pancreatic cancer cells in which BART is stably knocked down with a Rac1 inhibitor decreases invasiveness. Thus, BART-dependent inhibition of cell invasion is likely associated with decreased active Rac1. Suppression of BART induces membrane ruffling and lamellipodial protrusion and increases peripheral actin structures in membrane ruffles at the edges of lamellipodia. The Rac1 inhibitor inhibits the lamellipodia formation that is stimulated by suppression of BART. Our results imply that BART regulates actin-cytoskeleton rearrangements at membrane ruffles through modulation of the activity of Rac1, which, in turn, inhibits pancreatic cancer cell invasion.

  20. Directed Vertical Diffusion of Photovoltaic Active Layer Components into Porous ZnO-Based Cathode Buffer Layers.

    Science.gov (United States)

    Kang, Jia-Jhen; Yang, Tsung-Yu; Lan, Yi-Kang; Wu, Wei-Ru; Su, Chun-Jen; Weng, Shih-Chang; Yamada, Norifumi L; Su, An-Chung; Jeng, U-Ser

    2018-03-02

    Cathode buffer layers (CBLs) can effectively further the efficiency of polymer solar cells (PSCs), after optimization of the active layer. Hidden between the active layer and cathode of the inverted PSC device configuration is the critical yet often unattended vertical diffusion of the active layer components across CBL. Here, a novel methodology of contrast variation with neutron and anomalous X-ray reflectivity to map the multicomponent depth compositions of inverted PSCs, covering from the active layer surface down to the bottom of the ZnO-based CBL, is developed. Uniquely revealed for a high-performance model PSC are the often overlooked porosity distributions of the ZnO-based CBL and the differential diffusions of the polymer PTB7-Th and fullerene derivative PC 71 BM of the active layer into the CBL. Interface modification of the ZnO-based CBL with fullerene derivative PCBEOH for size-selective nanochannels can selectively improve the diffusion of PC 71 BM more than that of the polymer. The deeper penetration of PC 71 BM establishes a gradient distribution of fullerene derivatives over the ZnO/PCBE-OH CBL, resulting in markedly improved electron mobility and device efficiency of the inverted PSC. The result suggests a new CBL design concept of progressive matching of the conduction bands. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Effects of Preventative Ankle Taping on Planned Change-of-Direction and Reactive Agility Performance and Ankle Muscle Activity in Basketballers.

    Science.gov (United States)

    Jeffriess, Matthew D; Schultz, Adrian B; McGann, Tye S; Callaghan, Samuel J; Lockie, Robert G

    2015-12-01

    This study investigated the effects of preventative ankle taping on planned change-of-direction and reactive agility performance and peak ankle muscle activity in basketballers. Twenty male basketballers (age = 22.30 ± 3.97 years; height = 1.84 ± 0.09 meters; body mass = 85.96 ± 11.88 kilograms) with no ankle pathologies attended two testing sessions. Within each session, subjects completed six planned and six reactive randomized trials (three to the left and three to the right for each condition) of the Y-shaped agility test, which was recorded by timing lights. In one session, subjects had both ankles un-taped. In the other, both ankles were taped using a modified subtalar sling. Peak tibialis anterior, peroneus longus (PL), peroneus brevis (PB), and soleus muscle activity was recorded for both the inside and outside legs across stance phase during the directional change, which was normalized against 10-meter sprint muscle activity (nEMG). Both the inside and outside cut legs during the change-of-direction step were investigated. Repeated measures ANOVA determined performance time and nEMG differences between un-taped and taped conditions. There were no differences in planned change-of-direction or reactive agility times between the conditions. Inside cut leg PL nEMG decreased when taped for the planned left, reactive left, and reactive right cuts (p = 0.01). Outside leg PB and soleus nEMG increased during the taped planned left cut (p = 0.02). There were no other nEMG changes during the cuts with taping. Taping did not affect change-of-direction or agility performance. Inside leg PL activity was decreased, possibly due to the tape following the line of muscle action. This may reduce the kinetic demand for the PL during cuts. In conclusion, ankle taping did not significantly affect planned change-of-direction or reactive agility performance, and did not demonstrate large changes in activity of the muscle complex in healthy basketballers. Key pointsAnkle taping

  2. Very low speed performance of active flux based sensorless control: interior permanent magnet synchronous motor vector control versus direct torque and flux control

    DEFF Research Database (Denmark)

    Paicu, M. C.; Boldea, I.; Andreescu, G. D.

    2009-01-01

    This study is focused on very low speed performance comparison between two sensorless control systems based on the novel ‘active flux' concept, that is, the current/voltage vector control versus direct torque and flux control (DTFC) for interior permanent magnet synchronous motor (IPMSM) drives...... with space vector modulation (SVM), without signal injection. The active flux, defined as the flux that multiplies iq current in the dq-model torque expression of all ac machines, is easily obtained from the stator-flux vector and has the rotor position orientation. Therefore notable simplification...

  3. Direct regulation of transforming growth factor β-induced epithelial-mesenchymal transition by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells.

    Science.gov (United States)

    Kusunose, Masaaki; Hashimoto, Naozumi; Kimura, Motohiro; Ogata, Ryo; Aoyama, Daisuke; Sakamoto, Koji; Miyazaki, Shinichi; Ando, Akira; Omote, Norihito; Imaizumi, Kazuyoshi; Kawabe, Tsutomu; Hasegawa, Yoshinori

    2015-12-01

    Transforming growth factor β (TGFβ) causes the acquisition of epithelial-mesenchymal transition (EMT). Although the tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) can negatively regulate many signaling pathways activated by TGFβ, hyperactivation of these signaling pathways is observed in lung cancer cells. We recently showed that PTEN might be subject to TGFβ-induced phosphorylation of its C-terminus, resulting in a loss of its enzyme activities; PTEN with an unphosphorylated C-terminus (PTEN4A), but not PTEN wild, inhibits TGFβ-induced EMT. Nevertheless, whether or not the blockade of TGFβ-induced EMT by the PTEN phosphatase activity might be attributed to the unphosphorylated PTEN C-terminus itself has not been fully determined. Furthermore, the lipid phosphatase activity of PTEN is well characterized, whereas the protein phosphatase activity has not been determined. By using lung cancer cells carrying PTEN domain deletions or point mutants, we investigated the role of PTEN protein phosphatase activities on TGFβ-induced EMT in lung cancer cells. The unphosphorylated PTEN C-terminus might not directly retain the phosphatase activities and repress TGFβ-induced EMT; the modification that keeps the PTEN C-terminus not phosphorylated might enable PTEN to retain the phosphatase activity. PTEN4A with G129E mutation, which lacks lipid phosphatase activity but retains protein phosphatase activity, repressed TGFβ-induced EMT. Furthermore, the protein phosphatase activity of PTEN4A depended on an essential association between the C2 and phosphatase domains. These data suggest that the protein phosphatase activity of PTEN with an unphosphorylated C-terminus might be a therapeutic target to negatively regulate TGFβ-induced EMT in lung cancer cells. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  4. Direct Biomarkers of Microbial Translocation Correlate with Immune Activation in Adult Zambians with Environmental Enteropathy and Hepatosplenic Schistosomiasis.

    Science.gov (United States)

    Kaonga, Patrick; Kaimoyo, Evans; Besa, Ellen; Zyambo, Kanekwa; Sinkala, Edford; Kelly, Paul

    2017-11-01

    Microbial translocation is a poorly understood consequence of several disorders such as environmental enteropathy (EE) and hepatosplenic schistosomiasis (HSS). Herein, we compared biomarkers of microbial origin and immune activation in adults with these disorders and in healthy controls. A cross-sectional study was conducted in participants with EE recruited from Misisi compound, Lusaka, Zambia; HSS patients and healthy controls from the University Teaching Hospital, Lusaka. Plasma lipopolysaccharides (LPSs) was measured by limulus amoebocyte lysate assay, plasma 16S ribosomal RNA (16S rRNA) gene copy number was quantified by quantitative real-time polymerase chain reaction, Toll-like receptor ligand (TLRL) activity by QUANTI-Blue detection medium, and cytokines from cell culture supernatant by Cytometric Bead Array. In univariate analysis LPS, 16S rRNA gene copy number, and TLR activity were all high and correlated with each other and with cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, and IL-4 secreted by the RAW-Blue cells. After controlling for baseline characteristic, biomarkers of microbial translocation in blood were predictors of TNF-α, IL-6, and IL-10 activation in cell culture supernatant from EE participants and HSS patients but not in healthy controls. TLR activity showed the strongest correlation with TNF-α. These data provide correlative evidence that microbial translocation contributes to systemic cytokine activation in two disorders common in the tropics, with total TLR ligand estimation showing the strongest correlation with TNF-α ( r = 0.66, P < 0.001).

  5. Molecular docking and site-directed mutagenesis of a Bacillus thuringiensis chitinase to improve chitinolytic, synergistic lepidopteran-larvicidal and nematicidal activities.

    Science.gov (United States)

    Ni, Hong; Zeng, Siquan; Qin, Xu; Sun, Xiaowen; Zhang, Shan; Zhao, Xiuyun; Yu, Ziniu; Li, Lin

    2015-01-01

    Bacterial chitinases are useful in the biocontrol of agriculturally important pests and fungal pathogens. However, the utility of naturally occurring bacterial chitinases is often limited by their low enzyme activity. In this study, we constructed mutants of a Bacillus thuringiensis chitinase with enhanced activity based on homology modeling, molecular docking, and the site-directed mutagenesis of target residues to modify spatial positions, steric hindrances, or hydrophilicity/hydrophobicity. We first identified a gene from B. thuringiensis YBT-9602 that encodes a chitinase (Chi9602) belonging to glycosyl hydrolase family 18 with conserved substrate-binding and substrate-catalytic motifs. We constructed a structural model of a truncated version of Chi9602 (Chi9602(35-459)) containing the substrate-binding domain using the homologous 1ITX protein of Bacillus circulans as the template. We performed molecular docking analysis of Chi9602(35-459) using di-N-acetyl-D-glucosamine as the ligand. We then selected 10 residues of interest from the docking area for the site-directed mutagenesis experiments and expression in Escherichia coli. Assays of the chitinolytic activity of the purified chitinases revealed that the three mutants exhibited increased chitinolytic activity. The ChiW50A mutant exhibited a greater than 60 % increase in chitinolytic activity, with similar pH, temperature and metal ion requirements, compared to wild-type Chi9602. Furthermore, ChiW50A exhibited pest-controlling activity and antifungal activity. Remarkable synergistic effects of this mutant with B. thuringiensis spore-crystal preparations against Helicoverpa armigera and Caenorhabditis elegans larvae and obvious activity against several plant-pathogenic fungi were observed.

  6. Snail collaborates with EGR-1 and SP-1 to directly activate transcription of MMP 9 and ZEB1.

    Science.gov (United States)

    Wu, Wen-Sheng; You, Ren-In; Cheng, Chuan-Chu; Lee, Ming-Che; Lin, Teng-Yi; Hu, Chi-Tan

    2017-12-19

    The Snail transcription factor plays as a master regulator of epithelial mesenchymal transition (EMT), one of the steps of tumor metastasis. Snail enhances expressions of a lot of mesenchymal genes including the matrix degradation enzyme matrix metalloproteinases 9 (MMP9) and the EMT transcription factor zinc finger E-box binding homeobox 1 (ZEB1), however, the underlying mechanisms are not clarified. Herein, we investigated how Snail upregulated transcription of ZEB1 and MMP9 induced by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate (TPA) in hepatoma cell HepG2. According to deletion mapping and site directed mutagenesis analysis, the TPA-responsive elements on both MMP9 and ZEB1 promoters locate on a putative EGR1 and SP1 overlapping region coupled with an upstream proposed Snail binding motif TCACA. Consistently, chromatin immunoprecipitation (ChIP) assay showed TPA triggered binding of Snail, EGR1 and SP1 on MMP9 and ZEB1 promoters. Double ChIP further indicated TPA induced association of Snail with EGR1 and SP1 on both promoters. Also, electrophoresis mobility shift assay revealed TPA enhanced binding of Snail with a MMP9 promoter fragment. According to shRNA techniques, Snail was essential for gene expression of both ZEB1 and MMP9. In conclusion, Snail transactivates genes involved in tumor progression via direct binding to a specific promoter region.

  7. Direct assessment of cumulative aryl hydrocarbon receptor agonist activity in sera from experimentally exposed mice and environmentally exposed humans

    DEFF Research Database (Denmark)

    Schlezinger, Jennifer J; Bernard, Pamela L; Haas, Amelia

    2010-01-01

    BACKGROUND: Aryl hydrocarbon receptor (AhR) ligands adversely affect many biological processes. However, assessment of the significance of human exposures is hampered by an incomplete understanding of how complex mixtures affect AhR activation/inactivation. OBJECTIVES: These studies used biologic...

  8. Activation of carbon-supported catalysts by ozonized acidic solutions for the direct implementation in (electro-)chemical reactors.

    Science.gov (United States)

    Baldizzone, C; Mezzavilla, S; Hodnik, N; Zeradjanin, A R; Kostka, A; Schüth, F; Mayrhofer, K J J

    2015-01-25

    This work introduces a practical and scalable post-synthesis treatment for carbon-supported catalysts designed to achieve complete activation and, if necessary, simultaneously surface dealloying. The core concept behind the method is to control the potential without utilizing any electrochemical equipment, but rather by applying an appropriate gas mixture to a catalyst suspension.

  9. Evaluating the Direction of Effects in the Relationship between Religious versus Non-Religious Activities, Academic Success, and Substance Use

    Science.gov (United States)

    Good, Marie; Willoughby, Teena

    2011-01-01

    This longitudinal study tested the "influence of involvement" and "selection" hypotheses for the association between religious versus non-religious activity involvement and two salient indicators of adolescent psychosocial adjustment (substance use and academic achievement). Participants included 3,993 Canadian adolescents…

  10. Composition Directed Generation of Reactive Oxygen Species in Irradiated Mixed Metal Sulfides Correlated with Their Photocatalytic Activities.

    Science.gov (United States)

    He, Weiwei; Jia, Huimin; Yang, Dongfang; Xiao, Pin; Fan, Xiaoli; Zheng, Zhi; Kim, Hyun-Kyung; Wamer, Wayne G; Yin, Jun-Jie

    2015-08-05

    The ability of nanostructures to facilitate the generation of reactive oxygen species and charge carriers underlies many of their chemical and biological activities. Elucidating which factors are essential and how these influence the production of various active intermediates is fundamental to understanding potential applications of these nanostructures, as well as potential risks. Using electron spin resonance spectroscopy coupled with spin trapping and spin labeling techniques, we assessed 3 mixed metal sulfides of varying compositions for their abilities to generate reactive oxygen species, photogenerate electrons, and consume oxygen during photoirradiation. We found these irradiated mixed metal sulfides exhibited composition dependent generation of ROS: ZnIn2S4 can generate (•)OH, O2(-•) and (1)O2; CdIn2S4 can produce O2(-•) and (1)O2, while AgInS2 only produces O2(-•). Our characterizations of the reactivity of the photogenerated electrons and consumption of dissolved oxygen, performed using spin labeling, showed the same trend in activity: ZnIn2S4 > CdIn2S4 > AgInS2. These intrinsic abilities to generate ROS and the reactivity of charge carriers correlated closely with the photocatalytic degradation and photoassisted antibacterial activities of these nanomaterials.

  11. Teaching Programming by Emphasizing Self-Direction: How Did Students React to the Active Role Required of Them?

    Science.gov (United States)

    Isomottonen, Ville; Tirronen, Ville

    2013-01-01

    Lecturing is known to be a controversial form of teaching. With massed classrooms, in particular, it tends to constrain the active participation of students. One of the remedies applied to programming education is to use technology that can vitalize interaction in the classroom, while another is to base teaching increasingly on programming…

  12. Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair.

    Science.gov (United States)

    Li, Xing; Zhao, Yannan; Cheng, Shixiang; Han, Sufang; Shu, Muya; Chen, Bing; Chen, Xuyi; Tang, Fengwu; Wang, Nuo; Tu, Yue; Wang, Bin; Xiao, Zhifeng; Zhang, Sai; Dai, Jianwu

    2017-08-01

    Studies have shown that endogenous neural stem cells (NSCs) activated by spinal cord injury (SCI) primarily generate astrocytes to form glial scar. The NSCs do not differentiate into neurons because of the adverse microenvironment. In this study, we defined the activation timeline of endogenous NSCs in rats with severe SCI. These injury-activated NSCs then migrated into the lesion site. Cetuximab, an EGFR signaling antagonist, significantly increased neurogenesis in the lesion site. Meanwhile, implanting cetuximab modified linear ordered collagen scaffolds (LOCS) into SCI lesion sites in dogs resulted in neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation. The neuronal regeneration eventually led to a significant locomotion recovery. Furthermore, LOCS implantation could also greatly decrease chondroitin sulfate proteoglycan (CSPG) deposition at the lesion site. These findings suggest that endogenous neurogenesis following acute complete SCI is achievable in species ranging from rodents to large animals via functional scaffold implantation. LOCS-based Cetuximab delivery system has a promising therapeutic effect on activating endogenous neurogenesis, reducing CSPGs deposition and improving motor function recovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline.

    Science.gov (United States)

    Yang, Long; Bashaw, Greg J

    2006-11-22

    Son of sevenless (Sos) is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases and thus is uniquely poised to integrate signals that affect both gene expression and cytoskeletal reorganization. Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand. Intriguingly, the Ras and Rac-GEF activities of Sos can be uncoupled during Robo-mediated axon repulsion; Sos axon guidance function depends on its Rac-GEF activity, but not its Ras-GEF activity. These results provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules and support a model in which Robo recruits Sos to the membrane via Dock to activate Rac during midline repulsion.

  14. Tertiary Students and Social Development: An Area for Direct Action--Student Rural Service Activities in Malaysia.

    Science.gov (United States)

    Kong, Kee Poo

    The study is a survey of the different kinds of voluntary rural service (service-learning) corps of students from the institutions of higher education in Malaysia. The history, organization, and activities of the service corps are examined, and this type of student social action is viewed with reference to the role of higher education in the…

  15. Alginate microbeads are coagulation compatible, while alginate microcapsules activate coagulation secondary to complement or directly through FXII.

    Science.gov (United States)

    Gravastrand, Caroline; Hamad, Shamal; Fure, Hilde; Steinkjer, Bjørg; Ryan, Liv; Oberholzer, Josè; Lambris, John D; Lacík, Igor; Mollnes, Tom Eirik; Espevik, Terje; Brekke, Ole-Lars; Rokstad, Anne Mari

    2017-08-01

    Alginate microspheres are presently under evaluation for future cell-based therapy. Their ability to induce harmful host reactions needs to be identified for developing the most suitable devices and efficient prevention strategies. We used a lepirudin based human whole blood model to investigate the coagulation potentials of alginate-based microspheres: alginate microbeads (Ca/Ba Beads), alginate poly-l-lysine microcapsules (APA and AP microcapsules) and sodium alginate-sodium cellulose sulfate-poly(methylene-co-cyanoguanidine) microcapsules (PMCG microcapsules). Coagulation activation measured by prothrombin fragments 1+2 (PTF1.2) was rapidly and markedly induced by the PMCG microcapsules, delayed and lower induced by the APA and AP microcapsules, and not induced by the Ca/Ba Beads. Monocytes tissue factor (TF) expression was similarly activated by the microcapsules, whereas not by the Ca/Ba Beads. PMCG microcapsules-induced PTF1.2 was abolished by FXII inhibition (corn trypsin inhibitor), thus pointing to activation through the contact pathway. PTF1.2 induced by the AP and APA microcapsules was inhibited by anti-TF antibody, pointing to a TF driven coagulation. The TF induced coagulation was inhibited by the complement inhibitors compstatin (C3 inhibition) and eculizumab (C5 inhibition), revealing a complement-coagulation cross-talk. This is the first study on the coagulation potentials of alginate microspheres, and identifies differences in activation potential, pathways and possible intervention points. Alginate microcapsules are prospective candidate materials for cell encapsulation therapy. The material surface must be free of host cell adhesion to ensure free diffusion of nutrition and oxygen to the encapsulated cells. Coagulation activation is one gateway to cellular overgrowth through deposition of fibrin. Herein we used a physiologically relevant whole blood model to investigate the coagulation potential of alginate microcapsules and microbeads. The

  16. Electrical measurements in the atmosphere and the Ionosphere over an active thunderstorm. II - Direct current electric fields and conductivity

    Science.gov (United States)

    Holzworth, R. H.; Kelley, M. C.; Siefring, C. L.; Hale, L. C.; Mitchell, J. D.

    1985-01-01

    On August 9, 1981, a series of three rockets was launched over an air mass thunderstorm off the eastern seaboard of Virginia while simultaneous stratospheric and ground-based electric field measurements were made. The conductivity was substantially lower at most altitudes than the conductivity profiles used by theoretical models. Direct current electric fields over 80 mV/m were measured as far away as 96 km from the storm in the stratosphere at 23 km altitude. No dc electric fields above 75 km altitude could be identified with the thunderstorm, in agreement with theory. However, vertical current densities over 120 pA/sq m were seen well above the classical 'electrosphere' (at 50 or 60 km). Frequent dc shifts in the electric field following lightning transients were seen by both balloon and rocket payloads. These dc shifts are clearly identifiable with either cloud-to-ground (increases) or intercloud (decreases) lightning flashes.

  17. Activity-Dependent and Experience-Driven Myelination Provide New Directions for the Management of Multiple Sclerosis.

    Science.gov (United States)

    Jensen, Samuel K; Yong, V Wee

    2016-06-01

    Despite an appreciation of the importance of myelination and the consequences of pathological demyelination, the fundamental mechanisms regulating myelination are only now being resolved. Neuronal activity has long been considered a plausible regulatory signal for myelination. However, controversy surrounding its dispensability in certain contexts and the difficulty in determining to what degree it influences myelination has limited its widespread acceptance. Recent studies have shed new light on the role of neuronal activity in regulating oligodendrogenesis and myelination. Further, the dynamics of myelin in adulthood and the association between skilled learning and myelination have become increasingly well characterized. These advances present new considerations for the management of multiple sclerosis and open up new approaches to facilitate remyelination following pathological demyelination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Immunoliposomes directed toward VCAM-1 interact specifically with activated endothelial cells--a potential tool for specific drug delivery.

    Science.gov (United States)

    Voinea, Manuela; Manduteanu, Ileana; Dragomir, Elena; Capraru, Monica; Simionescu, Maya

    2005-11-01

    Immunoliposomes can be potentially used as carriers for drug delivery to specific cells. The aim of this paper was to exploit the overexpression of vascular cell adhesion molecule-1 (VCAM-1) on activated human endothelial cells (HEC) for targeting of anti-VCAM-1 coupled liposomes with the intent for further use as drug carriers. TNF-alpha-activated HEC were exposed to liposomes, either plain or coupled with antibodies to VCAM-1 (L-VCAM-1) or to irrelevant IgG (L-IgG); nonactivated HEC subjected to the same conditions were used as control. For binding studies, the cells were incubated with fluorescently labeled liposomes at 4 degrees C, and after 2 h, fluorescence intensity was assessed by flow cytometry; specificity of binding was determined by performing the experiments in the presence of excess anti-VCAM-1. Cellular internalization of liposomes was studied employing radioactively or fluorescently labelled liposomes; to detect the mechanisms of uptake, experiments were performed in the presence of agents that interfere in the endocytotic pathway. Transmigration of liposomes was monitored in a two-chamber culture model. The effect of L-VCAM-1 binding to HEC on intracellular calcium ([Ca(2+)](i)) and distribution of actin was determined by fluorimetry and fluorescence microscopy. (1) L-VCAM-1 binds selectively and specifically to TNF-alpha activated HEC. (2) Approximately 50% of L-VCAM-1 is taken up by receptor-mediated endocytosis via clathrin-coated vesicles. (3) Binding of L-VCAM-1 to HEC surface induces a rise in [Ca(2+)](i) and reorganization of actin filaments. (4) A small percentage of liposomes migrates across HEC. The data indicate that VCAM-1 may be an appropriate target for specific drug delivery to activated HEC using immunoliposomes.

  19. The relationship between apathy and participation in therapeutic activities in nursing home residents with dementia: Evidence for an association and directions for further research.

    Science.gov (United States)

    Ellis, Julie M; Doyle, Colleen J; Selvarajah, Suganya

    2016-07-01

    Apathy is one of the most frequent and early symptoms of dementia. Because apathy is characterised by lack of initiative and motivation, it leads to considerable burden being placed on carers to ensure that the person living with dementia has a reasonable quality of life. The aim of this study was to investigate the relationship between apathy and participation in therapeutic activities for older people with dementia living in nursing homes. Ninety residents were recruited into the study, and apathy was measured by nursing home staff using the Apathy Evaluation Scale Clinician version. Staff also compiled data on each resident's involvement in therapeutic activities. Among this sample, the mean age was 84.8 years, and mean length of stay in the nursing home was 1.8 years. The mean apathy score was 50.4, indicating that on average the residents had a moderate level of apathy. Overall, residents participated in six activities per week and those residents who were involved in the most activities had the lowest levels of apathy. This paper provides evidence that residents involved in therapeutic activities have lower levels of apathy. Further research should be conducted on the direction of causality, whether apathy levels can be changed through participation in therapeutic activities, the relationship between dementia severity and modifiability of apathy, and the intensity of therapeutic activities required to maintain functioning. © The Author(s) 2014.

  20. Bovine CCL28 Mediates Chemotaxis via CCR10 and Demonstrates Direct Antimicrobial Activity against Mastitis Causing Bacteria.

    Directory of Open Access Journals (Sweden)

    Kyler B Pallister

    Full Text Available In addition to the well characterized function of chemokines in mediating the homing and accumulation of leukocytes to tissues, some chemokines also exhibit potent antimicrobial activity. Little is known of the potential role of chemokines in bovine mammary gland health and disease. The chemokine CCL28 has previously been shown to play a key role in the homing and accumulation of IgA antibody secreting cells to the lactating murine mammary gland. CCL28 has also been shown to act as an antimicrobial peptide with activity demonstrated against a wide range of pathogens including bacteria, fungi and protozoans. Here we describe the cloning and function of bovine CCL28 and document the concentration of this chemokine in bovine milk. Bovine CCL28 was shown to mediate cellular chemotaxis via the CCR10 chemokine receptor and exhibited antimicrobial activity against a variety of bovine mastitis causing organisms. The concentration of bovine CCL28 in milk was found to be highly correlated with the lactation cycle. Highest concentrations of CCL28 were observed soon after parturition, with levels decreasing over time. These results suggest a potential role for CCL28 in the prevention/resolution of bovine mastitis.

  1. Evaluating the direction of effects in the relationship between religious versus non-religious activities, academic success, and substance use.

    Science.gov (United States)

    Good, Marie; Willoughby, Teena

    2011-06-01

    This longitudinal study tested the influence of involvement and selection hypotheses for the association between religious versus non-religious activity involvement and two salient indicators of adolescent psychosocial adjustment (substance use and academic achievement). Participants included 3,993 Canadian adolescents (49.4% girls) who were surveyed each year from grades 9-12. More frequent religious attendance (but not non-religious club involvement) in one grade predicted lower levels of substance use in the next grade. Higher levels of non-religious club involvement (but not religious service attendance) in one grade predicted higher academic achievement in the next grade, and higher academic achievement in one grade predicted more frequent non-religious club involvement in the next grade. The effects were robust, as they were invariant across grade and significant after controlling for individual, peer, and family characteristics. Most importantly, these results suggest that religious activities are not just another club, but, rather, that different developmental assets may be fostered in religious as compared to non-religious activities.

  2. Research on the Effects of Process Parameters on Surface Roughness in Wet-Activated Silicon Direct Bonding Base on Orthogonal Experiments

    Directory of Open Access Journals (Sweden)

    Lei NIE

    2015-11-01

    Full Text Available Surface roughness is a very important index in silicon direct bonding and it is affected by processing parameters in the wet-activated process. These parameters include the concentration of activation solution, holding time and treatment temperature. The effects of these parameters were investigated by means of orthogonal experiments. In order to analyze the wafer roughness more accurately, the bear ratio of the surface was used as the evaluation index. From the results of the experiments, it could be concluded that the concentration of the activation solution affected the roughness directly and the higher the concentration, the lower the roughness. Holding time did not affect the roughness as acutely as that of the concentration, but a reduced activation time decreased the roughness perceptibly. It was also discovered that the treatment temperature had a weak correlation with the surface roughness. Based on these conclusions, the parameters of concentration, temperature and holding time were optimized respectively as NH4OH:H2O2=1:1 (without water, 70 °C and 5 min. The results of bonding experiments proved the validity of the conclusions of orthogonal experiments.DOI: http://dx.doi.org/10.5755/j01.ms.21.4.9711

  3. HMGCS2 enhances invasion and metastasis via direct interaction with PPARα to activate Src signaling in colorectal cancer and oral cancer

    Science.gov (United States)

    Chang, Cheng-Chi; Li, Yue-Ju; Chen, Szu-Ta; Lin, I-Ching; Kok, Sang-Heng; Cheng, Shih-Jung; Lee, Jang-Jaer; Wu, Tai-Sheng; Kuo, Min-Liang; Lin, Been-Ren

    2017-01-01

    Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer. PMID:27816970

  4. Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium.

    Science.gov (United States)

    Hojo, Hironori; Ohba, Shinsuke; Taniguchi, Kiyomi; Shirai, Masataka; Yano, Fumiko; Saito, Taku; Ikeda, Toshiyuki; Nakajima, Keiji; Komiyama, Yuske; Nakagata, Naomi; Suzuki, Kentaro; Mishina, Yuji; Yamada, Masahisa; Konno, Tomohiro; Takato, Tsuyoshi; Kawaguchi, Hiroshi; Kambara, Hideki; Chung, Ung-il

    2013-04-05

    Specification of progenitors into the osteoblast lineage is an essential event for skeletogenesis. During endochondral ossification, cells in the perichondrium give rise to osteoblast precursors. Hedgehog (Hh) and bone morphogenetic protein (BMP) are suggested to regulate the commitment of these cells. However, properties of perichondrial cells and regulatory mechanisms of the specification process are still poorly understood. Here, we investigated the machineries by combining a novel organ culture system and single-cell expression analysis with mouse genetics and biochemical analyses. In a metatarsal organ culture reproducing bone collar formation, activation of BMP signaling enhanced the bone collar formation cooperatively with Hh input, whereas the signaling induced ectopic chondrocyte formation in the perichondrium without Hh input. Similar phenotypes were also observed in compound mutant mice, where signaling activities of Hh and BMP were genetically manipulated. Single-cell quantitative RT-PCR analyses showed heterogeneity of perichondrial cells in terms of natural characteristics and responsiveness to Hh input. In vitro analyses revealed that Hh signaling suppressed BMP-induced chondrogenic differentiation; Gli1 inhibited the expression of Sox5, Sox6, and Sox9 (SRY box-containing gene 9) as well as transactivation by Sox9. Indeed, ectopic expression of chondrocyte maker genes were observed in the perichondrium of metatarsals in Gli1(-/-) fetuses, and the phenotype was more severe in Gli1(-/-);Gli2(-/-) newborns. These data suggest that Hh-Gli activators alter the function of BMP to specify perichondrial cells into osteoblasts; the timing of Hh input and its target populations are critical for BMP function.

  5. Effects of isoflurane anesthesia on ensemble patterns of Ca2+ activity in mouse V1: reduced direction selectivity independent of increased correlations in cellular activity

    NARCIS (Netherlands)

    Goltstein, P.M.; Montijn, J.S.; Pennartz, C.M.A.

    2015-01-01

    Anesthesia affects brain activity at the molecular, neuronal and network level, but it is not well-understood how tuning properties of sensory neurons and network connectivity change under its influence. Using in vivo two-photon calcium imaging we matched neuron identity across episodes of

  6. Compensation of Cross-Coupling Stiffness and Increase of Direct Damping in Multirecess Journal Bearings using Active Hybrid Lubrication

    DEFF Research Database (Denmark)

    Santos, Ilmar; Watanabe, F.Y.

    2004-01-01

    Fluid film forces are generated in hydrostatic journal bearings by two types of lubrication mechanisms: the hydrostatic lubrication in the bearing recesses and hydrodynamic lubrication in the bearing lands, when operating in rotation. The combination of both lubrication mechanisms leads to hybrid...... journal bearings (HJB). When part of hydrostatic pressure is also dynamically modified by means of hydraulic control systems, one refers to the active lubrication. The main contribution of the present theoretical work is to show that it is possible to reduce cross-coupling stiffness and increase...

  7. Removal of direct blue-106 dye from aqueous solution using new activated carbons developed from pomegranate peel: Adsorption equilibrium and kinetics

    International Nuclear Information System (INIS)

    Amin, Nevine Kamal

    2009-01-01

    The use of cheap, high efficiency and ecofriendly adsorbent has been studied as an alternative source of activated carbon for the removal of dyes from wastewater. This study investigates the use of activated carbons prepared from pomegranate peel for the removal of direct blue dye from aqueous solution. A series of experiments were conducted in a batch system to assess the effect of the system variables, i.e. initial pH, temperature, initial dye concentration adsorbent dosage and contact time. The results showed that the adsorption of direct blue dye was maximal at pH 2, as the amount of adsorbent increased, the percentage of dye removal increased accordingly but it decreased with the increase in initial dye concentration and solution temperature. The adsorption kinetics was found to follow pseudo-second-order rate kinetic model, with a good correlation (R 2 > 0.99) and intra-particle diffusion as one of the rate determining steps. Langmuir, Freundlich, Temkin, Dubinin-RadushKevich (D-R) and Harkins-Jura isotherms were used to analyze the equilibrium data at different temperatures. In addition, various thermodynamic parameters, such as standard Gibbs free energy (ΔG o ), standard enthalpy (ΔH o ), standard entropy (ΔS o ), and the activation energy (E a ) have been calculated. The adsorption process of direct blue dye onto different activated carbons prepared from pomegranate peel was found to be spontaneous and exothermic process. The findings of this investigation suggest that the physical sorption plays a role in controlling the sorption rate.

  8. Removal of direct blue-106 dye from aqueous solution using new activated carbons developed from pomegranate peel: Adsorption equilibrium and kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Amin, Nevine Kamal, E-mail: nkamalamin@yahoo.com [Chemical Engineering Department, Faculty of Engineering, Alexandria University, Alexandria (Egypt)

    2009-06-15

    The use of cheap, high efficiency and ecofriendly adsorbent has been studied as an alternative source of activated carbon for the removal of dyes from wastewater. This study investigates the use of activated carbons prepared from pomegranate peel for the removal of direct blue dye from aqueous solution. A series of experiments were conducted in a batch system to assess the effect of the system variables, i.e. initial pH, temperature, initial dye concentration adsorbent dosage and contact time. The results showed that the adsorption of direct blue dye was maximal at pH 2, as the amount of adsorbent increased, the percentage of dye removal increased accordingly but it decreased with the increase in initial dye concentration and solution temperature. The adsorption kinetics was found to follow pseudo-second-order rate kinetic model, with a good correlation (R{sup 2} > 0.99) and intra-particle diffusion as one of the rate determining steps. Langmuir, Freundlich, Temkin, Dubinin-RadushKevich (D-R) and Harkins-Jura isotherms were used to analyze the equilibrium data at different temperatures. In addition, various thermodynamic parameters, such as standard Gibbs free energy ({Delta}G{sup o}), standard enthalpy ({Delta}H{sup o}), standard entropy ({Delta}S{sup o}), and the activation energy (E{sub a}) have been calculated. The adsorption process of direct blue dye onto different activated carbons prepared from pomegranate peel was found to be spontaneous and exothermic process. The findings of this investigation suggest that the physical sorption plays a role in controlling the sorption rate.

  9. TCR signal strength alters T-DC activation and interaction times and directs the outcome of differentiation.

    Directory of Open Access Journals (Sweden)

    Nicholas eVan Panhuys

    2016-01-01

    Full Text Available The ability of CD4+ T cells to differentiate into effector subsets underpins their ability to shape the immune response and mediate host protection. During T cell receptor induced activation of CD4+ T cells both the quality and quantity of specific activatory peptide/MHC ligands have been shown to control the polarization of naïve CD4+ T cells in addition to co-stimulatory and cytokine based signals. Recently, advances in two photon microscopy and tetramer based cell tracking methods have allowed investigators to greatly extend the study of the role of TCR signaling in effector differentiation under in vivo conditions. In this review we consider data from recent in vivo studies analyzing the role of TCR signal strength in controlling the outcome of CD4+ T cell differentiation and discuss the role of the TCR in controlling the critical nature of CD4+ T cell interactions with dendritic cells during activation. We further propose a model whereby TCR signal strength controls the temporal aspects of T:DC interactions and the implications for this in mediating the downstream signaling events which influence the transcriptional and epigenetic regulation of effector differentiation.

  10. Improved efficacy of soluble human receptor activator of nuclear factor kappa B (RANK) fusion protein by site-directed mutagenesis.

    Science.gov (United States)

    Son, Young Jun; Han, Jihye; Lee, Jae Yeon; Kim, HaHyung; Chun, Taehoon

    2015-06-01

    Soluble human receptor activator of nuclear factor kappa B fusion immunoglobulin (hRANK-Ig) has been considered as one of the therapeutic agents to treat osteoporosis or diseases associated with bone destruction by blocking the interaction between RANK and the receptor activator of nuclear factor kappa B ligand (RANKL). However, no scientific record showing critical amino acid residues within the structural interface between the human RANKL and RANK complex is yet available. In this study, we produced several mutants of hRANK-Ig by replacement of amino acid residue(s) and tested whether the mutants had increased binding affinity to human RANKL. Based on the results from flow cytometry and surface plasmon resonance analyses, the replacement of E(125) with D(125), or E(125) and C(127) with D(125) and F(127) within loop 3 of cysteine-rich domain 3 of hRANK-Ig increases binding affinity to human RANKL over the wild-type hRANK-Ig. This result may provide the first example of improvement in the efficacy of hRANK-Ig by protein engineering and may give additional information to understand a more defined structural interface between hRANK and RANKL.

  11. Active-site-directed inhibition of 3-hydroxy-3-methylglutaryl coenzyme A synthase by 3-chloropropionyl coenzyme A

    International Nuclear Information System (INIS)

    Miziorko, H.M.; Behnke, C.E.

    1985-01-01

    3-Chloropropionyl coenzyme A (3-chloropropionyl-CoA) irreversibly inhibits avian liver 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase). Enzyme inactivation follows pseudo-first-order kinetics and is retarded in the presence of substrates, suggesting that covalent labeling occurs at the active site. A typical rate saturation effect is observed when inactivation kinetics are measured as a function of 3-chloropropionyl-CoA concentration. These data indicate a Ki = 15 microM for the inhibitor and a limiting kinact = 0.31 min-1. [1- 14 C]-3-Chloropropionyl-CoA binds covalently to the enzyme with a stoichiometry (0.7 per site) similar to that measured for acetylation of the enzyme by acetyl-CoA. While the acetylated enzyme formed upon incubation of HMG-CoA synthase with acetyl-CoA is labile to performic acid oxidation, the adduct formed upon 3-chloropropionyl-CoA inactivation is stable to such treatment. Therefore, such an adduct cannot solely involve a thio ester linkage. Exhaustive Pronase digestion of [ 14 C]-3-chloropropionyl-CoA-labeled enzyme produces a radioactive compound which cochromatographs with authentic carboxyethylcysteine using reverse-phase/ion-pairing high-pressure liquid chromatography and both silica and cellulose thin-layer chromatography systems. This suggests that enzyme inactivation is due to alkylation of an active-site cysteine residue

  12. Fluctuation-driven directional flow of energy in biochemical cycle: Electric activation of Na,K ATPase

    Science.gov (United States)

    Yow Tsong, Tian

    1998-03-01

    Na,K ATPase is an ion pump which uses chemical bond energy of ATP to pump Na ion out of, and K ion into living cell thus maintaining ionic and osmotic balances of the cell. Both are uphill transport reactions. Surprisingly we have found that electric energy can also substitute chemical energy to fuel the pump activity. However, in this case only electric fields of certain waveforms, amplitudes, and frequencies are effective. Waveform, amplitude and frequency are three elements of signal. In other words, Na,K ATPase can recognize, process, and harvest energy from an oscillating or a fluctuating electric field to drive an endergonic reaction. The enzyme is a molecular transducer of electric signal. This report will describe electric activation experiment to define electric signal. Electric signal will then mixed with electric noise of broad power spectrum for experiment. Effect of white noise (WN) on the efficiency of Na,K ATPase will be investigated. It will be shown that WN of appropriate power level can improve the pump efficiency when a sub-optimal electric field is used. WN can also carry a sub-threshold signal to cross over the threshold. Stochastic resonance will be discussed in reference to these observations.

  13. Comparison of the antimicrobial activity of direct pulp-capping materials: Mineral trioxide aggregate-Angelus and Biodentine.

    Science.gov (United States)

    Özyürek, Taha; Demiryürek, Ebru Özsezer

    2016-01-01

    To compare the antimicrobial activity of the tricalcium silicate-based Biodentine (BD) and mineral trioxide aggregate (MTA)-Angelus cement with the aid of agar diffusion test. Staphylococcus aureus , Pseudomonas aeruginosa , Escherichia coli , and Enterococcus faecium were inoculated in the Brucella liquid medium and were incubated at 37°C for 24 h. Thereafter, 100 >μl of the liquid culture of bacteria inoculated in the Mueller-Hinton agar with spread plate technique. Petri plates were dried in room temperature. For every microorganism, 3 petri plates were prepared (12 in total). In the medium, in every petri plate, 2 holes with 5 mm diameter and 2 mm depth were made. Afterward, BD and MTA-Angelus were filled into these holes under aseptic conditions according to the instructions of the manufacturing company. Then, the plates were kept in the incubator at 37°C for 24 h, and the diameters of the inhibition zones were measured with a digital caliper. Inhibition zones formed by BD against E. coli and S. aureus were significantly larger than the zones formed by MTA-Angelus ( P < 0.05). However, the inhibition zones formed by MTA-Angelus against P. aureus and E. faecium were larger than the zones formed by BD ( P < 0.05). Within the limits of the present study, tricalcium silicate-based MTA-Angelus and BD have antimicrobial activity against E. coli , S. aureus , P. aureus , and E. faecium .

  14. Response of piping system with semi-active variable stiffness damper under tri-directional seismic excitation

    Energy Technology Data Exchange (ETDEWEB)

    Praveen Kumar, E-mail: praveen@barc.gov.in [Department of Civil Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076 (India); Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Jangid, R.S. [Department of Civil Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076 (India); Reddy, G.R. [Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)

    2013-05-15

    Highlights: ► Piping system with semi-active variable stiffness damper is investigated under different seismic excitations. ► Switching control law and modified switching control law are adopted. ► There exist an optimum parameters of the SAVSD. ► Substantial reduction of the seismic response of piping system with SAVSD is observed. ► Good amount of energy dissipation is observed. -- Abstract: Seismic loads on piping system due to earthquakes can cause excessive vibrations, which can lead to serious instability resulting in damage or complete failure. In this paper, semi-active variable stiffness dampers (SAVSDs) have been studied to mitigate seismic response and vibration control of piping system used in the process industries, fossil and fissile fuel power plant. The SAVSD changes its stiffness depending upon the piping response and accordingly adds the control forces in the piping system. A study is conducted on the performance of SAVSD due to variation in device stiffness ratios in the switching control law and modified switching control law, which plays an important role in the present control algorithm of the damper. The effectiveness of the SAVSD in terms of reduction in the responses, namely, displacements, accelerations and base shear of the piping system is investigated by comparing uncontrolled responses under four different artificial earthquake motions with increasing amplitudes. The analytical results demonstrate that the SAVSDs under particular optimum parameters are very effective and practically implementable for the seismic response mitigation, vibration control and seismic requalification of piping systems.

  15. The cost of care of systemic lupus erythematosus (SLE) in the UK: annual direct costs for adult SLE patients with active autoantibody-positive disease.

    Science.gov (United States)

    Khamashta, M A; Bruce, I N; Gordon, C; Isenberg, D A; Ateka-Barrutia, O; Gayed, M; Donatti, C; Guillermin, A-L; Foo, J; Perna, A

    2014-03-01

    The aim of the Systemic LUpus Erythematosus Cost of Care In Europe (LUCIE) study was to evaluate the annual direct medical costs of managing adults with active autoantibody-positive disease on medication for SLE in secondary care. This paper presents the UK analyses only. A cost-of-illness study was conducted from the perspective of the National Health Service. Health resource utilization data were retrieved over a two-year period from four centres in England and unit cost data were taken from published sources. At baseline, 86 patients were included, 38 (44.2%) had severe SLE and 48 (55.8%) had non-severe SLE. The mean (SD) SELENA-SLEDAI score was 7.7 (5.7). The mean (SD) annual direct medical cost of was estimated at £3231 (£2333) per patient and was 2.2 times higher in patients with severe SLE compared with patients with non-severe SLE (p < 0.001). Multivariate model analyses showed that renal disease involvement (p = 0.0016) and severe flares (p = 0.0001) were associated with higher annual direct costs. Improvement of the overall stability of SLE and early intervention to minimize the impact of renal disease may be two approaches to mitigate the long-term direct cost of managing SLE patients in the UK.

  16. A summary of the active fault investigation in the extension sea area of Kikugawa fault and the Nishiyama fault , N-S direction fault in south west Japan

    Science.gov (United States)

    Abe, S.

    2010-12-01

    In this study, we carried out two sets of active fault investigation by the request from Ministry of Education, Culture, Sports, Science and Technology in the sea area of the extension of Kikugawa fault and the Nishiyama fault. We want to clarify the five following matters about both active faults based on those results. (1)Fault continuity of the land and the sea. (2) The length of the active fault. (3) The division of the segment. (4) Activity characteristics. In this investigation, we carried out a digital single channel seismic reflection survey in the whole area of both active faults. In addition, a high-resolution multichannel seismic reflection survey was carried out to recognize the detailed structure of a shallow stratum. Furthermore, the sampling with the vibrocoring to get information of the sedimentation age was carried out. The reflection profile of both active faults was extremely clear. The characteristics of the lateral fault such as flower structure, the dispersion of the active fault were recognized. In addition, from analysis of the age of the stratum, it was recognized that the thickness of the sediment was extremely thin in Holocene epoch on the continental shelf in this sea area. It was confirmed that the Kikugawa fault extended to the offing than the existing results of research by a result of this investigation. In addition, the width of the active fault seems to become wide toward the offing while dispersing. At present, we think that we can divide Kikugawa fault into some segments based on the distribution form of the segment. About the Nishiyama fault, reflection profiles to show the existence of the active fault was acquired in the sea between Ooshima and Kyushu. From this result and topographical existing results of research in Ooshima, it is thought that Nishiyama fault and the Ooshima offing active fault are a series of structure. As for Ooshima offing active fault, the upheaval side changes, and a direction changes too. Therefore, we