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Sample records for constitutively active v2

  1. V1 and v2b interneurons secure the alternating flexor-extensor motor activity mice require for limbed locomotion.

    Science.gov (United States)

    Zhang, Jingming; Lanuza, Guillermo M; Britz, Olivier; Wang, Zhi; Siembab, Valerie C; Zhang, Ying; Velasquez, Tomoko; Alvarez, Francisco J; Frank, Eric; Goulding, Martyn

    2014-04-02

    Reciprocal activation of flexor and extensor muscles constitutes the fundamental mechanism that tetrapod vertebrates use for locomotion and limb-driven reflex behaviors. This aspect of motor coordination is controlled by inhibitory neurons in the spinal cord; however, the identity of the spinal interneurons that serve this function is not known. Here, we show that the production of an alternating flexor-extensor motor rhythm depends on the composite activities of two classes of ventrally located inhibitory neurons, V1 and V2b interneurons (INs). Abrogating V1 and V2b IN-derived neurotransmission in the isolated spinal cord results in a synchronous pattern of L2 flexor-related and L5 extensor-related locomotor activity. Mice lacking V1 and V2b inhibition are unable to articulate their limb joints and display marked deficits in limb-driven reflex movements. Taken together, these findings identify V1- and V2b-derived neurons as the core interneuronal components of the limb central pattern generator (CPG) that coordinate flexor-extensor motor activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. V2O5 nanowires with an intrinsic peroxidase-like activity

    NARCIS (Netherlands)

    André, R.; Natálio, F.; Humanes, M.; Leppin, J.; Heinze, K.; Wever, R.; Schröder, H.C.; Müller, W.E.G.; Tremel, W.

    2011-01-01

    V2O5 nanowires exhibit an intrinsic catalytic activity towards classical peroxidase substrates such as 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 3,3,5,5,-tetramethylbenzdine (TMB) in the presence of H2O2. These V2O5 nanowires show an optimum reactivity at a pH of 4.0 and the

  3. In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V1 and V2.

    Science.gov (United States)

    Jamil, Khurram; Pappas, Stephen Chris; Devarakonda, Krishna R

    2018-01-01

    Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V 1 ) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys 8 ]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg 8 ]-vasopressin (AVP) at V 1 and vasopressin-2 (V 2 ) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V 1 and V 2 receptors were used in competitive binding assays to measure receptor-binding activity. These cells were used in functional assays to measure receptor-mediated cellular activity of terlipressin, LVP, and AVP. Binding was measured by [ 3 H]AVP counts, and the activity was measured by fluorometric detection of intracellular calcium mobilization (V 1 ) and cyclic adenosine monophosphate (V 2 ). Binding potency at V 1 and V 2 was AVP>LVP>terlipressin. LVP and terlipressin had approximately sixfold higher affinity for V 1 than for V 2 . Cellular activity potency was also AVP>LVP>terlipressin. Terlipressin was a partial agonist at V 1 and a full agonist at V 2 ; LVP was a full agonist at both V 1 and V 2 . The in vivo response to terlipressin is likely due to the partial V 1 agonist activity of terlipressin and full V 1 agonist activity of its metabolite, LVP. These results provide supportive evidence for previous findings and further establish terlipressin pharmacology for vasopressin receptors.

  4. Rare Earth Free Zn3V2O8 Phosphor with Controlled Microstructure and Its Photocatalytic Activity

    Directory of Open Access Journals (Sweden)

    Hom Nath Luitel

    2013-01-01

    Full Text Available Microsphere of rare earth free phosphor, Zn3V2O8, with broadband yellowish white emission was synthesized by combustion route and compared with the hydrothermal, sol-gel, and solid state reaction methods. The phosphor samples were characterized by X-ray diffraction and scanning electron microscopy. UV-visible absorption and photoluminescence (PL emission and excitation spectra were investigated for these phosphors. Zn3V2O8 phosphor containing 10 mol% of H3BO3 flux exhibited enhanced PL emission showing broadband from 450 nm to 750 nm. Effect of stoichiometry of Zn and V on the host lattice and its effect on the PL emission spectra were studied. Series of Mg3V2O8, Ca3V2O8, and Sr3V2O8 phosphors were also synthesized and compared to the Zn3V2O8 phosphor in terms of PL emission and internal quantum yield, and it was found that Zn3V2O8 is the most efficient phosphor among the other phosphors studied with quantum yield of 60%. The visible light irradiated photocatalytic activity of these phosphors was investigated and it was found that the hydrothermal Zn3V2O8 exhibited enhanced activity.

  5. Controversial constitutive TSHR activity: patients, physiology, and in vitro characterization.

    Science.gov (United States)

    Huth, S; Jaeschke, H; Schaarschmidt, J; Paschke, R

    2014-06-01

    G protein-coupled receptors constitute a large family of transmembrane receptors, which activate cellular responses by signal transmission and regulation of second messenger metabolism after ligand binding. For several of these receptors it is known that they also signal ligand-independently. The G protein-coupled thyroid stimulating hormone receptor (TSHR) is characterized by a high level of constitutive activity in the wild type state. However, little is known yet concerning the physiological relevance of the constitutive wild type TSHR activity. Certainly, knowledge of the physiological relevance of constitutive wild type receptor activity is necessary to better understand thyroid physiology and it is a prerequisite for the development of better therapies for nonautoimmune hyperthyroidism and thyroid cancer. Based on a literature search regarding all published TSHR mutations, this review covers several mutations which are clearly associated with a hyperthyroidism-phenotype, but interestingly show a lack of constitutive activity determined by in vitro characterization. Possible reasons for the observed discrepancies between clinical phenotypes and in vitro characterization results for constitutive TSHR activity are reviewed. All current in vitro characterization methods for constitutive TSHR mutations are "preliminary attempts" and may well be revised by more comprehensive and even better approaches. However, a standardized approach for the determination of constitutive activity can help to identify TSHR mutations for which the investigation of additional signaling mechanisms would be most interesting to find explanations for the current clinical phenotype/in vitro discrepancies and thereby also define suitable methods to explore the physiological relevance of constitutive wild type TSHR activity. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Synthesis of the ASTEC integral code activities in SARNET – Focus on ASTEC V2 plant applications

    International Nuclear Information System (INIS)

    Chatelard, P.; Reinke, N.; Ezzidi, A.; Lombard, V.; Barnak, M.; Lajtha, G.; Slaby, J.; Constantin, M.; Majumdar, P.

    2014-01-01

    Highlights: • Independent assessment of the ASTEC severe accident code vs. experiments is summarised. • Main remaining modelling issues and development perspectives are identified. • Independent assessment of ASTEC code at full scale conditions is described. • Main requirements to address BWR and PHWR types of reactors are identified. - Abstract: Among the 43 organisations which joined the SARNET2 FP7 project from 2009 to 2013, 31 have been involved in the activities on the ASTEC code. This paper presents a synthesis of the main achievements that have been obtained on the ASTEC V2 integral code, jointly developed by IRSN (France) and GRS (Germany), on development, validation vs. experimental data and applications at full scale conditions for both Gen.II and Gen.III plants. As to code development, while the current V2.0 series of ASTEC versions was continuously improved (elaboration and release by IRSN and GRS of three successive V2.0 revisions), IRSN and GRS have also intensively continued in parallel the elaboration of the second ASTEC V2 major version (version V2.1) to be delivered end of 2014. Regarding code validation vs. experiments, the partners have assessed the V2.0 version and subsequent revisions vs. more than 50 experiments; this extended assessment notably confirmed that most models are today close to the State of the Art, while it also corroborated the yet known key-topics on which modelling efforts should focus in priority. As to plant applications, the comparison of ASTEC results with other codes allows concluding on a globally good agreement for in-vessel and ex-vessel severe accident progression. As to ASTEC adaptations to BWR and PHWR, significant achievements have been obtained through the elaboration and integration in the future V2.1 version of dedicated core degradation models, notably to account for multi coolant flows

  7. Optical properties and visible-light-driven photocatalytic activity of Bi8V2O17 nanoparticles

    International Nuclear Information System (INIS)

    Pu, Yinfu; Liu, Ting; Huang, Yanlin; Chen, Cuili; Kim, Sun Il; Seo, Hyo Jin

    2015-01-01

    Bi 8 V 2 O 17 (4Bi 2 O 3 ·V 2 O 5 ) nanoparticles with the uniform size of about 50 nm were fabricated through the Pechini method. The crystal structure was investigated by X-ray powder diffraction and the structural refinement. The surface of the as-synthesized samples was characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy, and X-ray photoelectron spectroscopy. The optical properties, band structure, and the degradation mechanisms were discussed. The experimental results demonstrate that Bi 8 V 2 O 17 nanoparticles have an efficient visible-light absorption with band-gap energy of 1.85 eV and a direct allowed electronic transition. The photocatalytic activity was evaluated by the photodegradation of the methylene blue (MB) under visible-light irradiation (λ > 420 nm) as a function of time. These results indicate that Bi 8 V 2 O 17 could be a potential photocatalyst driven by visible light. The effective photocatalytic activity was discussed on the base of the crystal structure characteristic

  8. Decision-Related Activity in Macaque V2 for Fine Disparity Discrimination Is Not Compatible with Optimal Linear Readout.

    Science.gov (United States)

    Clery, Stephane; Cumming, Bruce G; Nienborg, Hendrikje

    2017-01-18

    Fine judgments of stereoscopic depth rely mainly on relative judgments of depth (relative binocular disparity) between objects, rather than judgments of the distance to where the eyes are fixating (absolute disparity). In macaques, visual area V2 is the earliest site in the visual processing hierarchy for which neurons selective for relative disparity have been observed (Thomas et al., 2002). Here, we found that, in macaques trained to perform a fine disparity discrimination task, disparity-selective neurons in V2 were highly selective for the task, and their activity correlated with the animals' perceptual decisions (unexplained by the stimulus). This may partially explain similar correlations reported in downstream areas. Although compatible with a perceptual role of these neurons for the task, the interpretation of such decision-related activity is complicated by the effects of interneuronal "noise" correlations between sensory neurons. Recent work has developed simple predictions to differentiate decoding schemes (Pitkow et al., 2015) without needing measures of noise correlations, and found that data from early sensory areas were compatible with optimal linear readout of populations with information-limiting correlations. In contrast, our data here deviated significantly from these predictions. We additionally tested this prediction for previously reported results of decision-related activity in V2 for a related task, coarse disparity discrimination (Nienborg and Cumming, 2006), thought to rely on absolute disparity. Although these data followed the predicted pattern, they violated the prediction quantitatively. This suggests that optimal linear decoding of sensory signals is not generally a good predictor of behavior in simple perceptual tasks. Activity in sensory neurons that correlates with an animal's decision is widely believed to provide insights into how the brain uses information from sensory neurons. Recent theoretical work developed simple

  9. Helix 11 Dynamics is Critical for Constitutive Androstane Receptor Activity

    OpenAIRE

    Wright, Edward; Busby, Scott A.; Wisecarver, Sarah; Vincent, Jeremy; Griffin, Patrick R.; Fernandez, Elias J.

    2011-01-01

    The constitutive androstane receptor (CAR) transactivation can occur in the absence of exogenous ligand and this activity is enhanced by agonists TCPOBOP and meclizine. We use biophysical and cell-based assays to show that increased activity of CAR(TCPOBOP) relative to CAR(meclizine) corresponds to a higher affinity of CAR(TCPOBOP) for the steroid receptor coactivator-1. Additionally, steady-state fluorescence spectra suggest conformational differences between CAR(TCPOBOP):RXR and CAR(meclizi...

  10. Electrophysiological characterization of activation state-dependent Ca(v)2 channel antagonist TROX-1 in spinal nerve injured rats.

    Science.gov (United States)

    Patel, R; Rutten, K; Valdor, M; Schiene, K; Wigge, S; Schunk, S; Damann, N; Christoph, T; Dickenson, A H

    2015-06-25

    Prialt, a synthetic version of Ca(v)2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Ca(v)2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Ca(v)2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Synthesis of hierarchical ZnV2O6 nanosheets with enhanced activity and stability for visible light driven CO2 reduction to solar fuels

    Science.gov (United States)

    Bafaqeer, Abdullah; Tahir, Muhammad; Amin, Nor Aishah Saidina

    2018-03-01

    Hierarchical nanostructures have lately garnered enormous attention because of their remarkable performances in energy storage and catalysis applications. In this study, novel hierarchical ZnV2O6 nanosheets, formulated by one-step solvothermal method, for enhanced photocatalytic CO2 reduction with H2O to solar fuels has been investigated. The structure and properties of the catalysts were characterized by XRD, FESEM, TEM, BET, UV-vis, Raman and PL spectroscopy. The hierarchical ZnV2O6 nanosheets show excellent performance towards photoreduction of CO2 with H2O to CH3OH, CH3COOH and HCOOH under visible light. The main product yield, CH3OH of 3253.84 μmol g-cat-1 was obtained over ZnV2O6, 3.4 times the amount of CH3OH produced over the ZnO/V2O5 composite (945.28 μmol g-cat-1). In addition, CH3OH selectivity of 39.96% achieved over ZnO/V2O5, increased to 48.78% in ZnV2O6 nanosheets. This significant improvement in photo-activity over ZnV2O6 structure was due to hierarchical structure with enhanced charge separation by V2O5. The obtained ZnV2O6 hierarchical nanosheets exhibited excellent photocatalytic stability for selective CH3OH production.

  12. Enhanced Visible Light Photocatalytic Activity of V2O5 Cluster Modified N-Doped TiO2 for Degradation of Toluene in Air

    Directory of Open Access Journals (Sweden)

    Fan Dong

    2012-01-01

    Full Text Available V2O5 cluster-modified N-doped TiO2 (N-TiO2/V2O5 nanocomposites photocatalyst was prepared by a facile impregnation-calcination method. The effects of V2O5 cluster loading content on visible light photocatalytic activity of the as-prepared samples were investigated for degradation of toluene in air. The results showed that the visible light activity of N-doped TiO2 was significantly enhanced by loading V2O5 clusters. The optimal V2O5 loading content was found to be 0.5 wt.%, reaching a removal ratio of 52.4% and a rate constant of 0.027 min−1, far exceeding that of unmodified N-doped TiO2. The enhanced activity is due to the deposition of V2O5 clusters on the surface of N-doped TiO2. The conduction band (CB potential of V2O5 (0.48 eV is lower than the CB level of N-doped TiO2 (−0.19 V, which favors the photogenerated electron transfer from CB of N-doped TiO2 to V2O5 clusters. This function of V2O5 clusters helps promote the transfer and separation of photogenerated electrons and holes. The present work not only displays a feasible route for the utilization of low cost V2O5 clusters as a substitute for noble metals in enhancing the photocatalysis but also demonstrates a facile method for preparation of highly active composite photocatalyst for large-scale applications.

  13. Uniformly active phase loaded selective catalytic reduction catalysts (V_2O_5/TNTs) with superior alkaline resistance performance

    International Nuclear Information System (INIS)

    Wang, Haiqiang; Wang, Penglu; Chen, Xiongbo; Wu, Zhongbiao

    2017-01-01

    Highlights: • VOSO_4 exhibited better synergistic effect with titanate nanotubes than NH_4VO_3. • Ion-exchange reaction occurs between VOSO_4 and titanate nanotubes. • Ion-exchange resulting in uniformly vanadium distribution on titanate nanotubes. • VOSO_4-based catalyst exhibited impressive SCR activity and alkaline resistance. - Abstract: In this work, protonated titanate nanotubes was performed as a potential useful support and different vanadium precursors (NH_4VO_3 and VOSO_4) were used to synthesize deNO_x catalysts. The results showed that VOSO_4 exhibited better synergistic effect with titanate nanotubes than NH_4VO_3, which was caused by the ion-exchange reaction. Then high loading content of vanadium, uniformly active phase distribution, better dispersion of vanadium, more acid sites, better V"5"+/V"4"+ redox cycles and superior oxygen mobility were achieved. Besides, VOSO_4-based titanate nanotubes catalysts also showed enhanced alkaline resistance than particles (P25) based catalysts. It was strongly associated with its abundant acid sites, large surface area, flexible redox cycles and oxygen transfer ability. For the loading on protonated titanate nanotubes, active metal with cation groups was better precursors than anion ones. V_2O_5/TNTs catalyst was a promising substitute for the commercial vanadium catalysts and the work conducted herein provided a useful idea to design uniformly active phase loaded catalyst.

  14. Bamboo-like Composites of V2O5/Polyindole and Activated Carbon Cloth as Electrodes for All-Solid-State Flexible Asymmetric Supercapacitors.

    Science.gov (United States)

    Zhou, Xi; Chen, Qiang; Wang, Anqi; Xu, Jian; Wu, Shishan; Shen, Jian

    2016-02-17

    A bamboo-like nanomaterial composed of V2O5/polyindole (V2O5/PIn) decorated onto the activated carbon cloth was fabricated for supercapacitors. The PIn could effectively enhance the electronic conductivity and prevent the dissolution of vanadium. And the activation of carbon cloth with functional groups is conducive to anchoring the V2O5 and improving surface area, which results in an enhancement of electrochemical performance and leads to a high specific capacitance of 535.5 F/g. Moreover, an asymmetric flexible supercapacitor based on V2O5/PIn@activate carbon cloth and reduced graphene oxide (rGO)@activate carbon cloth exhibits a high energy density (38.7 W h/kg) at a power density of 900 W/kg and good cyclic stability (capacitance retention of 91.1% after 5000 cycles). And the prepared device is shown to power the light-emitting diode bulbs efficiently.

  15. Constitutive Activity in an Ancestral Form of Abl Tyrosine Kinase.

    Directory of Open Access Journals (Sweden)

    Saadat U Aleem

    Full Text Available The c-abl proto-oncogene encodes a nonreceptor tyrosine kinase that is found in all metazoans, and is ubiquitously expressed in mammalian tissues. The Abl tyrosine kinase plays important roles in the regulation of mammalian cell physiology. Abl-like kinases have been identified in the genomes of unicellular choanoflagellates, the closest relatives to the Metazoa, and in related unicellular organisms. Here, we have carried out the first characterization of a premetazoan Abl kinase, MbAbl2, from the choanoflagellate Monosiga brevicollis. The enzyme possesses SH3, SH2, and kinase domains in a similar arrangement to its mammalian counterparts, and is an active tyrosine kinase. MbAbl2 lacks the N-terminal myristoylation and cap sequences that are critical regulators of mammalian Abl kinase activity, and we show that MbAbl2 is constitutively active. When expressed in mammalian cells, MbAbl2 strongly phosphorylates cellular proteins on tyrosine, and transforms cells much more potently than mammalian Abl kinase. Thus, MbAbl2 appears to lack the autoinhibitory mechanism that tightly constrains the activity of mammalian Abl kinases, suggesting that this regulatory apparatus arose more recently in metazoan evolution.

  16. Nuclear power plant V-2

    International Nuclear Information System (INIS)

    1998-01-01

    The nuclear power plant Bohunice V -2 is briefly described. This NPP consists from two reactor units. Their main time characteristics are (Reactor Unit 1, Reactor Unit 2): beginning of construction - December 1976; first controlled reactor power - 7 August 1984, 2 August 1985; connection to the grid - 20 August 1984, 9 August 1985; commercial operation - 14 February 1985, 18 December 1985. This leaflet contains: NPP V-2 construction; Major technological equipment [WWER 440 V230 type reactor; Nuclear Power plant operation safety (Safety barriers; Safety systems [Active safety systems, Passive safety systems]); Centralized heat supply system; Scheme of Bohunice V-2 NPP and technical data

  17. V(2)O(5) nanowires with an intrinsic iodination activity leading to the formation of self-assembled melanin-like biopolymers

    NARCIS (Netherlands)

    Natalio, F.; André, R.; Pihan, S.A.; Humanes, M.; Wever, R.; Tremel, W.

    2011-01-01

    V2O5 nanowires act as biomimetic catalysts resembling vanadium haloperoxidases (V-HPO). The nanowires display iodinating activity as confirmed by a colorimetric assay using thymol blue (TB), UV/Vis spectrophotometry and mass spectrometry (FD-MS). In the presence of dopamine these nanowires catalyze

  18. Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

    Directory of Open Access Journals (Sweden)

    Moens Ugo

    2007-11-01

    Full Text Available Abstract Background The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour. Methods We performed primary SHIRPA observations during background breeding into the C57BL/6 background and assessed the behaviour of the background-bred animals on the elevated plus maze and in the light-dark test. Our results were analyzed using Chi-square tests and homo- and heteroscedatic T-tests. Results Female transgenic mice displayed increased amounts of head dips and open arm time on the maze, compared to littermate controls. In addition, they also explored further into the open arm on the elevated plus maze and were less active in the closed arm compared to littermate controls. Male transgenic mice displayed no differences in anxiety, but their locomotor activity increased compared to non-transgenic littermates. Conclusion Our results revealed anxiety-related traits and locomotor differences between transgenic mice expressing constitutive active MAPKAPK5 and control littermates.

  19. Morphine withdrawal enhances constitutive μ-opioid receptor activity in the ventral tegmental area

    NARCIS (Netherlands)

    Meye, F.J.; van Zessen, R.; Smidt, M.P.; Adan, R.A.H.; Ramakers, G.M.J.

    2012-01-01

    μ-opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally involved in addictive behavior. While MORs are typically activated by opioids, they can also become constitutively active in the absence of any agonist. In the current study, we present evidence that MOR constitutive

  20. Constitutive law for thermally-activated plasticity of recrystallized tungsten

    Science.gov (United States)

    Zinovev, Aleksandr; Terentyev, Dmitry; Dubinko, Andrii; Delannay, Laurent

    2017-12-01

    A physically-based constitutive law relevant for ITER-specification tungsten grade in as-recrystallized state is proposed. The material demonstrates stages III and IV of the plastic deformation, in which hardening rate does not drop to zero with the increase of applied stress. Despite the classical Kocks-Mecking model, valid at stage III, the strain hardening asymptotically decreases resembling a hyperbolic function. The material parameters are fitted by relying on tensile test data and by requiring that the strain and stress at the onset of diffuse necking (uniform elongation and ultimate tensile strength correspondingly) as well as the yield stress be reproduced. The model is then validated in the temperature range 300-600 °C with the help of finite element analysis of tensile tests which confirms the reproducibility of the experimental engineering curves up to the onset of diffuse necking, beyond which the development of ductile damage accelerates the material failure. This temperature range represents the low temperature application window for tungsten as divertor material in fusion reactor ITER.

  1. Tumorigenesis induced by the HHV8-encoded chemokine receptor requires ligand modulation of high constitutive activity

    DEFF Research Database (Denmark)

    Holst, P J; Rosenkilde, M M; Manfra, D

    2001-01-01

    sarcoma (KS). Here we demonstrate that several lines of mice carrying mutated receptors deficient in either constitutive activity or chemokine regulation fail to develop KS-like disease. In addition, animals expressing a receptor that preserves chemokine binding and constitutive activity but that does...... not respond to agonist stimulation have a much lower incidence of angiogenic lesions and tumors. These results indicate that induction of the KS-like disease in transgenic mice by ORF74 requires not only high constitutive signaling activity but also modulation of this activity by endogenous chemokines....

  2. Constitutive NADPH-Dependent Electron Transferase Activity of the Nox4 Dehydrogenase Domain?

    OpenAIRE

    Nisimoto, Yukio; Jackson, Heather M.; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J. David

    2010-01-01

    NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47 phox and p67 phox and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K m for NADPH of 55 ? 10 ?M. The concentration of Nox4 in cell lysates was esti...

  3. "Slow" Voltage-Dependent Inactivation of CaV2.2 Calcium Channels Is Modulated by the PKC Activator Phorbol 12-Myristate 13-Acetate (PMA.

    Directory of Open Access Journals (Sweden)

    Lei Zhu

    Full Text Available CaV2.2 (N-type voltage-gated calcium channels (Ca2+ channels play key roles in neurons and neuroendocrine cells including the control of cellular excitability, neurotransmitter / hormone secretion, and gene expression. Calcium entry is precisely controlled by channel gating properties including multiple forms of inactivation. "Fast" voltage-dependent inactivation is relatively well-characterized and occurs over the tens-to- hundreds of milliseconds timeframe. Superimposed on this is the molecularly distinct, but poorly understood process of "slow" voltage-dependent inactivation, which develops / recovers over seconds-to-minutes. Protein kinases can modulate "slow" inactivation of sodium channels, but little is known about if/how second messengers control "slow" inactivation of Ca2+ channels. We investigated this using recombinant CaV2.2 channels expressed in HEK293 cells and native CaV2 channels endogenously expressed in adrenal chromaffin cells. The PKC activator phorbol 12-myristate 13-acetate (PMA dramatically prolonged recovery from "slow" inactivation, but an inactive control (4α-PMA had no effect. This effect of PMA was prevented by calphostin C, which targets the C1-domain on PKC, but only partially reduced by inhibitors that target the catalytic domain of PKC. The subtype of the channel β-subunit altered the kinetics of inactivation but not the magnitude of slowing produced by PMA. Intracellular GDP-β-S reduced the effect of PMA suggesting a role for G proteins in modulating "slow" inactivation. We postulate that the kinetics of recovery from "slow" inactivation could provide a molecular memory of recent cellular activity and help control CaV2 channel availability, electrical excitability, and neurotransmission in the seconds-to-minutes timeframe.

  4. GRK2 Constitutively Governs Peripheral Delta Opioid Receptor Activity

    Directory of Open Access Journals (Sweden)

    Allison Doyle Brackley

    2016-09-01

    Full Text Available Opioids remain the standard for analgesic care; however, adverse effects of systemic treatments contraindicate long-term administration. While most clinical opioids target mu opioid receptors (MOR, those that target the delta class (DOR also demonstrate analgesic efficacy. Furthermore, peripherally restrictive opioids represent an attractive direction for analgesia. However, opioid receptors including DOR are analgesically incompetent in the absence of inflammation. Here, we report that G protein-coupled receptor kinase 2 (GRK2 naively associates with plasma membrane DOR in peripheral sensory neurons to inhibit analgesic agonist efficacy. This interaction prevents optimal Gβ subunit association with the receptor, thereby reducing DOR activity. Importantly, bradykinin stimulates GRK2 movement away from DOR and onto Raf kinase inhibitory protein (RKIP. protein kinase C (PKC-dependent RKIP phosphorylation induces GRK2 sequestration, restoring DOR functionality in sensory neurons. Together, these results expand the known function of GRK2, identifying a non-internalizing role to maintain peripheral DOR in an analgesically incompetent state.

  5. Efficient room temperature oxidation of cyclohexane over highly active hetero-mixed WO3/V2O5 oxide catalyst

    CSIR Research Space (South Africa)

    Makgwane, PR

    2014-09-01

    Full Text Available catalytic activity to initiate the free-radical oxyfunctionalization of cyclohexane to afford up to 90% conversions within 6 h. The KA selectivity was found to depend on reaction time and the amount of catalyst. The WO(sub3)/V(sub2)O(sub5) catalyst...

  6. Discovery and development of inhibitors selective for human constitutive proteasome and immunoproteasome active sites

    NARCIS (Netherlands)

    Xin, B.

    2017-01-01

    This thesis describes the design and development of subunit‐selective inhibitors of particular catalytically active subunits of human constitutive proteasomes and immunoproteasomes. Most existing proteasome inhibitors are oligopeptides composed of 2‐4 amino acid residues, N‐terminally

  7. Common structural basis for constitutive activity of the ghrelin receptor family

    DEFF Research Database (Denmark)

    Holst, Birgitte; Holliday, Nicholas D; Bach, Anders

    2004-01-01

    Three members of the ghrelin receptor family were characterized in parallel: the ghrelin receptor, the neurotensin receptor 2 and the orphan receptor GPR39. In transiently transfected COS-7 and human embryonic kidney 293 cells, all three receptors displayed a high degree of ligand......-independent signaling activity. The structurally homologous motilin receptor served as a constitutively silent control; upon agonist stimulation, however, it signaled with a similar efficacy to the three related receptors. The constitutive activity of the ghrelin receptor and of neurotensin receptor 2 through the G...... demonstrated that the epitope-tagged ghrelin receptor was constitutively internalized but could be trapped at the cell surface by an inverse agonist, whereas GPR39 remained at the cell surface. Mutational analysis showed that the constitutive activity of both the ghrelin receptor and GPR39 could systematically...

  8. The expression and activity of thioredoxin reductase 1 splice variants v1 and v2 regulate the expression of genes associated with differentiation and adhesion

    Science.gov (United States)

    Nalvarte, Ivan; Damdimopoulos, Anastasios E.; Rüegg, Joëlle; Spyrou, Giannis

    2015-01-01

    The mammalian redox-active selenoprotein thioredoxin reductase (TrxR1) is a main player in redox homoeostasis. It transfers electrons from NADPH to a large variety of substrates, particularly to those containing redox-active cysteines. Previously, we reported that the classical form of cytosolic TrxR1 (TXNRD1_v1), when overexpressed in human embryonic kidney cells (HEK-293), prompted the cells to undergo differentiation [Nalvarte et al. (2004) J. Biol. Chem. 279, 54510–54517]. In the present study, we show that several genes associated with differentiation and adhesion are differentially expressed in HEK-293 cells stably overexpressing TXNRD1_v1 compared with cells expressing its splice variant TXNRD1_v2. Overexpression of these two splice forms resulted in distinctive effects on various aspects of cellular functions including gene regulation patterns, alteration of growth rate, migration and morphology and susceptibility to selenium-induced toxicity. Furthermore, differentiation of the neuroblastoma cell line SH-SY5Y induced by all-trans retinoic acid (ATRA) increased both TXNRD1_v1 and TXNRD1_v2 expressions along with several of the identified genes associated with differentiation and adhesion. Selenium supplementation in the SH-SY5Y cells also induced a differentiated morphology and changed expression of the adhesion protein fibronectin 1 and the differentiation marker cadherin 11, as well as different temporal expression of the studied TXNRD1 variants. These data suggest that both TXNRD1_v1 and TXNRD1_v2 have distinct roles in differentiation, possibly by altering the expression of the genes associated with differentiation, and further emphasize the importance in distinguishing each unique action of different TrxR1 splice forms, especially when studying the gene silencing or knockout of TrxR1. PMID:26464515

  9. Nuclear power plant V-2

    International Nuclear Information System (INIS)

    1999-01-01

    In this leaflet the short history of commissioning of Bohunice V-2 NPP is reviewed (beginning of construction December 1976; First controlled reactor power, Reactor Unit 1 (RU1): 7 August 1984, Reactor Unit 2 (RU2): 2 August 1985; Connection to the grid: RU1 20 August 1984, RU2 9 August 1985; Commercial operation: RU1 14 February 1985, RU2 18 December 1985. The scheme of the nuclear reactor WWER 440/V213 is depicted. The major technological equipment are described. Principles of nuclear power plant operation safety (safety barriers, active and passive safety systems, centralized heat supply system, as well as technical data of the Bohunice V-2 NPP are presented

  10. Morphine withdrawal enhances constitutive μ-opioid receptor activity in the ventral tegmental area.

    Science.gov (United States)

    Meye, Frank J; van Zessen, Ruud; Smidt, Marten P; Adan, Roger A H; Ramakers, Geert M J

    2012-11-14

    μ-Opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally involved in addictive behavior. While MORs are typically activated by opioids, they can also become constitutively active in the absence of any agonist. In the current study, we present evidence that MOR constitutive activity is highly relevant in the mouse VTA, as it regulates GABAergic input to dopamine neurons. Specifically, suppression of MOR constitutive activity with the inverse agonist KC-2-009 enhanced GABAergic neurotransmission onto VTA dopamine neurons. This inverse agonistic effect was fully blocked by the specific MOR neutral antagonist CTOP, which had no effect on GABAergic transmission itself. We next show that withdrawal from chronic morphine further increases the magnitude of inverse agonistic effects at the MOR, suggesting enhanced MOR constitutive activity. We demonstrate that this increase can be an adaptive response to the detrimental elevation in cAMP levels known to occur during morphine withdrawal. These findings offer important insights in the physiological occurrence and function of MOR constitutive activity, and have important implications for therapeutic strategies aimed at normalizing MOR signaling during addiction and opioid overdose.

  11. Analgesic tone conferred by constitutively active mu opioid receptors in mice lacking β-arrestin 2

    Directory of Open Access Journals (Sweden)

    Hales Tim G

    2011-04-01

    Full Text Available Abstract Hedonic reward, dependence and addiction are unwanted effects of opioid analgesics, linked to the phasic cycle of μ opioid receptor activation, tolerance and withdrawal. In vitro studies of recombinant G protein coupled receptors (GPCRs over expressed in cell lines reveal an alternative tonic signaling mechanism that is independent of agonist. Such studies demonstrate that constitutive GPCR signaling can be inhibited by inverse agonists but not by neutral antagonists. However, ligand-independent activity has been difficult to examine in vivo, at the systems level, due to relatively low levels of constitutive activity of most GPCRs including μ receptors, often necessitating mutagenesis or pharmacological manipulation to enhance basal signaling. We previously demonstrated that the absence of β-arrestin 2 (β-arr2 augments the constitutive coupling of μ receptors to voltage-activated Ca2+ channels in primary afferent dorsal root ganglion neurons from β-arr2-/- mice. We used this in vitro approach to characterize neutral competitive antagonists and inverse agonists of the constitutively active wild type μ receptors in neurons. We administered these agents to β-arr2-/- mice to explore the role of constitutive μ receptor activity in nociception and hedonic tone. This study demonstrates that the induction of constitutive μ receptor activity in vivo in β-arr2-/- mice prolongs tail withdrawal from noxious heat, a phenomenon that was reversed by inverse agonists, but not by antagonists that lack negative efficacy. By contrast, the aversive effects of inverse agonists were similar in β-arr2-/- and β-arr2+/+ mice, suggesting that hedonic tone was unaffected.

  12. Transgenic Expression of Constitutively Active RAC1 Disrupts Mouse Rod Morphogenesis

    Science.gov (United States)

    Song, Hongman; Bush, Ronald A.; Vijayasarathy, Camasamudram; Fariss, Robert N.; Kjellstrom, Sten; Sieving, Paul A.

    2014-01-01

    Purpose. Dominant-active RAC1 rescues photoreceptor structure in Drosophila rhodopsin-null mutants, indicating an important role in morphogenesis. This report assesses the morphogenetic effect of activated RAC1 during mammalian rod photoreceptor development using transgenic mice that express constitutively active (CA) RAC1. Methods. Transgenic mice were generated by expressing CA RAC1 under control of the Rhodopsin promoter, and morphological features of the photoreceptors were evaluated by histology, immunohistochemistry, and transmission electron microscopy. Function was evaluated by electroretinography. Potential protein partners of CA RAC1 were identified by co-immunoprecipitation of retinal extracts. Results. Constitutively active RAC1 expression in differentiating rods disrupted outer retinal lamination as early as postnatal day (P)6, and many photoreceptor cell nuclei were displaced apically into the presumptive subretinal space. These photoreceptors did not develop normal inner and outer segments and had abnormal placement of synaptic elements. Some photoreceptor nuclei were also mislocalized into the inner nuclear layer. Extensive photoreceptor degeneration was subsequently observed in the adult animal. Constitutively active RAC1 formed a complex with the polarity protein PAR6 and with microtubule motor dynein in mouse retina. The normal localization of the PAR6 complex was disrupted in CA RAC1-expressing rod photoreceptors. Conclusions. Constitutively active RAC1 had a profound negative effect on mouse rod cell viability and development. Rod photoreceptors in the CA RAC1 retina exhibited a defect in polarity and migration. Constitutively active RAC1 disrupted rod morphogenesis and gave a phenotype resembling that found in the Crumbs mutant. PAR6 and dynein are two potential downstream effectors that may be involved in CA RAC1-mediated defective mouse photoreceptor morphogenesis. PMID:24651551

  13. Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Benned-Jensen, Tau; Holst, Peter J

    2006-01-01

    Epstein-Barr virus (EBV)-induced receptor 2 (EBI2) is an orphan seven-transmembrane (7TM) receptor originally identified as the most up-regulated gene (>200-fold) in EBV-infected cells. Here we show that EBI2 signals with constitutive activity through Galpha(i) as determined by a receptor...

  14. Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.

    Directory of Open Access Journals (Sweden)

    Adam L Martin

    Full Text Available The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1 200% elevation over baseline reporter gene expression; 2 40% inhibition of baseline expression; and 3 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1 inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176; 2 no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119; 3 elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12; 4 elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65; and 5 no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87. Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40. This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65% than stimulation of expression (15%. Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.

  15. Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.

    Science.gov (United States)

    Martin, Adam L; Steurer, Michael A; Aronstam, Robert S

    2015-01-01

    The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.

  16. A method for the quantification of biased signalling at constitutively active receptors.

    Science.gov (United States)

    Hall, David A; Giraldo, Jesús

    2018-06-01

    Biased agonism, the ability of an agonist to differentially activate one of several signal transduction pathways when acting at a given receptor, is an increasingly recognized phenomenon at many receptors. The Black and Leff operational model lacks a way to describe constitutive receptor activity and hence inverse agonism. Thus, it is impossible to analyse the biased signalling of inverse agonists using this model. In this theoretical work, we develop and illustrate methods for the analysis of biased inverse agonism. Methods were derived for quantifying biased signalling in systems that demonstrate constitutive activity using the modified operational model proposed by Slack and Hall. The methods were illustrated using Monte Carlo simulations. The Monte Carlo simulations demonstrated that, with an appropriate experimental design, the model parameters are 'identifiable'. The method is consistent with methods based on the measurement of intrinsic relative activity (RA i ) (ΔΔlogR or ΔΔlog(τ/K a )) proposed by Ehlert and Kenakin and their co-workers but has some advantages. In particular, it allows the quantification of ligand bias independently of 'system bias' removing the requirement to normalize to a standard ligand. In systems with constitutive activity, the Slack and Hall model provides methods for quantifying the absolute bias of agonists and inverse agonists. This provides an alternative to methods based on RA i and is complementary to the ΔΔlog(τ/K a ) method of Kenakin et al. in systems where use of that method is inappropriate due to the presence of constitutive activity. © 2018 The British Pharmacological Society.

  17. Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.

    Science.gov (United States)

    Karaca, Anara; Malladi, Vijayram Reddy; Zhu, Yan; Tafaj, Olta; Paltrinieri, Elena; Wu, Joy Y; He, Qing; Bastepe, Murat

    2018-05-01

    GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα R201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα R201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα R201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Constitutive NADPH-dependent electron transferase activity of the Nox4 dehydrogenase domain.

    Science.gov (United States)

    Nisimoto, Yukio; Jackson, Heather M; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J David

    2010-03-23

    NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47(phox) and p67(phox) and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K(m) for NADPH of 55 +/- 10 microM. The concentration of Nox4 in cell lysates was estimated using Western blotting and allowed calculation of a turnover of approximately 200 mol of H(2)O(2) min(-1) (mol of Nox4)(-1). A chimeric protein (Nox2/4) consisting of the Nox2 transmembrane (TM) domain and the Nox4 dehydrogenase (DH) domain showed H(2)O(2) production in the absence of cytosolic regulatory subunits. In contrast, chimera Nox4/2, consisting of the Nox4 TM and Nox2 DH domains, exhibited PMA-dependent activation that required coexpression of regulatory subunits. Nox DH domains from several Nox isoforms were purified and evaluated for their electron transferase activities. Nox1 DH, Nox2 DH, and Nox5 DH domains exhibited barely detectable activities toward artificial electron acceptors, while the Nox4 DH domain exhibited significant rates of reduction of cytochrome c (160 min(-1), largely superoxide dismutase-independent), ferricyanide (470 min(-1)), and other electron acceptors (artificial dyes and cytochrome b(5)). Rates were similar to those observed for H(2)O(2) production by the Nox4 holoenzyme in cell lysates. The activity required added FAD and was seen with NADPH but not NADH. These results indicate that the Nox4 DH domain exists in an intrinsically activated state and that electron transfer from NADPH to FAD is likely to be rate-limiting in the NADPH-dependent reduction of oxygen by holo-Nox4.

  19. CINPA1 Is an Inhibitor of Constitutive Androstane Receptor That Does Not Activate Pregnane X Receptor

    OpenAIRE

    Cherian, Milu T; Lin, Wenwei; Wu, Jing; Chen, Taosheng

    2015-01-01

    Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic sensors that enhance the detoxification and elimination of xenobiotics and endobiotics by modulating the expression of genes encoding drug-metabolizing enzymes and transporters. Elevated levels of drug-metabolizing enzymes and efflux transporters, resulting from CAR activation in various cancers, promote the elimination of chemotherapeutic agents, leading to reduced therapeutic effectiveness and acquired drug ...

  20. Constitutively active transforming growth factor β receptor 1 in the mouse ovary promotes tumorigenesis

    Science.gov (United States)

    Gao, Yang; Vincent, David F.; Davis, Anna Jane; Sansom, Owen J.; Bartholin, Laurent; Li, Qinglei

    2016-01-01

    Despite the well-established tumor suppressive role of TGFβ proteins, depletion of key TGFβ signaling components in the mouse ovary does not induce a growth advantage. To define the role of TGFβ signaling in ovarian tumorigenesis, we created a mouse model expressing a constitutively active TGFβ receptor 1 (TGFBR1) in ovarian somatic cells using conditional gain-of-function approach. Remarkably, these mice developed ovarian sex cord-stromal tumors with complete penetrance, leading to reproductive failure and mortality. The tumors expressed multiple granulosa cell markers and caused elevated serum inhibin and estradiol levels, reminiscent of granulosa cell tumors. Consistent with the tumorigenic effect, overactivation of TGFBR1 altered tumor microenvironment by promoting angiogenesis and enhanced ovarian cell proliferation, accompanied by impaired cell differentiation and dysregulated expression of critical genes in ovarian function. By further exploiting complementary genetic models, we substantiated our finding that constitutively active TGFBR1 is a potent oncogenic switch in mouse granulosa cells. In summary, overactivation of TGFBR1 drives gonadal tumor development. The TGFBR1 constitutively active mouse model phenocopies a number of morphological, hormonal, and molecular features of human granulosa cell tumors and are potentially valuable for preclinical testing of targeted therapies to treat granulosa cell tumors, a class of poorly defined ovarian malignancies. PMID:27344183

  1. OPTIGRAMI V2 user's guide

    Science.gov (United States)

    Penny S. Lawson; R. Edward Thomas; Elizabeth S Walker

    1996-01-01

    OPTIGRAMI V2 is a computer program available for IBM persaonl computer with 80286 and higher processors. OPTIGRAMI V2 determines the least-cost lumber grade mix required to produce a given cutting order for clear parts from rough lumber of known grades in a crosscut-first rough mill operation. It is a user-friendly integrated application that includes optimization...

  2. Constitutive nitric oxide synthase (cNOS activity in Langerhans islets from streptozotocin diabetic rats

    Directory of Open Access Journals (Sweden)

    Fonovich de Schroeder T.M.

    1998-01-01

    Full Text Available Nitric oxide synthase activity was measured in Langerhans islets isolated from control and streptozotocin diabetic rats. The activity of the enzyme was linear up to 150 µg of protein from control rats and was optimal at 0.1 µM calcium, when it was measured after 45 min of incubation at 37oC in the presence of 200 µM arginine. Specific activity of the enzyme was 25 x 10-4 nmol [3H]citrulline 45 min-1 mg protein-1. Streptozotocin diabetic rats exhibited less enzyme activity both in total pancreas homogenate and in isolated Langerhans islets when compared to control animals. Nitric oxide synthase activity measured in control and diabetic rats 15 days after the last streptozotocin injection in the second group of animals corresponded only to a constitutive enzyme since it was not inhibited by aminoguanidine in any of the mentioned groups. Hyperglycemia in diabetic rats may be the consequence of impaired insulin release caused at least in part by reduced positive modulation mediated by constitutive nitric oxide synthase activity, which was dramatically reduced in islets severely damaged after streptozotocin treatment.

  3. ASTEC V2 severe accident integral code main features, current V2.0 modelling status, perspectives

    International Nuclear Information System (INIS)

    Chatelard, P.; Reinke, N.; Arndt, S.; Belon, S.; Cantrel, L.; Carenini, L.; Chevalier-Jabet, K.; Cousin, F.; Eckel, J.; Jacq, F.; Marchetto, C.; Mun, C.; Piar, L.

    2014-01-01

    The severe accident integral code ASTEC, jointly developed since almost 20 years by IRSN and GRS, simulates the behaviour of a whole nuclear power plant under severe accident conditions, including severe accident management by engineering systems and procedures. Since 2004, the ASTEC code is progressively becoming the reference European severe accident integral code through in particular the intensification of research activities carried out in the frame of the SARNET European network of excellence. The first version of the new series ASTEC V2 was released in 2009 to about 30 organizations worldwide and in particular to SARNET partners. With respect to the previous V1 series, this new V2 series includes advanced core degradation models (issued from the ICARE2 IRSN mechanistic code) and necessary extensions to be applicable to Gen. III reactor designs, notably a description of the core catcher component to simulate severe accidents transients applied to the EPR reactor. Besides these two key-evolutions, most of the other physical modules have also been improved and ASTEC V2 is now coupled to the SUNSET statistical tool to make easier the uncertainty and sensitivity analyses. The ASTEC models are today at the state of the art (in particular fission product models with respect to source term evaluation), except for quenching of a severely damage core. Beyond the need to develop an adequate model for the reflooding of a degraded core, the main other mean-term objectives are to further progress on the on-going extension of the scope of application to BWR and CANDU reactors, to spent fuel pool accidents as well as to accidents in both the ITER Fusion facility and Gen. IV reactors (in priority on sodium-cooled fast reactors) while making ASTEC evolving towards a severe accident simulator constitutes the main long-term objective. This paper presents the status of the ASTEC V2 versions, focussing on the description of V2.0 models for water-cooled nuclear plants

  4. Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma

    Directory of Open Access Journals (Sweden)

    Kahl Brad S

    2008-05-01

    Full Text Available Abstract Background The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL. However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Results Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA. Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231 and a breast carcinoma cell line (MDA-MB-468, the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10 displayed bortezomib-resistant constitutive NF-κB activity. Conclusion Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.

  5. Constitutive activation of Gli2 impairs bone formation in postnatal growing mice.

    Directory of Open Access Journals (Sweden)

    Kyu Sang Joeng

    Full Text Available Indian hedgehog (Ihh signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation of Hedgehog (Hh signaling may enhance bone formation, we generated mice that expressed a constitutively active form of Gli2 in the Osx-lineage cells. Unexpectedly, these mice exhibited severe osteopenia due to a marked decrease in osteoblast number and function, although bone resorption was not affected. Quantitative analyses of the molecular markers indicated that osteoblast differentiation was impaired in the mutant mouse. However, the osteoblast-lineage cells isolated from these mice exhibited more robust osteoblast differentiation than normal in vitro. Similarly, pharmacological stimulation of Hh signaling enhanced osteoblast differentiation from Osx-expressing cells isolated from the wild-type mouse. Thus, even though Hh signaling directly promotes osteoblast differentiation in vitro, constitutive activation of this pathway impairs bone formation in vivo, perhaps through an indirect mechanism.

  6. Constitutive activation of the ERK pathway in melanoma and skin melanocytes in Grey horses.

    Science.gov (United States)

    Jiang, Lin; Campagne, Cécile; Sundström, Elisabeth; Sousa, Pedro; Imran, Saima; Seltenhammer, Monika; Pielberg, Gerli; Olsson, Mats J; Egidy, Giorgia; Andersson, Leif; Golovko, Anna

    2014-11-21

    Constitutive activation of the ERK pathway, occurring in the vast majority of melanocytic neoplasms, has a pivotal role in melanoma development. Different mechanisms underlie this activation in different tumour settings. The Grey phenotype in horses, caused by a 4.6 kb duplication in intron 6 of Syntaxin 17 (STX17), is associated with a very high incidence of cutaneous melanoma, but the molecular mechanism behind the melanomagenesis remains unknown. Here, we investigated the involvement of the ERK pathway in melanoma development in Grey horses. Grey horse melanoma tumours, cell lines and normal skin melanocytes were analyzed with help of indirect immunofluorescence and immunoblotting for the expression of phospho-ERK1/2 in comparison to that in non-grey horse and human counterparts. The mutational status of BRAF, RAS, GNAQ, GNA11 and KIT genes in Grey horse melanomas was determined by direct sequencing. The effect of RAS, RAF and PI3K/AKT pathways on the activation of the ERK signaling in Grey horse melanoma cells was investigated with help of specific inhibitors and immunoblotting. Individual roles of RAF and RAS kinases on the ERK activation were examined using si-RNA based approach and immunoblotting. We found that the ERK pathway is constitutively activated in Grey horse melanoma tumours and cell lines in the absence of somatic activating mutations in BRAF, RAS, GNAQ, GNA11 and KIT genes or alterations in the expression of the main components of the pathway. The pathway is mitogenic and is mediated by BRAF, CRAF and KRAS kinases. Importantly, we found high activation of the ERK pathway also in epidermal melanocytes, suggesting a general predisposition to melanomagenesis in these horses. These findings demonstrate that the presence of the intronic 4.6 kb duplication in STX17 is strongly associated with constitutive activation of the ERK pathway in melanocytic cells in Grey horses in the absence of somatic mutations commonly linked to the activation of this

  7. Constitutive STAT5 Activation Correlates With Better Survival in Cervical Cancer Patients Treated With Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Helen H.W. [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Chou, Cheng-Yang [Department of Obstetrics and Gynecology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Wu, Yuan-Hua; Hsueh, Wei-Ting; Hsu, Chiung-Hui [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Guo, How-Ran [Department of Environmental and Occupational Health, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Lee, Wen-Ying, E-mail: 7707@so-net.net.tw [Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan (China) and Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Wu-Chou, E-mail: sunnysu@mail.ncku.edu.tw [Department of Internal Medicine, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China)

    2012-02-01

    Purpose: Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3, and STAT5, have been detected in a wide variety of human primary tumors and have been demonstrated to directly contribute to oncogenesis. However, the expression pattern of these STATs in cervical carcinoma is still unknown, as is whether or not they have prognostic significance. This study investigated the expression patterns of STAT1, STAT3, and STAT5 in cervical cancer and their associations with clinical outcomes in patients treated with radical radiation therapy. Methods and Materials: A total of 165 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) Stages IB to IVA cervical cancer underwent radical radiation therapy, including external beam and/or high-dose-rate brachytherapy between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and to evaluate the effects of these factors affecting patient survival. Results: Constitutive activations of STAT1, STAT3, and STAT5 were observed in 11%, 22%, and 61% of the participants, respectively. While STAT5 activation was associated with significantly better metastasis-free survival (p < 0.01) and overall survival (p = 0.04), STAT1 and STAT3 activation were not. Multivariate analyses showed that STAT5 activation, bulky tumor ({>=}4 cm), advanced stage (FIGO Stages III and IV), and brachytherapy (yes vs. no) were independent prognostic factors for cause-specific overall survival. None of the STATs was associated with local relapse. STAT5 activation (odds ratio = 0.29, 95% confidence interval = 0.13-0.63) and advanced stage (odds ratio = 2.54; 95% confidence interval = 1.03-6.26) were independent predictors of distant metastasis. Conclusions: This is the first report to provide the overall expression patterns and prognostic significance of

  8. Constitutive Activation of Smoothened in the Renal Collecting Ducts Leads to Renal Hypoplasia, Hydronephrosis, and Hydroureter.

    Science.gov (United States)

    Gupta, Deepak Prasad; Hwang, Jae-Won; Cho, Eui-Sic; Kim, Won; Song, Chang Ho; Chai, Ok Hee

    2017-01-01

    Sonic Hedgehog (Shh) signaling plays a major role in and is essential for regulation, patterning, and proliferation during renal development. Smoothened (Smo) plays a pivot role in transducing the Shh-glioma-associated oncogene Kruppel family member. However, the cellular and molecular mechanism underlying the role of sustained Smo activation in postnatal kidney development is still not clearly understood. Using a conditional knockin mouse model that expresses a constitutively activated form of Smo (SmoM2) upon Homeobox-B7-mediated recombination (Hoxb7-Cre), the effects of Shh signaling were determined in postnatal kidney development. SmoM2;Hoxb7-Cre mutant mice showed growth retardation with a reduction of body weight. Constitutive activation of Smo in the renal collecting ducts caused renal hypoplasia, hydronephrosis, and hydroureter. The parenchymal area and glomerular numbers were reduced, but the glomerular density was increased in SmoM2;Hoxb7-Cre mutant mice. The expression of Patched 1, the receptor of Shh and a downstream target gene of the Shh signaling pathway, was highly restricted and it was upregulated in the inner medullary collecting ducts of the kidney. The proliferative cells in the mesenchyme and collecting ducts were decreased in SmoM2;Hoxb7-Cre mutant mice. This study showed for the first time that sustained Smo inhibits postnatal kidney development by suppressing the proliferation of the mesenchyme and medullary collecting ducts in mice. © 2017 S. Karger AG, Basel.

  9. Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Kazuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Tsukui, Tohru [Experimental Animal Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Imazawa, Yukiko; Horie-Inoue, Kuniko [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Inoue, Satoshi, E-mail: INOUE-GER@h.u-tokyo.ac.jp [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively active mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  10. Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice

    International Nuclear Information System (INIS)

    Ikeda, Kazuhiro; Tsukui, Tohru; Imazawa, Yukiko; Horie-Inoue, Kuniko; Inoue, Satoshi

    2012-01-01

    Highlights: ► Conditional transgenic mice expressing constitutively active estrogen receptor α (caERα) in chondrocytes were developed. ► Expression of caERα in chondrocytes impaired longitudinal bone growth in mice. ► caERα affects chondrocyte proliferation and differentiation. ► This mouse model is useful for understanding the physiological role of ERαin vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caERα ColII , expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERα ColII mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caERα ColII mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERα ColII mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  11. NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

    Science.gov (United States)

    Song, Hongman; Vijayasarathy, Camasamudram; Zeng, Yong; Marangoni, Dario; Bush, Ronald A.; Wu, Zhijian; Sieving, Paul A.

    2016-01-01

    Purpose The active form of small GTPase RAC1 is required for activation of NADPH oxidase (NOX), which in turn generates reactive oxygen species (ROS) in nonphagocytic cells. We explored whether NOX-induced oxidative stress contributes to rod degeneration in retinas expressing constitutively active (CA) RAC1. Methods Transgenic (Tg)–CA-RAC1 mice were given apocynin (10 mg/kg, intraperitoneal), a NOX inhibitor, or vehicle daily for up to 13 weeks. Superoxide production and oxidative damage were assessed by dihydroethidium staining and by protein carbonyls and malondialdehyde levels, respectively. Outer nuclear layer (ONL) cells were counted and electroretinogram (ERG) amplitudes measured in Tg-CA-RAC1 mice. Outer nuclear layer cells were counted in wild-type (WT) mice after transfer of CA-Rac1 gene by subretinal injection of AAV8-pOpsin-CA Rac1-GFP. Results Transgenic-CA-RAC1 retinas had significantly fewer photoreceptor cells and more apoptotic ONL cells than WT controls from postnatal week (Pw) 3 to Pw13. Superoxide accumulation and protein and lipid oxidation were increased in Tg-CA-RAC1 retinas and were reduced in mice treated with apocynin. Apocynin reduced the loss of photoreceptors and increased the rod ERG a- and b-wave amplitudes when compared with vehicle-injected transgenic controls. Photoreceptor loss was also observed in regions of adult WT retina transduced with AAV8-pOpsin-CA Rac1-GFP but not in neighboring regions that were not transduced or in AAV8-pOpsin-GFP–transduced retinas. Conclusions Constitutively active RAC1 promotes photoreceptor cell death by oxidative damage that occurs, at least partially, through NOX-induced ROS. Reactive oxygen species are likely involved in multiple forms of retinal degenerations, and our results support investigating RAC1 inhibition as a therapeutic approach that targets this disease pathway. PMID:27233035

  12. Constitutive cellulase production from glucose using the recombinant Trichoderma reesei strain overexpressing an artificial transcription activator.

    Science.gov (United States)

    Zhang, Xiaoyue; Li, Yonghao; Zhao, Xinqing; Bai, Fengwu

    2017-01-01

    The high cost of cellulase production presents biggest challenge in biomass deconstruction. Cellulase production by Trichoderma reesei using low cost carbon source is of great interest. In this study, an artificial transcription activator containing the Cre1 binding domain linked to the Xyr1 effector and binding domains was designed and constitutively overexpressed in T. reesei RUT C30. The recombinant strain T. reesei zxy-2 displayed constitutive cellulase production using glucose as a sole carbon source, and the production titer was 12.75-fold of that observed with T. reesei RUT C30 in shake flask culture. Moreover, FPase and xylanase titers of 2.63 and 108.72IU/mL, respectively, were achieved using glucose as sole carbon source within 48h in a 7-L fermenter by batch fermentation using T. reesei zxy-2. The crude enzyme obtained was used to hydrolyze alkali pretreated corn stover, and a high glucose yield of 99.18% was achieved. Copyright © 2016. Published by Elsevier Ltd.

  13. Active learning of constitutive relation from mesoscopic dynamics for macroscopic modeling of non-Newtonian flows

    Science.gov (United States)

    Zhao, Lifei; Li, Zhen; Caswell, Bruce; Ouyang, Jie; Karniadakis, George Em

    2018-06-01

    We simulate complex fluids by means of an on-the-fly coupling of the bulk rheology to the underlying microstructure dynamics. In particular, a continuum model of polymeric fluids is constructed without a pre-specified constitutive relation, but instead it is actively learned from mesoscopic simulations where the dynamics of polymer chains is explicitly computed. To couple the bulk rheology of polymeric fluids and the microscale dynamics of polymer chains, the continuum approach (based on the finite volume method) provides the transient flow field as inputs for the (mesoscopic) dissipative particle dynamics (DPD), and in turn DPD returns an effective constitutive relation to close the continuum equations. In this multiscale modeling procedure, we employ an active learning strategy based on Gaussian process regression (GPR) to minimize the number of expensive DPD simulations, where adaptively selected DPD simulations are performed only as necessary. Numerical experiments are carried out for flow past a circular cylinder of a non-Newtonian fluid, modeled at the mesoscopic level by bead-spring chains. The results show that only five DPD simulations are required to achieve an effective closure of the continuum equations at Reynolds number Re = 10. Furthermore, when Re is increased to 100, only one additional DPD simulation is required for constructing an extended GPR-informed model closure. Compared to traditional message-passing multiscale approaches, applying an active learning scheme to multiscale modeling of non-Newtonian fluids can significantly increase the computational efficiency. Although the method demonstrated here obtains only a local viscosity from the polymer dynamics, it can be extended to other multiscale models of complex fluids whose macro-rheology is unknown.

  14. Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling.

    Science.gov (United States)

    Mutoh, Shingo; Sobhany, Mack; Moore, Rick; Perera, Lalith; Pedersen, Lee; Sueyoshi, Tatsuya; Negishi, Masahiko

    2013-05-07

    Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. We found that phenobarbital activated CAR by inhibiting epidermal growth factor receptor (EGFR) signaling. Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of receptor for activated C kinase 1 (RACK1) at Tyr(52), which then promoted the dephosphorylation of CAR at Thr(38) by the catalytic core subunit of protein phosphatase 2A. The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR.

  15. A Global Genomic Screening Strategy Reveals Diverse Activators of Constitutive Activated Receptor (CAR)

    Science.gov (United States)

    A comprehensive survey of conditions that activate CAR in the mouse liver has not been carried out but would be useful in understanding their impact on CAR-dependent liver tumor induction. A gene signature dependent on CAR activation was identified by comparing the transcript pr...

  16. Modulation of constitutive activity and signaling bias of the ghrelin receptor by conformational constraint in the second extracellular loop

    DEFF Research Database (Denmark)

    Mokrosinski, Jacek; Frimurer, Thomas M; Sivertsen, Bjoern

    2012-01-01

    Based on a rare, natural Glu for Ala204(C+6) variant located six residues after the conserved Cys residue in extracellular loop 2 (ECL2b) associated with selective elimination of the high constitutive signaling of the ghrelin receptor, this loop was subjected to a detailed structure functional....... Moreover, the constitutive activity of the receptor was inhibited by Zn(2+) binding in an engineered metal-ion site stabilizing an a-helical conformation of this loop segment. It is concluded that the high constitutive activity of the ghrelin receptor is dependent upon flexibility in the C-terminal segment...

  17. Human pregnane X receptor is activated by dibenzazepine carbamate-based inhibitors of constitutive androstane receptor.

    Science.gov (United States)

    Jeske, Judith; Windshügel, Björn; Thasler, Wolfgang E; Schwab, Matthias; Burk, Oliver

    2017-06-01

    Unintentional activation of xenosensing nuclear receptors pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR) by clinical drug use is known to produce severe side effects in patients, which may be overcome by co-administering antagonists. However, especially antagonizing CAR is hampered by the lack of specific inhibitors, which do not activate PXR. Recently, compounds based on a dibenzazepine carbamate scaffold were identified as potent CAR inhibitors. However, their potential to activate PXR was not thoroughly investigated, even if the lead compound was named "CAR inhibitor not PXR activator 1" (CINPA1). Thus, we performed a comprehensive analysis of the interaction of CINPA1 and four analogs with PXR. Cellular assays were used to investigate intra- and intermolecular interactions and transactivation activity of PXR as a function of the compounds. Modulation of PXR target gene expression was analyzed in primary human hepatocytes. Ligand binding to PXR was investigated by molecular docking and limited proteolytic digestion. We show here that CINPA1 induced the assembly of the PXR ligand-binding domain, released co-repressors from and recruited co-activators to the receptor. CINPA1 and its analogs induced the PXR-dependent activation of a CYP3A4 reporter gene and CINPA1 induced the expression of endogenous cytochrome P450 genes in primary hepatocytes, while not consistently inhibiting CAR-mediated induction. Molecular docking revealed favorable binding of CINPA1 and analogs to the PXR ligand-binding pocket, which was confirmed in vitro. Altogether, our data provide consistent evidence that compounds with a dibenzazepine carbamate scaffold, such as CINPA1 and its four analogs, bind to and activate PXR.

  18. Importance of constitutive activity and arrestin-independent mechanisms for intracellular trafficking of the ghrelin receptor

    DEFF Research Database (Denmark)

    Holliday, Nicholas D; Holst, Birgitte; Rodionova, Elena A

    2007-01-01

    . Furthermore the interaction between phosphorylated receptors and beta-arrestin adaptor proteins has been examined. Replacement of the FLAG-tagged GhrelinR C tail with the equivalent GPR39 domain (GhR-39 chimera) preserved G(q) signaling. However in contrast to the GhrelinR, GhR-39 receptors exhibited no basal......,9), Leu(11)] substance P and a naturally occurring mutant GhrelinR (A204E) with eliminated constitutive activity inhibited basal GhrelinR internalization. Surprisingly, we found that noninternalizing GPR39 was highly phosphorylated and that basal and agonist-induced phosphorylation of the GhR-39 chimera......, but the high levels of GPR39 phosphorylation, and of the GhR-39 chimera, are not sufficient to drive endocytosis. In addition, basal GhrelinR internalization occurs independently of beta-arrestins....

  19. Single amino acid change in STING leads to constitutive active signaling.

    Directory of Open Access Journals (Sweden)

    Eric D Tang

    Full Text Available The production of cytokines by the immune system in response to cytosolic DNA plays an important role in host defense, autoimmune disease, and cancer immunogenicity. Recently a cytosolic DNA signaling pathway that is dependent on the endoplasmic reticulum adaptor and cyclic dinucleotide sensor protein STING has been identified. Association of cytosolic DNA with cyclic-GMP-AMP synthase (cGAS activates its enzymatic activity to synthesize the cyclic dinucleotide second messenger cGAMP from GTP and ATP. Direct detection of cGAMP by STING triggers the activation of IRF3 and NF-kB, and the production of type I interferons and proinflammatory cytokines. The mechanism of how STING is able to mediate downstream signaling remains incompletely understood although it has been shown that dimerization is a prerequisite. Here, we identify a single amino acid change in STING that confers constitutive active signaling. This mutation appears to both enhance ability of STING to both dimerize and associate with its downstream target TBK1.

  20. Single amino acid change in STING leads to constitutive active signaling.

    Science.gov (United States)

    Tang, Eric D; Wang, Cun-Yu

    2015-01-01

    The production of cytokines by the immune system in response to cytosolic DNA plays an important role in host defense, autoimmune disease, and cancer immunogenicity. Recently a cytosolic DNA signaling pathway that is dependent on the endoplasmic reticulum adaptor and cyclic dinucleotide sensor protein STING has been identified. Association of cytosolic DNA with cyclic-GMP-AMP synthase (cGAS) activates its enzymatic activity to synthesize the cyclic dinucleotide second messenger cGAMP from GTP and ATP. Direct detection of cGAMP by STING triggers the activation of IRF3 and NF-kB, and the production of type I interferons and proinflammatory cytokines. The mechanism of how STING is able to mediate downstream signaling remains incompletely understood although it has been shown that dimerization is a prerequisite. Here, we identify a single amino acid change in STING that confers constitutive active signaling. This mutation appears to both enhance ability of STING to both dimerize and associate with its downstream target TBK1.

  1. Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines

    DEFF Research Database (Denmark)

    Nielsen, M; Kaltoft, K; Nordahl, M

    1997-01-01

    . Jaks link cytokine receptors to Stats, and abnormal Jak/Stat signaling has been observed in some hemopoietic cancers. In MF tumor cells, a slowly migrating isoform of Stat3, Stat3(sm), was found to be constitutively activated, i.e., (i) Stat3(sm) was constitutively phosphorylated on tyrosine residues...... specific. Thus, neither the fast migrating isoform of Stat3 (Stat3(fm)) nor other Stats (Stat1, Stat2, and Stat4 through Stat6) were constitutively activated. The Jak kinase inhibitor, tyrphostin AG490, blocked the constitutive activation of Stat3(sm) and inhibited spontaneous as well as interleukin 2...

  2. Constitutive activation of a plasma membrane H+-ATPase prevents abscisic acid-mediated stomatal closure

    Science.gov (United States)

    Merlot, Sylvain; Leonhardt, Nathalie; Fenzi, Francesca; Valon, Christiane; Costa, Miguel; Piette, Laurie; Vavasseur, Alain; Genty, Bernard; Boivin, Karine; Müller, Axel; Giraudat, Jérôme; Leung, Jeffrey

    2007-01-01

    Light activates proton (H+)-ATPases in guard cells, to drive hyperpolarization of the plasma membrane to initiate stomatal opening, allowing diffusion of ambient CO2 to photosynthetic tissues. Light to darkness transition, high CO2 levels and the stress hormone abscisic acid (ABA) promote stomatal closing. The overall H+-ATPase activity is diminished by ABA treatments, but the significance of this phenomenon in relationship to stomatal closure is still debated. We report two dominant mutations in the OPEN STOMATA2 (OST2) locus of Arabidopsis that completely abolish stomatal response to ABA, but importantly, to a much lesser extent the responses to CO2 and darkness. The OST2 gene encodes the major plasma membrane H+-ATPase AHA1, and both mutations cause constitutive activity of this pump, leading to necrotic lesions. H+-ATPases have been traditionally assumed to be general endpoints of all signaling pathways affecting membrane polarization and transport. Our results provide evidence that AHA1 is a distinct component of an ABA-directed signaling pathway, and that dynamic downregulation of this pump during drought is an essential step in membrane depolarization to initiate stomatal closure. PMID:17557075

  3. Constitutive activation of IKK2/NF-κB impairs osteogenesis and skeletal development.

    Directory of Open Access Journals (Sweden)

    Gaurav Swarnkar

    Full Text Available Pathologic conditions impair bone homeostasis. The transcription factor NF-κB regulates bone homeostasis and is central to bone pathologies. Whereas contribution of NF-κB to heightened osteoclast activity is well-documented, the mechanisms underlying NF-κB impact on chondrocytes and osteoblasts are scarce. In this study, we examined the effect of constitutively active IKK2 (IKK2ca on chondrogenic and osteogenic differentiation. We show that retroviral IKK2ca but not GFP, IKK2WT, or the inactive IKK2 forms IKK2KM and IKK2SSAA, strongly suppressed osteogenesis and chondrogenesis, in vitro. In order to explore the effect of constitutive NF-κB activation on bone formation in vivo, we activated this pathway in a conditional fashion. Specifically, we crossed the R26StopIKK2ca mice with mice carrying the Col2-cre in order to express IKK2ca in osteoblasts and chondrocytes. Both chondrocytes and osteoblasts derived from Col2Cre/IKK2ca expressed IKK2ca. Mice were born alive yet died shortly thereafter. Histologically, newborn Col2Cre+/RosaIKK2ca heterozygotes (Cre+IKK2ca_w/f (het and homozygotes (Cre+IKK2ca_f/f (KI showed smaller skeleton, deformed vertebrate and reduced or missing digit ossification. The width of neural arches, as well as ossification in vertebral bodies of Cre+IKK2ca_w/f and Cre+IKK2ca_f/f, was reduced or diminished. H&E staining of proximal tibia from new born pups revealed that Cre+IKK2ca_f/f displayed disorganized hypertrophic zones within the smaller epiphysis. Micro-CT analysis indicated that 4-wk old Cre+IKK2ca_w/f has abnormal trabecular bone in proximal tibia compared to WT littermates. Mechanistically, ex-vivo experiments showed that expression of differentiation markers in calvarial osteoblasts derived from newborn IKK2ca knock-in mice was diminished compared to WT-derived cells. In situ hybridization studies demonstrated that the hypertrophic chondrocyte marker type-X collagen, the pre-hypertrophic chondrocyte markers

  4. CINPA1 Is an Inhibitor of Constitutive Androstane Receptor That Does Not Activate Pregnane X Receptor

    Science.gov (United States)

    Cherian, Milu T; Lin, Wenwei; Wu, Jing

    2015-01-01

    Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic sensors that enhance the detoxification and elimination of xenobiotics and endobiotics by modulating the expression of genes encoding drug-metabolizing enzymes and transporters. Elevated levels of drug-metabolizing enzymes and efflux transporters, resulting from CAR activation in various cancers, promote the elimination of chemotherapeutic agents, leading to reduced therapeutic effectiveness and acquired drug resistance. CAR inhibitors, in combination with existing chemotherapeutics, could therefore be used to attenuate multidrug resistance in cancers. Interestingly, all previously reported CAR inverse-agonists are also activators of PXR, rendering them mechanistically counterproductive in tissues where both these xenobiotic receptors are present and active. We used a directed high-throughput screening approach, followed by subsequent mechanistic studies, to identify novel, potent, and specific small-molecule CAR inhibitors that do not activate PXR. We describe here one such inhibitor, CINPA1 (CAR inhibitor not PXR activator 1), capable of reducing CAR-mediated transcription with an IC50 of ∼70 nM. CINPA1 1) is a specific xenobiotic receptor inhibitor and has no cytotoxic effects up to 30 µM; 2) inhibits CAR-mediated gene expression in primary human hepatocytes, where CAR is endogenously expressed; 3) does not alter the protein levels or subcellular localization of CAR; 4) increases corepressor and reduces coactivator interaction with the CAR ligand-binding domain in mammalian two-hybrid assays; and 5) disrupts CAR binding to the promoter regions of target genes in chromatin immunoprecipitation assays. CINPA1 could be used as a novel molecular tool for understanding CAR function. PMID:25762023

  5. CINPA1 is an inhibitor of constitutive androstane receptor that does not activate pregnane X receptor.

    Science.gov (United States)

    Cherian, Milu T; Lin, Wenwei; Wu, Jing; Chen, Taosheng

    2015-05-01

    Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic sensors that enhance the detoxification and elimination of xenobiotics and endobiotics by modulating the expression of genes encoding drug-metabolizing enzymes and transporters. Elevated levels of drug-metabolizing enzymes and efflux transporters, resulting from CAR activation in various cancers, promote the elimination of chemotherapeutic agents, leading to reduced therapeutic effectiveness and acquired drug resistance. CAR inhibitors, in combination with existing chemotherapeutics, could therefore be used to attenuate multidrug resistance in cancers. Interestingly, all previously reported CAR inverse-agonists are also activators of PXR, rendering them mechanistically counterproductive in tissues where both these xenobiotic receptors are present and active. We used a directed high-throughput screening approach, followed by subsequent mechanistic studies, to identify novel, potent, and specific small-molecule CAR inhibitors that do not activate PXR. We describe here one such inhibitor, CINPA1 (CAR inhibitor not PXR activator 1), capable of reducing CAR-mediated transcription with an IC50 of ∼70 nM. CINPA1 1) is a specific xenobiotic receptor inhibitor and has no cytotoxic effects up to 30 µM; 2) inhibits CAR-mediated gene expression in primary human hepatocytes, where CAR is endogenously expressed; 3) does not alter the protein levels or subcellular localization of CAR; 4) increases corepressor and reduces coactivator interaction with the CAR ligand-binding domain in mammalian two-hybrid assays; and 5) disrupts CAR binding to the promoter regions of target genes in chromatin immunoprecipitation assays. CINPA1 could be used as a novel molecular tool for understanding CAR function. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  6. History of CERN. V. 2

    International Nuclear Information System (INIS)

    Hermann, A.; Krige, J.; Mersits, U.; Pestre, D.; Weiss, L.

    1990-01-01

    This volume of the History of CERN starts at 8 October 1954, when the Council of the new organization met for the first time, and takes the history through the mid-1960's. when it was decided to equip the laboratory with a second generation of accelerators and a new Director-General was nominated. It covers the building and the running of the laboratory during these dozen years, it studies the construction and exploitation of the 600 MeV Synchro-cyclotron and the 28 GeV Proton Synchrotron, it considers the setting up of the material and organizational infrastructure which made this possible, and it covers the reigns of four Director-Generals, Felix Bloch, Cornelis Bakker, John Adams and Victor Weisskopf. Part I describes the various aspects which together constitute the history of CERN and aims to offer a synchronic panorama year by year account of CERN's main activities. Part II deals primarily with technological achievements and scientific results and it includes the most technical chapters in the volume. Part III defines how the CERN 'system' functioned, how this science-based organization worked, how it chose, planned and concretely realized its experimental programme on the shop-floor and how it identified the equipment it would need in the long term and organized its relations with the outside world, notably the political world. The concluding Part IV brings out the specificity of CERN, to identify the ways in which it differed from other big science laboratories in the 1950's and 1960's, and to try to understand where its uniqueness and originality lay. (author). refs.; figs.; tabs

  7. Evodia alkaloids suppress gluconeogenesis and lipogenesis by activating the constitutive androstane receptor.

    Science.gov (United States)

    Yu, Lushan; Wang, Zhangting; Huang, Minmin; Li, Yingying; Zeng, Kui; Lei, Jinxiu; Hu, Haihong; Chen, Baian; Lu, Jing; Xie, Wen; Zeng, Su

    2016-09-01

    The constitutive androstane receptor (CAR) is a key sensor in xenobiotic detoxification and endobiotic metabolism. Increasing evidence suggests that CAR also plays a role in energy metabolism by suppressing the hepatic gluconeogenesis and lipogenesis. In this study, we investigated the effects of two evodia alkaloids, rutaecarpine (Rut) and evodiamine (Evo), on gluconeogenesis and lipogenesis through their activation of the human CAR (hCAR). We found that both Rut and Evo exhibited anti-lipogenic and anti-gluconeogenic effects in the hyperlipidemic HepG2 cells. Both compounds can potently activate hCAR, and treatment of cells with hCAR antagonists reversed the anti-lipogenic and anti-gluconeogenic effects of Rut and Evo. The anti-gluconeogenic effect of Rut and Evo was due to the CAR-mediated inhibition of the recruitment of forkhead box O1 (FoxO1) and hepatocyte nuclear factor 4α (HNF4α) onto the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene promoters. In vivo, we showed that treatment of mice with Rut improved glucose tolerance in a CAR-dependent manner. Our results suggest that the evodia alkaloids Rut and Evo may have a therapeutic potential for the treatment of hyperglycemia and type 2 diabetes. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Structural basis for constitutive activity and agonist-induced activation of the enteroendocrine fat sensor GPR119

    DEFF Research Database (Denmark)

    Engelstoft, Maja Storm; Norn, C; Pedersen, Maria Hauge

    2014-01-01

    BACKGROUND AND PURPOSE: GPR119 is a Gαs-coupled 7TM receptor activated by endogenous lipids such as oleoylethanolamide (OEA) and by the dietary triglyceride metabolite 2-monoacylglycerol. GPR119 stimulates enteroendocrine hormone and insulin secretion. But despite massive drug discovery efforts...... activation (AR231453 and OEA). Novel Rosetta-based receptor modelling was applied, using a composite template approach with segments from different X-ray structures and fully flexible ligand docking. KEY RESULTS: The increased signalling induced by increasing the cell surface expression of GPR119...... in the absence of agonist and the inhibitory effect of two synthetic inverse agonists demonstrated that GRP119 signals with a high degree of constitutive activity through the Gαs pathway. The mutational maps for AR231453 and OEA were very similar and, surprisingly, also similar to the mutational map for residues...

  9. Functional characterization of a constitutively active kinase variant of Arabidopsis phototropin 1.

    Science.gov (United States)

    Petersen, Jan; Inoue, Shin-Ichiro; Kelly, Sharon M; Sullivan, Stuart; Kinoshita, Toshinori; Christie, John M

    2017-08-18

    Phototropins (phots) are plasma membrane-associated serine/threonine kinases that coordinate a range of processes linked to optimizing photosynthetic efficiency in plants. These photoreceptors contain two light-, oxygen-, or voltage-sensing (LOV) domains within their N terminus, with each binding one molecule of flavin mononucleotide as a UV/blue light-absorbing chromophore. Although phots contain two LOV domains, light-induced activation of the C-terminal kinase domain and subsequent receptor autophosphorylation is controlled primarily by the A'α-LOV2-Jα photosensory module. Mutations that disrupt interactions between the LOV2 core and its flanking helical segments can uncouple this mode of light regulation. However, the impact of these mutations on phot function in Arabidopsis has not been explored. Here we report that histidine substitution of Arg-472 located within the A'α-helix of Arabidopsis phot1 constitutively activates phot1 kinase activity in vitro without affecting LOV2 photochemistry. Expression analysis of phot1 R472H in the phot-deficient mutant confirmed that it is autophosphorylated in darkness in vivo but unable to initiate phot1 signaling in the absence of light. Instead, we found that phot1 R472H is poorly functional under low-light conditions but can restore phototropism, chloroplast accumulation, stomatal opening, and leaf positioning and expansion at higher light intensities. Our findings suggest that Arabidopsis can adapt to the elevated phosphorylation status of the phot1 R472H mutant in part by reducing its stability, whereas the activity of the mutant under high-light conditions can be attributed to additional increases in LOV2-mediated photoreceptor autophosphorylation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Light Controls Cytokinin Signaling via Transcriptional Regulation of Constitutively Active Sensor Histidine Kinase CKI1.

    Science.gov (United States)

    Dobisova, Tereza; Hrdinova, Vendula; Cuesta, Candela; Michlickova, Sarka; Urbankova, Ivana; Hejatkova, Romana; Zadnikova, Petra; Pernisova, Marketa; Benkova, Eva; Hejatko, Jan

    2017-05-01

    In plants, the multistep phosphorelay (MSP) pathway mediates a range of regulatory processes, including those activated by cytokinins. The cross talk between cytokinin response and light has been known for a long time. However, the molecular mechanism underlying the interaction between light and cytokinin signaling remains elusive. In the screen for upstream regulators we identified a LONG PALE HYPOCOTYL ( LPH ) gene whose activity is indispensable for spatiotemporally correct expression of CYTOKININ INDEPENDENT1 ( CKI1 ), encoding the constitutively active sensor His kinase that activates MSP signaling. lph is a new allele of HEME OXYGENASE1 ( HY1 ) that encodes the key protein in the biosynthesis of phytochromobilin, a cofactor of photoconvertible phytochromes. Our analysis confirmed the light-dependent regulation of the CKI1 expression pattern. We show that CKI1 expression is under the control of phytochrome A (phyA), functioning as a dual (both positive and negative) regulator of CKI1 expression, presumably via the phyA-regulated transcription factors (TF) PHYTOCHROME INTERACTING FACTOR3 and CIRCADIAN CLOCK ASSOCIATED1. Changes in CKI1 expression observed in lph / hy1 - 7 and phy mutants correlate with misregulation of MSP signaling, changed cytokinin sensitivity, and developmental aberrations that were previously shown to be associated with cytokinin and/or CKI1 action. Besides that, we demonstrate a novel role of phyA-dependent CKI1 expression in the hypocotyl elongation and hook development during skotomorphogenesis. Based on these results, we propose that the light-dependent regulation of CKI1 provides a plausible mechanistic link underlying the well-known interaction between light- and cytokinin-controlled plant development. © 2017 American Society of Plant Biologists. All Rights Reserved.

  11. Identification and Characterization of CINPA1 Metabolites Facilitates Structure-Activity Studies of the Constitutive Androstane Receptor

    OpenAIRE

    Cherian, Milu T.; Yang, Lei; Chai, Sergio C.; Lin, Wenwei; Chen, Taosheng

    2016-01-01

    The constitutive androstane receptor (CAR) regulates the expression of genes involved in drug metabolism and other processes. A specific inhibitor of CAR is critical for modulating constitutive CAR activity. We recently described a specific small-molecule inhibitor of CAR, CINPA1 (ethyl (5-(diethylglycyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)carbamate), which is capable of reducing CAR-mediated transcription by changing the coregulator recruitment pattern and reducing CAR occupancy at the...

  12. 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.

  13. Constitutive androstane receptor activation promotes bilirubin clearance in a murine model of alcoholic liver disease.

    Science.gov (United States)

    Wang, Xiuyan; Zheng, Liyu; Wu, Jinming; Tang, Binbin; Zhang, Mengqin; Zhu, Debin; Lin, Xianfan

    2017-06-01

    Increased plasma levels of bilirubin have been reported in rat models and patients with alcoholic liver disease (ALD). The constitutive androstane receptor (CAR) is a known xenobiotic receptor, which induces the detoxification and transport of bilirubin. In the present study, the bilirubin transport regulatory mechanisms, and the role of CAR activation in hepatic and extrahepatic bilirubin clearance were investigated in a murine model of ALD. The mice were fed a Lieber-DeCarli ethanol diet or an isocaloric control diet for 4 weeks, followed by the administration of CAR agonists, 1,4-bis-[2‑(3,5-dichlorpyridyloxy)]benzene (TCPOBOP) and phenobarbital (PB), and their vehicles to examine the effect of the pharmacological activation of CAR on serum levels of bilirubin and on the bilirubin clearance pathway in ALD by serological survey, western blotting and reverse transcription‑quantitative polymerase chain reaction. The results showed that chronic ethanol ingestion impaired the nuclear translocation of CAR, which was accompanied by elevated serum levels of bilirubin, suppression of the expression of hepatic and renal organic anion transporting polypeptide (OATP) 1A1 and hepatic multidrug resistance‑associated protein 2 (MRP2), and induction of the expression of UDP-glucuronosyltransferase (UGT) 1A1. The activation of CAR by TCPOBOP and PB resulted in downregulation of the serum levels of bilirubin followed by selective upregulation of the expression levels of OATP1A1, OATP1A4, UGT1A1 and MRP2 in ALD. These results revealed the bilirubin transport regulatory mechanisms and highlighted the importance of CAR in modulating the bilirubin clearance pathway in the ALD mouse model.

  14. Constitutive activation of Nrf2 induces a stable reductive state in the mouse myocardium

    Directory of Open Access Journals (Sweden)

    Gobinath Shanmugam

    2017-08-01

    Full Text Available Redox homeostasis regulates key cellular signaling pathways in both physiology and pathology. The cell's antioxidant response provides a defense against oxidative stress and establishes a redox tone permissive for cell signaling. The molecular regulation of the well-known Keap1/Nrf2 system acts as sensor responding to changes in redox homeostasis and is poorly studied in the heart. Importantly, it is not yet known whether Nrf2 alone can serve as a master regulator of cellular redox homeostasis without compensation of the transcriptional regulation of antioxidant response element (ARE genes through alternate mechanisms. Here, we addressed this question using cardiac-specific transgenic expression at two different levels of constitutively active nuclear erythroid related factor 2 (caNrf2 functioning independently of Keap1. The caNrf2 mice showed augmentation of glutathione (GSH, the key regulator of the cellular thiol redox state. The Trans-AM assay for Nrf2-binding to the antioxidant response element (ARE showed a dose-dependent increase associated with upregulation of several major antioxidant genes and proteins. This was accompanied by a significant decrease in dihydroethidium staining and malondialdehyde (MDA in the caNrf2-TG mice myocardium. Interestingly, caNrf2 gene-dosage dependent redox changes were noted resulting in generation of a multi-stage model of pro-reductive and reductive conditions in the myocardium of TG-low and TG-high mice, respectively. These data clearly show that Nrf2 levels alone are capable of serving as the master regulator of the ARE. These models provide an important platform to investigate the impact of the Nrf2 system independent of the need to regulate the activity of Keap1 and the consequent exposure to pro-oxidants or electrophiles, which have numerous off-target effects.

  15. NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells

    International Nuclear Information System (INIS)

    Nishina, Takashi; Yamaguchi, Noritaka; Gohda, Jin; Semba, Kentaro; Inoue, Jun-ichiro

    2009-01-01

    Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-κB is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-κB activation. Here, we show that the alternative pathway is constitutively activated and NF-κB-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

  16. NIK is involved in constitutive activation of the alternative NF-{kappa}B pathway and proliferation of pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Nishina, Takashi [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamaguchi, Noritaka [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Gohda, Jin [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Semba, Kentaro [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Inoue, Jun-ichiro, E-mail: jun-i@ims.u-tokyo.ac.jp [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)

    2009-10-09

    Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-{kappa}B is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-{kappa}B activation. Here, we show that the alternative pathway is constitutively activated and NF-{kappa}B-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

  17. Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion

    Directory of Open Access Journals (Sweden)

    Shepherd Trevor G

    2010-02-01

    Full Text Available Abstract Background Activation of bone morphogenetic protein (BMP4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, ALK3QD, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT and cell adhesion. Results Unexpectedly, doxycycline-induced ALK3QD expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced ALK3QD expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that ALK3QD-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of ALK3QD-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, ALK3QD signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and

  18. Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation

    DEFF Research Database (Denmark)

    Behncken, S N; Billestrup, Nils; Brown, R

    2000-01-01

    Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers of the gro......Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers...

  19. Virally delivered, constitutively active NFκB improves survival of injured retinal ganglion cells.

    Science.gov (United States)

    Dvoriantchikova, Galina; Pappas, Steve; Luo, Xueting; Ribeiro, Marcio; Danek, Dagmara; Pelaez, Daniel; Park, Kevin K; Ivanov, Dmitry

    2016-12-01

    As axon damage and retinal ganglion cell (RGC) loss lead to blindness, therapies that increase RGC survival and axon regrowth have direct clinical relevance. Given that NFκB signaling is critical for neuronal survival and may regulate neurite growth, we investigated the therapeutic potential of NFκB signaling in RGC survival and axon regeneration. Although both NFκB subunits (p65 and p50) are present in RGCs, p65 exists in an inactive (unphosphorylated) state when RGCs are subjected to neurotoxic conditions. In this study, we used a phosphomimetic approach to generate DNA coding for an activated (phosphorylated) p65 (p65mut), then employed an adeno-associated virus serotype 2 (AAV2) to deliver the DNA into RGCs. We tested whether constitutive p65mut expression prevents death and facilitates neurite outgrowth in RGCs subjected to transient retinal ischemia or optic nerve crush (ONC), two models of neurotoxicity. Our data indicate that RGCs treated with AAV2-p65mut displayed a significant increase in survival compared to controls in ONC model (77 ± 7% vs. 25 ± 3%, P-value = 0.0001). We also found protective effect of modified p65 in RGCs of ischemic retinas (55 ± 12% vs. 35 ± 6%), but not to a statistically significant degree (P-value = 0.14). We did not detect a difference in axon regeneration between experimental and control animals after ONC. These findings suggest that increased NFκB signaling in RGCs attenuates retinal damage in animal models of neurodegeneration, but insignificantly impacts axon regeneration. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Selective elimination of high constitutive activity or chemokine binding in the human herpesvirus 8 encoded seven transmembrane oncogene ORF74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Holst, Peter Johannes

    2000-01-01

    Open reading frame 74 (ORF74) encoded by human herpesvirus 8 is a highly constitutively active seven transmembrane (7TM) receptor stimulated by angiogenic chemokines, e.g. growth-related oncogene-alpha, and inhibited by angiostatic chemokines e.g. interferon-gamma-inducible protein. Transgenic mice...

  1. Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Bräuner-Osborne, Hans

    1999-01-01

    A number of CXC chemokines competed with similar, nanomolar affinity against 125I-interleukin-8 (IL-8) binding to ORF-74, a constitutively active seven-transmembrane receptor encoded by human herpesvirus 8. However, in competition against 125I-labeled growth-related oncogene (GRO)-alpha, the ORF-74...

  2. Constitutive Activity of the Arabidopsis MAP Kinase 3 Confers Resistance to Pseudomonas syringae and Drives Robust Immune Responses

    KAUST Repository

    Lang, Julien; Genot, Baptiste; Hirt, Heribert; Colcombet, Jean

    2017-01-01

    of a constitutively active (CA) form of the protein led to auto-immune phenotypes. CA-MPK3 plants are dwarf and display defense responses that are characterized by the accumulation of salicylic acid and phytoalexins as well as by the upregulation

  3. Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Quanwei; Chen, Sixu; Qin, Hao [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Feng, Jianquan [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A& M Health Science Center, Dallas, TX 75246 (United States); Liu, Huayu; Liu, Daocheng; Li, Ang; Shen, Yue; Zhong, Xiaozheng; Li, Junfeng [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Zong, Zhaowen, E-mail: zongzhaowen@sina.cn [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China)

    2017-01-01

    Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-β-catenin mice. Then the effect of CA-β-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength. - Highlights: • Wnt/β-catenin signaling plays a central role in controlling bone mass. • CA-β-catenin has side effects on the bone

  4. Constitutive activation of the thyroid-stimulating hormone receptor (TSHR by mutating Ile691 in the cytoplasmic tail segment.

    Directory of Open Access Journals (Sweden)

    Zheng Liu

    Full Text Available BACKGROUND: Autosomal dominant non-autoimmune hyperthyroidism (ADNAH is a rare genetic disorder of the endocrine system. Molecular genetic studies in ADNAH have revealed heterozygous germline mutations in the TSHR. To data, mutations leading to an increase in the constitutive activation of the TSHR have been described in the transmembrane segments, exoloops and cytoplasmic loop of TSHR. These mutations result in constitutive activation of the G(αs/cAMP or G(αq/11/inositol phosphate (IP pathways, which stimulate thyroid hormone production and thyroid proliferation. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study, we reported a new TSHR mutation located in the C-terminal domain of TSHR, which results in a substitution of the conserved Ile(691 for Phe. In this study, to address the question of whether the I691F mutated receptor could be responsible for G(αs/cAMP or G(αq/11/IP constitutive activity, wild-type and TSHR mutants were expressed in COS-7 cells to determine cAMP constitutive activity and IP formation. Compared to the cell surface with expression of the A623V mutated receptor as positive control, the I691F mutated receptor showed a slight increase of cAMP accumulation. Furthermore, I691F resulted in constitutive activation of the G(αq/11/IP signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results indicate that Ile(691 not only contributes to keeping TSHR inactive in the G(αs/cAMP pathways but also in the G(αq/11/IP cascade.

  5. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

    Directory of Open Access Journals (Sweden)

    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  6. Recombinant Nox4 cytosolic domain produced by a cell or cell-free base systems exhibits constitutive diaphorase activity

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Minh Vu Chuong, E-mail: mvchuong@yahoo.fr [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Zhang, Leilei [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Lhomme, Stanislas; Mouz, Nicolas [PX' Therapeutics, MINATEC/Batiment de Haute Technologie, Grenoble (France); Lenormand, Jean-Luc [HumProTher Laboratory, TheReX/TIMC-IMAG UMR 5525 CNRS UJF, Universite Joseph Fourier, UFR de Medecine, Domaine de la Merci, 38706 La Tronche (France); Lardy, Bernard; Morel, Francoise [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer A comparison of two bacterial cell and cell-free protein expression systems is presented. Black-Right-Pointing-Pointer Soluble and active truncated Nox4 proteins are produced. Black-Right-Pointing-Pointer Nox4 has a constitutive diaphorase activity which is independent of cytosolic factors. Black-Right-Pointing-Pointer Isoform Nox4B is unable to initiate the first electronic transfer step. Black-Right-Pointing-Pointer Findings contribute to the understanding of the mechanism of Nox4 oxidase activity. -- Abstract: The membrane protein NADPH (nicotinamide adenine dinucleotide phosphate) oxidase Nox4 constitutively generates reactive oxygen species differing from other NADPH oxidases activity, particularly in Nox2 which needs a stimulus to be active. Although the precise mechanism of production of reactive oxygen species by Nox2 is well characterized, the electronic transfer throughout Nox4 remains unclear. Our study aims to investigate the initial electronic transfer step (diaphorase activity) of the cytosolic tail of Nox4. For this purpose, we developed two different approaches to produce soluble and active truncated Nox4 proteins. We synthesized soluble recombinant proteins either by in vitro translation or by bacteria induction. While proteins obtained by bacteria induction demonstrate an activity of 4.4 {+-} 1.7 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 20.5 {+-} 2.8 nmol/min/nmol with cytochrome c, the soluble proteins produced by cell-free expression system exhibit a diaphorase activity with a turn-over of 26 {+-} 2.6 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 48 {+-} 20.2 nmol/min/nmol with cytochrome c. Furthermore, the activity of the soluble proteins is constitutive and does not need any stimulus. We also show that the cytosolic tail of the isoform Nox4B lacking the first NADPH binding site is unable to demonstrate any diaphorase activity pointing out the

  7. The electrochemical catalytic activity of single-walled carbon nanotubes towards VO2+/VO2+ and V3+/V2+ redox pairs for an all vanadium redox flow battery

    International Nuclear Information System (INIS)

    Li Wenyue; Liu Jianguo; Yan Chuanwei

    2012-01-01

    Highlights: ► SWCNT shows excellent electrochemical catalytic activity towards VO 2 + /VO 2+ and V 3+ /V 2+ redox couples. ► The anodic reactions are more sensitive to the surface oxygen atom content change compared with the cathodic reactions. ► The enhanced battery performance clearly demonstrated that the SWCNT is suitable to be used as an electrode catalyst for VRFB. - Abstract: Single-walled carbon nanotube (SWCNT) was used as an electrode catalyst for an all vanadium redox flow battery (VRFB). The electrochemical property of SWCNT towards VO 2 + /VO 2+ and V 3+ /V 2+ was carefully characterized by cyclic voltammetric (CV) and electrochemical impedance spectroscopy (EIS) measurements. The peak current values for these redox pairs were significantly higher on the modified glassy carbon electrode compared with those obtained on the bare electrode, suggesting the excellent electrochemical activity of the SWCNT. Moreover, it was proved that the anodic process was more dependent on the surface oxygen of the SWCNT than the cathodic process through changing its surface oxygen content. Detailed EIS analysis of different modified electrodes revealed that the charge and mass transfer processes were accelerated at the modified electrode–electrolyte interface, which could be ascribed to the large specific surface area, the surface defects and the oxygen functional groups of the SWCNT. The enhanced battery performance effectively demonstrated that the SWCNT was suitable to serve as an electrode catalyst for the VRFB.

  8. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie

    2010-01-01

    brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...... and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development.......Malignant gliomas, the deadliest of brain neoplasms, show rampant genetic instability and resistance to genotoxic therapies, implicating potentially aberrant DNA damage response (DDR) in glioma pathogenesis and treatment failure. Here, we report on gross, aberrant constitutive activation of DNA...

  9. Arabidopsis thaliana cdd1 mutant uncouples the constitutive activation of salicylic acid signalling from growth defects.

    Science.gov (United States)

    Swain, Swadhin; Roy, Shweta; Shah, Jyoti; Van Wees, Saskia; Pieterse, Corné M; Nandi, Ashis K

    2011-12-01

    Arabidopsis genotypes with a hyperactive salicylic acid-mediated signalling pathway exhibit enhanced disease resistance, which is often coupled with growth and developmental defects, such as dwarfing and spontaneous necrotic lesions on the leaves, resulting in reduced biomass yield. In this article, we report a novel recessive mutant of Arabidopsis, cdd1 (constitutive defence without defect in growth and development1), that exhibits enhanced disease resistance associated with constitutive salicylic acid signalling, but without any observable pleiotropic phenotype. Both NPR1 (NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES1)-dependent and NPR1-independent salicylic acid-regulated defence pathways are hyperactivated in cdd1 mutant plants, conferring enhanced resistance against bacterial pathogens. However, a functional NPR1 allele is required for the cdd1-conferred heightened resistance against the oomycete pathogen Hyaloperonospora arabidopsidis. Salicylic acid accumulates at elevated levels in cdd1 and cdd1 npr1 mutant plants and is necessary for cdd1-mediated PR1 expression and disease resistance phenotypes. In addition, we provide data which indicate that the cdd1 mutation negatively regulates the npr1 mutation-induced hyperactivation of ethylene/jasmonic acid signalling. © 2011 The Authors. Molecular Plant Pathology © 2011 BSPP and Blackwell Publishing Ltd.

  10. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    Science.gov (United States)

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  11. Constitutive activation of a variant of the env-mpl oncogene product by disulfide-linked homodimerization.

    OpenAIRE

    Courtois, G; Bénit, L; Mikaeloff, Y; Pauchard, M; Charon, M; Varlet, P; Gisselbrecht, S

    1995-01-01

    The myeloproliferative leukemia retrovirus (MPLV) has the v-mpl cellular sequences transduced in frame with the deleted and rearranged Friend murine leukemia virus env gene. The resulting env-mpl fusion oncogene is responsible for an acute myeloproliferative disorder induced in mice by MPLV. v-mpl is a truncated form of the c-mpl gene which encodes the receptor for thrombopoietin. We investigated the contribution of the Env-Mpl extracellular domain in the constitutive activation of this trunc...

  12. The role of opioid antagonist efficacy and constitutive opioid receptor activity in the opioid withdrawal syndrome in mice

    OpenAIRE

    Navani, Dipesh M.; Sirohi, Sunil; Madia, Priyanka A.; Yoburn, Byron C.

    2011-01-01

    On the basis of efficacy, opioid antagonists are classified as inverse opioid agonists (e.g. naltrexone) or neutral opioid antagonists (e.g. 6β-naltrexol). This study examined the interaction between naltrexone and 6β-naltrexol in the precipitated opioid withdrawal syndrome in morphine dependent mice. Furthermore, the possible contribution of constitutive opioid receptor activity to precipitated withdrawal was evaluated using increasing levels of morphine dependence. In the first experiment, ...

  13. Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors

    Science.gov (United States)

    Yin, Yanting; de Waal, Parker W.; He, Yuanzheng; Zhao, Li-Hua; Yang, Dehua; Cai, Xiaoqing; Jiang, Yi; Melcher, Karsten; Wang, Ming-Wei; Xu, H. Eric

    2017-01-01

    The glucagon receptor (GCGR) belongs to the secretin-like (class B) family of G protein-coupled receptors (GPCRs) and is activated by the peptide hormone glucagon. The structures of an activated class B GPCR have remained unsolved, preventing a mechanistic understanding of how these receptors are activated. Using a combination of structural modeling and mutagenesis studies, we present here two modes of ligand-independent activation of GCGR. First, we identified a GCGR-specific hydrophobic lock comprising Met-338 and Phe-345 within the IC3 loop and transmembrane helix 6 (TM6) and found that this lock stabilizes the TM6 helix in the inactive conformation. Disruption of this hydrophobic lock led to constitutive G protein and arrestin signaling. Second, we discovered a polar core comprising conserved residues in TM2, TM3, TM6, and TM7, and mutations that disrupt this polar core led to constitutive GCGR activity. On the basis of these results, we propose a mechanistic model of GCGR activation in which TM6 is held in an inactive conformation by the conserved polar core and the hydrophobic lock. Mutations that disrupt these inhibitory elements allow TM6 to swing outward to adopt an active TM6 conformation similar to that of the canonical β2-adrenergic receptor complexed with G protein and to that of rhodopsin complexed with arrestin. Importantly, mutations in the corresponding polar core of several other members of class B GPCRs, including PTH1R, PAC1R, VIP1R, and CRFR1, also induce constitutive G protein signaling, suggesting that the rearrangement of the polar core is a conserved mechanism for class B GPCR activation. PMID:28356352

  14. Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors.

    Science.gov (United States)

    Yin, Yanting; de Waal, Parker W; He, Yuanzheng; Zhao, Li-Hua; Yang, Dehua; Cai, Xiaoqing; Jiang, Yi; Melcher, Karsten; Wang, Ming-Wei; Xu, H Eric

    2017-06-16

    The glucagon receptor (GCGR) belongs to the secretin-like (class B) family of G protein-coupled receptors (GPCRs) and is activated by the peptide hormone glucagon. The structures of an activated class B GPCR have remained unsolved, preventing a mechanistic understanding of how these receptors are activated. Using a combination of structural modeling and mutagenesis studies, we present here two modes of ligand-independent activation of GCGR. First, we identified a GCGR-specific hydrophobic lock comprising Met-338 and Phe-345 within the IC3 loop and transmembrane helix 6 (TM6) and found that this lock stabilizes the TM6 helix in the inactive conformation. Disruption of this hydrophobic lock led to constitutive G protein and arrestin signaling. Second, we discovered a polar core comprising conserved residues in TM2, TM3, TM6, and TM7, and mutations that disrupt this polar core led to constitutive GCGR activity. On the basis of these results, we propose a mechanistic model of GCGR activation in which TM6 is held in an inactive conformation by the conserved polar core and the hydrophobic lock. Mutations that disrupt these inhibitory elements allow TM6 to swing outward to adopt an active TM6 conformation similar to that of the canonical β 2 -adrenergic receptor complexed with G protein and to that of rhodopsin complexed with arrestin. Importantly, mutations in the corresponding polar core of several other members of class B GPCRs, including PTH1R, PAC1R, VIP1R, and CRFR1, also induce constitutive G protein signaling, suggesting that the rearrangement of the polar core is a conserved mechanism for class B GPCR activation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Enhanced constitutive invasion activity in human nontumorigenic keratinocytes exposed to a low level of barium for a long time.

    Science.gov (United States)

    Thang, Nguyen D; Yajima, Ichiro; Ohnuma, Shoko; Ohgami, Nobutaka; Kumasaka, Mayuko Y; Ichihara, Gaku; Kato, Masashi

    2015-02-01

    We have recently demonstrated that exposure to barium for a short time (≤4 days) and at a low level (5 µM = 687 µg/L) promotes invasion of human nontumorigenic HaCaT cells, which have characteristics similar to those of normal keratinocytes, suggesting that exposure to barium for a short time enhances malignant characteristics. Here we examined the effect of exposure to low level of barium for a long time, a condition mimicking the exposure to barium through well water, on malignant characteristics of HaCaT keratinocytes. Constitutive invasion activity, focal adhesion kinase (FAK) protein expression and activity, and matrix metalloproteinase 14 (MMP14) protein expression in primary cultured normal human epidermal keratinocytes, HaCaT keratinocytes, and HSC5 and A431 human squamous cell carcinoma cells were augmented following an increase in malignancy grade of the cells. Constitutive invasion activity, FAK phosphorylation, and MMP14 expression levels of HaCaT keratinocytes after treatment with 5 µM barium for 4 months were significantly higher than those of control untreated HaCaT keratinocytes. Taken together, our results suggest that exposure to a low level of barium for a long time enhances constitutive malignant characteristics of HaCaT keratinocytes via regulatory molecules (FAK and MMP14) for invasion. © 2013 Wiley Periodicals, Inc.

  16. Using constitutive activity to define appropriate high-throughput screening assays for orphan g protein-coupled receptors.

    Science.gov (United States)

    Ngo, Tony; Coleman, James L J; Smith, Nicola J

    2015-01-01

    Orphan G protein-coupled receptors represent an underexploited resource for drug discovery but pose a considerable challenge for assay development because their cognate G protein signaling pathways are often unknown. In this methodological chapter, we describe the use of constitutive activity, that is, the inherent ability of receptors to couple to their cognate G proteins in the absence of ligand, to inform the development of high-throughput screening assays for a particular orphan receptor. We specifically focus on a two-step process, whereby constitutive G protein coupling is first determined using yeast Gpa1/human G protein chimeras linked to growth and β-galactosidase generation. Coupling selectivity is then confirmed in mammalian cells expressing endogenous G proteins and driving accumulation of transcription factor-fused luciferase reporters specific to each of the classes of G protein. Based on these findings, high-throughput screening campaigns can be performed on the already miniaturized mammalian reporter system.

  17. Basic algebraic geometry, v.2

    CERN Document Server

    Shafarevich, Igor Rostislavovich

    1994-01-01

    Shafarevich Basic Algebraic Geometry 2 The second edition of Shafarevich's introduction to algebraic geometry is in two volumes. The second volume covers schemes and complex manifolds, generalisations in two different directions of the affine and projective varieties that form the material of the first volume. Two notable additions in this second edition are the section on moduli spaces and representable functors, motivated by a discussion of the Hilbert scheme, and the section on Kähler geometry. The book ends with a historical sketch discussing the origins of algebraic geometry. From the Zentralblatt review of this volume: "... one can only respectfully repeat what has been said about the first part of the book (...): a great textbook, written by one of the leading algebraic geometers and teachers himself, has been reworked and updated. As a result the author's standard textbook on algebraic geometry has become even more important and valuable. Students, teachers, and active researchers using methods of al...

  18. Constitutional changes and the dilemmas of constitutionalism

    Directory of Open Access Journals (Sweden)

    Arsen Bačić

    2009-01-01

    Full Text Available The need to develop constitutional mechanisms whose aim is to resolve fundamental relations in society demands the widest possible inclusion of all of society’s active participants in the discussion on the need to adopt or revise the Constitution. The opening of every new round of constitutional changes is of great importance because it always unlocks certain new and important questions. The answers to those questions should be offered by state authority (policy and civil society including science and its disciplines. In this paper, the author mentions several topics which are of interest in the current discussion on the significance of current constitutional changes for the future of the development of constitutionalism and democracy in the Republic of Croatia. These are above all topics of political and legal constitutionalism and suggestions linked to strengthening the independence of judicial powers. The author advocates consistent application of constitutional control and check mechanisms which exclude all insularity of judicial powers in relation to democratic control.

  19. Constitutively active Arabidopsis MAP Kinase 3 triggers defense responses involving salicylic acid and SUMM2 resistance protein

    KAUST Repository

    Genot, Baptiste

    2017-04-12

    Mitogen-activated protein kinases (MAPKs) are important regulators of plant immunity. Most of the knowledge about the function of these pathways is derived from loss-of-function approaches. Using a gain-of-function approach, we investigated the responses controlled by a constitutively active (CA) MPK3 in Arabidopsis thaliana. CA-MPK3 plants are dwarfed and display a massive de-repression of defense genes associated with spontaneous cell death as well as accumulation of reactive oxygen species (ROS), phytoalexins and the stress-related hormones ethylene and salicylic acid (SA). Remarkably CA-MPK3/sid2 and CA-MPK3/ein2-50 lines which are impaired in SA synthesis and ethylene signaling, respectively, retain most of the CA-MPK3-associated phenotypes, indicating that constitutive activity of MPK3 can bypass SA and ethylene signaling to activate defense responses. A comparative analysis of the molecular phenotypes of CA-MPK3 and mpk4 autoimmunity suggested convergence between the MPK3 and MPK4-guarding modules. In support of this model, CA-MPK3 crosses with summ1 and summ2, two known suppressors of mpk4, resulted in a partial reversion of the CA-MPK3 phenotypes. Overall, our data unravel a novel mechanism by which the MAPK signaling network contributes to a robust defense response system.

  20. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie

    2010-01-01

    damage signalling in low- and high-grade human gliomas, and analyze the sources of such endogenous genotoxic stress. Based on analyses of human glioblastoma multiforme (GBM) cell lines, normal astrocytes and clinical specimens from grade II astrocytomas (n=41) and grade IV GBM (n=60), we conclude...... that the DDR machinery is constitutively activated in gliomas, as documented by phosphorylated histone H2AX (gammaH2AX), activation of the ATM-Chk2-p53 pathway, 53BP1 foci and other markers. Oxidative DNA damage (8-oxoguanine) was high in some GBM cell lines and many GBM tumors, while it was low in normal...... brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...

  1. Constitutional Conservatism

    Science.gov (United States)

    Berkowitz, Peter

    2009-01-01

    After their dismal performance in election 2008, conservatives are taking stock. As they examine the causes that have driven them into the political wilderness and as they explore paths out, they should also take heart. After all, election 2008 shows that America's constitutional order is working as designed. Indeed, while sorting out their errors…

  2. Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Aihua Hu

    Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

  3. Characterization of the Chemical Constitution and Profile of Pharmacological Activity of PGBx.

    Science.gov (United States)

    1980-04-30

    Mitochondrial Oxydative Phosphorylation System Columna Percent Activity- Comments Fractiorr 20 g 40 4g 7 50 100 slightly lower specific activity 8 115 115...amber alcoholic solution con- taining 155.6 mg of PGBx acid per ml. It was converted to the water- soluble sodium salt by us and both the freeze dried...salt and alcoholic solution were stored at 50C in a dessicator. For all biological studies, PGBx-Na was dissolved in appropriate volumes of Sorenson’s

  4. Distinct patterns of constitutive phosphodiesterase activity in mouse sinoatrial node and atrial myocardium.

    Directory of Open Access Journals (Sweden)

    Rui Hua

    Full Text Available Phosphodiesterases (PDEs are critical regulators of cyclic nucleotides in the heart. In ventricular myocytes, the L-type Ca(2+ current (I(Ca,L is a major target of regulation by PDEs, particularly members of the PDE2, PDE3 and PDE4 families. Conversely, much less is known about the roles of PDE2, PDE3 and PDE4 in the regulation of action potential (AP properties and I(Ca,L in the sinoatrial node (SAN and the atrial myocardium, especially in mice. Thus, the purpose of our study was to measure the effects of global PDE inhibition with Isobutyl-1-methylxanthine (IBMX and selective inhibitors of PDE2, PDE3 and PDE4 on AP properties in isolated mouse SAN and right atrial myocytes. We also measured the effects of these inhibitors on I(Ca,L in SAN and atrial myocytes in comparison to ventricular myocytes. Our data demonstrate that IBMX markedly increases spontaneous AP frequency in SAN myocytes and AP duration in atrial myocytes. Spontaneous AP firing in SAN myocytes was also increased by the PDE2 inhibitor erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA, the PDE3 inhibitor milrinone (Mil and the PDE4 inhibitor rolipram (Rol. In contrast, atrial AP duration was increased by EHNA and Rol, but not by Mil. IBMX also potently, and similarly, increased I(Ca,L in SAN, atrial and ventricular myocytes; however, important differences emerged in terms of which inhibitors could modulate I(Ca,L in each myocyte type. Consistent with our AP measurements, EHNA, Mil and Rol each increased I(Ca,L in SAN myocytes. Also, EHNA and Rol, but not Mil, increased atrial I(Ca,L. In complete contrast, no selective PDE inhibitors increased I(Ca,L in ventricular myocytes when given alone. Thus, our data show that the effects of selective PDE2, PDE3 and PDE4 inhibitors are distinct in the different regions of the myocardium indicating important differences in how each PDE family constitutively regulates ion channel function in the SAN, atrial and ventricular myocardium.

  5. Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension

    Science.gov (United States)

    Anwar, Adil; Li, Min; Frid, Maria G.; Kumar, Binod; Gerasimovskaya, Evgenia V.; Riddle, Suzette R.; McKeon, B. Alexandre; Thukaram, Roopa; Meyrick, Barbara O.; Fini, Mehdi A.

    2012-01-01

    Increased cell proliferation and migration, of several cell types are key components of vascular remodeling observed in pulmonary hypertension (PH). Our previous data demonstrate that adventitial fibroblasts isolated from pulmonary arteries of chronically hypoxic hypertensive calves (termed PH-Fibs) exhibit a “constitutively activated” phenotype characterized by high proliferative and migratory potential. Osteopontin (OPN) has been shown to promote several cellular activities including growth and migration in cancer cells. We thus tested the hypothesis that elevated OPN expression confers the “activated” highly proproliferative and promigratory/invasive phenotype of PH-Fibs. Our results demonstrate that, both in vivo and ex vivo, PH-Fibs exhibited increased expression of OPN, as well as its cognate receptors, αVβ3 and CD44, compared with control fibroblasts (CO-Fibs). Augmented OPN expression in PH-Fibs corresponded to their high proliferative, migratory, and invasive properties and constitutive activation of ERK1/2 and AKT signaling. OPN silencing via small interfering RNA or sequestering OPN production by specific antibodies led to decreased proliferation, migration, invasion, and attenuated ERK1/2, AKT phosphorylation in PH-Fibs. Furthermore, increasing OPN levels in CO-Fibs via recombinant OPN resulted in significant increases in their proliferative, migratory, and invasive capabilities to the levels resembling those of PH-Fibs. Thus our data suggest OPN as an essential contributor to the activated (highly proliferative, migratory, and proinvasive) phenotype of pulmonary adventitial fibroblasts in hypoxic PH. PMID:22582113

  6. Increased HSF activation in muscles with a high constitutive Hsp70 expression

    OpenAIRE

    Locke, Marius; Tanguay, Robert M.

    1996-01-01

    Stress-induced transcriptional regulation of the Hsps is mediated by trimerization and binding of a pre-existing heat shock transcription factor (HSF1) to a specific DNA sequence located in the 5′ region of hsp genes, known as the heat shock element. Hsp70 has been implicated in regulating the activation of the HSF and, according to cell culture models, high steady-state levels of Hsp70 are inversely correlated with HSF activation. To determine if this applies in an intact animal, muscles of ...

  7. V2 and cP/CP

    DEFF Research Database (Denmark)

    Vikner, Sten; Christensen, Ken Ramshøj; Nyvad, Anne Mette

    2017-01-01

    As in Nyvad et al. (2017), we will explore a particular derivation of (embedded) V2, in terms of a cP/CP-distinction, which may be seen as a version of the CP-recursion analysis (de Haan & Weerman 1986; Vikner 1995 and many others). e idea is that because embedded V2 clauses do not allow extraction......, whereas other types of CP-recursion clauses do (Christensen et al. 2013a; 2013b; Christensen & Nyvad 2014), CP-recursion in embedded V2 is assumed to be fundamentally di erent from other kinds of CP-recursion, in that main clause V2 and embedded V2 involve a CP (“big CP”), whereas other clausal...... projections above IP are instances of cP (“little cP”)....

  8. Constitutive Activity of the Arabidopsis MAP Kinase 3 Confers Resistance to Pseudomonas syringae and Drives Robust Immune Responses

    KAUST Repository

    Lang, Julien

    2017-08-02

    Mitogen Activated Protein Kinases (MAPKs) are known to be important mediators of plant responses to biotic and abiotic stresses. In a recent report, we enlarged the understanding of the Arabidopsis thaliana MPK3 functions showing that the expression of a constitutively active (CA) form of the protein led to auto-immune phenotypes. CA-MPK3 plants are dwarf and display defense responses that are characterized by the accumulation of salicylic acid and phytoalexins as well as by the upregulation of several defense genes. Consistently with these data, we present here results demonstrating that, compared to wild type controls, CA-MPK3 plants are more resistant to the hemibiotrophic pathogen Pseudomonas syringae DC3000. Based on our previous work, we also discuss the mechanisms of robust plant immunity controlled by sustained MPK3 activity, focusing especially on the roles of disease resistance proteins.

  9. Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver

    Science.gov (United States)

    Ito, Yuki; Nakamura, Toshiki; Yanagiba, Yukie; Ramdhan, Doni Hikmat; Yamagishi, Nozomi; Naito, Hisao; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

    2012-01-01

    Dibutylphthalate (DBP), di(2-ethylhexyl)phthalate (DEHP), and di(2-ethylhexyl)adipate (DEHA) are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR) α, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPARα by these plasticizers using wild-type (mPPARα) and humanized PPARα (hPPARα) mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control), 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg), DEHP (977, 1953 mg/kg), and DEHA (926, 1853 mg/kg), respectively. Generally, hepatic PPARα of mPPARα mice was more strongly activated than that of hPPARα mice when several target genes involving β-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR) more in hPPARα mice than in mPPARα mice. Taken together, these plasticizers activated mouse and human hepatic PPARα as well as CAR. The activation of PPARα was stronger in mPPARα mice than in hPPARα mice, while the opposite was true of CAR. PMID:22792086

  10. Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver

    Directory of Open Access Journals (Sweden)

    Yuki Ito

    2012-01-01

    Full Text Available Dibutylphthalate (DBP, di(2-ethylhexylphthalate (DEHP, and di(2-ethylhexyladipate (DEHA are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR α, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPARα by these plasticizers using wild-type (mPPARα and humanized PPARα (hPPARα mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control, 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg, DEHP (977, 1953 mg/kg, and DEHA (926, 1853 mg/kg, respectively. Generally, hepatic PPARα of mPPARα mice was more strongly activated than that of hPPARα mice when several target genes involving β-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR more in hPPARα mice than in mPPARα mice. Taken together, these plasticizers activated mouse and human hepatic PPARα as well as CAR. The activation of PPARα was stronger in mPPARα mice than in hPPARα mice, while the opposite was true of CAR.

  11. Identification of a type 1 diabetes-associated CD4 promoter haplotype with high constitutive activity

    DEFF Research Database (Denmark)

    Kristiansen, O P; Karlsen, A E; Larsen, Z M

    2004-01-01

    screened the human CD4 promoter for mutations and identified three frequent single nucleotide polymorphisms (SNPs): CD4-181C/G, CD4-521C/G and CD4-1050T/C. The SNPs are in strong linkage disequilibrium (LD) and association with the CD4-1188(TTTTC)(5-14) alleles, and we observed nine CD4 promoter haplotypes...... promoter activity and (2) the CD4-181G variant encodes higher stimulated promoter activity than the CD4-181C variant. This difference is in part neutralized in the frequently occurring CD4 promoter haplotypes by the more upstream genetic variants. Thus, we report functional impact of a novel CD4-181C/G SNP...

  12. The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera

    Science.gov (United States)

    Pieri, Lisa; Bogani, Costanza; Guglielmelli, Paola; Zingariello, Maria; Rana, Rosa Alba; Bartalucci, Niccolò; Bosi, Alberto; Vannucchi, Alessandro M.

    2009-01-01

    Background The JAK2V617F mutation has been associated with constitutive and enhanced activation of neutrophils, while no information is available concerning other leukocyte subtypes. Design and Methods We evaluated correlations between JAK2V617F mutation and the count of circulating basophils, the number of activated CD63+ basophils, their response in vitro to agonists as well as the effects of a JAK2 inhibitor. Results We found that basophil count was increased in patients with JAK2V617F -positive myeloproliferative neoplasms, particularly in those with polycythemia vera, and was correlated with the V617F burden. The burden of V617F allele was similar in neutrophils and basophils from patients with polycythemia vera, while total JAK2 mRNA content was remarkably greater in the basophils; however, the content of JAK2 protein in basophils was not increased. The number of CD63+ basophils was higher in patients with polycythemia vera than in healthy subjects or patients with essential thrombocythemia or primary myelofibrosis and was correlated with the V617F burden. Ultrastructurally, basophils from patients with polycythemia vera contained an increased number of granules, most of which were empty suggesting cell degranulation in vivo. Ex vivo experiments revealed that basophils from patients with polycythemia vera were hypersensitive to the priming effect of interleukin-3 and to f-MLP-induced activation; pre-treatment with a JAK2 inhibitor reduced polycythemia vera basophil activation. Finally, we found that the number of circulating CD63+ basophils was significantly greater in patients suffering from aquagenic pruritus, who also showed a higher V617F allele burden. Conclusions These data indicate that the number of constitutively activated and hypersensitive circulating basophils is increased in polycythemia vera, underscoring a role of JAK2V617F in these cells’ abnormal function and, putatively, in the pathogenesis of pruritus. PMID:19608683

  13. MnV2O6.V2O5 cross-like nanobelt arrays: synthesis, characterization and photocatalytic properties

    International Nuclear Information System (INIS)

    Abbood, Hayder A.; Ahmed, Khalid Abdelazez Mohamed; Ren, Yong; Huang, Kaixun

    2013-01-01

    Single-crystalline MnV 2 O 6 .V 2 O 5 cross-like nanobelt arrays were successfully synthesized by hydrothermal reaction. The products were characterized by X-ray diffraction, transmission electron microscopy and high-resolution transmission electron microscopy. The effects of the reaction conditions such as pH, V 5+ /Mn 2+ ratio, carboxymethyl cellulose concentration and reaction time on the morphology of the products were studied. The band gap of the as-prepared products was calculated via diffuse reflectance spectral analysis and their activity of photocatalytic oxidation was evaluated by photodegradation of methylene blue under visible-light irradiation. The results showed that the degradation efficiency of methylene blue catalyzed by the calcinated products is remarkably enhanced due to Mn doping, suggesting that MnV 2 O 6 .V 2 O 5 cross-like nanobelt arrays are a good candidate for visible-light-driven photocatalysts. (orig.)

  14. Retinoblastoma pathway defects show differential ability to activate the constitutive DNA damage response in human tumorigenesis

    DEFF Research Database (Denmark)

    Tort, F.; Bartkova, J.; Sehested, M.

    2006-01-01

    culture models with differential defects of retinoblastoma pathway components, as overexpression of cyclin D1 or lack of p16(Ink4a), either alone or combined, did not elicit detectable DDR. In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse...... with their hierarchical positions along the retinoblastoma pathway. Our data provide new insights into oncogene-evoked DDR in human tumorigenesis, with potential implications for individualized management of tumors with elevated cyclin D1 versus cyclin E, due to their distinct clinical variables and biological behavior....

  15. Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways

    International Nuclear Information System (INIS)

    Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella

    2005-01-01

    Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop-helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-Jκ-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV

  16. Electrochemistry of V2ON with lithium

    International Nuclear Information System (INIS)

    Zhou Yongning; Liu Chang; Chen Huajun; Zhang Long; Li Wenjing; Fu Zhengwen

    2011-01-01

    Highlights: → We have prepared V 2 ON thin film by reactive dc sputtering method and annealing process. → We investigated for its electrochemistry with lithium. → V 2 ON thin films exhibit a large reversible specific capacity of 830 mAh g -1 with much less polarization than VN thin films. → The reversible transformation between nanocrystalline V 2 ON and well dispersed V, Li 2 O, Li 3 N nano-composites were revealed. - Abstract: V 2 ON thin film has been successfully fabricated by reactive dc sputtering method and annealing process and was investigated for its electrochemistry with lithium. The reversible discharge capacities of V 2 ON/Li cells cycled between 0.01 and 4.0 V were found in the range of 803-915 mAh g -1 during the first 50 cycles. By using ex situ scanning electron microscopy, transmission electron microscopy, selected-area electron diffraction and X-ray photoelectron spectroscopy measurements, the reversible transformation between nanocrystalline V 2 ON and well dispersed V, Li 2 O, Li 3 N nano-composites were revealed in the lithium electrochemical reaction. V 2 ON thin film exhibits high reversible capacity and good cycle performance with remarkable lower polarization than VN thin film.

  17. Modulation of the constitutive activity of the ghrelin receptor by use of pharmacological tools and mutagenesis.

    Science.gov (United States)

    Mokrosiński, Jacek; Holst, Birgitte

    2010-01-01

    Ghrelin and its receptor are important regulators of metabolic functions, including appetite, energy expenditure, fat accumulation, and growth hormone (GH) secretion. The ghrelin receptor is characterized by an ability to signal even without any ligand present with approximately 50% of the maximally ghrelin-induced efficacy-a feature that may have important physiological implications. The high basal signaling can be modulated either by administration of specific ligands or by engineering of mutations in the receptor structure. [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P was the first inverse agonist to be identified for the ghrelin receptor, and this peptide has been used as a starting point for identification of the structural requirements for inverse agonist properties in the ligand. The receptor binding core motif was identified as D-Trp-Phe-D-Trp-Leu-Leu, and elongation of this peptide in the amino-terminal end determined the efficacy. Attachment of a positively charged amino acid was responsible for full inverse agonism, whereas an alanin converted the peptide into a partial agonist. Importantly, by use of mutational mapping of the residues critical for the modified D-Trp-Phe-D-Trp-Leu-Leu peptides, it was found that space-generating mutations in the deeper part of the receptor improved inverse agonism, whereas similar mutations located in the more extracellular part improved agonism. Modulation of the basal signaling by mutations in the receptor structure is primarily obtained by substitutions in an aromatic cluster that keep TMs VI and VII in close proximity to TM III and thus stabilize the active conformation. Also, substitution of a Phe in TM V is crucial for the high basal activity of the receptor as this residue serves as a partner for Trp VI:13 in the active conformation. It is suggested that inverse agonist and antagonist against the ghrelin receptor provide an interesting possibility in the development of drugs for treatment of obesity and

  18. Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha.

    Directory of Open Access Journals (Sweden)

    Mei-Fei Yueh

    Full Text Available Triclocarban (3,4,4'-trichlorocarbanilide, TCC is used as a broad-based antimicrobial agent that is commonly added to personal hygiene products. Because of its extensive use in the health care industry and resistance to degradation in sewage treatment processes, TCC has become a significant waste product that is found in numerous environmental compartments where humans and wildlife can be exposed. While TCC has been linked to a range of health and environmental effects, few studies have been conducted linking exposure to TCC and induction of xenobiotic metabolism through regulation by environmental sensors such as the nuclear xenobiotic receptors (XenoRs. To identify the ability of TCC to activate xenobiotic sensors, we monitored XenoR activities in response to TCC treatment using luciferase-based reporter assays. Among the XenoRs in the reporter screening assay, TCC promotes both constitutive androstane receptor (CAR and estrogen receptor alpha (ERα activities. TCC treatment to hUGT1 mice resulted in induction of the UGT1A genes in liver. This induction was dependent upon the constitutive active/androstane receptor (CAR because no induction occurred in hUGT1Car(-/- mice. Induction of the UGT1A genes by TCC corresponded with induction of Cyp2b10, another CAR target gene. TCC was demonstrated to be a phenobarbital-like activator of CAR in receptor-based assays. While it has been suggested that TCC be classified as an endocrine disruptor, it activates ERα leading to induction of Cyp1b1 in female ovaries as well as in promoter activity. Activation of ERα by TCC in receptor-based assays also promotes induction of human CYP2B6. These observations demonstrate that TCC activates nuclear xenobiotic receptors CAR and ERα both in vivo and in vitro and might have the potential to alter normal physiological homeostasis. Activation of these xenobiotic-sensing receptors amplifies gene expression profiles that might represent a mechanistic base for

  19. The StreamCat Dataset: Accumulated Attributes for NHDPlusV2 (Version 2.1) Catchments Riparian Buffer for the Conterminous United States: Mine Density Active Mines and Mineral Plants in the US

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset represents the mine density within individual, local NHDPlusV2 catchments and upstream, contributing watersheds riparian buffers based on mine plants...

  20. The StreamCat Dataset: Accumulated Attributes for NHDPlusV2 (Version 2.1) Catchments for the Conterminous United States: Mine Density Active Mines and Mineral Plants in the US

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset represents the mine density within individual, local NHDPlusV2 catchments and upstream, contributing watersheds based on mine plants and operations...

  1. A knockout mutation of a constitutive GPCR in Tetrahymena decreases both G-protein activity and chemoattraction.

    Directory of Open Access Journals (Sweden)

    Thomas J Lampert

    Full Text Available Although G-protein coupled receptors (GPCRs are a common element in many chemosensory transduction pathways in eukaryotic cells, no GPCR or regulated G-protein activity has yet been shown in any ciliate. To study the possible role for a GPCR in the chemoresponses of the ciliate Tetrahymena, we have generated a number of macronuclear gene knockouts of putative GPCRs found in the Tetrahymena Genome database. One of these knockout mutants, called G6, is a complete knockout of a gene that we call GPCR6 (TTHERM_00925490. Based on sequence comparisons, the Gpcr6p protein belongs to the Rhodopsin Family of GPCRs. Notably, Gpcr6p shares highest amino acid sequence homologies to GPCRs from Paramecium and several plants. One of the phenotypes of the G6 mutant is a decreased responsiveness to the depolarizing ions Ba²⁺ and K⁺, suggesting a decrease in basal excitability (decrease in Ca²⁺ channel activity. The other major phenotype of G6 is a loss of chemoattraction to lysophosphatidic acid (LPA and proteose peptone (PP, two known chemoattractants in Tetrahymena. Using microsomal [³⁵S]GTPγS binding assays, we found that wild-type (CU427 have a prominent basal G-protein activity. This activity is decreased to the same level by pertussis toxin (a G-protein inhibitor, addition of chemoattractants, or the G6 mutant. Since the basal G-protein activity is decreased by the GPCR6 knockout, it is likely that this gene codes for a constitutively active GPCR in Tetrahymena. We propose that chemoattractants like LPA and PP cause attraction in Tetrahymena by decreasing the basal G-protein stimulating activity of Gpcr6p. This leads to decreased excitability in wild-type and longer runs of smooth forward swimming (less interrupted by direction changes towards the attractant. Therefore, these attractants may work as inverse agonists through the constitutively active Gpcr6p coupled to a pertussis-sensitive G-protein.

  2. High-level expression, purification and characterization of a constitutively active thromboxane A2 receptor polymorphic variant.

    Directory of Open Access Journals (Sweden)

    Bing Xu

    Full Text Available G protein-coupled receptors (GPCRs exhibit some level of basal signaling even in the absence of a bound agonist. This basal or constitutive signaling can have important pathophysiological roles. In the past few years, a number of high resolution crystal structures of GPCRs have been reported, including two crystal structures of constitutively active mutants (CAM of the dim-light receptor, rhodopsin. The structural characterizations of CAMs are impeded by the lack of proper expression systems. The thromboxane A2 receptor (TP is a GPCR that mediates vasoconstriction and promotes thrombosis in response to the binding of thromboxane. Here, we report on the expression and purification of a genetic variant and CAM in TP, namely A160T, using tetracycline-inducible HEK293S-TetR and HEK293S (GnTI¯-TetR cell lines. Expression of the TP and the A160T genes in these mammalian cell lines resulted in a 4-fold increase in expression to a level of 15.8 ±0.3 pmol of receptor/mg of membrane protein. The receptors expressed in the HEK293S (GnTI(--TetR cell line showed homogeneous glycosylation. The functional yield of the receptors using a single step affinity purification was 45 µg/10⁶ cells. Temperature- dependent secondary structure changes of the purified TP and A160T receptors were characterized using circular dichroism (CD spectropolarimetry. The CD spectra shows that the loss of activity or thermal sensitivity that was previously observed for the A160T mutant, is not owing to large unfolding of the protein but rather to a more subtle effect. This is the first study to report on the successful high-level expression, purification, and biophysical characterization of a naturally occurring, diffusible ligand activated GPCR CAM.

  3. Overexpression of OLE1 enhances stress tolerance and constitutively activates the MAPK HOG pathway in Saccharomyces cerevisiae.

    Science.gov (United States)

    Nasution, Olviyani; Lee, Young Mi; Kim, Eunjung; Lee, Yeji; Kim, Wankee; Choi, Wonja

    2017-03-01

    OLE1 of Saccharomyces cerevisiae encodes the sole and essential Δ-9 desaturase catalyzing the conversion of saturated to unsaturated fatty acids. Upon ectopic overexpression of OLE1 in S. cerevisiae, significant increases in the membrane oleic acid content were observed. OLE1-overexpressing strains displayed enhanced tolerance to various stresses, better proton efflux, lower membrane permeability, and lessened internal hydrogen peroxide content. The OLE1-mediated enhanced stress tolerance was considerably diminished upon deletion of HOG1, which encodes the mitogen-activated protein kinase (MAPK) Hog1 of the high osmolarity glycerol (HOG) pathway. Furthermore, OLE1 overexpression constitutively activated Hog1, which remained in the cytoplasm. Hog1 activation was accomplished through the MAPK kinase kinase (MAPKKK) Ssk2, but not Ste11 and Ssk22, the other MAPKKKs of the HOG pathway. Despite its cytoplasmic location, activated Hog1 was able to activate the expression of its canonical targets, including CTT1, HSP12, and STL1, and further, the cAMP and stress response elements present in the promoter. OLE1 overexpression neither caused nor relieved endoplasmic reticulum stress. Individually or in combination, the physiological and molecular changes caused by OLE1 overexpression may contribute to enhanced tolerance to various types of stress. Biotechnol. Bioeng. 2017;114: 620-631. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Constitutive Activation of NF-kappaB in Prostate Carcinoma Cells Through a Positive Feedback Loop: Implication of Inducible IKK-Related Kinase (IKKi)

    National Research Council Canada - National Science Library

    Budunova, Irina V

    2004-01-01

    The overall goal of this project is to understand the role of inducible IKK-related kinase IKKi in constitutive activation of anti-apoptotic transcription factor NF-kB prostate carcinoma (PC) cells...

  5. Constitutive Activation of NF-KB in Prostate Carcinoma Cells Through a Positive Feedback Loop: Implication of Inducible IKK-Related Kinase (IKKi)

    National Research Council Canada - National Science Library

    Budunova, Irina V

    2005-01-01

    The overall goal of this project is to understand the role of inducible IKK-related kinase IKKi in constitutive activation of anti-apoptotic transcription factor NF-KB prostate carcinoma (PC) cells...

  6. Functional characterization of human RSK4, a new 90-kDa ribosomal S6 kinase, reveals constitutive activation in most cell types

    DEFF Research Database (Denmark)

    Dümmler, Bettina A; Hauge, Camilla; Silber, Joachim

    2005-01-01

    characterization of a predicted new human RSK homologue, RSK4. We showed that RSK4 is a predominantly cytosolic protein with very low expression and several characteristics of the RSK family kinases, including the presence of two functional kinase domains and a C-terminal docking site for ERK. Surprisingly......, however, in all cell types analyzed, endogenous RSK4 was maximally (constitutively) activated under serum-starved conditions where other RSKs are inactive due to their requirement for growth factor stimulation. Constitutive activation appeared to result from constitutive phosphorylation of Ser232, Ser372...

  7. The Precedent 443 of the Superior Labor Court and Judicial Activism: The Defense of a Non Selective Constitutional Hermeneutics

    Directory of Open Access Journals (Sweden)

    Humberto Lima de Lucena Filho

    2015-12-01

    Full Text Available This paper is dedicated to the analysis of the Precedent 443 of the Superior Labor Court, which deals with the discriminatory dismissal presumption of those labor with social stigma diseases from the perspective of judicial activism in the brazilian labor law and its objective influence on law and labor procedure law from the from the perspective of a not univocal constitutional hermeneutics. It aims, also, to conceptualize the stability institute in order to configure the dangers and misconceptions arising from it. Therefore, it concludes that the analogy that embodied the repeated judicial position was excessive. The research points out the logical-deductive method operated by the aid of the literature review, case law and positioning applicable law.

  8. Identification and Characterization of CINPA1 Metabolites Facilitates Structure-Activity Studies of the Constitutive Androstane Receptor

    Science.gov (United States)

    Cherian, Milu T.; Yang, Lei; Chai, Sergio C.; Lin, Wenwei

    2016-01-01

    The constitutive androstane receptor (CAR) regulates the expression of genes involved in drug metabolism and other processes. A specific inhibitor of CAR is critical for modulating constitutive CAR activity. We recently described a specific small-molecule inhibitor of CAR, CINPA1 (ethyl (5-(diethylglycyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)carbamate), which is capable of reducing CAR-mediated transcription by changing the coregulator recruitment pattern and reducing CAR occupancy at the promoter regions of its target genes. In this study, we showed that CINPA1 is converted to two main metabolites in human liver microsomes. By using cell-based reporter gene and biochemical coregulator recruitment assays, we showed that although metabolite 1 was very weak in inhibiting CAR function and disrupting CAR-coactivator interaction, metabolite 2 was inactive in this regard. Docking studies using the CAR ligand-binding domain structure showed that although CINPA1 and metabolite 1 can bind in the CAR ligand-binding pocket, metabolite 2 may be incapable of the molecular interactions required for binding. These results indicate that the metabolites of CINPA1 may not interfere with the action of CINPA1. We also used in vitro enzyme assays to identify the cytochrome P450 enzymes responsible for metabolizing CINPA1 in human liver microsomes and showed that CINPA1 was first converted to metabolite 1 by CYP3A4 and then further metabolized by CYP2D6 to metabolite 2. Identification and characterization of the metabolites of CINPA1 enabled structure-activity relationship studies of this family of small molecules and provided information to guide in vivo pharmacological studies. PMID:27519550

  9. Identification and Characterization of CINPA1 Metabolites Facilitates Structure-Activity Studies of the Constitutive Androstane Receptor.

    Science.gov (United States)

    Cherian, Milu T; Yang, Lei; Chai, Sergio C; Lin, Wenwei; Chen, Taosheng

    2016-11-01

    The constitutive androstane receptor (CAR) regulates the expression of genes involved in drug metabolism and other processes. A specific inhibitor of CAR is critical for modulating constitutive CAR activity. We recently described a specific small-molecule inhibitor of CAR, CINPA1 (ethyl (5-(diethylglycyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)carbamate), which is capable of reducing CAR-mediated transcription by changing the coregulator recruitment pattern and reducing CAR occupancy at the promoter regions of its target genes. In this study, we showed that CINPA1 is converted to two main metabolites in human liver microsomes. By using cell-based reporter gene and biochemical coregulator recruitment assays, we showed that although metabolite 1 was very weak in inhibiting CAR function and disrupting CAR-coactivator interaction, metabolite 2 was inactive in this regard. Docking studies using the CAR ligand-binding domain structure showed that although CINPA1 and metabolite 1 can bind in the CAR ligand-binding pocket, metabolite 2 may be incapable of the molecular interactions required for binding. These results indicate that the metabolites of CINPA1 may not interfere with the action of CINPA1. We also used in vitro enzyme assays to identify the cytochrome P450 enzymes responsible for metabolizing CINPA1 in human liver microsomes and showed that CINPA1 was first converted to metabolite 1 by CYP3A4 and then further metabolized by CYP2D6 to metabolite 2. Identification and characterization of the metabolites of CINPA1 enabled structure-activity relationship studies of this family of small molecules and provided information to guide in vivo pharmacological studies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Generation of Trichoderma atroviride mutants with constitutively activated G protein signaling by using geneticin resistance as selection marker

    Directory of Open Access Journals (Sweden)

    Gruber Sabine

    2012-11-01

    Full Text Available Abstract Background Species of the fungal genus Trichoderma are important industrial producers of cellulases and hemicellulases, but also widely used as biocontrol agents (BCAs in agriculture. In the latter function Trichoderma species stimulate plant growth, induce plant defense and directly antagonize plant pathogenic fungi through their mycoparasitic capabilities. The recent release of the genome sequences of four mycoparasitic Trichoderma species now forms the basis for large-scale genetic manipulations of these important BCAs. Thus far, only a limited number of dominant selection markers, including Hygromycin B resistance (hph and the acetamidase-encoding amdS gene, have been available for transformation of Trichoderma spp. For more extensive functional genomics studies the utilization of additional dominant markers will be essential. Results We established the Escherichia coli neomycin phosphotransferase II-encoding nptII gene as a novel selectable marker for the transformation of Trichoderma atroviride conferring geneticin resistance. The nptII marker cassette was stably integrated into the fungal genome and transformants exhibited unaltered phenotypes compared to the wild-type. Co-transformation of T. atroviride with nptII and a constitutively activated version of the Gα subunit-encoding tga3 gene (tga3Q207L resulted in a high number of mitotically stable, geneticin-resistant transformants. Further analyses revealed a co-transformation frequency of 68% with 15 transformants having additionally integrated tga3Q207L into their genome. Constitutive activation of the Tga3-mediated signaling pathway resulted in increased vegetative growth and an enhanced ability to antagonize plant pathogenic host fungi. Conclusion The neomycin phosphotransferase II-encoding nptII gene from Escherichia coli proved to be a valuable tool for conferring geneticin resistance to the filamentous fungus T. atroviride thereby contributing to an enhanced genetic

  11. Expression of a constitutively activated plasma membrane H+-ATPase in Nicotiana tabacum BY-2 cells results in cell expansion.

    Science.gov (United States)

    Niczyj, Marta; Champagne, Antoine; Alam, Iftekhar; Nader, Joseph; Boutry, Marc

    2016-11-01

    Increased acidification of the external medium by an activated H + -ATPase results in cell expansion, in the absence of upstream activating signaling. The plasma membrane H + -ATPase couples ATP hydrolysis with proton transport outside the cell, and thus creates an electrochemical gradient, which energizes secondary transporters. According to the acid growth theory, this enzyme is also proposed to play a major role in cell expansion, by acidifying the external medium and so activating enzymes that are involved in cell wall-loosening. However, this theory is still debated. To challenge it, we made use of a plasma membrane H + -ATPase isoform from Nicotiana plumbaginifolia truncated from its C-terminal auto-inhibitory domain (ΔCPMA4), and thus constitutively activated. This protein was expressed in Nicotiana tabacum BY-2 suspension cells using a heat shock inducible promoter. The characterization of several independent transgenic lines showed that the expression of activated ΔCPMA4 resulted in a reduced external pH by 0.3-1.2 units, as well as in an increased H + -ATPase activity by 77-155 % (ATP hydrolysis), or 70-306 % (proton pumping) of isolated plasma membranes. In addition, ΔCPMA4-expressing cells were 17-57 % larger than the wild-type cells and displayed abnormal shapes. A proteomic comparison of plasma membranes isolated from ΔCPMA4-expressing and wild-type cells revealed the altered abundance of several proteins involved in cell wall synthesis, transport, and signal transduction. In conclusion, the data obtained in this work showed that H + -ATPase activation is sufficient to induce cell expansion and identified possible actors which intervene in this process.

  12. Curcumin Modulates the Radiosensitivity of Colorectal Cancer Cells by Suppressing Constitutive and Inducible NF-κB Activity

    International Nuclear Information System (INIS)

    Sandur, Santosh K.; Deorukhkar, Amit; Pandey, Manoj K.; Pabon, Ana Maria B.S.; Shentu, Shujun; Guha, Sushovan; Aggarwal, Bharat B.; Krishnan, Sunil

    2009-01-01

    Purpose: Radiation therapy is an integral part of the preoperative treatment of rectal cancers. However, only a minority of patients achieve a complete pathologic response to therapy because of resistance of these tumors to radiation therapy. This resistance may be mediated by constitutively active pro-survival signaling pathways or by inducible/acquired mechanisms in response to radiation therapy. Simultaneous inhibition of these pathways can sensitize these tumors to radiation therapy. Methods and Materials: Human colorectal cancer cells were exposed to clinically relevant doses of gamma rays, and the mechanism of their radioresistance was investigated. We characterized the transcription factor nuclear factor-κB (NF-κB) activation as a mechanism of inducible radioresistance in colorectal cancer and used curcumin, the active ingredient in the yellow spice turmeric, to overcome this resistance. Results: Curcumin inhibited the proliferation and the post-irradiation clonogenic survival of multiple colorectal cancer cell lines. Radiation stimulated NF-κB activity in a dose- and time-dependent manner, whereas curcumin suppressed this radiation-induced NF-κB activation via inhibition of radiation-induced phosphorylation and degradation of inhibitor of κB alpha, inhibition of inhibitor of κB kinase activity, and inhibition of Akt phosphorylation. Curcumin also suppressed NF-κB-regulated gene products (Bcl-2, Bcl-x L , inhibitor of apoptosis protein-2, cyclooxygenase-2, and cyclin D1). Conclusions: Our results suggest that transient inducible NF-κB activation provides a prosurvival response to radiation that may account for development of radioresistance. Curcumin blocks this signaling pathway and potentiates the antitumor effects of radiation therapy.

  13. Vestigialization of an allosteric switch: genetic and structural mechanisms for the evolution of constitutive activity in a steroid hormone receptor.

    Directory of Open Access Journals (Sweden)

    Jamie T Bridgham

    2014-01-01

    Full Text Available An important goal in molecular evolution is to understand the genetic and physical mechanisms by which protein functions evolve and, in turn, to characterize how a protein's physical architecture influences its evolution. Here we dissect the mechanisms for an evolutionary shift in function in the mollusk ortholog of the steroid hormone receptors (SRs, a family of biologically essential transcription factors. In vertebrates, the activity of SRs allosterically depends on binding a hormonal ligand; in mollusks, however, the SR ortholog (called ER, because of high sequence similarity to vertebrate estrogen receptors activates transcription in the absence of ligand and does not respond to steroid hormones. To understand how this shift in regulation evolved, we combined evolutionary, structural, and functional analyses. We first determined the X-ray crystal structure of the ER of the Pacific oyster Crassostrea gigas (CgER, and found that its ligand pocket is filled with bulky residues that prevent ligand occupancy. To understand the genetic basis for the evolution of mollusk ERs' unique functions, we resurrected an ancient SR progenitor and characterized the effect of historical amino acid replacements on its functions. We found that reintroducing just two ancient replacements from the lineage leading to mollusk ERs recapitulates the evolution of full constitutive activity and the loss of ligand activation. These substitutions stabilize interactions among key helices, causing the allosteric switch to become "stuck" in the active conformation and making activation independent of ligand binding. Subsequent changes filled the ligand pocket without further affecting activity; by degrading the allosteric switch, these substitutions vestigialized elements of the protein's architecture required for ligand regulation and made reversal to the ancestral function more complex. These findings show how the physical architecture of allostery enabled a few large

  14. Vestigialization of an Allosteric Switch: Genetic and Structural Mechanisms for the Evolution of Constitutive Activity in a Steroid Hormone Receptor

    Science.gov (United States)

    Bridgham, Jamie T.; Keay, June; Ortlund, Eric A.; Thornton, Joseph W.

    2014-01-01

    An important goal in molecular evolution is to understand the genetic and physical mechanisms by which protein functions evolve and, in turn, to characterize how a protein's physical architecture influences its evolution. Here we dissect the mechanisms for an evolutionary shift in function in the mollusk ortholog of the steroid hormone receptors (SRs), a family of biologically essential transcription factors. In vertebrates, the activity of SRs allosterically depends on binding a hormonal ligand; in mollusks, however, the SR ortholog (called ER, because of high sequence similarity to vertebrate estrogen receptors) activates transcription in the absence of ligand and does not respond to steroid hormones. To understand how this shift in regulation evolved, we combined evolutionary, structural, and functional analyses. We first determined the X-ray crystal structure of the ER of the Pacific oyster Crassostrea gigas (CgER), and found that its ligand pocket is filled with bulky residues that prevent ligand occupancy. To understand the genetic basis for the evolution of mollusk ERs' unique functions, we resurrected an ancient SR progenitor and characterized the effect of historical amino acid replacements on its functions. We found that reintroducing just two ancient replacements from the lineage leading to mollusk ERs recapitulates the evolution of full constitutive activity and the loss of ligand activation. These substitutions stabilize interactions among key helices, causing the allosteric switch to become “stuck” in the active conformation and making activation independent of ligand binding. Subsequent changes filled the ligand pocket without further affecting activity; by degrading the allosteric switch, these substitutions vestigialized elements of the protein's architecture required for ligand regulation and made reversal to the ancestral function more complex. These findings show how the physical architecture of allostery enabled a few large-effect mutations

  15. Constitutive phosphorylation of ATM in lymphoblastoid cell lines from patients with ICF syndrome without downstream kinase activity.

    Science.gov (United States)

    Goldstine, Jimena V; Nahas, Shareef; Gamo, Kristin; Gartler, Stanley M; Hansen, R Scott; Roelfsema, Jeroen H; Gatti, Richard A; Marahrens, York

    2006-04-08

    Double strand DNA breaks in the genome lead to the activation of the ataxia-telangiectasia mutated (ATM) kinase in a process that requires ATM autophosphorylation at serine-1981. ATM autophosphorylation only occurs if ATM is previously acetylated by Tip60. The activated ATM kinase phosphorylates proteins involved in arresting the cell cycle, including p53, and in repairing the DNA breaks. Chloroquine treatment and other manipulations that produce chromatin defects in the absence of detectable double strand breaks also trigger ATM phosphorylation and the phosphorylation of p53 in primary human fibroblasts, while other downstream substrates of ATM that are involved in the repair of DNA double strand breaks remain unphosphorylated. This raises the issue of whether ATM is constitutively activated in patients with genetic diseases that display chromatin defects. We examined lymphoblastoid cell lines (LCLs) generated from patients with different types of chromatin disorders: Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome, Coffin Lowry syndrome, Rubinstein Taybi syndrome and Fascioscapulohumeral Muscular Dystrophy. We show that ATM is phosphorylated on serine-1981 in LCLs derived from ICF patients but not from the other syndromes. The phosphorylated ATM in ICF cells did not phosphorylate the downstream targets NBS1, SMC1 and H2AX, all of which require the presence of double strand breaks. We demonstrate that ICF cells respond normally to ionizing radiation, ruling out the possibility that genetic deficiency in ICF cells renders activated ATM incapable of phosphorylating its downstream substrates. Surprisingly, p53 was also not phosphorylated in ICF cells or in chloroquine-treated wild type LCLs. In this regard the response to chromatin-altering agents differs between primary fibroblasts and LCLs. Our findings indicate that although phosphorylation at serine-1981 is essential in the activation of the ATM kinase, serine-1981 phosphorylation is

  16. Increased skin barrier disruption by sodium lauryl sulfate in mice expressing a constitutively active STAT6 in T cells.

    Science.gov (United States)

    DaSilva, Sonia C; Sahu, Ravi P; Konger, Raymond L; Perkins, Susan M; Kaplan, Mark H; Travers, Jeffrey B

    2012-01-01

    Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease that affects 10-20% of children and 1-3% of adults worldwide. Recent studies have indicated that the ability of Th2 cytokines, such as interleukin-4 (IL-4) to regulate skin barrier function may be a predisposing factor for AD development. The present studies examined the ability of increased Th2 activity to affect cutaneous barrier function in vivo and epidermal thickening. Mice that express a constitutively active Signal Transducer and Activator of Transcription 6 (STAT6VT) have increased Th2 cells and a predisposition to allergic inflammation were used in these studies, they demonstrate that topical treatment with the irritant sodium lauryl sulfate (SLS) caused increased transepidermal water loss and epidermal thickening in STAT6VT mice over similarly treated wild-type mice. The proliferation marker Ki-67 was increased in the epidermis of STAT6VT compared to the wild-type mice. However, these differences do not appear to be linked to the addition of an irritant as control-treated STAT6VT skin also exhibited elevated Ki-67 levels, suggesting that the increased epidermal thickness in SLS-treated STAT6VT mice is primarily driven by epidermal cell hypertrophy rather than an increase in cellular proliferation. Our results suggest that an environment with increased Th2 cytokines results in abnormal responses to topical irritants.

  17. Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors.

    Directory of Open Access Journals (Sweden)

    Sachin Gupta

    Full Text Available Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG, including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (ΔLMP1. Supernatant from ΔLMP1-MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from ΔLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of ΔLMP1-MAVS-transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, ΔLMP1-MAVS markedly enhanced secretion of IFN-β and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5 expressing ΔLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-ΔLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ΔLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration.

  18. High constitutive activity of a virus-encoded seven transmembrane receptor in the absence of the conserved DRY motif (Asp-Arg-Tyr) in transmembrane helix 3

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Kledal, Thomas N; Schwartz, Thue W

    2005-01-01

    -driven transcriptional activity through a pertussis toxin-sensitive manner. Gs and Gq were not activated constitutively as determined by the lack of inositol phosphate turnover and activities of the three transcription factors: cAMP response element-binding protein (CREB), nuclear factor-kappaB, and nuclear factor...

  19. Hadoop MapReduce v2 cookbook

    CERN Document Server

    Gunarathne, Thilina

    2015-01-01

    If you are a Big Data enthusiast and wish to use Hadoop v2 to solve your problems, then this book is for you. This book is for Java programmers with little to moderate knowledge of Hadoop MapReduce. This is also a one-stop reference for developers and system admins who want to quickly get up to speed with using Hadoop v2. It would be helpful to have a basic knowledge of software development using Java and a basic working knowledge of Linux.

  20. Polycrystalline V2O5/Na0.33V2O5 electrode material for Li+ ion redox supercapacitor

    International Nuclear Information System (INIS)

    Manikandan, Ramu; Justin Raj, C.; Rajesh, Murugesan; Kim, Byung Chul; Park, Sang Yeup; Cho, Bo-Bae; Yu, Kook Hyun

    2017-01-01

    Highlights: • Different polycrystalline V 2 O 5 /Na 0.33 V 2 O 5 nanostructures were synthesized via simple co-precipitation technique. • The various molar ratios of NaOH precipitator determine the morphology, structural and electrochemical properties of V/Na. • The equimolar ratio of reactant and precipitator shows the formation of ∼96% of pure crystalline phase of V 2 O 5 . • Li + ions intercalation and deintercalation process enhanced the specific capacitance. - Abstract: This work essentially offers a new kind of V 2 O 5 /Na 0.33 V 2 O 5 as electrochemical active material for the development of Li + ion redox supercapacitors. Here, polycrystalline mixed phase of V 2 O 5 /Na 0.33 V 2 O 5 (V/Na) nanostructures are synthesized via simple co-precipitation technique. The various molar ratio of precipitator (NaOH) in the synthesis process displays different nanostructures of V/Na. The structural and morphological properties of V/Na samples are studied using physico-chemical analysis methods. The electrochemical properties of V/Na nanostructured samples are performed using cyclic voltammetry, galvanostatic charge/discharge test and electrochemical impedance spectroscopy techniques in 1 M LiClO 4 aqueous electrolyte. The sample V/Na synthesized using equimolar ratio of vanadium salt and precipitator displayed nanopellet morphology, which exhibited the highest capacitance value of 334 Fg −1 at 1 Ag −1 discharge current density. Moreover, these polycrystalline V/Na nanostructured electrodes show excellent electrochemical properties with comparable stability after 1000 charge/discharge cycles.

  1. Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lynch, Caitlin; Pan, Yongmei; Li, Linhao [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Heyward, Scott; Moeller, Timothy [Bioreclamation In Vitro Technologies, Baltimore, MD 21227 (United States); Swaan, Peter W. [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Wang, Hongbing, E-mail: hwang@rx.umaryland.edu [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States)

    2014-08-15

    Objective: Accumulating evidence suggests that activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fatty acid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. The present study aims to investigate the effects of selective hCAR activators on hepatic energy metabolism in human primary hepatocytes (HPH). Methods: Ligand-based structure–activity models were used for virtual screening of the Specs database ( (www.specs.net)) followed by biological validation in cell-based luciferase assays. The effects of two novel hCAR activators (UM104 and UM145) on hepatic energy metabolism were evaluated in HPH. Results: Real-time PCR and Western blotting analyses reveal that activation of hCAR by UM104 and UM145 significantly repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible effects on the expression of genes associated with lipogenesis and fatty acid synthesis. Functional experiments show that UM104 and UM145 markedly inhibit hepatic synthesis of glucose but not triglycerides in HPH. In contrast, activation of mCAR by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a selective mCAR activator, repressed the expression of genes associated with gluconeogenesis, lipogenesis, and fatty acid synthesis in mouse primary hepatocytes, which were consistent with previous observations in mouse model in vivo. Conclusion: Our findings uncover an important species difference between hCAR and mCAR in hepatic energy metabolism, where hCAR selectively inhibits gluconeogenesis without suppressing fatty acid synthesis. Implications: Such species selectivity should be considered when exploring CAR as a potential therapeutic target for metabolic disorders. - Highlights: • Novel hCAR activators were identified by computational and biological approaches. • The role

  2. Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes

    International Nuclear Information System (INIS)

    Lynch, Caitlin; Pan, Yongmei; Li, Linhao; Heyward, Scott; Moeller, Timothy; Swaan, Peter W.; Wang, Hongbing

    2014-01-01

    Objective: Accumulating evidence suggests that activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fatty acid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. The present study aims to investigate the effects of selective hCAR activators on hepatic energy metabolism in human primary hepatocytes (HPH). Methods: Ligand-based structure–activity models were used for virtual screening of the Specs database ( (www.specs.net)) followed by biological validation in cell-based luciferase assays. The effects of two novel hCAR activators (UM104 and UM145) on hepatic energy metabolism were evaluated in HPH. Results: Real-time PCR and Western blotting analyses reveal that activation of hCAR by UM104 and UM145 significantly repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible effects on the expression of genes associated with lipogenesis and fatty acid synthesis. Functional experiments show that UM104 and UM145 markedly inhibit hepatic synthesis of glucose but not triglycerides in HPH. In contrast, activation of mCAR by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a selective mCAR activator, repressed the expression of genes associated with gluconeogenesis, lipogenesis, and fatty acid synthesis in mouse primary hepatocytes, which were consistent with previous observations in mouse model in vivo. Conclusion: Our findings uncover an important species difference between hCAR and mCAR in hepatic energy metabolism, where hCAR selectively inhibits gluconeogenesis without suppressing fatty acid synthesis. Implications: Such species selectivity should be considered when exploring CAR as a potential therapeutic target for metabolic disorders. - Highlights: • Novel hCAR activators were identified by computational and biological approaches. • The role

  3. Sensing Traffic Density Combining V2V and V2I Wireless Communications

    Directory of Open Access Journals (Sweden)

    Julio A. Sanguesa

    2015-12-01

    Full Text Available Wireless technologies are making the development of new applications and services in vehicular environments possible since they enable mobile communication between vehicles (V2V, as well as communication between vehicles and infrastructure nodes (V2I. Usually, V2V communications are dedicated to the transmission of small messages mainly focused on improving traffic safety. Instead, V2I communications allow users to access the Internet and benefit from higher level applications. The combination of both V2V and V2I, known as V2X communications, can increase the benefits even further, thereby making intelligent transportation systems (ITS a reality. In this paper, we introduce V2X-d, a novel architecture specially designed to estimate traffic density on the road. In particular, V2X-d exploits the combination of V2V and V2I communications. Our approach is based on the information gathered by sensors (i.e., vehicles and road side units (RSUs and the characteristics of the roadmap topology to accurately make an estimation of the instant vehicle density. The combination of both mechanisms improves the accuracy and coverage area of the data gathered, while increasing the robustness and fault tolerance of the overall approach, e.g., using the information offered by V2V communications to provide additional density information in areas where RSUs are scarce or malfunctioning. By using our collaborative sensing scheme, future ITS solutions will be able to establish adequate dissemination protocols or to apply more efficient traffic congestion reduction policies, since they will be aware of the instantaneous density of vehicles.

  4. Sensing Traffic Density Combining V2V and V2I Wireless Communications.

    Science.gov (United States)

    Sanguesa, Julio A; Barrachina, Javier; Fogue, Manuel; Garrido, Piedad; Martinez, Francisco J; Cano, Juan-Carlos; Calafate, Carlos T; Manzoni, Pietro

    2015-12-16

    Wireless technologies are making the development of new applications and services in vehicular environments possible since they enable mobile communication between vehicles (V2V), as well as communication between vehicles and infrastructure nodes (V2I). Usually, V2V communications are dedicated to the transmission of small messages mainly focused on improving traffic safety. Instead, V2I communications allow users to access the Internet and benefit from higher level applications. The combination of both V2V and V2I, known as V2X communications, can increase the benefits even further, thereby making intelligent transportation systems (ITS) a reality. In this paper, we introduce V2X-d, a novel architecture specially designed to estimate traffic density on the road. In particular, V2X-d exploits the combination of V2V and V2I communications. Our approach is based on the information gathered by sensors (i.e., vehicles and road side units (RSUs)) and the characteristics of the roadmap topology to accurately make an estimation of the instant vehicle density. The combination of both mechanisms improves the accuracy and coverage area of the data gathered, while increasing the robustness and fault tolerance of the overall approach, e.g., using the information offered by V2V communications to provide additional density information in areas where RSUs are scarce or malfunctioning. By using our collaborative sensing scheme, future ITS solutions will be able to establish adequate dissemination protocols or to apply more efficient traffic congestion reduction policies, since they will be aware of the instantaneous density of vehicles.

  5. Desensitization of menthol-activated cold receptors in lower extremities during local cooling in young women with a cold constitution.

    Science.gov (United States)

    Yamazaki, Fumio; Sone, Ryoko

    2017-03-01

    To test the hypothesis that topical menthol-induced reactivity of cold sensation and cutaneous vasoconstriction to local cooling is augmented in individuals with a cold constitution, we examined thermal sensation and cutaneous vasoconstrictor responses at menthol-treated and untreated sites in the legs during local skin cooling in young women complaining of chilliness (C group) and young women with no complaint as a normal control group (N group). During local skin cooling, the sensitivity to cold sensation was greater in the C group than in the N group. The application of menthol enhanced the cold sensation at a low temperature in the N group, but not in the C group. Cutaneous vasoconstrictor responses to local skin cooling were not altered by menthol treatment in either of the two groups. These findings suggest the desensitization of menthol-activated cold receptors in the legs of C group subjects, and a minor role of cold receptor activity in cutaneous vasoconstrictor response to local cooling.

  6. Constitutive androstane receptor upregulates Abcb1 and Abcg2 at the blood-brain barrier after CITCO activation.

    Science.gov (United States)

    Lemmen, Julia; Tozakidis, Iasson E P; Bele, Prachee; Galla, Hans-Joachim

    2013-03-21

    ATP-driven efflux transporters are considered to be the major hurdle in the treatment of central nervous system (CNS) diseases. Abcb1 (P-glycoprotein) and Abcg2 (breast cancer resistance protein/brain multidrug resistance protein) belong to the best known ABC-transporters. These ABC-transporters limit the permeability of the blood-brain barrier and protect the brain against toxic compounds in the blood but on the other hand they also reduce the efficacy of CNS pharmacotherapy. Even after 40 years of extensive research, the regulatory mechanisms of these efflux transporters are still not completely understood. To unravel the efflux transporter regulation, we analyzed the effect of the nuclear receptor CAR (constitutive androstane receptor) on the expression of Abcb1 and Abcg2 in primary cultures of porcine brain capillary endothelial cells (PBCEC). CAR is a xenobiotic-activated transcription factor, which is, like the other important nuclear receptor pregnane X receptor (PXR), highly expressed in barrier tissue and known to be a positive regulator of ABC-transporters. We demonstrate that activation of porcine CAR by the human CAR (hCAR) ligand CITCO (6-(4-chlorophenyl)-imidazo[2,1-b]thiazole-5-carbaldehyde) leads to an up-regulation of both transporters, whereas the mouse-specific CAR ligand TCPOBOP (1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene) had no effect on transporter expression. The stimulation of PBCEC with CITCO caused a significant up-regulation of both efflux-transporters on RNA-level, protein level and transport level. Furthermore the additional application of a CAR inhibitor significantly decreased the transporter expression to control niveau. In conclusion our data prove CAR activation only by the human ligand CITCO leading to an increased ABC-transporter expression and transport activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Constitutive STAT3-activation in Sezary syndrome: tyrphostin AG490 inhibits STAT3-activation, interleukin-2 receptor expression and growth of leukemic Sezary cells

    DEFF Research Database (Denmark)

    Eriksen, K W; Kaltoft, K; Mikkelsen, G

    2001-01-01

    are IL-2Ralpha negative. An aberrant expression of IL-2Ralpha has recently been described in cutaneous T-cell lymphoma (CTCL). Here, we study the regulation of IL-2Ralpha expression and STATs in a tumor cell line obtained from peripheral blood from a patient with Sezary syndrome (SS), a leukemic variant...... of CTCL. We show that (1) STAT3 (a transcription factor known to regulate IL-2Ralpha transcription) is constitutively tyrosine-phosphorylated in SS tumor cells, but not in non-malignant T cells; (2) STAT3 binds constitutively to a STAT-binding sequence in the promotor of the IL-2Ralpha gene; (3) the Janus...... kinase inhibitor, tyrphostine AG490, inhibits STAT3 activation, STAT3 DNA binding, and IL-2Ralpha mRNA and protein expression in parallel; and (4) tyrphostine AG490 inhibits IL-2 driven mitogenesis and triggers apoptosis in SS tumor cells. In conclusion, we provide the first example of a constitutive...

  8. The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Kee Hoon Sohn

    2014-10-01

    Full Text Available Plant nucleotide-binding leucine-rich repeat (NB-LRR disease resistance (R proteins recognize specific "avirulent" pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs. How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4 and RRS1 (resistance to Ralstonia solanacearum 1, function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NB-LRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1 mutant encodes an RRS1 allele (RRS1SLH1 with a single amino acid (leucine insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed

  9. Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2−/− Lung Fibroblasts

    Directory of Open Access Journals (Sweden)

    Mandar Dave

    2017-12-01

    Full Text Available The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF in lung fibroblasts derived from COX-2−/− but not wild-type (WT or COX-1−/− mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2−/− fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2−/− was “prostaglandin-independent.” GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2−/− cells. Furthermore, COX-2−/− fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

  10. The adhesion G protein-coupled receptor G2 (ADGRG2/GPR64) constitutively activates SRE and NFκB and is involved in cell adhesion and migration

    DEFF Research Database (Denmark)

    Cornelia Peeters, Miriam; Fokkelman, Michiel; Boogaard, Bob

    2015-01-01

    Adhesion G protein-coupled receptors (ADGRs) are believed to be activated by auto-proteolytic cleavage of their very large extracellular N-terminal domains normally acting as a negative regulator of the intrinsically constitutively active seven transmembrane domain. ADGRG2 (or GPR64) which...

  11. Development of a Systems Computational Model to Investigate Early Biological Events in Hepatic Activation of Constitutive Androstane Receptor (CAR) by Phenobarbital

    Science.gov (United States)

    Activation of the nuclear receptor CAR (constitutive active/androstane receptor) is implicated in the control several key biological events such as metabolic pathways. Here, we combined data from literature with information obtained from in vitro assays in the US EPA ToxCast dat...

  12. Structural motifs of importance for the constitutive activity of the orphan 7TM receptor EBI2: analysis of receptor activation in the absence of an agonist

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Rosenkilde, Mette M

    2008-01-01

    were identified by a systematic mutational analysis of 29 residues in EBI2. The cAMP response element-binding protein transcription factor was used as a measure of receptor activity and was correlated to the receptor surface expression. PheVI:13 (Phe257), and the neighboring CysVI:12 (Cys256......, but not to Lys, decreased the constitutive activity more than 7-fold compared with wt EBI2. IleIII:03 (Ile106) is located only 4 A from ArgII:20, and a favorable electrostatic interaction with ArgII:20 was created by introduction of Glu in III:03, given that the activity increased to 4.4-fold of that wt EBI2...

  13. SO2 and NO removal from flue gas over V2O5/AC at lower temperatures - role of V2O5 on SO2 removal

    International Nuclear Information System (INIS)

    Ma, Jianrong; Liu, Zhenyu; Liu, Qingya; Guo, Shijie; Huang, Zhanggen; Xiao, Yong

    2008-01-01

    Supporting V 2 O 5 onto an activated coke (AC) has been reported to significantly increase the AC's activity in simultaneous SO 2 and NO removal from flue gas. To understand the role of V 2 O 5 on SO 2 removal, V 2 O 5 /AC is studied through SO 2 removal reaction, surface analysis, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) techniques. It is found that the main role of V 2 O 5 in SO 2 removal over V 2 O 5 /AC is to catalyze SO 2 oxidation through a VOSO 4 -like intermediate species, which reacts with O 2 to form SO 3 and V 2 O 5 . The SO 3 formed transfers from the V sites to AC sites and then reacts with H 2 O to form H 2 SO 4 . At low V 2 O 5 loadings, a V atom is able to catalyze as many as 8 SO 2 molecules to SO 3 . At high V 2 O 5 loadings, however, the number of SO 2 molecules catalyzed by a V atom is much less, due possibly to excessive amounts of V 2 O 5 sites in comparison to the pores available for SO 3 and H 2 SO 4 storage. (author)

  14. The PLTEMP V2.1 code

    International Nuclear Information System (INIS)

    Olson, A.P.

    2003-01-01

    Recent improvements to the computer code PLTEMP/ANL V2.1 are described. A new iterative, error-minimization solution technique is used to obtain the thermal distribution both within each fuel plate, and along the axial length of each coolant channel. A new, radial geometry solution is available for tube-type fuel assemblies. Software comparisons of these and other new models are described. Applications to Russian-designed IRT-type research reactors are described. (author)

  15. Constitutive expression of TNF-related activation-induced cytokine (TRANCE/receptor activating NF-κB ligand (RANK-L by rat plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Thomas Anjubault

    Full Text Available Plasmacytoid dendritic cells (pDCs are a subset of DCs whose major function relies on their capacity to produce large amount of type I IFN upon stimulation via TLR 7 and 9. This function is evolutionary conserved and place pDC in critical position in the innate immune response to virus. Here we show that rat pDC constitutively express TNF-related activation-induced cytokine (TRANCE also known as Receptor-activating NF-κB ligand (RANKL. TRANCE/RANKL is a member of the TNF superfamily which plays a central role in osteoclastogenesis through its interaction with its receptor RANK. TRANCE/RANK interaction are also involved in lymphoid organogenesis as well as T cell/DC cross talk. Unlike conventional DC, rat CD4(high pDC were shown to constitutively express TRANCE/RANKL both at the mRNA and the surface protein level. TRANCE/RANKL was also induced on the CD4(low subsets of pDC following activation by CpG. The secreted form of TRANCE/RANKL was also produced by rat pDC. Of note, levels of mRNA, surface and secreted TRANCE/RANKL expression were similar to that observed for activated T cells. TRANCE/RANKL expression was found on pDC in all lymphoid organs as well blood and BM with a maximum expression in mesenteric lymph nodes. Despite this TRANCE/RANKL expression, we were unable to demonstrate in vitro osteoclastogenesis activity for rat pDC. Taken together, these data identifies pDC as novel source of TRANCE/RANKL in the immune system.

  16. Impairments in cognition and neural precursor cell proliferation in mice expressing constitutively active glycogen synthase kinase-3

    Directory of Open Access Journals (Sweden)

    Marta ePardo

    2015-03-01

    Full Text Available ABSTRACTBrain glycogen synthase kinase-3 (GSK3 is hyperactive in several neurological conditions that involve impairments in both cognition and neurogenesis. This raises the hypotheses that hyperactive GSK3 may directly contribute to impaired cognition, and that this may be related to deficiencies in neural precursor cells (NPC. To study the effects of hyperactive GSK3 in the absence of disease influences, we compared adult hippocampal NPC proliferation and performance in three cognitive tasks in male and female wild-type mice and GSK3 knockin mice, which express constitutively active GSK3. NPC proliferation was ~40% deficient in both male and female GSK3 knockin mice compared with wild-type mice. Environmental enrichment (EE increased NPC proliferation in male, but not female, GSK3 knockin mice and wild-type mice. Male and female GSK3 knockin mice exhibited impairments in novel object recognition, temporal order memory, and coordinate spatial processing compared with gender-matched wild-type mice. EE restored impaired novel object recognition and temporal ordering in both sexes of GSK3 knockin mice, indicating that this repair was not dependent on NPC proliferation, which was not increased by EE in female GSK3 knockin mice. Acute 1 hr pretreatment with the GSK3 inhibitor TDZD-8 also improved novel object recognition and temporal ordering in male and female GSK3 knockin mice. These findings demonstrate that hyperactive GSK3 is sufficient to impair adult hippocampal NPC proliferation and to impair performance in three cognitive tasks in both male and female mice, but these changes in NPC proliferation do not directly regulate novel object recognition and temporal ordering tasks.

  17. Constitutive Activation of the Fission Yeast Pheromone-Responsive Pathway Induces Ectopic Meiosis and Reveals Ste11 as a Mitogen-Activated Protein Kinase Target

    DEFF Research Database (Denmark)

    Kjærulff, Søren; Lautrup-Larsen, I.; Truelsen, S.

    2005-01-01

    In the fission yeast Schizosaccharomyces pombe, meiosis normally takes place in diploid zygotes resulting from conjugation of haploid cells. In the present study, we report that the expression of a constitutively activated version of the pheromone-responsive mitogen-activated protein kinase kinase...... found that haploid meiosis was dramatically reduced when Ste11 was mutated to mimic phosphorylation by Pat1. The mutation of two putative MAPK sites in Ste11 also dramatically reduced the level of haploid meiosis, suggesting that Ste11 is a direct target of Spk1. Supporting this, we show that Spk1 can...... interact physically with Ste11 and also phosphorylate the transcription factor in vitro. Finally, we demonstrate that ste11 is required for pheromone-induced G1 arrest. Interestingly, when we mutated Ste11 in the sites for Pat1 and Spk1 phosphorylation simultaneously, the cells could still arrest in G1...

  18. Cell-type specific expression of constitutively-active Rheb promotes regeneration of bulbospinal respiratory axons following cervical SCI.

    Science.gov (United States)

    Urban, Mark W; Ghosh, Biswarup; Strojny, Laura R; Block, Cole G; Blazejewski, Sara M; Wright, Megan C; Smith, George M; Lepore, Angelo C

    2018-05-01

    Damage to respiratory neural circuitry and consequent loss of diaphragm function is a major cause of morbidity and mortality in individuals suffering from traumatic cervical spinal cord injury (SCI). Repair of CNS axons after SCI remains a therapeutic challenge, despite current efforts. SCI disrupts inspiratory signals originating in the rostral ventral respiratory group (rVRG) of the medulla from their phrenic motor neuron (PhMN) targets, resulting in loss of diaphragm function. Using a rat model of cervical hemisection SCI, we aimed to restore rVRG-PhMN-diaphragm circuitry by stimulating regeneration of injured rVRG axons via targeted induction of Rheb (ras homolog enriched in brain), a signaling molecule that regulates neuronal-intrinsic axon growth potential. Following C2 hemisection, we performed intra-rVRG injection of an adeno-associated virus serotype-2 (AAV2) vector that drives expression of a constitutively-active form of Rheb (cRheb). rVRG neuron-specific cRheb expression robustly increased mTOR pathway activity within the transduced rVRG neuron population ipsilateral to the hemisection, as assessed by levels of phosphorylated ribosomal S6 kinase. By co-injecting our novel AAV2-mCherry/WGA anterograde/trans-synaptic axonal tracer into rVRG, we found that cRheb expression promoted regeneration of injured rVRG axons into the lesion site, while we observed no rVRG axon regrowth with AAV2-GFP control. AAV2-cRheb also significantly reduced rVRG axonal dieback within the intact spinal cord rostral to the lesion. However, cRheb expression did not promote any recovery of ipsilateral hemi-diaphragm function, as assessed by inspiratory electromyography (EMG) burst amplitudes. This lack of functional recovery was likely because regrowing rVRG fibers did not extend back into the caudal spinal cord to synaptically reinnervate PhMNs that we retrogradely-labeled with cholera toxin B from the ipsilateral hemi-diaphragm. Our findings demonstrate that enhancing neuronal

  19. Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes

    International Nuclear Information System (INIS)

    Smetanina, Mariya A.; Pakharukova, Mariya Y.; Kurinna, Svitlana M.; Dong, Bingning; Hernandez, Juan P.; Moore, David D.; Merkulova, Tatyana I.

    2011-01-01

    2'-3-dimethyl-4-aminoazobenzene (ortho-aminoazotoluene, OAT) is an azo dye and a rodent carcinogen that has been evaluated by the International Agency for Research on Cancer (IARC) as a possible (class 2B) human carcinogen. Its mechanism of action remains unclear. We examined the role of the xenobiotic receptor Constitutive Androstane Receptor (CAR, NR1I3) as a mediator of the effects of OAT. We found that OAT increases mouse CAR (mCAR) transactivation in a dose-dependent manner. This effect is specific because another closely related azo dye, 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB), did not activate mCAR. Real-time Q-PCR analysis in wild-type C57BL/6 mice revealed that OAT induces the hepatic mRNA expression of the following CAR target genes: Cyp2b10, Cyp2c29, Cyp3a11, Ugt1a1, Mrp4, Mrp2 and c-Myc. CAR-null (Car -/- ) mice showed no increased expression of these genes following OAT treatment, demonstrating that CAR is required for their OAT dependent induction. The OAT-induced CAR-dependent increase of Cyp2b10 and c-Myc expression was confirmed by Western blotting. Immunohistochemistry analysis of wild-type and Car -/- livers showed that OAT did not acutely induce hepatocyte proliferation, but at much later time points showed an unexpected CAR-dependent proliferative response. These studies demonstrate that mCAR is an OAT xenosensor, and indicate that at least some of the biological effects of this compound are mediated by this nuclear receptor. - Highlights: → The azo dye and mouse carcinogen OAT is a very effective mCAR activator. → OAT increases mCAR transactivation in a dose-dependent manner. → OAT CAR-dependently increases the expression of a specific subset of CAR target genes. → OAT induces an unexpectedly deferred, but CAR-dependent hepatocyte proliferation.

  20. The Arabidopsis mutant cev1 has constitutively active jasmonate and ethylene signal pathways and enhanced resistance to pathogens.

    Science.gov (United States)

    Ellis, C; Turner, J G

    2001-05-01

    Jasmonates (JAs) inhibit plant growth and induce plant defense responses. To define genes in the Arabidopsis JA signal pathway, we screened for mutants with constitutive expression of a luciferase reporter for the JA-responsive promoter from the vegetative storage protein gene VSP1. One mutant, named constitutive expression of VSP1 (cev1), produced plants that were smaller than wild type, had stunted roots with long root hairs, accumulated anthocyanin, had constitutive expression of the defense-related genes VSP1, VSP2, Thi2.1, PDF1.2, and CHI-B, and had enhanced resistance to powdery mildew diseases. Genetic evidence indicated that the cev1 phenotype required both COI1, an essential component of the JA signal pathway, and ETR1, which encodes the ethylene receptor. We conclude that cev1 stimulates both the JA and the ethylene signal pathways and that CEV1 regulates an early step in an Arabidopsis defense pathway.

  1. Auxin-activated NADH oxidase activity of soybean plasma membranes is distinct from the constitutive plasma membrane NADH oxidase and exhibits prion-like properties

    Science.gov (United States)

    Morre, D. James; Morre, Dorothy M.; Ternes, Philipp

    2003-01-01

    The hormone-stimulated and growth-related cell surface hydroquinone (NADH) oxidase activity of etiolated hypocotyls of soybeans oscillates with a period of about 24 min or 60 times per 24-h day. Plasma membranes of soybean hypocotyls contain two such NADH oxidase activities that have been resolved by purification on concanavalin A columns. One in the apparent molecular weight range of 14-17 kDa is stimulated by the auxin herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The other is larger and unaffected by 2,4-D. The 2,4-D-stimulated activity absolutely requires 2,4-D for activity and exhibits a period length of about 24 min. Also exhibiting 24-min oscillations is the rate of cell enlargement induced by the addition of 2,4-D or the natural auxin indole-3-acetic acid (IAA). Immediately following 2,4-D or IAA addition, a very complex pattern of oscillations is frequently observed. However, after several hours a dominant 24-min period emerges at the expense of the constitutive activity. A recruitment process analogous to that exhibited by prions is postulated to explain this behavior.

  2. Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia

    International Nuclear Information System (INIS)

    Rajasingh, Johnson; Raikwar, Himanshu P.; Muthian, Gladson; Johnson, Caroline; Bright, John J.

    2006-01-01

    Adult T cell leukemia is an aggressive and frequently fatal malignancy that expressess constitutively activated growth-signaling pathways in association with deregulated growth and resistance to apoptosis. Curcumin (diferuloylmethane) is a naturally occurring yellow pigment, isolated from the rhizomes of the plant Curcuma longa that has traditionally been used in the treatment of injury and inflammation. But the effect and mechanism of action of curcumin on T cell leukemia is not known. To investigate the antitumor activity of curcumin in T cell leukemia, we examined its effect on constitutive phosphorylation of JAK and STAT proteins, proliferation, and apoptosis in HTLV-I-transformed T cell lines. HTLV-I-transformed T cell leukemia lines, MT-2, HuT-102, and SLB-1, express constitutively phosphorylated JAK3, TYK2, STAT3, and STAT5 signaling proteins. In vitro treatment with curcumin induced a dose-dependent decrease in JAK and STAT phosphorylation resulting in the induction of growth-arrest and apoptosis in T cell leukemia. The induction of growth-arrest and apoptosis in association with the blockade of constitutively active JAK-STAT pathway suggests this be a mechanism by which curcumin induces antitumor activity in T cell leukemia

  3. The extracellular loop 2 (ECL2 of the human histamine H4 receptor substantially contributes to ligand binding and constitutive activity.

    Directory of Open Access Journals (Sweden)

    David Wifling

    Full Text Available In contrast to the corresponding mouse and rat orthologs, the human histamine H4 receptor (hH4R shows extraordinarily high constitutive activity. In the extracellular loop (ECL, replacement of F169 by V as in the mouse H4R significantly reduced constitutive activity. Stabilization of the inactive state was even more pronounced for a double mutant, in which, in addition to F169V, S179 in the ligand binding site was replaced by M. To study the role of the FF motif in ECL2, we generated the hH4R-F168A mutant. The receptor was co-expressed in Sf9 insect cells with the G-protein subunits Gαi2 and Gβ1γ2, and the membranes were studied in [3H]histamine binding and functional [35S]GTPγS assays. The potency of various ligands at the hH4R-F168A mutant decreased compared to the wild-type hH4R, for example by 30- and more than 100-fold in case of the H4R agonist UR-PI376 and histamine, respectively. The high constitutive activity of the hH4R was completely lost in the hH4R-F168A mutant, as reflected by neutral antagonism of thioperamide, a full inverse agonist at the wild-type hH4R. By analogy, JNJ7777120 was a partial inverse agonist at the hH4R, but a partial agonist at the hH4R-F168A mutant, again demonstrating the decrease in constitutive activity due to F168A mutation. Thus, F168 was proven to play a key role not only in ligand binding and potency, but also in the high constitutive activity of the hH4R.

  4. Neuronal responses in visual area V2 (V2) of macaque monkeys with strabismic amblyopia.

    Science.gov (United States)

    Bi, H; Zhang, B; Tao, X; Harwerth, R S; Smith, E L; Chino, Y M

    2011-09-01

    Amblyopia, a developmental disorder of spatial vision, is thought to result from a cascade of cortical deficits over several processing stages beginning at the primary visual cortex (V1). However, beyond V1, little is known about how cortical development limits the visual performance of amblyopic primates. We quantitatively analyzed the monocular and binocular responses of V1 and V2 neurons in a group of strabismic monkeys exhibiting varying depths of amblyopia. Unlike in V1, the relative effectiveness of the affected eye to drive V2 neurons was drastically reduced in the amblyopic monkeys. The spatial resolution and the orientation bias of V2, but not V1, neurons were subnormal for the affected eyes. Binocular suppression was robust in both cortical areas, and the magnitude of suppression in individual monkeys was correlated with the depth of their amblyopia. These results suggest that the reduced functional connections beyond V1 and the subnormal spatial filter properties of V2 neurons might have substantially limited the sensitivity of the amblyopic eyes and that interocular suppression was likely to have played a key role in the observed alterations of V2 responses and the emergence of amblyopia.

  5. TYLCV-Is movement in planta does not require V2 protein

    Energy Technology Data Exchange (ETDEWEB)

    Hak, Hagit [Institute of Plant Sciences, Agricultural Research Organization, The Volcani Center, Bet Dagan (Israel); Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem (Israel); Levy, Yael; Chandran, Sam A.; Belausov, Eduard [Institute of Plant Sciences, Agricultural Research Organization, The Volcani Center, Bet Dagan (Israel); Loyter, Abraham [Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem (Israel); Lapidot, Moshe [Institute of Plant Sciences, Agricultural Research Organization, The Volcani Center, Bet Dagan (Israel); Gafni, Yedidya, E-mail: ygafni@volcani.agri.gov.il [Institute of Plant Sciences, Agricultural Research Organization, The Volcani Center, Bet Dagan (Israel)

    2015-03-15

    Tomato yellow leaf curl virus (TYLCV), a major tomato pathogen causing extensive crop losses, is a whitefly-transmitted geminivirus. V2 mutants of TYLCV-Is and related viruses tend to induce symptomless infection with attenuated viral DNA levels, while accumulating close to wild-type DNA levels in protoplasts, suggesting V2 as a movement protein. The discovery of plant-silencing mechanisms and viral silencing suppressors, V2 included, led us to reconsider V2's involvement in viral movement. We studied two mutant versions of the virus, one impaired in V2 silencing-suppression activity, and another carrying a non-translatable V2. While both mutant viruses spread in the infected plant to newly emerged leaves at the same rate as the wild-type virus, their DNA-accumulation levels were tenfold lower than in the wild-type virus. Thus, we suggest that the setback in virus proliferation, previously ascribed to a movement impediment, is due to lack of silencing-suppression activity. - Highlights: • TYLCV-Is V2 protein is localized in distinct microbodies throughout the cell cytoplasm, around the nucleus and in association with cytoplasmic strands but is not associated with the plasmodesmata. • Disruption of RNA-silencing suppression activity of TYLCV-Is V2 protein causes low titer of the virus in the infected plants. • The movement of TYLCV-Is in planta does not require a functional V2 protein.

  6. Phase diagrams of systems of Sr2V2O7-M2V2O7 and of Ba2V2O7-M2V2O7 (M=Ca,Cd)

    International Nuclear Information System (INIS)

    Fotiev, A.A.; Zhuravlev, V.D.; Zhukov, V.P.

    1982-01-01

    Using the methods of X-ray phase and differential thermal anlyses phase equilibria in the systems Sr 2 V 2 O 7 -M 2 V 2 O 7 and Ba 2 V 2 O 7 -M 2 V 2 O 7 , where M--Ca, Cd, are studied, their phase diagrams being built. New double pyrovanadates Mosub(0.5)Srsub(1.5)Vsub(2)Osub(7) and MBaV 2 O 7 are found [ru

  7. The V-1 NPP and V-2 NPP upgrading

    International Nuclear Information System (INIS)

    1998-01-01

    A brief account of activities in the V-1 NPP and V-2 NPP upgrading as well as maintenance carried out by the Nuclear power plants Jaslovske Bohunice in 1997 is presented. The V-1 NPP applied the so called 'Small Backfitting Programme'covering 81 points of the Czechoslovak Atomic energy Commission Decree No 5/91. Continual upgrading continued after the Backfitting Programme completion with the Safety Report and following Nuclear Regulatory Authority of Slovak Republic (NRA SR) Decrees No 1/94 and 110/94 setting spheres and procedure for adopting and implementation of measures enabling the units to operate further on. Results of expert missions, analyses and assessments of components identified by Basic Engineering became the basis for the development of the Gradual Reconstruction Programme. The Programme outputs underwent economic and probabilistic assessing their contribution to nuclear safety. This process resulted in finalizing the Gradual Reconstruction Programme which started to be implemented in 1996 and will be completed in 1999. It is implemented by the REKON consortium and covers 17 areas including Instrumentation and Control, self-consumption emergency supply, leakage monitoring, emergency core cooling system, seismic reinforcement and radioactivity localisation. Both units will reach internationally acceptable safety standards for the remaining life-time period. The V-2 NPP Upgrading and Safety Enhancement Programme includes results of activities performed in the course of last years to define all important activities leading to enhancement of nuclear safety and performance reliability and effectiveness within the plant life-time period and to establish conditions for extending the life-time of these units for 40 years. The V-2 NPP Upgrading and Safety Enhancement Programme aims to assure safe operation with a probability of the core damages less than 10 -4 /reactor · year

  8. Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission

    Science.gov (United States)

    Naranjo, David; Wen, Hua; Brehm, Paul

    2015-01-01

    The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions. PMID:25650925

  9. Neuronal Responses in Visual Area V2 (V2) of Macaque Monkeys with Strabismic Amblyopia

    OpenAIRE

    Bi, H.; Zhang, B.; Tao, X.; Harwerth, R. S.; Smith, E. L.; Chino, Y. M.

    2011-01-01

    Amblyopia, a developmental disorder of spatial vision, is thought to result from a cascade of cortical deficits over several processing stages beginning at the primary visual cortex (V1). However, beyond V1, little is known about how cortical development limits the visual performance of amblyopic primates. We quantitatively analyzed the monocular and binocular responses of V1 and V2 neurons in a group of strabismic monkeys exhibiting varying depths of amblyopia. Unlike in V1, the relative eff...

  10. The Constitutional Amendment Process

    Science.gov (United States)

    Chism, Kahlil

    2005-01-01

    This article discusses the constitutional amendment process. Although the process is not described in great detail, Article V of the United States Constitution allows for and provides instruction on amending the Constitution. While the amendment process currently consists of six steps, the Constitution is nevertheless quite difficult to change.…

  11. Noisy Spiking in Visual Area V2 of Amblyopic Monkeys.

    Science.gov (United States)

    Wang, Ye; Zhang, Bin; Tao, Xiaofeng; Wensveen, Janice M; Smith, Earl L; Chino, Yuzo M

    2017-01-25

    Interocular decorrelation of input signals in developing visual cortex can cause impaired binocular vision and amblyopia. Although increased intrinsic noise is thought to be responsible for a range of perceptual deficits in amblyopic humans, the neural basis for the elevated perceptual noise in amblyopic primates is not known. Here, we tested the idea that perceptual noise is linked to the neuronal spiking noise (variability) resulting from developmental alterations in cortical circuitry. To assess spiking noise, we analyzed the contrast-dependent dynamics of spike counts and spiking irregularity by calculating the square of the coefficient of variation in interspike intervals (CV 2 ) and the trial-to-trial fluctuations in spiking, or mean matched Fano factor (m-FF) in visual area V2 of monkeys reared with chronic monocular defocus. In amblyopic neurons, the contrast versus response functions and the spike count dynamics exhibited significant deviations from comparable data for normal monkeys. The CV 2 was pronounced in amblyopic neurons for high-contrast stimuli and the m-FF was abnormally high in amblyopic neurons for low-contrast gratings. The spike count, CV 2 , and m-FF of spontaneous activity were also elevated in amblyopic neurons. These contrast-dependent spiking irregularities were correlated with the level of binocular suppression in these V2 neurons and with the severity of perceptual loss for individual monkeys. Our results suggest that the developmental alterations in normalization mechanisms resulting from early binocular suppression can explain much of these contrast-dependent spiking abnormalities in V2 neurons and the perceptual performance of our amblyopic monkeys. Amblyopia is a common developmental vision disorder in humans. Despite the extensive animal studies on how amblyopia emerges, we know surprisingly little about the neural basis of amblyopia in humans and nonhuman primates. Although the vision of amblyopic humans is often described as

  12. Constitutional Rights in Indonesia

    OpenAIRE

    Judhariksawan

    2018-01-01

    The constitution is fundamental to the life of the modern state as a major foothold in state governance. Includes the guarantee of constitutional rights of citizens. The The constitution is the basis of state organizers to be implemented so that the state is obliged to guarantee the fulfillment of citizens' constitutional rights. Human rights have become an important part of the modern constitution. This study will describe how human rights guarantees become part of consti...

  13. ITER EDA newsletter. V. 2, no. 2

    International Nuclear Information System (INIS)

    1993-02-01

    This issue of the ITER EDA (Engineering Design Activities) Newsletter contains a progress report by the Director, a report on the completion of the first activities of the Special Work Group 2 (SWG-2), a report on a magnet technical meeting, held at Naka, Japan, 26-29 January 1993, and on the US Home Team National Meeting, 25-26 January 1993

  14. ITER EDA Newsletter. V. 2, no. 1

    International Nuclear Information System (INIS)

    1993-01-01

    This ITER EDA (Engineering Design Activities) Newsletter issue is dedicated to the description of the ITER EDA Home Teams (European Community, Japan, Russian Federation, USA), in particular their composition, tasks, responsibilities, national support and activities, aimed to design the ITER tokamak

  15. The TLR4 D299G and T399I SNPs are constitutively active to up-regulate expression of Trif-dependent genes.

    Directory of Open Access Journals (Sweden)

    Georgina L Hold

    Full Text Available Dysregulated Toll-Like Receptor (TLR signalling and genetic polymorphisms in these proteins are linked to many human diseases. We investigated TLR4 functional variants D299G and T399I to assess the impact on LPS-induced responsiveness in comparison to wild-type TLR4. The mechanism by which this occurs in unclear as these SNPs do not lie within the lipid A binding domain or dimerisation sites of the LPS-TLR4/MD2 receptor complexes. Transfection of TLR4D299G, TLR4T399I or TLR4D299G. T399I into HEK cells resulted in constitutive activation of an NF-κB reporter gene and a blunting of the LPS-induced reporter activation compared to WT-TLR4. Unstimulated human monocyte/macrophages, from patients with the D299G and T399I SNPs demonstrated a downregulation of many genes, particularly Tram/Trif signalling pathway constitutents compared to the TLR4 wild-type subjects supporting the concept of basal receptor activity. Monocyte/macrophages from carriers of the TLR4 D299G and T399I polymorphisms stimulated with LPS showed >6 fold lower levels of NF-κB and ∼12 fold higher IFN-β gene expression levels compared to wild-type subjects (P<0.05; MWU test and dramatically altered resultant cytokine profiles. We conclude that these TLR4 SNPs affect constitutive receptor activity which impacts on the hosts ability to respond to LPS challenge leading to a dysregulated sub-optimal immune response to infection.

  16. Follow-up: Prospective compound design using the ‘SAR Matrix’ method and matrix-derived conditional probabilities of activity [v2; ref status: indexed, http://f1000r.es/59v

    Directory of Open Access Journals (Sweden)

    Disha Gupta-Ostermann

    2015-04-01

    Full Text Available In a previous Method Article, we have presented the ‘Structure-Activity Relationship (SAR Matrix’ (SARM approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these series and associated SAR information in matrices reminiscent of R-group tables. SARM calculations also yield many virtual candidate compounds that form a “chemical space envelope” around related series. To further extend the SARM approach, different methods are developed to predict the activity of virtual compounds. In this follow-up contribution, we describe an activity prediction method that derives conditional probabilities of activity from SARMs and report representative results of first prospective applications of this approach.

  17. ITER EDA newsletter. V. 2, no. 11

    International Nuclear Information System (INIS)

    1993-11-01

    This issue of the ITER EDA (Engineering Design Activities) Newsletter contains an ITER EDA Status Report, and a report on the Fourth International Fusion Neutronics Workshop at the University of California, Los Angeles Campus, October 20-21, 1993

  18. ITER EDA Newsletter. V. 2, no. 3

    International Nuclear Information System (INIS)

    1993-03-01

    This ITER EDA (Engineering Design Activities) Newsletter issue includes a description of the ITER Joint Central Team's management, the ITER Management System and supporting software progress, activities of the Special Working Group 2, a brief summary of a technical meeting on the experimental approach to the physics of the high density divertor, a summary on the status of the International Fusion Evaluated Nuclear Data Library (FENDL), and an obituary on Dr. Henry Seligman (IAEA)

  19. The net return from animal activity in agro-ecosystems: trading off benefits from ecosystem services against costs from crop damage [v2; ref status: indexed, http://f1000r.es/3c4

    Directory of Open Access Journals (Sweden)

    Gary W Luck

    2014-04-01

    Full Text Available Animals provide benefits to agriculture through the provision of ecosystem services, but also inflict costs such as damaging crops. These benefits and costs are mostly examined independently, rather than comparing the trade-offs of animal activity in the same system and quantifying the net return from beneficial minus detrimental activities. Here, I examine the net return associated with the activity of seed-eating birds in almond orchards by quantifying the economic costs and benefits of bird consumption of almonds. Pre-harvest, the consumption of harvestable almonds by birds cost growers AUD$57.50 ha-1 when averaged across the entire plantation. Post-harvest, the same bird species provide an ecosystem service by removing mummified nuts from trees that growers otherwise need to remove to reduce threats from fungal infection or insect pest infestations. The value of this ecosystem service ranged from AUD$82.50 ha-1–$332.50 ha-1 based on the replacement costs of mechanical or manual removal of mummified nuts, respectively. Hence, bird consumption of almonds yielded a positive net return of AUD$25–$275 ha-1 averaged across the entire plantation. However, bird activity varied spatially resulting in positive net returns occurring primarily at the edges of crops where activity was higher, compared to negative net returns in crop interiors. Moreover, partial mummy nut removal by birds meant that bird activity may only reduce costs to growers rather than replace these costs completely. Similar cost-benefit trade-offs exist across nature, and quantifying net returns can better inform land management decisions such as when to control pests or promote ecosystem service provision.

  20. Defective interleukin-4/Stat6 activity correlates with increased constitutive expression of negative regulators SOCS-3, SOCS-7, and CISH in colon cancer cells.

    Science.gov (United States)

    Liu, Xiao Hong; Xu, Shuang Bing; Yuan, Jia; Li, Ben Hui; Zhang, Yan; Yuan, Qin; Li, Pin Dong; Li, Feng; Zhang, Wen Jie

    2009-12-01

    Interleukin-4 (IL-4)-induced Stat6 activities (phenotypes) vary among human cancer cells, of which the HT-29 cell line carries an active Stat6(high) phenotype, while Caco-2 carries a defective Stat6(null) phenotype, respectively. Cancer cells with Stat6(high) show resistance to apoptosis and exaggerated metastasis, suggesting the clinical significance of Stat6 phenotypes. We previously showed that Stat6(high) HT-29 cells exhibited low constitutive expression of Stat6-negative regulators SOCS-1 and SHP-1 because of gene hypermethylation. This study further examined the constitutive expression of other closely related SOCS family numbers including SOCS-3, SOCS-5, SOCS-7, and CISH using RT-PCR. Similar to SOCS-1 and SHP-1, Stat6(high) HT-29 cells expressed low constitutive mRNA of SOCS-3, SOCS-7, and CISH than Stat6(null) Caco-2 cells. Interestingly, DNA demethylation using 5-aza-2'-deoxycytidine in HT-29 cells up-regulated mRNA expression of the above genes, indicating a hypermethylation status, which was confirmed by methylation-specific sequencing in selected SOCS-3 gene. Furthermore, defective Stat6(null) Caco-2 exhibited impaired phosphorylation of Stat6 after IL-4 stimulation by flow cytometry, in keeping with the notion of an over-performed negative regulation. The findings that IL-4/Stat6 phenotypes show differential expression of multiple negative regulators suggest a model that a collective force of powerful negative regulators, directly and indirectly, acts on Stat6 activation, which may result in differential Stat6 phenotypes.

  1. Increase of anthraquinone content in Rubia cordifolia cells transformed by native and constitutively active forms of the AtCPK1 gene.

    Science.gov (United States)

    Shkryl, Yury N; Veremeichik, G N; Makhazen, D S; Silantieva, S A; Mishchenko, N P; Vasileva, E A; Fedoreyev, S A; Bulgakov, V P

    2016-09-01

    Overexpression of both native and mutant forms of AtCPK1 in Rubia cordifolia cells increased anthraquinone production and transcript abundance of the RcIPPI, RcOSBL, RcOSBS , and RcICS genes to different extents. Calcium-dependent protein kinases (CDPKs) are involved in various cell processes and are regulated by a calcium signal system. CDPKs also function in plant defense against stress factors such as pathogens, temperature, and salinity. In this study, we compared the effect of heterologous expression of two forms of the Arabidopsis AtCPK1 gene, native and constitutively active (Ca(2+)-independent), on anthraquinone production in transgenic Rubia cordifolia cells. Significant qualitative and quantitative differences were found in the content of anthraquinone derivatives in control and AtCPK1-transgenic calli. Expression of the AtCPK1 gene increased anthraquinone production by 3 and 12 times for native and constitutively active forms, respectively, compared with control cells. In addition, we identified and quantified the expression of genes encoding key enzymes of the anthraquinone biosynthesis pathway, including isochorismate synthase (ICS), o-succinylbenzoate synthase (OSBS), o-succinylbenzoate ligase (OSBL), and isopentenyl diphosphate isomerase (IPPi). In all AtCPK1-transgenic cell lines, expression of ICS, OSBS, OSBL, and IPPi increased considerably at 14-15 days of subculture and decreased at the end of cultivation (30 days). The results suggest that both native and constitutively active AtCPK1 forms induced anthraquinone accumulation at the logarithmic growth stage via enhancement of expression of genes involved in the metabolism of anthraquinones or their regulatory mechanisms.

  2. ITER EDA Newsletter. V.2, no.6

    International Nuclear Information System (INIS)

    1993-06-01

    This issue of the newsletter on the Engineering Design Activities for the ITER Project includes (i) a status report on these activities describing the development of the design and design parameters, the research and development program, the joint central team, and the joint work sites; (ii) a description of the In-Vessel Ancillaries Division (consisting of the RF Heating and Current Drive Group and the In-Vessel Diagnostics Group) including its organizational chart and priorities of activities; (iii) a report on the Technical Meeting on Design Standards and Remote Handling held at the San Diego Co-Centre from May 24-28, 1993; (iv) and a report on a Technical Committee Meeting on Plasma Equilibrium and Control held at the Naka Co-Centre on April 26-29, 1993

  3. Identification of novel selective V2 receptor non-peptide agonists.

    Science.gov (United States)

    Del Tredici, Andria L; Vanover, Kim E; Knapp, Anne E; Bertozzi, Sine M; Nash, Norman R; Burstein, Ethan S; Lameh, Jelveh; Currier, Erika A; Davis, Robert E; Brann, Mark R; Mohell, Nina; Olsson, Roger; Piu, Fabrice

    2008-10-30

    Peptides with agonist activity at the vasopressin V(2) receptor are used clinically to treat fluid homeostasis disorders such as polyuria and central diabetes insipidus. Of these peptides, the most commonly used is desmopressin, which displays poor bioavailability as well as potent activity at the V(1b) receptor, with possible stress-related adverse effects. Thus, there is a strong need for the development of small molecule chemistries with selective V(2) receptor agonist activity. Using the functional cell-based assay Receptor Selection and Amplification Technology (R-SAT((R))), a screening effort identified three small molecule chemotypes (AC-94544, AC-88324, and AC-110484) with selective agonist activity at the V(2) receptor. One of these compounds, AC-94544, displayed over 180-fold selectivity at the V(2) receptor compared to related vasopressin and oxytocin receptors and no activity at 28 other G protein-coupled receptors (GPCRs). All three compounds also showed partial agonist activity at the V(2) receptor in a cAMP accumulation assay. In addition, in a rat model of central diabetes insipidus, AC-94544 was able to significantly reduce urine output in a dose-dependent manner. Thus, AC-94544, AC-88324, and AC-110484 represent novel opportunities for the treatment of disorders associated with V(2) receptor agonist deficiency.

  4. Congestion based mechanism for route discovery in a V2I-V2V system applying smart devices and IoT.

    Science.gov (United States)

    Parrado, Natalia; Donoso, Yezid

    2015-03-31

    The Internet of Things is a new paradigm in which objects in a specific context can be integrated into traditional communication networks to actively participate in solving a determined problem. The Vehicle-to-Vehicle (V2V) and Vehicle-to-Infrastructure (V2I) technologies are specific cases of IoT and key enablers for Intelligent Transportation Systems (ITS). V2V and V2I have been widely used to solve different problems associated with transportation in cities, in which the most important is traffic congestion. A high percentage of congestion is usually presented by the inappropriate use of resources in vehicular infrastructure. In addition, the integration of traffic congestion in decision making for vehicular traffic is a challenge due to its high dynamic behavior. In this paper, an optimization model over the load balancing in the congestion percentage of the streets is formulated. Later, we explore a fully congestion-oriented route discovery mechanism and we make a proposal on the communication infrastructure that should support it based on V2I and V2V communication. The mechanism is also compared with a modified Dijkstra's approach that reacts at congestion states. Finally, we compare the results of the efficiency of the vehicle's trip with the efficiency in the use of the capacity of the vehicular network.

  5. Congestion Based Mechanism for Route Discovery in a V2I-V2V System Applying Smart Devices and IoT

    Directory of Open Access Journals (Sweden)

    Natalia Parrado

    2015-03-01

    Full Text Available The Internet of Things is a new paradigm in which objects in a specific context can be integrated into traditional communication networks to actively participate in solving a determined problem. The Vehicle-to-Vehicle (V2V and Vehicle-to-Infrastructure (V2I technologies are specific cases of IoT and key enablers for Intelligent Transportation Systems (ITS. V2V and V2I have been widely used to solve different problems associated with transportation in cities, in which the most important is traffic congestion. A high percentage of congestion is usually presented by the inappropriate use of resources in vehicular infrastructure. In addition, the integration of traffic congestion in decision making for vehicular traffic is a challenge due to its high dynamic behavior. In this paper, an optimization model over the load balancing in the congestion percentage of the streets is formulated. Later, we explore a fully congestion-oriented route discovery mechanism and we make a proposal on the communication infrastructure that should support it based on V2I and V2V communication. The mechanism is also compared with a modified Dijkstra’s approach that reacts at congestion states. Finally, we compare the results of the efficiency of the vehicle’s trip with the efficiency in the use of the capacity of the vehicular network.

  6. Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression.

    Science.gov (United States)

    DeSmet, Marsha L; Fleet, James C

    2017-10-01

    High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH) 2 D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH) 2 D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene. Young Adult Mouse Colon (YAMC) and Rat Intestinal Epithelial (RIE) cell lines with stable expression of mutant H-RAS had suppressed 1,25(OH) 2 D-mediated induction of CYP24A1 mRNA. The RAS effects were associated with lower Vitamin D receptor (VDR) mRNA and protein levels in YAMC and RIE cells and they could be partially reversed by VDR overexpression. RAS-mediated suppression of VDR levels was not due to either reduced VDR mRNA stability or increased VDR gene methylation. However, chromatin accessibility to the VDR gene at the proximal promoter (-300bp), an enhancer region at -6kb, and an enhancer region located in exon 3 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). These data show that constitutively active RAS signaling suppresses 1,25(OH) 2 D-mediated gene transcription in colon epithelial cells by reducing VDR gene transcription but the mechanism for this suppression is not yet known. These data suggest that cancers with RAS-activating mutations may be less responsive to vitamin D mediated treatment or chemoprevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. ITER EDA newsletter. V. 2, no. 12

    International Nuclear Information System (INIS)

    1993-12-01

    This issue of the ITER EDA (Engineering Design Activities) Newsletter contains a report of the Second ITER Technical Committee Meeting on Safety, Environment, and Regulatory Approval, San Diego, USA, November 3-12, 1993, and a summary report on an ITER Magnet Technical Meeting, Naka, Japan, October 5-8, 1993

  8. ITER EDA newsletter. V. 2, no. 9

    International Nuclear Information System (INIS)

    1993-09-01

    This ITER EDA (Engineering Design Activities) Newsletter issue contains a report on the third meeting of the ITER Technical Advisory Committee, a summary report for the ITER Magnetic Technical Meeting, a brief account of the International Workshop on Nuclear Data for Fusion Reactor Technology, and a description of approved arrangements for visiting home team personnel

  9. Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype

    Science.gov (United States)

    Murakami, Shunichi; Balmes, Gener; McKinney, Sandra; Zhang, Zhaoping; Givol, David; de Crombrugghe, Benoit

    2004-01-01

    We generated transgenic mice that express a constitutively active mutant of MEK1 in chondrocytes. These mice showed a dwarf phenotype similar to achondroplasia, the most common human dwarfism, caused by activating mutations in FGFR3. These mice displayed incomplete hypertrophy of chondrocytes in the growth plates and a general delay in endochondral ossification, whereas chondrocyte proliferation was unaffected. Immunohistochemical analysis of the cranial base in transgenic embryos showed reduced staining for collagen type X and persistent expression of Sox9 in chondrocytes. These observations indicate that the MAPK pathway inhibits hypertrophic differentiation of chondrocytes and negatively regulates bone growth without inhibiting chondrocyte proliferation. Expression of a constitutively active mutant of MEK1 in chondrocytes of Fgfr3-deficient mice inhibited skeletal overgrowth, strongly suggesting that regulation of bone growth by FGFR3 is mediated at least in part by the MAPK pathway. Although loss of Stat1 restored the reduced chondrocyte proliferation in mice expressing an achondroplasia mutant of Fgfr3, it did not rescue the reduced hypertrophic zone, the delay in formation of secondary ossification centers, and the achondroplasia-like phenotype. These observations suggest a model in which Fgfr3 signaling inhibits bone growth by inhibiting chondrocyte differentiation through the MAPK pathway and by inhibiting chondrocyte proliferation through Stat1. PMID:14871928

  10. alpha-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption.

    Science.gov (United States)

    Torielli, Lucia; Tivodar, Simona; Montella, Rosa Chiara; Iacone, Roberto; Padoani, Gloria; Tarsini, Paolo; Russo, Ornella; Sarnataro, Daniela; Strazzullo, Pasquale; Ferrari, Patrizia; Bianchi, Giuseppe; Zurzolo, Chiara

    2008-08-01

    Genetic variation in alpha-adducin cytoskeletal protein is implicated in the polymerization and bundling of actin and alteration of the Na/K pump, resulting in abnormal renal sodium transport and hypertension in Milan hypertensive rats and humans. To investigate the molecular involvement of alpha-adducin in controlling Na/K pump activity, wild-type or mutated rat and human alpha-adducin forms were, respectively, transfected into several renal cell lines. Through multiple experimental approaches (microscopy, enzymatic assays, coimmunoprecipitation), we showed that rat and human mutated forms increased Na/K pump activity and the number of pump units; moreover, both variants coimmunoprecipitate with Na/K pump. The increased Na/K pump activity was not due to changes in its basolateral localization, but to an alteration of Na/K pump residential time on the plasma membrane. Indeed, both rat and human mutated variants reduced constitutive Na/K pump endocytosis and similarly affected transferrin receptor trafficking and fluid-phase endocytosis. In fact, alpha-adducin was detected in clathrin-coated vesicles and coimmunoprecipitated with clathrin. These results indicate that adducin, besides its modulatory effects on actin cytoskeleton dynamics, might play a direct role in clathrin-dependent endocytosis. The constitutive reduction of the Na/K pump endocytic rate induced by mutated adducin variants may be relevant in Na-dependent hypertension.

  11. Mutations that silence constitutive signaling activity in the allosteric ligand-binding site of the thyrotropin receptor.

    Science.gov (United States)

    Haas, Ann-Karin; Kleinau, Gunnar; Hoyer, Inna; Neumann, Susanne; Furkert, Jens; Rutz, Claudia; Schülein, Ralf; Gershengorn, Marvin C; Krause, Gerd

    2011-01-01

    The thyrotropin receptor (TSHR) exhibits elevated cAMP signaling in the basal state and becomes fully activated by thyrotropin. Previously we presented evidence that small-molecule ligands act allosterically within the transmembrane region in contrast to the orthosteric extracellular hormone-binding sites. Our goal in this study was to identify positions that surround the allosteric pocket and that are sensitive for inactivation of TSHR. Homology modeling combined with site-directed mutagenesis and functional characterization revealed seven mutants located in the allosteric binding site that led to a decrease of basal cAMP signaling activity. The majority of these silencing mutations, which constrain the TSHR in an inactive conformation, are found in two clusters when mapped onto the 3D structural model. We suggest that the amino acid positions identified herein are indicating locations where small-molecule antagonists, both neutral antagonists and inverse agonists, might interfere with active TSHR conformations.

  12. Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway.

    Directory of Open Access Journals (Sweden)

    Lisa Trisciuoglio

    Full Text Available A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering. We have performed an epistasis analysis to investigate whether these events cluster together in pathways. We find that all depend directly or indirectly on caspase-3 activation. CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.

  13. A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase

    DEFF Research Database (Denmark)

    Maile, C A; Hingst, Janne Rasmuss; Mahalingan, K K

    2017-01-01

    BACKGROUND: Equine type 1 polysaccharide storage myopathy (PSSM1) is associated with a missense mutation (R309H) in the glycogen synthase (GYS1) gene, enhanced glycogen synthase (GS) activity and excessive glycogen and amylopectate inclusions in muscle. METHODS: Equine muscle biochemical...... had significantly higher glycogen content than control horse muscle despite no difference in GS expression. GS activity was significantly higher in muscle from homozygous mutants than from heterozygote and control horses, in the absence and presence of the allosteric regulator, glucose 6 phosphate (G6...

  14. Constitutional reform as process

    OpenAIRE

    Schultze, Rainer-Olaf (Prof.)

    2000-01-01

    Constitutional reform as process. - In: The politics of constitutional reform in North America / Rainer-Olaf Schultze ... (eds.). - Opladen : Leske + Budrich, 2000. - S. 11-31. - (Politikwissenschaftliche paperbacks ; 30)

  15. ITER EDA Newsletter. V.2, no.5

    International Nuclear Information System (INIS)

    1993-05-01

    This ITER EDA (Engineering Design Activities), Newsletter issue includes reports on the third ITER council meeting in Tokyo on the involvement of other countries, on an outline of the report by the Management Advisory Committee (MAC), on such involvement, and on the improvement by the MAC and the ITER Council to proceed with Task Agreements on the Research and Development programme of the Superconductor Coils and Structures Division

  16. ITER EDA newsletter. V. 2, no. 10

    International Nuclear Information System (INIS)

    1993-10-01

    This issue of the ITER EDA (Engineering Design Activities) Newsletter contains progress reports on the Fourth ITER Council Meeting in San Diego, 29 September - 1 October 1993, on the Third Meeting of the ITER Management Advisory Committee (MAC) in Naka, Japan, 16-17 September 1993, and on the flag raising ceremony at the US hosted joint work site in San Diego, California, 1 October 1993

  17. Constitutive cannabinoid 1 and mu opioid receptor activity in the ventral tegmental area: occurrence, function and therapeutic relevance

    NARCIS (Netherlands)

    Meye, F.J.

    2012-01-01

    Cannabinoid 1 receptors (CB1Rs) play a crucial role in regulating systems dedicated to processing rewards and emotions. It was known that in artificial systems, CB1Rs can exhibit activity that is independent of the typical agonist-driven form. However, it remained largely unclear whether this

  18. Relationships between Endogenous Plasma Biomarkers of Constitutive Cytochrome P450 3A Activity and Single-Time-Point Oral Midazolam Microdose Phenotype in Healthy Subjects.

    Science.gov (United States)

    Woolsey, Sarah J; Beaton, Melanie D; Choi, Yun-Hee; Dresser, George K; Gryn, Steven E; Kim, Richard B; Tirona, Rommel G

    2016-04-01

    Due to high basal interindividual variation in cytochrome P450 3A (CYP3A) activity and susceptibility to drug interactions, there has been interest in the application of efficient probe drug phenotyping strategies, as well as endogenous biomarkers for assessment of in vivo CYP3A activity. The biomarkers 4β-hydroxycholesterol (4βHC) and 6β-hydroxycortisol (6βHCL) are sensitive to CYP3A induction and inhibition. However, their utility for the assessment of constitutive CYP3A activity remains uncertain. We investigated whether endogenous plasma biomarkers (4βHC and 6βHCL) are associated with basal CYP3A metabolic activity in healthy subjects assessed by a convenient single-time-point oral midazolam (MDZ) phenotyping strategy. Plasma 4βHC and 6βHCL metabolic ratios (MRs) were analysed in 51 healthy adult participants. CYP3A activity was determined after administration of an oral MDZ microdose (100 μg). Simple linear and multiple linear regression analyses were performed to assess relationships between MDZ oral clearance, biomarkers and subject covariates. Among study subjects, basal MDZ oral clearance, 4βHC and 6βHCL MRs ranged 6.5-, 10- and 13-fold, respectively. Participant age and alcohol consumption were negatively associated with MDZ oral clearance (p = 0.03 and p = 0.045, respectively), while weight and female sex were associated with lower plasma 4βHC MR (p = 0.0003 and p = 0.032, respectively). Neither 4βHC nor 6βHCL MRs were associated with MDZ oral clearance. Plasma 4βHC and 6βHCL MRs do not relate to MDZ single-time-point metabolic phenotype in the assessment of constitutive CYP3A activity among healthy individuals. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  19. Transnational Constitutional Law

    NARCIS (Netherlands)

    Zumbansen, P (Peer); K.I. Bhatt (Kinnari)

    2018-01-01

    textabstractThis chapter provides an overview of the emerging field of transnational constitutional law (TCL). Whilst questions of constitutional law are typically discussed in the context of a specific domestic legal setting, a salient strategy of TCL is to understand constitutional law and its

  20. Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.

    Directory of Open Access Journals (Sweden)

    Azhar R Hussain

    Full Text Available BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL. In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene, a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS. Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.

  1. Fine structure of V2+ energy levels in CsCaF3:V2+

    International Nuclear Information System (INIS)

    Avram, C.N.; Brik, M.G.

    2004-01-01

    Theoretical investigations of the fine structure of the lasing 4 T 2g level in a CsCaF 3 :V 2+ crystal were carried out. The spin-orbit splitting of the 4 T 2g term in the static low crystal field was obtained from the Eisenstein matrices and using parameters (Dq, B, C, ζ SO ) appropriate for the 4 T 2g - 4 A 2g zero-phonon line. The 4 T 2g spinor splitting has been modeled by the second-order spin-orbit Hamiltonian. The effect of the dynamical Jahn-Teller interaction on the spin-orbit splitting of the 4 T 2g term was taken into account; the Jahn-Teller stabilization energy, ZPL splitting and the Huang-Rhys parameter for the e g normal mode were all evaluated

  2. UNDERSTANDING INFORMAL CONSTITUTIONAL CHANGE

    Directory of Open Access Journals (Sweden)

    Stephen M. Griffin

    2016-01-01

    Full Text Available Amid much recent American work on the problem of informal constitutional change, this article stakes out a distinctive position. I argue that theories of constitutional change in the US must address the question of the relationship between the “small c” and “big C” Constitution and treat seriously the possibility of conflict between them. I stress the unavoidable role the text of the Constitution and structural doctrines of federalism and separation of powers play in this relationship and thus in constitutional change, both formal and informal. I therefore counsel against theories that rely solely on a practice-based approach or analogies between “small c” constitutional developments and British or Commonwealth traditions of the “unwritten” constitution and constitutional “conventions.” The alternative I advocate is to approach constitutional change from a historicist perspective that focuses attention on state building and the creation of new institutional capacities. This approach will allow us to make progress by highlighting that there can be multiple constitutional orders in a given historical era, thus accounting for the conflictual nature of contemporary constitutional development in the US.

  3. Potential performance analysis and future trend prediction of electric vehicle with V2G/V2H/V2B capability

    Directory of Open Access Journals (Sweden)

    Dalong Guo

    2016-03-01

    Full Text Available Due to the intermittent nature, renewable energy sources (RES has brought new challenges on load balancing and energy dispatching to the Smart Grid. Potentially served as distributed energy storage, Electric Vehicle’s (EV battery can be used as a way to help mitigate the pressure of fluctuation brought by RES and reinforce the stability of power systems. This paper gives a comprehensive review of the current situation of EV technology and mainly emphasizing three EV discharging operations which are Vehicle to Grid (V2G, Vehicle to Home (V2H, and Vehicle to Building (V2B, respectively. When needed, EV’s battery can discharge and send its surplus energy back to power grid, residential homes, or buildings. Based on our data analysis, we argue that V2G with the largest transmission power losses is potentially less efficient compared with the other two modes. We show that the residential users have the incentive to schedule the charging, V2G, and V2H according to the real-time price (RTP and the market sell-back price. In addition, we discuss some challenges and potential risks resulting from EVs’ fast growth. Finally we propose some suggestions on future power systems and also argue that some incentives or rewards need to be provided to motivate EV owners to behave in the best interests of the overall power systems.

  4. Complementary activities of TPX2 and chTOG constitute an efficient importin-regulated microtubule nucleation module.

    Science.gov (United States)

    Roostalu, Johanna; Cade, Nicholas I; Surrey, Thomas

    2015-11-01

    Spindle assembly and function require precise control of microtubule nucleation and dynamics. The chromatin-driven spindle assembly pathway exerts such control locally in the vicinity of chromosomes. One of the key targets of this pathway is TPX2. The molecular mechanism of how TPX2 stimulates microtubule nucleation is not understood. Using microscopy-based dynamic in vitro reconstitution assays with purified proteins, we find that human TPX2 directly stabilizes growing microtubule ends and stimulates microtubule nucleation by stabilizing early microtubule nucleation intermediates. Human microtubule polymerase chTOG (XMAP215/Msps/Stu2p/Dis1/Alp14 homologue) only weakly promotes nucleation, but acts synergistically with TPX2. Hence, a combination of distinct and complementary activities is sufficient for efficient microtubule formation in vitro. Importins control the efficiency of the microtubule nucleation by selectively blocking the interaction of TPX2 with microtubule nucleation intermediates. This in vitro reconstitution reveals the molecular mechanism of regulated microtubule formation by a minimal nucleation module essential for chromatin-dependent microtubule nucleation in cells.

  5. Inhibition of STAT3 reduces astrocytoma cell invasion and constitutive activation of STAT3 predicts poor prognosis in human astrocytoma.

    Directory of Open Access Journals (Sweden)

    Qinchuan Liang

    Full Text Available Astrocytoma cells characteristically possess high invasion potentials. Recent studies have revealed that knockdown of signal transducers and activators of transcription 3 (STAT3 expression by RNAi induces apoptosis in astrocytoma cell. Nevertheless, the distinct roles of STAT3 in astrocytoma's invasion and recurrence have not been elucidated. In this study, we silenced STAT3 using Small interfering RNAs in two human glioblastoma multiforme (GBM cell lines (U251 and U87, and investigated the effect on GBM cell adhesion and invasion. Our results demonstrate that disruption of STAT3 inhibits GBM cell's adhesion and invasion. Knockdown of STAT3 significantly increased E-cadherin but decreased N-cadherin, vascular endothelial growth factor, matrix metalloproteinase 2 and matrix metalloproteinase 9. Additionally, expression of pSTAT3(Tyr705 correlates with astrocytoma WHO classification, Karnofsky performance status scale score, tumor recurrence and survival. Furthermore, pSTAT3(Tyr705 is a significant prognostic factor in astrocytoma. In conclusion, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705 is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients. Therefore, STAT3 may provide a potential target for molecular therapy in human astrocytoma, and pSTAT3(Tyr705could be an important biomarker for astrocytoma prognosis.

  6. Movimientos sociales, activismo constitucional y narrativa democrática en la Argentina contemporánea Social movements, constitutional activism and democratic narrative in contemporary Argentina

    Directory of Open Access Journals (Sweden)

    Gabriela Delamata

    2013-04-01

    Full Text Available El artículo analiza tres procesos recientes de movilización socio-legal en Argentina y subraya el rol de la Constitución y la comunidad legal garantista en su despliegue. El enfoque utilizado propone entender los procesos bajo la forma de una reactivación del patrón activista gestado en la transición democrática y señala sus efectos actuales sobre los procedimientos democráticos y la gramática de ciudadanía.The article analyzes three contemporary processes of socio-legal mobilization in Argentina and underlines the role of the Constitution and of the legal community in its enforcement. The adopted approach aims at understanding those processes as a sort of reactivation of the activist tradition born during the transition to democracy, and emphasizing the present effects of this constitutional activism on democratic procedures and the citizenship grammar.

  7. Resistance irrelevant CYP417A2v2 was found degrading insecticide in Laodelphax striatellus.

    Science.gov (United States)

    Miah, Mohammad Asaduzzaman; Elzaki, Mohammed Esmail Abdalla; Han, Zhaojun

    2017-07-01

    Cytochrome P450 monooxygenases (CYPs) usually overexpressed in resistant strain were found involved in oxidative detoxification of insecticides. In this study, an investigation was conducted to confirm if resistance irrelevant CYPs which were not overexpressed in resistant strain before, were capable of degrading insecticides. Three resistance irrelevant CYPs viz. CYP417A2v2, CYP425A1v2, and CYP4DJ1 from CYP4 family of Laodelphax striatellus were randomly selected for experiments. CYP417A2v2 and CYP425A1v2 were found expressed successfully in Sf9 cell line while CYP4DJ1 was not expressed successfully and out of two expressed CYPs, only CYP417A2v2 showed its efficient catalytic activity. For catalytic activity, three traditional model probe substrates and five insecticides were assayed. For the probe substrates screened, p -nitroanisole and ethoxycoumarin were preferentially metabolized by CYP417A2v2 (specific activity 3.76 ± 1.22 and 1.63 ± 0.37 nmol min -1  mg protein -1 , respectively) and they may be potential diagnostic probes for this enzyme. Among insecticides, only imidacloprid was efficiently degraded by CYP417A2v2. Incubation of imidacloprid with CYP417A2v2 of L. striatellus and subsequent HPLC, LC-MS, and MS/MS analysis revealed the formation of imidacloprid metabolites, that is, 4' or 5'hydroxy-imidacloprid by hydroxylation. This result implies the exemption of CYPs character that it is not always, all the CYPs degrading insecticides being selected and overexpressed in resistant strains and the degrading CYPs without mutations to upregulate could be candidates during insecticide resistance evolution. This characterization of individual insect CYPs in insecticide degradation can provide insight for better understand of insecticide resistance development.

  8. Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3

    International Nuclear Information System (INIS)

    Dahlberg, Angela; Auble, Mark R.; Petro, Thomas M.

    2006-01-01

    Macrophages responding to viral infections may contribute to autoimmune demyelinating diseases (ADD). Macrophages from ADD-susceptible SJL/J mice responding to Theiler's Virus (TMEV) infection, the TLR7 agonist loxoribine, or the TLR4 agonist-LPS expressed less IL-12 p35 but more IL-12/23 p40 and IFN-β than macrophages from ADD-resistant B10.S mice. While expression of IRF-1 and -7 was similar between B10.S and SJL/J TMEV-infected macrophages, SJL/J but not B10.S macrophages exhibited constitutively active IRF-3. In contrast to overexpressed IRF-1, IRF-5, and IRF-7, which stimulated p35 promoter reporter activity, overexpressed IRF-3 repressed p35 promoter activity in response to TMEV infection, loxoribine, IFN-γ/LPS, but not IFN-γ alone. IRF-3 lessened but did not eliminate IRF-1-stimulated p35 promoter activity. Repression by IRF-3 required bp -172 to -122 of the p35 promoter. The data suggest that pre-activated IRF-3 is a major factor in the differences in IL-12 production between B10.S and SJL/J macrophages responding to TMEV

  9. Ionic liquid intercalated V2O5 nanorods: synthesis and ...

    Indian Academy of Sciences (India)

    Administrator

    materials for lithium ion battery, catalyst for photocata- lytic degradation ... ties.5,6 This compound is widely studied and is a promising material, both in the pure .... Figure 3 shows the Raman spectra of IL-V2O5 nanorods and calcined V2O5 ...

  10. 2-minute Gridded Global Relief Data (ETOPO2) v2

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Two-minute gridded global relief for both ocean and land areas are available in the ETOPO2v2 (2006) database. ETOPO2v2 replaced ETOPO2 (2001). The historic 2-minute...

  11. Transnational Constitutional Law

    OpenAIRE

    Zumbansen, P (Peer); Bhatt, Kinnari

    2018-01-01

    textabstractThis chapter provides an overview of the emerging field of transnational constitutional law (TCL). Whilst questions of constitutional law are typically discussed in the context of a specific domestic legal setting, a salient strategy of TCL is to understand constitutional law and its values by placing them ‘in context’ with existing and evolving cultural norms and political, social and economic discourses and struggles. Drawing on socio-legal investigations into the relationships ...

  12. Constitution, 5 October 1988.

    Science.gov (United States)

    1989-01-01

    This document contains major provisions of the constitution adopted by Brazil on 5 October 1988. This constitution seeks to promote the welfare of all citizens without discrimination. The equality of all citizens is guaranteed, and the equal rights of women are specifically mentioned. Property rights are also guaranteed and defined. Female inmates are granted the right to remain with their children while breast feeding. Workers are guaranteed a minimum wage, a family allowance for dependents, maternity/paternity leave, specific incentives to protect the labor market for women, retirement benefits, free day care for preschool-age children, pay equity, and equal rights between tenured and sporadically employed workers. Agrarian reform provisions are given, including the authority to expropriate land. Social and economic policies to promote health are called for, and public health services are to be decentralized, to be integrated, and to foster community participation. Pension plan and social assistance provisions are outlined as are duties of the state in regard to education. The amount of money to be dedicated to education is set out, and a national educational plan is called for to achieve such goals as the eradication of illiteracy, the universalization of school attendance, the improvement of instruction, and the provision of vocational training. Specific measures are set out to protect and preserve the environment. Family policy deals with issues of marriage, the definition of a family, divorce, the right to family planning services, and the deterrence of domestic violence. Social protection provisions cover mothers and children, handicapped persons, and protection of minors. Finally, the customs and rights of Indians are protected, with special provisions given to protect land tenure and to protect the rights of Indians in water resource development and prospecting and mining activities.

  13. Synthesis of V2O5 microspheres by spray pyrolysis as cathode material for supercapacitors

    Science.gov (United States)

    Yin, Zhendong; Xu, Jie; Ge, Yali; Jiang, Qiaoya; Zhang, Yaling; Yang, Yawei; Sun, Yuping; Hou, Siyu; Shang, Yuanyuan; Zhang, Yingjiu

    2018-03-01

    Vanadium oxide (V2O5) microspheres have attracted considerable attention in the energy field due to their unique properties such as high stability and electrochemical activity. Here, massive V2O5 microspheres with smooth surface, hollow cavity and uniform particle sizes (0.4–1.5 μm), were synthesized by a facile spray pyrolysis process. Post-treatment at predefined temperatures effectively turned the microsphere shell into stacked nanorods with widths of 100 nm and lengths of 500 nm when processed at 500 °C for 3 h under nitrogen atmosphere, with enhanced crystallinity. When applied as cathode materials for supercapacitors, the post-treated V2O5 microspheres at 500 °C exhibited improved specific capacitance and longer discharge time. This is an effective method to manufacture massive V2O5 microspheres with tailored structure and potential applications in high-performance energy storage materials.

  14. Structure of recombinant Ves v 2 at 2.0 Angstrom resolution

    DEFF Research Database (Denmark)

    Skov, Lars K; Seppälä, Ulla; Coen, Jeremy J F

    2006-01-01

    Wasp venom from Vespula vulgaris contains three major allergens: Ves v 1, Ves v 2 and Ves v 5. Here, the cloning, expression, biochemical characterization and crystal structure determination of the hyaluronidase Ves v 2 from family 56 of the glycoside hydrolases are reported. The allergen...... was expressed in Escherichia coli as an insoluble protein and refolded and purified to obtain full enzymatic activity. Three N-glycosylation sites at Asn79, Asn99 and Asn127 were identified in Ves v 2 from a natural source by enzymatic digestions combined with MALDI-TOF mass spectrometry. The crystal structure...... of recombinant Ves v 2 was determined at 2.0 A resolution and reveals a central (beta/alpha)(7) core that is further stabilized by two disulfide bonds (Cys19-Cys308 and Cys185-Cys197). Based on sequence alignments and structural comparison with the honeybee allergen Api m 2, it is proposed that a conserved...

  15. Dimensional stability of Ti--6Al--6V--2Sn

    International Nuclear Information System (INIS)

    Rack, H.J.

    1978-08-01

    The dimensional stability of Ti-6Al-6V-2Sn has been examined. It is shown that in the duplex annealed condition Ti-6Al-6V-2Sn is dimensionally stable at temperatures up to 448 0 K for 512 hrs. Solution treated Ti-6Al-6V-2Sn undergoes large dimensional changes during both initial aging between 673 and 973 0 K and subsequent exposure to low temperatures ( 0 K). These results indicate that if close dimensional tolerances must be maintained, duplex annealed Ti-6Al-6V-2Sn should be selected. Selection of treated and aged Ti-6Al-6V-2Sn should only be considered if accompanied by full scale environmental testing

  16. Constitutive mRNA expression and protein activity levels of nine ABC efflux transporters in seven permanent cell lines derived from different tissues of rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Fischer, Stephan; Loncar, Jovica; Zaja, Roko; Schnell, Sabine; Schirmer, Kristin; Smital, Tvrtko; Luckenbach, Till

    2011-01-25

    Permanent fish cell lines have become common model systems for determining ecotoxicological effects of pollutants. For these cell lines little is known on the cellular active transport mechanisms that control the amount of a compound entering the cell, such as the MXR (multixenobiotic resistance) system mediated by ATP binding cassette (ABC) transport proteins. Therefore, for toxic evaluation of chemicals with those cells information on MXR is important. We here present data on constitutive mRNA expression and protein activity levels of a series of ABC efflux transporters in seven permanent cell lines derived from liver (RTL-W1; R1) and liver hepatoma (RTH-149), gill (RTgill-W1), gonad (RTG-2), gut (RTgutGC) and brain (RTbrain) of rainbow trout (Oncorhynchus mykiss). In addition to known transporters abcb1 (designated here abcb1a), abcb11, abcc1-3, abcc5 and abcg2, we quantified expression levels of a newly identified abcb1 isoform (abcb1b) and abcc4, previously unknown in trout. Quantitative real time PCR (qPCR) indicated that mRNA of the examined ABC transporters was constitutively expressed in all cell lines. Transporter mRNA expression patterns were similar in all cell lines, with expression levels of abcc transporters being 80 to over 1000 fold higher than for abcg2, abcb1a/b and abcb11 (abcc1-5>abcg2>abcb1a/b, 11). Transporter activity in the cell lines was determined by measuring uptake of transporter type specific fluorescent substrates in the presence of activity inhibitors. The combination of the ABCB1 and ABCC transporter substrate calcein-AM with inhibitors cyclosporine A, PSC833 and MK571 resulted in a concentration-dependent fluorescence increase of up to 3-fold, whereas reversin 205 caused a slight, but not concentration-dependent fluorescence increase. Accumulation of the dyes Hoechst 33342 and 2',7'-dichlorodihydrofluorescein diacetate was basically unchanged in the presence of Ko134 and taurocholate, respectively, indicating low Abcg2 and Abcb11

  17. A high constitutive catalase activity confers resistance to methyl viologen-promoted oxidative stress in a mutant of the cyanobacterium Nostoc punctiforme ATCC 29133.

    Science.gov (United States)

    Moirangthem, Lakshmipyari Devi; Bhattacharya, Sudeshna; Stensjö, Karin; Lindblad, Peter; Bhattacharya, Jyotirmoy

    2014-04-01

    A spontaneous methyl viologen (MV)-resistant mutant of the nitrogen-fixing cyanobacterium Nostoc punctiforme ATCC 29133 was isolated and the major enzymatic antioxidants involved in combating MV-induced oxidative stress were evaluated. The mutant displayed a high constitutive catalase activity as a consequence of which, the intracellular level of reactive oxygen species in the mutant was lower than the wild type (N. punctiforme) in the presence of MV. The superoxide dismutase (SOD) activity that consisted of a SodA (manganese-SOD) and a SodB (iron-SOD) was not suppressed in the mutant following MV treatment. The mutant was, however, characterised by a lower peroxidase activity compared with its wild type, and its improved tolerance to externally added H₂O₂ could only be attributed to enhanced catalase activity. Furthermore, MV-induced toxic effects on the wild type such as (1) loss of photosynthetic performance assessed as maximal quantum yield of photosystem II, (2) nitrogenase inactivation, and (3) filament fragmentation and cell lysis were not observed in the mutant. These findings highlight the importance of catalase in preventing MV-promoted oxidative damage and cell death in the cyanobacterium N. punctiforme. Such oxidative stress resistant mutants of cyanobacteria are likely to be a better source of biofertilisers, as they can grow and fix nitrogen in an unhindered manner in agricultural fields that are often contaminated with the herbicide MV, also commonly known as paraquat.

  18. Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver.

    Science.gov (United States)

    Lickteig, Andrew J; Csanaky, Iván L; Pratt-Hyatt, Matthew; Klaassen, Curtis D

    2016-06-01

    Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect of CAR activation on bile flow, BA profile, as well as expression of BA synthesis and transport genes. Synthetic CAR ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was administered to mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). CAR activation decreases total BAs in livers of male (49%) and female mice (26%), largely attributable to decreases of the 12α-hydroxylated BA taurocholic acid (T-CA) (males (M) 65%, females (F) 45%). Bile flow in both sexes was increased by CAR activation, and the increases were BA-independent. CAR activation did not alter biliary excretion of total BAs, but overall BA composition changed. Excretion of muricholic (6-hydroxylated) BAs was increased in males (101%), and the 12α-OH proportion of biliary BAs was decreased in both males (37%) and females (28%). The decrease of T-CA in livers of males and females correlates with the decreased mRNA of the sterol 12α-hydroxylase Cyp8b1 in males (71%) and females (54%). As a response to restore BAs to physiologic concentrations in liver, mRNA of Cyp7a1 is upregulated following TCPOBOP (males 185%, females 132%). In ilea, mRNA of the negative feedback regulator Fgf15 was unaltered by CAR activation, indicating biliary BA excretion was sufficient to maintain concentrations of total BAs in the small intestine. In summary, the effects of CAR activation on BAs in male and female mice are quite similar, with a marked decrease in the major BA T-CA in the liver. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Integration of V2H/V2G Hybrid System for Demand Response in Distribution Network

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yubo; Sheikh, Omar; Hu, Boyang; Chu, Chi-Cheng; Gadh, Rajit

    2014-11-03

    Integration of Electrical Vehicles (EVs) with power grid not only brings new challenges for load management, but also opportunities for distributed storage and generation in distribution network. With the introduction of Vehicle-to-Home (V2H) and Vehicle-to-Grid (V2G), EVs can help stabilize the operation of power grid. This paper proposed and implemented a hybrid V2H/V2G system with commercialized EVs, which is able to support both islanded AC/DC load and the power grid with one single platform. Standard industrial communication protocols are implemented for a seamless respond to remote Demand Respond (DR) signals. Simulation and implementation are carried out to validate the proposed design. Simulation and implementation results showed that the hybrid system is capable of support critical islanded DC/AC load and quickly respond to the remote DR signal for V2G within 1.5kW of power range.

  20. A constitutively activating mutation alters the dynamics and energetics of a key conformational change in a ligand-free G protein-coupled receptor.

    Science.gov (United States)

    Tsukamoto, Hisao; Farrens, David L

    2013-09-27

    G protein-coupled receptors (GPCRs) undergo dynamic transitions between active and inactive conformations. Usually, these conversions are triggered when the receptor detects an external signal, but some so-called constitutively activating mutations, or CAMs, induce a GPCR to bind and activate G proteins in the absence of external stimulation, in ways still not fully understood. Here, we investigated how a CAM alters the structure of a GPCR and the dynamics involved as the receptor transitions between different conformations. Our approach used site-directed fluorescence labeling (SDFL) spectroscopy to compare opsin, the ligand-free form of the GPCR rhodopsin, with opsin containing the CAM M257Y, focusing specifically on key movements that occur in the sixth transmembrane helix (TM6) during GPCR activation. The site-directed fluorescence labeling data indicate opsin is constrained to an inactive conformation both in detergent micelles and lipid membranes, but when it contains the M257Y CAM, opsin is more dynamic and can interact with a G protein mimetic. Further study of these receptors using tryptophan-induced quenching (TrIQ) methods indicates that in detergent, the CAM significantly increases the population of receptors in the active state, but not in lipids. Subsequent Arrhenius analysis of the TrIQ data suggests that, both in detergent and lipids, the CAM lowers the energy barrier for TM6 movement, a key transition required for conversion between the inactive and active conformations. Together, these data suggest that the lowered energy barrier is a primary effect of the CAM on the receptor dynamics and energetics.

  1. Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+

    Directory of Open Access Journals (Sweden)

    Nigou Jérôme

    2007-08-01

    Full Text Available Abstract Background The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase. Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. Results We determined the crystal structure, to 2.6 Å resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own. Conclusion The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity.

  2. The constitutive activation of the CEF-4/9E3 chemokine gene depends on C/EBPbeta in v-src transformed chicken embryo fibroblasts

    DEFF Research Database (Denmark)

    Gagliardi, M; Maynard, S; Bojovic, B

    2001-01-01

    The CEF-4/9E3 chemokine gene is expressed constitutively in chicken embryo fibroblasts (CEF) transformed by the Rous sarcoma virus (RSV). This aberrant induction is controlled at the transcriptional and post-transcriptional levels. Transcriptional activation depends on multiple elements of the CEF....../EBPbeta binds to a second element located in proximity of the TRE. A mutation of this distal CAAT box impaired the activation of the CEF-4 promoter by pp60(v-src) indicating that this element is also part of the SRU. Using the RCASBP retroviral vector, we expressed a dominant negative mutant of C....../EBPbeta (designated Delta184-C/EBPbeta) in RSV-transformed CEF. Delta184-C/EBPbeta decreased the accumulation of the CEF-4 mRNA and activation of the CEF-4 promoter by pp60(v-src). The induction of the Cox-2 gene (CEF-147) was also reduced by Delta184-C/EBPbeta. The effect of the dominant negative mutant was observed...

  3. Synthesis and Characterization of Ag-Modified V2O5 Photocatalytic Materials

    Directory of Open Access Journals (Sweden)

    Dora Alicia Solis-Casados

    2017-01-01

    Full Text Available V2O5 powders modified with different theoretical silver contents (1, 5, 10, 15, and 20 wt% as Ag2O were obtained with acicular morphologies observed by scanning electron microscopy (SEM. Shcherbinaite crystalline phase is transformed into the Ag0.33V2O5 crystalline one with the incorporation and increase in silver content as was suggested by X-ray diffraction (XRD and X-ray photoelectron spectroscopy (XPS analysis. With further increase in silver contents the Ag2O phase appears. Catalysts were active in photocatalytic degradation of malachite green dye under simulated solar light, which is one of the most remarkable facts of this work. It was found that V2O5-20Ag was the most active catalytic formulation and its activity was attributed to the mixture of coupled semiconductors that promotes the slight decrease in the rate of the electron-hole pair recombination.

  4. Activation of the Constitutive Androstane Receptor induces hepatic lipogenesis and regulates Pnpla3 gene expression in a LXR-independent way

    Energy Technology Data Exchange (ETDEWEB)

    Marmugi, Alice; Lukowicz, Céline; Lasserre, Frederic; Montagner, Alexandra; Polizzi, Arnaud; Ducheix, Simon; Goron, Adeline; Gamet-Payrastre, Laurence [INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse (France); Université de Toulouse, INP, UPS, TOXALIM, Toulouse (France); Gerbal-Chaloin, Sabine [Institute of Regenerative Medicine and Biotherapy, INSERM, U1183 Montpellier (France); Pascussi, Jean Marc [Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle, Montpellier (France); Moldes, Marthe [Centre de Recherche Saint-Antoine, INSERM, UMR 938, Sorbonne Universités, Université Paris 6, Paris (France); Institut Hospitalo-Universitaire ICAN, Paris (France); Pineau, Thierry; Guillou, Hervé [INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse (France); Université de Toulouse, INP, UPS, TOXALIM, Toulouse (France); Mselli-Lakhal, Laila, E-mail: laila.lakhal@toulouse.inra.fr [INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse (France); Université de Toulouse, INP, UPS, TOXALIM, Toulouse (France)

    2016-07-15

    The Constitutive Androstane Receptor (CAR, NR1I3) has been newly described as a regulator of energy metabolism. A relevant number of studies using animal models of obesity suggest that CAR activation could be beneficial on the metabolic balance. However, this remains controversial and the underlying mechanisms are still unknown. This work aimed to investigate the effect of CAR activation on hepatic energy metabolism during physiological conditions, i.e. in mouse models not subjected to metabolic/nutritional stress. Gene expression profiling in the liver of CAR knockout and control mice on chow diet and treated with a CAR agonist highlighted CAR-mediated up-regulations of lipogenic genes, concomitant with neutral lipid accumulation. A strong CAR-mediated up-regulation of the patatin-like phospholipase domain-containing protein 3 (Pnpla3) was demonstrated. Pnpla3 is a gene whose polymorphism is associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD) development. This observation was confirmed in human hepatocytes treated with the antiepileptic drug and CAR activator, phenobarbital and in immortalized human hepatocytes treated with CITCO. Studying the molecular mechanisms controlling Pnpla3 gene expression, we demonstrated that CAR does not act by a direct regulation of Pnpla3 transcription or via the Liver X Receptor but may rather involve the transcription factor Carbohydrate Responsive Element-binding protein. These data provide new insights into the regulation by CAR of glycolytic and lipogenic genes and on pathogenesis of steatosis. This also raises the question concerning the impact of drugs and environmental contaminants in lipid-associated metabolic diseases. - Highlights: • Induction of hepatic glycolytic and lipogenic genes upon CAR activation by TCPOBOP. • These effects are not mediated by the nuclear receptor LXR. • CAR activation resulted in hepatic lipid accumulation. • Pnpla3 expression is regulated by CAR in mouse liver and

  5. Activation of the Constitutive Androstane Receptor induces hepatic lipogenesis and regulates Pnpla3 gene expression in a LXR-independent way

    International Nuclear Information System (INIS)

    Marmugi, Alice; Lukowicz, Céline; Lasserre, Frederic; Montagner, Alexandra; Polizzi, Arnaud; Ducheix, Simon; Goron, Adeline; Gamet-Payrastre, Laurence; Gerbal-Chaloin, Sabine; Pascussi, Jean Marc; Moldes, Marthe; Pineau, Thierry; Guillou, Hervé; Mselli-Lakhal, Laila

    2016-01-01

    The Constitutive Androstane Receptor (CAR, NR1I3) has been newly described as a regulator of energy metabolism. A relevant number of studies using animal models of obesity suggest that CAR activation could be beneficial on the metabolic balance. However, this remains controversial and the underlying mechanisms are still unknown. This work aimed to investigate the effect of CAR activation on hepatic energy metabolism during physiological conditions, i.e. in mouse models not subjected to metabolic/nutritional stress. Gene expression profiling in the liver of CAR knockout and control mice on chow diet and treated with a CAR agonist highlighted CAR-mediated up-regulations of lipogenic genes, concomitant with neutral lipid accumulation. A strong CAR-mediated up-regulation of the patatin-like phospholipase domain-containing protein 3 (Pnpla3) was demonstrated. Pnpla3 is a gene whose polymorphism is associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD) development. This observation was confirmed in human hepatocytes treated with the antiepileptic drug and CAR activator, phenobarbital and in immortalized human hepatocytes treated with CITCO. Studying the molecular mechanisms controlling Pnpla3 gene expression, we demonstrated that CAR does not act by a direct regulation of Pnpla3 transcription or via the Liver X Receptor but may rather involve the transcription factor Carbohydrate Responsive Element-binding protein. These data provide new insights into the regulation by CAR of glycolytic and lipogenic genes and on pathogenesis of steatosis. This also raises the question concerning the impact of drugs and environmental contaminants in lipid-associated metabolic diseases. - Highlights: • Induction of hepatic glycolytic and lipogenic genes upon CAR activation by TCPOBOP. • These effects are not mediated by the nuclear receptor LXR. • CAR activation resulted in hepatic lipid accumulation. • Pnpla3 expression is regulated by CAR in mouse liver and

  6. The time point of β-catenin knockout in hepatocytes determines their response to xenobiotic activation of the constitutive androstane receptor

    International Nuclear Information System (INIS)

    Ganzenberg, Katrin; Singh, Yasmin; Braeuning, Albert

    2013-01-01

    The constitutive androstane receptor (CAR) controls the expression of drug-metabolizing enzymes and regulates hepatocyte proliferation. Studies with transgenic mice with an early postnatal conditional hepatocyte-specific knockout of the β-catenin gene Ctnnb1 revealed that β-catenin deficiency decreases the magnitude of induction of drug-metabolizing enzymes by CAR activators, abrogates zonal differences in the hepatocytes’ susceptibility to these compounds, and impacts on hepatocyte proliferation. These data, however, do not allow distinguishing between effects caused by β-catenin deficiency during postnatal liver development and acute effects of β-catenin deficiency in the adult animal at the time point of CAR activation. Therefore, CAR activation was now studied in a different mouse model allowing for the hepatocyte-specific knockout of β-catenin in adult mice. Treatment of these mice with 3 mg/kg body weight of the model CAR activator 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) confirmed previous findings related to the coordinate regulation of drug metabolism by β-catenin and CAR. More importantly, the present study clarified that the impact of β-catenin signaling on CAR-mediated enzyme induction in the liver is not merely due to developmental defects caused by a postnatal lack of β-catenin, but depends on the presence of β-catenin at the time point of xenobiotic treatment. The study also revealed interesting differences between the two mouse models: hepatic zonation of TCPOBOP-dependent induction of drug-metabolizing enzymes was restored in mice with late knockout of β-catenin, and the strong proliferative response of female mice was exclusively abolished when using animals with a late β-catenin knockout. This suggests a β-catenin-dependent postnatal priming of hepatocytes during postnatal liver development, later affecting the proliferative response of adult animals to CAR-activating xenobiotics

  7. Electrochemical and spectroscopic investigations of the K2SO4-V2O5 molten electrolyte

    DEFF Research Database (Denmark)

    Schmidt, Douglas S.; Winnick, Jack; Boghosian, Soghomon

    1999-01-01

    A 60 mol % K(2)SO(4)J/40 mol % V2O5 molten salt mixture was tested for electrochemical activity to determine its propensity for sulfate transport. Results of cyclic voltammetry showed a high electrochemical activity due likely to the reduction and oxidation of bulk, as opposed to minor, species...

  8. Development of operational models of receptor activation including constitutive receptor activity and their use to determine the efficacy of the chemokine CCL17 at the CC chemokine receptor CCR4.

    Science.gov (United States)

    Slack, R J; Hall, D A

    2012-07-01

    BACKGROUND AND PURPOSE The operational model provides a key conceptual framework for the analysis of pharmacological data. However, this model does not include constitutive receptor activity, a frequent phenomenon in modern pharmacology, particularly in recombinant systems. Here, we developed extensions of the operational model which include constitutive activity and applied them to effects of agonists at the chemokine receptor CCR4. EXPERIMENTAL APPROACH The effects of agonists of CCR4 on [(35) S]GTPγS binding to recombinant cell membranes and on the filamentous (F-) actin content of human CD4(+) CCR4(+) T cells were determined. The basal [(35) S]GTPγS binding was changed by varying the GDP concentration whilst the basal F-actin contents of the higher expressing T cell populations were elevated, suggesting constitutive activity of CCR4. Both sets of data were analysed using the mathematical models. RESULTS The affinity of CCL17 (also known as TARC) derived from analysis of the T cell data (pK(a) = 9.61 ± 0.17) was consistent with radioligand binding experiments (9.50 ± 0.11) while that from the [(35) S]GTPγS binding experiments was lower (8.27 ± 0.09). Its intrinsic efficacy differed between the two systems (110 in T cells vs. 11). CONCLUSIONS AND IMPLICATIONS The presence of constitutive receptor activity allows the absolute intrinsic efficacy of agonists to be determined without a contribution from the signal transduction system. Intrinsic efficacy estimated in this way is consistent with Furchgott's definition of this property. CCL17 may have a higher intrinsic efficacy at CCR4 in human T cells than that expressed recombinantly in CHO cells. © 2012 GSK Services Unlimited. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  9. Metamorphosis of NPP A1, V1, V2

    International Nuclear Information System (INIS)

    Dobak, D.; Moncekova, M.

    2005-01-01

    In this book the history of construction, commissioning and exploitation of NPP A1, NPP V1 and NPP V2 in Jaslovske Bohunice is presented on documentary photos. Vicinity around of these NPPs is presented, too

  10. The constitutive activation of Egr-1/C/EBPa mediates the development of type 2 diabetes mellitus by enhancing hepatic gluconeogenesis.

    Science.gov (United States)

    Shen, Ning; Jiang, Shan; Lu, Jia-Ming; Yu, Xiao; Lai, Shan-Shan; Zhang, Jing-Zi; Zhang, Jin-Long; Tao, Wei-Wei; Wang, Xiu-Xing; Xu, Na; Xue, Bin; Li, Chao-Jun

    2015-02-01

    The sequential secretion of insulin and glucagon delicately maintains glucose homeostasis by inhibiting or enhancing hepatic gluconeogenesis during postprandial or fasting states, respectively. Increased glucagon/insulin ratio is believed to be a major cause of the hyperglycemia seen in type 2 diabetes. Herein, we reveal that the early growth response gene-1 (Egr-1) can be transiently activated by glucagon in hepatocytes, which mediates glucagon-regulated gluconeogenesis by increasing the expression of gluconeogenesis genes. Blockage of Egr-1 function in the liver of mice led to lower fasting blood glucose, better pyruvate tolerance, and higher hepatic glycogen content. The mechanism analysis demonstrated that Egr-1 can directly bind to the promoter of C/EBPa and regulate the expression of gluconeogenesis genes in the later phase of glucagon stimulation. The transient increase of Egr-1 by glucagon kept the glucose homeostasis after fasting for longer periods of time, whereas constitutive Egr-1 elevation found in the liver of db/db mice and high serum glucagon level overactivated the C/EBPa/gluconeogenesis pathway and resulted in hyperglycemia. Blockage of Egr-1 activation in prediabetic db/db mice was able to delay the progression of diabetes. Our results suggest that dysregulation of Egr-1/C/EBPa on glucagon stimulation may provide an alternative mechanistic explanation for type 2 diabetes. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Clofibric acid induces hepatic CYP 2B1/2 via constitutive androstane receptor not via peroxisome proliferator activated receptor alpha in rat.

    Science.gov (United States)

    Ibrahim, Zein Shaban; Ahmed, Mohamed Mohamed; El-Shazly, Samir Ahmed; Ishizuka, Mayumi; Fujita, Shoichi

    2014-01-01

    Peroxisome proliferator activated receptor α (PPARα) ligands, fibrates used to control hyperlipidemia. We demonstrated CYP2B induction by clofibric acid (CFA) however, the mechanism was not clear. In this study, HepG2 cells transfected with expression plasmid of mouse constitutive androstane receptor (CAR) or PPARα were treated with CFA, phenobarbital (PB) or TCPOBOP. Luciferase assays showed that CFA increased CYP2B1 transcription to the same level as PB, or TCPOBOP in HepG2 transfected with mouse CAR But failed to induce it in PPARα transfected cells. CYP2B expressions were increased with PB or CFA in Wistar female rats (having normal levels of CAR) but not in Wistar Kyoto female rats (having low levels of CAR). The induction of CYP2B by PB or CFA was comparable to nuclear CAR levels. CAR nuclear translocation was induced by CFA in both rat strains. This indicates that fibrates can activate CAR and that fibrates-insulin sensitization effect may occur through CAR, while hypolipidemic effect may operate through PPARα.

  12. Constitutive activation of jasmonate signaling in an Arabidopsis mutant correlates with enhanced resistance to Erysiphe cichoracearum, Pseudomonas syringae, and Myzus persicae.

    Science.gov (United States)

    Ellis, Christine; Karafyllidis, Ioannis; Turner, John G

    2002-10-01

    In Arabidopsis spp., the jasmonate (JA) response pathway generally is required for defenses against necrotrophic pathogens and chewing insects, while the salicylic acid (SA) response pathway is generally required for specific, resistance (R) gene-mediated defenses against both biotrophic and necrotrophic pathogens. For example, SA-dependent defenses are required for resistance to the biotrophic fungal pathogen Erysiphe cichoracearum UCSC1 and the bacterial pathogen Pseudomonas syringae pv. maculicola, and also are expressed during response to the green peach aphid Myzus persicae. However, recent evidence indicates that the expression of JA-dependent defenses also may confer resistance to E. cichoracearum. To confirm and to extend this observation, we have compared the disease and pest resistance of wild-type Arabidopsis plants with that of the mutants coil, which is insensitive to JA, and cev1, which has constitutive JA signaling. Measurements of the colonization of these plants by E. cichoracearum, P. syringae pv. maculicola, and M. persicae indicated that activation of the JA signal pathway enhanced resistance, and was associated with the activation of JA-dependent defense genes and the suppression of SA-dependent defense genes. We conclude that JA and SA induce alternative defense pathways that can confer resistance to the same pathogens and pests.

  13. The distribution of FDG at PET examinations constitutes a relative mechanism: significant effects at activity quantification in patients with a high muscular uptake

    International Nuclear Information System (INIS)

    Lindholm, Henry; Johansson, Ove; Jacobsson, Hans; Jonsson, Cathrine

    2012-01-01

    At 18 F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) examinations a high tracer uptake of the skeletal muscles is sometimes encountered which can lead to reduced uptake in pathological lesions. This was evaluated in retrospect in patients being recalled for a repeat examination after reducing the muscular uptake. Ten patients with increased muscular tracer uptake were examined with FDG PET/CT on two occasions with a mean of 6 days. All patients showed at least one pathological lesion with increased tracer uptake. The muscular uptake was reduced at the second examination by informing the patient to refrain from physical activity together with pretreatment with diazepam. The maximum standardized uptake value (SUV max ) of the pathological lesion and SUV mean of certain skeletal muscles, liver, spleen, lungs, blood and certain bone marrow portions were calculated. In all patients, the muscular uptake was reduced to a normal level at visual evaluation as well as at comparison of SUVs with 25 consecutive clinical patients exhibiting a normal FDG distribution (p max increased from 2.4 to 3.7 (54 %) between the examinations (p max to the activity of any of the reference tissues/organs there was no significant difference between the studies. The distribution of FDG constitutes a relative mechanism. This must be especially considered at longitudinal examinations in the same patient at therapy evaluations. In examinations with a somehow distorted general distribution of the activity, it may be more relevant to relate the lesion activity to a reference tissue/organ than relying on SUV assessments. (orig.)

  14. Partial rescue of postnatal growth plate abnormalities in Ihh mutants by expression of a constitutively active PTH/PTHrP receptor.

    Science.gov (United States)

    Maeda, Yukiko; Schipani, Ernestina; Densmore, Michael J; Lanske, Beate

    2010-02-01

    Indian hedgehog (Ihh) is essential for chondrocyte proliferation/differentiation and osteoblast differentiation during prenatal endochondral bone formation. Ihh expression in postnatal chondrocytes has a non-redundant role in maintaining a growth plate and sustaining trabecular bone after birth. Loss of Ihh in postnatal chondrocytes results in fusion of the growth plate and a decrease in trabecular bone. In order to normalize this abnormal chondrocyte phenotype and to investigate whether a putative rescue of the growth plate anomalies is sufficient to correct the severe alterations in the bone, we expressed a constitutively active PTH/PTHrP receptor (an Ihh downstream target) in the chondrocytes of Col2 alpha 1-Cre ER; Ihh(dld) mice by mating Col2 alpha 1-Cre ER; Ihh(fl/fl) mice with Col2 alpha 1-constitutively active PTH/PTHrP receptor transgenic mice (Jansen, J). Col2 alpha 1-Cre ER; Ihh(f/f); J mice were then injected with tamoxifen at P0 to generate Col2 alpha 1-Cre ER; Ihh(d/d); J mice. In contrast with the previously reported growth plate phenotype of Col2 alpha 1-Cre ER; Ihh(d/d) mice that displayed ectopic chondrocyte hypertrophy at P7, growth plates of Col2 alpha 1-Cre ER; Ihh(d/d); J double mutants were well organized, and exhibited a gene expression pattern similar to the one of control mice. However, expression of osteoblast markers and Dkk1, a Wnt signaling target, remains decreased in the bone collar of Col2 alpha 1-Cre ER; Ihh(d/d); J mice when compared to control mice despite the rescue of abnormal chondrocyte differentiation. Moreover, proliferation of chondrocytes was still significantly impaired in Col2 alpha 1-Cre ER; Ihh(d/d); J mice, and this eventually led to the fusion of the growth plate at P14. In summary, we have demonstrated that expression of a Jansen receptor in chondrocytes was able to rescue abnormal chondrocyte differentiation but not impaired chondrocyte proliferation and the bone anomalies in mice lacking the Ihh gene in

  15. A strong loss-of-function mutation in RAN1 results in constitutive activation of the ethylene response pathway as well as a rosette-lethal phenotype

    Science.gov (United States)

    Woeste, K. E.; Kieber, J. J.; Evans, M. L. (Principal Investigator)

    2000-01-01

    A recessive mutation was identified that constitutively activated the ethylene response pathway in Arabidopsis and resulted in a rosette-lethal phenotype. Positional cloning of the gene corresponding to this mutation revealed that it was allelic to responsive to antagonist1 (ran1), a mutation that causes seedlings to respond in a positive manner to what is normally a competitive inhibitor of ethylene binding. In contrast to the previously identified ran1-1 and ran1-2 alleles that are morphologically indistinguishable from wild-type plants, this ran1-3 allele results in a rosette-lethal phenotype. The predicted protein encoded by the RAN1 gene is similar to the Wilson and Menkes disease proteins and yeast Ccc2 protein, which are integral membrane cation-transporting P-type ATPases involved in copper trafficking. Genetic epistasis analysis indicated that RAN1 acts upstream of mutations in the ethylene receptor gene family. However, the rosette-lethal phenotype of ran1-3 was not suppressed by ethylene-insensitive mutants, suggesting that this mutation also affects a non-ethylene-dependent pathway regulating cell expansion. The phenotype of ran1-3 mutants is similar to loss-of-function ethylene receptor mutants, suggesting that RAN1 may be required to form functional ethylene receptors. Furthermore, these results suggest that copper is required not only for ethylene binding but also for the signaling function of the ethylene receptors.

  16. The Verb Always Leaves IP in V2 Clauses

    DEFF Research Database (Denmark)

    Schwartz, Bonnie D.; Vikner, Sten

    2007-01-01

    The verb second (V2) phenomenon, as it is found in the Germanic languages, has been the focus of much attention within recent syntactic research. In most of the literature on V2, it is assumed that the verb in all V2 clauses has moved to a head position outside IP, e.g. Cº. In Schwartz & Vikner...... (1989) we claimed that all V2 clauses were CPs, and we referred to this analysis as the 'traditional' analysis. In this paper we shall call it the 'V2 outside IP' analysis, and by using this term we want to convey that although in what follows we will adhere to the view that the verb moves to Cº, any...... analysis in which the verb moves into an Xº which is the sister of IP may be compatible with what we say here. Various alternatives to this analysis have been explored in the literature, and here we will address two in particular: One alternative is that there is an asymmetry between subject...

  17. Assessment of realizability constraints in v2-f turbulence models

    International Nuclear Information System (INIS)

    Sveningsson, A.; Davidson, L.

    2004-01-01

    The use of the realizability constraint in v 2 -f turbulence models is assessed by computing a stator vane passage flow. In this flow the stagnation region is large and it is shown that the time scale bound suggested by [Int. J. Heat Fluid Flow 17 (1995) 89] is well suited to prevent unphysical growth of turbulence kinetic energy. However, this constraint causes numerical instabilities when used in the equation for the relaxation parameter, f. It is also shown that the standard use of the realizability constraint in the v 2 -f model is inconsistent and some modifications are suggested. These changes of the v 2 -f model are examined and shown to have negligible effect on the overall performance of the v 2 -f model. In this work two different versions of the v 2 -f model are investigated and the results obtained are compared with experimental data. The model on a form similar to that originally suggested by Durbin (e.g. [AIAA J. 33 (1995) 659]) produced the overall best agreement with stator vane heat transfer data

  18. Improving the police activities in ensuring the constitutional rights and freedoms of man and citizen and interaction with civil society institutions: comprehensive measures

    Directory of Open Access Journals (Sweden)

    Kirichek E.V.

    2014-12-01

    Full Text Available Russian police reform is another important step to modernize the country and public administration system. The main purpose of ongoing reforms is to create the modern and efficient law enforcement system, to form a new image of police officer in the XXI century and to change the social role of law enforcement agencies in society. Unfortunately, the results expected by society aren’t achieved. It’s stated that the reform is only at its beginning, many decisions are still to be made and implemented. The main focus is on comprehensive measures aimed at improving the police activities in ensuring the constitutional rights and freedoms of man and citizen and interaction with civil society institutions. Some features and problems of interaction between police and civil society institutions are considered. Statistics is provided. A number of constructive conclusions concerning further progressive development of interaction of police with civil society institutions are made. Despite the significant number of papers devoted to these issues, it’s necessary to note the insufficient elaboration of problems in this area. The reason is the ongoing reforms in Russia in general and police reform in particular, the instability of the current legislation regulating these issues. A lack of a clear concept of the reform, arising from a clear understanding of the police role and functions, is evident. These and other circumstances determine the topicality and practical importance of the research, the necessity of studying the peculiarities of police activities to improve its efficiency. They also indicate the need for scientific and practical recommendations.

  19. Mode of Action and Human Relevance Analysis for Nuclear Receptor-Mediated Liver Toxicity: A Case Study with Phenobarbital as a Model Constitutive Androstane Receptor (CAR) Activator

    Science.gov (United States)

    The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are key nuclear receptors involved in the regulation of cellular responses. to exposure to many xenobiotics and various physiological processes. Phenobarbital (PB) is a non­ genotoxic i...

  20. PI-RADS v2: Current standing and future outlook.

    Science.gov (United States)

    Smith, Clayton P; Türkbey, Barış

    2018-05-01

    The Prostate Imaging-Reporting and Data System (PI-RADS) was created in 2012 to establish standardization in prostate multiparametric magnetic resonance imaging (mpMRI) acquisition, interpretation, and reporting. In hopes of improving upon some of the PI-RADS v1 shortcomings, the PI-RADS Steering Committee released PI-RADS v2 in 2015. This paper reviews the accuracy, interobserver agreement, and clinical outcomes of PI-RADS v2 and comments on the limitations of the current literature. Overall, PI-RADS v2 shows improved sensitivity and similar specificity compared to PI-RADS v1. However, concerns exist regarding interobserver agreement and the heterogeneity of the study methodology.

  1. Radio Resource Management for V2V Discovery

    DEFF Research Database (Denmark)

    Alvarez, Beatriz Soret; Gatnau, Marta; Kovács, Istvan

    2016-01-01

    Big expectations are put into vehicular communications (V2X) for a safer and more intelligent driving. With human lives at risk, the system cannot afford to fail, which translates into very stringent reliability and latency requirements to the radio network. One of the challenges is to find...... efficient radio resource management (RRM) strategies for direct vehicle-to-vehicle (V2V) communication that can fulfil the requirements even with high traffic density. In cellular networks, a device-to-device (D2D) communication is usually split into two phases: the discovery process, for node awareness...... of each other; and the communication phase itself, where data exchange takes place. In the case of V2V, the discovery phase can utilize the status information that cars broadcast periodically as the beacons to detect the presence of neighbouring cars. For the delivery of specific messages (e...

  2. Charge transportation in polyaniline/V2O5 composites

    International Nuclear Information System (INIS)

    Huguenin, Fritz; Torresi, Roberto M.

    2004-01-01

    In this work, composites formed from a mixture of V 2 O 5 and polyaniline (PANI) were investigated, for applications as cathode materials for secondary lithium batteries. Electrochemical quartz crystal microbalance (EQCM) data show that charge compensation in the [PANI] 0.3 V 2 O 5 nanocomposite is achieved predominantly by Li + migration. However, the charge compensation in the [PANI]V 2 O 5 microcomposite occurs by Li + and Cl O 4 - transport. Electrochemical Impedance Spectroscopy (EIS) measurements reveal several benefits of nanohybrid formation, including the achievement of shorter ionic diffusion pathways, the higher diffusion rate of the lithium ion and also the higher electronic conductivity, which are responsible for a synergetic effect of the energy storage properties. (author)

  3. Toward a solution to the RAA and v2 puzzle for heavy quarks

    Directory of Open Access Journals (Sweden)

    Santosh K. Das

    2015-07-01

    Full Text Available The heavy quarks constitute a unique probe of the quark–gluon plasma properties. A puzzling relation between the nuclear modification factor RAA(pT and the elliptic flow v2(pT has been observed both at RHIC and LHC energies. Predicting correctly both observables has been a challenge to all existing models, especially for D mesons. We discuss how the temperature dependence of the heavy quark drag coefficient is responsible for a large part of such a puzzle. In particular, we have considered four different models to evaluate the temperature dependence of drag and diffusion coefficients propagating through a quark gluon plasma (QGP. All the four different models are set to reproduce the same RAA(pT observed in experiments at RHIC and LHC energy. We point out that for the same RAA(pT one can generate 2–3 times more v2 depending on the temperature dependence of the heavy quark drag coefficient. A non-decreasing drag coefficient as T→Tc is a major ingredient for a simultaneous description of RAA(pT and v2(pT.

  4. K2V2O2(AsO42

    Directory of Open Access Journals (Sweden)

    Thierry Roisnel

    2012-07-01

    Full Text Available The vanadium oxide arsenate with formula K2V2O2(AsO42, dipotassium divanadium(IV dioxide diarsenate, has been synthesized by solid-state reaction in an evacuated silica ampoule. Its structure is isotypic with K2V2O2(PO42. The framework is built up from corner-sharing VO6 octahedra and AsO4 tetrahedra, creating an infinite [VAsO8]∞ chain running along the a- and c-axis directions. The K+ cations are located in hexagonal tunnels, which are delimited by the connection of the [VAsO8]∞ chains.

  5. Crushed Salt Constitutive Model

    International Nuclear Information System (INIS)

    Callahan, G.D.

    1999-01-01

    The constitutive model used to describe the deformation of crushed salt is presented in this report. Two mechanisms -- dislocation creep and grain boundary diffusional pressure solution -- are combined to form the basis for the constitutive model governing the deformation of crushed salt. The constitutive model is generalized to represent three-dimensional states of stress. Upon complete consolidation, the crushed-salt model reproduces the Multimechanism Deformation (M-D) model typically used for the Waste Isolation Pilot Plant (WIPP) host geological formation salt. New shear consolidation tests are combined with an existing database that includes hydrostatic consolidation and shear consolidation tests conducted on WIPP and southeastern New Mexico salt. Nonlinear least-squares model fitting to the database produced two sets of material parameter values for the model -- one for the shear consolidation tests and one for a combination of the shear and hydrostatic consolidation tests. Using the parameter values determined from the fitted database, the constitutive model is validated against constant strain-rate tests. Shaft seal problems are analyzed to demonstrate model-predicted consolidation of the shaft seal crushed-salt component. Based on the fitting statistics, the ability of the model to predict the test data, and the ability of the model to predict load paths and test data outside of the fitted database, the model appears to capture the creep consolidation behavior of crushed salt reasonably well

  6. Communicative Constitution of Organizations

    DEFF Research Database (Denmark)

    Schoeneborn, Dennis; Vasquez, Consuelo

    2017-01-01

    The notion of the communicative constitution of organizations (CCO) is at the center of a growing theoretical development within organizational communication studies. CCO scholarship is based on the idea that organization emerges in and is sustained and transformed by communication. This entry...

  7. Gender and the Constitution

    Science.gov (United States)

    Ginsburg, Ruth Bader

    1975-01-01

    In discussing the constitutional aspects of the sex-role debate in the U.S. the author traces the tradition, compares the present criterion of equal protection to the equal rights argument, and analyzes the equality principle with reference to affirmative action and to childbearing and childrearing, supporting the proposed equal rights amendment.…

  8. constitutional adjudication in ethiopia

    African Journals Online (AJOL)

    eliasn

    2000-01-25

    Jan 25, 2000 ... Thus the seeds of what some authors call. “federal .... Pre-WWII Europe trusted its legislature and led to .... European and Civil Law Forum v. 11 ...... on the sovereignty of nationalities and the fact that language constitutes one.

  9. The constitutive sofa cushion

    DEFF Research Database (Denmark)

    Hanghøj, Sara

    2009-01-01

    personal values materialize through a hand-made everyday artefact, and how can the artefact constitute action and self-perception? The empirical research and analysis concerns how a former textile crafts teacher's subjective values and professional identity materialize through a hand-woven sofa cushion...

  10. A Prospect and Challenges for Adopting Constitutional Complaint and Constitutional Question in the Indonesian Constitutional Court

    OpenAIRE

    Faiz, Pan Mohamad

    2016-01-01

    A jurisdiction of the Indonesian Constitutional Court concerning constitutional adjudication is only limited to review the constitutionality of national law. There is no mechanism for challenging any decision or action made by public authorities that violate fundamental rights enshrined in the Indonesian Constitution. This article argues that constitutional complaint and constitutional question might be adopted as new jurisdictions of the Indonesian Constitutional Court in order to strengthen...

  11. Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines

    International Nuclear Information System (INIS)

    Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

    2011-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin 1β. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression.

  12. A new Xist allele driven by a constitutively active promoter is dominated by Xist locus environment and exhibits the parent-of-origin effects.

    Science.gov (United States)

    Amakawa, Yuko; Sakata, Yuka; Hoki, Yuko; Arata, Satoru; Shioda, Seiji; Fukagawa, Tatsuo; Sasaki, Hiroyuki; Sado, Takashi

    2015-12-15

    The dosage difference of X-linked genes between the sexes in mammals is compensated for by genetic inactivation of one of the X chromosomes in XX females. A noncoding RNA transcribed from the Xist gene at the onset of X chromosome inactivation coats the X chromosome in cis and induces chromosome-wide heterochromatinization. Here, we report a new Xist allele (Xist(CAG)) driven by a CAG promoter, which is known to be constitutively active in many types of cells. The paternal transmission of Xist(CAG) resulted in the preferential inactivation of the targeted paternal X (Xp) not only in the extra-embryonic but also the embryonic lineage, whereas maternal transmission ended with embryonic lethality at the early postimplantation stage with a phenotype that resembled mutant embryos carrying a maternal deficiency in Tsix, an antisense negative regulator of Xist, in both sexes. Interestingly, we found that the upregulation of Xist(CAG) in preimplantation embryos temporally differed depending on its parental origin: its expression started at the 4- to 8-cell stages when paternally inherited, and Xist(CAG) was upregulated at the blastocyst stage when maternally inherited. This might indicate that the Xist locus on Xp is permissive to transcription, but the Xist locus on the maternal X (Xm) is not. We extrapolated from these findings that the maternal Xist allele might manifest a chromatin structure inaccessible by transcription factors relative to the paternal allele. This might underlie the mechanism for the maternal repression of Xist at the early cleavage stage when Tsix expression has not yet occurred on Xm. © 2015. Published by The Company of Biologists Ltd.

  13. HRAS mutations in Costello syndrome: detection of constitutional activating mutations in codon 12 and 13 and loss of wild-type allele in malignancy.

    Science.gov (United States)

    Estep, Anne L; Tidyman, William E; Teitell, Michael A; Cotter, Philip D; Rauen, Katherine A

    2006-01-01

    Costello syndrome (CS) is a complex developmental disorder involving characteristic craniofacial features, failure to thrive, developmental delay, cardiac and skeletal anomalies, and a predisposition to develop neoplasia. Based on similarities with other cancer syndromes, we previously hypothesized that CS is likely due to activation of signal transduction through the Ras/MAPK pathway [Tartaglia et al., 2003]. In this study, the HRAS coding region was sequenced for mutations in a large, well-characterized cohort of 36 CS patients. Heterogeneous missense point mutations predicting an amino acid substitution were identified in 33/36 (92%) patients. The majority (91%) had a 34G --> A transition in codon 12. Less frequent mutations included 35G --> C (codon 12) and 37G --> T (codon 13). Parental samples did not have an HRAS mutation supporting the hypothesis of de novo heterogeneous mutations. There is phenotypic variability among patients with a 34G --> A transition. The most consistent features included characteristic facies and skin, failure to thrive, developmental delay, musculoskeletal abnormalities, visual impairment, cardiac abnormalities, and generalized hyperpigmentation. The two patients with 35G --> C had cardiac arrhythmias whereas one patient with a 37G --> T transversion had an enlarged aortic root. Of the patients with a clinical diagnosis of CS, neoplasia was the most consistent phenotypic feature for predicating an HRAS mutation. To gain an understanding of the relationship between constitutional HRAS mutations and malignancy, HRAS was sequenced in an advanced biphasic rhabdomyosarcoma/fibrosarcoma from an individual with a 34G --> A mutation. Loss of the wild-type HRAS allele was observed, suggesting tumorigenesis in CS patients is accompanied by additional somatic changes affecting HRAS. Finally, due to phenotypic overlap between CS and cardio-facio-cutaneous (CFC) syndromes, the HRAS coding region was sequenced in a well-characterized CFC cohort

  14. CRISTAL V2 Package: Principles and validation domain

    International Nuclear Information System (INIS)

    Gomit, Jean-Michel; Cochet, Bertrand; Leclaire, Nicolas; Carmouze, Coralie; Damian, Frederic; Entringer, Arnaud; Gagnier, Emmanuel

    2017-04-01

    The purpose of this document is to provide a comprehensive and global view of the CRISTAL V2 package. In particular, it sets out the principles of the computational approaches available to the user, through four calculation 'routes': - the 'multigroup Monte Carlo' route, - the 'multigroup deterministic' route, - the 'point-wise Monte Carlo' route, - the 'criticality standard calculation' route. (authors)

  15. A Innovative Engineering Summer School V2.0

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Larsen, Peter Gorm

    2010-01-01

    This article describes a summer school which focuses on a conceive-design project. The summer school has been run three times; each of the implementations is described. The last implementation (v2.0) is discussed and four challenges are identified and discussed in detail: assignments, the role...

  16. What constitutes information integrity?

    Directory of Open Access Journals (Sweden)

    S. Flowerday

    2008-01-01

    Full Text Available This research focused on what constitutes information integrity as this is a problem facing companies today. Moreover, information integrity is a pillar of information security and is required in order to have a sound security management programme. However, it is acknowledged that 100% information integrity is not currently achievable due to various limitations and therefore the auditing concept of reasonable assurance is adopted. This is in line with the concept that 100% information security is not achievable and the notion that adequate security is the goal, using appropriate countermeasures. The main contribution of this article is to illustrate the importance of and provide a macro view of what constitutes information integrity. The findings are in harmony with Samuel Johnson's words (1751: 'Integrity without knowledge is weak and useless, and knowledge without integrity is dangerous and dreadful.'

  17. What constitutes information integrity?

    Directory of Open Access Journals (Sweden)

    S. Flowerday

    2007-12-01

    Full Text Available This research focused on what constitutes information integrity as this is a problem facing companies today. Moreover, information integrity is a pillar of information security and is required in order to have a sound security management programme. However, it is acknowledged that 100% information integrity is not currently achievable due to various limitations and therefore the auditing concept of reasonable assurance is adopted. This is in line with the concept that 100% information security is not achievable and the notion that adequate security is the goal, using appropriate countermeasures. The main contribution of this article is to illustrate the importance of and provide a macro view of what constitutes information integrity. The findings are in harmony with Samuel Johnson's words (1751: 'Integrity without knowledge is weak and useless, and knowledge without integrity is dangerous and dreadful.'

  18. The constitutional view

    Directory of Open Access Journals (Sweden)

    Roberto Horácio Sá Pereira

    2016-05-01

    Full Text Available http://dx.doi.org/10.5007/1808-1711.2016v20n2p165   This brief paper is devoted to criticizing the widespread reading of Kant’s first Critique, according to which reference to subject-independent objects is “constituted” by higherorder cognitive abilities (concepts. Let us call this the “constitutional view”. In this paper, I argue that the constitutional reading confuses the un-Kantian problem of how we come to represent objects (which I call the intentionality thesis, with the quite different problem of how we cognize (erkennen (which I call the “cognition thesis” that we do represent objects, that is, things that exist independently of the subject.

  19. Transnational Governance and Constitutionalism

    DEFF Research Database (Denmark)

    Joerges, Christian; Sand, Inger-Johanne; Teubner, Gunther

    of democratic governance. The book refers to this term as a yardstick to which then contributors feel committed even where they plead for a reconceptualisation of constitutionalism or a discussion of its functional equivalents. 'Transnational governance' is neither public nor private, nor purely international......The term transnational governance designates untraditional types of international and regional collaboration among both public and private actors. These legally-structured or less formal arrangements link economic, scientific and technological spheres with political and legal processes...

  20. Modernization and safety improvement project of the NPP V-2 Jaslovske Bohunice

    International Nuclear Information System (INIS)

    Michal, V.; Losonsky, B.; Magdolen, J.

    2000-01-01

    This contribution deals with the form, present state, and results of the Nuclear Power Plants Research Institute (the Slovak acronym is VUJE - Vyskumny Ustav Jadrovych Elektrarni) participation in the NPP V-2 Jaslovske Bohunice Modernization and Safety Improvement Project. A short description of VUJE history, activity, and results is also presented as well as NPPs Jaslovske Bohunice characterization. VUJE was established in 1977 and deals with scientific and research needs of nuclear power plants, such as design, construction, commissioning and operation. The next fields of VUJE activity are, NPP reconstruction, NPP personnel training, radioactive waste management technology, and NPP decommissioning. The nuclear power plant, Jaslovske Bohunice, is situated approximately 15 km from the district town of Trnava in the southwestern region of the Slovak Republic. The construction of the first Czechoslovak NPP A-1 began on this site in 1957 .The construction of the double-unit NPP V-1 with WWER-440 (type V-230) reactor began in 1972. The first unit of NPP V-1 began operation in 1978 and the second in 1980. NPPs construction on the Bohunice site continued with NPP V-2, which has two units with WWER-440 (type V-213) reactors. Unit 1 and Unit 2 of NPP V-2 were commissioned in 1984 and 1985, respectively. Slovak electric utility Slovenske elektrarne (SE) is the owner/commissioner of NPP V-2. This NPP is responsible for more than 20% of the total electrical energy production of SE, making it an essential supporter of the Slovak economy. (authors)

  1. PROMIS®-29 v2.0 profile physical and mental health summary scores.

    Science.gov (United States)

    Hays, Ron D; Spritzer, Karen L; Schalet, Benjamin D; Cella, David

    2018-03-22

    The PROMIS-29 v2.0 profile assesses pain intensity using a single 0-10 numeric rating item and seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) using four items per domain. This paper describes the development of physical and mental health summary scores for the PROMIS-29 v2.0. We conducted factor analyses of PROMIS-29 scales on data collected from two internet panels (n = 3000 and 2000). Confirmatory factor analyses provided support for a physical health factor defined by physical function, pain (interference and intensity), and ability to participate in social roles and activities, and a mental health factor defined primarily by emotional distress (anxiety and depressive symptoms). Reliabilities for these two summary scores were 0.98 (physical health) and 0.97 (mental health). Correlations of the PROMIS-29 v2.0 physical and mental health summary scores with chronic conditions and other health-related quality of life measures were consistent with a priori hypotheses. This study develops and provides preliminary evidence supporting the reliability and validity of PROMIS-29 v2.0 physical and mental health summary scores that can be used in future studies to assess impacts of health care interventions and track changes in health over time. Further evaluation of these and alternative summary measures is recommended.

  2. Local structural and electronic properties of V2O3 and ZnV2O4

    International Nuclear Information System (INIS)

    Pfalzer, P.

    2004-01-01

    In this thesis the electronically correlated transition metal oxide compounds V 2 O 3 and ZnV 2 O 4 , which are of basic interest for solid state physics, are investigated using X-ray absorption techniques. Measurements of the fine structure at Vanadium and Oxygen K absorption edges together with a comparison to theoretically calculated spectra show that the local properties of these materials, which under certain conditions deviate drastically from the long-range properties known so far, crucially influence the characteristic behaviour. It is shown that the two insulating phases of V 2 O 3 (the paramagnetic insulating (PI) and the antiferromagnetic insulating (AFI) phase) exhibit very similar local properties which are well distinguished from those of the paramagnetic metallic (PM) phase. In particular, a disagreement is found between the local and the long-range spatial symmetry of the PI phase. It is further shown that at the metal-insulator transition from the PM to the AFI phase structural changes preceed changes of the electronic and magnetic properties. This suggests that the metal-insulator transition is structurally driven. In ZnV 2 O 4 characteristic differences are found between the local properties of single crystalline and powdered samples. These originate either from strain in the single crystals or from anisotropy of the electronic states

  3. Constitutive Activation of the G-Protein Subunit G[alpha]s within Forebrain Neurons Causes PKA-Dependent Alterations in Fear Conditioning and Cortical "Arc" mRNA Expression

    Science.gov (United States)

    Kelly, Michele P.; Cheung, York-Fong; Favilla, Christopher; Siegel, Steven J.; Kanes, Stephen J.; Houslay, Miles D.; Abel, Ted

    2008-01-01

    Memory formation requires cAMP signaling; thus, this cascade has been of great interest in the search for cognitive enhancers. Given that medications are administered long-term, we determined the effects of chronically increasing cAMP synthesis in the brain by expressing a constitutively active isoform of the G-protein subunit G[alpha]s…

  4. Listeria-vectored vaccine expressing the Mycobacterium tuberculosis 30 kDa major secretory protein via the constitutively active prfA* regulon boosts BCG efficacy against tuberculosis.

    Science.gov (United States)

    Jia, Qingmei; Dillon, Barbara Jane; Masleša-Galić, Saša; Horwitz, Marcus A

    2017-06-19

    A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm Δ actA (LmI), rLm Δ actA Δ inlB (LmII), and rLm Δ actA Δ inlB prfA * (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30). All five rLm30 vaccines secreted r30 in broth and macrophages; while rLm expressing r30 via a constitutively active prfA * regulon (rLmIII/a30) expressed the greatest amount of r30 in broth culture, all five rLm vaccines expressed equivalent amounts of r30 in infected macrophages. In comparative studies, boosting BCG-immunized mice with rLmIII/a30 induced the strongest antigen-specific T-cell responses, including splenic and lung polyfunctional CD4+ T-cells expressing the three cytokines of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) ( P vaccines were generally more potent booster vaccines than r30 in adjuvant and a recombinant adenovirus vaccine expressing r30. In a setting in which BCG alone was highly immunoprotective, boosting mice with rLmIII/a30, the most potent of the vaccines, significantly enhanced protection against aerosolized Mtb ( P <0.01). Copyright © 2017 American Society for Microbiology.

  5. Vanadium oxide V2O5 reaction with calcium metavanadate

    International Nuclear Information System (INIS)

    Krasnenko, T.I.; Slobodin, B.V.; Zhilyaev, V.A.

    1983-01-01

    Complex physicochemical studies on the V 2 O 5 Ca(VO 3 ) 2 mixtures, annealed under different conditions, were conducted. It was established that the V 2 O 5 -Ca(VO 3 ) 2 system is characterized by the following features: defective structure of initial components, which are in equilibrium state; irreversible structural transformation without changes in the macrosymmetry (530 deg C) of calcium metavanadate, deficient in calcium and oxygen; melting of eutectic mixture of components which are in equilibrium at 616+-3 deg C; Ca(VO 3 ) 2 melting with decomposition at 775+-3 deg C. Besides this, the formation of oxide vanadium bronze of β-type calcium is possible under some conditions (narrow temperature range, certain partial oxygen pressure, etc)

  6. V2 word order in subordinate clauses in spoken Danish

    DEFF Research Database (Denmark)

    Jensen, Torben Juel; Christensen, Tanya Karoli

    are asymmetrically distributed, we argue that the word order difference should rather be seen as a signal of (subtle) semantic differences. In main clauses, V3 is highly marked in comparison to V2, and occurs in what may be called emotives. In subordinate clauses, V2 is marked and signals what has been called...... ”assertiveness”, but is rather a question of foregrounding (cf. Simons 2007: Main Point of Utterance). The paper presents the results of a study of word order in subordinate clauses in contemporary spoken Danish and focuses on how to include the proposed semantic difference as a factor influencing the choice...... studies of two age cohorts of speakers in Copenhagen, recorded in the 1980s and again in 2005-07, and on recent recordings with two age cohorts of speakers from the western part of Jutland. This makes it possible to study variation and change with respect to word order in subordinate clauses in both real...

  7. Testing the QA Method for Calculating Jet v_{2}

    CERN Document Server

    Mueller, Jason

    2014-01-01

    For the summer, I was assigned to work on the ALICE experiment with Alice Ohlson. I wrote several programs throughout the summer that were used to calculate jet v 2 using a non-standard method described by my supervisor in her Ph.D. thesis. Though the project is not yet complete, significant progress has been made, and the results so far seem promising.

  8. KASS v.2.2. scheduling software for construction

    OpenAIRE

    Krzemiński Michał

    2016-01-01

    The paper presents fourth version of specialist useful software in scheduling KASS v.2.2 (Algorithm Scheduling Krzeminski System). KASS software is designed for construction scheduling, specially form flow shop models. The program is being dedicated closely for the purposes of the construction. In distinguishing to other used programs in tasks of this type operational research criteria were designed closely with the thought about construction works and about the specificity of the building pr...

  9. Muon-oxygen bonding in V2O3

    International Nuclear Information System (INIS)

    Chan, K.C.B.; Lichti, R.L.; Boekema, C.

    1986-01-01

    A muon site search using calculated internal fields has been performed for V 2 O 3 , where purely dipolar fields allow a site determination free from covalent complications. The obtained sites are a subset of the Rodriguez and Bates sites found in α-Fe 2 O 3 and indicate muon oxygen bond formation. The sites missing at low temperatures are consistent with the vanadium pairing mechanism for the metal-to-insulator (corundum-to-monoclinic) phase transition. (orig.)

  10. The Normative Constitution of Agency

    OpenAIRE

    Korsgaard, Christine M.

    2014-01-01

    On a naturalistic conception of agency, someone is an agent when certain of his own mental states are the cause of his movements. On a normative conception, a person constitutes his agency by following certain principles or laws. In Kant’s conception, for example, a movement counts as the agent’s own when it is chosen autonomously, that is, in accordance with the categorical imperative. To say that someone acts is to imply that his movements are a manifestation of his own activity and that it...

  11. Main modelling features of the ASTEC V2.1 major version

    International Nuclear Information System (INIS)

    Chatelard, P.; Belon, S.; Bosland, L.; Carénini, L.; Coindreau, O.; Cousin, F.; Marchetto, C.; Nowack, H.; Piar, L.; Chailan, L.

    2016-01-01

    Highlights: • Recent modelling improvements of the ASTEC European severe accident code are outlined. • Key new physical models now available in the ASTEC V2.1 major version are described. • ASTEC progress towards a multi-design reactor code is illustrated for BWR and PHWR. • ASTEC strong link with the on-going EC CESAM FP7 project is emphasized. • Main remaining modelling issues (on which IRSN efforts are now directing) are given. - Abstract: A new major version of the European severe accident integral code ASTEC, developed by IRSN with some GRS support, was delivered in November 2015 to the ASTEC worldwide community. Main modelling features of this V2.1 version are summarised in this paper. In particular, the in-vessel coupling technique between the reactor coolant system thermal-hydraulics module and the core degradation module has been strongly re-engineered to remove some well-known weaknesses of the former V2.0 series. The V2.1 version also includes new core degradation models specifically addressing BWR and PHWR reactor types, as well as several other physical modelling improvements, notably on reflooding of severely damaged cores, Zircaloy oxidation under air atmosphere, corium coolability during corium concrete interaction and source term evaluation. Moreover, this V2.1 version constitutes the back-bone of the CESAM FP7 project, which final objective is to further improve ASTEC for use in Severe Accident Management analysis of the Gen.II–III nuclear power plants presently under operation or foreseen in near future in Europe. As part of this European project, IRSN efforts to continuously improve both code numerical robustness and computing performances at plant scale as well as users’ tools are being intensified. Besides, ASTEC will continue capitalising the whole knowledge on severe accidents phenomenology by progressively keeping physical models at the state of the art through a regular feed-back from the interpretation of the current and

  12. Economic impact of V2G technology in a smart microgrid

    Science.gov (United States)

    Anastasiadis, Anestis G.; Polyzakis, Apostolos; Vokas, Georgios A.

    2018-05-01

    With serious concerns on global warming and energy crisis, there are plenty of motivations for developing and commercializing plug-in Electric Vehicles (EVs). It is believed that substitution of EVs for conventional fuel vehicles can help reduce the greenhouse gases emission, increase the energy efficiency, enhance the integration of renewable energy, and so forth. These advantages originate from the double role of the electrical vehicle's battery. Thus, it may constitute firstly a controllable load that we are able to optimally control at convenient time frames and secondly, it may store and inject energy, acting as a storage device. Nowadays, a number of EVs use power grids around the world to charge and discharge their batteries. Smart Microgrids (SMs) seem to be the best solution for the management of modern Low Voltage (LV) grids with Distributed Energy Resources (DER) and EVs. Among these technologies, EVs pose both a risk by increasing the peak load as well as an opportunity for the existing energy management systems by charging and discharging electricity with the help of Vehicle-to-Grid (V2G) technology. The key to the implementation of V2G is how to effectively integrate information into energy conversion, transmission and distribution. V2G should be carried out within the framework of SM, so that the status information of power grid can be perceived. In this paper, a Low Voltage (LV) SM derived from an interconnection bus is considered which is characterized by the presence of DERs units and EVs. Firstly, an overview of plug in EV technologies is examined and then the main purpose of the paper is to investigate the effects of V2G charging and discharging strategies in a SM. With EVs and absence of DERs is considered as the base case. For each scenario, two different charging technologies are examined (Dump Charging and V2G) in terms of operational cost. All data are taken from Hellenic Distribution/Transmission System Operators and Hellenic Operator of

  13. Constitutive overexpression of cytochrome P450 associated with imidacloprid resistance in Laodelphax striatellus (Fallén).

    Science.gov (United States)

    Elzaki, Mohammed Esmail Abdalla; Zhang, Wanfang; Feng, Ai; Qiou, Xiaoyan; Zhao, Wanxue; Han, Zhaojun

    2016-05-01

    Imidacloprid is a principal insecticide for controlling rice planthoppers worldwide. Resistance to imidacloprid has been reported in a field population of Laodelphax striatellus. The present work was conducted to study the molecular mechanisms of imidacloprid resistance. An imidacloprid-resistant strain was produced by selecting a field population with imidacloprid for 24 generations. Piperonyl butoxide (PBO) showed a 1.70-fold synergistic effect. Enzyme activity assays were conducted, and cytochrome P450 monooxygenase showed 1.88-fold activity. The mRNA expression levels of 57 P450 genes were compared. Four CYP genes were found to be overexpressed and significantly different to the susceptible strain. Four strains were selected with imidacloprid for a short period, and the expression levels of ten identified detoxification genes were then compared. Only CYP353D1v2 overexpressed and was significantly different to the susceptible strain. Strong correlation was found between CYP353D1v2 expression levels and imidacloprid treatments. Additionally, gene-silencing RNAi via dsRNA feeding showed that depressing the expression of CYP353D1v2 could significantly enhance the sensitivity of L. striatellus to imidacloprid. Constitutive overexpression of four CYP genes was associated with imidacloprid resistance in long-term selection, and expression of CYP353D1v2 with imidacloprid resistance in short-term selection in L. striatellus. © 2015 Society of Chemical Industry.

  14. Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2.

    Science.gov (United States)

    Zarella, Mark D; Ts'o, Daniel Y

    2017-01-01

    Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure-ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure-ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure-ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization.

  15. Controlling the formation of rodlike V2O5 nanocrystals on reduced graphene oxide for high-performance supercapacitors.

    Science.gov (United States)

    Li, Meili; Sun, Guoying; Yin, Pingping; Ruan, Changping; Ai, Kelong

    2013-11-13

    Vanadium pentoxide (V2O5) has attracted much attention for energy storage application because of its high Faradaic activity and stable crystal structure, which make it a promising electrode material for supercapacitors. However, the low electronic conductivity and small lithium-ion diffusion coefficient of V2O5 limit its practical applications. To overcome these limitations, a facile and efficient method is here demonstrated for the fabrication of V2O5/reduced graphene oxide (rGO) nanocomposites as electrode materials for supercapacitors. With this method, the reduction of graphene oxide can be achieved in a cost-effective and environmentally friendly solvent, without the addition of any other toxic reducing agent. Importantly, this solvent can control the formation of the uniform rodlike V2O5 nanocrystals on the surface of rGO. Compared to pure V2O5 microspheres, the V2O5/rGO nanocomposites exhibited a higher specific capacitance of 537 F g(-1) at a current density of 1 A g(-1) in neutral aqueous electrolytes, a higher energy density of 74.58 Wh kg(-1) at a power density of 500 W kg(-1), and better stability even after 1000 charge/discharge cycles. Their excellent performances can be attributed to the synergistic effect of rGO and rodlike V2O5 nanocrystals. Such impressive results may promote new opportunities for these electrode materials in high-energy-density storage systems.

  16. The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture.

    Science.gov (United States)

    Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

    2014-05-01

    Voltage-gated Ca(2+) channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca(2+) channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca(2+) channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca(2+) channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3(-/-) mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca(2+) influx into RTN neurons can trigger small-conductance Ca(2+)-activated K(+)-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca(2+) channels in rodent sleep. The role of CaV2.3 Ca(2+) channels was analyzed in CaV2.3(-/-) mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3(-/-) mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca(2+) channel expression. The detailed mechanisms of SWS increase in CaV2.3(-/-) mice remain to be determined. Low-voltage activated CaV2.3 R-type Ca(2+) channels in the thalamocortical loop and extra

  17. Functional importance of the Ala(116)-Pro(136) region in the calcium-sensing receptor. Constitutive activity and inverse agonism in a family C G-protein-coupled receptor

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Spalding, T A; Burstein, E S

    2000-01-01

    The calcium-sensing receptor (CaR) belongs to family C of the G-protein-coupled receptor superfamily. To date 14 activating mutations in CaR showing increased sensitivity to Ca(2+) have been identified in humans with autosomal dominant hypocalcemia. Four of these activating mutations are found......, suppressed the elevated basal response of the constitutively activated Ca/1a mutants demonstrating inverse agonist activity of CPCCOEt. Taken together, our results demonstrate that the Ala(116)-Pro(136) region is of key importance for the maintenance of the inactive conformation of CaR....

  18. PISCES-v2: an ocean biogeochemical model for carbon and ecosystem studies

    Directory of Open Access Journals (Sweden)

    O. Aumont

    2015-08-01

    of marine ecosystems (phytoplankton, microzooplankton and mesozooplankton and the biogeochemical cycles of carbon and of the main nutrients (P, N, Fe, and Si. The model is intended to be used for both regional and global configurations at high or low spatial resolutions as well as for short-term (seasonal, interannual and long-term (climate change, paleoceanography analyses. There are 24 prognostic variables (tracers including two phytoplankton compartments (diatoms and nanophytoplankton, two zooplankton size classes (microzooplankton and mesozooplankton and a description of the carbonate chemistry. Formulations in PISCES-v2 are based on a mixed Monod–quota formalism. On the one hand, stoichiometry of C / N / P is fixed and growth rate of phytoplankton is limited by the external availability in N, P and Si. On the other hand, the iron and silicon quotas are variable and the growth rate of phytoplankton is limited by the internal availability in Fe. Various parameterizations can be activated in PISCES-v2, setting, for instance, the complexity of iron chemistry or the description of particulate organic materials. So far, PISCES-v2 has been coupled to the Nucleus for European Modelling of the Ocean (NEMO and Regional Ocean Modeling System (ROMS systems. A full description of PISCES-v2 and of its optional functionalities is provided here. The results of a quasi-steady-state simulation are presented and evaluated against diverse observational and satellite-derived data. Finally, some of the new functionalities of PISCES-v2 are tested in a series of sensitivity experiments.

  19. Constitution, 5 May 1989.

    Science.gov (United States)

    1989-01-01

    This document contains provisions of Cambodia's Constitution of May 5, 1989. Article 7 gives men and women equal rights in marriage and the family, calls for monogamous marriages, and affords social protection to mothers and children. Article 8 guides parent-child relationships. The 14th article defines state property, and the 15th gives citizens full rights to own, use, and inherit land. The use of agricultural and forested land can only be changed with permission. Article 22 assigns educational responsibilities to the state, including free elementary education and a gradual expansion of higher education. Adult literacy classes are also promoted. Article 26 guarantees free medical consultations, and article 27 gives women a 90-day paid maternity leave. Breast-feeding women are also given special privileges. Article 33 guarantees the right to pay equity and to social security benefits. Article 36 grants the freedom to travel, the inviolability of homes, and privacy in correspondence of all types.

  20. The Constitutional Court and the Imperative of its Reform

    Directory of Open Access Journals (Sweden)

    Claudia Gilia

    2012-12-01

    Full Text Available Recent debates on the upcoming review of the Constitution have determined us to pay close attention to the basic institution in a democratic state, that is the Constitutional Court. Being caught in the crossfire between power and opposition, the Constitutional Court had a hard time lately, facing severe attacks. The aim of our study is to analyze the evolution of the Constitutional Court within the inland constitutional system, particularly bringing up the flaws describing the Court’s activity. We have also analyzed the proposals put forth by several bodies or experts regarding the constitutional contentious court. At the end of our study, following an analysis of different constitutional types of constitutional review, used by a number of states in Europe, we introduced several resolutions that may improve the role, the course and, last but not least, the activity of the Romanian Constitutional Court.

  1. Critical Elements of Vehicle-to-Grid (V2G) Economics

    Energy Technology Data Exchange (ETDEWEB)

    Steward, Darlene M. [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-07

    This report explores the critical elements of V2G economics. Section 2 summarizes the elements and costs of a V2G system. Section 3 describes V2G revenue-generating services and the business cases for providing these services. Section 4 notes real-world V2G applications. Section 5 lists concerns related to V2G. Section 6 concludes and summarizes V2G cost and revenue elements.

  2. Radiation supervision - NPPs A-1, V-1, V-2

    International Nuclear Information System (INIS)

    2000-01-01

    In this leaflet the radiation supervision of the nuclear power plants A-1, V-1, V-2 is presented. Off-site radiation supervision laboratory is a part of monitoring scheme of the NPPs. More than 1150 samples are taken from the environment annually. The tele-dosimetric system was constructed to improve the quality of the Bohunice NPPs operation impacts supervision. It has been running in a continuous operation from 1992 and providing supervision of the nuclear power plant off-site area within 25 kilometres. The tele-dosimetric system is described

  3. COUNTERMAJORITARIAN INSTITUTIONS IN THE RUSSIAN CONSTITUTION OF 1993 AS AN INSTRUMENT ENSURING CONSTITUTIONAL AND POLITICAL STABILITY

    Directory of Open Access Journals (Sweden)

    S. Shakhray

    2018-01-01

    Full Text Available The article enriches the discussion on the legal reasons and conditions fostering the viability of democratic constitutions by analyzing the rich experience of the Russian Constitution of 1993. Particular attention is paid to the concept of countermajoritarian institutions. The authors elaborate the idea that countermajoritarian institutions can play an important role in ensuring the viability (put in other terms, the proper balance between stability, adaptability, and dynamic development of modern democratic constitutions as well as political regimes.The article presents evidence-based data showing that the President and the Constitutional Court of the Russian Federation systematically acted as countermajoritarian institutions at the initial stage of the implementation of the “blueprint for the future” set down in the 1993 Russian Constitution. As a result of the activities of these institutions, strong legal frameworks were created that are necessary for the establishment of anew constitutional system of the Russian state and law.Today, the Russian Constitution of 1993 is one of the longest lasting democratic constitutions in the world (the average “life expectancy” of democratic constitutions adopted over the past 250 years is about seventeen years. The study of the countermajoritarian provisions in the 1993 Russian Constitution is of both theoretical and practical importance. In particular, the results of the study can be useful in creating efficient legal instruments for the maintenance of political stability and social development management both within sovereign states and within interstate communities.

  4. Core-logs of the vertical borehole V2

    International Nuclear Information System (INIS)

    Carlsson, L.; Egerth, T.; Westlund, B.; Olsson, T.

    1982-08-01

    In the hydrogeological programme of the Stripa Project, borehole V2 was prolonged to a final depth of 822 m. The previous core from 0-471.4 m was relogged. The drill core was logged with regard to rock characteristics, fracture frequency, dipping and filling. The results are presented as core-logs and fracture diagrams. Borehole V2 shows similar characteristics as found in other drillings in the Stripa Mine. It penetrates Stripa granite to its full depth. recorded fractures shows a clear predominance of medium-steep fractures, while flat-lying fractures are more sparsly occuring, a fact which is even more pronounced below 400 m depth. Due to the vertical direction of the borehole, steeply dipping fractures are underestimated in the core. The mean fracture frequency, related to the total length of the core, is 2.1 fractures/m. Chlorite, calcite and epidote are the dominating coating minerals in the fractures, each making up about 25-30 percent of all coated fractures. (Authors)

  5. Constitutive models in LAME.

    Energy Technology Data Exchange (ETDEWEB)

    Hammerand, Daniel Carl; Scherzinger, William Mark

    2007-09-01

    The Library of Advanced Materials for Engineering (LAME) provides a common repository for constitutive models that can be used in computational solid mechanics codes. A number of models including both hypoelastic (rate) and hyperelastic (total strain) constitutive forms have been implemented in LAME. The structure and testing of LAME is described in Scherzinger and Hammerand ([3] and [4]). The purpose of the present report is to describe the material models which have already been implemented into LAME. The descriptions are designed to give useful information to both analysts and code developers. Thus far, 33 non-ITAR/non-CRADA protected material models have been incorporated. These include everything from the simple isotropic linear elastic models to a number of elastic-plastic models for metals to models for honeycomb, foams, potting epoxies and rubber. A complete description of each model is outside the scope of the current report. Rather, the aim here is to delineate the properties, state variables, functions, and methods for each model. However, a brief description of some of the constitutive details is provided for a number of the material models. Where appropriate, the SAND reports available for each model have been cited. Many models have state variable aliases for some or all of their state variables. These alias names can be used for outputting desired quantities. The state variable aliases available for results output have been listed in this report. However, not all models use these aliases. For those models, no state variable names are listed. Nevertheless, the number of state variables employed by each model is always given. Currently, there are four possible functions for a material model. This report lists which of these four methods are employed in each material model. As far as analysts are concerned, this information is included only for the awareness purposes. The analyst can take confidence in the fact that model has been properly implemented

  6. ECHR and national constitutional courts

    Directory of Open Access Journals (Sweden)

    Nastić Maja

    2015-01-01

    Full Text Available Comprising fundamental rights and freedoms and establishing the effective control system, the European Convention on Human Rights (ECHR encroaches upon the area that is traditional reserved for constitutional law. Although built on the doctrine reserved for international treaty law, the Convention goes beyond the traditional boundaries that exist between international and constitutional law. It has gradually infiltrated into the national legal systems. Constitutional courts have had the crucial role in this process. This paper will focus on the applicability of the ECHR in proceedings before national constitutional courts. Having in mind the jurisdiction of the national constitutional court, the ECHR may be applied in two ways: first, in the process of constitutional review by national constitutional courts and, second, in the process of deciding on constitutional complaints.

  7. VALUATION IN THE CONSTITUTIONAL ERA

    African Journals Online (AJOL)

    Brimer

    16 ..... stem from the pre-constitutional era, and the constitutional framework and its legitimate reform efforts. A decision on what is just ...... Carroll L Alice's Adventures in Wonderland (Digital Scanning Scituate MA. 2007). Dagan 1999 Va L Rev.

  8. New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists.

    Science.gov (United States)

    Yea, Christopher M; Allan, Christine E; Ashworth, Doreen M; Barnett, James; Baxter, Andy J; Broadbridge, Janice D; Franklin, Richard J; Hampton, Sally L; Hudson, Peter; Horton, John A; Jenkins, Paul D; Penson, Andy M; Pitt, Gary R W; Rivière, Pierre; Robson, Peter A; Rooker, David P; Semple, Graeme; Sheppard, Andy; Haigh, Robert M; Roe, Michael B

    2008-12-25

    Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. The analogue of AVP, desmopressin, has proven an effective drug for diseases where a reduction of urine output is desired. However, its peptidic nature limits its bioavailability. We report herein the discovery of potent, nonpeptidic, benzylurea derived agonists of the vasopressin V2 receptor. We describe substitutions on the benzyl group to give improvements in potency and subsequent modifications to the urea end group to provide improvements in solubility and increased oral efficacy in a rat model of diuresis. The lead compound 20e (VA106483) is reported for the first time and has been selected for clinical development.

  9. Legal theology in imposed constitutionalism

    DEFF Research Database (Denmark)

    Abat Ninet, Antoni

    2018-01-01

    The focus of this paper is the question of legitimacy, and how can we consider legitimate an imposed constitution and the subsequent constitutional principles, practices and values that go hand-in-hand with the legal and political acculturation. Constitutional texts around the world are good...

  10. The diffusion of constitutional rights

    NARCIS (Netherlands)

    Goderis, B.V.G.; Versteeg, M.

    Constitutions are commonly regarded as uniquely national products, shaped by domestic ideals and politics. This paper develops and empirically investigates a novel hypothesis, which is that constitutions are also shaped by transnational influence, or “diffusion.” Constitutional rights can diffuse

  11. Ontoteleological Constitution of Entrepreneurship

    Directory of Open Access Journals (Sweden)

    Diego Luiz Teixeira Boava

    2017-06-01

    Full Text Available Entrepreneurship is a pluri-disciplinary phenomenon, object of research in several areas of knowledge. However, studies on this theme present approaches that start to consider entrepreneurship as a field of private knowledge in the phase of epistemological construction. In this context, the aim of this investigation is to contribute to the discussions on the theme, through studies on the ontoteleological constitution of entrepreneurship, in propaedeutic character, deflagrating new approaches. Thus, there is a presentation concerning the study of entrepreneurship, which may emphasize its ontical and ontological aspects. In addition, the reason why it is complex to define entrepreneurship is investigated. Subjects regarding the philosophy of entrepreneurship are introduced, seeking to present the bases for an ontoteleological approach to the phenomenon. Such an approach assumes that the finality of the entrepreneurial act relates to the main principles and transformations required into the organization. Finally, it is concluded that man is an entrepreneurial being, the meta-entrepreneur, and his entrepreneurial actions are not determined by external factors, but rather by the condition of his potentiality.

  12. Synthesis, surface properties and optical characteristics of CuV_2O_6 nanofibers

    International Nuclear Information System (INIS)

    Wang, Fengyun; Zhang, Hongchao; Liu, Lei; Shin, Byoungchul; Shan, Fukai

    2016-01-01

    In"3"+-doped CuV_2O_6 nanofibers were prepared via the hydrothermal synthesis method, which produced fibers with a typical diameter of 100 nm, and a length of 1–5 μm. The nanofibers grew in a preferred [020] direction. The crystal phase together with the structure was studied via X-ray polycrystalline diffraction (XRD) and the Rietveld refinement. The surface characteristics of this nanostructure were measured with a scanning electron microscope (SEM), energy dispersive spectra (EDS), transmission electron microscopy (TEM), and N_2–adsorption–desorption isotherms. Photo-activities were evaluated by optical absorption, luminescence, and decay behaviors. The band-gap structures and positions were investigated. The vanadate has an efficient optical absorption from the UV to the visible wavelength region with an indirect allowed transition characterized by the narrow gap energy of 1.96 eV. The photocatalysis was investigated by the photo-degradation of RhB solutions irradiated by visible light. Correspondingly, CuV_2O_6:In"3"+ nanofibers possess quenched luminescence and have a more efficient photocatalytic activity on the RhB degradation. Photocatalytic mechanisms were proposed based on the experimental results, the band-energy positions, and the trapping experiments. The coexistence of V"4"+/V"5"+ ions and induced-color centers was discussed on the proposed photocatalytic mechanism. The results demonstrated the promising potency of such In"3"+-doped CuV_2O_6 nanofibers for technological applications due to their high photo-activity and good cycling performance with the fiber morphology. - Highlights: • Recyclable α-CuV_2O_6 nanofibers were successfully prepared via hydrothermal synthesis. • In-doped α-CuV_2O_6 as a visible-light-driven photocatalyst was firstly developed. • The nanofibers display typical indirect allowed transitions with narrow band of 1.96 eV. • It presents high activity on RhB degradation under visible light irradiation. • The

  13. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis].

    Science.gov (United States)

    Morin, Denis

    2014-12-01

    Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  14. NONCODE v2.0: decoding the non-coding.

    Science.gov (United States)

    He, Shunmin; Liu, Changning; Skogerbø, Geir; Zhao, Haitao; Wang, Jie; Liu, Tao; Bai, Baoyan; Zhao, Yi; Chen, Runsheng

    2008-01-01

    The NONCODE database is an integrated knowledge database designed for the analysis of non-coding RNAs (ncRNAs). Since NONCODE was first released 3 years ago, the number of known ncRNAs has grown rapidly, and there is growing recognition that ncRNAs play important regulatory roles in most organisms. In the updated version of NONCODE (NONCODE v2.0), the number of collected ncRNAs has reached 206 226, including a wide range of microRNAs, Piwi-interacting RNAs and mRNA-like ncRNAs. The improvements brought to the database include not only new and updated ncRNA data sets, but also an incorporation of BLAST alignment search service and access through our custom UCSC Genome Browser. NONCODE can be found under http://www.noncode.org or http://noncode.bioinfo.org.cn.

  15. Developments and applications of DAQ framework DABC v2

    International Nuclear Information System (INIS)

    Adamczewski-Musch, J; Kurz, N; Linev, S

    2015-01-01

    The Data Acquisition Backbone Core (DABC) is a software framework for distributed data acquisition. In 2013 Version 2 of DABC has been released with several improvements. For monitoring and control, an HTTP web server and a proprietary command channel socket have been provided. Web browser GUIs have been implemented for configuration and control of DABC and MBS DAQ nodes via such HTTP server. Several specific plug-ins, for example interfacing PEXOR/KINPEX optical readout PCIe boards, or HADES trbnet input and hld file output, have been further developed. In 2014, DABC v2 was applied for production data taking of the HADES collaboration's pion beam time at GSI. It fully replaced the functionality of the previous event builder software and added new features concerning online monitoring. (paper)

  16. Implications of V2G for owners and utilities

    Energy Technology Data Exchange (ETDEWEB)

    Usher, J. [Rapid Electric Vehicles Inc., Vancouver, BC (Canada)

    2010-07-01

    Rapid Electric Vehicles is an energy management company whose focus is on the convergence of the automotive and energy industries. This presentation discussed Rapid Electric Vehicles and challenges it faces in its industries. Challenges that were discussed included oil production versus consumption; supply versus demand; and energy crossroads. Concerns expressed by BC Hydro, Quebec Hydro and Manitoba Hydro were also presented. The presentation noted that the missing link is in the development and delivery of electric vehicles. The advancement of energy storage holds the promise of revolutionizing the power delivery system. Drivers for change include electric vehicles and V2G. An economic case study was also presented. The case study identified ISO markets in North America, market benefits, business case background, and business case key assumptions. Key outputs, key sensitivities, and a sensitivity analysis were also presented. tabs., figs.

  17. Constitutive properties of salt from four sites

    International Nuclear Information System (INIS)

    Pfeifle, T.W.; Mellegard, K.D.; Senseny, P.E.

    1983-04-01

    Results are presented from laboratory strength and creep tests performed on salt specimens from the Richton dome in Mississippi, the Vacherie dome in Louisiana, the Permian basin in Texas, and the Paradox basin in Utah. The constitutive properties obtained are the elastic moduli and the failure envelope at 24 0 C and parameter values for the baseline creep law. Some additional data are presented to indicate how the elastic moduli and strength change with temperature. The constitutive properties given in this report and subsequent numerical simulations will serve as input to the screening of site locations for a nuclear-waste repository. The matrix of tests performed is the minimum effort required to obtain these constitutive properties. Comparison of results with those obtained for sites that have been characterized in greater detail suggests that the constitutive parameter values obtained are adequate for site-screening activity

  18. Constitution, 1989. [Selected provisions].

    Science.gov (United States)

    1989-01-01

    Chapter XII of the Hungarian Constitution, 1989, details the Fundamental Rights and Duties of Citizens. Everyone lawfully within the territory of Hungary has the right to liberty of movement and the freedom to choose his or her residence, except when restricted by law, including the right to leave his or her residence or county. The Republic of Hungary grants asylum to foreign citizens who were persecuted for racial, religious ethnic, linguistic, or political reasons. Men and women shall equally enjoy all civil, political, economic, social and political rights. Mothers are entitled to special care and protection before and after childbirth; women and juveniles are protected at work by special regulations. Every child has the right to special care an assistance from his or her family, the State, and society, for appropriate physical, spiritual, and moral development. Parents shall decide the kind of education their children receive. Hungary grants equal rights to all person within its territories, without regard to race, color, sex, language, religion, political, or other opinion, national, and social origin, property, birth and other status. Prejudicial discrimination shall be severely punished. Everyone has the right to work, to the free choice of employment and profession and to equal pay for equal work. Citizens have the right to social security, including social services necessary in old age, sickness, disability, widowhood, orphanhood an unemployment through no fault of their own. Hungary guarantees the right to culture for its citizens and realized this right by free and compulsory elementary education, by secondary and higher education which is accessible to all on the basis of capacity, and by the financial support of those receiving an education.

  19. Functional organization of area V2 in the alert macaque.

    Science.gov (United States)

    Peterhans, E; von der Heydt, R

    1993-05-01

    We studied the relation between anatomical structure and functional properties of cells in area V2 of the macaque. Visual function was assessed in the alert animal during fixation of gaze. Recording sites were reconstructed with respect to cortical lamination and the cytochrome oxidase pattern. We measured orientation and direction selectivity, end-stopping, sensitivity to binocular disparity and ocular dominance, and determined more complex functions like sensitivity to anomalous contours and lines defined by coherent motion. Orientation selectivity was found in all parts of area V2, with high frequencies in the pale and thick stripes of the cytochrome oxidase pattern, and with lower frequency in the thin stripes. Representations of anomalous contours were found in the pale and thick stripes with similar frequencies, but generally not in the thin stripes, which have been thought to process colour. Lines defined by coherent motion were most frequently represented in the thick stripes; they were less frequent in the pale stripes, and (as with anomalous contours) were not found in the thin stripes. Sensitivity to binocular disparity was found in all types of stripes, but more frequently in the thick stripes, where the exclusively binocular neurons were also concentrated. By contrast, no segregation was found for direction selectivity and end-stopping. All neuronal properties were distributed evenly across cortical laminae. We conclude that mechanisms for figure-ground segregation involve the pale and the thick stripes of the cytochrome oxidase pattern, perhaps with greater emphasis on 'shape from motion' and 'stereoscopic depth' in the thick stripes, while more elementary neuronal properties are distributed almost evenly across the stripe pattern.

  20. V2O5-C-SnO2 Hybrid Nanobelts as High Performance Anodes for Lithium-ion Batteries

    Science.gov (United States)

    Zhang, Linfei; Yang, Mingyang; Zhang, Shengliang; Wu, Zefei; Amini, Abbas; Zhang, Yi; Wang, Dongyong; Bao, Shuhan; Lu, Zhouguang; Wang, Ning; Cheng, Chun

    2016-09-01

    The superior performance of metal oxide nanocomposites has introduced them as excellent candidates for emerging energy sources, and attracted significant attention in recent years. The drawback of these materials is their inherent structural pulverization which adversely impacts their performance and makes the rational design of stable nanocomposites a great challenge. In this work, functional V2O5-C-SnO2 hybrid nanobelts (VCSNs) with a stable structure are introduced where the ultradispersed SnO2 nanocrystals are tightly linked with glucose on the V2O5 surface. The nanostructured V2O5 acts as a supporting matrix as well as an active electrode component. Compared with existing carbon-V2O5 hybrid nanobelts, these hybrid nanobelts exhibit a much higher reversible capacity and architectural stability when used as anode materials for lithium-ion batteries. The superior cyclic performance of VCSNs can be attributed to the synergistic effects of SnO2 and V2O5. However, limited data are available for V2O5-based anodes in lithium-ion battery design.

  1. A novel CaV2.2 channel inhibition by piracetam in peripheral and central neurons.

    Science.gov (United States)

    Bravo-Martínez, Jorge; Arenas, Isabel; Vivas, Oscar; Rebolledo-Antúnez, Santiago; Vázquez-García, Mario; Larrazolo, Arturo; García, David E

    2012-10-01

    No mechanistic actions for piracetam have been documented to support its nootropic effects. Voltage-gated calcium channels have been proposed as a promising pharmacological target of nootropic drugs. In this study, we investigated the effect of piracetam on Ca(V)2.2 channels in peripheral neurons, using patch-clamp recordings from cultured superior cervical ganglion neurons. In addition, we tested if Ca(V)2.2 channel inhibition could be related with the effects of piracetam on central neurons. We found that piracetam inhibited native Ca(V)2.2 channels in superior cervical ganglion neurons in a dose-dependent manner, with an IC(50) of 3.4 μmol/L and a Hill coefficient of 1.1. GDPβS dialysis did not prevent piracetam-induced inhibition of Ca(V)2.2 channels and G-protein-coupled receptor activation by noradrenaline did not occlude the piracetam effect. Piracetam altered the biophysical characteristics of Ca(V)2.2 channel such as facilitation ratio. In hippocampal slices, piracetam and ω-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam's actions on Ca(V)2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.

  2. Constitutional judges (guarantee of the Constitution and responsibility

    Directory of Open Access Journals (Sweden)

    Francisco Javier Ansuátegui Roig

    2012-06-01

    Full Text Available My aim in this paper is to propose a reflection on the position and the importance that the constitutional judge has in the legal systems of contemporary constitutionalism. The figure of the judge responsible of protecting the Constitution is a key institution, without which we cannot understand the laws of constitutional democracies, their current lines of development, and the guarantee of rights and freedoms that constitute the normative core of these systems. Moreover, the reflection on the exercise of the powers of the judge, its scope and its justification is an important part of contemporary legal discussion, still relevant, albeit not exclusively - in the field of legal philosophy. The object of attention of my reflection is the judge who has the power of judicial review, in a scheme of defense of the Constitution, regardless the specific ways of this defense.

  3. High Temperature Corrosion of Nickel in NaVO3-V2O5 Melts

    Directory of Open Access Journals (Sweden)

    J. Porcayo-Calderon

    2017-01-01

    Full Text Available Many alloys used at high temperature in industrial processes are Ni-based and many others contain it in appreciable quantities, so it is of interest to evaluate the performance of pure nickel in order to determine the behavior of its alloys once the elements responsible for their protection have been depleted due to accelerated corrosion processes in the presence of vanadium-rich molten salts. Due to this, this work presents the study of Ni behavior in NaVO3-V2O5 mixtures at different temperatures. The behavior of pure nickel was determined by both electrochemical and mass loss measurements. The results show that the aggressiveness of the vanadium salts is increased by increasing both the V2O5 content and temperature. V2O5 addition considerably increases the current densities of the anodic and cathodic reactions. The corrosion process of Ni is modified due to the presence of its corrosion products, and its presence increases the activation energy by at least one order of magnitude. Although nickel shows a high reactivity in vanadium-rich salts, its reaction products are highly stable and protect it from the corrosive medium because the corrosion reactions trap the vanadium and block the migration of nickel ions.

  4. Buprofezin Is Metabolized by CYP353D1v2, a Cytochrome P450 Associated with Imidacloprid Resistance in Laodelphax striatellus

    OpenAIRE

    Mohammed Esmail Abdalla Elzaki; Mohammad Asaduzzaman Miah; Zhaojun Han

    2017-01-01

    CYP353D1v2 is a cytochrome P450 related to imidacloprid resistance in Laodelphax striatellus. This work was conducted to examine the ability of CYP353D1v2 to metabolize other insecticides. Carbon monoxide difference spectra analysis indicates that CYP353D1v2 was successfully expressed in insect cell Sf9. The catalytic activity of CYP353D1v2 relating to degrading buprofezin, chlorpyrifos, and deltamethrin was tested by measuring substrate depletion and analyzing the formation of metabolites. T...

  5. Essential Medicines in National Constitutions

    Science.gov (United States)

    Toebes, Brigit; Hogerzeil, Hans

    2016-01-01

    Abstract A constitutional guarantee of access to essential medicines has been identified as an important indicator of government commitment to the progressive realization of the right to the highest attainable standard of health. The objective of this study was to evaluate provisions on access to essential medicines in national constitutions, to identify comprehensive examples of constitutional text on medicines that can be used as a model for other countries, and to evaluate the evolution of constitutional medicines-related rights since 2008. Relevant articles were selected from an inventory of constitutional texts from WHO member states. References to states’ legal obligations under international human rights law were evaluated. Twenty-two constitutions worldwide now oblige governments to protect and/or to fulfill accessibility of, availability of, and/or quality of medicines. Since 2008, state responsibilities to fulfill access to essential medicines have expanded in five constitutions, been maintained in four constitutions, and have regressed in one constitution. Government commitments to essential medicines are an important foundation of health system equity and are included increasingly in state constitutions. PMID:27781006

  6. Understanding Vehicle Related Crime to Elaborate on Countermeasures Based on ADAS and V2X Communication

    NARCIS (Netherlands)

    Knapik, Peter; Schoch, Elmar; Müller, Maik; Kargl, Frank

    2012-01-01

    Among numerous types of criminal activities, vehicle related crime contributes to personal injury as well as to economic losses. Over the last 10 years vehicle related crime continuously constitutes over 10% of all crime in Germany. However, vehicle related crime is not particularly a German

  7. Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2

    Directory of Open Access Journals (Sweden)

    Zarella MD

    2017-04-01

    Full Text Available Mark D Zarella, Daniel Y Ts’o Department of Neurosurgery, SUNY Upstate Medical University, Syracuse, NY, USA Abstract: Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure–ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure–ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure–ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization. Keywords: striate, extrastriate, segmentation, figure–ground, functional organization

  8. h5-HT1B receptor-mediated constitutive Gαi3-protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5-HT

    Science.gov (United States)

    Newman-Tancredi, Adrian; Cussac, Didier; Marini, Laetitia; Touzard, Manuelle; Millan, Mark J

    2003-01-01

    Serotonin 5-HT1B receptors couple to G-proteins of the Gi/o family. However, their activation of specific G-protein subtypes is poorly characterised. Using an innovative antibody capture/guanosine-5′-0-(3-[35S]thio)-triphosphate ([35S]GTPγS) binding strategy, we characterised Gαi3 subunit activation by h5-HT1B receptors stably expressed in Chinese hamster ovary (CHO) cells. The agonists, 5-HT, alniditan and BMS181,101, stimulated Gαi3, whereas methiothepin and SB224,289 behaved as inverse agonists. The selective 5-HT1B receptor ligand, S18127, modestly stimulated Gαi3 and reversed the actions of both 5-HT and methiothepin. S18127 (1 μM) also produced parallel, dextral shifts of the 5-HT and methiothepin isotherms. Isotopic dilution experiments ([35S]GTPγS versus GTPγS) revealed high-affinity [35S]GTPγS binding to Gαi3 subunits in the absence of receptor ligands indicating constitutive activity. High-affinity [35S]GTPγS binding was increased 2.8-fold by 5-HT with an increase in the affinity of GTPγS for Gαi3 subunits. In contrast, methiothepin halved the number of high-affinity binding sites and decreased their affinity. h5-HT1B receptor-mediated Gαi3 subunit activation was dependent on the concentration of NaCl. At 300 mM, 5-HT stimulated [35S]GTPγS binding, basal Gαi3 activation was low and methiothepin was inactive. In contrast, at 10 mM NaCl, basal activity was enhanced and the inverse agonist activity of methiothepin was accentuated. Under these conditions, 5-HT decreased Gαi3 activation. In conclusion, at h5-HT1B receptors expressed in CHO cells: (i) inverse agonist induced inhibition of Gαi3, and its reversal by S18127, reveals constitutive activation of this Gα subunit; (ii) constitutive Gαi3 activation can be quantified by isotopic dilution [35S]GTPγS binding and (iii) decreasing NaCl concentrations enhances Gαi3 activation and leads to protean agonist properties of 5-HT: that is a switch to inhibition of Gαi3. PMID:12684263

  9. h5-HT(1B) receptor-mediated constitutive Galphai3-protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5-HT.

    Science.gov (United States)

    Newman-Tancredi, Adrian; Cussac, Didier; Marini, Laetitia; Touzard, Manuelle; Millan, Mark J

    2003-03-01

    1. Serotonin 5-HT(1B) receptors couple to G-proteins of the Gi/o family. However, their activation of specific G-protein subtypes is poorly characterised. Using an innovative antibody capture/guanosine-5'-0-(3-[(35)S]thio)-triphosphate ([(35)S]GTPgammaS) binding strategy, we characterised Galpha(i3) subunit activation by h5-HT(1B) receptors stably expressed in Chinese hamster ovary (CHO) cells. 2. The agonists, 5-HT, alniditan and BMS181,101, stimulated Galpha(i3), whereas methiothepin and SB224,289 behaved as inverse agonists. The selective 5-HT(1B) receptor ligand, S18127, modestly stimulated Galpha(i3) and reversed the actions of both 5-HT and methiothepin. S18127 (1 micro M) also produced parallel, dextral shifts of the 5-HT and methiothepin isotherms. 3. Isotopic dilution experiments ([(35)S]GTPgammaS versus GTPgammaS) revealed high-affinity [(35)S]GTPgammaS binding to Galpha(i3) subunits in the absence of receptor ligands indicating constitutive activity. High-affinity [(35)S]GTPgammaS binding was increased 2.8-fold by 5-HT with an increase in the affinity of GTPgammaS for Galpha(i3) subunits. In contrast, methiothepin halved the number of high-affinity binding sites and decreased their affinity. 4. h5-HT(1B) receptor-mediated Galpha(i3) subunit activation was dependent on the concentration of NaCl. At 300 mM, 5-HT stimulated [(35)S]GTPgammaS binding, basal Galpha(i3) activation was low and methiothepin was inactive. In contrast, at 10 mM NaCl, basal activity was enhanced and the inverse agonist activity of methiothepin was accentuated. Under these conditions, 5-HT decreased Galpha(i3) activation. 5. In conclusion, at h5-HT(1B) receptors expressed in CHO cells: (i) inverse agonist induced inhibition of Galpha(i3), and its reversal by S18127, reveals constitutive activation of this Galpha subunit; (ii) constitutive Galpha(i3) activation can be quantified by isotopic dilution [(35)S]GTPgammaS binding and (iii) decreasing NaCl concentrations enhances Galpha(i3

  10. On the constitutionality of dose limiting values

    International Nuclear Information System (INIS)

    Goetz, V.

    1976-01-01

    The fundamental right according to Art. 2 par. 2 sentence 1 of the German Constitution is relevant for the set-up and application of radiation protection law. Resulting from Art. 2 par. 2 sentence 1 of the Constitution it is a general obligation of the state to protect life (Federal Constitutional Court, judgment of 25th Feb., 1975, BVerfGE 39.1) and physical soundness. The subjective basic right of everybody to defend against official encroachments his personal integrity corresponds to the right of the individual within the framework of the official obligation for protection from the state (to ward off danger). The term of danger, as to the degree of its determination, corresponds to that of the encroachment. To speak of danger in a legal sense, the causal connection between a certain source of danger and certain damage must be ascertained and proved. Topical controversies as to the admissibility of activity discharges of low doses range in the field of risk reduction and thus in the field of the duty of the state to take precautionary steps against risks (Art. 2 par. 2 sentence 1 of the Constitution). The constitution, however, does not contain any basic right that every risk has to be avoided. On the other hand, the necessity of cautions valuation of radiation risks can be derived from the Constitution. The fixation of dose limits and their application in connection with general radiation protection principles (paragraph 28 E of the Radiation Protection Ordinance) do not contain any 'interference' with the basic right in the sense of Art. 2 par. 2 sentence 3 of the Constitution. Neither from aspects of the principle of the legal state nor from Art. 80 par. 1 of the Constitution can the use of the legal form of the Ordinance be doubted. (orig./HP) [de

  11. Screening for MPL mutations in essential thrombocythemia and primary myelofibrosis: normal Mpl expression and absence of constitutive STAT3 and STAT5 activation in MPLW515L-positive platelets.

    Science.gov (United States)

    Glembotsky, Ana C; Korin, Laura; Lev, Paola R; Chazarreta, Carlos D; Marta, Rosana F; Molinas, Felisa C; Heller, Paula G

    2010-05-01

    To evaluate the frequency of MPL W515L, W515K and S505N mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) and to determine whether MPLW515L leads to impaired Mpl expression, constitutive STAT3 and STAT5 activation and enhanced response to thrombopoietin (TPO). Mutation detection was performed by allele-specific PCR and sequencing. Platelet Mpl expression was evaluated by flow cytometry, immunoblotting and real-time RT-PCR. Activation of STAT3 and STAT5 before and after stimulation with increasing concentrations of TPO was studied by immunoblotting. Plasma TPO was measured by ELISA. MPLW515L was detected in 1 of 100 patients with ET and 1 of 11 with PMF. Platelets from the PMF patient showed 100% mutant allele, which was Mpl surface and total protein expression were normal, and TPO levels were mildly increased in the MPLW515L-positive ET patient, while MPL transcripts did not differ from controls in both MPLW515L-positive patients. Constitutive STAT3 and STAT5 phosphorylation was absent and dose response to TPO-induced phosphorylation was not enhanced. The low frequency of MPL mutations in this cohort is in agreement with previous studies. The finding of normal Mpl levels in MPLW515L-positive platelets indicates this mutation does not lead to dysregulated Mpl expression, as frequently shown for myeloproliferative neoplasms. The lack of spontaneous STAT3 and STAT5 activation and the normal response to TPO is unexpected as MPLW515L leads to constitutive receptor activation and hypersensitivity to TPO in experimental models.

  12. Constitutional aneuploidy and cancer predisposition.

    Science.gov (United States)

    Ganmore, Ithamar; Smooha, Gil; Izraeli, Shai

    2009-04-15

    Constitutional aneuploidies are rare syndromes associated with multiple developmental abnormalities and the alterations in the risk for specific cancers. Acquired somatic chromosomal aneuploidies are the most common genetic aberrations in sporadic cancers. Thus studies of these rare constitutional aneuploidy syndromes are important not only for patient counseling and clinical management, but also for deciphering the mechanisms by which chromosomal aneuploidy affect cancer initiation and progression. Here we review the major constitutional aneuploidy syndromes and suggest some general mechanisms for the associated cancer predisposition.

  13. Economic Reforms and Constitutional Transition

    OpenAIRE

    Jeffrey D. Sachs; Wing Thye Woo; Xiaokai Yang

    2000-01-01

    This paper investigates the relationship between economic reforms and constitutional transition, which has been neglected by many transition economists. It is argued that assessment of reform performance might be very misleading if it is not recognized that economic reforms are just a small part of large scale of constitutional transition. Rivalry and competition between states and between political forces within each country are the driving forces for constitutional transition. We use Russia...

  14. ECHR and national constitutional courts

    OpenAIRE

    Nastić, Maja

    2015-01-01

    Comprising fundamental rights and freedoms and establishing the effective control system, the European Convention on Human Rights (ECHR) encroaches upon the area that is traditional reserved for constitutional law. Although built on the doctrine reserved for international treaty law, the Convention goes beyond the traditional boundaries that exist between international and constitutional law. It has gradually infiltrated into the national legal systems. Constitutional courts have had the cruc...

  15. The Budapest Reference Connectome Server v2.0.

    Science.gov (United States)

    Szalkai, Balázs; Kerepesi, Csaba; Varga, Bálint; Grolmusz, Vince

    2015-05-19

    The connectomes of different human brains are pairwise distinct: we cannot talk about an abstract "graph of the brain". Two typical connectomes, however, have quite a few common graph edges that may describe the same connections between the same cortical areas. The Budapest Reference Connectome Server v2.0 generates the common edges of the connectomes of 96 distinct cortexes, each with 1015 vertices, computed from 96 MRI data sets of the Human Connectome Project. The user may set numerous parameters for the identification and filtering of common edges, and the graphs are downloadable in both csv and GraphML formats; both formats carry the anatomical annotations of the vertices, generated by the FreeSurfer program. The resulting consensus graph is also automatically visualized in a 3D rotating brain model on the website. The consensus graphs, generated with various parameter settings, can be used as reference connectomes based on different, independent MRI images, therefore they may serve as reduced-error, low-noise, robust graph representations of the human brain. The webserver is available at http://connectome.pitgroup.org. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. KASS v.2.2. scheduling software for construction

    Directory of Open Access Journals (Sweden)

    Krzemiński Michał

    2016-01-01

    Full Text Available The paper presents fourth version of specialist useful software in scheduling KASS v.2.2 (Algorithm Scheduling Krzeminski System. KASS software is designed for construction scheduling, specially form flow shop models. The program is being dedicated closely for the purposes of the construction. In distinguishing to other used programs in tasks of this type operational research criteria were designed closely with the thought about construction works and about the specificity of the building production. The minimal time, the minimal slack of brigades, the minimal slacks of the chosen working brigade and costs of the transfer operation of working fronts are included in operational research criteria between work centers. It is possible to enter data into the program both by hand as well as to load the Excel from files, similarly is with results, they are presented on-screen as well as a possibility of enrolling them in the file exists Excel. An element is very valid for it since allows for further simple processing of received results. In providing software for performing operational research calculations a technique of the complete review and simulation technology are being exploited. Described algorithms a program is using which will stay in the article as well as shown computational examples will remain.

  17. Constitutional Issues--Watergate and the Constitution. Teaching with Documents.

    Science.gov (United States)

    National Archives and Records Administration, Washington, DC.

    When U.S. President Richard Nixon resigned in 1974 in the wake of the Watergate scandal, it was only the second time that impeachment of a president had been considered. Although the U.S. Constitution has provisions for a person removed from office to be indicted, there are no guidelines in the Constitution about a President who has resigned. The…

  18. National constitutional courts in the European Constitutional Democracy

    DEFF Research Database (Denmark)

    Komárek, Jan

    2014-01-01

    This article critically assesses the transformation of national constitutional courts’ place in the law and politics of the EU and its member states. This process eliminates the difference between constitutional and ordinary national courts, which is crucial for the institutional implementation...... of the discourse theory of law and democracy. It also disrupts the symbiotic relationship between national constitutional democracies established after World War II and European integration. The article argues that maintaining the special place of national constitutional courts is in the vital interest of both...... the EU and its member states, understood together as the European Constitutional Democracy—the central notion developed in this article in order to support an argument that should speak to both EU lawyers and national constitutionalists....

  19. Legitimacy of Constitutional Justice: Democracy, Constitutional Court and Theory Against Majority Interest

    Directory of Open Access Journals (Sweden)

    Thaminne Nathalia Cabral Moraes e Silva

    2016-12-01

    Full Text Available This article has as its theme the analysis of the separation of powers and the rule of democracy, in addition to the possibility of the Constitutional Court be composed of people appointed by the President of the Republic, not fulfilling the democratic rule, and make the control of constitutionality of laws, created through democratic process. Will be answered: the separation of powers obey the democratic rule? When the Legislature fails to fulfill its function of legislating, opens the opportunity for the Supreme Court, as the Constitutional Court that is, create, through judicial activism, silent rules? That injured the democratic rule?

  20. Reticular V2O5·0.6H2O Xerogel as Cathode for Rechargeable Potassium Ion Batteries.

    Science.gov (United States)

    Tian, Bingbing; Tang, Wei; Su, Chenliang; Li, Ying

    2018-01-10

    Potassium ion batteries (KIBs), because of their low price, may exhibit advantages over lithium ion batteries as potential candidates for large-scale energy storage systems. However, owing to the large ionic radii of K-ions, it is challenging to find a suitable intercalation host for KIBs and thus the rechargeable KIB electrode materials are still largely unexplored. In this work, a reticular V 2 O 5 ·0.6H 2 O xerogel was synthesized via a hydrothermal process as a cathode material for rechargeable KIBs. Compared with the orthorhombic crystalline V 2 O 5 , the hydrated vanadium pentoxide (V 2 O 5 ·0.6H 2 O) exhibits the ability of accommodating larger alkali metal ions of K + because of the enlarged layer space by hosting structural H 2 O molecules in the interlayer. By intercalation of H 2 O into the V 2 O 5 layers, its potassium electrochemical activity is significantly improved. It exhibits an initial discharge capacity of ∼224.4 mA h g -1 and a discharge capacity of ∼103.5 mA h g -1 even after 500 discharge/charge cycles at a current density of 50 mA g -1 , which is much higher than that of the V 2 O 5 electrode without structural water. Meanwhile, X-ray diffraction and X-ray photoelectron spectroscopy combined with energy dispersive spectroscopy techniques are carried out to investigate the potassiation/depotassiation process of the V 2 O 5 ·0.6H 2 O electrodes, which confirmed the potassium intercalation storage mechanisms of this hydrated material. The results demonstrate that the interlayer-spacing-enlarged V 2 O 5 ·0.6H 2 O is a promising cathode candidate for KIBs.

  1. Linking retinotopic fMRI mapping and anatomical probability maps of human occipital areas V1 and V2.

    Science.gov (United States)

    Wohlschläger, A M; Specht, K; Lie, C; Mohlberg, H; Wohlschläger, A; Bente, K; Pietrzyk, U; Stöcker, T; Zilles, K; Amunts, K; Fink, G R

    2005-05-15

    Using functional MRI, we characterized field sign maps of the occipital cortex and created three-dimensional maps of these areas. By averaging the individual maps into group maps, probability maps of functionally defined V1 or V2 were determined and compared to anatomical probability maps of Brodmann areas BA17 and BA18 derived from cytoarchitectonic analysis (Amunts, K., Malikovic, A., Mohlberg, H., Schormann, T., Zilles, K., 2000. Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable? NeuroImage 11, 66-84). Comparison of areas BA17/V1 and BA18/V2 revealed good agreement of the anatomical and functional probability maps. Taking into account that our functional stimulation (due to constraints of the visual angle of stimulation achievable in the MR scanner) only identified parts of V1 and V2, for statistical evaluation of the spatial correlation of V1 and BA17, or V2 and BA18, respectively, the a priori measure kappa was calculated testing the hypothesis that a region can only be part of functionally defined V1 or V2 if it is also in anatomically defined BA17 or BA18, respectively. kappa = 1 means the hypothesis is fully true, kappa = 0 means functionally and anatomically defined visual areas are independent. When applying this measure to the probability maps, kappa was equal to 0.84 for both V1/BA17 and V2/BA18. The data thus show a good correspondence of functionally and anatomically derived segregations of early visual processing areas and serve as a basis for employing anatomical probability maps of V1 and V2 in group analyses to characterize functional activations of early visual processing areas.

  2. Constitutive Effects of Performance Indicators

    DEFF Research Database (Denmark)

    Dahler-Larsen, Peter

    2014-01-01

    that are demonstrably problematic. Based on a distinction between trivial and advanced measure fixation, an argument is made for constitutive effects that are based on less problematic assumptions. Through this conceptual move, the political dimension of performance indicators is appreciated. The conceptual dimensions...... of constitutive effects are carved out, empirical illustrations of their applicability are offered and implications discussed....

  3. Great Constitutional Ideas: Justice, Equality, and Property.

    Science.gov (United States)

    Starr, Isidore

    1987-01-01

    Examines the ideas of justice, equality, and property as they are represented in the Declaration of Independence, the U.S. Constitution and the Bill of Rights. Discusses how these ideas affect the way public schools operate and the lessons educators teach or don't teach about our society. Includes ideas for classroom activities. (JDH)

  4. Political dimension of European constitutionalism

    Directory of Open Access Journals (Sweden)

    Kaplánová Patricia

    2015-04-01

    Full Text Available Author in the article tries to analyse different elements of document called European Constitution. Analysis is supported with theoretical framework of federalism, presented by Brezovšek. Authors is playing with idea of (confederal and international organization elements of European Constitution and their mix. They are also trying to set some connections between so called common European identity as necessary condition to give legitimacy to the European Constitution. This became important question after „votes of non-confidence“ to the European Constitution in France, despite it should be addressed already before. However, European Constitution is important document on the path of European integration and lack of support to it will slow down this process of widening and deepening European ties.

  5. Postnatal Expression of V2 Vasopressin Receptor Splice Variants in the Rat Cerebellum

    Science.gov (United States)

    Vargas, Karina J.; Sarmiento, José M.; Ehrenfeld, Pamela; Añazco, Carolina C.; Villanueva, Carolina I.; Carmona, Pamela L.; Brenet, Marianne; Navarro, Javier; Müller-Esterl, Werner; Figueroa, Carlos D.; González, Carlos B.

    2010-01-01

    The V2 vasopressin receptor gene contains an alternative splice site in exon-3, which leads to the generation of two splice variants (V2a and V2b) first identified in the kidney. The open reading frame of the alternatively spliced V2b transcripten codes a truncated receptor, showing the same amino acid sequence as the canonical V2a receptor up to the 6th transmembrane segment, but displaying a distinct sequence to the corresponding 7th transmembrane segment and C-terminal domain relative to the V2a receptor. Here, we demonstrate the postnatal expression of V2a and V2b variants in the rat cerebellum. Most importantly, we showed by in situ hybridization and immunocytochemistry that both V2 splice variants were preferentially expressed in Purkinje cells, from early to late postnatal development. In addition, both variants were transiently expressed in the neuroblastic external granule cells and Bergmann fibers. These results indicate that the cellular distributions of both splice variants are developmentally regulated, and suggest that the transient expression of the V2 receptor is involved in the mechanisms of cerebellar cytodifferentiation by AVP. Finally, transfected CHO-K1 .expressing similar amounts of both V2 splice variants, as that found in the cerebellum, showed a significant reduction in the surface expression of V2a receptors, suggesting that the differential expression of the V2 splice variants regulate the vasopressin signaling in the cerebellum. PMID:19281786

  6. Constitutive activation of extracellular signal-regulated kinase predisposes diffuse large B-cell lymphoma cell lines to CD40-mediated cell death

    DEFF Research Database (Denmark)

    Hollmann, C Annette; Owens, Trevor; Nalbantoglu, Josephine

    2006-01-01

    CD40 promotes survival, proliferation, and differentiation of normal B cells but can cause activation-induced cell death in malignant B lymphocytes. CD40 ligand and anti-CD40 antibodies have been used successfully to induce apoptosis in lymphoma lines both in vitro and in xenograft tumor models. ...

  7. ITER EDA newsletter. V. 2, Nos. 7/8

    International Nuclear Information System (INIS)

    1993-01-01

    This ITER EDA (Engineering Design Activities) Newsletter issue includes a description of the ITER Design Integration Division, and reports on the 5th IAEA Technical Committee Meeting on Developments in Fusion Safety held in Toronto, Canada, 7 - 11 June 1993, and on the International Atomic Energy Agency's Atomic and Plasma-Material Interaction Data Activities in support of the ITER Engineering Design Activities

  8. The functionalized amino acid (S-Lacosamide subverts CRMP2-mediated tubulin polymerization to prevent constitutive and activity-dependent increase in neurite outgrowth

    Directory of Open Access Journals (Sweden)

    Sarah M Wilson

    2014-07-01

    Full Text Available Activity-dependent neurite outgrowth is a highly complex, regulated process with important implications for neuronal circuit remodeling in development as well as in seizure-induced sprouting in epilepsy. Recent work has linked outgrowth to collapsin response mediator protein 2 (CRMP2, an intracellular phosphoprotein originally identified as axon guidance and growth cone collapse protein. The neurite outgrowth promoting function of CRMP2 is regulated by its phosphorylation state. In this study, depolarization (potassium chloride-driven activity increased the level of active CRMP2 by decreasing its phosphorylation by GSK3β via a reduction in priming by Cdk5. To determine the contribution of CRMP2 in activity-driven neurite outgrowth, we screened a limited set of compounds for their ability to reduce neurite outgrowth but not modify voltage-gated sodium channel (VGSC biophysical properties. This led to the identification of (S-lacosamide ((S-LCM, a stereoisomer of the clinically used antiepileptic drug (R-LCM (Vimpat®, as a novel tool for preferentially targeting CRMP2-mediated neurite outgrowth. Whereas (S-LCM was ineffective in targeting VGSCs, the presumptive pharmacological targets of (R-LCM, (S-LCM was more efficient than (R-LCM in subverting neurite outgrowth. Biomolecular interaction analyses revealed that (S-LCM bound to wildtype CRMP2 with low micromolar affinity, similar to (R-LCM. Through the use of this novel tool, the activity-dependent increase in neurite outgrowth observed following depolarization was characterized to be reliant on CRMP2 function. Knockdown of CRMP2 by siRNA in cortical neurons resulted in reduced CRMP2-dependent neurite outgrowth; incubation with (S-LCM phenocopied this effect. Other CRMP2-mediated processes were unaffected. (S-LCM subverted neurite outgrowth not by affecting the canonical CRMP2-tubulin association but rather by impairing the ability of CRMP2 to promote tubulin polymerization, events that are

  9. Constitutive activation and accelerated maturation of peripheral blood t cells in healthy adults in burkina faso compared to Germany: The case of malaria?

    Directory of Open Access Journals (Sweden)

    Tiba F

    2011-12-01

    Full Text Available Abstract Objective It is not exactly known how frequent exposure to Plasmodium falciparum shapes the peripheral blood T-cell population in healthy West Africans. Methods The frequency of peripheral blood CD4+ lymphocytes responding to Plasmodium falciparum merozoite surface protein 1 (PfMSP-1 by production of interferon-gamma (IFN-γ, interleukin-2 (IL-2 or tumor necrosis factor-alpha (TNF-α was determined using a commercially available flow cytometric activation assay (Fastlmmune in 17 healthy adults in Nouna, Burkina Faso. T-cell activation and maturation in peripheral blood of healthy adults in Burkina Faso (n = 40 and Germany (n = 20 were compared using immunophenotyping and three-colour flow cytometry. Results Significant numbers of PfMSV-1 -specific CD4+ lymphocytes producing IFN-γ, IL-2 and/or TNF-α were detected in 14 healthy adults in Nouna. Cytokine profiles showed predominant production of IFN-γ and TNF-α. Compared to Germans, Burkinabé showed markedly lower proportions of CCR7+ CD45RA+ naïve CD4+ cells and slightly higher frequencies of CD95+ CD4+ T-cells and of CD38+ CD8+ T-cells. The median antibody-binding capacity of CD95dim CD4+ T-cells in Burkinabé was more than twice the value observed in Germans (263 vs. 108 binding sites per cell, p Conclusions We hypothesize that an IFN-γ-induced increase in the expression level of CD95 on CD4+ lymphocytes may lower the activation threshold of resting naïve CD4+ T-cells in healthy adults living in Burkina Faso. Bystander activation of these cells deserves further study as a molecular mechanism linking strong IFN-γ responses against Plasmodium falciparum to decreased susceptibility to parasitemia observed in specific ethnic groups in West Africa.

  10. V2R mutations and nephrogenic diabetes insipidus.

    Science.gov (United States)

    Bichet, Daniel G

    2009-01-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. Nephrogenic failure to concentrate urine maximally may be due to a defect in vasopressin-induced water permeability of the distal tubules and collecting ducts, to insufficient buildup of the corticopapillary interstitial osmotic gradient, or to a combination of these two factors. Thus, the broadest definition of the term NDI embraces any antidiuretic hormone-resistant urinary-concentrating defect, including medullary disease with low interstitial osmolality, renal failure, and osmotic diuresis. About 90% of patients with congenital NDI are males with X-linked recessive NDI (OMIM 304800)(1) and have mutations in the AVP receptor 2 (AVPR2) gene that codes for the vasopressin V(2) receptor; the gene is located in chromosome region Xq28. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800)(1). Mutations have been identified in the aquaporin-2 gene (AQP2, OMIM 107777)(1), which is located in chromosome region 12q13 and codes for the vasopressin-sensitive water channel. NDI is clinically distinguishable from neurohypophyseal diabetes insipidus (OMIM 125700(1); also referred to as central or neurogenic diabetes insipidus) by a lack of response to exogenous AVP and by plasma levels of AVP that rise normally with increase in plasma osmolality. Hereditary neurohypophyseal diabetes insipidus is secondary to mutations in the gene encoding AVP (OMIM 192340)(1). Neurohypophyseal diabetes insipidus is also a component of autosomal recessive Wolfram syndrome 1 or DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) (OMIM

  11. Superior Cycle Stability Performance of Quasi-Cuboidal CoV2O6 Microstructures as Electrode Material for Supercapacitors.

    Science.gov (United States)

    Wang, Yucheng; Chai, Hui; Dong, Hong; Xu, Jiayu; Jia, Dianzeng; Zhou, Wanyong

    2016-10-12

    In this study, a rapid, facile, and environment-friendly microwave-assisted method followed by annealing for synthesizing the quasi-cuboidal CoV 2 O 6 is developed. The as-prepared samples manifest high supercapacitor properties with a specific capacitance of 223 F g -1 , good rate capability, and superior cycle stability, retaining 123.3% capacitance when the number of cycles reaches 15,000 after determined by electrochemical tests. More importantly, the quasi-cuboidal CoV 2 O 6 for the first time is introduced into the supercapacitor as a kind of electrode material. The superior electrochemical performance of the quasi-cuboidal CoV 2 O 6 will render the metal vanadium oxides as new and attractive active material for promising application in supercapacitors.

  12. A feasibility Study: The Succinct Solver v2.0, XSB Prolog v2.6, and Flow-Logic Based Program Analysis for Carmel

    DEFF Research Database (Denmark)

    Pilegaard, Henrik

    2003-01-01

    We perform a direct comparison of the {Succinct Solver v2.0} and {XSB Prolog v2.6} based on experiments with {Control Flow Analyses} of scalable {Discretionary Ambient programs} and {Carmel programs}. To facilitate this comparison we expand ALFP clauses accepted by the Succinct Solver into more g...

  13. Radioactive waste disposal and constitution

    International Nuclear Information System (INIS)

    Stober, R.

    1983-01-01

    The radioactive waste disposal has many dimensions with regard to the constitutional law. The central problem is the corret delimitation between adequate governmental precautions against risks and or the permitted risk which the state can impose on the citizen, and the illegal danger which nobody has to accept. The solution requires to consider all aspects which are relevant to the constitutional law. Therefore, the following analysis deals not only with the constitutional risks and the risks of the nuclear energy, but also with the liberal, overall-economic, social, legal, and democratic aspects of radioactive waste disposal. (HSCH) [de

  14. Constitutional aneuploidy and cancer predisposition†

    Science.gov (United States)

    Ganmore, Ithamar; Smooha, Gil; Izraeli, Shai

    2009-01-01

    Constitutional aneuploidies are rare syndromes associated with multiple developmental abnormalities and the alterations in the risk for specific cancers. Acquired somatic chromosomal aneuploidies are the most common genetic aberrations in sporadic cancers. Thus studies of these rare constitutional aneuploidy syndromes are important not only for patient counseling and clinical management, but also for deciphering the mechanisms by which chromosomal aneuploidy affect cancer initiation and progression. Here we review the major constitutional aneuploidy syndromes and suggest some general mechanisms for the associated cancer predisposition. PMID:19297405

  15. Electrochemical sensing property of Mn doped V2O5 nanoparticles

    International Nuclear Information System (INIS)

    Suresh, R.; Giribabu, K.; Manigandan, R.; Narayanan, V.; Vijayalakshmi, L.; Stephen, A.

    2012-01-01

    In this study, pure V 2 O 5 and Mn doped V 2 O 5 nanoparticles were synthesized by thermal decomposition method. The FT-IR spectrum of Mn doped V 2 O 5 shows the bands at 822 and 1027 cm -1 which essentiaIIy of crystalline V 2 O 5 . Further, the bands observed in Mn doped V 2 O 5 are all shifted to lower wave number than the V 2 O 5 . The optical property of the nanocomposite was studied using UV-Visible absorption spectroscopy. The XRD data also revealed that the Mn doped V 2 O 5 obtained had an orthorhombic structure. The diffraction peaks in Mn doped V 2 O 5 nanoparticles are similar to that of V 2 O 5 . There was no indication of any other impurities in the sample. However, all the peaks of V 2 O 5 are slightly shifted to tower 2θ values. The FE-SEM image of V 2 O 5 shows that the particles adopt ellipse-like particles with different sizes due to aggregation. The synthesized nanoparticles were used to modify glassy carbon electrode (GCE) and the modified electrode was used to detect uric acid (UA) by voltammetric techniques. The effects of Mn on the optical, morphological and electrochemical detecting property of V 2 O 5 have also been studied. (author)

  16. Mutation of the regulatory phosphorylation site of tobacco nitrate reductase results in constitutive activation of the enzyme in vivo and nitrite accumulation.

    Science.gov (United States)

    Lillo, Cathrine; Lea, Unni S; Leydecker, Marie-Thérèse; Meyer, Christian

    2003-09-01

    In wild-type Nicotiana plumbaginifolia and other higher plants, nitrate reductase (NR) is rapidly inactivated/activated in response to dark/light transitions. Inactivation of NR is believed to be caused by phosphorylation at a special conserved regulatory Ser residue, Ser 521, and interactions with divalent cations and inhibitory 14-3-3 proteins. A transgenic N. plumbaginifolia line (S(521)) was constructed where the Ser 521 had been changed by site-directed mutagenesis into Asp. This mutation resulted in complete abolishment of inactivation in response to light/dark transitions or other treatments known to inactivate NR. During prolonged darkness, NR in wild-type plants is in the inactivated form, whereas NR in the S(521) line is always in the active form. Differences in degradation rate between NR from S(521) and lines with non-mutated NR were not found. Kinetic constants like Km values for NADH and NO3(-) were not changed, but a slightly different pH profile was observed for mutated NR as opposed to non-mutated NR. Under optimal growth conditions, the phenotype of the S(521) plants was not different from the wild type (WT). However, when plants were irrigated with high nitrate concentration, 150 mM, the transgenic plants accumulated nitrite in darkness, and young leaves showed chlorosis.

  17. The Variable Vector Countermeasure Suit (V2Suit for Space Habitation and Exploration

    Directory of Open Access Journals (Sweden)

    Kevin R Duda

    2015-04-01

    Full Text Available The Variable Vector Countermeasure Suit (V2Suit for Space Habitation and Exploration is a novel system concept that provides a platform for integrating sensors and actuators with daily astronaut intravehicular activities to improve health and performance, while reducing the mass and volume of the physiologic adaptation countermeasure systems, as well as the required exercise time during long-duration space exploration missions. The V2Suit system leverages wearable kinematic monitoring technology and uses inertial measurement units (IMUs and control moment gyroscopes (CMGs within miniaturized modules placed on body segments to provide a viscous resistance during movements against a specified direction of down – initially as a countermeasure to the sensorimotor adaptation performance decrements that manifest themselves while living and working in microgravity and during gravitational transitions during long-duration spaceflight, including post-flight recovery and rehabilitation. Several aspects of the V2Suit system concept were explored and simulated prior to developing a brassboard prototype for technology demonstration. This included a system architecture for identifying the key components and their interconnects, initial identification of key human-system integration challenges, development of a simulation architecture for CMG selection and parameter sizing, and the detailed mechanical design and fabrication of a module. The brassboard prototype demonstrates closed-loop control from down initialization through CMG actuation, and provides a research platform for human performance evaluations to mitigate sensorimotor adaptation, as well as a tool for determining the performance requirements when used as a musculoskeletal deconditioning countermeasure. This type of countermeasure system also has Earth benefits, particularly in gait or movement stabilization and rehabilitation.

  18. An experimental evaluation of the anti-atherogenic potential of the plant, Piper betle, and its active constitutent, eugenol, in rats fed an atherogenic diet.

    Science.gov (United States)

    Venkadeswaran, Karuppasamy; Thomas, Philip A; Geraldine, Pitchairaj

    2016-05-01

    Hypercholesterolemia is a major risk factor for systemic atherosclerosis and subsequent cardiovascular disease. Lipoperoxidation-mediated oxidative damage is believed to contribute strongly to the progression of atherogenesis. In the current investigation, putative anti-atherogenic and antioxidative properties of an ethanolic extract of Piper betle and of its active constituent, eugenol, were sought in an experimental animal model of chronic hypercholesterolemia. Atherogenic diet-fed rats that received either Piper betle extract orally (500mg/kg b.wt) or eugenol orally (5mg/kg b.wt) for 15days (commencing 30days after the atherogenic diet had been started) exhibited the following variations in different parameters, when compared to atherogenic diet-fed rats that received only saline: (1) significantly lower mean levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and very low density lipoprotein cholesterol in both serum and hepatic tissue samples; (2) lower mean serum levels of aspartate amino-transferase, alanine amino-transferase, alkaline phosphatase, lactate dehydrogenase and lipid-metabolizing enzymes (lipoprotein lipase, 3-hydroxy-3-methyl-glutaryl-CoA reductase; (3) significantly lower mean levels of enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase) and non-enzymatic antioxidants (reduced glutathione, vitamin C and vitamin E) and significantly higher mean levels of malondialdehyde in haemolysate and hepatic tissue samples. Histopathological findings suggested a protective effect of the Piper betle extract and a more pronounced protective effect of eugenol on the hepatic and aortic tissues of atherogenic diet-fed (presumed atherosclerotic) rats. These results strongly suggest that the Piper betle extract and its active constituent, eugenol, exhibit anti-atherogenic effects which may be due to their anti-oxidative properties. Copyright © 2016 Elsevier Masson SAS. All rights

  19. Constitutive Modelling in Geomechanics Introduction

    CERN Document Server

    Puzrin, Alexander M

    2012-01-01

    The purpose of this book is to bridge the gap between the traditional Geomechanics and Numerical Geotechnical Modelling with applications in science and practice. Geomechanics is rarely taught within the rigorous context of Continuum Mechanics and Thermodynamics, while when it comes to Numerical Modelling, commercially available finite elements or finite differences software utilize constitutive relationships within the rigorous framework. As a result, young scientists and engineers have to learn the challenging subject of constitutive modelling from a program manual and often end up with using unrealistic models which violate the Laws of Thermodynamics.  The book is introductory, by no means does it claim any completeness and state of the art in such a dynamically developing field as numerical and constitutive modelling of soils. The author gives basic understanding of conventional continuum mechanics approaches to constitutive modelling, which can serve as a foundation for exploring more advanced theories....

  20. The Constitution's Prescription for Freedom.

    Science.gov (United States)

    Peach, Lucinda

    1986-01-01

    Examines how the framers of the Constitution came to choose our system of government, how that system was designed to function, and how the separation of powers has served to maintain our democracy despite attempts to violate it. (JDH)

  1. Jonathan's Constitutional Conference in Nigeria

    African Journals Online (AJOL)

    ian

    2013-10-01

    Oct 1, 2013 ... Adeniyi S. Basiru is an independent researcher and a PhD candidate ... constitution-making are fundamentally the exclusive reserve of the elites, ..... agenda must be situated against the background of events that heralded his.

  2. A survey on constitutional justice

    Directory of Open Access Journals (Sweden)

    Kheirollah Parvin

    2015-05-01

    Full Text Available The idea of supervising the conformity of statutory law with constitutional law, is due to necessities rooted in two essential principles: the supremacy of constitution and the hierarchy of the law. Constitution as the supreme law in the sense of status and legal value , is placed at the top of the legal pyramid of every political system and therefore requires a special organization and discipline that will act as the sanction of the principles and the main content incorporated in this legal instrument. this special organization and discipline known as Constitutional justice in legal Literature now and have studing in two main patterns. Firs pattern based on Supervision of courts on rules and other pattern is Apply by Emphasis on role of Political Institutions in Supervision on rules. This two patterns have common purpose but have different backgrounds and methods.

  3. THE EMERGING INTERNATIONAL CONSTITUTIONAL ORDER ...

    African Journals Online (AJOL)

    Dr Tanya du Plessis

    CFI) affirmed ... primarily include the value system of the international legal order, meaning norms of ... the existence of such a traditional constitutional demos. Europe's ..... between the African Development Bank (BAD) and one of its employees,.

  4. Pinning down the Constitution: Interactively Teaching Congress's Power, Federalism, and Constitutional Interpretation

    Science.gov (United States)

    Emenaker, Ryan

    2014-01-01

    "Pin-the-Tail-on-the-Constitution" is an engaged-learning activity that has been conducted in 26 classes over the past four years. The activity teaches multiple themes commonly included in a variety of courses on American politics such as federalism, congressional powers, the role of the federal courts, and the relevance of the commerce…

  5. Constitutional Verbosity and Social Trust

    DEFF Research Database (Denmark)

    Bjørnskov, Christian; Voigt, Stefan

    2014-01-01

    A common argument in the trust literature is that high-trust cultures allow efficient commercial contracts to be shorter, covering fewer contingencies. We take this idea to the topic of social contracts. Specifically, we ask whether social trust affects the length and detail of constitutions. Cross......-country estimates suggest that national trust levels are indeed robustly and negatively associated with the length of countries’ constitutions....

  6. Constitutional orders in multinational firms

    DEFF Research Database (Denmark)

    Hull Kristensen, Peer; Morgan, Glenn

    Multinationals are faced with the problem of how to coordinate different actors and stop `fiefdoms' emerging that inhibits the achievement of transnational cooperation? We identify this as a problem of `constitutional ordering' in the firm. Drawing on Varieties of Capitalism approaches, we explore...... how multinationals from different contexts seek to create constitutional orders. We argue that the models which exist appear to be destructive of coordination. We explore the implications for MNCs....

  7. Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Götz Pilarczyk

    2016-01-01

    Full Text Available The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.

  8. Searching the protein structure database for ligand-binding site similarities using CPASS v.2

    Directory of Open Access Journals (Sweden)

    Caprez Adam

    2011-01-01

    Full Text Available Abstract Background A recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as "hypothetical" or "uncharacterized" protein. Our Comparison of Protein Active-Site Structures (CPASS v.2 database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR protocol and has been successfully applied to aid the annotation of a number of proteins of unknown function. Findings We report a major upgrade to our CPASS software and database that significantly improves its broad utility. CPASS v.2 is designed with a layered architecture to increase flexibility and portability that also enables job distribution over the Open Science Grid (OSG to increase speed. Similarly, the CPASS interface was enhanced to provide more user flexibility in submitting a CPASS query. CPASS v.2 now allows for both automatic and manual definition of ligand-binding sites and permits pair-wise, one versus all, one versus list, or list versus list comparisons. Solvent accessible surface area, ligand root-mean square difference, and Cβ distances have been incorporated into the CPASS similarity function to improve the quality of the results. The CPASS database has also been updated. Conclusions CPASS v.2 is more than an order of magnitude faster than the original implementation, and allows for multiple simultaneous job submissions. Similarly, the CPASS database of ligand-defined binding sites has increased in size by ~ 38%, dramatically increasing the likelihood of a positive search result. The modification to the CPASS similarity function is effective in reducing CPASS similarity scores

  9. Right Product, Wrong Packaging: Not 'Constitution', but 'Constitutional Charter'

    Directory of Open Access Journals (Sweden)

    John Law

    2007-05-01

    Full Text Available The article seeks to locate the principal cause of Europe’s prevailing ratification crisis in the inappropriate title arrived at in the European Convention, Treaty Establishing a Constitution for Europe. This over-ambitious styling led the media to characterise the text as simply an ‘EU Constitution’. Yet, the text was not a Constitution as we traditionally understand the term, i.e. the founding document of a State: scholars are agreed that the EU is not, and will not become upon ratification, a State.In terms of substance, whilst the text certainly strengthened some emerging constitutional aspects, it was not a major departure from the status quo like the Single European Act and Treaty on European Union had been; and it remained technically a treaty like all its predecessors. Arguably, therefore, it did not require referenda to ratify. However, confusion over the scale and importance of what was proposed, stemming from ambiguity in the title, pushed politicians down this unfortunate path.The article identifies a high level of consensus among commentators as to the true nature of the text: most are happy designating it a treaty (noun with constitutional (adjective aspects. The early proposed title Constitutional Treaty for Europe was arguably, therefore, the correct one; but it is now too late to choose this option, as the terms Constitution and Constitutional Treaty have already been muddled in debate. A more distinctive change is required. One idea could be to follow the principle employed elsewhere in the text of codifying the generally accepted but presently unwritten legal concepts of the European Court of Justice, as was done for example for ‘primacy’ and ‘direct effect’. The Court has characterised the EU treaties as a ‘constitutional charter’ for over twenty years now, and on this basis a modified title could read Treaty Establishing a Constitutional Charter for Europe. Importantly, the term ‘charter’ is recognised

  10. Oxidative desulfurization of diesel by potato based-carbon as green support for H5PMo10V2O40: Efficient composite nanorod catalyst

    Directory of Open Access Journals (Sweden)

    Ezzat Rafiee

    2017-07-01

    Full Text Available The C@POM (carbon@polyoxometalate containing H3PMo12O40 (PMo12, H5PMo10V2O40 (PMo10V2, H6PMo9V3O40 (PMo9V3, H7PMo8V4O40 (PMo8V4, H3PW12O40 (PW, and H4SiW12O40 (SiW were prepared from natural potato as green, and cheap catalyst support source. The C@PMo10V2 was found to be a unique, effective, and eco-friendly catalyst for selective oxidation of sulfides, using 30% aq. H2O2. C@PMo10V2 composite was characterized by X-ray diffraction spectroscopy (XRD, energy dispersive X-ray spectroscopy (EDX, scanning electron microscopy (SEM, thermal gravimetric analysis (TGA, Fourier transform infrared (FT-IR spectrophotometry, zeta sizer, and zeta potential. The XRD results show that during immobilization PMo10V2 on the carbon catalyst support (CCS, the crystallite structure of PMo10V2 and CCS was not changed. The SEM results show that PMo10V2 crystals deposited on the surface CCS rods as composite nanorod structure. A variety of sulfides, sulfur-containing model and real oil were oxidized with the C@PMo10V2/H2O2 at room temperature. Recovered catalyst show excellent activity for at least four repeating cycles.

  11. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    Science.gov (United States)

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  12. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    International Nuclear Information System (INIS)

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA

  13. Transverse acoustic phonon anomalies at intermediate wave vectors in MgV2O4

    Science.gov (United States)

    Weber, T.; Roessli, B.; Stock, C.; Keller, T.; Schmalzl, K.; Bourdarot, F.; Georgii, R.; Ewings, R. A.; Perry, R. S.; Böni, P.

    2017-11-01

    Magnetic spinels (with chemical formula A X2O4 , with X a 3 d transition metal ion) that also have an orbital degeneracy are Jahn-Teller active and hence possess a coupling between spin and lattice degrees of freedom. At high temperatures, MgV2O4 is a cubic spinel based on V3 + ions with a spin S =1 and a triply degenerate orbital ground state. A structural transition occurs at TOO=63 K to an orbitally ordered phase with a tetragonal unit cell followed by an antiferromagnetic transition of TN=42 K on cooling. We apply neutron spectroscopy in single crystals of MgV2O4 to show an anomaly for intermediate wave vectors at TOO associated with the acoustic phonon sensitive to the shear elastic modulus (C11-C12)/2 . On warming, the shear mode softens for momentum transfers near close to half the Brillouin zone boundary, but recovers near the zone center. High resolution spin-echo measurements further illustrate a temporal broadening with increased temperature over this intermediate range of wave vectors, indicative of a reduction in phonon lifetime. A subtle shift in phonon frequencies over the same range of momentum transfers is observed with magnetic fields. We discuss this acoustic anomaly in context of coupling to orbital and charge fluctuations.

  14. RJHS V2(4)ver12.cdr

    African Journals Online (AJOL)

    extract of MO restored TP concentrations and LDH activities to near normal values. Conclusion: We concluded that leaves of Moringa oleifera .... multiple range tests. Results were considered to be statistically significant when p values .... Caceres A, Cabrera O, Morales O,. M o l l i n e d o P, M e n d i a P. Pharmacological ...

  15. Constitutional compatibility of energy systems

    International Nuclear Information System (INIS)

    Rossnagel, A.

    1983-01-01

    The paper starts from the results of the Enquiry Commission on 'Future Nuclear Energy Policy' of the 8th Federal German Parliament outlining technically feasible energy futures in four 'pathways'. For the purpose of the project, which was to establish the comparative advantages and disadvantages of different energy systems, these four scenarios were reduced to two alternatives: cases K (= nuclear energy) and S (= solar energy). The question to Ge put is: Which changes within our legal system will be ushered in by certain technological developments and how do these changes relate to the legal condition intended so far. Proceeding in this manner will not lead to the result of a nuclear energy system or a solar energy system being in conformity or in contradiction with the constitutional law, but will provide a catalogue of implications orientated to the aims of legal standards: a person deciding in favour of a nuclear energy system or a solar energy system supports this or that development of constitutional policy, and a person purishing this or that aim of legal policy should be consistent and decide in favour of this or that energy system. The investigation of constitutional compatibility leads to the question what effects different energy systems will have on the forms of political intercourse laid down in the constitutional law, which are orientated to models of a liberal constitutional tradition of citizens. (orig./HSCH) [de

  16. Li3-xNaxV2(PO4)3 (0≤x≤3): Possible anode materials for rechargeable lithium-ion batteries

    International Nuclear Information System (INIS)

    Wang, Pengfei; Shao, Lianyi; Qian, Shangshu; Yi, Ting-Feng; Yu, Haoxiang; Yan, Lei; Li, Peng; Lin, Xiaoting; Shui, Miao; Shu, Jie

    2016-01-01

    Highlights: • Li 3-x Na x V 2 (PO 4 ) 3 (0 ≤ x ≤ 3) series are firstly evaluated as anode materials. • Li 3-x Na x V 2 (PO 4 ) 3 anodes show lithium storage activity in 1.0–3.0 V. • The lithium storage capability of different Li 3-x Na x V 2 (PO 4 ) 3 is compared. • Structural reversibility of Li 3-x Na x V 2 (PO 4 ) 3 is studied by in-situ XRD. - Abstract: In this paper, a series of Li 3-x Na x V 2 (PO 4 ) 3 (0 ≤ x ≤ 3) are prepared by a solid state reaction and systematically evaluated as anode materials for lithium-ion batteries. Structural analysis shows that the phase structure of Li 3-x Na x V 2 (PO 4 ) 3 changes along with the evolution of Na content. Charge-discharge tests exhibit that Li 3 V 2 (PO 4 ) 3 shows the highest initial charge specific capacity as high as 88.3 mAh g −1 among all the seven samples, and the reversible capacity is kept at 68.3 mAh g −1 after 45 cycles, corresponding to 77.3% of the initial charge capacity. With increasing of Na content in Li 3-x Na x V 2 (PO 4 ) 3 , the as-obtained sample show poorer lithium storage capability than Li 3 V 2 (PO 4 ) 3 . As a result, Na 3 V 2 (PO 4 ) 3 shows the inferior cycling performance than other Li 3-x Na x V 2 (PO 4 ) 3 . It can only deliver a reversible capacity of 20.9 mAh g −1 after 45 cycles, corresponding to 45.9% of the initial charge capacity. In-situ X-ray diffraction observations demonstrate that the poor electrochemical property of Na 3 V 2 (PO 4 ) 3 anode is due to the irreversible structural evolution during charge-discharge process. Therefore, reducing the Na 3 V 2 (PO 4 ) 3 phase in as-obtained sample is a feasible route to improve the lithium storage capability of Li 3-x Na x V 2 (PO 4 ) 3 .

  17. Fetal bovine serum and human constitutive androstane receptor: Evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system

    Energy Technology Data Exchange (ETDEWEB)

    Lau, Aik Jiang; Chang, Thomas K.H., E-mail: thomas.chang@ubc.ca

    2014-06-01

    The naturally occurring SV23 splice variant of human constitutive androstane receptor (hCAR-SV23) is activated by di-(2-ethylhexyl)phthalate (DEHP), which is detected as a contaminant in fetal bovine serum (FBS). In our initial experiment, we compared the effect of dialyzed FBS, charcoal-stripped, dextran-treated FBS (CS-FBS), and regular FBS on the basal activity and ligand-activation of hCAR-SV23 in a cell-based reporter gene assay. In transfected HepG2 cells cultured in medium supplemented with 10% FBS, basal hCAR-SV23 activity varied with the type of FBS (regular > dialyzed > CS). DEHP increased hCAR-SV23 activity when 10% CS-FBS, but not regular FBS or dialyzed FBS, was used. With increasing concentrations (1–10%) of regular FBS or CS-FBS, hCAR-SV23 basal activity increased, whereas in DEHP-treated cells, hCAR-SV23 activity remained similar (regular FBS) or slightly increased (CS-FBS). Subsequent experiments identified a serum-free culture condition to detect DEHP activation of hCAR-SV23. Under this condition, artemisinin, artemether, and arteether increased hCAR-SV23 activity, whereas they decreased it in cells cultured in medium supplemented with 10% regular FBS. By comparison, FBS increased the basal activity of the wild-type isoform of hCAR (hCAR-WT), whereas it did not affect the basal activity of the SV24 splice variant (hCAR-SV24) or ligand activation of hCAR-SV24 and hCAR-WT by 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO). The use of serum-free culture condition was suitable for detecting CITCO activation of hCAR-WT and hCAR-SV24. In conclusion, FBS leads to erroneous classification of pharmacological ligands of hCAR-SV23 in cell-based assays, but investigations on functional ligands of hCAR isoforms can be conducted in serum-free culture condition. - Highlights: • FBS leads to erroneous pharmacological classification of hCAR-SV23 ligands. • Artemisinin, artemether, and arteether activate h

  18. Constitutionalism and Development in Nigeria: The 1999 Constitution

    African Journals Online (AJOL)

    Fr. Ikenga

    the 3 arms of government the Executive, Legislative, Judiciary, Public Service and Marketing .... Rotation principle of a presidency position in Nigeria which will cultivate a sense of ... the issues survived inclusion in the 1999 Constitution of the Federal Republic of Nigeria. 13. S. 2 of Decree No. ..... Oxford, 5th Edition p.245.

  19. The Spanish Constitution, the Constitutional Court and the Catalan Referendum

    DEFF Research Database (Denmark)

    Abat Ninet, Antoni

    2015-01-01

    and politeia that Aristotle defined now clashes between two powerful symbolic and romantic phenomena. In the Spanish-Catalan binomial scenario, there are some elements that need to be analysed to obtain a complete picture of the constitutional possibilities to of accommodating a Catalan self...

  20. Glucose-assisted synthesis of Na3V2(PO4)3/C composite as an electrode material for high-performance sodium-ion batteries

    Science.gov (United States)

    Li, Guangqiang; Jiang, Danlu; Wang, Hui; Lan, Xinzheng; Zhong, Honghai; Jiang, Yang

    2014-11-01

    A novel electrode material for sodium-ion batteries (NIBs), Na3V2(PO4)3 with a rhombohedral, Na+ superionic conductor (NASICON)-type structure, was synthesised via a solid-state carbon-thermal reduction reaction assisted by mechanochemical activation. Electron microscopy analysis showed that the synthesised Na3V2(PO4)3 particles had an average size of 300 nm, being coated with a uniform layer of carbon 3 nm in thickness. As a cathode material, Na3V2(PO4)3/C exhibited an initial specific discharge capacity of 98.17 mAh g-1 at 0.1C for potentials ranging from 2.5 to 3.8 V. This was owing to the V3+/V4+ redox couple, which corresponded to the two-phase transition between Na3V2(PO4)3 and NaV2(PO4)3. The cathode lost 4.92% of its discharge specific capacity after 50 cycles. As an anode material, Na3V2(PO4)3/C exhibited an initial specific discharge capacity of 63.2 mAh g-1 at 0.1C for potentials ranging from 1.0 to 2.5 V. This was owing to the V2+/V3+ redox couple, which corresponded to the two-phase transition between Na3V2(PO4)3 and Na4V2(PO4)3. The anode lost approximately 5.41% of its discharge specific capacity after 50 cycles. The three-dimensional channel structure of NaV2(PO4)3 and the changes induced in its lattice parameters during the charge/discharge processes were simulated on the basis of density functional theory.

  1. Ancestral amphibian v2rs are expressed in the main olfactory epithelium

    Science.gov (United States)

    Syed, Adnan S.; Sansone, Alfredo; Nadler, Walter; Manzini, Ivan; Korsching, Sigrun I.

    2013-01-01

    Mammalian olfactory receptor families are segregated into different olfactory organs, with type 2 vomeronasal receptor (v2r) genes expressed in a basal layer of the vomeronasal epithelium. In contrast, teleost fish v2r genes are intermingled with all other olfactory receptor genes in a single sensory surface. We report here that, strikingly different from both lineages, the v2r gene family of the amphibian Xenopus laevis is expressed in the main olfactory as well as the vomeronasal epithelium. Interestingly, late diverging v2r genes are expressed exclusively in the vomeronasal epithelium, whereas “ancestral” v2r genes, including the single member of v2r family C, are restricted to the main olfactory epithelium. Moreover, within the main olfactory epithelium, v2r genes are expressed in a basal zone, partially overlapping, but clearly distinct from an apical zone of olfactory marker protein and odorant receptor-expressing cells. These zones are also apparent in the spatial distribution of odor responses, enabling a tentative assignment of odor responses to olfactory receptor gene families. Responses to alcohols, aldehydes, and ketones show an apical localization, consistent with being mediated by odorant receptors, whereas amino acid responses overlap extensively with the basal v2r-expressing zone. The unique bimodal v2r expression pattern in main and accessory olfactory system of amphibians presents an excellent opportunity to study the transition of v2r gene expression during evolution of higher vertebrates. PMID:23613591

  2. Solvothermal synthesis of V2O5/graphene nanocomposites for high performance lithium ion batteries

    International Nuclear Information System (INIS)

    Chen, Da; Yi, Ran; Chen, Shuru; Xu, Terrence; Gordin, Mikhail L.; Lv, Dongping; Wang, Donghai

    2014-01-01

    Highlights: • A homogeneous V 2 O 5 /graphene nanocomposite is successfully synthesized. • V 2 O 5 nanoparticles are highly encapsulated in the 2D graphene matrix. • V 2 O 5 /graphene nanocomposite shows much better performance than bare V 2 O 5 . - Abstract: In this work, V 2 O 5 /graphene nanocomposites have been synthesized by a facile solvothermal approach. The V 2 O 5 nanoparticles, around 20–40 nm in size, were encapsulated in the 2D graphene matrix. The reversible Li-cycling properties of V 2 O 5 /graphene have been evaluated by galvanostatic discharge–charge cycling, cyclic voltammetry, and impedance spectroscopy. Compared with the bare V 2 O 5 nanoparticles, the V 2 O 5 /graphene nanocomposites exhibited enhanced electrochemical performance with higher reversible capacity and improved cycling stability and rate capability. The graphene nanosheets act not only as an electronically conductive matrix to improve the electronic and ionic conductivity of the composite electrode, but also as a flexible buffer matrix to maintain the structural integrity of the composite electrodes by preventing particle agglomeration, thus leading to the improvement of the electrochemical performance of V 2 O 5

  3. Time and constitution of sense

    Directory of Open Access Journals (Sweden)

    Pedro Gerardo Acosta

    2014-06-01

    Full Text Available This article proposes a reflection over our time-consciousness under the Phenomenology of Edmund Husserl. The idea is make a release the key role of the sense constitution like the fundament and development of the ongoing intentionality, a shape that make the possibility to catch sight of the sense of every life situation like conscience experience that displays itself over the time, and open the world of the Phenomenon World, constituted in the flux and flow of our live experience. The immanent time in which the things served in a lived-present inevitably displays to its own immediate-past of retentions, then of commemorations, constituting and enabling, not just the sense of ever present, but the sense of our own past like memory and our future like expectative. This reflection is based and supporter over the text “Phenomenology Lesson of the Internal Time-Consiusness” (Husserl, 2002.

  4. Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies.

    Science.gov (United States)

    Seelig, Davis M; Ito, Daisuke; Forster, Colleen L; Yoon, Una A; Breen, Matthew; Burns, Linda J; Bachanova, Veronika; Lindblad-Toh, Kerstin; O'Brien, Timothy D; Schmechel, Stephen C; Rizzardi, Anthony E; Modiano, Jaime F; Linden, Michael A

    2017-07-01

    Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1). We further demonstrate that a small interfering RNA inhibits the activation of the NFκB pathway and induces apoptosis in canine DLBCL cells. In conclusion, the ANFκBP facilitates survival of canine DLBCL cells, and thus, dogs with spontaneous DLBCL can provide a useful large animal model to study therapies targeting the ANFκBP.

  5. Single crystals of the anisotropic Kagome staircase compounds Ni3V2O8 and Co3V2O8

    OpenAIRE

    Balakrishnan, G.; Petrenko, O. A.; Lees, M. R.; Paul, D. McK.

    2004-01-01

    Compounds with a Kagome type lattice are known to exhibit magnetic frustration. Large single crystals of two compounds Ni3V2O8 and Co3V2O8, which are variants of a Kagome net lattice, have been grown successfully by the floating zone technique using an optical image furnace. The single crystals are of high quality and exhibit intriguing magnetic properties.

  6. Removal of organics from radioactive waste. V. 2

    International Nuclear Information System (INIS)

    Williams, J.; Kitchin, J.; Burton, W.H.

    1989-05-01

    This report reviews the available literature concerning the removal of organic substances from radioactive waste streams. A substantial portion of low level wastes generated in the various parts of the nuclear fuel cycle, nuclear laboratories and other places where radionuclides are used for research, industrial medical and defense related activities is organic (paper, wood, plastics, rubber etc.) and combustible. These combustible wastes can be processed by incineration. Incineration converts combustible wastes into radioactive ashes and residues that are non-flammable, chemically inert and more homogenous than the initial waste. (author)

  7. Food and environmental protection newsletter. V. 2, no. 2

    International Nuclear Information System (INIS)

    1999-12-01

    This issue of the Newsletter mainly devoted to the FAO/IAEA/WHO Conference on Ensuring the Safety and Quality of Food through Radiation Processing, held in Antalya, Turkey, 19-22 October 1999. The conference had as its main objectives to evaluate progress and achievements on food irradiation during the 20th century and to identify key issues in further development of this technology to enhance food safety, security and trade for the next century. The summary report of the conference is included in this issue. It also presents recent training activities and meetings undertaken

  8. Food and environmental protection newsletter. V. 2, no. 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-12-01

    This issue of the Newsletter mainly devoted to the FAO/IAEA/WHO Conference on Ensuring the Safety and Quality of Food through Radiation Processing, held in Antalya, Turkey, 19-22 October 1999. The conference had as its main objectives to evaluate progress and achievements on food irradiation during the 20th century and to identify key issues in further development of this technology to enhance food safety, security and trade for the next century. The summary report of the conference is included in this issue. It also presents recent training activities and meetings undertaken.

  9. A Communicatively Constituted Online Crisis

    DEFF Research Database (Denmark)

    Valentini, Chiara; Romenti, Stefania; Kruckeberg, Dean

    2017-01-01

    into specific public crisis perceptions. Drawing from a communicative constitution perspective, the authors argue that if crises are perceptions or experiences of difficult situations that exceed a person’s current resources and coping mechanisms, and if perceptions and experiences in social media are typically...... by offering suggestions on how to study online critical conversations through the lens of a communicative constitution perspective that could inform how critical issues eventually transform and become crises and how crisis perceptions evolve and are discursively shaped by communicative practices occurring...

  10. Constitutional and acquired autosomal aneuploidy.

    Science.gov (United States)

    Jackson-Cook, Colleen

    2011-12-01

    Chromosomal imbalances can result from numerical or structural anomalies. Numerical chromosomal abnormalities are often referred to as aneuploid conditions. This article focuses on the occurrence of constitutional and acquired autosomal aneuploidy in humans. Topics covered include frequency, mosaicism, phenotypic findings, and etiology. The article concludes with a consideration of anticipated advances that might allow for the development of screening tests and/or lead to improvements in our understanding and management of the role that aneuploidy plays in the aging process and acquisition of age-related and constitutional conditions.

  11. A constitutively active cryptochrome in Drosophila melanogaster

    Czech Academy of Sciences Publication Activity Database

    Dissel, S.; Codd, V.; Fedič, Robert; Garner, K. J.; Costa, R.; Kyriacou, C. P.; Rosato, E.

    2004-01-01

    Roč. 7, č. 8 (2004), s. 834-840 ISSN 1097-6256 R&D Projects: GA AV ČR(CZ) KSK5052113 Keywords : Circadian clock * behavioral rhythms * light Subject RIV: ED - Physiology Impact factor: 16.980, year: 2004

  12. Stretchable V2O5/PEDOT supercapacitors: a modular fabrication process and charging with triboelectric nanogenerators.

    Science.gov (United States)

    Qi, Ruijie; Nie, Jinhui; Liu, Mingyang; Xia, Mengyang; Lu, Xianmao

    2018-04-26

    Stretchable energy storage devices are of great importance for the viable applications of wearable/stretchable electronics. Studies on stretchable energy storage devices, especially supercapacitors (SCs), have shown encouraging progress. However, challenges still remain in the pursuit of high specific capacitances and facile fabrication methods. Herein, we report a modular materials fabrication and assembly process for stretchable SCs. With a V2O5/PEDOT composite as the active material, the resulting stretchable SCs exhibited high areal specific capacitances up to 240 mF cm-2 and good capacitance retention at a strain of 50%. To demonstrate the facile assembly process, a stretchable wristband was fabricated by simply assembling SC cells in series to deliver a voltage higher than 2 V. Charging the wristband with a triboelectric nanogenerator (TENG) to light an LED was further demonstrated, indicating the potential to integrate our SCs with environmental energy harvesters for self-powered stretchable devices.

  13. Current and future possibilities of V2V and I2V technologies: an analysis directed toward Augmented Reality systems

    Science.gov (United States)

    Betancur, J. A.; Osorio-Gómez, Gilberto; Arnedo, Aida; Yarce Botero, Andrés.

    2014-06-01

    Nowadays, it is very important to explore the qualitative characteristics of autonomous mobility systems in automobiles, especially disruptive technology like Vehicle to Vehicle (V2V) and Infrastructure to Vehicle (I2V), in order to comprehend how the next generation of automobiles will be developed. In this sense, this research covers a general review about active safety in automobiles where V2V and I2V systems have been implemented; identifying the more realistic possibilities related to V2V and I2V technology and analyzing the current applications, some systems in development process and some future conceptual proposals. Mainly, it is notorious the potential development of mixing V2V and I2V systems pointing to increase the driver's attention; therefore, a configuration between these two technologies and some augmented reality system for automobiles (Head-Up Display and Head-Down Display) is proposed. There is a huge potential of implementation for this kind of configuration once the normative and the roadmap for its development can be widely established.

  14. Evolution of electrochemical performance in Li3V2(PO4)3/C composites caused by cation incorporation

    International Nuclear Information System (INIS)

    Zhang, Lu-Lu; Liang, Gan; Peng, Gang; Jiang, Yan; Fang, Hui; Huang, Yun-Hui; Croft, Mark C.; Ignatov, Alexander

    2013-01-01

    Graphical abstract: Four electrochemically active cations (M = Fe, Co, Ni, Mn) are doped into Li 3 V 2 (PO 4 ) 3 . M-incorporation does not change the monoclinic structure of Li 3 V 2 (PO 4 ) 3 , but forms some solid solutions. Minor LiMPO 4 impurity phases can be formed in the LVMP/C samples. Moreover, FePO 4 also exists as impurity in the LVFeP/C sample. Compared with pristine LVP/C, LVNiP/C electrode exhibits the lowest capacity, resulting from the decreased electronic conductivity and the lowest Li-ion diffusion coefficient, whereas LVFeP/C shows the best electrochemical performance. -- Highlights: • Cation-incorporated Li 3 V 2 (PO 4 ) 3 /C have been systematically investigated. • Cation incorporation in Li 3 V 2 (PO 4 ) 3 does not change the monoclinic structure but form solid solution. • Fe-incorporation shows the best electrochemical performance whereas Ni-incorporation shows the poorest performance. • A clear profile of cation incorporation with Fe, Co, Ni, Mn ions in Li 3 V 2 (PO 4 ) 3 /C is obtained. -- Abstract: Li 3 V 2 (PO 4 ) 3 /C (LVP/C) composites incorporated by a series of electrochemically active cations (Fe, Co, Ni, Mn) have been successfully prepared by a conventional solid-state reaction. M-incorporation (M = Fe, Co, Ni, Mn) in Li 3 V 2 (PO 4 ) 3 does not change the monoclinic structure. Analyzed with X-ray photoelectron spectroscopy, X-ray absorption spectroscopy and high-resolution transmission electron microscopy, we find that the valence is between +2.67 and +3 for Fe, and is +2 for Co, Ni and Mn. M-doped LVP and LiMPO 4 phases coexist in the incorporated LVP/C composites. Compared with pristine LVP/C, Fe-incorporated LVP/C shows the best electrochemical performance with the highest initial discharge capacity of 131.4 mAh g −1 at 0.1 C between 2.5 and 4.3 V. The Fe-incorporated LVP/C sample also exhibits excellent rate capability with an average capacity of 122.4 mAh g −1 at 1 C and 93.5 mAh g −1 at 5 C, resulting from the

  15. Proceedings of the 39. Brazilian congress on geology. v. 2

    International Nuclear Information System (INIS)

    1996-01-01

    The book presents the 39. Brazilian Congress on Geology works, occurred in Salvador, Bahia, during the period of September 1 to 6, 1996. The meeting main subject - geology and society - reflects the current change epoch. The symposiums revealed the more important actions about geosciences applications to the society in the country. The round tables, structured for the polemical subjects debates that involves the geosciences and the mineral sector crisis aspects, were achieved by several invited participants completely embraced with the subject. During the congress activities development there were some course, technical excursions and external actions in Salvador, aiming to show the geosciences role to the social welfare. The works were presented in the following thematic sections: geochemistry and petrology

  16. Facile sonochemical synthesis of Zn2SnO4-V2O5 nanocomposite as an effective photocatalyst for degradation of Eosin Yellow.

    Science.gov (United States)

    Ramasamy Raja, V; Rosaline, D Rani; Suganthi, A; Rajarajan, M

    2018-06-01

    This study presents a novel method for the preparation of Zn 2 SnO 4 /V 2 O 5 nanocomposites via a sonochemical aqueous route. This method is mild, convenient, cheap and efficient. The as prepared samples were characterized by XRD, SEM, EDAX, TEM, BET, FT-IR and UV-DRS spectra. DRS spectrum shows the adsorption edge of Zn 2 SnO 4 -V 2 O 5 in visible region of spectrum. The structural and morphological features of the as synthesized Zn 2 SnO 4 -V 2 O 5 nanocomposites have been observed using both scanning and transmission electron microscopy. BET surface area analysis inferred that the prepared hetero-junctions are meso-porous in nature. The photocatalytic activity of Zn 2 SnO 4 -V 2 O 5 nanocomposites for the degradation of Eosin Yellow (EY) dye under visible light was investigated in detail. 3% Zn 2 SnO 4 -V 2 O 5 nanocomposite exhibited the highest photocatalytic performance (92% of EY degradation) when compared with 2% Zn 2 SnO 4 -V 2 O 5 and 5% Zn 2 SnO 4 -V 2 O 5 . The adsorption of Eosin Yellow followed the pseudo-first order kinetic model. Simultaneously, high stability of the sample was also investigated by four successive photodegradation of EY under visible light. The relationship between photocatalytic activity and the structure of 3% Zn 2 SnO 4 -V 2 O 5 nanocomposite is discussed, and possible reaction mechanisms are also proposed. Therefore, the facile sonochemical preparation process provides some insight into the application of Zn 2 SnO 4 -V 2 O 5 nanocomposites in photocatalytic degradation of organic pollutants. Copyright © 2018. Published by Elsevier B.V.

  17. [Constitutional mismatch repair deficiency syndrome

    NARCIS (Netherlands)

    Jongmans, M.C.J.; Gidding, C.E.M.; Loeffen, J.; Wesseling, P.; Mensenkamp, A.; Hoogerbrugge, N.

    2015-01-01

    BACKGROUND: Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. CASE DESCRIPTION: An 8-year-old

  18. The Constitution and Academic Freedom.

    Science.gov (United States)

    Gilbertson, Eric R.

    During the past 150 years U.S. courts have demonstrated a special protectiveness toward academics and academic institutions. Academic freedom was not a concern when the U.S. Constitution and the First Amendment were drafted and is not mentioned in the "Federalist Papers." However, decisions by a series of Supreme Court justices led to…

  19. fdtd Semiconductor Microlaser Simulator v. 2.0

    Energy Technology Data Exchange (ETDEWEB)

    2009-01-29

    This software simulates the transient optical response of a system of in-plane semiconductor lasers/waveguides of almost arbitrary 2D complexity using the effective index approximation. Gain is calculated by solving a 3D transport equation from an arbitrary contact geometry and epi structure to get an input current density to the active region, followed by a diffusion equation for carriers in that layer. The gain is saturable and frequency dependent so that output powers and frequency spectrum/longitudinal modes are predicted. Solution is by the finite-difference time-domain method on a 2D triangular grid, so that propagation in any direction along the epi plan is allowed, and arbitrary laser/waveguide shapes can be modeled, including rings. Runtime considerations, however, limit the practical solution region to approximately 500 microns**2 so that the applicability of this code is primarily limited to micro-resinators. Modeling of standard-edge-emitting semiconductor lasers is better accomplished using algorithms based on bi-directional beam propagation.

  20. Ube2V2 Is a Rosetta Stone Bridging Redox and Ubiquitin Codes, Coordinating DNA Damage Responses.

    Science.gov (United States)

    Zhao, Yi; Long, Marcus J C; Wang, Yiran; Zhang, Sheng; Aye, Yimon

    2018-02-28

    Posttranslational modifications (PTMs) are the lingua franca of cellular communication. Most PTMs are enzyme-orchestrated. However, the reemergence of electrophilic drugs has ushered mining of unconventional/non-enzyme-catalyzed electrophile-signaling pathways. Despite the latest impetus toward harnessing kinetically and functionally privileged cysteines for electrophilic drug design, identifying these sensors remains challenging. Herein, we designed "G-REX"-a technique that allows controlled release of reactive electrophiles in vivo. Mitigating toxicity/off-target effects associated with uncontrolled bolus exposure, G-REX tagged first-responding innate cysteines that bind electrophiles under true k cat / K m conditions. G-REX identified two allosteric ubiquitin-conjugating proteins-Ube2V1/Ube2V2-sharing a novel privileged-sensor-cysteine. This non-enzyme-catalyzed-PTM triggered responses specific to each protein. Thus, G-REX is an unbiased method to identify novel functional cysteines. Contrasting conventional active-site/off-active-site cysteine-modifications that regulate target activity, modification of Ube2V2 allosterically hyperactivated its enzymatically active binding-partner Ube2N, promoting K63-linked client ubiquitination and stimulating H2AX-dependent DNA damage response. This work establishes Ube2V2 as a Rosetta-stone bridging redox and ubiquitin codes to guard genome integrity.

  1. Adsorption of ethanol on V2O5 (010) surface for gas-sensing applications: Ab initio investigation

    International Nuclear Information System (INIS)

    Qin, Yuxiang; Cui, Mengyang; Ye, Zhenhua

    2016-01-01

    Highlights: • Ethanol adsorbed on V 2 O 5 (010) surface was investigated by ab initio calculations. • Ethanol prefers to adsorb on “Hill”-like surface, rather than“Valley”-like region. • Surface O 1(H) site plays a key role to dominate the ethanol adsorption process. • Sensing mechanism is related with electronic structure and electron redistribution. • Gas sensitivity is reflected by quantitative electron population analysis. - Abstract: The adsorption of ethanol on V 2 O 5 (010) surface was investigated by means of density functional theory (DFT) with a combined generalized gradient approximation (GGA) plus Hubbard U approach to exploit the potential sensing applications. The adsorption configurations were first constructed by considering different orientations of ethanol molecule to V and O sites on the “Hill”- and “Valley”-like regions of corrugated (010) surface. It is found that ethanol molecule can adsorb on whole surface in multiple stable configurations. Nevertheless the molecular adsorption on the “Hill”-like surface is calculated to occur preferentially, and the single coordinated oxygen on “Hill”-like surface (O 1(H) ) acting as the most energetically favorable adsorption site shows the strongest adsorption ability to ethanol molecule. Surface adsorption of ethanol tunes the electronic structure of V 2 O 5 and cause an n-doping effect. As a consequence, the Fermi levels shift toward the conductive bond increasing the charge carrier concentration of electrons in adsorbed V 2 O 5 . The sensitive electronic structure and the multiple stable configurations to ethanol adsorption highlight the high adsorption activity and then the potential of V 2 O 5 (010) surface applied to high sensitive sensor for ethanol vapor detection. Further Mulliken population and Natural bond orbital (NBO) calculations quantify the electron transfer from the adsorbed ethanol to the surface, and correlates the adsorption ability of surface sites

  2. Intercomparison of delayed neutron summation calculations among JEF2.2, ENDF/B-VI and JNDC-V2

    Energy Technology Data Exchange (ETDEWEB)

    Sagisaka, Mitsuyuki [Nagoya Univ. (Japan); Oyamatsu, K.; Kukita, Y.

    1998-03-01

    We perform intercomparison of delayed neutron activities calculated with JEF2.2, ENDF/B-VI and JNDC-V2 with a simple new method. Significant differences are found at t < 20 (s) for major fissioning systems. The differences are found to stem from fission yields or decay data of several nuclides. The list of these nuclides are also given for the future experimental determination of these nuclear data. (author)

  3. Contested constitutions: Legitimacy of constitution-making and constitutional conflict in Central Europe

    NARCIS (Netherlands)

    de Raadt, J.B.

    2009-01-01

    What were the effects of constitution-making procedures on the acceptance of the new "rules of the political game" in postcommunist Central Europe? This article sets out to scrutinise the increasingly popular claim among politicians and scholars of democratisation that inclusiveness and popular

  4. Novel synthesis of manganese and vanadium mixed oxide (V2O5/OMS-2) as an efficient and selective catalyst for the oxidation of alcohols in liquid phase

    International Nuclear Information System (INIS)

    Mahdavi, Vahid; Soleimani, Shima

    2014-01-01

    Graphical abstract: Oxidation of various alcohols is studied in the liquid phase over new composite mixed oxide (V 2 O 5 /OMS-2) catalyst using tert-butyl hydroperoxide (TBHP). The activity of V 2 O 5 /OMS-2 samples was considerably increased with respect to OMS-2 catalyst and these samples are found to be suitable for the selective oxidation of alcohols. - Highlights: • V 2 O 5 /K-OMS-2 with different V/Mn molar ratios prepared by the impregnation method. • Oxidation of alcohols was studied in the liquid phase over V 2 O 5 /K-OMS-2 catalyst. • V 2 O 5 /K-OMS-2 catalyst had excellent activity for alcohol oxidation. • Benzyl alcohol oxidation using excess TBHP followed a pseudo-first order kinetic. • The selected catalyst was reused without significant loss of activity. - Abstract: This work reports the synthesis and characterization of mixed oxide vanadium–manganese V 2 O 5 /K-OMS-2 at various V/Mn molar ratios and prepared by the impregnation method. Characterization of these new composite materials was made by elemental analysis, BET, XRD, FT-IR, SEM and TEM techniques. Results of these analyses showed that vanadium impregnated samples contained mixed phases of cryptomelane and crystalline V 2 O 5 species. Oxidation of various alcohols was studied in the liquid phase over the V 2 O 5 /K-OMS-2 catalyst using tert-butyl hydroperoxide (TBHP) and H 2 O 2 as the oxidant. Activity of the V 2 O 5 /K-OMS-2 samples was increased considerably with respect to K-OMS-2 catalyst due to the interaction of manganese oxide and V 2 O 5 . The kinetic of benzyl alcohol oxidation using excess TBHP over V 2 O 5 /K-OMS-2 catalyst was investigated at different temperatures and a pseudo-first order reaction was determined with respect to benzyl alcohol. The effects of reaction time, oxidant/alcohol molar ratio, reaction temperature, solvents, catalyst recycling potential and leaching were investigated

  5. Valuation In The Constitutional Era

    Directory of Open Access Journals (Sweden)

    Elmien du Plessis

    2015-12-01

    Full Text Available The Constitution brought about a new compensation regime for expropriations. Compensation for expropriation must now be "just and equitable". Whereas before the Constitution came into force market value played a central role in compensation for expropriation, market value is now only one factor or aspect of compensation that the court needs to take into account. Yet we find that courts tend to focus on market value and to still employ the valuation methods used to calculate market value. This article argues that the methods used to calculate the market value, once thought to be objective, are not as objective as was believed. While it is impossible to give judges specific tools for the assessment of market value, this article provides guidelines on how the calculation of compensation should be approached.

  6. The Constitutive Power of Twitter

    DEFF Research Database (Denmark)

    Albu, Oana Brindusa; Etter, Michael Andreas

    Twitter is an increasingly used new information and communication technology (ICT) in organizational settings. Predominant research, however, tends to adopt functionalist standpoints and investigates new ICTs as platforms of information transmission through which organizations interact with their......Twitter is an increasingly used new information and communication technology (ICT) in organizational settings. Predominant research, however, tends to adopt functionalist standpoints and investigates new ICTs as platforms of information transmission through which organizations interact...... with their constituents. Such focus leaves little knowledge concerning the tensions new ICTs bring to organizational life. For a more nuanced understanding of the constitutive role of new ICTs in organizing, this paper unfolds a communication centered perspective and examines the strategic Twitter use in two...... organizations. The analysis illustrates how specific Twitter interactions, i.e., hashtags, become hypertexts—a type of authoritative texts—which simultaneously constitute an organizational actor or act as a pastiche of it. The study contributes to extant research by illustrating how hypertextuality...

  7. Editor's Highlight: Mode of Action Analysis for Rat Hepatocellular Tumors Produced by the Synthetic Pyrethroid Momfluorothrin: Evidence for Activation of the Constitutive Androstane Receptor and Mitogenicity in Rat Hepatocytes.

    Science.gov (United States)

    Okuda, Yu; Kushida, Masahiko; Sumida, Kayo; Nagahori, Hirohisa; Nakamura, Yoshimasa; Higuchi, Hashihiro; Kawamura, Satoshi; Lake, Brian G; Cohen, Samuel M; Yamada, Tomoya

    2017-08-01

    High dietary levels of momfluorothrin, a nongenotoxic synthetic pyrethroid, induced hepatocellular tumors in male and female Wistar rats in a 2-year bioassay. The mode of action (MOA) for rat hepatocellular tumors was postulated to occur via activation of the constitutive androstane receptor (CAR), as momfluorothrin is a close structural analogue of the pyrethroid metofluthrin, which is known to produce rat liver tumors through a CAR-mediated MOA. To elucidate the MOA for rat hepatocellular tumor formation by momfluorothrin, this study was conducted to examine effects on key and associative events of the CAR-mediated MOA for phenobarbital based on the International Programme on Chemical Safety framework. A 2-week in vivo study in Wistar rats revealed that momfluorothrin induced CYP2B activities, increased liver weights, produced hepatocyte hypertrophy and increased hepatocyte replicative DNA synthesis. These effects correlated with the dose-response relationship for liver tumor formation and also showed reversibility upon cessation of treatment. Moreover, momfluorothrin did not increase CYP2B1/2 mRNA expression and hepatocyte replicative DNA synthesis in CAR knockout rats. Using cultured Wistar rat hepatocytes and the RNA interference technique, knockdown of CAR resulted in a suppression of induction of CYP2B1/2 mRNA levels by momfluorothrin. Alternative MOAs for liver tumor formation were excluded. A global gene expression profile analysis of the liver of male Wistar rats treated with momfluorothrin for 2 weeks also showed similarity to the prototypic CAR activator phenobarbital. Overall, these data strongly support that the postulated MOA for momfluorothrin-induced rat hepatocellular tumors as being mediated by CAR activation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. [Women, gender, and the Constitution].

    Science.gov (United States)

    1993-12-01

    Although all the constitutions of Latin America directly or indirectly acknowledge the juridical equality of the sexes, these patriarchal societies continue to maintain institutional power in male hands and to neutralize legal actions favoring women. International instruments such as the Convention on Elimination of All Forms of Discrimination Against Women, approved by the UN in 1979, have given a firmer basis to policies and actions to improve the status of women. Obstacles to full equality of Latin American women are rooted in economic and sociopolitical factors, but lack of true political will also plays a significant role. A number of new laws in the past several years as well as the new Constitution have improved the legal position of Colombian women. The new Constitution recognizes fundamental rights that may be claimed directly before a judge, and social, economic, and collective rights requiring legislative development. Article 43 of the new Constitution states that women will not be subjected to any form of discrimination. Another norm states that women will enjoy special assistance and protection before and after childbirth, in recognition of the social functions of maternity. Article 43 also states that women who are heads of households will receive special assistance, but the corresponding regulations have not yet been promulgated. The mechanism of tutelage has become an important recourse that has been used in several cases in which fundamental rights of women have been violated or threatened because of their sex. The order of tutelage has been used in cases of adolescents expelled from school for pregnancy and of abused wives, as well as to force recognition of the social and economic contributions of housework.

  9. European constitution and EURATOM treaty

    International Nuclear Information System (INIS)

    Heller, W.

    2003-01-01

    The European Council held in Laeken in December 2001 had decided to call a convention preparing the next conference of the heads of state and government which, among other topics, was to deliberate the question of a fully formulated European constitution. Under the presidency of Giscard d'Estaing, all delegates to the European Convention on July 10, 2003 signed the draft treaty for a European constitution. This final document is the basis of the conference of the heads of state and government to begin in October 2003. On this occasion, the draft of a separate chapter on energy could well come up again for examination. This chapter had been introduced only at the end of the deliberations of the convention and adds to the competences of the EU institutions. Also the Euratom Treaty was a topic of the convention preparing the constitution. As the presidency felt that no specific issues had been raised in the Laeken declaration, it is proposed to adapt the Euratom Treaty to the new provisions of the constitution by adding a protocol. This would mean that the European Atomic Energy Community, for the time being, would retain its independent legal status. The contents would have to be examined at some later date. Consequently, the real discussion of the Euratom Treaty is yet to come. Also, the speedy completion of the single market for electricity would make it desirable for the Community to adopt a uniform, positive stance in the use of nuclear power at the best possible safety standards so as to ensure a level playing field. Current events entailing power failures in the United States and the United Kingdom have alerted the public to the problem of the continuity of power supply. This could well be the beginning of a new, unbiased, balanced energy discussion in a bigger Europe. (orig.)

  10. Transporte de carga em compósitos de polianilina/V2O5 Charge transportation in polyaniline/V2O5 composites

    Directory of Open Access Journals (Sweden)

    Fritz Huguenin

    2004-06-01

    Full Text Available In this work, composites formed from a mixture of V2O5 and polyaniline (PANI were investigated, for applications as cathode materials for secondary lithium batteries. Electrochemical quartz crystal microbalance (EQCM data show that charge compensation in the [PANI]0.3V2O5 nanocomposite is achieved predominantly by Li+ migration. However, the charge compensation in the [PANI]V2O5 microcomposite occurs by Li+ and ClO4- transport. Electrochemical Impedance Spectroscopy (EIS measurements reveal several benefits of nanohybrid formation, including the achievement of shorter ionic diffusion pathways, the higher diffusion rate of the lithium ion and also the higher electronic conductivity, which are responsible for a synergetic effect of the energy storage properties.

  11. Constitutional collisions of criminal law

    Directory of Open Access Journals (Sweden)

    Sergey M. Inshakov

    2016-12-01

    Full Text Available Objective to identify and resolve conflicts between the norms of constitutional and criminal law which regulate the issue of legal liability of senior officials of the state. Methods formallogical systematic comparativelegal. Results the article analyzes the embodiment of the principle of citizensrsquo equality under the law regarding the criminal responsibility of the President of the Russian Federation as one of the segments of the elite right other criminal and legal conflicts are considered associated with the creation of conditions for derogation from the principle of equality. Basing on this analysis the means of overcoming collisions between the norms of constitutional and criminal law are formulated. Scientific novelty in the article for the first time it has been shown that in the Russian criminal law there are exceptions to the principle of citizensrsquo equality under the law relating to the President of the Russian Federation the conflicts are identified between the norms of constitutional and criminal law regulating the issue of legal liability of senior officials of the state ways of overcoming conflicts are suggested. Practical significance the main provisions and conclusions of the article can be used in research and teaching in the consideration of issues of senior state officialsrsquo criminal liability.

  12. 76 FR 2800 - Amendment of VOR Federal Airways V-2 and V-21; Hawaii

    Science.gov (United States)

    2011-01-18

    ...-1263; Airspace Docket No. 10-AWP-17] Amendment of VOR Federal Airways V-2 and V-21; Hawaii AGENCY... Omnidirectional Range (VOR) Federal airway legal descriptions in the State of Hawaii. The FAA is taking this... Regulations (14 CFR) part 71 by amending two VOR Federal Airways, V-2 and V-21, located in the State of Hawaii...

  13. Mobility Patterns Informing V2X Research Projects: Eco-Routing and Electrified Roadway Project Examples

    Energy Technology Data Exchange (ETDEWEB)

    Gonder, Jeff; Brooker, Aaron; Burton, Evan; Wang, Lijuan; Wood, Eric

    2016-05-19

    Presentation given at an 'Expert Workshop on V2X Enabled Electric Vehicles' hosted at NREL on behalf of the International Energy Agency (IEA) Hybrid and Electric Vehicle Implementing Agreement for Task 28: Home Grids and V2X Technologies.

  14. Electrochemical Performance of a V2O5 Cathode for a Sodium Ion Battery

    Science.gov (United States)

    Van Nghia, Nguyen; Long, Pham Duy; Tan, Ta Anh; Jafian, Samuel; Hung, I.-Ming

    2017-06-01

    In this paper, layered vanadium pentoxide (V2O5) is employed as a cathode material for a sodium ion battery. The V2O5 particle sizes range from 200 nm to 500 nm and the shapes of the aggregated V2O5 particles are non-homogeneous and irregular. The material exhibits a first discharge capacity of approximately 208.1 mAh g-1. The structure of V2O5 changes to a NaxV2O5 structure after Na+ insertion at the first discharge; the structure of NaxV2O5 remains stable␣during cycling. After 40 cycles, the discharge capacity retains 61.2% of the capacity of the second cycle. The capacity of V2O5 at a high charge/discharge current rate of 1.0 C is 49.1% of capacity at 0.1 C. Furthermore, the capacity returns to the initial value as the discharge rate returns to 0.1 C. The results of electrochemical performance tests indicate that V2O5 is a potential cathode material for sodium ion batteries.

  15. Charge ordering and opening of spin gap in NaV2O5

    NARCIS (Netherlands)

    Mostovoy, M.V.; Khomskii, D.I.

    1999-01-01

    We argue that the origin of the phase transition in quasi-one-dimensional antiferromagnet NaV2O5 is not the spin-Peierls (SP) instability, but a charge ordering. The opening of the spin gap and the lattice dimerization, characteristic for the spin-Peierls systems, in NaV2O5 result from the interplay

  16. Facile synthesis and characterization of rough surface V2O5 ...

    Indian Academy of Sciences (India)

    2017-09-20

    Sep 20, 2017 ... V2O5 nanomaterials with rough surface were synthesized using commercial V2O5, ethanol (EtOH) and H2O ... properties make them available as power sources for the next- ... by the electrospinning method and obtained high capacitance .... performed in the potential range of −0.6 to 0.8 V at a current.

  17. Beam Tracking in Switched-Beam Antenna System for V2V Communication

    Directory of Open Access Journals (Sweden)

    Settawit Poochaya

    2016-01-01

    Full Text Available This paper presents the proposed switched beam antenna system for V2V communication including optimum antenna half power beamwidth determination in urban road environments. SQP optimization method is selected for the computation of optimum antenna half power beamwidth. In addition, beam tracking algorithm is applied to guarantee the best beam selection with maximum RSSI. The results present the success of the proposed system with the increasing of V2V performance metrics. Also, V2V data dissemination via the proposed system introduces the enhancement of V2V link in terms of RSSI, PER, BER, Tsafe, and Rsafe. The results indicate the improvement of V2V link reliability. Consequently, the road safety is improved.

  18. Potential of Microbispora sp. V2 as biocontrol agent against Sclerotium rolfsii, the causative agent of southern blight of Zea mays L (Baby corn)--in vitro studies.

    Science.gov (United States)

    Patil, N N; Waghmode, M S; Gaikwad, P S; Gajbhiye, M H; Gunjal, A B; Nawani, N N; Kapadnis, B P

    2014-11-01

    The study was undertaken with the aim of exploring novel and beneficial agro activities of rare actinomycetes like Microbispora sp. V2. The antagonistic activity of Microbispora sp. V2 was evaluated as a biocontrol agents against Sclerotium rolfsii, a soil-borne fungal plant pathogen. The methodology performed for evaluation of biocontrol agent was in vitro evaluation assay which comprised of three tests viz., cellophane overlay technique, seed germination test and Thiram (fungicide) tolerance of Microbispora sp. V2. The isolate was found to inhibit the fungal pathogen Sclerotium rolfsii to 91.43% in cellophane assay. In seed germination assay, Microbispora sp. V2 treated seeds resulted in 25.75% increased germination efficiency, as compared to seeds infected by Sclerotium rolfsii. The isolate Microbispora sp. V2 could tolerate 1000 microg mL(-1) of Thiram (fungicide). The in vitro assay studies proved that Microbispora sp. V2 can be used as antifungal antagonist and thus posses' great potential as biocontrol agent against southern blight caused by Sclerotium rolfsii in Zea mays L (Baby corn) which causes large economical losses.

  19. [Adsorption and removal of gas-phase Hg(0) over a V2O5/AC catalyst in the presence of SO2].

    Science.gov (United States)

    Wang, Jun-wei; Yang, Jian-li; Liu, Zhen-yu

    2009-12-01

    The adsorption and removal behaviors of gas-phase Hg(0) over V2O5/AC and AC were studied under a simulated flue gas (containing N2, SO2, O2) in a fixed-bed reactor. The influences of the V2O5, loading, SO2 concentration and adsorption temperature on Hg0 adsorption were investigated. The speciation of mercury adsorbed was determined by X-ray photoelectron spectroscopy (XPS). It was found that the V2O5/AC catalyst has a much higher capability than AC for Hg(0) adsorption and removal, mainly because of the catalytic oxidation activity of V2O5. The Hg(0) adsorption capability depends on the V2O5 content of the V2O5/AC catalyst. The amounts of mercury adsorbed increase from 75.9 microg x g(-1) to 89.6 microg x g(-1) (in the absence of O2) and from 115.9 microg x g(-1) to 185.5 microg x g(-1) (in the presence of O2) as the V2O5 loading increases from 0.5% to 1.0%, which are much higher than those over AC under the same conditions (9.6 microg x g(-1) and 23.3 microg x g(-1)). SO2 in the flue gas enhances Hg(0) adsorption over the V2O5/AC catalyst, which is due to the reaction of SO2 and Hg(0) on V2O3/AC. But as the SO2 concentration increases from 500 x 10(-6) to 2000 x 10(-6), the amount of mercury adsorbed has only a slight increase. The optimal temperature for Hg(0) adsorption over the V2O5/AC catalyst is around 150 degrees C, at which the amounts of mercury adsorbed are up to 98.5 microg x g(-1) (in the absence of O2) and 187.7 microg x g(-1) (in the presence of O2). The XPS results indicate the formation of Hg(0) and HgSO4 on the surface of the V2O5/AC catalyst, which confirms the role of V2O5 and SO2.

  20. PI-RADS v2 and ADC values: is there room for improvement?

    Science.gov (United States)

    Jordan, Eric J; Fiske, Charles; Zagoria, Ronald; Westphalen, Antonio C

    2018-03-17

    To determine the diagnostic accuracy of ADC values in combination with PI-RADS v2 for the diagnosis of clinically significant prostate cancer (CS-PCa) compared to PI-RADS v2 alone. This retrospective study included 155 men whom underwent 3-Tesla prostate MRI and subsequent MR/US fusion biopsies at a single non-academic center from 11/2014 to 3/2016. All scans were performed with a surface coil and included T2, diffusion-weighted, and dynamic contrast-enhanced sequences. Suspicious findings were classified using Prostate Imaging Reporting and Data System (PI-RADS) v2 and targeted using MR/US fusion biopsies. Mixed-effect logistic regression analyses were used to determine the ability of PIRADS v2 alone and combined with ADC values to predict CS-PCa. As ADC categories are more practical in clinical situations than numeric values, an additional model with ADC categories of ≤ 800 and > 800 was performed. A total of 243 suspicious lesions were included, 69 of which were CS-PCa, 34 were Gleason score 3+3 PCa, and 140 were negative. The overall PIRADS v2 score, ADC values, and ADC categories are independent statistically significant predictors of CS-PCa (p values or categories is better discrimination of PI-RADS v2 4 lesions. ADC values and categories help to diagnose CS-PCa when lesions are assigned a PI-RADS v2 score of 4.

  1. A review of the growth of V2O5 films from 1885 to 2010

    International Nuclear Information System (INIS)

    Beke, Szabolcs

    2011-01-01

    This year is the 125th anniversary of the first synthesis of V 2 O 5 gels. The fascinating properties and wide application range of V 2 O 5 thin films have attracted significant attention over the past decades. Its wide optical band gap, layered structure, good chemical and thermal stability and excellent thermoelectric and electrochromic properties have made V 2 O 5 a promising material for industrial applications such as gas sensors, electrochromic devices, optical switching devices, and reversible cathode materials for Li batteries. Gels were the first form in which V 2 O 5 was synthesized at the end of the 19th century. Interest started to grow in the 1980s due to the discovery of their semiconducting properties and their use in antistatic coatings in the photographic industry. The rapid development of the sol-gel process brought new interest in V 2 O 5 gels. Following a short discussion of vanadium oxides and V 2 O 5 , I summarize all thin film preparation techniques known up to now and use reported optical band gaps to characterize different growth methods. An estimation of the Bohr radius for V 2 O 5 is also presented. This article provides an up-to-date review of more than a century (1885-2010) of research on the growth of vanadium oxide thin films. Nonetheless, due to the huge number of publications in the field, only those are selected and described which, according to the author, contribute the most to the field's further development.

  2. Constitutive Modeling of Geomaterials Advances and New Applications

    CERN Document Server

    Zhang, Jian-Min; Zheng, Hong; Yao, Yangping

    2013-01-01

    The Second International Symposium on Constitutive Modeling of Geomaterials: Advances and New Applications (IS-Model 2012), is to be held in Beijing, China, during October 15-16, 2012. The symposium is organized by Tsinghua University, the International Association for Computer Methods and Advances in Geomechanics (IACMAG), the Committee of Numerical and Physical Modeling of Rock Mass, Chinese Society for Rock Mechanics and Engineering, and the Committee of Constitutive Relations and Strength Theory, China Institution of Soil Mechanics and Geotechnical Engineering, China Civil Engineering Society. This Symposium follows the first successful International Workshop on Constitutive Modeling held in Hong Kong, which was organized by Prof. JH Yin in 2007.   Constitutive modeling of geomaterials has been an active research area for a long period of time. Different approaches have been used in the development of various constitutive models. A number of models have been implemented in the numerical analyses of geote...

  3. All solid-state V2O5-based flexible hybrid fiber supercapacitors

    Science.gov (United States)

    Li, Huan; He, Jin; Cao, Xin; Kang, Liping; He, Xuexia; Xu, Hua; Shi, Feng; Jiang, Ruibin; Lei, Zhibin; Liu, Zong-Huai

    2017-12-01

    Vanadium pentoxide/single-walled carbon nanotube (V2O5-SWCNT) hybrid fibers with good electrochemical performance and flexibility are firstly prepared by using wet-spinning method. V2O5 nanobelt suspension is obtained by mixing V2O5 bulk, 30% H2O2, H2O and followed by hydrothermally treating at 190 °C for 15 h. SWCNT suspension is suspended into V2O5 nanobelt suspension under vigorous stirring, the V2O5-SWCNT homogenous suspension is obtained. It is injected into a coagulation bath composed of 5 wt % CaCl2 ethanol-water solution using syringe pump, V2O5-SWCNT hybrid fibers are prepared by washing with deionized water and drying at room temperature. Reduced graphene oxide (RGO)-SWCNT hybrid fibers are also prepared by the similar wet-spinning approach and followed by reducing GO-SWCNT hybrid fibers in an aqueous solution of hydriodic acid. All solid-state asymmetric V2O5/SWCNT//RGO/SWCNT fiber supercapacitors are assembled with V2O5-SWCNT fiber as positive electrode and RGO-SWCNT fiber as negative electrode by using PVA-H3PO4 as gel electrolyte. The assembled device not only shows maximum volumetric energy density of 1.95 mW h cm-3 at a volumetric power density of 7.5 mW cm-3, superior rate performance and cycling stability, but also exhibits remarkable flexibility to tolerate long-term and repeated bending. This work will open a new application filed of V2O5-based fibers in wearable energy storage devices.

  4. Modalités de collaboration entre étudiants et constitution d'une communauté dans une activité à distance Students' collaborative processes and community building during an online activity

    Directory of Open Access Journals (Sweden)

    Charlotte Dejean-Thircuir

    2008-06-01

    Full Text Available Cette étude s'inscrit dans le champ de la communication pédagogique médiatisée par ordinateur et s'intéresse aux échanges entre étudiants engagés dans la réalisation d'une tâche collaborative, dans le cadre d'un master 2 professionnel de didactique des langues, à distance. L'analyse des interactions d'un groupe d'étudiants, au moyen d'outils issus de la pragmatique linguistique interactionniste et de l'analyse conversationnelle, permet d'identifier certaines pratiques langagières et formes d'activités communicationnelles qui soutiennent le processus collaboratif et favorisent la constitution d'une communauté en ligne. En se focalisant sur l'étude d'un groupe particulièrement collaboratif, il s'agit de mieux comprendre les processus de collaboration afin de proposer des pistes de réflexion pour les concepteurs et tuteurs de ce type d'activité en ligne.This study belongs to the field of computer mediated pedagogical communication and focuses on students' interactions while engaged in a collaborative task as part of a professional master 2 program in online language education. Using a set of analytic tools grounded on a pragmatic and an interactionist framework, the researcher identified some linguistic practices and communicative activities that foster the collaborative process and support the construction of an online community. By focusing on a particularly collaborative group, the researcher had a better understanding of the collaborative processes involved in the completion of such tasks and was able to suggest directions for further reflection to designers and instructors of similar online activities.

  5. Essence and constitution in Zubiri

    Directory of Open Access Journals (Sweden)

    Alfonso Gómez Fernández

    2015-03-01

    Full Text Available The aim of this article is to expound Zubiri’s concept of essence and to begin a critical discussion and evaluation of his proposal. Before explaining what essence is, it is necessary to observe that, for our author, not all things have an essence: only «reality-things» but not «meaning-things» form part of the «essentiable domain». This distinction between «reality-things» and «meaning-things» supposes a new conception of nature. (Nature is not the opposite of the artificial, as the Greek term physis is.«Reality-things» form a constitutional and «closed» system of non-causal and non-«external» characteristics or traits. These «foundational characteristics» of constitution, then, are precisely the essence. The article discusses critically the assumptions of this doctrine (reality, ontological pluralism, foundation and its possible limits in the light of contemporary science. It can be a useful theory for the philosophy of language.

  6. Genetic Ablation of V2a Ipsilateral Interneurons Disrupts Left-Right Locomotor Coordination in Mammalian Spinal Cord

    DEFF Research Database (Denmark)

    Crone, Steven A.; Quinlan, Katharina A.; Zagoraiou, Laskaro

    2008-01-01

    The initiation and coordination of activity in limb muscles are the main functions of neural circuits that control locomotion. Commissural neurons connect locomotor circuits on the two sides of the spinal cord, and represent the known neural substrate for left-right coordination. Here we......-extensor coordination is unaffected. Anatomical tracing studies reveal a direct excitatory input of V2a interneurons onto commissural interneurons, including a set of molecularly defined V0 neurons that drive left-right alternation. Our findings imply that the neural substrate for left-right coordination consists...... of at least two components; commissural neurons and a class of ipsilateral interneurons that activate commissural pathways....

  7. Color-Space-Based Visual-MIMO for V2X Communication

    OpenAIRE

    Jai-Eun Kim; Ji-Won Kim; Youngil Park; Ki-Doo Kim

    2016-01-01

    In this paper, we analyze the applicability of color-space-based, color-independent visual-MIMO for V2X. We aim to achieve a visual-MIMO scheme that can maintain the original color and brightness while performing seamless communication. We consider two scenarios of GCM based visual-MIMO for V2X. One is a multipath transmission using visual-MIMO networking and the other is multi-node V2X communication. In the scenario of multipath transmission, we analyze the channel capacity numerically and w...

  8. Buprofezin Is Metabolized by CYP353D1v2, a Cytochrome P450 Associated with Imidacloprid Resistance in Laodelphax striatellus

    Directory of Open Access Journals (Sweden)

    Mohammed Esmail Abdalla Elzaki

    2017-11-01

    Full Text Available CYP353D1v2 is a cytochrome P450 related to imidacloprid resistance in Laodelphax striatellus. This work was conducted to examine the ability of CYP353D1v2 to metabolize other insecticides. Carbon monoxide difference spectra analysis indicates that CYP353D1v2 was successfully expressed in insect cell Sf9. The catalytic activity of CYP353D1v2 relating to degrading buprofezin, chlorpyrifos, and deltamethrin was tested by measuring substrate depletion and analyzing the formation of metabolites. The results showed the nicotinamide–adenine dinucleotide phosphate (NADPH-dependent depletion of buprofezin (eluting at 8.7 min and parallel formation of an unknown metabolite (eluting 9.5 min. However, CYP353D1v2 is unable to metabolize deltamethrin and chlorpyrifos. The recombinant CYP353D1v2 protein efficiently catalyzed the model substrate p-nitroanisole with a maximum velocity of 9.24 nmol/min/mg of protein and a Michaelis constant of Km = 6.21 µM. In addition, imidacloprid was metabolized in vitro by the recombinant CYP353D1v2 microsomes (catalytic constant Kcat 0.064 pmol/min/pmol P450, Km = 6.41 µM. The mass spectrum of UPLC-MS analysis shows that the metabolite was a product of buprofezin, which was buprofezin sulfone. This result provided direct evidence that L. striatellus cytochrome P450 CYP353D1v2 is capable of metabolizing imidacloprid and buprofezin.

  9. Buprofezin Is Metabolized by CYP353D1v2, a Cytochrome P450 Associated with Imidacloprid Resistance in Laodelphax striatellus.

    Science.gov (United States)

    Elzaki, Mohammed Esmail Abdalla; Miah, Mohammad Asaduzzaman; Han, Zhaojun

    2017-11-29

    CYP353D1v2 is a cytochrome P450 related to imidacloprid resistance in Laodelphax striatellus . This work was conducted to examine the ability of CYP353D1v2 to metabolize other insecticides. Carbon monoxide difference spectra analysis indicates that CYP353D1v2 was successfully expressed in insect cell Sf9. The catalytic activity of CYP353D1v2 relating to degrading buprofezin, chlorpyrifos, and deltamethrin was tested by measuring substrate depletion and analyzing the formation of metabolites. The results showed the nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent depletion of buprofezin (eluting at 8.7 min) and parallel formation of an unknown metabolite (eluting 9.5 min). However, CYP353D1v2 is unable to metabolize deltamethrin and chlorpyrifos. The recombinant CYP353D1v2 protein efficiently catalyzed the model substrate p -nitroanisole with a maximum velocity of 9.24 nmol/min/mg of protein and a Michaelis constant of Km = 6.21 µM. In addition, imidacloprid was metabolized in vitro by the recombinant CYP353D1v2 microsomes (catalytic constant Kcat) 0.064 pmol/min/pmol P450, Km = 6.41 µM. The mass spectrum of UPLC-MS analysis shows that the metabolite was a product of buprofezin, which was buprofezin sulfone. This result provided direct evidence that L. striatellus cytochrome P450 CYP353D1v2 is capable of metabolizing imidacloprid and buprofezin.

  10. Heteropoly acid promoted V2O5/TiO2 catalysts for NO abatement with ammonia in alkali containing flue gases

    DEFF Research Database (Denmark)

    Putluru, Siva Sankar Reddy; Jensen, Anker Degn; Riisager, Anders

    2011-01-01

    V2O5/TiO2 and heteropoly acid promoted V2O5/TiO2 catalysts were prepared and characterized by N2 physisorption, XRPD and NH3-TPD. The influence of the calcination temperature from 400 to 700 1C on crystallinity and acidic properties was studied and compared with the activity for the selective...... catalytic reduction (SCR) of NO with ammonia. The SCR activity of heteropoly acid promoted catalysts was found to be much higher than for unpromoted catalysts. The stability of heteropoly acid promoted catalysts is dependent on calcination temperature and there is a gradual decrease in SCR activity...... and acidity with increase in calcination temperatures. Furthermore, the heteropoly acid promoted V2O5/TiO2 catalysts showed excellent alkali deactivation resistance and might therefore be alternative deNOx catalysts in biomass fired power plants....

  11. Structural and immunological characterization of the N-glycans from the major yellow jacket allergen Ves v 2: The N-glycan structures are needed for the human antibody recognition

    DEFF Research Database (Denmark)

    Seppälä, Ulla; Selby, David; Monsalve, Rafael

    2009-01-01

    of the study was to characterize the glycosylation patterns in Ves v 2 isoallergens and to assess their immunological properties regarding antibody binding and T cell activation. The glycosylation sites and the carbohydrate structures were verified by use of tandem mass spectrometry (MS/MS). The immunological....... Non-glycosylated rVes v 2, however, induced T cell and cytokine responses comparable to glycosylated nVes v 2. The present study shows that N-glycan structures are needed for the antibody recognition but not for the T cell reactivity of Ves v 2 in vitro. The occurrences of carbohydrate......-specific antibodies against nVes v 2, however, suggest that non-mammalian glycan structures as in nVes v 2 may provide a link between T cells and other effector cells in allergic responses....

  12. Unborn children as constitutional persons.

    Science.gov (United States)

    Roden, Gregory J

    2010-01-01

    In Roe v. Wade, the state of Texas argued that "the fetus is a 'person' within the language and meaning of the Fourteenth Amendment." To which Justice Harry Blackmun responded, "If this suggestion of personhood is established, the appellant's case, of course, collapses, for the fetus' right to life would then be guaranteed specifically by the Amendment." However, Justice Blackmun then came to the conclusion "that the word 'person,' as used in the Fourteenth Amendment, does not include the unborn." In this article, it is argued that unborn children are indeed "persons" within the language and meaning of the Fourteenth and Fifth Amendments. As there is no constitutional text explicitly holding unborn children to be, or not to be, "persons," this argument will be based on the "historical understanding and practice, the structure of the Constitution, and thejurisprudence of [the Supreme] Court." Specifically, it is argued that the Constitution does not confer upon the federal government a specifically enumerated power to grant or deny "personhood" under the Fourteenth Amendment. Rather, the power to recognize or deny unborn children as the holders of rights and duties has been historically exercised by the states. The Roe opinion and other Supreme Court cases implicitly recognize this function of state sovereignty. The states did exercise this power and held unborn children to be persons under the property, tort, and criminal law of the several states at the time Roe was decided. As an effect of the unanimity of the states in holding unborn children to be persons under criminal, tort, and property law, the text of the Equal Protection Clause of the Fourteenth Amendment compels federal protection of unborn persons. Furthermore, to the extent Justice Blackmun examined the substantive law in these disciplines, his findings are clearly erroneous and as a whole amount to judicial error. Moreover, as a matter of procedure, according to the due process standards recognized in

  13. Promoted V2O5/TiO2 catalysts for selective catalytic reduction of NO with NH3 at low temperatures

    DEFF Research Database (Denmark)

    Putluru, Siva Sankar Reddy; Schill, Leonhard; Godiksen, Anita

    2016-01-01

    characterized by N2 physisorption, XRPD, NH3-TPD, H2-TPR, Raman, FTIR and EPR spectroscopy to investigate the properties of the catalysts. XRPD, Raman and FTIR showed that promotion with 15 wt.% HPA does not cause V2O5 to be present in crystalline form, also at a loading of 5 wt.% V2O5. Hence, use of HPAs does......The influence of varying the V2O5 content (3–6 wt.%) was studied for the selective catalytic reduction (SCR) of nitrogen oxides by ammonia on heteropoly acid (HPA)- and tungsten oxide (WO3)-promoted V2O5/TiO2 catalysts. The SCR activity and alkali deactivation resistance of HPA-promoted V2O5/TiO2...... catalysts was found to be much higher than for WO3-promoted catalysts. By increasing the vanadium content from 3 to 5 wt.% the catalysts displayed a two fold increase in activity at 225 °C and retained their initial activity after alkali doping at a molar K/V ratio of 0.181. Furthermore, the catalysts were...

  14. Channel modelling and performance analysis of V2I communication systems in blind bend scattering environments

    KAUST Repository

    Chelli, Ali; Hamdi, Rami; Alouini, Mohamed-Slim

    2014-01-01

    In this paper, we derive a new geometrical blind bend scattering model for vehicle-to- infrastructure (V2I) communications. The proposed model takes into account single-bounce and double- bounce scattering stemming from fixed scatterers located

  15. Interconnected V2O5 nanoporous network for high-performance supercapacitors.

    Science.gov (United States)

    Saravanakumar, B; Purushothaman, Kamatchi K; Muralidharan, G

    2012-09-26

    Vanadium pentoxide (V(2)O(5)) has attracted attention for supercapcitor applications because of its extensive multifunctional properties. In the present study, V(2)O(5) nanoporous network was synthesized via simple capping-agent-assisted precipitation technique and it is further annealed at different temperatures. The effect of annealing temperature on the morphology, electrochemical and structural properties, and stability upon oxidation-reduction cycling has been analyzed for supercapacitor application. We achieved highest specific capacitance of 316 F g(-1) for interconnected V(2)O(5) nanoporous network. This interconnected nanoporous network creates facile nanochannels for ion diffusion and facilitates the easy accessibility of ions. Moreover, after six hundred consecutive cycling processes the specific capacitance has changed only by 24%. A simple cost-effective preparation technique of V(2)O(5) nanoporous network with excellent capacitive behavior, energy density, and stability encourages its possible commercial exploitation for the development of high-performance supercapacitors.

  16. Structure of V2AlC studied by theory and experiment

    International Nuclear Information System (INIS)

    Schneider, Jochen M.; Mertens, Raphael; Music, Denis

    2006-01-01

    We have studied V 2 AlC (space group P6 3 /mmc, prototype Cr 2 AlC) by ab initio calculations. The density of states (DOS) of V 2 AlC for antiferromagnetic, ferromagnetic, and paramagnetic configurations have been discussed. According to the analysis of DOS and cohesive energy, no significant stability differences between spin-polarized and non-spin-polarized configurations were found. Based on the partial DOS analysis, V 2 AlC can be classified as a strongly coupled nanolaminate according to our previous work [Z. Sun, D. Music, R. Ahuja, S. Li, and J. M. Schneider, Phys. Rev. B 70, 092102 (2004)]. Furthermore, this phase has been synthesized in the form of thin films by magnetron sputtering. The equilibrium volume, determined by x-ray diffraction, is in good agreement with the theoretical data, implying that ab initio calculations provide an accurate description of V 2 AlC

  17. Vehicle-to-vehicle communications : readiness of V2V technology for application.

    Science.gov (United States)

    2014-08-01

    The purpose of this research report is to assess the readiness for application of vehicle-to-vehicle (V2V) : communications, a system designed to transmit basic safety information between vehicles to facilitate warnings to : drivers concerning impend...

  18. WP5 Evaluation: D54-D55 Evaluation Results V2 (V3)

    NARCIS (Netherlands)

    Van Rosmalen, Peter

    2011-01-01

    Van Rosmalen, P. (2010, 19 May). WP5 Evaluation: D54-D55 Evaluation Results V2 (V3). Presentation at idSpace Final Review, Heerlen, The Netherlands: Open University of the Netherlands. idSpace-project.

  19. Promoting Vehicle to Grid (V2G) in the Nordic Region

    DEFF Research Database (Denmark)

    Kester, Johannes; Noel, Lance; Zarazua de Rubens, Gerardo

    2018-01-01

    Vehicle to Grid (V2G) holds the promise of cheap, flexible, and fast-responding storage through the use of electric vehicle batteries. Unfortunately, infrastructure, battery degradation and consumer awareness are only some of the challenges to a faster development of this technology. This paper...... offers a qualitative comparative analysis that draws on a subsample of 227 semistructured interviews on electric vehicles with both transportation and electricity experts from 201 institutions and 17 cities within the Nordic region to discuss the reasoning and arguments behind V2G incentives and policy...... mechanisms. A frequency analysis of the most coded V2G responses favoured an update of the electricity market regulation – in particular in relation to electricity taxation and aggregator markets – and support for pilot projects. However, the analysis overall implies that V2G, in contrast to EVs...

  20. The NPPR Trnava participation in the NPP V-2 modernisation and safety improvement project

    International Nuclear Information System (INIS)

    Michal, V.; Losonsky, B.; Magdolen, J.

    1999-01-01

    The presented contribution deals with form, present state and results of Nuclear Power Plants Research Inst.e participation in the NPP V-2 Jaslovske Bohunice Modernization and Safety Improvement Project.(author)

  1. The Constitutive Values of Science

    Directory of Open Access Journals (Sweden)

    Hugh Lacey

    1997-06-01

    Full Text Available Cognitive values are the characteristics that are constitutive of good theories, the criteria to which we appeal when choosing among competing theories. I argue that, in order to count as a cognitive value, a characteristic must be needed to explain actually made theory choices, and its cognitive significance must be well defended especially in view of considerations derived from the objective of science. A number of proposed objectives of science are entertained, and it is argued that adopting a par-ticular objective is dialectically intertwined with commitment to certain social values.Then, the ways in which science is, and is not value free is explored briefly, leading to the identification of a level of analysis where values may influence theory choice without causing paradox or threatening the impartiality of soundly-made scientific judgments.

  2. [Constitutional mismatch repair deficiency syndrome].

    Science.gov (United States)

    Jongmans, Marjolijn C; Gidding, Corrie E; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

    2015-01-01

    Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. An 8-year-old girl was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of 11. In children with cancer CMMR-D syndrome can be recognized particularly if there are multiple primary malignancies and skin hyperpigmentations and hypopigmentations. The parents of these children are at high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.

  3. Kinanthropometry - Components of body constitution

    Directory of Open Access Journals (Sweden)

    Maria Tereza Silveira Böhme

    2000-12-01

    Full Text Available The objective of this study is to present the conceptual and historical background to Kinanthropometry and to characterize this area of research. The components of body constitution relating to dimensions, proportions, shape and body composition that should be considered in Physical Education and Sports programs are also described. ARESUMO Este trabalho tem por objetivo apresentar os aspectos conceituais referentes à Cineantropometria, assim como os aspectos históricos e caracterização desta área de estudos. São também descritos os componentes de constituição corporal referentes à dimensões, proporções, forma e composição corporal que devem ser considerados em programas de Educação Física e Esporte.

  4. Fleet operator risks for using fleets for V2G regulation

    International Nuclear Information System (INIS)

    Hill, Davion M.; Agarwal, Arun S.; Ayello, Francois

    2012-01-01

    Future fleets of vehicles may include electric vehicles (EVs) or hybrid electric vehicles (HEVs) because of potential fuel savings. Recent demonstration of diesel parallel hybrids in a delivery fleet led to fuel economy improvements, and hybrid bus demonstrations exhibited twice the fuel economy of the conventional bus. Fleet ownership may include management of a fleet of vehicles as small as 10 units and as large as hundreds or thousands. In addition to fuel savings, the newer extended range electric vehicles (EREVs) and pure EVs permit vehicle to grid (V2G) opportunities. These V2G opportunities may present additional revenue for fleets by providing ancillary services to local grid independent system operators (ISOs), provided that the burden of driving and V2G services do not accelerate the degradation of the battery systems in these vehicles. The subject of this study is to determine the financial risks associated with accelerated battery degradation in a V2G-enabled EREV fleet expected to perform ancillary service duty while charging in addition to the normal loads of drive cycle duty. We determine that battery cycle life during V2G duty is a critical parameter, which can determine whether or not the business model is viable. - Highlights: ► V2G regulation cycle life of EREV batteries must be >50,000 cycles to be profitable. ► Present knowledge and test data about the impact of V2G cycles on battery life are limited. ► Replacement of batteries and energy throughput are major factors in the cost–benefit analysis. ► V2G fleet is not viable with present data but can be viable with some technical advancement.

  5. Pressure-induced charge ordering of LiV2O4

    International Nuclear Information System (INIS)

    Takeda, K.; Hidaka, H.; Kotegawa, H.; Kobayashi, T.C.; Shimizu, K.; Harima, H.; Fujiwara, K.; Miyoshi, K.; Takeuchi, J.; Ohishi, Y.; Adachi, T.; Takata, M.; Nishibori, E.; Sakata, M.; Watanuki, T.; Shimomura, O.

    2005-01-01

    The powder X-ray diffraction experiments of LiV 2 O 4 have been performed at low temperature and high pressure using synchrotron radiation. In the isothermal experiment at 10K, the cubic-rhombohedral phase transition corresponding to the metal-insulator transition is found at around 13GPa. This transition seems to be due to charge ordering of V ions on the analogy of the metal-insulator transition in AlV 2 O 4

  6. Li+ ions diffusion into sol-gel V2O5 thin films: electrochromic properties

    Science.gov (United States)

    Benmoussa, M.; Outzourhit, A.; Bennouna, A.; Ihlal, A.

    2009-10-01

    V{2}O{5} thin films were prepared by the sol-gel spin coating process. The Li+ ions insertion effect on optical and electrochromic properties of those films was studied. The diffusion coefficient was calculated using both cyclic voltammograms and chronoamperometric curves. The amount x of Li+ ions in LixV{2}O{5} was also calculated. Finally, the electrochromic performance evolution characteristics such as the reversibility, coloration efficiency, coloration memory stability and response time were studied.

  7. Validation of ASTEC V2 models for the behaviour of corium in the vessel lower head

    International Nuclear Information System (INIS)

    Carénini, L.; Fleurot, J.; Fichot, F.

    2014-01-01

    The paper is devoted to the presentation of validation cases carried out for the models describing the corium behaviour in the “lower plenum” of the reactor vessel implemented in the V2.0 version of the ASTEC integral code, jointly developed by IRSN (France) and GRS (Germany). In the ASTEC architecture, these models are grouped within the single ICARE module and they are all activated in typical accident scenarios. Therefore, it is important to check the validity of each individual model, as long as experiments are available for which a single physical process is involved. The results of ASTEC applications against the following experiments are presented: FARO (corium jet fragmentation), LIVE (heat transfer between a molten pool and the vessel), MASCA (separation and stratification of corium non miscible phases) and OLHF (mechanical failure of the vessel). Compared to the previous ASTEC V1.3 version, the validation matrix is extended. This work allows determining recommended values for some model parameters (e.g. debris particle size in the fragmentation model and criterion for debris bed liquefaction). Almost all the processes governing the corium behaviour, its thermal interaction with the vessel wall and the vessel failure are modelled in ASTEC and these models have been assessed individually with satisfactory results. The main uncertainties appear to be related to the calculation of transient evolutions

  8. MetaPathways v2.5: quantitative functional, taxonomic and usability improvements.

    Science.gov (United States)

    Konwar, Kishori M; Hanson, Niels W; Bhatia, Maya P; Kim, Dongjae; Wu, Shang-Ju; Hahn, Aria S; Morgan-Lang, Connor; Cheung, Hiu Kan; Hallam, Steven J

    2015-10-15

    Next-generation sequencing is producing vast amounts of sequence information from natural and engineered ecosystems. Although this data deluge has an enormous potential to transform our lives, knowledge creation and translation need software applications that scale with increasing data processing and analysis requirements. Here, we present improvements to MetaPathways, an annotation and analysis pipeline for environmental sequence information that expedites this transformation. We specifically address pathway prediction hazards through integration of a weighted taxonomic distance and enable quantitative comparison of assembled annotations through a normalized read-mapping measure. Additionally, we improve LAST homology searches through BLAST-equivalent E-values and output formats that are natively compatible with prevailing software applications. Finally, an updated graphical user interface allows for keyword annotation query and projection onto user-defined functional gene hierarchies, including the Carbohydrate-Active Enzyme database. MetaPathways v2.5 is available on GitHub: http://github.com/hallamlab/metapathways2. shallam@mail.ubc.ca Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  9. WATERLOPP V2/64: A highly parallel machine for numerical computation

    Science.gov (United States)

    Ostlund, Neil S.

    1985-07-01

    Current technological trends suggest that the high performance scientific machines of the future are very likely to consist of a large number (greater than 1024) of processors connected and communicating with each other in some as yet undetermined manner. Such an assembly of processors should behave as a single machine in obtaining numerical solutions to scientific problems. However, the appropriate way of organizing both the hardware and software of such an assembly of processors is an unsolved and active area of research. It is particularly important to minimize the organizational overhead of interprocessor comunication, global synchronization, and contention for shared resources if the performance of a large number ( n) of processors is to be anything like the desirable n times the performance of a single processor. In many situations, adding a processor actually decreases the performance of the overall system since the extra organizational overhead is larger than the extra processing power added. The systolic loop architecture is a new multiple processor architecture which attemps at a solution to the problem of how to organize a large number of asynchronous processors into an effective computational system while minimizing the organizational overhead. This paper gives a brief overview of the basic systolic loop architecture, systolic loop algorithms for numerical computation, and a 64-processor implementation of the architecture, WATERLOOP V2/64, that is being used as a testbed for exploring the hardware, software, and algorithmic aspects of the architecture.

  10. Preventing structural degradation from Na3V2(PO4)3 to V2(PO4)3: F-doped Na3V2(PO4)3/C cathode composite with stable lifetime for sodium ion batteries

    Science.gov (United States)

    Chen, Yanjun; Xu, Youlong; Sun, Xiaofei; Zhang, Baofeng; He, Shengnan; Li, Long; Wang, Chao

    2018-02-01

    A prospective NASICON-type F-doped Na3V2(PO4)2.93F0.07/C (F-0.07-NVP/C) composite is synthesized by a solid-state reaction method. F-doping can restrain the structural degradation from Na3V2(PO4)3 to V2(PO4)3 and enhance the structural stability. Meanwhile, it can decrease the particle size to diminish the pathway of Na+ diffusion, which can increase ionic conductivity efficiently. The kinetic behavior is significantly improved and it is beneficial to reinforcing the electrochemical performance of F-doping composites. Compared with Undoped-NVP/C sample, F-0.07-NVP/C composite delivers a 113 mAh g-1 discharge capacity at 10 mA g-1, which is very close to the theoretical capacity (117 mAh g-1). As for cycle performance, a reversible capacity of 97.8 mAh g-1 can be obtained and it retains 86% capacity after 1000 cycles at 200 mA g-1. F-0.07-NVP/C composite presents the highest DNa+ (2.62 × 10-15 cm2s-1), two orders of magnitude higher than the undoped sample (4.8 × 10-17 cm2s-1). This outstanding electrochemical performance is ascribed to the synergetic effect from improved kinetic behavior and enhanced structural stability due to F-doping. Hence, the F-doped composite would be a promising cathode material in SIB for energy storage and conversion.

  11. Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.

    Science.gov (United States)

    Hristov, Kiril L; Chen, Muyan; Afeli, Serge A Y; Cheng, Qiuping; Rovner, Eric S; Petkov, Georgi V

    2012-06-01

    The functional role of the voltage-gated K(+) (K(V)) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of K(V)2.1, K(V)2.2, and the electrically silent K(V)9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of K(V)2.1, K(V)2.2, and K(V)4.2 homotetrameric channels and of K(V)2.1/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca(2+) imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of K(V)2.1, K(V)2.2, and K(V)9.3 (but not K(V)4.2) channel subunits in human isolated DSM cells. K(V)2.1 and K(V)2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced K(V) current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca(2+) level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5-30 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive K(V)2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction.

  12. The foundational tenets of Johannes Althusius' constitutionalism ...

    African Journals Online (AJOL)

    Potchefstroom Electronic Law Journal/Potchefstroomse Elektroniese Regsblad ... sovereignty, in contrast to undivided (statist) sovereignty and his views on public office provided the framework for constitutionalism and limited government which could arguably improve on that of contemporary statist constitutionalism.

  13. Unconstitutional constitutional amendments in Ethiopia: the practice ...

    African Journals Online (AJOL)

    Haramaya Law Review ... The Constitution of the Federal Democratic Republic of Ethiopia (FDRE) under Article 104 and 105 sets ... that sets procedures to be observed in the process of constitutional amendments: both initiation and approval.

  14. The Obligations on Government and Society in our Constitutional State to Respect and Support Independent Constitutional Structures

    Directory of Open Access Journals (Sweden)

    LWH Ackermann

    2000-05-01

    these institutions is vitally important for creating and sustaining an ethos of constitutionalism among the inhabitants of the Republic.The Constitution makes explicit provision for the protection of the judiciary and the other independent state institutions and thereby indirectly for the development of habits of constitutionalism. The constitutional protection and support given to the independent state institutions are very similar to that given to the courts. One important distinction is to be noted. In the case of the courts, the Constitution provides that they "are subject only to the Constitution and the law" and no provision is made for them to be accountable to any other organ of state or any other institution or person, for that matter. By contrast, the independent institutions envisaged in section 181 of the Constitution are expressly made accountable to the National Assembly and are obliged to report on their activities and the performance of their functions to the Assembly at least once a year. While the formal independence of state institutions may at all times be scrupulously recognised by the legislature and the executive, their substantive independence can easily be undermined by fiscal starvation and their ability to function properly impeded by bureaucratic administrative obstruction or obfuscation or even, quite innocently, by a lack of appreciation of what the Constitution demands from public administration in support of these institutions. Adequate financial and administrative resources are required to achieve aspects of judicial independence. All South Africans must still be vigilant to ensure, from the outset, that all state organs develop habits and practices of constitutionalism and that they do not, whether by omission, error, or otherwise endanger the independence of our independent state institutions by neglecting their constitutional obligations.For the Constitutional Court to fulfil its role as the ultimate guardian of the Constitution, it

  15. The constitutional court review of judicial decisions

    Directory of Open Access Journals (Sweden)

    Stojanović Dragan M.

    2016-01-01

    Full Text Available In principle, the constitutional precepts envisage that judicial decisions are not subject to extrajudicial control. However, in the course of deciding on constitutional complaints, the Constitutional Court reviews the compliance of individual legal acts and actions of state authorities with the Constitution, including court decisions on cases involving the constitutionally guaranteed rights. Hence, in order to eliminate tension or even contradiction between the constitutional precepts, the constitutional review of judicial decisions should be considered as a special form of judicial control, regardless of the fact that the Constitutional Court is not part of the judicial structure in the strict organizational sense. Thus, unlike the cases where the Court is involved in the normative control of the applicable law, in the process of reviewing judicial decision of lower courts the constitutional judiciary acts in the capacity of a specific judicial authority. According to another possible interpretation of the aforementioned constitutional norms, the direct constitutional protection of the constitutionally guaranteed rights may only be pursued in the process of reviewing individual legal acts and actions of state authorities, but not by pursuing a judicial review of court decisions which the Constitutional Court has no jurisdiction to decide upon. Thus, the dogma of judicial independence would prevail over the dogma of direct protection of fundamental rights. The third interpretation of this relationship maintains that that judicial decisions may be subject to control but, in this specific case, the Constitutional Court may only issue an opinion (a statement rather than a binding decision which would cancel the lower court judgment. Then, it is up to the judicial authorities of the lower instance to adjust their judicial decision, which in the opinion of the Constitutional Court constitutes a violation of the constitutionally guaranteed rights

  16. Unanimous Constitutional Consent and the Immigration Problem

    OpenAIRE

    Josten, Stefan D.; Zimmermann, Klaus W.

    2004-01-01

    This paper utilizes the cross-cutting cleavages approach to evaluate the probability of a unanimous constitutional consent and, based on these results, discusses the implications of immigration on an existing constitutional consent. It is shown that previous conclusions of beneficial effects stemming from a multitude of political dimensions for a unanimous constitutional consent crucially depend on the assumption of an extreme mode of intrapersonal compensation of constitutional majority and ...

  17. Constitutional Referendums:A Theoretical Enquiry

    OpenAIRE

    Tierney, Stephen

    2009-01-01

    In recent decades the use of referendums to settle major constitutional questions has increased dramatically. Addressing this phenomenon as a case study in the relationship between democracy and constitutional sovereignty, this article has two aims.The first is to argue that these constitutional referendums are categorically different from ordinary, legislative referendums, and that this has important implications for theories of constitutional sovereignty. Secondly, the article suggests that...

  18. Analysis on constitution of American college republicans

    Directory of Open Access Journals (Sweden)

    Minghua Su

    2017-02-01

    Full Text Available This paper, based on internet survey and comparative analysis, according to the firsthand materials, comprehensively and systematically probes the formation of the constitution form and structure, and analyzes its contents of Constitution of American College Republicans among 15 colleges respectively, which includes the illustration of constitution, membership, personnel, meeting, financial amendment, etc. Finally, this essay analyzes the characteristics of constitution of college republicans and its advantages.

  19. First-Principles Studies on Deoxidizing Mechanism of V2O5 via Hydrogen

    Science.gov (United States)

    Zhang, Yanning; Jin, Mengting

    With its high melting point, good plasticity and good corrosion resistance at low temperatures, vanadium has been widely used in the industries of iron and steel, aviation, energy storage, etc. However, the traditional manufacturing technologies of pure vanadium are usually connected with complex manufacturing processes, high costs and serious environment pollution, which more or less hindered its further applications. Recently, hydrogen gas has been considered as a promising reducing agent of V2O5, but experimental studies of deoxidization process of V2O5 single crystal surfaces were found to be extremely difficult. In this work, we perform extensive ab initio studies on the structural and electronic properties of different V2O5 surfaces, as well as the adsorption sites, diffusion and desorption processes of H on these surfaces as a dependence of depth. We found that H atoms adsorb at oxygen site to form surface hydroxyl (OH-) and further to form H2O on V2O5(010) surfaces, and the latter is easier to be desorbed compared with the former. But the desorption of H2O causes significant surface reconstructions, which makes the further deoxidization of V2O5 difficult, particularly on the V2O5 single-layer. Our theoretical results are instructive for understandings of the reduction mechanism of V2O5 by using a green agent of H2, and furthermore for the design of new experiments. Work was supported by the startup fund of China Thousand Young Talents, and National Basic Research Program of China (973 program, No: 2013CB934700). The calculations were supported by Tianhe2-JK in Beijing Computational Science Research Center.

  20. Imidacloprid is hydroxylated by Laodelphax striatellus CYP6AY3v2.

    Science.gov (United States)

    Wang, R; Zhu, Y; Deng, L; Zhang, H; Wang, Q; Yin, M; Song, P; Elzaki, M E A; Han, Z; Wu, M

    2017-10-01

    Laodelphax striatellus (Fallén) is one of the most destructive pests of rice, and has developed high resistance to imidacloprid. Our previous work indicated a strong association between imidacloprid resistance and the overexpression of a cytochrome P450 gene CYP6AY3v2 in a L. striatellus imidacloprid resistant strain (Imid-R). In this study, a transgenic Drosophila melanogaster line that overexpressed the L. striatellus CYP6AY3v2 gene was established and was found to confer increased levels of imidacloprid resistance. Furthermore, CYP6AY3v2 was co-expressed with D. melanogaster cytochrome P450 reductase (CPR) in Spodoptera frugiperda 9 (SF9) cells. A carbon monoxide difference spectra analysis indicated that CYP6AY3v2 was expressed predominately in its cytochrome P450 (P450) form, which is indicative of a good-quality functional enzyme. The recombinant CYP6AY3v2 protein efficiently catalysed the model substrate P-nitroanisole to p-nitrophenol with a maximum velocity (V max ) of 60.78 ± 3.93 optical density (mOD)/min/mg protein. In addition, imidacloprid itself was metabolized by the recombinant CYP6AY3v2/nicotinamide adenine dinucleotide 2'-phosphate reduced tetrasodium salt (NADPH) CPR microsomes in in vitro assays (catalytic constant (K cat ) = 0.34 pmol/min/pmol P450, michaelis constant (K m ) = 41.98 μM), and imidacloprid depletion and metabolite peak formation were with a time dependence. The data provided direct evidence that CYP6AY3v2 is capable of hydroxylation of imidacloprid and conferring metabolic resistance in L. striatellus. © 2017 The Royal Entomological Society.

  1. The Constitution of the Republic of Estonia

    Index Scriptorium Estoniae

    2009-01-01

    Sisaldab ka: The Constitution of the Republic of Estonia Amendment Act. The Constitution of the Republic of Estonia Implementation Act. Act to Amend the Constitution of the Republic of Estonia for Election of Local Government Councils for Term of Four Years

  2. The Constitution of the Republic of Estonia

    Index Scriptorium Estoniae

    2005-01-01

    Raamat sisaldab ka: The Constitution of the Republic of Estonia amendment act ; The Constitution of the Republic of Estonia implementation act ; Act to amend the Constitution of the Republic of Estonia for election of local government councils for term of four years

  3. National simple: Constitutionality Analysis of Exclusions Sectorial

    Directory of Open Access Journals (Sweden)

    Guilherme Adolfo dos Santos Mendes

    2016-06-01

    Full Text Available The Constitution defines the favored legal treatment for small businesses without making any explicit exception, including and especially for tax obligations. Nevertheless, all the laws, which have introduced tax benefits guided by this higher provision, have discriminated small companies due to the economic sector of activity. Known as “National Simple” and introduced by the Complementary Law No. 123/06, the current legislation did not extend its benefits to small production units of a number of industries, such as the automotive industry, the passenger transport industry, the energy industry and the industry of manufacture of weapons, beverages and tobacco products. By demonstrating the mistakes of the arguments in favor of such exclusions, the article holds up that none of these provisions meets constitutional standards. Furthermore, based on a critical analysis of the Positive Law, it is shown that the hidden desire behind the exclusions was to keep the economic sectors of high profitability under control of big corporations to the detriment of smaller initiatives.

  4. Constitutive model for porous materials

    International Nuclear Information System (INIS)

    Weston, A.M.; Lee, E.L.

    1982-01-01

    A simple pressure versus porosity compaction model is developed to calculate the response of granular porous bed materials to shock impact. The model provides a scheme for calculating compaction behavior when relatively limited material data are available. While the model was developed to study porous explosives and propellants, it has been applied to a much wider range of materials. The early development of porous material models, such as that of Hermann, required empirical dynamic compaction data. Erkman and Edwards successfully applied the early theory to unreacted porous high explosives using a Gruneisen equation of state without yield behavior and without trapped gas in the pores. Butcher included viscoelastic rate dependance in pore collapse. The theoretical treatment of Carroll and Holt is centered on the collapse of a circular pore and includes radial inertia terms and a complex set of stress, strain and strain rate constitutive parameters. Unfortunately data required for these parameters are generally not available. The model described here is also centered on the collapse of a circular pore, but utilizes a simpler elastic-plastic static equilibrium pore collapse mechanism without strain rate dependence, or radial inertia terms. It does include trapped gas inside the pore, a solid material flow stress that creates both a yield point and a variation in solid material pressure with radius. The solid is described by a Mie-Gruneisen type EOS. Comparisons show that this model will accurately estimate major mechanical features which have been observed in compaction experiments

  5. The Na+/H+ exchanger NHE1, but not the Na+, HCO3- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2

    DEFF Research Database (Denmark)

    Lauritzen, Gitte; Stock, Christian-Martin; Lemaire, Justine

    2012-01-01

    We and others have shown central roles of the Na(+)/H(+) exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (¿NErbB2...

  6. Protein Kinase Cα and P-Type Ca2+ Channel CaV2.1 in Red Blood Cell Calcium Signalling

    Directory of Open Access Journals (Sweden)

    Lisa Wagner-Britz

    2013-06-01

    Full Text Available Background/Aims: Protein kinase Cα (PKCα is activated by an increase in cytosolic Ca2+ in red blood cells (RBCs. Previous work has suggested that PKCα directly stimulates the CaV2.1 channel, whereas other studies revealed that CaV2.1 is insensitive to activation by PKC. The aim of this study was to resolve this discrepancy. Methods: We performed experiments based on a single cell read-out of the intracellular Ca2+ concentration in terms of Fluo-4 fluorescence intensity and phosphatidylserine exposure to the external membrane leaflet. Measurement modalities included flow cytometry and live cell imaging. Results: Treatment of RBCs with phorbol 12-myristate 13-acetate (PMA led to two distinct populations of cells with an increase in intracellular Ca2+: a weak-responding and a strong-responding population. The EC50 of PMA for the number of cells with Ca2+ elevation was 2.7±1.2 µM; for phosphatidylserine exposure to the external membrane surface, it was 2.8±0.5 µM; and for RBC haemolysis, it was 2.9±0.5 µM. Using pharmacological manipulation with the CaV2.1 inhibitor ω-agatoxin TK and the broad protein kinase C inhibitor Gö6983, we are able to show that there are two independent PMA-activated Ca2+ entry processes: the first is independent of CaV2.1 and directly PKCα-activated, while the second is associated with a likely indirect activation of CaV2.1. Further studies using lysophosphatidic acid (LPA as a stimulation agent have provided additional evidence that PKCα and CaV2.1 are not directly interconnected in a signalling chain. Conclusion: Although we provide evidence for a lack of interaction between PKCα and CaV2.1 in RBCs, further studies are required to decipher the signalling relationship between LPA, PKCα and CaV2.1.

  7. An approach to communications security for a communications data delivery system for V2V/V2I safety : technical description and identification of policy and institutional issues.

    Science.gov (United States)

    This report identifies the security approach associated with a communications data delivery system that supports vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communications. The report describes the risks associated with communication...

  8. RECEPTING THE PRINCIPLE OF SUPREMACY OF CONSTITUTION ON THE NEW PENAL CODE

    Directory of Open Access Journals (Sweden)

    Marius ANDREESCU

    2016-07-01

    Full Text Available The supremacy of Constitution has as main consequence the compliance of entire law with the constitutional norms. Guaranteeing of the observance of this principle is essential for the rule of law, is primarily an attribute of the Constitutional Court, but also an obligation of the legislator to receive by texts adopted, within its content and form, the constitutional norms. Entering into force of the new criminal codes generated a significant jurisprudence of the Constitutional Court on the verification of constitutionality of some regulations in the Criminal Code and Criminal Procedure Code. Through this study we intend to analyze the following key issues: a how were the constitutional principles and values embodied in some criminal and criminal procedural norms of the new codes; b the effects of Constitutional Court decisions in the process of constitutionalizing of the criminal law; c applying into judicial activities of the Constitutional Court decisions, particularly those through which the new Criminal Code regulations were found unconstitutional.

  9. Overview of the independent ASTEC V2.0 validation by SARNET partners

    International Nuclear Information System (INIS)

    Chatelard, Patrick; Arndt, Siegfried; Atanasova, Boryana; Bandini, Giacomino; Bleyer, Alexandre; Brähler, Thimo; Buck, Michael; Kljenak, Ivo; Kujal, Bohumir

    2014-01-01

    Significant efforts are put into the assessment of the severe accident integral code ASTEC, jointly developed since several years by IRSN and GRS, either through comparison with results of the most important international experiments or through benchmarks with other severe accident simulation codes on plant applications. These efforts are done in first priority by the code developers’ organisations, IRSN and GRS, and also by numerous partners, in particular in the frame of the SARNET European network. The first version of the new series ASTEC V2 had been released in July 2009 to SARNET partners. Two subsequent V2.0 code revisions, including several modelling improvements, have been then released to the same partners, respectively in 2010 and 2011. This paper summarises first the approach of ASTEC validation vs. experiments, along with a description of the validation matrix, and presents then a few examples of applications of the ASTEC V2.0-rev1 version carried out in 2011 by the SARNET users. These calculation examples are selected in a way to cover diverse aspects of severe accident phenomenology, i.e. to cover both in-vessel and ex-vessel processes, in order to provide a good picture of the current ASTEC V2 capabilities. Finally, the main lessons drawn from this joint validation task are summarised, along with an evaluation of the current physical modelling relevance and thus an identification of the ASTEC V2.0 validity domain

  10. Change of position of constitutional judiciary

    Directory of Open Access Journals (Sweden)

    Orlović Slobodan P.

    2013-01-01

    Full Text Available Constitutional judiciary is the youngest branch of authority in the horizontal level of state power. Constitutional judiciary has, during its existence - during two centuries as an ordinary court and during one century as a special authority, changed its position, role and importance. Those characteristics of constitutional judiciary had an increasing way - the position became better, in political and law sense, its role has expanded and the importance has increased. Today, constitutional judiciary is an inevitable subject of constitutional regimes in huge number of states (between them are almost all federations but, in the same time, constitutional judiciary is an authority which is at least limited by the constitution. The constitution is "soft" to the constitutional judiciary because the judiciary interpreted the constitution in accordance to its political and law attitudes, hidden by the guise of protection. Different separation of power, a rise of executive power, requests for better protections of fundamental human rights, a changed role of state and executive power, altogether, have influenced to change of position of constitutional judiciary.

  11. Correlating Lithium Hydroxyl Accumulation with Capacity Retention in V2O5 Aerogel Cathodes.

    Science.gov (United States)

    Wangoh, Linda W; Huang, Yiqing; Jezorek, Ryan L; Kehoe, Aoife B; Watson, Graeme W; Omenya, Fredrick; Quackenbush, Nicholas F; Chernova, Natasha A; Whittingham, M Stanley; Piper, Louis F J

    2016-05-11

    V2O5 aerogels are capable of reversibly intercalating more than 5 Li(+)/V2O5 but suffer from lifetime issues due to their poor capacity retention upon cycling. We employed a range of material characterization and electrochemical techniques along with atomic pair distribution function, X-ray photoelectron spectroscopy, and density functional theory to determine the origin of the capacity fading in V2O5 aerogel cathodes. In addition to the expected vanadium redox due to intercalation, we observed LiOH species that formed upon discharge and were only partially removed after charging, resulting in an accumulation of electrochemically inactive LiOH over each cycle. Our results indicate that the tightly bound water that is necessary for maintaining the aerogel structure is also inherently responsible for the capacity fade.

  12. Simple O2 Plasma-Processed V2O5 as an Anode Buffer Layer for High-Performance Polymer Solar Cells

    DEFF Research Database (Denmark)

    Bao, Xichang; Zhu, Qianqian; Wang, Ting

    2015-01-01

    A simple O2 plasma processing method for preparation of a vanadium oxide (V2O5) anode buffer layer on indium tin oxide (ITO)-coated glass for polymer solar cells (PSCs) is reported. The V2O5 layer with high transmittance and good electrical and interfacial properties was prepared by spin coating...... the illumination of AM 1.5G (100 mW/cm2). Compared to that of the control device with PBDTTT-C:PC71BM as the active layer and PEDOT:PSS (PCE of 6.52%) and thermally annealed V2O5 (PCE of 6.27%) as the anode buffer layer, the PCE was improved by 15.6 and 20.2%, respectively, after the introduction of a V2O5 (O2...... plasma) anode buffer layer. The improved PCE is ascribed to the greatly improved fill factor and enhanced short-circuit current density of the devices, which benefited from the change in the work function of V2O5, a surface with many dangling bonds for better interfacial contact, and the excellent charge...

  13. Restoration of peripheral V2 receptor vasopressin signaling fails to correct behavioral changes in Brattleboro rats.

    Science.gov (United States)

    Balázsfi, Diána; Pintér, Ottó; Klausz, Barbara; Kovács, Krisztina B; Fodor, Anna; Török, Bibiána; Engelmann, Mario; Zelena, Dóra

    2015-01-01

    Beside its hormonal function in salt and water homeostasis, vasopressin released into distinct brain areas plays a crucial role in stress-related behavior resulting in the enhancement of an anxious/depressive-like state. We aimed to investigate whether correction of the peripheral symptoms of congenital absence of AVP also corrects the behavioral alterations in AVP-deficient Brattleboro rats. Wild type (WT) and vasopressin-deficient (KO) male Brattleboro rats were tested. Half of the KO animals were treated by desmopressin (V2-receptor agonist) via osmotic minipump (subcutaneous) to eliminate the peripheral symptoms of vasopressin-deficiency. Anxiety was studied by elevated plus maze (EPM), defensive withdrawal (DW) and marble burying (MB) tests, while depressive-like changes were monitored in forced swimming (FS) and anhedonia by sucrose preference test. Cell activity was examined in septum and amygdala by c-Fos immunohistochemistry after 10 min FS. KO rats spent more time in the open arm of the EPM, spent less time at the periphery of DW and showed less burying behavior in MB suggesting a reduced anxiety state. KO animals showed less floating behavior during FS revealing a less depressive phenotype. Desmopressin treatment compensated the peripheral effects of vasopressin-deficiency without a significant influence on the behavior. The FS-induced c-Fos immunoreactivity in the medial amygdala was different in WT and KO rats, with almost identical levels in KO and desmopressin treated animals. There were no differences in central and basolateral amygdala as well as in lateral septum. Our data confirmed the role of vasopressin in the development of affective disorders through central mechanisms. The involvement of the medial amygdala in the behavioral alterations of vasopressin deficient animals deserves further attention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. ASTEC V2 severe accident integral code: Fission product modelling and validation

    International Nuclear Information System (INIS)

    Cantrel, L.; Cousin, F.; Bosland, L.; Chevalier-Jabet, K.; Marchetto, C.

    2014-01-01

    One main goal of the severe accident integral code ASTEC V2, jointly developed since almost more than 15 years by IRSN and GRS, is to simulate the overall behaviour of fission products (FP) in a damaged nuclear facility. ASTEC applications are source term determinations, level 2 Probabilistic Safety Assessment (PSA2) studies including the determination of uncertainties, accident management studies and physical analyses of FP experiments to improve the understanding of the phenomenology. ASTEC is a modular code and models of a part of the phenomenology are implemented in each module: the release of FPs and structural materials from degraded fuel in the ELSA module; the transport through the reactor coolant system approximated as a sequence of control volumes in the SOPHAEROS module; and the radiochemistry inside the containment nuclear building in the IODE module. Three other modules, CPA, ISODOP and DOSE, allow respectively computing the deposition rate of aerosols inside the containment, the activities of the isotopes as a function of time, and the gaseous dose rate which is needed to model radiochemistry in the gaseous phase. In ELSA, release models are semi-mechanistic and have been validated for a wide range of experimental data, and noticeably for VERCORS experiments. For SOPHAEROS, the models can be divided into two parts: vapour phase phenomena and aerosol phase phenomena. For IODE, iodine and ruthenium chemistry are modelled based on a semi-mechanistic approach, these FPs can form some volatile species and are particularly important in terms of potential radiological consequences. The models in these 3 modules are based on a wide experimental database, resulting for a large part from international programmes, and they are considered at the state of the art of the R and D knowledge. This paper illustrates some FPs modelling capabilities of ASTEC and computed values are compared to some experimental results, which are parts of the validation matrix

  15. Arginine vasopressin and its analogues--the influence of position 2 modification with 3,3-diphenylalanine enantiomers. Highly potent V2 agonists

    Czech Academy of Sciences Publication Activity Database

    Kwiatkowska, A.; Sobolewski, D.; Prahl, A.; Borovičková, Lenka; Slaninová, Jiřina; Lammek, B.

    2009-01-01

    Roč. 44, č. 7 (2009), s. 2862-2867 ISSN 0223-5234 Institutional research plan: CEZ:AV0Z40550506 Keywords : arginine vasopressin analogues * AVP * 3,3-diphenylalanine enantiomers * V2 agonists * antidiuretic activity Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2009

  16. CdSe/beta-Pb0.33V2O5 heterostructures: Nanoscale semiconductor interfaces with tunable energetic configurations for solar energy conversion and storage

    Science.gov (United States)

    Milleville, Christopher C.

    charge transfer of CdSe/β-Pb0.33V¬2O5 and CdSe/V2O5 heterostructures. TA measurements indicate that, for both types of heterostructures, photoexcitation of CdSe QDs was followed by a transfer of electrons to the conduction band of β-Pb0.33V¬2O5 and holes to the mid-gap states of β-Pb0.33V¬2O5. Ultrafast transient absoprtion measurements revealed that holes actually transferred before electrons, on time scales of ca. 2 ps. In contrast, for analogous heterostructures consisting of CdSe QDs interfaced with V2O5, only electron transfer was observed. In addition, electron transfer was readily achieved for SILAR-prepared heterostructures; however, for LAA-prepared heterostructures, electron transfer was observed only upon excitation at energies substantially greater than the bandgap absorption threshold of CdSe. Transient absorbance decay traces revealed longer excited-state lifetimes (1-3 μs) for CdSe/β Pb0.33V2O5 heterostructures relative to bare β-Pb0.33V2O5 NWs (0.2 to 0.6 μs); the difference was attributed to surface passivation of intrinsic surface defects in β-Pb0.33V2O5 upon interfacing with CdSe. In an effort to improve the energetic offset in QD/β-Pb0.33V2O5 heterostructures, cadmium sulfide (CdS) QDs were used in place of CdSe QDs. X-ray photoelectron spectroscopy (XPS) valence band spectra of CdS/β-Pb0.33V2O5 and CdSe/β-Pb0.33V2O5 revealed a greater binding energy onset for CdS compared to CdSe. Binding energy onsets of 1.33 (± 0.03) and 0.92 (± 0.02) eV were determined for Cys-CdS/β Pb0.33V2O5 and Cys-CdSe/β Pb0.33V2O5, respectively; suggesting a 0.41 (±0.04) eV decrease in the free energy (ΔG) needed for hole transfer from the valence band edge of the QDs to the mid-gap states. Linear sweep voltammetry was employed to measure the photocatalytic activity of CdSe/β Pb0.33V2O5 heterostructures in electrolytes containing ascorbic acid as a sacrificial proton donor. Preliminary photoelectrochemical measurements on CdSe/β-Pb0.33V2O5 electrodes

  17. Information about environmental effects of Bohunice NPPs V-1 and V-2 within February 2002

    International Nuclear Information System (INIS)

    2002-01-01

    In this leaflet the results of monitoring of chemical gaseous and liquid effluents into the rivers Vah and Dudvah as well as of radiation monitoring of Bohunice V-1 and V-2 NPPs are presented. The radioactive effluents within a February 2002 (for NPP V-1 and NPP V-2, respectively) were: 0.571 TBq and 0.664 TBq of rare gases, 0.711 MBq and 0.244 MBq of aero-soles, 2.121 MBq and 0.138 MBq of iodine, 2.022 MBq and 0.564 MBq of corrosive and fission products, and 1.420 TBq and 1.643 TBq of tritium. For the period January - February 2002 these radioactive effluents represent for rare gases 1.286 TBq for NPP V-1 and 1.475 TBq for NPP V-2 (2.761 TBq (0.069% of annually limit (AL) for the locality Bohunice), for aerosols 2.645 MBq for NPP V-1 and 0.542 MBq for NPP V-2 (3.187 MBq (0.002% of AL for the locality Bohunice), for corrosive and fission products 3.848 MBq for NPP V-1 and 1.510 MBq for NPP V-2 (5.358 MBq (0.01% of AL) for the locality Bohunice), and for iodine 2.616 MBq for NPP V-1 and 0.279 MBq (2.894 MBq (0.002% of AL) for the locality Bohunice), and for tritium it is 2.395 TBq for NPP V-1 and 3.532 TBq for NPP V-2 (5.358 TBq (13.56% of AL) for the locality Bohunice

  18. Imidacloprid is degraded by CYP353D1v2, a cytochrome P450 overexpressed in a resistant strain of Laodelphax striatellus.

    Science.gov (United States)

    Elzaki, Mohammed Esmail Abdalla; Miah, Mohammad Asaduzzaman; Wu, Min; Zhang, Haomiao; Pu, Jian; Jiang, Ling; Han, Zhaojun

    2017-07-01

    Cytochrome P450s are associated with the metabolising of a wide range of compounds, including insecticides. CYP353D1v2 has been found to be overexpressed in an imidacloprid-resistant strain of Laodelphax striatellus. Thus, this study was conducted to express CYP353D1v2 in Sf9 cells as a recombinant protein, to assess its ability to metabolise imidacloprid. Western blot and carbon monoxide difference spectrum analysis indicated that the intact CYP353D1v2 protein had been successfully expressed in Sf9 insect cells. Catalytic activity tests with four traditional P450-activity-probing substrates found that the expressed CYP353D1v2 preferentially metabolised p-nitroanisole, ethoxycoumarin and ethoxyresorufin with specific activities of 32.70, 0.317 and 1.22 pmol min -1 pmol -1 protein respectively, but no activity to luciferin-H EGE. The enzyme activity for degrading imidacloprid was tested by measuring substrate depletion and formation of the metabolite. Kinetic parameters for imidacloprid were K m 5.99 ± 0.95 µm and k cat 0.03 ± 0.0004 min -1 . The chromatogram analysis showed clearly the NADPH-dependent depletion of imidacloprid and the formation of an unknown metabolite. The UPLC-MS mass spectrum demonstrated that the metabolite was an oxidative product of imidacloprid, 5-hydroxy-imidacloprid. These results suggest that CYP353D1v2 in L. striatellus is capable of degrading imidacloprid, and that enzyme activity can be evaluated well only by some traditional probing substrates. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  19. Pressure-induced metal-insulator transition in spinel compound CuV2S4

    International Nuclear Information System (INIS)

    Okada, H.; Koyama, K.; Hedo, M.; Uwatoko, Y.; Watanabe, K.

    2008-01-01

    In order to investigate the pressure effect on electrical properties of CuV 2 S 4 , we performed the electrical resistivity measurements under high pressures up to 8 GPa for a high-quality polycrystalline sample. The charge density wave (CDW) transition temperatures increase with increasing pressure. The residual resistivity rapidly increases with increasing pressure over 4 GPa, and the temperature dependence of the electrical resistivity at 8 GPa exhibits a semiconducting behavior below about 150 K, indicating that a pressure-induced metal-insulator transition occurs in CuV 2 S 4 at 8 GPa

  20. Influence of the vacuum interface on the charge distribution in V2O3 thin films

    KAUST Repository

    Schwingenschlögl, Udo

    2009-09-22

    The electronic structure of V2O3 thin films is studied by means of the augmented spherical wave method as based on density functional theory and the local density approximation. We establish that the effects of charge redistribution, induced by the vacuum interface, in such films are restricted to a very narrow surface layer of ≈15 Å thickness. As a consequence, charge redistribution can be ruled out as a source of the extraordinary thickness dependence of the metal–insulator transition observed in V2O3 thin films of ~100–1000 Å thickness.

  1. Fine-Grained vs. Average Reliability for V2V Communications around Intersections

    OpenAIRE

    Abdulla, Mouhamed; Wymeersch, Henk

    2017-01-01

    Intersections are critical areas of the transportation infrastructure associated with 47% of all road accidents. Vehicle-to-vehicle (V2V) communication has the potential of preventing up to 35% of such serious road collisions. In fact, under the 5G/LTE Rel.15+ standardization, V2V is a critical use-case not only for the purpose of enhancing road safety, but also for enabling traffic efficiency in modern smart cities. Under this anticipated 5G definition, high reliability of 0.99999 is expecte...

  2. The elastic constants of V2O3 in the insulating phase

    International Nuclear Information System (INIS)

    Yelon, W.B.; Keem, J.E.

    1979-01-01

    The initial slopes of the acoustic phonon dispersion curves in (Vsub(0.98)Crsub(0.02)) 2 O 3 have been measured at room temperature in several of the high symmetry directions by inelastic neutron scattering. From these data several sound velocities and four independent elastic constants have been determined. Although the Cr doped specimen is in the insulating phase and pure V 2 O 3 is metallic, these results are in good agreement with recent data obtained by ultrasonic measurements on pure V 2 O 3 . (author)

  3. Low-temperature thermal expansion measurements in PrV2Al20

    International Nuclear Information System (INIS)

    Magata, A.; Matsumoto, Y.; Tsujimoto, M.; Tomita, T.; Sakai, A.; Nakatsuji, S.; Kiichler, R.

    2016-01-01

    We have measured thermal expansion of PrV 2 Al 20 and LaV 2 Al 20 from room temperature down to 2 K, using a capacitance dilatometer. Linear thermal expansion ΔL/L along [111] direction decreases monotonically on cooling in both materials. The extracted 4ƒ electrons contribution of the linear thermal expansion coefficient a clearly shows a broad peak at ∼ 30 K which may correspond to the crystal electric field excited state at 40 K suggested in the previous specific heat study. (paper)

  4. Interfacial structure of V2AlC thin films deposited on (112-bar 0)-sapphire

    International Nuclear Information System (INIS)

    Sigumonrong, Darwin P.; Zhang, Jie; Zhou, Yanchun; Music, Denis; Emmerlich, Jens; Mayer, Joachim; Schneider, Jochen M.

    2011-01-01

    Local epitaxy between V 2 AlC and sapphire without intentionally or spontaneously formed seed layers was observed by transmission electron microscopy. Our ab initio calculations suggest that the most stable interfacial structure is characterized by the stacking sequence ...C-V-Al-V//O-Al..., exhibiting the largest work of separation for the configurations studied and hence strong interfacial bonding. It is proposed that a small misfit accompanied by strong interfacial bonding enable the local epitaxial growth of V 2 AlC on (112-bar 0)-sapphire.

  5. Order-disorder phase transition in ZrV2Dsub(3.6)

    International Nuclear Information System (INIS)

    Didisheim, J.-J.; Yvon, K.; Tissot, P.

    1981-01-01

    The deuterated C15-type Laves phase ZrV 2 Dsub(3.6) undergoes a structural phase transition near room temperature (T of the order of 325 K). In the cubic high-temperature phase the deuterium atoms are disordered over two types of tetrahedral interstices, the centres of which are 1.3 A apart. In the tetragonal low-temperature phase the D atoms are ordered and occupy only the energetically more favourable interstices. The tetragonal structure is isotypic with the low-temperature phase of HfV 2 D 4 . The shortest D-D distance is 2.1 A. (author)

  6. Al3+ doped V2O5 nanostructure: Synthesis and structural, morphological and optical characterization

    International Nuclear Information System (INIS)

    Venkatesan, A.; Chandar, N. Krishna; Jayavel, R.; Kumar, M. Krishna; Kumar, R. Mohan; Arjunan, S.

    2013-01-01

    Al x V 2-x O 5 (x = 0,2mol%) nanorods were synthesized at room temperature by facile surfactant free non-aqueous route. The phase pure orthorhombic structure and nanorods-like morphology have been studied by X-ray diffraction (XRD) and High resolution scanning electron microscopy. EDXS spectrum confirms the purity and presence of Al into V 2 O 5 lattice. Optical absorption from DRS UV-Vis spectra showed the band gap broadening due to quantum confinement effect. The results ensure that the dopant cation (Al 3+ ) successfully intercalated with the host cation (V 5+ ) and the products are promising for electrochromic and catalytic applications.

  7. Figure and Ground in the Visual Cortex: V2 Combines Stereoscopic Cues with Gestalt Rules

    OpenAIRE

    Qiu, Fangtu T.; von der Heydt, Rüdiger

    2005-01-01

    Figure-ground organization is a process by which the visual system identifies some image regions as foreground and others as background, inferring three-dimensional (3D) layout from 2D displays. A recent study reported that edge responses of neurons in area V2 are selective for side-of-figure, suggesting that figure-ground organization is encoded in the contour signals (border-ownership coding). Here we show that area V2 combines two strategies of computation, one that exploits binocular ster...

  8. Density functional calculation of the electronic and magnetic properties of α-CoV2O6

    Science.gov (United States)

    Saul, Andres; Radtke, Guillaume

    2012-02-01

    In this work, the magnetic properties of the low dimensional α-CoV2O6 system have been investigated using density-functional calculations. This system is constituted of CoO6 octahedra connected by the edges and forming one dimensional linear chains. The experimental magnetization curves recorded at very low temperature show a surprising magnetization plateau at one-third of the saturation magnetization and a strong anisotropy. The estimated Co magnetic moment is large reaching a value of 4.5 μB suggesting a large orbital contribution. Our calculations show that three different magnetic configurations for the Co are possible, the lowest energy one being a high spin configuration in agreement with the S=3/2 character of the Co+2 ion observed in this compound. Spin-orbit interactions have been included in order to calculate the magnetic anisotropy and the orbital contribution to the magnetic moment. The results are discussed in terms of crystal field splitting of the 3d orbital and a tight-binding Hamiltonian. Using a broken-symmetry formalism we have evaluated the effective exchange interactions of the Heisenberg Hamiltonian. They allow us to propose the magnetic structures corresponding to the ground state and to the observed magnetization plateaus.

  9. The comparative constitutional law on national constitutional system: with regard to the IX World Congress of Constitutional Law

    OpenAIRE

    Landa Arroyo, César

    2015-01-01

    From  the  process  of  globalization  of  law,  the  comparative constitutional law has gained a leading role for a better understanding and solving old and new constitutional national and international challenges. Therefore, some assumptions and considerations to take into account are presented for the development of the national constitutional order within the framework of the comparative constitutional law, such as universality and relativism of human rights; the concept of power and cons...

  10. CATHARE 2 V2.5 : a fully validated CATHARE version for various applications

    International Nuclear Information System (INIS)

    Robert, M.; Farvacque, M.; Parent, M.; Faydide, B.

    2003-01-01

    The CATHARE code is devoted to best estimate calculations of thermal-hydraulic transients in nuclear reactors. The code is based on a 2-fluid 6-equation model including non-condensable gases equations and additional equations for radio-chemical components transport. It allows the coolant circuits of any reactor to be represented by assembling 1D, 0D and 3D modules. The outcome of more than 20 years of joint development effort by CEA, EDF, FRAMATOME-ANP and IRSN, is the CATHARE 2 V2.5 version, to be released at the end of 2003. The development strategy of this version was to include in one single version the functionalities and the models needed for all the various applications the CATHARE partners have to deal with, in the scope of thermal-hydraulic nuclear safety analysis. Physical assessment is a highly time consuming activity for this kind of code. The 'single version' strategy results in putting together the validation efforts required for each application, thus significantly reducing the global validation effort. It also makes the maintenance process more efficient. The main objective of CATHARE 2 V2.5 is to perform safety analyses for Pressurized Water Reactors postulated accidents or other incidents, such as primary LOCAs, SGTR, loss of RHR, secondary breaks, loss of feed-water, etc. The 3D module of CATHARE has been developed in connection with the future safety methodologies based on the 3D modelling of the vessel. The main application is the large break LOCA where significant 3D effects take place, and in particular the phenomena related to the core radial temperature profile, the 3D core quenching pattern, the bypass of the accumulator water to the break and CCFL phenomena in the down-comer during the refill phase. These effects are exemplified with a PWR large break LOCA calculation using a 3D modeling of the vessel. Another major application of this version of CATHARE is to be used without modification in the SIPA French reactor simulator. This

  11. Constitutional Principles of State Control in the Republic of Armenia

    Directory of Open Access Journals (Sweden)

    Gabriel K. Balayan

    2015-12-01

    Full Text Available In the present article some of the provision of the RA Constitution’s basic principles of state control, which, in my opinion, should be guided by regulatory authorities during the inspection are discussed. These principles are considered by the author as the basis of the constitutionality of state control. Some of the control principles are divided by the author into positive and negative. Positive defines the principles that provide the freedom of action of man and citizen. Negative same principles are for government agencies, since they restrict their activities. A separate analysis is subject to the presidency on the basis of the principle of separation and balance of powers. In conclusion, author concludes that, based on the interpretation of the constitutional principles discussed, the term "law" applies only to natural and legal persons on the other hand can not be used as an analogue of the terms "authority" and "authority." According to the author, the fundamental constitutional principles of state control are expressed formally in a single system as defined in the first chapter of the Constitution of the Republic of Armenia. Compliance and reform of constitutional principles provide the synergy and the constitutionality of the process of governance.

  12. Childrens' Rights in the South African Constitution

    Directory of Open Access Journals (Sweden)

    JA Robinson

    2003-10-01

    Full Text Available Children were in many respects defenceless victims of discriminatory practices in ‘apartheid South Africa’. In fact, discrimination on the basis of gender, race and other inequalities were inscribed in the social fabric of the previous constitutional dispensation. The constitutional dispensation that came into effect on the 27th April 1994 was therefore designed to innovate social, political and legal structures that would be radically different from those of the country’s past history.In this contribution the impact of the Constitution upon the rights of children are considered. In order to fathom the impact. a general overview of constitutional principles and provisions necessary for the comprehension of the rights of children is provided. Thereafter the rights of children expressly mentioned in the Constitution will be addressed. Attention is also paid to the equal protection and non-discrimination provisions of the Constitution, albeit only indirectly.

  13. An integrated simulation environment for testing V2X protocols and applications

    NARCIS (Netherlands)

    Choudhury, A.; Maszczyk, T.; Dauwels, J.; Belagal Math, C.; Li, H.

    2016-01-01

    Implementation of Vehicle-to-everything (V2X) communication technologies, for traffic management, has been envisioned to have a plethora of far-reaching and useful consequences. However, before any hardware/software infrastructure can be developed and implemented, a thorough phase of testing is

  14. Color-Space-Based Visual-MIMO for V2X Communication †

    Science.gov (United States)

    Kim, Jai-Eun; Kim, Ji-Won; Park, Youngil; Kim, Ki-Doo

    2016-01-01

    In this paper, we analyze the applicability of color-space-based, color-independent visual-MIMO for V2X. We aim to achieve a visual-MIMO scheme that can maintain the original color and brightness while performing seamless communication. We consider two scenarios of GCM based visual-MIMO for V2X. One is a multipath transmission using visual-MIMO networking and the other is multi-node V2X communication. In the scenario of multipath transmission, we analyze the channel capacity numerically and we illustrate the significance of networking information such as distance, reference color (symbol), and multiplexing-diversity mode transitions. In addition, in the V2X scenario of multiple access, we may achieve the simultaneous multiple access communication without node interferences by dividing the communication area using image processing. Finally, through numerical simulation, we show the superior SER performance of the visual-MIMO scheme compared with LED-PD communication and show the numerical result of the GCM based visual-MIMO channel capacity versus distance. PMID:27120603

  15. Color-Space-Based Visual-MIMO for V2X Communication

    Directory of Open Access Journals (Sweden)

    Jai-Eun Kim

    2016-04-01

    Full Text Available In this paper, we analyze the applicability of color-space-based, color-independent visual-MIMO for V2X. We aim to achieve a visual-MIMO scheme that can maintain the original color and brightness while performing seamless communication. We consider two scenarios of GCM based visual-MIMO for V2X. One is a multipath transmission using visual-MIMO networking and the other is multi-node V2X communication. In the scenario of multipath transmission, we analyze the channel capacity numerically and we illustrate the significance of networking information such as distance, reference color (symbol, and multiplexing-diversity mode transitions. In addition, in the V2X scenario of multiple access, we may achieve the simultaneous multiple access communication without node interferences by dividing the communication area using image processing. Finally, through numerical simulation, we show the superior SER performance of the visual-MIMO scheme compared with LED-PD communication and show the numerical result of the GCM based visual-MIMO channel capacity versus distance.

  16. Price-based Energy Control for V2G Networks in the Industrial Smart Grid

    Directory of Open Access Journals (Sweden)

    Rong Yu

    2015-08-01

    Full Text Available The energy crisis and global warming call for a new industrial revolution in production and distribution of renewable energy. Distributed power generation will be well developed in the new smart electricity distribution grid, in which robust power distribution will be the key technology. In this paper, we present a new vehicle-to-grid (V2G network for energy transfer, in which distributed renewable energy helps the power grid balance demand and supply. Plug-in hybrid electric vehicles (PHEVs will act as transporters of electricity for distributed renewable energy dispatching. We formulate and analyze the V2G network within the theoretical framework of complex network. We also employ the generalized synchronization method to study the dynamic behavior of V2G networks. Furthermore, we develop a new price-based energy control method to stimulate the PHEV's behavior of charging and discharging. Simulation results indicate that the V2G network can achieve synchronization and each region is able to balance energy supply and demand through price-based control.

  17. Crowdsourcing-Assisted Radio Environment Database for V2V Communication

    Directory of Open Access Journals (Sweden)

    Keita Katagiri

    2018-04-01

    Full Text Available In order to realize reliable Vehicle-to-Vehicle (V2V communication systems for autonomous driving, the recognition of radio propagation becomes an important technology. However, in the current wireless distributed network systems, it is difficult to accurately estimate the radio propagation characteristics because of the locality of the radio propagation caused by surrounding buildings and geographical features. In this paper, we propose a measurement-based radio environment database for improving the accuracy of the radio environment estimation in the V2V communication systems. The database first gathers measurement datasets of the received signal strength indicator (RSSI related to the transmission/reception locations from V2V systems. By using the datasets, the average received power maps linked with transmitter and receiver locations are generated. We have performed measurement campaigns of V2V communications in the real environment to observe RSSI for the database construction. Our results show that the proposed method has higher accuracy of the radio propagation estimation than the conventional path loss model-based estimation.

  18. VAPOR PHASE OXIDATION OF DIMETHYL SULFIDE WITH OZONE OVER V2O5/TIO2 CATALYST

    Science.gov (United States)

    Removal of volatile and odorous compounds emissions from the pulp and paper industry usually creates secondary pollution for scrubbing and adsorption processes or sulfur poising for catalytic incineration. Product studies performed in a flow reactor packed with 10 % V2O5/TiO2 cat...

  19. Ultrafast electron-lattice coupling dynamics in VO2 and V2O3 thin films

    Science.gov (United States)

    Abreu, Elsa; Gilbert Corder, Stephanie N.; Yun, Sun Jin; Wang, Siming; Ramírez, Juan Gabriel; West, Kevin; Zhang, Jingdi; Kittiwatanakul, Salinporn; Schuller, Ivan K.; Lu, Jiwei; Wolf, Stuart A.; Kim, Hyun-Tak; Liu, Mengkun; Averitt, Richard D.

    2017-09-01

    Ultrafast optical pump-optical probe and optical pump-terahertz probe spectroscopy were performed on vanadium dioxide (VO2) and vanadium sesquioxide (V2O3 ) thin films over a wide temperature range. A comparison of the experimental data from these two different techniques and two different vanadium oxides, in particular a comparison of the spectral weight oscillations generated by the photoinduced longitudinal acoustic modulation, reveals the strong electron-phonon coupling that exists in both materials. The low-energy Drude response of V2O3 appears more amenable than VO2 to ultrafast strain control. Additionally, our results provide a measurement of the temperature dependence of the sound velocity in both systems, revealing a four- to fivefold increase in VO2 and a three- to fivefold increase in V2O3 across the insulator-to-metal phase transition. Our data also confirm observations of strong damping and phonon anharmonicity in the metallic phase of VO2, and suggest that a similar phenomenon might be at play in the metallic phase of V2O3 . More generally, our simple table-top approach provides relevant and detailed information about dynamical lattice properties of vanadium oxides, paving the way to similar studies in other complex materials.

  20. Ytarget optimization for E93050 experiment. Pt. 1. Q2 = 1 GeV2

    International Nuclear Information System (INIS)

    Jaminion, S.; Fonvieille, H.

    1998-01-01

    The Espace y tg optimization that has been performed for experiment E93050 at Q 2 = 1 GeV 2 is summarized. The method and results are presented. The optic Y tensor elements obtained can be used for first pass analysis, although a more refined analysis may need further optimized optic elements. (author)

  1. Solving da Vinci stereopsis with depth-edge-selective V2 cells

    Science.gov (United States)

    Assee, Andrew; Qian, Ning

    2007-01-01

    We propose a new model for da Vinci stereopsis based on a coarse-to-fine disparity-energy computation in V1 and disparity-boundary-selective units in V2. Unlike previous work, our model contains only binocular cells, relies on distributed representations of disparity, and has a simple V1-to-V2 feedforward structure. We demonstrate with random dot stereograms that the V2 stage of our model is able to determine the location and the eye-of-origin of monocularly occluded regions and improve disparity map computation. We also examine a few related issues. First, we argue that since monocular regions are binocularly defined, they cannot generally be detected by monocular cells. Second, we show that our coarse-to-fine V1 model for conventional stereopsis explains double matching in Panum’s limiting case. This provides computational support to the notion that the perceived depth of a monocular bar next to a binocular rectangle may not be da Vinci stereopsis per se (Gillam et al., 2003). Third, we demonstrate that some stimuli previously deemed invalid have simple, valid geometric interpretations. Our work suggests that studies of da Vinci stereopsis should focus on stimuli more general than the bar-and-rectangle type and that disparity-boundary-selective V2 cells may provide a simple physiological mechanism for da Vinci stereopsis. PMID:17698163

  2. Inversion symmetry in the spin-Peierls compound $alpha' - NaV_{2}O_{5}$

    NARCIS (Netherlands)

    Meetsma, A.; Boer, J. L. de; Damascelli, A.; Jegoudez, J.; Revcolevschi, A.; Palstra, T. T. M.

    1998-01-01

    Published in: Acta Crystallogr., C 54 (1998) , pp.1558 citations recorded in [Science Citation Index] Abstract: At room-temperature NaV2O5 was found to have the centrosymmetric space group Pmmn. This space group implies the presence of only one kind of V site in contrast with previous reports of the

  3. Robust model predictive cooperative adaptive cruise control subject to V2V impairments

    NARCIS (Netherlands)

    Van Nunen, Ellen; Verhaegh, Jan; Silvas, Emilia; Semsar-Kazerooni, Elham; Van De Wouw, Nathan

    2018-01-01

    To improve traffic throughput, Cooperative Adaptive Cruise Control (CACC) has been proposed as a solution. The usage of Vehicle-to-Vehicle (V2V) communication enables short following distances, thereby increasing road capacity and fuel reduction (especially for trucks). Control designs for CACC use

  4. The gravity dual of the non-perturbative V = 2 supersymmetric Yang ...

    Indian Academy of Sciences (India)

    -Mills theory. sATCHIDANANDA NAIK. Harish-Chandra Research Institute, Jhusi, Allahabad 211 019, India. Abstract. The anomalous Ward identity is derived for V = 2 SUSY Yang-Mills theo- ries, which is resulted out of wrapping of D5 branes ...

  5. Color-Space-Based Visual-MIMO for V2X Communication.

    Science.gov (United States)

    Kim, Jai-Eun; Kim, Ji-Won; Park, Youngil; Kim, Ki-Doo

    2016-04-23

    In this paper, we analyze the applicability of color-space-based, color-independent visual-MIMO for V2X. We aim to achieve a visual-MIMO scheme that can maintain the original color and brightness while performing seamless communication. We consider two scenarios of GCM based visual-MIMO for V2X. One is a multipath transmission using visual-MIMO networking and the other is multi-node V2X communication. In the scenario of multipath transmission, we analyze the channel capacity numerically and we illustrate the significance of networking information such as distance, reference color (symbol), and multiplexing-diversity mode transitions. In addition, in the V2X scenario of multiple access, we may achieve the simultaneous multiple access communication without node interferences by dividing the communication area using image processing. Finally, through numerical simulation, we show the superior SER performance of the visual-MIMO scheme compared with LED-PD communication and show the numerical result of the GCM based visual-MIMO channel capacity versus distance.

  6. Optical properties, electronic structure and magnetism of alpha '-NaxV2O5

    NARCIS (Netherlands)

    Konstantinovic, MI; Popovic, ZV; Presura, C; Gajic, R; Isobe, M; Ueda, Y; Moshchalkov, VV

    2002-01-01

    The optical properties of sodium-deficient alpha'-NaxV2O5 (0.85 less than or equal to x less than or equal to 1.00) single crystals are analyzed using ellipsometry, and infrared reflectivity techniques. In sodium deficient samples, the optical absorption peak associated to the fundamental electronic

  7. C112 C123 generated by two particle correlations through v2 and v3

    Energy Technology Data Exchange (ETDEWEB)

    Longacre, Ronald S.

    2018-01-31

    Abstract: In this note we consider the three particle correlators C112 and C123 and how they can be generated from a pure two particle correlation by interacting with a v2 and a v3 of the overall system.

  8. Data rate based congestion control in V2V communication for traffic safety applications

    NARCIS (Netherlands)

    Belagal Math, C.; Özgür, A.; Heemstra de Groot, S.M.; Li, H.

    2015-01-01

    Vehicle-to-Vehicle (V2V) communication systems intend to increase safety and efficiency of the transportation networks. At high vehicle density, the communication channel may become congested, impairing the reliability of the safety applications. As a counter measure, the European Telecommunications

  9. UVI ThunnderBird Cup v2.0 Workshop: Worshop Analysis 2016.

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Wellington K. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Morris, Tyler Jake [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Chu, Andrew Chun-An [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Russ, Joshua [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Emerson-Lewis, Michelle

    2016-11-01

    The ThunderBird Cup v2.0 (TBC2) program falls under the Minority Serving Institution Pipeline Program (MSIPP) that aims to establish a world-class workforce development, education and research program that combines the strengths of Historically Black Colleges and Universities (HBCUs) and national laboratories to create a K-20 pipeline of students to participate in cybersecurity and related fields.

  10. Automated Transportation Management System (ATMS) V2.0 logistics module PBI acceptance criteria

    International Nuclear Information System (INIS)

    Weidert, R.S.

    1995-01-01

    This document defines the acceptance criteria for the Automated Transportation Management System V2.0 Logistics Module Performance Based Incentive (PBI). This acceptance criteria will be the primary basis for the generation of acceptance test procedures. The purpose of this document is to define the minimum criteria that must be fulfilled to guarantee acceptance of the Logistics Module

  11. Electronic decal: a security function based on V2X communication

    NARCIS (Netherlands)

    Knapik, Peter; Schoch, Elmar; Kargl, Frank

    New technologies such as vehicle-to-X (V2X) communication and advanced driver assistance systems (ADAS) are on the rise. They are mainly used to increase road safety as well as traffic efficiency and to provide customers with infotainment features. However, these new technologies also provide the

  12. The constitutional control system in Colombia

    OpenAIRE

    Luis Javier Moreno Ortiz

    2010-01-01

    The system of constitutional control in Colombia designed in the Legislative Act n.º 3 of 1910 is a milestone in a long and fruitful political and constitutional tradition owes much to his Hispanic roots and its American developments. Both the public action of unconstitutionality as the plea of unconstitutionality have clear precedents in the constitutionalism of Spain and the Colony were prepared by a Constituent Assembly acted with knowledge and faithfulness to that tradition and have been ...

  13. Competition And Antitrust Law In Ecuadorian Constitution

    OpenAIRE

    Marcelo Marín Sevilla

    2013-01-01

    This work allows us to establish the Economic Constitution and the Competition Law (C.L) in the Constitution. Additionally, the paper analyzes whether the rules outlined in the C. L. and in doctrine are consistent and appropriate with the Constitution of Ecuador. The Competition and Antitrust Laws has rules for investigating and punishing the cartels, the abuses of power market (dominant position), the rules for merger control, the behaviors of Abuse of economic dependence, and unfair competi...

  14. Complexities of Constitutional Change in the Philippines

    OpenAIRE

    Saunders, Cheryl; Yusingco, Michael Henry

    2018-01-01

    President Rodrigo Duterte assumed office in July 2016, His party, PDP-Laban, had campaigned under the slogan: “No to Drugs, Yes to Federalism”. Duterte thus is committed to shepherding the Philippines towards a federal form of government; an undertaking that would require an extensive overhaul of the country’s constitution. The future of constitutional change under Duterte in any event is uncertain for a series of constitutional and political reasons. Critically, some of the most pressing of ...

  15. Human Rights in Indonesian Constitutional Amendments

    OpenAIRE

    Kharlie, Ahmad Tholabi

    2013-01-01

    Human Rights in Indonesian Constitutional Amendments. Indonesian constitutional amendments incorporated human rights principles into the Constitution of the Republic of Indonesia 1945 (UUD NRI), especially in the second amendment in 2000. Under that amendment, the UUD NRI currently stipulates human rights principles as provided for in the Universal Declaration of Human Rights (UDHR). However, there are some important notes, which at its core is a lack of emphasis on the vision and mission of ...

  16. Constitutionalism and Democracy in Contemporary International Community

    OpenAIRE

    Padjen, Ivan

    1992-01-01

    Starting from the insight that jurisprudence of legal theory should be concerned primarily with,on the one hand, international law, and, on the other, constitutional developments, the paper; analyzes some prominent conceptions of constitutionalism and democracy in international community and municipal legal orders; formulates a new set of criteria for the analysis of constitutionalism and democracy in international law; and argues that Laswell and McDougal's policy oriented jurisprudence offe...

  17. C=C bond cleavage on neutral VO3(V2O5)n clusters.

    Science.gov (United States)

    Dong, Feng; Heinbuch, Scott; Xie, Yan; Bernstein, Elliot R; Rocca, Jorge J; Wang, Zhe-Chen; Ding, Xun-Lei; He, Sheng-Gui

    2009-01-28

    The reactions of neutral vanadium oxide clusters with alkenes (ethylene, propylene, 1-butene, and 1,3-butadiene) are investigated by experiments and density function theory (DFT) calculations. Single photon ionization through extreme ultraviolet radiation (EUV, 46.9 nm, 26.5 eV) is used to detect neutral cluster distributions and reaction products. In the experiments, we observe products (V(2)O(5))(n)VO(2)CH(2), (V(2)O(5))(n)VO(2)C(2)H(4), (V(2)O(5))(n)VO(2)C(3)H(4), and (V(2)O(5))(n)VO(2)C(3)H(6), for neural V(m)O(n) clusters in reactions with C(2)H(4), C(3)H(6), C(4)H(6), and C(4)H(8), respectively. The observation of these products indicates that the C=C bonds of alkenes can be broken on neutral oxygen rich vanadium oxide clusters with the general structure VO(3)(V(2)O(5))(n=0,1,2...). DFT calculations demonstrate that the reaction VO(3) + C(3)H(6) --> VO(2)C(2)H(4) + H(2)CO is thermodynamically favorable and overall barrierless at room temperature. They also provide a mechanistic explanation for the general reaction in which the C=C double bond of alkenes is broken on VO(3)(V(2)O(5))(n=0,1,2...) clusters. A catalytic cycle for alkene oxidation on vanadium oxide is suggested based on our experimental and theoretical investigations. The reactions of V(m)O(n) with C(6)H(6) and C(2)F(4) are also investigated by experiments. The products VO(2)(V(2)O(5))(n)C(6)H(4) are observed for dehydration reactions between V(m)O(n) clusters and C(6)H(6). No product is detected for V(m)O(n) clusters reacting with C(2)F(4). The mechanisms of the reactions between VO(3) and C(2)F(4)/C(6)H(6) are also investigated by calculations at the B3LYP/TZVP level.

  18. Atypical Rulings of the Indonesian Constitutional Court

    Directory of Open Access Journals (Sweden)

    Bisariyadi

    2016-08-01

    Full Text Available In deciding judicial review cases, the Court may issue rulings that is not in accordance to what is stipulated in the Constitutional Court Law (Law Number 8 Year 2011. Atypical rulings means that the court may reconstruct a provision, delay the legislation/rulings enactment or give instruction to lawmakers. In addition, the court also introduce the “conditionally (unconstitutional” concept. This essay attempts to identify and classify these atypical rulings, including conditionally (un constitutional rulings, by examined the constitutional court judicial review rulings from 2003 to 2015. This study will provide a ground work for advance research on typical rulings by the Indonesian constitutional court.

  19. Projections to early visual areas V1 and V2 in the calcarine fissure from parietal association areas in the macaque.

    Directory of Open Access Journals (Sweden)

    Elena eBorra

    2011-06-01

    Full Text Available Non-extrastriate projections to area V1 in monkeys, now demonstrated by several anatomical studies, are potential substrates of physiologically documented multisensory effects in primary sensory areas. The full network of projections among association and primary areas, however, is likely to be complex and is still only partially understood. In the present report, we used the anterograde tracer biotinylated dextran amine to investigate projections to areas V1 and V2 from subdivisions of the parietal association cortex in macaque. Parietal cortex was chosen to allow comparisons between projections from this higher association area and from other previously reported areas. In addition, we were interested in further elucidating pathways to areas V1 and V2 from parietal areas, as potentially contributing to attention and active vision. Of eight cases, three brains had projections only to area V2, and the five others projected to both areas V1 and V2. Terminations in area V1 were sparse. These were located in supragranular layers I, II, upper III; occasionally in IVB; and in layer VI. Terminations in V2 were denser, and slightly more prevalent in the supragranular layers. For both areas, terminations were in the calcarine region, corresponding to the representation of the peripheral visual field. By reconstructions of single axons, we demonstrated that four of nine axons had collaterals, either to V1 and V2 (n=1 or to area V1 and a ventral area likely to be TEO (n=3. In area V1, axons extended divergently in layer VI as well as layer I. Overall, these and previous results suggest a nested connectivity architecture, consisting of multiple direct and indirect recurrent projections from association areas to area V1. Terminations in area V1 are not abundant, but could be potentiated by the network of indirect connections.

  20. The Australian Constitution and the Aid/Watch Case

    Directory of Open Access Journals (Sweden)

    George Williams

    2011-11-01

    Full Text Available The Australian Constitution played a significant role in underpinning the result in the Aid/Watch Case. It was invoked by the majority to support their conclusion that a body can be a ‘charitable institution’ despite engaging in political activities. The use of the Constitution in this way came as a surprise. The case extended an existing constitutional principle relating to freedom of political communication from its electoral base into the protection of the political activities of non-government organisations. This may have future ramifications for those organisations in other areas, as well as further implications for the development of what it means to be a charity in Australia. This article examines the use of the Australian Constitution in the Aid/Watch Case. It explains how the High Court was able to invoke the Constitution in defining what it means to be a ‘charitable institution’. It also examines the implications of that reasoning for the development of charitable law in Australia.