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...

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.

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...

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

Correction of Flow Curves and Constitutive Modelling of a Ti-6Al-4V Alloy

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Ming Hu

2018-04-01

Full Text Available Isothermal uniaxial compressions of a Ti-6Al-4V alloy were carried out in the temperature range of 800–1050 °C and strain rate range of 0.001–1 s−1. The effects of friction between the specimen and anvils as well as the increase in temperature caused by the high strain rate deformation were considered, and flow curves were corrected as a result. Constitutive models were discussed based on the corrected flow curves. The correlation coefficient and average absolute relative error for the strain compensated Arrhenius-type constitutive model are 0.986 and 9.168%, respectively, while the values for a modified Johnson-Cook constitutive model are 0.924 and 22.673%, respectively. Therefore, the strain compensated Arrhenius-type constitutive model has a better prediction capability than a modified Johnson-Cook constitutive model.

FATAL FOETAL ABNORMALITY, IRISH CONSTITUTIONAL LAW, AND MELLET v IRELAND.

Science.gov (United States)

de Londras, Fiona

2016-12-27

Under the Irish Constitution abortion is allowed only where the life of the pregnant woman is at risk. The provision in question, Article 40.3.3 (or the 8th Amendment) has long been criticised for failing to respect women's autonomy, and in Mellet v Ireland, the UN Human Rights Committee found that Amanda Jane Mellet, who travelled to Liverpool to access abortion following a finding that her foetus suffered a fatal abnormality, had suffered a violation of her rights under the International Covenant on Civil and Political Rights (ICCPR). In this commentary I demonstrate the value of Mellet when compared to the possible legal findings in such circumstances under both the Constitution and the European Convention on Human Rights, and argue that the findings are not restricted to cases of fatal foetal abnormality. Rather, the Committee's decision illustrates the suffering that all women in Ireland who travel to access abortion experience, arguably constituting a violation of their right to be free from cruel, inhuman, and degrading treatment. On that reading, Mellet signifies the need to implement a comprehensive rethink of Irish abortion law including, but going beyond, access to abortion in cases of fatal foetal abnormality. © The Author 2016. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

A modified parallel constitutive model for elevated temperature flow behavior of Ti-6Al-4V alloy based on multiple regression

Energy Technology Data Exchange (ETDEWEB)

Cai, Jun; Shi, Jiamin; Wang, Kuaishe; Wang, Wen; Wang, Qingjuan; Liu, Yingying [Xi' an Univ. of Architecture and Technology, Xi' an (China). School of Metallurgical Engineering; Li, Fuguo [Northwestern Polytechnical Univ., Xi' an (China). School of Materials Science and Engineering

2017-07-15

Constitutive analysis for hot working of Ti-6Al-4V alloy was carried out by using experimental stress-strain data from isothermal hot compression tests. A new kind of constitutive equation called a modified parallel constitutive model was proposed by considering the independent effects of strain, strain rate and temperature. The predicted flow stress data were compared with the experimental data. Statistical analysis was introduced to verify the validity of the developed constitutive equation. Subsequently, the accuracy of the proposed constitutive equations was evaluated by comparing with other constitutive models. The results showed that the developed modified parallel constitutive model based on multiple regression could predict flow stress of Ti-6Al-4V alloy with good correlation and generalization.

JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis.

Science.gov (United States)

Xia, Jun; Lu, Mi-Ze; Jiang, Yuan-Qiang; Yang, Guo-Hua; Zhuang, Yun; Sun, Hong-Li; Shen, Yun-Feng

2012-03-01

JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF). We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

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

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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.

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

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.…

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

Teaching "United States v. Windsor": The Defense of Marriage Act and Its Constitutional Implications

Science.gov (United States)

Ciocchetti, Corey

2014-01-01

This article represents background material that can be used e along with the "United States v. Windsor" case to teach Constitutional Law (particularly federalism, due process, and equal protection) and the legal debate surrounding same-sex marriage in America. Professors may assign it as background reading before or after a…

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...

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...

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

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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.

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...

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

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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.

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

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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.

Constitutive Activity in an Ancestral Form of Abl Tyrosine Kinase.

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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.

Creep constitutive equations for a 0.5Cr 0.5 Mo 0.25V ferritic steel in the temperature range 565 deg. C-675 deg. C

International Nuclear Information System (INIS)

Mustata, R.; Hayhurst, D.R.

2005-01-01

A two damage state variable model is used to describe the softening mechanisms, damage initiation and growth for a low alloy ferritic steel 1/2Cr-1/2Mo-1/4V at 565 and 590 deg. C within the Continuum Damage Mechanics framework. The level of complexity of the constitutive equations and the degree of coupling through damage is high and it is difficult to calibrate values of the constitutive constants without recourse to optimisation techniques. A methodology for the analysis of uni-axial experimental data, coupled with a traditional gradient-based optimisation technique, is presented for the unique determination of the constitutive constants. Two sets of experimental data on parent material are used for inversion purposes: at 565 deg. C, c.f. Cane [Cane BJ. Collaborative programme on the corelation of test data for high temperature design of welded steam pipes. Presentation and analysis of the material data. Note No. RD/L/2101N81, March, CEGB Laboratory; 1981]; and, at 590 deg. C, c.f. Miller [Miller DA. Private communication: 'Creep rupture testing of Cr M V pipe steel. ERA Project 63-01-040320009'. Barnwood, Gloucs, UK: British Energy; 2000]. The variation of the constitutive parameters with temperature in the range 565-590 deg. C has been deduced by considering the values of constitutive parameters for the same alloy deduced by Perrin and Hayhurst [Perrin IJ, Hayhurst DR. Creep constitutive equations for a 0.5Cr-0.5Mo-0.25V ferritic steel in the temperature range 600-675 deg. C. J Strain Anal 1996;31:299-314] in the temperature range 620-675 deg. C

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.

The constitutional view

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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.

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

A visible-light-driven photocatalytic activity of vanadate garnet AgCa2Ni2V3O12 nanoparticles

International Nuclear Information System (INIS)

Lu, Yuting; Chen, Luyang; Li, Yuze; Huang, Yanlin; Cheng, Han; Seo, Hyo Jin

2015-01-01

A visible-light-driven photocatalyst of nanosized vanadate garnet AgCa 2 Ni 2 V 3 O 12 was prepared by a modified Pechini method. The nanoparticles were characterized with the measurements such as X-ray powder diffraction (XRD) and structural refinements, scanning electron microscope (SEM), and UV–visible (UV–Vis) absorption spectrum. The sample has an efficient absorption in the UV–Vis light region with a narrow band-gap energy of 2.16 eV and an indirect allowed electronic transition. Besides, the photocatalysis of AgCa 2 Ni 2 V 3 O 12 nanoparticles was evaluated by photo-degradation of methylene blue under visible-light irradiation, which shows excellent photocatalytic activity. The effective photocatalytic activity was discussed on the base of the garnet crystal structure such as the activated optical centers of Ni–O octahedron and V–O tetrahedral, highly distorted Ag–O dodecahedra, and long V–V distance in the lattices

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.

Nuclear and activation characteristics of materials in 14.1-MeV and 2.5-MeV neutron field

International Nuclear Information System (INIS)

Seki, Yasushi; Takeyasu, Yuuichi.

1988-11-01

The nuclear and activation characteristics of various materials and elements of interest in terms of fusion reactor design are calculated and the results are graphically shown. The elements and materials are placed in a simple geometry modelling a blanket and shield of a fusion reactor. The neutrons with 14.1-MeV and 2.5-MeV energy are generated from the region represented as D-T and D-D plasma, respectively. The following activation characteristics after neutron irradiation are shown for each material and element; 1. Time evolution of induced activity, 2. Time evolution of decay heat, 3. Delayed gamma-ray dose distribution, 4. Decay heat distribution. In addition to the above activation characteristics, nuclear characteristics during the neutron irradiation, e.g. neutron energy spectra, neutron and gamma-ray flux distribution, nuclear heating distributions, and neutron and gamma-ray dose rate are also shown. (author)

Constitutional limits on federal legislation practically compelling medical employment: Wong v Commonwealth; Selim v Professional Services Review Committee.

Science.gov (United States)

Faunce, Thomas

2009-10-01

A recent decision by the High Court of Australia (Wong v Commonwealth; Selim v Professional Services Review Committee (2009) 236 CLR 573) (the PSR case) has not only clarified the scope of the Australian constitutional prohibition on "any form of civil conscription" in relation to federal legislation concerning medical or dental services (s 51xxiiiA), but has highlighted its importance as a great constitutional guarantee ensuring the mixed State-federal and public-private nature of medical service delivery in Australia. Previous decisions of the High Court have clarified that the prohibition does not prevent federal laws regulating the manner in which medical services are provided. The PSR case determined that the anti-overservicing provisions directed at bulk-billing general practitioners under Pt VAA of the Health Insurance Act 1973 (Cth) did not offend the prohibition. Importantly, the High Court also indicated that the s 51(xxiiiA) civil conscription guarantee should be construed widely and that it would invalidate federal laws requiring providers of medical and dental services (either expressly or by practical compulsion) to work for the federal government or any specified State, agency or private industrial employer. This decision is likely to restrict the capacity of any future federal government to restructure the Australian health care system, eg by implementing recommendations from the National Health and Hospitals Reform Commission for either federal government or private corporate control of presently State-run public hospitals.

Constitutional Law--State Action--Golden v. Biscayne Bay Yacht Club: Preventing Discrimination by Private Clubs

Science.gov (United States)

Patrick, Michael W.

1976-01-01

Although the Supreme Court has refrained from answering whether the membership policies of private clubs can be attacked on state action grounds, the Fifth Circuit Court of Appeals held in the affirmative in Golden v. Biscayne Bay Yacht Club. It ruled that leasing publicly owned bay bottom land to a yacht club constituted sufficient state…

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

Students' Constitutional Right to a Sound Basic Education: New York State's Unfinished Agenda. Part 1. A Roadmap to Constitutional Compliance Ten Years after "CFE v. State"

Science.gov (United States)

Rebell, Michael A.; Wolff, Jessica R.

2016-01-01

Ten years have passed since New York's highest court ruled in the landmark school-funding and educational-rights case, "Campaign for Fiscal Equity (CFE) v. State of New York," that the state was violating students' constitutional right to the "opportunity for a sound basic education" and ordered significant reforms of the…

The JH2 domain and SH2-JH2 linker regulate JAK2 activity: A detailed kinetic analysis of wild type and V617F mutant kinase domains.

Science.gov (United States)

Sanz Sanz, Arturo; Niranjan, Yashavanthi; Hammarén, Henrik; Ungureanu, Daniela; Ruijtenbeek, Rob; Touw, Ivo P; Silvennoinen, Olli; Hilhorst, Riet

2014-10-01

JAK2 tyrosine kinase regulates many cellular functions. Its activity is controlled by the pseudokinase (JH2) domain by still poorly understood mechanisms. The V617F mutation in the pseudokinase domain activates JAK2 and causes myeloproliferative neoplasms. We conducted a detailed kinetic analysis of recombinant JAK2 tyrosine kinase domain (JH1) and wild-type and V617F tandem kinase (JH1JH2) domains using peptide microarrays to define the functions of the kinase domains. The results show that i) JAK2 follows a random Bi-Bi reaction mechanism ii) JH2 domain restrains the activity of the JH1 domain by reducing the affinity for ATP and ATP competitive inhibitors iii) V617F decreases affinity for ATP but increases catalytic activity compared to wild-type and iv) the SH2-JH2 linker region participates in controlling activity by reducing the affinity for ATP. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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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.

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

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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.

Constitutional changes and the dilemmas of constitutionalism

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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.

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.

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.

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.

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.

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

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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.

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....

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.

Free at Last: Rejecting Equal Sovereignty and Restoring the Constitutional Right to Vote: Shelby County v. Holder

OpenAIRE

Guinier, C. Lani; Blacksher, James

2014-01-01

The "equal sovereignty" principle the Supreme Court majority relied on in Shelby County v. Holder to strike down the coverage formula in Section 4 of the Voting Rights Act is rooted in the jurisprudence of slavery. In the infamous 1857 case of Dred Scott v. Sandford, Chief Justice Roger Taney held that black Americans, slave or free, were not members of the sovereign people and could never be "citizens" within the meaning of the Constitution. Otherwise, he said, blacks would be entitled to al...

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

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.

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.

Constitutive equations for Zr1Nb. II

International Nuclear Information System (INIS)

Novak, J.

1986-01-01

Based on existing knowledge and constitutive equations for non-irradiated material, constitutive equations were written for Zr1Nb irradiated at 573 K at deformation in the direction of forming. Constitutive equations express the following material characteristics: dependence of shear strength on fast neutron fluence, superposition of deformation hardening and subsequent radiation hardening, the effect of stress on deformation rate, and for fluences above ca. 10 24 n.m -2 (E>1 MeV) the course of the deformation curve for various fluence levels. The values apply for temperatures and rates of deformation which are characteristic of transient processes during changes in the power output of fuel elements of pressurized water reactors. (J.B.)

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

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

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...

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

A visible-light-driven photocatalytic activity of vanadate garnet AgCa{sub 2}Ni{sub 2}V{sub 3}O{sub 12} nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Lu, Yuting; Chen, Luyang; Li, Yuze; Huang, Yanlin [Soochow University, College of Chemistry, Chemical Engineering and Materials Science (China); Cheng, Han; Seo, Hyo Jin, E-mail: hjseo@pknu.ac.kr [Pukyong National University, Department of Physics and Interdisciplinary Program of Biomedical, Mechanical and Electrical Engineering (Korea, Republic of)

2015-10-15

A visible-light-driven photocatalyst of nanosized vanadate garnet AgCa{sub 2}Ni{sub 2}V{sub 3}O{sub 12} was prepared by a modified Pechini method. The nanoparticles were characterized with the measurements such as X-ray powder diffraction (XRD) and structural refinements, scanning electron microscope (SEM), and UV–visible (UV–Vis) absorption spectrum. The sample has an efficient absorption in the UV–Vis light region with a narrow band-gap energy of 2.16 eV and an indirect allowed electronic transition. Besides, the photocatalysis of AgCa{sub 2}Ni{sub 2}V{sub 3}O{sub 12} nanoparticles was evaluated by photo-degradation of methylene blue under visible-light irradiation, which shows excellent photocatalytic activity. The effective photocatalytic activity was discussed on the base of the garnet crystal structure such as the activated optical centers of Ni–O octahedron and V–O tetrahedral, highly distorted Ag–O dodecahedra, and long V–V distance in the lattices.

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)

Adrenal incidentaloma and the Janus Kinase 2 V617F mutation: A case-based review of the literature

Directory of Open Access Journals (Sweden)

Mustafa Unubol

2013-01-01

Full Text Available Adrenal incidentaloma was detected in an 81-year-old male patient and a 37-year-old female patient who had been diagnosed with essential thrombocytosis. Each patient′s Janus Kinase 2 (JAK2 V617F mutation was positive, and they were evaluated as having non-functional adrenal incidentaloma. The JAK2 activates the signal transducers and activators of transcription (STAT proteins which then activate the phosphoinositol-3 kinases, Ras, mitogen-activated protein (MAP kinases, and transcription. Constitutive activation causes cell proliferation and dysregulation of apoptosis. It is thought that STAT3 activation-mediated JAK family kinases have a central role in the solid tumor cell series. Permanent activation of STAT3 and STAT5 causes tumor cell proliferation, survival, metastasis, and an increase in tumor-mediated inflammation in solid and hematologic tumors. According to our literature screening, irregular JAK signaling, seen at the pathogenesis of many solid and hematologic tumors, has not been previously evaluated with regard to adrenal tumors. As a result, our cases are the first coexistence of JAK V617F mutation with adrenal incidentaloma in the literature. Because of this, we think that JAK2 mutation must be evaluated to clarify the etiology of adrenal incidentalomas.

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...

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.

Constitutive MHC class I molecules negatively regulate TLR-triggered inflammatory responses via the Fps-SHP-2 pathway.

Science.gov (United States)

Xu, Sheng; Liu, Xingguang; Bao, Yan; Zhu, Xuhui; Han, Chaofeng; Zhang, Peng; Zhang, Xuemin; Li, Weihua; Cao, Xuetao

2012-04-22

The molecular mechanisms that fine-tune Toll-like receptor (TLR)-triggered innate inflammatory responses remain to be fully elucidated. Major histocompatibility complex (MHC) molecules can mediate reverse signaling and have nonclassical functions. Here we found that constitutively expressed membrane MHC class I molecules attenuated TLR-triggered innate inflammatory responses via reverse signaling, which protected mice from sepsis. The intracellular domain of MHC class I molecules was phosphorylated by the kinase Src after TLR activation, then the tyrosine kinase Fps was recruited via its Src homology 2 domain to phosphorylated MHC class I molecules. This led to enhanced Fps activity and recruitment of the phosphatase SHP-2, which interfered with TLR signaling mediated by the signaling molecule TRAF6. Thus, constitutive MHC class I molecules engage in crosstalk with TLR signaling via the Fps-SHP-2 pathway and control TLR-triggered innate inflammatory responses.

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.

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

GRK2 Constitutively Governs Peripheral Delta Opioid Receptor Activity

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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.

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

Conformational constraining of inactive and active States of a seven transmembrane receptor by metal ion site engineering in the extracellular end of transmembrane segment V

DEFF Research Database (Denmark)

Rosenkilde, Mette M; David, Ralf; Oerlecke, Ilka

2006-01-01

The extracellular part of transmembrane segment V (TM-V) is expected to be involved in the activation process of 7TM receptors, but its role is far from clear. Here, we study the highly constitutively active CXC-chemokine receptor encoded by human herpesvirus 8 (ORF74-HHV8), in which a metal ion ...

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.

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.

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

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

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.

VANGL2 interacts with integrin αv to regulate matrix metalloproteinase activity and cell adhesion to the extracellular matrix.

Science.gov (United States)

Jessen, Tammy N; Jessen, Jason R

2017-12-15

Planar cell polarity (PCP) proteins are implicated in a variety of morphogenetic processes including embryonic cell migration and potentially cancer progression. During zebrafish gastrulation, the transmembrane protein Vang-like 2 (VANGL2) is required for PCP and directed cell migration. These cell behaviors occur in the context of a fibrillar extracellular matrix (ECM). While it is thought that interactions with the ECM regulate cell migration, it is unclear how PCP proteins such as VANGL2 influence these events. Using an in vitro cell culture model system, we previously showed that human VANGL2 negatively regulates membrane type-1 matrix metalloproteinase (MMP14) and activation of secreted matrix metalloproteinase 2 (MMP2). Here, we investigated the functional relationship between VANGL2, integrin αvβ3, and MMP2 activation. We provide evidence that VANGL2 regulates cell surface integrin αvβ3 expression and adhesion to fibronectin, laminin, and vitronectin. Inhibition of MMP14/MMP2 activity suppressed the cell adhesion defect in VANGL2 knockdown cells. Furthermore, our data show that MMP14 and integrin αv are required for increased proteolysis by VANGL2 knockdown cells. Lastly, we have identified integrin αvβ3 as a novel VANGL2 binding partner. Together, these findings begin to dissect the molecular underpinnings of how VANGL2 regulates MMP activity and cell adhesion to the ECM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

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.

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.

PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+ channels with full-length CaV1.2 C-terminus.

Science.gov (United States)

Guo, Xiaoguang; Kashihara, Toshihide; Nakada, Tsutomu; Aoyama, Toshifumi; Yamada, Mitsuhiko

2018-06-01

In atherosclerosis, vascular smooth muscle cells (VSMC) migrate from the media toward the intima of the arteries in response to cytokines, such as platelet-derived growth factor (PDGF). However, molecular mechanism underlying the PDGF-induced migration of VSMCs remains unclear. The migration of rat aorta-derived synthetic VSMCs, A7r5, in response to PDGF was potently inhibited by a Ca V 1.2 channel inhibitor, nifedipine, and a Src family tyrosine kinase (SFK)/Abl inhibitor, bosutinib, in a less-than-additive manner. PDGF significantly increased Ca V 1.2 channel currents without altering Ca V 1.2 protein expression levels in A7r5 cells. This reaction was inhibited by C-terminal Src kinase, a selective inhibitor of SFKs. In contractile VSMCs, the C-terminus of Ca V 1.2 is proteolytically cleaved into proximal and distal C-termini (PCT and DCT, respectively). Clipped DCT is noncovalently reassociated with PCT to autoinhibit the channel activity. Conversely, in synthetic A7r5 cells, full-length Ca V 1.2 (Ca V 1.2FL) is expressed much more abundantly than truncated Ca V 1.2. In a heterologous expression system, c-Src activated Ca V 1.2 channels composed of Ca V 1.2FL but not truncated Ca V 1.2 (Ca V 1.2Δ1763) or Ca V 1.2Δ1763 plus clipped DCT. Further, c-Src enhanced the coupling efficiency between the voltage-sensing domain and activation gate of Ca V 1.2FL channels by phosphorylating Tyr1709 and Tyr1758 in PCT. Compared with Ca V 1.2Δ1763, c-Src could more efficiently bind to and phosphorylate Ca V 1.2FL irrespective of the presence or absence of clipped DCT. Therefore, in atherosclerotic lesions, phenotypic switching of VSMCs may facilitate pro-migratory effects of PDGF on VSMCs by suppressing posttranslational Ca V 1.2 modifications.

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.

An Analysis on the Constitutive Models for Forging of Ti6Al4V Alloy Considering the Softening Behavior

Science.gov (United States)

Souza, Paul M.; Beladi, Hossein; Singh, Rajkumar P.; Hodgson, Peter D.; Rolfe, Bernard

2018-05-01

This paper developed high-temperature deformation constitutive models for a Ti6Al4V alloy using an empirical-based Arrhenius equation and an enhanced version of the authors' physical-based EM + Avrami equations. The initial microstructure was a partially equiaxed α + β grain structure. A wide range of experimental data was obtained from hot compression of the Ti6Al4 V alloy at deformation temperatures ranging from 720 to 970 °C, and at strain rates varying from 0.01 to 10 s-1. The friction- and adiabatic-corrected flow curves were used to identify the parameter values of the constitutive models. Both models provided good overall accuracy of the flow stress. The generalized modified Arrhenius model was better at predicting the flow stress at lower strain rates. However, the model was inaccurate in predicting the peak strain. In contrast, the enhanced physical-based EM + Avrami model revealed very good accuracy at intermediate and high strain rates, but it was also better at predicting the peak strain. Blind sample tests revealed that the EM + Avrami maintained good predictions on new (unseen) data. Thus, the enhanced EM + Avrami model may be preferred over the Arrhenius model to predict the flow behavior of Ti6Al4V alloy during industrial forgings, when the initial microstructure is partially equiaxed.

Study on activities of vanadium (IV/V) doped TiO2(R) nanorods induced by UV and visible light

International Nuclear Information System (INIS)

Li, Li; Liu Chunyan; Liu Yun

2009-01-01

Vanadium (IV/V) doped rutile TiO 2 naonorods had been successfully synthesized through a single step hydrothermal method. The photocatalyst was characterized by transmission electron microscopy (TEM), selected area electron diffraction (SAED), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), UV-vis diffusive reflectance spectroscopy (DRS) and X-ray photoelectron spectroscopy (XPS). The results showed that the doping of V ions had significant influence on the band gap energy and the surface state of TiO 2 . The photo-activities of the new catalysts were investigated under ultraviolet (UV) and visible light. The UV-photocatalytic activity of the as-prepared catalysts was hardly influenced by doping V ions; while under visible light, the samples with 1 wt% and 0.1 wt% V exhibited enhanced activity to the oxidation of methylene blue (MB) and the reduction of Cr (VI), respectively

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.

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.

14 MeV proton activation analysis

International Nuclear Information System (INIS)

Constantinescu, B.; Ivanov, E.; Plostinaru, D.; Popa-Nemoiu, A.; Pascovichi, G.

1985-01-01

A fast nuclear nondestructive method for protein analysis using the 14 MeV proton activation has been developed. The total nitrogen content was measured through the reaction: 14 N (p,n) 14 O, (Tsub(1/2)=71 s). The 14 O activity was detected by means of its characteristic 2.312 MeV gamma-ray line with a NaI(Tl) detector. For a fast determination of a large number of samples a mechanized sistem reacting a rate of one sample per minute has been developed. The laboratory electronics comprises a multichannel analyser, a PDP computer and an electronic module comtroller. Comparison of the results obtained by the method described and the classical Kjeldal technique for samples of various cereal grains (soya bean seads, wheat, barley and corn) showed good correlation. A problem of the analysis of the whole protein region on corn and soya-bean seads, where this region is thicker (0,2 - 2 mm), is mentioned. In this case flour was proposed to be used to obtain a protein homogeneous sample and the irradiaton dose for a sample was about 33,000 Gy, mainly (99%) from protons (27 s x 100 nA x 14 MeV)

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.

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.

Generation of an activating Zn(2+) switch in the dopamine transporter

DEFF Research Database (Denmark)

Loland, Claus Juul; Norregaard, Lene; Litman, Thomas

2002-01-01

Binding of Zn(2+) to the endogenous Zn(2+) binding site in the human dopamine transporter leads to potent inhibition of [(3)H]dopamine uptake. Here we show that mutation of an intracellular tyrosine to alanine (Y335A) converts this inhibitory Zn(2+) switch into an activating Zn(2+) switch, allowing...... Zn(2+)-dependent activation of the transporter. The tyrosine is part of a conserved YXX Phi trafficking motif (X is any residue and Phi is a residue with a bulky hydrophobic group), but Y335A did not show alterations in surface targeting or protein kinase C-mediated internalization. Despite wild...... for several substrates was increased. However, the presence of Zn(2+) in micromolar concentrations increased the V(max) up to 24-fold and partially restored the apparent affinities. The capability of Zn(2+) to restore transport is consistent with a reversible, constitutive shift in the distribution...

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

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.

Recombinant human B7.2 IgV-like domain expressed in bacteria maintains its co-stimulatory activity in vitro.

Science.gov (United States)

Yan, Xiaocai; Ma, Jun; Zheng, Jin; Lai, Baochang; Geng, Yiping; Wang, Yili; Si, Lüsheng

2002-07-01

To investigate which of the two immunoglobulin (Ig)-like domains, the immunoglobulin variable region homologous domain IgV (hB7.2 IgV) and the immunoglobulin constant region homologous domain IgC (hB7.2 IgC) on the human B7.2 molecule contains receptor binding sites, and to evaluate whether the B7.2 protein expressed in bacteria has biological activity in vitro. Three fragments of hB7.2 IgV,hB7.2 IgC and the complete extracellular region of human B7.2 containing both the IgV and IgC domains,hB7.2 Ig (V+C), were amplified by PCR and subcloned into pGEM-Teasy. Three recombinants,pGEX-4T-3-hB7.2 IgV,pGEX-4T-3-hB7.2 IgC and pGEX-4T-3-hB7.2 Ig (V+C), were generated by cloning the fragments into a prokaryote expression plasmid (pGEX-4T-3) and transformed into the host strain E. coli DH5alpha. The relevant target fusion proteins consisting of GST and hB7.2 IgV,hB7.2 IgC and hB7.2 Ig (V+C), were identified by SDS-PAGE and Western blotting. With the presence of the first signal imitated by anti-CD3 antibody, T cell activation was observed by exposing purified T lymphocytes to each soluble form of the three bacterially-produced human B7.2 fusion proteins by [(3)H]-TdR incorporation. Three recombinant fusion proteins of human B7.2, GST-hB7.2 IgV, GST-hB7.2 IgC and GST-hB7.2 Ig (V+C) were produced and detected in inclusion body form from engineered bacteria. With the first signal present,T lymphocytes proliferated when co-stimulated by bacterially-produced either GST-hB7.2 Ig (V+C) or GST-hB7.2 IgV fusion proteins, but not by GST-hB7.2 IgC. Functional human B7.2 fusion protein can be produced in bacteria. The IgV-like domain of human B7.2 is sufficient for B7.2 to interact with its counter-receptors and co-stimulate T lymphocytes.

Structure of the T cell receptor in a Ti alpha V beta 2, alpha V beta 8-positive T cell line

DEFF Research Database (Denmark)

Hou, X; Dietrich, J; Kuhlmann, J

1994-01-01

not known; however, it has been suggested that each TcR contains two Ti dimers. To gain insight into the structure of the TcR we constructed a Ti alpha V beta 2, alpha V beta 8-positive T cell line which expressed the endogenous human TiV beta 8 and the transfected mouse TiV beta 2 both in association......The T cell receptor (TcR) is composed of at least six different polypeptide chains consisting of the clonotypic Ti heterodimer (Ti alpha beta or Ti gamma delta) and the noncovalently associated CD3 chains (CD3 gamma delta epsilon zeta). The exact number of subunits constituting the TcR is still...... with the endogenous Ti alpha and CD3 chains at the cell surface. Preclearing experiments with radioiodinated cell lysate prepared with digitonin lysis buffer demonstrated that depleting the lysate of Ti alpha V beta 8 by immunoprecipitation with anti V beta 8 monoclonal antibody (mAb) did not reduce the amount of Ti...

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

Changing the constitutional landscape for firearms: the US Supreme Court's recent Second Amendment decisions.

Science.gov (United States)

Vernick, Jon S; Rutkow, Lainie; Webster, Daniel W; Teret, Stephen P

2011-11-01

In 2 recent cases-with important implications for public health practitioners, courts, and researchers-the US Supreme Court changed the landscape for judging the constitutionality of firearm laws under the Constitution's Second Amendment. In District of Columbia v Heller (2008), the court determined for the first time that the Second Amendment grants individuals a personal right to possess handguns in their home. In McDonald v City of Chicago (2010), the court concluded that this right affects the powers of state and local governments. The court identified broad categories of gun laws-other than handgun bans-that remain presumptively valid but did not provide a standard to judge their constitutionality. We discuss ways that researchers can assist decision makers.

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

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

AR-v7 protein expression is regulated by protein kinase and phosphatase

Science.gov (United States)

Li, Yinan; Xie, Ning; Gleave, Martin E.; Rennie, Paul S.; Dong, Xuesen

2015-01-01

Failure of androgen-targeted therapy and progression of castration-resistant prostate cancer (CRPC) are often attributed to sustained expression of the androgen receptor (AR) and its major splice variant, AR-v7. Although the new generation of anti-androgens such as enzalutamide effectively inhibits AR activity, accumulating pre-clinical and clinical evidence indicates that AR-v7 remains constitutively active in driving CRPC progression. However, molecular mechanisms which control AR-v7 protein expression remain unclear. We apply multiple prostate cancer cell models to demonstrate that enzalutamide induces differential activation of protein phosphatase-1 (PP-1) and Akt kinase depending on the gene context of cancer cells. The balance between PP-1 and Akt activation governs AR phosphorylation status and activation of the Mdm2 ubiquitin ligase. Mdm2 recognizes phosphorylated serine 213 of AR-v7, and induces AR-v7 ubiquitination and protein degradation. These findings highlight the decisive roles of PP-1 and Akt for AR-v7 protein expression and activities when AR is functionally blocked. PMID:26378044

Optical properties and visible-light-driven photocatalytic activity of Bi{sub 8}V{sub 2}O{sub 17} nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Pu, Yinfu; Liu, Ting; Huang, Yanlin [Soochow University, College of Chemistry, Chemical Engineering and Materials Science (China); Chen, Cuili; Kim, Sun Il; Seo, Hyo Jin, E-mail: hjseo@pknu.ac.kr [Pukyong National University, Department of Physics and Interdisciplinary Program of Biomedical, Mechanical & Electrical Engineering (Korea, Republic of)

2015-05-15

Bi{sub 8}V{sub 2}O{sub 17} (4Bi{sub 2}O{sub 3}·V{sub 2}O{sub 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{sub 8}V{sub 2}O{sub 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{sub 8}V{sub 2}O{sub 17} could be a potential photocatalyst driven by visible light. The effective photocatalytic activity was discussed on the base of the crystal structure characteristic.

Software V and V of PPS for Shin-Hanul Nuclear Power Plant Units 1 and 2

International Nuclear Information System (INIS)

Park, Cheollak; Kang, Dongpa; Choe, Changhui; Sohn, Sedo; Beak, Seungmin

2013-01-01

Software V and V processes determine whether the development products of a given activity conform to the requirements of that activity and whether the software satisfies its intended use and user needs. This paper introduces the software V and V activities and tasks performed during the software development life cycle performed during the software development life cycle of the Plant Protection System (PPS) for Shin-Hanul Nuclear Power Plant Units 1 and 2 (SHN 1 and 2). The PPS generates signals to actuate Reactor Trip (RT) and Engineered Safety Features (ESF) whenever monitored processes exceed predetermined limits, and the PPS software is classified safety critical and an independent V and V is thus required according to regulations, code and standards. The software V and V efforts, sufficiently disciplined and rigorous, are quite essential to demonstrate that the software development process is of a high quality. The software V and V of PPS for SHN 1 and 2 has been accomplished successfully with systematic V and V procedures and methods established until test phase in compliance with related code and standards. In particular, the use of automated tools such as LDRA and DOORS greatly has contributed to an improvement of a software quality, and a reduction of a verification time and human errors

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...

Sprouty regulates cell migration by inhibiting the activation of Rac1 GTPase

International Nuclear Information System (INIS)

Poppleton, Helen M.; Edwin, Francis; Jaggar, Laura; Ray, Ramesh; Johnson, Leonard R.; Patel, Tarun B.

2004-01-01

Sprouty (SPRY) protein negatively modulates fibroblast growth factor and epidermal growth factor actions. We showed that human SPRY2 inhibits cell growth and migration in response to serum and several growth factors. Using rat intestinal epithelial (IEC-6) cells, we investigated the involvement of the Rho family of GTPases, RhoA, Rac1, and cdc42 in SPRY2-mediated inhibition of cell migration and proliferation. The ability of TAT-tagged SPRY2 to inhibit proliferation and migration of IEC-6 cells transfected with constitutively active mutants of RhoA(G14V), Rac1(G12V), and cdc42 (F28L) was determined. Constitutively active RhoA(G14V), Rac1(G12V), or cdc42(F28L) did not protect cells from the anti-proliferative actions of TAT-SPRY2. The ability of TAT-hSPRY2 to inhibit migration was not altered by of RhoA(G14V) and cdc42(F28L). However, Rac1(G12V) obliterated the ability of SPRY2 to inhibit cell autonomous or serum-induced migration. Also, the activation of endogenous Rac1 was attenuated by TAT-SPRY2. Thus, SPRY2 mediates its anti-migratory actions by inhibiting Rac1 activation

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.

Hot workability of γ + α2 titanium aluminide: Development of processing map and constitutive equations

International Nuclear Information System (INIS)

Gupta, R.K.; Narayana Murty, S.V.S.; Pant, Bhanu; Agarwala, Vijaya; Sinha, P.P.

2012-01-01

Highlights: ► Deformation studies of five TiAl alloys carried out through processing map. ► DRX domain and superplastic domain identified in power efficiency map. ► Safe working zone for alloys found at 1223–1423 K at strain rates (10 −2 –10 −3 s −1 ). ► Strain rate sensitivity, activation energy, Zener Hollomon parameter (Z) are obtained. ► Constitutive equations derived and verified. DRX grain size correlated with Z. - Abstract: Gamma titanium alumindes are intermetallics, which have very narrow working range. Hot isothermal working is the most suitable process for hot working of alloy. Accordingly, hot isothermal compression test is carried out on reaction synthesized and homogenized titanium aluminide alloys at different temperatures and strain rates using Gleeble thermomechanical simulator. Three alloys of Ti48Al2Cr2Nb0.1B (atom%) have been used in the study. Stress–strain data obtained from the test has been used to construct processing map, which indicates the safe and unsafe working zone. Strain rate sensitivity and Zener–Hollomon parameter has been calculated. Further, constitutive equations have been generated and verified. It is found that alloy has good workability in the temperature range of 1223–1423 K at strain rates of 0.01–0.001 s −1 . In this range of parameters, the alloys nearly follow the constitutive equations.

Regulation of Constitutive GPR3 Signaling and Surface Localization by GRK2 and β-arrestin-2 Overexpression in HEK293 Cells.

Directory of Open Access Journals (Sweden)

Katie M Lowther

Full Text Available G protein-coupled receptor 3 (GPR3 is a constitutively active receptor that maintains high 3'-5'-cyclic adenosine monophosphate (cAMP levels required for meiotic arrest in oocytes and CNS function. Ligand-activated G protein-coupled receptors (GPCRs signal at the cell surface and are silenced by phosphorylation and β-arrestin recruitment upon endocytosis. Some GPCRs can also signal from endosomes following internalization. Little is known about the localization, signaling, and regulation of constitutively active GPCRs. We demonstrate herein that exogenously-expressed GPR3 localizes to the cell membrane and undergoes internalization in HEK293 cells. Inhibition of endocytosis increased cell surface-localized GPR3 and cAMP levels while overexpression of GPCR-Kinase 2 (GRK2 and β-arrestin-2 decreased cell surface-localized GPR3 and cAMP levels. GRK2 by itself is sufficient to decrease cAMP production but both GRK2 and β-arrestin-2 are required to decrease cell surface GPR3. GRK2 regulates GPR3 independently of its kinase activity since a kinase inactive GRK2-K220R mutant significantly decreased cAMP levels. However, GRK2-K220R and β-arrestin-2 do not diminish cell surface GPR3, suggesting that phosphorylation is required to induce GPR3 internalization. To understand which residues are targeted for desensitization, we mutated potential phosphorylation sites in the third intracellular loop and C-terminus and examined the effect on cAMP and receptor surface localization. Mutation of residues in the third intracellular loop dramatically increased cAMP levels whereas mutation of residues in the C-terminus produced cAMP levels comparable to GPR3 wild type. Interestingly, both mutations significantly reduced cell surface expression of GPR3. These results demonstrate that GPR3 signals at the plasma membrane and can be silenced by GRK2/β-arrestin overexpression. These results also strongly implicate the serine and/or threonine residues in the third

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.

Constitutive non-inducible expression of the Arabidopsis thaliana Nia 2 gene in two nitrate reductase mutants of Nicotiana plumbaginifolia.

Science.gov (United States)

Kaye, C; Crawford, N M; Malmberg, R L

1997-04-01

We have isolated a haploid cell line of N. plumbaginifolia, hNP 588, that is constitutive and not inducible for nitrate reductase. Nitrate reductase mutants were isolated from hNP 588 protoplasts upon UV irradiation. Two of these nitrate reductase-deficient cell lines, nia 3 and nia 25, neither of which contained any detectable nitrate reductase activity, were selected for complementation studies. A cloned Arabidopsis thaliana nitrate reductase gene Nia 2 was introduced into each of the two mutants resulting in 56 independent kanamycin-resistant cell lines. Thirty of the 56 kanamycin-resistant cell lines were able to grow on nitrate as the sole nitrogen source. Eight of these were further analyzed for nitrate reductase enzyme activity and nitrate reductase mRNA production. All eight lines had detectable nitrate reductase activity ranging from 7% to 150% of wild-type hNP 588 callus. The enzyme activity levels were not influenced by the nitrogen source in the medium. The eight lines examined expressed a constitutive, non-inducible 3.2 kb mRNA species that was not present in untransformed controls.

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?

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.

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.

A Note on the Constitution of the Sun

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Magnus H. G.

2011-07-01

Full Text Available Patrice Robitaille (TAV College, Montreal, Canada provides a translation of Heinrich Gustav Magnus’ classic work Notiz ̈uber die Beschaffenheit der Sonne , as it appeared in March 1864 within Poggendorff’s Annalen der Physik und Chemie ,1864, v.131, 510– 512. The article had previously been translated into French: Notice sur la constitution du soleil. Archives des science physique et naturelles (Gen`eve , 1864, v.20, 171–175. This work formed the basis of the present translation. Heinrich Gustav Magnus (May 2, 1802 – April 4, 1870 was a professor at the University of Berlin and had studied in Paris under Joseph Louis Gay-Lussac. He would count amongst his students Wil- helm Beetz, Hermann Helmholtz, Gustav Wiedemann, John Tyndall, Rudolph Weber, and Adolph W ̈ ullner (Heinrich Gustav Magnus, Platinum Metals Review , 1976, v.20(1, 21–24. In his Notiz , Magnus demonstrated that the addition of sodium hydroxide to the gaseous flame resulted in a tremendous increase in luminosity. Magnus’ work would inspire Father Secchi to propose that the Sun was a gaseous globe whose photosphere contained condensed particulate matter (Secchi A. Sulla Struttura della Fotosfera So- lare. Bulletino Meteorologico dell’ Osservatorio del Collegio Romano , 1864, v.3(11, 1–3; English translation in Progr. Phys. , 2011, v.3, 30–32. Magnus’ report on the constitution of the Sun would continue to impact solar physics for two generations.

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.)

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

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.

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

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.

Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F

International Nuclear Information System (INIS)

Ma, L; Clayton, J R; Walgren, R A; Zhao, B; Evans, R J; Smith, M C; Heinz-Taheny, K M; Kreklau, E L; Bloem, L; Pitou, C; Shen, W; Strelow, J M; Halstead, C; Rempala, M E; Parthasarathy, S; Gillig, J R; Heinz, L J; Pei, H; Wang, Y; Stancato, L F; Dowless, M S; Iversen, P W; Burkholder, T P

2013-01-01

Owing to the prevalence of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs), its constitutive activity, and ability to recapitulate the MPN phenotype in mouse models, JAK2V617F kinase is an attractive therapeutic target. We report the discovery and initial characterization of the orally bioavailable imidazopyridazine, LY2784544, a potent, selective and ATP-competitive inhibitor of janus kinase 2 (JAK2) tyrosine kinase. LY2784544 was discovered and characterized using a JAK2-inhibition screening assay in tandem with biochemical and cell-based assays. LY2784544 in vitro selectivity for JAK2 was found to be equal or superior to known JAK2 inhibitors. Further studies showed that LY2784544 effectively inhibited JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC 50 =20 and 55 nM, respectively). In comparison, LY2784544 was much less potent at inhibiting interleukin-3-stimulated wild-type JAK2-mediated signaling and cell proliferation (IC 50 =1183 and 1309 nM, respectively). In vivo, LY2784544 effectively inhibited STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP (green fluorescent protein) ascitic tumor cells (TED 50 =12.7 mg/kg) and significantly reduced (P<0.05) Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model (TED 50 =13.7 mg/kg, twice daily). In contrast, LY2784544 showed no effect on erythroid progenitors, reticulocytes or platelets. These data suggest that LY2784544 has potential for development as a targeted agent against JAK2V617F and may have properties that allow suppression of JAK2V617F-induced MPN pathogenesis while minimizing effects on hematopoietic progenitor cells

Exploring the influence of constitutive models and associated parameters for the orthogonal machining of Ti6Al4V

Science.gov (United States)

Pervaiz, S.; Anwar, S.; Kannan, S.; Almarfadi, A.

2018-04-01

Ti6Al4V is known as difficult-to-cut material due to its inherent properties such as high hot hardness, low thermal conductivity and high chemical reactivity. Though, Ti6Al4V is utilized by industrial sectors such as aeronautics, energy generation, petrochemical and bio-medical etc. For the metal cutting community, competent and cost-effective machining of Ti6Al4V is a challenging task. To optimize cost and machining performance for the machining of Ti6Al4V, finite element based cutting simulation can be a very useful tool. The aim of this paper is to develop a finite element machining model for the simulation of Ti6Al4V machining process. The study incorporates material constitutive models namely Power Law (PL) and Johnson – Cook (JC) material models to mimic the mechanical behaviour of Ti6Al4V. The study investigates cutting temperatures, cutting forces, stresses, and plastic strains with respect to different PL and JC material models with associated parameters. In addition, the numerical study also integrates different cutting tool rake angles in the machining simulations. The simulated results will be beneficial to draw conclusions for improving the overall machining performance of Ti6Al4V.

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.

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.

Association between Albuminuria and Different Body Constitution in Type 2 Diabetes Patients: Taichung Diabetic Body Constitution Study

Directory of Open Access Journals (Sweden)

Cheng-Hung Lee

2015-01-01

Full Text Available Objective. Albuminuria in type 2 diabetes mellitus (T2DM patients increases the risk of diabetic nephropathy, the leading cause of end-stage renal disease worldwide. Because albuminuria is modifiable, identifying relevant risk factors could facilitate prevention and/or management. This cross-sectional study investigated whether body constitution (BC independently predicts albuminuria. Method. Patients with T2DM (n=846 received urinalysis, a blood test, and diabetic retinopathy examination. Albuminuria was defined by an elevated urinary albumin/creatinine ratio (≥30 μg/mg. BC type (Yang deficiency, Yin deficiency, and Phlegm stasis was assessed using a body constitution questionnaire (BCQ. Traditional risk factors for albuminuria were also recorded. Odds ratios (ORs of albuminuria for BC were estimated using multivariate logistic regression. Results. Albuminuria was more prevalent in patients with Yang deficiency or Phlegm stasis (both P<0.01. After adjustment, patients with both Yang deficiency and Phlegm stasis exhibited a significantly higher risk of albuminuria (OR = 3.037; 95% confidence interval = 1.572–5.867, and P<0.001. Conclusion. BC is strongly associated with albuminuria in T2DM patients. Using a BCQ to assess BC is noninvasive, convenient, and inexpensive and can provide information for health care professionals to identify T2DM patients who are at a high risk of albuminuria.

Code Verification Capabilities and Assessments in Support of ASC V&V Level 2 Milestone #6035

Energy Technology Data Exchange (ETDEWEB)

Doebling, Scott William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Budzien, Joanne Louise [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ferguson, Jim Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Harwell, Megan Louise [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hickmann, Kyle Scott [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Israel, Daniel M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Magrogan, William Richard III [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Singleton, Jr., Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Srinivasan, Gowri [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Walter, Jr, John William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Woods, Charles Nathan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-09-26

This document provides a summary of the code verification activities supporting the FY17 Level 2 V&V milestone entitled “Deliver a Capability for V&V Assessments of Code Implementations of Physics Models and Numerical Algorithms in Support of Future Predictive Capability Framework Pegposts.” The physics validation activities supporting this milestone are documented separately. The objectives of this portion of the milestone are: 1) Develop software tools to support code verification analysis; 2) Document standard definitions of code verification test problems; and 3) Perform code verification assessments (focusing on error behavior of algorithms). This report and a set of additional standalone documents serve as the compilation of results demonstrating accomplishment of these objectives.

Connective tissue activation. XXXII. Structural and biologic characteristics of mesenchymal cell-derived connective tissue activating peptide-V.

Science.gov (United States)

Cabral, A R; Cole, L A; Walz, D A; Castor, C W

1987-12-01

Connective tissue activating peptide-V (CTAP-V) is a single-chain, mesenchymal cell-derived anionic protein with large and small molecular forms (Mr of 28,000 and 16,000, respectively), as defined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteins have similar specific activities with respect to stimulation of hyaluronic acid and DNA formation in human synovial fibroblast cultures. S-carboxymethylation or removal of sialic acid residues did not modify CTAP-V biologic activity. Rabbit antibodies raised separately against each of the purified CTAP-V proteins reacted, on immunodiffusion and on Western blot, with each antigen and neutralized mitogenic activity. The amino-terminal amino acid sequence of the CTAP-V proteins, determined by 2 laboratories, confirmed their structural similarities. The amino-terminal sequence through 37 residues was demonstrated for the smaller protein. The first 10 residues of CTAP-V (28 kd) were identical to the N-terminal decapeptide of CTAP-V (16 kd). The C-terminal sequence, determined by carboxypeptidase Y digestion, was the same for both CTAP-V molecular species. The 2 CTAP-V peptides had similar amino acid compositions, whether residues were expressed as a percent of the total or were normalized to mannose. Reduction of native CTAP-V protein released sulfhydryl groups in a protein:disulfide ratio of 1:2; this suggests that CTAP-V contains 2 intramolecular disulfide bonds. Clearly, CTAP-V is a glycoprotein. The carbohydrate content of CTAP-V (16 kd) and CTAP-V (28 kd) is 27% and 25%, respectively. CTAP-V may have significance in relation to autocrine mechanisms for growth regulation of connective tissue cells and other cell types.

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...

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

What Are the Ultimate Meaning and Significance of "Brown v. Board of Education?" A Note on Justice, Constitutionalism, and the Human Person

Science.gov (United States)

Cook, Samuel DuBois

2005-01-01

Much of the country has participated in the 50th anniversary celebration of "Brown v. Board of Education," a decision handed down by the Supreme Court on May 17, 1954. This historic, landmark, controversial, and revolutionary case nullified and reversed so much of the content, character, and spirit of American constitutional history,…

Synthesis and Insecticidal Activities of New Ester-Derivatives of Celangulin-V

Directory of Open Access Journals (Sweden)

Wenjun Wu

2011-12-01

Full Text Available In order to develop new biorational pesticides, ten new 6-substituted ester derivatives of Celangulin-V were designed and synthesized. The structures of the new derivatives were confirmed by IR, 1H-NMR, 13C-NMR and ESI-MS spectral analysis. Insecticidal activities of these compounds were tested against the third-instar larvae of Mythimna separata. Two derivatives (1.1, 1.2 showed higher insecticidal activities than Celangulin-V, with mortality of 75.0% and 83.3%, respectively. While four compounds (1.3, 1.4, 1.7, 1.8 denoted lower insecticidal activities, the others (1.5, 1.6, 1.9, 1.10 revealed no activities at a concentration of 10 mg.mL−1. The results suggest that C-6 substitutions of Celangulin-V are very important in determining the insecticidal activities of its ester-derivatives. That the acetyl (1.1 and propionyl (1.2 derivatives possessed much higher insecticidal activities than Celangulin-V itself supported the view that Celangulin-V has the potential to be a lead structure of semi-synthetic green insecticides.

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.

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...

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.

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.

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

CaV 3.1 and CaV 3.3 account for T-type Ca2+ current in GH3 cells

Directory of Open Access Journals (Sweden)

M.A. Mudado

2004-06-01

Full Text Available T-type Ca2+ channels are important for cell signaling by a variety of cells. We report here the electrophysiological and molecular characteristics of the whole-cell Ca2+ current in GH3 clonal pituitary cells. The current inactivation at 0 mV was described by a single exponential function with a time constant of 18.32 ± 1.87 ms (N = 16. The I-V relationship measured with Ca2+ as a charge carrier was shifted to the left when we applied a conditioning pre-pulse of up to -120 mV, indicating that a low voltage-activated current may be present in GH3 cells. Transient currents were first activated at -50 mV and peaked around -20 mV. The half-maximal voltage activation and the slope factors for the two conditions are -35.02 ± 2.4 and 6.7 ± 0.3 mV (pre-pulse of -120 mV, N = 15, and -27.0 ± 0.97 and 7.5 ± 0.7 mV (pre-pulse of -40 mV, N = 9. The 8-mV shift in the activation mid-point was statistically significant (P < 0.05. The tail currents decayed bi-exponentially suggesting two different T-type Ca2+ channel populations. RT-PCR revealed the presence of a1G (CaV3.1 and a1I (CaV3.3 T-type Ca2+ channel mRNA transcripts.

New Constitutionalism for Biosiversity vs. Neoconstitutionalism of Risk

Directory of Open Access Journals (Sweden)

Michele Carducci

2016-08-01

Full Text Available http://dx.doi.org/10.5007/2177-7055.2016v37n73p255 Based on an “eco-systemic” democracy that seeks to preserve biodiversity through the recognition of the co-evolutionary link between nature and culture, the Andean Constitutionalism emerges as the expression of a counter-hegemonic constitutionalism committed to the construction of a new institutional framework through the inclusion of new participatory and intercultural mechanisms. Departing from western constitutional paradigms, this groundbreaking constitutionalism revisits the “Gaia hypothesis” and legitimizes a real “social contract” among the people and nature, and instead of considering it as an “object” of ownership, exploitation, or conservation, it regards nature as a legal “subject” and primary source of society itself and the Constitution as its “legal grantor and protector”.

Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome.

Science.gov (United States)

Murray, Jeffrey C; Donahue, David J; Malik, Saleem I; Dzurik, Yvette B; Braly, Emily Z; Dougherty, Margaret J; Eaton, Katherine W; Biegel, Jaclyn A

2011-05-01

DiGeorge syndrome, or velocardiofacial syndrome (DGS/VCFS), is a rare and usually sporadic congenital genetic disorder resulting from a constitutional microdeletion at chromosome 22q11.2. While rare cases of malignancy have been described, likely due to underlying immunodeficiency, central nervous system tumors have not yet been reported. We describe an adolescent boy with DGS/VCFS who developed a temporal lobe pleomorphic xanthoastrocytoma. High-resolution single nucleotide polymorphism array studies of the tumor confirmed a constitutional 22q11.21 deletion, and revealed acquired gains, losses and copy number neutral loss of heterozygosity of several chromosomal regions, including a homozygous deletion of the CDKN2A/B locus. The tumor also demonstrated a common V600E mutation in the BRAF oncogene. This is the first reported case of a patient with DiGeorge syndrome developing a CNS tumor of any histology and expands our knowledge about low-grade CNS tumor molecular genetics.

Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

Energy Technology Data Exchange (ETDEWEB)

Vuong, Tram Thu [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Bertelsen, Vibeke; Rødland, Marianne Skeie [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Stang, Espen [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene, E-mail: i.h.madshus@medisin.uio.no [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway)

2013-02-01

The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub{sub 4}) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub{sub 4} chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub{sub 4} was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub{sub 4} was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub{sub 4} was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ► Receptor fragmentation is not required for endocytosis of ErbB2. ► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ► ErbB2-Ub4 is internalized clathrin-dependently.

Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

International Nuclear Information System (INIS)

Vuong, Tram Thu; Berger, Christian; Bertelsen, Vibeke; Rødland, Marianne Skeie; Stang, Espen; Madshus, Inger Helene

2013-01-01

The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub 4 ) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub 4 chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub 4 was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub 4 was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub 4 was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ► Receptor fragmentation is not required for endocytosis of ErbB2. ► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ► ErbB2-Ub4 is internalized clathrin-dependently.

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

Expression and characterization of recombinant human factor V and a mutant lacking a major portion of the connecting region

International Nuclear Information System (INIS)

Kane, W.H.; Devore-Carter, D.; Ortel, T.L.

1990-01-01

Human coagulation factor V is a protein cofactor that is an essential component of the prothrombinase complex. A full-length factor V cDNA has been subcloned into the mammalian expression vector pDX and used to transfect COS cells. Approximately 95 ± 4% of the recombinant human factor V (rHFV) synthesized in COS cells is secreted into the culture medium. Factor V activity determined by fibrometer assay increased approximately 5-fold from 0.027 ± 0.012 to 0.124 ± 0.044 unit/mL following activation by the factor V activating enzyme from Russell's viper venom (RVV-V). A chromogenic assay specific for factor Va indicated that recombinant factor V had 3.8 ± 1.3% of the activity of the activated protein. The estimated specific activity of the recombinant factor Va was approximately 1,800 ± 500 units/mg, which is similar to the specific activity of purified plasma factor Va of 1,700-2,000 units/mg. Immunoprecipitation of [ 35 S]methionine-labeled rHFV revealed a single high molecular mass component. Treatment of rHFV with thrombin or RVV-V resulted in the formation of proteolytic products that were similar to those seen with plasma factor V. The authors have also expressed a mutant, rHFV-des-B 811-1441 , that lacks a large portion of the highly glycosylated connecting region that is present in factor V. This mutant constitutively expressed 38 ± 7% of the activity of the RVV-V-activated protein. These results suggest that one of the functions of the large connecting region in factor V is to inhibit constitutive procoagulant activity

Mechanical properties and microstructure changes of low-activation 3Cr-2W-V-Ti ferritic steels developed for nuclear applications

International Nuclear Information System (INIS)

Asakura, Kentaro; Kohyama, Akira; Yamada, Takemi.

1990-01-01

The effects of alloying elements such as Cr, W, V and Mn on tensile strength at elevated temperatures, creep-rupture properties and toughness of low activation (2.25-3)Cr-(2-2.5)W-V-Ti steels were investigated together with their microstructure change during high temperature exposure. These steels were normalized to produce bainitic structures in the same manner as that for a conventional 2.25Cr-1Mo steel. They presented superior tensile strength at elevated temperatures and creep-rupture strength in comparison with a conventional 2.25Cr-1Mo steel. The creep-rupture strength of the steels at 500degC for 100 000 h demonstrated about twice that of the conventional 2.25Cr-1Mo steel. The 3Cr-2.5W-0.2V-0.01Ti steel is recommended as a potential low activation ferritic steel for nuclear applications with well optimized mechanical properties, such as tensile strength at elevated temperatures, creep-rupture strength and toughness. The effects of alloying elements were discussed with correlating microstructural and mechanical aspects. (author)

Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal.

Science.gov (United States)

Zhu, Mei Hong; Sung, In Kyung; Zheng, Haifeng; Sung, Tae Sik; Britton, Fiona C; O'Driscoll, Kate; Koh, Sang Don; Sanders, Kenton M

2011-09-15

Interstitial cells of Cajal (ICC) provide pacemaker activity and functional bridges between enteric motor nerve terminals and gastrointestinal smooth muscle cells. The ionic conductance(s) in ICC that are activated by excitatory neural inputs are unknown. Transgenic mice (Kit(copGFP/+)) with constitutive expression of a bright green fluorescent protein were used to investigate cellular responses of ICC to cholinergic stimulation. ICC displayed spontaneous transient inward currents (STICs) under voltage clamp that corresponded to spontaneous transient depolarizations (STDs) under current clamp. STICs reversed at 0 mV when E(Cl) = 0 mV and at -40 mV when E(Cl) was -40 mV, suggesting the STICs were due to a chloride conductance. Carbachol (CCh, 100 nm and 1 μm) induced a sustained inward current (depolarization in current clamp) and increased the amplitude and frequency of STICs and STDs. CCh responses were blocked by atropine (10 μm) or 4-DAMP (100 nm), an M(3) receptor antagonist. STDs were blocked by niflumic acid and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (both 100 μm), and CCh had no effect in the presence of these drugs. The responses of intact circular muscles to CCh and stimulation of intrinsic excitatory nerves by electrical field stimulation (EFS) were also compared. CCh (1 μm) caused atropine-sensitive depolarization and increased the maximum depolarization of slow waves. Similar atropine-sensitive responses were elicited by stimulation of intrinsic excitatory neurons. Niflumic acid (100 μm) blocked responses to EFS but had minor effect on responses to exogenous CCh. These data suggest that different ionic conductances are responsible for electrical responses elicited by bath-applied CCh and cholinergic nerve stimulation.

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.

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.

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

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...

Heterozygous and homozygous JAK2(V617F states modeled by induced pluripotent stem cells from myeloproliferative neoplasm patients.

Directory of Open Access Journals (Sweden)

Joseph Saliba

Full Text Available JAK2(V617F is the predominant mutation in myeloproliferative neoplasms (MPN. Modeling MPN in a human context might be helpful for the screening of molecules targeting JAK2 and its intracellular signaling. We describe here the derivation of induced pluripotent stem (iPS cell lines from 2 polycythemia vera patients carrying a heterozygous and a homozygous mutated JAK2(V617F, respectively. In the patient with homozygous JAK2(V617F, additional ASXL1 mutation and chromosome 20 allowed partial delineation of the clonal architecture and assignation of the cellular origin of the derived iPS cell lines. The marked difference in the response to erythropoietin (EPO between homozygous and heterozygous cell lines correlated with the constitutive activation level of signaling pathways. Strikingly, heterozygous iPS cells showed thrombopoietin (TPO-independent formation of megakaryocytic colonies, but not EPO-independent erythroid colony formation. JAK2, PI3K and HSP90 inhibitors were able to block spontaneous and EPO-induced growth of erythroid colonies from GPA(+CD41(+ cells derived from iPS cells. Altogether, this study brings the proof of concept that iPS can be used for studying MPN pathogenesis, clonal architecture, and drug efficacy.

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

"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.

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.

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

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.

The Constitutional Court and the Imperative of its Reform

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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.

De Vos NO v Minister of Justice and Constitutional Development ...

African Journals Online (AJOL)

Section 35 of the Constitution protects an accused's right to a fair trial. In order for an accused to make a substantial defence, both his physical and his mental presence is required in court. The incapacity of an accused person to understand criminal proceedings in a court will affect his right to a fair trial. Section 77 of the ...

Influence of different chemical agents (H2O2, t-BHP and MMS) on the activity of antioxidant enzymes in human HepG2 and hamster V79 cells; relationship to cytotoxicity and genotoxicity.

Science.gov (United States)

Slamenova, D; Kozics, K; Melusova, M; Horvathova, E

2015-01-01

We investigated activities of antioxidant enzymes (AEs), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in human HepG2 and hamster V79 cells treated with a scale of concentrations of hydrogen peroxide (H2O2), tert-butyl hydroperoxide (t-BHP) and methyl methanesulfonate (MMS). Cytotoxicity and genotoxicity of these substances were evaluated simultaneously. We have found out that H2O2, t-BHP and MMS predictably induce significant concentration-dependent increase of DNA lesions in both cell lines. Cytotoxicity detected in V79 cells with help of PE test was in a good conformity with the level of DNA damage. MTT test has proved unsuitable, except for MMS-treated V79 cells. Compared with human cells HepG2, hamster cells V79 manifested approximately similar levels of SOD and CAT but ten times higher activity of GPx. Across all concentrations tested the most significant increase of activity of the enzyme CAT was found in H2O2- and t-BHP-treated HepG2 cells, of the enzyme SOD in t-BHP- and MMS-treated V79 cells, and of the enzyme GPx in H2O2-treated V79 cells. We suggest that stimulation of enzyme activity by the relevant chemical compounds may result from transcriptional or post-transcriptional regulation of the expression of the genes CAT, SOD and GPx. Several authors suggest that moderate levels of toxic reactants can induce increase of AEs activities, while very high levels of reactants can induce their decrease, as a consequence of damage of the molecular machinery required to induce AEs. Based on a great amount of experiments, which were done and described within this paper, we can say that the above mentioned principle does not apply in general. Only the reactions of t-BHP affected HepG2 cells were consistent with this idea.

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

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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…

Constitutional principles of the state policy in the area of guaranteeing the ownership

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Ю. С. Гаєвська

2015-05-01

that has the same name. In our opinion, the main principles of the economic system of Ukraine that determine the grounds of the state policy in guaranteeing the ownership are the following: legality; equality; priority of human rights; providing the guarantees and protection of these rights by the state; protection of the national economic interests; state’s non-interference in production and economic activity; realization of legal state regulation of economic relations; policy-making. These principles have their normative “embodiment” within the text of certain provisions of the Constitution, which can be related to the principles of the state policy in the area of the ownership: 1 state regulation of the economy; 2 responsibility of the state to the individual and society; 3 state protection of the economic rights; 4 social orientation of the economy. Conclusions: Thus, the necessity to improve the constitutional regulation of the economic system of Ukraine, development of the effective procedures to prevent and protect against violations of economic rights of citizens, improvement of the mechanism of realizing the economic rights, determine the need to characterize the state policy in the area of the ownership in Ukraine.

Resistance irrelevant CYP417A2v2 was found degrading insecticide in Laodelphax striatellus.

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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.

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

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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

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

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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

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...

Possible involvement of MSX-2 homeoprotein in v-ras-induced transformation.

Science.gov (United States)

Takahashi, C; Akiyama, N; Kitayama, H; Takai, S; Noda, M

1997-04-01

A truncated MSX-2 homeoprotein was found to induce flat reversion when expressed in v-Ki-ras-transformed NIH3T3 cells. Although the expression of endogenous MSX-2 gene is low in most of the normal adult tissues examined, it is frequently activated in carcinoma-derived cell lines. Likewise, the gene is inactive in untransformed cells but is transcriptionally activated after transformation by v-Ki-ras oncogene, suggesting that the intact MSX-2 may play a positive, rather than suppressive, role in cell transformation. To test this possibility, we isolated a full-length human MSX-2 cDNA and tested its activities in two cell systems: fibroblast and myoblast. In NIH3T3 fibroblasts, although the gene by itself failed to confer a transformed phenotype, antisense MSX-2 cDNA as well as truncated MSX-2 cDNA interfered with the transforming activities of both v-Ki-ras and v-raf oncogene. In C2C12 myoblasts, MSX-2 was found to suppress MyoD gene expression, as do activated ras oncogenes, under certain culture conditions, and truncated MSX-2 cDNA was found to inhibit the activities of both MSX-2 and ras in this system as well. Our findings not only suggest that the truncated version MSX-2 may act as a dominant suppressor of intact MSX-2 but also raise the possibility that MSX-2 gene may be an important downstream target for the Ras signaling pathways.

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

The Possibility of Vice-Presidents’ Authority Arrangement in the 1945 Constitution through Constitutional Amendment

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Fajar L. Suroso

2016-04-01

Full Text Available The debate over the vice-presidents’ authority reappeared in the administration of President Jokowi after the “authority expansion of the Chief of Presidency Staff” and the case of “Rizal Ramli vs Jusuf Kalla”. This article is intended to provide arguments for the idea of some parties to organize more explicit and detailed the authority of vice-president in the 1945 Constitution. The idea arises from the absence of further arrangement on the authority of vice-president in the 1945 Constitution. This article is systematized into 3 (three sub-theme; 1 the arrangement of the vice-presidents’ authority in the constitution for several countries; 2 The authority of the vice-president according to the 1945 Constitution, and 3 New resultant and the possibility of 1945 Constitution amendment. The result revealed a number of interesting things; 1 the constitutions of other countries do not specify the authority of the vice-president and put the vice-president as a “spare tire” when the president is absent; 2 no new resultant about the position and authority of the vice-president so that theoretically is not reason enough to regulate in detail the authority of the vice-president through the 1945 Constitution amendment; 3 arrangement in detail in the authority of vice-president in the 1945 Constitution holds the potential to confuse the presidential system design as the 1945 Constitution. Therefore, the possibility of vice-presidents’ authority arrangement in the 1945 Constitution through amendment is very small, both in terms of momentum and the substance of issues.

A mutação JAK2 V617F e as síndromes mieloproliferativas JAK2 V617F mutation and the myeloproliferative disorders

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Bárbara C. R. Monte-Mór

2008-01-01

Full Text Available Síndromes mieloproliferativas (SMPs são doenças hematopoéticas de origem clonal que apresentam amplificação de uma ou mais linhagens mielóides. Policitemia vera (PV, trombocitemia essencial (TE, mielofibrose idiopática (MF e leucemia mielóide crônica (LMC são consideradas SMPs clássicas e apresentam características clínicas e biológicas comuns. Ao contrário de LMC, cuja etiologia está relacionada à proteína constitutivamente ativa Bcr-Abl, o mecanismo molecular de PV, TE e MF permaneceu por muito tempo desconhecido. Esta revisão se foca na recente descoberta da mutação JAK2 V617F em pacientes com PV, TE e MF, sua relação com o fenótipo mieloproliferativo e implicações na abordagem clínica de pacientes.Myeloproliferative disorders are clonal hematopoietic diseases that are characterized by the amplification of one or more myeloid lineages. Polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis and chronic myeloid leukemia are considered classic myeloproliferative disorders and share common clinical and biological features. While the genetic basis of chronic myeloid leukemia is shown to be the constitutive active protein BCR-ABL, the main molecular lesions in polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis remain unknown. This review focuses on the recent discovery of the JAK2 V617F mutation, its relationship to the myeloproliferative phenotype and implications in the clinical approach of patients.

Muscarinic activation of Ca2+-activated Cl− current in interstitial cells of Cajal

Science.gov (United States)

Zhu, Mei Hong; Sung, In Kyung; Zheng, Haifeng; Sung, Tae Sik; Britton, Fiona C; O'Driscoll, Kate; Koh, Sang Don; Sanders, Kenton M

2011-01-01

Abstract Interstitial cells of Cajal (ICC) provide pacemaker activity and functional bridges between enteric motor nerve terminals and gastrointestinal smooth muscle cells. The ionic conductance(s) in ICC that are activated by excitatory neural inputs are unknown. Transgenic mice (KitcopGFP/+) with constitutive expression of a bright green fluorescent protein were used to investigate cellular responses of ICC to cholinergic stimulation. ICC displayed spontaneous transient inward currents (STICs) under voltage clamp that corresponded to spontaneous transient depolarizations (STDs) under current clamp. STICs reversed at 0 mV when ECl = 0 mV and at –40 mV when ECl was –40 mV, suggesting the STICs were due to a chloride conductance. Carbachol (CCh, 100 nm and 1 μm) induced a sustained inward current (depolarization in current clamp) and increased the amplitude and frequency of STICs and STDs. CCh responses were blocked by atropine (10 μm) or 4-DAMP (100 nm), an M3 receptor antagonist. STDs were blocked by niflumic acid and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (both 100 μm), and CCh had no effect in the presence of these drugs. The responses of intact circular muscles to CCh and stimulation of intrinsic excitatory nerves by electrical field stimulation (EFS) were also compared. CCh (1 μm) caused atropine-sensitive depolarization and increased the maximum depolarization of slow waves. Similar atropine-sensitive responses were elicited by stimulation of intrinsic excitatory neurons. Niflumic acid (100 μm) blocked responses to EFS but had minor effect on responses to exogenous CCh. These data suggest that different ionic conductances are responsible for electrical responses elicited by bath-applied CCh and cholinergic nerve stimulation. PMID:21768263

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

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

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.

Taking a Second Bite at the Appeal Cherry: Molaudzi v S

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Donrich W Jordaan

2016-09-01

Full Text Available The principle of res judicata is well-established in our law: essentially it means that parties to a dispute have only one metaphorical "bite at the cherry". The "bite" can entail appealing through the hierarchy of courts, but once the parties have exhausted their appeals, they cannot re-litigate the same dispute. However, in the recent case of Molaudzi v S 2015 2 SACR 341 (CC the appellant attempted to appeal to the Constitutional Court twice: the first time the application for leave to appeal was dismissed; the second time the application was granted and the appeal upheld. The appellant got a second "bite at the cherry". In Molaudzi v S the Constitutional Court developed the common law by creating an interest-of-justice exception to the principle of res judicata and – for the first time in the Constitutional Court's history – overturned one of its own judgements. In this case note I present the background of the case of Molaudzi v S, analyse the judgement, and differentiate it from another Constitutional Court case that dealt with res judicata, namely Mpofu v Minister for Justice and Constitutional Development 2013 2 SACR 407 (CC.

Event activity dependence of Y(nS) production in $\\sqrt{s_{NN}}$=5.02 TeV pPb and $\\sqrt{s}$=2.76 TeV pp collisions

CERN Document Server

Chatrchyan, Serguei; Sirunyan, Albert M; Tumasyan, Armen; Adam, Wolfgang; Bergauer, Thomas; Dragicevic, Marko; Erö, Janos; Fabjan, Christian; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hartl, Christian; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; Kiesenhofer, Wolfgang; Knünz, Valentin; Krammer, Manfred; Krätschmer, Ilse; Liko, Dietrich; Mikulec, Ivan; Rabady, Dinyar; Rahbaran, Babak; Rohringer, Herbert; Schöfbeck, Robert; Strauss, Josef; Taurok, Anton; Treberer-Treberspurg, Wolfgang; Waltenberger, Wolfgang; Wulz, Claudia-Elisabeth; Mossolov, Vladimir; Shumeiko, Nikolai; Suarez Gonzalez, Juan; Alderweireldt, Sara; Bansal, Monika; Bansal, Sunil; Cornelis, Tom; De Wolf, Eddi A; Janssen, Xavier; Knutsson, Albert; Luyckx, Sten; Mucibello, Luca; Ochesanu, Silvia; Roland, Benoit; Rougny, Romain; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Blekman, Freya; Blyweert, Stijn; D'Hondt, Jorgen; Heracleous, Natalie; Kalogeropoulos, Alexis; Keaveney, James; Kim, Tae Jeong; Lowette, Steven; Maes, Michael; Olbrechts, Annik; Strom, Derek; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Onsem, Gerrit Patrick; Villella, Ilaria; Caillol, Cécile; Clerbaux, Barbara; De Lentdecker, Gilles; Favart, Laurent; Gay, Arnaud; Hreus, Tomas; Léonard, Alexandre; Marage, Pierre Edouard; Mohammadi, Abdollah; Perniè, Luca; Reis, Thomas; Seva, Tomislav; Thomas, Laurent; Vander Velde, Catherine; Vanlaer, Pascal; Wang, Jian; Adler, Volker; Beernaert, Kelly; Benucci, Leonardo; Cimmino, Anna; Costantini, Silvia; Dildick, Sven; Garcia, Guillaume; Klein, Benjamin; Lellouch, Jérémie; Mccartin, Joseph; Ocampo Rios, Alberto Andres; Ryckbosch, Dirk; Sigamani, Michael; Strobbe, Nadja; Thyssen, Filip; Tytgat, Michael; Walsh, Sinead; Yazgan, Efe; Zaganidis, Nicolas; Basegmez, Suzan; Beluffi, Camille; Bruno, Giacomo; Castello, Roberto; Caudron, Adrien; Ceard, Ludivine; Da Silveira, Gustavo Gil; Delaere, Christophe; Du Pree, Tristan; Favart, Denis; Forthomme, Laurent; Giammanco, Andrea; Hollar, Jonathan; Jez, Pavel; Komm, Matthias; Lemaitre, Vincent; Liao, Junhui; Militaru, Otilia; Nuttens, Claude; Pagano, Davide; Pin, Arnaud; Piotrzkowski, Krzysztof; Popov, Andrey; Quertenmont, Loic; Selvaggi, Michele; Vidal Marono, Miguel; Vizan Garcia, Jesus Manuel; Beliy, Nikita; Caebergs, Thierry; Daubie, Evelyne; Hammad, Gregory Habib; Alves, Gilvan; Correa Martins Junior, Marcos; Martins, Thiago; Pol, Maria Elena; Henrique Gomes E Souza, Moacyr; Aldá Júnior, Walter Luiz; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; De Jesus Damiao, Dilson; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Malbouisson, Helena; Malek, Magdalena; Matos Figueiredo, Diego; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santaolalla, Javier; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Vilela Pereira, Antonio; Bernardes, Cesar Augusto; De Almeida Dias, Flavia; Tomei, Thiago; De Moraes Gregores, Eduardo; Lagana, Caio; Mercadante, Pedro G; Novaes, Sergio F; Padula, Sandra; Genchev, Vladimir; Iaydjiev, Plamen; Marinov, Andrey; Piperov, Stefan; Rodozov, Mircho; Sultanov, Georgi; Vutova, Mariana; Dimitrov, Anton; Glushkov, Ivan; Hadjiiska, Roumyana; Kozhuharov, Venelin; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Du, Ran; Jiang, Chun-Hua; Liang, Dong; Liang, Song; Meng, Xiangwei; Plestina, Roko; Tao, Junquan; Wang, Xianyou; Wang, Zheng; Asawatangtrakuldee, Chayanit; Ban, Yong; Guo, Yifei; Li, Wenbo; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Teng, Haiyun; Wang, Dayong; Zhang, Linlin; Zou, Wei; Avila, Carlos; Carrillo Montoya, Camilo Andres; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; Gomez, Juan Pablo; Gomez Moreno, Bernardo; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Polic, Dunja; Puljak, Ivica; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Kadija, Kreso; Luetic, Jelena; Mekterovic, Darko; Morovic, Srecko; Tikvica, Lucija; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Finger, Miroslav; Finger Jr, Michael; Abdelalim, Ahmed Ali; Assran, Yasser; Elgammal, Sherif; Ellithi Kamel, Ali; Mahmoud, Mohammed; Radi, Amr; Kadastik, Mario; Müntel, Mait; Murumaa, Marion; Raidal, Martti; Rebane, Liis; Tiko, Andres; Eerola, Paula; Fedi, Giacomo; Voutilainen, Mikko; Härkönen, Jaakko; Karimäki, Veikko; Kinnunen, Ritva; Kortelainen, Matti J; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Mäenpää, Teppo; Peltola, Timo; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Wendland, Lauri; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Ferri, Federico; Ganjour, Serguei; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Locci, Elizabeth; Malcles, Julie; Nayak, Aruna; Rander, John; Rosowsky, André; Titov, Maksym; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Charlot, Claude; Daci, Nadir; Dahms, Torsten; Dalchenko, Mykhailo; Dobrzynski, Ludwik; Filipovic, Nicolas; Florent, Alice; Granier de Cassagnac, Raphael; Haguenauer, Maurice; Miné, Philippe; Mironov, Camelia; Naranjo, Ivo Nicolas; Nguyen, Matthew; Ochando, Christophe; Paganini, Pascal; Sabes, David; Salerno, Roberto; Sirois, Yves; Veelken, Christian; Yilmaz, Yetkin; Zabi, Alexandre; Agram, Jean-Laurent; Andrea, Jeremy; Bloch, Daniel; Brom, Jean-Marie; Chabert, Eric Christian; Collard, Caroline; Conte, Eric; Drouhin, Frédéric; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Goetzmann, Christophe; Juillot, Pierre; Le Bihan, Anne-Catherine; Van Hove, Pierre; Gadrat, Sébastien; Beauceron, Stephanie; Beaupere, Nicolas; Boudoul, Gaelle; Brochet, Sébastien; Chasserat, Julien; Chierici, Roberto; Contardo, Didier; Depasse, Pierre; El Mamouni, Houmani; Fan, Jiawei; Fay, Jean; Gascon, Susan; Gouzevitch, Maxime; Ille, Bernard; Kurca, Tibor; Lethuillier, Morgan; Mirabito, Laurent; Perries, Stephane; Ruiz Alvarez, José David; Sgandurra, Louis; Sordini, Viola; Vander Donckt, Muriel; Verdier, Patrice; Viret, Sébastien; Xiao, Hong; Tsamalaidze, Zviad; Autermann, Christian; Beranek, Sarah; Bontenackels, Michael; Calpas, Betty; Edelhoff, Matthias; Feld, Lutz; Hindrichs, Otto; Klein, Katja; Ostapchuk, Andrey; Perieanu, Adrian; Raupach, Frank; Sammet, Jan; Schael, Stefan; Sprenger, Daniel; Weber, Hendrik; Wittmer, Bruno; Zhukov, Valery; Ata, Metin; Caudron, Julien; Dietz-Laursonn, Erik; Duchardt, Deborah; Erdmann, Martin; Fischer, Robert; Güth, Andreas; Hebbeker, Thomas; Heidemann, Carsten; Hoepfner, Kerstin; Klingebiel, Dennis; Knutzen, Simon; Kreuzer, Peter; Merschmeyer, Markus; Meyer, Arnd; Olschewski, Mark; Padeken, Klaas; Papacz, Paul; Pieta, Holger; Reithler, Hans; Schmitz, Stefan Antonius; Sonnenschein, Lars; Teyssier, Daniel; Thüer, Sebastian; Weber, Martin; Cherepanov, Vladimir; Erdogan, Yusuf; Flügge, Günter; Geenen, Heiko; Geisler, Matthias; Haj Ahmad, Wael; Hoehle, Felix; Kargoll, Bastian; Kress, Thomas; Kuessel, Yvonne; Lingemann, Joschka; Nowack, Andreas; Nugent, Ian Michael; Perchalla, Lars; Pooth, Oliver; Stahl, Achim; Asin, Ivan; Bartosik, Nazar; Behr, Joerg; Behrenhoff, Wolf; Behrens, Ulf; Bell, Alan James; Bergholz, Matthias; Bethani, Agni; Borras, Kerstin; Burgmeier, Armin; Cakir, Altan; Calligaris, Luigi; Campbell, Alan; Choudhury, Somnath; Costanza, Francesco; Diez Pardos, Carmen; Dooling, Samantha; Dorland, Tyler; Eckerlin, Guenter; Eckstein, Doris; Eichhorn, Thomas; Flucke, Gero; Geiser, Achim; Grebenyuk, Anastasia; Gunnellini, Paolo; Habib, Shiraz; Hauk, Johannes; Hellwig, Gregor; Hempel, Maria; Horton, Dean; Jung, Hannes; Kasemann, Matthias; Katsas, Panagiotis; Kleinwort, Claus; Kluge, Hannelies; Krämer, Mira; Krücker, Dirk; Lange, Wolfgang; Leonard, Jessica; Lipka, Katerina; Lohmann, Wolfgang; Lutz, Benjamin; Mankel, Rainer; Marfin, Ihar; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mnich, Joachim; Mussgiller, Andreas; Naumann-Emme, Sebastian; Novgorodova, Olga; Nowak, Friederike; Olzem, Jan; Perrey, Hanno; Petrukhin, Alexey; Pitzl, Daniel; Placakyte, Ringaile; Raspereza, Alexei; Ribeiro Cipriano, Pedro M; Riedl, Caroline; Ron, Elias; Sahin, Mehmet Özgür; Salfeld-Nebgen, Jakob; Schmidt, Ringo; Schoerner-Sadenius, Thomas; Schröder, Matthias; Sen, Niladri; Stein, Matthias; Vargas Trevino, Andrea Del Rocio; Walsh, Roberval; Wissing, Christoph; Aldaya Martin, Maria; Blobel, Volker; Enderle, Holger; Erfle, Joachim; Garutti, Erika; Görner, Martin; Gosselink, Martijn; Haller, Johannes; Goebel, Kristin; Höing, Rebekka Sophie; Kirschenmann, Henning; Klanner, Robert; Kogler, Roman; Lange, Jörn; Marchesini, Ivan; Ott, Jochen; Peiffer, Thomas; Pietsch, Niklas; Rathjens, Denis; Sander, Christian; Schettler, Hannes; Schleper, Peter; Schlieckau, Eike; Schmidt, Alexander; Schum, Torben; Seidel, Markus; Sibille, Jennifer; Sola, Valentina; Stadie, Hartmut; Steinbrück, Georg; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Barth, Christian; Baus, Colin; Berger, Joram; Böser, Christian; Butz, Erik; Chwalek, Thorsten; De Boer, Wim; Descroix, Alexis; Dierlamm, Alexander; Feindt, Michael; Guthoff, Moritz; Hartmann, Frank; Hauth, Thomas; Held, Hauke; Hoffmann, Karl-Heinz; Husemann, Ulrich; Katkov, Igor; Kornmayer, Andreas; Kuznetsova, Ekaterina; Lobelle Pardo, Patricia; Martschei, Daniel; Mozer, Matthias Ulrich; Müller, Thomas; Niegel, Martin; Nürnberg, Andreas; Oberst, Oliver; Quast, Gunter; Rabbertz, Klaus; Ratnikov, Fedor; Röcker, Steffen; Schilling, Frank-Peter; Schott, Gregory; Simonis, Hans-Jürgen; Stober, Fred-Markus Helmut; Ulrich, Ralf; Wagner-Kuhr, Jeannine; Wayand, Stefan; Weiler, Thomas; Wolf, Roger; Zeise, Manuel; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Kesisoglou, Stilianos; Kyriakis, Aristotelis; Loukas, Demetrios; Markou, Athanasios; Markou, Christos; Ntomari, Eleni; Topsis-Giotis, Iasonas; Gouskos, Loukas; Panagiotou, Apostolos; Saoulidou, Niki; Stiliaris, Efstathios; Aslanoglou, Xenofon; Evangelou, Ioannis; Flouris, Giannis; Foudas, Costas; Kokkas, Panagiotis; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Bencze, Gyorgy; Hajdu, Csaba; Hidas, Pàl; Horvath, Dezso; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Molnar, Jozsef; Palinkas, Jozsef; Szillasi, Zoltan; Karancsi, János; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Swain, Sanjay Kumar; Beri, Suman Bala; Bhatnagar, Vipin; Dhingra, Nitish; Gupta, Ruchi; Kaur, Manjit; Mehta, Manuk Zubin; Mittal, Monika; Nishu, Nishu; Sharma, Archana; Singh, Jasbir; Kumar, Ashok; Kumar, Arun; Ahuja, Sudha; Bhardwaj, Ashutosh; Choudhary, Brajesh C; Kumar, Ajay; Malhotra, Shivali; Naimuddin, Md; Ranjan, Kirti; Saxena, Pooja; Sharma, Varun; Shivpuri, Ram Krishen; Banerjee, Sunanda; Bhattacharya, Satyaki; Chatterjee, Kalyanmoy; Dutta, Suchandra; Gomber, Bhawna; Jain, Sandhya; Jain, Shilpi; Khurana, Raman; Modak, Atanu; Mukherjee, Swagata; Roy, Debarati; Sarkar, Subir; Sharan, Manoj; Singh, Anil; Abdulsalam, Abdulla; Dutta, Dipanwita; Kailas, Swaminathan; Kumar, Vineet; Mohanty, Ajit Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Chatterjee, Rajdeep Mohan; Ganguly, Sanmay; Ghosh, Saranya; Guchait, Monoranjan; Gurtu, Atul; Kole, Gouranga; Kumar, Sanjeev; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Mohanty, Gagan Bihari; Parida, Bibhuti; Sudhakar, Katta; Wickramage, Nadeesha; Banerjee, Sudeshna; Dugad, Shashikant; Arfaei, Hessamaddin; Bakhshiansohi, Hamed; Behnamian, Hadi; Etesami, Seyed Mohsen; Fahim, Ali; Jafari, Abideh; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Safarzadeh, Batool; Zeinali, Maryam; Grunewald, Martin; Abbrescia, Marcello; Barbone, Lucia; Calabria, Cesare; Chhibra, Simranjit Singh; Colaleo, Anna; Creanza, Donato; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Maggi, Giorgio; Maggi, Marcello; Marangelli, Bartolomeo; My, Salvatore; Nuzzo, Salvatore; Pacifico, Nicola; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Selvaggi, Giovanna; Silvestris, Lucia; Singh, Gurpreet; Venditti, Rosamaria; Verwilligen, Piet; Zito, Giuseppe; Abbiendi, Giovanni; Benvenuti, Alberto; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Meneghelli, Marco; Montanari, Alessandro; Navarria, Francesco; Odorici, Fabrizio; Perrotta, Andrea; Primavera, Federica; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Travaglini, Riccardo; Albergo, Sebastiano; Cappello, Gigi; Chiorboli, Massimiliano; Costa, Salvatore; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Gallo, Elisabetta; Gonzi, Sandro; Gori, Valentina; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Sguazzoni, Giacomo; Tropiano, Antonio; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Fabbricatore, Pasquale; Ferretti, Roberta; Ferro, Fabrizio; Lo Vetere, Maurizio; Musenich, Riccardo; Robutti, Enrico; Tosi, Silvano; Benaglia, Andrea; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Ghezzi, Alessio; Govoni, Pietro; Lucchini, Marco Toliman; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Martelli, Arabella; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Ragazzi, Stefano; Redaelli, Nicola; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; Fabozzi, Francesco; Iorio, Alberto Orso Maria; Lista, Luca; Meola, Sabino; Merola, Mario; Paolucci, Pierluigi; Azzi, Patrizia; Bacchetta, Nicola; Bellato, Marco; Biasotto, Massimo; Bisello, Dario; Branca, Antonio; Carlin, Roberto; Checchia, Paolo; Dorigo, Tommaso; Fanzago, Federica; Galanti, Mario; Gasparini, Fabrizio; Gasparini, Ugo; Giubilato, Piero; Gozzelino, Andrea; Kanishchev, Konstantin; Lacaprara, Stefano; Lazzizzera, Ignazio; Margoni, Martino; Meneguzzo, Anna Teresa; Pazzini, Jacopo; Pozzobon, Nicola; Ronchese, Paolo; Simonetto, Franco; Torassa, Ezio; Tosi, Mia; Triossi, Andrea; Zotto, Pierluigi; Zucchetta, Alberto; Zumerle, Gianni; Gabusi, Michele; Ratti, Sergio P; Riccardi, Cristina; Vitulo, Paolo; Biasini, Maurizio; Bilei, Gian Mario; Fanò, Livio; Lariccia, Paolo; Mantovani, Giancarlo; Menichelli, Mauro; Nappi, Aniello; Romeo, Francesco; Saha, Anirban; Santocchia, Attilio; Spiezia, Aniello; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Broccolo, Giuseppe; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Fiori, Francesco; Foà, Lorenzo; Giassi, Alessandro; Grippo, Maria Teresa; Kraan, Aafke; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Moon, Chang-Seong; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Serban, Alin Titus; Spagnolo, Paolo; Squillacioti, Paola; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Vernieri, Caterina; Barone, Luciano; Cavallari, Francesca; Del Re, Daniele; Diemoz, Marcella; Grassi, Marco; Jorda, Clara; Longo, Egidio; Margaroli, Fabrizio; Meridiani, Paolo; Micheli, Francesco; Nourbakhsh, Shervin; Organtini, Giovanni; Paramatti, Riccardo; Rahatlou, Shahram; Rovelli, Chiara; Soffi, Livia; Traczyk, Piotr; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Casasso, Stefano; Costa, Marco; Degano, Alessandro; Demaria, Natale; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Musich, Marco; Obertino, Maria Margherita; Ortona, Giacomo; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Potenza, Alberto; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Solano, Ada; Staiano, Amedeo; Tamponi, Umberto; Belforte, Stefano; Candelise, Vieri; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Gobbo, Benigno; La Licata, Chiara; Marone, Matteo; Montanino, Damiana; Penzo, Aldo; Schizzi, Andrea; Umer, Tomo; Zanetti, Anna; Chang, Sunghyun; Kim, Tae Yeon; Nam, Soon-Kwon; Kim, Dong Hee; Kim, Gui Nyun; Kim, Ji Eun; Kong, Dae Jung; Lee, Sangeun; Oh, Young Do; Park, Hyangkyu; Son, Dong-Chul; Kim, Jae Yool; Kim, Zero Jaeho; Song, Sanghyeon; Choi, Suyong; Gyun, Dooyeon; Hong, Byung-Sik; Jo, Mihee; Kim, Hyunchul; Kim, Yongsun; Lee, Kyong Sei; Park, Sung Keun; Roh, Youn; Choi, Minkyoo; Kim, Ji Hyun; Park, Chawon; Park, Inkyu; Park, Sangnam; Ryu, Geonmo; Choi, Young-Il; Choi, Young Kyu; Goh, Junghwan; Kim, Min Suk; Kwon, Eunhyang; Lee, Byounghoon; Lee, Jongseok; Lee, Sungeun; Seo, Hyunkwan; Yu, Intae; Grigelionis, Ignas; Juodagalvis, Andrius; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-de La Cruz, Ivan; Lopez-Fernandez, Ricardo; Martínez-Ortega, Jorge; Sánchez Hernández, Alberto; Villasenor-Cendejas, Luis Manuel; Carrillo Moreno, Salvador; Vazquez Valencia, Fabiola; Salazar Ibarguen, Humberto Antonio; Casimiro Linares, Edgar; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Doesburg, Robert; Reucroft, Steve; Silverwood, Hamish; Ahmad, Muhammad; Asghar, Muhammad Irfan; Butt, Jamila; Hoorani, Hafeez R; Khalid, Shoaib; Khan, Wajid Ali; Khurshid, Taimoor; Qazi, Shamona; Shah, Mehar Ali; Shoaib, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bożena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Wrochna, Grzegorz; Zalewski, Piotr; Brona, Grzegorz; Bunkowski, Karol; Cwiok, Mikolaj; Dominik, Wojciech; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Wolszczak, Weronika; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Nguyen, Federico; Rodrigues Antunes, Joao; Seixas, Joao; Varela, Joao; Vischia, Pietro; Afanasiev, Serguei; Bunin, Pavel; Golutvin, Igor; Gorbunov, Ilya; Kamenev, Alexey; Karjavin, Vladimir; Konoplyanikov, Viktor; Kozlov, Guennady; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Moisenz, Petr; Palichik, Vladimir; Perelygin, Victor; Shmatov, Sergey; Skatchkov, Nikolai; Smirnov, Vitaly; Zarubin, Anatoli; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Vorobyev, Andrey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Safronov, Grigory; Semenov, Sergey; Spiridonov, Alexander; Stolin, Viatcheslav; Vlasov, Evgueni; Zhokin, Alexander; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Mesyats, Gennady; Rusakov, Sergey V; Vinogradov, Alexey; Belyaev, Andrey; Boos, Edouard; Ershov, Alexander; Gribushin, Andrey; Klyukhin, Vyacheslav; Kodolova, Olga; Korotkikh, Vladimir; Lokhtin, Igor; Markina, Anastasia; Obraztsov, Stepan; Petrushanko, Sergey; Savrin, Viktor; Snigirev, Alexander; Vardanyan, Irina; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Tourtchanovitch, Leonid; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Djordjevic, Milos; Ekmedzic, Marko; Milosevic, Jovan; Aguilar-Benitez, Manuel; Alcaraz Maestre, Juan; Battilana, Carlo; Calvo, Enrique; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Domínguez Vázquez, Daniel; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Ferrando, Antonio; Flix, Jose; 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Lin, Willis; Lu, Yun-Ju; Volpe, Roberta; Yu, Shin-Shan; Bartalini, Paolo; Chang, Paoti; Chang, You-Hao; Chang, Yu-Wei; Chao, Yuan; Chen, Kai-Feng; Dietz, Charles; Grundler, Ulysses; Hou, George Wei-Shu; Hsiung, Yee; Kao, Kai-Yi; Lei, Yeong-Jyi; Liu, Yueh-Feng; Lu, Rong-Shyang; Majumder, Devdatta; Petrakou, Eleni; Shi, Xin; Shiu, Jing-Ge; Tzeng, Yeng-Ming; Wang, Minzu; Wilken, Rachel; Asavapibhop, Burin; Suwonjandee, Narumon; Adiguzel, Aytul; Bakirci, Mustafa Numan; Cerci, Salim; Dozen, Candan; Dumanoglu, Isa; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Gurpinar, Emine; Hos, Ilknur; Kangal, Evrim Ersin; Kayis Topaksu, Aysel; Onengut, Gulsen; Ozdemir, Kadri; Ozturk, Sertac; Polatoz, Ayse; Sogut, Kenan; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Vergili, Mehmet; Akin, Ilina Vasileva; Aliev, Takhmasib; Bilin, Bugra; Bilmis, Selcuk; Deniz, Muhammed; Gamsizkan, Halil; Guler, Ali Murat; Karapinar, Guler; Ocalan, Kadir; Ozpineci, Altug; Serin, Meltem; Sever, Ramazan; Surat, Ugur Emrah; 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Suarez, Indara; Tatarinov, Aysen; Toback, David; Akchurin, Nural; Cowden, Christopher; Damgov, Jordan; Dragoiu, Cosmin; Dudero, Phillip Russell; Kovitanggoon, Kittikul; Kunori, Shuichi; Lee, Sung Won; Libeiro, Terence; Volobouev, Igor; Appelt, Eric; Delannoy, Andrés G; Greene, Senta; Gurrola, Alfredo; Johns, Willard; Maguire, Charles; Mao, Yaxian; Melo, Andrew; Sharma, Monika; Sheldon, Paul; Snook, Benjamin; Tuo, Shengquan; Velkovska, Julia; Arenton, Michael Wayne; Boutle, Sarah; Cox, Bradley; Francis, Brian; Goodell, Joseph; Hirosky, Robert; Ledovskoy, Alexander; Lin, Chuanzhe; Neu, Christopher; Wood, John; Gollapinni, Sowjanya; Harr, Robert; Karchin, Paul Edmund; Kottachchi Kankanamge Don, Chamath; Lamichhane, Pramod; Sakharov, Alexandre; Belknap, Donald; Borrello, Laura; Carlsmith, Duncan; Cepeda, Maria; Dasu, Sridhara; Duric, Senka; Friis, Evan; Grothe, Monika; Hall-Wilton, Richard; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Klukas, Jeffrey; Lanaro, Armando; Loveless, Richard; Mohapatra, Ajit; Ojalvo, Isabel; Perry, Thomas; Pierro, Giuseppe Antonio; Polese, Giovanni; Ross, Ian; Sarangi, Tapas; Savin, Alexander; Smith, Wesley H; Swanson, Joshua

2014-04-15

The production of Y(1S), Y(2S), and Y(3S) is investigated in pPb and pp collisions at centre-of-mass energies per nucleon pair of 5.02 TeV and 2.76 TeV, respectively. The datasets correspond to integrated luminosities of about 31 inverse nanobarns (pPb) and 5.4 inverse picobarns (pp), collected in 2013 by the CMS experiment at the LHC. Upsilons that decay into muons are reconstructed within the rapidity interval abs(y[CM])<1.93 in the nucleon-nucleon centre-of-mass frame. Their production is studied as a function of two measures of event activity, namely the charged-particle multiplicity measured in the pseudorapidity interval abs(eta)<2.4, and the sum of transverse energy deposited at forward pseudorapidity, 4.02. The Y cross sections normalized by their event activity integrated values, Y(nS)/, are found to rise with both measures of the event activity in pp and pPb. In both collision systems, the ratios of the excited to the ground state cross s...

Hydrolysis of lipoproteins by sPLA2's enhances mitogenesis and eicosanoid release from vascular smooth muscle cells: Diverse activity of sPLA2's IIA, V and X.

Science.gov (United States)

Pruzanski, Waldemar; Kopilov, Julia; Kuksis, Arnis

2016-01-01

Mitogenesis of Vascular Smooth Muscle Cells (VSMC) plays an important role in atherogenesis. Until recently, the effect of lipid subfractions has not been clarified. Secretory phospholipases A2 (sPLA2's) hydrolyse glycerophospholipids and release pro-inflammatory lyso-lipids, oxidized and non-oxidized fatty acids and isoprostanes. They localize in the vascular wall. We hypothesized that structurally similar sPLA2's may exert different impact on VSMC. The influence of sPLA2's, IIA, V, X, HDL, LDL, and hydrolysis products was tested on mitogenesis of VSMC, i.e., the early effect on the cell membrane phospholipids, and on PGE2 and LTB4 release, i.e., late effect of Cyclooxygenase and 5-lipooxygenase activity in VSMC. Mitogenesis was significantly enhanced by HDL and LDL, and by products of sPLA2 hydrolysis. Hydrolysis of HDL or LDL enhanced mitogenic activity in order V>X>IIA. The release of PGE2 was enhanced by group X sPLA2 and by HDL hydrolyzed by groups V and X. LDL and its hydrolysis products enhanced the release of PGE2 in order X>V>IIA. The release of LTB4 was markedly increased by LDL and HDL, and by hydrolytic products of group V and X, but not group IIA sPLA2. Our study demonstrates a diverse interaction of pro-inflammatory sPLA2's with HDL and LDL affecting both mitogenesis and eicosanoid release from VSMC, therefore potentially enhancing their pro-atherogenic activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Biological activities of lignoids from Amazon Myristicaceae species: Virota michelii, V. mollissima, V. pavonis and Iryanthera juruensis

International Nuclear Information System (INIS)

Morais, Sabrina K.R.; Yoshida, Massayoshi; Teixeira, Ana F.; Torres, Zelina E. dos S.; Numomura, Sergio M.; Yamashiro-Kanashiro, Edite H.; Lindoso, Jose Angelo I.

2009-01-01

This work revisits the fruits of Iryanthera juruensis and Virola pavonis and the leaves from V. michelii, as well as describing a study of the fruits of V. mollissima. In I. juruensis aryltetraline neolignan (1) and tetrahydrofuran neolignan (2), were found while from V. pavonis neolignans of benzofuran type (6-9), the tetrahydrofuran type (2, 11-13, 17) and the biphenyl type (10), in addition to diastereoisomers of the 8.O.4'-oxyneolignan type (14 and 15) and others were isolated. The V. mollissima accumulates the aryltetralone neolignan 4 and its seco derivative (5). The lignoids 1 and 2 obtained from I. juruensis arils possess antileishmanial activity against the promastigote form of Leishmania amazonensis. (author)

Biological activities of lignoids from Amazon Myristicaceae species: Virota michelii, V. mollissima, V. pavonis and Iryanthera juruensis

Energy Technology Data Exchange (ETDEWEB)

Morais, Sabrina K.R.; Yoshida, Massayoshi [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Quimica; Centro de Biotecnologia da Amazonia, Manaus, AM (Brazil)], e-mail: myoshida@iq.usp.br; Teixeira, Ana F. [Universidade do Estado do Amazonas, Manaus, AM (Brazil). Escola Normal Superior; Torres, Zelina E. dos S. [Universidade do Estado do Amazonas, Manaus, AM (Brazil). Escola Superior de Ciencias da Saude; Numomura, Sergio M. [Instituto Nacional de Pesquisas da Amazonia (INPA), Manaus, AM (Brazil). Coordenacao de Pesquisa de Produtos Naturais; Yamashiro-Kanashiro, Edite H.; Lindoso, Jose Angelo I. [Universidade de Sao Paulo, SP (Brazil). Hospital das Clinicas. Lab. de Epidemiologia e Imunobiologia

2009-07-01

This work revisits the fruits of Iryanthera juruensis and Virola pavonis and the leaves from V. michelii, as well as describing a study of the fruits of V. mollissima. In I. juruensis aryltetraline neolignan (1) and tetrahydrofuran neolignan (2), were found while from V. pavonis neolignans of benzofuran type (6-9), the tetrahydrofuran type (2, 11-13, 17) and the biphenyl type (10), in addition to diastereoisomers of the 8.O.4'-oxyneolignan type (14 and 15) and others were isolated. The V. mollissima accumulates the aryltetralone neolignan 4 and its seco derivative (5). The lignoids 1 and 2 obtained from I. juruensis arils possess antileishmanial activity against the promastigote form of Leishmania amazonensis. (author)

Reduction of V{sub 2}O{sub 5} thin films deposited by aqueous sol–gel method to VO{sub 2}(B) and investigation of its photocatalytic activity

Energy Technology Data Exchange (ETDEWEB)

Monfort, Olivier [Department of Inorganic Chemistry, Faculty of Natural Sciences, Comenius University, 842 15 Bratislava (Slovakia); Roch, Tomas; Satrapinskyy, Leonid; Gregor, Maros; Plecenik, Tomas; Plecenik, Andrej [Department of Experimental Physics, Faculty of Mathematics, Physics and Informatics, Comenius University, 842 48 Bratislava (Slovakia); Plesch, Gustav, E-mail: plesch@fns.uniba.sk [Department of Inorganic Chemistry, Faculty of Natural Sciences, Comenius University, 842 15 Bratislava (Slovakia)

2014-12-15

Graphical abstract: - Highlights: • Preparation of VO{sub 2}(B) films by aqueous sol–gel method and their characterization. • Influence of annealing conditions on the mechanism of V{sub 2}O{sub 5} film reduction. • The VO{sub 2}(B) films with energy gap of 2.8 eV show photocatalytic activity. • The films with higher roughness exhibit increased photoactivity. - Abstract: A way of preparation of VO{sub 2}(B) thin films by reduction of V{sub 2}O{sub 5} films synthesized from an aqueous sol–gel system has been developed and photocatalytic properties of the obtained films were studied. The reduction was performed by annealing of the V{sub 2}O{sub 5} film in vacuum as well as in H{sub 2}/Ar atmosphere, which was followed by temperature dependent XRD. It has been shown that the reduction is influenced by the layered-structure of the vanadium oxides. It is a two-step process, where the mixed-valence vanadium oxide V{sub 4}O{sub 9} is first formed before reaching the VO{sub 2}(B) phase. The film microstructure was characterized by SEM and AFM and the valence states of vanadium in VO{sub 2}(B) films were evaluated by XPS. The VO{sub 2}(B) polymorph shows an energy band-gap around 2.8 eV and it exhibits photocatalytic properties. It was measured by following the degradation of rhodamine B under UVA as well as metalhalogenide lamp irradiation, which has similar spectral distribution as natural sunlight. The VO{sub 2}(B) films show distinct photoactivities under both lamps, although they were found to be more active under the UVA irradiation. The film annealed under reducing hydrogen atmosphere, which exhibits higher granularity and surface roughness, shows higher photoactivity than the vacuum-annealed film.

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.

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...

Constitutional Law: Right of Privacy--Possession of Marijuana

Science.gov (United States)

Rohrer, David E.

1976-01-01

The Alaska Supreme Court in Ravin v. State accepted the defendant's contention that the prohibition of possession of marihuana infringed on his constitutional right to privacy. The significance of the case is discussed. (LBH)

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.

Identification of functional DNA variants in the constitutive promoter region of MDM2

Directory of Open Access Journals (Sweden)

Lalonde Marie-Eve

2012-09-01

Full Text Available Abstract Although mutations in the oncoprotein murine double minute 2 (MDM2 are rare, MDM2 gene overexpression has been observed in several human tumors. Given that even modest changes in MDM2 levels might influence the p53 tumor suppressor signaling pathway, we postulated that sequence variation in the promoter region of MDM2 could lead to disregulated expression and variation in gene dosage. Two promoters have been reported for MDM2; an internal promoter (P2, which is located near the end of intron 1 and is p53-responsive, and an upstream constitutive promoter (P1, which is p53-independent. Both promoter regions contain DNA variants that could influence the expression levels of MDM2, including the well-studied single nucleotide polymorphism (SNP SNP309, which is located in the promoter P2; i.e., upstream of exon 2. In this report, we screened the promoter P1 for DNA variants and assessed the functional impact of the corresponding SNPs. Using the dbSNP database and genotyping validation in individuals of European descent, we identified three common SNPs (−1494 G > A; indel 40 bp; and −182 C > G. Three major promoter haplotypes were inferred by using these three promoter SNPs together with rs2279744 (SNP309. Following subcloning into a gene reporter system, we found that two of the haplotypes significantly influenced MDM2 promoter activity in a haplotype-specific manner. Site-directed mutagenesis experiments indicated that the 40 bp insertion/deletion variation is causing the observed allelic promoter activity. This study suggests that part of the variability in the MDM2 expression levels could be explained by allelic p53-independent P1 promoter activity.

Сontemporary forms of protection of the constitution: comparative legal aspects

Directory of Open Access Journals (Sweden)

Д. П. Таран

2015-11-01

Full Text Available Systematic analysis of protection forms of the constitution allows to identify legal tools that can be applied in order to prevent encroachments on the constitutional values or in the commission of such an offense or to identify the real threat. Up to now there is no a single approach to understanding of protection of the constitution, its relationship with the protection, system of its forms and so on. There remain unclear regularities that have their influence on different protection forms of the constitution in foreign countries as well as the consistency and adequacy of the use of such forms in Ukraine. Recent research and publications analysis. Scientists name various forms of protection of the constitution. Approaches of scientists that give their lists differ very much. Hence there is no necessity in talking about some constant regarding this matter. Some aspects of the issue that is related to the system of protection forms of the constitution found their reflection in the works of local and foreign scientists such as Y.G. Barabash, M.V. Vitruk, I.V. Koreyba, K.O. Pavshuk, P.B. Stetsyuk, K. Hesse, T. Y. Habriyeva, V.E. Chyrkin and others. Paper objective. The objectives of the paper are: clarification of the nature of the protection of the constitution and what means or what forms and what subjects it should be implemented by; the comparison of the experience of foreign countries regarding the issue and determination of the reasons for which different countries use different protection forms of the constitutions; expression of suggestions regarding legislation improvement in regards to specific protection forms of the Constitution of Ukraine. Paper main body. Countries with established democracy traditionally use a smaller set of protection forms of the constitution and the concept of "protection of the constitution" itself is almost not applied. The opposite approach is inherent to countries emerging from totalitarian and authoritarian

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.

Taking a second bite at the appeal cherry: Molaudzi v S | Jordaan ...

African Journals Online (AJOL)

In this case note I present the background of the case of Molaudzi v S, analyse the judgement, and differentiate it from another Constitutional Court case that dealt with res judicata, namely Mpofu v Minister for Justice and Constitutional Development 2013 2 SACR 407 (CC). Keywords: Res judicata; interests of justice ...

Increased expression of the auxiliary beta(2-subunit of ventricular L-type Ca(2+ channels leads to single-channel activity characteristic of heart failure.

Directory of Open Access Journals (Sweden)

Roger Hullin

2007-03-01

Full Text Available Increased activity of single ventricular L-type Ca(2+-channels (L-VDCC is a hallmark in human heart failure. Recent findings suggest differential modulation by several auxiliary beta-subunits as a possible explanation.By molecular and functional analyses of human and murine ventricles, we find that enhanced L-VDCC activity is accompanied by altered expression pattern of auxiliary L-VDCC beta-subunit gene products. In HEK293-cells we show differential modulation of single L-VDCC activity by coexpression of several human cardiac beta-subunits: Unlike beta(1 or beta(3 isoforms, beta(2a and beta(2b induce a high-activity channel behavior typical of failing myocytes. In accordance, beta(2-subunit mRNA and protein are up-regulated in failing human myocardium. In a model of heart failure we find that mice overexpressing the human cardiac Ca(V1.2 also reveal increased single-channel activity and sarcolemmal beta(2 expression when entering into the maladaptive stage of heart failure. Interestingly, these animals, when still young and non-failing ("Adaptive Phase", reveal the opposite phenotype, viz: reduced single-channel activity accompanied by lowered beta(2 expression. Additional evidence for the cause-effect relationship between beta(2-subunit expression and single L-VDCC activity is provided by newly engineered, double-transgenic mice bearing both constitutive Ca(V1.2 and inducible beta(2 cardiac overexpression. Here in non-failing hearts induction of beta(2-subunit overexpression mimicked the increase of single L-VDCC activity observed in murine and human chronic heart failure.Our study presents evidence of the pathobiochemical relevance of beta(2-subunits for the electrophysiological phenotype of cardiac L-VDCC and thus provides an explanation for the single L-VDCC gating observed in human and murine heart failure.

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.

DECIPHERING CONTRIBUTIONS TO THE EXTRAGALACTIC GAMMA-RAY BACKGROUND FROM 2 GeV TO 2 TeV

Energy Technology Data Exchange (ETDEWEB)

Lisanti, Mariangela; Mishra-Sharma, Siddharth [Department of Physics, Princeton University, Princeton, NJ 08544 (United States); Necib, Lina; Safdi, Benjamin R. [Center for Theoretical Physics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

2016-12-01

Astrophysical sources outside the Milky Way, such as active galactic nuclei and star-forming galaxies, leave their imprint on the gamma-ray sky as nearly isotropic emission referred to as the extragalactic gamma-ray background (EGB). While the brightest of these sources may be individually resolved, their fainter counterparts contribute diffusely. In this work, we use a recently developed analysis method, called the Non-Poissonian Template Fit, on up to 93 months of publicly available data from the Fermi Large Area Telescope to determine the properties of the point sources (PSs) that comprise the EGB. This analysis takes advantage of photon-count statistics to probe the aggregate properties of these source populations below the sensitivity threshold of published catalogs. We measure the source-count distributions and PS intensities, as a function of energy, from ∼2 GeV to 2 TeV. We find that the EGB is dominated by PSs, likely blazars, in all seven energy sub-bins considered. These results have implications for the interpretation of IceCube’s PeV neutrinos, which may originate from sources that contribute to the non-blazar component of the EGB. Additionally, we comment on implications for future TeV observatories such as the Cherenkov Telescope Array. We provide sky maps showing locations most likely to contain these new sources at both low (≲50 GeV) and high (≳50 GeV) energies for use in future observations and cross-correlation studies.

DECIPHERING CONTRIBUTIONS TO THE EXTRAGALACTIC GAMMA-RAY BACKGROUND FROM 2 GeV TO 2 TeV

International Nuclear Information System (INIS)

Lisanti, Mariangela; Mishra-Sharma, Siddharth; Necib, Lina; Safdi, Benjamin R.

2016-01-01

Astrophysical sources outside the Milky Way, such as active galactic nuclei and star-forming galaxies, leave their imprint on the gamma-ray sky as nearly isotropic emission referred to as the extragalactic gamma-ray background (EGB). While the brightest of these sources may be individually resolved, their fainter counterparts contribute diffusely. In this work, we use a recently developed analysis method, called the Non-Poissonian Template Fit, on up to 93 months of publicly available data from the Fermi Large Area Telescope to determine the properties of the point sources (PSs) that comprise the EGB. This analysis takes advantage of photon-count statistics to probe the aggregate properties of these source populations below the sensitivity threshold of published catalogs. We measure the source-count distributions and PS intensities, as a function of energy, from ∼2 GeV to 2 TeV. We find that the EGB is dominated by PSs, likely blazars, in all seven energy sub-bins considered. These results have implications for the interpretation of IceCube’s PeV neutrinos, which may originate from sources that contribute to the non-blazar component of the EGB. Additionally, we comment on implications for future TeV observatories such as the Cherenkov Telescope Array. We provide sky maps showing locations most likely to contain these new sources at both low (≲50 GeV) and high (≳50 GeV) energies for use in future observations and cross-correlation studies.

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.

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

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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.

The Anti-sigma Factor RsiV Is a Bacterial Receptor for Lysozyme: Co-crystal Structure Determination and Demonstration That Binding of Lysozyme to RsiV Is Required for σV Activation.

Directory of Open Access Journals (Sweden)

Jessica L Hastie

2016-09-01

Full Text Available σ factors provide RNA polymerase with promoter specificity in bacteria. Some σ factors require activation in order to interact with RNA polymerase and transcribe target genes. The Extra-Cytoplasmic Function (ECF σ factor, σV, is encoded by several Gram-positive bacteria and is specifically activated by lysozyme. This activation requires the proteolytic destruction of the anti-σ factor RsiV via a process of regulated intramembrane proteolysis (RIP. In many cases proteases that cleave at site-1 are thought to directly sense a signal and initiate the RIP process. We previously suggested binding of lysozyme to RsiV initiated the proteolytic destruction of RsiV and activation of σV. Here we determined the X-ray crystal structure of the RsiV-lysozyme complex at 2.3 Å which revealed that RsiV and lysozyme make extensive contacts. We constructed RsiV mutants with altered abilities to bind lysozyme. We find that mutants that are unable to bind lysozyme block site-1 cleavage of RsiV and σV activation in response to lysozyme. Taken together these data demonstrate that RsiV is a receptor for lysozyme and binding of RsiV to lysozyme is required for σV activation. In addition, the co-structure revealed that RsiV binds to the lysozyme active site pocket. We provide evidence that in addition to acting as a sensor for the presence of lysozyme, RsiV also inhibits lysozyme activity. Thus we have demonstrated that RsiV is a protein with multiple functions. RsiV inhibits σV activity in the absence of lysozyme, RsiV binds lysozyme triggering σV activation and RsiV inhibits the enzymatic activity of lysozyme.

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.

A Novel Phase-Transformation Activation Process toward Ni-Mn-O Nanoprism Arrays for 2.4 V Ultrahigh-Voltage Aqueous Supercapacitors.

Science.gov (United States)

Zuo, Wenhua; Xie, Chaoyue; Xu, Pan; Li, Yuanyuan; Liu, Jinping

2017-09-01

One of the key challenges of aqueous supercapacitors is the relatively low voltage (0.8-2.0 V), which significantly limits the energy density and feasibility of practical applications of the device. Herein, this study reports a novel Ni-Mn-O solid-solution cathode to widen the supercapacitor device voltage, which can potentially suppress the oxygen evolution reaction and thus be operated stably within a quite wide potential window of 0-1.4 V (vs saturated calomel electrode) after a simple but unique phase-transformation electrochemical activation. The solid-solution structure is designed with an ordered array architecture and in situ nanocarbon modification to promote the charge/mass transfer kinetics. By paring with commercial activated carbon anode, an ultrahigh voltage asymmetric supercapacitor in neutral aqueous LiCl electrolyte is assembled (2.4 V; among the highest for single-cell supercapacitors). Moreover, by using a polyvinyl alcohol (PVA)-LiCl electrolyte, a 2.4 V hydrogel supercapacitor is further developed with an excellent Coulombic efficiency, good rate capability, and remarkable cycle life (>5000 cycles; 95.5% capacity retention). Only one cell can power the light-emitting diode indicator brightly. The resulting maximum volumetric energy density is 4.72 mWh cm -3 , which is much superior to previous thin-film manganese-oxide-based supercapacitors and even battery-supercapacitor hybrid devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Splanchnic venous thrombosis driven by a constitutively activated ...

African Journals Online (AJOL)

sated chronic liver disease found to have SVT- portal vein thrombosis and how JAK2 V617F was useful in unmasking an ... to over proliferation of the myeloid series. .... gression to acute leukemia and myelofibrosis. .... factors and treatment.

Health care law versus constitutional law.

Science.gov (United States)

Hall, Mark A

2013-04-01

National Federation of Independent Business v. Sebelius, the Supreme Court's ruling on the Patient Protection and Affordable Care Act, is a landmark decision - both for constitutional law and for health care law and policy. Others will study its implications for constitutional limits on a range of federal powers beyond health care. This article considers to what extent the decision is also about health care law, properly conceived. Under one view, health care law is the subdiscipline that inquires how courts and government actors take account of the special features of medicine that make legal or policy issues especially problematic - rather than regarding health care delivery and finance more generically, like most any other economic or social enterprise. Viewed this way, the opinions from the Court's conservative justices are mainly about general constitutional law principles. In contrast, Justice Ruth Bader Ginsburg's dissenting opinion for the four more liberal justices is just as much about health care law as it is about constitutional law. Her opinion gives detailed attention to the unique features of health care finance and delivery in order to inform her analysis of constitutional precedents and principles. Thus, the Court's multiple opinions give a vivid depiction of the compelling contrasts between communal versus individualistic conceptions of caring for those in need, and between health care and health insurance as ordinary commodities versus ones that merit special economic, social, and legal status.

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....

A regression approach for Zircaloy-2 in-reactor creep constitutive equations

International Nuclear Information System (INIS)

Yung Liu, Y.; Bement, A.L.

1977-01-01

In this paper the methodology of multiple regressions as applied to Zircaloy-2 in-reactor creep data analysis and construction of constitutive equation are illustrated. While the resulting constitutive equation can be used in creep analysis of in-reactor Zircaloy structural components, the methodology itself is entirely general and can be applied to any creep data analysis. The promising aspects of multiple regression creep data analysis are briefly outlined as follows: (1) When there are more than one variable involved, there is no need to make the assumption that each variable affects the response independently. No separate normalizations are required either and the estimation of parameters is obtained by solving many simultaneous equations. The number of simultaneous equations is equal to the number of data sets. (2) Regression statistics such as R 2 - and F-statistics provide measures of the significance of regression creep equation in correlating the overall data. The relative weights of each variable on the response can also be obtained. (3) Special regression techniques such as step-wise, ridge, and robust regressions and residual plots, etc., provide diagnostic tools for model selections. Multiple regression analysis performed on a set of carefully selected Zircaloy-2 in-reactor creep data leads to a model which provides excellent correlations for the data. (Auth.)

Implication of TLR- but not of NOD2-signaling pathways in dendritic cell activation by group B Streptococcus serotypes III and V.

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Paul Lemire

Full Text Available Group B Streptococcus (GBS is an important agent of life-threatening invasive infection. It has been previously shown that encapsulated type III GBS is easily internalized by dendritic cells (DCs, and that this internalization had an impact on cytokine production. The receptors underlying these processes are poorly characterized. Knowledge on the mechanisms used by type V GBS to activate DCs is minimal. In this work, we investigated the role of Toll-like receptor (TLR/MyD88 signaling pathway, the particular involvement of TLR2, and that of the intracellular sensing receptor NOD2 in the activation of DCs by types III and V GBS. The role of capsular polysaccharide (CPS, one of the most important GBS virulence factors in bacterial-DC interactions was evaluated using non-encapsulated mutants. Despite differences in the role of CPS between types III and V GBS in bacterial internalization and intracellular survival, no major differences were observed in their capacity to modulate release of cytokines by DC. For both serotypes, CPS had a minor role in this response. Production of cytokines by DCs was shown to strongly rely on MyD88-dependent signaling pathways, suggesting that DCs recognize GBS and become activated mostly through TLR signaling. Yet, GBS-infected TLR2-/- DCs only showed a partial reduction in the production of IL-6 and CXCL1 compared to control DCs. Surprisingly, CXCL10 release by type III or type V GBS-infected DCs was MyD88-independent. No differences in DC activation were observed between NOD2-/- and control DCs. These results demonstrate the involvement of various receptors and the complexity of the cytokine production pathways activated by GBS upon DC infection.

The constitutive compatibility method for identification of material parameters based on full-field measurements

KAUST Repository

Moussawi, Ali

2013-10-01

We revisit here the concept of the constitutive relation error for the identification of elastic material parameters based on image correlation. An additional concept, so called constitutive compatibility of stress, is introduced defining a subspace of the classical space of statically admissible stresses. The key idea is to define stresses as compatible with the observed deformation field through the chosen class of constitutive equation. This makes possible the uncoupling of the identification of stress from the identification of the material parameters. As a result, the global cost of the identification is strongly reduced. This uncoupling also leads to parametrized solutions in cases where the solution is non-unique as demonstrated on 2D numerical examples. © 2013 Elsevier B.V.

Room temperature photoluminescence in crystalline/amorphous Er-doped Cd{sub 2}V{sub 2}O{sub 7}

Energy Technology Data Exchange (ETDEWEB)

Cid-Garcia, A. [Benemerita Universidad Autonoma de Puebla. Postgrado en Fisica Aplicada. Facultad de Ciencias Fisico-Matematicas, Mexico (Mexico); Lozada-Morales, R., E-mail: rlozada@fcfm.buap.mx [Benemerita Universidad Autonoma de Puebla. Postgrado en Fisica Aplicada. Facultad de Ciencias Fisico-Matematicas, Mexico (Mexico); Lopez-Calzada, G. [Centro de Investigacion y de Estudios Avanzados del IPN, Unidad Queretaro, Apartado Postal 1-798, Queretaro, Qro. 76001 (Mexico); Zayas, Ma. E. [Departamento de Investigacion en Fisica de la Universidad de Sonora, Edificio 3I, Blvd. Edificio 5 E, Luis Encinas s/n, Col. Centro, 83000. Hermosillo, Sonora, Mexico (Mexico); Zelaya Angel, O. [Departamento de Fisica, Centro de Investigacion y de Estudios Avanzados, P.O. Box 14-740, Mexico 07360 D. F. (Mexico); and others

2012-06-15

Er{sup 3+} ions were introduced into a new type of oxide matrixes prepared with different proportions of CdO and V{sub 2}O{sub 5}. The source of Er{sup 3+} employed was Er(NO{sub 3}){sub 3}{center_dot}5H{sub 2}O, which yielded an Er{sup 3+} concentration of {approx}1 at%. Depending on the reactants proportions, the samples resulted in crystalline or amorphous structures. X-ray diffraction indicated that the crystalline samples were constituted by polycrystalline Cd{sub 2}V{sub 2}O{sub 7}, in agreement with Raman spectroscopy measurements. Depending on the proportions of the component oxides, the band gap changed in the 2.49-1.77 eV energy range, as determined through photoacoustic spectroscopy. From photoluminescence spectra, the following electronic transitions of Er{sup 3+} were observed in both types of samples: {l_brace}{sup 2}H{sub 11/2}, {sup 4}S{sub 3/2}, {sup 4}F{sub 9/2}, {sup 4}I{sub 9/2}{r_brace}{yields}{sup 4}I{sub 15/2} and {sup 4}S{sub 3/2}{yields}{sup 4}I{sub 13/2}. In the case of crystalline samples manifolds, originating from the Stark effect, were measured for the {l_brace}{sup 2}H{sub 11/2}, {sup 4}S{sub 3/2}, {sup 4}F{sub 9/2}{r_brace}{yields}{sup 4}I{sub 15/2} and {sup 4}S{sub 3/2}{yields}{sup 4}I{sub 13/2} transitions. - Highlights: Black-Right-Pointing-Pointer The Cd{sub 2}V{sub 2}O{sub 7} has been fabricated in amorphous and crystalline phases. Black-Right-Pointing-Pointer The band gap of crystalline samples varied in the 2.49-2.41 eV range. Black-Right-Pointing-Pointer The absorption edge for the glasses had lower values with a minimum of 1.77 eV. Black-Right-Pointing-Pointer The {l_brace}{sup 2}H{sub 11/2}, {sup 4}S{sub 3/2}, {sup 4}F{sub 9/2}, {sup 4}I{sub 9/2}{r_brace}{yields}{sup 4}I{sub 15/2} and {sup 4}S{sub 3/2}{yields}{sup 4}I{sub 13/2,} were observed in PL.

Activation of human factor V by factor Xa and thrombin

International Nuclear Information System (INIS)

Monkovic, D.D.; Tracy, P.B.

1990-01-01

The activation of human factor V by factor Xa and thrombin was studied by functional assessment of cofactor activity and sodium dodecyl sulfate-polycarylamide gel electrophoresis followed by either autoradiography of 125 I-labeled factor V activation products or Western blot analyses of unlabeled factor V activation products. Cofactor activity was measured by the ability of the factor V/Va peptides to support the activation of prothrombin. The factor Xa catalyzed cleavage of factor V was observed to be time, phospholipid, and calcium ion dependent, yielding a cofactor with activity equal to that of thrombin-activated factor V (factor Va). The cleavage pattern differed markedly from the one observed in the bovine system. The factor Xa activated factor V subunits expressing cofactor activity were isolated and found to consist of peptides of M r 220,000 and 105,000. Although thrombin cleaved the M r 220,000 peptide to yield peptides previously shown to be products of thrombin activation, cofactor activity did not increase. N-Terminal sequence analysis confirmed that both factor Xa and thrombin cleave factor V at the same bond to generate the M r 220,000 peptide. The factor Xa dependent functional assessment of 125 I-labeled factor V coupled with densitometric analyses of the cleavage products indicated that the cofactor activity of factor Xa activated factor V closely paralleled the appearance of the M r 220,000 peptide. The data indicate that factor Xa is as efficient an enzyme toward factor V as thrombin

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

The South African constitutional Court and the Rule of Law: The ...

African Journals Online (AJOL)

The rule of law as a foundational constitutional value constrains the exercise of public power but the precise limits of the constraints it sets are not well defined. In Masethla v President of the Republic of South Africa,1 the majority of the Constitutional Court opted for an interpretation of this value that frees the President from ...

Protein Kinase Cα and P-Type Ca2+ Channel CaV2.1 in Red Blood Cell Calcium Signalling

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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.

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

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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.

Measurement of (n,2n) cross-sections for Sc, Mn, Cr and In between 12 and 19 MeV with activation technique

Energy Technology Data Exchange (ETDEWEB)

Iwasaki, S.; Win, Than; Matsuyama, S. [Tohoku Univ., Sendai (Japan). Faculty of Engineering; Odano, N.

1997-03-01

Activation cross-sections for scandium, manganese, chromium and indium have been measured in the neutron energies from 12 to 19 MeV. Source neutrons were produced via the T(d,n){sup 4}He reaction by bombarding a 3.2-MeV deuteron beam from the Dynamitron accelerator of Fast Neutron Laboratory at Tohoku University. Ten packages of high or ultra-high purity metal foils for chromium and indium, alloy foils for manganese, and oxide powder for scandium were set around the neutron source at 5 cm from the target in the angular range from 0 to 140 deg covering the incident neutron energies from 19 to 12 MeV at the center position of each package. Activation rates of the samples were obtained by the gamma-ray measurements using a high purity germanium detector. Neutron flux at each sample was determined using the activation rates of two niobium foils locating both sides of that sample; the reference reaction was {sup 93}Nb(n,2n){sup 92m}Nb of which cross-section data was taken from the 1991 NEANDC/INDC standard files. The source neutrons distributions have been measured in detail by the time-of-flight technique. The measured cross-sections are the following important dosimetry or activation reactions: {sup 45}Sc(n,2n){sup 44m}Sc, {sup 55}Mn(n,2n){sup 54}Mn, {sup 52}Cr(n,2n){sup 51}Cr, and {sup 115}In(n,2n){sup 114m}In. These cross-sections are compared with available activation file, dosimetry files and previous experimental data. (author)

Determination of the physiological 2:2 TLR5:flagellin activation stoichiometry revealed by the activity of a fusion receptor

International Nuclear Information System (INIS)

Ivičak-Kocjan, Karolina; Panter, Gabriela; Benčina, Mojca; Jerala, Roman

2013-01-01

Highlights: •The chimeric protein fusing flagellin to the TLR5 ectodomain is constitutively active. •Mutation P736H within the BB-loop of TLR5 TIR domain renders the receptor inactive. •The R90D mutation in flagellin inactivated autoactivation of the chimeric protein. •The 2:2 stoichiometry of the TLR5:flagellin complex is physiologically relevant. -- Abstract: Toll-like receptor 5 (TLR5) recognizes flagellin of most flagellated bacteria, enabling activation of the MyD88-dependent signaling pathway. The recently published crystal structure of a truncated zebrafish TLR5 ectodomain in complex with an inactive flagellin fragment indicated binding of two flagellin molecules to a TLR5 homodimer, however this complex did not dimerize in solution. In the present study, we aimed to determine the physiological stoichiometry of TLR5:flagellin activation by the use of a chimeric protein composed of an active flagellin fragment linked to the N-terminus of human TLR5 (SF-TLR5). This construct was constitutively active. Inactivation by the R90D mutation within flagellin demonstrated that autoactivation of the chimeric protein depended solely on the specific interaction between TLR5 and flagellin. Addition of wild-type hTLR5 substantially lowered autoactivation of SF-TLR5 in a concentration dependent manner, an effect which was reversible by the addition of exogenous Salmonella typhimurium flagellin, indicating the biological activity of a TLR5:flagellin complex with a 2:2 stoichiometry. These results, in addition to the combinations of inactive P736H mutation within the BB-loop of the TIR domain of TLR5 and SF-TLR5, further confirm the mechanism of TLR5 activation

Determination of the physiological 2:2 TLR5:flagellin activation stoichiometry revealed by the activity of a fusion receptor

Energy Technology Data Exchange (ETDEWEB)

Ivičak-Kocjan, Karolina; Panter, Gabriela; Benčina, Mojca [Laboratory of Biotechnology, National Institute of Chemistry, 1000 Ljubljana (Slovenia); The Centre of Excellence EN-FIST, 1000 Ljubljana (Slovenia); Jerala, Roman, E-mail: roman.jerala@ki.si [Laboratory of Biotechnology, National Institute of Chemistry, 1000 Ljubljana (Slovenia); The Centre of Excellence EN-FIST, 1000 Ljubljana (Slovenia); The Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana (Slovenia)

2013-05-24

Highlights: •The chimeric protein fusing flagellin to the TLR5 ectodomain is constitutively active. •Mutation P736H within the BB-loop of TLR5 TIR domain renders the receptor inactive. •The R90D mutation in flagellin inactivated autoactivation of the chimeric protein. •The 2:2 stoichiometry of the TLR5:flagellin complex is physiologically relevant. -- Abstract: Toll-like receptor 5 (TLR5) recognizes flagellin of most flagellated bacteria, enabling activation of the MyD88-dependent signaling pathway. The recently published crystal structure of a truncated zebrafish TLR5 ectodomain in complex with an inactive flagellin fragment indicated binding of two flagellin molecules to a TLR5 homodimer, however this complex did not dimerize in solution. In the present study, we aimed to determine the physiological stoichiometry of TLR5:flagellin activation by the use of a chimeric protein composed of an active flagellin fragment linked to the N-terminus of human TLR5 (SF-TLR5). This construct was constitutively active. Inactivation by the R90D mutation within flagellin demonstrated that autoactivation of the chimeric protein depended solely on the specific interaction between TLR5 and flagellin. Addition of wild-type hTLR5 substantially lowered autoactivation of SF-TLR5 in a concentration dependent manner, an effect which was reversible by the addition of exogenous Salmonella typhimurium flagellin, indicating the biological activity of a TLR5:flagellin complex with a 2:2 stoichiometry. These results, in addition to the combinations of inactive P736H mutation within the BB-loop of the TIR domain of TLR5 and SF-TLR5, further confirm the mechanism of TLR5 activation.

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

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.

The Physiological and Biochemical Mechanisms Providing the Increased Constitutive Cold Resistance in the Potato Plants, Expressing the Yeast SUC2 Gene Encoding Apoplastic Invertase

Directory of Open Access Journals (Sweden)

A.N. Deryabin

2016-05-01

Full Text Available The expression of heterologous genes in plants is an effective method to improve our understanding of plant resistance mechanisms. The purpose of this work was to investigate the involvement of cell-wall invertase and apoplastic sugars into constitutive cold resistance of potato (Solanum tuberosum L., cv. Dйsirйe plants, which expressed the yeast SUC2 gene encoding apoplastic invertase. WT-plants of a potato served as the control. The increase in the essential cell-wall invertase activity in the leaves of transformed plants indicates significant changes in the cellular carbohydrate metabolism and regulatory function of this enzyme. The activity of yeast invertase changed the composition of intracellular sugars in the leaves of the transformed potato plant. The total content of sugars (sucrose, glucose, fructose in the leaves and apoplast was higher in the transformants, in comparison by WT-plants. Our data indicate higher constitutive resistance of transformants to severe hypothermia conditions compared to WT-plants. This fact allows us to consider cell-wall invertase as a enzyme of carbohydrate metabolism playing an important regulatory role in the metabolic signaling upon forming increased plant resistance to low temperature. Thus, the potato line with the integrated SUC2 gene is a convenient tool to study the role of the apoplastic invertase and the products of its activity during growth, development and formation constitutive resistance to hypothermia.

Assessing activation of hepatic stellate cells by 99mTc-3PRGD2 scintigraphy targeting integrin αvβ3: a feasibility study

International Nuclear Information System (INIS)

Zhang, Xin; Xin, Jun; Shi, Yu; Xu, Weina; Yu, Shupeng; Yang, Zhiguang; Liu, Changping; Cao, Li; Guo, Qiyong

2015-01-01

Objective: Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. 99m Tc-3PRGD2 is such a radiotracer specific for integrin αvβ3. In this study, we aimed to compare the differences in liver uptake and retention of the 99m Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of 99m Tc-3PRGD2 scintigraphy for this purpose. Methods: We used planar scintigraphy to assess changes in integrin αvβ3 binding of intravenously-administered 99m Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with 99m Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvβ3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvβ3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers. Results: The fibrotic livers showed enhanced 99m Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvβ3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98 ± 0.08 vs. control, 1.50 ± 0.12, p < 0.01). The liver t 1/2 was longer than in the controls (TAA, 27.07 ± 10.69 min vs. control, 12.67 ± 4.10 min, p < 0.01). The difference of heart t 1/2 between the two groups was not statistically significant (TAA, 3.13 ± 0.63 min vs. control, 3.41 ± 0.77 min, p = 0.94). Conclusions: 99m Tc-3PRGD2

K-n and K-p elastic scattering in K-d collisions from 1.2 to 2.2 GeV/c

International Nuclear Information System (INIS)

Declais, Y.; Duchon, J.; Louvel, M.; Patry, J.-P.; Seguinot, J.; Baillon, P.; Bruman, C.; Ferro-Luzzi, M.; Perreau, J.-M.; Ypsilantis, T.

1977-01-01

This report contains the detailed description of an experiment which has determined the differential cross section of the K - n→K - n elastic scattering reaction. The results are 12 angular distributions spanning the K - n c.m. energy interval from approximately 1.86 to approximately 2.32 GeV. The measurements have been performed at the CERN PS using a beam of negative kaons with momenta from 1.2 to 2.2 GeV/c incident on a liquid deuterium target. By means of electronic apparatus the process K - d→K - n psub(s) was identified and recorded; this process is basically the same as the K - n elastic reaction insofar as the spectator proton psub(s) has low momentum. The elastic reaction was derived from the above process by taking into account the Fermi motion of the target neutron and by introducing the appropriate corrections to compensate for the effects due to the composite nature of the neutron (double-scattering, final state interaction). These results, constituting the first extensive collection of data on the pure isospin 1 anti KN state have been used in conjunction with other data in a preliminary partial wave analysis of the anti KN elastic system over the c.m. energy range from 1.84 to 2.23 GeV. Mainly for testing purposes, a similar amount of data has been collected for the K - p elastic reaction also from K - d collisions (K - d→K - p nsub(s)). (Auth.)

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.

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...

Thermal stability of the grain structure in the W-2V and W-2V-0.5Y{sub 2}O{sub 3} alloys produced by hot isostatic pressing

Energy Technology Data Exchange (ETDEWEB)

Martínez, J.; Savoini, B.; Monge, M.A. [Departamento de Física, Universidad Carlos III de Madrid, 28911-Leganés Madrid (Spain); Muñoz, A., E-mail: angel.munoz@uc3m.es [Departamento de Física, Universidad Carlos III de Madrid, 28911-Leganés Madrid (Spain); Armstrong, D.E.J. [Department of Materials, University of Oxford, Park Road, Oxford OX1 3PH (United Kingdom); Pareja, R. [Departamento de Física, Universidad Carlos III de Madrid, 28911-Leganés Madrid (Spain)

2013-10-15

Highlights: • W-2V and ODS W-2V-0.5Y{sub 2}O{sub 3} alloys have been produced following a powder metallurgy route. • Grain microstructure and microhardness have been studied after isothermal treatments in vacuum. • Both alloys exhibit a duplex grain size population: a submicron-sized grain and a coarse grained one. • The Y{sub 2}O{sub 3} addition inhibits growth of the coarse grains for T < 1973 K. • The Y{sub 2}O{sub 3} nanoparticles enhance the microhardness of W-2V-0.5Y{sub 2}O{sub 3}. -- Abstract: W-2V and ODS W-2V-0.5Y{sub 2}O{sub 3} alloys have been produced following a powder metallurgy route consisting of mechanical alloying and a subsequent high isostatic pressing HIP at 1573 K. The grain microstructure and microhardness recovery of the alloys have been studied in samples subjected to isothermal treatments in vacuum in temperature range 1073–1973 K. Both alloys exhibit a duplex grain size distribution consisting of a submicron-sized grain and a coarse-grained population. It has been found that the Y{sub 2}O{sub 3} addition inhibits growth of the coarse grains at T < 1973 K. Submicron grain growth, with activation enthalpy of 1.9 and 2.49 eV for W-2V and W-2V-0.5Y{sub 2}O{sub 3}, respectively, was observed at T ≥ 1573 K. It resulted that the rate constant for grain growth is 30 times higher in W-2V-0.5Y{sub 2}O{sub 3} than in W-2V. The considerable enhancement of the microhardness in the W-2V-0.5Y{sub 2}O{sub 3} appears to be associated to dispersion strengthening.

Enzymatic activity of a novel halotolerant lipase from Haloarcula hispanica 2TK2

Directory of Open Access Journals (Sweden)

Ozgen Melis

2016-06-01

Full Text Available A strain of Haloarcula hispanica isolated from Tuzkoy salt mine, Turkey exhibited extracellular lipolytic activity. Important parameters such as carbon sources and salt concentration for lipase production were investigated. Optimal conditions for the enzyme production from Haloarcula hispanica 2TK2 were determined. It was observed that the lipolytic activity of Haloarcula hispanica was stimulated by some of the carbon sources. The high lipase acitivity values were obtained in the presence of 2% (v/v walnut oil (6.16 U/ml, 1% (v/v fish oil (5.07 U/ml, 1% (v/v olive oil (4.52 U/ml and 1% (w/v stearic acid (4.88 U/ml at 4M NaCl concentration. Lipase was partially purified by ammonium sulfate precipitation and ultrafiltration. Optimal temperature and pH values were determined as 45°C and 8.0, respectively. Lipase activity decreased with the increasing salt concentration, but 85% activity of the enzyme was maintained at 5M NaCl concentration. The enzyme preserved 41% of its relative activity at 90°C. The partially purified lipase maintained its activity in the presence of surfactants such as Triton X-100 and SDS. Therefore, the lipase which is an extremozyme may have potential applications especially in detergent industry.

Power cables with extruded insulation and their accessories for rated voltages from 1 kV (Um = 1,2 kV) up to 30 kV (Um = 36 kV) : Part 2: cables for rated voltages from 6 kV (Um = 7,2 kV) up to 30 kV (Um = 36 kV)

CERN Document Server

International Electrotechnical Commission. Geneva

2005-01-01

Power cables with extruded insulation and their accessories for rated voltages from 1 kV (Um = 1,2 kV) up to 30 kV (Um = 36 kV) : Part 2: cables for rated voltages from 6 kV (Um = 7,2 kV) up to 30 kV (Um = 36 kV)

A rationally designed self-standing V2O5 electrode for high voltage non-aqueous all-solid-state symmetric (2.0 V) and asymmetric (2.8 V) supercapacitors.

Science.gov (United States)

Ghosh, Meena; Vijayakumar, Vidyanand; Soni, Roby; Kurungot, Sreekumar

2018-05-10

The maximum capacitive potential window of certain pseudocapacitive materials cannot be accessed in aqueous electrolytes owing to the low dissociation potential of 1.2 V possessed by water molecules. However, the inferior pseudocapacitance exhibited by the commonly used electrode materials when integrated with non-aqueous electrolytes still remains a challenge in the development of supercapacitors (SC). Proper selection of materials for the electrode and a rational design process are indeed important to overcome these practical intricacies so that such systems can perform well with non-aqueous electrolytes. We address this challenge by fabricating a prototype all-solid-state device designed with high-capacitive V2O5 as the electrode material along with a Li-ion conducting organic electrolyte. V2O5 is synthesized on a pre-treated carbon-fibre paper by adopting an electrochemical deposition technique that effects an improved contact resistance. A judicious electrode preparation strategy makes it possible to overcome the constraints of the low ionic and electrical conductivities imposed by the electrolyte and electrode material, respectively. The device, assembled in a symmetrical fashion, achieves a high specific capacitance of 406 F g-1 (at 1 A g-1). The profitable aspect of using an organic electrolyte is also demonstrated with an asymmetric configuration by using activated carbon as the positive and V2O5 as the negative electrode materials, respectively. The asymmetric device displays a wide working-voltage window of 2.8 V and delivers a high energy density of 102.68 W h kg-1 at a power density of 1.49 kW kg-1. Moreover, the low equivalent series resistance of 9.9 Ω and negligible charge transfer resistance are observed in the impedance spectra, which is a key factor that accounts for such an exemplary performance.

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.

Constitutive type VI secretion system expression gives Vibrio cholerae intra- and interspecific competitive advantages.

Directory of Open Access Journals (Sweden)

Daniel Unterweger

Full Text Available The type VI secretion system (T6SS mediates protein translocation across the cell membrane of Gram-negative bacteria, including Vibrio cholerae - the causative agent of cholera. All V. cholerae strains examined to date harbor gene clusters encoding a T6SS. Structural similarity and sequence homology between components of the T6SS and the T4 bacteriophage cell-puncturing device suggest that the T6SS functions as a contractile molecular syringe to inject effector molecules into prokaryotic and eukaryotic target cells. Regulation of the T6SS is critical. A subset of V. cholerae strains, including the clinical O37 serogroup strain V52, express T6SS constitutively. In contrast, pandemic strains impose tight control that can be genetically disrupted: mutations in the quorum sensing gene luxO and the newly described regulator gene tsrA lead to constitutive T6SS expression in the El Tor strain C6706. In this report, we examined environmental V. cholerae isolates from the Rio Grande with regard to T6SS regulation. Rough V. cholerae lacking O-antigen carried a nonsense mutation in the gene encoding the global T6SS regulator VasH and did not display virulent behavior towards Escherichia coli and other environmental bacteria. In contrast, smooth V. cholerae strains engaged constitutively in type VI-mediated secretion and displayed virulence towards prokaryotes (E. coli and other environmental bacteria and a eukaryote (the social amoeba Dictyostelium discoideum. Furthermore, smooth V. cholerae strains were able to outcompete each other in a T6SS-dependent manner. The work presented here suggests that constitutive T6SS expression provides V. cholerae with an advantage in intraspecific and interspecific competition.

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.

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

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

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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.

Northeast Women's Center v. McMonagle, 2 March 1989.

Science.gov (United States)

1989-01-01

In March 1989, the US Court of Appeals ruled in Northeast Women's Center vs. McMonagle that the defendant anti-abortion activists could be liable under the Racketeer Influenced and Corrupt Organizations (RICO) Act for alleged acts of intimidation and harassment of the plaintiff abortion clinic resulting in destruction of property. Also during 1989, a US District Court in Washington issued a similar ruling, but a US District Court in Connecticut held that injunctive relief was not available under RICO but granted an injunction under a common law nuisance theory. Other 1989 US court decisions about the activities of anti-abortion protestors include 1) that the constitutional rights of clients are not infringed upon by loud demonstrations and gratuitous offers of counseling as long as the clients are not physically restrained or interfered with; 2) that prohibitions on the use of a hand-held amplifier are constitutional; 3) that blocking the entrances to abortion clinics is not a free speech right but rather violates the right of women to interstate travel and is actionable; 4) that abortion-seekers do not constitute a class that can invoke special protection under the federal civil rights conspiracy statute; and 5) conversely that abortion-seekers are the victims of gender-based animus and can invoke the protection of the federal civil rights conspiracy statute.

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...

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...

DEVELOPMENTS IN THE CONSTITUTIONAL REVIEW. CONSTITUTIONAL COURT BETWEEN THE STATUS OF NEGATIVE LEGISLATOR AND THE STATUS OF POSITIVE CO-LEGISLATOR

Directory of Open Access Journals (Sweden)

Marieta Safta

2012-11-01

Full Text Available The study wants to emphasize that Constitutional Courts belonging to the European model depart from their traditional role as ”negative legislator” – which refers to the effect of their acts consisting in removal from the legal system of those rules contrary to the Basic Law -, becoming, to a certain extent, a ”positive legislator”. Official interpreters of the Constitution, Constitutional Courts assume, sometimes, a role of co-legislators, creating provisions they deduct from the Constitution - when controlling the absence of legislation or legislative omissions -, and revealing the content of constitutional and even infraconstitutional rules accordingly with the Constitution in their case-law, whose effects are nothing but specific forms of „impulse” or „coercion” of the legislator to proceed in a certain sense, and whose continuous development guides the evolution of the entire legal system. Case – law selected presents ways in which the Constitutional Court of Romania is associated to law-making activity. Without minimizing in any way its traditional role as "negative legislator", the study refers mainly to acts and situations that give expression to the creative role of the Constitutional Court of Romania.

Electrostatic environment surrounding the activation loop phosphotyrosine in the oncoprotein v-Fps.

Science.gov (United States)

Leon, B C; Tsigelny, I; Adams, J A

2001-08-28

Autophosphorylation of Tyr-1073 in the activation loop of the oncoprotein v-Fps enhances the phosphoryl transfer reaction without influencing substrate, ATP, or metal ion binding affinities [Saylor, P., et al. (1998) Biochemistry 37, 17875-17881]. A structural model of v-Fps, generated from the insulin receptor, indicates that pTyr-1073 chelates two arginines. Mutation of these residues to alanine (R1042A and R1066A) results in weakly phosphorylated enzymes, indicating that one electropositive center is insufficient for attaining maximum loop phosphorylation and concomitant high catalytic activity. While the turnover rate for R1066A is similar to that for a mutant lacking a phosphorylatable residue in the activation loop, the rate for R1042A is 50-fold slower. While solvent perturbation studies suggest that the former is due to a slow phosphoryl transfer step, the latter effect results from a slow conformational change in the mutant, potentially linked to motions in the catalytic loop. Binding of a stoichiometric quantity of Mg(2+) is essential for ATP binding and catalysis, while binding of an additional Mg(2+) ion activates further the wild-type enzyme. The affinity of the R1066A enzyme for the second Mg(2+) ion is 23-fold higher than that of the phosphorylated or unphosphorylated form of wild-type v-Fps, with substrate binding unaffected. Conversely, the affinity of R1066A for a substrate mimic lacking a phosphorylation site is 12-fold higher than that for the phosphorylated or unphosphorylated form of wild-type v-Fps, with binding of the second Mg(2+) ion unaffected. A comparison of these enzyme-independent parameters indicates that Arg-1042 and Arg-1066 induce strain in the active site in the repressed form of the enzyme. While this strain is not relieved in the phosphorylated form, the improvements in catalysis in activated v-Fps compensate for reduced metal and substrate binding affinities.

Dynamic nanoplatforms in biosensor and membrane constitutional systems.

Science.gov (United States)

Mahon, Eugene; Aastrup, Teodor; Barboiu, Mihail

2012-01-01

Molecular recognition in biological systems occurs mainly at interfacial environments such as membrane surfaces, enzyme active sites, or the interior of the DNA double helix. At the cell membrane surface, carbohydrate-protein recognition principles apply to a range of specific non-covalent interactions including immune response, cell proliferation, adhesion and death, cell-cell interaction and communication. Protein-protein recognition meanwhile accounts for signalling processes and ion channel structure. In this chapter we aim to describe such constitutional dynamic interfaces for biosensing and membrane transport applications. Constitutionally adaptive interfaces may mimic the recognition capabilities intrinsic to natural recognition processes. We present some recent examples of 2D and 3D constructed sensors and membranes of this type and describe their sensing and transport capabilities.

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.

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...

DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7.

Science.gov (United States)

Moon, Sue Jin; Jeong, Byong Chang; Kim, Hwa Jin; Lim, Joung Eun; Kwon, Ghee Young; Kim, Jeong Hoon

2018-03-01

Constitutively active AR-V7, one of the major androgen receptor (AR) splice variants lacking the ligand-binding domain, plays a key role in the development of castration-resistant prostate cancer (CRPC) and anti-androgen resistance. However, our understanding of the regulatory mechanisms of AR-V7-driven transcription is limited. Here we report DBC1 as a key regulator of AR-V7 transcriptional activity and stability in CRPC cells. DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. DBC1 is required for recruitment of AR-V7 to its target enhancers and for long-range chromatin looping between the CDH2 enhancer and promoter. Mechanistically, DBC1 enhances DNA-binding activity of AR-V7 by direct interaction and inhibits CHIP E3 ligase-mediated ubiquitination and degradation of AR-V7 by competing with CHIP for AR-V7 binding, thereby stabilizing and activating AR-V7. Importantly, DBC1 depletion suppresses the tumorigenic and metastatic properties of CRPC cells. Our results firmly establish DBC1 as a critical AR-V7 coactivator that plays a key role in the regulation of DNA binding and stability of AR-V7 and has an important physiological role in CRPC progression.

Constitutional relevance of atomic energy law

International Nuclear Information System (INIS)

Lettow, S.

1980-01-01

In a decision publicized on December 20, 1979 the German Federal Constitutional Court rejected a claim of unconstitutionality in connection with the licensing procedure of the Muelheim-Kaerlich Nuclear Power Station currently under construction. This constitutes confirmation, by the 1st Department of the Court, of a decision in 1978 by the 2nd Department about the Kalkar fast breeder power plant, in which the peaceful utilization of nuclear energy had been found to be constitutional. However, the new decision by the Federal Constitutional Court particularly emphasizes the constitutional relevance of the rules of procedure under the Atomic Energy Act and their function with respect to the protection of civil rights. (orig.) [de

The prion protein constitutively controls neuronal store-operated Ca2+ entry through Fyn kinase

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Agnese eDe Mario

2015-10-01

Full Text Available The prion protein (PrPC is a cell surface glycoprotein mainly expressed in neurons, whose misfolded isoforms generate the prion responsible for incurable neurodegenerative disorders. Whereas PrPC involvement in prion propagation is well established, PrPC physiological function is still enigmatic despite suggestions that it could act in cell signal transduction by modulating phosphorylation cascades and Ca2+ homeostasis. Because PrPC binds neurotoxic protein aggregates with high-affinity, it has also been proposed that PrPC acts as receptor for amyloid-β (Aβ oligomers associated with Alzheimer’s disease (AD, and that PrPC-Aβ binding mediates AD-related synaptic dysfunctions following activation of the tyrosine kinase Fyn.Here, use of gene-encoded Ca2+ probes targeting different cell domains in primary cerebellar granule neurons expressing, or not, PrPC allowed us to investigate whether PrPC regulates store-operated Ca2+ entry (SOCE and the implication of Fyn in this control. Our findings show that PrPC attenuates SOCE, and Ca2+ accumulation in the cytosol and mitochondria, by constitutively restraining Fyn activation and tyrosine phosphorylation of STIM1, a key molecular component of SOCE. This data establishes the existence of a PrPC-Fyn-SOCE triad in neurons.We also demonstrate that treating cerebellar granule and cortical neurons with soluble Aβ(1-42 oligomers abrogates the control of PrPC over Fyn and SOCE, suggesting a PrPC-dependent mechanism for Aβ-induced neuronal Ca2+ dyshomeostasis.

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

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

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.

A Determination of V205 Activity in Corrosive Molten Vanadate-Sulfate Phases

National Research Council Canada - National Science Library

Jones, Robert

1994-01-01

.... We have recently devised a thermogravimetric (TGA)/S03 equilibrium technique that could potentially be used to 'chart' the V2O5 activity in vanadate-sulfate melts over a wide range of Na/V ratios, SO3 partial pressures and temperatures...

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

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.

Evaluation of sunlight induced structural changes and their effect on the photocatalytic activity of V{sub 2}O{sub 5} for the degradation of phenols

Energy Technology Data Exchange (ETDEWEB)

Aslam, M. [Centre of Excellence in Environmental Studies (CEES), King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Ismail, Iqbal M.I. [Centre of Excellence in Environmental Studies (CEES), King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Salah, Numan [Centre of Nanotechnology, King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Chandrasekaran, S. [Centre of Excellence in Environmental Studies (CEES), King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Qamar, M.Tariq [Centre of Excellence in Environmental Studies (CEES), King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Hameed, A., E-mail: afmuhammad@kau.edu.sa [Centre of Excellence in Environmental Studies (CEES), King Abdulaziz University, Jeddah 21589 (Saudi Arabia); National Centre for Physics, Quaid-e-Azam University, Islamabad 44000 (Pakistan)

2015-04-09

Highlights: • The interaction of UV photons of sunlight induces defects in V{sub 2}O{sub 5}. • The photon induced defects promotes the trapping and transfer of excited electrons. • The nature of the substituent at 2-position affects the degradation process. • The formation of the intermediates is influenced by the nature of substituents. • The released ions are subjected further transformation. - Abstract: Despite knowing the fact that vanadium pentoxide is slightly soluble in aqueous medium, its photocatalytic activity was evaluated for the degradation of phenol and its derivatives (2-hydroxyphenol, 2-chlorophenol, 2-aminophenol and 2-nitrophenol) in natural sunlight exposure. The prime objective of the study was to differentiate between the homogeneous and heterogeneous photocatalysis incurred by dissolved and undissolved V{sub 2}O{sub 5} in natural sunlight exposure. V{sub 2}O{sub 5} was synthesized by chemical precipitation procedure using Triton X-100 as morphology mediator and characterized by DRS, PLS, Raman, FESEM and XRD. A lower solubility of ∼5% per 100 ml of water at 23 °C was observed after calcination at 600 °C. The study revealed no contribution of the dissolved V{sub 2}O{sub 5} in the photocatalytic process. In sunlight exposure, V{sub 2}O{sub 5} powder exhibited substantial activity for the degradation, however, a low mineralization of phenolic substrates was observed. The initial low activity of V{sub 2}O{sub 5} followed by a sharp increase both in degradation and mineralization in complete spectrum sunlight exposure, was further investigated that revealed the decrease in the bandgap and the reduction in the particle size with the interaction of UV photons (<420 nm) as this effect was not observable in the exposure of visible region of sunlight. The role of the chemically different substituents attached to an aromatic ring at 2-positions and the secondary interaction of released ions during the degradation process with the reactive

Photocatalytic activity of V doped ZnO nanoparticles thin films for the removal of 2- chlorophenol from the aquatic environment under natural sunlight exposure.

Science.gov (United States)

Salah, Numan; Hameed, A; Aslam, M; Babkair, Saeed S; Bahabri, F S

2016-07-15

Vanadium doped ZnO powders were used as precursors to deposit thin films of V(5+) incorporated ZnO nanoparticles on glass substrates by the pulsed laser deposition technique. The observed variations in Raman signals, visible region shift in the diffuse reflectance spectra along with a small shift in the (101) reflections of the X-ray diffraction (XRD) confirmed the insertion of V(5+) ions in ZnO lattice. No other additional reflection in the XRD results other than ZnO further endorsed the occupation of lattice positions by V entities rather than independent oxide formation. The asymmetric XPS peaks of Zn2p and V2p core levels confirmed the existence of both in the vicinity. The existence of minimal proportion of V(3+) along with V(5+) states varied the alteration of the oxidation states V in the synthetic route. The SEM images at various resolutions displayed the uniform distribution identical nanoparticles without the presence of additional phases in the deposited films. The SEM cross-section measurements revealed the uniform thickness of ∼90 nm of each film, whereas the surface studies of the films were performed by AFM. The as-synthesized films were tested for photocatalytic activity in sunlight illumination for the removal of 2-chlorophenol. The unique feature of the study was the estimation of the photocatalytic activity 20 ppm of 2-chlorophenol by exposing the low exposed area. The degradation of the substrate was measured by liquid phase UV-vis spectroscopy, whereas total organic carbon measurement revealed the mineralization of the substrate. The released Cl(-) ions were also measured by ion chromatography. The estimated flatband potentials and pHzpc values of the V doped materials, by Mott-Schottky analysis and zeta potential measurements respectively, were correlated with the photocatalytic activity. The kinetics of the photocatalytic degradation/mineralization process was estimated and results were correlated with the plausible mechanism. Copyright �

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

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.

Radiological characterisation of V1 NPP technological systems and buildings - Activation

International Nuclear Information System (INIS)

Kristofova, Kristina; Rapant, Tibor; Svitek, Jaroslav

2012-01-01

V1 NPP at Jaslovske Bohunice site has been finally shutdown after 28 years of successful operation in 2006 (Unit 1) and 2008 (Unit 2). At present, both units are finally shutdown and since July 2011 under decommissioning license. The preparation of V1 NPP decommissioning has been supported and partly financed by the Bohunice International Decommissioning Support Fund (BIDSF), under the administration of the European Bank for Reconstruction and Development. From 06/2008 to 12/2011 AMEC Nuclear Slovakia, together with partners STM Power and EWN GmbH, carried out BIDSF B6.4 project - Decommissioning database development (DDB). The main purpose of the B6.4 project was to develop a physical and radiological inventory database to support V1 NPP decommissioning process planning and performance. One of the specific deliverable tasks within the B6.4 project was deliverable D12 - Characterization of activated equipment and civil structures based on measurement, sampling and analyses performed on the samples. The scope of deliverable services within D12 task consisted of: 1. Categorization of activated components ; 2. Development of single working programs for their radiological monitoring and sampling ; 3. Preparation of sampling device and revision of all handling equipment; 4. Dose rate monitoring and sampling of: - Civil structures from reactors shaft on both units ; - Components placed in HLW storage, (so called 'Mogilnik') - connection rods, absorbers ; of control rod assemblies and neutron flux measurement channels ; - Reactor pressure vessel and shielding assemblies at both units of V1 NPP, reactor; internals from Unit 2 of V1 NPP; 5. Analysis of samples ; 6. Determination of radiological inventory ; 7. Import of radiological data for activated components into DDB. During sampling, mainly remotely controlled sampling device and radiation resistant camera with LED lightening for visual checking of all performed activities was used. In total, 125 samples have been taken

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

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.

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.

Beam Tracking in Switched-Beam Antenna System for V2V Communication

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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.

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.

Identification of amino acids essential for the human parainfluenza type 2 virus V protein to lower the intracellular levels of the STAT2

International Nuclear Information System (INIS)

Kozuka, Yuji; Yamashita, Yasufumi; Kawano, Mitsuo; Tsurudome, Masato; Ito, Morihiro; Nishio, Machiko; Komada, Hiroshi; Ito, Yasuhiko

2003-01-01

The V protein of SV41 targets STAT1, while a specific loss of STAT2 is induced by the hPIV2 V protein. We established HeLa cells constitutively expressing various chimeric proteins between the hPIV2 and SV41 V proteins, and which STAT (STAT1 or 2) was expressed in these cells was analyzed. Both the P-V common domain and the V specific domain of hPIV2 V protein are necessary for STAT2 lowering. The internal domain (aa145-173) containing a large number of nonidentical amino acids between hPIV2 and SV41 does not direct STAT tropism, and the regions necessary for STAT2 lowering are discontinuous. The N-terminal domain (aa1-104) and the internal domain (aa126-196) of the hPIV2 V protein do not determine STAT tropism. HeLa cells expressing A105E or H108P show distinct expression of STAT2, but do show low expression or a loss of STAT1, indicating that the amino acid residues 105 and 108 of the hPIV2 V protein are essential for STAT2 lowering. Interestingly, there is an important amino acid(s) in the region (aa121-125) for STAT2 lowering, and the presence of either amino acid residue 123 or 125 of the hPIV2 V protein is necessary for lowering of STAT2. In addition, HeLa cells expressing S216D or 1217R expressed STAT2, but no STAT1, indicating that the amino acid residues 216 and 217 of the hPIV2 V protein are indispensable for STAT2 lowering. HeLa/hPIV2V cells and HeLa/S104/P are resistant to IFN-β, while they are sensitive to IFN-γ. On the other hand, HeLa/SV41V, HeLa/S216D, and HeLa1217R cells are resistant to both IFNs. Intriguingly, HeLa/A105E and HeLa/H108P cells were found to be sensitive to IFN-γ

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

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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.

Constitutive phosphorylation of Shc proteins in human tumors

DEFF Research Database (Denmark)

Pelicci, G; Lanfrancone, L; Salcini, A E

1995-01-01

The Shc gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are ubiquitously expressed and are downstream targets and effectors of activated tyrosine kinases (TK). We investigated tyrosine-phosphorylation of Shc proteins in normal and transformed...... of the Shc-associated phosphoproteins (EGFR, PDGFR, erbB-2, Met, bcr-abl, H4-ret) bound both the Shc- and Grb2-SH2 domains in vitro; others (p175; p70-p80) only the Shc-SH2 domain and yet others (p140) only the Grb2-SH3 domains. These results indicate that Shc proteins are common substrates of constitutively...

Predominant constitutive CFTR conductance in small airways

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Lytle Christian

2005-01-01

Full Text Available Abstract Background The pathological hallmarks of chronic obstructive pulmonary disease (COPD are inflammation of the small airways (bronchiolitis and destruction of lung parenchyma (emphysema. These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter. Methods We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. Results In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25, but when gluconate replaced luminal Cl-, the bionic Cl- diffusion potentials (-58 ± 3 mV; n = 25 were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl- permeability was at least 5 times greater than Na+ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM+IBMX (100 μM, ATP (100 μM, or adenosine (100 μM, but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM, GlyH-101* (5–50 μM, and CFTRInh-172* (5 μM. RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. Conclusion These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR.

Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms

International Nuclear Information System (INIS)

Nakaya, Y; Shide, K; Niwa, T; Homan, J; Sugahara, S; Horio, T; Kuramoto, K; Kotera, T; Shibayama, H; Hori, K; Naito, H; Shimoda, K

2011-01-01

Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC 50 ) of <1 n, and had 30–50-fold greater selectivity for JAK2 over other JAK-family kinases, such as JAK1, JAK3 and tyrosine kinase 2. In addition to JAK2, NS-018 inhibited Src-family kinases. NS-018 showed potent antiproliferative activity against cell lines expressing a constitutively activated JAK2 (the JAK2V617F or MPLW515L mutations or the TEL–JAK2 fusion gene; IC 50 =11–120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs

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 ...

Mn-Ce-V-WOx/TiO2 SCR Catalysts: Catalytic Activity, Stability and Interaction among Catalytic Oxides

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Xuteng Zhao

2018-02-01

Full Text Available A series of Mn-Ce-V-WOx/TiO2 composite oxide catalysts with different molar ratios (active components/TiO2 = 0.1, 0.2, 0.3, 0.6 have been prepared by wet impregnation method and tested in selective catalytic reduction (SCR of NO by NH3 in a wide temperature range. These catalysts were also characterized by X-ray diffraction (XRD, Transmission Electron Microscope (TEM, in situ Fourier Transform infrared spectroscopy (in situ FTIR, H2-Temperature programmed reduction (H2-TPR and X-ray photoelectron spectroscopy (XPS. The results show the catalyst with a molar ratio of active components/TiO2 = 0.2 exhibits highest NO conversion value between 150 °C to 400 °C and good resistance to H2O and SO2 at 250 °C with a gas hourly space velocity (GHSV value of 40,000 h−1. Different oxides are well dispersed and interact with each other. NH3 and NO are strongly adsorbed on the catalyst surface and the adsorption of the reactant gas leads to a redox cycle with the valence state change among the surface oxides. The adsorption of SO2 on Mn4+ and Ce4+ results in good H2O and SO2 resistance of the catalyst, but the effect of Mn and Ce are more than superior water and sulfur resistance. The diversity of valence states of the four active components and their high oxidation-reduction performance are the main reasons for the high NO conversion in this system.

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.

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...

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

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...

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

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...

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...

Impact of JAK2V617F Mutation Burden on Disease Phenotype in Chinese Patients with JAK2V617F-positive Polycythemia Vera (PV) and Essential thrombocythemia (ET).

Science.gov (United States)

Zhao, Shixiang; Zhang, Xiang; Xu, Yang; Feng, Yufeng; Sheng, Wenhong; Cen, Jiannong; Wu, Depei; Han, Yue

2016-01-01

Most patients with polycythemia vera (PV) and half of essential thrombocythemia (ET) possess an activating JAK2V617F mutation. The objective of this study was to better define the effect of JAK2V617F mutant allele burden on clinical phenotypes in Chinese patients, especially thrombosis. By real-time polymerase chain reaction (RT-PCR), the JAK2V617F mutation burden was detected in 170 JAK2V617F-positive patients, including 54 PV and 116 ET. The results showed that JAK2V617F allele burden was higher in PV than in ET (PET (68.5% VS 26.7%) (PET patients showed increased JAK2V617F allele burden in the group with higher hemoglobin (HGB above 150 g/L) (PET. In PV patients, JAK2V617F mutation burden had influence on WBC counts. And the clinical characteristics of ET patients, such as WBC counts, hemoglobin level, splenomegaly and thrombosis, were influenced by JAK2V617F mutation burden. Male, high hemoglobin (HGB above 150 g/L), and increased JAK2V617F mutation burden (JAK2V617F allele burden ≥ 16.5%) were risks of thrombosis (PET patients by Logistic Regression.

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.

Uniformly active phase loaded selective catalytic reduction catalysts (V{sub 2}O{sub 5}/TNTs) with superior alkaline resistance performance

Energy Technology Data Exchange (ETDEWEB)

Wang, Haiqiang; Wang, Penglu [Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental & Resources Science, Zhejiang University, 310058 Hangzhou (China); Zhejiang Provincial Engineering Research Center of Industrial Boiler & Furnace Flue Gas Pollution Control, Hangzhou 310027 (China); Chen, Xiongbo [South China Institute of Environmental Sciences, Ministry of Environmental Protection, Guangzhou 510655 (China); Wu, Zhongbiao, E-mail: zbwu@zju.edu.cn [Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental & Resources Science, Zhejiang University, 310058 Hangzhou (China); Zhejiang Provincial Engineering Research Center of Industrial Boiler & Furnace Flue Gas Pollution Control, Hangzhou 310027 (China)

2017-02-15

Highlights: • VOSO{sub 4} exhibited better synergistic effect with titanate nanotubes than NH{sub 4}VO{sub 3}. • Ion-exchange reaction occurs between VOSO{sub 4} and titanate nanotubes. • Ion-exchange resulting in uniformly vanadium distribution on titanate nanotubes. • VOSO{sub 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{sub 4}VO{sub 3} and VOSO{sub 4}) were used to synthesize deNO{sub x} catalysts. The results showed that VOSO{sub 4} exhibited better synergistic effect with titanate nanotubes than NH{sub 4}VO{sub 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{sup 5+}/V{sup 4+} redox cycles and superior oxygen mobility were achieved. Besides, VOSO{sub 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{sub 2}O{sub 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.

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

Comparative stability, toxicity and anti-leishmanial activity of triphenyl antimony(v) and bismuth(v) α-hydroxy carboxylato complexes.

Science.gov (United States)

Duffin, Rebekah N; Blair, Victoria L; Kedzierski, Lukasz; Andrews, Philip C

2018-01-15

A series of triphenyl Sb(v) and Bi(v) α-hydroxy carboxylato complexes of the general formula [MPh 3 (O 2 CROH) 2 ] and [MPh 3 (O 2 CRO)] have been successfully synthesised and characterised, and subsequently assayed for their comparative activity towards Leishmania parasites and human fibroblast cells. Four complexes are novel; [SbPh 3 Gly], [BiPh 3 (GlyH) 2 ], [SbPh 3 (R-ManH) 2 ] and [SbPh 3 (S-ManH) 2 ], and have been structurally characterised through X-ray diffraction. These were combined in the study with the known complexes; ([SbPh 3 (R-Man)], [SbPh 3 (S-Man)], [BiPh 3 (R-ManH) 2 ], [BiPh 3 (R-ManH) 2 ], [SbPh 3 (BenzH) 2 ], [BiPh 3 (BenzH) 2 ], for which the crystal structures of [BiPh 3 (S-ManH) 2 ] and [BiPh 3 (R-Man) 2 ] have now been authenticated (GlyH 2 = glycolic acid, R/S-ManH 2 = mandelic acid, BenzH 2 = benzilic acid). The complexes adopt a typical bipyramidal 7-coordinate geometry with the phenyl rings occupying the equatorial plane, and the ligands on the axial. In contrast to previous studies the Bi(v) compounds show a relatively high degree of stability in DMEM culture media. Promastigote and human fibroblast cell assays showed the Bi(v) analogues to be non-selectively toxic with a respective IC 50 range of 3.58-6.33 μM and 5.83-7.01 μM. In contrast, the Sb(v) analogues provided much greater selectivity (promastigotes 12.5-20.7; fibroblasts 72.8-≥100 μM). Assessment of the Sb(v) complexes against amastigotes at 10 μM showed them to be effective with % infection values ranging from 9.5 ± 0.5-30 ± 1.3.

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)

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.

Characterization of 2 MeV, 4 MeV, 6 MeV and 18 MeV buildup caps for use with a 0.6 cubic centimeter thimble ionization chamber

International Nuclear Information System (INIS)

Salyer, R.L.; VanDenburg, J.W.; Prinja, A.K.; Kirby, T.; Busch, R.; Hong-Nian Jow

1996-07-01

The purpose of this research is to characterize existing 2 MeV, 4 MeV and 6 MeV buildup caps, and to determine if a buildup cap can be made for the 0.6 cm 3 thimble ionization chamber that will accurately measure exposures in a high-energy photon radiation field. Two different radiation transport codes were used to computationally characterize existing 2 MeV, 4 MeV, and 6 MeV buildup caps for a 0.6 cm 3 active volume thimble ionization chamber: ITS, The Integrated TIGER Series of Coupled Electron-Photon Monte Carlo Transport Codes; and CEPXS/ONEDANT, A One-Dimensional Coupled Electron-Photon Discrete Ordinates Code Package. These codes were also used to determine the design characteristics of a buildup cap for use in the 18 MeV photon beam produced by the 14 TW pulsed power HERMES-III electron accelerator. The maximum range of the secondary electron, the depth at which maximum dose occurs, and the point where dose and collision kerma are equal have been determined to establish the validity of electronic equilibrium. The ionization chamber with the appropriate buildup cap was then subjected to a 4 MeV and a 6 MeV bremmstrahlung radiation spectrum to determine the detector response

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...

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

The Effect of Acidic and Redox Properties of V2O5/CeO2-ZrO2 Catalysts in Selective Catalytic Reduction of NO by NH3

DEFF Research Database (Denmark)

Putluru, Siva Sankar Reddy; Riisager, Anders; Fehrmann, Rasmus

2009-01-01

V2O5 supported ZrO2 and CeO2–ZrO2 catalysts were prepared and characterized by N2 physisorption, XRPD, TPR, and NH3-TPD methods. The influence of calcination temperature from 400 to 600 °C on crystallinity, acidic and redox properties were studied and compared with the catalytic activity...... in the selective catalytic reduction (SCR) of NO with ammonia. The surface area of the catalysts decreased gradually with increasing calcination temperature. The SCR activity of V2O5/ZrO2 catalysts was found to be related with the support crystallinity, whereas V2O5/CeO2–ZrO2 catalysts were also dependent...... on acidic and redox properties of the catalyst. The V2O5/CeO2–ZrO2 catalysts showed high activity and selectivity for reduction of NO with NH3....

Measurement of 24.3 keV activation cross sections with the iron filter technique

International Nuclear Information System (INIS)

Rimawi, K.; Chrien, R.E.

1975-01-01

By using high-resolution detection techniques, intensities of specific activation lines from 197 Au(n,gamma), 238 U(n,gamma), 127 I(n,gamma), and 115 In(n,gamma) [54 min + 2.2 sec] were recorded, by using the BNL HFBR iron-filtered neutron beam. From a com- parison with the reaction 10 B(n,αgamma), cross sections at 24.3 keV were determined. (24.3 keV neutron activation cross sections, relative 10 B standard). (4 figures) (U.S.)

Synthesis, characterization and catalytic activity of two novel cis - dioxovanadium(V) complexes: [VO{sub 2}(L)] and [VO{sub 2}(HLox)

Energy Technology Data Exchange (ETDEWEB)

Silva, Natalia M.L.; Chacon, Eluzir P.; Resende, Jackson A.L.C.; Carneiro, Jose Walkimar de M.; Lanznaster, Mauricio, E-mail: mlanz@vm.uff.b [Universidade Federal Fluminense (IQ/UFF), Niteroi, RJ (Brazil). Inst. de Quimica; Pinheiro, Carlos B. [Universidade Federal de Minas Gerais (DF/UFMG), Belo Horizonte (Brazil). Dept. de Fisica; Fernandez, Tatiana L.; Scarpellini, Marciela [Universidade Federal do Rio de Janeiro (IQ/UFRJ), RJ (Brazil). Inst. de Quimica

2011-07-01

Two novel complexes, [VO{sub 2}(L)] (1) and [VO{sub 2}(HLox)] (2), were synthesized and characterized by IV, UV-Vis and NMR spectroscopy, cyclic voltammetry, elemental analysis and X-ray diffraction. The synthesis of a new ligand, H{sub 2}Lox, is also described. Complexes 1 and 2 were obtained by the reaction of [VO(acac){sub 2}] with the ligands HL and H{sub 2}Lox, respectively. Alternatively, 2 was also obtained by the reaction of HL with [VO(acac)2] in the presence of hydroxylamine, and by the reaction of 1 with hydroxylamine. Crystallographic data show that complexes 1 and 2 have similar molecular structures, in which the cis-dioxovanadium(V) center is coordinated to L- or HLox{sup -}, respectively, in a distorted octahedral environment. The catalytic activity of these compounds towards cyclohexane oxidation was evaluated using H{sub 2}O{sub 2} and t-BuOOH as oxidants. Both complexes presented > 70% selectivity for cyclohexylhydroperoxide formation. B3LYP/6.31G(d) calculations were used to confirm the geometry and to help assign the electronic spectra. (author)

The Constitutional Court in light of interpretive decisions in normative control proceedings

Directory of Open Access Journals (Sweden)

Stojanović Dragan

2016-01-01

Full Text Available In a legal system based on the principle of the separation of powers, constitutional judicature is necessarily (given the nature of its social function at the intersection of law and politics. Thus, constitutional judiciary is required to preserve political neutrality, particularly in relation to political (legislative and executive authorities. The paper analyzes the principal issues pertaining to constitutional court interpretation, particularly in light of observing the principle of the separation of powers that the constitutional judiciary is bound to abide by and considering the role of the constitutional court as an institution standing at the intersection of law and politics. Every constitutional court is required to be politically neutral and independent from daily politics, which is the major factor in delineating not only the overall boundaries of the constitutional control of the normative framework but also in ensuring the independent and unbiased activity of the constitutional court in the process of interpreting the Constitution and the laws. The constitutional control function shall not be politicized, and it must be exercised only through legal reasoning. Consequently, in the process of constitutional interpretation, the Constitutional Court of Serbia has to develop and consistently pursue a doctrine of self-restraint, thus refraining from politically-driven assessment which is the exclusive duty of political authorities. A closer examination of the doctrine of self-restraint in recent constitutional practice shows that the most prominent elements of this doctrine are relatively new interpretative constructions and legal formulations of constitutional court, which reinforce not only the political neutrality of the constitutional judiciary but also its role as 'the negative legislator'. Yet, some of these constructions may be challenged because their excessive and often inadequate application has resulted in a kind of 'self

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.

Military Guilty Plea Inquiry: Some Constitutional Considerations.

Science.gov (United States)

1987-01-01

have given some constitutional definition to the requirement that a plea be voluntarily made. A threat by FBI agents to publish untrue statements about...Townsend v. Burke, the Supreme Court held that, where an accused was held incommunicado for forty hours by government 53 agents , his guilty plea...understands the sentence limitations imposed by the agreement; (4) strike down conditions in the pretrial agree- ment which are violative of the law, public

From Opera to Real Democracy: Popular Constitutionalism and Web 2.0

Directory of Open Access Journals (Sweden)

Elizabeth Dale

2013-01-01

Full Text Available On March 17, 2011 the conductor Riccardo Muti stood in the orchestra pit at the Teatro dell’Opera di Roma and, in the presence of the Italian Prime Minister, Silvio Berlusconi, and the Italian President, Giorgio Napolitano, denounced the Italian government’s cuts to funding for the arts and culture. He then invited the entire audience to join the opera’s chorus in an encore of Va’ Pensiero, the hymn of the Hebrew slaves in Nabucco, to protest the cuts. Within two days of the sing-a-long, the Italian government reversed the course it set more than ten months before and agreed to a tax that would be used to restore funds to the arts and culture budget. This article traces how and why these acts of protest in Italy developed, succeeded, and then were appropriated by transnational activists interested in encouraging popular constitutionalism. Because the entire process made considerable use of Facebook, blogs, YouTube, and Twitter, this case study simultaneously explores how a popular protest became a successful expression of popular constitutionalism, and considers how the messages of that protest evolved across a transnational public sphere that encompassed Web 2.0.

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...

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....

Rights of Minors and Constitutional Politics in the German Länder. Legal Framework, Party Strategies, and Constitutional Amendments

Directory of Open Access Journals (Sweden)

Lorenz Astrid

2015-11-01

Full Text Available The article analyses constitutional politics in the German Länder in the field of minors’ rights. Since this issue seems a purely legal matter dealt with at the federal, European and international level, we should expect similar, almost identically shaped policies at the Länder level. However, the analysis brings considerable variations of constitutional activities in this field to the fore: time, frequency, and contents of respective initiatives vary significantly in the period from 1999 to 2014. These variations were due to different party strategies, diverging party platforms and majority constellations in the Länder. The analysis also shows that the public arguments brought forward in favour of constitutional amendments refer only weakly and randomly to legal provisions and processes at other levels. The political debate supporting extended children's rights rather refers to general observations, to the specific regional context, and constitutional provisions in other Länder. At least with regard to this issue, the multi-level system did not systematically impact on constitutional politics in the Länder. It rather can be understood as an opportunity structure providing parties with multiple realms in which they can pursue their goals. Thus the study shows that federal and regional party strategies are key factors in explaining policy diffusion in multilevel systems.

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.

Type IIIa cracking at 2CrMo welds in 1/2CrMoV pipework

Energy Technology Data Exchange (ETDEWEB)

Brett, S J; Smith, P A [National Power plc, Swindon (United Kingdom)

1999-12-31

The most common form of in-service defect found today on the welds of National Power`s 1/2CrMoV pipework systems is Type IV cracking which occurs in intercritically transformed material at the edge of the heat affected zone. However an alternate form of cracking, termed IIIa, which occurs close to the weld fusion line in fully grain refined heat affected zones, has also been observed. The incidence of Type IIIa cracking has increased in recent years and these defects now constitute a significant part of the total recorded crack population. This presentation describes Type IIIa cracking and compares and contrasts it with the better documented Type IV cracking. Particular reference is made to the role of carbon diffusion at the weld fusion line in promoting Type IIIa damage in preference to Type IV. (orig.) 5 refs.

Type IIIa cracking at 2CrMo welds in 1/2CrMoV pipework

Energy Technology Data Exchange (ETDEWEB)

Brett, S.J.; Smith, P.A. [National Power plc, Swindon (United Kingdom)

1998-12-31

The most common form of in-service defect found today on the welds of National Power`s 1/2CrMoV pipework systems is Type IV cracking which occurs in intercritically transformed material at the edge of the heat affected zone. However an alternate form of cracking, termed IIIa, which occurs close to the weld fusion line in fully grain refined heat affected zones, has also been observed. The incidence of Type IIIa cracking has increased in recent years and these defects now constitute a significant part of the total recorded crack population. This presentation describes Type IIIa cracking and compares and contrasts it with the better documented Type IV cracking. Particular reference is made to the role of carbon diffusion at the weld fusion line in promoting Type IIIa damage in preference to Type IV. (orig.) 5 refs.

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....

Pharmacokinetic properties of radiolabeled mutant Interleukin-2v: a PET imaging study.

Science.gov (United States)

Hartimath, Siddesh V; Manuelli, Valeria; Zijlma, Rolf; Signore, Alberto; Nayak, Tapan K; Freimoser-Grundschober, Anne; Klein, Christian; Dierckx, Rudi A J O; de Vries, Erik F J

2018-01-23

Interleukin-2 (IL2) is a cytokine that can stimulate cytotoxic immune cells to attack infected and malignant cells. Unfortunately, IL2 can also cause serious immune-related toxicity. Recently, a mutant of IL2 (IL2v) with abolished CD25 binding, increased plasma half-life and less toxicity was engineered. Unlike wild-type IL2 (wt-IL2), mutant IL2v does not bind to the α-subunit (CD25) of the high affinity IL2αβγ receptor, but only to its β and γ subunit. Here, we investigated the biological properties of IL2v and compared with the wt-IL2 using fluorine-18 and PET. [ 18 F]FB-IL2v binds specifically to IL2 receptors (IL2R) on activated human peripheral blood monocytes (hPBMCs) and is cleared mainly by the kidneys (Balb/c mice). [ 18 F]FB-IL2v PET studies in SCID mice injected with hPBMCs revealed high uptake in the implant (0.85 ± 0.15 SUV), which was significantly reduced after pretreatment with wt-IL2 or mutant IL2v (SUV 0.26 ± 0.1 and 0.46 ± 0.1, p FB-IL2v to IL2R was reversible. The volume of distribution (V T ) and the non-displaceable binding potential (BP nd ) of mutant [ 18 F]FB-IL2v in the implant were approximately 3 times lower than those of wild-type [ 18 F]FB-IL2 ( p FB-IL2v in the implant ( p FB-IL2 binds stronger to IL2R and has faster kinetics than [18F]FB-IL2v, which makes it less suitable as a therapeutic drug. [ 18 F]FB-IL2v, on the other hand, seems to have better properties for use as a therapeutic drug.

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...

Forum: Reconsidering the Supreme Court's "Rodriguez" Decision--Is There a Federal Constitutional Right to Education?

Science.gov (United States)

Ogletree, Charles J., Jr.; Robinson, Kimberly Jenkins; Lindseth, Alfred A.; Testani, Rocco E.; Peifer, Lee A.

2017-01-01

Does the U.S. Constitution guarantee a right to education? The Supreme Court declared that it does not in "San Antonio Independent School District v. Rodriguez," a 1973 case alleging that disparities in spending levels among Texas school districts violated students' constitutional rights. This issue's forum contains two essays. The first…

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.

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.

Key role of group v secreted phospholipase A2 in Th2 cytokine and dendritic cell-driven airway hyperresponsiveness and remodeling.

Directory of Open Access Journals (Sweden)

William R Henderson

Full Text Available Previous work has shown that disruption of the gene for group X secreted phospholipase A2 (sPLA2-X markedly diminishes airway hyperresponsiveness and remodeling in a mouse asthma model. With the large number of additional sPLA2s in the mammalian genome, the involvement of other sPLA2s in the asthma model is possible - in particular, the group V sPLA2 (sPLA2-V that like sPLA2-X is highly active at hydrolyzing membranes of mammalian cells.The allergen-driven asthma phenotype was significantly reduced in sPLA2-V-deficient mice but to a lesser extent than observed previously in sPLA2-X-deficient mice. The most striking difference observed between the sPLA2-V and sPLA2-X knockouts was the significant impairment of the primary immune response to the allergen ovalbumin (OVA in the sPLA2-V(-/- mice. The impairment in eicosanoid generation and dendritic cell activation in sPLA2-V(-/- mice diminishes Th2 cytokine responses in the airways.This paper illustrates the diverse roles of sPLA2s in the immunopathogenesis of the asthma phenotype and directs attention to developing specific inhibitors of sPLA2-V as a potential new therapy to treat asthma and other allergic disorders.

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”)....

Constitutional Politics, Constitutional Texts and Democratic Variety in Central and Eastern Europe

OpenAIRE

Blokker, Paul

2008-01-01

In the paper, it is argued that democratization in Central and Eastern Europe involves important forms of differentiation of democracy, rather than merely convergence to a singular – liberal-democratic, constitutional - model. One way of taking up democratic differentiation in post-communist societies is by analysing the constitutional documents of the new democratic orders, and the constitutional politics leading to the foundational documents. In a first step, the paper analyses constitution...

AISI/DOE Advanced Process Control Program Vol. 3 of 6: MICROSTRUCTURAL ENGINEERING IN HOT-STRIP MILLS Part 2 of 2: Constitutive Behavior Modeling of Steels Under Hot-Rolling Conditions; FINAL

International Nuclear Information System (INIS)

Yi-Wen Cheng; Patrick Purtscher

1999-01-01

This report describes the development of models for predicting (1) constitutive behaviors and (2) mechanical properties of hot-rolled steels as functions of chemical composition, microstructural features, and processing variables. The study includes the following eight steels: A36, DQSK, HSLA-V, HSLA-Nb, HSLA-50/Ti-Nb, and two interstitial-free (IF) grades. These developed models have been integrated into the Hot-Strip Mill Model (HSMM), which simulates the hot strip rolling mills and predicts the mechanical properties of hot-rolled products. The HSMM model has been developed by the University of British Columbia-Canada as a part of project on the microstructural engineering in hot-strip mills

Highly active sulfided CoMo catalysts supported on (ZrO{sub 2}–TiO{sub 2})/Al{sub 2}O{sub 3} ternary oxides

Energy Technology Data Exchange (ETDEWEB)

Escobar, José, E-mail: jeaguila@imp.mx [Instituto Mexicano del Petróleo, Eje Central Lázaro Cárdenas 152, Col. San Bartolo Atepehuacan, Gustavo A. Madero, México, D.F. 07730 (Mexico); De Los Reyes, José A., E-mail: jarh@xanum.uam.mx [Area de Ing. Química, UAM – Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa, México, D.F. 09340 (Mexico); Ulín, Carlos A. [Area de Ing. Química, UAM – Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa, México, D.F. 09340 (Mexico); Barrera, María C., E-mail: mcbdgavilan@gmail.com [Facultad de Ciencias Químicas, Universidad Veracruzana, Av. Universidad km. 7.5, Col. Santa Isabel, Coatzacoalcos, Veracruz, México, D.F. 96538 (Mexico)

2013-12-16

(ZrO{sub 2}–TiO{sub 2})/Al{sub 2}O{sub 3} ternary oxide at 20 mol% Al{sub 2}O{sub 3} (80% ZrO{sub 2}–TiO{sub 2}, in turn at 40–60 mol ratio) prepared by controlled co-precipitation (by urea thermal decomposition) of zirconium (ZrOCl{sub 2}·8H{sub 2}O) and titanium (TiCl{sub 4}) chlorides over a ground alumina substrate constitutes a promising material to be used as carrier of sulfided hydrodesulfurization (HDS) catalysts. After calcining (at 500 °C), the ternary oxide presented textural properties (S{sub g} = 387 m{sup 2} g{sup −1}, V{sub p} = 0.74 ml g{sup −1}, mean pore diameter = 7.6 nm) suitable to its utilization as carrier of catalysts applied in the oil-derived middle distillates HDS. As determined by temperature programmed-reduction and Raman and UV–vis spectroscopies ZrO{sub 2}–TiO{sub 2} deposition over alumina substrate resulted in decreased proportion of Mo{sup 6+} species in tetrahedral coordination on the oxidic impregnated material. As those species constitute hardly reducible precursors, their diminished concentration could be reflected in enhanced amount of Mo species susceptible of activation by sulfiding (H{sub 2}S/H{sub 2} at 400 °C) over our ternary carrier. Limiting the concentration of zirconia-titania (at 40–60 mol ratio) to 20 mol% in the mixed oxides support allowed the preparation of highly active promoted (by cobalt, at Co/(Co + Mo) = 0.3) MoS{sub 2} phase (at 2.8 atoms/nm{sup 2}), that formulation showing excellent properties in hydrodesulfurization (HDS) of both dibenzothiophene and highly-refractory 4,6-dimethyl-dibenzothiophene. Due to alike yields to various HDS products over CoMo/(ZrO{sub 2}–TiO{sub 2})/Al{sub 2}O{sub 3} and the corresponding Al{sub 2}O{sub 3}-supported formulation, presence of similar actives sites over those catalysts was strongly suggested. It seemed that enhanced concentration of octahedral Mo{sup 6+} over the oxidic impregnated precursor with (ZrO{sub 2}–TiO{sub 2})/Al{sub 2}O{sub 3

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...

A regression approach for zircaloy-2 in-reactor creep constitutive equations

International Nuclear Information System (INIS)

Yung Liu, Y.; Bement, A.L.

1977-01-01

In this paper the methodology of multiple regressions as applied to zircaloy-2 in-reactor creep data analysis and construction of constitutive equation are illustrated. While the resulting constitutive equation can be used in creep analysis of in-reactor zircaloy structural components, the methodology itself is entirely general and can be applied to any creep data analysis. From data analysis and model development point of views, both the assumption of independence and prior committment to specific model forms are unacceptable. One would desire means which can not only estimate the required parameters directly from data but also provide basis for model selections, viz., one model against others. Basic understanding of the physics of deformation is important in choosing the forms of starting physical model equations, but the justifications must rely on their abilities in correlating the overall data. The promising aspects of multiple regression creep data analysis are briefly outlined as follows: (1) when there are more than one variable involved, there is no need to make the assumption that each variable affects the response independently. No separate normalizations are required either and the estimation of parameters is obtained by solving many simultaneous equations. The number of simultaneous equations is equal to the number of data sets, (2) regression statistics such as R 2 - and F-statistics provide measures of the significance of regression creep equation in correlating the overall data. The relative weights of each variable on the response can also be obtained. (3) Special regression techniques such as step-wise, ridge, and robust regressions and residual plots, etc., provide diagnostic tools for model selections

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.

A thermomechanical crystal plasticity constitutive model for ultrasonic consolidation

KAUST Repository

Siddiq, Amir

2012-01-01

We present a micromechanics-based thermomechanical constitutive model to simulate the ultrasonic consolidation process. Model parameters are calibrated using an inverse modeling approach. A comparison of the simulated response and experimental results for uniaxial tests validate and verify the appropriateness of the proposed model. Moreover, simulation results of polycrystalline aluminum using the identified crystal plasticity based material parameters are compared qualitatively with the electron back scattering diffraction (EBSD) results reported in the literature. The validated constitutive model is then used to simulate the ultrasonic consolidation process at sub-micron scale where an effort is exerted to quantify the underlying micromechanisms involved during the ultrasonic consolidation process. © 2011 Elsevier B.V. All rights reserved.

Synthesis, surface properties and optical characteristics of CuV{sub 2}O{sub 6} nanofibers

Energy Technology Data Exchange (ETDEWEB)

Wang, Fengyun, E-mail: fywang@qdu.edu.cn [College of Physics and Cultivation Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China); Zhang, Hongchao [College of Physics and Cultivation Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China); Liu, Lei [School of Materials Science and Engineering, Shandong University of Science and Technology, Qingdao 266590 (China); Shin, Byoungchul [Electronic Ceramics Center, Dong-Eui University, Busan, 614-714 (Korea, Republic of); Shan, Fukai, E-mail: fkshan@qdu.edu.cn [College of Physics and Cultivation Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China)

2016-07-05

In{sup 3+}-doped CuV{sub 2}O{sub 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{sub 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{sub 2}O{sub 6}:In{sup 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{sup 4+}/V{sup 5+} ions and induced-color centers was discussed on the proposed photocatalytic mechanism. The results demonstrated the promising potency of such In{sup 3+}-doped CuV{sub 2}O{sub 6} nanofibers for technological applications due to their high photo-activity and good cycling performance with the fiber morphology. - Highlights: • Recyclable α-CuV{sub 2}O{sub 6} nanofibers were successfully prepared via hydrothermal synthesis. • In-doped α-CuV{sub 2}O{sub 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

Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory epithelium

Directory of Open Access Journals (Sweden)

Hayoz Sébastien

2012-05-01

Full Text Available Abstract Background ATP is an extracellular signaling molecule with many ascribed functions in sensory systems, including the olfactory epithelium. The mechanism(s by which ATP is released in the olfactory epithelium has not been investigated. Quantitative luciferin-luciferase assays were used to monitor ATP release, and confocal imaging of the fluorescent ATP marker quinacrine was used to monitor ATP release via exocytosis in Swiss Webster mouse neonatal olfactory epithelial slices. Results Under control conditions, constitutive release of ATP occurs via exocytosis, hemichannels and ABC transporters and is inhibited by vesicular fusion inhibitor Clostridium difficile toxin A and hemichannel and ABC transporter inhibitor probenecid. Constitutive ATP release is negatively regulated by the ATP breakdown product ADP through activation of P2Y receptors, likely via the cAMP/PKA pathway. In vivo studies indicate that constitutive ATP may play a role in neuronal homeostasis as inhibition of exocytosis inhibited normal proliferation in the OE. ATP-evoked ATP release is also present in mouse neonatal OE, triggered by several ionotropic P2X purinergic receptor agonists (ATP, αβMeATP and Bz-ATP and a G protein-coupled P2Y receptor agonist (UTP. Calcium imaging of P2X2-transfected HEK293 “biosensor” cells confirmed the presence of evoked ATP release. Following purinergic receptor stimulation, ATP is released via calcium-dependent exocytosis, activated P2X1,7 receptors, activated P2X7 receptors that form a complex with pannexin channels, or ABC transporters. The ATP-evoked ATP release is inhibited by the purinergic receptor inhibitor PPADS, Clostridium difficile toxin A and two inhibitors of pannexin channels: probenecid and carbenoxolone. Conclusions The constitutive release of ATP might be involved in normal cell turn-over or modulation of odorant sensitivity in physiological conditions. Given the growth-promoting effects of ATP, ATP-evoked ATP

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.

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.

Constitutive endocytosis and turnover of the neuronal glycine transporter GlyT2 is dependent on ubiquitination of a C-terminal lysine cluster.

Directory of Open Access Journals (Sweden)

Jaime de Juan-Sanz

Full Text Available Inhibitory glycinergic neurotransmission is terminated by sodium and chloride-dependent plasma membrane glycine transporters (GlyTs. The mainly glial glycine transporter GlyT1 is primarily responsible for the completion of inhibitory neurotransmission and the neuronal glycine transporter GlyT2 mediates the reuptake of the neurotransmitter that is used to refill synaptic vesicles in the terminal, a fundamental role in the physiology and pathology of glycinergic neurotransmission. Indeed, inhibitory glycinergic neurotransmission is modulated by the exocytosis and endocytosis of GlyT2. We previously reported that constitutive and Protein Kinase C (PKC-regulated endocytosis of GlyT2 is mediated by clathrin and that PKC accelerates GlyT2 endocytosis by increasing its ubiquitination. However, the role of ubiquitination in the constitutive endocytosis and turnover of this protein remains unexplored. Here, we show that ubiquitination of a C-terminus four lysine cluster of GlyT2 is required for constitutive endocytosis, sorting into the slow recycling pathway and turnover of the transporter. Ubiquitination negatively modulates the turnover of GlyT2, such that increased ubiquitination driven by PKC activation accelerates transporter degradation rate shortening its half-life while decreased ubiquitination increases transporter stability. Finally, ubiquitination of GlyT2 in neurons is highly responsive to the free pool of ubiquitin, suggesting that the deubiquitinating enzyme (DUB ubiquitin C-terminal hydrolase-L1 (UCHL1, as the major regulator of neuronal ubiquitin homeostasis, indirectly modulates the turnover of GlyT2. Our results contribute to the elucidation of the mechanisms underlying the dynamic trafficking of this important neuronal protein which has pathological relevance since mutations in the GlyT2 gene (SLC6A5 are the second most common cause of human hyperekplexia.

Identification of the kinase that activates a nonmetazoan STAT gives insights into the evolution of phosphotyrosine-SH2 domain signaling.

Science.gov (United States)

Araki, Tsuyoshi; Kawata, Takefumi; Williams, Jeffrey G

2012-07-10

SH2 domains are integral to many animal signaling pathways. By interacting with specific phosphotyrosine residues, they provide regulatable protein-protein interaction domains. Dictyostelium is the only nonmetazoan with functionally characterized SH2 domains, but the cognate tyrosine kinases are unknown. There are no orthologs of the animal tyrosine kinases, but there are very many tyrosine kinase-like kinases (TKLs), a group of kinases which, despite their family name, are classified mainly as serine-threonine kinases. STATs are transcription factors that dimerize via phosphotyrosine-SH2 domain interactions. STATc is activated by phosphorylation on Tyr922 when cells are exposed to the prestalk inducer differentiation inducing factor (DIF-1), a chlorinated hexaphenone. We show that in a null mutant for Pyk2, a tyrosine-specific TKL, exposure to DIF-1 does not activate STATc. Conversely, overexpression of Pyk2 causes constitutive STATc activation. Pyk2 phosphorylates STATc on Tyr922 in vitro and complexes with STATc both in vitro and in vivo. This demonstration that a TKL directly activates a STAT has significant implications for understanding the evolutionary origins of SH2 domain-phosphotyrosine signaling. It also has mechanistic implications. Our previous work suggested that a predicted constitutive STATc tyrosine kinase activity is counterbalanced in vivo by the DIF-1-regulated activity of PTP3, a Tyr922 phosphatase. Here we show that the STATc-Pyk2 complex is formed constitutively by an interaction between the STATc SH2 domain and phosphotyrosine residues on Pyk2 that are generated by autophosphorylation. Also, as predicted, Pyk2 is constitutively active as a STATc kinase. This observation provides further evidence for this highly atypical, possibly ancestral, STAT regulation mechanism.

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