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Sample records for eif2b gef activity

  1. Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.

    Science.gov (United States)

    Tsai, Jordan C; Miller-Vedam, Lakshmi E; Anand, Aditya A; Jaishankar, Priyadarshini; Nguyen, Henry C; Renslo, Adam R; Frost, Adam; Walter, Peter

    2018-03-30

    Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo-electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  2. Multiple Sclerosis and EIF2B5: A Paradox or a Missing Link.

    Science.gov (United States)

    Zahoor, Insha; Haq, Ehtishamul; Asimi, Ravouf

    2017-01-01

    Multiple sclerosis (MS) is an encumbering inflammatory condition of the central nervous system (CNS) caused by axonal demyelination. There is sufficient evidence suggesting role of eukaryotic translation initiation factor 2B (EIF2B) gene family encoding the five subunits of eIF2B complex-α, β, γ, δ and ε respectively, in causing vanishing white matter (VWM) disease of the brain. Incidentally researchers have proposed overlapping between MS and VWM in terms of clinical, biochemical and genetic aspects, which incited us to write this chapter to explore the association between EIF2B5 and MS. eIF2B plays an essential role in translation initiation and its regulation in eukaryotes. Among EIF2B gene family, EIF2B5 gene encodes the catalytic and a crucial epsilon subunit of the eIF2B protein as most of the alterations have been found in this gene. The recent findings on the association between EIF2B5 and MS susceptibility point towards unfathomable and contentious role of EIF2B5 in MS development. This chapter briefly reviews the insights gleaned from recent studies conducted in understanding the association between EIF2B5 and MS risk. The need of hour is to conduct large scale conclusive studies aimed at expounding the mechanisms behind this relationship.

  3. Fusel Alcohols Regulate Translation Initiation by Inhibiting eIF2B to Reduce Ternary Complex in a Mechanism That May Involve Altering the Integrity and Dynamics of the eIF2B Body

    Science.gov (United States)

    Taylor, Eleanor J.; Campbell, Susan G.; Griffiths, Christian D.; Reid, Peter J.; Slaven, John W.; Harrison, Richard J.; Sims, Paul F.G.; Pavitt, Graham D.; Delneri, Daniela

    2010-01-01

    Recycling of eIF2-GDP to the GTP-bound form constitutes a core essential, regulated step in eukaryotic translation. This reaction is mediated by eIF2B, a heteropentameric factor with important links to human disease. eIF2 in the GTP-bound form binds to methionyl initiator tRNA to form a ternary complex, and the levels of this ternary complex can be a critical determinant of the rate of protein synthesis. Here we show that eIF2B serves as the target for translation inhibition by various fusel alcohols in yeast. Fusel alcohols are endpoint metabolites from amino acid catabolism, which signal nitrogen scarcity. We show that the inhibition of eIF2B leads to reduced ternary complex levels and that different eIF2B subunit mutants alter fusel alcohol sensitivity. A DNA tiling array strategy was developed that overcame difficulties in the identification of these mutants where the phenotypic distinctions were too subtle for classical complementation cloning. Fusel alcohols also lead to eIF2α dephosphorylation in a Sit4p-dependent manner. In yeast, eIF2B occupies a large cytoplasmic body where guanine nucleotide exchange on eIF2 can occur and be regulated. Fusel alcohols impact on both the movement and dynamics of this 2B body. Overall, these results confirm that the guanine nucleotide exchange factor, eIF2B, is targeted by fusel alcohols. Moreover, they highlight a potential connection between the movement or integrity of the 2B body and eIF2B regulation. PMID:20444979

  4. Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1 and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats

    Directory of Open Access Journals (Sweden)

    Philippe A. Melas

    2018-03-01

    Full Text Available Summary: Reduced eukaryotic Initiation Factor 2 (eIF2α phosphorylation (p-eIF2α enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN] reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A, the recruiter of protein phosphatase 1 (PP1. The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2α in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ΔFosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2α and the gateway drug properties of psychoactive cannabinoids. : Melas et al. show that psychoactive cannabinoids modulate levels of two eukaryotic initiation factors (eIF2α and eIF2B1 known to be involved in protein synthesis, memory formation, and drug sensitivity. Cannabinoid modulation of eIF2α in vivo is only observed in adolescent animals, and is associated with cross-sensitization to cocaine. Keywords: drug use, addiction, cannabis, marijuana, cocaine, epigenetics, eIF2a, CREB, GADD34, gateway drugs

  5. Vav1 GEF activity is required for T cell mediated allograft rejection.

    Science.gov (United States)

    Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L J; Weckbecker, Gisbert

    2012-06-01

    The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. No evidence for a role of Ile587Val polymorphism of EIF2B5 gene in multiple sclerosis in Kashmir Valley of India.

    Science.gov (United States)

    Zahoor, Insha; Asimi, Ravouf; Haq, Ehtishamul

    2015-12-15

    Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the nervous system with a profound genetic element. It is already known that alterations in Eukaryotic Translation Initiation Factor 2B (EIF2B) gene encoding the five subunits of eIF2B complex cause Vanishing White Matter (VWM) disease of the brain and emerging evidences have advocated certain resemblances between MS and VWM in terms of clinical and epidemiological characteristics, thus validating the association study between EIF2B and MS. Moreover, a recent study has implicated EIF2B5 Ile587Val (rs843358) polymorphism as a susceptibility factor for MS. In order to investigate the association of EIF2B5 Ile587Val polymorphism with MS susceptibility in Kashmir region in India, we screened EIF2B5 Exon 13 in 30 MS patients and 65 controls (a total of 95 participants). During the present course of study, we could not find statistically significant difference in the frequency of Ile587Val between MS patients and controls, thus indicating that such alteration does not appear to influence MS development in Kashmiri population. Our results provide evidence against a major role for Ile587Val polymorphism in MS susceptibility. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Infantile onset Vanishing White Matter disease associated with a novel EIF2B5 variant, remarkably long life span, severe epilepsy, and hypopituitarism.

    Science.gov (United States)

    Woody, April L; Hsieh, David T; McIver, Harkirtin K; Thomas, Linda P; Rohena, Luis

    2015-04-01

    Vanishing White Matter disease (VWM) is an inherited progressive leukoencephalopathy caused by mutations in the genes EIF2B1-5, which encode for the 5 subunits of the eukaryotic initiation factor 2B (eIF2B), a regulator of protein synthesis. VWM typically presents with acute neurological decline following febrile infections or minor head trauma, and subsequent progressive neurological and cognitive regression. There is a varied clinical spectrum of VWM, with earlier onset associated with more severe phenotypes. Brain magnetic resonance imaging is usually diagnostic with diffusely abnormal white matter, progressing over time to cystic degeneration. We are reporting on a patient with infantile onset VWM associated with three heterozygous missense variants in EIF2B5, including a novel missense variant on exon 6 of EIF2B5 (D262N), as well as an interstitial duplication at 7q21.12. In addition, our case is unusual because of a severe epilepsy course, a novel clinical finding of hypopituitarism manifested by hypothyroidism and adrenal insufficiency, and a prolonged life span with current age of survival of 4 years and 11 months. © 2015 Wiley Periodicals, Inc.

  8. [Association between homozygous c.318A>GT mutation in exon 2 of the EIF2B5 gene and the infantile form of vanishing white matter leukoencephalopathy].

    Science.gov (United States)

    Esmer, Carmen; Blanco Hernández, Gabriela; Saavedra Alanís, Víctor; Reyes Vaca, Jorge Guillermo; Bravo Oro, Antonio

    Vanishing white matter disease is one of the most frequent leukodystrophies in childhood with an autosomal recessive inheritance. A mutation in one of the genes encoding the five subunits of the eukaryotic initiation factor 2 (EIF2B5) is present in 90% of the cases. The diagnosis can be accomplished by the clinical and neuroradiological findings and molecular tests. We describe a thirteen-month-old male with previous normal neurodevelopment, who was hospitalized for vomiting, hyperthermia and irritability. On examination, cephalic perimeter and cranial pairs were normal. Hypotonia, increased muscle stretching reflexes, generalized white matter hypodensity on cranial tomography were found. Fifteen days after discharge, he suffered minor head trauma presenting drowsiness and focal seizures. Magnetic resonance showed generalized hypointensity of white matter. Vanishing white matter disease was suspected, and confirmed by sequencing of the EIF2B5 gene, revealing a homozygous c.318A> T mutation in exon 2. Subsequently, visual acuity was lost and cognitive and motor deterioration was evident. The patient died at six years of age due to severe pneumonia. This case contributes to the knowledge of the mutational spectrum present in Mexican patients and allows to extend the phenotype associated to this mutation. Copyright © 2017. Publicado por Masson Doyma México S.A.

  9. A Yeast Purification System for Human Translation Initiation Factors eIF2 and eIF2B epsilon and Their Use in the Diagnosis of CACH/VWM Disease

    NARCIS (Netherlands)

    de Almeida, R.A.; Fogli, A.; Gaillard, M.; Scheper, G.C.; Boesflug-Tanguy, O.; Pavitt, G.D.

    2013-01-01

    Recessive inherited mutations in any of five subunits of the general protein synthesis factor eIF2B are responsible for a white mater neurodegenerative disease with a large clinical spectrum. The classical form is called Childhood Ataxia with CNS hypomyelination (CACH) or Vanishing White Matter

  10. eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control.

    Science.gov (United States)

    Jennings, Martin D; Kershaw, Christopher J; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P; Costello, Joseph L; Donaldson, Ian J; Zhou, Yu; Pavitt, Graham D

    2016-11-16

    In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. GEFs: Dual regulation of Rac1 signaling.

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    Marei, Hadir; Malliri, Angeliki

    2017-04-03

    GEFs play a critical role in regulating Rac1 signaling. They serve as signaling nodes converting upstream signals into downstream Rac1-driven cellular responses. Through associating with membrane-bound Rac1, GEFs facilitate the exchange of GDP for GTP, thereby activating Rac1. As a result, Rac1 undergoes conformational changes that mediate its interaction with downstream effectors, linking Rac1 to a multitude of physiological and pathological processes. Interestingly, there are at least 20 GEFs involved in Rac1 activation, suggesting a more complex role of GEFs in regulating Rac1 signaling apart from promoting the exchange of GDP for GTP. Indeed, accumulating evidence implicates GEFs in directing the specificity of Rac1-driven signaling cascades, although the underlying mechanisms were poorly defined. Recently, through conducting a comparative study, we highlighted the role of 2 Rac-specific GEFs, Tiam1 and P-Rex1, in dictating the biological outcome downstream of Rac1. Importantly, further proteomic analysis uncovered a GEF activity-independent function for both GEFs in modulating the Rac1 interactome, which results in the stimulation of GEF-specific signaling cascades. Here, we provide an overview of our recent findings and discuss the role of GEFs as master regulators of Rac1 signaling with a particular focus on GEF-mediated modulation of cell migration following Rac1 activation.

  12. The Drosophila Arf GEF Steppke controls MAPK activation in EGFR signaling.

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    Hahn, Ines; Fuss, Bernhard; Peters, Annika; Werner, Tamara; Sieberg, Andrea; Gosejacob, Dominic; Hoch, Michael

    2013-06-01

    Guanine nucleotide exchange factors (GEFs) of the cytohesin protein family are regulators of GDP/GTP exchange for members of the ADP ribosylation factor (Arf) of small GTPases. They have been identified as modulators of various receptor tyrosine kinase signaling pathways including the insulin, the vascular epidermal growth factor (VEGF) and the epidermal growth factor (EGF) pathways. These pathways control many cellular functions, including cell proliferation and differentiation, and their misregulation is often associated with cancerogenesis. In vivo studies on cytohesins using genetic loss of function alleles are lacking, however, since knockout mouse models are not available yet. We have recently identified mutants for the single cytohesin Steppke (Step) in Drosophila and we could demonstrate an essential role of Step in the insulin signaling cascade. In the present study, we provide in vivo evidence for a role of Step in EGFR signaling during wing and eye development. By analyzing step mutants, transgenic RNA interference (RNAi) and overexpression lines for tissue specific as well as clonal analysis, we found that Step acts downstream of the EGFR and is required for the activation of mitogen-activated protein kinase (MAPK) and the induction of EGFR target genes. We further demonstrate that step transcription is induced by EGFR signaling whereas it is negatively regulated by insulin signaling. Furthermore, genetic studies and biochemical analysis show that Step interacts with the Connector Enhancer of KSR (CNK). We propose that Step may be part of a larger signaling scaffold coordinating receptor tyrosine kinase-dependent MAPK activation.

  13. UNC-73/Trio RhoGEF-2 Activity Modulates Caenorhabditis elegans Motility Through Changes in Neurotransmitter Signaling Upstream of the GSA-1/Gαs Pathway

    Science.gov (United States)

    Hu, Shuang; Pawson, Tony; Steven, Robert M.

    2011-01-01

    Rho-family GTPases play regulatory roles in many fundamental cellular processes. Caenorhabditis elegans UNC-73 RhoGEF isoforms function in axon guidance, cell migration, muscle arm extension, phagocytosis, and neurotransmission by activating either Rac or Rho GTPase subfamilies. Multiple differentially expressed UNC-73 isoforms contain a Rac-specific RhoGEF-1 domain, a Rho-specific RhoGEF-2 domain, or both domains. The UNC-73E RhoGEF-2 isoform is activated by the G-protein subunit Gαq and is required for normal rates of locomotion; however, mechanisms of UNC-73 and Rho pathway regulation of locomotion are not clear. To better define UNC-73 function in the regulation of motility we used cell-specific and inducible promoters to examine the temporal and spatial requirements of UNC-73 RhoGEF-2 isoform function in mutant rescue experiments. We found that UNC-73E acts within peptidergic neurons of mature animals to regulate locomotion rate. Although unc-73 RhoGEF-2 mutants have grossly normal synaptic morphology and weak resistance to the acetylcholinesterase inhibitor aldicarb, they are significantly hypersensitive to the acetylcholine receptor agonist levamisole, indicating alterations in acetylcholine neurotransmitter signaling. Consistent with peptidergic neuron function, unc-73 RhoGEF-2 mutants exhibit a decreased level of neuropeptide release from motor neuron dense core vesicles (DCVs). The unc-73 locomotory phenotype is similar to those of rab-2 and unc-31, genes with distinct roles in the DCV-mediated secretory pathway. We observed that constitutively active Gαs pathway mutations, which compensate for DCV-mediated signaling defects, rescue unc-73 RhoGEF-2 and rab-2 lethargic movement phenotypes. Together, these data suggest UNC-73 RhoGEF-2 isoforms are required for proper neurotransmitter signaling and may function in the DCV-mediated neuromodulatory regulation of locomotion rate. PMID:21750262

  14. UNC-73/trio RhoGEF-2 activity modulates Caenorhabditis elegans motility through changes in neurotransmitter signaling upstream of the GSA-1/Galphas pathway.

    Science.gov (United States)

    Hu, Shuang; Pawson, Tony; Steven, Robert M

    2011-09-01

    Rho-family GTPases play regulatory roles in many fundamental cellular processes. Caenorhabditis elegans UNC-73 RhoGEF isoforms function in axon guidance, cell migration, muscle arm extension, phagocytosis, and neurotransmission by activating either Rac or Rho GTPase subfamilies. Multiple differentially expressed UNC-73 isoforms contain a Rac-specific RhoGEF-1 domain, a Rho-specific RhoGEF-2 domain, or both domains. The UNC-73E RhoGEF-2 isoform is activated by the G-protein subunit Gαq and is required for normal rates of locomotion; however, mechanisms of UNC-73 and Rho pathway regulation of locomotion are not clear. To better define UNC-73 function in the regulation of motility we used cell-specific and inducible promoters to examine the temporal and spatial requirements of UNC-73 RhoGEF-2 isoform function in mutant rescue experiments. We found that UNC-73E acts within peptidergic neurons of mature animals to regulate locomotion rate. Although unc-73 RhoGEF-2 mutants have grossly normal synaptic morphology and weak resistance to the acetylcholinesterase inhibitor aldicarb, they are significantly hypersensitive to the acetylcholine receptor agonist levamisole, indicating alterations in acetylcholine neurotransmitter signaling. Consistent with peptidergic neuron function, unc-73 RhoGEF-2 mutants exhibit a decreased level of neuropeptide release from motor neuron dense core vesicles (DCVs). The unc-73 locomotory phenotype is similar to those of rab-2 and unc-31, genes with distinct roles in the DCV-mediated secretory pathway. We observed that constitutively active Gαs pathway mutations, which compensate for DCV-mediated signaling defects, rescue unc-73 RhoGEF-2 and rab-2 lethargic movement phenotypes. Together, these data suggest UNC-73 RhoGEF-2 isoforms are required for proper neurotransmitter signaling and may function in the DCV-mediated neuromodulatory regulation of locomotion rate.

  15. p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1 chemokine-induced vascular smooth muscle cell migration and proliferation.

    Science.gov (United States)

    Singh, Nikhlesh K; Janjanam, Jagadeesh; Rao, Gadiparthi N

    2017-08-25

    Although the involvement of Rho proteins in the pathogenesis of vascular diseases is well studied, little is known about the role of their upstream regulators, the Rho guanine nucleotide exchange factors (RhoGEFs). Here, we sought to identify the RhoGEFs involved in monocyte chemotactic protein 1 (MCP1)-induced vascular wall remodeling. We found that, among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smooth muscle cells (HASMCs). Moreover, p115 RhoGEF inhibition suppressed MCP1-induced HASMC migration and proliferation. Consistent with these observations, balloon injury (BI) induced p115 RhoGEF tyrosine phosphorylation in rat common carotid arteries, and siRNA-mediated down-regulation of its levels substantially attenuated BI-induced smooth muscle cell migration and proliferation, resulting in reduced neointima formation. Furthermore, depletion of p115 RhoGEF levels also abrogated MCP1- or BI-induced Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling, which, as we reported previously, is involved in vascular wall remodeling. Our findings also show that protein kinase N1 (PKN1) downstream of Rac1-cyclin D1/CDK6 and upstream of CDK4-PAK1 in the p115 RhoGEF-Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling axis is involved in the modulation of vascular wall remodeling. Of note, we also observed that CCR2-G i/o -Fyn signaling mediates MCP1-induced p115 RhoGEF and Rac1 GTPase activation. These findings suggest that p115 RhoGEF is critical for MCP1-induced HASMC migration and proliferation in vitro and for injury-induced neointima formation in vivo by modulating Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Analysis of the Antigenic and Prophylactic Properties of the Leishmania Translation Initiation Factors eIF2 and eIF2B in Natural and Experimental Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Esther Garde

    2018-04-01

    Full Text Available Different members of intracellular protein families are recognized by the immune system of the vertebrate host infected by parasites of the genus Leishmania. Here, we have analyzed the antigenic and immunogenic properties of the Leishmania eIF2 and eIF2B translation initiation factors. An in silico search in Leishmania infantum sequence databases allowed the identification of the genes encoding the α, β, and γ subunits and the α, β, and δ subunits of the putative Leishmania orthologs of the eukaryotic initiation factors F2 (LieIF2 or F2B (LieIF2B, respectively. The antigenicity of these factors was analyzed by ELISA using recombinant versions of the different subunits. Antibodies against the different LieIF2 and LieIF2B subunits were found in the sera from human and canine visceral leishmaniasis patients, and also in the sera from hamsters experimentally infected with L. infantum. In L. infantum (BALB/c and Leishmania major (BALB/c or C57BL/6 challenged mice, a moderate humoral response against these protein factors was detected. Remarkably, these proteins elicited an IL-10 production by splenocytes derived from infected mice independently of the Leishmania species employed for experimental challenge. When DNA vaccines based on the expression of the LieIF2 or LieIF2B subunit encoding genes were administered in mice, an antigen-specific secretion of IFN-γ and IL-10 cytokines was observed. Furthermore, a partial protection against murine CL development due to L. major infection was generated in the vaccinated mice. Also, in this work we show that the LieIF2α subunit and the LieIF2Bβ and δ subunits have the capacity to stimulate IL-10 secretion by spleen cells from naïve mice. B-lymphocytes were identified as the major producers of this anti-inflammatory cytokine. Taking into account the data found in this study, it may be hypothesized that these proteins act as virulence factors implicated in the induction of humoral responses as well as in the production of the down-regulatory IL-10 cytokine, favoring a pathological outcome. Therefore, these proteins might be considered markers of disease.

  17. Analysis of the Antigenic and Prophylactic Properties of the Leishmania Translation Initiation Factors eIF2 and eIF2B in Natural and Experimental Leishmaniasis.

    Science.gov (United States)

    Garde, Esther; Ramírez, Laura; Corvo, Laura; Solana, José C; Martín, M Elena; González, Víctor M; Gómez-Nieto, Carlos; Barral, Aldina; Barral-Netto, Manoel; Requena, José M; Iborra, Salvador; Soto, Manuel

    2018-01-01

    Different members of intracellular protein families are recognized by the immune system of the vertebrate host infected by parasites of the genus Leishmania . Here, we have analyzed the antigenic and immunogenic properties of the Leishmania eIF2 and eIF2B translation initiation factors. An in silico search in Leishmania infantum sequence databases allowed the identification of the genes encoding the α, β, and γ subunits and the α, β, and δ subunits of the putative Leishmania orthologs of the eukaryotic initiation factors F2 (LieIF2) or F2B (LieIF2B), respectively. The antigenicity of these factors was analyzed by ELISA using recombinant versions of the different subunits. Antibodies against the different LieIF2 and LieIF2B subunits were found in the sera from human and canine visceral leishmaniasis patients, and also in the sera from hamsters experimentally infected with L. infantum . In L. infantum (BALB/c) and Leishmania major (BALB/c or C57BL/6) challenged mice, a moderate humoral response against these protein factors was detected. Remarkably, these proteins elicited an IL-10 production by splenocytes derived from infected mice independently of the Leishmania species employed for experimental challenge. When DNA vaccines based on the expression of the LieIF2 or LieIF2B subunit encoding genes were administered in mice, an antigen-specific secretion of IFN-γ and IL-10 cytokines was observed. Furthermore, a partial protection against murine CL development due to L. major infection was generated in the vaccinated mice. Also, in this work we show that the LieIF2α subunit and the LieIF2Bβ and δ subunits have the capacity to stimulate IL-10 secretion by spleen cells from naïve mice. B-lymphocytes were identified as the major producers of this anti-inflammatory cytokine. Taking into account the data found in this study, it may be hypothesized that these proteins act as virulence factors implicated in the induction of humoral responses as well as in the production of the down-regulatory IL-10 cytokine, favoring a pathological outcome. Therefore, these proteins might be considered markers of disease.

  18. Cyclic AMP signalling in Dictyostelium : G-proteins activate separate Ras pathways using specific RasGEFs

    NARCIS (Netherlands)

    Kae, Helmut; Kortholt, Arjan; Rehmann, Holger; Insall, RobertH.; Van Haastert, Peter J. M.; Spiegelman, George B.; Weeks, Gerald

    In general, mammalian Ras guanine nucleotide exchange factors (RasGEFs) show little substrate specificity, although they are often thought to regulate specific pathways. Here, we provide in vitro and in vivo evidence that two RasGEFs can each act on specific Ras proteins. During Dictyostelium

  19. GEF small grants programme - overview

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-01

    This paper describes the GEF small grants program which seeks to enhance the role of households and communities in conserving global biodiversity, mitigating global climate change, and protecting international waters. Grants up to $50k have been granted for projects in 33 countries, with plans for 12 other countries. The author describes the framework that the program works under, and the methodology followed in developing and planning projects. The approach to climate change concerns is to emphasize the development of non-carbon energy development activities to provide energy sources and economic development.

  20. ARF1 and ARF6 regulate recycling of GRASP/Tamalin and the Rac1-GEF Dock180 during HGF-induced Rac1 activation.

    Science.gov (United States)

    Koubek, Emily J; Santy, Lorraine C

    2018-05-04

    Hepatocyte growth factor (HGF) is a potent signaling factor that acts on epithelial cells, causing them to dissociate and scatter. This migration is coordinated by a number of small GTPases, such as ARF6 and Rac1. Active ARF6 is required for HGF-stimulated migration and intracellular levels of ARF6-GTP and Rac1-GTP increase following HGF treatment. During migration, cross talk between ARF6 and Rac1 occurs through formation of a multi-protein complex containing the ARF-GEF cytohesin-2, the scaffolding protein GRASP/Tamalin, and the Rac1-GEF Dock180. Previously, the role of ARF6 in this process was unclear. We have now found that ARF6 and ARF1 regulate trafficking of GRASP and Dock180 to the plasma membrane following HGF treatment. Trafficking of GRASP and Dock180 is impaired by blocking ARF6-mediated recycling pathways and is required for HGF-stimulated Rac1 activation. Finally, HGF treatment stimulates association of GRASP and Dock180. Inhibition of ARF6 trafficking pathways traps GRASP and Dock180 as a complex in the cell.

  1. Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold protein to polarize active Rac1 distribution.

    Science.gov (United States)

    Kroon, Jeffrey; Heemskerk, Niels; Kalsbeek, Martin J T; de Waard, Vivian; van Rijssel, Jos; van Buul, Jaap D

    2017-07-01

    Endothelial cells line the lumen of the vessel wall and are exposed to flow. In linear parts of the vessel, the endothelial cells experience laminar flow, resulting in endothelial cell alignment in the direction of flow, thereby protecting the vessel wall from inflammation and permeability. In order for endothelial cells to align, they undergo rapid remodeling of the actin cytoskeleton by local activation of the small GTPase Rac1. However, it is not clear whether sustained and local activation of Rac1 is required for long-term flow-induced cell alignment. Using a FRET-based DORA Rac1 biosensor, we show that local Rac1 activity remains for 12 h upon long-term flow. Silencing studies show that the RhoGEF Trio is crucial for keeping active Rac1 at the downstream side of the cell and, as a result, for long-term flow-induced cell alignment. Surprisingly, Trio appears to be not involved in flow-induced activation of Rac1. Our data show that flow induces Rac1 activity at the downstream side of the cell in a Trio-dependent manner and that Trio functions as a scaffold protein rather than a functional GEF under long-term flow conditions. © 2017 Kroon et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  2. Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Deng Xiaolu

    2011-04-01

    Full Text Available Abstract Background Tumor necrosis factor-α (TNF-α, a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC barrier dysfunction. Methods Bend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL. RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER. p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability. Results We observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER. Conclusions Taken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF

  3. Asociación entre la mutación homocigota c.318A>T en el exón 2 del gen EIF2B5 y la forma infantil de la leucoencefalopatía con sustancia blanca evanescente

    OpenAIRE

    Carmen Esmer; Gabriela Blanco Hernández; Víctor Saavedra Alanís; Jorge Guillermo Reyes Vaca; Antonio Bravo Oro

    2017-01-01

    Introducción: La leucoencefalopatía con sustancia blanca evanescente es una de las leucodistrofias más frecuentes. Generalmente inicia en la infancia y presenta un patrón de herencia autosómica recesiva. El 90% de los casos manifiesta mutaciones en uno de los genes que codifican para las cinco subunidades del factor de iniciación eucariótica 2 (EIF2B5). El diagnóstico se realiza por las manifestaciones clínicas, hallazgos en la resonancia magnética cerebral y estudios moleculares confirmatori...

  4. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

    KAUST Repository

    Lissanu Deribe, Yonathan

    2016-03-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  5. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.

    Science.gov (United States)

    Lissanu Deribe, Yonathan; Shi, Yanxia; Rai, Kunal; Nezi, Luigi; Amin, Samir B; Wu, Chia-Chin; Akdemir, Kadir C; Mahdavi, Mozhdeh; Peng, Qian; Chang, Qing Edward; Hornigold, Kirsti; Arold, Stefan T; Welch, Heidi C E; Garraway, Levi A; Chin, Lynda

    2016-03-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2(E824)*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57(KIP2)). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  6. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

    KAUST Repository

    Lissanu Deribe, Yonathan; Shi, Yanxia; Rai, Kunal; Nezi, Luigi; Amin, Samir B.; Wu, Chia-Chin; Akdemir, Kadir C.; Mahdavi, Mozhdeh; Peng, Qian; Chang, Qing Edward; Hornigold, Kirsti; Arold, Stefan T.; Welch, Heidi C. E.; Garraway, Levi A.; Chin, Lynda

    2016-01-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  7. Initiation factor eIF2B not p70 S6 kinase is involved in the activation of the PI-3K signalling pathway induced by the v=src oncogene

    Czech Academy of Sciences Publication Activity Database

    Vojtěchová, Martina; Šloncová, Eva; Kučerová, Dana; Jiřička, Jaroslav; Sovová, Vlasta; Tuháčková, Zdena

    2003-01-01

    Roč. 543, 1-3 (2003), s. 81-86 ISSN 0014-5793 R&D Projects: GA ČR GV312/96/K205; GA ČR GA301/00/0269; GA MZd NC5428 Institutional research plan: CEZ:AV0Z5052915 Keywords : phosphoinositide 3-kinase signalling pathway * mRNA translation * 70 kDa ribosomal protein S6 kinase Subject RIV: CE - Biochemistry Impact factor: 3.609, year: 2003

  8. Global Ensemble Forecast System (GEFS) [1 Deg.

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Global Ensemble Forecast System (GEFS) is a weather forecast model made up of 21 separate forecasts, or ensemble members. The National Centers for Environmental...

  9. Signaling efficiency of Galphaq through its effectors p63RhoGEF and GEFT depends on their subcellular location

    NARCIS (Netherlands)

    Goedhart, J.; Unen, J. van; Adjobo-Hermans, M.J.W.; Gadella, T.W.

    2013-01-01

    The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Galphaq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined

  10. Viral activation of MK2-hsp27-p115RhoGEF-RhoA signaling axis causes cytoskeletal rearrangements, p-body disruption and ARE-mRNA stabilization.

    Directory of Open Access Journals (Sweden)

    Jennifer A Corcoran

    2015-01-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the infectious cause of several AIDS-related cancers, including the endothelial cell (EC neoplasm Kaposi's sarcoma (KS. KSHV-infected ECs secrete abundant host-derived pro-inflammatory molecules and angiogenic factors that contribute to tumorigenesis. The precise contributions of viral gene products to this secretory phenotype remain to be elucidated, but there is emerging evidence for post-transcriptional regulation. The Kaposin B (KapB protein is thought to contribute to the secretory phenotype in infected cells by binding and activating the stress-responsive kinase MK2, thereby selectively blocking decay of AU-rich mRNAs (ARE-mRNAs encoding pro-inflammatory cytokines and angiogenic factors. Processing bodies (PBs are cytoplasmic ribonucleoprotein foci in which ARE-mRNAs normally undergo rapid 5' to 3' decay. Here, we demonstrate that PB dispersion is a feature of latent KSHV infection, which is dependent on kaposin protein expression. KapB is sufficient to disperse PBs, and KapB-mediated ARE-mRNA stabilization could be partially reversed by treatments that restore PBs. Using a combination of genetic and chemical approaches we provide evidence that KapB-mediated PB dispersion is dependent on activation of a non-canonical Rho-GTPase signaling axis involving MK2, hsp27, p115RhoGEF and RhoA. PB dispersion in latently infected cells is likewise dependent on p115RhoGEF. In addition to PB dispersion, KapB-mediated RhoA activation in primary ECs caused actin stress fiber formation, increased cell motility and angiogenesis; these effects were dependent on the activity of the RhoA substrate kinases ROCK1/2. By contrast, KapB-mediated PB dispersion occurred in a ROCK1/2-independent manner. Taken together, these observations position KapB as a key contributor to viral reprogramming of ECs, capable of eliciting many of the phenotypes characteristic of KS tumor cells, and strongly contributing to the post

  11. Signaling efficiency of Gαq through its effectors p63RhoGEF and GEFT depends on their subcellular location.

    NARCIS (Netherlands)

    Goedhart, J.; van Unen, J.; Adjobo-Hermans, M.J.W.; Gadella (jr.), T.W.J.

    2013-01-01

    The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Galphaq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined

  12. Activation of Rab GTPase Sec4 by its GEF Sec2 is required for prospore membrane formation during sporulation in yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Suda, Yasuyuki; Tachikawa, Hiroyuki; Inoue, Ichiro; Kurita, Tomokazu; Saito, Chieko; Kurokawa, Kazuo; Nakano, Akihiko; Irie, Kenji

    2018-02-01

    Sec2 activates Sec4 Rab GTPase as a guanine nucleotide exchange factor for the recruitment of downstream effectors to facilitate tethering and fusion of post-Golgi vesicles at the plasma membrane. During the meiosis and sporulation of budding yeast, post-Golgi vesicles are transported to and fused at the spindle pole body (SPB) to form a de novo membrane, called the prospore membrane. Previous studies have revealed the role of the SPB outer surface called the meiotic outer plaque (MOP) in docking and fusion of post-Golgi vesicles. However, the upstream molecular machinery for post-Golgi vesicular fusion that facilitates prospore membrane formation remains enigmatic. Here, we demonstrate that the GTP exchange factor for Sec4, Sec2, participates in the formation of the prospore membrane. A conditional mutant in which the SEC2 expression is shut off during sporulation showed sporulation defects. Inactivation of Sec2 caused Sec4 targeting defects along the prospore membranes, thereby causing insufficient targeting of downstream effectors and cargo proteins to the prospore membrane. These results suggest that the activation of Sec4 by Sec2 is required for the efficient supply of post-Golgi vesicles to the prospore membrane and thus for prospore membrane formation/extension and subsequent deposition of spore wall materials. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Global Ensemble Forecast System (GEFS) [2.5 Deg.

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Global Ensemble Forecast System (GEFS) is a weather forecast model made up of 21 separate forecasts, or ensemble members. The National Centers for Environmental...

  14. Synthesis and properties of Rb2GeF6:Mn4+ red-emitting phosphors

    Science.gov (United States)

    Sakurai, Shono; Nakamura, Toshihiro; Adachi, Sadao

    2018-02-01

    Rb2GeF6:Mn4+ red-emitting phosphors were synthesized by coprecipitation and their structural and optical properties were investigated by laser microscopy observation, X-ray diffraction (XRD) analysis, photoluminescence (PL) analysis, PL excitation (PLE) spectroscopy, and PL decay measurement. Single-crystalline ingots in the form of a hexagonal pyramid were prepared with a basal plane diameter of ˜2 mm. The XRD analysis suggested that Rb2GeF6 crystallizes in the hexagonal structure (C6v4 = P63mc) with a = 0.5955 nm and c = 0.9672 nm. The phosphor exhibited the strong Mn4+-related zero-phonon line (ZPL) emission peak typically observed in host crystals with piezoelectrically active lattices such as a hexagonal lattice. The quantum efficiencies of the bulk ingot and powdered samples were 87 and 74%, respectively, with nearly the same luminescence decay time of ˜6 ms. The exact ZPL energies and related crystal-field and Racah parameters were obtained from the PL and PLE spectra by Franck-Condon analysis. Temperature-dependent PL intensities were analyzed from T = 20 to 500 K using a thermal quenching model by considering Bose-Einstein phonon statistics. A comparative discussion on the phosphor properties of Rb2GeF6:Mn4+ and Rb2MF6:Mn4+ with M = Si and Ti was also given.

  15. A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

    Science.gov (United States)

    Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

    2005-02-22

    CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

  16. The Global Environment Facility (GEF): Right mechanism for improved implementation?

    Energy Technology Data Exchange (ETDEWEB)

    Andresen, Steinar; Rosendal, Kristin G.

    2012-11-01

    The purpose is to feed into the international discussions of environmental financial mechanisms such as for forestry and mercury by examining the performance of the GEF. We discuss performance against effectiveness and legitimacy and focus on institutional set-up and key actors as explanatory factors. Methodologically, we use document and literature analysis and interviews with key actors in organizations, state representatives and NGOs. The dominant position of the USA and the World Bank has probably contributed to the bias towards a northern environmental agenda and emphasis on effectiveness and climate change projects. The GEF has somewhat predictably diverted the flow of international money from the poorest countries to more rapidly developing countries. Still, despite turf battles between the organizations involved, the broad organisational and thematic composition of the GEF has comparative advantages. This enhances the score on legitimacy especially for biodiversity projects, although they receive less overall funding. The GEF may be seen as an indication of how, regardless of choosing established or new institutions, basic power structures and interests of dominating parties will be largely decisive for what can be achieved in global environmental governance.(auth)

  17. Signaling efficiency of Gαq through its effectors p63RhoGEF and GEFT depends on their subcellular location.

    Science.gov (United States)

    Goedhart, Joachim; van Unen, Jakobus; Adjobo-Hermans, Merel J W; Gadella, Theodorus W J

    2013-01-01

    The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Gαq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined to the cytoplasm. Live-cell imaging studies yielded quantitative information on diffusion coefficients, association rates and encounter times of GEFT and p63RhoGEF. Calcium signaling was examined as a measure of the signal transmission, revealing more efficient signaling through the membrane-associated p63RhoGEF. A rapamycin dependent recruitment system was used to dynamically alter the subcellular location and concentration of GEFT, showing efficient signaling through GEFT only upon membrane recruitment. Together, our results show efficient signal transmission through membrane located effectors, and highlight a role for increased concentration rather than increased encounter times due to membrane localization in the Gαq mediated pathways to p63RhoGEF and PLCβ.

  18. Gef gene therapy enhances the therapeutic efficacy of doxorubicin to combat growth of MCF-7 breast cancer cells

    OpenAIRE

    2009-01-01

    Abstract Purpose The potential use of combined therapy is under intensive study including the association between classical cytotoxic and genes encoding toxic proteins which enhanced the antitumour activity. The main aim of this work was to evaluate whether the gef gene, a suicide gene which has a demonstrated antiproliferative activity in tumour cells, improved the antitumour effect of chemotherapeutic drugs used as first-line treatment in the management...

  19. Which Way In? The RalF Arf-GEF Orchestrates Rickettsia Host Cell Invasion

    Science.gov (United States)

    Rennoll-Bankert, Kristen E.; Rahman, M. Sayeedur; Gillespie, Joseph J.; Guillotte, Mark L.; Kaur, Simran J.; Lehman, Stephanie S.; Beier-Sexton, Magda; Azad, Abdu F.

    2015-01-01

    Bacterial Sec7-domain-containing proteins (RalF) are known only from species of Legionella and Rickettsia, which have facultative and obligate intracellular lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS) effector, is a guanine nucleotide exchange factor (GEF) of ADP-ribosylation factors (Arfs), activating and recruiting host Arf1 to the Legionella-containing vacuole. In contrast, previous in vitro studies showed R. prowazekii (Typhus Group) RalF is a functional Arf-GEF that localizes to the host plasma membrane and interacts with the actin cytoskeleton via a unique C-terminal domain. As RalF is differentially encoded across Rickettsia species (e.g., pseudogenized in all Spotted Fever Group species), it may function in lineage-specific biology and pathogenicity. Herein, we demonstrate RalF of R. typhi (Typhus Group) interacts with the Rickettsia T4SS coupling protein (RvhD4) via its proximal C-terminal sequence. RalF is expressed early during infection, with its inactivation via antibody blocking significantly reducing R. typhi host cell invasion. For R. typhi and R. felis (Transitional Group), RalF ectopic expression revealed subcellular localization with the host plasma membrane and actin cytoskeleton. Remarkably, R. bellii (Ancestral Group) RalF showed perinuclear localization reminiscent of ectopically expressed Legionella RalF, for which it shares several structural features. For R. typhi, RalF co-localization with Arf6 and PI(4,5)P2 at entry foci on the host plasma membrane was determined to be critical for invasion. Thus, we propose recruitment of PI(4,5)P2 at entry foci, mediated by RalF activation of Arf6, initiates actin remodeling and ultimately facilitates bacterial invasion. Collectively, our characterization of RalF as an invasin suggests that, despite carrying a similar Arf-GEF unknown from other bacteria, different intracellular lifestyles across Rickettsia and Legionella species have driven divergent roles for Ral

  20. Brief introduction of GEF efficient industrial boiler project in China

    Energy Technology Data Exchange (ETDEWEB)

    Meijian, T.

    1996-12-31

    The present situation of installed industrial boilers, their efficiency and environmental impact are assessed. And the factors contribute to the low efficiency and serious pollution are summarized. Based on WB-assisted GEF project, {open_quotes}Efficient Industrial Boiler Project{close_quotes} aimed at CO{sub 2} mitigation in China, a series of effective measures to bring the GHG emission under control are addressed, in technology, system performance, and operation management aspects.

  1. An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

    Science.gov (United States)

    Kutys, Matthew L; Yamada, Kenneth M

    2014-09-01

    Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

  2. General Description of Fission Observables - JEFF Report 24. GEF Model

    International Nuclear Information System (INIS)

    Schmidt, Karl-Heinz; Jurado, Beatriz; Amouroux, Charlotte

    2014-06-01

    The Joint Evaluated Fission and Fusion (JEFF) Project is a collaborative effort among the member countries of the OECD Nuclear Energy Agency (NEA) Data Bank to develop a reference nuclear data library. The JEFF library contains sets of evaluated nuclear data, mainly for fission and fusion applications; it contains a number of different data types, including neutron and proton interaction data, radioactive decay data, fission yield data and thermal scattering law data. The General fission (GEF) model is based on novel theoretical concepts and ideas developed to model low energy nuclear fission. The GEF code calculates fission-fragment yields and associated quantities (e.g. prompt neutron and gamma) for a large range of nuclei and excitation energy. This opens up the possibility of a qualitative step forward to improve further the JEFF fission yields sub-library. This report describes the GEF model which explains the complex appearance of fission observables by universal principles of theoretical models and considerations on the basis of fundamental laws of physics and mathematics. The approach reveals a high degree of regularity and provides a considerable insight into the physics of the fission process. Fission observables can be calculated with a precision that comply with the needs for applications in nuclear technology. The relevance of the approach for examining the consistency of experimental results and for evaluating nuclear data is demonstrated. (authors)

  3. Improving GEFS Weather Forecasts for Indian Monsoon with Statistical Downscaling

    Science.gov (United States)

    Agrawal, Ankita; Salvi, Kaustubh; Ghosh, Subimal

    2014-05-01

    Weather forecast has always been a challenging research problem, yet of a paramount importance as it serves the role of 'key input' in formulating modus operandi for immediate future. Short range rainfall forecasts influence a wide range of entities, right from agricultural industry to a common man. Accurate forecasts actually help in minimizing the possible damage by implementing pre-decided plan of action and hence it is necessary to gauge the quality of forecasts which might vary with the complexity of weather state and regional parameters. Indian Summer Monsoon Rainfall (ISMR) is one such perfect arena to check the quality of weather forecast not only because of the level of intricacy in spatial and temporal patterns associated with it, but also the amount of damage it can cause (because of poor forecasts) to the Indian economy by affecting agriculture Industry. The present study is undertaken with the rationales of assessing, the ability of Global Ensemble Forecast System (GEFS) in predicting ISMR over central India and the skill of statistical downscaling technique in adding value to the predictions by taking them closer to evidentiary target dataset. GEFS is a global numerical weather prediction system providing the forecast results of different climate variables at a fine resolution (0.5 degree and 1 degree). GEFS shows good skills in predicting different climatic variables but fails miserably over rainfall predictions for Indian summer monsoon rainfall, which is evident from a very low to negative correlation values between predicted and observed rainfall. Towards the fulfilment of second rationale, the statistical relationship is established between the reasonably well predicted climate variables (GEFS) and observed rainfall. The GEFS predictors are treated with multicollinearity and dimensionality reduction techniques, such as principal component analysis (PCA) and least absolute shrinkage and selection operator (LASSO). Statistical relationship is

  4. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Matthew J Spindler

    Full Text Available A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  5. Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi

    Directory of Open Access Journals (Sweden)

    Antonio Galindo

    2016-07-01

    Full Text Available The GTPase Arf1 is the major regulator of vesicle traffic at both the cis- and trans-Golgi. Arf1 is activated at the cis-Golgi by the guanine nucleotide exchange factor (GEF GBF1 and at the trans-Golgi by the related GEF BIG1 or its paralog, BIG2. The trans-Golgi-specific targeting of BIG1 and BIG2 depends on the Arf-like GTPase Arl1. We find that Arl1 binds to the dimerization and cyclophilin binding (DCB domain in BIG1 and report a crystal structure of human Arl1 bound to this domain. Residues in the DCB domain that bind Arl1 are required for BIG1 to locate to the Golgi in vivo. DCB domain-binding residues in Arl1 have a distinct conformation from those in known Arl1-effector complexes, and this plasticity allows Arl1 to interact with different effectors of unrelated structure. The findings provide structural insight into how Arf1 GEFs, and hence active Arf1, achieve their correct subcellular distribution.

  6. A computational study of a recreated G protein-GEF reaction intermediate competent for nucleotide exchange: fate of the Mg ion.

    Directory of Open Access Journals (Sweden)

    Mériam Ben Hamida-Rebaï

    Full Text Available Small G-proteins of the superfamily Ras function as molecular switches, interacting with different cellular partners according to their activation state. G-protein activation involves the dissociation of bound GDP and its replacement by GTP, in an exchange reaction that is accelerated and regulated in the cell by guanine-nucleotide exchange factors (GEFs. Large conformational changes accompany the exchange reaction, and our understanding of the mechanism is correspondingly incomplete. However, much knowledge has been derived from structural studies of blocked or inactive mutant GEFs, which presumably closely represent intermediates in the exchange reaction and yet which are by design incompetent for carrying out the nucleotide exchange reaction. In this study we have used comparative modelling to recreate an exchange-competent form of a late, pre-GDP-ejection intermediate species in Arf1, a well-characterized small G-protein. We extensively characterized three distinct models of this intermediate using molecular dynamics simulations, allowing us to address ambiguities related to the mutant structural studies. We observed in particular the unfavorable nature of Mg2+ associated forms of the complex and the establishment of closer Arf1-GEF contacts in its absence. The results of this study shed light on GEF-mediated activation of this small G protein and on predicting the fate of the Mg ion at a critical point in the exchange reaction. The structural models themselves furnish additional targets for interfacial inhibitor design, a promising direction for exploring potentially druggable targets with high biological specificity.

  7. Genetic screening of Scandinavian families with febrile seizures and epilepsy or GEFS+

    DEFF Research Database (Denmark)

    Selmer, K K; Egeland, T; Solaas, M H

    2008-01-01

    Background - Mutations in the three genes SCN1A, SCN1B and GABRG2, all encoding subunits of ion channels, have been known to cause generalized epilepsy with febrile seizures plus (GEFS+) in families of different origin. Objective - To study the occurrence of mutations in these genes in families...... with GEFS+ or a GEFS+ resembling phenotype of Scandinavian origin. Material and methods - We performed linkage analysis in 19 Scandinavian families with a history of febrile seizures (FS) and epilepsy or GEFS+. Where linkage could not be excluded, the genes of interest were sequenced. Results - We...... identified only one mutation in SCN1A, which seems to be a rare variant with no functional consequence. Conclusion - This suggests that mutations in these three genes are not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia....

  8. Transforming on-grid renewable energy markets. A review of UNDP-GEF support for feed-in tariffs and related price and market-access instruments

    Energy Technology Data Exchange (ETDEWEB)

    Glemarec, Yannick; Rickerson, Wilson; Waissbein, Oliver

    2012-11-15

    As a Global Environment Facility (GEF) founding implementing agency, UNDP has worked on over 230 GEF-supported clean energy projects in close to 100 developing countries since 1992. About 100 of these projects in 80 countries have focused on renewable energy, supported by approximately US $ 293 million in GEF funds and leveraging US $1.48 billion in associated co-financing from national governments, international organizations, the private sector and non-governmental organizations. As part of UNDP efforts to codify and share lessons learnt from these initiatives, this report addresses how scarce public resources can be used to catalyze larger private financial flows for renewable energy. It provides an overview of UNDP-GEF’s extensive work supporting development of national renewable energy policies such as feed-in tariffs. In these activities UNDP-GEF assists developing countries to assess key risks and barriers to technology diffusion and then to identify a mix of policy and financial de-risking measures to remove these barriers and drive investment. This approach is illustrated through three case studies in Uruguay, Mauritius and Kazakhstan. This report is complemented by a companion publication presenting an innovative UNDP financial modeling tool to assist policymakers in appraising different public instruments to promote clean energy.

  9. Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

    Science.gov (United States)

    Marcus-Gueret, Nancy; Schmidt, Kristopher L.; Stringham, Eve G.

    2012-01-01

    The cytoskeleton regulator UNC-53/NAV2 is required for both the anterior and posterior outgrowth of several neurons as well as that of the excretory cell while the kinesin-like motor VAB-8 is essential for most posteriorly directed migrations in Caenorhabditis elegans. Null mutations in either unc-53 or vab-8 result in reduced posterior excretory canal outgrowth, while double null mutants display an enhanced canal extension defect, suggesting the genes act in separate pathways to control this posteriorly directed outgrowth. Genetic analysis of putative interactors of UNC-53 or VAB-8, and cell-specific rescue experiments suggest that VAB-8, SAX-3/ROBO, SLT-1/Slit, and EVA-1 are functioning together in the outgrowth of the excretory canals, while UNC-53 appears to function in a parallel pathway with UNC-71/ADAM. The known VAB-8 interactor, the Rac/Rho GEF UNC-73/TRIO operates in both pathways, as isoform specific alleles exhibit enhancement of the phenotype in double-mutant combination with either unc-53 or vab-8. On the basis of these results, we propose a bipartite model for UNC-73/TRIO activity in excretory canal extension: a cell autonomous function that is mediated by the Rho-specific GEF domain of the UNC-73E isoform in conjunction with UNC-53 and UNC-71 and a cell nonautonomous function that is mediated by the Rac-specific GEF domain of the UNC-73B isoform, through partnering with VAB-8 and the receptors SAX-3 and EVA-1. PMID:21996675

  10. Closing the Gap GEF Experiences in Global Energy Efficiency

    CERN Document Server

    Yang, Ming

    2013-01-01

    Energy efficiency plays and will continue to play an important role in the world to save energy and mitigate greenhouse gas (GHG) emissions. However, little is known on how much additional capital should be invested to ensure using energy efficiently as it should be, and very little is known which sub-areas, technologies, and countries shall achieve maximum greenhouse gas emissions mitigation per dollar of investment in energy efficiency worldwide. Analyzing completed and slowly moving energy efficiency projects by the Global Environment Facility during 1991-2010, Closing the Gap: GEF Experiences in Global Energy Efficiency evaluates impacts of multi-billion-dollar investments in the world energy efficiency. It covers the following areas: 1.       Reviewing the world energy efficiency investment and disclosing the global energy efficiency gap and market barriers that cause the gap; 2.       Leveraging private funds with public funds and other resources in energy efficiency investments; using...

  11. Status of the general description of fission observables by the GEF code

    CERN Document Server

    Jurado, B

    2014-01-01

    The GEneral Fission (GEF) model treats spontaneous fission and fission up to an excitation energy of about 100 MeV of a wide range of heavy nuclei. GEF makes use of general laws of statistical and quantum mechanics, assuring a high predictive power. It is unique in providing a general description of essentially all fission observables in a consistent way while preserving the correlations between all of them. In this contribution we present some of the physical aspects on which the model is based, give an overview on the results that can be obtained with the code and show an example that illustrates how the GEF code can serve as a framework for revealing the sensitivity of the fission observables to some basic nuclear properties.

  12. DRhoGEF2 regulates cellular tension and cell pulsations in the Amnioserosa during Drosophila dorsal closure.

    Directory of Open Access Journals (Sweden)

    Dulce Azevedo

    Full Text Available Coordination of apical constriction in epithelial sheets is a fundamental process during embryogenesis. Here, we show that DRhoGEF2 is a key regulator of apical pulsation and constriction of amnioserosal cells during Drosophila dorsal closure. Amnioserosal cells mutant for DRhoGEF2 exhibit a consistent decrease in amnioserosa pulsations whereas overexpression of DRhoGEF2 in this tissue leads to an increase in the contraction time of pulsations. We probed the physical properties of the amnioserosa to show that the average tension in DRhoGEF2 mutant cells is lower than wild-type and that overexpression of DRhoGEF2 results in a tissue that is more solid-like than wild-type. We also observe that in the DRhoGEF2 overexpressing cells there is a dramatic increase of apical actomyosin coalescence that can contribute to the generation of more contractile forces, leading to amnioserosal cells with smaller apical surface than wild-type. Conversely, in DRhoGEF2 mutants, the apical actomyosin coalescence is impaired. These results identify DRhoGEF2 as an upstream regulator of the actomyosin contractile machinery that drives amnioserosa cells pulsations and apical constriction.

  13. PH Domain-Arf G Protein Interactions Localize the Arf-GEF Steppke for Cleavage Furrow Regulation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Donghoon M Lee

    Full Text Available The recruitment of GDP/GTP exchange factors (GEFs to specific subcellular sites dictates where they activate small G proteins for the regulation of various cellular processes. Cytohesins are a conserved family of plasma membrane GEFs for Arf small G proteins that regulate endocytosis. Analyses of mammalian cytohesins have identified a number of recruitment mechanisms for these multi-domain proteins, but the conservation and developmental roles for these mechanisms are unclear. Here, we report how the pleckstrin homology (PH domain of the Drosophila cytohesin Steppke affects its localization and activity at cleavage furrows of the early embryo. We found that the PH domain is necessary for Steppke furrow localization, and for it to regulate furrow structure. However, the PH domain was not sufficient for the localization. Next, we examined the role of conserved PH domain amino acid residues that are required for mammalian cytohesins to bind PIP3 or GTP-bound Arf G proteins. We confirmed that the Steppke PH domain preferentially binds PIP3 in vitro through a conserved mechanism. However, disruption of residues for PIP3 binding had no apparent effect on GFP-Steppke localization and effects. Rather, residues for binding to GTP-bound Arf G proteins made major contributions to this Steppke localization and activity. By analyzing GFP-tagged Arf and Arf-like small G proteins, we found that Arf1-GFP, Arf6-GFP and Arl4-GFP, but not Arf4-GFP, localized to furrows. However, analyses of embryos depleted of Arf1, Arf6 or Arl4 revealed either earlier defects than occur in embryos depleted of Steppke, or no detectable furrow defects, possibly because of redundancies, and thus it was difficult to assess how individual Arf small G proteins affect Steppke. Nonetheless, our data show that the Steppke PH domain and its conserved residues for binding to GTP-bound Arf G proteins have substantial effects on Steppke localization and activity in early Drosophila embryos.

  14. Photovoltaics in Africa and the GEF: the right path to sustainable development?

    International Nuclear Information System (INIS)

    Bacon, I.

    1998-01-01

    This paper explores the relevance of promoting photovoltaic (PV) projects within Africa by focusing on the issues arising from the GEF/Zimbabwe PV project 1992-1997. It questions the utility of such projects and the reasons for the continued promotion of this technology within Africa. It concludes that financial aid for PV technology needs to be thoroughly reviewed and redirected. (author)

  15. La Theorie des Gefühls hegeliana in dialogo con le recenti teorie sulle emozioni

    Directory of Open Access Journals (Sweden)

    Caterina Maurer

    2017-04-01

    Full Text Available Considering the relevance of the interaction between neuroscience, psychology, and philosophy in the contemporary debate on emotions, this paper aims at establishing a fruitful dialogue between Hegel’s Philosophie des subjektiven Geistes and the most important neuroscientific and psychological research on emotions. By means of an analysis of the role of Empfindungen (sensations and Gefühle (feelings in the Enzyklopädie der philosophischen Wissenschaften (1830, we will show that Hegel developed a Theorie des Gefühls. The proposed dialogue between Hegel’s thought and contemporary theories is useful for distinguishing the various types of emotions and their cognitive and affective aspects. In fact, it will emerge that both Hegel and recent studies on emotion consider emotions to be characterized by a cognitive valence which enables a person to orient herself/himself in the world.

  16. Promoting energy-efficient products: GEF experience and lessons for market transformation in developing countries

    International Nuclear Information System (INIS)

    Birner, Sabrina; Martinot, Eric

    2005-01-01

    The Global Environment Facility (GEF) has allocated more than $90 million over the past 10 years to eight projects promoting energy-efficient products in developing and transition countries. We review the early experience from these projects and suggest lessons relevant to market transformation programs. Based on GEF project designs, we also propose a menu of generic supply-side and demand-side interventions useful for designing and analyzing market transformation programs. Experience suggests that institutional and policy changes, leading to sustained price reductions and higher market volumes, are important outcomes for market transformation; that market impacts can appear early in programs due to increased expectations and awareness; and that projects can have a catalytic effect. We recommend eight principles for designers of future projects but caution that no single approach guarantees success

  17. Function of the Nucleotide Exchange Activity of Vav1 in T cell Development and Activation*

    Science.gov (United States)

    Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J.; Rittinger, Katrin; Tybulewicz, Victor L. J.

    2012-01-01

    The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal–regulated kinase (ERK) and protein kinase D1 (PKD1), and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions. PMID:20009105

  18. Function of the nucleotide exchange activity of vav1 in T cell development and activation.

    Science.gov (United States)

    Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J; Rittinger, Katrin; Tybulewicz, Victor L J

    2009-12-15

    The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal-regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.

  19. Coronin-1C and RCC2 guide mesenchymal migration by trafficking Rac1 and controlling GEF exposure

    Science.gov (United States)

    Williamson, Rosalind C.; Cowell, Christopher A. M.; Hammond, Christina L.; Bergen, Dylan J. M.; Roper, James A.; Feng, Yi; Rendall, Thomas C. S.; Race, Paul R.; Bass, Mark D.

    2014-01-01

    ABSTRACT Sustained forward migration through a fibrillar extracellular matrix requires localization of protrusive signals. Contact with fibronectin at the tip of a cell protrusion activates Rac1, and for linear migration it is necessary to dampen Rac1 activity in off-axial positions and redistribute Rac1 from non-protrusive membrane to the leading edge. Here, we identify interactions between coronin-1C (Coro1C), RCC2 and Rac1 that focus active Rac1 to a single protrusion. Coro1C mediates release of inactive Rac1 from non-protrusive membrane and is necessary for Rac1 redistribution to a protrusive tip and fibronectin-dependent Rac1 activation. The second component, RCC2, attenuates Rac1 activation outside the protrusive tip by binding to the Rac1 switch regions and competitively inhibiting GEF action, thus preventing off-axial protrusion. Depletion of Coro1C or RCC2 by RNA interference causes loss of cell polarity that results in shunting migration in 1D or 3D culture systems. Furthermore, morpholinos against Coro1C or RCC2, or mutation of any of the binding sites in the Rac1–RCC2–Coro1C complex delays the arrival of neural crest derivatives at the correct location in developing zebrafish, demonstrating the crucial role in migration guidance in vivo. PMID:25074804

  20. A novel double-enhanced suicide gene therapy in a colon cancer cell line mediated by gef and apoptin.

    Science.gov (United States)

    Boulaiz, Houria; Aránega, Antonia; Cáceres, Blanca; Blanca, Cáceres; Alvarez, Pablo; Pablo, Alvarez; Serrano-Rodríguez, Fernando; Fernando, Rodríguez-Serrano; Carrillo, Esmeralda; Esmeralda, Carrillo; Melguizo, Consolación; Consolación, Melguizo; Prados, Jose; Jose, Prados

    2014-02-01

    Double-suicide gene therapy is a promising strategy for the treatment of advanced cancer. It has become an important research line in the development of gene therapy to overcome the drawbacks of single-gene therapy. The aim of this study was to investigate the usefulness of double-suicide gene therapy with the two suicide genes, gef and apoptin, in colon carcinoma. gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system. Expression of both genes in the DLD-1 cell line was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Cell viability was determined with the sulforhodamine B colorimetric assay, and the cell cycle was studied by propidium iodide (PI) staining. Annexin V-FITC and PI assays were used to evaluate apoptosis, and the results were confirmed by electron microscopy. The mitochondrial membrane potential was measured by JC-1 assay. Our results showed that the combined expression of gef and apoptin genes was strikingly more effective than the expression of either gene alone. Co-expression of gef and apoptin synergistically enhanced the decrease in cell viability, increasing necrosis and inducing apoptosis in colon cancer cells via the mitochondrial pathway, which can be deficient in advanced or metastatic colon cancer. Double-suicide gene therapy based on gef and apoptin genes may be a candidate for the development of new colon cancer strategies, and further studies are warranted to establish the usefulness of double-suicide gene therapy in vivo.

  1. Robuste Verzweigungserkennung von Gefäßen in CTA-Datensätzen zur modellbasierten Extraktion der Centerline

    Science.gov (United States)

    Beck, Thomas; Fritz, Dominik; Biermann, Christina; Dillmann, Rüdiger

    Bei der Befundung und Visualisierung von Blutgefäßen ist deren Centerline von zentraler Bedeutung. Die Unterscheidung zwischen unverzweigten Abschnitten des Gefäßes und Verzweigungsbereichen ermöglicht den Einsatz spezialisierter und sehr effizienter Algorithmen zur modellbasierten Extraktion der Centerline. In diesem Artikel wird ein robustes Verfahren zur Verzweigungserkennung vorgestellt. Das Verfahren beruht auf einem Front-Propagation-Ansatz mit dynamisch angepassten Schwellwerten und einer anschließenden Clusteranalyse. Die vorgestellte Methode zur Verzweigungserkennung wurde als Komponente einer Architektur zur Extraktion der Centerline auf handannotierten Datensätzen getestet. Erste Ergebnisse sind sehr vielversprechend und ermöglichen auch bei pathologischen Gefäßen eine robuste Detektion von Gefäßverzweigungen.

  2. An Assessment of the Subseasonal Forecast Performance in the Extended Global Ensemble Forecast System (GEFS)

    Science.gov (United States)

    Sinsky, E.; Zhu, Y.; Li, W.; Guan, H.; Melhauser, C.

    2017-12-01

    Optimal forecast quality is crucial for the preservation of life and property. Improving monthly forecast performance over both the tropics and extra-tropics requires attention to various physical aspects such as the representation of the underlying SST, model physics and the representation of the model physics uncertainty for an ensemble forecast system. This work focuses on the impact of stochastic physics, SST and the convection scheme on forecast performance for the sub-seasonal scale over the tropics and extra-tropics with emphasis on the Madden-Julian Oscillation (MJO). A 2-year period is evaluated using the National Centers for Environmental Prediction (NCEP) Global Ensemble Forecast System (GEFS). Three experiments with different configurations than the operational GEFS were performed to illustrate the impact of the stochastic physics, SST and convection scheme. These experiments are compared against a control experiment (CTL) which consists of the operational GEFS but its integration is extended from 16 to 35 days. The three configurations are: 1) SPs, which uses a Stochastically Perturbed Physics Tendencies (SPPT), Stochastic Perturbed Humidity (SHUM) and Stochastic Kinetic Energy Backscatter (SKEB); 2) SPs+SST_bc, which uses a combination of SPs and a bias-corrected forecast SST from the NCEP Climate Forecast System Version 2 (CFSv2); and 3) SPs+SST_bc+SA_CV, which combines SPs, a bias-corrected forecast SST and a scale aware convection scheme. When comparing to the CTL experiment, SPs shows substantial improvement. The MJO skill has improved by about 4 lead days during the 2-year period. Improvement is also seen over the extra-tropics due to the updated stochastic physics, where there is a 3.1% and a 4.2% improvement during weeks 3 and 4 over the northern hemisphere and southern hemisphere, respectively. Improvement is also seen when the bias-corrected CFSv2 SST is combined with SPs. Additionally, forecast performance enhances when the scale aware

  3. Investigation of ambient temperature on the performance of GE-F5 gas turbine

    International Nuclear Information System (INIS)

    Ghazikhani, M.; Taffazoli, D.; Manshori, N.

    2002-01-01

    The role of ambient temperature in determining the performance of GE-F5 gas turbine is analysed by investigating the Shirvan gas turbine power plant 10 MW , 15 MW and 20 MW power output. These parameters have been brought as a function of ambient temperature. The results show when ambient temperature increases 1 deg C, The compressor pressure decreases about 20 k Pa, compressor outlet temperature increases about 1.13 deg C and exhaust temperature increases about 2.5 deg C. It is revealed that variations are due to decreasing the efficiency of compressor and less due to mass flow rate of air reduction as ambient temperature increases at constant power output. The results shows cycle efficiency reduces 3% with increasing 50 of ambient temperature, also the m increases as ambient temperature increase for constant turbine work. These are also because of reducing the compressor efficiency as ambient temperature increases

  4. Regulation of Ras exchange factors and cellular localization of Ras activation by lipid messengers in T cells

    Directory of Open Access Journals (Sweden)

    Jesse E. Jun

    2013-09-01

    Full Text Available The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and SOS-family GEFs.Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood.One large group of biomolecules critically involved in the control of Ras-GEFs´functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells.

  5. The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs.

    Science.gov (United States)

    Levine, Timothy P; Daniels, Rachel D; Gatta, Alberto T; Wong, Louise H; Hayes, Matthew J

    2013-02-15

    Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS, also called motor neuron disease, MND) are severe neurodegenerative diseases that show considerable overlap at the clinical and cellular level. The most common single mutation in families with FTD or ALS has recently been mapped to a non-coding repeat expansion in the uncharacterized gene C9ORF72. Although a plausible mechanism for disease is that aberrant C9ORF72 mRNA poisons splicing, it is important to determine the cellular function of C9ORF72, about which nothing is known. Sensitive homology searches showed that C9ORF72 is a full-length distant homologue of proteins related to Differentially Expressed in Normal and Neoplasia (DENN), which is a GDP/GTP exchange factor (GEF) that activates Rab-GTPases. Our results suggest that C9ORF72 is likely to regulate membrane traffic in conjunction with Rab-GTPase switches, and we propose to name the gene and its product DENN-like 72 (DENNL72).

  6. Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4.

    Science.gov (United States)

    Mills, Shirley C; Howell, Lesley; Beekman, Andrew; Stokes, Leanne; Mueller, Anja

    2018-01-01

    Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling does not regulate cell migration in either suspension or adherent cells. We have confirmed the involvement of Rac1 with the use of a specific Rac1 blocking peptide. We also used a Rac1 inhibitor EHT 1864 and a Rac1-GEF inhibitor NSC23766 to probe the importance of Rac1 in chemotaxis. Both inhibitors did not block CCL3-induced chemotaxis, but they were able to block CXCL12-induced chemotaxis. This confirms that Rac1 activation is not essential for CCL3-induced migration, however NSC23766 might have secondary effects on CXCR4. This small molecule exhibits agonistic features in internalisation and cAMP assays, whereas it acts as an antagonist for CXCR4 in migration and calcium release assays. Our findings strongly suggest that Rac1 activation is not necessary for CCL3 signalling, and reveal that NSC23766 could be a novel CXCR4 receptor ligand. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  7. Raumgefühle – Gefühlsräume. Perspektiven auf die Verschränkung von emotionalen Praktiken und Topografien der Moderne

    Directory of Open Access Journals (Sweden)

    Benno Gammerl

    2015-08-01

    Full Text Available Ausgehend von verschiedenen Ansätzen in der Forschung zu Gefühlen und Räumen umreißt der Artikel das theoretische, empirische und politische Potenzial des Spannungsfelds zwischen der affektiven Durchkreuzung geordneter Strukturen und der emotionalen Bearbeitung machtdurchwirkter Raumverhältnisse. Praktiken des urban gardening und Debatten über Gentrifizierung zeigen beispielhaft, wie Analysen der dynamischen Interaktionen zwischen Räumen und Gefühlen für eine kritische Perspektive auf Urbanität fruchtbar werden können. Die Beschäftigung mit der Körperlichkeit von Raumgefühlen und der Materialität von Gefühlsräumen bietet willkommene Gelegenheiten, nach Strategien zu suchen, die weder das beharrliche Wirken des Sozialen noch die widerständige Kraft des Materiellen in deterministischer Manier überbetonen, sondern sich stattdessen auf die ambivalenten Dynamiken und Effekte gefühlsräumlicher Prozesse konzentrieren.

  8. Measurement of Am-242 fission yields at the Lohengrin spectrometer; improvement and Benchmarking of the semi-empirical code GEF

    International Nuclear Information System (INIS)

    Amouroux, Charlotte

    2014-01-01

    The study of fission yields has a major impact on the characterization and understanding of the fission process and is mandatory for reactor applications. While the yields are known for the major actinides (U-235, Pu-239) in the thermal neutron-induced fission, only few measurements were performed on Am-242. Moreover, the two main data libraries do not agree among each other on the light peak. Am-241 and Am-242 are nuclei of interest for the MOX-fuel reactors and for the reduction of nuclear waste radiotoxicity using transmutation reactions. Thus, a campaign of precise measurement of the fission mass yields from the reaction Am-241(2n,f) was performed at the Lohengrin mass spectrometer (ILL, France) for both the light and the heavy peak. Forty-one masses were measured. Moreover, the measurement of the isotopic fission yields on the heavy peak by gamma-ray spectrometry led to the extraction of 20 independent isotopic yields. Our measurement was also meant to determine whether there is a difference in fission yields between the Am-242 isomeric state and its ground state as it exists in fission cross sections. The experimental method used to answer this question is based on the measurement a set of fission mass yields as a function of the ratio of Am-242gs to Am-242m fission rate. Results show that the mass yields are independent of the fission rate ratio. A future experimental campaign is proposed to observe a possible influence on the isomeric yields. The theoretical models are nowadays unable to predict the fission yields with enough accuracy and therefore we have to rely on experimental data and phenomenological models. The accuracy of the predictions of the semi empirical GEF fission model predictions makes it a useful tool for evaluation. This thesis also presents the physical content and part of the development of this model. Validation of the kinetic energy distributions, isomeric yields and fission yields predictions was performed. The extension of the GEF

  9. Electronic excitation to low-lying states of GeF4 molecule by electron impact: A comparative study with CF4 and SiF4 molecules

    International Nuclear Information System (INIS)

    Ohtomi, S; Matsui, M; Mochizuki, Y; Suga, A; Kato, H; Hoshino, M; Tanaka, H; Duflot, D; Limão-Vieira, P

    2015-01-01

    We report on the measurements of the electron impact electronic excitation cross sections for XF 4 (X = C, Si and Ge) molecules at 100 eV, 5° scattering angle and 30 eV, 30° in the electron energy loss range 8.0 - 18 eV. For a target of GeF 4 molecule, the optically-forbidden behavior has been observed in the lower electron energy loss range. (paper)

  10. A non-typical sequence of phase transitions in (NH4)3GeF7: optical and structural characterization.

    Science.gov (United States)

    Mel'nikova, S V; Molokeev, M S; Laptash, N M; Misyul, S V

    2016-03-28

    Single crystals of germanium double salt (NH4)3GeF7 = (NH4)2GeF6·NH4F = (NH4)3[GeF6]F were grown and studied by the methods of polarization optics and X-ray diffraction. The birefringence Δn = (no - ne), the rotation angle of the optical indicatrix ϕ(T) and unit cell parameters were measured in the temperature range 100-400 K. Three structural phase transitions were found at the temperatures: T1↓ = 279.2 K (T1↑ = 279.4 K), T2↑ = 270 K (T2↓ = 268.9 K), T3↓ = 218 K (T3↑ = 227 K). An unusual sequence of symmetry transformations with temperature change was established: P4/mbm (Z = 2) (G1) ↔ Pbam (Z = 4) (G2) ↔ P21/c (Z = 4) (G3) ↔ Pa3[combining macron] (Z = 8) (G4). The crystal structures of different phases were determined. The experimental data were additionally interpreted by a group-theoretical analysis of the complete condensate of order parameters taking into account the critical and noncritical atomic displacements. Strengthening of the N-HF hydrogen bonds can be a driving force of the observed phase transitions.

  11. An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress.

    Science.gov (United States)

    West, Junior J; Zulueta-Coarasa, Teresa; Maier, Janna A; Lee, Donghoon M; Bruce, Ashley E E; Fernandez-Gonzalez, Rodrigo; Harris, Tony J C

    2017-08-07

    In response to a pulling force, a material can elongate, hold fast, or fracture. During animal development, multi-cellular contraction of one region often stretches neighboring tissue. Such local contraction occurs by induced actomyosin activity, but molecular mechanisms are unknown for regulating the physical properties of connected tissue for elongation under stress. We show that cytohesins, and their Arf small G protein guanine nucleotide exchange activity, are required for tissues to elongate under stress during both Drosophila dorsal closure (DC) and zebrafish epiboly. In Drosophila, protein localization, laser ablation, and genetic interaction studies indicate that the cytohesin Steppke reduces tissue tension by inhibiting actomyosin activity at adherens junctions. Without Steppke, embryogenesis fails, with epidermal distortions and tears resulting from myosin misregulation. Remarkably, actomyosin network assembly is necessary and sufficient for local Steppke accumulation, where live imaging shows Steppke recruitment within minutes. This rapid negative feedback loop provides a molecular mechanism for attenuating the main tension generator of animal tissues. Such attenuation relaxes tissues and allows orderly elongation under stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Auftreten von Falschem Mehltau bei Gartenkresse (Lepidium sativum L. in der Saatgutvermehrung – Evaluierung von Saatgutbehandlung und Wachstumsbedingungen in einem Gefäßversuch

    Directory of Open Access Journals (Sweden)

    Zeller, Stefanie

    2014-09-01

    Full Text Available Die zur Familie der Brassicaceae gehörende Gartenkresse wird in Deutschland überwiegend im biologischen Anbau vermehrt. Seit einigen Jahren werden diese Gartenkressebestände von Erregern des Falschen Mehltaus (Hyaloperonospora parasitica, Perofascia lepidii befallen, was zu einem Totalausfall des Pflanzenbestandes führen kann. Daher ist die biologische Saatgutproduktion von Gartenkresse gefährdet, was eine Beeinträchtigung der Saatgutversorgung für die Keimsprossenerzeugung zur Folge hat. In den laufenden Untersuchungen wird der Einfluss von nicht chemischen Saatgutbehandlungsmaßnahmen (Wasserdampf, Elektronen, sowie Wachstumsbedingungen (Feuchte, Boden auf die Infektion mit Falschem Mehltau untersucht.

  13. Purification and crystallization of the catalytic PRONE domain of RopGEF8 and its complex with Rop4 from Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Thomas, Christoph; Weyand, Michael; Wittinghofer, Alfred; Berken, Antje

    2006-01-01

    Crystals of the catalytic PRONE domain of the guanine nucleotide exchange factor RopGEF8 and its complex with the Rho-family protein Rop4 from A. thaliana were obtained that diffract to 2.2 and 3.1 Å resolution, respectively. The PRONE domain of the guanine nucleotide exchange factor RopGEF8 (PRONE8) was purified and crystallized free and in complex with the Rho-family protein Rop4 using the hanging-drop vapour-diffusion method. PRONE8 crystals were obtained using NaCl as precipitating agent and belong to the hexagonal space group P6 5 22. Native and anomalous data sets were collected using synchrotron radiation at 100 K to 2.2 and 2.8 Å resolution, respectively. Crystals of the Rop4–PRONE8 complex belonging to space group P6 3 were obtained using Tacsimate and PEG 3350 as precipitating agents and diffracted to 3.1 Å resolution

  14. Purification and crystallization of the catalytic PRONE domain of RopGEF8 and its complex with Rop4 from Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Christoph; Weyand, Michael; Wittinghofer, Alfred; Berken, Antje, E-mail: antje.berken@mpi-dortmund.mpg.de [Department of Structural Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany)

    2006-06-01

    Crystals of the catalytic PRONE domain of the guanine nucleotide exchange factor RopGEF8 and its complex with the Rho-family protein Rop4 from A. thaliana were obtained that diffract to 2.2 and 3.1 Å resolution, respectively. The PRONE domain of the guanine nucleotide exchange factor RopGEF8 (PRONE8) was purified and crystallized free and in complex with the Rho-family protein Rop4 using the hanging-drop vapour-diffusion method. PRONE8 crystals were obtained using NaCl as precipitating agent and belong to the hexagonal space group P6{sub 5}22. Native and anomalous data sets were collected using synchrotron radiation at 100 K to 2.2 and 2.8 Å resolution, respectively. Crystals of the Rop4–PRONE8 complex belonging to space group P6{sub 3} were obtained using Tacsimate and PEG 3350 as precipitating agents and diffracted to 3.1 Å resolution.

  15. Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline.

    Science.gov (United States)

    Yang, Long; Bashaw, Greg J

    2006-11-22

    Son of sevenless (Sos) is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases and thus is uniquely poised to integrate signals that affect both gene expression and cytoskeletal reorganization. Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand. Intriguingly, the Ras and Rac-GEF activities of Sos can be uncoupled during Robo-mediated axon repulsion; Sos axon guidance function depends on its Rac-GEF activity, but not its Ras-GEF activity. These results provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules and support a model in which Robo recruits Sos to the membrane via Dock to activate Rac during midline repulsion.

  16. Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity.

    Science.gov (United States)

    Katrancha, Sara M; Wu, Yi; Zhu, Minsheng; Eipper, Betty A; Koleske, Anthony J; Mains, Richard E

    2017-12-01

    Bipolar disorder, schizophrenia, autism and intellectual disability are complex neurodevelopmental disorders, debilitating millions of people. Therapeutic progress is limited by poor understanding of underlying molecular pathways. Using a targeted search, we identified an enrichment of de novo mutations in the gene encoding the 330-kDa triple functional domain (TRIO) protein associated with neurodevelopmental disorders. By generating multiple TRIO antibodies, we show that the smaller TRIO9 isoform is the major brain protein product, and its levels decrease after birth. TRIO9 contains two guanine nucleotide exchange factor (GEF) domains with distinct specificities: GEF1 activates both Rac1 and RhoG; GEF2 activates RhoA. To understand the impact of disease-associated de novo mutations and other rare sequence variants on TRIO function, we utilized two FRET-based biosensors: a Rac1 biosensor to study mutations in TRIO (T)GEF1, and a RhoA biosensor to study mutations in TGEF2. We discovered that one autism-associated de novo mutation in TGEF1 (K1431M), at the TGEF1/Rac1 interface, markedly decreased its overall activity toward Rac1. A schizophrenia-associated rare sequence variant in TGEF1 (F1538Intron) was substantially less active, normalized to protein level and expressed poorly. Overall, mutations in TGEF1 decreased GEF1 activity toward Rac1. One bipolar disorder-associated rare variant (M2145T) in TGEF2 impaired inhibition by the TGEF2 pleckstrin-homology domain, resulting in dramatically increased TGEF2 activity. Overall, genetic damage to both TGEF domains altered TRIO catalytic activity, decreasing TGEF1 activity and increasing TGEF2 activity. Importantly, both GEF changes are expected to decrease neurite outgrowth, perhaps consistent with their association with neurodevelopmental disorders. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Rezension von: Barbara Holland-Cunz: Gefährdete Freiheit. Über Hannah Arendt und Simone de Beauvoir. Opladen u.a.: Verlag Barbara Budrich 2012.

    Directory of Open Access Journals (Sweden)

    Mirjam Dierkes

    2012-11-01

    Full Text Available Von Barbara Holland-Cunz, die sich mit Simone de Beauvoir und Hannah Arendt bereits einzeln beschäftigt hat, liegt nun ein Band vor, in dem sie sich diesen herausragenden Denkerinnen des 20. Jahrhunderts gemeinsam widmet. In einer beinahe synoptisch anmutenden Herangehensweise fokussiert sie dabei auf den Begriff der Freiheit, der bei beiden von eminenter Bedeutung für das jeweilige Theoriegebäude ist. Holland-Cunz zufolge verstehen beide, bei einigen Unterschieden, Freiheit so, dass sie sich vor allem durch eine in sich eingeschriebene Gefährdung auszeichnet: Diese resultiert aus einem heroisch-emphatischen Gestus, der in paradoxer Weise gepaart wird mit einem abgeklärten Realismus. Über weite Strecken liest sich der Weg zu dieser Deutung, v. a. auch wegen einer teilweise sympathisch unkonventionellen und originellen Herangehensweise, sehr anregend und überzeugend.

  18. A role for eukaryotic translation initiation factor 2B (eIF2B) in taste memory consolidation and in thermal control establishment during the critical period for sensory development.

    Science.gov (United States)

    Tirosh, Sharon; Elkobi, Alina; Rosenblum, Kobi; Meiri, Noam

    2007-05-01

    All species exhibit critical periods for sensory development, yet very little is known about the molecules involved in the changes in the network wiring that underlies this process. Here the role of transcription regulation of the translation machinery was determined by evaluating the expression of eIF2Bepsilon, an essential component of translation initiation, in both taste-preference development and thermal control establishment in chicks. Analysis of the expression pattern of this gene after passive-avoidance training revealed clear induction of eIF2Bepsilon in both the mesopallium intermediomediale (IMM) and in the striatum mediale (StM). In addition, a correlation was found between the concentration of methylanthranilate (MeA), which was the malaise substrate in the passive-avoidance training procedure, the duration of memory, and the expression level of eIF2Bepsilon. Training chicks on a low concentration of MeA induced short-term memory and low expression level of eIF2Bepsilon, whereas a high concentration of MeA induced long-term memory and a high expression level of eIF2Bepsilon in both the IMM and StM. Furthermore, eIF2Bepsilon-antisense "knock-down" not only reduced the amount of eIF2Bepsilon but also attenuated taste memory formation. In order to determine whether induction of eIF2Bepsilon is a general feature of neuronal plasticity, we checked whether it was induced in other forms of neuronal plasticity, with particular attention to its role in temperature control establishment, which represents hypothalamic-related plasticity. It was established that eIF2Bepsilon-mRNA was induced in the preopotic anterior hypothalamus during heat conditioning. Taken together, these results correlate eIF2Bepsilon with sensory development.

  19. Gefühlsgemeinschaft“ – Autobiographische Erinnerungen an den BDM und der Erinnerungsdiskurs Community of Feeling—Autobiographical Memories of the BDM and Memory Discourse

    Directory of Open Access Journals (Sweden)

    Leonie Wagner

    2008-11-01

    Full Text Available Gisela Miller-Kipp dokumentiert und analysiert 27 Auszüge aus veröffentlichten Erinnerungen ehemaliger BDM-Mitglieder mit dem Ziel, deren Empfindungen und Gefühle zu rekonstruieren. Dabei sind interessante Einblicke möglich, die jedoch die von der Autorin intendierte Repräsentativität nicht einlösen (können. Zudem handelt es sich um Erinnerungen und damit um retrospektiv vorgenommene Konstruktionen, die meist noch mit dem Ziel einer Veröffentlichung aufgeschrieben wurden. Der Band liefert insofern wichtige Anregungen, ist aber in wissenschaftlicher Hinsicht nicht zufriedenstellend.Gisela Miller-Kipp documents and analyzes 27 excerpts from the published memories of former BDM-members with the goal of reconstructing their feelings and perceptions. This approach makes interesting insights possible but it cannot honor the author’s intended representativeness. In addition, because the book is about memories it presents retrospectively collected constructions that were mostly written down after the fact with the goal of publication. The volume therefore provides important perspectives that are not satisfying in a scientific respect.

  20. "Das unausgesprochene Gefühl der Unzugehörigkeit" : Amerika als Zufluchtsmöglichkeit vor dem Selbst in Max Frischs Romanen Stiller und Homo faber

    Directory of Open Access Journals (Sweden)

    Vesna Kondrič Horvat

    1993-12-01

    Full Text Available In seiner Rede Emigranten, die er 1958 anläßlich der Georg-BtichnerPreis- Verleihung hielt und woraus das Titelzitat des vorliegenden Beitrags stammt, äußerte Max Frisch die Meinung, jeder frei gewahlte Wohnsitz solle dem Schriftsteller das unausgesprochene Gefühl der Unzugehörigkeit gestatten. Mit dem Satz: "Ich bin nicht Stiller!" (St 9 beginnt Frisch seinen 1954 veröffentlichten Roman Stiller. Ein Mann - ein Bildhauer -, der viele Versuche unternommen hat, seiner 'eigentlichen ', seelisch-existentiellen Identität zu entgehen, flieht schlieBlich, als alle anderen Versuche (sich im Spanischen Bürgerkrieg als ein mutiger Mann, sich in der Ehe als ein idealer Mann, sich in der Kunst als erfolgreicher Bildhauer zu bewahren scheitern, nach Amerika und läßt seine lungenkranke Frau Julika im Sanatorium in Davos zurück. Nach mehr als sechsjahrigem Fernbleiben kehrt er unter anderem Namen in die Heimat zurück und wird an der Schweizer Grenze - wegen vermeintlicher Verwicklung in eine Spionage-Affäre - verhaftet. An diesem Punkt beginnt der Roman.

  1. Deals and Dealings: Inconclusive Peace and Treacherous Trade along the South Sudan–Uganda Border Geschäfte und Deals: Gefährdeter Frieden und riskante Handelsbeziehungen entlang der südsudanesisch-ugandischen Grenze

    Directory of Open Access Journals (Sweden)

    Mareike Schomerus

    2012-01-01

    Full Text Available Since Sudan’s Comprehensive Peace Agreement (CPA was signed, its border with Uganda has become a hub of activity. Contrasting developments on the Ugandan side of the border with those on the South Sudanese side, the paper draws on empirical fieldwork to argue that the CPA has created new centres of power in the margins of both states. However, in day-to-day dealings on either side of the border, South Sudanese military actors have become dominant. In the particular case of Arua and the South Sudan–Uganda border, past wartime authority structures determine access to opportunities in a tightly regulated, inconclusive peace. This means that small-scale Ugandan traders – although vital to South Sudan – have become more vulnerable to South Sudan’s assertions of state authority. The experience of Ugandan traders calls into question the broad consensus that trade across the border is always beneficial for peace-building. The paper concludes that trade is not unconditionally helpful to the establishment of a peaceful environment for everyone.Seit Unterzeichnung des Comprehensive Peace Agreement (CPA im Sudan hat sich die Grenze zwischen Südsudan und Uganda zu einem lebendigen Drehkreuz entwickelt. Gestützt auf eigene Feldforschungen stellen die Autoren die Entwicklungen in den Grenzregionen beider Länder dar, wo seit Abschluss des CPA neue Machtzentren entstanden sind. In den alltäglichen Geschäftsbeziehungen entlang der Grenze dominieren allerdings militärische Akteure. Im konkreten Fall von Arua und der südsudanesisch-ugandischen Grenze bestimmen Machtstrukturen aus Kriegszeiten den Zugang zu Handelsgelegenheiten, die in der Nachkriegsphase noch starken Regulierungen unterliegen. Ugandische Kleinhändler – für die Versorgung des Südsudan von zentraler Bedeutung – sind in dieser Situation zunehmend durch Eingriffe der neuen südsudanesischen Staatsmacht gefährdet. Die Erfahrungen der Händler aus Arua stellen den breiten Konsens

  2. Geometry and electronic structure of an impurity-trapped exciton in the Cs2GeF6 crystal doped with U4+. The 5f17s1 manifold

    International Nuclear Information System (INIS)

    Ordejon, B.; Seijo, L.; Barandiaran, Z.

    2007-01-01

    Complete text of publication follows: Excitons trapped at impurity centres in highly ionic crystals were first described by McClure and Pedrini [Phys. Rev. B 32, 8465 (1985)] as excited states consisting of a bound electron-hole pair with the hole localized on the impurity and the electron on nearby lattice sites, and a very short impurity-ligand bond length. In this work we present a detailed microscopic characterization of an impurity - trapped exciton in Cs 2 GeF 6 doped with U 4+ . Its electronic structure has been studied by means of CASSCF/CASPT2/SOCI relativistic ab initio model potential (AIMP) embedded-cluster calculations on (UF 6 ) 2- and (UF 6 Cs 8 ) 6+ clusters embedded in Cs 2 GeF 6 . The local geometry of the impurity-trapped exciton, the potential energy curves, and the multi electronic wavefunctions, have been obtained as direct, non-empirical results of the methods. The calculated excited states appear to be significantly delocalized outside the UF 6 volume and their U-F bond length turns out to be very short, closer to that of a pentavalent uranium defect than to that of a tetravalent uranium defect. The wavefunctions of these excited states show a dominant U 5f 1 7s 1 configuration character. This result has never been anticipated by simpler models and reveals the unprecedented ability of diffuse orbitals of f-element impurities to act as electron traps in ionic crystals

  3. Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold protein to polarize active Rac1 distribution

    NARCIS (Netherlands)

    Kroon, Jeffrey; Heemskerk, Niels; Kalsbeek, Martin J. T.; de Waard, Vivian; van Rijssel, Jos; van Buul, Jaap D.

    2017-01-01

    Endothelial cells line the lumen of the vessel wall and are exposed to flow. In linear parts of the vessel, the endothelial cells experience laminar flow, resulting in endothelial cell alignment in the direction of flow, thereby protecting the vessel wall from inflammation and permeability. In order

  4. The Arf GTPase-activating protein family is exploited by Salmonella enterica serovar Typhimurium to invade nonphagocytic host cells.

    Science.gov (United States)

    Davidson, Anthony C; Humphreys, Daniel; Brooks, Andrew B E; Hume, Peter J; Koronakis, Vassilis

    2015-02-10

    To establish intracellular infections, Salmonella bacteria trigger host cell membrane ruffling and invasion by subverting cellular Arf guanine nucleotide exchange factors (GEFs) that activate Arf1 and Arf6 GTPases by promoting GTP binding. A family of cellular Arf GTPase-activating proteins (GAPs) can downregulate Arf signaling by stimulating GTP hydrolysis, but whether they do this during infection is unknown. Here, we uncovered a remarkable role for distinct Arf GAP family members in Salmonella invasion. The Arf6 GAPs ACAP1 and ADAP1 and the Arf1 GAP ASAP1 localized at Salmonella-induced ruffles, which was not the case for the plasma membrane-localized Arf6 GAPs ARAP3 and GIT1 or the Golgi-associated Arf1 GAP1. Surprisingly, we found that loss of ACAP1, ADAP1, or ASAP1 impaired Salmonella invasion, revealing that GAPs cannot be considered mere terminators of cytoskeleton remodeling. Salmonella invasion was restored in Arf GAP-depleted cells by expressing fast-cycling Arf derivatives, demonstrating that Arf GTP/GDP cycles facilitate Salmonella invasion. Consistent with this view, both constitutively active and dominant-negative Arf derivatives that cannot undergo GTP/GDP cycles inhibited invasion. Furthermore, we demonstrated that Arf GEFs and GAPs colocalize at invading Salmonella and collaborate to drive Arf1-dependent pathogen invasion. This study revealed that Salmonella bacteria exploit a remarkable interplay between Arf GEFs and GAPs to direct cycles of Arf GTPase activation and inactivation. These cycles drive Salmonella cytoskeleton remodeling and enable intracellular infections. To initiate infections, the Salmonella bacterial pathogen remodels the mammalian actin cytoskeleton and invades host cells by subverting host Arf GEFs that activate Arf1 and Arf6 GTPases. Cellular Arf GAPs deactivate Arf GTPases and negatively regulate cell processes, but whether they target Arfs during infection is unknown. Here, we uncovered an important role for the Arf GAP

  5. In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains.

    Science.gov (United States)

    Côté, Jean-François; Vuori, Kristiina

    2006-01-01

    Rho family GTPases regulate a large variety of biological processes, including the reorganization of the actin cytoskeleton. Like other members of the Ras superfamily of small GTP-binding proteins, Rho GTPases cycle between a GDP-bound (inactive) and a GTP-bound (active) state, and, when active, the GTPases relay extracellular signals to a large number of downstream effectors. Guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP on Rho GTPases, thereby activating them. Most Rho-GEFs mediate their effects through their signature domain known as the Dbl Homology-Pleckstrin Homology (DH-PH) module. Recently, we and others identified a family of evolutionarily conserved, DOCK180-related proteins that also display GEF activity toward Rho GTPases. The DOCK180-family of proteins lacks the canonical DH-PH module. Instead, they rely on a novel domain, termed DHR-2, DOCKER, or CZH2, to exchange GDP for GTP on Rho targets. In this chapter, the experimental approach that we used to uncover the exchange activity of the DHR-2 domain of DOCK180-related proteins will be described.

  6. Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor.

    Science.gov (United States)

    Croisé, Pauline; Brunaud, Laurent; Tóth, Petra; Gasman, Stéphane; Ory, Stéphane

    2017-04-03

    Altered Rho GTPase signaling has been linked to many types of cancer. As many small G proteins, Rho GTPases cycle between an active and inactive state thanks to specific regulators that catalyze exchange of GDP into GTP (Rho-GEF) or hydrolysis of GTP into GDP (Rho-GAP). Recent studies have shown that alteration takes place either at the level of Rho proteins themselves (expression levels, point mutations) or at the level of their regulators, mostly RhoGEFs and RhoGAPs. Most reports describe Rho GTPases gain of function that may participate to the tumorigenesis processes. In contrast, we have recently reported that decreased activities of Cdc42 and Rac1 as well as decreased expression of 2 Rho-GEFs, FARP1 and ARHGEF1, correlate with pheochromocytomas, a tumor developing in the medulla of the adrenal gland (Croisé et al., Endocrine Related Cancer, 2016). Here we highlight the major evidence and further study the correlation between Rho GTPases activities and expression levels of ARHGEF1 and FARP1. Finally we also discuss how the decrease of Cdc42 and Rac1 activities may help human pheochromocytomas to develop and comment the possible relationship between FARP1, ARHGEF1 and the 2 Rho GTPases Cdc42 and Rac1 in tumorigenesis.

  7. Structural diversities induced by cation sizes in a series of fluorogermanophosphates: A2[GeF2(HPO4)2] (A = Na, K, Rb, NH4, and Cs).

    Science.gov (United States)

    Chen, Zhang-Gai; Huang, Xia; Zhuang, Rong-Chuan; Zhang, Yu; Liu, Xin; Shi, Tao; Wang, Shuai-Hua; Wu, Shao-Fan; Mi, Jin-Xiao; Huang, Ya-Xi

    2017-09-12

    Germanophosphates, in comparison with other metal phosphates, have been less studied but potentially exhibit more diverse structural chemistry with wide applications. Herein we applied a hydro-/solvo-fluorothermal route to make use of both the "tailor effect" of fluoride for the formation of low dimensional anionic clusters and the presence of alkali cations of different sizes to align the anionic clusters to control the overall crystal symmetries of germanophosphates. The synergetic effects of fluoride and alkali cations led to structural changes from chain-like structures to layered structures in a series of five novel fluorogermanophosphates: A 2 [GeF 2 (HPO 4 ) 2 ] (A = Na, K, Rb, NH 4 , and Cs, denoted as Na, K, Rb, NH4, and Cs). Although these fluorogermanophosphates have stoichiometrically equivalent formulas, they feature different anionic clusters, diverse structural dimensionalities, and contrasting crystal symmetries. Chain-like structures were observed for the compounds with the smaller sized alkali ions (Na + , K + , and Rb + ), whereas layered structures were found for those containing the larger sized cations ((NH 4 ) + and Cs + ). Specifically, monoclinic space groups were observed for the Na, K, Rb, and NH4 compounds, whereas a tetragonal space group P4/mbm was found for the Cs compound. These compounds provide new insights into the effects of cation sizes on the anionic clusters built from GeO 4 F 2 octahedra and HPO 4 tetrahedra as well as their influences on the overall structural symmetries in germanophosphates. Further characterization including IR spectroscopy and thermal analyses for all five compounds is also presented.

  8. Suppression of chemotaxis by SSeCKS via scaffolding of phosphoinositol phosphates and the recruitment of the Cdc42 GEF, Frabin, to the leading edge.

    Science.gov (United States)

    Ko, Hyun-Kyung; Guo, Li-wu; Su, Bing; Gao, Lingqiu; Gelman, Irwin H

    2014-01-01

    Chemotaxis is controlled by interactions between receptors, Rho-family GTPases, phosphatidylinositol 3-kinases, and cytoskeleton remodeling proteins. We investigated how the metastasis suppressor, SSeCKS, attenuates chemotaxis. Chemotaxis activity inversely correlated with SSeCKS levels in mouse embryo fibroblasts (MEF), DU145 and MDA-MB-231 cancer cells. SSeCKS loss induced chemotactic velocity and linear directionality, correlating with replacement of leading edge lamellipodia with fascin-enriched filopodia-like extensions, the formation of thickened longitudinal F-actin stress fibers reaching to filopodial tips, relative enrichments at the leading edge of phosphatidylinositol (3,4,5)P3 (PIP3), Akt, PKC-ζ, Cdc42-GTP and active Src (SrcpoY416), and a loss of Rac1. Leading edge lamellipodia and chemotaxis inhibition in SSeCKS-null MEF could be restored by full-length SSeCKS or SSeCKS deleted of its Src-binding domain (ΔSrc), but not by SSeCKS deleted of its three MARCKS (myristylated alanine-rich C kinase substrate) polybasic domains (ΔPBD), which bind PIP2 and PIP3. The enrichment of activated Cdc42 in SSeCKS-null leading edge filopodia correlated with recruitment of the Cdc42-specific guanine nucleotide exchange factor, Frabin, likely recruited via multiple PIP2/3-binding domains. Frabin knockdown in SSeCKS-null MEF restores leading edge lamellipodia and chemotaxis inhibition. However, SSeCKS failed to co-immunoprecipitate with Rac1, Cdc42 or Frabin. Consistent with the notion that chemotaxis is controlled by SSeCKS-PIP (vs. -Src) scaffolding activity, constitutively-active phosphatidylinositol 3-kinase could override the ability of the Src inhibitor, SKI-606, to suppress chemotaxis and filopodial enrichment of Frabin in SSeCKS-null MEF. Our data suggest a role for SSeCKS in controlling Rac1 vs. Cdc42-induced cellular dynamics at the leading chemotactic edge through the scaffolding of phospholipids and signal mediators, and through the reorganization of the

  9. Knochen, Herz und Gefäße – „Bone-Vascular Axis“: Eine systematische Übersicht prospektiver Beobachtungsstudien // The Bone-Cardiovascular Axis: A Systematic Review of Prospective Studies

    Directory of Open Access Journals (Sweden)

    Tomaschitz A

    2016-01-01

    bone diseases the current evidence however indicates a potential benefit in screening for cardiovascular diseases and osteoporosis in respective risk groups. p bKurzfassung/b: Osteoporose und atherosklerotische Erkrankungen sind mit massiv erhöhter Morbidität, Mortalität und Gesundheitskosten verbunden. Mit der „bone-vascular axis“ entstand in den letzten Jahren ein intensiv beforschtes, klinisch hoch relevantes Gebiet. Mechanistische Studien identifizierten komplexe wechselseitige Beziehungen zwischen der vaskulären Physiologie, der Knochenneubildung und der Knochenmineralisation. Herz und Gefäße spielen eine relevante Rolle für die muskuloskelettale Funktion und umgekehrt beeinflusst das Knochengewebe u. a. über endo- und parakrine Signalwege das Herz-Kreislaufsystem. Epidemiologische Studien wiesen auch nach Berücksichtigung gemeinsamer Risikofaktoren auf unabhängige, wechselseitige Interaktionen zwischen Herz, Gefäßen und Knochengewebe hin.brIm Rahmen einer systematischen Literaturrecherche (Medline, Pubmed wurden insgesamt 49 prospektive Studien, die den Zusammenhang zwischen Osteoporose, Knochenmineraldichte und Auftreten von Frakturen mit atherosklerotischen Erkrankungen beschreiben, selektiert. Dabei konnten diese Untersuchungen mehrheitlich eine erhöhte kardiovaskuläre Morbidität und Mortalität bei Frauen und Männern mit verminderter Knochenmineraldichte an verschiedenen Lokalisationen sowie nach osteoporotischen Frakturen nachweisen. Umgekehrt konnten zahlreiche Studien ein erhöhtes Risiko für die Entstehung einer Osteoporose sowie von osteoporotischen Frakturen bei Patienten mit atherosklerotischen Erkrankungen nachweisen. Schließlich konnten konsistente Assoziationen zwischen Herzinsuffizienz (7 Studien, Schlaganfall (16 Studien, peripherer arterieller Verschlusskrankheit (3 Studien und Knochenmineraldichte sowie Frakturrisiko detektiert werden.brGrundsätzlich lassen Beobachtungsstudien keine Rückschlüsse auf die Kausalität der

  10. The UNDP/GEF Baltic wind atlas

    DEFF Research Database (Denmark)

    Rathmann, O.

    2003-01-01

    based on 7 stations in the coastal area: the 3 Lithuanian sites Kretinga, Vilkyciai and Taurage; the Latvian site Särnate; and the 3 Estonian sites Prangli, Virtsu and Uulu. In addition, private data measured at theEstonian site Türisalu was made available to the project. Although the campaign...... was running for about two years it was only possible to get one full one-year data series for each site with start time ranging from primo May 2001 to primo October 2001. Themeasured data have been analysed according to the “Wind Atlas Method”, implying cleansing the wind data for nearby terrain effects......-institute stations with long-term records as well as datafor the short-term measurement period of the present campaign. Similarly, inter-comparison techniques were used to adjust for data fall-out for longer unbroken periods. The data from this project have been supplemented by in-land data from measuringstations...

  11. GEF climate change operational strategy: Whither UNDP?

    Energy Technology Data Exchange (ETDEWEB)

    Hosier, R.

    1996-12-31

    The paper discusses aspects of the implementation of the program for climatic change which has been come about as part of the U.N. Framework Convention on Climate Change. Initial effort has focused on providing strategic information and help to countries, on achieving offsets in greenhouse gas emissions by energy conservation or carbon sinking, and an emphasis on development of renewable energy supplies. The U.N. Development Agency has limited funding to help support startup on projects submitted. Specific examples are discussed in the areas of energy conservation and energy efficiency, adoption of renewable energy sources, and reducing the long-term costs of low greenhouse gas-emitting energy technologies.

  12. Activation of Extracellular Signal-Regulated Kinase but Not of p38 Mitogen-Activated Protein Kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS

    Science.gov (United States)

    Jun, Jesse E.; Yang, Ming; Chen, Hang; Chakraborty, Arup K.

    2013-01-01

    Thymocytes convert graded T cell receptor (TCR) signals into positive selection or deletion, and activation of extracellular signal-related kinase (ERK), p38, and Jun N-terminal protein kinase (JNK) mitogen-activated protein kinases (MAPKs) has been postulated to play a discriminatory role. Two families of Ras guanine nucleotide exchange factors (RasGEFs), SOS and RasGRP, activate Ras and the downstream RAF-MEK-ERK pathway. The pathways leading to lymphocyte p38 and JNK activation are less well defined. We previously described how RasGRP alone induces analog Ras-ERK activation while SOS and RasGRP cooperate to establish bimodal ERK activation. Here we employed computational modeling and biochemical experiments with model cell lines and thymocytes to show that TCR-induced ERK activation grows exponentially in thymocytes and that a W729E allosteric pocket mutant, SOS1, can only reconstitute analog ERK signaling. In agreement with RasGRP allosterically priming SOS, exponential ERK activation is severely decreased by pharmacological or genetic perturbation of the phospholipase Cγ (PLCγ)-diacylglycerol-RasGRP1 pathway. In contrast, p38 activation is not sharply thresholded and requires high-level TCR signal input. Rac and p38 activation depends on SOS1 expression but not allosteric activation. Based on computational predictions and experiments exploring whether SOS functions as a RacGEF or adaptor in Rac-p38 activation, we established that the presence of SOS1, but not its enzymatic activity, is critical for p38 activation. PMID:23589333

  13. Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors

    Energy Technology Data Exchange (ETDEWEB)

    Malaby, Andrew W.; Das, Sanchaita; Chakravarthy, Srinivas; Irving, Thomas C.; Bilsel, Osman; Lambright, David G.

    2018-01-01

    Membrane dynamic processes including vesicle biogenesis depend on Arf guanosine triphosphatase (GTPase) activation by guanine nucleotide exchange factors (GEFs) containing a catalytic Sec7 domain and a membrane-targeting module such as a pleckstrin homology (PH) domain. The catalytic output of cytohesin family Arf GEFs is controlled by autoinhibitory interactions that impede accessibility of the exchange site in the Sec7 domain. These restraints can be relieved through activator Arf-GTP binding to an allosteric site comprising the PH domain and proximal autoinhibitory elements (Sec7-PH linker and C-terminal helix). Small-angle X-ray scattering and negative-stain electron microscopy were used to investigate the structural organization and conformational dynamics of cytohesin-3 (Grp1) in autoinhibited and active states. The results support a model in which hinge dynamics in the autoinhibited state expose the activator site for Arf-GTP binding, while subsequent C-terminal helix unlatching and repositioning unleash conformational entropy in the Sec7-PH linker to drive exposure of the exchange site.

  14. Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.

    Directory of Open Access Journals (Sweden)

    Masao Terasawa

    Full Text Available The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain the Dbl homology domain typically found in guanine nucleotide exchange factors (GEFs, DOCK2 mediates the GTP-GDP exchange reaction for Rac via its DOCK homology region (DHR-2 (also known as CZH2 or Docker domain. DOCK2 DHR-2 domain is composed of three lobes, and Rac binding site and catalytic center are generated entirely from lobes B and C. On the other hand, lobe A has been implicated in dimer formation, yet its physiological significance remains unknown. Here, we report that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration. We found that unlike wild-type DOCK2, DOCK2 mutant lacking lobe A failed to restore motility and polarity when expressed in thymoma cells and primary T cells lacking endogenous expression of DOCK2. Similar results were obtained with the DOCK2 point mutant having a defect in dimerization. Deletion of lobe A from the DHR-2 domain did not affect Rac GEF activity in vitro. However, fluorescence resonance energy transfer analyses revealed that lobe A is required for DOCK2 to activate Rac effectively during cell migration. Our results thus indicate that DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and Rac are localized to the plasma membrane.

  15. ARF6 Activated by the LHCG Receptor through the Cytohesin Family of Guanine Nucleotide Exchange Factors Mediates the Receptor Internalization and Signaling*

    Science.gov (United States)

    Kanamarlapudi, Venkateswarlu; Thompson, Aiysha; Kelly, Eamonn; López Bernal, Andrés

    2012-01-01

    The luteinizing hormone chorionic gonadotropin receptor (LHCGR) is a Gs-coupled GPCR that is essential for the maturation and function of the ovary and testis. LHCGR is internalized following its activation, which regulates the biological responsiveness of the receptor. Previous studies indicated that ADP-ribosylation factor (ARF)6 and its GTP-exchange factor (GEF) cytohesin 2 regulate LHCGR internalization in follicular membranes. However, the mechanisms by which ARF6 and cytohesin 2 regulate LHCGR internalization remain incompletely understood. Here we investigated the role of the ARF6 signaling pathway in the internalization of heterologously expressed human LHCGR (HLHCGR) in intact cells using a combination of pharmacological inhibitors, siRNA and the expression of mutant proteins. We found that human CG (HCG)-induced HLHCGR internalization, cAMP accumulation and ARF6 activation were inhibited by Gallein (βγ inhibitor), Wortmannin (PI 3-kinase inhibitor), SecinH3 (cytohesin ARF GEF inhibitor), QS11 (an ARF GAP inhibitor), an ARF6 inhibitory peptide and ARF6 siRNA. However, Dynasore (dynamin inhibitor), the dominant negative mutants of NM23-H1 (dynamin activator) and clathrin, and PBP10 (PtdIns 4,5-P2-binding peptide) inhibited agonist-induced HLHCGR and cAMP accumulation but not ARF6 activation. These results indicate that heterotrimeric G-protein, phosphatidylinositol (PI) 3-kinase (PI3K), cytohesin ARF GEF and ARF GAP function upstream of ARF6 whereas dynamin and clathrin act downstream of ARF6 in the regulation of HCG-induced HLHCGR internalization and signaling. In conclusion, we have identified the components and molecular details of the ARF6 signaling pathway required for agonist-induced HLHCGR internalization. PMID:22523074

  16. Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome–associated Sos1 mutation

    Science.gov (United States)

    Chen, Peng-Chieh; Wakimoto, Hiroko; Conner, David; Araki, Toshiyuki; Yuan, Tao; Roberts, Amy; Seidman, Christine E.; Bronson, Roderick; Neel, Benjamin G.; Seidman, Jonathan G.; Kucherlapati, Raju

    2010-01-01

    Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, unique facial features, and congenital heart disease. About 10%–15% of individuals with NS have mutations in son of sevenless 1 (SOS1), which encodes a RAS and RAC guanine nucleotide exchange factor (GEF). To understand the role of SOS1 in the pathogenesis of NS, we generated mice with the NS-associated Sos1E846K gain-of-function mutation. Both heterozygous and homozygous mutant mice showed many NS-associated phenotypes, including growth delay, distinctive facial dysmorphia, hematologic abnormalities, and cardiac defects. We found that the Ras/MAPK pathway as well as Rac and Stat3 were activated in the mutant hearts. These data provide in vivo molecular and cellular evidence that Sos1 is a GEF for Rac under physiological conditions and suggest that Rac and Stat3 activation might contribute to NS phenotypes. Furthermore, prenatal administration of a MEK inhibitor ameliorated the embryonic lethality, cardiac defects, and NS features of the homozygous mutant mice, demonstrating that this signaling pathway might represent a promising therapeutic target for NS. PMID:21041952

  17. Identification of a negative regulatory region for the exchange activity and characterization of T332I mutant of Rho guanine nucleotide exchange factor 10 (ARHGEF10).

    Science.gov (United States)

    Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu

    2011-08-26

    The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1-332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant.

  18. Identification of a Negative Regulatory Region for the Exchange Activity and Characterization of T332I Mutant of Rho Guanine Nucleotide Exchange Factor 10 (ARHGEF10)*

    Science.gov (United States)

    Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu

    2011-01-01

    The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1–332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant. PMID:21719701

  19. Guanine nucleotide exchange factor αPIX leads to activation of the Rac 1 GTPase/glycogen phosphorylase pathway in interleukin (IL)-2-stimulated T cells

    DEFF Research Database (Denmark)

    Llavero, Francisco; Urzelai, Bakarne; Osinalde, Nerea

    2015-01-01

    Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation. In the lymphoid system, Rac 1 and in general other small GTPases of the Rho family participate...... in the signaling cascades that are activated after engagement of the T cell antigen receptor. However, little is known about the IL-2-dependent Rac 1 activator molecules. For the first time, a signaling pathway leading to the activation of Rac 1/PYGM in response to IL-2-stimulated T cell proliferation is described....... More specifically, αPIX, a known guanine nucleotide exchange factor for the small GTPases of the Rho family, preferentially Rac 1, mediates PYGM activation in Kit 225 T cells stimulated with IL-2. Using directed mutagenesis, phosphorylation of αPIX Rho-GEF serines 225 and 488 is required for activation...

  20. Biochemical characterization of a heterotrimeric G(i)-protein activator peptide designed from the junction between the intracellular third loop and sixth transmembrane helix in the m4 muscarinic acetylcholine receptor.

    Science.gov (United States)

    Terawaki, Shin-ichi; Matsubayashi, Rina; Hara, Kanako; Onozuka, Tatsuki; Kohno, Toshiyuki; Wakamatsu, Kaori

    Muscarinic acetylcholine receptors (mAChRs) are G-protein coupled receptors (GPCRs) that are activated by acetylcholine released from parasympathetic nerves. The mAChR family comprises 5 subtypes, m1-m5, each of which has a different coupling selectivity for heterotrimeric GTP-binding proteins (G-proteins). m4 mAChR specifically activates the Gi/o family by enhancing the guanine nucleotide exchange factor (GEF) reaction with the Gα subunit through an interaction that occurs via intracellular segments. Here, we report that the m4 mAChR mimetic peptide m4i3c(14)Gly, comprising 14 residues in the junction between the intracellular third loop (i3c) and transmembrane helix VI (TM-VI) extended with a C-terminal glycine residue, presents GEF activity toward the Gi1 α subunit (Gαi1). The m4i3c(14)Gly forms a stable complex with guanine nucleotide-free Gαi1 via three residues in the VTI(L/F) motif, which is conserved within the m2/4 mAChRs. These results suggest that this m4 mAChR mimetic peptide, which comprises the amino acid of the mAChR intracellular segments, is a useful tool for understanding the interaction between GPCRs and G-proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Epac activation sensitizes rat sensory neurons via activation of Ras

    Science.gov (United States)

    Shariati, Behzad; Thompson, Eric L.; Nicol, Grant D.; Vasko, Michael R.

    2015-01-01

    Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2′-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. PMID:26596174

  2. Epac activation sensitizes rat sensory neurons through activation of Ras.

    Science.gov (United States)

    Shariati, Behzad; Thompson, Eric L; Nicol, Grant D; Vasko, Michael R

    2016-01-01

    Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2'-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation.

    Science.gov (United States)

    Wu, Nan; Ren, Dong; Li, Su; Ma, Wenli; Hu, Shaoyan; Jin, Yan; Xiao, Sheng

    2018-01-10

    Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds the switch regions of Rac1 to prevent access from GEFs. Three cancer cell lines with up- or down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1 signaling and sensitivity to a group of nine chemotherapeutic drugs. RCC2 expression in lung cancer and ovarian cancer were studied using immunochemistry stain of tumor tissue arrays. Forced RCC2 expression in tumor cells blocked spontaneous- or Staurosporine (STS)-induced apoptosis. In contrast, RCC2 knock down in these cells resulted in increased apoptosis to STS treatment. The protective activity of RCC2 on apoptosis was revoked by a constitutively activated Rac1, confirming a role of RCC2 in apoptosis by regulating Rac1. In an immunohistochemistry evaluation of tissue microarray, RCC2 was over-expressed in 88.3% of primary lung cancer and 65.2% of ovarian cancer as compared to non-neoplastic lung and ovarian tissues, respectively. Because chemotherapeutic drugs can kill tumor cells by activating Rac1/JNK pathway, we suspect that tumors with RCC2 overexpression would be more resistant to these drugs. Tumor cells with forced RCC2 expression indeed had significant difference in drug sensitivity compared to parental cells using a panel of common chemotherapeutic drugs. RCC2 regulates apoptosis by blocking Rac1 signaling. RCC2 expression in tumor can be a useful marker for predicting chemotherapeutic response.

  4. The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner.

    Directory of Open Access Journals (Sweden)

    Aniko Keller-Pinter

    Full Text Available The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs. Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu mutant of syndecan-4 (SDC4. SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1 to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways.

  5. The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction–dependent manner

    Science.gov (United States)

    Keller-Pinter, Aniko; Ughy, Bettina; Domoki, Monika; Pettko-Szandtner, Aladar; Letoha, Tamas; Tovari, Jozsef; Timar, Jozsef

    2017-01-01

    The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1–RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways. PMID:29121646

  6. The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner.

    Science.gov (United States)

    Keller-Pinter, Aniko; Ughy, Bettina; Domoki, Monika; Pettko-Szandtner, Aladar; Letoha, Tamas; Tovari, Jozsef; Timar, Jozsef; Szilak, Laszlo

    2017-01-01

    The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways.

  7. Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin

    Science.gov (United States)

    Lin, Changsheng; Ear, Jason; Midde, Krishna; Lopez-Sanchez, Inmaculada; Aznar, Nicolas; Garcia-Marcos, Mikel; Kufareva, Irina; Abagyan, Ruben; Ghosh, Pradipta

    2014-01-01

    A long-standing issue in the field of signal transduction is to understand the cross-talk between receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major and distinct signaling hubs that control eukaryotic cell behavior. Although stimulation of many RTKs leads to activation of trimeric G proteins, the molecular mechanisms behind this phenomenon remain elusive. We discovered a unifying mechanism that allows GIV/Girdin, a bona fide metastasis-related protein and a guanine-nucleotide exchange factor (GEF) for Gαi, to serve as a direct platform for multiple RTKs to activate Gαi proteins. Using a combination of homology modeling, protein–protein interaction, and kinase assays, we demonstrate that a stretch of ∼110 amino acids within GIV C-terminus displays structural plasticity that allows folding into a SH2-like domain in the presence of phosphotyrosine ligands. Using protein–protein interaction assays, we demonstrated that both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Gαi, and growth factor receptors and for activation of Gαi after growth factor stimulation. Expression of a SH2-deficient GIV mutant (Arg 1745→Leu) that cannot bind RTKs impaired all previously demonstrated functions of GIV—Akt enhancement, actin remodeling, and cell migration. The mechanistic and structural insights gained here shed light on the long-standing questions surrounding RTK/G protein cross-talk, set a novel paradigm, and characterize a unique pharmacological target for uncoupling GIV-dependent signaling downstream of multiple oncogenic RTKs. PMID:25187647

  8. Modelling the widths of fission observables in GEF

    Directory of Open Access Journals (Sweden)

    Schmidt K.-H.

    2013-03-01

    Full Text Available The widths of the mass distributions of the different fission channels are traced back to the probability distributions of the corresponding quantum oscillators that are coupled to the heat bath, which is formed by the intrinsic degrees of freedom of the fissioning system under the influence of pairing correlations and shell effects. Following conclusion from stochastic calculations of Adeev and Pashkevich, an early freezing due to dynamical effects is assumed. It is shown that the mass width of the fission channels in low-energy fission is strongly influenced by the zero-point motion of the corresponding quantum oscillator. The observed variation of the mass widths of the asymmetric fission channels with excitation energy is attributed to the energy-dependent properties of the heat bath and not to the population of excited states of the corresponding quantum oscillator.

  9. The Phosphatidylinositol (3,4,5)-Trisphosphate-dependent Rac Exchanger 1·Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1·Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells.

    Science.gov (United States)

    Lucato, Christina M; Halls, Michelle L; Ooms, Lisa M; Liu, Heng-Jia; Mitchell, Christina A; Whisstock, James C; Ellisdon, Andrew M

    2015-08-21

    The P-Rex (phosphatidylinositol (3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger) family (P-Rex1 and P-Rex2) of the Rho guanine nucleotide exchange factors (Rho GEFs) activate Rac GTPases to regulate cell migration, invasion, and metastasis in several human cancers. The family is unique among Rho GEFs, as their activity is regulated by the synergistic binding of PIP3 and Gβγ at the plasma membrane. However, the molecular mechanism of this family of multi-domain proteins remains unclear. We report the 1.95 Å crystal structure of the catalytic P-Rex1 DH-PH tandem domain in complex with its cognate GTPase, Rac1 (Ras-related C3 botulinum toxin substrate-1). Mutations in the P-Rex1·Rac1 interface revealed a critical role for this complex in signaling downstream of receptor tyrosine kinases and G protein-coupled receptors. The structural data indicated that the PIP3/Gβγ binding sites are on the opposite surface and markedly removed from the Rac1 interface, supporting a model whereby P-Rex1 binding to PIP3 and/or Gβγ releases inhibitory C-terminal domains to expose the Rac1 binding site. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP).

    Science.gov (United States)

    Roberts, Owain Llŷr; Dart, Caroline

    2014-02-01

    The second messenger cAMP plays a central role in mediating vascular smooth muscle relaxation in response to vasoactive transmitters and in strengthening endothelial cell-cell junctions that regulate the movement of solutes, cells and macromolecules between the blood and the surrounding tissue. The vasculature expresses three cAMP effector proteins: PKA (protein kinase A), CNG (cyclic-nucleotide-gated) ion channels, and the most recently discovered Epacs (exchange proteins directly activated by cAMP). Epacs are a family of GEFs (guanine-nucleotide-exchange factors) for the small Ras-related GTPases Rap1 and Rap2, and are being increasingly implicated as important mediators of cAMP signalling, both in their own right and in parallel with the prototypical cAMP target PKA. In the present paper, we review what is currently known about the role of Epac within blood vessels, particularly with regard to the regulation of vascular tone, endothelial barrier function and inflammation.

  11. Planning, budgeting and performance management at Swiss hospitals – Are Swiss hospitals at a crossroads – Will these medical specialist organisations in future develop into institutions with a business orientation? [Die Krankenhäuser der Schweiz am Wendepunkt von der medizinischen Expertenorganisation hin zu betriebswirtschaftlich geführten Institutionen? – Untersuchung zu deren Performance-Management-System

    Directory of Open Access Journals (Sweden)

    Walser, Konrad

    2013-11-01

    äuser leistungsorientiert geführt werden.

  12. The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes

    Directory of Open Access Journals (Sweden)

    Proud Christopher G

    2002-05-01

    Full Text Available Abstract Background Activation of human resting T lymphocytes results in an immediate increase in protein synthesis. The increase in protein synthesis after 16–24 h has been linked to the increased protein levels of translation initiation factors. However, the regulation of protein synthesis during the early onset of T cell activation has not been studied in great detail. We studied the regulation of protein synthesis after 1 h of activation using αCD3 antibody to stimulate the T cell receptor and αCD28 antibody to provide the co-stimulus. Results Activation of the T cells with both antibodies led to a sustained increase in the rate of protein synthesis. The activities and/or phosphorylation states of several translation factors were studied during the first hour of stimulation with αCD3 and αCD28 to explore the mechanism underlying the activation of protein synthesis. The initial increase in protein synthesis was accompanied by activation of the guanine nucleotide exchange factor, eukaryotic initiation factor (eIF 2B, and of p70 S6 kinase and by dephosphorylation of eukaryotic elongation factor (eEF 2. Similar signal transduction pathways, as assessed using signal transduction inhibitors, are involved in the regulation of protein synthesis, eIF2B activity and p70 S6 kinase activity. A new finding was that the p38 MAPK α/β pathway was involved in the regulation of overall protein synthesis in primary T cells. Unexpectedly, no changes were detected in the phosphorylation state of the cap-binding protein eIF4E and the eIF4E-binding protein 4E-BP1, or the formation of the cap-binding complex eIF4F. Conclusions Both eIF2B and p70 S6 kinase play important roles in the regulation of protein synthesis during the early onset of T cell activation.

  13. Present activities of the Danube environmental Programme

    International Nuclear Information System (INIS)

    Botterweg, T.; Turcan, J.

    1997-01-01

    The international character of the Danube river basin reflects among other aspects also the importance and the need of international co-operation at various levels. The response of this need has been expressed by the formation of different international commissions and organisations in the basin, covering mainly technical but in the recent time also the environmental interests of the riparian states. The Danube countries, several G-24 governments, as well as international and non governmental organisations decided in the autumn of 1991 to start the Environmental Programme for the Danube River Basin (EPDRB) and form the Danube Task Force. A joint Programme work plan was agreed by the Task Force in February 1992, thereby launching a series of priority projects designed to built environmental co-operation among the Danube countries. The main objective was to establish an operational basis for strategic and integrated management of the Danube river basin environment. The planning and working documents, which were outlining the activities within the EPDRB are the Strategic Action Plan (SAP-1994) and the Strategic Action Plan Implementation Programme (SIP-1996). These documents frame the works of the 13 Tasks of the Applied Research Programme, Sub-Groups of the Accident Emergency Warning System, Monitoring, Laboratories and Information Management and Data Management as well as the major areas of work, divided in Groups and Clusters, each of which will involve projects to be carried out in a number of Danube countries. All activities are oriented to the improvement of the environment, however special attention is paid to task dealing with biodiversity, wetlands restoration, water and soil protection. The main funding, which is secured until the year 2000 comes from the Danube countries, the EU Phare and Tacis programmes, the UN GEF, international banks and foundations. (author)

  14. Neuronal adaptor FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating ELMO1.

    Science.gov (United States)

    Li, Wen; Tam, Ka Ming Vincent; Chan, Wai Wan Ray; Koon, Alex Chun; Ngo, Jacky Chi Ki; Chan, Ho Yin Edwin; Lau, Kwok-Fai

    2018-04-03

    Neurite outgrowth is a crucial process in developing neurons for neural network formation. Understanding the regulatory mechanisms of neurite outgrowth is essential for developing strategies to stimulate neurite regeneration after nerve injury and in neurodegenerative disorders. FE65 is a brain-enriched adaptor that stimulates Rac1-mediated neurite elongation. However, the precise mechanism by which FE65 promotes the process remains elusive. Here, we show that ELMO1, a subunit of ELMO1-DOCK180 bipartite Rac1 GEF, interacts with the FE65 N-terminal region. Overexpression of FE65 and/or ELMO1 enhances whereas knockdown of FE65 or ELMO1 inhibits neurite outgrowth and Rac1 activation. The effect of FE65 alone or together with ELMO1 is attenuated by an FE65 double mutation that disrupts FE65-ELMO1 interaction. Notably, FE65 is found to activate ELMO1 by diminishing ELMO1 intramolecular autoinhibitory interaction and to promote the targeting of ELMO1 to the plasma membrane where Rac1 is activated. We also show that FE65, ELMO1 and DOCK180 form a tripartite complex. Knockdown of DOCK180 reduces the stimulatory effect of FE65-ELMO1 on Rac1 activation and neurite outgrowth. Thus, we identify a novel mechanism that FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating of ELMO1. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  15. RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during aggregation.

    Science.gov (United States)

    Lim, C J; Spiegelman, G B; Weeks, G

    2001-08-15

    Disruption of Dictyostelium rasC, encoding a Ras subfamily protein, generated cells incapable of aggregation. While rasC expression is enriched in a cell type-specific manner during post-aggregative development, the defect in rasC(-) cells is restricted to aggregation and fully corrected by application of exogenous cAMP pulses. cAMP is not produced in rasC(-) cells stimulated by 2'-deoxy-cAMP, but is produced in response to GTPgammaS in cell lysates, indicating that G-protein-coupled cAMP receptor activation of adenylyl cyclase is regulated by RasC. However, cAMP-induced ERK2 phosphorylation is unaffected in rasC(-) cells, indicating that RasC is not an upstream activator of the mitogen-activated protein kinase required for cAMP relay. rasC(-) cells also exhibit reduced chemotaxis to cAMP during early development and delayed response to periodic cAMP stimuli produced by wild-type cells in chimeric mixtures. Furthermore, cAMP-induced Akt/PKB phosphorylation through a phosphatidylinositide 3-kinase (PI3K)-dependent pathway is dramatically reduced in rasC(-) cells, suggesting that G-protein-coupled serpentine receptor activation of PI3K is regulated by RasC. Cells lacking the RasGEF, AleA, exhibit similar defects as rasC(-) cells, suggesting that AleA may activate RasC.

  16. PI3-kinase γ promotes Rap1a-mediated activation of myeloid cell integrin α4β1, leading to tumor inflammation and growth.

    Directory of Open Access Journals (Sweden)

    Michael C Schmid

    Full Text Available Tumor inflammation, the recruitment of myeloid lineage cells into the tumor microenvironment, promotes angiogenesis, immunosuppression and metastasis. CD11b+Gr1lo monocytic lineage cells and CD11b+Gr1hi granulocytic lineage cells are recruited from the circulation by tumor-derived chemoattractants, which stimulate PI3-kinase γ (PI3Kγ-mediated integrin α4 activation and extravasation. We show here that PI3Kγ activates PLCγ, leading to RasGrp/CalDAG-GEF-I&II mediated, Rap1a-dependent activation of integrin α4β1, extravasation of monocytes and granulocytes, and inflammation-associated tumor progression. Genetic depletion of PLCγ, CalDAG-GEFI or II, Rap1a, or the Rap1 effector RIAM was sufficient to prevent integrin α4 activation by chemoattractants or activated PI3Kγ (p110γCAAX, while activated Rap (RapV12 promoted constitutive integrin activation and cell adhesion that could only be blocked by inhibition of RIAM or integrin α4β1. Similar to blockade of PI3Kγ or integrin α4β1, blockade of Rap1a suppressed both the recruitment of monocytes and granulocytes to tumors and tumor progression. These results demonstrate critical roles for a PI3Kγ-Rap1a-dependent pathway in integrin activation during tumor inflammation and suggest novel avenues for cancer therapy.

  17. Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS.

    Science.gov (United States)

    Huang, William Y C; Yan, Qingrong; Lin, Wan-Chen; Chung, Jean K; Hansen, Scott D; Christensen, Sune M; Tu, Hsiung-Lin; Kuriyan, John; Groves, Jay T

    2016-07-19

    The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. The generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes.

  18. A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay.

    Science.gov (United States)

    Reichman, Melvin; Schabdach, Amanda; Kumar, Meera; Zielinski, Tom; Donover, Preston S; Laury-Kleintop, Lisa D; Lowery, Robert G

    2015-12-01

    Ras homologous (Rho) family GTPases act as molecular switches controlling cell growth, movement, and gene expression by cycling between inactive guanosine diphosphate (GDP)- and active guanosine triphosphate (GTP)-bound conformations. Guanine nucleotide exchange factors (GEFs) positively regulate Rho GTPases by accelerating GDP dissociation to allow formation of the active, GTP-bound complex. Rho proteins are directly involved in cancer pathways, especially cell migration and invasion, and inhibiting GEFs holds potential as a therapeutic strategy to diminish Rho-dependent oncogenesis. Methods for measuring GEF activity suitable for high-throughput screening (HTS) are limited. We developed a simple, generic biochemical assay method for measuring GEF activity based on the fact that GDP dissociation is generally the rate-limiting step in the Rho GTPase catalytic cycle, and thus addition of a GEF causes an increase in steady-state GTPase activity. We used the Transcreener GDP Assay, which relies on selective immunodetection of GDP, to measure the GEF-dependent stimulation of steady-state GTP hydrolysis by small GTPases using Dbs (Dbl's big sister) as a GEF for Cdc42, RhoA, and RhoB. The assay is well suited for HTS, with a homogenous format and far red fluorescence polarization (FP) readout, and it should be broadly applicable to diverse Rho GEF/GTPase pairs. © 2015 Society for Laboratory Automation and Screening.

  19. Epac : effectors and biological functions

    NARCIS (Netherlands)

    Roscioni, Sara S.; Elzinga, Carolina R. S.; Schmidt, Martina

    Epac1 (also known as cAMP-GEF-I) and Epac2 (also known as cAMP-GEF-II) are cyclic AMP-activated guanine nucleotide exchange factors for Ras-like GTPases. Since their discovery about 10 years ago, it is now accepted that Epac proteins are novel cAMP sensors that regulate several pivotal cellular

  20. Energizing change

    International Nuclear Information System (INIS)

    El-Ashry, M.T.

    1998-01-01

    Since its creation in 1991, the Global Environment Facility (GEF) has committed over US D 725 million to nearly 200 projects in 49 nations in concrete action to combat climate changes. Its activities are implemented by the United Nations Environmental Programme, the United Nations Development Programme and the World Bank. This paper describes the GEF's work to combat climatic changes

  1. VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells

    Directory of Open Access Journals (Sweden)

    Ayumi Yoshida

    2015-09-01

    Full Text Available Neuropilin-1 (NRP1 has been identified as a VEGF-A receptor. DJM-1, a human skin cancer cell line, expresses endogenous VEGF-A and NRP1. In the present study, the RNA interference of VEGF-A or NRP1 suppressed DJM-1 cell proliferation. Furthermore, the overexpression of the NRP1 wild type restored shNRP1-treated DJM-1 cell proliferation, whereas NRP1 cytoplasmic deletion mutants did not. A co-immunoprecipitation analysis revealed that VEGF-A induced interactions between NRP1 and GIPC1, a scaffold protein, and complex formation between GIPC1 and Syx, a RhoGEF. The knockdown of GIPC1 or Syx reduced active RhoA and DJM-1 cell proliferation without affecting the MAPK or Akt pathway. C3 exoenzyme or Y27632 inhibited the VEGF-A-induced proliferation of DJM-1 cells. Conversely, the overexpression of the constitutively active form of RhoA restored the proliferation of siVEGF-A-treated DJM-1 cells. Furthermore, the inhibition of VEGF-A/NRP1 signaling upregulated p27, a CDK inhibitor. A cell-penetrating oligopeptide that targeted GIPC1/Syx complex formation inhibited the VEGF-A-induced activation of RhoA and suppressed DJM-1 cell proliferation. In conclusion, this new signaling pathway of VEGF-A/NRP1 induced cancer cell proliferation by forming a GIPC1/Syx complex that activated RhoA to degrade the p27 protein.

  2. Extracellular adenosine-induced Rac1 activation in pulmonary endothelium: Molecular mechanisms and barrier-protective role.

    Science.gov (United States)

    Kovacs-Kasa, Anita; Kim, Kyung Mi; Cherian-Shaw, Mary; Black, Stephen M; Fulton, David J; Verin, Alexander D

    2018-08-01

    We have previously shown that Gs-coupled adenosine receptors (A2a) are primarily involved in adenosine-induced human pulmonary artery endothelial cell (HPAEC) barrier enhancement. However, the downstream events that mediate the strengthening of the endothelial cell (EC) barrier via adenosine signaling are largely unknown. In the current study, we tested the overall hypothesis that adenosine-induced Rac1 activation and EC barrier enhancement is mediated by Gs-dependent stimulation of cAMP-dependent Epac1-mediated signaling cascades. Adenoviral transduction of HPAEC with constitutively-active (C/A) Rac1 (V12Rac1) significantly increases transendothelial electrical resistance (TER) reflecting an enhancement of the EC barrier. Conversely, expression of an inactive Rac1 mutant (N17Rac1) decreases TER reflecting a compromised EC barrier. The adenosine-induced increase in TER was accompanied by activation of Rac1, decrease in contractility (MLC dephosphorylation), but not Rho inhibition. Conversely, inhibition of Rac1 activity attenuates adenosine-induced increase in TER. We next examined the role of cAMP-activated Epac1 and its putative downstream targets Rac1, Vav2, Rap1, and Tiam1. Depletion of Epac1 attenuated the adenosine-induced Rac1 activation and the increase in TER. Furthermore, silencing of Rac1 specific guanine nucleotide exchange factors (GEFs), Vav2 and Rap1a expression significantly attenuated adenosine-induced increases in TER and activation of Rac1. Depletion of Rap1b only modestly impacted adenosine-induced increases in TER and Tiam1 depletion had no effect on adenosine-induced Rac1 activation and TER. Together these data strongly suggest that Rac1 activity is required for adenosine-induced EC barrier enhancement and that the activation of Rac1 and ability to strengthen the EC barrier depends, at least in part, on cAMP-dependent Epac1/Vav2/Rap1-mediated signaling. © 2017 Wiley Periodicals, Inc.

  3. T1R3 homomeric sweet taste receptor regulates adipogenesis through Gαs-mediated microtubules disassembly and Rho activation in 3T3-L1 cells.

    Directory of Open Access Journals (Sweden)

    Yosuke Masubuchi

    Full Text Available We previously reported that 3T3-L1 cells express a functional sweet taste receptor possibly as a T1R3 homomer that is coupled to Gs and negatively regulates adipogenesis by a Gαs-mediated but cAMP-independent mechanism. Here, we show that stimulation of this receptor with sucralose or saccharin induced disassembly of the microtubules in 3T3-L1 preadipocytes, which was attenuated by overexpression of the dominant-negative mutant of Gαs (Gαs-G226A. In contrast, overexpression of the constitutively active mutant of Gαs (Gαs-Q227L as well as treatment with cholera toxin or isoproterenol but not with forskolin caused disassembly of the microtubules. Sweetener-induced microtubule disassembly was accompanied by activation of RhoA and Rho-associated kinase (ROCK. This was attenuated with by knockdown of GEF-H1, a microtubule-localized guanine nucleotide exchange factor for Rho GTPase. Furthermore, overexpression of the dominant-negative mutant of RhoA (RhoA-T19N blocked sweetener-induced dephosphorylation of Akt and repression of PPARγ and C/EBPα in the early phase of adipogenic differentiation. These results suggest that the T1R3 homomeric sweet taste receptor negatively regulates adipogenesis through Gαs-mediated microtubule disassembly and consequent activation of the Rho/ROCK pathway.

  4. Vanishing White Matter Disease

    Science.gov (United States)

    ... the ovaries, which can result in lack of menstrual periods, fertility problems and early menopause. Mental decline ... manner. This means that both parents carry one copy of a mutated eIF2B gene and pass it ...

  5. Genetics Home Reference: leukoencephalopathy with vanishing white matter

    Science.gov (United States)

    ... Torres C, Pröschel C. EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy. Nat Med. ... of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  6. Eukaryotic translation initiation factor 2B-beta (eIF2Bβ), a new class of plant virus resistance gene.

    Science.gov (United States)

    Shopan, Jannat; Mou, Haipeng; Zhang, Lili; Zhang, Changtong; Ma, Weiwei; Walsh, John A; Hu, Zhongyuan; Yang, Jinghua; Zhang, Mingfang

    2017-06-01

    Recessive resistances to plant viruses in the Potyvirus genus have been found to be based on mutations in the plant eukaryotic translation initiation factors, eIF4E and eIF4G or their isoforms. Here we report that natural, monogenic recessive resistance to the Potyvirus Turnip mosaic virus (TuMV) has been found in a number of mustard (Brassica juncea) accessions. Bulked segregant analysis and sequencing of resistant and susceptible plant lines indicated the resistance is controlled by a single recessive gene, recessive TuMV resistance 03 (retr03), an allele of the eukaryotic translation initiation factor 2B-beta (eIF2Bβ). Silencing of eIF2Bβ in a TuMV-susceptible mustard plant line and expression of eIF2Bβ from a TuMV-susceptible line in a TuMV-resistant mustard plant line confirmed the new resistance mechanism. A functional copy of a specific allele of eIF2Bβ is required for efficient TuMV infection. eIF2Bβ represents a new class of virus resistance gene conferring resistance to any pathogen. eIF2B acts as a guanine nucleotide exchange factor (GEF) for its GTP-binding protein partner eIF2 via interaction with eIF2·GTP at an early step in translation initiation. Further genotyping indicated that a single non-synonymous substitution (A120G) in the N-terminal region of eIF2Bβ was responsible for the TuMV resistance. A reproducible marker has been developed, facilitating marker-assisted selection for TuMV resistance in B. juncea. Our findings provide a new target for seeking natural resistance to potyviruses and new opportunities for the control of potyviruses using genome editing techniques targeted on eIF2Bβ. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  7. Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection.

    Directory of Open Access Journals (Sweden)

    Eva Rothmeier

    2013-09-01

    Full Text Available The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS to form in phagocytes a distinct "Legionella-containing vacuole" (LCV, which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila.

  8. Activation of Ran GTPase by a Legionella Effector Promotes Microtubule Polymerization, Pathogen Vacuole Motility and Infection

    Science.gov (United States)

    Rothmeier, Eva; Pfaffinger, Gudrun; Hoffmann, Christine; Harrison, Christopher F.; Grabmayr, Heinrich; Repnik, Urska; Hannemann, Mandy; Wölke, Stefan; Bausch, Andreas; Griffiths, Gareth; Müller-Taubenberger, Annette; Itzen, Aymelt; Hilbi, Hubert

    2013-01-01

    The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS) to form in phagocytes a distinct “Legionella-containing vacuole” (LCV), which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF) domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP) in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED) fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila. PMID:24068924

  9. Letzte Welt Die Wissenschaft gefährdet unser Überleben

    CERN Multimedia

    Rees, Martin J

    2003-01-01

    The mathematician and mystic Blaise Pascal had a famous argument about religious behavior: Even if you consider it extraordinarily improbable that an eagerness God exists, it would be careful and reasonable to behave as if he had existed

  10. Über die Gefügeausbildung technischer Magnesiumlegierungen in industriellen Gießprozessen

    OpenAIRE

    Klaus, Gerald

    2011-01-01

    The demand for lightweight constructions and light weight materials is probably as old as the transportation of people and goods. The aspiration in gaining even better light weight materials with increased mechanical properties is an old, but still actual topic. At this point magnesium alloys can be applied to fullfill this demand. Actually available commercial alloys have to be improved regarding their mechanical properties, especially for increased temperatures. This work aims to gain a bet...

  11. Requirement of the Caenorhabditis elegans RapGEF pxf-1 and rap-1 for epithelial integrity

    Czech Academy of Sciences Publication Activity Database

    Pellis-van Berkel, W.; Verheijen, M. H. G.; Cuppen, E.; Asahina, Masako; de Rooij, J.; Jansen, G.; Plasterk, R. H. A.; Bos, J. L.; Zwartkruis, F. J. T.

    2005-01-01

    Roč. 16, č. 1 (2005), s. 106-116 ISSN 1059-1524 R&D Projects: GA AV ČR KJB5022303 Institutional research plan: CEZ:AV0Z60220518 Keywords : Rap signaling pathway * epidermis * Caenorhabditis elegans Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.520, year: 2005

  12. NtGNL1a ARF-GEF acts in endocytosis in tobacco cells

    Czech Academy of Sciences Publication Activity Database

    Jelínková, Adriana; Müller, Karel; Pařezová, Markéta; Petrášek, Jan

    2015-01-01

    Roč. 15, NOV 5 (2015), s. 272 ISSN 1471-2229 R&D Projects: GA ČR GPP305/11/P797 Institutional support: RVO:61389030 Keywords : Endocytosis * PIN1 protein trafficking * Inhibitors of endomembrane trafficking Subject RIV: EA - Cell Biology Impact factor: 3.631, year: 2015

  13. Gefährlicher Trend : Smartphone im Strassenverkehr : auch zu Fuss ist das Ablenkungspotenzial sehr gross.

    NARCIS (Netherlands)

    2016-01-01

    Viele Menschen, die sich zu Fuß im Straßenverkehr bewegen, nutzen dabei das Smartphone. Dies ist das Ergebnis einer Erhebung von DEKRA in sechs europäischen Hauptstädten. Von den rund 14.000 erfassten Personen nutzten fast 17 Prozent ihr Handy — für Textnachrichten, zum Telefonieren oder Musikhören.

  14. Scham im Kino : Kleine Phänomenologie eines peinlichen Gefühls

    NARCIS (Netherlands)

    Hanich, Julian

    Wer ans Kino denkt, denkt nicht an Scham. Die Emotionsmaschine „Kino“ rührt das Publikum zu Tränen, versetzt es in Angst und Schrecken oder zwingt es zum Lachen. Zuschauer reagieren wütend, erfreut, angeekelt, sie staunen und bewundern. Vielleicht sind sie sogar heimlich in Cary Grant oder Claudia

  15. Ist der Euro gefährdet? Is the European currency euro put at risk?

    Directory of Open Access Journals (Sweden)

    Armin Rohde

    2012-01-01

    Full Text Available Due to high national debt in several member states of the Euro-Currency-Area which led to huge relief programmes the single European currency Euro seems to be at risk. Bur neither inflation rates nor exchange rate movements of the Euro since 1999 up to 2011 give reasons to believe that an up to now success story of the Euro will come to a sudden end in shortness. On the other hand it often had been argued that increasing national debt will inevitably lead to higher inflation rates and will endanger a currency by permanent devaluation. But the institutional and legal framework of the European monetary policy, if used correctly, will give sufficient protection against inflation pressure due to increasing national debt. The most danger for the European currency or for the European-Currency-Area can be seen in drifting apart of national competiveness between the member states of the Euro- Area, especially due to an existing lack of coordination in wage policy. Different wage policies in the member states of the Euro-Area in the past had led to different national inflation rates and had caused calculated real exchange rate movements which had lasting influence on national competiveness, which hamper international trade in the case of real appreciation or which promote international trade in the case of real depreciation..

  16. Das „neue“ Private. Familie als intime Gefühlsgemeinschaft

    Directory of Open Access Journals (Sweden)

    Regina Harzer

    2006-11-01

    Full Text Available Methodisch versteht sich die Habilitationsschrift als Beitrag zur Rekonstruktion moderner politischer Philosophie. Als zentraler Ansatzpunkt dient das Familienkonzept von Rousseau, seine Schriften werden auf Geschlechterkonstruktionen und bürgerliche Geschlechterordnungen hin untersucht. Grundanliegen der Studie ist es, Bürgerlichkeit unter ihrem zentralen Aspekt des Privaten zu betrachten und in den Kontext moderner kontraktualistischer Philosophie zu stellen. Die Autorin vertritt die Ausgangsthese, Rousseau müsse eine „Schlüsselstellung“ (S. 9 in der Geschichte der bürgerlichen Geschlechter- und Familienordnung zugesprochen werden. Durch ihn sei die Trennung des Privaten vom Öffentlichen eingeleitet und festgeschrieben worden.

  17. Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration*

    Science.gov (United States)

    Ou, Young; Chan, Gordon; Zuo, Jeremy; Rattner, Jerome B.; van der Hoorn, Frans A.

    2016-01-01

    The tight, relative positioning of the nucleus and centrosome in mammalian cells is important for the regulation of cell migration. Under pathophysiological conditions, the purinergic A2b receptor can regulate cell motility, but the underlying mechanism remains unknown. Expression of A2b, normally low, is increased in tissues experiencing adverse physiological conditions, including hypoxia and inflammation. ATP is released from such cells. We investigated whether extracellular cues can regulate centrosome-nucleus positioning and cell migration. We discovered that hypoxia as well as extracellular ATP cause a reversible increase in the distance between the centrosome and nucleus and reduced cell motility. We uncovered the underlying pathway: both treatments act through the A2b receptor and specifically activate the Epac1/RapGef3 pathway. We show that cells lacking A2b do not respond in this manner to hypoxia or ATP but transfection of A2b restores this response, that Epac1 is critically involved, and that Rap1B is important for the relative positioning of the centrosome and nucleus. Our results represent, to our knowledge, the first report demonstrating that pathophysiological conditions can impact the distance between the centrosome and nucleus. Furthermore, we identify the A2b receptor as a central player in this process. PMID:27226580

  18. Study of multiplet structures of Mn4+ activated in fluoride crystals

    International Nuclear Information System (INIS)

    Novita, Mega; Honma, Tetsuo; Hong, Byungchul; Ohishi, Atsushi; Ogasawara, Kazuyoshi

    2016-01-01

    We investigated the optical properties of Mn 4+ in some fluoride crystals such as Cs 2 MnF 6 , Cs 2 GeF 6 , Rb 2 GeF 6 , Cs 2 SiF 6 , K 2 SiF 6 , Rb 2 MnF 6 , Rb 2 SiF 6 , K 2 GeF 6 , K 2 TiF 6 , Li 2 MnF 6 , Na 2 GeF 6 , Na 2 SiF 6 , and Na 2 TiF 6 based on the first-principle calculation using the discrete-variational multi-electron method. In order to estimate the lattice relaxation, we performed EXAFS measurement of Mn 4+ doped in K 2 SiF 6 , K 2 TiF 6 , and K 2 GeF 6 . The relaxation rates of A 2 BF 6 :Mn 4+ were fixed to be the above estimated values, 102.24%, 107.37% or 96.80% for crystal having Si, Ge, or Ti at the B cation site, respectively. In this work, we also considered some corrections such as configuration dependent correction and correlation correction to improve the theoretical energies. It has been shown that to reproduce multiplet energy levels quantitatively, the lattice relaxation is very important. On the other hand, for a qualitative prediction of the tendencies of the multiplet energies, the combination of lattice relaxation effect, configuration dependent correction, and correlation correction is effective. - Highlights: • Multiplet structures of A 2 BF 6 :Mn 4+ were calculated from first-principles. • Lattice relaxation was estimated based on EXAFS experiment. • Lattice relaxation is important to reproduce multiplet energies quantitatively. • CDC and CC are important to reproduce tendencies of multiplet energies.

  19. Проектная деятельность школьников в рамках преемственности начального и основного общего образования

    OpenAIRE

    Григорьева, Е.; Клементьева, Н.

    2014-01-01

    The article raises the problem of continuity of project activities in primary and basic school, explores the history of «project method» and the mod- ern requirements of the GEF to the project activity

  20. Rsr1 Focuses Cdc42 Activity at Hyphal Tips and Promotes Maintenance of Hyphal Development in Candida albicans

    Science.gov (United States)

    Pulver, Rebecca; Heisel, Timothy; Gonia, Sara; Robins, Robert; Norton, Jennifer; Haynes, Paula

    2013-01-01

    The extremely elongated morphology of fungal hyphae is dependent on the cell's ability to assemble and maintain polarized growth machinery over multiple cell cycles. The different morphologies of the fungus Candida albicans make it an excellent model organism in which to study the spatiotemporal requirements for constitutive polarized growth and the generation of different cell shapes. In C. albicans, deletion of the landmark protein Rsr1 causes defects in morphogenesis that are not predicted from study of the orthologous protein in the related yeast Saccharomyces cerevisiae, thus suggesting that Rsr1 has expanded functions during polarized growth in C. albicans. Here, we show that Rsr1 activity localizes to hyphal tips by the differential localization of the Rsr1 GTPase-activating protein (GAP), Bud2, and guanine nucleotide exchange factor (GEF), Bud5. In addition, we find that Rsr1 is needed to maintain the focused localization of hyphal polarity structures and proteins, including Bem1, a marker of the active GTP-bound form of the Rho GTPase, Cdc42. Further, our results indicate that tip-localized Cdc42 clusters are associated with the cell's ability to express a hyphal transcriptional program and that the ability to generate a focused Cdc42 cluster in early hyphae (germ tubes) is needed to maintain hyphal morphogenesis over time. We propose that in C. albicans, Rsr1 “fine-tunes” the distribution of Cdc42 activity and that self-organizing (Rsr1-independent) mechanisms of polarized growth are not sufficient to generate narrow cell shapes or to provide feedback to the transcriptional program during hyphal morphogenesis. PMID:23223038

  1. E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor

    International Nuclear Information System (INIS)

    Jenei, Veronika; Andersson, Tommy; Jakus, Judit; Dib, Karim

    2005-01-01

    E3B1, a human homologue of the mouse gene product Abi-1, has been implicated in growth-factor-mediated regulation of the small GTPases p21 Ras and Rac. E3b1 is a regulator of Rac because it can form a complex with Sos-1 and eps8, and such a Sos-1-e3B1-eps8 complex serves as a guanine nucleotide exchange factor for Rac. In the present study, we found that overexpression of e3B1 in NIH3T3/EGFR cells sensitized EGF-induced activation of Rac1, whereas it had no impact on EGF-induced activation of p21 Ras . Remarkably, we found that EGF-induced activation of the p21 Ras -related GTPase Rap1 was also sensitized in NIH3T3/EGFR-e3B1 cells. Thus, in NIH3T3/EGFR-e3B1 cells, maximal EGF-induced activation of Rap1 occurs with a dose of EGF much lower than in NIH3T3/EGFR cells. We also report that overexpression of e3B1 in NIH3T3/EGFR cells renders EGF-induced activation of Rap1 completely dependent on Src tyrosine kinases but not on c-Abl. However, EGF-induced tyrosine phosphorylation of the Rap GEF C3G occurred regardless of whether e3B1 was overexpressed or not, and this did not involve Src tyrosine kinases. Accordingly, we propose that overexpression of e3B1 in NIH3T3/EGFR cells leads to mobilization of Src tyrosine kinases that participate in EGF-induced activation of Rap1 and inhibition of cell proliferation

  2. Methane recovery from landfill in China

    Energy Technology Data Exchange (ETDEWEB)

    Gaolai, L.

    1996-12-31

    GEF has approved a special project for a demonstration project for Methane Recovery from the Urban Refuse Land Fill. This paper will introduce the possibility of GHG reduction from the landfill in China, describe the activities of the GEF project, and the priorities for international cooperation in this field. The Global Environment Facility (GEF) approved the project, China Promoting Methane Recovery and Unlization from Mixed Municipal Refuse, at its Council meeting in last April. This project is the first one supported by international organization in this field.

  3. Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors.

    Science.gov (United States)

    Yoshimura, Shin-ichiro; Gerondopoulos, Andreas; Linford, Andrea; Rigden, Daniel J; Barr, Francis A

    2010-10-18

    A key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of the 63 human Rabs have no known GEF. We have performed a systematic characterization of the 17 human DENN domain proteins and demonstrated that they are specific GEFs for 10 Rabs. DENND1A/1B localize to clathrin patches at the plasma membrane and activate Rab35 in an endocytic pathway trafficking Shiga toxin to the trans-Golgi network. DENND2 GEFs target to actin filaments and control Rab9-dependent trafficking of mannose-6-phosphate receptor to lysosomes. DENND4 GEFs target to a tubular membrane compartment adjacent to the Golgi, where they activate Rab10, which suggests a function in basolateral polarized sorting in epithelial cells that compliments the non-DENN GEF Sec2 acting on Rab8 in apical sorting. DENND1C, DENND3, DENND5A/5B, MTMR5/13, and MADD activate Rab13, Rab12, Rab39, Rab28, and Rab27A/27B, respectively. Together, these findings provide a basis for future studies on Rab regulation and function.

  4. The Emerging Role of Guanine Exchange Factors in ALS and other neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Cristian eDroppelmann

    2014-09-01

    Full Text Available Small GTPases participate in a broad range of cellular processes such as proliferation, differentiation and migration. The exchange of GDP for GTP resulting in the activation of these GTPases is catalyzed by a group of enzymes called guanine nucleotide exchange factors (GEFs, of which two classes: Dbl-related exchange factors and the more recently described Dock family exchange factors. Increasingly, deregulation of normal GEF activity or function has been associated with a broad range of disease states, including neurodegeneration and neurodevelopmental disorders. In this review, we examine this evidence with special emphasis on the novel role of Rho guanine nucleotide exchange factor (RGNEF/p190RhoGEF in the pathogenesis of amyotrophic lateral sclerosis (ALS. RGNEF is the first neurodegeneration-linked GEF that regulates not only RhoA GTPase activation but also functions as an RNA binding protein that directly acts with low molecular weight neurofilament (NEFL mRNA 3’UTR to regulate its stability. This dual role for RGNEF, coupled with the increasing understanding of the key role for GEFs in modulating the GTPase function in cell survival suggests a prominent role for GEFs in mediating a critical balance between cytotoxicity and neuroprotection which, when disturbed, contributes to neuronal loss.

  5. RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin.

    Directory of Open Access Journals (Sweden)

    Hiroaki Kajiho

    Full Text Available The Rab family of small guanosine triphosphatases (GTPases plays a vital role in membrane trafficking. Its active GTP-bound state is driven by guanine nucleotide-exchange factors (GEFs. Ras and Rab interactor (or Ras interaction/interference-like (RINL, which contains a conserved VPS9 domain critical for GEF action, was recently identified as a new Rab5 subfamily GEF in vitro. However, its detailed function and interacting molecules have not yet been fully elucidated. Here we found that RINL has GEF activity for the Rab5 subfamily proteins by measuring their GTP-bound forms in cultured cells. We also found that RINL interacts with odin, a member of the ankyrin-repeat and sterile-alpha motif (SAM domain-containing (Anks protein family. In addition, the Eph tyrosine kinase receptor EphA8 formed a ternary complex with both RINL and odin. Interestingly, RINL expression in cultured cells reduced EphA8 levels in a manner dependent on both its GEF activity and interaction with odin. In addition, knockdown of RINL increased EphA8 level in HeLa cells. Our findings suggest that RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin.

  6. Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase

    LENUS (Irish Health Repository)

    McSherry, Elaine A

    2011-03-23

    and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. Conclusions Our findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and β1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis.

  7. Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase.

    LENUS (Irish Health Repository)

    McSherry, Elaine A

    2011-03-23

    -6 and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. CONCLUSIONS: Our findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and β1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis.

  8. Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase.

    LENUS (Irish Health Repository)

    McSherry, Elaine A

    2012-02-01

    JAM-A, AF-6 and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. CONCLUSIONS: Our findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and beta1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis.

  9. Active Teachers - Active Students

    DEFF Research Database (Denmark)

    as an initiative from the Polytechnic in Nantes, France and the University the Los Andes in Bogota, Colombia. The objective was to start a world wide collaboration allowing teachers in engineering to learn from each other about their experiences with active learning. In this thirteenth edition, ALE joins forces...... with the International Research Symposium on Problem Based Learning (IRSPB) and the International Symposium on Project Approaches in Engineering Education (PAEE) to organise the first International Joint Conference on the Learner in Engineering Education (IJCLEE 2015) hosted by Mondragon University, in San Sebastian...

  10. Is activation analysis still active?

    International Nuclear Information System (INIS)

    Chai Zhifang

    2001-01-01

    This paper reviews some aspects of neutron activation analysis (NAA), covering instrumental neutron activation analysis (INAA), k 0 method, prompt gamma-ray neutron activation analysis (PGNAA), radiochemical neutron activation analysis (RNAA) and molecular activation analysis (MAA). The comparison of neutron activation analysis with other analytical techniques are also made. (author)

  11. C3G knock-down enhances migration and invasion by increasing Rap1-mediated p38α activation, while it impairs tumor growth through p38α-independent mechanisms

    Science.gov (United States)

    Priego, Neibla; Arechederra, María; Sequera, Celia; Bragado, Paloma; Vázquez-Carballo, Ana; Gutiérrez-Uzquiza, Álvaro; Martín-Granado, Víctor; Ventura, Juan José; Kazanietz, Marcelo G.; Guerrero, Carmen; Porras, Almudena

    2016-01-01

    C3G, a Guanine nucleotide Exchange Factor (GEF) for Rap1 and R-Ras, has been shown to play important roles in development and cancer. Previous studies determined that C3G regulates cell death through down-regulation of p38α MAPK activity. Here, we found that C3G knock-down in MEFs and HCT116 cells promotes migration and invasion through Rap1-mediated p38α hyper-activation. These effects of C3G were inhibited by Rap1 knock-down or inactivation. The enhanced migration observed in C3G depleted HCT116 cells was associated with reduction in E-cadherin expression, internalization of ZO-1, actin cytoskeleton reorganization and decreased adhesion. We also found that matrix metalloproteases MMP2 and MMP9 are involved in the pro-invasive effect of C3G down-regulation. Additionally, our studies revealed that both C3G and p38α collaborate to promote growth of HCT116 cells in vitro and in vivo, possibly by enhancing cell survival. In fact, knocking-down C3G or p38α individually or together promoted cell death in vitro, although only the double C3G-p38α silencing was able to increase cell death within tumors. Notably, we found that the pro-tumorigenic function of C3G does not depend on p38α or Rap1 activation. Altogether, our studies uncover novel mechanisms by which C3G controls key aspects of tumorigenesis. PMID:27286263

  12. Neurotrophin responsiveness of sympathetic neurons is regulated by rapid mobilization of the p75 receptor to the cell surface through TrkA activation of Arf6.

    Science.gov (United States)

    Edward Hickman, F; Stanley, Emily M; Carter, Bruce D

    2018-05-22

    The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is up regulated resulting in formation of TrkA-p75 complexes, which are high affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 GEFs. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth while the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system. SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface

  13. The activation of RhoC in vascular endothelial cells is required for the S1P receptor type 2-induced inhibition of angiogenesis.

    Science.gov (United States)

    Del Galdo, Sabrina; Vettel, Christiane; Heringdorf, Dagmar Meyer Zu; Wieland, Thomas

    2013-12-01

    Sphingosine-1-phosphate (S1P) is a multifunctional phospholipid inducing a variety of cellular responses in endothelial cells (EC). S1P responses are mediated by five G protein coupled receptors of which three types (S1P1R-S1P3R) have been described to be of importance in vascular endothelial cells (EC). Whereas the S1P1R regulates endothelial barrier function by coupling to Gαi and the monomeric GTPase Rac1, the signaling pathways involved in the S1P-induced regulation of angiogenesis are ill defined. We therefore studied the sprouting of human umbilical vein EC (HUVEC) in vitro and analyzed the activation of the RhoGTPases RhoA and RhoC. Physiological relevant concentrations of S1P (100-300nM) induce a moderate activation of RhoA and RhoC. Inhibition or siRNA-mediated depletion of the S1P2R preferentially decreased the activation of RhoC. Both manipulations caused an increase of sprouting in a spheroid based in vitro sprouting assay. Interestingly, a similar increase in sprouting was detected after effective siRNA-mediated knockdown of RhoC. In contrast, the depletion of RhoA had no influence on sprouting. Furthermore, suppression of the activity of G proteins of the Gα12/13 subfamily by adenoviral overexpression of the regulator of G protein signaling domain of LSC as well as siRNA-mediated knockdown of the Rho specific guanine nucleotide exchange factor leukemia associated RhoGEF (LARG) inhibited the S1P-induced activation of RhoC and concomitantly increased sprouting of HUVEC with similar efficacy. We conclude that the angiogenic sprouting of EC is suppressed via the S1P2R subtype. Thus, the increase in basal sprouting can be attributed to blocking of the inhibitory action of autocrine S1P stimulating the S1P2R. This inhibitory pathway involves the activation of RhoC via Gα12/13 and LARG, while the simultaneously occurring activation of RhoA is apparently dispensable here. © 2013.

  14. Gefässpflanzen auf der Jütischen Halbinsel, Muster der Phytodiversität und aktuelle Naturschutzprobleme

    DEFF Research Database (Denmark)

    Hobohm, Carsten; Wind, Peter

    2014-01-01

    The paper deals with the composition and patterns of vascular plants at the Jutland (or Cimbric) Peninsula. Species diversity is not obviously increasing from North to South as in many regions and coutries in Europe. Species numbers represent higher values to the East than to the West...... or abandonment of agriculture and forestry. Thus, the populations of many vascular plant taxa de-creased, are threatend with extinction or already became extinct. The most affected habitat types are those embeded or connected to farmland. While some positive trends can be recognized we can not see a reversal...

  15. Der Körper als Gefäß. Eine Studie zur visuellen Anthropologie des Alten Orients

    OpenAIRE

    Schroer Silvia/Kipfer Sara

    2015-01-01

    The perception of the human body as container is widespread in cognitive linguistics psychology and anthropology and is estimated to be universal. But what can we say about the specific context of the Hebrew Bible as well as Ancient Near Eastern texts and material culture and more especially about anthropomorphic vessels in the Levant? Biblical Egyptian and Mesopotamian texts compare the human body with pottery in order to emphasize its status of having been created (Geschöpflichkeit) on the ...

  16. Ein gefährdetes Kulturgut : Neue Perspektiven für die Konservierung von Goldleder in den Niederlanden

    NARCIS (Netherlands)

    Groves, R.M.; Koldeweij, E.; Posthuma de Boer, M.

    2016-01-01

    Das 17. und 18. Jahrhundert gilt als „Goldenes Zeitalter“ des Goldleders in den Nord- und Südniederlanden. Obwohl dieses Material einst ähnlich berühmt war wie die Delfter Keramik, ist unglücklicherweise viel davon verloren gegangen. Gründe dafür sind Renovierungen, Materialzersetzungen und

  17. Efficacy of Early Intervention with Liskantin or Primidone to Decrease Developmental Delay in Children with Drowet and GEFS+ Syndrome

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Koushesh

    2014-03-01

    Full Text Available Objective: Febrile seizure (FS occurs between 6 months and 6 years of age. Febrile seizure is a common disease in pediatrics. Some patients are retarded with recurrent febrile seizure. For example Drawet syndrome was started with febrile seizure and progress into the intractable seizure and finally are retarded. Materials & Methods: This article is the clinical trial study. Population in this study are 86 children whit febrile seizure refer to pediatrics’ medical central. This study was carried out in 2013. In this study evaluated patients with febrile seizure’s criteria and included in the population. Children statistics with febrile seizure refer to pediatrics’ medical center registered and compared with other statistics. Data enter the SPSS program 18 version (SPSS Inc, Chicago, USA and used analysis statistical tests and also T-test, Chi Square tests. Finally evaluated total parameters by MIN+SD and reported significant difference (P-value<0.05. Numbers of patients determined according to previous study. Results: In this study 46 patients with complex febrile seizure and early initiation of treatment were not retarded and haven’t any complications. Conclusion: Early initiation of treatment in the patient whit febrile seizure very important to prophylaxis of developmental delay and developmental regression.

  18. Activated Charcoal

    Science.gov (United States)

    Common charcoal is made from peat, coal, wood, coconut shell, or petroleum. “Activated charcoal” is similar to common charcoal, but is made especially for use as a medicine. To make activated charcoal, manufacturers heat common ...

  19. Active ageing

    Directory of Open Access Journals (Sweden)

    Frode F. Jacobsen

    2017-09-01

    Full Text Available Background: The concept of active ageing has been gaining prominence in the Nordic countries and beyond. This has been reflected in policy papers in Norway and other Nordic nations. Aims: The aim of this article is to analyse the topic of active ageing in five Norwegian White Papers (2002 to 2015 and discuss those policy documents in context of relevant research literature. Methods: A qualitative document analyses is employed focusing on how active ageing, and ageing in general, is described and which concepts are employed. No ethical approval was needed. Findings: The general theme of ageing and the specific theme of active ageing are increasingly prominent in the Norwegian White Papers studied. In all documents, some assumptions regarding ageing and active ageing seem implicit, such as independence being more important than (interdependence. ‘Productive’ activities like participation in working life are stressed, while others, like reading, watching TV or watching children playing in the street, are ignored. Conclusions: The policy documents demonstrate that the topic of active ageing is growing in importance. The documents increasingly seem to stress ‘productive’ activities – those related to working life, voluntary work or sports and physical training. They exclude activities that are meaningful for many older people, like watching their grandchildren play or reading books. Implications for practice: Practitioners in older people’s care could consider reflecting on: Government documents dealing with their own practice The prevalent concept of active ageing The trend of active ageing as a facilitating or hindering factor for good care work How present discourse on active ageing may influence their attitude towards frail older persons How they wish to relate to active ageing in their own practice

  20. Physical Activity

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Anderssen, Sigmund Alfred; Wisløff, Ulrik

    2014-01-01

    Andersen LB, Anderssen SA, Wisløff U, Hellénius M-L, Fogelholm M, Ekelund U. (Expert Group) Nordic Nutrition Recommendations 2012. Integrating nutrition and physical activity. Chapter: Physical Activity p. 195-217.Nordic Counsil of Ministers.......Andersen LB, Anderssen SA, Wisløff U, Hellénius M-L, Fogelholm M, Ekelund U. (Expert Group) Nordic Nutrition Recommendations 2012. Integrating nutrition and physical activity. Chapter: Physical Activity p. 195-217.Nordic Counsil of Ministers....

  1. Activity report

    International Nuclear Information System (INIS)

    1990-11-01

    The Department of Physics and Measurement Technology, Biology and Chemistry (IFM) presents every year a progress report containing a brief description of activities in research and education within the department. The report is intended as an information for colleagues and institutions. The present report contains activities for the academic year July 1989 to June 1990

  2. [Active euthanasia].

    Science.gov (United States)

    Folker, A P; Hvidt, N

    1995-02-20

    The growing interest in the subject of active euthanasia in connection with the debate regarding legalization of such practices in Denmark necessitates taking a definite standpoint. The difference in concept between active and passive euthanasia is stressed, and the Dutch guidelines are reviewed. The article discusses how far the patient's autonomy should go, as it regards the consideration of self-determination as being too narrow a criterion in itself. The discussion on the quality of life is included, and the consequences of the process of expulsion as a sociological concept are considered--the risk of a patient feeling guilty for being alive and therefore feeling compelled to request active euthanasia. The changed function of the physician is underlined, and it is discussed whether active euthansia will cause a breach of confidence between the physician and his patient. In connection with the debate the following tendencies in society are emphasized: lack of clarity, increasing medicalization and utilitarian priorities.

  3. Proteomic analysis of Rac1 signaling regulation by guanine nucleotide exchange factors.

    Science.gov (United States)

    Marei, Hadir; Carpy, Alejandro; Macek, Boris; Malliri, Angeliki

    2016-08-02

    The small GTPase Rac1 is implicated in various cellular processes that are essential for normal cell function. Deregulation of Rac1 signaling has also been linked to a number of diseases, including cancer. The diversity of Rac1 functioning in cells is mainly attributed to its ability to bind to a multitude of downstream effectors following activation by Guanine nucleotide Exchange Factors (GEFs). Despite the identification of a large number of Rac1 binding partners, factors influencing downstream specificity are poorly defined, thus hindering the detailed understanding of both Rac1's normal and pathological functions. In a recent study, we demonstrated a role for 2 Rac-specific GEFs, Tiam1 and P-Rex1, in mediating Rac1 anti- versus pro-migratory effects, respectively. Importantly, via conducting a quantitative proteomic screen, we identified distinct changes in the Rac1 interactome following activation by either GEF, indicating that these opposing effects are mediated through GEF modulation of the Rac1 interactome. Here, we present the full list of identified Rac1 interactors together with functional annotation of the differentially regulated Rac1 binding partners. In light of this data, we also provide additional insights into known and novel signaling cascades that might account for the GEF-mediated Rac1-driven cellular effects.

  4. Evaluation of the economic and financial management in Mexican microenterprises

    Directory of Open Access Journals (Sweden)

    Malena Portal Boza

    2016-10-01

    Full Text Available The exhibit features Mexican microenterprises today give evidence of the problems that they face in terms of managing their activities, where the role of economic-financial elements is perceived. Although the issue has been addressed in previous studies the contribution of this study is to evaluate in an integrated manner the level of economic and financial management (GEF in micro and impact on business results. To do an index is constructed from indicators synthetic methodology using the principal components factor analysis, accompanied by linear regression exercises. The results confirm the presence of elements of GEF in micro studied. Moreover, it was found that the extent to which GEF elements are incorporated in its activities, the impact on their business results will be positive. These observations constitute the prelude to the creation of public policies seeking to establish improvement strategies for such companies, besides that fosters future research for analysis but by sectors of economic activity.

  5. Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1

    Czech Academy of Sciences Publication Activity Database

    Tellier, G.; Lenne, A.; Cailliau-Maggio, K.; Cabezas-Cruz, A.; Valdés, James J.; Martoriati, A.; Aliouat, El M.; Gosset, P.; Delaire, B.; Fréville, A.; Pierrot, C.; Khalife, J.

    2016-01-01

    Roč. 7, MAY 26 (2016), č. článku 777. ISSN 1664-302X Institutional support: RVO:60077344 Keywords : Plasmodium falciparum * Protein Phosphatase type1 * eIF2b * protein-protein interaction * translation complex Subject RIV: EE - Microbiology, Virology Impact factor: 4.076, year: 2016

  6. Astrocytes are central in the pathomechanisms of vanishing white matter

    NARCIS (Netherlands)

    Dooves, Stephanie; Bugiani, Marianna; Postma, Nienke L.; Polder, Emiel; Land, Niels; Horan, Stephen T.; van Deijk, Anne-Lieke F.; van de Kreeke, Aleid; Jacobs, Gerbren; Vuong, Caroline; Klooster, Jan; Kamermans, Maarten; Wortel, Joke; Loos, Maarten; Wisse, Lisanne E.; Scheper, Gert C.; Abbink, Truus E. M.; Heine, Vivi M.; van der Knaap, Marjo S.

    2016-01-01

    Vanishing white matter (VWM) is a fatal leukodystrophy that is caused by mutations in genes encoding subunits of eukaryotic translation initiation factor 2B (eIF2B). Disease onset and severity are codetermined by genotype. White matter astrocytes and oligodendrocytes are almost exclusively affected;

  7. No evidence that polymorphisms of the vanishing white matter disease genes are risk factors in multiple sclerosis

    NARCIS (Netherlands)

    Pronk, J.C.; Scheper, G.C.; Andel, R.J.; van Berkel, C.G.M.; Polman, C.H.; Uitdehaag, B.M.J.; van der Knaap, M.S.

    2008-01-01

    Febrile infections are known to cause exacerbations in the white matter disorders 'vanishing white matter' (VWM) and multiple sclerosis (MS). We hypothesized that polymorphisms in EIF2B1-5, the genes involved in VWM, might be risk factors for the development of MS or temperature sensitivity in

  8. Active colloids

    International Nuclear Information System (INIS)

    Aranson, Igor S

    2013-01-01

    A colloidal suspension is a heterogeneous fluid containing solid microscopic particles. Colloids play an important role in our everyday life, from food and pharmaceutical industries to medicine and nanotechnology. It is useful to distinguish two major classes of colloidal suspensions: equilibrium and active, i.e., maintained out of thermodynamic equilibrium by external electric or magnetic fields, light, chemical reactions, or hydrodynamic shear flow. While the properties of equilibrium colloidal suspensions are fairly well understood, active colloids pose a formidable challenge, and the research is in its early exploratory stage. One of the most remarkable properties of active colloids is the possibility of dynamic self-assembly, a natural tendency of simple building blocks to organize into complex functional architectures. Examples range from tunable, self-healing colloidal crystals and membranes to self-assembled microswimmers and robots. Active colloidal suspensions may exhibit material properties not present in their equilibrium counterparts, e.g., reduced viscosity and enhanced self-diffusivity, etc. This study surveys the most recent developments in the physics of active colloids, both in synthetic and living systems, with the aim of elucidation of the fundamental physical mechanisms governing self-assembly and collective behavior. (physics of our days)

  9. Physics activities

    International Nuclear Information System (INIS)

    1997-09-01

    As we move into the 21st Century, nuclear technology is on the verge of rejuvenation in advanced Member States and of expansion in developing Member States. The principal responsibilities of the IAEA are transferring technologies, co-ordinating scientific research, managing specialized projects and maintaining analytical quality control. The IAEA physics activities provide assistance with nuclear instrumentation, promote more effective utilization of research reactors and accelerators, and facilitate global co-operation in nuclear fusion research. These activities will help Member States improve their standards of living through the benefits of nuclear technology. This booklet presents a brief profile on the physics activities and involvement in these fields of the Physics Section, IAEA

  10. Regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

  11. Identity Activities

    Science.gov (United States)

    2016-08-03

    in reaction to their environment. They reflect an individual’s internal or external, conscious or subconscious , overt or covert, voluntary or...identity activities under a range of legal authorities, policy constraints, transnational threats, regional concerns and biases , and most likely...Biography. A baseline and descriptive analytic product that supports the development of the behavioral influences analysis ( BIA ) individual behavioral

  12. Active instruments

    DEFF Research Database (Denmark)

    Lim, Miguel Antonio; Ørberg, Jakob Williams

    2017-01-01

    themselves. We draw on two multi-year field studies of India and Denmark to investigate how national reforms and developments within the ranking industry interact in often surprising ways. Rankings do not always do what policy makers expect. We (1) highlight the activity of rankers in these two countries, (2...

  13. Active house

    DEFF Research Database (Denmark)

    Eriksen, Kurt Emil; Olesen, Gitte Gylling Hammershøj

    Formålet med dette abstrakt er at illustrere, at huse kan være konstrueret til at basere sig udelukkende på vedvarende energikilder og samtidig være CO2-neutrale og producere mere energi end de forbruger. Active House Visionen undersøger disse muligheder i otte demonstration huse i fem forskellige...

  14. Active particles

    CERN Document Server

    Degond, Pierre; Tadmor, Eitan

    2017-01-01

    This volume collects ten surveys on the modeling, simulation, and applications of active particles using methods ranging from mathematical kinetic theory to nonequilibrium statistical mechanics. The contributing authors are leading experts working in this challenging field, and each of their chapters provides a review of the most recent results in their areas and looks ahead to future research directions. The approaches to studying active matter are presented here from many different perspectives, such as individual-based models, evolutionary games, Brownian motion, and continuum theories, as well as various combinations of these. Applications covered include biological network formation and network theory; opinion formation and social systems; control theory of sparse systems; theory and applications of mean field games; population learning; dynamics of flocking systems; vehicular traffic flow; and stochastic particles and mean field approximation. Mathematicians and other members of the scientific commu...

  15. Active solar information dissemination activities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-07-01

    The principal objective of the project has been the development of an information dissemination strategy for the UK active solar heating industry. The project has also aimed to prepare the industry for the implementation of such a strategy and to produce initial information materials to support the early stages of the implementation process. (author)

  16. Chocolate active

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    There is a table of current radioactivity values for various foods and mushrooms. A special accent is on milk and chocolate. Chocolate sorts with more powdered milk are more active. Finally there is a chapter on radionucleides contained in the Chernobyl fallout, other than cesium 137, cesium 134 and strontium 90. The amounts of ruthenium 106, antimony 125, cerium 144, silver 110 m, cesium 134, strontium 90 and plutonium 239 relative to cesium 137 in soil samples in autumn 1987 are given. Special emphasis is on ruthenium 'hot particles' and on plutonium. (qui)

  17. Staying Active: Physical Activity and Exercise

    Science.gov (United States)

    ... Events Advocacy For Patients About ACOG Staying Active: Physical Activity and Exercise Home For Patients Search FAQs Staying ... Exercise FAQ045, November 2016 PDF Format Staying Active: Physical Activity and Exercise Women's Health What are the benefits ...

  18. Halal Activism

    DEFF Research Database (Denmark)

    Fischer, Johan

    2016-01-01

    The purpose of this article is to further our understanding of contemporary Muslim consumer activism in Malaysia with a particular focus on halal (in Arabic, literally “permissible” or “lawful”) products and services. Muslim activists and organisations promote halal on a big scale in the interface...... zones between new forms of Islamic revivalism, the ethnicised state and Muslim consumer culture. Organisations such as the Muslim Consumers Association of Malaysia play an important role in pushing and protecting halal in Malaysia, that is, halal activists constantly call on the state to tighten halal...... in particular historical/national settings and that these issues should be explored in the interfaces between Islam, the state and market. More specifically, this article examines the above issues building on ethnography from fieldwork with three Muslim organisations in Malaysia....

  19. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2006-01-01

    ... nucleotide exchange factors (RhoGEFs). We have developed a high throughput screening strategy identify novel inhibitors of Rho activation are currently following up on several compounds which appear to selectively inhibit Rho activation. These compounds may form the basis of future drug development strategies for the treatment of metastatic breast cancer.

  20. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2005-01-01

    ... nucleotide exchange factors (RhoGEFs). We have developed a high throughput screening strategy identify novel inhibitors of Rho activation are currently following up on several compounds which appear to selectively inhibit Rho activation. These compounds may form the basis of future drug development strategies for the treatment of metastatic breast cancer.

  1. Active sharing

    CERN Multimedia

    2012-01-01

    The big news this week is, of course, the conclusions from the LHC performance workshop held in Chamonix from 6 to 10 February . The main recommendation, endorsed by CERN’s Machine Advisory Committee and adopted by the Management, is that the LHC will run at 4 TeV per beam this year. You can find all the details from Chamonix in the slides presented on Wednesday at the summary session, which leaves me free to talk about another important development coming up soon.   In ten days time, a new kind of gathering will be taking place in Geneva, bringing together two previously separate conferences, one driven by physics, the other by the medical community, but both looking to apply physics to the advancement of health. The merger of the International Conference for Translational Research in Radio-Oncology and CERN’s workshop on Physics for Health in Europe (ICTR-PHE) makes for a very eclectic mix. Presentations range from active shielding for interplanetary flight to the rather...

  2. Active Segmentation.

    Science.gov (United States)

    Mishra, Ajay; Aloimonos, Yiannis

    2009-01-01

    The human visual system observes and understands a scene/image by making a series of fixations. Every fixation point lies inside a particular region of arbitrary shape and size in the scene which can either be an object or just a part of it. We define as a basic segmentation problem the task of segmenting that region containing the fixation point. Segmenting the region containing the fixation is equivalent to finding the enclosing contour- a connected set of boundary edge fragments in the edge map of the scene - around the fixation. This enclosing contour should be a depth boundary.We present here a novel algorithm that finds this bounding contour and achieves the segmentation of one object, given the fixation. The proposed segmentation framework combines monocular cues (color/intensity/texture) with stereo and/or motion, in a cue independent manner. The semantic robots of the immediate future will be able to use this algorithm to automatically find objects in any environment. The capability of automatically segmenting objects in their visual field can bring the visual processing to the next level. Our approach is different from current approaches. While existing work attempts to segment the whole scene at once into many areas, we segment only one image region, specifically the one containing the fixation point. Experiments with real imagery collected by our active robot and from the known databases 1 demonstrate the promise of the approach.

  3. IASS Activity

    Science.gov (United States)

    Hojaev, Alisher S.; Ibragimova, Elvira M.

    2015-08-01

    It’s well known, astronomy in Uzbekistan has ancient roots and traditions (e.g., Mirzo Ulugh Beg, Abū al-Rayhān al-Bīrūnī, Abū ‘Abdallāh al-Khwārizmī) and astronomical heritage carefully preserved. Nowadays uzbek astronomers play a key role in scientific research but also in OAD and Decadal Plan activity in the Central Asia region. International Aerospace School (IASS) is an amazing and wonderful event held annually about 30 years. IASS is unique project in the region, and at the beginning we spent the Summer and Winter Schools. At present in the summer camp we gather about 50 teenage and undergraduate students over the country and abroad (France, Malaysia, Turkey, Azerbaijan, Pakistan, Russia, etc.). They are selected on the basis of tests of astronomy and space issues. During two weeks of IASS camp the invited scientists, cosmonauts and astronauts as well as other specialists give lectures and engage in practical exercises with IASS students in astronomy, including daily observations of the Sun and night sky observations with meniscus telescope, space research and exploration, aerospace modelling, preparation and presentation of original projects. This is important that IASS gives not theoretical grounds only but also practically train the students and the hands-on training is the major aims of IASS. Lectures and practice in the field of astronomy carried out with the direct involvement and generous assistance of Uranoscope Association (Paris, France). The current 26-th IASS is planned to held in July 2015.

  4. Activation Energy

    Science.gov (United States)

    Gadeken, Owen

    2002-01-01

    Teaming is so common in today's project management environment that most of us assume it comes naturally. We further assume that when presented with meaningful and challenging work, project teams will naturally engage in productive activity to complete their tasks. This assumption is expressed in the simple (but false) equation: Team + Work = Teamwork. Although this equation appears simple and straightforward, it is far from true for most project organizations whose reality is a complex web of institutional norms based on individual achievement and rewards. This is illustrated by the very first successful team experience from my early Air Force career. As a young lieutenant, I was sent to Squadron Officer School, which was the first in the series of Air Force professional military education courses I was required to complete during my career. We were immediately formed into teams of twelve officers. Much of the course featured competition between these teams. As the most junior member of my team, I quickly observed the tremendous pressure to show individual leadership capability. At one point early in the course, almost everyone in our group was vying to become the team leader. This conflict was so intense that it caused us to fail miserably in our first outdoor team building exercise. We spent so much time fighting over leadership that we were unable to complete any of the events on the outdoor obstacle course. This complete lack of success was so disheartening to me that I gave our team little hope for future success. What followed was a very intense period of bickering, conflict, and even shouting matches as our dysfunctional team tried to cope with our early failures and find some way to succeed. British physician and researcher Wilfred Bion (Experiences in Groups, 1961) discovered that there are powerful psychological forces inherent in all groups that divert from accomplishing their primary tasks. To overcome these restraining forces and use the potential

  5. The Juxtamembrane and carboxy-terminal domains of Arabidopsis PRK2 are critical for ROP-induced growth in pollen tubes

    Science.gov (United States)

    Polarized growth of pollen tubes is a critical step for successful reproduction in angiosperms and is controlled by ROP GTPases. Spatiotemporal activation of ROP (Rho GTPases of plants) necessitates a complex and sophisticated regulatory system, in which guanine nucleotide exchange factors (RopGEFs)...

  6. Construction of an efficient biologically contained Pseudomonas putida strain and its survival in outdoor assays

    DEFF Research Database (Denmark)

    Molina, Lazaro; Rodriguez, Cayo Juan Ramos; Ronchel, Maria C.

    1998-01-01

    Active biological containment systems consist of two components, a killing element designed to induce cell death and a control element which modulates the expression of the killing function. We constructed a mini-Tn5 transposon bearing a fusion of the P(lac) promoter to the gef killing gene...

  7. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Needs for Pregnant or Postpartum Women Physical Activity & Health Adding Physical Activity to Your Life Activities for ... Guide Visual Guide Worksite Physical Activity Steps to Wellness Walkability Audit Tool Sample Audit Glossary Selected References ...

  8. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... for Older Adults Needs for Pregnant or Postpartum Women Physical Activity & Health Adding Physical Activity to Your ... Activity, 2014 Recommendations & Guidelines Fact Sheets & Infographics Social Media Tools Community Strategies BE Active: Connecting Routes + Destinations ...

  9. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Physical Activity Data, Trends and Maps Surveillance Systems Resources & Publications Reports Adults Need More Physical Activity MMWR ... Active: Connecting Routes + Destinations Real-World Examples Implementation Resource Guide Visual Guide Worksite Physical Activity Steps to ...

  10. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Physical Activity Basics Needs for Adults Needs for Children What Counts Needs for Older Adults Needs for ... Adding Physical Activity to Your Life Activities for Children Activities for Older Adults Overcoming Barriers Measuring Physical ...

  11. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... to Your Life Activities for Children Activities for Older Adults Overcoming Barriers ... required by a person to do an activity. When using relative intensity, people pay attention to how physical activity affects their ...

  12. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Adults Need More Physical Activity MMWR Data Highlights State Indicator Report on Physical Activity, 2014 Recommendations & Guidelines ... Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Measuring Physical Activity Intensity Recommend ...

  13. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Adults Needs for Children What Counts Needs for Older Adults Needs for Pregnant or Postpartum Women Physical Activity & ... to Your Life Activities for Children Activities for Older Adults Overcoming Barriers Measuring Physical Activity Intensity Target Heart ...

  14. BAM! Physical Activity

    Science.gov (United States)

    ... Smarts Links Fuel Up for Fun Power Packing Physical Activity Activity Calendar Activity Information Sheets I Heard Hurdle ... Links Sleep Game Questions Answered Under the Microscope Physical Activity Game Questions Answered Under the Microscope Lurking in ...

  15. Facts about Physical Activity

    Science.gov (United States)

    ... Micronutrient Malnutrition State and Local Programs Facts about Physical Activity Recommend on Facebook Tweet Share Compartir Some Americans ... Activity Guideline for aerobic activity than older adults. Physical activity and socioeconomic status Adults with more education are ...

  16. Physical Activity Guidelines

    Science.gov (United States)

    ... use this site. health.gov Physical Activity Guidelines Physical Activity Physical activity is key to improving the health of the Nation. Based on the latest science, the Physical Activity Guidelines for Americans is an essential resource for ...

  17. Active knee joint flexibility and sports activity

    DEFF Research Database (Denmark)

    Hahn, Thomas; Foldspang, Anders; Vestergaard, E

    1999-01-01

    was significantly higher in women than in men and significantly positively associated with weekly hours of swimming and weekly hours of competitive gymnastics. Active knee flexion was significantly positively associated with participation in basketball, and significantly negatively associated with age and weekly......The aim of the study was to estimate active knee flexion and active knee extension in athletes and to investigate the potential association of each to different types of sports activity. Active knee extension and active knee flexion was measured in 339 athletes. Active knee extension...... hours of soccer, European team handball and swimming. The results point to sport-specific adaptation of active knee flexion and active knee extension. Udgivelsesdato: 1999-Apr...

  18. Modulation of B-cell receptor and microenvironment signaling by a guanine exchange factor in B-cell malignancies

    International Nuclear Information System (INIS)

    Liao, Wei; Sharma, Sanjai

    2016-01-01

    Objective: Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) cells over-express a guanine exchange factor (GEF), Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods: N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor (BCR) and chemokine signaling pathways were compared in the Rasgrf-1 over-expressing and a control transfected cell line. Results: Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions: This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells

  19. Genes Whose Gain or Loss-Of-Function Increases Skeletal Muscle Mass in Mice: A Systematic Literature Review

    Directory of Open Access Journals (Sweden)

    Sander A. J. Verbrugge

    2018-05-01

    Full Text Available Skeletal muscle mass differs greatly in mice and humans and this is partially inherited. To identify muscle hypertrophy candidate genes we conducted a systematic review to identify genes whose experimental loss or gain-of-function results in significant skeletal muscle hypertrophy in mice. We found 47 genes that meet our search criteria and cause muscle hypertrophy after gene manipulation. They are from high to small effect size: Ski, Fst, Acvr2b, Akt1, Mstn, Klf10, Rheb, Igf1, Pappa, Ppard, Ikbkb, Fstl3, Atgr1a, Ucn3, Mcu, Junb, Ncor1, Gprasp1, Grb10, Mmp9, Dgkz, Ppargc1a (specifically the Ppargc1a4 isoform, Smad4, Ltbp4, Bmpr1a, Crtc2, Xiap, Dgat1, Thra, Adrb2, Asb15, Cast, Eif2b5, Bdkrb2, Tpt1, Nr3c1, Nr4a1, Gnas, Pld1, Crym, Camkk1, Yap1, Inhba, Tp53inp2, Inhbb, Nol3, Esr1. Knock out, knock down, overexpression or a higher activity of these genes causes overall muscle hypertrophy as measured by an increased muscle weight or cross sectional area. The mean effect sizes range from 5 to 345% depending on the manipulated gene as well as the muscle size variable and muscle investigated. Bioinformatical analyses reveal that Asb15, Klf10, Tpt1 are most highly expressed hypertrophy genes in human skeletal muscle when compared to other tissues. Many of the muscle hypertrophy-regulating genes are involved in transcription and ubiquitination. Especially genes belonging to three signaling pathways are able to induce hypertrophy: (a Igf1-Akt-mTOR pathway, (b myostatin-Smad signaling, and (c the angiotensin-bradykinin signaling pathway. The expression of several muscle hypertrophy-inducing genes and the phosphorylation of their protein products changes after human resistance and high intensity exercise, in maximally stimulated mouse muscle or in overloaded mouse plantaris.

  20. Emotion und pädagogische Professionalität : Die Bedeutung des Umgangs mit Gefühlen für sozialpädagogische Berufe

    OpenAIRE

    Daßler, Henning

    1999-01-01

    Der Pädagogik im allgemeinen und der Sozialpädagogik im besonderen fällt es schwer, Kriterien und Möglichkeiten ihrer eigenen Professionalität zu definieren. Eine wesentliche Ursache dafür liegt in der Schwierigkeit, die emotionale Dimension des beruflichen Handelns in ihrer Bedeutung zu erkennen und in einer angemessenen Weise wissenschaftlich zu erschließen. Die ungenügende Beachtung von Emotion läßt sich in drei Bereichen aufzeigen: In der Analyse der gesellschaftlichen Veränderungen, die ...

  1. Documento de conceptualización del sistema de monitoreo del Subsistema de Áreas Marinas Protegidas en Colombia. Invemar, GEF y PNUD.

    OpenAIRE

    Batista Morales, Angélica; Gómez López, Diana Isabel; Navarrete Ramírez, Sandra Milena; Alonso, David

    2014-01-01

    En los últimos 20 años Colombia ha logrado avances importantes para la consolidación del Sistema Nacional de Áreas Protegidas -Sinap. Específicamente para el tema de Áreas Marinas Protegidas (AMP), en el año 2001, la Política Nacional Ambiental para el Desarrollo Sostenible de los Espacios Oceánicos y las Zonas Costeras e Insulares de Colombia-Pnaoci” (MMA, 2001) platea como meta especifica el establecimiento de un Subsistema de Áreas Marinas Protegidas-SAMP como parte del Sin...

  2. Der gesellschaftlich-kulturelle Kontext der aktuellen Gefährdungen für ... die religiöse Erziehung und Bildung in der Familie

    Directory of Open Access Journals (Sweden)

    Józef Stala

    2013-04-01

    Full Text Available In a society shaken by tensions and conflicts caused by the clash of various kinds of individualism and selfishness, children need to be enriched with a sense of the personal dignity of each individual, true love and sincere service to the others, especially the poorest and those in most need. The family is the first and fundamental school of upbringing: as a community of life and love. Every Christian family finds its mission received from God in self-giving that inspires the love of husband and wife for each other and the self-giving that is practiced in the relationships between brothers and sisters and the different generations living together in the family. The author of this article shows the actual threats to religious upbringing and education in the family with special attention given to the postmodern socio-cultural context. He also highlights financial, social, moral and religious crisis influencing the family life and education. Then asks for the roots of these negative phenomena and searches for the pedagogical solution.

  3. Neue molekulare Mechanismen zellulärer Interaktionen an der Gefäßwand und ihre Bedeutung für die Pathogenese der Atherosklerose

    OpenAIRE

    Borst, Oliver Alexander

    2010-01-01

    Hintergrund: EMMPRIN (Extracellular matrix metalloproteinase Inducer) ist ein immunglobulinähnliches Glykoprotein, das auf verschiedenen Zellen exprimiert wird. Erstmals beschrieben wurde EMMPRIN auf Tumorzellen. Zwischenzeitlich ist bekannt, dass EMMPRIN auch auf verschiedenen weiteren Zellen (z.B. auf Fibroblasten, Monozyten oder glatten Muskelzellen) exprimiert wird. Erst vor kurzem konnte eine aktivierungsabhängige Expression von EMMPRIN nun auch auf Thrombozyten nachgewiesen w...

  4. Verantwortliche Personalführung – Zufriedene Kunden. Der Zusammenhang von Gesundheitsmanagement, Gefährdungsbeurteilung und Kundenzufriedenheit an der SUB Hamburg

    Directory of Open Access Journals (Sweden)

    Ulrike Lang

    2015-12-01

    Full Text Available Das Arbeitsschutzgesetz verpflichtet Arbeitgeber, auf der Basis einer Beurteilung der Arbeitsbedingungen erforderliche Maßnahmen des Arbeitsschutzes festzustellen, diese umzusetzen und auf ihre Wirksamkeit zu kontrollieren. Dabei sind auch die psychischen Belastungen der Arbeit zu berücksichtigen. Wie werden diese Anforderungen im laufenden Betrieb umgesetzt? Welche Konsequenzen hat dies für Leitung, für Kolleg/inn/en und Nutzer/innen? Wie integriert man die Maßnahmen in die Personalentwicklung und wie überzeugt man die Beschäftigten davon, sich zu beteiligen? Der Beitrag erläutert die Entwicklung des Gesundheitsmanagements der Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky und bietet Tipps zur Umsetzung in anderen Bibliotheken. The German Occupational Safety and Health Act requires employers to determine, based on an assessment of the working conditions, which occupational safety and health measures are required, to implement them and to monitor their effectiveness. The mental stress of work has to be considered as well. How are these requirements implemented under operating conditions? What are the implications for management, colleagues and for the users? How should the measures be integrated in human resources development and how can the employees be persuaded to participate? The paper explains the development of the health management at the State and University Library Hamburg Carl von Ossietzky and gives advice on the implementation to other libraries.

  5. Activation analysis. Chapter 4

    International Nuclear Information System (INIS)

    1976-01-01

    The principle, sample and calibration standard preparation, activation by neutrons, charged particles and gamma radiation, sample transport after activation, activity measurement, and chemical sample processing are described for activation analysis. Possible applications are shown of nondestructive activation analysis. (J.P.)

  6. Remedial Strategies in Structural Proteomics: Expression, Purification, And Crystallization of the Vav1/Rac1 Complex

    Energy Technology Data Exchange (ETDEWEB)

    Brooun, A.; Foster, S.A.; Chrencik, H.E.; Chien, E.Y.T.; Kolatkar, A.R.; Streiff, M.; Ramage, P.; Widmer, H.; Weckbecker, G.; Kuhn, P.

    2007-07-03

    The signal transduction pathway involving the Vav1 guanine nucleotide exchange factor (GEF) and the Rac1 GTPase plays several key roles in the immune response mediated by the T cell receptor. Vav1 is also a unique member of the GEF family in that it contains a cysteine-rich domain (CRD) that is critical for Rac1 binding and maximal guanine nucleotide exchange activity, and thus may provide a unique protein-protein interface compared to other GEF/GTPase pairs. Here, we have applied a number of remedial structural proteomics strategies, such as construct and expression optimization, surface mutagenesis, limited proteolysis, and protein formulation to successfully express, purify, and crystallize the Vav1-DH-PH-CRD/Rac1 complex in an active conformation. We have also systematically characterized various Vav1 domains in a GEF assay and Rac1 in vitro binding experiments. In the context of Vav1-DH-PH-CRD, the zinc finger motif of the CRD is required for the expression of stable Vav1, as well as for activity in both a GEF assay and in vitro formation of a Vav1/Rac1 complex suitable for biophysical and structural characterization. Our data also indicate that the isolated CRD maintains a low level of specific binding to Rac1, appears to be folded based on 1D NMR analysis and coordinates two zinc ions based on ICP-MS analysis. The protein reagents generated here are essential tools for the determination of a three dimensional Vav1/Rac1 complex crystal structure and possibly for the identification of inhibitors of the Vav1/Rac1 protein-protein interaction with potential to inhibit lymphocyte activation.

  7. Active transport and heat.

    Science.gov (United States)

    Tait, Peter W

    2011-07-01

    Increasing heat may impede peoples' ability to be active outdoors thus limiting active transport options. Co-benefits from mitigation of and adaptation to global warming should not be assumed but need to be actively designed into strategies.

  8. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... for Older Adults Needs for Pregnant or Postpartum Women Physical Activity & Health Adding Physical Activity to Your ... Physical Activity, 2014 Recommendations & Guidelines Fact Sheets & ... Fitness Club Network Assessing Need and Interest Selecting a DFCN Promotion ...

  9. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... About Physical Activity Data, Trends and Maps Surveillance Systems Resources & Publications Reports Adults Need More Physical Activity MMWR Data Highlights State Indicator Report on Physical Activity, 2014 Recommendations & Guidelines Fact Sheets & Infographics Social Media Tools Community ...

  10. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Needs for Pregnant or Postpartum Women Physical Activity & Health Adding Physical Activity to Your Life Activities for ... Obesity , National Center for Chronic Disease Prevention and Health Promotion Email Recommend Tweet YouTube Instagram Listen Watch ...

  11. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... gov . Physical Activity Physical Activity Basics Needs for Adults Needs for Children What Counts Needs for Older Adults Needs for Pregnant or Postpartum Women Physical Activity & ...

  12. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... an activity. When using relative intensity, people pay attention to how physical activity affects their heart rate ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs File Formats Help: How ...

  13. Physical Activity Basics

    Science.gov (United States)

    ... Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Physical Activity Basics Recommend on Facebook Tweet Share Compartir How much physical activity do you need? Regular physical activity helps improve ...

  14. Physical Activity Assessment

    Science.gov (United States)

    Current evidence convincingly indicates that physical activity reduces the risk of colon and breast cancer. Physical activity may also reduce risk of prostate cancer. Scientists are also evaluating potential relationships between physical activity and other cancers.

  15. Guide to Physical Activity

    Science.gov (United States)

    ... Families ( We Can! ) Health Professional Resources Guide to Physical Activity Physical activity is an important part of your ... to injury. Examples of moderate-intensity amounts of physical activity Common Chores Washing and waxing a car for ...

  16. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Physical Activity, 2014 Recommendations & Guidelines Fact Sheets & Infographics Social Media Tools Community Strategies BE Active: Connecting Routes + Destinations Real-World Examples ...

  17. Physical activity and obesity

    National Research Council Canada - National Science Library

    Bouchard, Claude; Katzmarzyk, Peter T

    2010-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2 The Physical Activity and Exercise Continuum 7 Darren Warburton Definition of Health, Physical Activity, and Exercise . . . . . . . 7 The Continuum...

  18. Physical Activity and Cancer

    Science.gov (United States)

    ... Cancer Genetics Services Directory Cancer Prevention Overview Research Physical Activity and Cancer On This Page What is physical activity? What is known about the relationship between physical ...

  19. Criminalisation of Activism

    DEFF Research Database (Denmark)

    Uldam, Julie

    Different forms of political participation involve different challenges. This paper focuses on challenges to radical activism and particularly the criminalisation of activism.......Different forms of political participation involve different challenges. This paper focuses on challenges to radical activism and particularly the criminalisation of activism....

  20. Increasing Youth Physical Activity with Activity Calendars

    Science.gov (United States)

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  1. Active nematic gels as active relaxing solids

    Science.gov (United States)

    Turzi, Stefano S.

    2017-11-01

    I propose a continuum theory for active nematic gels, defined as fluids or suspensions of orientable rodlike objects endowed with active dynamics, that is based on symmetry arguments and compatibility with thermodynamics. The starting point is our recent theory that models (passive) nematic liquid crystals as relaxing nematic elastomers. The interplay between viscoelastic response and active dynamics of the microscopic constituents is naturally taken into account. By contrast with standard theories, activity is not introduced as an additional term of the stress tensor, but it is added as an external remodeling force that competes with the passive relaxation dynamics and drags the system out of equilibrium. In a simple one-dimensional channel geometry, we show that the interaction between nonuniform nematic order and activity results in either a spontaneous flow of particles or a self-organization into subchannels flowing in opposite directions.

  2. Physical Activity During School

    DEFF Research Database (Denmark)

    Østergaard, Lars Domino

    It is important, not only on health grounds, to exercise and to be physically active. In school, physical activities have shown to improve the students’ academic behaviour resulting in improved attention and information processing as well as enhanced coping. To stimulate and motivate students...... to be even more active during school hours further enhancing their academic behaviour, it is important to know when, why and how they are active, and their attitude towards different types of physical activities. Therefore, the aim of this study was to categorize the physical activities attended by students...... during school hours and to elucidate their attitude towards the different types of activities. The data consisted of observations of lessons followed by group interviews. Analyses of the observations revealed six categories of physical activities, varying from mandatory physical activities, activities...

  3. The domain architecture of large guanine nucleotide exchange factors for the small GTP-binding protein Arf

    Directory of Open Access Journals (Sweden)

    Geldner Niko

    2005-02-01

    Full Text Available Abstract Background Small G proteins, which are essential regulators of multiple cellular functions, are activated by guanine nucleotide exchange factors (GEFs that stimulate the exchange of the tightly bound GDP nucleotide by GTP. The catalytic domain responsible for nucleotide exchange is in general associated with non-catalytic domains that define the spatio-temporal conditions of activation. In the case of small G proteins of the Arf subfamily, which are major regulators of membrane trafficking, GEFs form a heterogeneous family whose only common characteristic is the well-characterized Sec7 catalytic domain. In contrast, the function of non-catalytic domains and how they regulate/cooperate with the catalytic domain is essentially unknown. Results Based on Sec7-containing sequences from fully-annotated eukaryotic genomes, including our annotation of these sequences from Paramecium, we have investigated the domain architecture of large ArfGEFs of the BIG and GBF subfamilies, which are involved in Golgi traffic. Multiple sequence alignments combined with the analysis of predicted secondary structures, non-structured regions and splicing patterns, identifies five novel non-catalytic structural domains which are common to both subfamilies, revealing that they share a conserved modular organization. We also report a novel ArfGEF subfamily with a domain organization so far unique to alveolates, which we name TBS (TBC-Sec7. Conclusion Our analysis unifies the BIG and GBF subfamilies into a higher order subfamily, which, together with their being the only subfamilies common to all eukaryotes, suggests that they descend from a common ancestor from which species-specific ArfGEFs have subsequently evolved. Our identification of a conserved modular architecture provides a background for future functional investigation of non-catalytic domains.

  4. Active regions, ch. 7

    International Nuclear Information System (INIS)

    Martres, M.J.; Bruzek, A.

    1977-01-01

    The solar Active Region is an extremely complex phenomenon comprising a large variety of features (active,region phenomena) in the photosphere, chromosphere and corona. The occurrence of the various active phenomena depends on the phase and state of evolution of the AR; their appearance depends on the radiation used for the observation. The various phenomena are described and illustrated with photographs. Several paragraphs are dedicated to magnetic classification of AR, Mt. Wilson Spot Classification, solar activity indices, and solar activity data publications

  5. Crystal structure of the regulatory subunit of archaeal initiation factor 2B (aIF2B) from hyperthermophilic archaeon Pyrococcus horikoshii OT3: a proposed structure of the regulatory subcomplex of eukaryotic IF2B

    International Nuclear Information System (INIS)

    Kakuta, Yoshimitsu; Tahara, Maino; Maetani, Shigehiro; Yao, Min; Tanaka, Isao; Kimura, Makoto

    2004-01-01

    Eukaryotic translation initiation factor 2B (eIF2B) is the guanine-nucleotide exchange factor for eukaryotic initiation factor 2 (eIF2). eIF2B is a heteropentameric protein composed of α-ε subunits. The α, β, and δ subunits form a regulatory subcomplex, while the γ and ε form a catalytic subcomplex. Archaea possess homologues of α, β, and δ subunits of eIF2B. Here, we report the three-dimensional structure of an archaeal regulatory subunit (aIF2Bα) from the hyperthermophilic archaeon Pyrococcus horikoshii OT3 determined by X-ray crystallography at 2.2 A resolution. aIF2Bα consists of two subdomains, an N-domain (residues 1-95) and a C-domain (residues 96-276), connected by a long α-helix (α5: 78-106). The N-domain contains a five helix bundle structure, while the C-domain folds into the α/β structure, thus showing similarity to D-ribose-5-phosphate isomerase structure. The presence of two molecules in the crystallographic asymmetric unit and the gel filtration analysis suggest a dimeric structure of aIF2Bα in solution, interacting with each other by C-domains. Furthermore, the crystallographic 3-fold symmetry generates a homohexameric structure of aIF2Bα; the interaction is primarily mediated by the long α-helix at the N-domains. This structure suggests an architecture of the three subunits, α, β, and δ, in the regulatory subcomplex within eIF2B

  6. Lectures Abandoned: Active Learning by Active Seminars

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Corry, Aino Vonge

    2012-01-01

    Traditional lecture-based courses are widely criticised for be- ing less eective in teaching. The question is of course what should replace the lectures and various active learning tech- niques have been suggested and studied. In this paper, we report on our experiences of redesigning a software ......- tive seminars as a replacement of traditional lectures, an activity template for the contents of active seminars, an ac- count on how storytelling supported the seminars, as well as reports on our and the students' experiences....

  7. Antifeedant activity of quassinoids.

    Science.gov (United States)

    Leskinen, V; Polonsky, J; Bhatnagar, S

    1984-10-01

    The antifeedant activity of 13 quassinoids of different structural types has been studied against the Mexican bean beetle (Epilachna varivestis Mulsant) 4th instar larvae and the southern armyworm (Spodoptera eridania Crawer) 5th instar larvae. All quassinoids tested displayed significant activity against the Mexican bean beetle and, thus, do not reveal a simple structure-activity relationship. Five quassinoids were active against the southern armyworm. Interestingly, four of these-bruceantin (I), glaucarubinone (VI), isobruceine A (VIII), and simalikalactone D (XI)-possess the required structural features for antineoplastic activity. The noncytotoxic quassin (X) is an exception; it is active against both pests.

  8. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... What's this? Submit Button Our Division About Us Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient ... What's this? Submit Button Our Division About Us Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient ...

  9. Illicit Activities and Goondagardi

    International Development Research Centre (IDRC) Digital Library (Canada)

    The research analyzes the pathways through which exclusionary urban ... casual labour in construction or small-scale trade activities, etc) and ... PATHWAYS TO ILLICIT ACTIVITIES .... VGG Nagar had become a gambling den for some time.

  10. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Strategies BE Active: Connecting Routes + Destinations Real-World Examples Implementation Resource Guide Visual Guide Worksite Physical Activity ... Implementation Maintaining Interest Needs Assessment Evaluating Success CDC’s Example ... Stairwell Appearance Motivational Signs Installing Music Other ...

  11. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Guidelines Fact Sheets & Infographics Social Media Tools Community Strategies BE Active: Connecting Routes + Destinations Real-World Examples Implementation Resource Guide Visual Guide Worksite Physical Activity Steps ...

  12. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Button Our Division About Us Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and ... Button Our Division About Us Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and ...

  13. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Button Our Division About Us Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local ... Button Our Division About Us Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local ...

  14. Family Activities for Fitness

    Science.gov (United States)

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  15. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Our Division About Us Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local ... Our Division About Us Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local ...

  16. Major operations and activities

    Energy Technology Data Exchange (ETDEWEB)

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development.

  17. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Physical Activity, 2014 Recommendations & Guidelines Fact Sheets & Infographics Social Media Tools Community Strategies BE Active: Connecting Routes + ... Obesity , National Center for Chronic Disease Prevention and Health Promotion Email Recommend Tweet YouTube Instagram Listen Watch ...

  18. Active Marine Station Metadata

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Active Marine Station Metadata is a daily metadata report for active marine bouy and C-MAN (Coastal Marine Automated Network) platforms from the National Data...

  19. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Share Compartir For more help with what counts as aerobic activity, watch this video: Windows Media Player, ... The table below lists examples of activities classified as moderate-intensity or vigorous-intensity based upon the ...

  20. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Compartir For more help with what counts as aerobic activity, watch this video: Windows Media Player, 4: ... ways to understand and measure the intensity of aerobic activity: relative intensity and absolute intensity. Relative Intensity ...

  1. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Data, Trends and Maps Surveillance Systems Resources & Publications Reports Adults Need More Physical Activity MMWR Data Highlights State Indicator Report on Physical Activity, 2014 Recommendations & Guidelines Fact Sheets & ...

  2. Diabetes - keeping active

    Science.gov (United States)

    ... ways to add more activity to your day. Introduction There are many benefits to being active. Staying ... them emails. Take the stairs instead of the elevator. Stand up and move around while making phone ...

  3. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Intensity The amount of energy used by the body per minute of activity. The table below lists ... upon the amount of energy used by the body while doing the activity. Top of Page Moderate ...

  4. Activities for Calculators.

    Science.gov (United States)

    Hiatt, Arthur A.

    1987-01-01

    Ten activities that give learners in grades 5-8 a chance to explore mathematics with calculators are provided. The activity cards involve such topics as odd addends, magic squares, strange projects, and conjecturing rules. (MNS)

  5. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... for a breath. Absolute Intensity The amount of energy used by the body per minute of activity. ... or vigorous-intensity based upon the amount of energy used by the body while doing the activity. ...

  6. Major operations and activities

    International Nuclear Information System (INIS)

    Black, D.G.

    1995-01-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development

  7. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... on this page will be unavailable. For more information about this message, please visit this page: About CDC.gov . Physical Activity Physical Activity Basics Needs for Adults Needs for Children What Counts Needs ...

  8. USAID Activity Locations

    Data.gov (United States)

    US Agency for International Development — The USAID Activities dataset is a snapshot of activities supported by USAID including their geographical locations within countries at the time of the snapshot. The...

  9. Interpretable Active Learning

    OpenAIRE

    Phillips, Richard L.; Chang, Kyu Hyun; Friedler, Sorelle A.

    2017-01-01

    Active learning has long been a topic of study in machine learning. However, as increasingly complex and opaque models have become standard practice, the process of active learning, too, has become more opaque. There has been little investigation into interpreting what specific trends and patterns an active learning strategy may be exploring. This work expands on the Local Interpretable Model-agnostic Explanations framework (LIME) to provide explanations for active learning recommendations. W...

  10. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations: Active vs. Passive Safety & ...

  11. Activity-based design

    DEFF Research Database (Denmark)

    Andersen, Peter Bøgh

    2006-01-01

      In many types of activities communicative and material activities are so intertwined that the one cannot be understood without taking the other into account. This is true of maritime and hospital work that are used as examples in the paper. The spatial context of the activity is also important:...... and automatic machinery can replace one another in an activity. It also gives an example of how to use the framework for design....

  12. Ras activation by SOS

    DEFF Research Database (Denmark)

    Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen

    2014-01-01

    Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual ...

  13. Measurement of Physical Activity.

    Science.gov (United States)

    Dishman, Rod K.; Washburn, Richard A.; Schoeller, Dale A.

    2001-01-01

    Valid assessment of physical activity must be unobtrusive, practical to administer, and specific about physical activity type, frequency, duration, and intensity. Assessment methods can be categorized according to whether they provide direct or indirect (e.g., self-report) observation of physical activity, body motion, physiological response…

  14. Modeling Patterns of Activities using Activity Curves.

    Science.gov (United States)

    Dawadi, Prafulla N; Cook, Diane J; Schmitter-Edgecombe, Maureen

    2016-06-01

    Pervasive computing offers an unprecedented opportunity to unobtrusively monitor behavior and use the large amount of collected data to perform analysis of activity-based behavioral patterns. In this paper, we introduce the notion of an activity curve , which represents an abstraction of an individual's normal daily routine based on automatically-recognized activities. We propose methods to detect changes in behavioral routines by comparing activity curves and use these changes to analyze the possibility of changes in cognitive or physical health. We demonstrate our model and evaluate our change detection approach using a longitudinal smart home sensor dataset collected from 18 smart homes with older adult residents. Finally, we demonstrate how big data-based pervasive analytics such as activity curve-based change detection can be used to perform functional health assessment. Our evaluation indicates that correlations do exist between behavior and health changes and that these changes can be automatically detected using smart homes, machine learning, and big data-based pervasive analytics.

  15. Heterogeneous Active Matter

    Science.gov (United States)

    Kolb, Thomas; Klotsa, Daphne

    Active systems are composed of self-propelled (active) particles that locally convert energy into motion and exhibit emergent collective behaviors, such as fish schooling and bird flocking. Most works so far have focused on monodisperse, one-component active systems. However, real systems are heterogeneous, and consist of several active components. We perform molecular dynamics simulations of multi-component active matter systems and report on their emergent behavior. We discuss the phase diagram of dynamic states as well as parameters where we see mixing versus segregation.

  16. Active food packaging technologies.

    Science.gov (United States)

    Ozdemir, Murat; Floros, John D

    2004-01-01

    Active packaging technologies offer new opportunities for the food industry, in the preservation of foods. Important active packaging systems currently known to date, including oxygen scavengers, carbon dioxide emitters/absorbers, moisture absorbers, ethylene absorbers, ethanol emitters, flavor releasing/absorbing systems, time-temperature indicators, and antimicrobial containing films, are reviewed. The principle of operation of each active system is briefly explained. Recent technological advances in active packaging are discussed, and food related applications are presented. The effects of active packaging systems on food quality and safety are cited.

  17. Accessibility, activity participation and location of activities

    DEFF Research Database (Denmark)

    Næss, Petter

    2006-01-01

    By investigating relationships between residential location and the availability of facilities, location of activities, trip distances, activity participation and trip frequencies, this paper seeks to contribute to a more detailed and nuanced understanding of the relationships between residential...... location and the amount of daily-life travel in an urban region. The empirical data are from a comprehensive study of residential location and travel in Copenhagen Metropolitan Area. Differences between inner- and outer-area residents in activity frequencies and trip frequencies are modest and partly...... outweigh each other. However, differences in trip distances due to the location of the dwelling relative to concentrations of facilities translate into substantially longer total travelling distances among suburbanites than among inner-city residents....

  18. Defense Human Resources Activity > PERSEREC

    Science.gov (United States)

    Skip to main content (Press Enter). Toggle navigation Defense Human Resources Activity Search Search Defense Human Resources Activity: Search Search Defense Human Resources Activity: Search Defense Human Resources Activity U.S. Department of Defense Defense Human Resources Activity Overview

  19. NEA activities in 1980. 9. Activity Report

    International Nuclear Information System (INIS)

    1981-01-01

    This report describes the main features of the Agency's work during 1980 and discusses the state and prospects of the nuclear industry in OECD countries. Trends in nuclear power, radiological and environmental impacts of nuclear fuel cycle activities, nuclear safety research and licensing, nuclear law, nuclear development and fuel cycle studies technical co-operation, nuclear science organisation and administration are reviewed

  20. Marine Biology Activities. Ocean Related Curriculum Activities.

    Science.gov (United States)

    Pauls, John

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  1. Activated carbon from biomass

    Science.gov (United States)

    Manocha, S.; Manocha, L. M.; Joshi, Parth; Patel, Bhavesh; Dangi, Gaurav; Verma, Narendra

    2013-06-01

    Activated carbon are unique and versatile adsorbents having extended surface area, micro porous structure, universal adsorption effect, high adsorption capacity and high degree of surface reactivity. Activated carbons are synthesized from variety of materials. Most commonly used on a commercial scale are cellulosic based precursors such as peat, coal, lignite wood and coconut shell. Variation occurs in precursors in terms of structure and carbon content. Coir having very low bulk density and porous structure is found to be one of the valuable raw materials for the production of highly porous activated carbon and other important factor is its high carbon content. Exploration of good low cost and non conventional adsorbent may contribute to the sustainability of the environment and offer promising benefits for the commercial purpose in future. Carbonization of biomass was carried out in a horizontal muffle furnace. Both carbonization and activation were performed in inert nitrogen atmosphere in one step to enhance the surface area and to develop interconnecting porosity. The types of biomass as well as the activation conditions determine the properties and the yield of activated carbon. Activated carbon produced from biomass is cost effective as it is easily available as a waste biomass. Activated carbon produced by combination of chemical and physical activation has higher surface area of 2442 m2/gm compared to that produced by physical activation (1365 m2/gm).

  2. Active ageing technologies

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    In the recent decade the concept of active aging has become important in the Western hemisphere. The World Health Organization and The European Union have staged active aging as a core policy area and initiated programs of physical activity, independence and prolonged working lives among...... the elderly. As part of this rearticulation of old age, many new technologies take form. This paper uses a wide concept of technologies (devices, regimes, strategies and ways of doing) and argues that technologies form active aging subjectivities, and on the other hand, that these subjectivities...... in their socio-material practices form active aging. Hence, active aging is a mutual entanglement (Callon and Rabeharisoa 2004) between technologies, practices and subjectivities. The paper is based on four months of participant observations and 17 in-depth interviews with elderly persons conducted at three...

  3. Mechanics of active surfaces

    Science.gov (United States)

    Salbreux, Guillaume; Jülicher, Frank

    2017-09-01

    We derive a fully covariant theory of the mechanics of active surfaces. This theory provides a framework for the study of active biological or chemical processes at surfaces, such as the cell cortex, the mechanics of epithelial tissues, or reconstituted active systems on surfaces. We introduce forces and torques acting on a surface, and derive the associated force balance conditions. We show that surfaces with in-plane rotational symmetry can have broken up-down, chiral, or planar-chiral symmetry. We discuss the rate of entropy production in the surface and write linear constitutive relations that satisfy the Onsager relations. We show that the bending modulus, the spontaneous curvature, and the surface tension of a passive surface are renormalized by active terms. Finally, we identify active terms which are not found in a passive theory and discuss examples of shape instabilities that are related to active processes in the surface.

  4. Activated recombinant adenovirus proteinases

    Science.gov (United States)

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  5. Optimizing Active Cyber Defense

    OpenAIRE

    Lu, Wenlian; Xu, Shouhuai; Yi, Xinlei

    2016-01-01

    Active cyber defense is one important defensive method for combating cyber attacks. Unlike traditional defensive methods such as firewall-based filtering and anti-malware tools, active cyber defense is based on spreading "white" or "benign" worms to combat against the attackers' malwares (i.e., malicious worms) that also spread over the network. In this paper, we initiate the study of {\\em optimal} active cyber defense in the setting of strategic attackers and/or strategic defenders. Specific...

  6. Contemporary physical activities

    OpenAIRE

    Tainio, Matti

    2018-01-01

    The customary view of today’s recreational physical activities turns the human movement into a rational practice that is pursued for practical reasons only: for health, vitality, stamina and longevity. This prevalent point of view affects the understanding of the ends, content and quality of physical activities and it creates a bias where the biological, physiological and medical characteristics of physical activities are emphasized while the sensuous, experiential and creative aspects are su...

  7. Zinc triggers microglial activation.

    Science.gov (United States)

    Kauppinen, Tiina M; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A

    2008-05-28

    Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-kappaB (NF-kappaB) reporter gene showed a severalfold increase in NF-kappaB activity in response to 30 microm zinc. Cultured mouse microglia exposed to 15-30 microm zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-kappaB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-kappaB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

  8. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Measuring Physical Activity Intensity Recommend on Facebook Tweet Share Compartir For more help with what ...

  9. Active Photonic Crystal Waveguides

    DEFF Research Database (Denmark)

    Ek, Sara

    This thesis deals with the fabrication and characterization of active photonic crystal waveguides, realized in III-V semiconductor material with embedded active layers. The platform offering active photonic crystal waveguides has many potential applications. One of these is a compact photonic...... due to photonic crystal dispersion. The observations are explained by the enhancement of net gain by light slow down. Another application based on active photonic crystal waveguides is micro lasers. Measurements on quantum dot micro laser cavities with different mirror configurations and photonic...

  10. CDBG Economic Development Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to economic development, including commercial or industrial rehab, commercial or industrial land acquisition, commercial or industrial...

  11. Automatic NAA. Saturation activities

    International Nuclear Information System (INIS)

    Westphal, G.P.; Grass, F.; Kuhnert, M.

    2008-01-01

    A system for Automatic NAA is based on a list of specific saturation activities determined for one irradiation position at a given neutron flux and a single detector geometry. Originally compiled from measurements of standard reference materials, the list may be extended also by the calculation of saturation activities from k 0 and Q 0 factors, and f and α values of the irradiation position. A systematic improvement of the SRM approach is currently being performed by pseudo-cyclic activation analysis, to reduce counting errors. From these measurements, the list of saturation activities is recalculated in an automatic procedure. (author)

  12. Contact activation: a revision.

    Science.gov (United States)

    Schmaier, A H

    1997-07-01

    In conclusion, a revised view of the contact system has been presented. This system has little to do with the initiation of hemostasis. Like lupus anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be risk factors for thrombosis. BK from kininogens is a potent modulator of vascular biology inducing vasodilation, tissue plasminogen activator release, and prostacyclin liberation. Kininogens, themselves, are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha-thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's breakdown products. HK also is the pivotal protein for contact protein assembly on endothelium. It is the receptor for prekallikrein which when bound to HK becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor XII. Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation. Thus the "physiologic, negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes.

  13. Activated carbons and gold

    International Nuclear Information System (INIS)

    McDougall, G.J.; Hancock, R.D.

    1980-01-01

    The literature on activated carbon is reviewed so as to provide a general background with respect to the effect of source material and activation procedure on carbon properties, the structure and chemical nature of the surface of the activated carbon, and the nature of absorption processes on carbon. The various theories on the absorption of gold and silver from cyanide solutions are then reviewed, followed by a discussion of processes for the recovery of gold and silver from cyanide solutions using activated carbon, including a comparison with zinc precipitation

  14. CDBG Public Services Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to public services, including senior services, legal services, youth services, employment training, health services, homebuyer counseling, food...

  15. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Content source: Division of Nutrition, Physical Activity, and Obesity , National Center for Chronic Disease Prevention and Health Promotion Email Recommend Tweet YouTube Instagram ...

  16. CDBG Housing Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to housing, including multifamily rehab, housing services, code enforcement, operation and repair of foreclosed property and public housing...

  17. NEA activities in 1983. 12. Activity report

    International Nuclear Information System (INIS)

    1984-01-01

    This report describes the main features of the Agency's work during 1983 and discusses the state and prospects of the nuclear industry in OECD countries. Trends in nuclear power, nuclear development and the fuel cycles nuclear safety technology and licensing, radiological and environmental impacts of nuclear fuel cycle activities, legal affairs, nuclear science, joint undertakings and other NEA joint projects, organisation and administration are reviewed

  18. Russian: An Active Introduction.

    Science.gov (United States)

    De La Cruz, Nina

    The Active Introduction is one of the modules in an array of materials used in Russian training for beginners at the Foreign Service Institute. It is essentially a catalog of sentences relating to typical daily activities which can be combined to form different communication sequences in dialog form. Students learn to speak Russian through…

  19. Activation analysis. Detection limits

    International Nuclear Information System (INIS)

    Revel, G.

    1999-01-01

    Numerical data and limits of detection related to the four irradiation modes, often used in activation analysis (reactor neutrons, 14 MeV neutrons, photon gamma and charged particles) are presented here. The technical presentation of the activation analysis is detailed in the paper P 2565 of Techniques de l'Ingenieur. (A.L.B.)

  20. Obesity and physical activity.

    NARCIS (Netherlands)

    Westerterp, K.R.

    1999-01-01

    Department of Human Biology, Maastricht University, The Netherlands. k.westerterp@hb.unimaas.nl OBJECTIVES: Three aspects of obesity and physical activity are reviewed: whether the obese are inactive; how the activity level can be increased; and which are the effects of an increase in physical

  1. Rhythmic Activities for Children.

    Science.gov (United States)

    Practical Pointers, 1977

    1977-01-01

    Focusing on the development of fundamental rhythm skills involved in music and movement activities, this teaching guide emphasizes activities that will help children express their feelings and communicate with others, develop perceptual and motor skills, and enhance sensory awareness. Suggestions for involving handicapped children and examples of…

  2. Elementary Environmental Activities.

    Science.gov (United States)

    Larson, Robert J.

    This guide presents suggestions for field trips, out-of-doors activities, material for centers, and individualized activities in the teaching of elementary school science and particularly environmental education at the elementary level. The guide includes a section on preparation and procedures for conducting field trips, including sample…

  3. Enzyme with rhamnogalacturonase activity.

    NARCIS (Netherlands)

    Kofod, L.V.; Andersen, L.N.; Dalboge, H.; Kauppinen, M.S.; Christgau, S.; Heldt-Hansen, H.P.; Christophersen, C.; Nielsen, P.M.; Voragen, A.G.J.; Schols, H.A.

    1998-01-01

    An enzyme exhibiting rhamnogalacturonase activity, capable of cleaving a rhamnogalacturonan backbone in such a manner that galacturonic acids are left as the non-reducing ends, and which exhibits activity on hairy regions from a soy bean material and/or on saponified hairy regions from a sugar beet

  4. RTE activity report 2005

    International Nuclear Information System (INIS)

    2006-01-01

    The RTE (electric power transport network) is the french manger of the electric power transport. This activity report provides information on the company results for the year 2005: panorama of the year, management and organization, the place of RTE in the european market, the customers, the industrial tool, the environment the human resources, the international activity and the management report. (A.L.B.)

  5. Active and Healthy Schools

    Science.gov (United States)

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  6. Measuring children's physical activity

    DEFF Research Database (Denmark)

    Schneller, Mikkel Bo; Bentsen, Peter; Nielsen, Glen

    2017-01-01

    INTRODUCTION: Accelerometer-based physical activity monitoring has become the method of choice in many large-scale physical activity (PA) studies. However, there is an ongoing debate regarding the placement of the device, the determination of device wear time, and how to solve a lack of participant...

  7. Activity report 2002

    International Nuclear Information System (INIS)

    2002-01-01

    This annual report deals with the activities, the program management and the financial aspects of the ANDRA (National Agency for the radioactive wastes management) during 2002. After a presentation of the activities during the year 2002, it provides the financial accounting, data on company cash, the ANDRA missions and publications. (A.L.B.)

  8. Mental activity and culture

    NARCIS (Netherlands)

    Hofstede, Gert Jan

    2018-01-01

    How does culture affect mental activity? That question, applied to the design of social agents, is tackled in this chapter. Mental activity acts on the perceived outside world. It does so in three steps: perceive, interpret, select action. We see that when culture is taken into account, objective

  9. NEA activities in 1982

    International Nuclear Information System (INIS)

    1983-01-01

    This report presents an account of the activities of the Nuclear Energy Agency. It deals with current nuclear trends, nuclear development and the fuel cycle, nuclear safety research and licensing, radiological and environmental impacts of nuclear fuel cycle activities, legal affairs, nuclear science, joint undertakings, and, organization and administration

  10. Measuring Children's Physical Activity

    DEFF Research Database (Denmark)

    Schneller, Mikkel Bo; Bentsen, Peter; Nielsen, Glen

    2017-01-01

    INTRODUCTION: Accelerometer-based physical activity monitoring has become the method of choice in many large-scale physical activity (PA) studies. However, there is an ongoing debate regarding the placement of the device, the determination of device wear time, and how to solve a lack of participant...

  11. Respirometry in activated sludge

    NARCIS (Netherlands)

    Spanjers, H.

    1993-01-01

    The purpose of the study was (1) to develop a respiration meter capable of continuously measuring, using different procedures, the oxygen uptake rate of activated sludge and (2) to expand knowledge about respiration related characteristics of wastewater and activated sludge.

    A

  12. Emotionally Intense Science Activities

    Science.gov (United States)

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-01-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of…

  13. Automation of activation analysis

    International Nuclear Information System (INIS)

    Ivanov, I.N.; Ivanets, V.N.; Filippov, V.V.

    1985-01-01

    The basic data on the methods and equipment of activation analysis are presented. Recommendations on the selection of activation analysis techniques, and especially the technique envisaging the use of short-lived isotopes, are given. The equipment possibilities to increase dataway carrying capacity, using modern computers for the automation of the analysis and data processing procedure, are shown

  14. Carbon activity meter

    International Nuclear Information System (INIS)

    Roy, P.; Krankota, J.L.

    1975-01-01

    A carbon activity meter utilizing an electrochemical carbon cell with gaseous reference electrodes having particular application for measuring carbon activity in liquid sodium for the LMFBR project is described. The electrolyte container is electroplated with a thin gold film on the inside surface thereof, and a reference electrode consisting of CO/CO 2 gas is used. (U.S.)

  15. Children's recreational physical activity

    NARCIS (Netherlands)

    Kemperman, A.D.A.M.; Timmermans, H.J.P.

    2011-01-01

    This study explored children's participation in recreational (physical) activities and the extent to which this participation was influenced by individual and household socio-demographics and characteristics of the social and physical environment. Travel and activity diaries were used to collect

  16. The Activity of Play

    DEFF Research Database (Denmark)

    Pichlmair, Martin

    This paper presents Activity Theory as a framework for understanding the action of playing games with the intention of building a foundation for the creation of new game design tools and methods. Activity Theory, an epistemological framework rooted in Soviet psychology of the first half of the 20...

  17. Reflections on Activity Theory

    Science.gov (United States)

    Bakhurst, David

    2009-01-01

    It is sometimes suggested that activity theory represents the most important legacy of Soviet philosophy and psychology. But what exactly "is" activity theory? The canonical account in the West is given by Engestrom, who identifies three stages in the theory's development: from Vygotsky's insights, through Leontiev's articulation of the…

  18. Activation force splines

    DEFF Research Database (Denmark)

    Engell-Nørregård, Morten Pol; Erleben, Kenny

    We present a method for simulating the active contraction of deformable models, usable for interactive animation of soft deformable objects. We present a novel physical principle as the governing equation for the coupling between the low dimensional 1D activation force model and the higher...

  19. Activity Fund Accounting.

    Science.gov (United States)

    Cool, David W.

    1983-01-01

    Addresses the need of school districts in many states to decide on an appropriate mingling of centralization and decentralization in the operation of activity funds. Argues for analysis of activity fund operation through a breakdown into such major components as policy, the accounting system, and reporting and auditing. (JBM)

  20. Peak Longevity Physical Activity

    Science.gov (United States)

    People who engage in three to five times the recommended minimum level of leisure-time physical activity derive the greatest benefit in terms of mortality reduction when compared with people who do not engage in leisure-time physical activity.

  1. Physical activity among adolescents

    DEFF Research Database (Denmark)

    Henriksen, P W; Ingholt, L; Rasmussen, M

    2016-01-01

    The objectives of this study were (a) to examine the association between various kinds of parental social support and adolescents' physical activity (PA) and (b) to examine whether various kinds of social support from mothers and fathers were differently associated with boys' and girls' PA. Data...... to understand why some adolescents are physically active and others are not....

  2. AMP (Activity Manipulation Program)

    International Nuclear Information System (INIS)

    Engle, W.W. Jr.

    1976-03-01

    AMP is a FORTRAN IV program written to handle energy-group structured activity factors such as sources, conversion factors, and response functions, as used by ANISN, DOT III, and other nuclear reactor and shielding codes. Activities may be retrieved from ANISN-type cross-section and activity sets found on cards and tapes, and from tabular-type sets on cards. They may be altered by change of group structure, multiplication by a constant, or multiplication by delta E (the group-energy interval), and then output to ANISN-type cards or tape and tabular-type cards. A full edit of input and output activities is always printed by group and activity number

  3. ANDRA, 2006 activity report

    International Nuclear Information System (INIS)

    2006-01-01

    The French national agency of radioactive waste management (ANDRA) was marked in 2006 by two outstanding events: the publication of the national inventory of radioactive wastes and valorisable materials, and the vote of the law from June 28, 2006 relative to the sustainable management of radioactive wastes and materials. This road-map law has an impact on ANDRA's activities for the coming years. This activity report presents several 2006 highlights of ANDRA's missions as well: the public service mission, the by-law about the effluents of the Aube plant for the storage of low-medium activity wastes, the building of the first 'double-cell' at the very-low activity waste storage plant of Aube, the research studies about the project of deep underground disposal of high-medium activity, long-living wastes, and the public information about ANDRA's technical and scientific know-how. The management and financial reports are attached in appendix. (J.S.)

  4. Active chiral fluids.

    Science.gov (United States)

    Fürthauer, S; Strempel, M; Grill, S W; Jülicher, F

    2012-09-01

    Active processes in biological systems often exhibit chiral asymmetries. Examples are the chirality of cytoskeletal filaments which interact with motor proteins, the chirality of the beat of cilia and flagella as well as the helical trajectories of many biological microswimmers. Here, we derive constitutive material equations for active fluids which account for the effects of active chiral processes. We identify active contributions to the antisymmetric part of the stress as well as active angular momentum fluxes. We discuss four types of elementary chiral motors and their effects on a surrounding fluid. We show that large-scale chiral flows can result from the collective behavior of such motors even in cases where isolated motors do not create a hydrodynamic far field.

  5. Activation neutron detector

    International Nuclear Information System (INIS)

    Ambardanishvili, T.S.; Kolomiitsev, M.A.; Zakharina, T.Y.; Dundua, V.J.; Chikhladze, N.V.

    1976-01-01

    An activation neutron detector made as a moulded and cured composition of a material capable of being neutron-activated is described. The material is selected from a group consisting of at least two chemical elements, a compound of at least two chemical elements and their mixture, each of the chemical elements and their mixture, each of the chemical elements being capable of interacting with neutrons to form radioactive isotopes having different radiation energies when disintegrating. The material capable of being neutron-activated is distributed throughout the volume of a polycondensation resin inert with respect to neutrons and capable of curing. 17 Claims, No Drawings

  6. Mnemonic activation by SPECT

    International Nuclear Information System (INIS)

    Migneco, O.; Darcourt, J.; Benoit, M; Malandain, G.; Thirion, J.P.; Robert, Ph.; Vidal, R.; Desvignes, Ph.; Benoliel, J.; Ayache, N.; Bussiere, F.

    1997-01-01

    Data of literature show that SPECT is able to detect cerebral activations induced by sensory-motor stimuli. The facts are not clearly established in what concerns the cognitive activations the amplitude of which is lower. We have studied an activation paradigm such as the Grober and Bruschke test which implies the long term explicit memory. It comprises a visual presentation of words followed by their indexed recall. By using a two-day protocol, 2 SPECTs were achieved in 4 healthy right-handed voluntaries as follows: one of activation (A) and one of control (B). The fifth subject benefited by a SPECT B and of an MRI. The injection for the examination A has been done during the indexed recall stage and for the examination B at the moment when the patient repeated several times the same 3 words. The SPECT data were collected 1 hour after the injection of 370 MBq of ECD making use of a 3-head camera equipped with UHR fan collimators and ending by a LMH on the reconstructed images of 8 mm. The MRI has been achieved by means of a Signa 1.5 Tesla magnet. The SPECT A and B of the subjects 1 to 4 were matched elastically to that of the subject 5 and that of the subject 5 was rigidly matched on its MRI. In this way the individual activation cards of the 4 subjects could be averaged and superimposed on the MRI of the 5. subject. One observes an internal temporal activation (maximal activation of left tonsil, +25% and right uncus, +23%) and a right cingulum activation (maximal activation, +25%), in agreement with the neuro-physiological data. The elastic matching makes possible the inter-subject averaging, what increases the signal-to-noise ratio of activation. The inter-modality rigid matching facilitates the anatomical localisation of the activation site. With these adapted tools, the cognitive activation is thus possible by SPECT and opens perspectives for early diagnosis of neurological troubles, namely of Alzheimer's disease

  7. Forecast of auroral activity

    International Nuclear Information System (INIS)

    Lui, A.T.Y.

    2004-01-01

    A new technique is developed to predict auroral activity based on a sample of over 9000 auroral sites identified in global auroral images obtained by an ultraviolet imager on the NASA Polar satellite during a 6-month period. Four attributes of auroral activity sites are utilized in forecasting, namely, the area, the power, and the rates of change in area and power. This new technique is quite accurate, as indicated by the high true skill scores for forecasting three different levels of auroral dissipation during the activity lifetime. The corresponding advanced warning time ranges from 22 to 79 min from low to high dissipation levels

  8. Activity report 1977

    International Nuclear Information System (INIS)

    Krishnan, L.V.; Lee, S.M.; Sahoo, D.; Sreedharan, O.M.; Srinivasan, G.

    1979-05-01

    The Research and Development (R and D) activities of the Reactor Research Centre, Kalpakkam, during the year 1977 are reported. The report is presented in the form of individual summaries of R and D activities most of which are connected with the FBTR project. These R and D activities deal with various aspects of the FBTR project such as reactor physics, reactor design, reactor engineering, fabrication, testing and quality assurance of reactor materials and components, reactor chemistry, reactor safety, reprocessing, systems analysis and instrumentation. (M.G.B.)

  9. A neutron activation detector

    International Nuclear Information System (INIS)

    Ambardanishvili, T.S.; Kolomiitsev, M.A.; Zakharina, T.Y.; Dundua, V.J.; Chikhladze, N.V.

    1973-01-01

    The present invention concerns a neutron activation detector made from a moulded and hardened composition. According to the invention, that composition contains an activable substance constituted by at least two chemical elements and/or compounds of at least two chemical elements. Each of these chemical elements is capable of reacting with the neutrons forming radio-active isotopes with vatious levels of energy during desintegration. This neutron detector is mainly suitable for measuring integral thermal neutron and fast neutron fluxes during irradiation of the sample, and also for measuring the intensities of neutron fields [fr

  10. Active Directory cookbook

    CERN Document Server

    Hunter, Laura

    2008-01-01

    When you need practical hands-on support for Active Directory, the updated edition of this extremely popular Cookbook provides quick solutions to more than 300 common (and uncommon) problems you might encounter when deploying, administering, and automating Microsoft's network directory service. For the third edition, Active Directory expert Laura E. Hunter offers troubleshooting recipes based on valuable input from Windows administrators, in addition to her own experience. You'll find solutions for the Lightweight Directory Access Protocol (LDAP), ADAM (Active Directory Application Mode), m

  11. Physics of solar activity

    Science.gov (United States)

    Sturrock, Peter A.

    1993-01-01

    The aim of the research activity was to increase our understanding of solar activity through data analysis, theoretical analysis, and computer modeling. Because the research subjects were diverse and many researchers were supported by this grant, a select few key areas of research are described in detail. Areas of research include: (1) energy storage and force-free magnetic field; (2) energy release and particle acceleration; (3) radiation by nonthermal electrons; (4) coronal loops; (5) flare classification; (6) longitude distributions of flares; (7) periodicities detected in the solar activity; (8) coronal heating and related problems; and (9) plasma processes.

  12. Creative activity and inclusion

    Directory of Open Access Journals (Sweden)

    Shemanov A.Yu.

    2013-09-01

    Full Text Available The aim of the article was to analyze the inclusion potential of art creative activity, namely of theatre performance, in people with disabilities. The article provides examples of disagreements in understanding the significance of these art activities for exercising the rights of people with disabilities to contribute to culture and art and some problems arising here. The conclusion is made that theatre art performed by people with disabilities is gradually changing its function: from being a means of self-affirmation to the determination of its specific place in overall theatre process. These changes confirm the inclusion potential of theatre art activity.

  13. 1985. Activity progress report

    International Nuclear Information System (INIS)

    1986-01-01

    The research program of the Laboratory of nuclear and high energy physics (LPNHE) of the Institute of nuclear and particle physics (IN2P3) presents the research activities of its groups: principally, the Delphi group which constructs the outer detector of Delphi at LEP, the neutrino group which studies the neutrino mass, the Hera group whose work is collaboration to the construction of a detector for Hera collisioner; in parallel to these activities, other more little groups continue analysis of activities which are going to be finished: they are the CELLO group, the EHS group, the omega prime group and the nuclear emulsion group [fr

  14. Scientific activities 1979

    International Nuclear Information System (INIS)

    1981-01-01

    The scientific activities and achievements of the Nuclear Research Center Democritus for the year 1979 are presented in the form of a list of 78 projects giving title, objectives, commencement year, responsible of each project, developed activities and the pertaining lists of publications. The 15 chapters of this work cover the activities of the main Divisions of the Democritus NRC: Electronics, Biology, Physics, Chemistry, Health Physics, Reactor, Radioisotopes, Environmental Radioactivity, Soil Science, Computer Center, Uranium Exploration, Medical Service, Technological Applications and Training. (T.A.)

  15. Active Packaging Coatings

    Directory of Open Access Journals (Sweden)

    Luis J. Bastarrachea

    2015-11-01

    Full Text Available Active food packaging involves the packaging of foods with materials that provide an enhanced functionality, such as antimicrobial, antioxidant or biocatalytic functions. This can be achieved through the incorporation of active compounds into the matrix of the commonly used packaging materials, or by the application of coatings with the corresponding functionality through surface modification. The latter option offers the advantage of preserving the packaging materials’ bulk properties nearly intact. Herein, different coating technologies like embedding for controlled release, immobilization, layer-by-layer deposition, and photografting are explained and their potential application for active food packaging is explored and discussed.

  16. IPSN's 2001 activity report

    International Nuclear Information System (INIS)

    2001-01-01

    This report summarizes the 2001 activities and operation of the French institute of nuclear protection and safety (IPSN) which has become the institute of radioprotection and nuclear safety (IRSN) after its merging with the office of protection against ionizing radiations (OPRI). IPSN's activities cover: the safety of nuclear facilities, the safety of nuclear wastes, the management of emergencies, the management of sensible materials, the protection of the environment and of the public health, some research activities with foreign partners (central and eastern Europe, Asia..), and a partnership with the GRS, the German homologue of IPSN. (J.S.)

  17. Inspector measurement verification activities

    International Nuclear Information System (INIS)

    George, R.S.; Crouch, R.

    e most difficult and complex activity facing a safeguards inspector involves the verification of measurements and the performance of the measurement system. Remeasurement is the key to measurement verification activities. Remeasurerements using the facility's measurement system provide the bulk of the data needed for determining the performance of the measurement system. Remeasurements by reference laboratories are also important for evaluation of the measurement system and determination of systematic errors. The use of these measurement verification activities in conjunction with accepted inventory verification practices provides a better basis for accepting or rejecting an inventory. (U.S.)

  18. Diabetes Diet, Eating, & Physical Activity

    Science.gov (United States)

    ... Sexual, & Bladder Problems Clinical Trials Diabetes Diet, Eating, & Physical Activity Nutrition and physical activity are important parts of ... feet before, during, and after physical activity. What physical activities should I do if I have diabetes? Most ...

  19. Cryogenic Active Mirrors

    Data.gov (United States)

    National Aeronautics and Space Administration — This effort seeks to develop active mirrors that can correct for thermally-induced figure deformations upon cooling from room-temperature at the time of manufacture,...

  20. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... using relative intensity, people pay attention to how physical activity affects their heart rate and breathing. The talk test is a simple way to measure relative intensity. ...

  1. Mining activities at Neyveli

    International Nuclear Information System (INIS)

    Boopathy, P.V.; Rathinavel, R.

    1993-01-01

    Mining activities at lignite areas around Neyveli are described. Measures taken to safeguard the environment from despoliation of land, air pollution, noise pollution and effluents are described. (M.G.B.)

  2. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... 45 David, Age 65 Harold, Age 67 Data & Statistics Facts About Physical Activity Data, Trends and Maps ... relative intensity and absolute intensity. Relative Intensity The level of effort required by a person to do ...

  3. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... updated: June 4, 2015 Content source: Division of Nutrition, Physical Activity, and Obesity , National Center for Chronic Disease Prevention and Health Promotion ... Services HHS/Open USA.gov Top

  4. Active Fire Mapping Program

    Science.gov (United States)

    Active Fire Mapping Program Current Large Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS Data Fire Data in Google Earth ...

  5. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... content Start of Search Controls Search Form Controls Cancel Submit Search the CDC CDC A-Z Index ... Search Controls Search Form Controls Search The CDC Cancel Submit Search The CDC Physical Activity Note: Javascript ...

  6. Uranium market activities

    International Nuclear Information System (INIS)

    Patterson, J.A.

    1975-01-01

    Results are summarized from the 1974 ERDA annual survey of buyers and sellers and from a survey of uranium price data which provided information on additional domestic buying activity during the first half of 1975 through 1982

  7. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... The amount of energy used by the body per minute of activity. The table below lists examples ... of Page Moderate Intensity Walking briskly (3 miles per hour or faster, but not race-walking) Water ...

  8. CDBG Public Improvements Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to public improvements, including senior centers, youth centers, parks, street improvements, water/sewer improvements, child care centers, fire...

  9. Homebuyer Activities Report

    Data.gov (United States)

    Department of Housing and Urban Development — This monthly report is an Excel spreadsheet. PJs can use this report to view homebuyer activities with the 2012 or 2013 program year in IDIS that are in final draw,...

  10. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... aerobic activity, watch this video: Windows Media Player, 4:48 More videos Here are some ways to ... ePub file RIS file Page last reviewed: June 4, 2015 Page last updated: June 4, 2015 Content ...

  11. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... For this reason, some items on this page will be unavailable. For more information about this message, ... If you're doing vigorous-intensity activity, you will not be able to say more than a ...

  12. 1996 GRAMME activity report

    International Nuclear Information System (INIS)

    1997-01-01

    This note draws a balance of the activities made at CEA-DEM within the frame of GRAMME collaboration. Results in six interest fields are presented: solidification, Mephisto program, transport phenomena, isothermal diffusion, rhenium alloys and instrumentation. (A.C.)

  13. OTI Activity Database

    Data.gov (United States)

    US Agency for International Development — OTI's worldwide activity database is a simple and effective information system that serves as a program management, tracking, and reporting tool. In each country,...

  14. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... level of effort required by a person to do an activity. When using relative intensity, people pay ... State and Local Programs File Formats Help: How do I view different file formats (PDF, DOC, PPT, ...

  15. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Older Adults Overcoming Barriers Measuring Physical Activity Intensity Target Heart Rate & Estimated Maximum Heart Rate Perceived Exertion ( ... a heavy backpack Other Methods of Measuring Intensity Target Heart Rate and Estimated Maximum Heart Rate Perceived ...

  16. Home Activities Reports

    Data.gov (United States)

    Department of Housing and Urban Development — This monthly report is an Excel spreadsheet, broken up by state. PJs can use this report to view activities with the 2012 or 2013 program year in IDIS, including;...

  17. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Local Programs Measuring Physical Activity Intensity Recommend on Facebook Tweet Share Compartir For more help with what ... RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton Road ...

  18. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Walkability Audit Tool Sample Audit Glossary Selected References Discount Fitness Club Network Assessing Need and Interest Selecting ... attention to how physical activity affects their heart rate and breathing. The talk test is a simple ...

  19. Physical activity: genes & health

    CERN Multimedia

    2002-01-01

    Carl Johan SUNDBERG is an Associate Professor in Physiology and Licenced Physician. His research focus is Molecular mechanisms involved in the adaptation of human skeletal muscle to physical activity.

  20. Measuring Physical Activity Intensity

    Science.gov (United States)

    ... 67 Data & Statistics Facts About Physical Activity Data, Trends and Maps Surveillance Systems Resources & Publications Reports Adults ... CDC’s Example StairWELL Stairwell Appearance Motivational Signs Installing Music Other Ideas to Consider Tracking Stair Usage Project ...

  1. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Recommendations & Guidelines Fact Sheets & Infographics Social Media Tools Community Strategies BE Active: Connecting Routes + Destinations Real-World ... Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton ...

  2. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... 2015 Page last updated: June 4, 2015 Content source: Division of Nutrition, Physical Activity, and Obesity , National ... INFO U.S. Department of Health & Human Services HHS/Open USA.gov Top

  3. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... 2015 Page last updated: June 4, 2015 Content source: Division of Nutrition, Physical Activity, and Obesity , National Center for Chronic Disease Prevention and Health Promotion ... LEGAL Policies Privacy FOIA No Fear Act OIG ...

  4. Antitubercular activities of quinolones

    Indian Academy of Sciences (India)

    The paper gives a brief account of the recently introduced Szeged index. (Sz). Using this .... good correlation with antitubercular activities and yield physically meaningful regressions. ..... Parr R G and Pearson R G 1983 J. Am. Chem. Soc.

  5. Enerplan, activity report 2010

    International Nuclear Information System (INIS)

    2011-01-01

    Enerplan is the French union of solar energy professionals. Created in 1983, its social purpose is the study and defense of the rights and of the material and moral interests of its members. Enerplan structures its action through two poles representing members' activities: 'solar energy and building' where topics about heat and electricity generation in relation with buildings are treated, and 'photovoltaic energy' where topics specific to big solar power plants are considered. Thanks to the collaborative participation of its members, both poles allow Enerplan union to be source of proposals to develop solar energy in France. As an active interface between professionals and institutions, Enerplan includes in its membership: industrialists, plant makers, engineering consultants, installers, associations, energy suppliers etc, from small-medium size companies to big groups. This document presents Enerplan's activities in 2010 (public relations, lobbying, meetings and conferences, promotional activities, collaborations, projects..)

  6. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... on this page will be unavailable. For more information about this message, please visit this page: About CDC.gov . ... Resources & Publications Reports Adults Need More Physical Activity ...

  7. PRCR Classes and Activities

    Data.gov (United States)

    Town of Cary, North Carolina — This data is specific to Parks and Recreation classes, workshops, and activities within the course catalog. It contains an entry for upcoming classes.*This data set...

  8. Activity report 1979

    International Nuclear Information System (INIS)

    Delande, E.; Drent, W.

    1980-07-01

    The activites of the Eurochemic (European Company for the Chemical Processing of Irradiated Fuels) at Mol is summarized under the following headings: the decontamination and intervention in the Fuel Reception and Storage Building, the active operation of the bituminization facility, the construction of two additional storage bunkers, the full active operation of the section for the handling of solid waste and the construction of various units for the conditioning of organic liquid waste and plutonium hearing solid wastes. (AF)

  9. Activity report 1980

    International Nuclear Information System (INIS)

    Drent, W.; Delande, E.

    1981-07-01

    The EUROCHEMIC Company's activity report for fiscal year 1980 covers the following topics: administrative and commercial matters; personnel; cleaning and decontamination works in the reprocessing plant; operation of the bituminization facility; active treatment of the spent solvent in the Eurowatt facility; operation of the waste sorting and shredding unit, preparing the plutonium contaminated solid wastes for conditioning and recovery of plutonium; radiation protection and library and documentation. (AF)

  10. Reflections on Active Networking

    Science.gov (United States)

    2005-01-01

    with a Software Switch for Active Networks ”. We had initially called the project “ SoftSwitch ”, but after some concerns David Farber raised that this...Reflections on Active Networking Jonathan M. Smith CIS Department, University of Pennsylvania jms@cis.upenn.edu Abstract Interactions among...telecommunications networks , computers, and other peripheral devices have been of interest since the earliest distributed computing systems. A key

  11. Low activation ferritic alloys

    Science.gov (United States)

    Gelles, David S.; Ghoniem, Nasr M.; Powell, Roger W.

    1986-01-01

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  12. RAVEN Quality Assurance Activities

    Energy Technology Data Exchange (ETDEWEB)

    Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    This report discusses the quality assurance activities needed to raise the Quality Level of Risk Analysis in a Virtual Environment (RAVEN) from Quality Level 3 to Quality Level 2. This report also describes the general RAVEN quality assurance activities. For improving the quality, reviews of code changes have been instituted, more parts of testing have been automated, and improved packaging has been created. For upgrading the quality level, requirements have been created and the workflow has been improved.

  13. Intercreativity: Mapping Online Activism

    Science.gov (United States)

    Meikle, Graham

    How do activists use the Internet? This article maps a wide range of activist practice and research by applying and developing Tim Berners-Lee's concept of ‘intercreativity' (1999). It identifies four dimensions of Net activism: intercreative texts, tactics, strategies and networks. It develops these through examples of manifestations of Net activism around one cluster of issues: support campaigns for refugees and asylum seekers.

  14. Activity report 1975

    International Nuclear Information System (INIS)

    Ananthakrishna, G.; Ramanathan, N.; Rodriguez, P.; Shankar Singh, R.; Venkataraman, S.

    1977-08-01

    The report covers a wide range of R and D activities in the Reactor Research Centre, Kalpakkam (India). The scientific and technical activities in various fields such as: reactor physics, reactor design, reactor engineering, design of sodium circuits, reactor fuel handling, electrical and instrumentation engineering for FBTR, data processing system, reactor operation studies, reactor construction, materials science, metallurgy, reprocessing, instrumentation, safety research and engineering services, have been reported in brief. (A.K.)

  15. Fast neutron activation analysis

    International Nuclear Information System (INIS)

    Pepelnik, R.

    1986-01-01

    Since 1981 numerous 14 MeV neutron activation analyses were performed at Korona. On the basis of that work the advantages of this analysis technique and therewith obtained results are compared with other analytical methods. The procedure of activation analysis, the characteristics of Korona, some analytical investigations in environmental research and material physics, as well as sources of systematic errors in trace analysis are described. (orig.) [de

  16. Taxing Financial Activity

    OpenAIRE

    Jack M. Mintz

    2003-01-01

    In most countries, substantial business activity is related to financial intermediation: banking, trusts, investment companies and insurance. Financial businesses play a crucial role in the economy by matching lenders with borrowers as well as facilitating governance of businesses through close monitoring of funds lent to businesses. Financial institutions also reduce risk faced by investors by pooling investments over many different types of business activities and insuring against property,...

  17. Activity report 1976

    International Nuclear Information System (INIS)

    Ananthakrishna, G.; Ramanathan, N.; Rodriguez, P.; Shankar Singh, R.; Venkataraman, S.

    1978-11-01

    The research and development activities of the Reactor Research Centre, Kalpakkam, during 1976 are reported. The main thrust of the R and D activities is directed towards the FBTR Project and they deal with the various aspects of the project such as reactor physics, reactor design, fuel handling, reactor instrumentation, reactor operation, reactor construction, reactor safety, reactor materials, reactor chemistry and fuel reprocessing. (M.G.B.)

  18. Liquidity and Shareholder Activism

    OpenAIRE

    Norli, Øyvind; Ostergaard, Charlotte; Schindele, Ibolya

    2009-01-01

    This is the authors’ accepted, refereed and final manuscript to the article Blockholders' incentives to intervene in corporate governance are weakened by free-rider problems and high costs of activism. Theory suggests activists may recoup expenses through informed trading of target rms' stock when stocks are liquid. We show that stock liquidity increases the probability of activism but does less so for potentially overvalued rms for which privately informed blockholders may h...

  19. Shareholder activism in banking

    OpenAIRE

    Roman, Raluca

    2015-01-01

    This paper conducts the first assessment of shareholder activism in banking and its effects on risk and performance. The focus is on the conflicts among bank shareholders, managers, and creditors (e.g., regulators, deposit insurer, taxpayers, depositors). This paper finds activism may generally be a destabilizing force, increasing bank risk-taking, but creating market value for shareholders, and leaving operating returns unchanged, consistent with the empirical dominance of the Shareholder-Cr...

  20. Forensic neutron activation analysis

    International Nuclear Information System (INIS)

    Kishi, T.

    1987-01-01

    The progress of forensic neutron activation analysis (FNAA) in Japan is described. FNAA began in 1965 and during the past 20 years many cases have been handled; these include determination of toxic materials, comparison examination of physical evidences (e.g., paints, metal fragments, plastics and inks) and drug sample differentiation. Neutron activation analysis is applied routinely to the scientific criminal investigation as one of multielement analytical techniques. This paper also discusses these routine works. (author) 14 refs

  1. Antibacterial activity of antileukoprotease.

    Science.gov (United States)

    Hiemstra, P S; Maassen, R J; Stolk, J; Heinzel-Wieland, R; Steffens, G J; Dijkman, J H

    1996-01-01

    Antileukoprotease (ALP), or secretory leukocyte proteinase inhibitor, is an endogenous inhibitor of serine proteinases that is present in various external secretions. ALP, one of the major inhibitors of serine proteinases present in the human lung, is a potent reversible inhibitor of elastase and, to a lesser extent, of cathepsin G. In equine neutrophils, an antimicrobial polypeptide that has some of the characteristics of ALP has been identified (M. A. Couto, S. S. L. Harwig, J. S. Cullor, J. P. Hughes, and R. I. Lehrer, Infect. Immun. 60:5042-5047, 1992). This report, together with the cationic nature of ALP, led us to investigate the antimicrobial activity of ALP. ALP was shown to display marked in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus. On a molar basis, the activity of ALP was lower than that of two other cationic antimicrobial polypeptides, lysozyme and defensin. ALP comprises two homologous domains: its proteinase-inhibitory activities are known to be located in the second COOH-terminal domain, and the function of its first NH2-terminal domain is largely unknown. Incubation of intact ALP or its isolated first domain with E. coli or S. aureus resulted in killing of these bacteria, whereas its second domain displayed very little antibacterial activity. Together these data suggest a putative antimicrobial role for the first domain of ALP and indicate that its antimicrobial activity may equip ALP to contribute to host defense against infection. PMID:8890201

  2. Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration

    Science.gov (United States)

    Marei, Hadir; Carpy, Alejandro; Woroniuk, Anna; Vennin, Claire; White, Gavin; Timpson, Paul; Macek, Boris; Malliri, Angeliki

    2016-01-01

    The small GTPase Rac1 has been implicated in the formation and dissemination of tumours. Upon activation by guanine nucleotide exchange factors (GEFs), Rac1 associates with a variety of proteins in the cell thereby regulating various functions, including cell migration. However, activation of Rac1 can lead to opposing migratory phenotypes raising the possibility of exacerbating tumour progression when targeting Rac1 in a clinical setting. This calls for the identification of factors that influence Rac1-driven cell motility. Here we show that Tiam1 and P-Rex1, two Rac GEFs, promote Rac1 anti- and pro-migratory signalling cascades, respectively, through regulating the Rac1 interactome. In particular, we demonstrate that P-Rex1 stimulates migration through enhancing the interaction between Rac1 and the actin-remodelling protein flightless-1 homologue, to modulate cell contraction in a RhoA-ROCK-independent manner. PMID:26887924

  3. Psychomotor activities with seniors

    Directory of Open Access Journals (Sweden)

    Jitka Kopřivová

    2015-07-01

    Full Text Available BACKGROUND: Given that the population all over the world is aging, it is necessary to fi nd ways to help maintain or improve the quality of life of seniors. The main goal of this paper is to show how appropriate physical activity programs contribute to the improvement of the functionality and psychosocial wellbeing of seniors. We are particularly interested in the possibilities of preserving self-suffi ciency and self-service, independence and the ability to perform everyday activities. One of the most eff ective forms of physical activity is psychomotr activity.OBJECTIVE: The aim of our paper is to present basic information concerning the meaning and the application of the psychomotr activities in intervention movement programmes in order to improve seniors’ life quality.METHODS: We defi ne the term psychomotr activities according to Adamírová (1995 and Novotná (2010. In this paper we present some results of research that stress the positive eff ect of psychomotor exercises and games on the life satisfaction of the elderly (Stará 2011; Stará & Kopřivová, 2011.DESCRIPTION: According to the results of our research and practical experience gained from working with the elderly it is strongly recommended to include suitable psychomotor exercises and games focusing on the development of manual dexterity in training programs in order to improve the balance abilities and the psychosocial area. In terms of prevention, because of the growing number of neurological disorders at an old age it is appropriate to include psychomotor exercises that encourage the development of cognitive functions in the physical interventions.CONCLUSION: We were able to positively infl uence the emotional aspect from performing physical activities, to enhance self-esteem of the exercising subjects and to create new social relationships. Motion programs, which also included psychomotor exercises and games, had a positive eff ect on the physical assessment of the

  4. Youth physical activity resource use and activity measured by accelerometry.

    Science.gov (United States)

    Maslow, Andréa L; Colabianchi, Natalie

    2011-01-01

    To examine whether use of physical activity resources (eg, parks) was associated with daily physical activity measured by accelerometry. One hundred eleven adolescents completed a travel diary with concurrent accelerometry. The main exposure was self-reported use of a physical activity resource (none /1+ resources). The main outcomes were total minutes spent in daily (1) moderate-vigorous physical activity and (2) vigorous physical activity. Using a physical activity resource was significantly associated with total minutes in moderate-vigorous physical activity. African Americans and males had significantly greater moderate-vigorous physical activity. Results from this study support the development and use of physical activity resources.

  5. Youth Physical Activity Resources Use and Activity Measured by Accelerometry

    Science.gov (United States)

    Maslow, Andréa L.; Colabianchi, Natalie

    2014-01-01

    Objectives To examine whether utilization of physical activity resources (eg, parks) was associated with daily physical activity measured by accelerometry. Methods 111 adolescents completed a travel diary with concurrent accelerometry. The main exposure was self-reported utilization of a physical activity resource (none/1+ resources). The main outcomes were total minutes spent in daily 1) moderate-vigorous physical activity and 2) vigorous physical activity. Results Utilizing a physical activity resource was significantly associated with total minutes in moderate-vigorous physical activity. African-Americans and males had significantly greater moderate-vigorous physical activity. Conclusions Results from this study support the development and use of physical activity resources. PMID:21204684

  6. Walkability and Physical Activity

    Science.gov (United States)

    Reis, Rodrigo Siqueira; Hino, Adriano Akira Ferreira; Rech, Cassiano Ricardo; Kerr, Jacqueline; Hallal, Pedro Curi

    2013-01-01

    Background Evidence from developing countries is limited on how income level for a given neighborhood is related to physical activity among its residents. Purpose The goal of the study was to examine the association between walkability and physical activity outcomes, and the effect of income on the relationship between walkability and physical activity in adults. Methods The Spaces for Physical Activity in Adults Study (ESPACOS Project) took place in Curitiba, Brazil. Data were collected in 2010 in 32 census tracts selected to vary in income and walkability, as measured by GIS. Participants were 697 individuals aged 18–65 years (52.0% were women) randomly sampled from the selected neighborhoods. The International Physical Activity Questionnaire was used to measure physical activity. All analyses were conducted in 2012. Results The proportion of those who walked for transportation for ≥150 minutes/week was 21.1% in low-walkability areas, and ranged from 33.5% to 35.0% in high-walkability areas. A total of 12.6% of residents were found to walk for leisure for ≥150 minutes/week; this result did not vary across quadrants of walkability and income level. The prevalence of leisure-time moderate-to-vigorous physical activity (MVPA) was 7.1–10.5 percentage points higher in high-compared to low-walkability areas. After adjusting for all individual confounders, walkability showed an independent association with walking for transport (OR=2.10, 95% CI=1.31, 3.37, p=0.002) and leisure-time MVPA (OR=1.57; 95% CI=1.06, 2.32; p=0.024). Neighborhood income level was independently associated with leisure-time MVPA (OR=1.70; 95% CI=1.06, 2.74, p=0.029). No association was found between walkability and walking for leisure. No interaction was found between walkability and neighborhood income level. Conclusions This study, among adults living in Curitiba, Brazil, confirms findings from studies of high-income countries showing that walkability is positively associated with

  7. Active noise control primer

    CERN Document Server

    Snyder, Scott D

    2000-01-01

    Active noise control - the reduction of noise by generating an acoustic signal that actively interferes with the noise - has become an active area of basic research and engineering applications. The aim of this book is to present all of the basic knowledge one needs for assessing how useful active noise control will be for a given problem and then to provide some guidance for designing, setting up, and tuning an active noise-control system. Written for students who have no prior knowledge of acoustics, signal processing, or noise control but who do have a reasonable grasp of basic physics and mathematics, the book is short and descriptive. It leaves for more advanced texts or research monographs all mathematical details and proofs concerning vibrations, signal processing and the like. The book can thus be used in independent study, in a classroom with laboratories, or in conjunction with a kit for experiment or demonstration. Topics covered include: basic acoustics; human perception and sound; sound intensity...

  8. Global physical activity levels

    DEFF Research Database (Denmark)

    Hallal, Pedro C; Andersen, Lars Bo; Bull, Fiona C

    2012-01-01

    To implement effective non-communicable disease prevention programmes, policy makers need data for physical activity levels and trends. In this report, we describe physical activity levels worldwide with data for adults (15 years or older) from 122 countries and for adolescents (13-15-years......-income countries. The proportion of 13-15-year-olds doing fewer than 60 min of physical activity of moderate to vigorous intensity per day is 80·3% (80·1-80·5); boys are more active than are girls. Continued improvement in monitoring of physical activity would help to guide development of policies and programmes......-old) from 105 countries. Worldwide, 31·1% (95% CI 30·9-31·2) of adults are physically inactive, with proportions ranging from 17·0% (16·8-17·2) in southeast Asia to about 43% in the Americas and the eastern Mediterranean. Inactivity rises with age, is higher in women than in men, and is increased in high...

  9. Parsing Heterogeneous Striatal Activity

    Directory of Open Access Journals (Sweden)

    Kae Nakamura

    2017-05-01

    Full Text Available The striatum is an input channel of the basal ganglia and is well known to be involved in reward-based decision making and learning. At the macroscopic level, the striatum has been postulated to contain parallel functional modules, each of which includes neurons that perform similar computations to support selection of appropriate actions for different task contexts. At the single-neuron level, however, recent studies in monkeys and rodents have revealed heterogeneity in neuronal activity even within restricted modules of the striatum. Looking for generality in the complex striatal activity patterns, here we briefly survey several types of striatal activity, focusing on their usefulness for mediating behaviors. In particular, we focus on two types of behavioral tasks: reward-based tasks that use salient sensory cues and manipulate outcomes associated with the cues; and perceptual decision tasks that manipulate the quality of noisy sensory cues and associate all correct decisions with the same outcome. Guided by previous insights on the modular organization and general selection-related functions of the basal ganglia, we relate striatal activity patterns on these tasks to two types of computations: implementation of selection and evaluation. We suggest that a parsing with the selection/evaluation categories encourages a focus on the functional commonalities revealed by studies with different animal models and behavioral tasks, instead of a focus on aspects of striatal activity that may be specific to a particular task setting. We then highlight several questions in the selection-evaluation framework for future explorations.

  10. Photon-activation therapy

    International Nuclear Information System (INIS)

    Fairchild, R.G.; Bond, V.P.

    1982-01-01

    Photon Activation Therapy (PAT) is a technique in which radiation dose to tumor is enhanced via introduction of stable 127 I in the form of iodinated deoxyuridine (IdUrd). Stimulation of cytotoxic effects from IdUrd is accomplished by activation with external (or implanted) radiation sources. Thus, accumulations of this nucleoside in actively competing cellpools do not preclude therapy in so far as such tissues can be excluded from the radiation field. Calculations show that 5% replacement of thymidine (Tyd) in tumor DNA should enhance the biological effectiveness of a given photon radiotherapy dose by a factor of approx. 3. Proportionally higher gains would result from higher replacements of Tyd and IdUrd. In addition, biological response is enhanced by chemical sensitization with IdUrd. The data indicate that damage from photon activation as well as chemical sensitization does not repair. Thus, at low dose rates, a further increase in therapeutic gain should accrue as normal tissues are allowed to repair and regenerate. A samarium-145 source has been developed for PAT, with activating x-ray energies of from 38 to 45 keV. Favorable clinical results can be expected through the use of IdUrd and protracted irradiations with low energy x-rays. In particular, PAT may provide unique advantages at selected sites such as brain, or head and neck tumors

  11. Robust Active Label Correction

    DEFF Research Database (Denmark)

    Kremer, Jan; Sha, Fei; Igel, Christian

    2018-01-01

    for the noisy data lead to different active label correction algorithms. If loss functions consider the label noise rates, these rates are estimated during learning, where importance weighting compensates for the sampling bias. We show empirically that viewing the true label as a latent variable and computing......Active label correction addresses the problem of learning from input data for which noisy labels are available (e.g., from imprecise measurements or crowd-sourcing) and each true label can be obtained at a significant cost (e.g., through additional measurements or human experts). To minimize......). To select labels for correction, we adopt the active learning strategy of maximizing the expected model change. We consider the change in regularized empirical risk functionals that use different pointwise loss functions for patterns with noisy and true labels, respectively. Different loss functions...

  12. Arctic industrial activities compilation

    International Nuclear Information System (INIS)

    1991-01-01

    Most industrial activities in the Beaufort Sea region are directly or indirectly associated with the search for oil and gas. Activities in marine areas include dredging, drilling, seismic and sounding surveys, island/camp maintenance, vessel movements, helicoptor and fixed-wind flights, and ice-breaking. This inventory contains a summary of chemical usage at 119 offshore drilling locations in the Beaufort Sea, Arctic Islands and Davis Straight of the Canadian Arctic between 1973 and 1987. Data are graphically displayed for evaluating patterns of drill waste discharge in the three offshore drilling areas. These displays include a comparison of data obtained from tour sheets and well history records, summaries of drilling mud chemicals used by year, well and oil company, frequency of wells drilled as a function of water depth, and offshore drilling activity by year, company, and platform. 21 refs., 104 figs., 2 tabs

  13. Correlates of physical activity

    DEFF Research Database (Denmark)

    Bauman, Adrian E; Reis, Rodrigo S; Sallis, James F

    2012-01-01

    that age, sex, health status, self-efficacy, and motivation are associated with physical activity. Ecological models take a broad view of health behaviour causation, with the social and physical environment included as contributors to physical inactivity, particularly those outside the health sector...... effective programmes will target factors known to cause inactivity. Research into correlates (factors associated with activity) or determinants (those with a causal relationship) has burgeoned in the past two decades, but has mostly focused on individual-level factors in high-income countries. It has shown......, such as urban planning, transportation systems, and parks and trails. New areas of determinants research have identified genetic factors contributing to the propensity to be physically active, and evolutionary factors and obesity that might predispose to inactivity, and have explored the longitudinal tracking...

  14. Activating Welfare States

    DEFF Research Database (Denmark)

    Kvist, Jon

    for children and the elderly, which in turn allows in particular women to (re-)enter the labour market, de-commodification of labour through easy accessible and relative generous cash benefits providing a more flexible labour market, and re-commodification of labour through conditioning of benefits and active......This paper investigates how welfare states may actively contribute to promote employment opportunities, i.e. participation in the labour market through various operations and policies. The principal operations concern in particular the de-familiarisation of caring tasks through social services...... labour market policies giving long-term unemployed and people with low skills better opportunities to participate in the labour market, whether the ordinary or in special activities....

  15. Rheology of Active Fluids

    Science.gov (United States)

    Saintillan, David

    2018-01-01

    An active fluid denotes a viscous suspension of particles, cells, or macromolecules able to convert chemical energy into mechanical work by generating stresses on the microscale. By virtue of this internal energy conversion, these systems display unusual macroscopic rheological signatures, including a curious transition to an apparent superfluid-like state where internal activity exactly compensates viscous dissipation. These behaviors are unlike those of classical complex fluids and result from the coupling of particle configurations with both externally applied flows and internally generated fluid disturbances. Focusing on the well-studied example of a suspension of microswimmers, this review summarizes recent experiments, models, and simulations in this area and highlights the critical role played by the rheological response of these active materials in a multitude of phenomena, from the enhanced transport of passive suspended objects to the emergence of spontaneous flows and collective motion.

  16. IHY activities in Brazil

    Science.gov (United States)

    Dal Lago, Alisson

    The International Heliophysical Year is a program of international scientific colaboration planned to be held in the period from 2007-2009. Many brazilian institutions have shown interest in participating in the IHY activities. All of them provided information about their instrumental facilities and contact person. A list of institutions and their information is shown in the Latin-American IHY webpage (http://www.alage.org/IHYLA/ihyla.html), hosted by the Latin American Association on Space Geophysics - ALAGE. IHY Brazilian activities are being conducted in close colaboration with Latin-American Institutions. Five Coordinated Investigation programs (CIPs) have been proposed by scientists from brazilian institutions. Recentely, in February 2008, there has been the Latin American IHY School in Sao Paulo (Brazil), with the participation of 80 students from Brazil, Argentina, Peru, Mexico and Cuba. In this work, a report on the brazilian activities will be presented.

  17. CEREM activity report

    International Nuclear Information System (INIS)

    1997-01-01

    This 1997 issue of the activity report of the CEREM (CEA) gives a general overview of the CEREM organization, activities and human resources with some budgetary information. The main activities described concern the materials fabrication for the nuclear and automotive industries, the powders metallurgy (molding by injection, cold pressing modelling), the simulation of the hot and cold working processes, the surface treatments, the joining (brazed joints, sintering, welding), the electrochemical storage of the energy (fuel cells, lithium accumulators), the corrosion and the physico-chemistry of fluids, the mechanical properties and the cracks, the robots for nuclear units dismantlement, the alteration mechanisms of properties under different solicitations (thermal, mechanical, chemical, irradiation) and the solidification-crystallogenesis. (O.M.)

  18. Activity report 1977

    International Nuclear Information System (INIS)

    Delande, E.; Drent, W.

    1978-07-01

    The principal activities of Eurochemic plant in the fields of reprocessing and the solidification and conditioning of liquid wastes are presented in this report that covers the period 1 January to 31 December 1977. Works in the plant are closely related to the handling of fuel element and the treatment of solid wastes as well as the management of liquid wastes. Industrial development activities have been primarily devoted to the solidification of HEWC (highly enriched waste concentrate) by means of the Lotes process; the treatment of spent solvent by means of the Eurowatt process; the treatment of the plutonium-bearing solid wastes by the Eurowetcomb process and the conditioning of highly activity non-combustible solid wastes by incorporation into polymer-concrete matrix . (AF)

  19. Activity report 1978

    International Nuclear Information System (INIS)

    Delande, E.; Drent, W.

    1979-07-01

    The principal activities of Eurochemic plant in the fields of reprocessing and the solidification and conditioning of liquid and solid wastes are presented in this report that covers the period 1 January to 31 December 1978. Works in the plant are closely related to the decontamination in cooperation with specialized firms. Active operation of bituminization facility was started in June, and a total of 66 m 3 of medium level waste was incorporated into bitumen by the end of 1978. The associated storage facility was in active operation since June and preliminary studies for its extension were completed. A facility was completed for the conditioning of solid wastes arising from the decontamination operation of solid wastes whch were stored under water during plant operation. (AF)

  20. Safeguards activities in Japan

    International Nuclear Information System (INIS)

    Osabe, Takeshi

    1998-01-01

    Current Japanese State System for Accountancy and Control (SSAC) has been developing and fully satisfies requirements of both IAEA Safeguards and bilateral partners. However, the public attention on the national and international safeguards activities were increased and the safeguards authorities were required to promote the objective assessment of safeguards implementation to avoid mistrust in safeguards activities which directly influence the public acceptance of nuclear energy in itself. Additionally, since Japan has promoted to complete nuclear fuel cycle including spent fuel reprocessing, enrichment and mixed oxide fuel fabrication this would require further assurance of Japanese non-proliferation commitment. Japan supports the introduction of strengthened safeguards. In this context it is particularly important to strengthen the relationship between national and the IAEA safeguards to contribute actively to the IAEA safeguards in development and utilization of new technologies towards more effective and efficient IAEA safeguards

  1. Physical activity and osteoarthritis

    DEFF Research Database (Denmark)

    Gates, L S; Leyland, K M; Sheard, S

    2017-01-01

    Physical activity (PA) is increasingly recognised as an important factor within studies of osteoarthritis (OA). However, subjective methods used to assess PA are highly variable and have not been developed for use within studies of OA, which creates difficulties when comparing and interpreting PA...... established via an international expert consensus meeting and modified Delphi exercise using a geographically diverse committee selected on the basis of individual expertise in physical activity, exercise medicine, and OA. Agreement was met for all aims of study: (1) The use of Metabolic Equivalent of Task...... (MET) minutes per week (MET-min/week) as a method for harmonising PA variables among cohorts; (2) The determination of methods for treating missing components of MET-min/week calculation; a value will be produced from comparable activities within a representative cohort; (3) Exclusion of the domain...

  2. Report of Activity - 1997

    International Nuclear Information System (INIS)

    Hammer, Philippe

    1999-01-01

    The Report of Activity on 1997 published by Waste Management Division (Direction chargee de la Gestion des Dechets) of French Atomic Energy Authority (Commissariat a l'Energie Atomique) presents the current activity in the framework of CEA Recovery Plan for Civil Centers initiated in 1991, aiming at managing all the radioactive problems issued from its Research and Development Activities. This plan covers three principal directions: management of radioactive wastes resulting from CEA research activities, reprocessing or storing the spent or un-used fuel resulting from research or prototype reactors, recovery measures and dismantling of nuclear facilities. In the field of radioactive waste management important projects, assuring the waste processing equipment, were developed in 1997 at Saclay (STELLA Installation), Cadarache (AGATE Installation) and Marcoule (ATENA Installation). The Radioactive Waste Storage TFA was put into operation at Cadarache. In the field of out-of-use fuel, in 1997 the fuel reprocessing units CARAMEL and UNGG were finished while as temporary storage for fuels waiting to be processed the CASCAD facility at Cadarache was assigned. Finally, concerning the recovery/dismantling activities, priority was granted to recover: the Radiochemical Lab. at Fontenay, the pilot workshop and UP1 plant of COGEMA at Marcoule, the EL4 reactor (in a joint action with EDF), and the AT1 pilot workshop at Cherbourg. The report is structured on five chapters with the following content: 1. The radioactive wastes; 2. The out-of-use fuels; 3. The dismantling of the definitively stopped installations; 4. The waste management at DAM (Direction des Applications Militaires); 5. Recovery activities at Marcoule

  3. Activated carbon material

    International Nuclear Information System (INIS)

    Evans, A.G.

    1978-01-01

    Activated carbon particles for use as iodine trapping material are impregnated with a mixture of selected iodine and potassium compounds to improve the iodine retention properties of the carbon. The I/K ratio is maintained at less than about 1 and the pH is maintained at above about 8.0. The iodine retention of activated carbon previously treated with or coimpregnated with triethylenediamine can also be improved by this technique. Suitable flame retardants can be added to raise the ignition temperature of the carbon to acceptable standards

  4. Andra 1997 activity report

    International Nuclear Information System (INIS)

    1998-07-01

    This activity report comprises two parts. The first part describes the missions and activities of the ANDRA (the French agency for the management of radioactive wastes): quality control of wastes produced by EdF, CEA, Cogema and the 1100 other small producers, design, construction and management of storage centres, anticipation and development of new management solutions, research and evaluation studies on deep storage facilities, inventory and control of all radioactive materials present in the French territory. The second part is a presentation of financial data. (J.S.)

  5. Regulatory activities; Actividades regulatorias

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information.

  6. IPSN activity report 1999

    International Nuclear Information System (INIS)

    2000-01-01

    The IPSN (Institut de Protection et de Surete Nucleaire) carries out for the Government, studies and inspections on nuclear installations at many life steps (design, realisation, exploitation, shutdown and dismantling). To obtain quality researches, the Institut performs studies in all domains concerned by the safety and its improvement. The main projects of the year 1999, in the following topics are presented: the nuclear installations and the radioactive wastes safety, the crisis and nuclear materials management, the human and the environment protection, the international activities and cooperation, the quality insurance. It provides also information on the cooperation, the budget, the human resource policy and the communication activities. (A.L.B.)

  7. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala...... of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings...... of a regulatory effect of the PFC on the emotional control of our actions....

  8. Intergovernmental organisation activities

    International Nuclear Information System (INIS)

    2015-01-01

    This section treats of the following Intergovernmental organisation activities: 1 - European Atomic Energy Community: Non-legally binding instruments; International relations; 2 - International Atomic Energy Agency: Convention on Nuclear Safety (CNS); Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management (JC); The Convention on Supplementary Compensation for Nuclear Damage (CSC); International Expert Group on Nuclear Liability (INLEX); Legislative assistance activities; 3 - OECD Nuclear Energy Agency (NEA): GIF Framework Agreement extended for ten years; Technology Road-map: Nuclear Energy; Steering Committee Policy Debate: Health Effects of Low-dose Radiation

  9. 1996 Activity report

    International Nuclear Information System (INIS)

    1996-01-01

    The 1996 activity report of the Direction for Waste Management of the CEA, is presented. Its activities have been developed in the framework of the general CEA cleaning plan, and include the management of wastes generated before 1992 in R and D CEA facilities, the disposal of spent fuels generated by research reactors (Orphee and Siloe) or prototype reactors (EL4 at Brennilis), and the dismantling and cleaning of obsolete facilities such as the plutonium radiochemistry building at Fontenay-aux-Roses and the pilot workshop at Marcoule

  10. Reference neutron activation library

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-04-01

    Many scientific endeavors require accurate nuclear data. Examples include studies of environmental protection connected with the running of a nuclear installation, the conceptual designs of fusion energy producing devices, astrophysics and the production of medical isotopes. In response to this need, many national and international data libraries have evolved over the years. Initially nuclear data work concentrated on materials relevant to the commercial power industry which is based on the fission of actinides, but recently the topic of activation has become of increasing importance. Activation of materials occurs in fission devices, but is generally overshadowed by the primary fission process. In fusion devices, high energy (14 MeV) neutrons produced in the D-T fusion reaction cause activation of the structure, and (with the exception of the tritium fuel) is the dominant source of activity. Astrophysics requires cross-sections (generally describing neutron capture) or its studies of nucleosynthesis. Many analytical techniques require activation analysis. For example, borehole logging uses the detection of gamma rays from irradiated materials to determine the various components of rocks. To provide data for these applications, various specialized data libraries have been produced. The most comprehensive of these have been developed for fusion studies, since it has been appreciated that impurities are of the greatest importance in determining the overall activity, and thus data on all elements are required. These libraries contain information on a wide range of reactions: (n,{gamma}), (n,2n), (n,{alpha}), (n,p), (n,d), (n,t), (n,{sup 3}He)and (n,n')over the energy range from 10{sup -5} eV to 15 or 20 MeV. It should be noted that the production of various isomeric states have to be treated in detail in these libraries,and that the range of targets must include long-lived radioactive nuclides in addition to stable nuclides. These comprehensive libraries thus contain

  11. Activity report 1981

    International Nuclear Information System (INIS)

    Delande, E.; Drent, W.

    1982-07-01

    This report reviews the main activities of the Eurochemic company for the fiscal year 1981. These activities are: the plant operation including the safeguards for special nuclear materials, the management of radioactive wastes and the analytical services, new works such as vitrification project, Pamela building and the design for the storage of vitrified wastes. The industrial development concerns the Eurowatt process for solvent treatment, the wet combustion for plutonium bearing solid wastes, the separation of mercury, the incorporation of solid wastes into a polymer concrete matrix and the Pamela process. The health and safety division, the library and documentation service and the administrative matters are also presented. (AF)

  12. Activity report 1984

    International Nuclear Information System (INIS)

    Drent, W.

    1985-07-01

    For the fiscal year 1984, the technical activities of Eurochemic were: a) the cleaning of the vessels having contained medium level liquid wastes and the incorporation into bitumen of the resulting solution, b) the conditioning of plutonium contaminated solid waste, c) the civil engineering works of Building 29 were completed and the mounting of equipment was begun. The installation will assure the surface storage of the blocks resulting from vitrification, by means of Pamela installation of the high-level liquid wastes. The report includes administrative matters as well as health and safety activity. (AF)

  13. Reference neutron activation library

    International Nuclear Information System (INIS)

    2002-04-01

    Many scientific endeavors require accurate nuclear data. Examples include studies of environmental protection connected with the running of a nuclear installation, the conceptual designs of fusion energy producing devices, astrophysics and the production of medical isotopes. In response to this need, many national and international data libraries have evolved over the years. Initially nuclear data work concentrated on materials relevant to the commercial power industry which is based on the fission of actinides, but recently the topic of activation has become of increasing importance. Activation of materials occurs in fission devices, but is generally overshadowed by the primary fission process. In fusion devices, high energy (14 MeV) neutrons produced in the D-T fusion reaction cause activation of the structure, and (with the exception of the tritium fuel) is the dominant source of activity. Astrophysics requires cross-sections (generally describing neutron capture) or its studies of nucleosynthesis. Many analytical techniques require activation analysis. For example, borehole logging uses the detection of gamma rays from irradiated materials to determine the various components of rocks. To provide data for these applications, various specialized data libraries have been produced. The most comprehensive of these have been developed for fusion studies, since it has been appreciated that impurities are of the greatest importance in determining the overall activity, and thus data on all elements are required. These libraries contain information on a wide range of reactions: (n,γ), (n,2n), (n,α), (n,p), (n,d), (n,t), (n, 3 He)and (n,n')over the energy range from 10 -5 eV to 15 or 20 MeV. It should be noted that the production of various isomeric states have to be treated in detail in these libraries,and that the range of targets must include long-lived radioactive nuclides in addition to stable nuclides. These comprehensive libraries thus contain almost all the

  14. Intergovernmental Organisation Activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section treats of the following activities, sorted by Organisation: 1 - European Atomic Energy Community: Proposed binding instruments, Adopted legally binding instruments, Non-legally binding instruments; 2 - International Atomic Energy Agency: Convention on Nuclear Safety, Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management, International Expert Group on Nuclear Liability, Legislative assistance activities; 3 - OECD Nuclear Energy Agency: Appointment of new Director-General, International experts in Japan to review safety after Fukushima Daiichi, China Atomic Energy Authority co-operation workshop

  15. MCO Monitoring activity description

    International Nuclear Information System (INIS)

    SEXTON, R.A.

    1998-01-01

    Spent Nuclear Fuel remaining from Hanford's N-Reactor operations in the 1970s has been stored under water in the K-Reactor Basins. This fuel will be repackaged, dried and stored in a new facility in the 200E Area. The safety basis for this process of retrieval, drying, and interim storage of the spent fuel has been established. The monitoring of MCOS in dry storage is a currently identified issue in the SNF Project. This plan outlines the key elements of the proposed monitoring activity. Other fuel stored in the K-Reactor Basins, including SPR fuel, will have other monitoring considerations and is not addressed by this activity description

  16. Physical Activity and Health: The Benefits of Physical Activity

    Science.gov (United States)

    ... State and Local Programs Related Topics Diabetes Nutrition Physical Activity and Health Recommend on Facebook Tweet Share Compartir ... Your Chances of Living Longer The Benefits of Physical Activity Regular physical activity is one of the most ...

  17. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... June 4, 2015 Content source: Division of Nutrition, Physical Activity, and Obesity , National Center for Chronic Disease Prevention and Health Promotion Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act ...

  18. Sexual activity and aging.

    Science.gov (United States)

    Ni Lochlainn, Mary; Kenny, Rose Anne

    2013-08-01

    Sexuality is an important component of emotional and physical intimacy that men and women experience throughout their lives. Research suggesting that a high proportion of men and women remain sexually active well into later life refutes the prevailing myth that aging and sexual dysfunction are inexorably linked. Age-related physiological changes do not render a meaningful sexual relationship impossible or even necessarily difficult. Many of these physiological changes are modifiable. There are various therapeutic options available to patients to achieve maximum sexual capacity in old age. This article reviews the prevalence of sexual activity among older adults, the problems these adults encounter with sexual activity, and the role of the health care professional in addressing these problems. The physiological sex-related changes that occur as part of the normal aging process in men and women are reviewed, as well as the effect of age-related physical and psychological illness on sexual function. The attitudes and perceptions of the media and general public toward sexual activity and aging are summarized. An understanding of the sexual changes that accompany the aging process may help general practitioners and other doctors to give practical and useful advice on sexuality as well as refute the misconception that aging equates to celibacy. A thorough awareness of this aspect of older people's quality of life can raise meaningful expectations for aging patients. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  19. E-Activities.

    Science.gov (United States)

    Brewster, Joy

    2001-01-01

    Presents five technology-based activities to teach elementary students about the human body, including: creating a heartbeat graph; charting the benefits of exercise; playing a "sense"ational card game; reading online stories from three children living with various conditions or illnesses; and examining diagrams of the human body that have been…

  20. ANTHROPOGENIC ACTIVITIES THREATENING THE ...

    African Journals Online (AJOL)

    Osondu

    2012-02-17

    Feb 17, 2012 ... anthropogenic activities across the protected areas in the country. ... education and provision of fund to support sustainable livelihood practices. ... wildlife conservation and tourism. ... Fig: 1 Map of Oyo State showing location of Old Oyo National Park and adjoining community. #. #. # .... This was the view of.

  1. Acid-activated bentonite

    Indian Academy of Sciences (India)

    In this study, we propose Maghnite-H + , as an ecological, cost-effective and easily renewable catalyst, for the polymerization of decamethylcyclopentasiloxane (D5). The Maghnite is a clay consisting primarily of smectite minerals (montmorillonite group), which can be activated/reactivated through a simple process, ...

  2. Activity report 1983

    International Nuclear Information System (INIS)

    Delande, E.; Drent, W.

    1984-07-01

    The reports presents an account of the activities of the Eurochemic Company for the chemical processing of irradiated fuels, in the fiscal year l982. It deals with legal and administrative matters, industrial development, plant operation, new works, health and safety, library and documentation, and conferences and symposia. (AF)

  3. Active Math Learning

    DEFF Research Database (Denmark)

    The presentation is concerned with general course planning philosophy and a specific case study (boomerang flight geometro-dynamics) for active learning of mathematics via computer assisted and hands-on unfolding of first principles - in this case the understanding of rotations and Eulers equatio...

  4. Activation Analysis of Aluminium

    Energy Technology Data Exchange (ETDEWEB)

    Brune, Dag

    1961-01-15

    An analysis of pure aluminium alloyed with magnesium was per- formed by means of gamma spectrometry , Chemical separations were not employed. The isotopes to be determined were obtained in conditions of optimum activity by suitably choosing the time of irradiation and decay. The following elements were detected and measured quantitatively: Iron, zinc, copper, gallium, manganese, chromium, scandium and hafnium.

  5. Direct Activation Of Methane

    KAUST Repository

    Basset, Jean-Marie; Sun, Miao; Caps, Valerie; Pelletier, Jeremie; Abou-Hamad, Edy

    2013-01-01

    Heteropolyacids (HPAs) can activate methane at ambient temperature (e.g., 20.degree. C.) and atmospheric pressure, and transform methane to acetic acid, in the absence of any noble metal such as Pd). The HPAs can be, for example, those with Keggin

  6. Flipped Classroom, active Learning?

    DEFF Research Database (Denmark)

    Andersen, Thomas Dyreborg; Levinsen, Henrik; Philipps, Morten

    2015-01-01

    Action research is conducted in three physics classes over a period of eighteen weeks with the aim of studying the effect of flipped classroom on the pupils agency and learning processes. The hypothesis is that flipped classroom teaching will potentially allocate more time to work actively...

  7. Learning Activity Package, Algebra.

    Science.gov (United States)

    Evans, Diane

    A set of ten teacher-prepared Learning Activity Packages (LAPs) in beginning algebra and nine in intermediate algebra, these units cover sets, properties of operations, number systems, open expressions, solution sets of equations and inequalities in one and two variables, exponents, factoring and polynomials, relations and functions, radicals,…

  8. NEA activities in 1985

    International Nuclear Information System (INIS)

    1986-01-01

    This report presents the main features of the Agency's work during 1985. It deals with current nuclear trends, nuclear developments and the fuel cycle, nuclear safety research and licensing, radiological and environmental impacts of nuclear fuel cycle activities, legal affairs, nuclear science, joint undertakings, and, organization and administration

  9. NEA activities in 1984

    International Nuclear Information System (INIS)

    1985-01-01

    This report presents the main features of the Agency's work during 1984. It deals with current nuclear trends, nuclear developments and the fuel cycle, nuclear safety research and licencing, radiological and environmental impacts of nuclear fuel cycle activities, legal affairs, nuclear science, joint undertakings, and, organization and administration

  10. Model PET Scan Activity

    Science.gov (United States)

    Strunk, Amber; Gazdovich, Jennifer; Redouté, Oriane; Reverte, Juan Manuel; Shelley, Samantha; Todorova, Vesela

    2018-05-01

    This paper provides a brief introduction to antimatter and how it, along with other modern physics topics, is utilized in positron emission tomography (PET) scans. It further describes a hands-on activity for students to help them gain an understanding of how PET scans assist in detecting cancer. Modern physics topics provide an exciting way to introduce students to current applications of physics.

  11. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... Search Form Controls Search The CDC Cancel Submit Search The CDC Physical Activity Note: Javascript is disabled or is not supported by your browser. For this reason, some items on this page will be unavailable. For more information about this message, please visit this page: About ...

  12. Bonus Activity Book.

    Science.gov (United States)

    Learning, 1993

    1993-01-01

    Elementary level activity book presents suggestions for teaching students about endangered and threatened species worldwide. Students learn about what is causing the rapid extinction rate and what needs to be done. They also discover the value of rainforests and why conservationists are fighting to save them. (SM)

  13. Activities in Europe

    International Nuclear Information System (INIS)

    Wrochna, Grzegorz

    2017-01-01

    HTGR Activities in Europe: • Stimulated and coordinated by Nuclear Cogeneration Industrial Initiative (NC21) • a part of Sustainable Nuclear Energy Technology Platform (SNETP) • SNETP has 68 members: industry, research, TSO, ... Nuclear Cogeneration Industrial Initiative: Contribute to clean and competitive energy beyond electricity by facilitating deployment of nuclear cogeneration plants

  14. Activation analysis in Greece

    International Nuclear Information System (INIS)

    Grimanis, A.P.

    1985-01-01

    A review of research and development on NAA as well as examples of applications of this method are presented, taken from work carried out over the last 21 years at the Radioanalytical Laboratory of the Department of Chemistry in the Greek Nuclear Research Center ''Demokritos''. Improved and faster radiochemical NAA methods have been developed for the determination of Au, Ni, Cl, As, Cu, U, Cr, Eu, Hg and Mo in several materials, for the simultaneous determination of Br and I; Mg, Sr and Ni; As and Cu; As, Sb and Hg; Mn, Sr and Ba; Cd and Zn; Se and As; Mo and Cr in biological materials. Instrumental NAA methods have also been developed for the determination of Ag, Cl and Na in lake waters, Al, Ca, Mg and V in wines, 7 trace elements in biological materials, 17 trace elements in sediments and 20 minor and trace elements in ceramics. A comprehensive computer program for routine activation analysis using Ge(Li) detectors have been worked out. A rather extended charged-particle activation analysis program is carried out for the last 10 years, including particle induced X-ray emission (PIXE) analysis, particle induced prompt gamma-ray emission analysis (PIGE), other nuclear reactions and proton activation analysis. A special neutron activation method, the delayed fission neutron counting method is used for the analysis of fissionable elements, as U, Th, Pu, in samples of the whole nuclear fuel cycle including geological, enriched and nuclear safeguards samples

  15. Measuring Physical Activity Intensity

    Medline Plus

    Full Text Available ... 67 Data & Statistics Facts About Physical Activity Data, Trends and Maps Surveillance Systems Resources & Publications Reports Adults ... CDC’s Example StairWELL Stairwell Appearance Motivational Signs Installing Music Other Ideas to Consider Tracking Stair Usage Project ...

  16. Heavy ion activation analysis

    International Nuclear Information System (INIS)

    Lass, B.D.; Roche, N.G.; Sanni, A.O.; Schweikert, E.A.; Ojo, J.F.

    1982-01-01

    A report on radioactivation with ion beams of 3 6 Li and 14 N is presented with some analytical applications: the determination of C via 12 C( 6 Li,αn) 13 N; the determination of Li and Be, using 14 N activation. Next, examples, with limitations in selectivity. The detection limits using a 1 μA h of activation irradiation are 5 ppm for C and 1 ppm for Li or Be. With 9 Be suitable for analytical applications are: sup(10,11)B( 9 Be,xn) 18 F and 14 N( 9 Be,αn) 18 F. Assuming a 1 μA h irradiation the detection limits for N and B are 1.5 ng and 0.5 ng, respectively, using a 7.8 MeV 9 Be beam. For activation with 12 C, experimental results with 12 MeV 12 C beam demonstrate that the beam is best suited for 7 Li analysis by the reaction 7 Li( 12 C,n) 18 F. The detection limit for a 1 μA h irradiation is 1 ng and the only other low Z elements activated are B and C. Finally, 12 C radioactivation was further combined with autoradiography for positional analysis. The spatial resolution of the technique was estimated to be 40 μm for an exposure corresponding to 6x10 5 disintegrations. As low as 10 -12 g of Li was readily detected by autoradiography. (author)

  17. Multidisciplinary Wildlife Teaching Activities.

    Science.gov (United States)

    Hernbrode, William R., Ed.

    This guide provides information and activities descriptions designed to allow the teacher to use wildlife concepts in the teaching of various subjects. The author suggests that wildlife and animals are tremendous motivators for children and hold their attention. In the process, concepts of wildlife interaction with man and the environment are…

  18. Neuromodulation on Cerebral Activities

    NARCIS (Netherlands)

    Cremoux, Sylvain; Ibanez Pereda, Jaime; Ates, Sedar; Dessi, Alessia; Pons, José L.; Torricelli, Diego

    2014-01-01

    During a motor task, a causal relation occurs between the motor command generated in the cortex and the proprioceptive feedbacks that go from the activated muscles through the corticospinal pathway. This causal relation is of interest in neurorehabilitation to improve motor function for people with

  19. Mechanism of charity activity

    Directory of Open Access Journals (Sweden)

    Roman B. Golovkin

    2015-12-01

    Full Text Available Objective to establish the essential properties of the mechanism of charitable activities and to formulate the concept of quotmechanism of charitable activityquot. Methods the objective of the study is achieved using the complex of methods which are based on the interaction of dialectical and metaphysical analysis the epistemological properties of which allowed to reveal various aspects of the charitable activities mechanism functioning taking into account the principles of comprehensiveness complexity specificity and objectivity of the research. Results the rules are stated of using the term quotmechanismquot to characterize actions of state and law the essence of the charity mechanism is defined the definition of quotthe mechanism of charitable activity quot is formulated. Scientific novelty for the first time at theoretical level in legal science the definition of quotthe mechanism of charitable activityquot is formulated and its essential properties are set. Practical significance the research will contribute to improving the legal regulation in the field of philanthropy as well as to improving the efficiency and quality of charitable activity in the Russian Federation. nbsp

  20. Regional Activities Division. Papers.

    Science.gov (United States)

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on library network activities in Canada, the Third World, Japan, Malaysia, Brazil, and Sweden which were presented at the 1982 International Federation of Library Associations (IFLA) conference include: (1) "Canada: A Voluntary and Flexible Network," a review by Guy Sylvestre of the political, social, and economic structures…

  1. Bacteriology of activated sludge

    NARCIS (Netherlands)

    Gils, van H.W.

    1964-01-01

    The bacteriology and biochemistry of activated sludge grown in domestic waste water or fed with synthetic media were studied. The nature of the flocs was investigated by determining morphological and physiological characteristics of many strains isolated.

    Predominant bacteria were

  2. Institutional investor activism : Introduction

    NARCIS (Netherlands)

    Mc Cahery, Joseph; Bratton, William; Bratton, William; McCahery, Joseph A.

    2015-01-01

    The increase in institutional ownership of recent decades has been accompanied by an enhanced role played by institutions in monitoring companies’ corporate governance behaviour. Activist hedge funds and private equity firms have achieved a degree of success in actively shaping the business plans of

  3. DPHPE activities during 1977

    International Nuclear Information System (INIS)

    1978-06-01

    This annual report gives a short summary of experiments in progress and of approved proposals of experiments to be performed by the Elementary Particle Physics Department of Saclay, and also publication lists and informations about the Department activities during 1977 [fr

  4. NEA activities in 1981

    International Nuclear Information System (INIS)

    1982-01-01

    This report describes the main features of the Agency's work during 1981 and discusses the state and prospects of the nuclear industry in OECD countries. Trends in nuclear power, radiological and environmental impacts of nuclear fuel cycle activities, nuclear safety research and licensing, nuclear law, nuclear development and fuel cycle studies technical co-operation, nuclear science organisation and administration are reviewed

  5. [Cycloferon biological activity characteristics].

    Science.gov (United States)

    Utkina, T M; Potekhina, L P; Kartashova, O L; Vasilchenko, A S

    2014-01-01

    Study the effect of cycloferon in experimental and clinical conditions on persistence properties of aurococci as well as features of their morpho-functional reaction by atomic force microscopy. The study was carried out in 12 Staphylococcus aureus clones isolated from mucous membrane of nose anterior part of a resident carrier. The effect of cycloferon in vivo was evaluated in 26 resident staphylococci carriers under the control of anti-carnosine activity of staphylococci. Anti-carnosine activity was determined by O.V. Bukharin et al. (1999), biofilm formation -by G.A. O'Toole et al. (2000). Staphylococci treated with cycloferon were studied by atomic force microscopy in contact mode using scanning probe SMM-2000 microscope. The decrease of persistence properties of staphylococci under the effect of cycloferon in vitro and in vivo may be examined as one of the mechanisms of biological activity of the preparation. A significant increase of S. aureus surface roughness and changes in their morphology under the effect of cycloferon allow stating the disorder of barrier functions in the aurococci cell wall. The data obtained expand the understanding of cycloferon biological activity mechanisms.

  6. Active Learning Methods

    Science.gov (United States)

    Zayapragassarazan, Z.; Kumar, Santosh

    2012-01-01

    Present generation students are primarily active learners with varied learning experiences and lecture courses may not suit all their learning needs. Effective learning involves providing students with a sense of progress and control over their own learning. This requires creating a situation where learners have a chance to try out or test their…

  7. Lesion activity assessment

    DEFF Research Database (Denmark)

    Ekstrand, K R; Zero, D T; Martignon, S

    2009-01-01

    in response to cariogenic plaque as well as lesion arrest. Based on this understanding, different clinical scoring systems have been developed to assess the severity/depth and activity of lesions. A recent system has been devised by the International Caries Detection and Assessment System Committee...

  8. DPHPE activities during 1978

    International Nuclear Information System (INIS)

    1979-08-01

    This annual report gives a short summary of experiments in progress and of approved proposals of experiments to be performed by the Elementary Particle Physics Department of Saclay, and also publication lists and informations about the Department activities during 1978 [fr

  9. Grooming. Learning Activity Package.

    Science.gov (United States)

    Stark, Pamela

    This learning activity package on grooming for health workers is one of a series of 12 titles developed for use in health occupations education programs. Materials in the package include objectives, a list of materials needed, information sheets, reviews (self evaluations) of portions of the content, and answers to reviews. These topics are…

  10. Activity report 1992

    International Nuclear Information System (INIS)

    1993-01-01

    This activity report of the DSIN ( Direction of Nuclear Installations Safety) is divided into 4 parts bearing on: (1) Organisation, Safety principles, Regulations (2) Nuclear basis installations following (3) Surveillance by the regional directions of the Ministry of Industry, Research and Environment (4) Other missions of the DSIN

  11. Sexual activity during pregnancy.

    Science.gov (United States)

    Staruch, Monika; Kucharczyk, Aleksandra; Zawadzka, Katarzyna; Wielgos, Miroslaw; Szymusik, Iwona

    2016-01-01

    Pregnancy is usually associated with significant regression in genito-genital intercourse frequency, sexual desire and satisfaction. The aim of the study was to determine women's sexual habits during the third trimester of gestation and to compare their sexual activity before the current pregnancy and during previous pregnancies in case of multiparas. The study material consisted of women in the third trimester of pregnancy, recruited from the Outpatient Clinic of the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw between January 2013 and February 2014, who filled out a self-prepared questionnaire. The questionnaire consisted of three parts: demographic data, sexual activity prior to current pregnancy and during gestation, including sexual positions and sources of knowledge regarding the subject. The survey involved 25 questions and was distributed among 220 patients, out of which 165 were returned and 149 properly filled out and analyzed. The average age of the respondents was 29.6 ± 4.85 years; the majority (78.8%) were in an uncomplicated pregnancy. The decrease in sexual activity was evident in all age groups--the majority usually had sex 1 to 3 times a month in contrast to 1-2 times a week prior to conceiving. Sexual activity decreased significantly with increasing age. The main reasons for abandoning sexual activity included: decreased libido (35.5%), the doctor's suggestion (29%) and fears concerning child's health (29%). During pregnancy the frequency of vaginal intercourse significantly decreased (100% prior to vs. 86.6% during pregnancy; p < 0.001); as did oral sex (44.3% vs. 29.5%; p = 0.043) and anal sex (12% vs. 5.4%; p = 0.02). 54% of the respondents declared reduced satisfaction with sexual life during pregnancy in comparison with the previous period; almost half (43.5%) felt less attractive while pregnant. The same claim was related to libido--it decreased in 58.8% of respondents. Multiparas tended to have sexual

  12. Interdisciplinary Astronomy Activities

    Science.gov (United States)

    Nerantzis, Nikolaos; Mitrouda, Aikaterini; Reizopoulou, Ioanna; Sidiropoulou, Eirini; Hatzidimitriou, Antonios

    2016-04-01

    On November 9th, 2015, three didactical hours were dedicated to Interdisciplinary Astronomy Activities (http://wp.me/p6Hte2-1I). Our students and their teachers formed three groups and in rotation, were engaged with the following activities: (a) viewing unique images of the Cosmos in the mobile planetarium STARLAB (http://www.planitario.gr/tholos-starlab-classic-standard.html), (b) watching the following videos: Journey to the end of the universe (https://youtu.be/Ufl_Nwbl8xs), Rosetta update (https://youtu.be/nQ9ivd7wv30), The Solar System (https://youtu.be/d66dsagrTa0), Ambition the film (https://youtu.be/H08tGjXNHO4) in the school's library. Students and teachers were informed about our solar system, the Rosetta mission, the universe, etc. and (c) tactile activities such as Meet our home and Meet our neighbors (http://astroedu.iau.org, http://nuclio.org/astroneighbours/resources) and the creation of planets' 3D models (Geology-Geography A' Class Student's book, pg.15). With the activities above we had the pleasure to join the Cosmic Light Edu Kit / International Year of Light 2015 program. After our Interdisciplinary Astronomy Activities, we did a "small" research: our students had to fill an evaluation about their educational gains and the results can be found here http://wp.me/p6Hte2-2q. Moreover, we discussed about Big Ideas of Science (http://wp.me/p3oRiZ-dm) and through the "big" impact of the Rosetta mission & the infinity of our universe, we print posters with relevant topics and place them to the classrooms. We thank Rosa Doran (Nuclio - President of the Executive Council) for her continuous assistance and support on innovative science teaching proposals. She is an inspiration.

  13. Defining active progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie

    2017-01-01

    BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). OBJECTIVE: To compare CSF biomarkers in active and inactive...

  14. Tips for Starting Physical Activity

    Science.gov (United States)

    ... Legislative Information Advisory & Coordinating Committees Strategic Plans & Reports Research Areas FAQs ... Starting Physical Activity Related Topics Section Navigation Tips to Help You Get Active ...

  15. The world bank and the environment, exercise 1992. Annual report

    International Nuclear Information System (INIS)

    1992-01-01

    The report describes the Bank's activities in assisting countries with environmental management, such as programs to reduce poverty without exhausting natural resources. Included are assessments of the environmental impacts of projects supported by World Bank loans, and accounts of efforts to meet global environmental challenges with coordinated international action through the Global Environment Facility (GEF). Among the events in the period covered by the report are the affirmation of the World Bank's participation with United Nations organizations in the GEF and the Bank's administration of pilot programs aimed at finding solutions to such global environmental problems as pollution of international waters, global warming, depletion of the Earth's ozone layer, and dwindling biological diversity; the United Nations Conference on Environment and Development; and the publication of the World Development Report 1992, with its theme of development and the environment

  16. Gain-of-function SOS1 mutations cause a distinctive form of noonansyndrome

    Energy Technology Data Exchange (ETDEWEB)

    Tartaglia, Marco; Pennacchio, Len A.; Zhao, Chen; Yadav, KamleshK.; Fodale, Valentina; Sarkozy, Anna; Pandit, Bhaswati; Oishi, Kimihiko; Martinelli, Simone; Schackwitz, Wendy; Ustaszewska, Anna; Martin, Joes; Bristow, James; Carta, Claudio; Lepri, Francesca; Neri, Cinzia; Vasta,Isabella; Gibson, Kate; Curry, Cynthia J.; Lopez Siguero, Juan Pedro; Digilio, Maria Cristina; Zampino, Giuseppe; Dallapiccola, Bruno; Bar-Sagi, Dafna; Gelb, Brude D.

    2006-09-01

    Noonan syndrome (NS) is a developmental disordercharacterized by short stature, facial dysmorphia, congenital heartdefects and skeletal anomalies1. Increased RAS-mitogenactivated proteinkinase (MAPK) signaling due to PTPN11 and KRAS mutations cause 50 percentof NS2-6. Here, we report that 22 of 129 NS patients without PTPN11 orKRAS mutation (17 percent) have missense mutations in SOS1, which encodesa RAS-specific guanine nucleotide exchange factor (GEF). SOS1 mutationscluster at residues implicated in the maintenance of SOS1 in itsautoinhibited form and ectopic expression of two NS-associated mutantsinduced enhanced RAS activation. The phenotype associated with SOS1defects is distinctive, although within NS spectrum, with a highprevalence of ectodermal abnormalities but generally normal developmentand linear growth. Our findings implicate for the first timegain-of-function mutations in a RAS GEF in inherited disease and define anew mechanism by which upregulation of the RAS pathway can profoundlychange human development.

  17. The World Bank and the environment, fiscal 1992, exercise 92. Annual report

    International Nuclear Information System (INIS)

    1992-09-01

    The report describes the Bank's activities in assisting countries with environmental management, such as programs to reduce poverty without exhausting natural resources. Included are assessments of the environmental impacts of projects supported by World Bank loans, and accounts of efforts to meet global environmental challenges with coordinated international action through the Global Environment Facility (GEF). Among the events in the period covered by the report are the affirmation of the World Bank's participation with United Nations organizations in the GEF and the Bank's administration of pilot programs aimed at finding solutions to such global environmental problems as pollution of international waters, global warming, depletion of the Earth's ozone layer, and dwindling biological diversity; the United Nations Conference on Environment and Development; and the publication of the World Development Report 1992, with its theme of development and the environment

  18. Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate.

    Science.gov (United States)

    Lee, Young Kwang; Low-Nam, Shalini T; Chung, Jean K; Hansen, Scott D; Lam, Hiu Yue Monatrice; Alvarez, Steven; Groves, Jay T

    2017-04-28

    The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition. This inhibitory role of the PR domain limits Grb2-independent recruitment of SOS to the membrane through binding of Ras·GTP in the SOS allosteric binding site. More generally, this assay strategy enables characterization of the functional behaviour of GEFs with single-molecule precision but without the need for purification.

  19. High activity waste disposal

    International Nuclear Information System (INIS)

    Gaul, W.C.

    1990-01-01

    Chem-Nuclear Environmental Services (CNES) has developed a container that is capable of containing high activity waste and can be shipped as a regular DOT Type A shipment. By making the container special form the amount of activity that can be transported in a Type A shipment is greatly enhanced. Special form material presents an extra degree of protection to the environment by requiring the package to be destroyed to get access to the radioactive material and must undergo specific testing requirements, whereas normal form material can allow access to the radioactive material. With the special form container up to 10 caries of radium can be transported in a single package. This paper will describe the considerations that were taken to develop these products

  20. Techniques for active passivation

    Science.gov (United States)

    Roscioli, Joseph R.; Herndon, Scott C.; Nelson, Jr., David D.

    2016-12-20

    In one embodiment, active (continuous or intermittent) passivation may be employed to prevent interaction of sticky molecules with interfaces inside of an instrument (e.g., an infrared absorption spectrometer) and thereby improve response time. A passivation species may be continuously or intermittently applied to an inlet of the instrument while a sample gas stream is being applied. The passivation species may have a highly polar functional group that strongly binds to either water or polar groups of the interfaces, and once bound presents a non-polar group to the gas phase in order to prevent further binding of polar molecules. The instrument may be actively used to detect the sticky molecules while the passivation species is being applied.

  1. Activation/waste management

    International Nuclear Information System (INIS)

    Maninger, C.

    1984-10-01

    The selection of materials and the design of the blankets for fusion reactors have significant effects upon the radioactivity generated by neutron activation in the materials. This section considers some aspects of materials selection with respect to waste management. The activation of the materials is key to remote handling requirements for waste, to processing and disposal methods for waste, and to accident severity in waste management operations. In order to realize the desirable evnironmental potentials of fusion power systems, there are at least three major goals for waste management. These are: (a) near-surface burial; (b) disposal on-site of the fusion reactor; (c) acceptable radiation doses at least cost during and after waste management operations

  2. Powernext 2005 activity assessment

    International Nuclear Information System (INIS)

    2005-01-01

    Powernext SA is a Multilateral Trading Facility which organizes and warrants the transactions on the European power exchange and CO 2 exchange markets. This activity report presents the highlights of the market and of Powernext in 2005: market conditions (birth of the carbon market, price evolution on the power market), weather-related conditions, electricity production and consumption, situation at the borders, price of fuels, traded volumes at the three markets (Powernext Day-Ahead TM in the case of day-ahead contracts, Powernext Futures TM in the case of medium-term contracts, and Powernext Carbon in the case of CO 2 ), new active members, liquidity on the power market. (J.S.)

  3. Activity report 1998

    International Nuclear Information System (INIS)

    1998-01-01

    The ''Institut de Protection et de Surete Nucleaire'' (IPSN), carries out researches and expert studies needed to manage nuclear risks and their consequences on people and environment. These activities cover the installation safety, the radioactive matter transport, the public health and environmental control, the nuclear matters safety and control and the crisis situation management. The IPSN have got also a mission of public information and participates to international actions in the domain of scientific researches or expert's report. This annual report presents the highlights of the year 1998, information on staff, budgets and geographical situation. Then technical and scientific papers gathers the activities of the year covered by the IPSN: the ''Free Tribune'', installations and radioactive wastes safety, crisis and nuclear matter management, public health and environment control, international cooperation. (A.L.B.)

  4. Effects of Activating Schoolyards

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Schipperijn, Jasper; Andersen, Henriette Bondo

    schools. Two gender-segregated focus groups at each school, including in total 57 fourth to eight graders (28 girls), were conducted. The focus groups included go-along interviews in the schoolyard, and a post-it note activity. The data was collected between April and June 2016 (six months after...... as positive for their schoolyard as it provided more variation in play facilities and improved the appearance. However, at most schools the children experienced that the renewed schoolyards were dominated by the youngest children (under 10-year-old). To minimise crowding some schools had formally restricted...... access to the renovated areas for older children and allowed them to leave the school area during recess. Furthermore, most of the children felt that the renewed schoolyard areas were far from their classrooms. CONCLUSIONS: Renewing the schoolyard is not enough to stimulate physical activity. Schools...

  5. IPSN activity report 1999

    International Nuclear Information System (INIS)

    1999-01-01

    The ''Institut de Protection et de Surete Nucleaire'' (IPSN), carries out researches and expert studies needed to manage nuclear risks and their consequences on people and environment. These activities cover the installation safety, the radioactive matter transport, the public health and environmental control, the nuclear matters safety and control and the crisis situation management. The IPSN have got also a mission of public information and participates to international actions in the domain of scientific researches or expert's report. This annual report presents the highlights of the year 1999, information on staff, budgets and geographical situation. Then technical and scientific papers gathers the activities of the year covered by the IPSN: the ''Free Tribune'', installations and radioactive wastes safety, crisis and nuclear matter management, public health and environment control, international cooperation. (A.L.B.)

  6. Thermal Activated Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Pasold, Anke

    2015-01-01

    The research studies the making of a responsive architectural envelope based on bi-materials. The bi-materials are organized according to a method that combines different isotropic metals and plastic into an active composite structure that reacts to temperature variations. Through an evolutionary......, environmental dynamics and occupancy dynamics. Lastly, a physical prototype is created, which illustrates the physical expression of the bi-materials and the problems related to manufacturing of these composite structures.......The research studies the making of a responsive architectural envelope based on bi-materials. The bi-materials are organized according to a method that combines different isotropic metals and plastic into an active composite structure that reacts to temperature variations. Through an evolutionary...

  7. Industrial Activity at CERN

    CERN Document Server

    Kowalik, G

    2000-01-01

    The decrease in the number of CERN staff creates the need for optimization of the non-core, infrastructure-related activities. An industrial, service-orientated approach has long been considered as an appropriate way to cope with the problem of diminishing resources. This paper presents industrial and service activity issues at CERN based on the experience of the exploitation of the power network. The most important problems linked to the application of the industrial approach to the exploitation of equipment in the CERN research environment are covered. These include the interface between accelerators and electrical exploitation services, external and internal regulations, sharing of responsibility between CERN staff and external contractors, continuous modification of clients' requirements, the balance between the cost of accelerator downtime versus the cost of infrastructure upgrade. A benchmarking through a comparison with a big industrial manufacturer is followed by recommendations for possible improveme...

  8. Sulfur activation in Hiroshima

    International Nuclear Information System (INIS)

    Kerr, G.D.; Pace, J.V. III.

    1987-01-01

    In 1979, we attempted to establish the validity of source terms for the Hiroshima and Nagasaki bombs using experimental data on sulfur activation. Close agreement was observed between measured and calculated values for test firings of Nagasaki-type bombs. The calculated values were based on source terms developed by W.E. Preeg at the Los Alamos National Laboratory (LANL). A discrepancy was found, however, when we compared calculated values for the two bombs because a 1956 report by R.R. Wilson stated that sulfur acitvation by fast neutrons in Hiroshima was approximately three times greater than in Nagasaki. Our calculations based on Preeg's source-term data predicted about equal sulfur activation in the two cities

  9. Active3 noise reduction

    International Nuclear Information System (INIS)

    Holzfuss, J.

    1996-01-01

    Noise reduction is a problem being encountered in a variety of applications, such as environmental noise cancellation, signal recovery and separation. Passive noise reduction is done with the help of absorbers. Active noise reduction includes the transmission of phase inverted signals for the cancellation. This paper is about a threefold active approach to noise reduction. It includes the separation of a combined source, which consists of both a noise and a signal part. With the help of interaction with the source by scanning it and recording its response, modeling as a nonlinear dynamical system is achieved. The analysis includes phase space analysis and global radial basis functions as tools for the prediction used in a subsequent cancellation procedure. Examples are given which include noise reduction of speech. copyright 1996 American Institute of Physics

  10. Intergovernmental organisation activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section of the Bulletin presents a summary of the recent Intergovernmental organisation activities, sorted by organisation: - European Atomic Energy Community: Adopted legally binding instruments; Non-legally binding instruments; International relations. - International Atomic Energy Agency: Convention on Nuclear Safety (CNS); 58. regular session of the IAEA General Conference; IAEA Treaty Event; Side event on 'The Convention on Supplementary Compensation for Nuclear Damage (CSC) - in the Context of the Global Nuclear Liability Regime'; Legislative assistance activities; Nuclear Law Institute. - OECD Nuclear Energy Agency: Steering Committee approves decommissioning exclusion; European Nuclear Energy Tribunal (ENET) Judges approved; High-level Group on the Security of Supply of Medical Radioisotopes (HLG-MR); Joint Declaration; The Characteristics of an Effective Nuclear Regulator

  11. Neutron activation analysis

    International Nuclear Information System (INIS)

    Taure, I.; Riekstina, D.; Veveris, O.

    2004-01-01

    Neutron activation analysis (NAA) in Latvia began to develop after 1961 when nuclear reactor in Salaspils started to work. It provided a powerful neuron source, which is necessary for this analytical method. In 1963 at Institute of Physics of the Latvian Academy of Sciences the Laboratory of Neutron Activation Analysis was formed. At the first stage of development the main tasks were of theoretical and technical aspects of NAA. Later the NAA was used to solve problems in technology, biology, and medicine. In the beginning of the 80-ties more attention was focussed to the use of NAA in the environmental research. Environmental problems stayed the main task till the closing the nuclear reactor in Salaspils in 1998 that ceased the main the existence of the laboratory and of NAA, this significant and powerful analytical method in Latvia and Baltic in general. (authors)

  12. LANSCE Activity Report

    Energy Technology Data Exchange (ETDEWEB)

    Amy Robinson; Audrey Archuleta; Barbara Maes; Dan Strottman; Earl Hoffman; Garth Tietjen; Gene Farnum; Geoff Greene; Joyce Roberts; Ken Johnson; Paul Lewis; Roger Pynn; Stan Schriber; Steve Sterbenz; Steve Wender; Sue Harper

    1999-02-01

    The Los Alamos Neutron Science Center Activity Report describes scientific and technological progress and achievements in LANSCE Division during the period of 1995 to 1998. This report includes a message from the Division Director, an overview of LANSCE, sponsor overviews, research highlights, advanced projects and facility upgrades achievements, experimental and user program accomplishments, news and events, and a list of publications. The research highlights cover the areas of condensed-matter science and engineering, accelerator science, nuclear science, and radiography. This report also contains a compact disk that includes an overview, the Activity Report itself, LANSCE operations progress reports for 1996 and 1997, experiment reports from LANSCE users, as well as a search capability.

  13. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2003-01-01

    Among international regulatory activities we find resolutions adopted by the IAEA general conference (2003), through European Union we find proposals for directives on nuclear safety and radioactive waste management, new regulation on the application of EURATOM safeguards, control of high activity sealed radioactive sources, recommendation on the protection and information of the public with regard to the continued contamination of certain wild food products following the Chernobyl accident, proposals for decisions authorizing the Member states to sign and ratify the Protocol to amend the Paris convention, p)proposals for a directive on environment liability with regard to the prevention and remedying of environmental damage, proposal of a regulation on the law applicable to non-contractual obligation. (N.C.)

  14. Is Enhanced Physical Activity Possible Using Active Videogames?

    Science.gov (United States)

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-06-01

    Our research indicated that 10-12-year-old children receiving two active Wii ™ (Nintendo ® ; Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  15. Is Enhanced Physical Activity Possible Using Active Videogames?

    OpenAIRE

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-01-01

    Our research indicated that 10–12-year-old children receiving two active Wii™ (Nintendo®; Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  16. Integration of Active Video Games in Extracurricular Activity at Schools

    Science.gov (United States)

    Lee, Jung Eun; Huang, Charles; Pope, Zachary; Gao, Zan

    2015-01-01

    Active video games require players to be physically active. Dance Dance Revolution (DDR) is an interactive dancing game that requires fast-foot movement coordinated with energetic music and visuals. The Wii and Xbox Kinect games have also become good active video games for the promotion of physical activity participation. These games are much more…

  17. Active Neural Localization

    OpenAIRE

    Chaplot, Devendra Singh; Parisotto, Emilio; Salakhutdinov, Ruslan

    2018-01-01

    Localization is the problem of estimating the location of an autonomous agent from an observation and a map of the environment. Traditional methods of localization, which filter the belief based on the observations, are sub-optimal in the number of steps required, as they do not decide the actions taken by the agent. We propose "Active Neural Localizer", a fully differentiable neural network that learns to localize accurately and efficiently. The proposed model incorporates ideas of tradition...

  18. Semantic Activity Recognition

    OpenAIRE

    Thonnat , Monique

    2008-01-01

    International audience; Extracting automatically the semantics from visual data is a real challenge. We describe in this paper how recent work in cognitive vision leads to significative results in activity recognition for visualsurveillance and video monitoring. In particular we present work performed in the domain of video understanding in our PULSAR team at INRIA in Sophia Antipolis. Our main objective is to analyse in real-time video streams captured by static video cameras and to recogniz...

  19. 2001 activity report

    International Nuclear Information System (INIS)

    2002-01-01

    Managing radioactive waste for a better control in the future. The Quadrennial State/Andra contract, the double ISO 9001 (quality) and ISO 140001 (environment) certification and three diversified missions: industry, research and information. Those are the highlights of the activity report where the reader will be able to learn more about the Agency's major achievements in 2001. An appendix contains the management report of the Agency

  20. CRNL active waste incinerator

    International Nuclear Information System (INIS)

    McQuade, D.W.

    1965-02-01

    At CRNL the daily collection of 1200 pounds of active combustible waste is burned in a refractory lined multi-chamber incinerator. Capacity is 500-550 pounds per hour; volume reduction 96%. Combustion gases are cooled by air dilution and decontaminated by filtration through glass bags in a baghouse dust collector. This report includes a description of the incinerator plant, its operation, construction and operating costs, and recommendations for future designs. (author)

  1. Local Worlds of Activation

    DEFF Research Database (Denmark)

    Jacobsson, Kerstin; Hollertz, Katarina; Garsten, Christina

    2017-01-01

    arrangements and the role of private services and actors in service delivery differed significantly too, ranging from strictly market-based forms of governance to classical public administration. The article moreover shows how the different activation approaches were reflected in the radically different usages...... from local politics, established local traditions, patterns of networking and modes of collaborating, as the notion of ‘local words of activation’ intends to capture....

  2. NPPCI activities in Finland

    International Nuclear Information System (INIS)

    Wahlstroem, B.

    1986-01-01

    Research activities at the Technical Research Centre of Finland in the control and instrumentation field have been directed both towards immediate needs and towards long term goals. The immediate needs have been connected to different ongoing investigations and to development projects in connection with process industry. Of the more long term projects the following can be explicitly mentioned: the Nordic project on human reliability; work on software reliability; design guides for digital CI systems; simulation of technical processes; artificial intelligence in nuclear power

  3. Activity report for 1992

    International Nuclear Information System (INIS)

    1993-01-01

    ADEME means agency for defence of environment and for mastery of energy, these two aims are ADEME's mission; to serve its mission, this agency has to mobilize managers able to reduce tensions on natural resources and to limit impacts on environment; the concerned areas are transport, building, industry because of their weight in energy consumption, in pollutants emission and waste recovery. Here is the report of its activity for the year 1992

  4. Environmental health program activities

    Science.gov (United States)

    Bergtholdt, C. P.

    1969-01-01

    Activities reported include studies on toxic air contaminants, excessive noise, poor lighting, food sanitation, water pollution, and exposure to nonionizing radiation as health hazards. Formulations for a radiological health manual provide guidance to personnel in the procurement and safe handling of radiation producing equipment and Apollo mission planning. A literature search and development of a water analysis laboratory are outlined to obtain information regarding microbiological problems involving potable water, waste management, and personal hygiene.

  5. Soft Active Matter

    OpenAIRE

    Marchetti, M. C.; Joanny, J. -F.; Ramaswamy, S.; Liverpool, T. B.; Prost, J.; Rao, Madan; Simha, R. Aditi

    2012-01-01

    In this review we summarize theoretical progress in the field of active matter, placing it in the context of recent experiments. Our approach offers a unified framework for the mechanical and statistical properties of living matter: biofilaments and molecular motors in vitro or in vivo, collections of motile microorganisms, animal flocks, and chemical or mechanical imitations. A major goal of the review is to integrate the several approaches proposed in the literature, from semi-microscopic t...

  6. MANAGEMENT AND SPORTING ACTIVITIES

    Directory of Open Access Journals (Sweden)

    MONICA DELIA BÎCĂ

    2015-10-01

    Full Text Available “Using applied science in sport management as creates opportunities for rationalization and systematization of sports activity, relying on the knowledge and application of the laws that control the dynamics and phenomena. Management is on the border between art and science. Arts management is manifested by "science" as opposed to use and harness the creative compromise that can produce increased efficiency and effectiveness.”

  7. Human telomerase activity regulation

    OpenAIRE

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  8. Worker in nuclear activity

    International Nuclear Information System (INIS)

    Goes Fischer, M.D. de; Associacao Brasileira de Direito Nuclear, Rio de Janeiro)

    1984-01-01

    Juridical aspects with respect to the workers in nuclear activity are presented. Special emphasis is given to the clauses of the statute of workers (Consolidacao das Leis do Trabalho) the rules of the Ministerio do Trabalho and the rules of the Comissao Nacional de Energia Nuclear. The performance of the international authorities is also emphasized such as the International Labour Organization, the International Atomic Energy Agency and the International Radiological Protection Commission. (Author) [pt

  9. ACRO -Activities in 2009

    International Nuclear Information System (INIS)

    2009-01-01

    After a presentation of the ACRO (Association for the Control of Radioactivity in the West of France), of its missions and of its technical and human resources, this report presents the activities performed by this association in 2009: relative importance of the different missions, radio-ecological assessment, information and public meetings, participation to work groups and institutional commissions, radio-ecological surveys and assessments, training and education, measurements and regulatory controls, metrology and quality assurance. A press review is provided

  10. Fractionalization and Entrepreneurial Activities

    OpenAIRE

    Awaworyi Churchill, Sefa

    2015-01-01

    The vast majority of the literature on ethnicity and entrepreneurship focuses on the construct of ethnic entrepreneurship. However, very little is known about how ethnic heterogeneity affects entrepreneurship. This study attempts to fill the gap, and thus examines the effect of ethnic heterogeneity on entrepreneurial activities in a cross-section of 90 countries. Using indices of ethnic and linguistic fractionalization, we show that ethnic heterogeneity negatively influences entrepreneurship....

  11. Activity report 1993

    International Nuclear Information System (INIS)

    1994-01-01

    This activity report of the DSIN (Direction of Nuclear Installations Safety) is divided into 13 chapters bearing on: (1)Nuclear safety (2) Nuclear safety organisation (3) Regulations (4) Nuclear installations inspections (5) Crisis organisation (6) Information and communication (7) International relations (8) PWR (9)Other reactors (10) Experimental reactors, laboratories and other installations (11) Fuel cycle centers (12) Radioactive wastes storages (13) Nuclear installations definitively stopped

  12. NEA activities in 1994

    International Nuclear Information System (INIS)

    1995-01-01

    This report deals with the activities in 1994 of the OECD Nuclear Energy Agency including : trends in nuclear power, nuclear development and fuel cycle (data, tools, methodologies, nuclear industry and its context, fuel cycle policy, energy policy reviews), reactor safety and regulation (exchange of operating experience and human factors, accident prevention activities, severe-accident phenomenology and management, structural integrity, probabilistic safety assessment, fuel cycle safety, regulatory approaches to severe-accident issues, inspection practices), radiation protection (radiation protection today and tomorrow, application of radiation protection standards, protection of workers, international emergency exercises), radioactive waste management (the philosophical and ethical basis of disposal, safety assessment and site investigations, other radiation waste management activities), nuclear science (scientific studies, validation of working methods, the NEA data bank, projects in support of other NEA programmes), joint projects (the Rasplav project, the Halden reactor project, information system on occupational exposure, decommissioning of nuclear facilities), legal affairs (liability and nuclear safety assistance to Eastern Europe, training seminar on nuclear law, information on nuclear law), information programme (review of Nea information programme, publications programme, a major information forum), and relations with non m ember countries (NEA relations with non-members countries, the Central and Eastern European Countries and New Independent States of the former Soviet Union programme of co-operation and assistance). (O.L.). 22 figs

  13. Thin layer activation

    International Nuclear Information System (INIS)

    Schweickert, H.; Fehsenfeld, P.

    1995-01-01

    The reliability of industrial equip ment is substantially influenced by wear and corrosion; monitoring can prevent accidents and avoid down-time. One powerful tool is thin layer activation analysis (TLA) using accelerator systems. The information is used to improve mechanical design and material usage; the technology is used by many large companies, particularly in the automotive industry, e.g. Daimler Benz. A critical area of a machine component receives a thin layer of radioactivity by irradiation with charged particles from an accelerator - usually a cyclotron. The radioactivity can be made homogeneous by suitable selection of particle, beam energy and angle of incidence. Layer thickness can be varied from 20 microns to around 1 mm with different depth distributions; the position and size of the wear zone can be set to within 0.1 mm. The machine is then reassembled and operated so that wear can be measured. An example is a combustion engine comprising piston ring, cylinder wall, cooling water jacket and housing wall, where wear measurements on the cylinder wall are required in a critical zone around the dead-point of the piston ring. Proton beam bombardment creates a radioactive layer whose thickness is known accurately, and characteristic gamma radiation from this radioactive zone penetrates through the engine and is detected externally. Measurements can be made either of the activity removed from the surface, or of the (reduced) residual activity; wear measurement of the order of 10 -9 metres is possible

  14. Active inference and learning.

    Science.gov (United States)

    Friston, Karl; FitzGerald, Thomas; Rigoli, Francesco; Schwartenbeck, Philipp; O Doherty, John; Pezzulo, Giovanni

    2016-09-01

    This paper offers an active inference account of choice behaviour and learning. It focuses on the distinction between goal-directed and habitual behaviour and how they contextualise each other. We show that habits emerge naturally (and autodidactically) from sequential policy optimisation when agents are equipped with state-action policies. In active inference, behaviour has explorative (epistemic) and exploitative (pragmatic) aspects that are sensitive to ambiguity and risk respectively, where epistemic (ambiguity-resolving) behaviour enables pragmatic (reward-seeking) behaviour and the subsequent emergence of habits. Although goal-directed and habitual policies are usually associated with model-based and model-free schemes, we find the more important distinction is between belief-free and belief-based schemes. The underlying (variational) belief updating provides a comprehensive (if metaphorical) process theory for several phenomena, including the transfer of dopamine responses, reversal learning, habit formation and devaluation. Finally, we show that active inference reduces to a classical (Bellman) scheme, in the absence of ambiguity. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Intergovernmental organisation activities

    International Nuclear Information System (INIS)

    2016-01-01

    This section treats of the following Intergovernmental organisation activities: 1 - European Atomic Energy Community: Adopted legally binding instruments; Non-legally binding instruments; International relations; 2 - International Atomic Energy Agency (IAEA): Convention on Nuclear Safety (CNS); Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management (Joint Convention); Convention on Early Notification of a Nuclear Accident and the Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency (Early Notification and Assistance Conventions); Code of Conduct on the Safety and Security of Radioactive Sources (Code of Conduct); Amendment to the Convention on the Physical Protection of Nuclear Material (ACPPNM); Workshop on Civil Liability for Nuclear Damage; International Expert Group on Nuclear Liability (INLEX); Legislative Assistance Activities; 3 - OECD Nuclear Energy Agency: Five Years after the Fukushima Daiichi Accident; Regulatory and Institutional Framework for Nuclear Activities; Fifth session of the International Nuclear Law Essentials (INLE); Nuclear Law Committee meeting; NEA publications of interest; New NEA Deputy Director-General and Chief Nuclear Officer; New NEA offices

  16. Amphoteric surface active agents

    Directory of Open Access Journals (Sweden)

    Eissa, A.M. F.

    1995-10-01

    Full Text Available 2-[trimethyl ammonium, triethyl ammonium, pyridinium and 2-amino pyridinium] alkanoates, four series of surface active agents containing carbon chain C12, C14, C16 and C18carbon atoms, were prepared. Their structures were characterized by microanalysis, infrared (IR and nuclear magnetic resonance (NMR. Surface and interfacial tension, Krafft point, wetting time, emulsification power, foaming height and critical micelle concentration (cmc were determined and a comparative study was made between their chemical structure and surface active properties. Antimicrobial activity of these surfactants was also determined.

    Se prepararon cuatro series de agentes tensioactivos del tipo 2-[trimetil amonio, trietil amonio, piridinio y 2-amino piridinio] alcanoatos, que contienen cadenas carbonadas con C12, C14, C16 y C18 átomos de carbono.
    Se determinaron la tensión superficial e interfacial, el punto de Krafft, el tiempo humectante, el poder de emulsionamiento, la altura espumante y la concentración critica de miscela (cmc y se hizo un estudio comparativo entre la estructura química y sus propiedades tensioactivas. Se determinó también la actividad antimicrobiana de estos tensioactivos. Estas estructuras se caracterizaron por microanálisis, infrarrojo (IR y resonancia magnética nuclear (RMN.

  17. Cosmogenic activation of materials

    Science.gov (United States)

    Cebrián, Susana

    2017-10-01

    Experiments looking for rare events like the direct detection of dark matter particles, neutrino interactions or the nuclear double beta decay are operated deep underground to suppress the effect of cosmic rays. But, the production of radioactive isotopes in materials due to previous exposure to cosmic rays is a hazard when ultra-low background conditions are required. In this context, the generation of long-lived products by cosmic nucleons has been studied for many detector media and for other materials commonly used. Here, the main results obtained on the quantification of activation yields on the Earth’s surface will be summarized, considering both measurements and calculations following different approaches. The isotope production cross-sections and the cosmic ray spectrum are the two main ingredients when calculating this cosmogenic activation; the different alternatives for implementing them will be discussed. Activation that can take place deep underground mainly due to cosmic muons will be briefly commented too. Presently, the experimental results for the cosmogenic production of radioisotopes are scarce and discrepancies between different calculations are important in many cases, but the increasing interest on this background source which is becoming more and more relevant can help to change this situation.

  18. Active Cryovolcanism on Europa?

    Energy Technology Data Exchange (ETDEWEB)

    Sparks, W. B.; Cracraft, M.; Deustua, S. E [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Schmidt, B. E. [Georgia Institute of Technology, School of Earth and Atmospheric Sciences, 311 Ferst Drive, Atlanta, GA 30332 (United States); McGrath, M. A. [SETI Institute, 189 N. Bernardo Avenue, Mountain View, CA 94043 (United States); Hand, K. P. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Spencer, J. R., E-mail: sparks@stsci.edu [Southwest Research Institute, 1050 Walnut Street, Suite 300, Boulder, CO 80302 (United States)

    2017-04-20

    Evidence for plumes of water on Europa has previously been found using the Hubble Space Telescope using two different observing techniques. Roth et al. found line emission from the dissociation products of water. Sparks et al. found evidence for off-limb continuum absorption as Europa transited Jupiter. Here, we present a new transit observation of Europa that shows a second event at the same location as a previous plume candidate from Sparks et al., raising the possibility of a consistently active source of erupting material on Europa. This conclusion is bolstered by comparison with a nighttime thermal image from the Galileo Photopolarimeter-Radiometer that shows a thermal anomaly at the same location, within the uncertainties. The anomaly has the highest observed brightness temperature on the Europa nightside. If heat flow from a subsurface liquid water reservoir causes the thermal anomaly, its depth is ≈1.8–2 km, under simple modeling assumptions, consistent with scenarios in which a liquid water reservoir has formed within a thick ice shell. Models that favor thin regions within the ice shell that connect directly to the ocean, however, cannot be excluded, nor modifications to surface thermal inertia by subsurface activity. Alternatively, vapor deposition surrounding an active vent could increase the thermal inertia of the surface and cause the thermal anomaly. This candidate plume region may offer a promising location for an initial characterization of Europa’s internal water and ice and for seeking evidence of Europa’s habitability.

  19. Proteomics of Eosinophil Activation

    Directory of Open Access Journals (Sweden)

    Deane F. Mosher

    2017-09-01

    Full Text Available We recently identified and quantified >7,000 proteins in non-activated human peripheral blood eosinophils using liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS and described phosphoproteomic changes that accompany acute activation of eosinophils by interleukin-5 (IL5 (1. These data comprise a treasure trove of information about eosinophils. We illustrate the power of label-free LC–MS/MS quantification by considering four examples: complexity of eosinophil STATs, contribution of immunoproteasome subunits to eosinophil proteasomes, complement of integrin subunits, and contribution of platelet proteins originating from platelet–eosinophil complexes to the overall proteome. We describe how isobaric labeling enables robust sample-to-sample comparisons and relate the 220 phosphosites that changed significantly upon treatment with IL5 to previous studies of eosinophil activation. Finally, we review previous attempts to leverage the power of mass spectrometry to discern differences between eosinophils of healthy subjects and those with eosinophil-associated conditions and point out features of label-free quantification and isobaric labeling that are important in planning future mass spectrometric studies.

  20. Older people and 'active ageing': Subjective aspects of ageing actively.

    Science.gov (United States)

    Stenner, Paul; McFarquhar, Tara; Bowling, Ann

    2011-04-01

    Following a critical overview of the active ageing concept, a thematic decomposition of 42 transcribed interviews with British people aged 72 years and over indicates that active ageing is understood in relation to physical, cognitive, psychological and social factors, but that these co-exist in complex combinations. The notion of activity in active ageing is grasped in relation to an active/passive distinction which emphasizes the enhancement or diminishment of concrete powers of activity. A 'challenge and response' framework is suggested for future research on active ageing.

  1. Negotiating active ageing at a Danish activity centre

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    Question: With the ‘Year of active aging and solidarity between generations’ in the EU, active aging is staged as a key policy area in an aging Europe. This paper follows the discourse of active aging from the EU to a Danish municipality to an activity centre and its users, and asks what active...... aging means in the everyday live of the elderly. Active aging is formed in many arenas and takes a variety of forms with different actors focusing on physical, occupational, social and mental activity. This paper focuses on how the elderly takes part in this forming, by asking how the elderly negotiates...... and practices active ageing. The paper uses an activity centre in Copenhagen as its site of negotiation. Methods: These questions have been explored with the use of ethnographic fieldwork and through a documentary study. The ethnographic fieldwork has been conducted at an activity centre with 4 months...

  2. Interplay between Solo and keratin filaments is crucial for mechanical force–induced stress fiber reinforcement

    Science.gov (United States)

    Fujiwara, Sachiko; Ohashi, Kazumasa; Mashiko, Toshiya; Kondo, Hiroshi; Mizuno, Kensaku

    2016-01-01

    Mechanical force–induced cytoskeletal reorganization is essential for cell and tissue remodeling and homeostasis; however, the underlying cellular mechanisms remain elusive. Solo (ARHGEF40) is a RhoA-targeting guanine nucleotide exchange factor (GEF) involved in cyclical stretch–induced human endothelial cell reorientation and convergent extension cell movement in zebrafish gastrula. In this study, we show that Solo binds to keratin-8/keratin-18 (K8/K18) intermediate filaments through multiple sites. Solo overexpression promotes the formation of thick actin stress fibers and keratin bundles, whereas knockdown of Solo, expression of a GEF-inactive mutant of Solo, or inhibition of ROCK suppresses stress fiber formation and leads to disorganized keratin networks, indicating that the Solo-RhoA-ROCK pathway serves to precisely organize keratin networks, as well as to promote stress fibers. Of importance, knockdown of Solo or K18 or overexpression of GEF-inactive or deletion mutants of Solo suppresses tensile force–induced stress fiber reinforcement. Furthermore, knockdown of Solo or K18 suppresses tensile force-induced RhoA activation. These results strongly suggest that the interplay between Solo and K8/K18 filaments plays a crucial role in tensile force–induced RhoA activation and consequent actin cytoskeletal reinforcement. PMID:26823019

  3. Intergovernmental organisation activities

    International Nuclear Information System (INIS)

    2016-01-01

    This section treats of the following Intergovernmental organisation activities: 1 - European Atomic Energy Community: Non-legally binding instruments (Commission Recommendation on the application of Article 103 of the Euratom Treaty; Communication from the Commission on a Nuclear Illustrative Program; Report from the Commission to the European Parliament and the Council on the implementation of the work under the nuclear decommissioning assistance program to Bulgaria, Lithuania and Slovakia in 2015 and previous years); International Atomic Energy Agency (IAEA): Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management; 60. Regular Session of the IAEA General Conference (Resolutions of the Conference, Measures to strengthen international cooperation in nuclear, radiation, transport and waste safety (GC(60)/RES/9): conventions, regulatory frameworks and supporting non-legally-binding instruments for safety, Nuclear installation safety, Safe management of radioactive sources, Nuclear Security (GC(60)/RES/10)); IAEA Treaty Event; Legislative assistance activities; OECD Nuclear Energy Agency (NEA): New member of the Generation IV International Forum; New signatories to the extension of the GIF Framework Agreement; International Framework for Nuclear Energy Cooperation (IFNEC) 'Latin American Nuclear Energy Stakeholders Conference', 25-26 October 2016, Buenos Aires, Argentina; 10. national workshop of the NEA Forum on Stakeholder Confidence (FSC); Symposium on the Fukushima Nuclear Power Plant Accident and Law and Policy, 24-25 September 2016, Tokyo, Japan; Nuclear Law Committee meeting; NEA publications of interest; Regulatory and Institutional Framework for Nuclear Activities; 16. Session of the International School of Nuclear Law (ISNL); 2017 session of the International Nuclear Law Essentials (INLE); Table on Nuclear Operator Liability Amounts and Financial Security Limits

  4. RERTR activities in Argentina

    International Nuclear Information System (INIS)

    Adelfang, P.; Alvarez, L.; Pasqualini, E.

    2002-01-01

    The Atomic Energy Commission of Argentina has been an active participant of the RERTR program since 1978. An important milestone of the Argentinean RERTR program was the development and manufacturing at industrial scale of U 3 O 8 dispersed fuel and its subsequent application to the conversion of the RA-3 reactor core to LEU fuel. More recently, our activities were focused on the development of U 3 Si 2 fuel with a density of 4.8 gU/cm 3 and the improvement of the manufacturing process of this type of fuel. The program to qualify CNEA as a supplier U 3 Si 2 dispersed fuels is scheduled to finalize by mid 2003. To hasten this program the main research reactor of Argentina, the RA3, raised its power from 5 MW to 8 Mw in October this year. This is an intermediate step in the program to increase RA-3 power to 10 MW Currently, one of the main objectives is to develop and qualify the technology for the production of high-density LEU fuel elements using U-Mo alloy. An original way to produce U-Mo powder (the HMD process) was developed and its being upgraded to plant scale production. Another significant progress was the development of LEU targets for the production of 99 Mo, in the form of miniplates prepared with dispersed LEU U-Al x . The shipment to USA of 207 MTR spent fuels containing US origin highly enriched uranium, successfully carried out in the end of 2000, is another remarkable achievement of the Argentinean RERTR program. This activity was carried out in the framework of the United States Foreign Research Reactor Spent Nuclear Fuel Acceptance Program. The fuels were fabricated in Argentina and used in the RA-3 reactor from 1968 to 1987. The inventory of the shipped HEU spent fuel consisted in 166 standard assemblies and 41 control assemblies. (author)

  5. Current UNSCEAR Activities

    International Nuclear Information System (INIS)

    Mohamed, G.

    2010-01-01

    UNSCEAR stands for United Nation Scientific Committee of Effects of Atomic Radiation. It has been in service for 55 years. It reports to the General Assembly. Its role is to assess global levels and effects of ionizing radiation and to provide scientific basis UNSCEAR in Africa: Egypt joined UNSCEAR in 1955 while Sudan joined in 1973. UNSCEAR in IRPA-11: Norman Gentner (Canada), the Scientific Secretary from 2001- 2005 gave a presentation about UNSCEAR. It was in Madrid, Spain 2004 UNSCEAR in second IRPA Africa’S Congress: This was in Egypt 2007. Abel Gonzalez (Argentina) who is a Member of UNSCEAR gave two presentations. i.e. a refresher course (UNSCEAR ) and a general lecture about UNSCEAR activities UNSCEAR in IRPA-12: Was held in 2008 and Malcolm Crick (UNSCEAR Scientific secretary) from 2005 gave a lecture entitled „Epistemology of radiation protection status of levels and effects of ionizing radiation.. UNSCEAR at IRPA Egypt workshop was held in Egypt January 2010 and Gomaa presented Malcolm Crick lecture to IRPA-12 to the participants of IRPA Egypt workshop January 2010. UNSCEAR Latest publications: Among the publications are:- UNSCEAR 2006 Report: E ffects of ionizing radiation” 5 UNSCEAR 2008 Report: S ources and effects of ionizing radiation”. The 57 Session of UNSCEAR activities: a. The activities included reporting to the General Assembly on three levels. Part -1: Report on session deliberations Part-2: Scientific Report: Summary of low-dose radiation effects on health Part-3: Response to paragraph 13 of resolution 64/85 b. There were also discussions on some documents which included: -Assessment of levels of radiation from electrical energy production -Uncertainty in radiation risk estimation - Health effects attributable to radiation exposure -Methodology for estimating exposures due to discharges -Summary of radiation effects on health -Improving data collection, analysis and dissemination At the end of the lecture, there was an invitation

  6. Intergovernmental organisation activities

    International Nuclear Information System (INIS)

    2017-01-01

    This section treats of the following Intergovernmental organisation activities: 1 - European Atomic Energy Community, Non-legally binding instruments: Report on Cyber Security in the Energy Sector; International relations: Memorandum of Understanding on a Strategic Energy Partnership between the European Union together with the European Atomic Energy Community and Ukraine; 2 - International Atomic Energy Agency, Convention on Nuclear Safety (CNS): Seventh Review Meeting of the contracting parties to the CNS; Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management (Joint Convention): Third Extraordinary Meeting of the contracting parties to the Joint Convention; Code of Conduct on the Safety of Research Reactors (Code): Fourth International Meeting on Application of the Code; Convention on the Physical Protection of Nuclear Material (CPPNM) and the CPPNM Amendment: Second Technical Meeting of the representatives of states parties to the CPPNM and the CPPNM Amendment; International Conference on Nuclear Security: Commitments and Actions; Nuclear liability: Seventeenth meeting of the International Expert Group on Nuclear Liability (INLEX), Workshops on Civil Liability for Nuclear Damage; Legislative assistance activities; 3 - OECD Nuclear Energy Agency: Strategic Plan for 2017-2022, Argentina and Romania to become members of the Nuclear Energy Agency, Latest updates regarding the Paris Convention, The NEA and China's National Energy Administration sign MOU to strengthen co-operation, Stakeholder support and involvement essential to future of nuclear energy decision making, Nuclear Law Committee meeting, 2017 International Nuclear Law Essentials (INLE) course, Regulatory and institutional framework for nuclear activities, NEA publications of interest

  7. Spontaneous Plasticity of Multineuronal Activity Patterns in Activated Hippocampal Networks

    Directory of Open Access Journals (Sweden)

    Atsushi Usami

    2008-01-01

    Full Text Available Using functional multineuron imaging with single-cell resolution, we examined how hippocampal networks by themselves change the spatiotemporal patterns of spontaneous activity during the course of emitting spontaneous activity. When extracellular ionic concentrations were changed to those that mimicked in vivo conditions, spontaneous activity was increased in active cell number and activity frequency. When ionic compositions were restored to the control conditions, the activity level returned to baseline, but the weighted spatial dispersion of active cells, as assessed by entropy-based metrics, did not. Thus, the networks can modify themselves by altering the internal structure of their correlated activity, even though they as a whole maintained the same level of activity in space and time.

  8. Enzyme Activities in Waste Water and Activated Sludge

    DEFF Research Database (Denmark)

    Nybroe, Ole; Jørgensen, Per Elberg; Henze, Mogens

    1992-01-01

    The purpose of the present study was to evaluate the potential of selected enzyme activity assays to determine microbial abundance and heterotrophic activity in waste water and activated sludge. In waste water, esterase and dehydrogenase activities were found to correlate with microbial abundance...... measured as colony forming units of heterotrophic bacteria. A panel of four enzyme activity assays, α-glucosidase, alanine-aminopeptidase, esterase and dehydrogenase were used to characterize activated sludge and anaerobic hydrolysis sludge from a pilot scale plant. The enzymatic activity profiles were...... distinctly different, suggesting that microbial populations were different, or had different physiological properties, in the two types of sludge. Enzyme activity profiles in activated sludge from four full-scale plants seemed to be highly influenced by the composition of the inlet. Addition of hydrolysed...

  9. Activity report 1976

    International Nuclear Information System (INIS)

    Drent, W.; Delande, E.

    1977-07-01

    The principal activities of Eurochemic plant in the fields of reprocessing and the closing-down program are presented in this report that covers the period 1 January to 31 December 1976. Works in the plant are closely related to the decontamination of the process cells and the completation of the bituminization plant and storage facility. The solidification processes for the high-level liquid waste have been definied and the negotiations in view of setting up an international R and D program for the embedding of solidified high-level waste into metal patrices have been pursued. (A.F.)

  10. Physical activity in elderly

    Directory of Open Access Journals (Sweden)

    Jan Cvecka

    2015-08-01

    Full Text Available Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared.

  11. Activity report 1998

    International Nuclear Information System (INIS)

    1998-01-01

    The aim of this report is to outline the main developments of the ''Departement des Reacteurs Experimentaux'', (DRE) during the year 1998. DRE is one of the Department of the ''Direction des Reacteurs Nucleaires'', itself depending of the CEA Institution. After a presentation of the year highlights, this report gathers the main research and development programs. The second part concerns the production of radioisotopes, the silicon doping, the neutron radiography, the Orphee experiments and the activation analysis. The installations management, the closed reactors improvement program and the effluents and wastes processing of Grenoble, are presented in the other parts. Data on staff, budget and safety are also provided. (A.L.B.)

  12. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    In this last part is reviewed international regulatory activities and bilateral agreements including two parts: concerning European atomic energy community with European commission proposal for a council directive setting up a community framework for nuclear safety, update of the nuclear illustrative programme in the context of the second strategic energy review, european commission recommendation on criteria for the export of radioactive waste and spent fuel to third countries and a communication on nuclear non-proliferation and the second part in relation with international atomic energy agency with a joint convention on the safety of spent fuel management and on safety of radioactive waste management (third review meeting). (N.C.)

  13. Protostome classification activity

    OpenAIRE

    Biederman, Lori

    2017-01-01

    I wrote this activity to have students work through the defining characteristics of various protostomes that I cover in my Introduction to Biology course. For in class materials I remove the red box (upper right corner) and print slides 4-18, place them back-to-back and laminate them.  The students get a key (slides 2 & 3) and an organism sheet and they are to answer the questions for each organism based on the info provided.   After class a...

  14. Prokaryote metabolism activity

    OpenAIRE

    Biederman, Lori

    2017-01-01

    I wrote this activity to emphasize that prokaryotic organisms can carry out 6 different types of metabolisms (as presented in Freeman’s Biological Science textbook) and this contrasts to eukaryotes, which can only use 2 metabolism pathways (photoautotroph and heterotroph).    For in class materials I remove the  red box (upper right corner) and print slides 3-10, place them back-to-back and laminate them.  The students get a key (slide 2) and a two-sided organism sheet...

  15. Bi209 alpha activity

    International Nuclear Information System (INIS)

    Araujo Penna, M.M. de.

    1970-01-01

    The study for measuring Bi 209 alpha activity is presented. Ilford L4 nuclear emulsion pellicles loaded with bismuth citrate to obtain a load of 100 mg/cm 3 of dry emulsion, were prepared. Other pellicles were prepared with the same. Ilford L4 gel to estimate the background radiation. To observe 'fading' effect, pellicles loaded with bismuth were submitted to neutrons of high energy, aiming to record recoil proton tracks. The pellicles were confined in nitrogen atmosphere at temperature lower than -10 0 C. The Bi 209 experimental half-life was obtained and compared with the estimated theoretical data. (M.C.K.) [pt

  16. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    Different international regulatory activities are presented: recommendation on the protection of the public against exposure to radon in drinking water supplies, amendment to the legislation implementing the regulation on imports of agricultural products originating in third countries following the Chernobyl accident, resolution on the commission green paper towards a European strategy for the security of energy supply, declaration of mandatory nature of the international code for the safe carriage of packaged irradiated nuclear fuel, plutonium and high level radioactive wastes on board ships, adoption of action plan against nuclear terrorism. (N.C.)

  17. Direct Activation Of Methane

    KAUST Repository

    Basset, Jean-Marie

    2013-07-15

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

  18. ANCCLI. 2012 activity report

    International Nuclear Information System (INIS)

    2012-01-01

    This report first proposes a synthesis of the ANCCLI (the national association of local information committees) progress report, and then a presentation of the context (relationships between CLIs and the ANCCLI, situation at the local, European and international levels). It presents the various ANCCLI's bodies (scientific committee, permanent groups, task officers' club) and their activities. It proposes an overview of partnership with different agencies and bodies (ASN, IRSN, ministries, and HCTISN or High committee for transparency and information on nuclear safety). It presents the ANCCLI's European strategy, and the national and international participations of the ANCCLI to various actions and bodies

  19. Active galactic nuclei

    CERN Document Server

    Beckmann, Volker

    2012-01-01

    This AGN textbook includes phenomena based on new results in the X-Ray domain from new telescopes such as Chandra and XMM Newton not mentioned in any other book. Furthermore, it considers also the Fermi Gamma Ray Space Telescope with its revolutionary advances of unprecedented sensitivity, field of view and all-sky monitoring. Those and other new developments as well as simulations of AGN merging events and formations, enabled through latest super-computing capabilities. The book gives an overview on the current knowledge of the Active Galacitc Nuclei phenomenon. The spectral energy d

  20. WFIRST Project Science Activities

    Science.gov (United States)

    Gehrels, Neil

    2012-01-01

    The WFIRST Project is a joint effort between GSFC and JPL. The project scientists and engineers are working with the community Science Definition Team to define the requirements and initial design of the mission. The objective is to design an observatory that meets the WFIRST science goals of the Astr02010 Decadal Survey for minimum cost. This talk will be a report of recent project activities including requirements flowdown, detector array development, science simulations, mission costing and science outreach. Details of the interim mission design relevant to scientific capabilities will be presented.