Efficient silkworm expression of human GPCR (nociceptin receptor) by a Bombyx mori bacmid DNA system

International Nuclear Information System (INIS)

Kajikawa, Mizuho; Sasaki, Kaori; Wakimoto, Yoshitaro; Toyooka, Masaru; Motohashi, Tomoko; Shimojima, Tsukasa; Takeda, Shigeki; Park, Enoch Y.; Maenaka, Katsumi

2009-01-01

Guanine nucleotide-binding protein (G protein) coupled receptors (GPCRs) are frequently expressed by a baculovirus expression vector system (BEVS). We recently established a novel BEVS using the bacmid system of Bombyx mori nucleopolyhedrovirus (BmNPV), which is directly applicable for protein expression in silkworms. Here, we report the first example of GPCR expression in silkworms by the simple injection of BmNPV bacmid DNA. Human nociceptin receptor, an inhibitory GPCR, and its fusion protein with inhibitory G protein alpha subunit (G i α) were both successfully expressed in the fat bodies of silkworm larvae as well as in the BmNPV viral fraction. Its yield was much higher than that from Sf9 cells. The microsomal fractions including the nociceptin receptor fusion, which are easily prepared by only centrifugation steps, exhibited [ 35 S]GTPγS-binding activity upon specific stimulation by nociceptin. Therefore, this rapid method is easy-to-use and has a high expression level, and thus will be an important tool for human GPCR production.

Membrane-mediated oligomerization of G protein coupled receptors and its implications for GPCR function

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Stefan Gahbauer

2016-10-01

Full Text Available The dimerization or even oligomerization of G protein coupled receptors (GPCRs causes ongoing, controversial debates about its functional role and the coupled biophysical, biochemical or biomedical implications. A continously growing number of studies hints to a relation between oligomerization and function of GPCRs and strengthens the assumption that receptor assembly plays a key role in the regulation of protein function. Additionally, progress in the structural analysis of GPCR-G protein and GPCR-ligand interactions allows to distinguish between actively functional and non-signalling complexes. Recent findings further suggest that the surrounding membrane, i.e. its lipid composition may modulate the preferred dimerization interface and as a result the abundance of distinct dimeric conformations. In this review, the association of GPCRs and the role of the membrane in oligomerization will be discussed. An overview of the different reported oligomeric interfaces is provided and their capability for signaling discussed. The currently available data is summarized with regard to the formation of GPCR oligomers, their structures and dependency on the membrane microenvironment as well as the coupling of oligomerization to receptor function.

The current state of GPCR-based drug discovery to treat metabolic disease.

Science.gov (United States)

Sloop, Kyle W; Emmerson, Paul J; Statnick, Michael A; Willard, Francis S

2018-02-02

One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour. © 2018 The British Pharmacological Society.

TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation.

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Nadine Kirschmer

Full Text Available The Transient Receptor Potential Channel Subunit 4 (TRPC4 has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. Gαq protein-coupled receptor (GPCR stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT activation. Functional properties of TRPC4 are also based on the expression of the TRPC4 splice variants TRPC4α and TRPC4β. Aim of the present study was to analyze cytosolic Ca2+ signals, signaling, hypertrophy and vitality of cardiomyocytes in dependence on the expression level of either TRPC4α or TRPC4β. The analysis of Ca2+ transients in neonatal rat cardiomyocytes (NRCs showed that TRPC4α and TRPC4β affected Ca2+ cycling in beating cardiomyocytes with both splice variants inducing an elevation of the Ca2+ transient amplitude at baseline and TRPC4β increasing the Ca2+ peak during angiotensin II (Ang II stimulation. NRCs infected with TRPC4β (Ad-C4β also responded with a sustained Ca2+ influx when treated with Ang II under non-pacing conditions. Consistent with the Ca2+ data, NRCs infected with TRPC4α (Ad-C4α showed an elevated calcineurin/NFAT activity and a baseline hypertrophic phenotype but did not further develop hypertrophy during chronic Ang II/phenylephrine stimulation. Down-regulation of endogenous TRPC4α reversed these effects, resulting in less hypertrophy of NRCs at baseline but a markedly increased hypertrophic enlargement after chronic agonist stimulation. Ad-C4β NRCs did not exhibit baseline calcineurin/NFAT activity or hypertrophy but responded with an increased calcineurin/NFAT activity after GPCR stimulation. However, this effect was not

Efficient silkworm expression of human GPCR (nociceptin receptor) by a Bombyx mori bacmid DNA system

Energy Technology Data Exchange (ETDEWEB)

Kajikawa, Mizuho; Sasaki, Kaori [Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Wakimoto, Yoshitaro; Toyooka, Masaru [Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Motohashi, Tomoko; Shimojima, Tsukasa [National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540 (Japan); Takeda, Shigeki [Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Park, Enoch Y. [Laboratory of Biotechnology, Integrated Bioscience Section, Graduate School of Science and Technology, Shizuoka University, 836 Oya, Suruga-ku, Shizuoka, Shizuoka 422-8529 (Japan); Maenaka, Katsumi, E-mail: kmaenaka-umin@umin.net [Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

2009-07-31

Guanine nucleotide-binding protein (G protein) coupled receptors (GPCRs) are frequently expressed by a baculovirus expression vector system (BEVS). We recently established a novel BEVS using the bacmid system of Bombyx mori nucleopolyhedrovirus (BmNPV), which is directly applicable for protein expression in silkworms. Here, we report the first example of GPCR expression in silkworms by the simple injection of BmNPV bacmid DNA. Human nociceptin receptor, an inhibitory GPCR, and its fusion protein with inhibitory G protein alpha subunit (G{sub i}{alpha}) were both successfully expressed in the fat bodies of silkworm larvae as well as in the BmNPV viral fraction. Its yield was much higher than that from Sf9 cells. The microsomal fractions including the nociceptin receptor fusion, which are easily prepared by only centrifugation steps, exhibited [{sup 35}S]GTP{gamma}S-binding activity upon specific stimulation by nociceptin. Therefore, this rapid method is easy-to-use and has a high expression level, and thus will be an important tool for human GPCR production.

Functional understanding of the diverse exon-intron structures of human GPCR genes.

Science.gov (United States)

Hammond, Dorothy A; Olman, Victor; Xu, Ying

2014-02-01

The GPCR genes have a variety of exon-intron structures even though their proteins are all structurally homologous. We have examined all human GPCR genes with at least two functional protein isoforms, totaling 199, aiming to gain an understanding of what may have contributed to the large diversity of the exon-intron structures of the GPCR genes. The 199 genes have a total of 808 known protein splicing isoforms with experimentally verified functions. Our analysis reveals that 1301 (80.6%) adjacent exon-exon pairs out of the total of 1,613 in the 199 genes have either exactly one exon skipped or the intron in-between retained in at least one of the 808 protein splicing isoforms. This observation has a statistical significance p-value of 2.051762 * e(-09), assuming that the observed splicing isoforms are independent of the exon-intron structures. Our interpretation of this observation is that the exon boundaries of the GPCR genes are not randomly determined; instead they may be selected to facilitate specific alternative splicing for functional purposes.

Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist

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John D. Chan

2016-12-01

Full Text Available 5-hydroxytryptamine (5-HT is a key regulator of muscle contraction in parasitic flatworms. In Schistosoma mansoni, the myoexcitatory action of 5-HT is effected through activation of a serotonergic GPCR (Sm.5HTRL, prioritizing pharmacological characterization of this target for anthelmintic drug discovery. Here, we have examined the effects of several aporphine alkaloids on the signaling activity of a heterologously expressed Sm.5HTRL construct using a cAMP biosensor assay. Four structurally related natural products – nuciferine, D-glaucine, boldine and bulbocapnine – were demonstrated to block Sm.5HTRL evoked cAMP generation with the potency of GPCR blockade correlating well with the ability of each drug to inhibit contractility of schistosomule larvae. Nuciferine was also effective at inhibiting both basal and 5-HT evoked motility of adult schistosomes. These data advance our understanding of structure-affinity relationships at Sm.5HTRL, and demonstrate the effectiveness of Sm.5HTRL antagonists as hypomotility-evoking drugs across different parasite life cycle stages.

Prediction of GPCR-Ligand Binding Using Machine Learning Algorithms

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Sangmin Seo

2018-01-01

Full Text Available We propose a novel method that predicts binding of G-protein coupled receptors (GPCRs and ligands. The proposed method uses hub and cycle structures of ligands and amino acid motif sequences of GPCRs, rather than the 3D structure of a receptor or similarity of receptors or ligands. The experimental results show that these new features can be effective in predicting GPCR-ligand binding (average area under the curve [AUC] of 0.944, because they are thought to include hidden properties of good ligand-receptor binding. Using the proposed method, we were able to identify novel ligand-GPCR bindings, some of which are supported by several studies.

G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins from endosomes.

Science.gov (United States)

Tsvetanova, Nikoleta G; Irannejad, Roshanak; von Zastrow, Mark

2015-03-13

Some G protein-coupled receptors (GPCRs), in addition to activating heterotrimeric G proteins in the plasma membrane, appear to elicit a "second wave" of G protein activation after ligand-induced internalization. We briefly summarize evidence supporting this view and then discuss what is presently known about the functional significance of GPCR-G protein activation in endosomes. Endosomal activation can shape the cellular response temporally by prolonging its overall duration, and may shape the response spatially by moving the location of intracellular second messenger production relative to effectors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Targeting GPCR-Gβγ-GRK2 signaling as a novel strategy for treating cardiorenal pathologies.

Science.gov (United States)

Rudomanova, Valeria; Blaxall, Burns C

2017-08-01

The pathologic crosstalk between the heart and kidney is known as cardiorenal syndrome (CRS). While the specific mechanisms underlying this crosstalk remain poorly understood, CRS is associated with exacerbated dysfunction of either or both organs and reduced survival. Maladaptive fibrotic remodeling is a key component of both heart and kidney failure pathogenesis and progression. G-protein coupled receptor (GPCR) signaling is a crucial regulator of cardiovascular and renal function. Chronic/pathologic GPCR signaling elicits the interaction of the G-protein Gβγ subunit with GPCR kinase 2 (GRK2), targeting the receptor for internalization, scaffolding to pathologic signals, and receptor degradation. Targeting this pathologic Gβγ-GRK2 interaction has been suggested as a possible strategy for the treatment of HF. In the current review, we discuss recent updates in understanding the role of GPCR-Gβγ-GRK2 signaling as a crucial mediator of maladaptive organ remodeling detected in HF and kidney dysfunction, with specific attention to small molecule-mediated inhibition of pathologic Gβγ-GRK2 interactions. Further, we explore the potential of GPCR-Gβγ-GRK2 signaling as a possible therapeutic target for cardiorenal pathologies. Copyright © 2017 Elsevier B.V. All rights reserved.

Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits

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Brian S. Muntean

2018-01-01

Full Text Available Summary: Modulation of neuronal circuits is key to information processing in the brain. The majority of neuromodulators exert their effects by activating G-protein-coupled receptors (GPCRs that control the production of second messengers directly impacting cellular physiology. How numerous GPCRs integrate neuromodulatory inputs while accommodating diversity of incoming signals is poorly understood. In this study, we develop an in vivo tool and analytical suite for analyzing GPCR responses by monitoring the dynamics of a key second messenger, cyclic AMP (cAMP, with excellent quantitative and spatiotemporal resolution in various neurons. Using this imaging approach in combination with CRISPR/Cas9 editing and optogenetics, we interrogate neuromodulatory mechanisms of defined populations of neurons in an intact mesolimbic reward circuit and describe how individual inputs generate discrete second-messenger signatures in a cell- and receptor-specific fashion. This offers a resource for studying native neuronal GPCR signaling in real time. : Muntean et al. develop an in vivo reagent to study processing of neurotransmitter GPCR signals by monitoring real-time dynamics of cAMP responses. They demonstrate application of this approach, in combination with CRISPR/Cas9 gene editing and optogenetics, to interrogate the functional organization of a striatal circuit. Keywords: cAMP, GPCR, neuromodulation, dopamine, striatum, imaging, optogenetics

Seeking Ligand Bias: Assessing GPCR Coupling to Beta-Arrestins for Drug Discovery

OpenAIRE

Bohn, Laura M.; McDonald, Patricia H.

2010-01-01

G protein-coupled receptors (GPCR) are the major site of action for endogenous hormones and neurotransmitters. Early drug discovery efforts focused on determining whether ligands could engage G protein coupling and subsequently activate or inhibit cognate “second messengers.” Gone are those simple days as we now realize that receptors can also couple βarrestins. As we delve into the complexity of ligand-directed signaling and receptosome scaffolds, we are faced with what may seem like endless...

G protein-coupled receptor transmembrane binding pockets and their applications in GPCR research and drug discovery: a survey.

Science.gov (United States)

Kratochwil, Nicole A; Gatti-McArthur, Silvia; Hoener, Marius C; Lindemann, Lothar; Christ, Andreas D; Green, Luke G; Guba, Wolfgang; Martin, Rainer E; Malherbe, Pari; Porter, Richard H P; Slack, Jay P; Winnig, Marcel; Dehmlow, Henrietta; Grether, Uwe; Hertel, Cornelia; Narquizian, Robert; Panousis, Constantinos G; Kolczewski, Sabine; Steward, Lucinda

2011-01-01

G protein-coupled receptors (GPCRs) share a common architecture consisting of seven transmembrane (TM) domains. Various lines of evidence suggest that this fold provides a generic binding pocket within the TM region for hosting agonists, antagonists, and allosteric modulators. Hence, an automated method was developed that allows a fast analysis and comparison of these generic ligand binding pockets across the entire GPCR family by providing the relevant information for all GPCRs in the same format. This methodology compiles amino acids lining the TM binding pocket including parts of the ECL2 loop in a so-called 1D ligand binding pocket vector and translates these 1D vectors in a second step into 3D receptor pharmacophore models. It aims to support various aspects of GPCR drug discovery in the pharmaceutical industry. Applications of pharmacophore similarity analysis of these 1D LPVs include definition of receptor subfamilies, prediction of species differences within subfamilies in regard to in vitro pharmacology and identification of nearest neighbors for GPCRs of interest to generate starting points for GPCR lead identification programs. These aspects of GPCR research are exemplified in the field of melanopsins, trace amine-associated receptors and somatostatin receptor subtype 5. In addition, it is demonstrated how 3D pharmacophore models of the LPVs can support the prediction of amino acids involved in ligand recognition, the understanding of mutational data in a 3D context and the elucidation of binding modes for GPCR ligands and their evaluation. Furthermore, guidance through 3D receptor pharmacophore modeling for the synthesis of subtype-specific GPCR ligands will be reported. Illustrative examples are taken from the GPCR family class C, metabotropic glutamate receptors 1 and 5 and sweet taste receptors, and from the GPCR class A, e.g. nicotinic acid and 5-hydroxytryptamine 5A receptor. © 2011 Bentham Science Publishers

Global medicinal chemistry and GPCR conference: interview with Stevan Djuric.

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Djuric, Stevan

2018-04-01

Stevan Djuric speaks to Benjamin Walden, Commissioning Editor. Stevan Djuric is head of the global Medicinal Chemistry Leadership Team at AbbVie and is also Vice President of the Discovery Chemistry and Technology organization within their Discovery organization and chemistry outsourcing activities. He spoke at the Global-Medicinal-Chemistry and GPCR summit on the imperative to develop chemistry related technology that can reduce cycle time, cost of goods and improve probability of success. To this end, he discussed his efforts in the chemistry technology area with a focus on integrated synthesis-purification bioassay, and flow photochemistry and high temperature chemistry platforms.

iGPCR-drug: a web server for predicting interaction between GPCRs and drugs in cellular networking.

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Xuan Xiao

Full Text Available Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called "iGPCR-drug", was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug - target interaction networks.

MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR.

Science.gov (United States)

Krause, Claudia J; Popp, Oliver; Thirunarayanan, Nanthakumar; Dittmar, Gunnar; Lipp, Martin; Müller, Gerd

2016-03-01

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded chemokine receptor vGPCR acts as an oncogene in Kaposi's sarcomagenesis. Until now, the molecular mechanisms by which the vGPCR contributes to tumor development remain incompletely understood. Here, we show that the KSHV-vGPCR contributes to tumor progression through microRNA (miR)-34a-mediated induction of genomic instability. Large-scale analyses on the DNA, gene and protein level of cell lines derived from a mouse model of vGPCR-driven tumorigenesis revealed that a vGPCR-induced upregulation of miR-34a resulted in a broad suppression of genome maintenance genes. A knockdown of either the vGPCR or miR-34a largely restored the expression of these genes and confirmed miR-34a as a downstream effector of the KSHV-vGPCR that compromises genome maintenance mechanisms. This novel, protumorigenic role of miR-34a questions the use of miR-34a mimetics in cancer therapy as they could impair genome stability.

FLIPR assays of intracellular calcium in GPCR drug discovery

DEFF Research Database (Denmark)

Hansen, Kasper Bø; Bräuner-Osborne, Hans

2009-01-01

Fluorescent dyes sensitive to changes in intracellular calcium have become increasingly popular in G protein-coupled receptor (GPCR) drug discovery for several reasons. First of all, the assays using the dyes are easy to perform and are of low cost compared to other assays. Second, most non...

GPCR-SSFE 2.0-a fragment-based molecular modeling web tool for Class A G-protein coupled receptors.

Science.gov (United States)

Worth, Catherine L; Kreuchwig, Franziska; Tiemann, Johanna K S; Kreuchwig, Annika; Ritschel, Michele; Kleinau, Gunnar; Hildebrand, Peter W; Krause, Gerd

2017-07-03

G-protein coupled receptors (GPCRs) are key players in signal transduction and therefore a large proportion of pharmaceutical drugs target these receptors. Structural data of GPCRs are sparse yet important for elucidating the molecular basis of GPCR-related diseases and for performing structure-based drug design. To ameliorate this problem, GPCR-SSFE 2.0 (http://www.ssfa-7tmr.de/ssfe2/), an intuitive web server dedicated to providing three-dimensional Class A GPCR homology models has been developed. The updated web server includes 27 inactive template structures and incorporates various new functionalities. Uniquely, it uses a fingerprint correlation scoring strategy for identifying the optimal templates, which we demonstrate captures structural features that sequence similarity alone is unable to do. Template selection is carried out separately for each helix, allowing both single-template models and fragment-based models to be built. Additionally, GPCR-SSFE 2.0 stores a comprehensive set of pre-calculated and downloadable homology models and also incorporates interactive loop modeling using the tool SL2, allowing knowledge-based input by the user to guide the selection process. For visual analysis, the NGL viewer is embedded into the result pages. Finally, blind-testing using two recently published structures shows that GPCR-SSFE 2.0 performs comparably or better than other state-of-the art GPCR modeling web servers. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Trends in GPCR drug discovery: new agents, targets and indications

DEFF Research Database (Denmark)

Hauser, Alexander Sebastian; Gloriam, David E.; Attwood, Misty M.

2017-01-01

current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially...... are also highly represented. The 224 (56%) non-olfactory GPCRs that have not yet been explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug......G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals...

Promoter switching allows simultaneous transcription of LANA and K14/vGPCR of Kaposi's sarcoma-associated herpesvirus

International Nuclear Information System (INIS)

Staudt, Michelle R.; Dittmer, Dirk P.

2006-01-01

Latent transcription of the latency-associated nuclear antigen (LANA/ORF73) of Kaposi's sarcoma-associated herpesvirus is driven by the LANAp-c. Complexity arises during lytic reactivation, however, as the bicistronic K14/vGPCR transcript initiates 32 bp downstream of LANAp-c in the opposite orientation. We identify an Rta/ORF50-inducible LANA promoter (LANAp-i) that is distinct from the LANAp-c. LANAp-c is unaffected by Rta/ORF50. Utilization of the second, downstream LANAp-i explains how LANA and K14/vGPCR are simultaneously transcribed during de novo infection or lytic reactivation. Transactivation of LANAp-i and K14/vGPCRp requires the C-terminal activation domain of Rta/ORF50 and is mediated by DNA-binding-dependent and -independent Rta/ORF50 mechanisms. Transcriptional profiling following viral reactivation support promoter reporter phenotypes. In sum, cis-elements within the LANAp were selected to ensure faithful expression of LANA and other genes regulated by LANAp during all stages of the KSHV lifecycle despite potential interference from K14/vGPCRp activity

Balancing focused combinatorial libraries based on multiple GPCR ligands

Science.gov (United States)

Soltanshahi, Farhad; Mansley, Tamsin E.; Choi, Sun; Clark, Robert D.

2006-08-01

G-Protein coupled receptors (GPCRs) are important targets for drug discovery, and combinatorial chemistry is an important tool for pharmaceutical development. The absence of detailed structural information, however, limits the kinds of combinatorial design techniques that can be applied to GPCR targets. This is particularly problematic given the current emphasis on focused combinatorial libraries. By linking an incremental construction method (OptDesign) to the very fast shape-matching capability of ChemSpace, we have created an efficient method for designing targeted sublibraries that are topomerically similar to known actives. Multi-objective scoring allows consideration of multiple queries (actives) simultaneously. This can lead to a distribution of products skewed towards one particular query structure, however, particularly when the ligands of interest are quite dissimilar to one another. A novel pivoting technique is described which makes it possible to generate promising designs even under those circumstances. The approach is illustrated by application to some serotonergic agonists and chemokine antagonists.

High Content Analysis of Compositional Heterogeneities to Study GPCR Oligomerization

DEFF Research Database (Denmark)

Walsh, Samuel McEwen

In this thesis I demonstrate how the natural compositional heterogeneities of synthetic and living cell model systems can be used to quantitate the mechanics of G-protein coupled receptor (GPCR) oligomerization with Förster resonance energy transfer (FRET). The thesis is structured around three a...

Integrin and GPCR Crosstalk in the Regulation of ASM Contraction Signaling in Asthma.

Science.gov (United States)

Teoh, Chun Ming; Tam, John Kit Chung; Tran, Thai

2012-01-01

Airway hyperresponsiveness (AHR) is one of the cardinal features of asthma. Contraction of airway smooth muscle (ASM) cells that line the airway wall is thought to influence aspects of AHR, resulting in excessive narrowing or occlusion of the airway. ASM contraction is primarily controlled by agonists that bind G protein-coupled receptor (GPCR), which are expressed on ASM. Integrins also play a role in regulating ASM contraction signaling. As therapies for asthma are based on symptom relief, better understanding of the crosstalk between GPCRs and integrins holds good promise for the design of more effective therapies that target the underlying cellular and molecular mechanism that governs AHR. In this paper, we will review current knowledge about integrins and GPCRs in their regulation of ASM contraction signaling and discuss the emerging concept of crosstalk between the two and the implication of this crosstalk on the development of agents that target AHR.

Quantification of GPCR internalization by single-molecule microscopy in living cells.

NARCIS (Netherlands)

Serge, A.; Keijzer, S. de; Hemert, F. Van; Hickman, M.R.; Hereld, D.; Spaink, H.P.; Schmidt, T.; Snaar-Jagalska, B.E.

2011-01-01

Receptor internalization upon ligand stimulation is a key component of a cell's response and allows a cell to correctly sense its environment. Novel fluorescent methods have enabled the direct visualization of the agonist-stimulated G-protein-coupled receptors (GPCR) trafficking in living cells.

GPCR-Bench: A Benchmarking Set and Practitioners' Guide for G Protein-Coupled Receptor Docking.

Science.gov (United States)

Weiss, Dahlia R; Bortolato, Andrea; Tehan, Benjamin; Mason, Jonathan S

2016-04-25

Virtual screening is routinely used to discover new ligands and in particular new ligand chemotypes for G protein-coupled receptors (GPCRs). To prepare for a virtual screen, we often tailor a docking protocol that will enable us to select the best candidates for further screening. To aid this, we created GPCR-Bench, a publically available docking benchmarking set in the spirit of the DUD and DUD-E reference data sets for validation studies, containing 25 nonredundant high-resolution GPCR costructures with an accompanying set of diverse ligands and computational decoy molecules for each target. Benchmarking sets are often used to compare docking protocols; however, it is important to evaluate docking methods not by "retrospective" hit rates but by the actual likelihood that they will produce novel prospective hits. Therefore, docking protocols must not only rank active molecules highly but also produce good poses that a chemist will select for purchase and screening. Currently, no simple objective machine-scriptable function exists that can do this; instead, docking hit lists must be subjectively examined in a consistent way to compare between docking methods. We present here a case study highlighting considerations we feel are of importance when evaluating a method, intended to be useful as a practitioners' guide.

Structural basis for activation of G-protein-coupled receptors

DEFF Research Database (Denmark)

Gether, Ulrik; Asmar, Fazila; Meinild, Anne Kristine

2002-01-01

into conformational changes accompanying GPCR activation and the underlying molecular mechanism governing transition of the receptor between its active and inactive states. Using the beta2-adrenergic receptor as a model system we have obtained evidence for an evolutionary conserved activation mechanism where...... changes and receptor activation. At the current stage we are exploring the possibility of reaching this goal by direct in situ labeling of the beta2-adrenergic receptor in Xenopus laevis oocytes with conformationally sensitive fluorescent probes and parallel detection of receptor activation by co...

Pharmacogenomics of GPCR Drug Targets

DEFF Research Database (Denmark)

Hauser, Alexander Sebastian; Chavali, Sreenivas; Masuho, Ikuo

2018-01-01

Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs...... and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug......- and effector-binding sites in the human population. We experimentally show that certain variants of μ-opioid and Cholecystokinin-A receptors could lead to altered or adverse drug response. By analyzing UK National Health Service drug prescription and sales data, we suggest that characterizing GPCR variants...

Japan's nuclear PA activity in local governments

International Nuclear Information System (INIS)

Fujii, Nobuyuki

1995-01-01

This presentation emphasises some points of PA activities, based on the experience of 'cooperation projects for local governments'. Local governments distribute the public information directly to the residents. This is very important because officers of the local government can be the opinion leaders of the region. Local government exist very close to the residents, while the central government is a distant and faceless existence for the local people. It is believed that the local governments play an imperative role in PA activities. In other words, we must further utilize the organizations and functions of the local governments to implement PA activities. In conclusion, three recommendations are offered. Firstly, enough budget and authority should be given to the local governments as far as PA activities in their areas are concerned, and most of such activities should be entrusted to the local governments. Local governments should place more public relations officers, and continue the manpower development. Second, with regard to highly technical or specialized issues which a local governments cannot treat alone, related organizations like JAERO should support their PA activities. Third, such related organizations should also cooperate with local government including assistance in providing know-how, when their public information activities focus on educators, journalists, or the women. These three points should be given due consideration in our cooperation projects for the local governments, and JAERO is doing its best every day

Structural Elements in the Gαs and Gαq C Termini That Mediate Selective G Protein-coupled Receptor (GPCR) Signaling.

Science.gov (United States)

Semack, Ansley; Sandhu, Manbir; Malik, Rabia U; Vaidehi, Nagarajan; Sivaramakrishnan, Sivaraj

2016-08-19

Although the importance of the C terminus of the α subunit of the heterotrimeric G protein in G protein-coupled receptor (GPCR)-G protein pairing is well established, the structural basis of selective interactions remains unknown. Here, we combine live cell FRET-based measurements and molecular dynamics simulations of the interaction between the GPCR and a peptide derived from the C terminus of the Gα subunit (Gα peptide) to dissect the molecular mechanisms of G protein selectivity. We observe a direct link between Gα peptide binding and stabilization of the GPCR conformational ensemble. We find that cognate and non-cognate Gα peptides show deep and shallow binding, respectively, and in distinct orientations within the GPCR. Binding of the cognate Gα peptide stabilizes the agonist-bound GPCR conformational ensemble resulting in favorable binding energy and lower flexibility of the agonist-GPCR pair. We identify three hot spot residues (Gαs/Gαq-Gln-384/Leu-349, Gln-390/Glu-355, and Glu-392/Asn-357) that contribute to selective interactions between the β2-adrenergic receptor (β2-AR)-Gαs and V1A receptor (V1AR)-Gαq The Gαs and Gαq peptides adopt different orientations in β2-AR and V1AR, respectively. The β2-AR/Gαs peptide interface is dominated by electrostatic interactions, whereas the V1AR/Gαq peptide interactions are predominantly hydrophobic. Interestingly, our study reveals a role for both favorable and unfavorable interactions in G protein selection. Residue Glu-355 in Gαq prevents this peptide from interacting strongly with β2-AR. Mutagenesis to the Gαs counterpart (E355Q) imparts a cognate-like interaction. Overall, our study highlights the synergy in molecular dynamics and FRET-based approaches to dissect the structural basis of selective G protein interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Regulation of GPCR-mediated smooth muscle contraction : implications for asthma and pulmonary hypertension

NARCIS (Netherlands)

Wright, D B; Tripathi, S; Sikarwar, A; Santosh, K T; Perez-Zoghbi, J; Ojo, O O; Irechukwu, N; Ward, J P T; Schaafsma, D

Contractile G-protein-coupled receptors (GPCRs) have emerged as key regulators of smooth muscle contraction, both under healthy and diseased conditions. This brief review will discuss some key topics and novel insights regarding GPCR-mediated airway and vascular smooth muscle contraction as

Criteria for confirming sequence periodicity identified by Fourier transform analysis: application to GCR2, a candidate plant GPCR?

Science.gov (United States)

Illingworth, Christopher J R; Parkes, Kevin E; Snell, Christopher R; Mullineaux, Philip M; Reynolds, Christopher A

2008-03-01

Methods to determine periodicity in protein sequences are useful for inferring function. Fourier transformation is one approach but care is required to ensure the periodicity is genuine. Here we have shown that empirically-derived statistical tables can be used as a measure of significance. Genuine protein sequences data rather than randomly generated sequences were used as the statistical backdrop. The method has been applied to G-protein coupled receptor (GPCR) sequences, by Fourier transformation of hydrophobicity values, codon frequencies and the extent of over-representation of codon pairs; the latter being related to translational step times. Genuine periodicity was observed in the hydrophobicity whereas the apparent periodicity (as inferred from previously reported measures) in the translation step times was not validated statistically. GCR2 has recently been proposed as the plant GPCR receptor for the hormone abscisic acid. It has homology to the Lanthionine synthetase C-like family of proteins, an observation confirmed by fold recognition. Application of the Fourier transform algorithm to the GCR2 family revealed strongly predicted seven fold periodicity in hydrophobicity, suggesting why GCR2 has been reported to be a GPCR, despite negative indications in most transmembrane prediction algorithms. The underlying multiple sequence alignment, also required for the Fourier transform analysis of periodicity, indicated that the hydrophobic regions around the 7 GXXG motifs commence near the C-terminal end of each of the 7 inner helices of the alpha-toroid and continue to the N-terminal region of the helix. The results clearly explain why GCR2 has been understandably but erroneously predicted to be a GPCR.

The systematic annotation of the three main GPCR families in Reactome.

Science.gov (United States)

Jassal, Bijay; Jupe, Steven; Caudy, Michael; Birney, Ewan; Stein, Lincoln; Hermjakob, Henning; D'Eustachio, Peter

2010-07-29

Reactome is an open-source, freely available database of human biological pathways and processes. A major goal of our work is to provide an integrated view of cellular signalling processes that spans from ligand-receptor interactions to molecular readouts at the level of metabolic and transcriptional events. To this end, we have built the first catalogue of all human G protein-coupled receptors (GPCRs) known to bind endogenous or natural ligands. The UniProt database has records for 797 proteins classified as GPCRs and sorted into families A/1, B/2 and C/3 on the basis of amino acid sequence. To these records we have added details from the IUPHAR database and our own manual curation of relevant literature to create reactions in which 563 GPCRs bind ligands and also interact with specific G-proteins to initiate signalling cascades. We believe the remaining 234 GPCRs are true orphans. The Reactome GPCR pathway can be viewed as a detailed interactive diagram and can be exported in many forms. It provides a template for the orthology-based inference of GPCR reactions for diverse model organism species, and can be overlaid with protein-protein interaction and gene expression datasets to facilitate overrepresentation studies and other forms of pathway analysis. Database URL: http://www.reactome.org.

Mutations in the C-terminal region affect subcellular localization of crucian carp herpesvirus (CaHV) GPCR.

Science.gov (United States)

Wang, Jun; Gui, Lang; Chen, Zong-Yan; Zhang, Qi-Ya

2016-08-01

G protein-coupled receptors (GPCRs) are known as seven transmembrane domain receptors and consequently can mediate diverse biological functions via regulation of their subcellular localization. Crucian carp herpesvirus (CaHV) was recently isolated from infected fish with acute gill hemorrhage. CaHV GPCR of 349 amino acids (aa) was identified based on amino acid identity. A series of variants with truncation/deletion/substitution mutation in the C-terminal (aa 315-349) were constructed and expressed in fathead minnow (FHM) cells. The roles of three key C-terminal regions in subcellular localization of CaHV GPCR were determined. Lysine-315 (K-315) directed the aggregation of the protein preferentially at the nuclear side. Predicted N-myristoylation site (GGGWTR, aa 335-340) was responsible for punctate distribution in periplasm or throughout the cytoplasm. Predicted phosphorylation site (SSR, aa 327-329) and GGGWTR together determined the punctate distribution in cytoplasm. Detection of organelles localization by specific markers showed that the protein retaining K-315 colocalized with the Golgi apparatus. These experiments provided first evidence that different mutations of CaHV GPCR C-terminals have different affects on the subcellular localization of fish herpesvirus-encoded GPCRs. The study provided valuable information and new insights into the precise interactions between herpesvirus and fish cells, and could also provide useful targets for antiviral agents in aquaculture.

F4/80: the macrophage-specific adhesion-GPCR and its role in immunoregulation.

Science.gov (United States)

Lin, Hsi-Hsien; Stacey, Martin; Stein-Streilein, Joan; Gordon, Siamon

2010-01-01

As a macrophage-restricted reagent, the generation and application of the F4/80 mAb has greatly benefited the phenotypic characterization of mouse tissue macrophages for three decades. Following the molecular identification of the F4/80 antigen as an EGF-TM7 member of the adhesion-GPCR family, great interest was ignited to understand its cell type-specific expression pattern as well as its functional role in macrophage biology. Recent studies have shown that the F4/80 gene is regulated by a novel set of transcription factors that recognized a unique promoter sequence. Gene targeting experiments have produced two F4/80 knock out animal models and showed that F4/80 is not required for normal macrophage development. Nevertheless, the F4/80 receptor was found to be necessary for the induction of efferent CD8+ regulatory T cells responsible for peripheral immune tolerance. The identification of cellular ligands for F4/80 and delineation of its signaling pathway remain elusive but are critical to understand the in vivo role of this macrophage-specific adhesion-GPCR.

Self-Checking Cell-Based Assays for GPCR Desensitization and Resensitization.

Science.gov (United States)

Fisher, Gregory W; Fuhrman, Margaret H; Adler, Sally A; Szent-Gyorgyi, Christopher; Waggoner, Alan S; Jarvik, Jonathan W

2014-09-01

G protein-coupled receptors (GPCRs) play stimulatory or modulatory roles in numerous physiological states and processes, including growth and development, vision, taste and olfaction, behavior and learning, emotion and mood, inflammation, and autonomic functions such as blood pressure, heart rate, and digestion. GPCRs constitute the largest protein superfamily in the human and are the largest target class for prescription drugs, yet most are poorly characterized, and of the more than 350 nonolfactory human GPCRs, over 100 are orphans for which no endogenous ligand has yet been convincingly identified. We here describe new live-cell assays that use recombinant GPCRs to quantify two general features of GPCR cell biology-receptor desensitization and resensitization. The assays employ a fluorogen-activating protein (FAP) reporter that reversibly complexes with either of two soluble organic molecules (fluorogens) whose fluorescence is strongly enhanced when complexed with the FAP. Both assays require no wash or cleanup steps and are readily performed in microwell plates, making them adaptable to high-throughput drug discovery applications. © 2014 Society for Laboratory Automation and Screening.

GPCR Mutation information - GRIPDB | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us GRI...s and exposed in molecular surface. Data file File name: gripdb_mutation_info.zip File URL: ftp://ftp.biosciencedbc.jp/archive/gri...pdb/LATEST/gripdb_mutation_info.zip File size: 766 bytes Si...mple search URL http://togodb.biosciencedbc.jp/togodb/view/gripdb_mutation_info#en Data acquisition method P... Site Policy | Contact Us GPCR Mutation information - GRIPDB | LSDB Archive ...

GPCR Interaction - GRIPDB | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us GRI...ed information (disease etc.). Data file File name: gripdb_main.zip File URL: ftp://ftp.biosciencedbc.jp/archive/gripdb/LATEST/gri...godb.biosciencedbc.jp/togodb/view/gripdb_main#en Data acquisition method PDB, Refseq Data analysis method - ...Number of data entries 409 entries Data item Description GRIP ID Interaction ID Main Title Interaction title...tabase Database Description Download License Update History of This Database Site Policy | Contact Us GPCR Interaction - GRIPDB | LSDB Archive ...

Network governance of active employment policy

DEFF Research Database (Denmark)

Damgaard, Bodil; Torfing, Jacob

2010-01-01

The recent reform of the Danish governance system in the field of active employment policy has been subject to fierce criticism, as many commentators fear that it is the beginning of the end of the Danish Model of active stakeholder involvement. Drawing on both quantitative and qualitative data, ......, the tight metagovernance of the LECs does not seem to straightjacket the LECs as there is a considerable scope for local policy making which makes it worthwhile for the social partners to participate in the local networks.......The recent reform of the Danish governance system in the field of active employment policy has been subject to fierce criticism, as many commentators fear that it is the beginning of the end of the Danish Model of active stakeholder involvement. Drawing on both quantitative and qualitative data......, this study aims to analyse the impact of the governance reform by assessing the initial experiences with the Local Employment Councils (LECs). The analysis shows that the LECs are relatively well-functioning and contribute to an effective and democratic governance of local employment policy. Furthermore...

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.

Science.gov (United States)

Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S; Jain, Shalini; Lowell, Bradford B; Krashes, Michael J; Wess, Jürgen

2016-01-08

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.

Fighting obesity with a sugar-based library: discovery of novel MCH-1R antagonists by a new computational-VAST approach for exploration of GPCR binding sites.

Science.gov (United States)

Heifetz, Alexander; Barker, Oliver; Verquin, Geraldine; Wimmer, Norbert; Meutermans, Wim; Pal, Sandeep; Law, Richard J; Whittaker, Mark

2013-05-24

Obesity is an increasingly common disease. While antagonism of the melanin-concentrating hormone-1 receptor (MCH-1R) has been widely reported as a promising therapeutic avenue for obesity treatment, no MCH-1R antagonists have reached the market. Discovery and optimization of new chemical matter targeting MCH-1R is hindered by reduced HTS success rates and a lack of structural information about the MCH-1R binding site. X-ray crystallography and NMR, the major experimental sources of structural information, are very slow processes for membrane proteins and are not currently feasible for every GPCR or GPCR-ligand complex. This situation significantly limits the ability of these methods to impact the drug discovery process for GPCR targets in "real-time", and hence, there is an urgent need for other practical and cost-efficient alternatives. We present here a conceptually pioneering approach that integrates GPCR modeling with design, synthesis, and screening of a diverse library of sugar-based compounds from the VAST technology (versatile assembly on stable templates) to provide structural insights on the MCH-1R binding site. This approach creates a cost-efficient new avenue for structure-based drug discovery (SBDD) against GPCR targets. In our work, a primary VAST hit was used to construct a high-quality MCH-1R model. Following model validation, a structure-based virtual screen yielded a 14% hit rate and 10 novel chemotypes of potent MCH-1R antagonists, including EOAI3367472 (IC50 = 131 nM) and EOAI3367474 (IC50 = 213 nM).

Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling.

Science.gov (United States)

Bachmann, Verena A; Mayrhofer, Johanna E; Ilouz, Ronit; Tschaikner, Philipp; Raffeiner, Philipp; Röck, Ruth; Courcelles, Mathieu; Apelt, Federico; Lu, Tsan-Wen; Baillie, George S; Thibault, Pierre; Aanstad, Pia; Stelzl, Ulrich; Taylor, Susan S; Stefan, Eduard

2016-07-12

Scaffolding proteins organize the information flow from activated G protein-coupled receptors (GPCRs) to intracellular effector cascades both spatially and temporally. By this means, signaling scaffolds, such as A-kinase anchoring proteins (AKAPs), compartmentalize kinase activity and ensure substrate selectivity. Using a phosphoproteomics approach we identified a physical and functional connection between protein kinase A (PKA) and Gpr161 (an orphan GPCR) signaling. We show that Gpr161 functions as a selective high-affinity AKAP for type I PKA regulatory subunits (RI). Using cell-based reporters to map protein-protein interactions, we discovered that RI binds directly and selectively to a hydrophobic protein-protein interaction interface in the cytoplasmic carboxyl-terminal tail of Gpr161. Furthermore, our data demonstrate that a binary complex between Gpr161 and RI promotes the compartmentalization of Gpr161 to the plasma membrane. Moreover, we show that Gpr161, functioning as an AKAP, recruits PKA RI to primary cilia in zebrafish embryos. We also show that Gpr161 is a target of PKA phosphorylation, and that mutation of the PKA phosphorylation site affects ciliary receptor localization. Thus, we propose that Gpr161 is itself an AKAP and that the cAMP-sensing Gpr161:PKA complex acts as cilium-compartmentalized signalosome, a concept that now needs to be considered in the analyzing, interpreting, and pharmaceutical targeting of PKA-associated functions.

Rare platelet GPCR variants: what can we learn?

Science.gov (United States)

Nisar, S P; Jones, M L; Cunningham, M R; Mumford, A D; Mundell, S J

2015-07-01

Platelet-expressed GPCRs are critical regulators of platelet function. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis associated with coronary atherosclerosis and ischaemic stroke. However, anti-thrombotic drug therapy is associated with high inter-patient variability in therapeutic response and adverse bleeding side effects. In order to optimize the use of existing anti-platelet drugs and to develop new therapies, more detailed knowledge is required relating to the molecular mechanisms that regulate GPCR and therefore platelet function. One approach has been to identify rare, function-disrupting mutations within key platelet proteins in patients with bleeding disorders. In this review, we describe how an integrated functional genomics strategy has contributed important structure-function information about platelet GPCRs with specific emphasis upon purinergic and thromboxane A2 receptors. We also discuss the potential implications these findings have for pharmacotherapy and for understanding the molecular basis of mild bleeding disorders. © 2014 The British Pharmacological Society.

Role of spatial inhomogenity in GPCR dimerisation predicted by receptor association-diffusion models

Science.gov (United States)

Deshpande, Sneha A.; Pawar, Aiswarya B.; Dighe, Anish; Athale, Chaitanya A.; Sengupta, Durba

2017-06-01

G protein-coupled receptor (GPCR) association is an emerging paradigm with far reaching implications in the regulation of signalling pathways and therapeutic interventions. Recent super resolution microscopy studies have revealed that receptor dimer steady state exhibits sub-second dynamics. In particular the GPCRs, muscarinic acetylcholine receptor M1 (M1MR) and formyl peptide receptor (FPR), have been demonstrated to exhibit a fast association/dissociation kinetics, independent of ligand binding. In this work, we have developed a spatial kinetic Monte Carlo model to investigate receptor homo-dimerisation at a single receptor resolution. Experimentally measured association/dissociation kinetic parameters and diffusion coefficients were used as inputs to the model. To test the effect of membrane spatial heterogeneity on the simulated steady state, simulations were compared to experimental statistics of dimerisation. In the simplest case the receptors are assumed to be diffusing in a spatially homogeneous environment, while spatial heterogeneity is modelled to result from crowding, membrane micro-domains and cytoskeletal compartmentalisation or ‘corrals’. We show that a simple association-diffusion model is sufficient to reproduce M1MR association statistics, but fails to reproduce FPR statistics despite comparable kinetic constants. A parameter sensitivity analysis is required to reproduce the association statistics of FPR. The model reveals the complex interplay between cytoskeletal components and their influence on receptor association kinetics within the features of the membrane landscape. These results constitute an important step towards understanding the factors modulating GPCR organisation.

Governance of Arctic Offshore Oil & Gas Activities: Multilevel Governance & Legal Pluralism at Stake

DEFF Research Database (Denmark)

Pelaudeix, Cecile

2015-01-01

This article analyses the governance process of offshore oil and gas activities in the Arctic with the concept of multilevelgovernance and legal pluralism to address both issues of management of the environment and public participation. The analysis goes beyond the single issue of fragmentation p...... and from regional government, indigenous shareholders and corporation perspectives, could be helpful in providing relevant actors with arguments to weigh the decision on seismic and drilling activities in relation to risk acceptance.......This article analyses the governance process of offshore oil and gas activities in the Arctic with the concept of multilevelgovernance and legal pluralism to address both issues of management of the environment and public participation. The analysis goes beyond the single issue of fragmentation...... pertaining to the international and supranational levels, to encompass national and regional levels and evaluate how the interactions between those levels structure the policy process and impact the efficiency of environmental management and public participation. Four paths of reflection arise from...

Globalization of nuclear activities and global governance

International Nuclear Information System (INIS)

Sefidvash, Farhang

1997-01-01

The safe production of nuclear energy as well as the disarmament of nuclear weapons and the peaceful utilization of nuclear materials resulting from dismantling of such weapons are some of the formidable problems of global governance. The Commission on Global Governance was established in 1992 in the belief that international developments had created a unique opportunity for strengthening global co-operation to meet the challenge of securing peace, achieving sustainable development, and universalizing democracy. Here a summary of their proposals on the globalization of nuclear activities to face challenges of the coming century is given. To follow up their activities by the worlds community in general. The research Centre for Global Governance (RCGG) at the Federal University of Rio Grande do Sul was established. Already a great number of researchers from many different countries have adhered to the Centre. Here the program of the RCGG is described. (author)

Globalization of nuclear activities and global governance

Energy Technology Data Exchange (ETDEWEB)

Sefidvash, Farhang [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Dept. de Engenharia Nuclear

1997-07-01

The safe production of nuclear energy as well as the disarmament of nuclear weapons and the peaceful utilization of nuclear materials resulting from dismantling of such weapons are some of the formidable problems of global governance. The Commission on Global Governance was established in 1992 in the belief that international developments had created a unique opportunity for strengthening global co-operation to meet the challenge of securing peace, achieving sustainable development, and universalizing democracy. Here a summary of their proposals on the globalization of nuclear activities to face challenges of the coming century is given. To follow up their activities by the worlds community in general. The research Centre for Global Governance (RCGG) at the Federal University of Rio Grande do Sul was established. Already a great number of researchers from many different countries have adhered to the Centre. Here the program of the RCGG is described. (author)

A new inhibitor of the ?-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

OpenAIRE

Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, St?phane A.

2017-01-01

In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, ?-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of ?-arrestin recruitment to the receptor and ?-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecul...

Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

Directory of Open Access Journals (Sweden)

Groot-Kormelink Paul J

2012-10-01

Full Text Available Abstract Background Alveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansion in-vitro and therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60 are frequently used to model macrophage function. Methods The availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR and ion channel expression in alveolar macrophages and their widely used surrogates. Results The complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates. Conclusions The data described in this report provides insight into the appropriate choice of cell models for

Regulation of P450-mediated permethrin resistance in Culex quinquefasciatus by the GPCR/Gαs/AC/cAMP/PKA signaling cascade.

Science.gov (United States)

Li, Ting; Liu, Nannan

2017-12-01

This study explores the role of G-protein-coupled receptor-intracellular signaling in the development of P450-mediated insecticide resistance in mosquitoes, Culex quinquefasciatus , focusing on the essential function of the GPCRs and their downstream effectors of Gs alpha subunit protein (Gαs) and adenylyl cyclase (ACs) in P450-mediated insecticide resistance of Culex mosquitoes. Our RNAi-mediated functional study showed that knockdown of Gαs caused the decreased expression of the downstream effectors of ACs and PKAs in the GPCR signaling pathway and resistance P450 genes, whereas knockdown of ACs decreased the expression of PKAs and resistance P450 genes. Knockdown of either Gαs or ACs resulted in an increased susceptibility of mosquitoes to permethrin. These results add significantly to our understanding of the molecular basis of resistance P450 gene regulation through GPCR/Gαs/AC/cAMP-PKA signaling pathways in the insecticide resistance of mosquitoes. The temporal and spatial dynamic analyses of GPCRs, Gαs, ACs, PKAs, and P450s in two insecticide resistant mosquito strains revealed that all the GPCR signaling pathway components tested, namely GPCRs, Gαs, ACs and PKAs, were most highly expressed in the brain for both resistant strains, suggesting the role played by these genes in signaling transduction and regulation. The resistance P450 genes were mainly expressed in the brain, midgut and malpighian tubules (MTs), suggesting their critical function in the central nervous system and importance for detoxification. The temporal dynamics analysis for the gene expression showed a diverse expression profile during mosquito development, indicating their initially functional importance in response to exposure to insecticides during their life stages.

42 CFR 137.211 - How does a Self-Governance Tribe learn whether self-governance activities have resulted in...

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false How does a Self-Governance Tribe learn whether self-governance activities have resulted in savings as described in § 137.210. 137.211 Section 137.211 Public... OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Operational Provisions Savings § 137.211 How does...

Towards inclusive governance of hazardous activities, synthesis of the conclusions of the 2001-2003 Trustnet activities

International Nuclear Information System (INIS)

Heriard-Dubreuil, G.

2004-01-01

TRUSTNET is a European pluralistic think tank network on the governance of hazardous activities since 1997. It is involving the participation of some 150 key decision makers, stakeholders and experts at European, national and local levels in activities having impact on health and the environment. The participants of TRUSTNET are representatives of public authorities at national and European levels, industry, trade unions, local governments, NGOs. They are also consumers or lay citizens, together with a multidisciplinary group of experts in risk management, public health, political sciences, sociology, psychology, economics, law and ethics. TRUSTNET is supported by the European Commission (DG- Research - Radiation protection) as a Concerted Action. The work programme of TRUSTNET is based on a participatory methodology and a co-expertise of actual case studies involving experts and non-experts. From 1997 to 1999, TRUSTNET has identified the severe difficulties and multiple social blockages affecting the credibility, effectiveness and legitimacy of traditional regulatory framework of hazardous activities. It has also identified emerging features of inclusive risk governance as a major opportunity for overcoming the observed difficulties. The conclusions of the 1997-1999 exercise have been reported in 2000 in the 'TRUSTNET Framework: a New Perspective on Risk Governance'. From 2001 to 2003, TRUSTNET has carried on the reflection and more specifically investigated the possible strategies for implementing in Europe inclusive governance in the various activities entailing risks for health and the environment. The presentation ('Towards Inclusive Governance') will outline presenting the main conclusions of this 2001-2003 exercise. (author)

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

Science.gov (United States)

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

2018-04-20

The dopamine D2 receptor (D2R) is a G protein-coupled receptor (GPCR) that is critical for many central nervous system functions. The D2R carries out these functions by signaling through two transducers: G proteins and β-arrestins (βarrs). Selectively engaging either the G protein or βarr pathway may be a way to improve drugs targeting GPCRs. The current model of GPCR signal transduction posits a chain of events where G protein activation ultimately leads to βarr recruitment. GPCR kinases (GRKs), which are regulated by G proteins and whose kinase action facilitates βarr recruitment, bridge these pathways. Therefore, βarr recruitment appears to be intimately tied to G protein activation via GRKs. Here we sought to understand how GRK2 action at the D2R would be disrupted when G protein activation is eliminated and the effect of this on βarr recruitment. We used two recently developed biased D2R mutants that can preferentially interact either with G proteins or βarrs as well as a βarr-biased D2R ligand, UNC9994. With these functionally selective tools, we investigated the mechanism whereby the βarr-preferring D2R achieves βarr pathway activation in the complete absence of G protein activation. We describe how direct, G protein-independent recruitment of GRK2 drives interactions at the βarr-preferring D2R and also contributes to βarr recruitment at the WT D2R. Additionally, we found an additive interaction between the βarr-preferring D2R mutant and UNC9994. These results reveal that the D2R can directly recruit GRK2 without G protein activation and that this mechanism may have relevance to achieving βarr-biased signaling. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Impedance analysis of GPCR-mediated changes in endothelial barrier function: overview and fundamental considerations for stable and reproducible measurements.

Science.gov (United States)

Stolwijk, Judith A; Matrougui, Khalid; Renken, Christian W; Trebak, Mohamed

2015-10-01

The past 20 years has seen significant growth in using impedance-based assays to understand the molecular underpinning of endothelial and epithelial barrier function in response to physiological agonists and pharmacological and toxicological compounds. Most studies on barrier function use G protein-coupled receptor (GPCR) agonists which couple to fast and transient changes in barrier properties. The power of impedance-based techniques such as electric cell-substrate impedance sensing (ECIS) resides in its ability to detect minute changes in cell layer integrity label-free and in real-time ranging from seconds to days. We provide a comprehensive overview of the biophysical principles, applications, and recent developments in impedance-based methodologies. Despite extensive application of impedance analysis in endothelial barrier research, little attention has been paid to data analysis and critical experimental variables, which are both essential for signal stability and reproducibility. We describe the rationale behind common ECIS data presentation and interpretation and illustrate practical guidelines to improve signal intensity by adapting technical parameters such as electrode layout, monitoring frequency, or parameter (resistance versus impedance magnitude). Moreover, we discuss the impact of experimental parameters, including cell source, liquid handling, and agonist preparation on signal intensity and kinetics. Our discussions are supported by experimental data obtained from human microvascular endothelial cells challenged with three GPCR agonists, thrombin, histamine, and sphingosine-1-phosphate.

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

Science.gov (United States)

Tsukamoto, Hisao; Farrens, David L

2013-09-27

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

Navigating the conformational landscape of G protein-coupled receptor kinases during allosteric activation.

Science.gov (United States)

Yao, Xin-Qiu; Cato, M Claire; Labudde, Emily; Beyett, Tyler S; Tesmer, John J G; Grant, Barry J

2017-09-29

G protein-coupled receptors (GPCRs) are essential for transferring extracellular signals into carefully choreographed intracellular responses controlling diverse aspects of cell physiology. The duration of GPCR-mediated signaling is primarily regulated via GPCR kinase (GRK)-mediated phosphorylation of activated receptors. Although many GRK structures have been reported, the mechanisms underlying GRK activation are not well-understood, in part because it is unknown how these structures map to the conformational landscape available to this enzyme family. Unlike most other AGC kinases, GRKs rely on their interaction with GPCRs for activation and not phosphorylation. Here, we used principal component analysis of available GRK and protein kinase A crystal structures to identify their dominant domain motions and to provide a framework that helps evaluate how close each GRK structure is to being a catalytically competent state. Our results indicated that disruption of an interface formed between the large lobe of the kinase domain and the regulator of G protein signaling homology domain (RHD) is highly correlated with establishment of the active conformation. By introducing point mutations in the GRK5 RHD-kinase domain interface, we show with both in silico and in vitro experiments that perturbation of this interface leads to higher phosphorylation activity. Navigation of the conformational landscape defined by this bioinformatics-based study is likely common to all GPCR-activated GRKs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Combining on-chip synthesis of a focused combinatorial library with computational target prediction reveals imidazopyridine GPCR ligands.

Science.gov (United States)

Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Schneider, Gisbert

2014-01-07

Using the example of the Ugi three-component reaction we report a fast and efficient microfluidic-assisted entry into the imidazopyridine scaffold, where building block prioritization was coupled to a new computational method for predicting ligand-target associations. We identified an innovative GPCR-modulating combinatorial chemotype featuring ligand-efficient adenosine A1/2B and adrenergic α1A/B receptor antagonists. Our results suggest the tight integration of microfluidics-assisted synthesis with computer-based target prediction as a viable approach to rapidly generate bioactivity-focused combinatorial compound libraries with high success rates. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The orphan adhesion-GPCR GPR126 is required for embryonic development in the mouse.

Directory of Open Access Journals (Sweden)

Helen Waller-Evans

2010-11-01

Full Text Available Adhesion-GPCRs provide essential cell-cell and cell-matrix interactions in development, and have been implicated in inherited human diseases like Usher Syndrome and bilateral frontoparietal polymicrogyria. They are the second largest subfamily of seven-transmembrane spanning proteins in vertebrates, but the function of most of these receptors is still not understood. The orphan Adhesion-GPCR GPR126 has recently been shown to play an essential role in the myelination of peripheral nerves in zebrafish. In parallel, whole-genome association studies have implicated variation at the GPR126 locus as a determinant of body height in the human population. The physiological function of GPR126 in mammals is still unknown. We describe a targeted mutation of GPR126 in the mouse, and show that GPR126 is required for embryonic viability and cardiovascular development.

Directory of DOE and contractor personnel involved in non-government standards activities

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-08-01

This document contains a listing of DOE employees and DOE contractors who have submitted form DOE F 1300.2, Record of Non-Government Standards Activity. Additional names were added from rosters supplied by non-Government standards bodies.

Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor

Energy Technology Data Exchange (ETDEWEB)

Burg, John S.; Ingram, Jessica R.; Venkatakrishnan, A.J.; Jude, Kevin M.; Dukkipati, Abhiram; Feinberg, Evan N.; Angelini, Alessandro; Waghray, Deepa; Dror, Ron O.; Ploegh, Hidde L.; Garcia, K. Christopher (Stanford); (Stanford-MED); (Whitehead); (MIT)

2015-03-05

Chemokines are small proteins that function as immune modulators through activation of chemokine G protein-coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state-like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor’s inactive state.

Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling

Science.gov (United States)

Luchetti, Giovanni; Sircar, Ria; Kong, Jennifer H; Nachtergaele, Sigrid; Sagner, Andreas; Byrne, Eamon FX; Covey, Douglas F; Siebold, Christian; Rohatgi, Rajat

2016-01-01

Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals. Unlike many GPCRs, which are regulated by cholesterol through their heptahelical transmembrane domains, SMO is activated by cholesterol through its extracellular cysteine-rich domain (CRD). Residues shown to mediate cholesterol binding to the CRD in a recent structural analysis also dictate SMO activation, both in response to cholesterol and to native Hh ligands. Our results show that cholesterol can initiate signaling from the cell surface by engaging the extracellular domain of a GPCR and suggest that SMO activity may be regulated by local changes in cholesterol abundance or accessibility. DOI: http://dx.doi.org/10.7554/eLife.20304.001 PMID:27705744

A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

Science.gov (United States)

Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, Stéphane A.; Bouvier, Michel

2017-04-01

In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways.

A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein

DEFF Research Database (Denmark)

Whorton, Matthew R; Bokoch, Michael P; Rasmussen, Søren Gøgsig Faarup

2007-01-01

G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet...... the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, has led to speculation that GPCR dimers may be required for efficient activation of G proteins. However......, technical limitations have precluded a definitive analysis of G protein coupling to monomeric GPCRs in a biochemically defined and membrane-bound system. Here we demonstrate that a prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated into a reconstituted high-density lipoprotein...

DOE Technical Standards List. Directory of DOE and contractor personnel involved in non-government standards activities

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-06-01

This is a periodic report on the level of agency participation in non-Government standards activities. This technical standards list is intended to assist US Department of Energy (DOE) management and other personnel involved in the DOE technical Standards Program by identifying those participating individuals. The body of this document contains a listing of DOE employees and DOE contractors who have submitted a Record of Non-Government Standards Activity. Additional names were added from rosters supplied by non-Government standards bodies. Appendices to this document are provided to list the information by parent employment organization, by non-Government standards activity, and by the proper names of the non-Government standards organizations and committees.

Reviewing education and training for governance and active citizenship in Europe. A central and eastern European perspective. The implications of the research for Central and Eastern European policy design on active citizenship and governance

NARCIS (Netherlands)

Chioncel, N.E.; Jansen, T.J.M.

2004-01-01

The RE-ETGACE Project, "Reviewing Education and Training for Governance and Active Citizenship in Europe - A Central and Eastern European Perspective" is a complementary measure to the original ETGACE Project "Education and Training for Governance and Active Citizenship in Europe". The ETGAGE

Reviewing education and training for governance and active citizenship in Europe : a Central and Eastern European perspective : the implications of the research for Central and Eastern European policy design on active citizenship and governance

NARCIS (Netherlands)

Chioncel, Nicoleta; Jansen, Theo

2004-01-01

The RE-ETGACE Project, 'Reviewing Education and Training for Governance and Active Citizenship in Europe - A Central and Eastern European Perspective' is a complementary measure to the original ETGACE Project 'Education and Training for Governance and Active Citizenship in Europe'. The ETGAGE

Pivotal role of extended linker 2 in the activation of Gα by G protein-coupled receptor.

Science.gov (United States)

Huang, Jianyun; Sun, Yutong; Zhang, J Jillian; Huang, Xin-Yun

2015-01-02

G protein-coupled receptors (GPCRs) relay extracellular signals mainly to heterotrimeric G-proteins (Gαβγ) and they are the most successful drug targets. The mechanisms of G-protein activation by GPCRs are not well understood. Previous studies have revealed a signal relay route from a GPCR via the C-terminal α5-helix of Gα to the guanine nucleotide-binding pocket. Recent structural and biophysical studies uncover a role for the opening or rotating of the α-helical domain of Gα during the activation of Gα by a GPCR. Here we show that β-adrenergic receptors activate eight Gαs mutant proteins (from a screen of 66 Gαs mutants) that are unable to bind Gβγ subunits in cells. Five of these eight mutants are in the αF/Linker 2/β2 hinge region (extended Linker 2) that connects the Ras-like GTPase domain and the α-helical domain of Gαs. This extended Linker 2 is the target site of a natural product inhibitor of Gq. Our data show that the extended Linker 2 is critical for Gα activation by GPCRs. We propose that a GPCR via its intracellular loop 2 directly interacts with the β2/β3 loop of Gα to communicate to Linker 2, resulting in the opening and closing of the α-helical domain and the release of GDP during G-protein activation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A Molecular Mechanism for Sequential Activation of a G Protein-Coupled Receptor

DEFF Research Database (Denmark)

Grundmann, Manuel; Tikhonova, Irina G; Hudson, Brian D

2016-01-01

Ligands targeting G protein-coupled receptors (GPCRs) are currently classified as either orthosteric, allosteric, or dualsteric/bitopic. Here, we introduce a new pharmacological concept for GPCR functional modulation: sequential receptor activation. A hallmark feature of this is a stepwise ligand...

25 CFR 170.623 - How are IRR Program projects and activities included in a self-governance agreement?

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false How are IRR Program projects and activities included in a self-governance agreement? 170.623 Section 170.623 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... self-governance agreement? To include an IRR Program project or activity in a self-governance agreement...

Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor

Energy Technology Data Exchange (ETDEWEB)

Kuwasako, Kenji, E-mail: kuwasako@med.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, Miyazaki, 889-1692 (Japan); Sekiguchi, Toshio [Noto Marine Laboratory, Division of Marine Environmental Studies, Institute of Nature and Environmental Technology, Kanazawa University, Ishikawa, 927-0553 (Japan); Nagata, Sayaka [Division of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692 (Japan); Jiang, Danfeng; Hayashi, Hidetaka [Frontier Science Research Center, University of Miyazaki, Miyazaki, 889-1692 (Japan); Murakami, Manabu [Department of Pharmacology, Hirosaki University, Graduate School of Medicine, Hirosaki, 036-8562 (Japan); Hattori, Yuichi [Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194 (Japan); Kitamura, Kazuo [Division of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, Miyazaki, 889-1692 (Japan)

2016-02-19

Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor-like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM{sub 1} receptor). Here, we investigated the effects of the five non-visual GPCR kinases (GRKs 2 through 6) on the cell surface expression of the human (h)AM{sub 1} receptor by cotransfecting each of these GRKs into HEK-293 cells that stably expressed hRAMP2. Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM{sub 1} receptor was markedly decreased prior to stimulation with AM, thereby attenuating both the specific [{sup 125}I]AM binding and AM-induced cAMP production. These inhibitory effects of both GRKs were abolished by the replacement of the cytoplasmic C-terminal tail (C-tail) of CLR with that of the calcitonin receptor (a family B GPCR) or β{sub 2}-adrenergic receptor (a family A GPCR). Among the sequentially truncated CLR C-tail mutants, those lacking the five residues 449–453 (Ser-Phe-Ser-Asn-Ser) abolished the inhibition of the cell surface expression of CLR via the overexpression of GRK4 or GRK5. Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM{sub 1} receptor and further determined the region of the CLR C-tail responsible for this GRK function. - Highlights: • We discovered a novel function of GRKs in GPCR trafficking using human CLR/RAMP2. • GRKs 4 and 5 markedly inhibited the cell surface expression of human CLR/RAMP2. • Both GRKs exhibited highly significant receptor signaling inhibition. • Five residues of the C-terminal tail of CLR govern this function of GRKs.

Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor

International Nuclear Information System (INIS)

Kuwasako, Kenji; Sekiguchi, Toshio; Nagata, Sayaka; Jiang, Danfeng; Hayashi, Hidetaka; Murakami, Manabu; Hattori, Yuichi; Kitamura, Kazuo; Kato, Johji

2016-01-01

Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor-like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM_1 receptor). Here, we investigated the effects of the five non-visual GPCR kinases (GRKs 2 through 6) on the cell surface expression of the human (h)AM_1 receptor by cotransfecting each of these GRKs into HEK-293 cells that stably expressed hRAMP2. Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM_1 receptor was markedly decreased prior to stimulation with AM, thereby attenuating both the specific ["1"2"5I]AM binding and AM-induced cAMP production. These inhibitory effects of both GRKs were abolished by the replacement of the cytoplasmic C-terminal tail (C-tail) of CLR with that of the calcitonin receptor (a family B GPCR) or β_2-adrenergic receptor (a family A GPCR). Among the sequentially truncated CLR C-tail mutants, those lacking the five residues 449–453 (Ser-Phe-Ser-Asn-Ser) abolished the inhibition of the cell surface expression of CLR via the overexpression of GRK4 or GRK5. Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM_1 receptor and further determined the region of the CLR C-tail responsible for this GRK function. - Highlights: • We discovered a novel function of GRKs in GPCR trafficking using human CLR/RAMP2. • GRKs 4 and 5 markedly inhibited the cell surface expression of human CLR/RAMP2. • Both GRKs exhibited highly significant receptor signaling inhibition. • Five residues of the C-terminal tail of CLR govern this function of GRKs.

Chronic regulation of colonic epithelial secretory function by activation of G protein-coupled receptors.

LENUS (Irish Health Repository)

Toumi, F

2011-02-01

Enteric neurotransmitters that act at G protein-coupled receptors (GPCRs) are well known to acutely promote epithelial Cl(-) and fluid secretion. Here we examined if acute GPCR activation might have more long-term consequences for epithelial secretory function.

Setting the scene: Human activities, environmental impacts and governance arrangements in Antarctica

NARCIS (Netherlands)

Tin, T.; Lamers, M.A.J.; Liggett, D.; Maher, P.T.; Hughes, K.A.

2014-01-01

The scope and intensity of human activity in the Antarctic region has changed considerably over the past 100 years, resulting in significant modifications to the Antarctic environment and its ecosystems, and to the institutional arrangements governing human activities. Since the nineteenth century,

Interaction of Protease-Activated Receptor 2 with G Proteins and Beta-Arrestin 1 Studied by Bioluminescence Resonance Energy Transfer

Directory of Open Access Journals (Sweden)

Mohammed Akli eAyoub

2013-12-01

Full Text Available G protein-coupled receptors (GPCRs are well recognized as being able to activate several signaling pathways through the activation of different G proteins as well as other signaling proteins such as beta-arrestins. Therefore, understanding how such multiple GPCR-mediated signaling can be integrated constitute an important aspect. Here, we applied bioluminescence resonance energy transfer (BRET to shed more light on the G protein coupling profile of trypsin receptor, or protease-activated receptor 2 (PAR2, and its interaction with beta-arrestin1. Using YFP and Rluc fusion constructs expressed in COS-7 cells, BRET data revealed a pre-assembly of PAR2 with both Galphai1 and Galphao and a rapid and transient activation of these G proteins upon receptor activation. In contrast, no preassembly of PAR2 with Galpha12 could be detected and their physical association can be measured with a very slow and sustained kinetics similar to that of beta-arrestin1 recruitment. These data demonstrate the coupling of PAR2 with Galphai1, Galphao and Galpha12 in COS-7 cells with differences in the kinetics of GPCR-G protein coupling, a parameter that very likely influences the cellular response. Moreover, this further illustrates that preassembly or agonist-induced G protein interaction depends on receptor-G protein pairs indicating another level of complexity and regulation of the signaling of GPCR-G protein complexes and its multiplicity.

Cross-country differences in government sector activities

Directory of Open Access Journals (Sweden)

Primož Pevcin

2005-06-01

Full Text Available The purpose of the analysis presented in the article is to identify various economic, social, political, demographic and cultural factors that could shape the differences in the size of government sector across countries and, with the use of econometric analysis empirically verify the effect of those factors. The analysis focuses only on ”budgetary” government, meaning that the size of government is measured with a certain government spending ratio. The results of the analysis revealed that economic factors are more important in explaining the variation in the size of government consumption spending, whereas political, social and cultural factors are more important in explaining the variation in the size of transfer spending. In addition, the results indicate that the relative size of government spending is inversely related to the extent of the regulation of the economy.

Decentralization and centralization: governing the activation of social assistance recipients in Europe

NARCIS (Netherlands)

Minas, R.; Wright, S.; van Berkel, H.H.A.

2012-01-01

Purpose – The purpose of this article is to examine the governance of activation in relation to the decentralization and centralization of activation for social assistance recipients in Sweden, The Netherlands and the UK. Design/methodology/approach – This paper outlines broad trends in the

Rac1-stimulated macropinocytosis enhances Gβγ activation of PI3Kβ.

Science.gov (United States)

Erami, Zahra; Khalil, Bassem D; Salloum, Gilbert; Yao, Yanhua; LoPiccolo, Jaclyn; Shymanets, Aliaksei; Nürnberg, Bernd; Bresnick, Anne R; Backer, Jonathan M

2017-11-16

Phosphoinositide 3-kinases (PI 3-kinases) are regulated by a diverse range of upstream activators, including receptor tyrosine kinases (RTKs), G-protein-coupled receptors (GPCRs), and small GTPases from the Ras, Rho and Rab families. For the Class IA PI 3-kinase PI3Kβ, two mechanisms for GPCR-mediated regulation have been described: direct binding of Gβγ subunits to the C2-helical domain linker of p110β, and Dock180/Elmo1-mediated activation of Rac1, which binds to the Ras-Binding Domain of p110β. We now show that the integration of these dual pathways is unexpectedly complex. In breast cancer cells, expression of constitutively activated Rac1 (CA-Rac1) along with either GPCR stimulation or expression of Gβγ led to an additive PI3Kβ-dependent activation of Akt. Whereas CA-Rac1-mediated activation of Akt was blocked in cells expressing a mutated PI3Kβ that cannot bind Gβγ, Gβγ and GPCR-mediated activation of Akt was preserved when Rac1 binding to PI3Kβ was blocked. Surprisingly, PI3Kβ-dependent CA-Rac1 signaling to Akt was still seen in cells expressing a mutant p110β that cannot bind Rac1. Instead of directly binding to PI3Kβ, CA-Rac1 acts by enhancing Gβγ coupling to PI3Kβ, as CA-Rac1-mediated Akt activation was blocked by inhibitors of Gβγ. Cells expressing CA-Rac1 exhibited a robust induction of macropinocytosis, and inhibitors of macropinocytosis blocked the activation of Akt by CA-Rac1 or lysophosphatidic acid. Our data suggest that Rac1 can potentiate the activation of PI3Kβ by GPCRs through an indirect mechanism, by driving the formation of macropinosomes that serve as signaling platforms for Gβγ coupling to PI3Kβ. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Opportunism Motivation of Environmental Protection Activism and Corporate Governance: An Empirical Study from China

Directory of Open Access Journals (Sweden)

Shengnan Li

2018-05-01

Full Text Available In the study of environmental protection issues for more than forty years, research on the impact of financial performance on environmental protection has been one of the important branches. In the framework of principal-agent theory, this paper explores the opportunism motives in a company’s environmental protection activism and the moderating role of corporate governance using the data of Chinese listed companies from 2005 to 2016. The study finds that: (1 the company’s environmental protection activism is driven by the opportunist motives of policymakers who want to mask their inability; and (2 environmental protection activism does not enhance the company’s future performance and value creation capability. Further studies find that corporate governance mechanisms play different moderating roles. Fund Shareholders play a positive governance role and reduce the correlation between financial performance and environmental protection activism. However, independence of the board of directors intensifies the opportunist motives. This paper provides new theoretical explanations for environmental protection decision-making, provides novel enlightenment for the protection of environmental protection policies in developing countries and regions.

Ligand binding modes from low resolution GPCR models and mutagenesis: chicken bitter taste receptor as a test-case.

Science.gov (United States)

Di Pizio, Antonella; Kruetzfeldt, Louisa-Marie; Cheled-Shoval, Shira; Meyerhof, Wolfgang; Behrens, Maik; Niv, Masha Y

2017-08-15

Bitter taste is one of the basic taste modalities, warning against consuming potential poisons. Bitter compounds activate members of the bitter taste receptor (Tas2r) subfamily of G protein-coupled receptors (GPCRs). The number of functional Tas2rs is species-dependent. Chickens represent an intriguing minimalistic model, because they detect the bitter taste of structurally different molecules with merely three bitter taste receptor subtypes. We investigated the binding modes of several known agonists of a representative chicken bitter taste receptor, ggTas2r1. Because of low sequence similarity between ggTas2r1 and crystallized GPCRs (~10% identity, ~30% similarity at most), the combination of computational approaches with site-directed mutagenesis was used to characterize the agonist-bound conformation of ggTas2r1 binding site between TMs 3, 5, 6 and 7. We found that the ligand interactions with N93 in TM3 and/or N247 in TM5, combined with hydrophobic contacts, are typically involved in agonist recognition. Next, the ggTas2r1 structural model was successfully used to identify three quinine analogues (epiquinidine, ethylhydrocupreine, quinidine) as new ggTas2r1 agonists. The integrated approach validated here may be applicable to additional cases where the sequence identity of the GPCR of interest and the existing experimental structures is low.

cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells.

Science.gov (United States)

Inda, Carolina; Bonfiglio, Juan José; Dos Santos Claro, Paula A; Senin, Sergio A; Armando, Natalia G; Deussing, Jan M; Silberstein, Susana

2017-05-16

Corticotropin-releasing hormone receptor 1 (CRHR1) activates the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). Both cAMP sources were shown to be required for the phosphorylation of ERK1/2 triggered by activated G protein coupled receptor (GPCR) CRHR1 in neuronal and neuroendocrine contexts. Here, we show that activated CRHR1 promotes growth arrest and neurite elongation in neuronal hippocampal cells (HT22-CRHR1 cells). By characterising CRHR1 signalling mechanisms involved in the neuritogenic effect, we demonstrate that neurite outgrowth in HT22-CRHR1 cells takes place by a sAC-dependent, ERK1/2-independent signalling cascade. Both tmACs and sAC are involved in corticotropin-releasing hormone (CRH)-mediated CREB phosphorylation and c-fos induction, but only sAC-generated cAMP pools are critical for the neuritogenic effect of CRH, further highlighting the engagement of two sources of cAMP downstream of the activation of a GPCR, and reinforcing the notion that restricted cAMP microdomains may regulate independent cellular processes.

Regulator of G protein signaling 2 (RGS2 and RGS4 form distinct G protein-dependent complexes with protease activated-receptor 1 (PAR1 in live cells.

Directory of Open Access Journals (Sweden)

Sungho Ghil

Full Text Available Protease-activated receptor 1 (PAR1 is a G-protein coupled receptor (GPCR that is activated by natural proteases to regulate many physiological actions. We previously reported that PAR1 couples to Gi, Gq and G12 to activate linked signaling pathways. Regulators of G protein signaling (RGS proteins serve as GTPase activating proteins to inhibit GPCR/G protein signaling. Some RGS proteins interact directly with certain GPCRs to modulate their signals, though cellular mechanisms dictating selective RGS/GPCR coupling are poorly understood. Here, using bioluminescence resonance energy transfer (BRET, we tested whether RGS2 and RGS4 bind to PAR1 in live COS-7 cells to regulate PAR1/Gα-mediated signaling. We report that PAR1 selectively interacts with either RGS2 or RGS4 in a G protein-dependent manner. Very little BRET activity is observed between PAR1-Venus (PAR1-Ven and either RGS2-Luciferase (RGS2-Luc or RGS4-Luc in the absence of Gα. However, in the presence of specific Gα subunits, BRET activity was markedly enhanced between PAR1-RGS2 by Gαq/11, and PAR1-RGS4 by Gαo, but not by other Gα subunits. Gαq/11-YFP/RGS2-Luc BRET activity is promoted by PAR1 and is markedly enhanced by agonist (TFLLR stimulation. However, PAR1-Ven/RGS-Luc BRET activity was blocked by a PAR1 mutant (R205A that eliminates PAR1-Gq/11 coupling. The purified intracellular third loop of PAR1 binds directly to purified His-RGS2 or His-RGS4. In cells, RGS2 and RGS4 inhibited PAR1/Gα-mediated calcium and MAPK/ERK signaling, respectively, but not RhoA signaling. Our findings indicate that RGS2 and RGS4 interact directly with PAR1 in Gα-dependent manner to modulate PAR1/Gα-mediated signaling, and highlight a cellular mechanism for selective GPCR/G protein/RGS coupling.

DOE technical standards list: Directory of DOE and contractor personnel involved in non-government standards activities

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-08-01

The body of this document contains a listing of DOE employees and DOE contractors who have submitted form DOE F 1300.2, Record of Non-Government Standards Activity, which is attached to the end of this document and to DOE Order 1300.2A. Additional names were added from rosters supplied by non-Government standards bodies. The committees or governing bodies in which the person participates is listed after each name. An asterisk preceding the committee notation indicates that the person has identified himself or herself as the DOE representative on that committee. Appendices to this document are also provided to sort the information by the parent employment organization, by non-Government standards activity, and by the proper names of the non-Government standards organizations and committees. DOE employees and contractors listed in this TSL are those recorded as of July 1, 1996.

DOE technical standards list: Directory of DOE and contractor personnel involved in non-government standards activities

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-05-01

The body of this document contains a listing of DOE employees and DOE contractors who have submitted form DOE F 1300.2, Record of Non-Government Standards Activity, which is attached to the end of this document. Additional names were added from rosters supplied by non-Government standards bodies. The committees or governing bodies in which the person participates is listed after each name. An asterisk preceding the committee notation indicates that the person has identified himself or herself as the DOE representative on that committee. Appendices to this document are also provided to sort the information by the parent employment organization, by non-Government standards activity, and by the proper names of the non-Government standards organizations and committees. DOE employees and contractors listed in this technical standards list are those recorded as of May 1, 1999.

Transformative environmental governance

Science.gov (United States)

Chaffin, Brian C.; Garmestani, Ahjond S.; Gunderson, Lance H.; Harm Benson, Melinda; Angeler, David G.; Arnold, Craig Anthony (Tony); Cosens, Barbara; Kundis Craig, Robin; Ruhl, J.B.; Allen, Craig R.

2016-01-01

Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to alternative, more desirable, or more functional regimes by altering the structures and processes that define the system. Transformative governance is rooted in ecological theories to explain cross-scale dynamics in complex systems, as well as social theories of change, innovation, and technological transformation. Similar to adaptive governance, transformative governance involves a broad set of governance components, but requires additional capacity to foster new social-ecological regimes including increased risk tolerance, significant systemic investment, and restructured economies and power relations. Transformative governance has the potential to actively respond to regime shifts triggered by climate change, and thus future research should focus on identifying system drivers and leading indicators associated with social-ecological thresholds.

Effectiveness of physical activity intervention among government employees with metabolic syndrome

OpenAIRE

Chee Huei Phing; Hazizi Abu Saad; M.Y. Barakatun Nisak; M.T. Mohd Nasir

2017-01-01

Background/Objective: Our study aimed to assess the effects of physical activity interventions via standing banners (point-of-decision prompt) and aerobics classes to promote physical activity among individuals with metabolic syndrome. Methods: We conducted a cluster randomized controlled intervention trial (16-week intervention and 8-week follow-up). Malaysian government employees in Putrajaya, Malaysia, with metabolic syndrome were randomly assigned by cluster to a point-of-decision prom...

Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation

NARCIS (Netherlands)

Rossaint, Jan; Herter, Jan M.; van Aken, Hugo; Napirei, Markus; Döring, Yvonne; Weber, Christian; Soehnlein, Oliver; Zarbock, Alexander

2014-01-01

There is emerging evidence that neutrophil extracellular traps (NETs) play important roles in inflammatory processes. Here we report that neutrophils have to be simultaneously activated by integrin-mediated outside-in- and G-protein-coupled receptor (GPCR) signaling to induce NET formation in acute

25 CFR 170.622 - What IRR programs, functions, services, and activities are subject to the self-governance...

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What IRR programs, functions, services, and activities are subject to the self-governance construction regulations? 170.622 Section 170.622 Indians BUREAU OF..., functions, services, and activities are subject to the self-governance construction regulations? All IRR...

Performance Government: Activating and Regulating the Self-Governing Capacities of Teachers and School Leaders

Science.gov (United States)

O'Brien, Peter C.

2015-01-01

This article analyses "performance government" as an emergent form of rule in advanced liberal democracies. It discloses how teachers and school leaders in Australia are being governed by the practices of performance government which centre on the recently established Australian Institute for Teaching and School Leadership (AITSL) and…

The case for foreign exchange intervention: the government as an active reserve manager

OpenAIRE

Christopher J. Neely

2005-01-01

This paper argues that major governments should actively manage their foreign exchange portfolios to maximize the risk-adjusted return to the taxpayer by exploiting long-term, fundamental based predictability in floating exchange rates. Such transactions—equivalent to foreign exchange intervention—would improve welfare by transferring risk from private agents to the risk-tolerant government. Interventions explicitly designed to profit the reserve management authority would be more likely to b...

Accelerometer-determined physical activity level among government employees in Penang, Malaysia.

Science.gov (United States)

Hazizi, A S; Aina, Mardiah B; Mohd, Nasir M T; Zaitun, Y; Hamid, Jan J M; Tabata, I

2012-04-01

A cross-sectional study was carried out to investigate accelerometer-determined physical activity level of 233 Malay government employees (104 men, 129 women) working in the Federal Government Building Penang, Malaysia. Body weight, height, waist and hip circumference, body fat percentage and blood pressure were measured for each respondent. All the respondents were asked to wear an accelerometer for 3 days. Body mass index (BMI) and waist-hip ratio (WHR) were calculated using a standard formulas. Fasting blood sample was obtained to determine the lipid profile and glucose levels of the respondents. Based on the accelerometer-determined physical activity level, almost 65% of the respondents were categorised as sedentary. Approximately 50.2% of the respondents were overweight or obese. There were negative but significant relationships between body mass index (BMI) (r = -0.353, p obesity in this study. The high prevalence of physical inactivity and obesity found among respondents of this study indicate a need for implementing intervention programmes among this population.

The activation mechanisms of G protein-coupled receptors : the case of the adenosine A2B and HCA2/3 receptors

NARCIS (Netherlands)

Liu, R.

2016-01-01

Identifying and elucidating the functions and activation of GPCRs will provide opportunities for novel drug discovery. We confirmed that a yeast system with an extended library of G proteins is very well suited for the study of GPCR activation, G protein coupling profiles, receptor-G protein binding

Transformative environmental governance

Science.gov (United States)

Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to ...

Pervanadate induces Mammalian Ste20 Kinase 3 (MST3) tyrosine phosphorylation but not activation.

Science.gov (United States)

Kan, Wei-Chih; Lu, Te-Ling; Ling, Pin; Lee, Te-Hsiu; Cho, Chien-Yu; Huang, Chi-Ying F; Jeng, Wen-Yih; Weng, Yui-Ping; Chiang, Chun-Yen; Wu, Jin Bin; Lu, Te-Jung

2016-07-01

The yeast Ste20 (sterile) protein kinase, which is a serine/threonine kinase, responds to the stimulation of the G proteincoupled receptor (GPCR) pheromone receptor. Ste20 protein kinase serves as the critical component that links signaling from the GPCR/G proteins to the mitogen-activated protein kinase (MAPK) cascade in yeast. The yeast Ste20p functions as a MAP kinase kinase kinase kinase (MAP4K) in the pheromone response. Ste20-like kinases are structurally conserved from yeast to mammals. The mechanism by which MAP4K links GPCR to the MAPK pathway is less clearly defined in vertebrates. In addition to MAP4K, the tyrosine kinase cascade bridges G proteins and the MAPK pathway in vertebrate cells. Mammalian Ste20 Kinase 3 (MST3) has been categorized into the Ste20 family and has been reported to function in the regulation of cell polarity and migration. However, whether MST3 tyrosine phosphorylation regulates diverse signaling pathways is unknown. In this study, the tyrosine phosphatase inhibitor pervanadate was found to induce MST3 tyrosine phosphorylation in intact cells, and the activity of tyrosine-phosphorylated MST3 was measured. This tyrosine-directed phosphorylation was independent of MST3 activity. Parameters including protein conformation, Triton concentration and ionic concentration influenced the sensitivity of MST3 activity. Taken together, our data suggests that the serine/threonine kinase MST3 undergoes tyrosinedirected phosphorylation. The tyrosine-phosphorylated MST3 may create a docking site for the structurally conserved SH2/SH3 (Src Homology 2 and 3) domains within the Src oncoprotein. The unusual tyrosinephosphorylated MST3 may recruit MST3 to various signaling components. Copyright © 2016. Published by Elsevier Inc.

Gene network inference and biochemical assessment delineates GPCR pathways and CREB targets in small intestinal neuroendocrine neoplasia.

Directory of Open Access Journals (Sweden)

Ignat Drozdov

Full Text Available Small intestinal (SI neuroendocrine tumors (NET are increasing in incidence, however little is known about their biology. High throughput techniques such as inference of gene regulatory networks from microarray experiments can objectively define signaling machinery in this disease. Genome-wide co-expression analysis was used to infer gene relevance network in SI-NETs. The network was confirmed to be non-random, scale-free, and highly modular. Functional analysis of gene co-expression modules revealed processes including 'Nervous system development', 'Immune response', and 'Cell-cycle'. Importantly, gene network topology and differential expression analysis identified over-expression of the GPCR signaling regulators, the cAMP synthetase, ADCY2, and the protein kinase A, PRKAR1A. Seven CREB response element (CRE transcripts associated with proliferation and secretion: BEX1, BICD1, CHGB, CPE, GABRB3, SCG2 and SCG3 as well as ADCY2 and PRKAR1A were measured in an independent SI dataset (n = 10 NETs; n = 8 normal preparations. All were up-regulated (p<0.035 with the exception of SCG3 which was not differently expressed. Forskolin (a direct cAMP activator, 10(-5 M significantly stimulated transcription of pCREB and 3/7 CREB targets, isoproterenol (a selective ß-adrenergic receptor agonist and cAMP activator, 10(-5 M stimulated pCREB and 4/7 targets while BIM-53061 (a dopamine D(2 and Serotonin [5-HT(2] receptor agonist, 10(-6 M stimulated 100% of targets as well as pCREB; CRE transcription correlated with the levels of cAMP accumulation and PKA activity; BIM-53061 stimulated the highest levels of cAMP and PKA (2.8-fold and 2.5-fold vs. 1.8-2-fold for isoproterenol and forskolin. Gene network inference and graph topology analysis in SI NETs suggests that SI NETs express neural GPCRs that activate different CRE targets associated with proliferation and secretion. In vitro studies, in a model NET cell system, confirmed that transcriptional

National report card on energy efficiency : 2. annual report card on government activities

International Nuclear Information System (INIS)

2000-01-01

This second annual report card produced by the Canadian Energy Efficiency Alliance is a means by which to monitor the efforts of Canada's federal, provincial and territorial governments in energy efficiency activities. The Alliance works in partnership with manufacturers, utilities, governments, builders, labour, consumer groups and environmental organizations. Energy efficiency is one of the primary tools governments can use to meet the Kyoto climate change commitment. The issue of climate change was examined in greater depth in this second annual report card. Ten specific measures that each government should take in order to be efficiency leaders were identified. These included minimum standards and regulations for buildings and appliances, supporting energy efficiency in the marketplace, and leadership programs to improve energy efficiency and achieve emission reduction targets. Efficiency in transportation was not included in this report card. A brief summary of what the federal government, as well as each provincial and territorial government are doing to promote energy efficiency was included. Each jurisdiction was given a grade. The Yukon received the highest mark of A minus. Saskatchewan received the lowest, and only failed mark. It was emphasized that public and private utilities also play a key role in supporting energy efficiency in Canada. 2 tabs

The GPCR membrane receptor, DopEcR, mediates the actions of both dopamine and ecdysone to control sex pheromone perception in an insect

Directory of Open Access Journals (Sweden)

Antoine eAbrieux

2014-09-01

Full Text Available Olfactory information mediating sexual behavior is crucial for reproduction in many animals, including insects. In male moths, the macroglomerular complex of the primary olfactory center, the antennal lobe (AL is specialized in the treatment of information on the female-emitted sex pheromone. Evidence is accumulating that modulation of behavioral pheromone responses occurs through neuronal plasticity via the action of hormones and/or catecholamines. We recently showed that a G-protein-coupled receptor (GPCR, AipsDopEcR, with its homologue known in Drosophila for its double affinity to the main insect steroid hormone 20-hydroxyecdysone (20E, and dopamine (DA, present in the ALs, is involved in the behavioral response to pheromone in the moth, Agrotis ipsilon. Here we tested the role of AipsDopEcR as compared to nuclear 20E receptors in central pheromone processing combining receptor inhibition with intracellular recordings of AL neurons. We show that the sensitivity of AL neurons for the pheromone in males decreases strongly after AipsDopEcR-dsRNA injection but also after inhibition of nuclear 20E receptors. Moreover we tested the involvement of 20E and DA in the receptor-mediated behavioral modulation in wind tunnel experiments, using ligand applications and receptor inhibition treatments. We show that both ligands are necessary and act on AipsDopEcR-mediated behavior. Altogether these results indicate that the GPCR membrane receptor, AipsDopEcR, controls sex pheromone perception through the action of both 20E and DA in the central nervous system, probably in concert with 20E action through nuclear receptors.

The Influence of Institutional Shareholder Activism as a Corporate Governance Monitoring Mechanism in Malaysia

OpenAIRE

Maizatul A. Musa

2012-01-01

Not many studies have been undertaken on shareholder activism in emerging economies, including Malaysia. Shareholder activism in emerging economies is on the rise. This paper seeks to comprehend the elements of this activism that are unique to Malaysia, specifically with respect to how the agency problem is controlled through shareholder activism in improving corporate governance practices within target companies. Through shareholder activism, shareholders make contact with a target company t...

Structure-Based Sequence Alignment of the Transmembrane Domains of All Human GPCRs: Phylogenetic, Structural and Functional Implications

Science.gov (United States)

Cvicek, Vaclav; Goddard, William A.; Abrol, Ravinder

2016-01-01

The understanding of G-protein coupled receptors (GPCRs) is undergoing a revolution due to increased information about their signaling and the experimental determination of structures for more than 25 receptors. The availability of at least one receptor structure for each of the GPCR classes, well separated in sequence space, enables an integrated superfamily-wide analysis to identify signatures involving the role of conserved residues, conserved contacts, and downstream signaling in the context of receptor structures. In this study, we align the transmembrane (TM) domains of all experimental GPCR structures to maximize the conserved inter-helical contacts. The resulting superfamily-wide GpcR Sequence-Structure (GRoSS) alignment of the TM domains for all human GPCR sequences is sufficient to generate a phylogenetic tree that correctly distinguishes all different GPCR classes, suggesting that the class-level differences in the GPCR superfamily are encoded at least partly in the TM domains. The inter-helical contacts conserved across all GPCR classes describe the evolutionarily conserved GPCR structural fold. The corresponding structural alignment of the inactive and active conformations, available for a few GPCRs, identifies activation hot-spot residues in the TM domains that get rewired upon activation. Many GPCR mutations, known to alter receptor signaling and cause disease, are located at these conserved contact and activation hot-spot residue positions. The GRoSS alignment places the chemosensory receptor subfamilies for bitter taste (TAS2R) and pheromones (Vomeronasal, VN1R) in the rhodopsin family, known to contain the chemosensory olfactory receptor subfamily. The GRoSS alignment also enables the quantification of the structural variability in the TM regions of experimental structures, useful for homology modeling and structure prediction of receptors. Furthermore, this alignment identifies structurally and functionally important residues in all human GPCRs

Tracking G-protein-coupled receptor activation using genetically encoded infrared probes.

Science.gov (United States)

Ye, Shixin; Zaitseva, Ekaterina; Caltabiano, Gianluigi; Schertler, Gebhard F X; Sakmar, Thomas P; Deupi, Xavier; Vogel, Reiner

2010-04-29

Rhodopsin is a prototypical heptahelical family A G-protein-coupled receptor (GPCR) responsible for dim-light vision. Light isomerizes rhodopsin's retinal chromophore and triggers concerted movements of transmembrane helices, including an outward tilting of helix 6 (H6) and a smaller movement of H5, to create a site for G-protein binding and activation. However, the precise temporal sequence and mechanism underlying these helix rearrangements is unclear. We used site-directed non-natural amino acid mutagenesis to engineer rhodopsin with p-azido-l-phenylalanine residues incorporated at selected sites, and monitored the azido vibrational signatures using infrared spectroscopy as rhodopsin proceeded along its activation pathway. Here we report significant changes in electrostatic environments of the azido probes even in the inactive photoproduct Meta I, well before the active receptor state was formed. These early changes suggest a significant rotation of H6 and movement of the cytoplasmic part of H5 away from H3. Subsequently, a large outward tilt of H6 leads to opening of the cytoplasmic surface to form the active receptor photoproduct Meta II. Thus, our results reveal early conformational changes that precede larger rigid-body helix movements, and provide a basis to interpret recent GPCR crystal structures and to understand conformational sub-states observed during the activation of other GPCRs.

THE EVOLUTION OF LOCAL GOVERNMENT AND SELF-GOVERNMENT IN RUSSIA

Directory of Open Access Journals (Sweden)

Tatiana Yashchuk

2017-01-01

Full Text Available УДК 34The article highlights the main stages in the development of local government and self-gov-ernment in Russia. It shows the specifics of each stage. The formation of the Russian state was accompanied by the synthesis of the princely power and the community self-government. The genesis autocracy was accompanied by a struggle with the self-government institutions. The creation of rural and urban self-government in the second half of the XIX century was accom-panied by a debate on the social and public origin of these institutions.The Soviet state was based on the unity of the Soviet system. It concluded the discrete de-velopment of local self-government in Russia. There is no historical strong tradition of local government in this system.Objective of the article is to identify and characterize the main stages of development of local government and self-government in Russia. Show the discrete nature of the develop-ment of local self-government in Russia.The formation of the Russian state was accompanied by the synthesis of princely power and community self-government. Genesis autocracy was accompanied by a struggle with self-government institutions. The absence of territorial self-government in Russia was offset by the presence of social class municipality for a long time. Caste traditions tradition had a negative impact after the establishment of rural and urban self-government in the second half of the XIX century.During the preparation of the reforms and their implementation were discussions of the rela-tionship between the state and the community began in management. As a result, there is the inclusion of local authorities in the sphere of active state regulation. The desire of the county public to the political activity was suppressed by autocracy. The Provisional Government at-tempt to rely on the local self-government to create new authorities ended in failure.The Soviet state was based on a single management system. Certain powers

Fragmented International Governance of Arctic Offshore Oil : Governance Challenges and Institutional Improvement

NARCIS (Netherlands)

Humrich, Christoph

The governance architecture in the Arctic region is subject to broad public and academic debate. Existing governance arrangements are not considered sufficient to minimize risks and impacts from Arctic offshore oil activities. These governance arrangements are fragmented between law of the sea

Partnerships and Governance

DEFF Research Database (Denmark)

Damgaard, Bodil

Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark.......Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark....

AWARENESS AS A FACTOR OF INFLUENCE ON THE LEVEL OF PUBLIC SATISFACTION WITH LOCAL SELF-GOVERNMENT ACTIVITIES

Directory of Open Access Journals (Sweden)

Kiseleva N. V.

2014-12-01

Full Text Available In the modern period of the development of statehood in Russia the significant increase of attention is attributed to the issue of effectiveness of state power and government not only on the federal and regional levels, but on the local level as well. In 2009 there was developed and implemented the system of indicators of the effectiveness’ estimates of the activity of local self-government. The system of effectiveness’ estimates included sociological indices of satisfaction of population. Implementation of sociological indices in the system of effectiveness’ estimates of the activity of local self-government brought positive responses from academic community, politicians, managers, and the public. In the article the analysis of influence of cognitive factor (being kept informed on the level of social contentment of the activity of local self-government’ bodies is done. We do this, based on the results of sociological studies of the major Russian research organizations and data from the aggregate reports, which deal with the monitoring of effectiveness of local self-government of some subjects in the Central federal district of Russia.

Governing Knowledge: The Formalization Dilemma in the Governance of the Public Sciences

Science.gov (United States)

Woelert, Peter

2015-01-01

This paper offers a conceptually novel contribution to the understanding of the distinctive governance challenges arising from the increasing reliance on formalized knowledge in the governance of research activities. It uses the current Australian research governance system as an example--a system which exhibits a comparatively strong degree of…

CONDITIONS GOVERNING THE EXERCISE OF COMMERCIAL ACTIVITIES BY PROFESSIONALS

Directory of Open Access Journals (Sweden)

Mihaela Narcisa Stoicu

2012-01-01

Full Text Available The Romanian Constitution establishes that market economy in Romania is based on private property and is developed under the law of supply and demand. As such, the State has the obligation to ensure freedom of trade, protection of fair competition and to create an appropriate framework for the use of all factors of production. The Constitution also provides that the choice of profession should be free, and that the exercise of this freedom may be limited "only by law", with regard to the right to work. The operative principle in relation to commercial activities is the freedom of trade, according to which anyone is free to exercise a commercial profession, provided they respect the limitations and the special conditions prescribed by law. As regards the conditions governing the exercise of commercial activities, the law establishes certain conditions on the capacity of individuals to conduct economic activities, also establishing certain incapacities, as well as incompatibilities, forfeitures and bans on making trade. The law sets specific conditions regarding the capacity of individuals to conduct commercial professional activities, but it also establishes some incapacities to provide shelter from adverse consequences to some persons.

Chimeric microbial rhodopsins for optical activation of Gs-proteins

Science.gov (United States)

Yoshida, Kazuho; Yamashita, Takahiro; Sasaki, Kengo; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

2017-01-01

We previously showed that the chimeric proteins of microbial rhodopsins, such as light-driven proton pump bacteriorhodopsin (BR) and Gloeobacter rhodopsin (GR) that contain cytoplasmic loops of bovine rhodopsin, are able to activate Gt protein upon light absorption. These facts suggest similar protein structural changes in both the light-driven proton pump and animal rhodopsin. Here we report two trials to engineer chimeric rhodopsins, one for the inserted loop, and another for the microbial rhodopsin template. For the former, we successfully activated Gs protein by light through the incorporation of the cytoplasmic loop of β2-adrenergic receptor (β2AR). For the latter, we did not observe any G-protein activation for the light-driven sodium pump from Indibacter alkaliphilus (IndiR2) or a light-driven chloride pump halorhodopsin from Natronomonas pharaonis (NpHR), whereas the light-driven proton pump GR showed light-dependent G-protein activation. This fact suggests that a helix opening motion is common to G protein coupled receptor (GPCR) and GR, but not to IndiR2 and NpHR. Light-induced difference FTIR spectroscopy revealed similar structural changes between WT and the third loop chimera for each light-driven pump. A helical structural perturbation, which was largest for GR, was further enhanced in the chimera. We conclude that similar structural dynamics that occur on the cytoplasmic side of GPCR are needed to design chimeric microbial rhodopsins. PMID:29362703

17 CFR 1.59 - Activities of self-regulatory organization employees, governing board members, committee members...

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Activities of self-regulatory... COMMODITY EXCHANGE ACT Miscellaneous § 1.59 Activities of self-regulatory organization employees, governing...) Self-regulatory organization means “self-regulatory organization,” as defined in Commission regulation...

Improving Corporate Governance Practices

OpenAIRE

M. Huse; J. Gabrielsson; A. Minichilli

2009-01-01

Peak performing organizations may benefit from active value creating boards. Suggestions to improve board behaviour and corporate governance practices are presented in this article. The suggestions result from findings in the “Valued Creating Board” research programme. However, active boards working in a shareholder activism framework may destroy rather than support value creation processes within firms. In peak performing organizations corporate governance practices should be designed and de...

GPCRM: a homology modeling web service with triple membrane-fitted quality assessment of GPCR models.

Science.gov (United States)

Miszta, Przemyslaw; Pasznik, Pawel; Jakowiecki, Jakub; Sztyler, Agnieszka; Latek, Dorota; Filipek, Slawomir

2018-05-21

Due to the involvement of G protein-coupled receptors (GPCRs) in most of the physiological and pathological processes in humans they have been attracting a lot of attention from pharmaceutical industry as well as from scientific community. Therefore, the need for new, high quality structures of GPCRs is enormous. The updated homology modeling service GPCRM (http://gpcrm.biomodellab.eu/) meets those expectations by greatly reducing the execution time of submissions (from days to hours/minutes) with nearly the same average quality of obtained models. Additionally, due to three different scoring functions (Rosetta, Rosetta-MP, BCL::Score) it is possible to select accurate models for the required purposes: the structure of the binding site, the transmembrane domain or the overall shape of the receptor. Currently, no other web service for GPCR modeling provides this possibility. GPCRM is continually upgraded in a semi-automatic way and the number of template structures has increased from 20 in 2013 to over 90 including structures the same receptor with different ligands which can influence the structure not only in the on/off manner. Two types of protein viewers can be used for visual inspection of obtained models. The extended sortable tables with available templates provide links to external databases and display ligand-receptor interactions in visual form.

The Influence of Some Romanian Interest Groups Upon the Activity of Government and Parliament

Directory of Open Access Journals (Sweden)

Bianca COBÂRZAN

2005-10-01

Full Text Available The paper focuses on two specific interest groups, NGOs and trade unions, and on their influence upon the government and parliament. Our paper is based on an analyze of the activity of several interest groups during the period 2002-2004 and on the results of several researches and reports published on the last years. The analyze identifies petitioning for rule making, public meetings and debates, monitoring the activity of the public institutions and participating in advisory or regulatory committees as being the most common used mechanisms to influence the government and the parliament in Romania. Also, the analyze shows that administrative procedures affect the degree of bureaucratic autonomy. Overall, the results of this brief research show some pluralist forms of the interaction between the interest groups and the public institutions.

Development of novel ligands for peptide GPCRs.

Science.gov (United States)

Moran, Brian M; McKillop, Aine M; O'Harte, Finbarr Pm

2016-12-01

Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a G-protein coupled receptor (GPCR) are currently used in the treatment of type 2 diabetes. This review focuses on GPCRs from pancreatic β-cells, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin, pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY), oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are thought to have an increasing role in regulating peptide secretions namely short fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119). Several pre-clinical and clinical trials are currently ongoing in peptide GPCR based therapies, including dual and triple agonist peptides which activate two or more GPCRs simultaneously. Copyright © 2016 Elsevier Ltd. All rights reserved.

Water permeation through the internal water pathway in activated GPCR rhodopsin.

Directory of Open Access Journals (Sweden)

Katsufumi Tomobe

Full Text Available Rhodopsin is a light-driven G-protein-coupled receptor that mediates signal transduction in eyes. Internal water molecules mediate activation of the receptor in a rhodopsin cascade reaction and contribute to conformational stability of the receptor. However, it remains unclear how internal water molecules exchange between the bulk and protein inside, in particular through a putative solvent pore on the cytoplasmic. Using all-atom molecular dynamics simulations, we identified the solvent pore on cytoplasmic side in both the Meta II state and the Opsin. On the other hand, the solvent pore does not exist in the dark-adapted rhodopsin. We revealed two characteristic narrow regions located within the solvent pore in the Meta II state. The narrow regions distinguish bulk and the internal hydration sites, one of which is adjacent to the conserved structural motif "NPxxY". Water molecules in the solvent pore diffuse by pushing or sometimes jumping a preceding water molecule due to the geometry of the solvent pore. These findings revealed a total water flux between the bulk and the protein inside in the Meta II state, and suggested that these pathways provide water molecules to the crucial sites of the activated rhodopsin.

E-Governance Frameworks - Agenda Ahead

Directory of Open Access Journals (Sweden)

Nityesh BHATT

2007-01-01

Full Text Available Electronic governance may be defined as the delivery of the government services and information to the public using electronic means. Use of IT in the government facilitates an efficient, speedy and transparent process for disseminating information to the public and other agencies, and for performing the government administration activities.

Stakeholder involvement in international conventions governing civil nuclear activities

International Nuclear Information System (INIS)

Emmerechts, Sam

2017-01-01

Mr Emmerechts explained that international conventions have varying positions on stakeholders and their involvement depending upon the intent of the legislator and the field they cover, ranging from a narrow to a broad interpretation. He addressed stakeholder involvement in two other international conventions governing civil nuclear activities, namely the Convention on Nuclear Safety, and the Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management (the Joint Convention), both concluded under the auspices of the International Atomic Energy Agency (IAEA). He noted that the Convention on Nuclear Safety remains a 'traditional' international legal instrument, focusing on governments and governmental bodies as the main stakeholders and limiting obligations regarding the involvement of the public and intergovernmental organisations to their receiving information and observing. Likewise, the Joint Convention limits obligations regarding public involvement to access to information, notably as to the siting of proposed facilities. However, he noted that in the European Union, the Directive on Nuclear Safety (2014/87/Euratom) and the Directive for the Safe Management of Spent Fuel and Radioactive Waste (2011/70/Euratom) have more advanced public participation requirements in nuclear decision making. Mr Emmerechts explained that the substantial differences between nuclear legislation and the Aarhus and Espoo Conventions with regards to public involvement requirements could partly be explained by the technicality of nuclear information and by issues related to nuclear security

Chemogenomic analysis of G-protein coupled receptors and their ligands deciphers locks and keys governing diverse aspects of signalling.

Directory of Open Access Journals (Sweden)

Jörg D Wichard

Full Text Available Understanding the molecular mechanism of signalling in the important super-family of G-protein-coupled receptors (GPCRs is causally related to questions of how and where these receptors can be activated or inhibited. In this context, it is of great interest to unravel the common molecular features of GPCRs as well as those related to an active or inactive state or to subtype specific G-protein coupling. In our underlying chemogenomics study, we analyse for the first time the statistical link between the properties of G-protein-coupled receptors and GPCR ligands. The technique of mutual information (MI is able to reveal statistical inter-dependence between variations in amino acid residues on the one hand and variations in ligand molecular descriptors on the other. Although this MI analysis uses novel information that differs from the results of known site-directed mutagenesis studies or published GPCR crystal structures, the method is capable of identifying the well-known common ligand binding region of GPCRs between the upper part of the seven transmembrane helices and the second extracellular loop. The analysis shows amino acid positions that are sensitive to either stimulating (agonistic or inhibitory (antagonistic ligand effects or both. It appears that amino acid positions for antagonistic and agonistic effects are both concentrated around the extracellular region, but selective agonistic effects are cumulated between transmembrane helices (TMHs 2, 3, and ECL2, while selective residues for antagonistic effects are located at the top of helices 5 and 6. Above all, the MI analysis provides detailed indications about amino acids located in the transmembrane region of these receptors that determine G-protein signalling pathway preferences.

GOVERNMENT SUPPORT FOR SMALL AND MEDIUM-SIZED BUSINESS AND INNOVATIVE ACTIVITIES

Directory of Open Access Journals (Sweden)

Pоlina Kolisnichenko

2017-09-01

Full Text Available The purpose of the paper is to reveal the conditions of the innovative development of the small and mediumsized entrepreneurship in Ukraine; the problems that suppress the innovative activity and small and medium-sized enterprises development; peculiarities of the tax incentives for the development of the entrepreneurship in the advanced countries and in Ukraine; the main kinds and characteristics of the small and medium-sized enterprises public support. Methodology. The methods of scientific research include: analysis and generalization for studying the main kinds and characteristics of the government support of the small and medium-sized enterprises; dynamic and comparative analysis for studying the problems and factors influencing the development of small and medium enterprises and innovative activity, peculiarities of tax incentives for business development; systemanalytical method for studying the conditions of the innovative development of the small and medium-sized entrepreneurship. Results. The government's financial support priorities should be: optimal application of the fiscal regulation instruments (reduction of the amount of taxes, determination of the criteria for the maximum taxation amount, tax incentives etc., maintenance of the self-investment of small and medium-sized enterprises as well as investment, financial means of the public influence over the development of the enterprises, effective combination of both direct and indirect forms of the innovative development support. Practical implications. The obtained results can be used in the process of formation and implementation of the small and medium enterprise sector development strategy and innovative activity in the long-term perspective. Value/originality. The obtained data can provide a better understanding of the direction of innovative business development in Ukraine.

Effectiveness of physical activity intervention among government employees with metabolic syndrome.

Science.gov (United States)

Huei Phing, Chee; Abu Saad, Hazizi; Barakatun Nisak, M Y; Mohd Nasir, M T

2017-12-01

Our study aimed to assess the effects of physical activity interventions via standing banners (point-of-decision prompt) and aerobics classes to promote physical activity among individuals with metabolic syndrome. We conducted a cluster randomized controlled intervention trial (16-week intervention and 8-week follow-up). Malaysian government employees in Putrajaya, Malaysia, with metabolic syndrome were randomly assigned by cluster to a point-of-decision prompt group (n = 44), an aerobics group (n = 42) or a control group (n = 103) based on sample size calculation formula. Step counts were evaluated by Lifecorder e-STEP accelerometers for all participants. Metabolic syndrome was defined according to the 'harmonizing' definition, in which individuals who have at least three of the five metabolic risk factors (waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose levels, systolic and diastolic blood pressure) will be classified as having metabolic syndrome. A total of 80% of the enrolled government employees with metabolic syndrome completed the programme. Data were analyzed using SPSS for Windows (version 20, SPSS, Chicago, IL). There were significantly higher step counts on average in the aerobics group compared to the control group over assessments. Assessments at baseline, post-intervention and follow-up showed a significant difference in step counts between the intervention and control groups. The greatest reductions in the proportions of individuals with metabolic syndrome were observed in the aerobics group with a reduction of 79.4% in the post-intervention assessment compared to the assessment at baseline. The findings of this study suggest that physical activity intervention via aerobics classes is an effective strategy for improving step counts and reducing the prevalence of metabolic syndrome.

GPCR-I-TASSER: A Hybrid Approach to G Protein-Coupled Receptor Structure Modeling and the Application to the Human Genome.

Science.gov (United States)

Zhang, Jian; Yang, Jianyi; Jang, Richard; Zhang, Yang

2015-08-04

Experimental structure determination remains difficult for G protein-coupled receptors (GPCRs). We propose a new hybrid protocol to construct GPCR structure models that integrates experimental mutagenesis data with ab initio transmembrane (TM) helix assembly simulations. The method was tested on 24 known GPCRs where the ab initio TM-helix assembly procedure constructed the correct fold for 20 cases. When combined with weak homology and sparse mutagenesis restraints, the method generated correct folds for all the tested cases with an average Cα root-mean-square deviation 2.4 Å in the TM regions. The new hybrid protocol was applied to model all 1,026 GPCRs in the human genome, where 923 have a high confidence score and are expected to have correct folds; these contain many pharmaceutically important families with no previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin, and Neuropeptide Y receptors. The results demonstrate new progress on genome-wide structure modeling of TM proteins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulator of G-protein signaling-5 is a marker of hepatic stellate cells and expression mediates response to liver injury.

Directory of Open Access Journals (Sweden)

Arya J Bahrami

Full Text Available Liver fibrosis is mediated by hepatic stellate cells (HSCs, which respond to a variety of cytokine and growth factors to moderate the response to injury and create extracellular matrix at the site of injury. G-protein coupled receptor (GPCR-mediated signaling, via endothelin-1 (ET-1 and angiotensin II (AngII, increases HSC contraction, migration and fibrogenesis. Regulator of G-protein signaling-5 (RGS5, an inhibitor of vasoactive GPCR agonists, functions to control GPCR-mediated contraction and hypertrophy in pericytes and smooth muscle cells (SMCs. Therefore we hypothesized that RGS5 controls GPCR signaling in activated HSCs in the context of liver injury. In this study, we localize RGS5 to the HSCs and demonstrate that Rgs5 expression is regulated during carbon tetrachloride (CCl4-induced acute and chronic liver injury in Rgs5LacZ/LacZ reporter mice. Furthermore, CCl4 treated RGS5-null mice develop increased hepatocyte damage and fibrosis in response to CCl4 and have increased expression of markers of HSC activation. Knockdown of Rgs5 enhances ET-1-mediated signaling in HSCs in vitro. Taken together, we demonstrate that RGS5 is a critical regulator of GPCR signaling in HSCs and regulates HSC activation and fibrogenesis in liver injury.

Rac1-mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN loss

Science.gov (United States)

Cizmecioglu, Onur; Ni, Jing; Xie, Shaozhen; Zhao, Jean J; Roberts, Thomas M

2016-01-01

We aimed to understand how spatial compartmentalization in the plasma membrane might contribute to the functions of the ubiquitous class IA phosphoinositide 3-kinase (PI3K) isoforms, p110α and p110β. We found that p110β localizes to membrane rafts in a Rac1-dependent manner. This localization potentiates Akt activation by G-protein-coupled receptors (GPCRs). Thus genetic targeting of a Rac1 binding-deficient allele of p110β to rafts alleviated the requirement for p110β-Rac1 association for GPCR signaling, cell growth and migration. In contrast, p110α, which does not play a physiological role in GPCR signaling, is found to reside in nonraft regions of the plasma membrane. Raft targeting of p110α allowed its EGFR-mediated activation by GPCRs. Notably, p110β dependent, PTEN null tumor cells critically rely upon raft-associated PI3K activity. Collectively, our findings provide a mechanistic account of how membrane raft localization regulates differential activation of distinct PI3K isoforms and offer insight into why PTEN-deficient cancers depend on p110β. DOI: http://dx.doi.org/10.7554/eLife.17635.001 PMID:27700986

High content screening for G protein-coupled receptors using cell-based protein translocation assays

DEFF Research Database (Denmark)

Grånäs, Charlotta; Lundholt, Betina Kerstin; Heydorn, Arne

2005-01-01

G protein-coupled receptors (GPCRs) have been one of the most productive classes of drug targets for several decades, and new technologies for GPCR-based discovery promise to keep this field active for years to come. While molecular screens for GPCR receptor agonist- and antagonist-based drugs...... will continue to be valuable discovery tools, the most exciting developments in the field involve cell-based assays for GPCR function. Some cell-based discovery strategies, such as the use of beta-arrestin as a surrogate marker for GPCR function, have already been reduced to practice, and have been used...... as valuable discovery tools for several years. The application of high content cell-based screening to GPCR discovery has opened up additional possibilities, such as direct tracking of GPCRs, G proteins and other signaling pathway components using intracellular translocation assays. These assays provide...

PAFR activation of NF-?B p65 or p105 precursor dictates pro- and anti-inflammatory responses during TLR activation in murine macrophages

OpenAIRE

Ishizuka, Edson K.; Filgueiras, Luciano Ribeiro; Rios, Francisco J.; Serezani, Carlos H.; Jancar, Sonia

2016-01-01

Platelet-activating factor receptor (PAFR) is a G protein-coupled receptor (GPCR) implicated in many diseases. Toll-like receptors (TLRs) play a critical role in shaping innate and adaptive immune responses. In this study, we investigated whether PAFR signaling changes the macrophages responsiveness to agonists of TLR2 (Pam3Cys), TLR4 (LPS), and TLR3 agonist Poly(I:C). Exogenous PAF inhibited the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) and increased anti-inflammat...

Student Participation in Governance

Science.gov (United States)

Deegan, William L.; And Others

1970-01-01

The success of student government activities on any campus is significantly affected by the amount of student participation permitted in the institution's decision-making processes. The traditional" model of government--characterized by tokenism--often results in the separate jurisdictions" model-- characterized by fragmentation and interest…

Meeting at the Edges: Spaces, Places and Grassroots Governance Activism in Delhi

OpenAIRE

Webb, Martin

2013-01-01

Through ethnography of activist organisations promoting transparency, accountability and active citizenship, and comprising coalitions of the city’s middle classes and urban poor, this article explores the spaces in which activists from different social backgrounds meet and carry out their work. By locating the positions of meeting rooms, offices and activists’ homes in urban space, I open up a view of the everyday practices of grassroots governance initiatives aimed at producing shared citiz...

A G protein-coupled receptor (GPCR) in red: live cell imaging of the kappa opioid receptor-tdTomato fusion protein (KOPR-tdT) in neuronal cells

Science.gov (United States)

Huang, Peng; Chiu, Yi-Ting; Chen, Chongguang; Wang, Yujun; Liu-Chen, Lee-Yuan

2013-01-01

Introduction In contrast to green fluorescent protein and variants (GFPs), red fluorescent proteins (RFPs) have rarely been employed for generation of GPCR fusion proteins, likely because of formation of aggregates and cell toxicity of some RFPs. Among all the RFPs available, tdTomato (tdT), one of the non-aggregating RFP, has the highest brightness score (about 3 times that of eGFP) and unsurpassed photostability. Methods We fused tdT to the KOPR C-terminus. The KOPR-tdT cDNA construct was transfected into Neuro2A mouse neuroblastoma cell line (Neuro2A cells) and rat cortical primary neurons for characterization of pharmacological properties and imaging studies on KOPR trafficking. Results KOPR-tdT retained KOPR properties (cell surface expression, ligand binding, agonist-induced signaling and internalization) when expressed in Neuro2A cells and rat primary cortical neurons. Live cell imaging of KOPR-tdT enables visualization of time course of agonist-induced internalization of KOPR in real time for 60 min, without photobleaching and apparent cell toxicity. U50,488H-induced KOPR internalization occurred as early as 4 min and plateaued at about 30 min. A unique pattern of internalized KOPR in processes of primary neurons was induced by U50,488H. Discussion tdT is an alternative to, or even a better tool than, GFPs for fusing to GPCR for trafficking studies, because tdT has higher brightness and thus better resolution and less photobleaching problems due to reduced laser power used. It also has advantages associated with its longer-wavelength emission including spectral separation from autofluorescence and GFPs, reduced cell toxicity the laser may impose, and greater tissue penetration. These advantages of tdT over GPFs may be critical for live cell imaging studies of GPCRs in vitro and for studying GPCRs in vivo because of their low abundance. PMID:23856011

G protein-coupled receptor internalization assays in the high-content screening format.

Science.gov (United States)

Haasen, Dorothea; Schnapp, Andreas; Valler, Martin J; Heilker, Ralf

2006-01-01

High-content screening (HCS), a combination of fluorescence microscopic imaging and automated image analysis, has become a frequently applied tool to study test compound effects in cellular disease-modeling systems. This chapter describes the measurement of G protein-coupled receptor (GPCR) internalization in the HCS format using a high-throughput, confocal cellular imaging device. GPCRs are the most successful group of therapeutic targets on the pharmaceutical market. Accordingly, the search for compounds that interfere with GPCR function in a specific and selective way is a major focus of the pharmaceutical industry today. This chapter describes methods for the ligand-induced internalization of GPCRs labeled previously with either a fluorophore-conjugated ligand or an antibody directed against an N-terminal tag of the GPCR. Both labeling techniques produce robust assay formats. Complementary to other functional GPCR drug discovery assays, internalization assays enable a pharmacological analysis of test compounds. We conclude that GPCR internalization assays represent a valuable medium/high-throughput screening format to determine the cellular activity of GPCR ligands.

Government Strategic Support for Investment Activity

Science.gov (United States)

Turekulova, Assiya N.; Mukhambetova, Lyazzat K.; Doshan, Almagul S.; Issabekov, Baurzhan N.; Chimgentbayeva, Gulbakyt K.; Turegeldinova, Aliya Zh.

2016-01-01

When system risks are high most investors choose to exit the market; however, there are some contrarian investors who opt to make investments. The authors analyzed the main goals of the investment process and measures that should be provided by the government to stimulate investments and innovation especially by means of investment banking. The…

Activation of PKCβII and PKCθ is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation

International Nuclear Information System (INIS)

Heo, Kyung-Sun; Kim, Dong-Uk; Kim, Lila; Nam, Miyoung; Baek, Seung-Tae; Park, Song-Kyu; Park, Youngwoo; Myung, Chang-Seon; Hwang, Sung-Ook; Hoe, Kwang-Lae

2008-01-01

Native LDL may be a mitogenic stimulus of VSMC proliferation in lesions where endothelial disruption occurs. Recent studies have demonstrated that the mitogenic effects of LDL are accompanied by Erk1/2 activation via an unknown G-protein-coupled receptor (GPCR). In this article, we report that LDL translocated PKCβ II and PKCθ from cytosol to plasma membrane, and inhibition of PKCβ II and PKCθ decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKCβ II and PKCθ, suggesting that Gi protein plays a role in LDL effects. Of LPA, S1P, and LDL, whose signaling is conveyed via Gi/o proteins, only LDL induced translocation of PKCβ II and PKCθ. Inhibition of PKCβ II or PKCθ, as well as of Erk1/2 and GPCR, decreases LDL-induced upregulation of Egr-1, which is critical for cell proliferation. This is the first report, to our knowledge, that the participation of PKCθ in VSMC proliferation is unique

Open government objectives and participation motivations

NARCIS (Netherlands)

Wijnhoven, Alphonsus B.J.M.; Ehrenhard, Michel Léon; Kuhn, Johannes

2015-01-01

Open government aims, among others, at improving engagement of citizens in public sector activities. To realize this potential, we need to understand citizens' motivations to engage in the many different variants of open government. This article identifies motivations for open government

42 CFR 137.205 - Will this voluntary uniform data set reporting activity be required of all Self-Governance Tribes...

Science.gov (United States)

2010-10-01

... resources, hardware, software, and technical assistance to the Self-Governance Tribes to facilitate data... 42 Public Health 1 2010-10-01 2010-10-01 false Will this voluntary uniform data set reporting activity be required of all Self-Governance Tribes entering into a compact with the IHS under Title V? 137...

'Good Governance' dan 'Governability'

Directory of Open Access Journals (Sweden)

- Pratikno

2005-03-01

Full Text Available The article endeavors to trace the outset of governance concept, its dominant meanings and discourse, and its implication towards governability. The central role of government in the governing processes has predominantly been adopted. The concept of governance was emerged precisely in the context of the failure of government as key player in regulation, economic redistribution and political participation. Governance is therefore aimed to emphasize pattern of governing which are based both on democratic mechanism and sound development management. However, practices of such good governance concept –which are mainly adopted and promoted by donor states and agencies– tend to degrade state and/or government authority and legitimacy. Traditional function of the state as sole facilitator of equal societal, political and legal membership among citizens has been diminished. The logic of fair competition has been substituted almost completely by the logic of free competition in nearly all sectors of public life. The concept and practices of good governance have resulted in decayed state authority and failed state which in turn created a condition for "ungovernability". By promoting democratic and humane governance, the article accordingly encourages discourse to reinstall and bring the idea of accountable state back in.

Cloud Computing Governance Lifecycle

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Soňa Karkošková

2016-06-01

Full Text Available Externally provisioned cloud services enable flexible and on-demand sourcing of IT resources. Cloud computing introduces new challenges such as need of business process redefinition, establishment of specialized governance and management, organizational structures and relationships with external providers and managing new types of risk arising from dependency on external providers. There is a general consensus that cloud computing in addition to challenges brings many benefits but it is unclear how to achieve them. Cloud computing governance helps to create business value through obtain benefits from use of cloud computing services while optimizing investment and risk. Challenge, which organizations are facing in relation to governing of cloud services, is how to design and implement cloud computing governance to gain expected benefits. This paper aims to provide guidance on implementation activities of proposed Cloud computing governance lifecycle from cloud consumer perspective. Proposed model is based on SOA Governance Framework and consists of lifecycle for implementation and continuous improvement of cloud computing governance model.

Regulation of G Protein-Coupled Receptors by Ubiquitination

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Kamila Skieterska

2017-04-01

Full Text Available G protein-coupled receptors (GPCRs comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

The incidence of local government allocations in Tanzania

OpenAIRE

Jameson Boex

2003-01-01

Since 1999, Tanzania has been actively pursuing reforms of the way in which the central government finances local government activities. This paper looks at the current incidence of central government allocations to local authorities in Tanzania through: 1) examining of potential problems with the current financing method, 2) showing large variations between local government allocations, and 3) finding that surprisingly what drives t his distribution of resources maybe substantial pro-wealthy...

Measuring Innovation in Government

Energy Technology Data Exchange (ETDEWEB)

Mahroum, S.

2016-07-01

Over the past few decades, there has been growing interest in supporting innovation in the public sector as a means of increasing the efficiency and quality of government services. Generally speaking, innovation in government could be defined as “The creation and implementation of new processes, products, services and methods of delivery which result in significant improvements in outcome efficiency, effectiveness or quality’’ [3]. A ‘Process Innovation’ is an activity oriented mainly towards enhancing ‘efficiency’. A ‘Product or Service Innovation’ is an activity oriented mainly towards enhancing the ‘effectiveness’ of government. A ‘Policy Innovation’ is mainly oriented at enhancing outcomes. These categorisations are important for identifying and selecting the metrics of measurement and to make distinctions between inputs, outputs, and outcomes. (Author)

Coordination through IT governance: a literature review

OpenAIRE

L. Caporarello

2006-01-01

Organizations seek to mirror their corporate governance arrangements in the activities of their key subunits – as IT function – in order to lower their organizational coordination costs. Some researches evidence that the mode of corporate governance significantly influences the mode of IT governance: organizations that have centralized their corporate governance also tend to centralize their IT governance, whereas organizations that have decentralized their corporate governance tend to decent...

Digital Environmental Governance in China: Information Disclosure, Pollution Control, and Environmental Activism in the Yellow River Delta

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Jiaxin Tan

2017-10-01

Full Text Available The Chinese water bureaucracy increasingly utilises information and communications technology (ICT in order to strengthen interaction with the population, which is severely affected by industrial pollution. Government webpages, mailboxes, and online interviews with officers have become prevalent tools for environmental governance, including information disclosure, and a virtual communication forum between the state and its citizens. The present study employs a mixed methods approach with a qualitative emphasis to explore the process of communication and interaction between government agencies and local residents in Dongying, Shandong Province. The results show that information disclosure of pollution data remains far from being transparent, despite the fact that the local government has implemented digital environmental governance, as encouraged by the central Chinese state. Internet technologies empower resource-poor environmental activists in Dongying to strengthen their social network and build communication with the authorities. The application of bureaucratic techniques, however, is key for them to enter the communication interface with government agencies in order to influence political decisions. Results suggest that local cadres tend to send mixed signals to activists and display wariness towards them. They also tend to take preventive measures to keep the situation under control when environmental disputes arise. The proposed communication interface approach sheds a clearer light on the complexity among the emergent ICTs, environmental activism, and digital governance.

Defining decision making strategies in software ecosystem governance

DEFF Research Database (Denmark)

Manikas, Konstantinos; Wnuk, Krzysztof; Shollo, Arisa

Making the right decisions is an essential part of software ecosystem governance. Decisions related to the governance of a software ecosystem can influence the health of the ecosystem and can result in fostering the success or greatly contributing to the failure of the ecosystem. However, very few...... studies touch upon the decision making of software ecosystem governance. In this paper, we propose decomposing software ecosystem governance into three activities: input or data collection, decision making, and applying actions. We focus on the decision making activity of software ecosystem governance...... and review related literature consisted of software ecosystem governance, organizational decision making, and IT governance. Based on the identified studies, we propose a framework for defining the decision making strategies in the governance of software ecosystems. We identify five decision areas...

Governance or Governing – the Missing Link?

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Luminiţa Maria Crăciun

2010-07-01

Full Text Available Governance and governing are two distinct concepts, but they intertwine. “Good governing” exercises good influence on development. “Good governance” supposes first a relationship of power focused on a series of reforms structured at three levels: the political – administrative level, the economic level, and the level of civil society. As this dimension is difficult to measure, the qualitative evaluation of the governing act raised the interest of the World Bank researchers, who elaborated and monitored the dynamics of a set of indicators, which includes six major dimensions of the governing. A retrospective concerning the image of governing in Romania during the period from 1996 to 2005 suggests a modest increase of the score: from -0.138 (1996 to 0.008 (2002; that was partially achieved based on the voice and responsibility index and on the political stability index, not on those that measure more directly the administrative performance or the integrity of the governing act. For a comparative study, we chose seven countries for the purposes of analysis (two new European Union member states: Romania and Bulgaria; two older member countries of the European Union: Slovenia and Latvia; three non-member states: Moldova, Ukraine, and Georgia, which reveal the quality of the governing from a comparative perspective. Corruption control completes the image created by the analyzed indicators. The mere formal accomplishment of commitments made in the pre-accession activity, doubled by recent internal evolutions, bring doubts about the credibility of the anticorruption reforms, as Romania continues to be considered the country with the highest CPI in the European Union. The pessimism of public opinion and the fact that only 34% of the Romanian people consider that the level of corruption will decrease in the following three years constitutes an alarm signal addressed to the governance, in view of the real reformation of the administration system

Local Government System in Japan

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Vladimir V. Redko

2016-12-01

Full Text Available The article is devoted to the issues of the activities of the local government of Japan. Particular attention is drawn to the legal framework and the material basis for the functioning of local self-government bodies. The system of local self-government is considered as a special form of self-government with a specific functional and meaning; system of municipal management and delegation of authority, as well as features of interaction between civil and imperious levels. The allocation of the city with a special status, as well as the financial structure of the local government of Japan, is considered in detail.

Corporate governance and banks : How justified is the match?

NARCIS (Netherlands)

van der Elst, C.F.

2015-01-01

Banks and bank governance are different. We critically assess the arguments used to pervade these divergences in operational activities. We also question if and how, in light of the specificity of banking activities, bank governance translates the operational peculiarities in different governance

PKD1 mediates negative feedback of PI3K/Akt activation in response to G protein-coupled receptors.

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Yang Ni

Full Text Available We examined whether protein kinase D1 (PKD1 mediates negative feeback of PI3K/Akt signaling in intestinal epithelial cells stimulated with G protein-coupled receptor (GPCR agonists. Exposure of intestinal epithelial IEC-18 cells to increasing concentrations of the PKD family inhibitor kb NB 142-70, at concentrations that inhibited PKD1 activation, strikingly potentiated Akt phosphorylation at Thr(308 and Ser(473 in response to the mitogenic GPCR agonist angiotensin II (ANG II. Enhancement of Akt activation by kb NB 142-70 was also evident in cells with other GPCR agonists, including vasopressin and lysophosphatidic acid. Cell treatment with the structurally unrelated PKD family inhibitor CRT0066101 increased Akt phosphorylation as potently as kb NB 142-70 [corrected]. Knockdown of PKD1 with two different siRNAs strikingly enhanced Akt phosphorylation in response to ANG II stimulation in IEC-18 cells. To determine whether treatment with kb NB 142-70 enhances accumulation of phosphatidylinositol (3,4,5-trisphosphate (PIP3 in the plasma membrane, we monitored the redistribution of Akt-pleckstrin homology domain-green fluorescent protein (Akt-PH-GFP in single IEC-18 cells. Exposure to kb NB 142-70 strikingly increased membrane accumulation of Akt-PH-GFP in response to ANG II. The translocation of the PIP3 sensor to the plasma membrane and the phosphorylation of Akt was completed prevented by prior exposure to the class I p110α specific inhibitor A66. ANG II markedly increased the phosphorylation of p85α detected by a PKD motif-specific antibody and enhanced the association of p85α with PTEN. Transgenic mice overexpressing PKD1 showed a reduced phosphorylation of Akt at Ser(473 in intestinal epithelial cells compared to wild type littermates. Collectively these results indicate that PKD1 activation mediates feedback inhibition of PI3K/Akt signaling in intestinal epithelial cells in vitro and in vivo.

Non-transactivational, dual pathways for LPA-induced Erk1/2 activation in primary cultures of brown pre-adipocytes

International Nuclear Information System (INIS)

Holmstroem, Therese E.; Mattsson, Charlotte L.; Wang, Yanling; Iakovleva, Irina; Petrovic, Natasa; Nedergaard, Jan

2010-01-01

In many cell types, G-protein-coupled receptor (GPCR)-induced Erk1/2 MAP kinase activation is mediated via receptor tyrosine kinase (RTK) transactivation, in particular via the epidermal growth factor (EGF) receptor. Lysophosphatidic acid (LPA), acting via GPCRs, is a mitogen and MAP kinase activator in many systems, and LPA can regulate adipocyte proliferation. The mechanism by which LPA activates the Erk1/2 MAP kinase is generally accepted to be via EGF receptor transactivation. In primary cultures of brown pre-adipocytes, EGF can induce Erk1/2 activation, which is obligatory and determinant for EGF-induced proliferation of these cells. Therefore, we have here examined whether LPA, via EGF transactivation, can activate Erk1/2 in brown pre-adipocytes. We found that LPA could induce Erk1/2 activation. However, the LPA-induced Erk1/2 activation was independent of transactivation of EGF receptors (or PDGF receptors) in these cells (whereas in transformed HIB-1B brown adipocytes, the LPA-induced Erk1/2 activation indeed proceeded via EGF receptor transactivation). In the brown pre-adipocytes, LPA instead induced Erk1/2 activation via two distinct non-transactivational pathways, one G i -protein dependent, involving PKC and Src activation, the other, a PTX-insensitive pathway, involving PI3K (but not Akt) activation. Earlier studies showing LPA-induced Erk1/2 activation being fully dependent on RTK transactivation have all been performed in cell lines and transfected cells. The present study implies that in non-transformed systems, RTK transactivation may not be involved in the mediation of GPCR-induced Erk1/2 MAP kinase activation.

A comparative analysis between France and Japan on local governments' involvement in nuclear safety governance

International Nuclear Information System (INIS)

Sugawara, Shin-etsu; Shiroyama, Hideaki

2011-01-01

This paper shows a comparative analysis between France and Japan on the way of the local governments' involvement in nuclear safety governance through some interviews. In France, a law came into force that requires related local governments to establish 'Commision Locale d'Information' (CLI), which means the local governments officially involve in nuclear regulatory activity. Meanwhile, in Japan, related local governments substantially involve in the operation of nuclear facilities through the 'safety agreements' in spite of the lack of legal authority. As a result of comparative analysis, we can point out some institutional input from French cases as follows: to clarify the local governments' roles in the nuclear regulation system, to establish the official channels of communication among nuclear utilities, national regulatory authorities and local governments, and to stipulate explicitly the transparency as a purpose of safety regulation. (author)

Corporate governance of the environment.

OpenAIRE

Purvis, B.

2005-01-01

The global pursuit of a more sustainable future cannot be achieved without the active engagement of the business community. The challenge for business has been to strategically engage with and embed environmental responsibility within their wider corporate governance to create effective corporate governance of the environment. The assumption would appear to be, that we have already witnessed the construction of such governance, delivered through the attainment of a paradigmatic shift in corpo...

Regulatory activities of government: analysis of determinants

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Primož Pevcin

2006-12-01

Full Text Available International comparisons show that large cross-country differences exist in the overall macro extent of regulation of the economy. In this context, the main purpose of the article is to investigate, why such differences exist by identifying and empirically verifying the effect of various factors that could potentially shape those differences. Empirical analysis based on the sample of 32 developed and democratic countries revealed that almost 70 % of variation in the macro extent of regulation could be explained with 7 statistically significant explanatory variables. The econometric analysis revealed that the macro extent of regulation decreases with income inequality in society, with the level of economic development, with the sizeof economy, with the share of transfer spending in GDP and with the share of government employment in labour force. On the other hand, the extent of regulation is positively related to government ownership of enterprises and to presidential political regime

Dissecting signaling and functions of adhesion G protein-coupled receptors

DEFF Research Database (Denmark)

Araç, Demet; Aust, Gabriela; Calebiro, Davide

2012-01-01

G protein-coupled receptors (GPCRs) comprise an expanded superfamily of receptors in the human genome. Adhesion class G protein-coupled receptors (adhesion-GPCRs) form the second largest class of GPCRs. Despite the abundance, size, molecular structure, and functions in facilitating cell and matrix...... contacts in a variety of organ systems, adhesion-GPCRs are by far the most poorly understood GPCR class. Adhesion-GPCRs possess a unique molecular structure, with extended N-termini containing various adhesion domains. In addition, many adhesion-GPCRs are autoproteolytically cleaved into an N......-terminal fragment (NTF, NT, α-subunit) and C-terminal fragment (CTF, CT, β-subunit) at a conserved GPCR autoproteolysis-inducing (GAIN) domain that contains a GPCR proteolysis site (GPS). These two features distinguish adhesion-GPCRs from other GPCR classes. Though active research on adhesion-GPCRs in diverse areas...

Security Cooperation Activities: Strengthening a Partner Military and its Governing Institutions

Science.gov (United States)

2016-05-26

governments suffered from economic instability , corruption, poor rule of law, and low administration of justice. Government and economic stability ...types of programs applied. Conditions defining allied state characteristics are military structure, government polity rating, and economic stability ...regional instability . Dr. Michael Mihalka and Mr. Mark Wilcox covered the trends in liberal democracy in the South Caucasus in light of economic

Development and implementation of a local government survey to measure community supports for healthy eating and active living

Directory of Open Access Journals (Sweden)

Latetia V Moore

2017-06-01

Full Text Available The ability to make healthy choices is influenced by where one lives, works, shops, and plays. Locally enacted policies and standards can influence these surroundings but little is known about the prevalence of such policies and standards that support healthier behaviors. In this paper, we describe the development of a survey questionnaire designed to capture local level policy supports for healthy eating and active living and findings and lessons learned from a 2012 pilot in two states, Minnesota and California, including respondent burden, survey sampling and administration methods, and survey item feasibility issues. A 38-item, web-based, self-administered survey and sampling frame were developed to assess the prevalence of 22 types of healthy eating and active living policies in a representative sample of local governments in the two states. The majority of respondents indicated the survey required minimal effort to complete with half taking <20 min to complete the survey. A non-response follow-up plan including emails and phone calls was required to achieve a 68% response rate (versus a 37% response rate for email only reminders. Local governments with larger residential populations reported having healthy eating and active living policies and standards more often than smaller governments. Policies that support active living were more common than those that support healthy eating and varied within the two states. The methods we developed are a feasible data collection tool for estimating the prevalence of municipal healthy eating and active living policies and standards at the state and national level.

Privacy and Open Government

Directory of Open Access Journals (Sweden)

Teresa Scassa

2014-06-01

Full Text Available The public-oriented goals of the open government movement promise increased transparency and accountability of governments, enhanced citizen engagement and participation, improved service delivery, economic development and the stimulation of innovation. In part, these goals are to be achieved by making more and more government information public in reusable formats and under open licences. This paper identifies three broad privacy challenges raised by open government. The first is how to balance privacy with transparency and accountability in the context of “public” personal information. The second challenge flows from the disruption of traditional approaches to privacy based on a collapse of the distinctions between public and private sector actors. The third challenge is that of the potential for open government data—even if anonymized—to contribute to the big data environment in which citizens and their activities are increasingly monitored and profiled.

Network governance and capacity of local governments to deliver LED in Uganda

Directory of Open Access Journals (Sweden)

Rose B Namara

2016-02-01

Full Text Available This paper discusses network governance and its contribution to the capacity of local governments (LGs to deliver local economic development (LED in Uganda. Although a formal LED policy was only established in Uganda in February 2014, there have been LED-inspired practices in the past decade. Various scholars and practitioners have observed that the autonomy and capacity of LGs to deliver LED is limited, but have been hopeful that new governance strategies like network governance would increase the capacities of LGs. However, neither network governance arrangements among LGs, nor their potential to improve governance capacity, have been documented. In a case study of Kyenjojo District, this paper finds that existing network governance arrangements have been fundamental in improving financial autonomy at this LG, delivering some income to invest in LED activities, although no evidence was found of reduced transaction costs in transforming local economies. The study further reveals that network governance arrangements have not led to the development of specialised skills in regulation or law enforcement, and capacity gaps are evident amongst staff and members in understanding the private sector and how it works. On a positive note, there is clear evidence of attempts by the LG to be innovative. Based on these findings, this study recommends that LGs need to consider a multi-pronged or multi-network governance approach to LED, which in turn will require a refocusing of governance mechanisms to become more dynamic and responsive, and offer incentives to the various actors in the development sector.

Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells.

Directory of Open Access Journals (Sweden)

Asaph Zylbertal

2015-12-01

Full Text Available Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB, which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i, which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions.

IT governance definitions and frameworks: a literature review

OpenAIRE

L. Caporarello

2006-01-01

Organizations seek to mirror their corporate governance arrangements in the activities of their key subunits – as IT function – in order to lower their organizational coordination costs. Some researches evidence that the mode of corporate governance significantly influences the mode of IT governance: organizations that have centralized their corporate governance also tend to centralize their IT governance, whereas organizations that have decentralized their corporate governance tend to dec...

Voice lessons : local government organizations, social organizations, and the quality of local governance

OpenAIRE

Alatas, Vivi; Pritchett, Lant; Wetterberg, Anna

2003-01-01

As part the Local Level Institutions study of local life in villages in rural Indonesia information was gathered on sampled household's participation in social activities. We classified the reported activities into four distinct types of social activity: sociability, networks, social organizations, and village government organizations. Respondents were also asked about questions about thei...

76 FR 23541 - Proposed Information Collection; Comment Request; Government Units Survey

Science.gov (United States)

2011-04-27

... the United States; (2) To obtain descriptive information on the basic characteristics of governments... basic information on the governing board, authorizing legislation, the Web address, agency activity, and.../pension plan, government activity, public services, judicial or legal activities, and finance. The first...

The centralization of territorial governance of active labor market policies in Spain during the Great Recession (2011-2016

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Jorge José Hernández-Moreno

2017-11-01

Full Text Available Spain is among the West European countries that has achieved higher levels of decentralization in its Welfare State. The 1990s and 2000s witnessed an acceleration of this process, which has been accompanied by an expansion of social spending at the subnational level, especially by the Autonomous Communities (Autonomous Communities. This article aims to contribute to several debates regarding changes in the territorial dimension of governance in social policies and their explanatory factors. Specifically, it focuses on active labor market policies (ALMPs and addresses the question of whether the reforms introduced in the field of activation in the context of the economic crisis have affected the exercise of political, financial and administrative authority by the different levels of government.

Gq activity- and β-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility

Science.gov (United States)

Lin, Hui; Li, Rui-Rui; Liang, Zong-Lai; Gao, Yuan; Yang, Zhao; He, Dong-Fang; Lin, Amy; Mo, Hui; Lu, Yu-Jing; Li, Meng-Jing; Kong, Wei; Chung, Ka Young; Yi, Fan; Li, Jian-Yuan; Qin, Ying-Ying; Li, Jingxin; Thomsen, Alex R B; Kahsai, Alem W; Chen, Zi-Jiang; Xu, Zhi-Gang; Liu, Mingyao

2018-01-01

Luminal fluid reabsorption plays a fundamental role in male fertility. We demonstrated that the ubiquitous GPCR signaling proteins Gq and β-arrestin-1 are essential for fluid reabsorption because they mediate coupling between an orphan receptor ADGRG2 (GPR64) and the ion channel CFTR. A reduction in protein level or deficiency of ADGRG2, Gq or β-arrestin-1 in a mouse model led to an imbalance in pH homeostasis in the efferent ductules due to decreased constitutive CFTR currents. Efferent ductule dysfunction was rescued by the specific activation of another GPCR, AGTR2. Further mechanistic analysis revealed that β-arrestin-1 acts as a scaffold for ADGRG2/CFTR complex formation in apical membranes, whereas specific residues of ADGRG2 confer coupling specificity for different G protein subtypes, this specificity is critical for male fertility. Therefore, manipulation of the signaling components of the ADGRG2-Gq/β-arrestin-1/CFTR complex by small molecules may be an effective therapeutic strategy for male infertility. PMID:29393851

Shifting between self-governing and being governed: a qualitative study of older persons' self-determination.

Science.gov (United States)

Ottenvall Hammar, Isabelle; Dahlin-Ivanoff, Synneve; Wilhelmson, Katarina; Eklund, Kajsa

2014-11-28

Older persons' right to exercise self-determination in daily life is supported by several laws. Research shows that older persons' self-determination is not fully respected within the healthcare sector. In order to enable and enhance older persons' self-determination, extensive knowledge of older persons' self-determination is needed. The aim of this study was to explore experiences of self-determination when developing dependence in daily activities among community-dwelling persons 80 years and older. Qualitative interviews were performed in accordance with a grounded theory method, with 11 persons aged 84-95 years who were beginning to develop dependence in daily activities. The data analysis revealed the core category, "Self-determination - shifting between self-governing and being governed". The core category comprised three categories: "Struggling against the aging body", "Decision-making is relational", and "Guarding one's own independence". Self-determination in daily activities was related to a shifting, which was two-fold, and varied between self-governing and being governed by the aging body, or by others. The findings imply a need to adopt a person-centered approach where the older persons' own preferences and needs are in focus, in order to enhance their possibilities to exercise self-determination.

PENGARUH CORPORATE GOVERNANCE TERHADAP TAX AVOIDANCE

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Nuralifmida Ayu Annisa

2012-05-01

Full Text Available This study aims to find out how the influence of the corporate governance of tax avoidanceactivity in companies listed on Indonesia Stock Exchange in 2008. The samples are publiclytraded company listed on the Indonesia Stock Exchange in 2008 as many as 200 companies. Thisstudy uses data analysis and regression analysis of the elements of corporate governance and taxavoidance. The results of this study show that the elements of corporate governance that consist ofaudit quality and audit committee significantly influence the activity of tax avoidance as measuredusing proxy book tax gap. Other results show that the tax avoidance activity as measured withproxy book tax gap are not affected significantly by institutional ownership and board ofcommissioners. Limitation of this study is not to use each type of industries as control variable socan’t identify the direct effect from type of industry on tax avoidance. Another limitation of thisstudy is use corporate governance’s proxy separately, so it can’t capture the full effect ofcorporate governance. Keywords:corporate governance, ownership structure, board of commissioners, audit committee,tax avoidance, book tax gap.

METHODOLOGICAL ASPECTS OF RURAL DEVELOPMENT GOVERNANCE CASE STUDY

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Vitalina TSYBULYAK

2014-01-01

Full Text Available The article discusses current approaches to the process of assessing rural development governance, reveals its advantages and disadvantages. The article as well presents performance system indicators of governance process by means of two elements of dynamics assessment, rural development (economic, financial, and social sphere, ecology and population health and management process (assessment of strategic plan (concept of development, program of socioeconomic development of rural areas, current activity of local authorities, in particular. More over, it is suggested to use typology of approaches (objective (evolutionary, command and control, economic (infrastructural, complex, and qualitative to definition of process essence of rural development governance and correlation of traditional functions, performed by the subjects of the governance process of rural development (state authorities institutions, local authorities institutions, economic entities, and community. Adjusting traditional functions, performed by governance subjects of local development, their supplementing with new ones, relevant to the present-to-date model of «shared governance» is an important element of analysis of assessment tools for effectiveness of rural development governance. In addition, the author defines functioning of two forms of rural population involvement into the process of rural development governance: active and passive. Active one suggests that rural population participate in making and implementing governance decisions (public meetings, organization of social discussions, and development of territory community self-governance; passive one suggests that the emphasis is placed only on information distribution among population (meetings with parliament members, direct phone lines with territory governors, publication of normative and legal acts and reports on budget execution

Monitoring β-arrestin recruitment via β-lactamase enzyme fragment complementation: purification of peptide E as a low-affinity ligand for mammalian bombesin receptors.

Directory of Open Access Journals (Sweden)

Yuichi Ikeda

Full Text Available Identification of cognate ligands for G protein-coupled receptors (GPCRs provides a starting point for understanding novel regulatory mechanisms. Although GPCR ligands have typically been evaluated through the activation of heterotrimeric G proteins, recent studies have shown that GPCRs signal not only through G proteins but also through β-arrestins. As such, monitoring β-arrestin signaling instead of G protein signaling will increase the likelihood of identifying currently unknown ligands, including β-arrestin-biased agonists. Here, we developed a cell-based assay for monitoring ligand-dependent GPCR-β-arrestin interaction via β-lactamase enzyme fragment complementation. Inter alia, β-lactamase is a superior reporter enzyme because of its cell-permeable fluorescent substrate. This substrate makes the assay non-destructive and compatible with fluorescence-activated cell sorting (FACS. In a reporter cell, complementary fragments of β-lactamase (α and ω were fused to β-arrestin 2 and GPCR, respectively. Ligand stimulation initiated the interaction of these chimeric proteins (β-arrestin-α and GPCR-ω, and this inducible interaction was measured through reconstituted β-lactamase activity. Utilizing this system, we screened various mammalian tissue extracts for agonistic activities on human bombesin receptor subtype 3 (hBRS3. We purified peptide E as a low-affinity ligand for hBRS3, which was also found to be an agonist for the other two mammalian bombesin receptors such as gastrin-releasing peptide receptor (GRPR and neuromedin B receptor (NMBR. Successful purification of peptide E has validated the robustness of this assay. We conclude that our newly developed system will facilitate the discovery of GPCR ligands.

China’s Foreign Aid and Government-Sponsored Investment Activities: Scale, Content, Destinations, and Implications

Science.gov (United States)

2013-01-01

this document Browse Reports & Bookstore Make a charitable contribution Limited Electronic Distribution Rights This document and trademark(s...sponsors. Support RAND—make a tax-deductible charitable contribution at www.rand.org/giving/contribute.html R® is a registered trademark © Copyright 2013...cooperation organizations such as the xvi China’s Foreign Aid and Government-Sponsored Investment Activities Shanghai Cooperation Organisation have

Spatiotemporal Control of GPR37 Signaling and Its Behavioral Effects by Optogenetics

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Wu Zheng

2018-03-01

Full Text Available Despite the progress in deorphanization of G Protein-Coupled Receptors (GPCRs, ≈100 GPCRs are still classified as orphan receptors without identified endogenous ligands and with unknown physiological functions. The lack of endogenous ligands triggering GPCR signaling has hampered the study of orphan GPCR functions. Using GPR37 as an example, we provide here the first demonstration of the channelrhodopsin 2 (ChR2-GPCR approach to bypass the endogenous ligand and selectively activate the orphan GPCR signal by optogenetics. Inspired by the opto-XR approach, we designed the ChR2-GPR37 chimera, in which the corresponding parts of GPR37 replaced the intracellular portions of ChR2. We showed that optogenetic activation of ChR2/opto-GPR37 elicited specific GPR37 signaling, as evidenced by reduced cAMP level, enhanced ERK phosphorylation and increased motor activity, confirming the specificity of opto-GPR37 signaling. Besides, optogenetic activation of opto-GPR37 uncovered novel aspects of GPR37 signaling (such as IP-3 signaling and anxiety-related behavior. Optogenetic activation of opto-GPR37 permits the causal analysis of GPR37 activity in the defined cells and behavioral responses of freely moving animals. Importantly, given the evolutionarily conserved seven-helix transmembrane structures of ChR2 and orphan GPCRs, we propose that opto-GPR37 approach can be readily applied to other orphan GPCRs for their deorphanization in freely moving animals.

Regulation of Epithelial Morphogenesis by the G-Protein Coupled Receptor Mist and its Ligand Fog*

Science.gov (United States)

Manning, Alyssa J.; Peters, Kimberly A.; Peifer, Mark; Rogers, Stephen L.

2014-01-01

Epithelial morphogenesis is essential for shaping organs and tissues and for establishment of the three embryonic germ layers during gastrulation. Studies of gastrulation in Drosophila have provided insight into how epithelial morphogenesis is governed by developmental patterning mechanisms. We developed an assay to recapitulate morphogenetic shape changes in individual cultured cells, and used RNAi-based screening to identify Mist, a Drosophila G protein-coupled receptor (GPCR) that transduces signals from the secreted ligand Folded gastrulation (Fog) in cultured cells. Mist functioned in Fog-dependent embryonic morphogenesis, and the transcription factor Snail regulated expression of mist in zygotes. Our data revealed how a cell fate transcriptional program acts through a ligand-GPCR pair to stimulate epithelial morphogenetic shape changes. PMID:24222713

Corporate governance and firm characteristics as explanatory factors of shareholder activism: Validation through the French context

Directory of Open Access Journals (Sweden)

Siala Bouaziz Souha

2016-12-01

Full Text Available This study deals with the major determinants of company shareholder activism investigated with according to a set of SBF 120 listed firms. Based on a sample of 77 companies, observed over the period 2008–2012, we are led to conclude that some firm governance characteristics do appear to affect shareholding activism. In addition, it has been revealed that the presence of institutional investors, ownership concentration, leaders’ presence in the capital, control structure, leadership change, firm growth as well as leverage level appear to have a significant influence on the probability of activism to take place.

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

Science.gov (United States)

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

2017-01-01

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

G Protein-Coupled Receptor-G-Protein βγ-Subunit Signaling Mediates Renal Dysfunction and Fibrosis in Heart Failure.

Science.gov (United States)

Kamal, Fadia A; Travers, Joshua G; Schafer, Allison E; Ma, Qing; Devarajan, Prasad; Blaxall, Burns C

2017-01-01

Development of CKD secondary to chronic heart failure (CHF), known as cardiorenal syndrome type 2 (CRS2), clinically associates with organ failure and reduced survival. Heart and kidney damage in CRS2 results predominantly from chronic stimulation of G protein-coupled receptors (GPCRs), including adrenergic and endothelin (ET) receptors, after elevated neurohormonal signaling of the sympathetic nervous system and the downstream ET system, respectively. Although we and others have shown that chronic GPCR stimulation and the consequent upregulated interaction between the G-protein βγ-subunit (Gβγ), GPCR-kinase 2, and β-arrestin are central to various cardiovascular diseases, the role of such alterations in kidney diseases remains largely unknown. We investigated the possible salutary effect of renal GPCR-Gβγ inhibition in CKD developed in a clinically relevant murine model of nonischemic hypertrophic CHF, transverse aortic constriction (TAC). By 12 weeks after TAC, mice developed CKD secondary to CHF associated with elevated renal GPCR-Gβγ signaling and ET system expression. Notably, systemic pharmacologic Gβγ inhibition by gallein, which we previously showed alleviates CHF in this model, attenuated these pathologic renal changes. To investigate a direct effect of gallein on the kidney, we used a bilateral ischemia-reperfusion AKI mouse model, in which gallein attenuated renal dysfunction, tissue damage, fibrosis, inflammation, and ET system activation. Furthermore, in vitro studies showed a key role for ET receptor-Gβγ signaling in pathologic fibroblast activation. Overall, our data support a direct role for GPCR-Gβγ in AKI and suggest GPCR-Gβγ inhibition as a novel therapeutic approach for treating CRS2 and AKI. Copyright © 2016 by the American Society of Nephrology.

'Joined Up' Local Governments?

DEFF Research Database (Denmark)

Bjørnå, Hilde; Casale, Donatella; Hajnal, Gyorgy

eforms inspired by NPM have raised many challenges to governments, such as time lags between implementation and (any) results, fragmentation due to unbundling monolithic organizations and mediocre support from public sector stakeholders (Christensen/Lægreid 2007, Dunleavy et al. 2006, Hood...... measures (6 2004). JUG involves an emphasis on coordinating governmental activities, for example through partnerships and horizontal governing approaches, to eliminate contradictions between different policies, and to deliver integrated and seamless services from a citizen’s perspective (Lægreid et al......, for example one-stop-shops, often combined with e-government solutions (Norway, Italy, Hungary and Germany), public sector recentralisation and de-agencification (Ireland) or refined strategies for steering the ‘landscape of corporatized organizations‘ (Hungary and Austria)....

Evaluating e-Government and Good Governance Correlation

Directory of Open Access Journals (Sweden)

Suhardi Suhardi

2016-03-01

Full Text Available Assessing the achievement of Indonesian government institutions in implementing e-government has been conducted since around a decade ago. Several national assessments are available with almost the same ranking results. There is an agreement that the ultimate goal of e-government implementation is to achieve good government governance (GGG, while success stories of e-government require good governance practices. This study explored the correlation between e-government achievement and GGG achievement in Indonesia. Spearman’s rank correlation was used to characterize the relationship strength between e-government assessment results and good governance assessment results. The data were collected from institutions that participated in e-government and good governance assessments. The results showed that the correlation between these two entities is not very strong. Most cases showed that e-government implementation and the achievement of good governance have only a moderate positive correlation and none of the studied cases indicated a significant connection. This result can be attributed to the lack of emphasis on goals achievement in the assessments. Thus, it is recommended that future Indonesian e-government assessments should involve impact indicators.

Optodynamic simulation of β-adrenergic receptor signalling.

Science.gov (United States)

Siuda, Edward R; McCall, Jordan G; Al-Hasani, Ream; Shin, Gunchul; Il Park, Sung; Schmidt, Martin J; Anderson, Sonya L; Planer, William J; Rogers, John A; Bruchas, Michael R

2015-09-28

Optogenetics has provided a revolutionary approach to dissecting biological phenomena. However, the generation and use of optically active GPCRs in these contexts is limited and it is unclear how well an opsin-chimera GPCR might mimic endogenous receptor activity. Here we show that a chimeric rhodopsin/β2 adrenergic receptor (opto-β2AR) is similar in dynamics to endogenous β2AR in terms of: cAMP generation, MAP kinase activation and receptor internalization. In addition, we develop and characterize a novel toolset of optically active, functionally selective GPCRs that can bias intracellular signalling cascades towards either G-protein or arrestin-mediated cAMP and MAP kinase pathways. Finally, we show how photoactivation of opto-β2AR in vivo modulates neuronal activity and induces anxiety-like behavioural states in both fiber-tethered and wireless, freely moving animals when expressed in brain regions known to contain β2ARs. These new GPCR approaches enhance the utility of optogenetics and allow for discrete spatiotemporal control of GPCR signalling in vitro and in vivo.

GPCR Interaction: 80 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available o permit dimerization, and the corresponding monomers were characterized in a fun...ctional melanocyte dispersion assay. Peptide dimers have enhanced functional activity; monospecific dimers h

Minsky on "Big Government"

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Daniel de Santana Vasconcelos

2014-03-01

Full Text Available This paper objective is to assess, in light of the main works of Minsky, his view and analysis of what he called the "Big Government" as that huge institution which, in parallels with the "Big Bank" was capable of ensuring stability in the capitalist system and regulate its inherently unstable financial system in mid-20th century. In this work, we analyze how Minsky proposes an active role for the government in a complex economic system flawed by financial instability.

Crystal structure of the PAC1R extracellular domain unifies a consensus fold for hormone recognition by class B G-protein coupled receptors.

Directory of Open Access Journals (Sweden)

Shiva Kumar

Full Text Available Pituitary adenylate cyclase activating polypeptide (PACAP is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR. Crystal structures of a number of Class B GPCR extracellular domains (ECD bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors.

Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists.

Science.gov (United States)

Cheng, Han; Lear-Rooney, Calli M; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W; Olinger, Gene G; Rong, Lijun

2015-10-01

Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious

Nanotechnology and the need for risk governance

International Nuclear Information System (INIS)

Renn, O.; Roco, M. C.

2006-01-01

After identifying the main characteristics and prospects of nanotechnology as an emerging technology, the paper presents the general risks associated with nanotechnology applications and the deficits of the risk governance process today, concluding with recommendations to governments, industry, international organizations and other stakeholders. The International Risk Governance Council (IRGC) has identified a governance gap between the requirements pertaining to the nano- rather than the micro-/macro- technologies. The novel attributes of nanotechnology demand different routes for risk-benefit assessment and risk management, and at present, nanotechnology innovation proceeds ahead of the policy and regulatory environment. In the shorter term, the governance gap is significant for those passive nanostructures that are currently in production and have high exposure rates; and is especially significant for the several 'active' nanoscale structures and nanosystems that we can expect to be on the market in the near future. Active nanoscale structures and nanosystems have the potential to affect not only human health and the environment but also aspects of social lifestyle, human identity and cultural values. The main recommendations of the report deal with selected higher risk nanotechnology applications, short- and long-term issues, and global models for nanotechnology governance

Apply TQM to E-Government Outsourcing Management

Science.gov (United States)

Huai, Jinmei

This paper developed an approach to e-government outsourcing quality management. E-government initiatives have rapidly increased in the last decades and the success of these activities will largely depend on their operation quality. As an instrument to improve operation quality, outsourcing can be applied to e-government. This paper inspected process of e-government outsourcing and discussed how to improve the outsourcing performance through total quality management (TQM). The characteristics and special requirements of e-government outsourcing were analyzed as the basis for discussion. Then the principles and application of total quality management were interpreted. Finally the process of improving performance of e-government was analyzed in the context of outsourcing.

GPCR Interaction: 59 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available required for their anti-HIV-1 activity. 11854425, 14716309, 10725362, 12089144 Point mutation, bioinforma...tics approach BRET Western blot Cross-linking in the presence of agonist, immunoprecipitation, western blot NP_000570.1 ...

Receptor-G Protein Interaction Studied by Bioluminescence Resonance Energy Transfer: Lessons From Protease-Activated Receptor 1

Directory of Open Access Journals (Sweden)

Mohammed Akli eAYOUB

2012-06-01

Full Text Available Since its development, the bioluminescence resonance energy transfer (BRET approach has been extensively applied to study G protein-coupled receptors (GPCRs in real time and in live cells. One of the major aspects of GPCRs investigated in considerable details is their physical coupling to the heterotrimeric G proteins. As a result, new concepts have emerged, but few questions are still a matter of debate illustrating the complexity of GPCR-G protein interactions and coupling. Here, we summarized the recent advances on our understanding of GPCR-G protein coupling based on BRET approaches and supported by other FRET-based studies. We essentially focused on our recent studies in which we addressed the concept of preassembly versus the agonist-dependent interaction between the protease-activated receptor 1 (PAR1 and its cognate G proteins. We discussed the concept of agonist-induced conformational changes within the preassembled PAR1-G protein complexes as well as the critical question how the multiple coupling of PAR1 with two different G proteins, Gi1 and G12, but also -arrestin 1, can be regulated.

The Biased G-Protein-Coupled Receptor Agonism Bridges the Gap between the Insulin Receptor and the Metabolic Syndrome

Science.gov (United States)

Liauchonak, Iryna; Dawoud, Fady; Riat, Yatin; Sambi, Manpreet; Jain, Justin; Kalaydina, Regina-Veronicka; Mendonza, Nicole; Bajwa, Komal

2018-01-01

Insulin signaling, as mediated through the insulin receptor (IR), plays a critical role in metabolism. Aberrations in this signaling cascade lead to several pathologies, the majority of which are classified under the umbrella term “metabolic syndrome”. Although many of these pathologies are associated with insulin resistance, the exact mechanisms are not well understood. One area of current interest is the possibility of G-protein-coupled receptors (GPCRs) influencing or regulating IR signaling. This concept is particularly significant, because GPCRs have been shown to participate in cross-talk with the IR. More importantly, GPCR signaling has also been shown to preferentially regulate specific downstream signaling targets through GPCR agonist bias. A novel study recently demonstrated that this GPCR-biased agonism influences the activity of the IR without the presence of insulin. Although GPCR-IR cross-talk has previously been established, the notion that GPCRs can regulate the activation of the IR is particularly significant in relation to metabolic syndrome and other pathologies that develop as a result of alterations in IR signaling. As such, we aim to provide an overview of the physiological and pathophysiological roles of the IR within metabolic syndrome and its related pathologies, including cardiovascular health, gut microflora composition, gastrointestinal tract functioning, polycystic ovarian syndrome, pancreatic cancer, and neurodegenerative disorders. Furthermore, we propose that the GPCR-biased agonism may perhaps mediate some of the downstream signaling effects that further exacerbate these diseases for which the mechanisms are currently not well understood. PMID:29462993

GPCR Interaction: 188 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available ivation are reduced by activation of CXCR4 in advance. In addition, calcium mobilization assays show these cross-desensitization...ion is not responsible for desensitization between these receptors. 18533278 Calcium mobilization assay NP_000903.2 ...

GPCR Interaction: 187 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available tivation are reduced by activation of CXCR4 in advance. In addition, calcium mobilization assays show these cross-desensitization...tion is not responsible for desensitization between these receptors. 18533278 Calcium mobilization assay NP_001008540.1 ...

48 CFR 8.406-5 - Termination for the Government's convenience.

Science.gov (United States)

2010-10-01

... Government's convenience. 8.406-5 Section 8.406-5 Federal Acquisition Regulations System FEDERAL ACQUISITION... Termination for the Government's convenience. (a) An ordering activity contracting officer may terminate individual orders for the Government's convenience. Terminations for the Government's convenience shall...

Stable GPR101 over-Expressing Cell Lines As an Invaluable Tool for Functional Studies, Ligand Screening, and the Identification of Deregulated Genes/Pathways in Patients with X-Linked Acrogigantism

OpenAIRE

Trivellin, Giampaolo; Janjic, Maria; Larco, Darwin; Tomic, Melanija; Daly, Adrian; Palmeira, Leonor; Faucz; BECKERS, Albert; Wu, T John; Calebiro, Davide; Stojilkovic, Stanko; Stratakis, Constantine

2017-01-01

Background: GPR101 is an orphan G protein-coupled receptor (GPCR) that is duplicated in patients with X-linked acrogigantism (X-LAG) and over-expressed in their GH- and PRL-secreting tumors. GPR101 is a constitutively active GPCR that strongly activates the cAMP pathway. To elucidate the mechanisms through which GPR101 causes GH over-secretion we generated HEK293 and GH/PRL-secreting (GH3) cells with stable GPR101 expression. Methods: Both cell lines were created via direct integration of ...

Neuronal Functions of Activators of G Protein Signaling

Directory of Open Access Journals (Sweden)

Man K. Tse

2012-05-01

Full Text Available G protein-coupled receptors (GPCRs are one of the most important gateways for signal transduction across the plasma membrane. Over the past decade, several classes of alternative regulators of G protein signaling have been identified and reported to activate the G proteins independent of the GPCRs. One group of such regulators is the activator of G protein signaling (AGS family which comprises of AGS1-10. They have entirely different activation mechanisms for G proteins as compared to the classic model of GPCR-mediated signaling and confer upon cells new avenues of signal transduction. As GPCRs are widely expressed in our nervous system, it is believed that the AGS family plays a major role in modulating the G protein signaling in neurons. In this article, we will review the current knowledge on AGS proteins in relation to their potential roles in neuronal regulations.

Diversity and impact of rare variants in genes encoding the platelet G protein-coupled receptors.

Science.gov (United States)

Jones, Matthew L; Norman, Jane E; Morgan, Neil V; Mundell, Stuart J; Lordkipanidzé, Marie; Lowe, Gillian C; Daly, Martina E; Simpson, Michael A; Drake, Sian; Watson, Steve P; Mumford, Andrew D

2015-04-01

Platelet responses to activating agonists are influenced by common population variants within or near G protein-coupled receptor (GPCR) genes that affect receptor activity. However, the impact of rare GPCR gene variants is unknown. We describe the rare single nucleotide variants (SNVs) in the coding and splice regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome Sequencing Project databases and in 31 cases with inherited platelet function disorders (IPFDs). In the population databases, the GPCR gene target regions contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice region) of which 70 % had global minor allele frequency (MAF) < 0.05 %. Functional annotation using six computational algorithms, experimental evidence and structural data identified 156/740 (21 %) SNVs as potentially damaging to GPCR function, most commonly in regions encoding the transmembrane and C-terminal intracellular receptor domains. In 31 index cases with IPFDs (Gi-pathway defect n=15; secretion defect n=11; thromboxane pathway defect n=3 and complex defect n=2) there were 256 SNVs in the target regions of 15 stimulatory platelet GPCRs (34 unique; 12 with MAF< 1 % and 22 with MAF≥ 1 %). These included rare variants predicting R122H, P258T and V207A substitutions in the P2Y12 receptor that were annotated as potentially damaging, but only partially explained the platelet function defects in each case. Our data highlight that potentially damaging variants in platelet GPCR genes have low individual frequencies, but are collectively abundant in the population. Potentially damaging variants are also present in pedigrees with IPFDs and may contribute to complex laboratory phenotypes.

Isolation and structure–function characterization of a signaling-active rhodopsin–G protein complex

Science.gov (United States)

Gao, Yang; Westfield, Gerwin; Erickson, Jon W.; Cerione, Richard A.; Skiniotis, Georgios; Ramachandran, Sekar

2017-01-01

The visual photo-transduction cascade is a prototypical G protein–coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (GT). This results in the dissociation of GT into its component αT–GTP and β1γ1 subunit complex. Structural information for the Rho*–GT complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (GT*) comprising a GαT/Gαi1 chimera (αT*) and β1γ1. The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to GαT* is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one GT*. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β2-adrenergic receptor–GS complex, including a flexible αT* helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. PMID:28655769

Regulation to create environments conducive to physical activity: understanding the barriers and facilitators at the Australian state government level.

Science.gov (United States)

Shill, Jane; Mavoa, Helen; Crammond, Brad; Loff, Bebe; Peeters, Anna; Lawrence, Mark; Allender, Steven; Sacks, Gary; Swinburn, Boyd A

2012-01-01

Policy and regulatory interventions aimed at creating environments more conducive to physical activity (PA) are an important component of strategies to improve population levels of PA. However, many potentially effective policies are not being broadly implemented. This study sought to identify potential policy/regulatory interventions targeting PA environments, and barriers/facilitators to their implementation at the Australian state/territory government level. In-depth interviews were conducted with senior representatives from state/territory governments, statutory authorities and non-government organisations (n = 40) to examine participants': 1) suggestions for regulatory interventions to create environments more conducive to PA; 2) support for preselected regulatory interventions derived from a literature review. Thematic and constant comparative analyses were conducted. POLICY INTERVENTIONS MOST COMMONLY SUGGESTED BY PARTICIPANTS FELL INTO TWO AREAS: 1) urban planning and provision of infrastructure to promote active travel; 2) discouraging the use of private motorised vehicles. Of the eleven preselected interventions presented to participants, interventions relating to walkability/cycling and PA facilities received greatest support. Interventions involving subsidisation (of public transport, PA-equipment) and the provision of more public transport infrastructure received least support. These were perceived as not economically viable or unlikely to increase PA levels. Dominant barriers were: the powerful 'road lobby', weaknesses in the planning system and the cost of potential interventions. Facilitators were: the provision of evidence, collaboration across sectors, and synergies with climate change/environment agendas. This study points to how difficult it will be to achieve policy change when there is a powerful 'road lobby' and government investment prioritises road infrastructure over PA-promoting infrastructure. It highlights the pivotal role of the

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

Science.gov (United States)

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

2017-06-16

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

E-Government Partnerships Across Levels of Government

OpenAIRE

Charbit, Claire; Michalun, Varinia

2009-01-01

E-government Partnerships across Levels of Government, is an overview of the challenges and approaches to creating a collaborative and cooperative partnership across levels of government for e-government development and implementation.

Ethics in Government.

Science.gov (United States)

Update on Law-Related Education, 1990

1990-01-01

Presents a lesson developed by the Center for Civic Education giving secondary students the opportunity to explore ethical issues in government from the perspective of corrective justice. Outlines role plays and other class activities based on a fictitious ethics scandal involving bribery. Identifies specific questions to be asked on issues of…

Strategic urban governance of transition in household practices

DEFF Research Database (Denmark)

Quitzau, Maj-Britt; Hoffmann, Birgitte; Hansen, Trine Bang

2013-01-01

Several studies have indicated that urban governance is in different ways intertwined with transitions in socio-technical systems (see e.g. Bulkeley et al. 2011). For example, some local authorities attempt to gain degrees of influence and control over regimes in order to achieve territorial...... priorities (Hodson and Marvin 2010). It has been argued that such governance initiatives do seldom represent transition paths in themselves, due to the delimited focus on the urban scale (Geels 2011). However, these governance initiatives still represent important transition activities that need...... based on the work by Shove and Walker (2010), who note that practitioners are actively involved in making and reproducing socio-technical systems. We especially wish to put forward this point in relation to discussions about what role urban governance initiatives may play in transitions in socio...

GPCR Interaction: 40 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available at similar levels. A significant agonist-promoted internalization of the beta2AR activates ERK1/2 MAPK in be...expressing beta1AR and both receptors. Agonist-promoted internalization of the be...efore, heterodimerization between beta1AR and beta2AR inhibits the agonist-promoted internalization of the b

The G protein Gi1 exhibits basal coupling but not preassembly with G protein-coupled receptors.

Science.gov (United States)

Bondar, Alexey; Lazar, Josef

2017-06-09

The G i/o protein family transduces signals from a diverse group of G protein-coupled receptors (GPCRs). The observed specificity of G i/o -GPCR coupling and the high rate of G i/o signal transduction have been hypothesized to be enabled by the existence of stable associates between G i/o proteins and their cognate GPCRs in the inactive state (G i/o -GPCR preassembly). To test this hypothesis, we applied the recently developed technique of two-photon polarization microscopy (2PPM) to Gα i1 subunits labeled with fluorescent proteins and four GPCRs: the α 2A -adrenergic receptor, GABA B , cannabinoid receptor type 1 (CB 1 R), and dopamine receptor type 2. Our experiments with non-dissociating mutants of fluorescently labeled Gα i1 subunits (exhibiting impaired dissociation from activated GPCRs) showed that 2PPM is capable of detecting GPCR-G protein interactions. 2PPM experiments with non-mutated fluorescently labeled Gα i1 subunits and α 2A -adrenergic receptor, GABA B , or dopamine receptor type 2 receptors did not reveal any interaction between the G i1 protein and the non-stimulated GPCRs. In contrast, non-stimulated CB 1 R exhibited an interaction with the G i1 protein. Further experiments revealed that this interaction is caused solely by CB 1 R basal activity; no preassembly between CB 1 R and the G i1 protein could be observed. Our results demonstrate that four diverse GPCRs do not preassemble with non-active G i1 However, we also show that basal GPCR activity allows interactions between non-stimulated GPCRs and G i1 (basal coupling). These findings suggest that G i1 interacts only with active GPCRs and that the well known high speed of GPCR signal transduction does not require preassembly between G proteins and GPCRs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

THE ROLE OF GOOD GOVERNANCE AND DEVELOPMENT ...

African Journals Online (AJOL)

Prof

Emerging trends point to good governance as a panacea towards .... to Third World countries by the western countries after the cold war era between USA and USSR. ... active participation of the citizens with the government in policy making, .... Academic experts in public administration and several American public ...

GPCR Interaction: 39 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available s. A significant agonist-promoted internalization of the beta2AR activates ERK1/2 MAPK in beta2AR-expressing...AR and both receptors. Agonist-promoted internalization of the beta2AR was inhibi...erization between beta1AR and beta2AR inhibits the agonist-promoted internalization of the beta2AR and the a

Corporate Governance, Sustainability and Capital Markets Orientation

OpenAIRE

Daniela M. Salvioni; Francesca Gennari

2014-01-01

Generally accepted principles of effective corporate governance have taken hold in the context of different models of governance, whose implementation is also linked to the share structure of the companies and to the dynamics of risk’s capital markets. Global companies need a global approach in the acquisition of consensus and financial resources, first of all through a correct development of the corporate governance activities and promoting a market-driven management inspired by long-term su...

What governs governance, and how does it evolve? The sociology of governance-in-action.

Science.gov (United States)

Fox, Nick J; Ward, Katie J

2008-09-01

Governance addresses a wide range of issues including social, economic and political continuity, security and integrity, individual and collective safety and the liberty and rights to self-actualization of citizens. Questions to be answered include how governance can be achieved and sustained within a social context imbued with cultural values and in which power is distributed unevenly and dynamically, and how governance impacts on individuals and institutions. Drawing on Gramscian notions of hegemony and consent, and recent political science literatures on regulation and meta-regulation, this paper develops a sociological model of governance that emphasizes a dynamic and responsive governance in action. Empirical data from a study of pharmaceutical governance is used to show how multiple institutions and actors are involved in sustaining effective governance. The model addresses issues of how governance is sustained in the face of change, why governance of practices varies from setting to setting, and how governance is achieved without legislation.

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

Directory of Open Access Journals (Sweden)

Md Shamim Hossain

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

Measuring Economic Freedom: Better Without Size of Government.

Science.gov (United States)

Ott, Jan

2018-01-01

The Heritage Foundation and the Fraser Institute measure economic freedom in nations using indices with ten and five indicators respectively. Eight of the Heritage indicators and four of the Fraser-indicators are about specific types of institutional quality, like rule of law, the protection of property, and the provision of sound money. More of these is considered to denote more economic freedom. Both indices also involve indicators of 'big government', or levels of government activities. More of that is seen to denote less economic freedom. Yet, levels of government spending, consumption, and transfers and subsidies appear to correlate positively with the other indicators related to institutional quality, while this correlation is close to zero for the level of taxation as a percentage of GDP. Using government spending, consumption transfers and subsidies as positive indicators is no alternative, because these levels stand for very different government activities, liberal or less liberal. This means that levels of government activities can better be left out as negative or positive indicators. Thus shortened variants of the indices create a better convergent validity in the measurement of economic freedom, and create higher correlations between economic freedom and alternative types of freedom, and between economic freedom and happiness. The higher correlations indicate a better predictive validity, since they are predictable in view of the findings of previous research and theoretical considerations about the relations between types of freedom, and between freedom and happiness.

Involvement of a putative intercellular signal-recognizing G protein-coupled receptor in the engulfment of Salmonella by the protozoan Tetrahymena

Directory of Open Access Journals (Sweden)

P.N. Agbedanu

2013-07-01

Full Text Available In an effort to investigate the molecular basis of protozoa engulfment-mediated hypervirulence of Salmonella in cattle, we evaluated protozoan G protein-coupled receptors (GPCRs as transducers of Salmonella engulfment by the model protozoan Tetrahymena. Our laboratory previously demonstrated that non-pathogenic protozoa (including Tetrahymena engulf Salmonella and then exacerbate its virulence in cattle, but the mechanistic details of the phenomenon are not fully understood. GPCRs were investigated since these receptors facilitate phagocytosis of particulates by Tetrahymena, and a GPCR apparently modulates bacterial engulfment for the pathogenic protozoan Entamoeba histolytica. A database search identified three putative Tetrahymena GPCRs, based on sequence homologies and predicted transmembrane domains, that were the focus of this study. Salmonella engulfment by Tetrahymena was assessed in the presence of suramin, a non-specific GPCR inhibitor. Salmonella engulfment was also assessed in Tetrahymena in which expression of putative GPCRs was knocked-down using RNAi. A candidate GPCR was then expressed in a heterologous yeast expression system for further characterization. Our results revealed that Tetrahymena were less efficient at engulfing Salmonella in the presence of suramin. Engulfment was reduced concordantly with a reduction in the density of protozoa. RNAi-based studies revealed that knock-down of one the Tetrahymena GPCRs caused diminished engulfment of Salmonella. Tetrahymena lysates activated this receptor in the heterologous expression system. These data demonstrate that the Tetrahymena receptor is a putative GPCR that facilitates bacterial engulfment by Tetrahymena. Activation of the putative GPCR seemed to be related to protozoan cell density, suggesting that its cognate ligand is an intercellular signaling molecule.

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity.

Science.gov (United States)

Renton, Paul; Green, Brenda; Maddaford, Shawn; Rakhit, Suman; Andrews, John S

2012-03-08

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the μ-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the μ-opioid GPCR was predicated on the modulatory role of nitric oxide on μ-opioid receptor function. Structure-activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 μM), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent μ-opioid binding affinity, K i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 μM). This work represents a novel approach in the development of new analgesics for the treatment of pain.

Does Government Public Capital Expenditure Matter?: Evidence for Canada

OpenAIRE

Dadgostar, Bahram; Mirabelli, Frank

1998-01-01

Does the provision of Canadian government capital expenditures and government deficits displace private economic activity? In the U.S., Erenburg (1993) found that private sector investment spending is enhanced by expected increases in public spending on infrastructure, while also showing that deficit spending has no significant effect on private investment. There is no empirical study to date that addresses the relationship between government capital investment and government debt on private ...

The influence of corporate governance on project governance

OpenAIRE

Gonda, Pavel

2011-01-01

This work identifies the interaction between corporate governance and project management in project governance. It begins with introduction of basics of corporate governance and various principles of corporate governance in chosen countries and organizations. Further it introduces theoretical background of project governance and its connection and to corporate governance. In practical part work analyzes the level of compliancy with Swiss codex of best praxis in chosen company. The results con...

Fishers' information in governance-a matter of trust

NARCIS (Netherlands)

Holm, Petter; Soma, Katrine

2016-01-01

Informational governance is an analytical concept that addresses the role of recent rapidly increasing information activities in governance processes and institutions. Scientific information no longer has the status as the only source of relevant information in organizational and public decision

Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1.

Science.gov (United States)

Singh, Varsha; Aballay, Alejandro

2012-09-28

In response to pathogen infection, the host innate immune system activates microbial killing pathways and cellular stress pathways that need to be balanced because insufficient or excessive immune responses have deleterious consequences. Recent studies demonstrate that two G protein-coupled receptors (GPCRs) in the nervous system of Caenorhabditis elegans control immune homeostasis. To investigate further how GPCR signaling controls immune homeostasis at the organismal level, we studied arrestin-1 (ARR-1), which is the only GPCR adaptor protein in C. elegans. The results indicate that ARR-1 is required for GPCR signaling in ASH, ASI, AQR, PQR, and URX neurons, which control the unfolded protein response and a p38 mitogen-activated protein kinase signaling pathway required for innate immunity. ARR-1 activity also controlled immunity through ADF chemosensory and AFD thermosensory neurons that regulate longevity. Furthermore, we found that although ARR-1 played a key role in the control of immunity by AFD thermosensory neurons, it did not control longevity through these cells. However, ARR-1 partially controlled longevity through ADF neurons.

Engineering governance: introducing a governance meta framework.

OpenAIRE

Brand, N.; Beens, B.; Vuuregge, E.; Batenburg, R.

2011-01-01

There is a need for a framework that depicts strategic choices within an organisation with regard to potential governance structures. The governance meta framework provides the necessary structure in the current developments of governance. Performance as well as conformance are embedded in this framework and provide the balance for all governance domains. (aut.ref.)

Governing the water user

NARCIS (Netherlands)

Rap, Edwin; Wester, Flip

2017-01-01

This article traces a policy shift that makes the ‘water user’ the main subject of water governance. From a Foucauldian perspective on governmentality these new subjectivities accompany neo-liberal governmental technologies to devolve autonomy from state institutions to an active user base, whilst

investors behavior, earnings management and governance

Directory of Open Access Journals (Sweden)

Afraa Khzouri

2014-07-01

Full Text Available The aim of this paper is to study the relationship between earnings management, governance and investors behavior, since this latter can inform about the nature of earnings management and can be considered as a governance mechanism to reduce accounts manipulations. On the basis of a sample of 700 American firms for the period of 1996-2006, our empirical results show that investors who take short positions, are able to interpret the information detected from the earnings management. The activity of these investors may be considered as an indicator of the quality of the governance structure and the presence and nature of earnings management. The under-reaction of investors to information leads to short-term sale of the shares of poorly governed firms and characterized by an opportunistic earnings management and to invest in firms well-governed and characterized by an informational earnings management therefore an abnormal profit can be realized.

48 CFR 225.7303-3 - Government-to-government agreements.

Science.gov (United States)

2010-10-01

... Military Sales 225.7303-3 Government-to-government agreements. If a government-to-government agreement... support of a specifically defined weapon system, major end item, or support item, contains language in conflict with the provisions of this section, the language of the government-to-government agreement...

Government-to-Government E-Government: A Case Study of a Federal Financial Program

Science.gov (United States)

Faokunla, Olumide Adegboyega

2012-01-01

The problem with the study of the concept of electronic government (e-Gov) is that scholars in the field have not adequately explored various dimensions of the concept. Literature on e-Gov is replete with works on the form of government to consumer e-Gov. Much less work had been done on the government to government (G2G) e-Gov. This qualitative…

Isolation and structure-function characterization of a signaling-active rhodopsin-G protein complex.

Science.gov (United States)

Gao, Yang; Westfield, Gerwin; Erickson, Jon W; Cerione, Richard A; Skiniotis, Georgios; Ramachandran, Sekar

2017-08-25

The visual photo-transduction cascade is a prototypical G protein-coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (G T ). This results in the dissociation of G T into its component α T -GTP and β 1 γ 1 subunit complex. Structural information for the Rho*-G T complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (G T *) comprising a Gα T /Gα i1 chimera (α T *) and β 1 γ 1 The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to Gα T * is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one G T *. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β 2 -adrenergic receptor-G S complex, including a flexible α T * helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Interactive governance

DEFF Research Database (Denmark)

Sørensen, Eva; Torfing, Jacob; Peters, B. Guy

Governance has become one of the most commonly used concepts in contemporary political science. It is, however, often used to mean a variety of different things. This book helps to clarify this conceptual muddle by concentrating on one variety of governance-interactive governance. The authors argue...... that although the state may remain important for many aspects of governing, interactions between state and society represent an important, and perhaps increasingly important, dimension of governance. These interactions may be with social actors such as networks, with market actors or with other governments......, but all these forms represent means of governing involving mixtures of state action with the actions of other entities.This book explores thoroughly this meaning of governance, and links it to broader questions of governance. In the process of explicating this dimension of governance the authors also...

Governance of Arctic Offshore Oil and Gas

DEFF Research Database (Denmark)

Bringing together leading experts from various disciplines, this book offers a comprehensive study of the governance of offshore oil and gas activities in the circumpolar Arctic. As a consequence of energy globalisation, and of a sharp increase in world energy demand, the Arctic Ocean is also now...... being targeted for its offshore oil and gas resources, at the same time as an increasing demand for democratic legitimisation and recognition of the rights of indigenous peoples is emerging in the civil spheres of society. The volume analyses how, in the daunting context of climate change......, the interactions between the various levels of governance structure the policy process and impact on the efficiency of environmental management and the effectiveness of public participation, including the participation of indigenous peoples. Any governance system for Arctic offshore oil and gas activities...

Receptor Activity-modifying Protein-directed G Protein Signaling Specificity for the Calcitonin Gene-related Peptide Family of Receptors.

Science.gov (United States)

Weston, Cathryn; Winfield, Ian; Harris, Matthew; Hodgson, Rose; Shah, Archna; Dowell, Simon J; Mobarec, Juan Carlos; Woodlock, David A; Reynolds, Christopher A; Poyner, David R; Watkins, Harriet A; Ladds, Graham

2016-10-14

The calcitonin gene-related peptide (CGRP) family of G protein-coupled receptors (GPCRs) is formed through the association of the calcitonin receptor-like receptor (CLR) and one of three receptor activity-modifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM), and intermedin/adrenomedullin 2 (AM2), is well known to result in a Gα s -mediated increase in cAMP. Here we used modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway. We not only demonstrate functional couplings to both Gα s and Gα q but also identify a Gα i component to CLR signaling in both yeast and HEK-293 cells, which is absent in HEK-293S cells. We show that the CGRP family of receptors displays both ligand- and RAMP-dependent signaling bias among the Gα s , Gα i , and Gα q/11 pathways. The results are discussed in the context of RAMP interactions probed through molecular modeling and molecular dynamics simulations of the RAMP-GPCR-G protein complexes. This study further highlights the importance of RAMPs to CLR pharmacology and to bias in general, as well as identifying the importance of choosing an appropriate model system for the study of GPCR pharmacology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Factors affecting knowledge governance implementation among Malaysian SMEs

Directory of Open Access Journals (Sweden)

Khong Sin Tan

2018-05-01

Full Text Available Knowledge governance is a relatively new discipline in Malaysia with very little research work performed so far. As Malaysian government is actively involved in the implementation of Economic Transformation Program (ETP, Government Transformation Program (GTP and Urban Trans-formation Program (UTP, Small and Medium Enterprises (SMEs need to react to the government move by transforming their conventional knowledge management practices to knowledge govern-ance. As of today, there has been very limited study conducted in Malaysia on the extent of the company acceptance of such governance. This research was therefore conducted to measure the SME users' acceptance and identify the pros and cons of knowledge governance. With these findings, recommendations were given to policy makers and industries to increase the company's knowledge governance acceptance. Questionnaire was used for data collection. Systematic random sampling methods was used to select respondents. The questionnaire was developed and adapted based on knowledge management and IT governance frameworks. In this model, the dependent variable was company's intention to adopt knowledge governance. Independent variables included knowledge application needs, knowledge architecture, knowledge infrastructure, knowledge investment and knowledge principles.

The Generative Mechanisms of Open Government Data

DEFF Research Database (Denmark)

Jetzek, Thorhildur; Avital, Michel; Bjørn-Andersen, Niels

2013-01-01

The exponentially growing production of data enables global connectivity as well as increased openness and sharing, which turn into a powerful force that is changing the global economy and society. Governments around the world have become active participants in this evolution by opening up...... their data for access and re-use by public and private agents alike. The recent phenomenon of Open Government Data (OGD) has spread around the world, driven by the proposition that opening government data has the ability to generate both economic and social value. However, a review of the academic research...

Applying TOGAF for e-government implementation based on service oriented architecture methodology towards good government governance

Science.gov (United States)

Hodijah, A.; Sundari, S.; Nugraha, A. C.

2018-05-01

As a Local Government Agencies who perform public services, General Government Office already has utilized Reporting Information System of Local Government Implementation (E-LPPD). However, E-LPPD has upgrade limitation for the integration processes that cannot accommodate General Government Offices’ needs in order to achieve Good Government Governance (GGG), while success stories of the ultimate goal of e-government implementation requires good governance practices. Currently, citizen demand public services as private sector do, which needs service innovation by utilizing the legacy system as a service based e-government implementation, while Service Oriented Architecture (SOA) to redefine a business processes as a set of IT enabled services and Enterprise Architecture from the Open Group Architecture Framework (TOGAF) as a comprehensive approach in redefining business processes as service innovation towards GGG. This paper takes a case study on Performance Evaluation of Local Government Implementation (EKPPD) system on General Government Office. The results show that TOGAF will guide the development of integrated business processes of EKPPD system that fits good governance practices to attain GGG with SOA methodology as technical approach.

Denmark’s Master of Public Governance Program

DEFF Research Database (Denmark)

Greve, Carsten; Pedersen, Anne Reff

2017-01-01

This paper focuses on Denmark’s Master of Public Governance and its assessments and lessons learned. Denmark is seen to have an efficient economy and public sector, a digitalized public service delivery system, and an advanced work–life balance. The Danish government invested substantial resources...... into developing a Master of Public Governance program – a flexible and modular program for public managers to take over a period of up to six years. The paper focuses on the Copenhagen version of the Master of Public Governance program. More than 1000 public managers from central, regional and local government...... are now active in pursuing an executive public management education through this program. The development, structure, content and the innovative teaching ideas are presented. The available data, including an official evaluation of the MPG program, is used to assess the program and present some lessons...

Achievement motivation features of female servants of government and local self-government bodies

Directory of Open Access Journals (Sweden)

T.U. Kulakovsk

2018-03-01

Full Text Available The article makes the theoretical analysis of the features of professional performance of civil servants and officials of local self-government bodies. The significant level of staff turnover among civil servants and the significant level of registered unemployed among the persons who had previously worked in these structures was revealed. The article carries out the theoretical analysis of psychological researches, which testify to the existence of direct correlation between the level of achievement motivation and success in an entrepreneurial activity. The purpose has been set to study the peculiar properties of achievement motivation of civil servants and officials of local self-government bodies. The researches have shown that the level of motivation for the achievement has a straightforward connection with the success of entrepreneurship. The purpose is to study the peculiarities of the motivation of achievement of civil servants and officials of local self-government bodies. There is the possibility for engagement of fired civil servants to entrepreneurial activities. The empirical study of achievement motivation peculiarities of female employees has been conducted. A statistically significant inverse correlation between the level of achievement motivation and the length of civil service has been established. The paper substantiates the need in further research aimed at uncovering the factors responsible for the inverse correlation between the level of achievement motivation and the term of service in the civil service.

Provincial government performance on climate change: 2000

International Nuclear Information System (INIS)

Hornung, R.

2000-01-01

This assessment of provincial government performance on climate change is intended as a 'baseline' prior to the implementation of the National Implementation Strategy on Climate Change, (NIS) scheduled to be signed by the federal and provincial Ministers of Energy and Environment in Quebec City in October 2000. Participants are also expected to agree on a 'First Business Plan' for the NIS at that same meeting, including identification of measures each of the provincial governments plan to institute to address climate change issues over the next two to three years. The report is based on performance of government activity in climate change in Alberta, British Columbia, Saskatchewan, Ontario and Quebec , the five provinces that together account for 89 per cent of Canada's total GHG emissions, against the greenhouse gas emission measures identified by the various provincial governments on various occasions over the past 10 years. Nine areas of potential activity to address climate change with a total of 38 criteria were used. Each criterion was used to determine whether or not a provincial government has implemented a specific measure that will likely be an integral component of a national effort to address climate change. The nine categories forming the base of the assesment were: transportation, electricity generation,buildings, industry, readiness to facilitate emissions trading, 'own house in order' other sources of GHG, promoting GHG reduction technology development, and enhancing awareness and public education. All provincial governments received a very poor, failing grade . (The 'best': British Columbia with 30.5 per cent; the 'worst': Saskatchewan with 20.5 per cent). The report characterizes the last 10 years as 'the lost decade' with respect to government action on the issue of climate change. It points out that time is running out; provincial governments have to make the effort to be part of the solution to climate change, or they will have solutions

Exporting nuclear engineering and the government's viewpoint

International Nuclear Information System (INIS)

Schill, H.

1986-01-01

The reasons for the government's positive attitude to nuclear engineering exports are explained, especially with regard to them being a compensation of the decreasing domestic demand. The federal government considers such exports to be necessary and correct for economical and energy-political reasons. Their contribution reaches from accompanying measures to the provision of state guarantees of export financing activities. (UA) [de

Engineering governance: introducing a governance meta framework.

NARCIS (Netherlands)

Brand, N.; Beens, B.; Vuuregge, E.; Batenburg, R.

2011-01-01

There is a need for a framework that depicts strategic choices within an organisation with regard to potential governance structures. The governance meta framework provides the necessary structure in the current developments of governance. Performance as well as conformance are embedded in this

Government and governance strategies in medical tourism

NARCIS (Netherlands)

Ormond, M.E.; Mainil, T.

2015-01-01

This chapter provides an overview of current government and governance strategies relative to medical tourism development and management around the world. Most studies on medical tourism have privileged national governments as key actors in medical tourism regulation and, in some cases, even

12 CFR 208.37 - Government securities sales practices.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Government securities sales practices. 208.37... Securities-Related Activities § 208.37 Government securities sales practices. (a) Scope. This subpart is... dealer. (d) Recommendations to customers. In recommending to a customer the purchase, sale or exchange of...

Which type of government revenue leads government expenditure?

OpenAIRE

Abdi, Zeinab; Masih, Mansur

2014-01-01

This Malaysia is a developing Islamic state that faced government budget deficit since 1998. It is undeniable that a budget deficit or inability to cover government spending is not positively seen by external parties. The optimum level of government budget is the state where government spending is totally offset by government revenue and that can be achieved through an increase in tax revenue or decrease in spending. The paper aims to discover the existence of a theoretical relationship betwe...

Corporate and philanthropic models of hospital governance: a taxonomic evaluation.

Science.gov (United States)

Weiner, B J; Alexander, J A

1993-08-01

We assess the theoretical integrity and practical utility of the corporate-philanthropic governance typology frequently invoked in debates about the appropriate form of governance for nonprofit hospitals operating in increasingly competitive health care environments. Data were obtained from a 1985 national mailed survey of nonprofit hospitals conducted by the American Hospital Association (AHA) and the Hospital Research and Educational Trust (HRET). A sample 1,577 nonprofit community hospitals were selected for study. Representativeness was assessed by comparing the sample with the population of non-profit community hospitals on the dimensions of bed size, ownership type, urban-rural location, multihospital system membership, and census region. Measurement of governance types was based on hospital governance attributes conforming to those cited in the literature as distinguishing corporate from philanthropic models and classified into six central dimensions of governance: (1) size, (2) committee structure and activity, (3) board member selection, (4) board composition, (5) CEO power and influence, and (6) bylaws and activities. Cluster analysis and ANCOVA indicated that hospital board forms adhered only partially to corporate and philanthropic governance models. Further, board forms varied systematically by specific organizational and environmental conditions. Boards exhibiting more corporate governance forms were more likely to be large, privately owned, urban, and operating in competitive markets than were hospitals showing more philanthropic governance forms. Findings suggest that the corporate-philanthropic governance distinction must be seen as an ideal rather than an actual depiction of hospital governance forms. Implications for health care governance are discussed.

Development of full sweet, umami, and bitter taste responsiveness requires Regulator of G protein Signaling-21 (RGS21).

Science.gov (United States)

Schroer, Adam B; Gross, Joshua D; Kaski, Shane W; Wix, Kim; Siderovski, David P; Vandenbeuch, Aurelie; Setola, Vincent

2018-04-26

The mammalian tastes of sweet, umami, and bitter are initiated by activation of G protein-coupled receptors (GPCRs) of the T1R and T2R families on taste receptor cells. GPCRs signal via nucleotide exchange and hydrolysis, the latter hastened by GTPase-accelerating proteins (GAPs) that include the Regulators of G protein Signaling (RGS) protein family. We previously reported that RGS21, uniquely expressed in Type II taste receptor cells, decreases the potency of bitter-stimulated T2R signaling in cultured cells, consistent with its in vitro GAP activity. However, the role of RGS21 in organismal responses to GPCR-mediated tastants was not established. Here, we characterized mice lacking the Rgs21 fifth exon. Eliminating Rgs21 expression had no effect on body mass accumulation (a measure of alimentation), fungiform papillae number and morphology, circumvallate papillae morphology, and taste bud number. Two-bottle preference tests, however, revealed that Rgs21-null mice have blunted aversion to quinine and denatonium, and blunted preference for monosodium glutamate, the sweeteners sucrose and SC45647, and (surprisingly) NaCl. Observed reductions in GPCR-mediated tastant responses upon Rgs21 loss are opposite to original expectations, given that loss of RGS21 -- a GPCR signaling negative regulator -- should lead to increased responsiveness to tastant-mediated GPCR signaling (all else being equal). Yet, reduced organismal tastant responses are consistent with observations of reduced chorda tympani nerve recordings in Rgs21-null mice. Reduced tastant-mediated responses and behaviors exhibited by adult mice lacking Rgs21 expression since birth have thus revealed an underappreciated requirement for a GPCR GAP to establish the full character of tastant signaling.

ARF1 recruits RAC1 to leading edge in neutrophil chemotaxis.

Science.gov (United States)

Mazaki, Yuichi; Onodera, Yasuhito; Higashi, Tsunehito; Horinouchi, Takahiro; Oikawa, Tsukasa; Sabe, Hisataka

2017-10-02

The small GTPase ARF1 mediates membrane trafficking mostly from the Golgi, and is essential for the G protein-coupled receptor (GPCR)-mediated chemotaxis of neutrophils. In this process, ARF1 is activated by the guanine nucleotide exchanger GBF1, and is inactivated by the GTPase-activating protein GIT2. Neutrophils generate the Gβγ-PAK1-αPIX-GIT2 linear complex during GPCR-induced chemotaxis, in which αPIX activates RAC1/CDC42, which then employs PAK1. However, it has remained unclear as to why GIT2 is included in this complex. We investigated the association between ARF1 and RAC1/CDC42 during the fMLP-stimulated chemotaxis of HL60 cells. We found that the silencing of GBF1 significantly impaired the recruitment of RAC1 to the leading edges, but not PAK1, αPIX, RAC2, or CDC42. A significant population of RAC1 colocalized with ARF1 at the leading edges in stimulated cells, whereas fMLP activated both ARF1 and ARF5. Consistently, the silencing of ARF1, but not ARF5, impaired the recruitment of RAC1, whereas the silencing of RAC1 did not affect the recruitment of ARF1 to the leading edges. Our results indicated that the activation of ARF1 triggers the plasma membrane recruitment of RAC1 in GPCR-mediated chemotaxis, which is essential for cortical actin remodeling. Thus, membrane remodeling at the leading edges appears to precede actin remodeling in chemotaxis. Together with the fact that GIT2, which inactivates ARF1, is an integral component of the machinery activating RAC1, we proposed a model in which the ARF1-RAC1 linkage enables the regulation of ARF1 by repetitive on/off cycles during GPCR-mediated neutrophil chemotaxis.

Health promotion activities in annual reports of local governments: 'Health for All' targets as a tool for content analysis.

Science.gov (United States)

Andersson, Camilla M; Bjärås, Gunilla E M; Tillgren, Per; Ostenson, Claes-Göran

2003-09-01

This article presents an instrument to study the annual reporting of health promotion activities in local governments within the three intervention municipalities of the Stockholm Diabetes Prevention Program (SDPP). The content of health promotion activities are described and the strengths, weaknesses and relevance of the method to health promotion discussed. A content analysis of local governmental reports from 1995-2000 in three Swedish municipalities. A matrix with WHO's 38 'Health for All' (HFA) targets from 1991 was used when coding the local health promotion activities. There are many public health initiatives within the local governmental structure even if they are not always addressed as health promotion. The main focuses in the local governmental reports were environmental issues, unemployment, social care and welfare. Local governmental reports were found to be a useful source of information that could provide knowledge about the priorities and organizational capacities for health promotion within local authorities. Additionally the HFA targets were an effective tool to identify and categorize systematically local health promotion activities in the annual reports of local governments. Identifying local health promotion initiatives by local authorities may ease the development of a health perspective and joint actions within the existing political and administrative structure. This paper provides a complementary method of attaining and structuring information about the local community for developments in health promotion.

Governance mode vs. governance fit? : Performance implications of make-or-ally choices for product innovation in the worldwide aircraft industry, 1942-2000

OpenAIRE

Castaner, X.; Mulotte, L.; Garrette, B.; Dussauge, P.

2014-01-01

We examine the impact of governance mode and governance fit on performance in make-or-ally decisions. We argue that while horizontal collaboration and autonomous governance have direct and countervailing performance implications, the alignment of make-or-ally choices with the focal firm's resource endowment and the activity's resource requirements leads to better performance. Data on the aircraft industry show that relative to aircraft developed autonomously, collaborative aircraft exhibit gr...

Governing Board of the Pension Fund

CERN Multimedia

2006-01-01

The Governing Board of the Pension Fund held its one-hundred-and-fortieth meeting on 14 February 2006. Professor F. Ferrini, the Board's new Chairman, welcomed Mr C. Hauviller, new member of the Board, and Mr P. Martel and Professor D.-O. Riska, new alternate members. In his opening remarks as Chairman, Professor Ferrini set out his views on the role of the Governing Board. Within the general context of the Organization, whose priority continues to be LHC completion, the Fund has a duty to send a clear signal to the Council, the Management, the active members and the beneficiaries that it is committed to resolving the serious problems it faces. In concrete terms, the Governing Board's work should be guided by some general principles: it is of the utmost importance to re-establish an atmosphere of trust and cooperation between the various parties to the Fund; wherever possible, all opinions voiced will have to be taken into account; issues relating to pension guarantees will have to be given active attentio...

GOVERNANCE ON THE INTERNET. MEASURING THE PERFORMANCES OF E-GOVERNANCE IN BUCHAREST MUNICIPALITIES

Directory of Open Access Journals (Sweden)

ANDREI ELVADEANU

2011-04-01

Full Text Available This paper analyzes the electronic governance and how it’s functioning in Romania. Being part of a larger institutional reform process, the electronic governance represents a new approach of the relation between Government and the citizen, with the purpose of increasing the participative dimension of the politic action, and as a way to provide more efficient services by the public agencies. E-governance uses information technologies (especially the Internet in the public sector, in order to improve the activity of bureaucratic institutions and encourage citizen participation. This paper analyzes the concept of electronic governance and with a focus on the obvious differences between the ideal model and the way in which these policies are actually implemented in Romania. The analysis was made for the 6 town-halls in Bucharest, but can offer a good sample of how egovernance is made in Romania. The instrument used for measurements is the comprehensive Rutgers egovernance performance index, covered in detail in the article. The areas taken into consideration were the public services offered by the institutions, the usage degree by the citizens and the civic participation dimension, understood as a bi-directional communication between the institutions and the citizen. The final part of the paper is dedicated to explaining the results, with recommendations for the Romanian public institutions. The research has its limits, but the results can draw attention over an institutional process that can represent a huge positive change in the way that governance is usually understood to be made in Romania and a very important improvement in the relation between state and society.

Space Launch Vehicles: Government Activities, Commercial Competition, and Satellite Exports

National Research Council Canada - National Science Library

Behrens, Carl E

2006-01-01

Launching satellites into orbit, once the exclusive domain of the U.S. and Soviet governments, today is an industry in which companies in the United States, Europe, China, Russia, Ukraine, Japan, and India compete...

Data-Driven Innovation through Open Government Data

DEFF Research Database (Denmark)

Jetzek, Thorhildur; Avital, Michel; Bjørn-Andersen, Niels

2014-01-01

The exponentially growing production of data and the social trend towards openness and sharing are power-ful forces that are changing the global economy and society. Governments around the world have become active participants in this evolution, opening up their data for access and reuse by public...... and private agents alike. The phenomenon of Open Government Data has spread around the world in the last four years, driven by the widely held belief that use of Open Government Data has the ability to generate both economic and social value. However, a cursory review of the popular press, as well...... as an investigation of academic research and empirical data, reveals the need to further understand the relationship between Open Government Data and value. In this paper, we focus on how use of Open Government Data can bring about new innovative solutions that can generate social and economic value. We apply...

Towards a lean-government using new IT-architectures for compliance monitoring

NARCIS (Netherlands)

Bharosa, N; Hulstijn, J; Janssen, MFWHA; Tan, Y; van Wijk, R; de Winne, N; Estevez E. and Janssen, M.

2011-01-01

Recent turmoil in financial markets has invoked governments to monitor activities and transactions in the private sector more strictly. At the same time, policy makers strive to cut back on government spending by reducing the size of government agencies. These contradicting developments require

Interactive Governance

DEFF Research Database (Denmark)

Bang, Henrik

2016-01-01

Governance analysis has exploded in recent years, and it has become nearly impossible to tell what difference the concept and practice of governance makes from those of government and state. In addition governance analysis has been placed more and more in the shadow of the new institutionalisms and...... and growth. However, interactive governance is not a property or effect of institutions; nor does it apply solely to those individuals who seek success above everything else. It is connective more than individualistic or collectivistic in nature; and it manifests a governability capacity which...

48 CFR 9.307 - Government administration procedures.

Science.gov (United States)

2010-10-01

..., First Article Approval—Government Testing; and (3) Request that the activity inform the contract... other activity responsible for first article testing or evaluation shall inform the contracting office whether to approve, conditionally approve, or disapprove the first article. The contracting officer shall...

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

Science.gov (United States)

Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

2017-07-05

Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

Program governance

CERN Document Server

Khan, Muhammad Ehsan

2014-01-01

FOUNDATION OF GOVERNANCEGovernanceDefining GovernanceGovernance at Multiple LevelsSummaryReferencesTransaction Cost EconomicsTransactions-Core Elements and Attributes     Behavioral Assumptions     Governance Structure AttributesHazards of Concern     Incomplete Contracting     Bilateral Dependency and Fundamental Transformation     Adaptation or MaladaptationLinking Governance, Governance Structures, and ContractsThe Impact of Asset Specificity and Behavioral Assumptions on ContractsAp

Alignment between business process governance and IT governance

DEFF Research Database (Denmark)

Rahimi, Fatemeh; Møller, Charles; Hvam, Lars

2014-01-01

frameworks to enable business-IT strategic alignment, efficient process and IT requirements specification, and IT-enabled business value realization. We examine the actuality of this alignment in practice through a case study conducted in a relatively mature multinational corporation. The findings indicate......The importance of business processes and the increasing centrality of IT to an organization's performance have called for a specific focus on business process governance and IT governance in contemporary enterprises. Despite the wide scope of business process management, which covers both business...... and IT domains, and the profound impact of IT on process innovations, the association between business process governance and IT governance remains under-explored. Analyzing the constituting elements of the two governance concepts, we propose the necessity of alignment between business process and IT governance...

Conformation guides molecular efficacy in docking screens of activated β-2 adrenergic G protein coupled receptor.

Science.gov (United States)

Weiss, Dahlia R; Ahn, SeungKirl; Sassano, Maria F; Kleist, Andrew; Zhu, Xiao; Strachan, Ryan; Roth, Bryan L; Lefkowitz, Robert J; Shoichet, Brian K

2013-05-17

A prospective, large library virtual screen against an activated β2-adrenergic receptor (β2AR) structure returned potent agonists to the exclusion of inverse-agonists, providing the first complement to the previous virtual screening campaigns against inverse-agonist-bound G protein coupled receptor (GPCR) structures, which predicted only inverse-agonists. In addition, two hits recapitulated the signaling profile of the co-crystal ligand with respect to the G protein and arrestin mediated signaling. This functional fidelity has important implications in drug design, as the ability to predict ligands with predefined signaling properties is highly desirable. However, the agonist-bound state provides an uncertain template for modeling the activated conformation of other GPCRs, as a dopamine D2 receptor (DRD2) activated model templated on the activated β2AR structure returned few hits of only marginal potency.

The officials’ efforts to set up a good government

Science.gov (United States)

Suardini, D.; Mariana, D.; Sjoraida, D. F.

2018-03-01

This study investigates the Government of Bogor City’s efforts in disseminating the values of good governance to its bureaucracy. This is based on the fact that the enforcement of good governance is a challenge and an opportunity to be concerned because there are many who do not know the impact of it. Internal impacts would be felt in the employment sector competition while the external impact would be related to the competition in terms of the governance qualities from another region examined by the internal affair officials. With descriptive and qualitative approaches, this study finds that many officials of the local government of Bogor City are still not ready to face the culture of good governance. Such unpreparedness results from the fact that an understanding of good governance is not evenly spread among the officials. It is because that the government itself has not put this good governance issue as a top priority. Finally, there is the absence of a comprehensive evaluation process of good government socialization activities.

Control of territorial communities in local government

Directory of Open Access Journals (Sweden)

О. А. Смоляр

2015-11-01

Full Text Available According to Art. 5 of the Constitution of Ukraine all power in Ukraine belong to people, which is primary, unified, inalienable and carried people through free will through elections, referendum and other forms of direct democracy, including those intended to control the activity of bodies and officials of the government and local government. Paper objective. At the local level the main supervisory entity in local government is local community. Consolidation of the Constitution of Ukraine the primary subject of local self-government territorial community not only meets current international practice, but also the historical traditions of Ukrainian people. Control territorial community in all phases of local government is one of the most important functions of managing the development of appropriate settlements, and therefore needs an effective mechanism of legal regulation, clearly define mutual rights and responsibilities of controlling and controlled entities. Recent research and publications analysis. Problems Assessment of local communities and the activities of local government officials in their works viewed Y.G. Barabash, P.M. Liubchenko, O.D. Skopych, Y.P. Strilets. However, given the variety of aspects of this area of research remain many questions that need resolving, on which depends largely on the further process of local governance. The paper main body. The existing regulation territorial communities can exercise control in local government actually only through local governments. The control of the executive bodies of village, town council municipalities can only be made through the appropriate council. The existing regulation of territorial communities can exercise control in local government actually only through local governments. The control of the executive bodies of village, town council municipalities can only be made through the appropriate council. The author emphasizes that only by implementing self-control powers local

Sustainable Urban Agriculture in Ghana: What Governance System Works?

Directory of Open Access Journals (Sweden)

Eileen Bogweh Nchanji

2017-11-01

Full Text Available Urban farming takes advantage of its proximity to market, transport and other urban infrastructure to provide food for the city and sustain the livelihoods of urban and peri-urban dwellers. It is an agricultural activity which employs more than 50% of the local urban population with positive and negative impacts on local and national development. Urban agriculture is an informal activity not supported by law but in practice is regulated to a certain extent by state institutions, traditional rulers, farmers and national and international non-governmental organisations. Tamale’s rapid population growth, exacerbated by the unplanned development system and institutional conflicts, are factors contributing to the present bottlenecks in the urban agricultural system. In this paper, these bottlenecks are conceptualised as problems of governance. These issues will be illustrated using ethnographic data from land sales, crop-livestock competition, waste-water irrigation, and markets. I will explain how conflicts which arise from these different situations are resolved through the interactions of various governance systems. Informal governance arrangements are widespread, but neither they nor formal systems are always successful in resolving governance issues. A participatory governance does not seem possible due to actors’ divergent interests. A governance solution for this sector is not yet apparent, contributing to food and nutritional insecurity.

E-Government for Good Governance in Developing Countries ...

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

E-Government and E-Governance Benefits ..... Morocco's central government promotes the use of ICT in the public sector in order to enhance ...... The project's mission is to develop low-cost laptops with educational value for African children.

Project governance: selected South African government experiments

Directory of Open Access Journals (Sweden)

G. van der Walt

2008-07-01

Full Text Available Some form of accountability and power structure binds all organisations. Such structures are typically referred to as the “governance” structure of the organisation. In organisations that have relatively mature project applications and methodologies in place, governance mechanisms are established on more permanent bases. With its focus on performance, results and outcomes, project governance establishes decision-making structures, as well as accountability and responsibility mechanisms in public institutions to oversee projects. As government institutions increasingly place emphasis on project applications for policy implementation and service delivery initiatives, mechanisms or structures should be established to facilitate clear interfaces between the permanent organisation and the temporary project organisation. Such mechanisms or structures should enhance the governance of projects, that is, the strategic alignment of projects, the decentralisation of decision- making powers, rapid resource allocation, and the participation of external stakeholders. The purpose of this article is to explore the concept “project governance”, and to highlight examples of project governance as applied in selected government departments in provincial and national spheres. This would enable the establishment of best practice examples and assist to develop benchmarks for effective project applications for service delivery improvement.

PANeGOV : Understanding Democratic eGovernance in Asia | CRDI ...

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

As such, this research project is focussed on ICTs and "governance", which encompasses, but is not limited to, "e-government" services. PANeGOV will undertake 8 projects classified in three areas. All are research activities - intellectual investigations aimed at discovering, interpreting, revising and deepening our collective ...

PRACTICE OF GOOD GOVERNANCE AND CORPORATE GOVERNANCE

Directory of Open Access Journals (Sweden)

Bălăceanu Cristina

2010-12-01

Full Text Available Corporate governance reforms are occurring in countries around the globe and potentially impacting the population of the entire planet. In developing countries, such reforms occur in a larger context that is primarily defined by previous attempts at promoting “development” and recent processes of economic globalization. In this context, corporate governance reforms (in combination with the liberalising reforms associated with economic globalization, in effect represent a new development strategy for third world countries. The most basic questions that arise with respect to this situation are what the prospects for this new development model are and whether alternatives should be considered. Keywords: governance, corporate governance, economic globalization, development.

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

Directory of Open Access Journals (Sweden)

Bing Xu

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

17 CFR 240.3a43-1 - Customer-related government securities activities incidental to the futures-related business of a...

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Customer-related government securities activities incidental to the futures-related business of a futures commission merchant registered with the Commodity Futures Trading Commission. 240.3a43-1 Section 240.3a43-1 Commodity and Securities...

Status of conversion of DOE standards to non-Government standards

Energy Technology Data Exchange (ETDEWEB)

Moseley, H.L.

1992-07-01

One major goal of the DOE Technical Standards Program is to convert existing DOE standards into non-Government standards (NGS's) where possible. This means that a DOE standard may form the basis for a standards-writing committee to produce a standard in the same subject area using the non-Government standards consensus process. This report is a summary of the activities that have evolved to effect conversion of DOE standards to NGSs, and the status of current conversion activities. In some cases, all requirements in a DOE standard will not be incorporated into the published non-Government standard because these requirements may be considered too restrictive or too specific for broader application by private industry. If requirements in a DOE standard are not incorporated in a non-Government standard and the requirements are considered necessary for DOE program applications, the DOE standard will be revised and issued as a supplement to the non-Government standard. The DOE standard will contain only those necessary requirements not reflected by the non-Government standard. Therefore, while complete conversion of DOE standards may not always be realized, the Department's technical standards policy as stated in Order 1300.2A has been fully supported in attempting to make maximum use of the non-Government standard.

Status of conversion of DOE standards to non-Government standards

Energy Technology Data Exchange (ETDEWEB)

Moseley, H.L.

1992-07-01

One major goal of the DOE Technical Standards Program is to convert existing DOE standards into non-Government standards (NGS`s) where possible. This means that a DOE standard may form the basis for a standards-writing committee to produce a standard in the same subject area using the non-Government standards consensus process. This report is a summary of the activities that have evolved to effect conversion of DOE standards to NGSs, and the status of current conversion activities. In some cases, all requirements in a DOE standard will not be incorporated into the published non-Government standard because these requirements may be considered too restrictive or too specific for broader application by private industry. If requirements in a DOE standard are not incorporated in a non-Government standard and the requirements are considered necessary for DOE program applications, the DOE standard will be revised and issued as a supplement to the non-Government standard. The DOE standard will contain only those necessary requirements not reflected by the non-Government standard. Therefore, while complete conversion of DOE standards may not always be realized, the Department`s technical standards policy as stated in Order 1300.2A has been fully supported in attempting to make maximum use of the non-Government standard.

76 FR 2348 - National Assessment Governing Board: Proposed Information Collection

Science.gov (United States)

2011-01-13

... DEPARTMENT OF EDUCATION National Assessment Governing Board: Proposed Information Collection AGENCY: National Assessment Governing Board, Education. ACTION: Agency Information Collection Activities... collection techniques or other forms of information technology; and (5) estimates of capital or start-up...

Rural health prepayment schemes in China: towards a more active role for government.

Science.gov (United States)

Bloom, G; Shenglan, T

1999-04-01

A large majority of China's rural population were members of health prepayment schemes in the 1970's. Most of these schemes collapsed during the transition to a market economy. Some localities subsequently reestablished schemes. In early 1997 a new government policy identified health prepayment as a major potential source of rural health finance. This paper draws on the experience of existing schemes to explore how government can support implementation of this policy. The decision to support the establishment of health prepayment schemes is part of the government's effort to establish new sources of finance for social services. It believes that individuals are more likely to accept voluntary contributions to a prepayment scheme than tax increases. The voluntary nature of the contributions limits the possibilities for risk-sharing and redistribution between rich and poor. This underlines the need for the government to fund a substantial share of health expenditure out of general revenues, particularly in poor localities. The paper notes that many successful prepayment schemes depend on close supervision by local political leaders. It argues that the national programme will have to translate these measures into a regulatory system which defines the responsibilities of scheme management bodies and local governments. A number of prepayment schemes have collapsed because members did not feel they got value for money. Local health bureaux will have to cooperate with prepayment schemes to ensure that health facilities provide good quality services at a reasonable cost. Users' representatives can also monitor performance. The paper concludes that government needs to clarify the relationship between health prepayment schemes and other actors in rural localities in order to increase the chance that schemes will become a major source rural health finance.

The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma.

Science.gov (United States)

Guillermet-Guibert, Julie; Bjorklof, Katja; Salpekar, Ashreena; Gonella, Cristiano; Ramadani, Faruk; Bilancio, Antonio; Meek, Stephen; Smith, Andrew J H; Okkenhaug, Klaus; Vanhaesebroeck, Bart

2008-06-17

The p110 isoforms of phosphoinositide 3-kinase (PI3K) are acutely regulated by extracellular stimuli. The class IA PI3K catalytic subunits (p110alpha, p110beta, and p110delta) occur in complex with a Src homology 2 (SH2) domain-containing p85 regulatory subunit, which has been shown to link p110alpha and p110delta to Tyr kinase signaling pathways. The p84/p101 regulatory subunits of the p110gamma class IB PI3K lack SH2 domains and instead couple p110gamma to G protein-coupled receptors (GPCRs). Here, we show, using small-molecule inhibitors with selectivity for p110beta and cells derived from a p110beta-deficient mouse line, that p110beta is not a major effector of Tyr kinase signaling but couples to GPCRs. In macrophages, both p110beta and p110gamma contributed to Akt activation induced by the GPCR agonist complement 5a, but not by the Tyr kinase ligand colony-stimulating factor-1. In fibroblasts, which express p110beta but not p110gamma, p110beta mediated Akt activation by the GPCR ligands stromal cell-derived factor, sphingosine-1-phosphate, and lysophosphatidic acid but not by the Tyr kinase ligands PDGF, insulin, and insulin-like growth factor 1. Introduction of p110gamma in these cells reduced the contribution of p110beta to GPCR signaling. Taken together, these data show that p110beta and p110gamma can couple redundantly to the same GPCR agonists. p110beta, which shows a much broader tissue distribution than the leukocyte-restricted p110gamma, could thus provide a conduit for GPCR-linked PI3K signaling in the many cell types where p110gamma expression is low or absent.

The p110β isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110γ

Science.gov (United States)

Guillermet-Guibert, Julie; Bjorklof, Katja; Salpekar, Ashreena; Gonella, Cristiano; Ramadani, Faruk; Bilancio, Antonio; Meek, Stephen; Smith, Andrew J. H.; Okkenhaug, Klaus; Vanhaesebroeck, Bart

2008-01-01

The p110 isoforms of phosphoinositide 3-kinase (PI3K) are acutely regulated by extracellular stimuli. The class IA PI3K catalytic subunits (p110α, p110β, and p110δ) occur in complex with a Src homology 2 (SH2) domain-containing p85 regulatory subunit, which has been shown to link p110α and p110δ to Tyr kinase signaling pathways. The p84/p101 regulatory subunits of the p110γ class IB PI3K lack SH2 domains and instead couple p110γ to G protein-coupled receptors (GPCRs). Here, we show, using small-molecule inhibitors with selectivity for p110β and cells derived from a p110β-deficient mouse line, that p110β is not a major effector of Tyr kinase signaling but couples to GPCRs. In macrophages, both p110β and p110γ contributed to Akt activation induced by the GPCR agonist complement 5a, but not by the Tyr kinase ligand colony-stimulating factor-1. In fibroblasts, which express p110β but not p110γ, p110β mediated Akt activation by the GPCR ligands stromal cell-derived factor, sphingosine-1-phosphate, and lysophosphatidic acid but not by the Tyr kinase ligands PDGF, insulin, and insulin-like growth factor 1. Introduction of p110γ in these cells reduced the contribution of p110β to GPCR signaling. Taken together, these data show that p110β and p110γ can couple redundantly to the same GPCR agonists. p110β, which shows a much broader tissue distribution than the leukocyte-restricted p110γ, could thus provide a conduit for GPCR-linked PI3K signaling in the many cell types where p110γ expression is low or absent. PMID:18544649

Plural Governance

DEFF Research Database (Denmark)

Mols, Niels Peter; Menard, Claude

2014-01-01

Plural governance is a form of governance where a firm both makes and buys similar goods or services. Despite a widespread use of plural governance there are no transaction cost models of how plural governance affects performance. This paper reviews the literature about plural forms and proposes...... a model relating transaction cost and resource-based variables to the cost of the plural form. The model is then used to analyze when the plural form is efficient compared to alternative governance structures. We also use the model to discuss the strength of three plural form synergies....

The Capacity and Institution Building (CIB Working Group of United Cities and Local Governments: Towards Improving Aid Effectiveness in the Local Government Sector

Directory of Open Access Journals (Sweden)

Tim Kehoe

2009-11-01

Full Text Available The United Cities and Local Governments (UCLG Capacity and Institution Building (CIB Working Group gather together professional practitioners of local government associations (LGAs and individual local governments active in international cooperation, with the overall objective to improve the quality, coordination and alignment of their development cooperation interventions. The Working Group is the successor of the CIB Platform, which existed for many years within the former International Union of Local Authorities (IULA as an informal gathering of staff members of local government associations (LGAs involved in the field of municipal international cooperation (MIC and association capacity building (ACB. In addition to information exchange, the CIB Platform undertook specific initiatives such as a World Bank-funded program supporting ACB in several countries. In May 2004, the CIB was integrated into the structures of the newly-founded UCLG organisation, and its membership was expanded to also include staff members of international departments of cities active in international cooperation.

Governing Forest Ecosystem Services for Sustainable Environmental Governance: A Review

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Shankar Adhikari

2018-05-01

Full Text Available Governing forest ecosystem services as a forest socio-ecological system is an evolving concept in the face of different environmental and social challenges. Therefore, different modes of ecosystem governance such as hierarchical, scientific–technical, and adaptive–collaborative governance have been developed. Although each form of governance offers important features, no one form on its own is sufficient to attain sustainable environmental governance (SEG. Thus, the blending of important features of each mode of governance could contribute to SEG, through a combination of both hierarchical and collaborative governance systems supported by scientifically and technically aided knowledge. This should be further reinforced by the broad engagement of stakeholders to ensure the improved well-being of both ecosystems and humans. Some form of governance and forest management measures, including sustainable forest management, forest certification, and payment for ecosystem services mechanisms, are also contributing to that end. While issues around commodification and putting a price on nature are still contested due to the complex relationship between different services, if these limitations are taken into account, the governance of forest ecosystem services will serve as a means of effective environmental governance and the sustainable management of forest resources. Therefore, forest ecosystem services governance has a promising future for SEG, provided limitations are tackled with due care in future governance endeavors.

Sovereign Wealth Funds – the New Challenge for Corporate Governance

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Dariusz Urban

2010-10-01

Full Text Available The article discusses Sovereign Wealth Funds with reference do the process of corporate governance. In the first part the paper presents the rise, growth and current investment activity of those funds. In the second section the author consider reasons for implementation of corporate governance best practices. The last part of the paper compares Santiago Principles with OECD principles of corporate governance.

Petra Governance Handbook - WP7 – Governance structures & business models : D7.3: Governance Handbook

NARCIS (Netherlands)

Veeneman, W.; Hirschhorn, F.; Klievink, A.J.; Steenhuisen, B.M.; van der Voort, H.G.

2017-01-01

This document represents the governance handbook on mobility data platforms for the PETRA project. The governance handbook provides metropolitan authorities contemplating the implementation of a mobility data platform in line with the PETRA project about governance issues and design.
The

Governance and Institutional Autonomy: Governing and Governance in Portuguese Higher Education

Science.gov (United States)

Magalhaes, Antonio; Veiga, Amelia; Ribeiro, Filipa; Amaral, Alberto

2013-01-01

This paper aims at looking at governance instruments beyond managerial technicality. It intends to do so by analysing the impact of governance reforms on the universities autonomy assumed as a regulation instrument to politically steer systems and institutions. The regulation efforts undertaken at the European and national levels reflect a trend…

Who governs energy? The challenges facing global energy governance

International Nuclear Information System (INIS)

Florini, Ann; Sovacool, Benjamin K.

2009-01-01

This article conceptualizes the energy problems facing society from a global governance perspective. It argues that a notion of 'global energy governance,' taken to mean international collective action efforts undertaken to manage and distribute energy resources and provide energy services, offers a meaningful and useful framework for assessing energy-related challenges. The article begins by exploring the concepts of governance, global governance, and global energy governance. It then examines some of the existing institutions in place to establish and carry out rules and norms governing global energy problems and describes the range of institutional design options available to policymakers. It briefly traces the role of a selection of these institutions, from inter-governmental organizations to summit processes to multilateral development banks to global action networks, in responding to energy issues, and points out their strengths and weaknesses. The article concludes by analyzing how the various approaches to global governance differ in their applicability to addressing the conundrums of global energy problems.

Who governs energy? The challenges facing global energy governance

Energy Technology Data Exchange (ETDEWEB)

Florini, Ann; Sovacool, Benjamin K. [Centre on Asia and Globalisation, Lee Kuan Yew School of Public Policy, National University of Singapore, Singapore 259772 (Singapore)

2009-12-15

This article conceptualizes the energy problems facing society from a global governance perspective. It argues that a notion of 'global energy governance,' taken to mean international collective action efforts undertaken to manage and distribute energy resources and provide energy services, offers a meaningful and useful framework for assessing energy-related challenges. The article begins by exploring the concepts of governance, global governance, and global energy governance. It then examines some of the existing institutions in place to establish and carry out rules and norms governing global energy problems and describes the range of institutional design options available to policymakers. It briefly traces the role of a selection of these institutions, from inter-governmental organizations to summit processes to multilateral development banks to global action networks, in responding to energy issues, and points out their strengths and weaknesses. The article concludes by analyzing how the various approaches to global governance differ in their applicability to addressing the conundrums of global energy problems. (author)

Perspectives of Corporate Governance in Croatian Banking Sector

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Tea Golja

2011-01-01

Full Text Available Financial market of any country firstly has to be “secure”, but although financial market is regulated and monitored, we were witnesses of bad examples (Island. So, globally all aspects of corporate governance became interesting: ownership; nature of activities; liquidity ratios, etc. The goal of this paper is to give perspectives of corporate governance in Croatian banking sector. The results of the research conducted in October 2010 are presented. The situation regarding corporate governance issues in banks is highlighted. According to the research in Croatian banks in the future corporate governance should give more attention to responsiveness; equity; efficiency and effectiveness; and on accountability. Mentioned principles are not clearly defined and recognizable. These will assure differentiation on market and trust of all stakeholders.

A single amino acid residue controls Ca2+ signaling by an octopamine receptor from Drosophila melanogaster.

Science.gov (United States)

Hoff, Max; Balfanz, Sabine; Ehling, Petra; Gensch, Thomas; Baumann, Arnd

2011-07-01

Rhythmic activity of cells and cellular networks plays an important role in physiology. In the nervous system oscillations of electrical activity and/or second messenger concentrations are important to synchronize neuronal activity. At the molecular level, rhythmic activity can be initiated by different routes. We have recently shown that an octopamine-activated G-protein-coupled receptor (GPCR; DmOctα1Rb, CG3856) from Drosophila initiates Ca(2+) oscillations. Here, we have unraveled the molecular basis of cellular Ca(2+) signaling controlled by the DmOctα1Rb receptor using a combination of pharmacological intervention, site-directed mutagenesis, and functional cellular Ca(2+) imaging on heterologously expressed receptors. Phosphorylation of a single amino acid residue in the third intracellular loop of the GPCR by PKC is necessary and sufficient to desensitize the receptor. From its desensitized state, DmOctα1Rb is resensitized by dephosphorylation, and a new Ca(2+) signal occurs on octopamine stimulation. Our findings show that transient changes of the receptor's surface profile have a strong effect on its physiological signaling properties. We expect that the detailed knowledge of DmOctα1Rb-dependent signal transduction fosters the identification of specific drugs that can be used for GPCR-mediated pest control, since octopamine serves important physiological and behavioral functions in arthropods.

Records and good governance: Running away from accountability ...

African Journals Online (AJOL)

Records and good governance: Running away from accountability. The case of Zambia. ... Abstract. Records are created as a by-product of the business activities taking place as an organization in carry out its mandated activities. Subsequently, these records will provide the ultimate proof or evidence of the activities being ...

INTERNAL AUDIT IN CORPORATE GOVERNANCE

Directory of Open Access Journals (Sweden)

Felicia Gabriela UNGUREANU

2010-03-01

Full Text Available Internal Audit, compared with verification of transactions and compliance with established procedures, identify risks and assess the effectiveness of risk management.Internal audit based on risk analysis assesses the adequacy and effectiveness of internal control in all areas of activity, helps management in its task by analyzing the causes and consequences, with recommendations concerning the activities examined, whereas both shareholders and existing and potential investors are interested in how the entity is governed.

Theoretical reflections on governance in health regions.

Science.gov (United States)

Bretas, Nilo; Shimizu, Helena Eri

2017-04-01

This article analyzes governance in health regions, through the contributions of two studies: one on a governance model and the other on duties in the management of public policies networks. The former conducted a meta-analysis of 137 case studies in the literature on collaborative governance aimed at preparing an explanatory and analytical model. Authors identified critical variables that will influence the results: a previous history of conflict or cooperation, incentives for participation, power imbalances, leadership and institutional design. They also identified key factors: face-to-face dialogue, trust building and development of commitment and shared vision. The latter study examined networks of public policies in the analytic tradition and the perspective of governance, incorporating concepts from the field of political science, economics and interorganizational relations, in order to support the management of public policies networks. The study identified network management as equivalent to a strategic game involving functions: network activation, framework of relations, intermediation, facilitation and consensus building and mediation and arbitration. The combination of the two reflections provides a conceptual reference for better understanding of governance in health regions.

E-Government Dimension

OpenAIRE

Rosiyadi, Didi; Suryana, Nana; Cahyana, Ade; Nuryani, Nuryani

2007-01-01

Makalah ini mengemukakan E-Government Dimension yang merupakan salah satu hasil TahapanPengumpulan Data, dimana tahapan ini adalah bagian dari penelitian kompetitif di Lembaga Ilmu PengetahuanIndonesia 2007 yang sekarang sedang dilakukan. Data E-Government Dimension ini didapatkan dari berbagaisumber yang meliputi E-Government beberapa Negara di dunia, E-Government yang dibangun oleh beberapapenyedia aplikasi E-Government. E-Government Dimension terdiri dari tiga dimensi yaitu DemocraticDimen...

Interaction and activity coordination of territorial customs bodies of the State fiscal service of Ukraine with local state administrations and local self-government bodies

Directory of Open Access Journals (Sweden)

Олексій Павлович Федотов

2016-06-01

Based on the results of the study the author notes that the interaction of the Ukrainian SFS customs offices and local state administrations with local self-government bodies is an inherent quality, link and component of the Ukrainian SFS Customs offices functioning organization, which aims to improve the state customs service implementation standards by the Ukrainian SFS customs houses and to ensure the said implementation efficiency. However, in the course of interaction of the Ukrainian SFS customs with local state administrations and local self-government bodies each of the mentioned organizations specializes in solving their specific tasks in accordance with their subject expertise, and forms a clear organizational system. The complementarity of such kind helps to improve the state customs affairs conductance quality and is realized through the coordination of performance of the Ukrainian SFS customs offices, local state administrations and local self-government bodies as the interaction subjects through normative, informational and analytical provision for the interaction and concretization of the activities of each subject within the planned activities.

Private Governance and the South: Lessons from Global Forest Politics

NARCIS (Netherlands)

Pattberg, P.H.

2006-01-01

Private governance beyond the state is emerging as a prominent debate in International Relations, focusing on the activities of private non-state actors and the influences of private rules and standards. However, the conceptual framework of governance has until recently been employed predominantly

An overview of clinical governance policies, practices and initiatives.

Science.gov (United States)

Braithwaite, Jeffrey; Travaglia, Joanne F

2008-02-01

To map the emergence of, and define, clinical governance; to discuss current best practices, and to explore the implications of these for boards of directors and executives wishing to promote a clinical governance approach in their health services. Review and analysis of the published and grey literature on clinical governance from 1966 to 2006. Medline and CINAHL databases, key journals and websites were systematically searched. Central issues were identified in the literature as key to effective clinical governance. These include: ensuring that links are made between health services' clinical and corporate governance; the use of clinical governance to promote quality and safety through a focus on quality assurance and continuous improvement; the creation of clinical governance structures to improve safety and quality and manage risk and performance; the development of strategies to ensure the effective exchange of data, knowledge and expertise; and the sponsoring of a patient-centred approach to service delivery. A comprehensive approach to clinical governance necessarily includes the active participation of boards and executives in sponsoring and promoting clinical governance as a quality and safety strategy. Although this is still a relatively recent development, the signs are promising.

Information Systems Audit for University Governance in Bucharest Academy of Economic Studies

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Ion Gh. ROSCA

2010-01-01

Full Text Available Today's successful audit leaders never lose sight of the importance of continually assessing and improving the organizations' university governance structure. Focusing on small and large mission, and using practical exercises and individual activities, the auditors will help gain the skills necessary to review and improve university governance structure, while developing techniques to assess risk management activities. Attendees will leave with an understanding of legal and regulatory guidelines as they pertain to university governance and discuss in-depth issues such as business ethics, transparency and disclosure, IT governance and university risks management. Identification, evaluation and management of university risks, is an important element of the university governance system. Today, the Bucharest Academy of Economic Studies is in a complex process to realize a university governance integrate information system. In context of this paperwork there are presented the main aspects for developing and implementing in actual phase information systems audit, to recognize the risks and establish the necessary measures to eliminate them.

Leadership, Governance

Science.gov (United States)

: Environmental Documents, Reports LANL Home Calendar Search Contacts About » Leadership, Governance Leadership national security and energy challenges. Leadership, Governance Ethics, Accountability Los Alamos National . Director's Office terry wallace in leadership, governance Director Terry C. Wallace, Jr. Terry C. Wallace, Jr

Chemogenomic discovery of allosteric antagonists at the GPRC6A receptor

DEFF Research Database (Denmark)

Gloriam, David E.; Wellendorph, Petrine; Johansen, Lars Dan

2011-01-01

and pharmacological character: (1) chemogenomic lead identification through the first, to our knowledge, ligand inference between two different GPCR families, Families A and C; and (2) the discovery of the most selective GPRC6A allosteric antagonists discovered to date. The unprecedented inference of...... pharmacological activity across GPCR families provides proof-of-concept for in silico approaches against Family C targets based on Family A templates, greatly expanding the prospects of successful drug design and discovery. The antagonists were tested against a panel of seven Family A and C G protein-coupled receptors...

Challenges in developing e-government for good governance in North Sumatra

Science.gov (United States)

Siahaan, AY

2017-01-01

E-government as one form of public administration reform in Indonesia is increasingly related to the pursuance of good governance. This paper examines the relationship between of e-government and good governance by utilizing the case study design on the implementation of e-procurement in North Sumatra. It reveals centrality of local politics and business culture in understanding resistances of both local government officials and local business which creates loopholes’ for the practice of ‘bad governance’ in all phases of e-procurement in North Sumatra province. Data transparency does not equate and guarantee the realization of good governance. Public knowledge and understanding on government decision making processes and accountability (process and policy transparency) are central to achieve good governance through e-procurement. E-procurement system does not automatically change organizational and working culture of the implementers and suppliers. This paper provides insight to the attitude and the perception of private sector engage in e-procurement towards government in implementing e-government. Resistance, digital divide and local politics interrelatedly obstruct the realization of pursuing good governance through e-procurement.

Legal and institutional frameworks for government relations with citizens

International Nuclear Information System (INIS)

Caddy, J.

2000-01-01

Unacceptably low or declining confidence in public institutions in OECD Member countries has led governments to view the issue of government-citizen relations with growing concern and to take initiatives to strengthen this fundamental relationship. Governments have begun to realize that they can better anticipate citizens' evolving and multiple needs by pro-actively involving them in the policy-making process in order to develop solutions to issues as they first appear, and not when they become pressing problems. When government succeeds in anticipating citizens' needs and aspirations, it earns currency in the form of trust. The price of failure is a loss of legitimacy. The conditions for trust in government include a well-educated citizenry, transparent processes and accountability. Government needs to establish a 'level playing field' so that citizens can see that their interests are being treated fairly. Citizens, for their part, need to learn to value fairness in government over special favours for well-connected groups. Transparency in government helps to assure citizens that they are being treated fairly. Accountability helps ensure that government failures are corrected and that public services meet expectations. Governments increasingly realize that they will not be able to conduct and effectively implement policies, as good as they may be, if their citizens do not support them. (author)

Multidirectional Networks of Government Transparency: A Preliminary Model

Directory of Open Access Journals (Sweden)

Ahmad Subhan

2016-11-01

Full Text Available This article reviews some literature in theoretical level regarding two concepts: governance network and government transparency, in order to search for theoretical linkages and to build an alternative framework that can support the implementation of public disclosure. Transparency agenda has been implemented in various forms at international, national, and local level. Transparency application was also followed by Indonesia with the implementation of Public Information Disclosure Law since 2008. This enthusiasm is quite reasonable because transparency is believed to be one of the human rights principles; as well as a key to better governance, that can help democracy consolidation, prevent corruption, strengthen the legitimacy and improve efficiency. In order to maximize transparency, the government can use a network approach because of some changes at this time, such as democratization, decentralization, and liberalization has placed the government in a position where there is not one actor who manages the state power without stakeholder’s participation. In this context, the government needs to build synergies with other institutions in a reciprocal relationship with all stakeholders. Therefore, adopting the theory of government networks can be one of the strategies to strengthen government transparency. The findings of this article indicate that the government transparency application needs to develop networks in all directions: intragovernmental, intergovernmental and collaborative networks. These three types of network in contrast with the popular belief that government transparency is interpreted only as a procedural activity to outside parties. A preliminary model in this article gives an overview about the arena of government transparency with multi-directional networks more comprehensively.

Renewing governance.

Science.gov (United States)

Loos, Gregory P

2003-01-01

Globalization's profound influence on social and political institutions need not be negative. Critics of globalization have often referred to the "Impossible Trinity" because decision-making must 1. respect national sovereignty, 2. develop and implement firm regulation, and 3. allow capital markets to be as free as possible. To many, such goals are mutually exclusive because history conditions us to view policy-making and governance in traditional molds. Thus, transnational governance merely appears impossible because current forms of governance were not designed to provide it. The world needs new tools for governing, and its citizens must seize the opportunity to help develop them. The rise of a global society requires a greater level of generality and inclusion than is found in most policy bodies today. Politicians need to re-examine key assumptions about government. States must develop ways to discharge their regulatory responsibilities across borders and collaborate with neighboring jurisdictions, multilateral bodies, and business. Concepts such as multilateralism and tripartism show great promise. Governments must engage civil society in the spirit of shared responsibility and democratic decision-making. Such changes will result in a renewal of the state's purpose and better use of international resources and expertise in governance.

Open government and municipalities: Beyond e-governement

Directory of Open Access Journals (Sweden)

Christian Cruz Meléndez

2017-11-01

Full Text Available This article’s purpose is to analyze egovernment and open government as tolos to strengthen the role of municipal government. It reviews the evolution of both tolos in Mexico and contains a conceptual analysis of both terms to gain an understanding of their meaning and of the reason why they are promoted for the benefit of local governments. Finally, it explores the availability of these tools in the municipalities, and how they contribute to each municipality in the fulfillment of its responsibilities.

Director remuneration, corporate governance and performance: A comparison between government linked companies vs non government linked companies

Directory of Open Access Journals (Sweden)

Nazrul Hisyam Ab Razak

2014-07-01

Full Text Available This study has examined the relationship between director’s remuneration, corporate governance structure and performance of a sample of 150 companies listed on the Bursa Malaysia from year 2008 until 2013. The sample was selected to provide matched-pair of government linked companies (GLCs and non-government linked companies (non-GLCs, as it was anticipated that these group would have different governance structure, the key difference being government ownership. The result holds even when we control for company specific characteristic such as corporate governance, company size, leverage, director’s remuneration, board size and auditors. This study uses panel based regression model to examine the impact of government control mechanism on company performance using two important measurers. These are accounting based measure proxies by ROA and non-accounting based measures by Tobin’s Q. Statistically significant relationships were found across the groupings and for different performance measures. Findings appear to suggest that there is a significant impact of government ownership on company performance after controlling for company specific characteristics.

Estuarine morphometry governs optically active substances, Kd(PAR) and beam attenuation

DEFF Research Database (Denmark)

Lund-Hansen, L. C.; Nielsen, J. M.; Blüthgen, J.

2013-01-01

estuaries using OACs as input parameters. It is concluded that there are no large differences in OAC concentrations between the two estuaries. The spatial distributions of OACs and optical properties were significantly different and governed by the estuary morphometry, i.e. a power distribution......°N) at high discharges. The major difference was the spatial distribution of the optical properties against distance, best described by significant power functions in the ria, compared to significant linear functions in the coastal plain. It was hypothesized that estuarine morphometry could explain...... this spatial distribution. Partition and multiple regression analyses showed that Chl-a governed Kd(PAR) and beam attenuation coefficient in both estuaries. Significant, high correlations were obtained by multiple regression analyses in the estimation of Kd(PAR) and beam attenuation coefficients in the two...

Inequality in new global governance arrangements: the North South Divide in city networks for global environmental governance

NARCIS (Netherlands)

Bouteligier, S.

2011-01-01

Networks are often portrayed as more equal governance arrangements. Their horizontal character easily leads to the assumption that they go beyond traditional divides. Power relations within networks are neglected because the collaborative activities receive the bulk of attention. However, from a

Electronic Government

DEFF Research Database (Denmark)

Wimmer, Maria A.; Traunmüller, Roland; Grönlund, Åke

This book constitutes the refereed proceedings of the 4th International Conference on Electronic Government, EGOV 2005, held in Copenhagen, Denmark, in August 2005. The 30 revised papers presented were carefully reviewed and selected from numerous submissions, and assess the state-of-the-art in e-government/e-governance...

WHY DOES GOVERNMENT GROW?THE SOURCESOF GOVERNMENT GROWTHFROM PUBLIC CHOICEPERSPECTIVE

Directory of Open Access Journals (Sweden)

Coskun Can Aktan, PhD

2017-01-01

Full Text Available Many empirical studies that examined the government spending concludes that the sizeand scope of government has grown considerably since the beginning of the twentiethcentury in most developed countries. If this is the fact, then we must ask and explore thefollowing questions: Why does government grow? What are the main sources ofgovernment growth? What are the main reasons of the expansion of government? Thisintroductory paper aims to answerthose and other questions regarding governmentgrowth. The paperismostlydependon public choice literature of government growth.

Government information collections in the networked environment new issues and models

CERN Document Server

Cheverie, Joan F

2013-01-01

This insightful book explores the challenging issues related to effective access to government information.Amidst all the chaos of today's dynamic information transition period, the only constants related to government information are change and inconsistency, yet with Government Information Collections in the Networked Environment: New Issues and Models, you will defeat the challenging issues and take advantage of the opportunities that networked government information collections have to offer. This valuable book gives you a fresh opportunity to rethink collecting activities and to

Kegiatan Government Public Relation dalam Membangun Komunikasi dengan Dunia Pers: Studi Kasus Humas Pemerintah Kota Administrasi Jakarta Timur

Directory of Open Access Journals (Sweden)

Muhammad Aras

2014-10-01

Full Text Available This study focuses on the communications that was built by the Public Relations (PR in East Jakarta Administration City Government with the Press community through their roles in the administrative activities of government. The purpose of this study was to determine the PR activities of East Jakarta Administration City Government in establishing good communication with the Press as the government's partner in promoting the various activities that are beneficial to society. The research method used in this study is a case study (case study. The results showed that the role of Public Relations of East Jakarta Administration City Government in establishing good communication with the press, is done through activities, such as press conferences, press releases, and press gathering. All activities are done well, so as to create a communication and a good relationship, in any cooperation between the Press and the Government of East Jakarta, making it easier for local governments in disseminating various work programs. 

Government guarantees and public debt in Croatia

Directory of Open Access Journals (Sweden)

Anto Bajo

2011-09-01

Full Text Available Government fi nancial and performance guarantees have been issued in Croatia since 1996, to support funding and ensure favourable borrowing conditions in the fi nancial market for companies in majority state ownership. However, government guarantees have rarely been part of defi ned strategies and goals of public debt and risk management. Despite their steady growth, the structure of active guarantees and their infl uence on Croatian public debt are still unknown. This paper analyses the amount and structure of state guarantees, their maturities and the authority and accountability for their management, and it compares the structure of guarantees in terms of economic sectors. The main objective of the paper is to determine the infl uence of government guarantees on the public debt growth.

'Nurse entrepreneurs' a case of government rhetoric?

Science.gov (United States)

Traynor, Michael; Drennan, Vari; Goodman, Claire; Mark, Annabelle; Davis, Kathy; Peacock, Richard; Banning, Maggi

2008-01-01

Nursing has come to play a prominent role in government health policy since 1997. Extending the scope of nursing practice into activities previously carried out by doctors can assist a managerialist and 'modernizing' project of increasing National Health Service (NHS) efficiency by removing demarcations between professional groups. Drawing on elements of poststructuralist linguistics, this paper presents an analysis of a key government speech in the context of a discussion of overall policy intentions. The speech can be seen as an example of how government has attempted to use rhetoric to make its goals attractive to nurses. Policy-makers have to make their policies acceptable to those whom they expect to implement them. In this case, organizational efficiency, chiefly in terms of broader access to NHS services, as well as role substitution, is aligned with government policy promoting social enterprise and 'sold' to the nursing profession as enhancing its status compared with medicine.

The Russia Corporate Governance Manual : Part I. Corporate Governance Introduced

OpenAIRE

International Finance Corporation; U.S. Department of Commerce

2004-01-01

The Russia corporate governance manual has been divided into and is published in six parts: (i) corporate governance introduced; (ii) good board practices; (iii) shareholder rights; (iv) information disclosure and transparency; (v) special focus section; and (vi) annexes model corporate governance documents. The first four parts contain chapters that focus on core corporate governance issu...

E-Government, Audit Opinion, and Performance of Local Government Administration in Indonesia

Directory of Open Access Journals (Sweden)

Bambang Sutopo

2017-12-01

Full Text Available Local governments (LGs have an important role in providing services to the community. Nevertheless, some local governments still show relatively low performance. Scores of e-government implementation and audit opinions obtained by some local governments are also relatively low. This study examines whether there are relationships between e-government, the dimensions of e-government, and audit opinion and the performance of the local government administration. There are five dimensions of the e-government i.e. policy, institutions, infrastructure, applications, and planning. The sample used in this study includes 246 local governments from 2012 to 2014. Using regression analysis, the results of this study show that e-government has a positive association with the performance of the local government administration. This is supported by the positive association of e-government’s dimensions with performance. The audit opinion is also positively associated with performance as expected. These results suggest that e-government and audit opinion can be used as indicators of the performance of local government administration.

Crystal structure of the β₂ adrenergic receptor-Gs protein complex

Energy Technology Data Exchange (ETDEWEB)

Rasmussen, Søren G.F.; DeVree, Brian T; Zou, Yaozhong; Kruse, Andrew C; Chung, Ka Young; Kobilka, Tong Sun; Thian, Foon Sun; Chae, Pil Seok; Pardon, Els; Calinski, Diane; Mathiesen, Jesper M; Shah, Syed T.A.; Lyons, Joseph A; Caffrey, Martin; Gellman, Samuel H; Steyaert, Jan; Skiniotis, Georgios; Weis, William I; Sunahara, Roger K; Kobilka, Brian K [Brussels; (Trinity); (Michigan); (Stanford-MED); (Michigan-Med); (UW)

2011-12-07

G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β₂ adrenergic receptor (β₂AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β₂AR and nucleotide-free Gs heterotrimer. The principal interactions between the β₂AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β₂AR include a 14Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.

Expanding entrepreneurship opportunities through local governance: the case of Barbados

Directory of Open Access Journals (Sweden)

Paul Pounder

2015-06-01

Full Text Available This paper looks at the government and local governance structures of Barbados, arguing that local governance should be leveraged to expand entrepreneurship opportunities at the community level. It examines the links between local governance and entrepreneurship, and proposes a framework aimed at strengthening the relationship between Barbados’ newly formed constituency councils and its government institutions supporting entrepreneurship. The research concludes that there are many inefficiencies in the interaction between government agencies and constituency councils, which the proposed framework is a first step toward remedying.  The research suggests that local governance is a complex issue worldwide. More specifically in Barbados, even though the role of the constituency councils is defined, there are weak formal arrangements which undermine the processes and activities to support community entrepreneurship. The proposed framework highlighted in the research is a first step in formalising a way forward for entrepreneurship in the community. 

The role of local governments in traditional market revitalization

Science.gov (United States)

Prastyawan, A.; Isbandono, P.

2018-01-01

This paper presents the discussion the role of local government in traditional market revitalization. It is obvious that traditional market contributes economically into a certain region. However, the existence of the traditional market is decreasing since there are modern markets that are fully facilitated by the government. In order to increase the economic standard of the traders, the government and the legislative revitalized the improper traditional market, without the participation of the society and the stakeholders. Government’s intention to revitalize the market is to increase local revenue. While the Legislative Council considered politically motivated by profit, rent-seeking. Restrictions on the aspirations of the traders in the revitalization cause resistance to the government. The traders wished to be recognized as part of the stakeholder. In the future, the market revitalization activities should involve the traders as the main actors who have received services from the government. Government as policy makers should consider as it partners in developing business traders and increase local revenues.

Why Governments Intervene

DEFF Research Database (Denmark)

Knudsen, Jette Steen; Brown, Dana

2015-01-01

Why are national governments increasingly adopting policies on corporate social responsibility (CSR)? Government CSR policies have been explained either as a means of substituting or supporting (mirroring) domestic political-economic institutions and policies, or as a means for government...... to promote international competitiveness of domestic businesses. Both sets of explanations see governments as driving CSR policies to meet particular national government goals. Support is found for the thesis that CSR policies are often related to international competitiveness, yet our findings suggest...... that government goals in this regard are not necessarily pre-defined....

48 CFR 945.407 - Non-Government use of plant equipment.

Science.gov (United States)

2010-10-01

... plant equipment. 945.407 Section 945.407 Federal Acquisition Regulations System DEPARTMENT OF ENERGY...-Government use of plant equipment. The type of plant equipment and dollar threshold for non-Government use of DOE plant equipment will be determined by the Head of the Contracting Activity which awarded the...

Transitions governance: Towards a new governance paradigm

NARCIS (Netherlands)

N. Frantzeskaki (Niki); D.A. Loorbach (Derk)

2009-01-01

textabstractThis paper presents a framework for governance in the context of large scale and long term societal change (transitions). We argue that existing theories of governance offer interesting descriptive insights for such a framework, but do not present innovative prescriptive ideas

Gobernanza Versus Gobierno Governance Versus Government

Directory of Open Access Journals (Sweden)

Dany-Robert Dufour

2009-06-01

Full Text Available El desplazamiento del término moderno de gobierno por el postmoderno de gobernanza, pone de manifiesto un nuevo lenguaje postmoderno en el que se deja entrever que ambas nociones, gobierno y gobernanza, tienden a oponerse. La gobernanza corporativa designa la toma del poder del capitalismo financiero sobre el capitalismo industrial, que no es otra cosa que, por un lado, propender por la rentabilidad máxima para los accionistas, valorizar todo en el mercado sin consideraciones morales, obligar a los actores a la búsqueda de riesgo permanente y flexibilizar las relaciones jerárquicas en la Administración de la empresa; y por el otro, la marginación de la clase obrera. La gobernanza ha llegado a los asuntos políticos convirtiéndose en modelo de gestión pública por excelencia, ella trata que el gobierno reducido a su mínima expresión guie a una sociedad civil que adquiere un papel importante en la creación y seguimiento de las diferentes políticas, es decir, que el gobierno adquiere una forma flexible de regulación, es allá donde la gobernanza política nos conduce, a la supuesta autorregulación de los intereses privados que sumados pasan a configurar el interés general. En realidad se trata de una nueva forma de dominación marcada por un desvanecimiento político, donde la sociedad civil juega en contra del Estado. La gobernanza le está tendiendo una temible trampa a la democracia, en tanto se presenta como una ampliación de la democracia materializada en una mejor participación de la sociedad civil, destruyendo la persona pública que se forma por la unión de todos los otros y convirtiéndola en representante de intereses particulares.The displacement of the modern term of government for the postmodern one of governance, reveals a new postmodern language in which one is left to guess that both notions, government and governance, tend to be opposed. Corporate governance signifies the seizure of power of financial capitalism

Structural mechanism of ligand activation in human calcium-sensing receptor

Energy Technology Data Exchange (ETDEWEB)

Geng, Yong; Mosyak, Lidia; Kurinov, Igor; Zuo, Hao; Sturchler, Emmanuel; Cheng, Tat Cheung; Subramanyam, Prakash; Brown, Alice P.; Brennan, Sarah C.; Mun, Hee-chang; Bush, Martin; Chen, Yan; Nguyen, Trang X.; Cao, Baohua; Chang, Donald D.; Quick, Matthias; Conigrave, Arthur D.; Colecraft, Henry M.; McDonald, Patricia; Fan, Qing R.

2016-07-19

Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that maintains extracellular Ca²⁺homeostasis through the regulation of parathyroid hormone secretion. It functions as a disulfide-tethered homodimer composed of three main domains, the Venus Flytrap module, cysteine-rich domain, and seven-helix transmembrane region. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations. We provide direct evidence that L-amino acids are agonists of the receptor. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation. Our structures reveal multiple binding sites for Ca²⁺and PO₄^3-ions. Both ions are crucial for structural integrity of the receptor. While Ca²⁺ions stabilize the active state, PO₄^3-ions reinforce the inactive conformation. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits.

Holdings of the Federal German Government in 1988

International Nuclear Information System (INIS)

1989-01-01

The report provides an overview of the direct and more important indirect holdings of the Federal German Government and its special assets ERP, Compensation Fund, Federal Mail and Federal Railway. Part A provides a total survey of the number of government holdings. For the direct holdings of the Federal Government and its special assets the shares in nominal capital and registered foundation capital, number of employees and dividend on profits are presented. In Parts B to M, the narrative parts, the most important holdings are reported on more in detail (sphere of activities, economic development, composition of the corporate bodies). The listing order does not reflect any order of importance. The following part N contains alphabetic indexes. Indexes I and II list all the direct holdings of the Federal Government and its special assets irrespective of the nominal capital volume and share of holdings. In index III, are listed only companies with corporate activites and a nominal capital of at least 100.000 German Marks of which the Federal Government and/or its special assets hold directly or indirectly at least 25 percent. Holdings of these undertakings of which the Federal Government does not have majority ownership, and which are not dependent on it under the regulations governing shareholdings either, are not considered. (orig.) [de

Decentralization can help reduce deforestation when user groups engage with local government

Science.gov (United States)

Wright, Glenn D.; Gibson, Clark C.; Evans, Tom P.

2016-01-01

Policy makers around the world tout decentralization as an effective tool in the governance of natural resources. Despite the popularity of these reforms, there is limited scientific evidence on the environmental effects of decentralization, especially in tropical biomes. This study presents evidence on the institutional conditions under which decentralization is likely to be successful in sustaining forests. We draw on common-pool resource theory to argue that the environmental impact of decentralization hinges on the ability of reforms to engage local forest users in the governance of forests. Using matching techniques, we analyze longitudinal field observations on both social and biophysical characteristics in a large number of local government territories in Bolivia (a country with a decentralized forestry policy) and Peru (a country with a much more centralized forestry policy). We find that territories with a decentralized forest governance structure have more stable forest cover, but only when local forest user groups actively engage with the local government officials. We provide evidence in support of a possible causal process behind these results: When user groups engage with the decentralized units, it creates a more enabling environment for effective local governance of forests, including more local government-led forest governance activities, fora for the resolution of forest-related conflicts, intermunicipal cooperation in the forestry sector, and stronger technical capabilities of the local government staff. PMID:27956644

Decentralization can help reduce deforestation when user groups engage with local government.

Science.gov (United States)

Wright, Glenn D; Andersson, Krister P; Gibson, Clark C; Evans, Tom P

2016-12-27

Policy makers around the world tout decentralization as an effective tool in the governance of natural resources. Despite the popularity of these reforms, there is limited scientific evidence on the environmental effects of decentralization, especially in tropical biomes. This study presents evidence on the institutional conditions under which decentralization is likely to be successful in sustaining forests. We draw on common-pool resource theory to argue that the environmental impact of decentralization hinges on the ability of reforms to engage local forest users in the governance of forests. Using matching techniques, we analyze longitudinal field observations on both social and biophysical characteristics in a large number of local government territories in Bolivia (a country with a decentralized forestry policy) and Peru (a country with a much more centralized forestry policy). We find that territories with a decentralized forest governance structure have more stable forest cover, but only when local forest user groups actively engage with the local government officials. We provide evidence in support of a possible causal process behind these results: When user groups engage with the decentralized units, it creates a more enabling environment for effective local governance of forests, including more local government-led forest governance activities, fora for the resolution of forest-related conflicts, intermunicipal cooperation in the forestry sector, and stronger technical capabilities of the local government staff.

E-GOVERNMENT AS A BASIC FOR ECONOMIC DEVELOPMENT IN UKRAINE

Directory of Open Access Journals (Sweden)

Natalia ORLOVA

2012-07-01

Full Text Available Development of information society in Ukraine and introduction of new information and communication technologies in areas of social life and activity of the government is defined by effective work of the e-government in the country. The article is devoted to finding the role of e-government in the socio-economic development. The aim of of this paper is to find the the main directions of e-government in the information society to improve the efficiency of government in Ukraine and the access to international information society. The article is analyzed the factors constraining introduction of electronic government in Ukraine, obstacles for users of e-governments system in the conditions of information society  also. It is proved that e-government is the foundation of a new model of governance in Ukraine. The article is analysed a rating of the European countries (separately Eastern Europe by efficiency of introduction of the electronic government. The methodological basis of  research is made by a logical and dialectic method of knowledge of economic events and state regulation machineries in modern world and national economies, the provision of fundamental works on the economic theory, international law and public administration.

Pan-European E-Government Services Architecture

Science.gov (United States)

Vitvar, Tomáš; Mocan, Adrian; Nazir, Sanaullah; Wang, Xia

E-Government has been the center of interest for public administrations, citizens and businesses, as well as software vendors for several years. E-Government enables customers and members of the public and private sectors to take advantage of automated administration processes accessible on-line. These activities involve electronic exchange of information to acquire or provide products or services, to place or receive orders, or to complete financial transactions. All such communications must be performed securely, while at the same time maintaining the privacy of involved parties. E-Government allows citizens and businesses to process requests on-line, and with minimal physical interactions with public bodies. Since a complex information support often needs to be developed incrementally, e-Government services were first available as single services in specific sectors and for specific users. While these services are being further developed and expanded to be available in more sectors and for more users, their growing number leads to requirements of total or partial automation of certain tasks, for example, discovery, selection, composition and mediation of services. In addition, extensive numbers of such services are available in different sectors, and their provisioning in complex scenarios requires a good information strategy along with a good architectural and technological basis. The main goal is to identify and define methods, standards, technologies as well as legislation to be used within the whole development process and provisioning of complex e-Government systems. In the EU, the e-Government information strategy can be seen at two levels as (1) a European strategy driven by the European Commission to enable e-Government services across the EU member states and (2) national strategies to form a national e-Government available within a particular EU member state. The initiative which aims to develop the European strategy at the EU level is called IDABC.1

Governing Towards Sustainability-Conceptualizing Modes of Governance

NARCIS (Netherlands)

Lange, P. de; Driessen, P.P.J.; Sauer, A.; Bornemann, B.; Burger, P.

2013-01-01

There is a growing scientific debate regarding the suitability of certain modes of governance for promoting sustainable development (SD). However, thus far there is neither agreement on ways to meaningfully distinguish and understand governance modes nor a foundation of the aspects to be chosen

Towards a Typology of Adaptive Governance in the Digital Government Context

DEFF Research Database (Denmark)

Wang, Cancan; Medaglia, Rony; Zheng, Lei

2018-01-01

and of accountability between government and non-government actors is critical to developing different types of adaptive governance. Findings show that the distribution of decision-making power and of accountability can be decoupled, resulting in three types of adaptive governance – namely polycentric, agile......, and organic governance. We contribute to research by detailing and empirically testing the notion of adaptive governance in a digital government context, and to practice by highlighting the role of the distribution of decision-making power and of accountability in devising adaptive governance strategies....... there is an increasing need to establish forms of collaboration that can respond to swift changes in the environment related to technology and citizen demands. Drawing on the analysis of four cases of IT-related project collaboration, we put forward that the degree of sharing of decision-making power...

Governing Board of the Pension Fund

CERN Document Server

2004-01-01

The Governing Board of the Pension Fund held its one-hundred-and-twenty-seventh meeting on 4, 5 and 6 October. During the meeting, the Governing Board heard a report by the actuary on the Actuarial Review as at 1 January 2004. The Governing Board then examined the conclusions to be drawn and the action to be taken as a result of the Review. During its first half-day meeting the Board heard a report on the meetings of the CERN Finance Committee and Council on 15 and 16 September. As a result, the Board asked its Chairman to consult the President of the CERN Council in order to find out about the terms of reference and the composition of the working group on pensions set up by the Council. Next the Board examined a request for compensation to the Fund for the reduction in active members between 2001 and 2003. It was the third such request which the Governing Board would be making to the CERN Council following the latter's 1995 decision to reduce staff numbers. The request related to the previous three years (...

Governance Strategies for a Sustainable Digital World

Directory of Open Access Journals (Sweden)

Igor Linkov

2018-02-01

Full Text Available Digitalization is changing society by the increased connectivity and networking that digital technologies enable, such as enhancing communication, services, and trade. Increasingly, policymakers within various national governments and international organizations such as the United Nations (UN and Organization for Economic Co-operation and Development (OECD are examining the original sustainability policy concepts applied within the Brundtland Report of 1987 through the lens of digitalization. While the growth of a digital economy may increase productivity and benefit local and global economies, digitalization also raises potential sustainability challenges pertaining to social (i.e., the benefits or costs imposed by disruptive digital technologies upon social networks and ways of life, including threats to economic sustainability and the rise of economic disparity and environmental wellbeing (i.e., natural resource stewardship and concern for future generations driven by the automation of information processing and delivery of services. Various perspectives have been raised regarding how the process of digitalization might be governed, and national governments remain at odds regarding a single best strategy to promote sustainable digitalization using the Brundtland concept to meet the development needs of the present without compromising the needs of future generations (i.e., social and environmental well-being. This paper reviews three governance strategies that countries can use in conjunction with adaptive governance to respond to digitalization sustainability threats: (i a laissez-faire, industry-driven approach; (ii a precautionary and preemptive strategy on the part of government; and (iii a stewardship and “active surveillance” approach by government agencies that reduce the risks derived from digitalization while promoting private sector innovation. Regardless of a state’s digital governance response and how it is shaped by

Stakeholder Governance

DEFF Research Database (Denmark)

Flak, Leif Skiftenes; Rose, Jeremy

2005-01-01

to e-Government. Originally a management theory, stakeholder theory advocates addressing the concerns of all stakeholders in a firm, as opposed to concentration on the interests of senior managers and stockholders. Apart from the original profit focus, there is no serious conceptual mismatch between...... of governance. Finally, the paper makes recommendations for future work in adapting ST to the e-government context....

'Demand pull' government policies to support Product-Service System activity: The case of Energy Service Companies in the UK

OpenAIRE

Hannon, MJ; Foxon, TJ; Gale, WF

2015-01-01

Product-Service Systems (PSSs) constitute a family of service-based business models designed to satisfy our societal needs in an economically and environmentally sustainable manner. To date however PSS application has remained niche due to a variety of critical barriers. This paper explores how ‘demand pull’ national government policies could support PSS activity by addressing these barriers and cultivating market demand. Lessons are drawn from a case study of how regulatory, economic incenti...

WHY DOES GOVERNMENT GROW?THE SOURCESOF GOVERNMENT GROWTHFROM PUBLIC CHOICEPERSPECTIVE

OpenAIRE

Coskun Can Aktan, PhD

2017-01-01

Many empirical studies that examined the government spending concludes that the sizeand scope of government has grown considerably since the beginning of the twentiethcentury in most developed countries. If this is the fact, then we must ask and explore thefollowing questions: Why does government grow? What are the main sources ofgovernment growth? What are the main reasons of the expansion of government? Thisintroductory paper aims to answerthose and other questions regardin...

Forms of global governence

Directory of Open Access Journals (Sweden)

Maxim V. Kharkevich

2014-01-01

Full Text Available Global governance as a concept defines the meaning of contemporary world politics both as a discipline and as reality. Interdependent and globalized world requires governance, and a global government has not been formed yet. The theoretical possibility of global governance without global government is proved and justified. The purpose of this article is to analytically identify possible forms of global governance. Three such forms of global governance are identified: hierarchical, market and network. In a hierarchy the governance is due to the asymmetry of power between the parties. Market control happens via anonymous pricing mechanism. Network, in contrast to the market is characterized by a closer value link between the actors, but unlike the hierarchical relationship actors are free to leave the network. Global governance takes three forms and is being implemented by different actors. To determine the most efficient form of global governance is impossible. Efficiency depends on the match between a form and an object of government. It should be noted that meta governance is likely to remain a monopoly of institutionally strong states in global governance.

Leisure, Government and Governance: A Swedish Perspective

Science.gov (United States)

Lindstrom, Lisbeth

2011-01-01

The leisure sector has witnessed a tremendous expansion since 1960. The purpose of this article is to analyse the decisions and goals of Swedish government policy during the period 1962 to 2005. The empirical analysis covers government Propositions and governmental investigations. The fields covered are sports, culture, exercise, tourism and…

Governing the quality and safety of healthcare: A conceptual framework.

Science.gov (United States)

Brown, Alison; Dickinson, Helen; Kelaher, Margaret

2018-04-01

Recent research has advanced understanding of corporate governance of healthcare quality, highlighting the need for future empirical work to develop beyond a focus on board composition to a more detailed exploration of the internal workings of governance that influence board engagement and activities. This paper proposes a conceptual framework to guide empirical research examining the work of board and senior management in governing healthcare quality. To generate this framework, existing conceptual approaches and key constructs influencing effectiveness are identified in the governance literature. Commonalities between governance and team effectiveness literature are mapped and suggest a number of key constructs in the team effectiveness literature are applicable to, but not yet fully explored, within the governance literature. From these we develop a healthcare governance conceptual framework encompassing both literatures, that outlines input and mediating factors influencing governance. The mapping process highlights gaps in research related to board dynamics and external influences that require further investigation. Organizing the multiple complex factors that influence governance of healthcare quality in a conceptual framework brings a new perspective to structuring theory-led research and informing future policy initiatives. Copyright © 2018 Elsevier Ltd. All rights reserved.

Governing Board of the Pension Fund

CERN Multimedia

2007-01-01

The Governing Board of the Pension Fund held its 154th and 155th meetings on 13 and 26 June 2007 respectively. At the first of these two meetings, the Governing Board Chairman Professor F. Ferrini stated that a steering committee had been set up, under his own chairmanship, to examine the Fund’s IT issues. This Committee had decided to avail itself of the consultancy services of an independent audit company with recognised expertise in the IT field and that the latter should undertake a study of the Fund’s present IT situation, review its operational needs, offer a comparative analysis of the different solutions and submit an overall report and conclusions on the advantages and disadvantages of the various possible solutions. At the same meeting, the Governing Board was informed of the activities of the Working Group on Actuarial Matters. The Board heard that the results of the three-yearly actuarial review would be presented at its September meeting and that the Board�...

China's Insurance Regulatory Reform, Corporate Governance Behavior and Insurers' Governance Effectiveness.

Science.gov (United States)

Li, Huicong; Zhang, Hongliang; Tsai, Sang-Bing; Qiu, Aichao

2017-10-17

External regulation is an important mechanism to improve corporate behavior in emerging markets. China's insurance governance regulation, which began to supervise and guide insurance corporate governance behavior in 2006, has experienced a complex process of reform. This study tested our hypotheses with a sample of 85 firms during 2010-2011, which was obtained by providing a questionnaire to all of China's shareholding insurance companies. The empirical study results generally show that China's insurance governance effectiveness has significantly improved through strict regulation. Insurance corporate governance can improve business acumen and risk-control ability, but no significant evidence was found to prove its influence on profitability, as a result of focusing less attention on governance than on management. State ownership is associated with higher corporate governance effectiveness than non-state ownership. Listed companies tend to outperform non-listed firms, and life insurance corporate governance is more effective than that of property insurers. This study not only contributes to the comprehensive understanding of corporate governance effectiveness but also to the literature by highlighting the effect of corporate governance regulation in China's insurance industry and other emerging economies of the financial sector.

Transforming Government Service

DEFF Research Database (Denmark)

Pedersen, Keld

2017-01-01

The Danish government has defined an ambitious e-government strategy aiming to increase both citizen centricity and the efficiency of government service production and delivery. This research uses dynamic capability theory to compare a highly successful and a less successful e-government program...... both aiming at realizing this strategy by reengineering back office processes and implement one-stop shopping. The research contributes to the e-government literature by identifying key differences between the two cases in terms of dynamic capabilities, by identifying the importance...

Xenopus oocyte electrophysiology in GPCR drug discovery

DEFF Research Database (Denmark)

Hansen, Kasper Bø; Bräuner-Osborne, Hans

2009-01-01

Deorphanization of the large group of G protein-coupled receptors (GPCRs) for which an endogenous activating ligand has not yet been identified (orphan GPCRs) has become increasingly difficult. A specialized technique that has been successfully applied to deorphanize some of these GPCRs involves ...

G-protein-coupled receptors: new approaches to maximise the impact of GPCRS in drug discovery.

Science.gov (United States)

Davey, John

2004-04-01

IBC's Drug Discovery Technology Series is a group of conferences highlighting technological advances and applications in niche areas of the drug discovery pipeline. This 2-day meeting focused on G-protein-coupled receptors (GPCRs), probably the most important and certainly the most valuable class of targets for drug discovery. The meeting was chaired by J Beesley (Vice President, European Business Development for LifeSpan Biosciences, Seattle, USA) and included 17 presentations on various aspects of GPCR activity, drug screens and therapeutic analyses. Keynote Addresses covered two of the emerging areas in GPCR regulation; receptor dimerisation (G Milligan, Professor of Molecular Pharmacology and Biochemistry, University of Glasgow, UK) and proteins that interact with GPCRs (J Bockaert, Laboratory of Functional Genomics, CNRS Montpellier, France). A third Keynote Address from W Thomsen (Director of GPCR Drug Screening, Arena Pharmaceuticals, USA) discussed Arena's general approach to drug discovery and illustrated this with reference to the development of an agonist with potential efficacy in Type II diabetes.

G-Protein Coupled Receptors: Surface Display and Biosensor Technology

Science.gov (United States)

McMurchie, Edward; Leifert, Wayne

Signal transduction by G-protein coupled receptors (GPCRs) underpins a multitude of physiological processes. Ligand recognition by the receptor leads to the activation of a generic molecular switch involving heterotrimeric G-proteins and guanine nucleotides. With growing interest and commercial investment in GPCRs in areas such as drug targets, orphan receptors, high-throughput screening of drugs and biosensors, greater attention will focus on assay development to allow for miniaturization, ultrahigh-throughput and, eventually, microarray/biochip assay formats that will require nanotechnology-based approaches. Stable, robust, cell-free signaling assemblies comprising receptor and appropriate molecular switching components will form the basis of future GPCR/G-protein platforms, which should be able to be adapted to such applications as microarrays and biosensors. This chapter focuses on cell-free GPCR assay nanotechnologies and describes some molecular biological approaches for the construction of more sophisticated, surface-immobilized, homogeneous, functional GPCR sensors. The latter points should greatly extend the range of applications to which technologies based on GPCRs could be applied.

The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs

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Chunman Li

2017-10-01

Full Text Available G-protein-coupled receptors (GPCRs constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly.

Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase.

Science.gov (United States)

Navarro, Gemma; Cordomí, Arnau; Casadó-Anguera, Verónica; Moreno, Estefanía; Cai, Ning-Sheng; Cortés, Antoni; Canela, Enric I; Dessauer, Carmen W; Casadó, Vicent; Pardo, Leonardo; Lluís, Carme; Ferré, Sergi

2018-03-28

G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interactions between these signaling molecules are based on random collisions or the rearrangement of pre-coupled elements in a macromolecular complex. Furthermore, it remains controversial whether a GPCR homodimer coupled to a single heterotrimeric G protein constitutes a common functional unit. Using a peptide-based approach, we here report evidence for the existence of functional pre-coupled complexes of heteromers of adenosine A 2A receptor and dopamine D 2 receptor homodimers coupled to their cognate Gs and Gi proteins and to subtype 5 AC. We also demonstrate that this macromolecular complex provides the necessary frame for the canonical Gs-Gi interactions at the AC level, sustaining the ability of a Gi-coupled GPCR to counteract AC activation mediated by a Gs-coupled GPCR.

Stargate GTM: Bridging Descriptor and Activity Spaces.

Science.gov (United States)

Gaspar, Héléna A; Baskin, Igor I; Marcou, Gilles; Horvath, Dragos; Varnek, Alexandre

2015-11-23

Predicting the activity profile of a molecule or discovering structures possessing a specific activity profile are two important goals in chemoinformatics, which could be achieved by bridging activity and molecular descriptor spaces. In this paper, we introduce the "Stargate" version of the Generative Topographic Mapping approach (S-GTM) in which two different multidimensional spaces (e.g., structural descriptor space and activity space) are linked through a common 2D latent space. In the S-GTM algorithm, the manifolds are trained simultaneously in two initial spaces using the probabilities in the 2D latent space calculated as a weighted geometric mean of probability distributions in both spaces. S-GTM has the following interesting features: (1) activities are involved during the training procedure; therefore, the method is supervised, unlike conventional GTM; (2) using molecular descriptors of a given compound as input, the model predicts a whole activity profile, and (3) using an activity profile as input, areas populated by relevant chemical structures can be detected. To assess the performance of S-GTM prediction models, a descriptor space (ISIDA descriptors) of a set of 1325 GPCR ligands was related to a B-dimensional (B = 1 or 8) activity space corresponding to pKi values for eight different targets. S-GTM outperforms conventional GTM for individual activities and performs similarly to the Lasso multitask learning algorithm, although it is still slightly less accurate than the Random Forest method.

Issue Framing and Sector Character as Critical Parameters for Government Contracting-Out in the UK

DEFF Research Database (Denmark)

Bækkeskov, Erik

2011-01-01

This article shows that variations in how two UK governments justified contracting-out (issue framing), combined with shifting sector-derived incentives for union activism (sector character), can help explain the extent of contracting-out. Janitorial service, an activity of the UK government......, and its reform faced unions that stood to lose a great deal from movement of janitorial jobs to private firms. In contrast, the New Labour government framed contracting-out broadly, as a means to efficient social justice, and faced unions with low stakes in government janitors. As a consequence, UK...

E-Governance and Its Implementation Challenges in the Nigerian Public Service

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Ugochukwu David ABASILIM

2015-09-01

Full Text Available E-governance has become one of the reform tools geared towards effective public service delivery, which is premised on the assumption that the appreciable use of Information and Communication Technologies (ICT method in the day to day activities of government will bring effective service delivery. However, there are lots of challenges that hamper the effective implementation of e-governance in Nigerian public service. It is based on this, that this article identifies some of the challenges to e-governance implementation in Nigerian public service. Although, no robust statistical analysis was done, as the article relied on archival analysis of relevant literature on the subject matter and inferences drawn from it. Based on its findings, it was concluded that e-governance remain the best in encouraging transparency and accountability in government business. The paper therefore, recommends that, government should be more committed to the implementation e-governance as well as embark on adequate enlightenment about the concept.

A Paradigm Shift in Water Quality Governance in a Transitional Context: A Critical Study about the Empowerment of Local Governance in Georgia

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Sisira S. Withanachchi

2018-01-01

Full Text Available The management of water quality is an important part of natural resource governance. Assurance of water quality therefore requires formulation of the regulatory framework and institutional process. Water quality-related problems and their management are mainly recognized as local responsibilities in Integrated Water Resources Management (IWRM. The politics of environmental policy-making should consider the political economic dynamics and socio-ecological patterns. Decentralization by providing more power to the local level and moving to a new spatial management system that is based on water basins are the two strong entreaties in the new water governance paradigm. Transitional countries facing rapid institutional adjustment, restructuring of regulations, and political-economic changes are encountering these demands internally and externally in their policy formulations. In this context, this study critically examines the case of Georgia, a transitional country. In particular, the focus is on how local governance entities can be empowered and what obstacles water quality governance encounters in Georgia. Qualitative research design is the main research method implemented in this study. The key findings from the research analysis are as follows: the existing regulations and governance system do not facilitate the active engagement of local entities in water quality governance. The application of new water polices may fail again if a top-down governance model is put in place that only creates a narrow space for local governance entities to effectively govern water quality.

The missing link in nanomaterials governance: industrial dynamics and downstream policies

OpenAIRE

Rafols, Ismael; van Zwanenberg, Patrick; Morgan, Molly; Nightingale, Paul; Smith, Adrian

2009-01-01

In this article we explore the analytical and policy implications of widening the governance of nanomaterials from the focus on risk regulation to a broader focus on the governance of innovation. To do this, we have analysed the impact of industrial activities on nanotechnology governance, while previous studies have concentrated on risk appraisal, public perceptions, public engagement, regulatory frameworks and related policies. We argue that the specific characteristics of the industrial dy...

Diversity and functional properties of bistable pigments.

Science.gov (United States)

Tsukamoto, Hisao; Terakita, Akihisa

2010-11-01

Rhodopsin and related opsin-based pigments, which are photosensitive membrane proteins, have been extensively studied using a wide variety of techniques, with rhodopsin being the most understood G protein-coupled receptor (GPCR). Animals use various opsin-based pigments for vision and a wide variety of non-visual functions. Many functionally varied pigments are roughly divided into two kinds, based on their photoreaction: bistable and monostable pigments. Bistable pigments are thermally stable before and after photo-activation, but monostable pigments are stable only before activation. Here, we review the diversity of bistable pigments and their molecular characteristics. We also discuss the mechanisms underlying different molecular characteristics of bistable and monostable pigments. In addition, the potential of bistable pigments as a GPCR model is proposed.

Corporate Governance

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Dragoș-Mihail Daghie

2011-05-01

Full Text Available The purpose of this study is to analyze and understand the recently introduced form of managementof a company limited by shares. The Law no. 441/2006, which fundamentally amended Company Law,created this form of controlling the company, the corporate governance, but the legislation does not explicitlydefine what it wants to achieve through this instrument. This topic is recent in research as the theme ofgerman-roman commercial law systems (in French corporate governance system was introduced in 1966 andin Romania in 2006 but in terms of Anglo-Saxon law, the topic has been addressed years since 1776 (AdamSmith: The Wealth of Nations The concept of corporate governance would like, as a result, to establish somerules that companies must comply in order to achieve effective governance, transparent and beneficial forboth shareholders and for the minority. Corporate governance is a key element with an aim at improvingefficiency and economic growth in full accordance with the increase of investors’ confidence. Corporategovernance assumes a series of relationship between the company management, leadership, shareholders andthe other people concerned. Also corporate governance provides for that structure by means of which thecompany’s targets are set out and the means to achieve them and also the manner how to monitor such.

Improving Unsustainable Environmental Governance in South Africa: the Case for Holistic Governance

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LJ Kotze

2006-05-01

Full Text Available Environmental law in South Africa has developed in a rapid fashion since the inception of the new constitutional dispensation in 1994. This development is evident from, inter alia, the constitutionalisation of the environmental right in section 24 of the Constitution of the Republic of South Africa, 1996. Section 24 contains amongst other provisions, directive principles that impose duties on government to protect the environment for present and future generations through reasonable legislative and other measures. It is apparent from section 24 that these measures should ensure environmental governance practices that are aimed at the achievement of sustainable results. The South African environmental governance regime is, however, characterised by fragmentation that may negate the achievement of sustainable environmental governance. It is argued in this article that, for environmental governance to become sustainable, it is necessary to integrate environmental governance efforts, possibly by way of a holistic approach to environmental governance. In light of the above, this article: investigates the nature and extent of fragmentation; explores reasons for fragmentation; discusses disadvantages of fragmented governance efforts in South Africa; investigates the concept of integration and holistic governance as means to achieve sustainable environmental governance results; and makes recommendations regarding the eventual achievement of integrated, holistic and sustainable environmental governance.

Governance in Health - The Need for Exchange and Evidence Comment on "Governance, Government, and the Search for New Provider Models".

Science.gov (United States)

Chanturidze, Tata; Obermann, Konrad

2016-05-17

Governance in health is cited as one of the key factors in balancing the concerns of the government and public sector with the interests of civil society/private players, but often remains poorly described and operationalized. Richard Saltman and Antonio Duran look at two aspects in the search for new provider models in a context of health markets signalling liberalisation: (i) the role of the government to balance public and private interests and responsibilities in delivering care through modernised governance arrangements, and (ii) the finding that operational complexities may hinder well-designed provider governance models, unless governance reflects country-specific realities. This commentary builds on the discussion by Saltman and Duran, and argues that the concept of governance needs to be clearly defined and operationalized in order to be helpful for policy debate as well as for the development of an applicable framework for performance improvement. It provides a working definition of governance and includes a reflection on the prevailing cultural norms in an organization or society upon which any governance needs to be build. It proposes to explore whether the "evidence-based governance" concept can be introduced to generate knowledge about innovative and effective governance models, and concludes that studies similar to the one by Saltman and Duran can inform this debate. © 2016 by Kerman University of Medical Sciences.

Discovering Citizens Reaction Toward E-Government: Factors in E-Government Adoption

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Mohammad Kamel Alomari

2014-10-01

Full Text Available E-government has been considered as one approach for changing the face of government in the eyes of the citizenry. Therefore, citizens’ socialization in relation to their engagement with e-government should be explored. This study argues that citizens played a significant role in determining the success of an e-government project in the Middle Eastern country of Jordan. This paper aims to provide insight and evaluation into the factors that could influence e-government’s effective functioning in the Jordanian social community through its interaction with citizens. The study collected data from 356 Jordanian citizens via a survey, to ascertain their understanding of 10 factors that may influence their intention to use e-government services. To investigate the adoption of e-government services in depth, two departments in Jordan were selected: the Jordanian Government’s Income and Sales Tax Department (ISTD and its Driver and Vehicle Licenses Department (DVDL. The factor analysis technique was used to identify the main factors related to e-government services’ adoption. The results indicated that trust in the internet, website design, religious beliefs, internet and computer skill confidence, word of mouth, resistance to change, perceived usefulness, relative advantage and complexity are the main factors that should be considered when addressing the topic of e-government services’ adoption in Jordan. This study is different from most existing studies on e-government adoption as it empirically investigated the impact of word of mouth (WOM, wasta (favoritism, and resistance to change on e-government adoption. This study highlights the importance of considering the social cohesion of the Jordanian community when exploring factors related to e-government adoption.

Estimating a corporate governance index for companies in Greece

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Ramona Iulia Țarțavulea (Dieaconescu

2015-12-01

Full Text Available European countries have gone through serious efforts to overcome the financial crisis and special measures had to be taken in order to limit the negative impact on businesses and stabilize a healthy economic environment for the single market. The specific governmental policies aimed to keep under control the effects of the crisis and relaunch the economic growth, but they were unpopular among a part of the European citizens. The economic situation forced most managers of private companies to rethink the business strategy and restructure the activity. Lately, Greece has been going through a difficult period, as the crisis worsened the economic situation of the country. The population did not welcome the drastic economic measures which were proposed by IMF and institutional creditors and this conflict almost lead to national insolvency. The problems of Greece are deeply rooted in the business models and economic philosophy. This paper has the purpose of analyzing the corporate governance regulation and practices in Greece and to determine whether it is possible to enhance business profitability and stability by enforcing a better legal framework in the area of corporate governance. The research focuses on the calculation of a corporate governance index for a selection of Greek companies form different sectors of activity (oil &gas, telecommunications, beverages and the analysis of the results may lead to the identification of weaknesses in this domain. Improvements in the corporate governance practices are considered to lead to enhancing business stability and sustainability. The methodology for calculating the corporate governance index is adapted for Greek companies and is in accordance with the provisions of the Hellenic Corporate Governance Code.

Corporate Social Responsibility in Perspective of Public Administration (A Governance Study

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Dr.Sc. Said Achmad Lamo

2017-06-01

Full Text Available The Implementation of CSR in Indonesia, most of them are not run in accordance with the existing theory because the government and society in CSR activities are not fully authorised to engage in these activities, due to the fact that private sector directly manages the CSR fund. Thus, the theory of governance puts three pillars as a principal provider of public service life, those are, (1 the state, (2 the civil society and (3 the private sector. CSR has to involve all parts or elements which know about CSR, with a focus on the implementation of CSR has to be published and transparent; the CSR Fund is administered by a forum / team through a memorandum of understanding facilitated by the government in accordance with its role as mandating, facilitating, partnering, and endorsing; the CSR forum consists of government, private sector, and society; the form of regional regulation on CSR by reference to Constitution Number 40 of 2007 on the Limited Liability Private sectors and Government Regulation Number 47 of 2012 on Corporate Social Responsibility so that CSR is considered as one of the important instruments in public administration.

Use of Local Health Department Websites: A Study of E-Government Adoption and Diffusion

Science.gov (United States)

Aaltonen, Pamela Massie

2013-01-01

Two distinct but converging activities have the potential to alter the way local public health departments conduct business. These activities are the emergence of e-government and the addition of preparedness as a basic function of the public health system. Preparedness implies timely collaboration with government entities, community partners and…

Zhengdong New District Smart Government Application System Construction and Its Development Strategy Research

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Li Bing

2017-01-01

Full Text Available Smart government is the advanced stage of e-government development, whose essence is the fusion of Internet, Internet of things, cloud computing, big data and other high and new technology and e-government, to achieve the efficient management of all kinds of information resources and make the government services more transparent, scientific and wisdom. Based on the introduce, basic principle and construct meaning, application system construction, main problems and developing countermeasures and other aspects of smart government to make a comprehensive analysis in the construction of Zhengdong new district smart government, then advise the government departments to speed up the transformation of government management functions and social service mode to integrate the business processes, and promote the construction of service-oriented and smart-oriented government actively.

OPTIMALISASI FUNGSI HUMAS PEMERINTAH THE OPTIMIZATION OF GOVERNMENT PUBLIC RELATIONS FUNCTION

OpenAIRE

Anwar Sani

2014-01-01

Abstract, world democratization forces many organizations including the government in this case, of all types in many regions of the world, to consider giving more attention to the government public relations activities. The role will include contributing to good governance and respect for human rights. That would mean public relations in Indonesia, as elsewhere in Asia, will be involved in the development of public diplomacy. Aware of the problems as well as the demands of optimization and r...

Governance, Government, and the Search for New Provider Models

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Richard B. Saltman

2016-01-01

Full Text Available A central problem in designing effective models of provider governance in health systems has been to ensure an appropriate balance between the concerns of public sector and/or government decision-makers, on the one hand, and of non-governmental health services actors in civil society and private life, on the other. In tax-funded European health systems up to the 1980s, the state and other public sector decision-makers played a dominant role over health service provision, typically operating hospitals through national or regional governments on a command-and-control basis. In a number of countries, however, this state role has started to change, with governments first stepping out of direct service provision and now de facto pushed to focus more on steering provider organizations rather than on direct public management. In this new approach to provider governance, the state has pulled back into a regulatory role that introduces market-like incentives and management structures, which then apply to both public and private sector providers alike. This article examines some of the main operational complexities in implementing this new governance reality/strategy, specifically from a service provision (as opposed to mostly a financing or even regulatory perspective. After briefly reviewing some of the key theoretical dilemmas, the paper presents two case studies where this new approach was put into practice: primary care in Sweden and hospitals in Spain. The article concludes that good governance today needs to reflect practical operational realities if it is to have the desired effect on health sector reform outcome.

Governance, Government, and the Search for New Provider Models.

Science.gov (United States)

Saltman, Richard B; Duran, Antonio

2015-11-03

A central problem in designing effective models of provider governance in health systems has been to ensure an appropriate balance between the concerns of public sector and/or government decision-makers, on the one hand, and of non-governmental health services actors in civil society and private life, on the other. In tax-funded European health systems up to the 1980s, the state and other public sector decision-makers played a dominant role over health service provision, typically operating hospitals through national or regional governments on a command-and-control basis. In a number of countries, however, this state role has started to change, with governments first stepping out of direct service provision and now de facto pushed to focus more on steering provider organizations rather than on direct public management. In this new approach to provider governance, the state has pulled back into a regulatory role that introduces market-like incentives and management structures, which then apply to both public and private sector providers alike. This article examines some of the main operational complexities in implementing this new governance reality/strategy, specifically from a service provision (as opposed to mostly a financing or even regulatory) perspective. After briefly reviewing some of the key theoretical dilemmas, the paper presents two case studies where this new approach was put into practice: primary care in Sweden and hospitals in Spain. The article concludes that good governance today needs to reflect practical operational realities if it is to have the desired effect on health sector reform outcome. © 2016 by Kerman University of Medical Sciences.

ISSUES AND CHALLENGES IN WATER GOVERNANCE IN MALAYSIA

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N. W. Chan

2009-07-01

Full Text Available Water is one of the central issues in the 21st century in Malaysia. Of all the issues associated with water management, governance is considered of primary importance. This paper examines water governance in Malaysia and concludes that it is successful in the sense that water is served to more than 95 % of the population, water tariffs are some of the cheapest in the world, the poor is not denied access, and water supply is 24 hours per day. However, there are many areas that need improvement to achieve better governance in water management. One is to improve Government-controlled water departments by ensuring their workers are well-trained and committed to excellence, public service and integrity instead of the usual laid-back government-servant mentality. Another is to ensure politicians do not interfere in the water sector. Currently, it is widely believed that many water companies are linked to powerful politicians, making the awarding of contracts, tariffs and other management aspects non-transparent and ineffective. Ideally, politicians that govern should act on the professional advice of the water managers and not the other way around. Another area of water governance that needs to be intensified is the war against corruption. In the water sector, there should also be an all-out war on corruption at all levels of governance, in both the public and private sectors. Government should make all contracts in the water sector awarded through open tender with public consultation to ensure professionalism, fairness, transparency, accountability and good governance. Equally, all contracts and other relevant documents drawn up between the government and private companies should not be “classified” but instead be public documents available to the public for discussion, review and improvement. Another area to ensure better governance is for the government to engage and actively involved all stakeholders in the water sector, especially civil

Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase

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Guan Kunliang

2003-06-01

Full Text Available Abstract Background G protein-coupled receptors (GPCRs interact with heterotrimeric GTP-binding proteins (G proteins to modulate acute changes in intracellular messenger levels and ion channel activity. In contrast, long-term changes in cellular growth, proliferation and differentiation are often mediated by tyrosine kinase receptors and certain GPCRs by activation of mitogen-activated protein (MAP kinases. Complex interactions occur between these signaling pathways, but the specific mechanisms of such regulatory events are not well-understood. In particular it is not clear whether GPCRs are modulated by tyrosine kinase receptor-MAP kinase pathways. Results Here we describe tyrosine kinase receptor regulation of a GPCR via MAP kinase. Insulin reduced the activity of the 5-HT2C receptor in choroid plexus cells which was blocked by the MAP kinase kinase (MEK inhibitor, PD 098059. We demonstrate that the inhibitory effect of insulin and insulin-like growth factor type 1 (IGF-1 on the 5-HT2C receptor is dependent on tyrosine kinase, RAS and MAP kinase. The effect may be receptor-specific: insulin had no effect on another GPCR that shares the same G protein signaling pathway as the 5-HT2C receptor. This effect is also direct: activated MAP kinase mimicked the effect of insulin, and removing a putative MAP kinase site from the 5-HT2C receptor abolished the effect of insulin. Conclusion These results show that insulin signaling can inhibit 5-HT2C receptor activity and suggest that MAP kinase may play a direct role in regulating the function of a specific GPCR.

Government and Governance of Regional Triple Helix Interactions

Science.gov (United States)

Danson, Mike; Todeva, Emanuela

2016-01-01

This conceptual paper contributes to the discussion of the role of regional government and regional Triple Helix constellations driving economic development and growth within regional boundaries. The impact of regionalism and subsidiarity on regional Triple Helix constellations, and the questions of governmentality, governance and institutional…

GOVERNMENT SIZE VERSUS GOVERNMENT EFFICIENCY IN A MODEL OF ECONOMIC GROWTH

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Francisca Guedes de Oliveira

2016-04-01

Full Text Available We develop a Solow type growth model where firms produce a single homogenous good using labor, private capital and a public good. The "amount" of public good depends on current government spending and government quality. Quality is the result of the accumulation of public capital. Governments charge distortionary taxes and provide the public good, investing also in "quality" by accumulating public capital. We analyze how the composition of government spending between current expenditures and quality affects the equilibrium levels. We aim to understand the difference in terms of steady state levels between leviathan, quality driven and benevolent governments.

Governance matters: an ecological association between governance and child mortality.

Science.gov (United States)

Lin, Ro-Ting; Chien, Lung-Chang; Chen, Ya-Mei; Chan, Chang-Chuan

2014-09-01

Governance of a country may have widespread effects on the health of its population, yet little is known about the effect of governance on child mortality in a country that is undergoing urbanization, economic development, and disease control. We obtained indicators of six dimensions of governance (perceptions of voice and accountability, political stability and absence of violence, government effectiveness, regulatory quality, rule of law, and control of corruption) and national under-5 mortality rates for 149 countries between 1996 and 2010. We applied a semi-parametric generalized additive mixed model to examine associations after controlling for the effects of development factors (urbanization level and economy), disease control factors (hygienic conditions and vaccination rates), health expenditures, air quality, and time. Governance, development, and disease control showed clear inverse relations with the under-5 mortality rate (pcountry's need for better governance is as important as improvements in development and disease control. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

THE ROLE OF LOCAL GOVERNMENT IN THE PROCESS OF ENTREPRENEURSHIP DEVELOPMENT

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Tomasz Skica

2014-04-01

Full Text Available This article presents the role of local governments in supporting entrepreneurship development. The content of the article presents the factors which foster activities undertaken by local authorities to promote entrepreneurship and also shows different considerations of when the supporting instruments are in use. The article is also an assessment of current activities of local governments in the sphere of supporting business initiatives. It indicates potential of possible changes in local policy on supporting entrepreneurship. The article sets out areas of possible improvements in policy when stimulating economic activity by local authorities. It addresses the improvements of the objective restrictions which are laid out by the existing legal framework.

Towards a smart learning environment for smart city governance

OpenAIRE

Hammad, R.; Ludlow, D.; Computer Science and Creative Technology; Centre for Sustainable Planning

2016-01-01

Educational services provided to various stakeholders need to be actively developed to accommodate the diversity of learning models and to get the advantages of available resources (e.g. data) in smart cities governance. Despite the substantial literature on smart cities, for Technology-Enhanced Learning (TEL) and its related domains such as learning analytics and big data, little effort has been given to the creation of connectivity to smart cities governance to meet stakeholders’ demands, e...

Integrating adaptive governance and participatory multicriteria methods: a framework for climate adaptation governance

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Stefania Munaretto

2014-06-01

Full Text Available Climate adaptation is a dynamic social and institutional process where the governance dimension is receiving growing attention. Adaptive governance is an approach that promises to reduce uncertainty by improving the knowledge base for decision making. As uncertainty is an inherent feature of climate adaptation, adaptive governance seems to be a promising approach for improving climate adaptation governance. However, the adaptive governance literature has so far paid little attention to decision-making tools and methods, and the literature on the governance of adaptation is in its infancy in this regard. We argue that climate adaptation governance would benefit from systematic and yet flexible decision-making tools and methods such as participatory multicriteria methods for the evaluation of adaptation options, and that these methods can be linked to key adaptive governance principles. Moving from these premises, we propose a framework that integrates key adaptive governance features into participatory multicriteria methods for the governance of climate adaptation.

Recognition of Obstacles and Providing Different Guidelines and Promotion of Electronic Government in Iran

OpenAIRE

E. Asgharizadeh; M. Ajalli; S.R. Safavi.M.M; A. Medghalchi

2010-01-01

Electronic Government is one of the special concepts which has been performed successfully within recent decades. Electronic government is a digital, wall-free government with a virtual organization for presenting of online governmental services and further cooperation in different political/social activities. In order to have a successful implementation of electronic government strategy and benefiting from its complete potential and benefits and generally for establishme...

Cycle of Bad Governance and Corruption

Directory of Open Access Journals (Sweden)

Mohammed Nuruddeen Suleiman

2015-03-01

Full Text Available This article argues that bad governance and corruption particularly in the Northern part of Nigeria have been responsible for the persistent rise in the activities of Jama’atu Ahlis Sunna Lidda’awati wal-Jihad (JASLWJ, Arabic for “people committed to the propagation of the tradition and jihad.” It is also known as “Boko Haram,” commonly translated as “Western education is sin.” Based on qualitative data obtained through interviews with Nigerians, this article explicates how poor governance in the country has created a vicious cycle of corruption, poverty, and unemployment, leading to violence. Although JASLWJ avows a religious purpose in its activities, it takes full advantage of the social and economic deprivation to recruit new members. For any viable short- or long-term solution, this article concludes that the country must go all-out with its anti-corruption crusade. This will enable the revival of other critical sectors such as agriculture and manufacturing, likely ensuring more employment. Should the country fail to stamp out corruption, it will continue to witness an upsurge in the activities of JASLWJ, and perhaps even the emergence of other violent groups. The spillover effects may be felt not only across Nigeria but also within the entire West African region.

Practice of good governance and corporate governance

OpenAIRE

Bălăceanu Cristina; Predonu Andreea – Monica

2010-01-01

Corporate governance reforms are occurring in countries around the globe and potentially impacting the population of the entire planet. In developing countries, such reforms occur in a larger context that is primarily defined by previous attempts at promoting “development” and recent processes of economic globalization. In this context, corporate governance reforms (in combination with the liberalising reforms associated with economic globalization), in effect re...

A Study on Technology Architecture and Serving Approaches of Electronic Government System

Science.gov (United States)

Liu, Chunnian; Huang, Yiyun; Pan, Qin

As E-government becomes a very active research area, a lot of solutions to solve citizens' needs are being deployed. This paper provides technology architecture of E-government system and approaches of service in Public Administrations. The proposed electronic system addresses the basic E-government requirements of user friendliness, security, interoperability, transparency and effectiveness in the communication between small and medium sized public organizations and their citizens, businesses and other public organizations. The paper has provided several serving approaches of E-government, which includes SOA, web service, mobile E-government, public library and every has its own characteristics and application scenes. Still, there are a number of E-government issues for further research on organization structure change, including research methodology, data collection analysis, etc.

Role of G-protein-coupled receptor-related genes in insecticide resistance of the mosquito, Culex quinquefasciatus.

Science.gov (United States)

Li, Ting; Liu, Lena; Zhang, Lee; Liu, Nannan

2014-09-29

G-protein-coupled receptors regulate signal transduction pathways and play diverse and pivotal roles in the physiology of insects, however, the precise function of GPCRs in insecticide resistance remains unclear. Using quantitative RT-PCR and functional genomic methods, we, for the first time, explored the function of GPCRs and GPCR-related genes in insecticide resistance of mosquitoes, Culex quinquefasciatus. A comparison of the expression of 115 GPCR-related genes at a whole genome level between resistant and susceptible Culex mosquitoes identified one and three GPCR-related genes that were up-regulated in highly resistant Culex mosquito strains, HAmCq(G8) and MAmCq(G6), respectively. To characterize the function of these up-regulated GPCR-related genes in resistance, the up-regulated GPCR-related genes were knockdown in HAmCq(G8) and MAmCq(G6) using RNAi technique. Knockdown of these four GPCR-related genes not only decreased resistance of the mosquitoes to permethrin but also repressed the expression of four insecticide resistance-related P450 genes, suggesting the role of GPCR-related genes in resistance is involved in the regulation of resistance P450 gene expression. This results help in understanding of molecular regulation of resistance development in Cx. quinquefasciatus.

Cryptocurrencies & the Challenge of Global Governance

Directory of Open Access Journals (Sweden)

Garry Jacbs

2018-05-01

Full Text Available The recent explosive development of new forms of digital currency opens up unprecedented opportunities and poses significant regulatory challenges. This new form of digital currency lowers the costs and other barriers to the global movement of money, international trade, foreign investment and speculation, while simultaneously enhancing the anonymity on which tax evasion, money-laundering and other illegal activities thrive. It also liberates the creation of money and regulation of economic activities from the political control of national governments and central banks. Since the value of a currency is related to the size of the population, strength of the economy and value of transactions that utilize it, a basket of cryptocurrencies could emerge as the first prototype of a world currency whose value is backed by the total productive capacity of the entire human community. Moreover, the triad of Internet, distributed ledger technologies and cryptocurrencies could serve as the basis for the development of new global economic potentials in a manner similar and a degree far exceeding the economic impact of the World Wide Web over the past two decades. At the same time, the rapid deployment of cryptocurrencies could have profound impact on the capacity of governments to tax transactions, income and wealth, one of the main pillars of the modern nation state. The development of autonomous global cryptocurrencies could dramatically reduce the control and effectiveness of existing regulatory mechanisms at the national level and generate considerable pressure for the evolution of more effective institutions for global governance. They could provide compelling incentives for national governments to enhance international cooperation and strengthen the functioning of international institutions to fill the regulatory void. International organizations will play an important role in harnessing the potentials and minimizing the risks arising from the growing

GOVERNING BOARD OF THE PENSION FUND

CERN Document Server

2000-01-01

Since the last report, the Governing Board has held three meetings, on the 5 September, 4 October and 9 November. At its September meeting, the Board took note of the results of the half-year closure of the accounts on 30 June and examined the expenditure of the Fund's Administration to the end of July and its operating budget for 2001, which it approved. The Chairman of the Investment Committee, G. Maurin, reported on the Committee's activities in regard to the monitoring of the fund managers and their results. After an exchange of views, the Governing Board proposed to the Finance Committee and the Council an adjustment of pensions of 1.4% with effect from 1.1.2001. It took note with satisfaction of the decision of the French tax authorities to consider that CERN's investments in France on behalf of its social security scheme formed part of the official activities of the Organization and as such benefited from exemption from direct local taxes in addition to its exemption from national taxation. The Governi...

Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy.

Science.gov (United States)

Rwibasira Rudinga, Gamariel; Khan, Ghulam Jilany; Kong, Yi

2018-02-14

Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

Energy Efficiency Governance

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-07-01

The purpose of this report is to help EE practitioners, government officials and stakeholders to establish the most effective EE governance structures, given their specific country context. It also aims to provide readers with relevant and accessible information to support the development of comprehensive and effective governance mechanisms. The International Energy Agency (IEA) conducted a global review of many elements of EE governance,including legal frameworks, institutional frameworks, funding mechanisms, co-ordination mechanisms and accountability arrangements, such as evaluation and oversight. The research tools included a survey of over 500 EE experts in 110 countries, follow-up interviews of over 120 experts in 27 countries and extensive desk study and literature searches on good EE governance.

China’s Insurance Regulatory Reform, Corporate Governance Behavior and Insurers’ Governance Effectiveness

Science.gov (United States)

Zhang, Hongliang; Qiu, Aichao

2017-01-01

External regulation is an important mechanism to improve corporate behavior in emerging markets. China’s insurance governance regulation, which began to supervise and guide insurance corporate governance behavior in 2006, has experienced a complex process of reform. This study tested our hypotheses with a sample of 85 firms during 2010–2011, which was obtained by providing a questionnaire to all of China’s shareholding insurance companies. The empirical study results generally show that China’s insurance governance effectiveness has significantly improved through strict regulation. Insurance corporate governance can improve business acumen and risk-control ability, but no significant evidence was found to prove its influence on profitability, as a result of focusing less attention on governance than on management. State ownership is associated with higher corporate governance effectiveness than non-state ownership. Listed companies tend to outperform non-listed firms, and life insurance corporate governance is more effective than that of property insurers. This study not only contributes to the comprehensive understanding of corporate governance effectiveness but also to the literature by highlighting the effect of corporate governance regulation in China’s insurance industry and other emerging economies of the financial sector. PMID:29039781

China’s Insurance Regulatory Reform, Corporate Governance Behavior and Insurers’ Governance Effectiveness

Directory of Open Access Journals (Sweden)

Huicong Li

2017-10-01

Full Text Available External regulation is an important mechanism to improve corporate behavior in emerging markets. China’s insurance governance regulation, which began to supervise and guide insurance corporate governance behavior in 2006, has experienced a complex process of reform. This study tested our hypotheses with a sample of 85 firms during 2010–2011, which was obtained by providing a questionnaire to all of China’s shareholding insurance companies. The empirical study results generally show that China’s insurance governance effectiveness has significantly improved through strict regulation. Insurance corporate governance can improve business acumen and risk-control ability, but no significant evidence was found to prove its influence on profitability, as a result of focusing less attention on governance than on management. State ownership is associated with higher corporate governance effectiveness than non-state ownership. Listed companies tend to outperform non-listed firms, and life insurance corporate governance is more effective than that of property insurers. This study not only contributes to the comprehensive understanding of corporate governance effectiveness but also to the literature by highlighting the effect of corporate governance regulation in China’s insurance industry and other emerging economies of the financial sector.

Local government financial autonomy in Nigeria: The State Joint Local Government Account

Directory of Open Access Journals (Sweden)

Jude Okafor

2010-07-01

Full Text Available This paper addresses the statutory financial relations and financial autonomy of local government in Nigeria, and the freedom of local government to generate revenue from its assigned sources without external interference. It focuses particularly on a financial instrument called the State Joint Local Government Account (SJLGA and how its operations have positively or negatively affected the financial autonomy of local government councils and the inter-relations between state and local government in Nigeria.

Contributions of H G Khorana to Understanding Transmembrane ...

Indian Academy of Sciences (India)

IAS Admin

shared ground state structures and molecular mechanism of GPCR activation. Much of .... facilitated a number of early mutagenesis studies of rhodopsin ... of the dynamics of ... Computer simulations based on inputs from various experimental.

A Method for Assessing the Performance of e-Government Twitter Accounts

Directory of Open Access Journals (Sweden)

Konstantinos Antoniadis

2016-04-01

Full Text Available This paper introduces a method for assessing the influence of Twitter accounts of central e-government agencies. It first stresses the importance of activity and popularity of the e-government accounts, and also the importance of community formation among followers-citizens, as the two main stages of e-government adoption. The proposed approach combines activity and popularity of the accounts and followers’ community characteristics in a ranking system, using an idea originally introduced to measure blogosphere authority. A Twitter Authority Index is produced. The method is demonstrated through an extended example: 56 Twitter accounts of ministries of EU countries are sorted according to their indexes in the proposed ranking system. Detailed values for the ministries’ accounts and average values for the countries that the ministries belong to are reported and commented.

Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

Energy Technology Data Exchange (ETDEWEB)

Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kitamura, Kazuo; Nagata, Sayaka; Hikosaka, Tomomi [Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

2010-02-12

Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

Governing Board of the Pension Fund

CERN Multimedia

2005-01-01

The Governing Board of the Pension Fund held its one-hundred-and-thirty-fifth and one-hundred-and-thirty-sixth meetings on 9 June and 7 July 2005 respectively. At the first of these two meetings, the members of the Board were informed of the outcome of the meeting of the Investment Committee, which had been held on the previous day. The Investment Committee had reviewed the performance of the Far East equity mandate (excluding Japan) managed by Edmond de Rothschild Asset Management and had welcomed the good results achieved by the portfolio manager. The Committee had also decided to propose to the Governing Board that it approve a new table defining the split between active and passive management for each of the major geographical zones for its investments. The Governing Board followed the Committee's recommendation and approved the following allocations to passive management: 2/3 of assets in the United States, 1/2 of assets in Japan and 1/3 of assets in Europe. This increase in the use of passive managemen...

The politics of meta-governance in transnational private sustainability governance

OpenAIRE

Fransen, L.

2015-01-01

In order to address challenges resulting from interactions between transnational private sustainability standard organizations, initiatives emerge that meta-govern these standards. Contrary to prevailing understandings in public policy literature, such meta-governance initiatives are mostly run by nongovernmental rather than governmental actors. While literature presents the sustainability standards field as predominantly governed by one meta-governor, ISEAL, it is hardly recognized that, alo...

Theoretical Ideas of Local Government and State Government Development

Directory of Open Access Journals (Sweden)

Nikolay I. Churinov

2016-03-01

Full Text Available In this article the characteristic of a theoretical component of model of interaction of local government bodies with the central government, and also development of scientific base in the course of history is given. Relevance to this subject in the conditions of the Russian reality is added by federalism of a state system of Russia, namely a thin side in questions of competences between bodies of one hierarchy. This article, will be useful to those who deal with issues in the field of the theory of the state and the right and the municipal right. Historic facts in the form of the regulatory legal acts adopted earlier which subsequently, were a source for development of theoretical ideas of local self-government and the government are given in article.

An examination of a reciprocal relationship between network governance and network structure

DEFF Research Database (Denmark)

Bergenholtz, Carsten; Goduscheit, René Chester

2011-01-01

In the present article, we examine the network structure and governance of inter-organisational innovation networks over time. Network governance refers to the issue of how to manage and coordinate the relational activities and processes in the network while research on network structure deals...

Anticipatory Governance: Bioethical Expertise for Human/Animal Chimeras

Science.gov (United States)

Harvey, Alison; Salter, Brian

2012-01-01

The governance demands generated by the use of human/animal chimeras in scientific research offer both a challenge and an opportunity for the development of new forms of anticipatory governance through the novel application of bioethical expertise. Anticipatory governance can be seen to have three stages of development whereby bioethical experts move from a reactive to a proactive stance at the edge of what is scientifically possible. In the process, the ethicists move upstream in their engagement with the science of human-to-animal chimeras. To what extent is the anticipatory coestablishment of the principles and operational rules of governance at this early stage in the development of the human-to-animal research field likely to result in a framework for bioethical decision making that is in support of science? The process of anticipatory governance is characterised by the entwining of the scientific and the philosophical so that judgements against science are also found to be philosophically unfounded, and conversely, those activities that are permissible are deemed so on both scientific and ethical grounds. Through what is presented as an organic process, the emerging bioethical framework for human-to-animal chimera research becomes a legitimating framework within which ‘good’ science can safely progress. Science gives bioethical expertise access to new governance territory; bioethical expertise gives science access to political acceptability. PMID:23576848

Optimalisasi Penerapan Prinsip Good Governance Bidang Akademik dalam Upaya Mewujudkan Good University Governance

Directory of Open Access Journals (Sweden)

Hery Harjono Muljo

2014-05-01

Full Text Available This study wants to know and understand whether good governance principles have been well applied as well as the factors influencing optimization of the implementation of good governance principles on the academic field in an effort to realize good university governance in Bina Nusantara University. The study aims to evaluate the implementation of good governance principles on the academic field, know the factors that affect the implementation of good governance principles on the academic field, and improve and develop the academic areas in accordance with good governance principles in order to maximize the role of Bina Nusantara University as Good University Governance. The approach model used to understand the implementation of good governance principles was a model to educational institution using the 8 principles, namely academic freedom, shared governance, clear rights and responsibilities, selection at merit, financial stability, accountability, regular testing of standards, and the importance of close cooperation. Research used qualitative method with descriptive analysis, by analyzing the factors influencing optimization of the implementation of good governance principles, particularly on academic areas. The results achieved there were 18 factors that affect the optimization of the implementation of good governance principles. Then the factors affected the optimization ofthe implementation of good governance principles the most are operational centralization and academic decentralization which were the novelty of this study.

Statewide prevalence of school children at risk of anaphylaxis and rate of adrenaline autoinjector activation in Victorian government schools, Australia.

Science.gov (United States)

Loke, Paxton; Koplin, Jennifer; Beck, Cara; Field, Michael; Dharmage, Shyamali C; Tang, Mimi L K; Allen, Katrina J

2016-08-01

The prevalence of school students at risk of anaphylaxis in Victoria is unknown and has not been previously studied. Similarly, rates of adrenaline autoinjector usage in the school environment have yet to be determined given increasing prescription rates. We sought to determine time trends in prevalence of school children at risk of anaphylaxis across all year levels and the annual usage rate of adrenaline autoinjectors in the school setting relative to the number of students at risk of anaphylaxis. Statewide surveys from more than 1,500 government schools including more than 550,000 students were used and prevalence rates (%) with 95% CIs were calculated. The overall prevalence of students at risk of anaphylaxis has increased 41% from 0.98% (95% CI, 0.95-1.01) in 2009 to 1.38% (95% CI, 1.35-1.41) in 2014. There was a significant drop in reporting of anaphylaxis risk with transition from the final year of primary school to the first year of secondary school, suggesting a change in parental reporting of anaphylaxis risk among secondary school students. The number of adrenaline autoinjectors activated per 1000 students at risk of anaphylaxis ranged from 6 to 8 per year, with consistently higher activation use in secondary school students than in primary school students. Statewide prevalence of anaphylaxis risk has increased in children attending Victorian government schools. However, adrenaline autoinjector activation has remained fairly stable despite known increase in the rates of prescription. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Experimentalist governance

NARCIS (Netherlands)

Sabel, C.F.; Zeitlin, J.; Levi-Faur, D.

2012-01-01

A secular rise in volatility and uncertainty is overwhelming the capacities of conventional hierarchical governance and ‘command-and-control’ regulation in many settings. One significant response is the emergence of a novel, ‘experimentalist’ form of governance that establishes deliberately

Remaking Governance.

Science.gov (United States)

Carver, John

2000-01-01

The Policy Governance model's philosophical foundations lie in Rousseau's social contract, Greenleaf's servant-leadership, and modern management theory. Policy Governance stresses primacy of the owner-representative role; full-board authority; superintendents as chief executive officers; authoritative prescription of "ends," bounded…

Modern trends in international researches in the sphere of electronic governance (in the case of publications of the international journal Electronic Government

Directory of Open Access Journals (Sweden)

V. M. Dreshpak

2017-08-01

Full Text Available Current trends of studying the problems of electronic government by world scientific community have been revealed in the article using the analysis of publications in the international journal Electronic Government. It has been noted that the peculiarity of modern research in the sphere of electronic government is that this sphere is changing constantly and dynamically under the influence of many factors and is being modernized together with the development of information and communication technologies and social relations. This requires a bigger degree of integration of Ukrainian researches in the sphere of public administration with the global scientific context, more active introduction of the foreign researches’ materials on electronic government issues to the scientific Ukrainian use, study of foreign approaches on publications in scientific periodicals of the industry. The survey was conducted on the basis of Electronic Government, an International Journal, which has been published since 2004 in the UK and is submitted to the international Scientometrics Scopus database and publishes materials in the sphere of «Public administration». It has been found that the key topics of the journal relate to the current practice and studies of various aspects of electronic government in different countries. In particular, the analyzed publications of 2015 - 2017 years provide a broad picture of the situation with e-government in the world and reveal specific problems of different states according to the level of development of their e-government powers. The authors of these articles are scientists from 24 countries. They have studied the problems of electronic government in 14 states and the global problems of electronic government. For example, the magazine focuses on issues related to technological, social and humanitarian components of functioning and development of electronic governance, issues of methodology and methods of implementation of

PENGARUH PENGENDALIAN INTERNAL PERUSAHAAN DAN STRUKTUR CORPORATE GOVERNANCE TERHADAP FEE AUDIT

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Esti Widiasari

2016-02-01

Full Text Available Good internal control and good corporate governance will reduce activities which will be carried out by auditor. The activities reduction will bring about auditor fee cutback. The purpose of the study is to examine the influence of internal control function and corporate governance structures, i.e. major shareholders, independent commissioners and audit committe, toward audit fees. This study is replication of Hay’s et al. research in 2008. The data collection uses purposive sampling method. Data was collected from annual reports of manufacturing companies which listed on Bursa Efek Indonesia in 2005-2007. The method used in analysis is multiple linear regression. The results show that internal audit functions do not affect to audit fees. By contrast, audit committee negatively influence toward audit fees. The two corporate governance structures (major shareholders and independent commissioners have significant positive influncial on audit fees. The results consistent with previous studies and consistent with the explanation that controls are complementary (controls, corporate governance and auditing are complement, an increase in one control will lead to an increase in the others.

Political power beyond the State: problematics of government. 1992.

Science.gov (United States)

Rose, Nikolas; Miller, Peter

2010-01-01

This paper sets out an approach to the analysis of political power in terms of problematics of government. It argues against an overvaluation of the 'problem of the State' in political debate and social theory. A number of conceptual tools are suggested for the analysis of the many and varied alliances between political and other authorities that seek to govern economic activity, social life and individual conduct. Modern political rationalities and governmental technologies are shown to be intrinsically linked to developments in knowledge and to the powers of expertise. The characteristics of liberal problematics of government are investigated, and it is argued that they are dependent upon technologies for 'governing at a distance', seeking to create locales, entities and persons able to operate a regulated autonomy. The analysis is exemplified through an investigation of welfarism as a mode of 'social' government. The paper concludes with a brief consideration of neo-liberalism which demonstrates that the analytical language structured by the philosophical opposition of state and civil society is unable to comprehend contemporary transformations in modes of exercise of political power.(1).

Digital Government and Public Health

OpenAIRE

Fountain, Jane E.

2004-01-01

Digital government is typically defined as the production and delivery of information and services inside government and between government and the public using a range of information and communication technologies. Two types of government relationships with other entities are government-to-citizen and government-to-government relationships. Both offer opportunities and challenges. Assessment of a public health agencys readiness for digital government includes examination of technical, manage...

Corporate governance ratings as a means to reduce asymmetric information

Directory of Open Access Journals (Sweden)

Claus Holm

2014-12-01

Full Text Available Can corporate governance ratings reduce problems of asymmetric information between companies and investors? To answer this question, we set out to examine the information basis for providing such ratings by reviewing corporate governance attributes that are required or recommended in laws, accounting standards, and codes, respectively. After that, we scrutinize and organize the publicly available information on the methodologies actually used by rating providers. However, important details of these methodologies are treated as confidential property, thus we approach the evaluation of corporate governance ratings as a means to reduce asymmetric information in a more general manner. We propose that the rating process may be seen as consisting of two general activities, namely a data reduction phase, and a data weighting, aggregation, and classification phase. Findings based on a Danish data-set suggest that rating providers by selecting relevant attributes in an intelligent way can improve the screening of companies according to governance quality. In contrast, it seems questionable that weighting, aggregation, and classification of corporate governance attributes considerably improve discrimination according to governance quality.

Development of Corporate Governance Performance Indicators for Czech Manufacturing Companies

Directory of Open Access Journals (Sweden)

Pavláková Docekalová Marie

2015-03-01

Full Text Available Effective corporate governance is a key element in achieving long-term success for any company. The codes of conduct that corporate governance adopts directly determine the sustainability of business activities. With this in mind, this paper aims to demonstrate the results of research that identifies a set of key indicators of corporate governance performance. The presented research is quantitative. In order to identify key performance indicators, factor analysis was employed. It was found that corporate governance performance is influenced by two factors. For the first factor, the relationship between corporate governance and stakeholders is measured by key indicators: percentage of women within CG, contributions to political parties, politicians and related institutions and number of complaints received from stakeholders. The second factor, strategy & compliance, is generated from the following: percentage of strategic objectives met and total number of sanctions for breaching the law. This research aims to assist both academic and corporate practitioners who want to improve corporate governance performance and, through the use of key performance indicators, support the transparency and sustainability of their business.

IT Mangement for Transforming Local Government - a Danish Collaborative Practice Research Project

DEFF Research Database (Denmark)

Kræmmergaard, Pernille; Agger Nielsen, Jeppe

2011-01-01

The aim of this paper is to present the methodology and preliminary findings from an on-going Danish collaborative practice research project concerning IT-Management in Transformational e-Government - DISIMIT. The ambition of the DISIMIT project is to improve IT management in local governments...... (municipalities) and to contribute with knowledge about IT-Management to the IS literature in general and to the e-government literature in particular. The paper reports on the process of conducting collaborative practice research and the selected findings from the empirical research activities. Up till now...... of eGovernment maturity and diagnosed the six main challenges faced by local governments in their efforts of realizing transformational e-Government. From these challenges, the project chose three challenges to investigate further according to the principles from Collaborative Practice Research...

THE GLOBAL GOVERNANCE PROBLEM AND THE ROLE OF THE INTERNATIONAL MONETARY FUND

Directory of Open Access Journals (Sweden)

Sidorova E. A.

2015-06-01

Full Text Available Currently, globalization begins to permeate more and more areas of human activity, therefore it is important question of the complex mechanisms and principles of global governance formation.The article analyzes the essence, subjects and mechanisms for the implementation of the global economic governance. Moreover, it investigates the role and current state of the International Monetary Fund (IMF in the global economy. In conclusion, it clarifies the relationship of the IMF and processes of global governance. Research has shown that it is necessary to create within the IMF more representative, economically and politically balanced system of global governance of the world monetary and financial relations as part of the emerging mechanisms of global economic governance. This article extends the knowledge about the features of the IMF in the forming global governance.

Governance of Higher Education--Implementation of Project Governance

Science.gov (United States)

Macheridis, Nikos

2017-01-01

This article focuses on coordination between governance actors in higher education. The object of the study is a department at a public university, seen as a multi-project environment. The purpose of this article is to illustrate and analyze project governance as a tool that allows departmental management to coordinate with the authorities, the…

The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and Islet β-Cells

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Robert Drynda

2018-02-01

Full Text Available Background/Aims: Insulin-secreting islet β-cells adapt to the insulin resistance associated with pregnancy by increasing functional β-cell mass, but the placental signals involved in this process are not well defined. In the current study, we analysed expression of G-protein coupled receptor (GPCR mRNAs in mouse islets and islet GPCR ligand mRNAs in placenta during pregnancy to generate an atlas of potential interactions between the placenta and β-cells to inform future functional studies of islet adaptive responses to pregnancy. Methods: Quantative RT-PCR arrays were used to measure mRNA expression levels of: (i 342 GPCRs in islets from non-pregnant mice, and in islets isolated from mice on gestational days 12 and 18; (ii 126 islet GPCR ligands in mouse placenta at gestational days 12 and 18. Results: At gestational day 12, a time of rapid expansion of the β-cell mass, 189 islet GPCR mRNAs were quantifiable, while 79 of the 126 known islet GPCR ligand mRNAs were detectable in placental extracts. Approximately half of the quantifiable placental GPCR ligand genes were of unknown function in β-cells. The expression of some islet GPCR and placental ligand mRNAs varied during pregnancy, with altered expression of both GPCR and ligand mRNAs by gestational day 18. Conclusion: The current study has revealed numerous potential routes for interaction between the placenta and islets, and offers an atlas to inform further functional studies of their roles in adaptive responses to pregnancy, and in the regulation of the β-cell mass.

Melanocortin systems on pigment dispersion in fish chromatophores.

Science.gov (United States)

Kobayashi, Yuki; Mizusawa, Kanta; Saito, Yumiko; Takahashi, Akiyoshi

2012-01-01

α-Melanocyte-stimulating hormone (α-MSH) is responsible for pigment dispersion in the chromatophores of fish and other tetrapods such as amphibians and reptiles. Recently, we discovered that α-MSH did not always stimulate pigment dispersion because this hormonal peptide exerted no effects on the melanophores of flounders. We assumed that the reduction of α-MSH activity was related to the co-expression of different α-MSH receptor subtypes - termed melanocortin receptors (MCR) - a member of G-protein-coupled receptors (GPCR) - based on several reports demonstrating that GPCR forms heterodimers with various properties that are distinct from those of the corresponding monomers. In this review, we summarize the relationships between the pigment-dispersing activity of α-MSH-related peptides, molecular forms of α-MSH-related peptides, and mcr subtypes expressed in fish chromatophores.

Bridging communication between public and government: a case study on kim surabaya

Science.gov (United States)

Aji, G. G.; Tsuroyya; Dewi, P. A. R.

2018-01-01

In democratic era, the public communication paradigm has shifted from a one-way socialization to more interactive one. As a consequence of freedom of speech, the public can Actively communicate with the government and vice versa. The problem is government is almost impossible to reach all public groups. Therefore, they has created the concept of social institutions as a communication hub between the government and its public, named the Kelompok Informasi Masyarakat (KIM). This research examines the activity of KIM in Surabaya on bridging public between government and the public. Using a case study approach, this research utilized various techniques of data collection such as: interviews, observation, and documentation. The results Showed that KIM plays a role in the two-way flow of information; to diseminate program and submit complaints and suggestions from the public about the policy. This study confirm the urgency of utilization on various channels in communicating with the public.

Control mechanisms in corporate governance

Directory of Open Access Journals (Sweden)

Jovanović-Zattila Milena

2016-01-01

Full Text Available The structure of corporate governance is determined by the distribution of rights and responsibilities among different actors in the company structure. Organizationally complex structure of corporate entities, established as a reflection of composite forms of business corporations, give rise to the conflict of interest between the owners, the board of directors and managers, which is generally known as the principal-agency problem. Given the fact that operations of modern companies include interaction with a large number of stakeholders, matters of ethics and accountability to the owners, employees, creditors and the state are the basic postulates which have been subject to re-examination lately. The reasons for reassessing these issues are to be sought in numerous abuses by companies, which are on the other hand highly active in their effors to protect themselves from similar abuses (mainy cyber crime. In order to respond to new challenges and requirements, which include providing for the interests of both shareholders and stakeholders, corporate management is required to establish an adequate system of internal control covering all company activities. Contemporary trends in the development of internal audit, as a mechanism of good corporate governance, are reflected in providing advice in respect of anticipated future risks and risk management.

RFamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential

Science.gov (United States)

Findeisen, Maria; Rathmann, Daniel; Beck-Sickinger, Annette G.

2011-01-01

Different neuropeptides, all containing a common carboxy-terminal RFamide sequence, have been characterized as ligands of the RFamide peptide receptor family. Currently, five subgroups have been characterized with respect to their N-terminal sequence and hence cover a wide pattern of biological functions, like important neuroendocrine, behavioral, sensory and automatic functions. The RFamide peptide receptor family represents a multiligand/multireceptor system, as many ligands are recognized by several GPCR subtypes within one family. Multireceptor systems are often susceptible to cross-reactions, as their numerous ligands are frequently closely related. In this review we focus on recent results in the field of structure-activity studies as well as mutational exploration of crucial positions within this GPCR system. The review summarizes the reported peptide analogs and recently developed small molecule ligands (agonists and antagonists) to highlight the current understanding of the pharmacophoric elements, required for affinity and activity at the receptor family. Furthermore, we address the biological functions of the ligands and give an overview on their involvement in physiological processes. We provide insights in the knowledge for the design of highly selective ligands for single receptor subtypes to minimize cross-talk and to eliminate effects from interactions within the GPCR system. This will support the drug development of members of the RFamide family.

RFamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential

Directory of Open Access Journals (Sweden)

Maria Findeisen

2011-09-01

Full Text Available Different neuropeptides, all containing a common carboxy-terminal RFamide sequence, have been characterized as ligands of the RFamide peptide receptor family. Currently, five subgroups have been characterized with respect to their N-terminal sequence and hence cover a wide pattern of biological functions, like important neuroendocrine, behavioral, sensory and automatic functions. The RFamide peptide receptor family represents a multiligand/multireceptor system, as many ligands are recognized by several GPCR subtypes within one family. Multireceptor systems are often susceptible to cross-reactions, as their numerous ligands are frequently closely related. In this review we focus on recent results in the field of structure-activity studies as well as mutational exploration of crucial positions within this GPCR system. The review summarizes the reported peptide analogs and recently developed small molecule ligands (agonists and antagonists to highlight the current understanding of the pharmacophoric elements, required for affinity and activity at the receptor family. Furthermore, we address the biological functions of the ligands and give an overview on their involvement in physiological processes. We provide insights in the knowledge for the design of highly selective ligands for single receptor subtypes to minimize cross-talk and to eliminate effects from interactions within the GPCR system. This will support the drug development of members of the RFamide family.

Government--utility interaction on spent fuel disposition

International Nuclear Information System (INIS)

Mills, L.E.

1978-01-01

The question of the needs of the electrical power industry for spent fuel storage in light of the moratorium on fuel reprocessing is addressed. The author feels that since the Federal government has assumed the responsibility for spent fuel storage, it is imperative that a firm plan, program, legislation, and funding be forthcoming immediately. Designation of an existing government site with existing nuclear activities in order to expedite the establishment of a storage facility is recommended. It is felt that the timing for such a site should be ''at the earliest possible date.'' Without storage facilities being provided by the government, utilities will be forced to build storage facilities at the reactor sites. This course of action is not considered cost effective but certainly preferable to shutting down the reactors. It is emphasized that spent fuel storage must be an interim solution and certainly not a final solution to the fuel reprocessing and waste disposal aspects of nuclear technology

Collaboration of local governments and experts responding to the increase of the environmental radiation level secondary to the nuclear accident: a unique activity to relieve residents' anxiety

International Nuclear Information System (INIS)

Fujii, H.; Hamamichi, S.; Iimoto, T.; Tsuzuki, T.; Iiizumi, S.; Someya, S.; Kessler, M.M.

2015-01-01

After the Fukushima nuclear power plant accident, 'hot spots' were found in Tokatsu area in Chiba prefecture. Although ambient radiation dose in this area was too low to harm residents' health, local residents were particularly worried about possible adverse effects from exposure to radiation. To avoid unnecessary panic reactions in the public, local governments in Tokatsu area collaborated with radiation specialists and conducted activities to provide local residents with accurate information on health effects from radiation. In addition to these activities, the authors offered one-to-one consultations with a radiologist for parents of small children and expecting mothers. They herein report this unique attempt, focusing on parents' anxiety and the age of their children. Taken together, this unique collaborative activity between local government and experts would be one of the procedures to relieve residents' anxiety. (authors)

Cost of outpatient endoscopic sinus surgery from the perspective of the Canadian government: a time-driven activity-based costing approach.

Science.gov (United States)

Au, Jennifer; Rudmik, Luke

2013-09-01

The time-driven activity-based costing (TD-ABC) method is a novel approach to quantify the costs of a complex system. The aim of this study was to apply the TD-ABC technique to define the overall cost of a routine outpatient endoscopic sinus surgery (ESS) from the perspective of the Canadian government payer. Costing perspective was the Canadian government payer. All monetary values are in Canadian dollars as of December 2012. Costs were obtained by contacting staff unions, reviewing purchasing databases and provincial physician fee schedules. Practical capacity time values were collected from the College and Association of Registered Nurses of Alberta. Capacity cost rates ($/min) were calculated for all staff, capital equipment, and hospital space. The overall cost for routine outpatient ESS was $3510.31. The cost per ESS case for each clinical pathway encounter was as follows: preoperative holding ($49.19); intraoperative ($3296.60); sterilization ($90.20); postanesthesia care unit ($28.64); and postoperative day ward ($45.68). The 3 major cost drivers were physician fees, disposable equipment, and nursing costs. The intraoperative phase contributed to 94.5% of the overall cost. This study applied the TD-ABC method to evaluate the cost of outpatient ESS from the perspective of the Canadian government payer and defined the overall cost to be $3510.31 per case. © 2013 ARS-AAOA, LLC.

Data governance implementation concept

OpenAIRE

Ullrichová, Jana

2016-01-01

This master´s thesis discusses concept of implementation for data governance. The theoretical part of this thesis is about data governance. It explains why data are important for company, describes definitoons of data governance, its history, its components, its principles and processes and fitting in company. Theoretical part is amended with examples of data governance failures and banking specifics. The main goal of this thesis is to create a concept for implementing data governance and its...

CORPORATE GOVERNANCE – WAY OF GOVERNANCE FOR MODERN COMPANIES

Directory of Open Access Journals (Sweden)

Alina HAGIU

2016-05-01

Full Text Available Through corporate governance is aimed the building of a structure enabling a wide degree of freedom, within the law, and includes several changes of principle in accordance with international standards of transparency. A good governance within an organization mitigate risk, increase performance, pave the way towards financial markets, brings competitive goods and services on market, improves management style, show transparency towards all stakeholders and social responsibility. The lack of some mandatory rules and structures can lead to chaos in business. The paper aims to present the role and the importance of the corporate governance for modern companies, as well as the principles on which this is based. In order to do that we also identified the main ways to quantificate the level of corporate governance, including also the non-financial performance criteria used by investors to assess companies listed on stock exchange.

Smart governance for smart city

Science.gov (United States)

Mutiara, Dewi; Yuniarti, Siti; Pratama, Bambang

2018-03-01

Some of the local government in Indonesia claimed they already created a smart city. Mostly the claim based of IT utilization for their governance. In general, a smart city definition is to describe a developed urban area that creates sustainable economic development and high quality of life by excelling in multiple key; economy, mobility, environment, people, living, and government. For public services, the law guarantees good governance by setting the standard for e-government implicitly including for local government or a city. Based on the arguments, this research tries to test the condition of e-government of the Indonesian city in 34 provinces. The purpose is to map e-government condition by measuring indicators of smart government, which are: transparent governance and open data for the public. This research is departing from public information disclosure law and to correspond with the existence law. By examining government transparency, the output of the research can be used to measure the effectiveness of public information disclosure law and to determine the condition of e-government in local government in which as part of a smart city.

Governance of disaster risk reduction in Cameroon: The need to empower local government

Directory of Open Access Journals (Sweden)

Henry N. Bang

2013-02-01

Full Text Available The impact of natural hazards and/or disasters in Cameroon continues to hit local communities hardest, but local government lacks the ability to manage disaster risks adequately. This is partly due to the fact that the necessity to mainstream disaster risk reduction into local governance and development practices is not yet an underlying principle of Cameroon’s disaster management framework. Using empirical and secondary data, this paper analyses the governance of disaster risks in Cameroon with particular focus on the challenges local government faces in implementing disaster risk reduction strategies. The hypothesis is that the governance of disaster risks is too centralised at the national level, with huge implications for the effective governance of disaster risks at the local level. Although Cameroon has reinvigorated efforts to address growing disaster risks in a proactive way, it is argued that the practical actions are more reactive than proactive in nature. The overall aim is to explore the challenges and opportunities that local government has in the governance of disaster risks. Based on the findings from this research, policy recommendations are suggested on ways to mainstream disaster risk reduction strategies into local governance, and advance understanding and practice in the local governance of disaster risks in the country.

Architecture Governance: The Importance of Architecture Governance for Achieving Operationally Responsive Ground Systems

Science.gov (United States)

Kolar, Mike; Estefan, Jeff; Giovannoni, Brian; Barkley, Erik

2011-01-01

Topics covered (1) Why Governance and Why Now? (2) Characteristics of Architecture Governance (3) Strategic Elements (3a) Architectural Principles (3b) Architecture Board (3c) Architecture Compliance (4) Architecture Governance Infusion Process. Governance is concerned with decision making (i.e., setting directions, establishing standards and principles, and prioritizing investments). Architecture governance is the practice and orientation by which enterprise architectures and other architectures are managed and controlled at an enterprise-wide level

Shareholder Engagement on Environmental, Social, and Governance Performance

NARCIS (Netherlands)

Barkó, Tamás; Cremers, M.; Renneboog, Luc

2017-01-01

We study investor activism promoting environmental, social and governance (ESG) improvements using a proprietary dataset covering 660 companies globally over 2005-2014. Targets have a higher market share, analyst coverage, stock returns, and liquidity. The engagements lead to significant ESG rating

Good government and good governance: record keeping in a ...

African Journals Online (AJOL)

This article addresses the challenges that arise when record keeping systems are advocated as a necessary under-pinning for good government and good governance. The relationship between record keeping and accountability is analysed and contextualised in relation to transparency and Freedom of Information ...

Corporate Governance and Shariah Governance at Islamic Financial Institutions : Assessing from Current Practice in Malaysia

OpenAIRE

Mizushima, Tadashi; Tadashi, Mizushima

2014-01-01

The purpose of this study is to examine the relation between corporate governance and Shariah governance, and how those governance concepts are handled at Islamic financial institutions.Although using the same word “governance,” Western corporate governance and Islamic Shariah governance may be different. The main research question is how different or similar are governance at conventional banks and Shariah governance at Islamic banks? We would like to find an answer to this question by under...

Governance and organizational theory

Directory of Open Access Journals (Sweden)

Carlos E. Quintero Castellanos

2017-07-01

Full Text Available The objective of this essay is to propose a way to link the theoretical body that has been weaved around governance and organizational theory. For this, a critical exposition is done about what is the theoretical core of governance, the opportunity areas are identified for the link of this theory with organizational theory. The essay concludes with a proposal for the organizational analysis of administrations in governance. The essay addresses with five sections. The first one is the introduction. In the second one, I present a synthesis of the governance in its current use. In the next one are presented the work lines of the good governance. In the fourth part, I show the organizational and managerial limits in the governance theory. The last part develops the harmonization proposal for the governance and organizational theories.

The Development of an IT Governance Maturity Model for Hard and Soft Governance

NARCIS (Netherlands)

Smits, Daniël; van Hillegersberg, Jos; Devos, Jan; DeHaes, Steven

2014-01-01

To be able to advance in maturity, organizations should pay attention to both the hard and soft aspects of governance. Current literature on IT governance (ITG) is mostly directed at the hard part of governance, focusing on structures and processes. The soft part of governance is related to social

Governing Academic Medical Center Systems: Evaluating and Choosing Among Alternative Governance Approaches.

Science.gov (United States)

Chari, Ramya; O'Hanlon, Claire; Chen, Peggy; Leuschner, Kristin; Nelson, Christopher

2018-02-01

The ability of academic medical centers (AMCs) to fulfill their triple mission of patient care, medical education, and research is increasingly being threatened by rising financial pressures and resource constraints. Many AMCs are, therefore, looking to expand into academic medical systems, increasing their scale through consolidation or affiliation with other health care systems. As clinical operations grow, though, the need for effective governance becomes even more critical to ensure that the business of patient care does not compromise the rest of the triple mission. Multi-AMC systems, a model in which multiple AMCs are governed by a single body, pose a particular challenge in balancing unity with the needs of component AMCs, and therefore offer lessons for designing AMC governance approaches. This article describes the development and application of a set of criteria to evaluate governance options for one multi-AMC system-the University of California (UC) and its five AMCs. Based on a literature review and key informant interviews, the authors identified criteria for evaluating governance approaches (structures and processes), assessed current governance approaches using the criteria, identified alternative governance options, and assessed each option using the identified criteria. The assessment aided UC in streamlining governance operations to enhance their ability to respond efficiently to change and to act collectively. Although designed for UC and a multi-AMC model, the criteria may provide a systematic way for any AMC to assess the strengths and weaknesses of its governance approaches.

Governing environmental conflicts in China: Under what conditions do local government compromise?

NARCIS (Netherlands)

Y. Li (Yanwei); J.F.M. Koppenjan (Joop); S. Verweij (Stefan)

2016-01-01

markdownabstractIn recent years, governing environmental conflicts concerning the planning, construction, and operation of urban facilities has increasingly become a challenge for Chinese local governments. Chinese governments seek adequate responses to deal with these conflicts, for instance by

Putting citizens at the heart of food system governance

Energy Technology Data Exchange (ETDEWEB)

Pimbert, Michel

2012-05-15

Establishing inclusive governance of food systems — where farmers and other citizens play an active role in designing and implementing food and agricultural policies — is not just a matter of equity or social justice. Evidence shows that it can also lead to more sustainable livelihoods and environments. And yet, across the world, food system governance is marked by exclusionary processes that favour the values and interests of more powerful corporations, investors, big farmers and large research institutes. How can we tip the balance and amplify the voice and influence of marginalised citizens in setting the food and agricultural policies that affect them? Research points to six tried and tested ways that, when combined, can empower citizens in the governance of food systems.

State Independent Electoral Commissions and local government elections in Nigeria

Directory of Open Access Journals (Sweden)

Johnson O. Olaniyi

2017-11-01

Full Text Available Many state governments have not been allowing their State Independent Electoral Commissions (SIECs to conduct elections as at when due but rather settle for ‘caretaker committees’. Where elections have been conducted, the party in control of a state apparatus has been known to have cleared the polls. The general objective of this study is to assess the impact of electoral contest at the local government level on the political development of Nigeria. Specific objectives include (1 assessing the role of the political executives of a state in the determination of representation at the local government level in Nigeria; and (2 assessing the activities of SIECs in the management of local government polls. This study adopts comparative cum case study approach to analysing local government polls in Nigeria. This is discussed on a geopolitical basis. Some of the findings of the study include: (1 local government election in Nigeria is not given premium position by many state governments in the political landscape of their state because of the fear of playing into the hands of their political rivals; and (2 SIECs are only independent in name and not in practice. The study recommends, among others, that (1 the country should adopt the arrangement in the aborted Third Republic where the country’s EMB was empowered to conduct all elections at all levels of government and (2 local government elections in Nigeria should key into the electoral process of the country in all ramifications.

Governing environmental conflicts in China : Under what conditions do local governments compromise?

NARCIS (Netherlands)

Li, Yanwei; Koppenjan, Joop; Verweij, Stefan

2016-01-01

In recent years, governing environmental conflicts concerning the planning, construction, and operation of urban facilities has increasingly become a challenge for Chinese local governments. Chinese governments seek adequate responses to deal with these conflicts, for instance by ignoring criticism

Public management and governance

National Research Council Canada - National Science Library

Bovaird, A. G; Löffler, Elke

2009-01-01

... how the process of governing needs to be fundamentally altered if a government is to retain public trust and make better use of society's resources. Key themes covered include: ■ ■ ■ ■ the challenges and pressures which governments experience in an international context; the changing functions of modern government in the global economy; the 'mixed ec...

Corporate governance in Balkan financial institution, case of Albania

Directory of Open Access Journals (Sweden)

Rezart Dibra

2013-06-01

this paper is to make such connections and ground the policy debate on scientific evidence. The Corporate Governance in banks is one of the most important discussions overall the world, being reinforced especially after the crises period. It is related with the sensitive situation and the stage of developments of the local economy and moreover with the impact of the crises that is still ongoing. As an answer, during late 2008 and beginning 2009, it has been noticed a fast reaction and total focus from all banks on building (if missing and improving their structures of Corporate Governance. The liquidity problems suddenly affecting the banking sector constrained Banks to enlarge their activities / operations and forced them in better evaluating their investments. The importance of a strong financial sector in impacting the country’s economy growth through both level of banking development and stock market liquidity (Levine and Sara Zervos 1996, 1998 is quite evident even in the developing countries. Moreover, Peter Rousseau and Watchel (2000 findings’ confirm the positive impact of the stock market activity and the banking development. For this reason the governments in the developing countries are insisting in increasing credits of banks towards the private firms. The banking system in Bulgaria, Romania, Serbia and Albania has certain similarities in terms of development stage, related with the economic growth rate as well. The banking system, there is operating for more than 100 years instead of 15-20 years of development in the remaining countries.

Benchmarking government action for obesity prevention--an innovative advocacy strategy.

Science.gov (United States)

Martin, J; Peeters, A; Honisett, S; Mavoa, H; Swinburn, B; de Silva-Sanigorski, A

2014-01-01

Successful obesity prevention will require a leading role for governments, but internationally they have been slow to act. League tables of benchmark indicators of action can be a valuable advocacy and evaluation tool. To develop a benchmarking tool for government action on obesity prevention, implement it across Australian jurisdictions and to publicly award the best and worst performers. A framework was developed which encompassed nine domains, reflecting best practice government action on obesity prevention: whole-of-government approaches; marketing restrictions; access to affordable, healthy food; school food and physical activity; food in public facilities; urban design and transport; leisure and local environments; health services, and; social marketing. A scoring system was used by non-government key informants to rate the performance of their government. National rankings were generated and the results were communicated to all Premiers/Chief Ministers, the media and the national obesity research and practice community. Evaluation of the initial tool in 2010 showed it to be feasible to implement and able to discriminate the better and worse performing governments. Evaluation of the rubric in 2011 confirmed this to be a robust and useful method. In relation to government action, the best performing governments were those with whole-of-government approaches, had extended common initiatives and demonstrated innovation and strong political will. This new benchmarking tool, the Obesity Action Award, has enabled identification of leading government action on obesity prevention and the key characteristics associated with their success. We recommend this tool for other multi-state/country comparisons. Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Hard and Soft Governance

DEFF Research Database (Denmark)

Moos, Lejf

2009-01-01

of Denmark, and finally the third layer: the leadership used in Danish schools. The use of 'soft governance' is shifting the focus of governance and leadership from decisions towards influence and power and thus shifting the focus of the processes from the decision-making itself towards more focus......The governance and leadership at transnational, national and school level seem to be converging into a number of isomorphic forms as we see a tendency towards substituting 'hard' forms of governance, that are legally binding, with 'soft' forms based on persuasion and advice. This article analyses...... and discusses governance forms at several levels. The first layer is the global: the methods of 'soft governance' that are being utilised by transnational agencies. The second layer is the national and local: the shift in national and local governance seen in many countries, but here demonstrated in the case...

Interoperability, Enterprise Architectures, and IT Governance in Government

OpenAIRE

Scholl , Hans ,; Kubicek , Herbert; Cimander , Ralf

2011-01-01

Part 4: Architecture, Security and Interoperability; International audience; Government represents a unique, and also uniquely complex, environment for interoperation of information systems as well as for integration of workflows and processes across governmental levels and branches. While private-sector organizations by and large have the capacity to implement “enterprise architectures” in a relatively straightforward fashion, for notable reasons governments do not enjoy such luxury. For thi...

Governance in Health – The Need for Exchange and Evidence; Comment on “Governance, Government, and the Search for New Provider Models”

Directory of Open Access Journals (Sweden)

Tata Chanturidze

2016-08-01

Full Text Available Governance in health is cited as one of the key factors in balancing the concerns of the government and public sector with the interests of civil society/private players, but often remains poorly described and operationalized. Richard Saltman and Antonio Duran look at two aspects in the search for new provider models in a context of health markets signalling liberalisation: (i the role of the government to balance public and private interests and responsibilities in delivering care through modernised governance arrangements, and (ii the finding that operational complexities may hinder well–designed provider governance models, unless governance reflects country-specific realities. This commentary builds on the discussion by Saltman and Duran, and argues that the concept of governance needs to be clearly defined and operationalized in order to be helpful for policy debate as well as for the development of an applicable framework for performance improvement. It provides a working definition of governance and includes a reflection on the prevailing cultural norms in an organization or society upon which any governance needs to be build. It proposes to explore whether the “evidence-based governance” concept can be introduced to generate knowledge about innovative and effective governance models, and concludes that studies similar to the one by Saltman and Duran can inform this debate.

Features Of The Local Government Development In Pre-Revolutionary Russia

Directory of Open Access Journals (Sweden)

Lyubov I. Rogacheva

2014-09-01

Full Text Available In the present article historical development of the municipal government institutes in the pre-revolutionary Russia are analyzed. Author emphasizes that in Russia at different stages of the statehood historical development a great experience of various forms and institutes of self-government were developed. History shows that municipal government in Russian conditions cannot develop in full in the conditions of weakening government. Without support of the strong state, municipal government have weak chances, but strong government may also suppress, crush self-government. In the Russian history the balance of public administration and self-government was quite often broken into the favor of the first, what may be explained by political and geographical factors of the country development which caused need of the strong centralized government existence. Reforms in the middle of the XIX century aggravated a question of the municipal government reforming, on the creation of new system instead of imperfect and outdated former structure. Elimination of the serfdom which changed legal status of the considerable part of population in the country caused the need of country estate involvement in the solution of various economic tasks at the municipal level. This task in a certain degree was solved during the reforms of the second half of the XIX century. However model created during this period was not ideal, it suffered from many defects, inherent for the long time by the system of the state and public relations in Russia. At the beginning of the XX century questions of the municipal government reforming were again actively discussed by scientists and public figures, on this subject there were numerous publications. However, revolutionary events made questions of municipal government almost irrelevant for the long time.

Governance: Blending Bureaucratic Rules with Day to Day Operational Realities Comment on "Governance, Government, and the Search for New Provider Models".

Science.gov (United States)

Chinitz, David P

2016-05-31

Richard Saltman and Antonio Duran take up the challenging issue of governance in their article "Governance, Government and the Search for New Provider Models," and use two case studies of health policy changes in Sweden and Spain to shed light on the subject. In this commentary, I seek to link their conceptualization of governance, especially its interrelated roles at the macro, meso, and micro levels of health systems, with the case studies on which they report. While the case studies focus on the shifts in governance between the macro and meso levels and their impacts on achievement of desired policy outcomes, they also highlight the need to better integrate the dynamics of day to day operations within micro organizations into the overall governance picture. © 2016 by Kerman University of Medical Sciences.

Too difficult to govern? An assessment of the governability of transport biofuels in the EU

International Nuclear Information System (INIS)

Di Lucia, Lorenzo

2013-01-01

Transport biofuels are currently the subject of heated debate in the EU. In the past decade the deployment of these technologies has been justified by claims of attractive environmental, geopolitical and rural development benefits. However, expectations have rapidly turned into deep criticism regarding the sustainability of these technologies and the desirability of pursuing the biofuel path. This situation has generated an on-going controversy and policy deadlock at EU level. This study explores these issues from a governance perspective. Employing the concept of system governability, derived from interactive governance theory, it attempts to shed some light on the problems facing the governance of biofuels and on how the quality of the governance system could be improved. The analysis showed that the governability of the system decreased substantially in the period 2003–2012 due to increasing governing needs and decreasing governing capacity. The quality of the governance system can be improved by (i) improving governing capacity by reducing conflicts among governing actors, advancing consistency among institutions and creating capacity at international and global level; and (ii) promoting advanced technologies and adjusting societal ambitions and expectations regarding biofuels. - highlights: • Biofuels in the EU are significantly more difficult to govern today than in 2003. • This is due to the qualities of the system to be governed and the governing system. • Sustainable biofuel systems are inherently difficult to govern

Exposing government response action contractors to environmental tort liability

International Nuclear Information System (INIS)

Roy, M.J.

1991-01-01

Government contractors, particularly those involved with hazardous waste response action activities, are encountering increased risks for environmental tort liabilities. Contracts often include tasks and work assignments requiring the management of industrial, chemical, nuclear or mining wastes, spent fuels, munitions or other toxic substances. Contractors exposure to liability for damages results directly from the environmental laws and regulations pursuant to which the Government has contracted them to respond. Additionally, contractors may be exposed to common law liability under such dogmas as nuisance, trespass and strict liability in tort

Modeling structure of G protein-coupled receptors in huan genome

KAUST Repository

Zhang, Yang

2016-01-26

G protein-coupled receptors (or GPCRs) are integral transmembrane proteins responsible to various cellular signal transductions. Human GPCR proteins are encoded by 5% of human genes but account for the targets of 40% of the FDA approved drugs. Due to difficulties in crystallization, experimental structure determination remains extremely difficult for human GPCRs, which have been a major barrier in modern structure-based drug discovery. We proposed a new hybrid protocol, GPCR-I-TASSER, to construct GPCR structure models by integrating experimental mutagenesis data with ab initio transmembrane-helix assembly simulations, assisted by the predicted transmembrane-helix interaction networks. The method was tested in recent community-wide GPCRDock experiments and constructed models with a root mean square deviation 1.26 Å for Dopamine-3 and 2.08 Å for Chemokine-4 receptors in the transmembrane domain regions, which were significantly closer to the native than the best templates available in the PDB. GPCR-I-TASSER has been applied to model all 1,026 putative GPCRs in the human genome, where 923 are found to have correct folds based on the confidence score analysis and mutagenesis data comparison. The successfully modeled GPCRs contain many pharmaceutically important families that do not have previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin and Neuropeptide Y receptors. All the human GPCR models have been made publicly available through the GPCR-HGmod database at http://zhanglab.ccmb.med.umich.edu/GPCR-HGmod/ The results demonstrate new progress on genome-wide structure modeling of transmembrane proteins which should bring useful impact on the effort of GPCR-targeted drug discovery.

Status of will governance in determination of law governing business documents validity

OpenAIRE

Peyman Mohammadi; Saeed Kheradmandi

2014-01-01

Law governing substantive conditions of business documents issuance is one of important problems facing investigators. Since law governing business contracts and documents is governing out of limits of national law today, value and effect of will governance is of interest to jurisprudents because contract parties are allowed to determine contract effects and terms consensually to the extent to which these effects and terms do not contradict public order and imperative law and, in fact, they c...

Planned Parenthood works with Korean government.

Science.gov (United States)

Yang, J M

1968-01-01

In early 1961 special representatives of the International Planned Parenthood Federation (IPPF) organized the Planned Parenthood Federation of Korea (PPFK). The leaders, mostly young university professors, physicians, and government officials well recognized in the fields of public health gynecology/obstetrics, pediatrics, nursing, sociology, social work, and economics, shared an interest in improving the national economy, the national welfare, countermeasures against the population crisis, and the urgent need for family planning services in Korea. The leadership of General Park Chung-hee led to adoption of a national policy in support of family planning at an early stage in November 1961. Since 1961, the government budget for family planning has doubled every year. The PPFK was asked to play a major role in planning, administration, training, information, and education of the national program until the government established the new section of Maternal and Child Health in the Ministry of Health and Social Affairs in 1963. The role of the PPFK has never diminished. The training of family planning personnel at various levels is still carried out entirely by the PPFK. The PPFK operates mobile vans to provide educational activities, IUD insertions, and male sterilization services to people in villages without doctors. The PPFK operates pilot projects to test new methods either in clinics or in the field. The PPFK exists to supplement and cooperate with the government in family planning. With its flexibility, the PPFK team of experts stands ready to provide quick and positive services without red tape.

G Protein-Coupled Receptors in Cancer

Directory of Open Access Journals (Sweden)

Rachel Bar-Shavit

2016-08-01

Full Text Available Despite the fact that G protein-coupled receptors (GPCRs are the largest signal-conveying receptor family and mediate many physiological processes, their role in tumor biology is underappreciated. Numerous lines of evidence now associate GPCRs and their downstream signaling targets in cancer growth and development. Indeed, GPCRs control many features of tumorigenesis, including immune cell-mediated functions, proliferation, invasion and survival at the secondary site. Technological advances have further substantiated GPCR modifications in human tumors. Among these are point mutations, gene overexpression, GPCR silencing by promoter methylation and the number of gene copies. At this point, it is imperative to elucidate specific signaling pathways of “cancer driver” GPCRs. Emerging data on GPCR biology point to functional selectivity and “biased agonism”; hence, there is a diminishing enthusiasm for the concept of “one drug per GPCR target” and increasing interest in the identification of several drug options. Therefore, determining the appropriate context-dependent conformation of a functional GPCR as well as the contribution of GPCR alterations to cancer development remain significant challenges for the discovery of dominant cancer genes and the development of targeted therapeutics.

The institutional logics of local government budget in Indonesia

Directory of Open Access Journals (Sweden)

Palupi Ade

2017-01-01

Full Text Available This study asks how and why a local government settings budget. It aims to deliver an understanding on how a government entity perceives that budget is important element to manage public expenditures. It uses the S local government in Indonesia as a case study. This study applies Institutional Logics Theory as a theoretical framework in order to analyze data. Data is collected by interviewing seven key persons who directly involves in budgeting process. This research shows that the budgeting process includes determining the purposes of annual budget, setting up planned programs and actvities, determining the amount of revenue that will be collected, allocating resources to expenditures and setting up standar pricing. Some important points in the budgeting process are identified. Those are considering political aspect to determine local tax rate, focusing on competition with other local governments, fulfilling the political promise of local government leader to the constituents, involving community to determine planned program and activities, and allocating resources based on community basic needs. This study concludes that those points develop the institutional logics of politic and managerial in budget setting process.

Natural resources and government revenue : recent trends in Saskatchewan

International Nuclear Information System (INIS)

Warnock, J.W.

2005-01-01

This document discusses recent trends in Saskatchewan regarding natural resources and government revenue. It discusses the history of politics in terms of government expenditure and investment in natural resources; the polarization between urban and rural areas; natural resources and capital accumulation and economic rent and royalties from resource extraction. The document also discusses several industries in Saskatchewan including petroleum, natural gas discovery and extraction. Uranium and coal mining activities were also documented along with other minerals such as gold, diamonds, and sodium sulphate. The article focused on the share of economic rent going to the general public compared to the amount going to private corporations. The author argued that with rising prices for natural resources, the provincial government has been transferring billions of dollars of resources rent to private investors by reducing royalties, fees and taxes. This has resulted in less revenue for the provincial government to spend on programs such as health, education and public services. The author suggested that concerted efforts must be put forward to put the issue of the public role in resource development back on the government agenda. 99 refs., 7 tabs

GPCRdb

DEFF Research Database (Denmark)

Isberg, Vignir; Mordalski, Stefan; Munk, Christian

2016-01-01

Recent developments in G protein-coupled receptor (GPCR) structural biology and pharmacology have greatly enhanced our knowledge of receptor structure-function relations, and have helped improve the scientific foundation for drug design studies. The GPCR database, GPCRdb, serves a dual role...... in disseminating and enabling new scientific developments by providing reference data, analysis tools and interactive diagrams. This paper highlights new features in the fifth major GPCRdb release: (i) GPCR crystal structure browsing, superposition and display of ligand interactions; (ii) direct deposition...... a smooth browsing experience and development. GPCRdb is available at http://www.gpcrdb.org/ and it's open source code at https://bitbucket.org/gpcr/protwis....

Integrative environmental governance: enhancing governance in the era of synergies

NARCIS (Netherlands)

Visseren-Hamakers, I.J.

2015-01-01

The issue of regime complexity in global environmental governance is widely recognized. The academic debate on regime fragmentation has itself however been rather fragmented, with discussions circling around different concepts, including inter-organizational relations, polycentric governance,

Advocacy for mental health: roles for consumer and family organizations and governments.

Science.gov (United States)

Funk, Michelle; Minoletti, Alberto; Drew, Natalie; Taylor, Jacob; Saraceno, Benedetto

2006-03-01

The World Health Organization urges countries to become more active in advocacy efforts to put mental health on governments' agendas. Health policy makers, planners and managers, advocacy groups, consumer and family organizations, through their different roles and actions, can move the mental health agenda forward. This paper outlines the importance of the advocacy movement, describes some of the roles and functions of the different groups and identifies some specific actions that can be adopted by Ministries of Health. The mental health advocacy movement has developed over the last 30 years as a means of combating stigma and prejudice against people with mental disorders and improving services. Consumer and family organizations and related NGOs have been able to influence governments on mental health policies and laws and educating the public on social integration of people with mental disorders. Governments can promote the development of a strong mental health advocacy sector without compromising this sector's independence. For instance, they can publish and distribute a directory of mental health advocacy groups, include them in their mental health activities and help fledgling groups become more established. There are also some advocacy functions that government officials can, and indeed, should perform themselves. Officials in the ministry of health can persuade officials in other branches of government to make mental health more of a priority, support advocacy activities with both general health workers and mental health workers and carry out public information campaigns about mental disorders and how to maintain good mental health. In conclusion, the World Health Organization believes mental health advocacy is one of the pillars to improve mental health care and the human rights of people with mental disorders. It is hoped that the recommendations in this article will help government officials and activists to strengthen national advocacy movements.

Can "reputation management" overcome failures in corporate governance?\\ud

OpenAIRE

Watson, Tom

2006-01-01

Poor corporate governance appears to undo all the efforts of corporate communication activities in promoting and managing reputation. Is it a factor of poor leadership by senior management or a generalised failure of organisational relationships?

A Primer on E-Government: Sectors, Stages, Opportunities, and Challenges of Online Governance

National Research Council Canada - National Science Library

Seifert, Jeffrey W

2003-01-01

...), public access to government information, service delivery, and information security. E-government solutions are prominently represented in efforts to improve the management and efficiency of government information technology resources...

E-Government Maturity Model for Sustainable E-Government Services from the Perspective of Developing Countries