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Sample records for gpcr governs morphogenic

  1. Structural analysis of eyespots: dynamics of morphogenic signals that govern elemental positions in butterfly wings

    Directory of Open Access Journals (Sweden)

    Otaki Joji M

    2012-03-01

    Full Text Available Abstract Background To explain eyespot colour-pattern determination in butterfly wings, the induction model has been discussed based on colour-pattern analyses of various butterfly eyespots. However, a detailed structural analysis of eyespots that can serve as a foundation for future studies is still lacking. In this study, fundamental structural rules related to butterfly eyespots are proposed, and the induction model is elaborated in terms of the possible dynamics of morphogenic signals involved in the development of eyespots and parafocal elements (PFEs based on colour-pattern analysis of the nymphalid butterfly Junonia almana. Results In a well-developed eyespot, the inner black core ring is much wider than the outer black ring; this is termed the inside-wide rule. It appears that signals are wider near the focus of the eyespot and become narrower as they expand. Although fundamental signal dynamics are likely to be based on a reaction-diffusion mechanism, they were described well mathematically as a type of simple uniformly decelerated motion in which signals associated with the outer and inner black rings of eyespots and PFEs are released at different time points, durations, intervals, and initial velocities into a two-dimensional field of fundamentally uniform or graded resistance; this produces eyespots and PFEs that are diverse in size and structure. The inside-wide rule, eyespot distortion, structural differences between small and large eyespots, and structural changes in eyespots and PFEs in response to physiological treatments were explained well using mathematical simulations. Natural colour patterns and previous experimental findings that are not easily explained by the conventional gradient model were also explained reasonably well by the formal mathematical simulations performed in this study. Conclusions In a mode free from speculative molecular interactions, the present study clarifies fundamental structural rules related to

  2. Structural analysis of eyespots: dynamics of morphogenic signals that govern elemental positions in butterfly wings.

    Science.gov (United States)

    Otaki, Joji M

    2012-03-13

    To explain eyespot colour-pattern determination in butterfly wings, the induction model has been discussed based on colour-pattern analyses of various butterfly eyespots. However, a detailed structural analysis of eyespots that can serve as a foundation for future studies is still lacking. In this study, fundamental structural rules related to butterfly eyespots are proposed, and the induction model is elaborated in terms of the possible dynamics of morphogenic signals involved in the development of eyespots and parafocal elements (PFEs) based on colour-pattern analysis of the nymphalid butterfly Junonia almana. In a well-developed eyespot, the inner black core ring is much wider than the outer black ring; this is termed the inside-wide rule. It appears that signals are wider near the focus of the eyespot and become narrower as they expand. Although fundamental signal dynamics are likely to be based on a reaction-diffusion mechanism, they were described well mathematically as a type of simple uniformly decelerated motion in which signals associated with the outer and inner black rings of eyespots and PFEs are released at different time points, durations, intervals, and initial velocities into a two-dimensional field of fundamentally uniform or graded resistance; this produces eyespots and PFEs that are diverse in size and structure. The inside-wide rule, eyespot distortion, structural differences between small and large eyespots, and structural changes in eyespots and PFEs in response to physiological treatments were explained well using mathematical simulations. Natural colour patterns and previous experimental findings that are not easily explained by the conventional gradient model were also explained reasonably well by the formal mathematical simulations performed in this study. In a mode free from speculative molecular interactions, the present study clarifies fundamental structural rules related to butterfly eyespots, delineates a theoretical basis for the

  3. Fractional calculus and morphogen gradient formation

    Science.gov (United States)

    Yuste, Santos Bravo; Abad, Enrique; Lindenberg, Katja

    2012-12-01

    Some microscopic models for reactive systems where the reaction kinetics is limited by subdiffusion are described by means of reaction-subdiffusion equations where fractional derivatives play a key role. In particular, we consider subdiffusive particles described by means of a Continuous Time Random Walk (CTRW) model subject to a linear (first-order) death process. The resulting fractional equation is employed to study the developmental biology key problem of morphogen gradient formation for the case in which the morphogens are subdiffusive. If the morphogen degradation rate (reactivity) is constant, we find exponentially decreasing stationary concentration profiles, which are similar to the profiles found when the morphogens diffuse normally. However, for the case in which the degradation rate decays exponentially with the distance to the morphogen source, we find that the morphogen profiles are qualitatively different from the profiles obtained when the morphogens diffuse normally.

  4. Interpretation of the FGF8 morphogen gradient is regulated by endocytic trafficking.

    Science.gov (United States)

    Nowak, Matthias; Machate, Anja; Yu, Shuizi Rachel; Gupta, Mansi; Brand, Michael

    2011-02-01

    Forty years ago, it was proposed that during embryonic development and organogenesis, morphogen gradients provide positional information to the individual cells within a tissue leading to specific fate decisions. Recently, much insight has been gained into how such morphogen gradients are formed and maintained; however, which cellular mechanisms govern their interpretation within target tissues remains debated. Here we used in vivo fluorescence correlation spectroscopy and automated image analysis to assess the role of endocytic sorting dynamics on fibroblast growth factor 8 (Fgf8) morphogen gradient interpretation. By interfering with the function of the ubiquitin ligase Cbl, we found an expanded range of Fgf target gene expression and a delay of Fgf8 lysosomal transport. However, the extracellular Fgf8 morphogen gradient remained unchanged, indicating that the observed signalling changes are due to altered gradient interpretation. We propose that regulation of morphogen signalling activity through endocytic sorting allows fast feedback-induced changes in gradient interpretation during the establishment of complex patterns.

  5. Positive modulator of bone morphogenic protein-2

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2009-01-27

    Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

  6. Positive modulator of bone morphogenic protein-2

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Kazuyuki, Takahashi

    2017-06-06

    Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

  7. 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...

  8. Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment

    DEFF Research Database (Denmark)

    Kufareva, Irina; Katritch, Vsevolod; Biggin, Phil

    2014-01-01

    Despite tremendous successes of GPCR crystallography, the receptors with available structures represent only a small fraction of human GPCRs. An important role of the modeling community is to maximize structural insights for the remaining receptors and complexes. The community-wide GPCR Dock asse...

  9. GPCR homomers and heteromers: a better choice as targets for drug development than GPCR monomers?

    Science.gov (United States)

    Casadó, Vicent; Cortés, Antoni; Mallol, Josefa; Pérez-Capote, Kamil; Ferré, Sergi; Lluis, Carmen; Franco, Rafael; Canela, Enric I

    2009-11-01

    G protein-coupled receptors (GPCR) are targeted by many therapeutic drugs marketed to fight against a variety of diseases. Selection of novel lead compounds are based on pharmacological parameters obtained assuming that GPCR are monomers. However, many GPCR are expressed as dimers/oligomers. Therefore, drug development may consider GPCR as homo- and hetero-oligomers. A two-state dimer receptor model is now available to understand GPCR operation and to interpret data obtained from drugs interacting with dimers, and even from mixtures of monomers and dimers. Heteromers are distinct entities and therefore a given drug is expected to have different affinities and different efficacies depending on the heteromer. All these concepts would lead to broaden the therapeutic potential of drugs targeting GPCRs, including receptor heteromer-selective drugs with a lower incidence of side effects, or to identify novel pharmacological profiles using cell models expressing receptor heteromers.

  10. Conformational biosensors reveal GPCR signalling from endosomes

    DEFF Research Database (Denmark)

    Irannejad, R; Tomshine, Jin C; Tomshine, Jon R

    2013-01-01

    A long-held tenet of molecular pharmacology is that canonical signal transduction mediated by G-protein-coupled receptor (GPCR) coupling to heterotrimeric G proteins is confined to the plasma membrane. Evidence supporting this traditional view is based on analytical methods that provide limited...... or no subcellular resolution. It has been subsequently proposed that signalling by internalized GPCRs is restricted to G-protein-independent mechanisms such as scaffolding by arrestins, or GPCR activation elicits a discrete form of persistent G protein signalling, or that internalized GPCRs can indeed contribute...... in the early endosome membrane, and that internalized receptors contribute to the overall cellular cyclic AMP response within several minutes after agonist application. These findings provide direct support for the hypothesis that canonical GPCR signalling occurs from endosomes as well as the plasma membrane...

  11. GPCR-autoantibodies in chronic heart failure.

    Science.gov (United States)

    Boivin-Jahns, Valerie; Jahns, Roland

    2018-06-01

    Chronic heart failure (CHF) is a syndrome characterized by shortness of breath, fluid retention, and a progressive reduction in cardiac function. More than 60% of the cases are ischemic in origin (i.e., due to myo-cardial infarction) and about 30% are caused by non-ischemic myocardial damage (i.e., due to genetic or non-genetic causes like myocardial inflammation). Because of alterations in both cellular and humoral immunity patients with non-ischemic CHF often develop abnormal or misled immune responses, including cross-reacting antibodies and/or autoantibodies to various cardiac anti-gens. Non-ischemic myo-cardial damage was found to progress to CHF particularly, when associated (a) with the generation of autoantibodies directed against distinct myocyte membrane proteins critically involved in cardiac function - like G-protein coup-led membrane receptors (GPCRs), or (b) with virus persistence in the myocardium. This article will review current knowledge on the pathophysiological relevance of GPCR-autoreactivity in CHF by giving an overview on the so far available evidence from pre-clinical, clinical and epidemiological studies on the CHF-inducing potential of GPCR-autoantibodies and thereon based novel therapeutic approaches in GPCR autoantibody-associated CHF.

  12. Morphogengineering roots: comparing mechanisms of morphogen gradient formation

    Science.gov (United States)

    2012-01-01

    Background In developmental biology, there has been a recent focus on the robustness of morphogen gradients as possible providers of positional information. It was shown that functional morphogen gradients present strong biophysical constraints and lack of robustness to noise. Here we explore how the details of the mechanism which underlies the generation of a morphogen gradient can influence those properties. Results We contrast three gradient-generating mechanisms, (i) a source-decay mechanism; and (ii) a unidirectional transport mechanism; and (iii) a so-called reflux-loop mechanism. Focusing on the dynamics of the phytohormone auxin in the root, we show that only the reflux-loop mechanism can generate a gradient that would be adequate to supply functional positional information for the Arabidopsis root, for biophysically reasonable kinetic parameters. Conclusions We argue that traits that differ in spatial and temporal time-scales can impose complex selective pressures on the mechanism of morphogen gradient formation used for the development of the particular organism. PMID:22583698

  13. GPCR & company: databases and servers for GPCRs and interacting partners.

    Science.gov (United States)

    Kowalsman, Noga; Niv, Masha Y

    2014-01-01

    G-protein-coupled receptors (GPCRs) are a large superfamily of membrane receptors that are involved in a wide range of signaling pathways. To fulfill their tasks, GPCRs interact with a variety of partners, including small molecules, lipids and proteins. They are accompanied by different proteins during all phases of their life cycle. Therefore, GPCR interactions with their partners are of great interest in basic cell-signaling research and in drug discovery.Due to the rapid development of computers and internet communication, knowledge and data can be easily shared within the worldwide research community via freely available databases and servers. These provide an abundance of biological, chemical and pharmacological information.This chapter describes the available web resources for investigating GPCR interactions. We review about 40 freely available databases and servers, and provide a few sentences about the essence and the data they supply. For simplification, the databases and servers were grouped under the following topics: general GPCR-ligand interactions; particular families of GPCRs and their ligands; GPCR oligomerization; GPCR interactions with intracellular partners; and structural information on GPCRs. In conclusion, a multitude of useful tools are currently available. Summary tables are provided to ease navigation between the numerous and partially overlapping resources. Suggestions for future enhancements of the online tools include the addition of links from general to specialized databases and enabling usage of user-supplied template for GPCR structural modeling.

  14. Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks.

    Science.gov (United States)

    Bahouth, Suleiman W; Nooh, Mohammed M

    2017-08-01

    Proper signaling by G protein coupled receptors (GPCR) is dependent on the specific repertoire of transducing, enzymatic and regulatory kinases and phosphatases that shape its signaling output. Activation and signaling of the GPCR through its cognate G protein is impacted by G protein-coupled receptor kinase (GRK)-imprinted "barcodes" that recruit β-arrestins to regulate subsequent desensitization, biased signaling and endocytosis of the GPCR. The outcome of agonist-internalized GPCR in endosomes is also regulated by sequence motifs or "barcodes" within the GPCR that mediate its recycling to the plasma membrane or retention and eventual degradation as well as its subsequent signaling in endosomes. Given the vast number of diverse sequences in GPCR, several trafficking mechanisms for endosomal GPCR have been described. The majority of recycling GPCR, are sorted out of endosomes in a "sequence-dependent pathway" anchored around a type-1 PDZ-binding module found in their C-tails. For a subset of these GPCR, a second "barcode" imprinted onto specific GPCR serine/threonine residues by compartmentalized kinase networks was required for their efficient recycling through the "sequence-dependent pathway". Mutating the serine/threonine residues involved, produced dramatic effects on GPCR trafficking, indicating that they played a major role in setting the trafficking itinerary of these GPCR. While endosomal SNX27, retromer/WASH complexes and actin were required for efficient sorting and budding of all these GPCR, additional proteins were required for GPCR sorting via the second "barcode". Here we will review recent developments in GPCR trafficking in general and the human β 1 -adrenergic receptor in particular across the various trafficking roadmaps. In addition, we will discuss the role of GPCR trafficking in regulating endosomal GPCR signaling, which promote biochemical and physiological effects that are distinct from those generated by the GPCR signal transduction

  15. Platforms for the identification of GPCR targets, and of orthosteric and allosteric modulators.

    Science.gov (United States)

    Franco, Rafael; Canela, Enric I; Casado, Vicent; Ferre, Sergi

    2010-04-01

    The review provides a summary of old and new approaches for GPCR target identification and for the screening of molecules acting on GPCR targets. The new findings in the field are presented as well as an opinion about how these developments may help GPCR drug discovery. Importance in the field: GPCRs have been the most useful family of proteins in terms of targets for drug discovery. The expectations for GPCR target identification and discovery of new drugs acting on 'old' or 'new' GPCR targets are very high. Given the fact that the pace at which new 'GPCR drugs' appear in the market is decreasing and since the new developments in the field are not being translated into drug discovery there is a need to review the field from a critical perspective. To overcome the limitation of the old approaches used in GPCR target identification and drugs discovery new approaches are required. In particular successful approaches in GPCR drug discovery should take into account that the real GPCR targets for a given disease are not GPCR monomers but GPCR heteromers. The reader will gain an overview of the strategies currently used and their pros and cons. The reader will also understand that new strategies may help in accelerating the access of GPCR into the market, and also notice that successful strategies should take advantage of the new findings in the field of GPCRs.

  16. 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...

  17. 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...

  18. GPCR crystal structures: Medicinal chemistry in the pocket.

    Science.gov (United States)

    Shonberg, Jeremy; Kling, Ralf C; Gmeiner, Peter; Löber, Stefan

    2015-07-15

    Recent breakthroughs in GPCR structural biology have significantly increased our understanding of drug action at these therapeutically relevant receptors, and this will undoubtedly lead to the design of better therapeutics. In recent years, crystal structures of GPCRs from classes A, B, C and F have been solved, unveiling a precise snapshot of ligand-receptor interactions. Furthermore, some receptors have been crystallized in different functional states in complex with antagonists, partial agonists, full agonists, biased agonists and allosteric modulators, providing further insight into the mechanisms of ligand-induced GPCR activation. It is now obvious that there is enormous diversity in the size, shape and position of the ligand binding pockets in GPCRs. In this review, we summarise the current state of solved GPCR structures, with a particular focus on ligand-receptor interactions in the binding pocket, and how this can contribute to the design of GPCR ligands with better affinity, subtype selectivity or efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Hauser, Alexander S; Attwood, Misty M; Rask-Andersen, Mathias; Schiöth, Helgi B; Gloriam, David E

    2017-12-01

    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 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 novel GPCR targets without an approved drug, and the number of biological drugs, allosteric modulators and biased agonists has increased. The major disease indications for GPCR modulators show a shift towards diabetes, obesity and Alzheimer disease, although several central nervous system disorders 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 discovery.

  20. Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity

    Directory of Open Access Journals (Sweden)

    Hui Wu

    2015-03-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV is a tumor virus and the etiologic agent of Kaposi’s Sarcoma (KS. KSHV G protein-coupled receptor (vGPCR is an oncogene that is implicated in malignancies associated with KHSV infection. In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling.

  1. Effects of Bone Morphogenic Proteins on Engineered Cartilage

    Science.gov (United States)

    Gooch, Keith, J.; Blunk, Torsten; Courter, Donald L.; Sieminski, Alisha; Vunjak-Novakovic, Gordana; Freed, Lisa E.

    2007-01-01

    A report describes experiments on the effects of bone morphogenic proteins (BMPs) on engineered cartilage grown in vitro. In the experiments, bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid scaffolds and cultured in, variously, a control medium or a medium supplemented with BMP-2, BMP-12, or BMP-13 in various concentrations. Under all conditions investigated, cell-polymer constructs cultivated for 4 weeks macroscopically and histologically resembled native cartilage. At a concentration of 100 ng/mL, BMP-2, BMP-12, or BMP-13 caused (1) total masses of the constructs to exceed those of the controls by 121, 80, or 62 percent, respectively; (2) weight percentages of glycosaminoglycans in the constructs to increase by 27, 18, or 15, respectively; and (3) total collagen contents of the constructs to decrease to 63, 89, or 83 percent of the control values, respectively. BMP-2, but not BMP-12 or BMP-13, promoted chondrocyte hypertrophy. These observations were interpreted as suggesting that the three BMPs increase the growth rates and modulate the compositions of engineered cartilage. It was also concluded that in vitro engineered cartilage is a suitable system for studying effects of BMPs on chondrogenesis in a well-defined environment.

  2. Prediction of GPCR-Ligand Binding Using Machine Learning Algorithms

    Directory of Open Access Journals (Sweden)

    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.

  3. 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...

  4. 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.

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

    Science.gov (United States)

    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.

  6. 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 ...

  7. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches.

    Directory of Open Access Journals (Sweden)

    Ruben Perez-Carrasco

    2016-10-01

    Full Text Available During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can

  8. 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.

  9. Color-pattern analysis of eyespots in butterfly wings: a critical examination of morphogen gradient models.

    Science.gov (United States)

    Otaki, Joji M

    2011-06-01

    Butterfly wing color patterns consist of many color-pattern elements such as eyespots. It is believed that eyespot patterns are determined by a concentration gradient of a single morphogen species released by diffusion from the prospective eyespot focus in conjunction with multiple thresholds in signal-receiving cells. As alternatives to this single-morphogen model, more flexible multiple-morphogen model and induction model can be proposed. However, the relevance of these conceptual models to actual eyespots has not been examined systematically. Here, representative eyespots from nymphalid butterflies were analyzed morphologically to determine if they are consistent with these models. Measurement of ring widths of serial eyespots from a single wing surface showed that the proportion of each ring in an eyespot is quite different among homologous rings of serial eyespots of different sizes. In asymmetric eyespots, each ring is distorted to varying degrees. In extreme cases, only a portion of rings is expressed remotely from the focus. Similarly, there are many eyespots where only certain rings are deleted, added, or expanded. In an unusual case, the central area of an eyespot is composed of multiple "miniature eyespots," but the overall macroscopic eyespot structure is maintained. These results indicate that each eyespot ring has independence and flexibility to a certain degree, which is less consistent with the single-morphogen model. Considering a "periodic eyespot", which has repeats of a set of rings, damage-induced eyespots in mutants, and a scale-size distribution pattern in an eyespot, the induction model is the least incompatible with the actual eyespot diversity.

  10. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches

    Science.gov (United States)

    Page, Karen M.

    2016-01-01

    During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules—morphogens—guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can qualitatively

  11. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

    Science.gov (United States)

    Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

    2013-04-30

    The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

  12. 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.

  13. 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.

  14. Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

    International Nuclear Information System (INIS)

    Yang Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

    2008-01-01

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE -/- ) versus wild type (AChE +/+ ) mice indicated that while these OPs inhibited axonal growth in AChE +/+ DRG neurons, they had no effect on axonal growth in AChE -/- DRG neurons. However, transfection of AChE -/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs

  15. Quantitative Measurement of GPCR Endocytosis via Pulse-Chase Covalent Labeling.

    Directory of Open Access Journals (Sweden)

    Hidetoshi Kumagai

    Full Text Available G protein-coupled receptors (GPCRs play a critical role in many physiological systems and represent one of the largest families of signal-transducing receptors. The number of GPCRs at the cell surface regulates cellular responsiveness to their cognate ligands, and the number of GPCRs, in turn, is dynamically controlled by receptor endocytosis. Recent studies have demonstrated that GPCR endocytosis, in addition to affecting receptor desensitization and resensitization, contributes to acute G protein-mediated signaling. Thus, endocytic GPCR behavior has a significant impact on various aspects of physiology. In this study, we developed a novel GPCR internalization assay to facilitate characterization of endocytic GPCR behavior. We genetically engineered chimeric GPCRs by fusing HaloTag (a catalytically inactive derivative of a bacterial hydrolase to the N-terminal end of the receptor (HT-GPCR. HaloTag has the ability to form a stable covalent bond with synthetic HaloTag ligands that contain fluorophores or a high-affinity handle (such as biotin and the HaloTag reactive linker. We selectively labeled HT-GPCRs at the cell surface with a HaloTag PEG ligand, and this pulse-chase covalent labeling allowed us to directly monitor the relative number of internalized GPCRs after agonist stimulation. Because the endocytic activities of GPCR ligands are not necessarily correlated with their agonistic activities, applying this novel methodology to orphan GPCRs, or even to already characterized GPCRs, will increase the likelihood of identifying currently unknown ligands that have been missed by conventional pharmacological assays.

  16. Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.

    Science.gov (United States)

    Bénazet, Jean-Denis; Zeller, Rolf

    2009-10-01

    A wealth of classical embryological manipulation experiments taking mainly advantage of the chicken limb buds identified the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) as the respective ectodermal and mesenchymal key signaling centers coordinating proximodistal (PD) and anteroposterior (AP) limb axis development. These experiments inspired Wolpert's French flag model, which is a classic among morphogen gradient models. Subsequent molecular and genetic analysis in the mouse identified retinoic acid as proximal signal, and fibroblast growth factors (FGFs) and sonic hedgehog (SHH) as the essential instructive signals produced by AER and ZPA, respectively. Recent studies provide good evidence that progenitors are specified early with respect to their PD and AP fates and that morpho-regulatory signaling is also required for subsequent proliferative expansion of the specified progenitor pools. The determination of particular fates seems to occur rather late and depends on additional signals such as bone morphogenetic proteins (BMPs), which indicates that cells integrate signaling inputs over time and space. The coordinate regulation of PD and AP axis patterning is controlled by an epithelial-mesenchymal feedback signaling system, in which transcriptional regulation of the BMP antagonist Gremlin1 integrates inputs from the BMP, SHH, and FGF pathways. Vertebrate limb-bud development is controlled by a 4-dimensional (4D) patterning system integrating positive and negative regulatory feedback loops, rather than thresholds set by morphogen gradients.

  17. The essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity.

    Science.gov (United States)

    Wang, Dashan

    2018-06-01

    The aim of this paper is to clarify the critical role of GPCR signaling in T cell immunity. The G protein-coupled receptors (GPCRs) are the most common targets in current pharmaceutical industry, and represent the largest and most versatile family of cell surface communicating molecules. GPCRs can be activated by a diverse array of ligands including neurotransmitters, chemokines as well as sensory stimuli. Therefore, GPCRs are involved in many key cellular and physiological processes, such as sense of light, taste and smell, neurotransmission, metabolism, endocrine and exocrine secretion. In recent years, GPCRs have been found to play an important role in immune system. T cell is an important type of immune cell, which plays a central role in cell-mediated immunity. A variety of GPCRs and their signaling mediators (RGS proteins, GRKs and β-arrestin) have been found to express in T cells and involved T cell-mediated immunity. We will summarize the role of GPCR signaling and their regulatory molecules in T cell activation, homeostasis and function in this article. GPCR signaling plays an important role in T cell activation, homeostasis and function. GPCR signaling is critical in regulating T cell immunity.

  18. 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.

  19. Multiplexed profiling of GPCR activities by combining split TEV assays and EXT-based barcoded readouts.

    Science.gov (United States)

    Galinski, Sabrina; Wichert, Sven P; Rossner, Moritz J; Wehr, Michael C

    2018-05-25

    G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors and are implicated in the physiological regulation of many biological processes. The high diversity of GPCRs and their physiological functions make them primary targets for therapeutic drugs. For the generation of novel compounds, however, selectivity towards a given target is a critical issue in drug development as structural similarities between members of GPCR subfamilies exist. Therefore, the activities of multiple GPCRs that are both closely and distantly related to assess compound selectivity need to be tested simultaneously. Here, we present a cell-based multiplexed GPCR activity assay, termed GPCRprofiler, which uses a β-arrestin recruitment strategy and combines split TEV protein-protein interaction and EXT-based barcode technologies. This approach enables simultaneous measurements of receptor activities of multiple GPCR-ligand combinations by applying massively parallelized reporter assays. In proof-of-principle experiments covering 19 different GPCRs, both the specificity of endogenous agonists and the polypharmacological effects of two known antipsychotics on GPCR activities were demonstrated. Technically, normalization of barcode reporters across individual assays allows quantitative pharmacological assays in a parallelized manner. In summary, the GPCRprofiler technique constitutes a flexible and scalable approach, which enables simultaneous profiling of compound actions on multiple receptor activities in living cells.

  20. 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

  1. 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.

  2. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

    DEFF Research Database (Denmark)

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner

    2016-01-01

    -the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay...

  3. Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

    Science.gov (United States)

    Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

    2012-09-01

    Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. 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.

  5. 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

  6. 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...

  7. 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.

  8. 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.

  9. Onco-GPCR signaling and dysregulated expression of microRNAs in human cancer.

    Science.gov (United States)

    Nohata, Nijiro; Goto, Yusuke; Gutkind, J Silvio

    2017-01-01

    The G-protein-coupled receptor (GPCR) family is the largest family of cell-surface receptors involved in signal transduction. Aberrant expression of GPCRs and G proteins are frequently associated with prevalent human diseases, including cancer. In fact, GPCRs represent the therapeutic targets of more than a quarter of the clinical drugs currently on the market. MiRNAs (miRNAs) are also aberrantly expressed in many human cancers, and they have significant roles in the initiation, development and metastasis of human malignancies. Recent studies have revealed that dysregulation of miRNAs and their target genes expression are associated with cancer progression. The emerging information suggests that miRNAs play an important role in the fine tuning of many signaling pathways, including GPCR signaling. We summarize our current knowledge of the individual functions of miRNAs regulated by GPCRs and GPCR signaling-associated molecules, and miRNAs that regulate the expression and activity of GPCRs, their endogenous ligands and their coupled heterotrimeric G proteins in human cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    OpenAIRE

    Simian, Marina; Hirai, Yohei; Navre, Marc; Werb, Zena; Lochter, Andre; Bissell, Mina J.

    2001-01-01

    The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth fa...

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

    Directory of Open Access Journals (Sweden)

    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

  13. Agronomic, morphogenic and structural characteristics of Marandu grass in silvopastoral systems composed of babassu palm and grass monoculture

    Directory of Open Access Journals (Sweden)

    Rosane Cláudia Rodrigues

    2016-09-01

    Full Text Available This study evaluated the agronomic, morphogenic and structural characteristics of palisadegrass (Urochloa brizantha in silvopastoral systems (SSP’s composed of babassu palms (Attalea speciosa and grass monoculture in the Pre-Amazon region of the state of Maranhão, Brazil. The study followed a completely randomized design, with the arrangement in split plots with six replicates for the evaluation of agronomic characteristics and 30 repetitions for the morphogenic and structural characteristics. The plots were divided into pasture environments with different palm densities (monoculture, 80, 131, 160 palms.ha-¹, and the subplots were divided into the different seasons (rainy and dry. Total forage production was affected (P 0.05 by pastoral system during the rainy season, but in the dry period, higher responses were obtained in SSPs. Overall, SSPs with 80 palms.ha-¹ favored the agronomic characteristics of pastures. Morphogenic and structural characteristics were favored by increasing palm densities. Leaf senescence and duration were not affected by the system.

  14. Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.

    Science.gov (United States)

    Nemashkalo, Anastasiia; Ruzo, Albert; Heemskerk, Idse; Warmflash, Aryeh

    2017-09-01

    Paracrine signals maintain developmental states and create cell fate patterns in vivo and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ('µColonies') to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in µColonies and standard culture conditions and find that in µColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions BMP4 acts as a morphogen but this requires secondary signals and particular cell densities. We find that a 'community effect' enforces a common fate within µColonies, both in the state of pluripotency and when cells are differentiated, and that this effect allows a more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation. © 2017. Published by The Company of Biologists Ltd.

  15. Morphogenic Protein RodZ Interacts with Sporulation Specific SpoIIE in Bacillus subtilis.

    Science.gov (United States)

    Muchová, Katarína; Chromiková, Zuzana; Bradshaw, Niels; Wilkinson, Anthony J; Barák, Imrich

    2016-01-01

    The first landmark in sporulation of Bacillus subtilis is the formation of an asymmetric septum followed by selective activation of the transcription factor σF in the resulting smaller cell. How the morphological transformations that occur during sporulation are coupled to cell-specific activation of transcription is largely unknown. The membrane protein SpoIIE is a constituent of the asymmetric sporulation septum and is a crucial determinant of σF activation. Here we report that the morphogenic protein, RodZ, which is essential for cell shape determination, is additionally required for asymmetric septum formation and sporulation. In cells depleted of RodZ, formation of asymmetric septa is disturbed and σF activation is perturbed. During sporulation, we found that SpoIIE recruits RodZ to the asymmetric septum. Moreover, we detected a direct interaction between SpoIIE and RodZ in vitro and in vivo, indicating that SpoIIE-RodZ may form a complex to coordinate asymmetric septum formation and σF activation. We propose that RodZ could provide a link between the cell shape machinery and the coordinated morphological and developmental transitions required to form a resistant spore.

  16. Mild salinity stimulates a stress-induced morphogenic response in Arabidopsis thaliana roots.

    Science.gov (United States)

    Zolla, Gaston; Heimer, Yair M; Barak, Simon

    2010-01-01

    Plant roots exhibit remarkable developmental plasticity in response to local soil conditions. It is shown here that mild salt stress stimulates a stress-induced morphogenic response (SIMR) in Arabidopsis thaliana roots characteristic of several other abiotic stresses: the proliferation of lateral roots (LRs) with a concomitant reduction in LR and primary root length. The LR proliferation component of the salt SIMR is dramatically enhanced by the transfer of seedlings from a low to a high NO3- medium, thereby compensating for the decreased LR length and maintaining overall LR surface area. Increased LR proliferation is specific to salt stress (osmotic stress alone has no stimulatory effect) and is due to the progression of more LR primordia from the pre-emergence to the emergence stage, in salt-stressed plants. In salt-stressed seedlings, greater numbers of LR primordia exhibit expression of a reporter gene driven by the auxin-sensitive DR5 promoter than in unstressed seedlings. Moreover, in the auxin transporter mutant aux1-7, the LR proliferation component of the salt SIMR is completely abrogated. The results suggest that salt stress promotes auxin accumulation in developing primordia thereby preventing their developmental arrest at the pre-emergence stage. Examination of ABA and ethylene mutants revealed that ABA synthesis and a factor involved in the ethylene signalling network also regulate the LR proliferation component of the salt SIMR.

  17. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response

    Science.gov (United States)

    Sorescu, George P.; Sykes, Michelle; Weiss, Daiana; Platt, Manu O.; Saha, Aniket; Hwang, Jinah; Boyd, Nolan; Boo, Yong C.; Vega, J. David; Taylor, W. Robert; hide

    2003-01-01

    Atherosclerosis is now viewed as an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions, including oscillatory shear stress (OS), in branched arteries. In contrast, the arterial regions exposed to laminar shear (LS) are relatively lesion-free. The mechanisms underlying the opposite effects of OS and LS on the inflammatory and atherogenic processes are not clearly understood. Here, through DNA microarrays, protein expression, and functional studies, we identify bone morphogenic protein 4 (BMP4) as a mechanosensitive and pro-inflammatory gene product. Exposing endothelial cells to OS increased BMP4 protein expression, whereas LS decreased it. In addition, we found BMP4 expression only in the selective patches of endothelial cells overlying foam cell lesions in human coronary arteries. The same endothelial patches also expressed higher levels of intercellular cell adhesion molecule-1 (ICAM-1) protein compared with those of non-diseased areas. Functionally, we show that OS and BMP4 induced ICAM-1 expression and monocyte adhesion by a NFkappaB-dependent mechanism. We suggest that BMP4 is a mechanosensitive, inflammatory factor playing a critical role in early steps of atherogenesis in the lesion-prone areas.

  18. A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

    Science.gov (United States)

    Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

    2012-02-23

    The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    Thomas J Lampert

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

  1. 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.

  2. 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 ...

  3. 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.

  4. 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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. GPCR-SSFE: A comprehensive database of G-protein-coupled receptor template predictions and homology models

    Directory of Open Access Journals (Sweden)

    Kreuchwig Annika

    2011-05-01

    Full Text Available Abstract Background G protein-coupled receptors (GPCRs transduce a wide variety of extracellular signals to within the cell and therefore have a key role in regulating cell activity and physiological function. GPCR malfunction is responsible for a wide range of diseases including cancer, diabetes and hyperthyroidism and a large proportion of drugs on the market target these receptors. The three dimensional structure of GPCRs is important for elucidating the molecular mechanisms underlying these diseases and for performing structure-based drug design. Although structural data are restricted to only a handful of GPCRs, homology models can be used as a proxy for those receptors not having crystal structures. However, many researchers working on GPCRs are not experienced homology modellers and are therefore unable to benefit from the information that can be gleaned from such three-dimensional models. Here, we present a comprehensive database called the GPCR-SSFE, which provides initial homology models of the transmembrane helices for a large variety of family A GPCRs. Description Extending on our previous theoretical work, we have developed an automated pipeline for GPCR homology modelling and applied it to a large set of family A GPCR sequences. Our pipeline is a fragment-based approach that exploits available family A crystal structures. The GPCR-SSFE database stores the template predictions, sequence alignments, identified sequence and structure motifs and homology models for 5025 family A GPCRs. Users are able to browse the GPCR dataset according to their pharmacological classification or search for results using a UniProt entry name. It is also possible for a user to submit a GPCR sequence that is not contained in the database for analysis and homology model building. The models can be viewed using a Jmol applet and are also available for download along with the alignments. Conclusions The data provided by GPCR-SSFE are useful for investigating

  9. GPCR-SSFE: a comprehensive database of G-protein-coupled receptor template predictions and homology models.

    Science.gov (United States)

    Worth, Catherine L; Kreuchwig, Annika; Kleinau, Gunnar; Krause, Gerd

    2011-05-23

    G protein-coupled receptors (GPCRs) transduce a wide variety of extracellular signals to within the cell and therefore have a key role in regulating cell activity and physiological function. GPCR malfunction is responsible for a wide range of diseases including cancer, diabetes and hyperthyroidism and a large proportion of drugs on the market target these receptors. The three dimensional structure of GPCRs is important for elucidating the molecular mechanisms underlying these diseases and for performing structure-based drug design. Although structural data are restricted to only a handful of GPCRs, homology models can be used as a proxy for those receptors not having crystal structures. However, many researchers working on GPCRs are not experienced homology modellers and are therefore unable to benefit from the information that can be gleaned from such three-dimensional models. Here, we present a comprehensive database called the GPCR-SSFE, which provides initial homology models of the transmembrane helices for a large variety of family A GPCRs. Extending on our previous theoretical work, we have developed an automated pipeline for GPCR homology modelling and applied it to a large set of family A GPCR sequences. Our pipeline is a fragment-based approach that exploits available family A crystal structures. The GPCR-SSFE database stores the template predictions, sequence alignments, identified sequence and structure motifs and homology models for 5025 family A GPCRs. Users are able to browse the GPCR dataset according to their pharmacological classification or search for results using a UniProt entry name. It is also possible for a user to submit a GPCR sequence that is not contained in the database for analysis and homology model building. The models can be viewed using a Jmol applet and are also available for download along with the alignments. The data provided by GPCR-SSFE are useful for investigating general and detailed sequence-structure-function relationships

  10. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Simian, M.; Harail, Y.; Navre, M.; Werb, Z.; Lochter, A.; Bissell, M.J.

    2002-03-06

    The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

  11. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    International Nuclear Information System (INIS)

    Simian, Marina; Hirai, Yohei; Navre, Marc; Werb, Zena; Lochter, Andre; Bissell, Mina J.

    2002-01-01

    The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland

  12. 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.

  13. 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

  14. 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.

  15. Voice Prosthetic Biofilm Formation and Candida Morphogenic Conversions in Absence and Presence of Different Bacterial Strains and Species on Silicone-Rubber

    NARCIS (Netherlands)

    van der Mei, Henny C.; Buijssen, Kevin J. D. A.; van der Laan, Bernard F. A. M.; Ovchinnikova, Ekatarina; Geertsema-Doornbusch, Gesinda I.; Atema-Smit, Jelly; van de Belt-Gritter, Betsy; Busscher, Henk J.

    2014-01-01

    Morphogenic conversion of Candida from a yeast to hyphal morphology plays a pivotal role in the pathogenicity of Candida species. Both Candida albicans and Candida tropicalis, in combination with a variety of different bacterial strains and species, appear in biofilms on silicone-rubber voice

  16. '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.

  17. A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium

    Science.gov (United States)

    Ramsay, Joshua P.; Williamson, Neil R.; Spring, David R.; Salmond, George P. C.

    2011-01-01

    Gas vesicles are hollow intracellular proteinaceous organelles produced by aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas vesicles increase buoyancy and allow taxis toward air–liquid interfaces, enabling subsequent niche colonization. Here we report a unique example of gas vesicle-mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This strain is a member of the Enterobacteriaceae previously studied for its production of prodigiosin and carbapenem antibiotics. Genes required for gas vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct homologs of the main structural protein, GvpA. Heterologous expression of this locus in Escherichia coli induced copious vesicle production and efficient cell buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle-like layer of highly vacuolated cells, which was dependent on oxygen limitation and the expression of ntrB/C and cheY-like regulatory genes within the gas-vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by intercellular chemical signaling, through an N-acyl homoserine lactone, indicating that in this system the quorum-sensing molecule acts as a morphogen initiating organelle development. Flagella-based motility and gas vesicle morphogenesis were also oppositely regulated by the small RNA-binding protein, RsmA, suggesting environmental adaptation through physiological control of the choice between motility and flotation as alternative taxis modes. We propose that gas vesicle biogenesis in this strain represents a distinct mechanism of mobility, regulated by oxygen availability, nutritional status, the RsmA global regulatory system, and the quorum-sensing morphogen. PMID:21873216

  18. A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium.

    Science.gov (United States)

    Ramsay, Joshua P; Williamson, Neil R; Spring, David R; Salmond, George P C

    2011-09-06

    Gas vesicles are hollow intracellular proteinaceous organelles produced by aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas vesicles increase buoyancy and allow taxis toward air-liquid interfaces, enabling subsequent niche colonization. Here we report a unique example of gas vesicle-mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This strain is a member of the Enterobacteriaceae previously studied for its production of prodigiosin and carbapenem antibiotics. Genes required for gas vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct homologs of the main structural protein, GvpA. Heterologous expression of this locus in Escherichia coli induced copious vesicle production and efficient cell buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle-like layer of highly vacuolated cells, which was dependent on oxygen limitation and the expression of ntrB/C and cheY-like regulatory genes within the gas-vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by intercellular chemical signaling, through an N-acyl homoserine lactone, indicating that in this system the quorum-sensing molecule acts as a morphogen initiating organelle development. Flagella-based motility and gas vesicle morphogenesis were also oppositely regulated by the small RNA-binding protein, RsmA, suggesting environmental adaptation through physiological control of the choice between motility and flotation as alternative taxis modes. We propose that gas vesicle biogenesis in this strain represents a distinct mechanism of mobility, regulated by oxygen availability, nutritional status, the RsmA global regulatory system, and the quorum-sensing morphogen.

  19. 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.

  20. 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...

  1. 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.

  2. Conformational entropic maps of functional coupling domains in GPCR activation: A case study with beta2 adrenergic receptor

    Science.gov (United States)

    Liu, Fan; Abrol, Ravinder; Goddard, William, III; Dougherty, Dennis

    2014-03-01

    Entropic effect in GPCR activation is poorly understood. Based on the recent solved structures, researchers in the GPCR structural biology field have proposed several ``local activating switches'' that consisted of a few number of conserved residues, but have long ignored the collective dynamical effect (conformational entropy) of a domain comprised of an ensemble of residues. A new paradigm has been proposed recently that a GPCR can be viewed as a composition of several functional coupling domains, each of which undergoes order-to-disorder or disorder-to-order transitions upon activation. Here we identified and studied these functional coupling domains by comparing the local entropy changes of each residue between the inactive and active states of the β2 adrenergic receptor from computational simulation. We found that agonist and G-protein binding increases the heterogeneity of the entropy distribution in the receptor. This new activation paradigm and computational entropy analysis scheme provides novel ways to design functionally modified mutant and identify new allosteric sites for GPCRs. The authors thank NIH and Sanofi for funding this project.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma.

    Directory of Open Access Journals (Sweden)

    Bruno C Jham

    2011-04-01

    Full Text Available Kaposi's sarcoma (KS is a vascular neoplasm characterized by the dysregulated expression of angiogenic and inflammatory cytokines. The driving force of the KS lesion, the KSHV-infected spindle cell, secretes elevated levels of vascular endothelial growth factor (VEGF, essential for KS development. However, the origin of VEGF in this tumor remains unclear.Here we report that the KSHV G protein-coupled receptor (vGPCR upregulates VEGF in KS through an intricate paracrine mechanism. The cytokines secreted by the few vGPCR-expressing tumor cells activate in neighboring cells multiple pathways (including AKT, ERK, p38 and IKKβ that, in turn, converge on TSC1/2, promoting mTOR activation, HIF upregulation, and VEGF secretion. Conditioned media from vGPCR-expressing cells lead to an mTOR-dependent increase in HIF-1α and HIF-2α protein levels and VEGF upregulation. In a mouse allograft model for KS, specific inhibition of the paracrine activation of mTOR in non-vGPCR-expressing cells was sufficient to inhibit HIF upregulation in these cells, and abolished the ability of the vGPCR-expressing cells to promote tumor formation in vivo. Similarly, pharmacologic inhibition of HIF in this model blocked VEGF secretion and also lead to tumor regression.Our findings provide a compelling explanation for how the few tumor cells expressing vGPCR can contribute to the dramatic amplification of VEGF secretion in KS, and further provide a molecular mechanism for how cytokine dysregulation in KS fuels angiogenesis and tumor development. These data further suggest that activation of HIF by vGPCR may be a vulnerable target for the treatment of patients with KS.

  9. Complications Associated With the Use of Recombinant Human Bone Morphogenic Protein-2 in Ridge Augmentation: A Case Report.

    Science.gov (United States)

    Dragonas, Panagiotis; Palin, Charles; Khan, Saba; Gajendrareddy, Praveen K; Weiner, Whitney D

    2017-10-01

    This case report aims to describe in detail a complication associated with resorption of regenerated bone following implant placement and ridge augmentation using recombinant human bone morphogenic protein-2 (rhBMP-2) in combination with allograft and xenograft. Bilateral maxillary sinus and ridge augmentation procedures were completed using rhBMP-2 combined with allograft and xenograft. Five months later, significant bone augmentation was achieved, which allowed for the placement of 4 implants. Upon stage 2 surgery, significant dehiscence was noted in all implants. Treatment steps to address this complication included implant removal, guided bone regeneration with xenograft only, and placement of new implants followed by soft-tissue grafting. At the time of publication, this patient is status 1½ years post case completion with maintenance of therapy outcomes. Off-label use of rhBMP-2 has gained significant acceptance in implant dentistry. However, there is limited evidence regarding the bone maturation process when rhBMP-2 is combined with other biomaterials. More research may be needed regarding the timing and process of bone healing in the presence of rhBMP-2, in an effort to avoid surgical complications.

  10. Bone Morphogenic Protein-2 (rhBMP2)-Loaded Silk Fibroin Scaffolds to Enhance the Osteoinductivity in Bone Tissue Engineering

    Science.gov (United States)

    Du, Guang-Yu; He, Sheng-Wei; Sun, Chuan-Xiu; Mi, Li-Dong

    2017-10-01

    There is an increasing demand for formulations of silk fibroin (SF) scaffolds in biomedical applications. SF was crosslinked via glutaraldehyde with osteoinductive recombinant human bone morphogenic protein-2 (rhBMP2) of different ratios viz. (i) 3% SF with no rhBMP2 (SF), (ii) 3% SF with equal amount of rhBMP2 (SF+BMP2), and (iii) 12% SF with 3% of rhBMP2 (4SF+BMP2), and these solutions were used in electrospinning-based fabrication of nanoscaffolds for evaluating increased osteoinductive potential of SF scaffolds with rhBMP2. Stress-strain relationship suggested there is no loss in mechanical strength of fibers with addition of rhBMP2, and mechanical strength of scaffold was improved with increase in concentration of SF. rhBMP2 association increased the water retention capacity of scaffold as evident from swelling studies. Viability of hMSCs was found to be higher in conjugated scaffolds, and scaffolds do not exhibit any cytotoxicity towards guest cells. Cells were found to have higher alkaline phosphatase activity in conjugated scaffolds under in vitro and in vivo conditions which establishes the increased osteoinductivity of the novel construct. The scaffolds were found to be effective for in vivo bone formation as well.

  11. Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

    Science.gov (United States)

    Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

    2015-03-01

    The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines. © 2014 Wiley Periodicals, Inc.

  12. 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.

  13. 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

  14. 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.

  15. 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...

  16. Bone Morphogenic Protein 4-Smad-Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function.

    Science.gov (United States)

    Hu, Weining; Zhang, Yang; Wang, Li; Lau, Chi Wai; Xu, Jian; Luo, Jiang-Yun; Gou, Lingshan; Yao, Xiaoqiang; Chen, Zhen-Yu; Ma, Ronald Ching Wan; Tian, Xiao Yu; Huang, Yu

    2016-03-01

    Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus. We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα. The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice. © 2016 American Heart Association, Inc.

  17. Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chang; Chen, Lin; Zeng, Jing; Cui, Jian; Ning, Jiao-nin [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Wang, Guan-song [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Belguise, Karine; Wang, Xiaobo [Université P. Sabatier Toulouse III and CNRS, LBCMCP, 31062 Toulouse Cedex 9 (France); Qian, Gui-sheng [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Lu, Kai-zhi [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Yi, Bin, E-mail: yibin1974@163.com [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China)

    2015-08-01

    Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling. - Highlights: • CBDL-rat serum promotes the myogenic

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

    Directory of Open Access Journals (Sweden)

    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

  19. 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.

  20. 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).

  1. 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...

  2. 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...

  3. 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

  4. 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....

  5. 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

  6. 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....

  7. CADM1 is essential for KSHV-encoded vGPCR-and vFLIP-mediated chronic NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Richard Hunte

    2018-04-01

    Full Text Available Approximately 12% of all human cancers worldwide are caused by infections with oncogenic viruses. Kaposi's sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8 is one of the oncogenic viruses responsible for human cancers, including Kaposi's sarcoma (KS, Primary Effusion Lymphoma (PEL, and the lymphoproliferative disorder multicentric Castleman's disease (MCD. Chronic inflammation mediated by KSHV infection plays a decisive role in the development and survival of these cancers. NF-κB, a family of transcription factors regulating inflammation, cell survival, and proliferation, is persistently activated in KSHV-infected cells. The KSHV latent and lytic expressing oncogenes involved in NF-κB activation are vFLIP/K13 and vGPCR, respectively. However, the mechanisms by which NF-κB is activated by vFLIP and vGPCR are poorly understood. In this study, we have found that a host molecule, Cell Adhesion Molecule 1 (CADM1, is robustly upregulated in KSHV-infected PBMCs and KSHV-associated PEL cells. Further investigation determined that both vFLIP and vGPCR interacted with CADM1. The PDZ binding motif localized at the carboxyl terminus of CADM1 is essential for both vGPCR and vFLIP to maintain chronic NF-κB activation. Membrane lipid raft associated CADM1 interaction with vFLIP is critical for the initiation of IKK kinase complex and NF-κB activation in the PEL cells. In addition, CADM1 played essential roles in the survival of KSHV-associated PEL cells. These data indicate that CADM1 plays key roles in the activation of NF-κB pathways during latent and lytic phases of the KSHV life cycle and the survival of KSHV-infected cells.

  8. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

    Regulatory governance frameworks have become essential building blocks of world society. From supply chains to the regimes surrounding international organizations, extensive governance frameworks have emerged which structure and channel a variety of social exchanges, including economic, political...... by the International Transitional Administrations (ITAs) in Kosovo and Iraq as well as global supply chains and their impact on the garment industry in Bangladesh....

  9. 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

  10. 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…

  11. 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.

  12. 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.

  13. 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.

  14. Organizational governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Klein, Peter G.

    This chapter reviews and discusses rational-choice approaches to organizational governance. These approaches are found primarily in organizational economics (virtually no rational-choice organizational sociology exists), particularly in transaction cost economics, principal-agent theory...

  15. Waste governance

    CSIR Research Space (South Africa)

    Oelofse, Suzanna HH

    2018-06-01

    Full Text Available of governance in Africa. The next section focuses on regulation, and the status of the regulatory frameworks in different African countries. Shortcomings in the regulatory framework are highlighted through examples in various countries. Specific policy...

  16. Corporate Governance

    Directory of Open Access Journals (Sweden)

    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.

  17. Tax Governance

    DEFF Research Database (Denmark)

    Boll, Karen; Brehm Johansen, Mette

    to wider international trends within tax administration, especially concerning the development of risk assessments and internal control in the corporations and a greater focus on monitoring of these elements by the tax authorities. Overall, the working paper concludes that Tax Governance as a model......This working paper presents an analysis of the experiences of Cooperative Compliance in Denmark. Cooperative Compliance denotes a specific kind of collaborative program for the regulation of large corporate taxpayers by the tax authorities. Cooperative Compliance programs have been implemented...... in several countries worldwide. In Denmark the program is called Tax Governance. Tax Governance has been studied using qualitative method and the analyses of the working paper build on an extensive base of in-depth interviews – primarily with tax directors from corporations participating in the program...

  18. Mobilizing Government

    DEFF Research Database (Denmark)

    Wang, Cancan; Medaglia, Rony; Jensen, Tina Blegind

    2016-01-01

    The nature of inter-organizational collaboration between government and other stakeholders is rapidly changing with the introduction of open social media (OSM) platforms. Characterized by a high degree of informality as well as a blurred personal/professional nature, OSM can potentially introduce...... changes and tensions in the well-established routines of the public sector. This paper aims at shedding light on such changes, presenting findings from a study on the use of an OSM platform, WeChat, in an interorganizational collaboration project between government, university, and industry stakeholders...

  19. Bank Governance

    OpenAIRE

    Laura Ard; Alexander Berg

    2010-01-01

    Principles of good governance have been a major component of international financial standards and are seen as essential to the stability and integrity of financial systems. Over the past 10 years much energy and attention have gone to improving the ability of company boards, managers, and owners to prudently navigate rapidly changing and volatile market conditions. So, how to explain the ...

  20. Government Organizations

    DEFF Research Database (Denmark)

    Krause Hansen, Hans; Salskov-Iversen, Dorte

    2017-01-01

    , with clearly defined boundaries between the public and private; and in terms of polycentrism, where power and authority are seen as dispersed among state and nonstate organizations, including business and civil society organizations. Globalization and new media technologies imply changes in the relationship...... democracy and the public sphere; and discourse approaches to studying the intersections of government, organizational change, and information and communication technology....

  1. Corporate Governance

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

    Andy Knight; David Malone; Faith Mitchell. Finance and Audit Committee. Members: Denis Desautels (Chairman); Ahmed Galal;. Frieda Granot; Elizabeth Parr-Johnston; Andrés Rozental;. Gordon Shirley. Governance Committee. Members: The Honourable Barbara McDougall (Chairman);. Claude-Yves Charron; Denis ...

  2. 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.

  3. Changes in Serum Levels of Bone Morphogenic Protein 4 and Inflammatory Cytokines after Bariatric Surgery in Severely Obese Korean Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Mee Kyoung Kim

    2013-01-01

    Full Text Available Serum bone morphogenic protein- (BMP- 4 levels are associated with human adiposity. The aim of this study was to investigate changes in serum levels of BMP-4 and inflammatory cytokines after Roux-en-Y gastric bypass (RYGB. Fifty-seven patients with type 2 diabetes underwent RYGB. Serum levels of BMP-4 and various inflammatory markers, including high-sensitivity C-reactive protein (hsCRP, free fatty acids (FFAs, and plasminogen activator inhibitor- (PAI- 1, were measured before and 12 months after RYGB. Remission was defined as glycated hemoglobin <6.5% for at least 1 year in the absence of medications. Levels of PAI-1, hsCRP, and FFAs were significantly decreased at 1 year after RYGB. BMP-4 levels were also significantly lower at 1 year after RYGB than at baseline (P=0.024. Of the 57 patients, 40 (70% had diabetes remission at 1 year after surgery (remission group. Compared with patients in the nonremission group, patients in the remission group had lower PAI-1 levels and smaller visceral fat areas at baseline. There was a difference in the change in the BMP-4 level according to remission status. Our data demonstrate a significant beneficial effect of bariatric surgery on established cardiovascular risk factors and a reduction in chronic nonspecific inflammation after surgery.

  4. Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

    Science.gov (United States)

    Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

    2013-11-01

    Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

  5. Plural Governance

    DEFF Research Database (Denmark)

    Mols, Niels Peter; Hansen, Jesper Rosenberg; Villadsen, Anders Ryom

    We suggest that both making and buying the same product or service has several effects on market performance. A model is developed and tested by use of 170 answers gathered from the Danish municipalities. The results support the hypotheses that both making and buying: (1) moderates the negative r...... on how the plurality is measured. The results indicate that internal production may facilitate effective governance of the relationships with suppliers. Implications for research on firm boundaries and for practice are also discussed....

  6. IT Governance

    OpenAIRE

    Šimková, Hana

    2008-01-01

    IT governance (control of information technology) is a frequently discussed topic today which represents current needs to take control of IT, judge impacts of all resolutions and lead up investments running to the information technology. It is very important for both small and large organizations to have IT which encourages business strategy and helps to meet objectives of a company. The theoretical part of this paper is focused on characterization of the main areas, benefits, rules and vario...

  7. 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

  8. The potentiation of Mangifera casturi bark extract on interleukin- 1β and bone morphogenic protein-2 expressions during bone remodeling after tooth extraction

    Directory of Open Access Journals (Sweden)

    Bayu Indra Sukmana

    2017-03-01

    Full Text Available Background: The main oral health problem in Indonesia is the high number of tooth decay. Tooth extraction is the treatment often received by patients who experience tooth decay and the wound caused by alveolar bone resorption. Bark of Mangifera casturi has been studied and proven to contain secondary metabolite which has the ability to increase osteoblast’s activity and suppress osteoclast’s activity. Purpose: The purpose of this study was to analyze interleukin-1 beta (IL-1β and bone morphogenic protein-2 (BMP-2 activities during bone remodeling after Mangifera casturi’s bark extract treatment. Method: This study was laboratory experimental research with randomized post-test only control group design. The Mangifera casturi bark was extracted using 96% ethanol maceration and n-hexane fractionation. This study used 40 male Wistar rats which are divided into 4 groups and the tooth extraction was performed on the rats’ right mandible incisive tooth. The four groups consisted of 6.35%, 12.7%, 25.4% extract treatment group, and a control group. Wistar’s mandibles were decapitated on the 7th and 14th day after extraction. Antibody staining on preparations for the examination of IL-1β and BMP-2 expressions was done using immunohistochemistry. Result: There was a significant difference of IL-1β and BMP-2 expressions in 6,35%, 12,7%, and 25,4% treatment groups compared to control group with p<0.05. Conclusion: Mangifera casturi’s bark extract was able to suppress the IL-1β expression and increase the BMP-2 expression during bone remodeling after tooth extraction.

  9. Morphogenes bolA and mreB mediate the photoregulation of cellular morphology during complementary chromatic acclimation in Fremyella diplosiphon.

    Science.gov (United States)

    Singh, Shailendra P; Montgomery, Beronda L

    2014-07-01

    Photoregulation of pigmentation during complementary chromatic acclimation (CCA) is well studied in Fremyella diplosiphon; however, mechanistic insights into the CCA-associated morphological changes are still emerging. F. diplosiphon cells are rectangular under green light (GL), whereas cells are smaller and spherical under red light (RL). Here, we investigate the role of morphogenes bolA and mreB during CCA using gene expression and gene function analyses. The F. diplosiphon bolA gene is essential as its complete removal from the genome was unsuccessful. Depletion of bolA resulted in slow growth, morphological defects and the accumulation of high levels of reactive oxygen species in a partially segregated ΔbolA strain. Higher expression of bolA was observed under RL and was correlated with lower expression of mreB and mreC genes in wild type. In a ΔrcaE strain that lacks the red-/green-responsive RcaE photoreceptor, the expression of bolA and mre genes was altered under both RL and GL. Observed gene expression relationships suggest that mreB and mreC expression is controlled by RcaE-dependent photoregulation of bolA expression. Expression of F. diplosiphon bolA and mreB homologues in Escherichia coli demonstrated functional conservation of the encoded proteins. Together, these studies establish roles for bolA and mreB in RcaE-dependent regulation of cellular morphology. © 2014 John Wiley & Sons Ltd.

  10. Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Biver, Emmanuel, E-mail: ebiver@yahoo.fr [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Soubrier, Anne-Sophie [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Thouverey, Cyril [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Cortet, Bernard [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Broux, Odile [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Caverzasio, Joseph [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Hardouin, Pierre [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.

  11. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders

    2012-01-01

    Most people agree that our world face daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel dominant...... perspectives in challenge per-ception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping of engineering education...... and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter strives to elicit the bodies...

  12. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders

    2011-01-01

    Abstract: Most people agree that our world faces daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel...... dominant perspectives in challenge perception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping...... of engineering education and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter...

  13. Review of Signaling Pathways Governing MSC Osteogenic and Adipogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Aaron W. James

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSC are multipotent cells, functioning as precursors to a variety of cell types including adipocytes, osteoblasts, and chondrocytes. Between osteogenic and adipogenic lineage commitment and differentiation, a theoretical inverse relationship exists, such that differentiation towards an osteoblast phenotype occurs at the expense of an adipocytic phenotype. This balance is regulated by numerous, intersecting signaling pathways that converge on the regulation of two main transcription factors: peroxisome proliferator-activated receptor-γ (PPARγ and Runt-related transcription factor 2 (Runx2. These two transcription factors, PPARγ and Runx2, are generally regarded as the master regulators of adipogenesis and osteogenesis. This review will summarize signaling pathways that govern MSC fate towards osteogenic or adipocytic differentiation. A number of signaling pathways follow the inverse balance between osteogenic and adipogenic differentiation and are generally proosteogenic/antiadipogenic stimuli. These include β-catenin dependent Wnt signaling, Hedgehog signaling, and NELL-1 signaling. However, other signaling pathways exhibit more context-dependent effects on adipogenic and osteogenic differentiation. These include bone morphogenic protein (BMP signaling and insulin growth factor (IGF signaling, which display both proosteogenic and proadipogenic effects. In summary, understanding those factors that govern osteogenic versus adipogenic MSC differentiation has significant implications in diverse areas of human health, from obesity to osteoporosis to regenerative medicine.

  14. 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.

  15. 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.)

  16. 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

  17. 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

  18. Federalism and multilevel governance

    NARCIS (Netherlands)

    van der Wusten, H.; Agnew, J.; Mamadouh, V.; Secor, A.J.; Sharp, J.

    2015-01-01

    Federalism and multilevel governance both emphasize polycentricity in governing arrangements. With their different intellectual pedigrees, these concepts are discussed in two separate sections. Fragments are now increasingly mixed up in hybrid forms of governance that also encompass originally

  19. Developing digital forensic governance

    CSIR Research Space (South Africa)

    Grobler, M

    2010-03-01

    Full Text Available This paper presents a Digital Forensic (DF) governance framework and its mapping on the SANS ISO/IEC 38500:2009 Corporate governance of information technology structure. DF governance assists organisations in guiding the management team...

  20. Voluntary Environmental Governance Arrangements

    NARCIS (Netherlands)

    van der Heijden, J.

    2012-01-01

    Voluntary environmental governance arrangements have focal attention in studies on environmental policy, regulation and governance. The four major debates in the contemporary literature on voluntary environmental governance arrangements are studied. The literature falls short of sufficiently

  1. 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...

  2. Engineering of blood vessel patterns by angio-morphogens [angiotropins]: non-mitogenic copper-ribonucleoprotein cytokins [CuRNP ribokines] with their metalloregulated constituents of RAGE-binding S100-EF-hand proteins and extracellular RNA bioaptamers in vascular remodeling of tissue and angiogenesis in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wissler, J.H. [ARCONS Applied Research, Bad Nauheim (Germany)

    2001-12-01

    Tissue vascularization is requisite to successful cell-based therapies, biomaterial design and implant integration. Thus, known problems in ossointegration of avascular implants in connection with the generation of bone tissue reflect arrays of general problems of socio-economic relevance existing in reparative medicine still waiting for to be solved. For this purpose, morphogenesis and remodeling of endothelial angio-architectures in tissue and in vitro by isolated non-mitogenic angio-morphogens [angiotropins] are considered in terms of their structure, function and action mechanisms. Extracellular angiotropins are secreted by activated leukocytes/monocytes/macrophages. They are a family of cytokines with morphogen bioactivity selectively directed to endothelial cells. Their structure was deciphered as metalloregulated copper-ribonucleoproteins [CuRNP ribokines]. They are built up of angiotropin-related S100-EF-hand protein [ARP] and highly modified and edited 5'end-phosphorylated RNA [ARNA], complexed together by copper ions. Oxidant-sensitive ARNA and their precursors represent novel types in a RNA world: They are the first isolated and sequenced forms of extracellular RNA [eRNA], may act as cytokine and bioaptamer, contain isoguanosine [crotonoside] as modified nucleoside and show up copper as RNA-structuring transition metal ion. By metalloregulated bioaptamer functions, ARNA impart novel biofunctions to RAGE-binding S100-EF-hand proteins. Angiotropin morphogens were shown suitable for neointiation and remodeling of blood vessel patterns in different, adult, embryonal and artificial tissues. These neovascular patterns manifest regulated hemodynamics for preventing tissue necrosis, supporting tissue functions and promoting wound healing. As evaluated in skin and muscle vascularization, the neovascular patterns are integrated into homeostatic control mechanisms of tissue. Thus, the morphogens show up beneficial perspectives and are suggested useful tools

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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

  8. 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…

  9. 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....

  10. 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.

  11. The N-terminal region of the dopamine D2 receptor, a rhodopsin-like GPCR, regulates correct integration into the plasma membrane and endocytic routes

    Science.gov (United States)

    Cho, DI; Min, C; Jung, KS; Cheong, SY; Zheng, M; Cheong, SJ; Oak, MH; Cheong, JH; Lee, BK; Kim, KM

    2012-01-01

    BACKGROUND AND PURPOSE Functional roles of the N-terminal region of rhodopsin-like GPCR family remain unclear. Using dopamine D2 and D3 receptors as a model system, we probed the roles of the N-terminal region in the signalling, intracellular trafficking of receptor proteins, and explored the critical factors that determine the functionality of the N-terminal region. EXPERIMENTAL APPROACH The N-terminal region of the D2 receptor was gradually shortened or switched with that of the D3 receptor or a non-specific sequence (FLAG), or potential N-terminal glycosylation sites were mutated. Effects of these manipulations on surface expression, internalization, post-endocytic behaviours and signalling were determined. KEY RESULTS Shortening the N-terminal region of the D2 receptor enhanced receptor internalization and impaired surface expression and signalling; ligand binding, desensitization and down-regulation were not affected but their association with a particular microdomain, caveolae, was disrupted. Replacement of critical residues within the N-terminal region with the FLAG epitope failed to restore surface expression but partially restored the altered internalization and signalling. When the N-terminal regions were switched between D2 and D3 receptors, cell surface expression pattern of each receptor was switched. Mutations of potential N-terminal glycosylation sites inhibited surface expression but enhanced internalization of D2 receptors. CONCLUSIONS AND IMPLICATIONS Shortening of N-terminus or mutation of glycosylation sites located within the N-terminus enhanced receptor internalization but impaired the surface expression of D2 receptors. The N-terminal region of the D2 receptor, in a sequence-specific manner, controls the receptor's conformation and integration into the plasma membrane, which determine its subcellular localization, intracellular trafficking and signalling properties. PMID:22117524

  12. Government and Business

    DEFF Research Database (Denmark)

    Campbell, John L.

    2015-01-01

    There is a vast literature about the relationships between government and business in advanced capitalist societies.......There is a vast literature about the relationships between government and business in advanced capitalist societies....

  13. Nordic Corporate Governance Revisited

    DEFF Research Database (Denmark)

    Thomsen, Steen

    2016-01-01

    This paper reviews the key elements of the Nordic governance model, which include a distinct legal system, high governance ratings and low levels of corruption. Other characteristics include concentrated ownership, foundation ownership, semi two-tier board structures, employee representation...

  14. Exploring Knowledge Governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahoney, Joseph T

    Knowledge governance is characterized as a distinctive research subject, the understanding of which cuts across diverse fields in management. In particular, it represents an intersection of knowledge management, strategic management, and theories of the firm. Knowledge governance considers how de...

  15. 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.

  16. 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...

  17. The Knowledge Governance Approach

    DEFF Research Database (Denmark)

    Foss, Nicolai J.

    with diverse capabilities of handling these transactions. Various open research issues that a knowledge governance approach may illuminate are sketched. Although knowledge governance draws clear inspiration from organizational economics and `rational' organization theory, it recognizes that knowledge......An attempt is made to characterize a `knowledge governance approach' as a distinctive, emerging field that cuts across the fields of knowledge management, organisation studies, strategy and human resource management. Knowledge governance is taken up with how the deployment of administrative...

  18. 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.

  19. 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 ...

  20. 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...

  1. 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.

  2. 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...

  3. Governance or Governing – the Missing Link?

    Directory of Open Access Journals (Sweden)

    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

  4. Innovation in City Governments

    DEFF Research Database (Denmark)

    Lewis, Jenny M; Ricard, Lykke Margot; Klijn, Erik Hans

    Innovation has become an important focus for governments around the world over the last decade, with greater pressure on governments to do more with less, and expanding community expectations. Some are now calling this ‘social innovation’ – innovation that is related to creating new services...... that have value for stakeholders (such as citizens) in terms of the social and political outcomes they produce. Innovation in City Governments: Structures, Networks, and Leadership establishes an analytical framework of innovation capacity based on three dimensions: Structure - national governance...... project in Copenhagen, Barcelona and Rotterdam. The book provides major new insights on how structures, networks and leadership in city governments shape the social innovation capacity of cities. It provides ground-breaking analyses of how governance structures and local socio-economic challenges...

  5. Transnational Governance and Constitutionalism

    DEFF Research Database (Denmark)

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

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

  6. Governance, Trust, and Taxes

    OpenAIRE

    Schrøter Joensen, Juanna; Weihe, Guðrið

    2013-01-01

    This paper examines the role of social capital (trust) vis-à-vis the propensity of a country to be a tax haven. The empirical analysis corroborates that better governed countries have a higher ceteris paribus probability to be tax havens. However, social capital counteracts the effect of governance quality. This effect is so strong that the partial effect of governance quality is reversed for countries with the trust index in the top quartile – making these high trust countries le...

  7. Civil Society and Governance

    DEFF Research Database (Denmark)

    Hulgård, Lars

    An illustration of how important the relationship is between civil society anbd governance. A short historic journey with four snapshots of times and situations that have provided interesting evidence about the connection between civil society and governance. My goal for the short historic journey...... is to make clear and hopefully even verify that providing knowledge about the impact of civil society and citizens’ participation on governance is one of the most urgent research tasks in the current period of time....

  8. Energy Efficiency Governance: Handbook

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    This handbook has been written to assist EE practitioners, government officials and stakeholders to establish effective EE governance structures for their country. The handbook provides readers with relevant information in an accessible format that will help develop comprehensive and effective governance mechanisms. For each of the specific topics dealt with (see Figure 1 in the Handbook), the IEA offers guidelines for addressing issues, or directs readers to examples of how such issues have been dealt with by specific countries.

  9. Codes of Good Governance

    DEFF Research Database (Denmark)

    Beck Jørgensen, Torben; Sørensen, Ditte-Lene

    2013-01-01

    Good governance is a broad concept used by many international organizations to spell out how states or countries should be governed. Definitions vary, but there is a clear core of common public values, such as transparency, accountability, effectiveness, and the rule of law. It is quite likely......, transparency, neutrality, impartiality, effectiveness, accountability, and legality. The normative context of public administration, as expressed in codes, seems to ignore the New Public Management and Reinventing Government reform movements....

  10. Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-β/activin/nodal signalling inhibition.

    Science.gov (United States)

    Koel, Mariann; Võsa, Urmo; Krjutškov, Kaarel; Einarsdottir, Elisabet; Kere, Juha; Tapanainen, Juha; Katayama, Shintaro; Ingerpuu, Sulev; Jaks, Viljar; Stenman, Ulf-Hakan; Lundin, Karolina; Tuuri, Timo; Salumets, Andres

    2017-09-01

    Several studies have demonstrated that human embryonic stem cells (hESC) can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 (BMP4) and/or inhibitors of fibroblast growth factor 2 (FGF2) and the transforming growth factor beta (TGF-β)/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days. Genes differentially expressed compared with untreated cells were identified at seven time points. Additionally, expression of total human chorionic gonadotrophin (HCG) and its hyperglycosylated form (HCG-H) were determined by immunoassay from cell culture media. We showed that FGF2 inhibition with BMP4 activation up-regulates syncytiotrophoblast-specific genes (CGA, CGB and LGALS16), induces several molecular pathways involved in embryo implantation and triggers HCG-H production. In contrast, inhibition of the TGF-β/activin/nodal pathway decreases the ability of hESC to form trophoblast-like cells. Information about the conditions needed for hESC differentiation toward trophoblast-like cells helps us to find an optimal model for studying the early development of human trophoblasts in normal and in complicated pregnancy. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  11. 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

  12. 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.

  13. Governance, Trust and Taxes

    DEFF Research Database (Denmark)

    Weihe, Guri; Joensen, E. Juanna Schröter

    This paper examines the role of social capital (trust) vis-à-vis the propensity of a country to be a tax haven. The empirical analysis corroborates that better governed countries have a higher ceteris paribus probability to be tax havens. However, social capital counteracts the effect of governance...... quality. This effect is so strong that the partial effect of governance quality is reversed for countries with the trust index in the top quartile – making these high trust countries less likely to be tax havens – even as governance quality is increased. Thus it is crucial to consider the interaction...

  14. 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 a...

  15. Biophysical characterization of GPCR oligomerization

    DEFF Research Database (Denmark)

    Mathiasen, Signe

    level, and revealed the existence of several dimerization interfaces, each with specific kinetics. Finally we investigated how a property of the membrane solubilizing GPCRs affected oligomerization. We observed a dramatic decrease in oligomer stability with increasing geometrical membrane curvature. We...

  16. Paradoxes around good governance

    NARCIS (Netherlands)

    A.G. Dijkstra (Geske)

    2013-01-01

    textabstract Good governance is not a new concept Ambrogio Lorenzetti made his frescoes on good and bad governance already in the years 1338-1340 They can be viewed in the Palazzo Publicco on one of the most beautiful squares of the world, the Piazza del Campo in Siena, Italy I assume many of you

  17. Human-centred Governance

    DEFF Research Database (Denmark)

    Bason, Christian

    2017-01-01

    Design approaches are now being applied all over the world as a powerful approach to innovating public policies and services. Christian Bason, author of Leading public design: Discovering human-centred governance, argues that by bringing design methods into play, public managers can lead change...... with citizens at the centre, and discover a new model for steering public organisations: human-centred governance....

  18. 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....

  19. Educational Governance in Denmark

    Science.gov (United States)

    Moos, Lejf

    2014-01-01

    Denmark has entered global competition by expanding collaboration with European countries, which is profoundly impacting the public sector and school governance. Relations between the state and institutions are transforming from traditional democratic, public-sector models of governance into new forms characterized as corporate and market-driven…

  20. Tension-filled Governance?

    DEFF Research Database (Denmark)

    Celik, Tim Holst

    on the statesituated tension-filled functional relationship between legitimation and accumulation, the study both historically and theoretically reworks this approach and reapplies it for the post-1970s/1990s governance period. It asks whether and to what extent governance has served as a distinctive post- 1970s/1990s...

  1. Benefit from the Government

    NARCIS (Netherlands)

    Evert Pommer; Jedid-Jah Jonker

    2003-01-01

    Original title: Profijt van de overheid. Income levels are determined to a considerable extent by the government, which exerts an influence through social security and taxation. The traditional purchasing power tables are a reflection of this. However, the influence of the government goes

  2. Global Governance, Educational Change

    Science.gov (United States)

    Mundy, Karen

    2007-01-01

    In the last half decade, a rising literature has focused on the idea that processes of economic, political and social globalization require analysis in terms of governance at the global level. It is argued in this article that emerging forms of global governance have produced significant challenges to conventional conceptions of international…

  3. Learning Democratic Global Governance.

    Science.gov (United States)

    Haavelsrud, Magnus

    1996-01-01

    Outlines a model process of developing knowledge from within different groups and cultures to allow more equitable participation of all world societies in the definition of global governance. Reviews concepts relevant to education's contributions toward learning and creating democratic global governance. Discusses the educational utility of…

  4. Governing EU employment policy

    DEFF Research Database (Denmark)

    Sørensen, Eva; Triantafillou, Peter; Damgaard, Bodil

    2015-01-01

    In the European Union (EU), employment policy is a prerogative of the member states. Therefore the EU's ability to govern in this area depends on its capability to involve national governments and relevant stakeholders in a collaborative effort to formulate and implement shared policy objectives....... of collaboration, the implementation phase mainly consists in the less demanding forms of cooperation and coordination....

  5. Tax administration good governance

    NARCIS (Netherlands)

    Végh, Gyöngyi; Gribnau, Hans

    2018-01-01

    There is no doubt that tax administration is a complex matter. It is institutionalised by a governance framework which is strongly influenced by legal traditions, state governance approaches, historical developments, and norms and values of society. While there are many common aspects of national

  6. Australian Government Information Resources

    OpenAIRE

    Chapman, Bert

    2017-01-01

    Provides an overview of Australian Government information resources. Features content from Australian Government agency websites such as the Department of Environment and Energy, Department of Defence, Australian National Maritime Museum, ANZAC Memorial in Sydney, Department of Immigration & Border Protection, Australian Bureau of Statistics, Australian Dept. of Agriculture and Water Resources, Australian Parliament, Australian Treasury, Australian Transport Safety Board, and Australian Parl...

  7. DOD Open Government

    Science.gov (United States)

    increase transparency and openness. We encourage you to explore other information on our website to learn Defense Search DOD Open Government: Home Open Government @ DoD Transparency Congressional Inquiries IT Dashboard.gov Regulations.gov Challenge.gov Performance.gov ForeignAssistance.gov Transparency

  8. Negotiating Collaborative Governance Designs

    DEFF Research Database (Denmark)

    Plotnikof, Mie

    2017-01-01

    This chapter addresses the design and implementation issues of collaborative governance, a public management practice aimed at involving stakeholders in problem-solving and public innovation.......This chapter addresses the design and implementation issues of collaborative governance, a public management practice aimed at involving stakeholders in problem-solving and public innovation....

  9. Using IT Governance

    Science.gov (United States)

    Brobst, Jan; Council, Chip

    2005-01-01

    The discussion in this article is intended to provide an examination of why top management, IT management, and internal auditors should be interested in IT governance. Some aspects of IT management will be described including implementation, auditing, availability, security, and alignment. One governance framework, COBIT, will be utilized as a…

  10. Governing through standards

    DEFF Research Database (Denmark)

    Brøgger, Katja

    This abstract adresses the ways in which new education standards have become integral to new modes of education governance. The paper explores the role of standards for accelerating the shift from national to transnational governance in higher education. Drawing on the case of higher education...

  11. 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…

  12. The governance of adaptation

    NARCIS (Netherlands)

    Huitema, Dave; Adger, William Neil; Berkhout, Frans; Massey, Eric; Mazmanian, Daniel; Munaretto, Stefania; Plummer, Ryan; Termeer, Katrien

    2016-01-01

    The governance of climate adaptation involves the collective efforts of multiple societal actors to address problems, or to reap the benefits, associated with impacts of climate change. Governing involves the creation of institutions, rules and organizations, and the selection of normative

  13. Making Government Liquid

    DEFF Research Database (Denmark)

    du Gay, Paul; Millo, Yuval; Tuck, Penelope

    2012-01-01

    The financialised character of contemporary rationalities of public governance has been the subject of increased attention within a range of disciplinary and interdisciplinary fields. With this paper we propose a particular analytical framework, focused on the notion of 'governance devices', for ...

  14. 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...

  15. 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.

  16. 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.

  17. 'Governance' sebagai Pengelolaan Konflik

    Directory of Open Access Journals (Sweden)

    Riza Noer Arfani

    2005-03-01

    Full Text Available The article explores the notion of understanding governance as part of conflict management, or vice versa, of undustanding conflict management aspects as benefiting from governance concepts and practices. Governance, with its much broader meaning than government, suggests diverse relevant and significant clues, hints and ideas in the context of conflict management endeavors. one of which is the idea to involve larger audiences and stakeholders –beyond the conventional institutions such as governmental bodies– in policy making processes and public discourses. Such comprehension and appreciation of governance concepts and practices is certainly parallel with the conflict management philosophies, concepis and practices which based on and oriented toward integrative, non-formal and non-litigative mechanisms.

  18. A new corporate governance

    Directory of Open Access Journals (Sweden)

    Ion Bucur

    2015-12-01

    Full Text Available The issue of corporate governance has become increasingly important as globalisation has begun to accelerate and the economic and financial turmoil have intensified. Post-crisis context has imposed the need to expand the prospects for analysis over governance and companies, as well as the need to identify new ways of administration and resource management. From this perspective, the author aims to highlight the conditions, factors and events that have generated profound changes within the business environment, while the analysis is focusing on contemporary changes in the systems of corporate governance and economic mutations, especially in terms of the companies. The establishment of new governance rules is demanding a theoretical approach based on new methodological requirements which are needed to reform theoretical foundations and to promote creative and effective shapes and governance systems.

  19. Cloud Computing Governance Lifecycle

    Directory of Open Access Journals (Sweden)

    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.

  20. Ambidextrous IT Governance

    DEFF Research Database (Denmark)

    Andersen, Peter; Svejvig, Per; Tordrup Heeager, Lise

    2017-01-01

    Through a case study at a global technology company, we investigate how organizations can adapt their IT governance approach to the information system at hand. This is done by considering the degree of information system integration and whether the system is related to supporting operational...... efficiency (exploitation) or innovation (exploration). Based on the findings of the case study, we introduce the concept of ambidextrous IT governance to describe how IT governance can be adapted to fit the dual needs of both exploration and exploitation through the use of IS....

  1. Institutionalizing Global Governance

    DEFF Research Database (Denmark)

    Rasche, Andreas; Gilbert, Dirk Ulrich

    2012-01-01

    The United Nations Global Compact – which is a Global Public Policy Network advocating 10 universal principles in the areas of human rights, labor standards, environmental protection, and anticorruption – has turned into the world's largest corporate responsibility initiative. Although the Global...... Compact is often characterized as a promising way to address global governance gaps, it remains largely unclear why this is the case. To address this problem, we discuss to what extent the initiative represents an institutional solution to exercise global governance. We suggest that new governance modes...

  2. Diversification and Corporate Governance

    NARCIS (Netherlands)

    G.W.J. Hendrikse (George); A.A.C.J. van Oijen

    2002-01-01

    textabstractThis article addresses the impact of governance structure on diversification behavior. Hypotheses are developed regarding the differences in diversification strategy of cooperatives and stock listed companies. The analysis shows that stock listed companies are more diversified than

  3. Governance of the future

    DEFF Research Database (Denmark)

    Galløe, Lotte Rannveig

    a different future for both parents and children. Thus, the approach to PMTO as a technology of the future indicates its expected prevalence in the future and its attempt to reach in to the future becoming of the child. The technology’s involvement of the relatives and its orientation towards shaping......In my presentation I will explore the concept, ‘technology of the future’, in public governance. Public governance within social services aims at changing the existing conditions for the marginalized citizens including children with special needs. I pose the question: what happens if public...... governance seek to chance the possible future conditions and targets the marginalized child’s relatives? Parent Management Training (PMTO) is studied as a technology of the future that expands and transforms governance. PMTO targets parents with aggressive and asocial children and aims to “create the parent...

  4. Sustainability : Politics and governance

    NARCIS (Netherlands)

    Heinrichs, Harald; Biermann, Frank

    2016-01-01

    he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

  5. Government Risk-Bearing

    CERN Document Server

    1993-01-01

    The u.s. government bulks large in the nation's financial markets. The huge volume of government-issued and -sponsored debt affects the pricing and volume ofprivate debt and, consequently, resource allocation between competing alternatives. What is often not fully appreciated is the substantial influence the federal government wields overresource allocation through its provisionofcreditandrisk-bearing services to the private economy. Because peopleand firms generally seekto avoid risk, atsomeprice they are willing to pay another party to assume the risk they would otherwise face. Insurance companies are a class of private-sector firms one commonly thinks of as providing these services. As the federal government has expanded its presence in the U.S. economy during this century, it has increasingly developed programs aimed at bearing risks that the private sector either would not take on at any price, or would take on but atapricethoughtto besogreatthatmostpotentialbeneficiarieswouldnotpurchase the coverage. To...

  6. Lean Government Methods Guide

    Science.gov (United States)

    This Guide focuses primarily on Lean production, which is an organizational improvement philosophy and set of methods that originated in manufacturing but has been expanded to government and service sectors.

  7. Enacting Governance through Strategy

    DEFF Research Database (Denmark)

    Brandtner, Christof; Höllerer, Markus A.; Meyer, Renate E.

    2017-01-01

    of strategy documents in city administration addresses these challenges. Our central claim is that strategy documents can be understood as a distinct discursive device through which local governments enact aspired governance configurations. We illustrate our argument empirically using two prominent examples...... that, while showing similar features and characteristics, are anchored in different administrative traditions and institutional frameworks: the city administrations of Sydney, Australia, and Vienna, Austria. The contribution of the paper is to show how strategy documents enact governance configurations...... along four core dimensions: the setting in space and time, the definition of the public, the framing of the res publica and legitimacy issues. Moreover, our comparative analysis of Sydney and Vienna gives evidence of differences in governance configurations enacted through strategy documents....

  8. The government of life

    DEFF Research Database (Denmark)

    Villadsen, Kaspar; Wahlberg, Ayo

    2015-01-01

    . Subsequent research on biopolitics and governmentality has tended to separate the concepts, differentiating into distinct research traditions each with different intellectual pathways. We propose to bring these conceptual innovations together to understand contemporary problems of the government of life...... of death power, the interplay of sovereignty, discipline and security, governmentalization through medical normalization, and ‘securitization’ of life as circulations and open series. The article also introduces this special feature on the government of life in which significant scholars explores issues...

  9. Remittances Deteriorate Governance

    OpenAIRE

    Faisal Z. Ahmed

    2013-01-01

    I use a natural experiment of oil-price-driven remittance flows to poor, non-oil-producing Muslim countries to demonstrate that remittances deteriorate the quality of governance, especially in countries with weak democratic institutions. The results indicate that a 1 standard deviation increase in remittances raises corruption by 1.5 index points (on a 6-point scale), which is equivalent to a [dollar]600 decrease in per capita GDP. Concomitantly, remittances may enable governments to reduce t...

  10. 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...

  11. Minsky on "Big Government"

    Directory of Open Access Journals (Sweden)

    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.

  12. Histological and radiographic evaluation of the muscle tissue of rats after implantation of bone morphogenic protein (rhBMP-2 in a scaffold of inorganic bone and after stimulation with low-power laser light

    Directory of Open Access Journals (Sweden)

    Bengtson Antonio

    2010-01-01

    Full Text Available Objective: The present study histologically and radiologically evaluates the muscle tissue of rats after implantation of bone morphogenic protein (rhBMP-2 in a natural inorganic bone mineral scaffold from a bull calf femur and irradiation with low-power light laser. Materials and Methods: The right and left hind limbs of 16 rats were shaved and an incision was made in the muscle on the face corresponding to the median portion of the tibia, into which rhBMP-2 in a scaffold of inorganic bone was implanted. Two groups of limbs were formed: control (G1 and laser irradiation (G2. G2 received diode laser light applied in the direction of the implant, at a dose of 8 J/cm2 for three minutes. On the 7th, 21st, 40th and 112th days after implantation, hind limbs of 4 animals were radiographed and their implants removed together with the surrounding tissue for study under the microscope. The histological results were graded as 0=absence, 1=slight presence, 2=representative and 3=very representative, with regard to the following events: formation of osteoid structure, acute inflammation, chronic inflammation, fibrin deposition, neovascularization, foreign-body granuloma and fibrosis. Results: There were no statistically significant differences in these events at each evaluation times, between the two groups (P > 0.05; Mann-Whitney test. Nevertheless, it could be concluded that the natural inorganic bone matrix with rhBMP-2, from the femur of a bull calf, is a biocompatible combination. Conclusions: Under these conditions, the inductive capacity of rhBMP-2 for cell differentiation was inhibited. There was a slight acceleration in tissue healing in the group that received irradiation with low-power laser light.

  13. Open Government and (Linked (Open (Government (Data

    Directory of Open Access Journals (Sweden)

    Christian Philipp Geiger

    2012-12-01

    Full Text Available This article explores the opening and the free usage of stored public sector data, supplied by state. In the age of Open Government and Open Data it’s not enough just to put data online. It should be rather weighed out whether, how and which supplied public sector data can be published. Open Data are defined as stored data which could be made accessible in a public interest without any restrictions for usage and distribution. These Open Data can possibly be statistics, geo data, maps, plans, environmental data and weather data in addition to materials of the parliaments, ministries and authorities. The preparation and the free access to existing data permit varied approaches to the reuse of data, discussed in the article. In addition, impulses can be given for Open Government – the opening of state and administration, to more transparency, participation and collaboration as well as to innovation and business development. The Open Data movement tries to get to the bottom of current publication processes in the public sector which could be formed even more friendly to citizens and enterprises.

  14. Global health governance as shared health governance.

    Science.gov (United States)

    Ruger, Jennifer Prah

    2012-07-01

    With the exception of key 'proven successes' in global health, the current regime of global health governance can be understood as transnational and national actors pursuing their own interests under a rational actor model of international cooperation, which fails to provide sufficient justification for an obligation to assist in meeting the health needs of others. An ethical commitment to providing all with the ability to be healthy is required. This article develops select components of an alternative model of shared health governance (SHG), which aims to provide a 'road map,' 'focal points' and 'the glue' among various global health actors to better effectuate cooperation on universal ethical principles for an alternative global health equilibrium. Key features of SHG include public moral norms as shared authoritative standards; ethical commitments, shared goals and role allocation; shared sovereignty and constitutional commitments; legitimacy and accountability; country-level attention to international health relations. A framework of social agreement based on 'overlapping consensus' is contrasted against one based on self-interested political bargaining. A global health constitution delineating duties and obligations of global health actors and a global institute of health and medicine for holding actors responsible are proposed. Indicators for empirical assessment of select SHG principles are described. Global health actors, including states, must work together to correct and avert global health injustices through a framework of SHG based on shared ethical commitments.

  15. 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.

  16. Corporate Governance Country Assessment : Malaysia

    OpenAIRE

    World Bank

    2012-01-01

    This report assesses Ghana s corporate governance policy framework. It highlights recent improvements in corporate governance regulation, makes policy recommendations, and provides investors with a benchmark against which to measure corporate governance in Ghana. It is an update of the 2005 Corporate Governance ROSC. Good corporate governance enhances investor trust, helps to protects mino...

  17. 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...

  18. Dangerous Liaisons? Governments, companies and Internet governance

    Directory of Open Access Journals (Sweden)

    Francesca Musiani

    2013-02-01

    Full Text Available Private actors in the information technology sector are currently playing an increasingly important role in content mediation, as well as in regulation of online forms of expression, with implications for both internet rights and economic freedom. The “privatisation of internet governance” (DeNardis, 2010, is not a new dynamic; however, in a scenario in which users are taking advantage of increasingly sophisticated technology, the centralisation and concentration characterising today’s most widespread internet services are contributing to the accentuation of this tendency. The 'inherently political' qualities of search engine algorithm development, video content removals, blocking of domain names – actions that originate and rest with the private sector’s handling of the internet’s infrastructure – should not be neglected in our assessment of the field of internet governance today.

  19. Romanian government bond market

    Directory of Open Access Journals (Sweden)

    Cornelia POP

    2012-12-01

    Full Text Available The present paper aims to present the level of development reached by Romanian government bond market segment, as part of the country financial market. The analysis will be descriptive (the data series available for Romania are short, based on the secondary data offered by the official bodies involved in the process of issuing and trading the Romanian government bonds (Romanian Ministry of Public Finance, Romanian National Bank and Bucharest Stock Exchange, and also on secondary data provided by the Federation of European Stock Exchanges.To enhance the market credibility as a benchmark, a various combination of measures is necessary; among these measures are mentioned: the extension of the yield curve; the issuance calendars in order to improve transparency; increasing the disclosure of information on public debt issuance and statistics; holding regular meetings with dealers, institutional investors and rating agencies; introducing a system of primary dealers; establishing a repurchase (repo market in the government bond market. These measures will be discussed based on the evolution presented inside the paper.The paper conclude with the fact that, until now, the Romanian government bond market did not provide a benchmark for the domestic financial market and that further efforts are needed in order to increase the government bond market transparency and liquidity.

  20. Climate change governance

    Energy Technology Data Exchange (ETDEWEB)

    Knieling, Joerg [HafenCity Univ. Hamburg (Germany). Urban Planning and Regional Development; Leal Filho, Walter (eds.) [HAW Hamburg (Germany). Research and Transfer Centre Applications of Life Science

    2013-07-01

    Climate change is a cause for concern both globally and locally. In order for it to be tackled holistically, its governance is an important topic needing scientific and practical consideration. Climate change governance is an emerging area, and one which is closely related to state and public administrative systems and the behaviour of private actors, including the business sector, as well as the civil society and non-governmental organisations. Questions of climate change governance deal both with mitigation and adaptation whilst at the same time trying to devise effective ways of managing the consequences of these measures across the different sectors. Many books have been produced on general matters related to climate change, such as climate modelling, temperature variations, sea level rise, but, to date, very few publications have addressed the political, economic and social elements of climate change and their links with governance. This book will address this gap. Furthermore, a particular feature of this book is that it not only presents different perspectives on climate change governance, but it also introduces theoretical approaches and brings these together with practical examples which show how main principles may be implemented in practice.

  1. 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

  2. Decentralization and Governance in Indonesia

    NARCIS (Netherlands)

    Holzhacker, Ronald; Wittek, Rafael; Woltjer, Johan

    2016-01-01

    I. Theoretical Reflections on Decentralization and Governance for Sustainable Society 1. Decentralization and Governance for Sustainable Society in Indonesia Ronald Holzhacker, Rafael Wittek and Johan Woltjer 2. Good Governance Contested: Exploring Human Rights and Sustainability as Normative Goals

  3. Four logics of governance

    DEFF Research Database (Denmark)

    Friche, Nanna; Normann Andersen, Vibeke

    unintended consequences. Theoretically, we draw on different management and governance theories, e.g. performance management. Empirically, the study is based on surveys to teachers and students at all Danish vocational colleges and interviews with school leaders, teachers and students at six colleges (cases...... and well-being of students enrolled in the VETs must be strengthened. We focus on target 1, 2 and 4. The reform is being implemented in a field of VET that can be characterized by four logics of governance. Firstly, a governance logic characterized by institutional independence of vocational colleges......For the last fifteen years completion rates in Danish vocational education and training (VET) has stayed on a rather low level. In 2014, only half of the students enrolled in a vocational program on upper secondary level, graduated from the program (Flarup et al 2016). In Denmark, like in other...

  4. Electoral Governance in Brazil

    Directory of Open Access Journals (Sweden)

    Vitor Marchetti

    2012-06-01

    Full Text Available Electoral governance has increasingly more frequently been the object of study of the comparative politics literature. This article examines the electoral governance institutional model adopted in Brazil and its consequences for political/electoral competition. It is argued herein that Brazil’s Electoral Justice System, motivated by the institutional design, has ended up becoming one of the main actors of the country’s recent democratic consolidation, being decisive not only with regard to rule adjudication and application, but also to rulemaking. With the purpose of assessing this governance model in action, three important recent rulings by Brazil’s Electoral Justice System are analysed here: verticalization of the coalitions, reduction in the number of councillors, and party loyalty.

  5. 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)

  6. '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)....

  7. Corporate governance and liquidity

    DEFF Research Database (Denmark)

    Farooq, Omar; Derrabi, Mohamed; Naciri, Monir

    2012-01-01

    This paper examines the impact of corporate governance mechanisms on liquidity in the MENA region, i.e. Morocco, Egypt, Saudi Arabia, United Arab Emirates, Jordan, Kuwait, and Bahrain. Using turnover as a proxy for liquidity, we document significant difference in liquidity between the pre......- and the post-crisis periods in the MENA region. In addition, our results show that bulk of this reduction in turnover can be explained due to weaknesses of corporate governance mechanisms. For example, that dividend payout ratio and choice of auditors – proxies for agency problems – can explain the entire...... difference in liquidity between the two periods. Furthermore, our results indicate that more than 50% of this difference between the two periods can be explained by operational and informational complexity of a firm – proxy for transparency. We argue that poor corporate governance mechanisms increase...

  8. Pension Fund Governing Board

    CERN Multimedia

    HR Department

    2008-01-01

    Note The CERN pension scheme is based on the principle of defined benefits, so beneficiaries continue to receive the benefits to which they are entitled in accordance with the Rules of the Pension Fund. This means that pension entitlements under the Rules are not directly affected by the financial crisis and the current economic situation. However, the adjustment of pensions to the cost of living is not automatic and, under the method applied since 2006, must take into account the Fund’s financial position. Meeting of the Pension Fund Governing Board The Pension Fund Governing Board held its eighth meeting at ESO in Garching, Germany (near Munich) on 24 October 2008. Before starting its work, the Governing Board had the privilege of hearing an opening address by Professor Tim de Zeeuw, the Director General of ESO. Professor de Zeeuw described the mission of ESO and the ambitious projects of his organisation, which performs astronomy observations using telescopes located in...

  9. Managing e-government

    DEFF Research Database (Denmark)

    Rose, Jeremy; Persson, John Stouby; Heeager, Lise Tordrup

    2015-01-01

    Public sector managers take much of the responsibility for selecting, commissioning, implementing and realising benefits from information technology (IT) projects. However, e-Government initiatives often suffer from complexity, vision failure, lack of goal clarity and insufficient commitment....... These problems may stem from value traditions that are deeply ingrained in managers' cultural environments but not always in harmony with each other. A first step towards working with value complexity is to understand it; we synthesise a model of value positions for e-Government derived from major traditions...... in the public administration literature. Four value positions relevant to e-Government together with their IT assumptions are identified; they reflect the ideals of professionalism, efficiency, service and engagement. A qualitative investigation of Danish local authority managers displays both value congruence...

  10. Tactics of the governed

    DEFF Research Database (Denmark)

    Rasmussen, Mattias Borg

    2017-01-01

    Abandonment has become a performative idiom in Andean Peru, where it retains its purchase despite the investments of the state. Local development is tied to the desire to be governed. In spite of prolonged state presence, the villages’ relationship to authorities is continuously and persistently...... figured as one of abandonment: villages are abandoned because someone is deliberately holding them in such unfortunate conditions. To figure abandonment in village politics is to draw on this idiom as an effective means of both communicating the historical experience of governance and putting forward...

  11. Governing IT outsourcing relationships

    CERN Document Server

    Kuhlmann, Daniel

    2012-01-01

    Hauptbeschreibung The dynamics of the relationship between service recipient and service provider in IS outsourcing relationships recently gained increased attention as relationships are believed to have a considerable influence on IS outsourcing success. This study adds to this growing field of interest by developing an IS outsourcing relationship framework in the form of a process model. Three rather disjointed areas of research, namely contractual governance, relational norms, and control, have been set in a common context by interrelating them as the three main governance modes

  12. Instruments of Transformative Governance

    DEFF Research Database (Denmark)

    Borrás, Susana

    production and distribution channels. PDPs aim at overcoming current market and government failures by pooling resources in the attempt to solve this global social challenge. Thus, PDPs are a case of instruments of transformative research and innovation, operating in a transnational governance context....... They exhibit three novelties: they address strategic long-term problems in a holistic manner, set substantive output-oriented goals, and are implemented through new organizational structures. After characterizing the different types of current PDPs and the context in which they emerged, the paper examines...

  13. Why Governments Intervene

    DEFF Research Database (Denmark)

    Brown, Dana; Knudsen, Jette Steen

    for this phenomenon. Research has tended either to rely on cross-country comparisons that generalize tendencies within given countries; or to over-generalize global trends. The current paper analyzes particular CSR policies in two countries – Denmark and the United Kingdom. We find that the rationales for government...... initiatives on CSR are neither consistent across countries or within them. Instead, CSR policies are utilized to address multiple issues crossing various areas of governance, including domestic social policy, global competitiveness policies and foreign policy....

  14. Making Migrants Governable

    DEFF Research Database (Denmark)

    Stenum, Helle

    2012-01-01

    This paper will investigate the production of knowledge regarding the number of illegalized migrants. Estimation of the number has been the common frame for production of this kind of knowledge, performed by social scientists, government officials, NGOs and others, but now biometric technology...... by biometric technology will produce increased objectivity and depolitization in numbers of irregular migrants which could not be obtained in the field of estimation. The level of truth reflects the level of control and surveillance fixed as a strategy of government of mobility in the biometric technology....

  15. Local government`s pollution prevention program

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, D. [Boulder Country Pollution Prevention Program, Boulder, CO (United States)

    1996-12-31

    The pollution prevention program operated by the Health Department of Boulder County is called Business Partners for a Clean Environment (Business Partners). It is a cooperative effort among local businesses, the City of Boulder, Boulder County, and the Boulder Chamber of Commerce. This nonregulatory, incentive-based program provides industry with pollution prevention information and technical assistance necessary to reduce and/or eliminate environmental waste. This paper provides an overview of the program development, creation of partnerships and trust, and some of the results from implementation of the program. Following the first 18 months of the program, 35 businesses were recognized as Business Partners. The Business Partners program has also received an achievement award from the National Association of Counties for promoting {open_quotes}responsible, responsive, and effective government{close_quotes} and two governor`s awards from the State of Colorado. Participating businesses have demonstrated that a pollution prevention program can reduce environmental waste, increase employee safety, and decrease costs. 4 refs., 4 figs., 5 tabs.

  16. 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...

  17. Global Food Governance

    NARCIS (Netherlands)

    Oosterveer, P.J.M.

    2005-01-01

    Globalisation in food production and consumption is fundamentally transforming a wide variety of social practices at different levels in society. Simply adding another level of governance will therefore not solve the problems related to food production and consumption in global modernity. Different

  18. Governing Logistics Information Platforms

    NARCIS (Netherlands)

    Klievink, A.J.; Aldewereld, H.M.; Knol, A.; Tan, Y.H.

    2014-01-01

    The Extended Single Window (ESW) project aims to support goods flows by Information and Communication Technology (ICT). Specifically, the project takes the concept of Single Windows (often used in the sense that governments offer a single portal or interface to which businesses can submit

  19. 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…

  20. Data Quality Assurance Governance

    OpenAIRE

    Montserrat Gonzalez; Stephanie Suhr

    2016-01-01

    This deliverable describes the ELIXIR-EXCELERATE Quality Management Strategy, addressing EXCELERATE Ethics requirement no. 5 on Data Quality Assurance Governance. The strategy describes the essential procedures and practices within ELIXIR-EXCELERATE concerning planning of quality management, performing quality assurance and controlling quality. It also depicts the overall organisation of ELIXIR with emphasis on authority and specific responsibilities related to quality assurance.

  1. GOOD GOVERNANCE AND TRANSFORMATION

    Directory of Open Access Journals (Sweden)

    Hans-Jürgen WAGENER

    2005-12-01

    Full Text Available Transformation of a totalitarian, basically administratively coordinated system into a democratic one that is coordinated predominantly by markets and competition has been triggered by, among others, the perception of a serious deficit in welfare and happiness. Public policy has a special task transforming the economic order by liberalisation, privatisation, stabilisation and the installation of institutions that are supportive for competition. After 15 years since transformation began, there are sufficiently differentiated success stories to test the hypothesis: it was good governance that is responsible for success and bad governance for failure. The empirical results support the “Lorenzetti hypothesis”: where freedom, security and trust prevail, the economy flourishes, where they are lacking, the costs of long-term investment are too high. The initial conditions of transition countries seem to be quite similar, nevertheless, even there one can discern good and bad governance. The extent of socialist lawfulness, planning security, cronyism and corruption differed widely between East Berlin and Tashkent. And a good deal of such variations can be found in the pre-socialist history of these countries. However, the main conclusion is that the co-evolution hypothesis states that both, welfare and good governance, go together.

  2. 3 CFR - Government Contracting

    Science.gov (United States)

    2010-01-01

    ... contract oversight could reduce such sums significantly. Government outsourcing for services also raises... a risk that taxpayer funds will be spent on contracts that are wasteful, inefficient, subject to... mission. In such cases, the agency must ensure that the risks associated with noncompetitive contracts are...

  3. 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

  4. Corporate governance through codes

    NARCIS (Netherlands)

    Haxhi, I.; Aguilera, R.V.; Vodosek, M.; den Hartog, D.; McNett, J.M.

    2014-01-01

    The UK's 1992 Cadbury Report defines corporate governance (CG) as the system by which businesses are directed and controlled. CG codes are a set of best practices designed to address deficiencies in the formal contracts and institutions by suggesting prescriptions on the preferred role and

  5. Getting Port Governance Right

    DEFF Research Database (Denmark)

    de Langen, Peter; Saragiotis, Periklis

    2018-01-01

    This chapter discusses the relevance of ports for economic development and next identifies port governance as a critical determinant of a well-functioning port industry. While in the past decades privately owned terminal operating companies have emerged and contributed to more efficient supply ch...

  6. Contractual Corporate Governance

    NARCIS (Netherlands)

    Goergen, M.; Renneboog, L.D.R.

    2008-01-01

    Companies have the choice to deviate from their national corporate governance standards by opting into another system. They can do so via contractual devices – such as cross-border mergers and acquisitions, (re)incorporations, and cross-listings – which enable firms to choose their preferred level

  7. Corporate Media Governance

    NARCIS (Netherlands)

    Kempen, Petrus Cornelis

    2011-01-01

    The media can make or break a reputation. This being said, it seems to be essential for companies, governments and institutions to pay specific attention to corporate media management in their daily operations. However, this thesis shows that they often neglect to pay adequate attention to corporate

  8. Decentralized environmental governance

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

    Tula

    Human Development, a Road to the. Future. Systematization of ... Opportunities for Sustainability and Natural Resources Access for Poor. Rural Areas ... natural resource management. Under this ... Governance is defined as the formal and informal ... approval of the Environmental Impact Study, the strong oppo- sition of the ...

  9. Governability in Contemporary Mexico

    Directory of Open Access Journals (Sweden)

    Leonardo Curzio Gutiérrez

    1998-04-01

    Full Text Available Given the difficulties to establish a concept of governability and the frequent ideological usage of the term, it is much more operative to turn to the principle of governability, in the broad sense, which supports itself on five pillars: the political legitimacy of the government, the governmental efficiency to attend to the demands of society, the existence of shared social project, the agreement with the principle special interest groups, and international viability. The analysis of the structure and relevance of these five points during the long period of political transition that Mexico underwent between 1988 and 1997 shows how it was possible for this country to play off certain factors against each other in order to secure governability and safeguard against the consequences of any resultant imbalances. Between 1998-1993, the government of Salinas de Gotari based itself on the viability of a neoliberal project within an international context, and on this projectís attention to domestic demands as well as on the governmentís pact with elites. Institutional integration and legitimacy made up, then, for a process of discreet liberalization and the lack of democratic electoral commitment, which culminated in the PRI’s 1994 elections victory.The assassination of Colosia, though, and the appearance of the EZLN and the subsequent crisis surrounding the peso’s devaluation that accompanied Ernesto Zedilloís rise to power soon led to the collapse of those pillars of support. Crowning the process of the silenttransition were the elections of 1997, which makes it possible to say that in Mexico today there are now smooth elections, but that reform of the State is still unresolved —a subject that includes the reduction of the president’s competence. Seen in the short term, the most direct threats to Mexico’s governability will come as a result of the lack of attention to those demands of society’s underprivileged and the ill

  10. 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...

  11. 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.

  12. Corporate Governance and Shareholder Litigation

    OpenAIRE

    Kalchev, Georgi

    2009-01-01

    The probability for shareholder litigation is studied and how corporate governance characteristics and other factors explain it. Shareholder litigation results from failure of corporate governance. Thus a better quality of corporate governance is hypothesized to decrease the litigation probability. Corporate governance index is constructed based on principal components. It is found to be a significant predictor of shareholder litigation.

  13. Governance, resource curse and donor

    OpenAIRE

    Wiig, Arne

    2008-01-01

    Plan Part 1. Governance What is good governance? Why is it important? How can we measure good governance? Part 2. The resource curse and the importance of governance in resource rich countries Focus on political economy (PE) models of the resource curse Policy implications Some donor initiatives Transparency and the EITI Petroleum related aid - Window dressing initiatives or research based? Conclusion Governance, resource curse and donor

  14. Auditing IT Governance

    Directory of Open Access Journals (Sweden)

    Florin-Mihai ILIESCU

    2010-01-01

    Full Text Available Effective IT governance helps ensure that IT supports business goals, optimizes business investment in IT, and appropriately manages IT-related risks and opportunities. Organizations that realize the IT is no longer a support process and embeds value and risks need a structured approach for better managing Information Technology, enable its capability to deliver added value enterprise wide and for setting up a risk management program to address new risks arising for usage of IT in business processes. In order to assess if IT Governance is in line with industry practices, IT Auditors need a good understanding of processes and applicable standards, particular audit work programs and experience in assessing potential problem indicators.

  15. Whole of Government Accounts

    DEFF Research Database (Denmark)

    Pontoppidan, Caroline Aggestam; Chow, Danny; Day, Ronald

    In our comparative study, we surveyed an emerging literature on the use of consolidation in government accounting and develop a research agenda. We find heterogeneous approaches to the development of consolidation models across the five countries (Australia, New Zealand, UK, Canada and Sweden...... of financial reporting (GAAP)-based reforms when compared with budget-centric systems of accounting, which dominate government decision-making. At a trans-national level, there is a need to examine the embedded or implicit contests or ‘trials of strength’ between nations and/or institutions jockeying...... for influence. We highlight three arenas where such contests are being played out: 1. Statistical versus GAAP notions of accounting value, which features in all accounting debates over the merits and costs of ex-ante versus ex-post notions of value (i.e., the relevance versus reliability debate); 2. Private...

  16. Website Quality in Government

    DEFF Research Database (Denmark)

    Sørum, Hanne; Andersen, Kim Normann; Clemmensen, Torkil

    2013-01-01

    . Social implications – The overall digital enabled transformation of government appears to be guided by a rather heterogeneous set of quality standards. While a variance of quality standards might stimulate innovation in websites, it can also lead to a substantial difference in digital services provided...... to citizens. Thus, the authors' research stimulates the awareness of diversity of quality parameters and could have as an implication that national and international standards beyond accessibility standards are more explicitly shared and debated. Originality/value – The aim of this paper is to provide......Purpose – The objective of this paper is to investigate how webmasters within government bodies explain quality of websites. Despite the central position for advancing the communication, bridging usability tests and design, there are surprisingly few studies on how webmasters perceive, experience...

  17. Governance by algorithms

    Directory of Open Access Journals (Sweden)

    Francesca Musiani

    2013-08-01

    Full Text Available Algorithms are increasingly often cited as one of the fundamental shaping devices of our daily, immersed-in-information existence. Their importance is acknowledged, their performance scrutinised in numerous contexts. Yet, a lot of what constitutes 'algorithms' beyond their broad definition as “encoded procedures for transforming input data into a desired output, based on specified calculations” (Gillespie, 2013 is often taken for granted. This article seeks to contribute to the discussion about 'what algorithms do' and in which ways they are artefacts of governance, providing two examples drawing from the internet and ICT realm: search engine queries and e-commerce websites’ recommendations to customers. The question of the relationship between algorithms and rules is likely to occupy an increasingly central role in the study and the practice of internet governance, in terms of both institutions’ regulation of algorithms, and algorithms’ regulation of our society.

  18. Competence, governance, and entrepreneurship

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahnke, Volker

    This title illustrates modern economics. Because it informs strategic choices, it is relevant to business administration in general, and for strategic management in particular. Two dominant streams may be identified in the literature, namely the "competence" and "governance" perspectives...... on the firm. While there has been little direct discussion between the main proponents of these perspectives, both claim that they are reaching for a "strategic theory of the firm". Such a theory would not only shed light on the classical questions considered in the theory of the firm (e.g. why firms exist......, what determines their boundaries and internal organization), but would also be helpful for informing strategy issues, such as understanding strategic flexibility, strategic options, and the sources of competitive advantage. This volume brings together prominent voices on competence, governance...

  19. Local Governance and Corruption

    OpenAIRE

    Marius PROFIROIU; Tudorel ANDREI; Gheorghe POPESCU; Alina PROFIROIU

    2006-01-01

    This paper attempts to examine, from the Romanian perspective, the degree to which decentralization process and improvement of local governance contributes to the reduction of corruption in the short and medium term. Through the methodology that is used the paper is consistent with the international trend that endeavors to analyze the impact of corruption on economic and social processes at the local level. In addition, recent research on corruption issues has focused upon the measurement of ...

  20. General Principles Governing Liability

    International Nuclear Information System (INIS)

    Reyners, P.

    1998-01-01

    This paper contains a brief review of the basic principles which govern the special regime of liability and compensation for nuclear damage originating on nuclear installations, in particular the strict and exclusive liability of the nuclear operator, the provision of a financial security to cover this liability and the limits applicable both in amount and in time. The paper also reviews the most important international agreements currently in force which constitute the foundation of this special regime. (author)

  1. Banking governance: New Approaches

    Directory of Open Access Journals (Sweden)

    Victor Mihăiţă Duţă

    2016-11-01

    Full Text Available Banks are companies like any other. However, banks are distinguished by certain intrinsic characteristics of companies that have a different impact on the motivation of stakeholders. Among these features, we mention:partnership and shareholders governance agreements; banks are heavily regulated companies; banking assets is the main source of haze banking and information asymmetry; between the bank and depositors there is a problem of moral hazard.

  2. Cloud Computing Governance Lifecycle

    OpenAIRE

    Soňa Karkošková; George Feuerlicht

    2016-01-01

    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 uncle...

  3. The roles of government

    International Nuclear Information System (INIS)

    Aigrain, P.

    1988-01-01

    The author chooses to address his talk to governments as a broad category, not differentiating the more centralized, socialized, federal, or for that matter the role of smaller governmental entities within countries, and the role they can have in impacting science. He chooses to try to say what governments should do, and with a few exceptions, what they should avoid doing, in order to support the development of physics, and for that matter other sciences within their countries. The major role is in education, where governments can prepare people for work in these disciplines, and also present the disciplines in an interesting manner so that the best minds can be attracted to these areas. The second major role is in the support of basic research in high technology areas. Some of this involves very large resource investments, but not all areas are equally expensive to support. There is a particular pitfall when governments become the consumer for basic research, for example in the case of national defense concerns, when the consumer can have a profound effect on the research effort in a country, not always for the betterment of science or society. Fiscal matters are equally important, not only in the support of the individual worker, support of the basic research, support of education, but also in the general attititude to supporting physics high tech work in the private sector within countries. Governmantal fiscal policies can have profound influences on the way private capital flows into such initiatives. Finally he touches on the need for those in basic research and high tech work to have contacts, all kinds of contacts, which foster the exchange of information and ideas, and the development of new approaches to old and new problems

  4. The governance of nanotechnology

    OpenAIRE

    Jim Whitman

    2007-01-01

    Despite the promises made for nanotechology, its direction and momentum as it has developed to date already pose very considerable problems of regulation and control in quite fundamental ways. This article will review these difficulties under four themes. First, the principal agents for framing governance agreements (states) are also the principal proponents of nanoscience and nanotechnology. Second, the speed of new advances in nanotechnology and the reach of their implications are already o...

  5. Government Is Whose Problem?

    OpenAIRE

    Jon D. Wisman

    2013-01-01

    This article addresses the political meaning of President Ronald Reagan's 1981 declaration that "government is the problem." Whereas historically the state had been used by elites to extract as much surplus as possible from producers, with democratization of the franchise, the state became the sole instrument that could limit, or even potentially end, the extraction of workers' surplus. Once control of the state is in principle democratized by the ballot box, the fortunes of the elite depend ...

  6. Pension Fund Governing Board

    CERN Multimedia

    HR Department

    2008-01-01

    Note The CERN pension scheme is based on the principle of defined benefits, so beneficiaries continue to receive the benefits to which they are entitled in accordance with the Rules of the Pension Fund. This means that pension entitlements under the Rules are not directly affected by the financial crisis and the current economic situation. However, the adjustment of pensions to the cost of living is not automatic and, under the method applied since 2006, must take into account the Fund’s financial position. Meeting of the Pension Fund Governing Board The Pension Fund Governing Board held its eighth meeting at ESO in Garching (near Munich), Germany on 24 October 2008. Before starting its work, the Governing Board had the privilege of hearing an opening address by Professor Tim de Zeeuw, the Director General of ESO. Professor de Zeeuw described the mission of ESO and the ambitious projects of his organisation, which performs astronomy observations using telescopes located in Chile. The Director-General receiv...

  7. 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.

  8. Digital government and public health.

    Science.gov (United States)

    Fountain, Jane E

    2004-10-01

    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 agency's readiness for digital government includes examination of technical, managerial, and political capabilities. Public health agencies are especially challenged by a lack of funding for technical infrastructure and expertise, by privacy and security issues, and by lack of Internet access for low-income and marginalized populations. Public health agencies understand the difficulties of working across agencies and levels of government, but the development of new, integrated e-programs will require more than technical change - it will require a profound change in paradigm.

  9. 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,

  10. Brexit and government procurement

    OpenAIRE

    Dawar, Kamala

    2017-01-01

    This briefing paper looks at some of the legal issues that will affect the UK’s public procurement laws and policies following Brexit. For, once the UK revokes the European Communities Act 1972, it will no longer be obligated to follow the EU Procurement Directives, nor will it be subject to the commitments the EU has signed up to on behalf of the UK in the WTO Government Procurement Agreement (GPA) and in Preferential Trade Agreements (PTAs). Additionally, under the Devolution Settlement of ...

  11. World governance for energy

    International Nuclear Information System (INIS)

    Kerebel, C.; Keppler, J.H.

    2009-01-01

    As energy is a strategic stake for industrial societies through supply security, economical competitiveness and environmental performance, it is well-founded and useful to consider the way that energy production and consumption are organized. This document introduces the notion of energy governance and its different interpretations, then analyses its stakes and challenges (petroleum, natural gas, investment needs), and discusses some of the debates already in progress, such as the UNO's negotiations on greenhouse gas emission reduction or the impact of the WTO talks on energy exchanges

  12. Governing Forest Ecosystem Services for Sustainable Environmental Governance: A Review

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. Steuern und Governance

    Directory of Open Access Journals (Sweden)

    Eduard Müller

    2014-05-01

    Full Text Available ENGLISH: Taxation, in the modern state, has long been a mass phenomenon with an interdisciplinary outlook. On the macro level of the state, a new generation of administrative reforms has crystallized under the label “good public governance”. These reforms seek to resolve regulatory interdependence of state and non - state actors by way of cooperation and interaction. In parallel, on the micro level of businesses, “corporate governance” – voluntary compliance with legal and ethical standards – has become an increasingly important issue. With a view to tax law and tax collection, these developments open up new possibilities to raise tax compliance by means of consensual and cooperative instruments and, accordingly, address taxation as a mass phenomenon. DEUTSCH: Besteuerung ist im modernen Staat ein Massenphänomen und längst interdisziplinär ausgerichtet. Auf der Makro-Ebene des Staates hat sich unter dem Begriff Good Public Governance eine neue Generation von Staats- und Verwaltungsreformen herausgebildet, die Regelungsbeziehungen von staatlichen und nichtstaatlichen Akteuren durch Kooperationen und Interaktionen zu lösen versucht. Parallel dazu hat auf der Mikro-Ebene der Unternehmen mit dem Thema Corporate Governance die freiwillige Einhaltung von rechtlichen und ethischen Regeln an Bedeutung gewonnen. Für das Steuerrecht und den Steuervollzug resultieren aus diesen Entwicklungen neue Möglichkeiten, durch Nutzung konsens- und kooperationsorientierter Instrumente die Tax Compliance zu erhöhen und so dem Massenphänomen Besteuerung gerecht zu werden.

  15. Características morfogênicas e estruturais do capim-tifton 85 sob doses de nitrogênio e alturas de corte Morphogenic and structural characteristics of tifton 85 bermudagrass under different nitrogen doses and harvesting heights

    Directory of Open Access Journals (Sweden)

    Odilon Gomes Pereira

    2011-09-01

    Full Text Available Objetivou-se avaliar características morfogênicas e estruturais do capim-tifton 85 adubado com nitrogênio nas doses de 0, 33, 66, 100 ou 133 kg/ha.ano em três alturas à data de corte (30, 40 ou 50 cm. O delineamento foi inteiramente casualizado em esquema de parcelas subdivididas com três repetições. As doses de nitrogênio (N corresponderam às parcelas e as alturas ao tempo de corte, às subparcelas. A taxa de aparecimento foliar do capim-tifton 85 foi influenciada de forma negativa pela altura da planta na época do corte e de maneira positiva pela dose de nitrogênio. A taxa de senescência foliar e o número total de folhas por perfilho diminuíram, enquanto a taxa de alongamento foliar aumentou com a adubação nitrogenada. Por outro lado, a taxa de senescência foliar e o número total de folhas por perfilho aumentaram com a altura das plantas na época da colheita. Já o número de folhas vivas por perfilho não foi influenciado pela dose de nitrogênio nem pela altura da planta na época do corte. Para uma mesma altura do capim-tifton 85 na época da colheita, a adubação nitrogenada aumenta o fluxo de tecidos e a frequência de desfolhação. Na condição de desfolhação intermitente, o capim-tifton 85 deve ser colhido com altura de até 30 cm.The objective of this study was to evaluate the morphogenic and structural characteristics of tifton 85 bermudagrass under different nitrogen doses (0, 33, 66, 100 or 133 kg/ha.year of N and three different plant heights (30, 40 or 50 cm at harvesting time. A split plot scheme in a completely randomized design with three replications was used. The nitrogen (N doses stood for the portions and the haversting heights, for the subportions. The leaf appearance rate of tifton 85 bermudagrass was negatively influenced by plant height at harvesting time, but positively influenced by N dose. Leaf senescence rate and total number of leaves per tiller decreased, whereas leaf elongation rate

  16. Trialogue model for ecosystem governance.

    CSIR Research Space (South Africa)

    Hattingh, J

    2007-01-01

    Full Text Available form and timescale to ensure good governance. In essence, good governance promotes democratic management of ecosystems and, by inference, prudentwater resourcemanagement. Consequently, it is likely that the type of governance that occurs most often... that, unless the imperative for civic science to support democratic governance is institutionalised through policy and strategy, it is unlikely that there will be sufficient human and financial investment in civic science as a means to promote...

  17. Corporate Governance in Costa Rica

    OpenAIRE

    Gilberto E. Arce; Edgar Robles C.

    2005-01-01

    This paper examines corporate governance practices in Costa Rica. First, it estimates corporate governance charter measures using firm-level data for 87 Costa Rican firms and studies their impact on the firms` performance; here, the mean of the corporate governance charters for the publicly traded firms is equal to 56. 14. Second, new evidence is presented on de jure and de facto corporate governance charter measures at the firm level and on their effect on the performance of the firm. The re...

  18. Theoretical Framework for Corporate Governance

    OpenAIRE

    Georgescu Cristina Elena

    2012-01-01

    History has revealed that there is a never-ending evolution of theories or models of corporate governance. Companies are trying to instill the sense of governance into their corporate structure. This article is a review of literature on the range of theories in corporate governance. The fundamental theories in corporate governance began with the agency theory, expanded into stewardship theory and stakeholder theory and evolved to transaction cost theory. However, these theories address the ca...

  19. The governance of hybrid organisations

    DEFF Research Database (Denmark)

    Spear, Roger; Cornforth, Chris

    2010-01-01

    The focus of this chapter is on the governance of third sector organizations (TSOs) and the challenges that are raised by hybridity. In particular it will focus on the question how does hybridity affect governance structures and processes and the challenges that governing bodies face?...

  20. Canadian Government Electronic Information Policy.

    Science.gov (United States)

    Nilsen, Kirsti

    1993-01-01

    Examines development and evolution of Canadian government information policy in response to issues of preservation of data, information industry involvement in government data development and marketing, role of Crown copyright, and public access to government information in electronic formats. Six key information policy instruments are also…

  1. Uruguay - Corporate Governance Country Assessment

    OpenAIRE

    World Bank

    2005-01-01

    This report provides an assessment of Uruguay's corporate governance policy framework, enforcement and compliance practices. It highlights recent improvements in corporate governance regulation, makes policy recommendations, and provides investors with a benchmark against which to measure corporate governance in Uruguay. The report identifies several key next steps that focus on implementa...

  2. Corporate Governance Country Assessment : Uruguay

    OpenAIRE

    World Bank

    2005-01-01

    This report provides an assessment of Uruguay's corporate governance policy framework, enforcement and compliance practices. It highlights recent improvements in corporate governance regulation, makes policy recommendations, and provides investors with a benchmark against which to measure corporate governance in Uruguay. The report identifies several key next steps that focus on implementation including: Improving corporate information, particularly ownership disclosure, related party transac...

  3. Characterizing Government Social Media Research

    DEFF Research Database (Denmark)

    Medaglia, Rony; Zheng, Lei

    2016-01-01

    As research on government social media continues to grow in quantity and scope, this area calls for mapping and systematization, in order to stimulate better-informed studies in the future. This paper draws on a comprehensive review of government social media literature in the e...... a four-point research agenda for future government social media research....

  4. Government, Money, and International Politics

    OpenAIRE

    Hoppe, Hans-Hermann

    2003-01-01

    In this paper, the author deals with: (1) Definition of government; incentive structure under government: taxation, war and territorial expansion. (2) Origin of money; government and money; the devolution of money from commodity to fiat money. (3) International politics and monetary regimes; monetary imperialism and the drive toward a one-world central bank and fiat currency.

  5. 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.

  6. Government by standards

    DEFF Research Database (Denmark)

    Triantafillou, Peter

    2016-01-01

    Since 2009, all Danish hospitals have been subjected to a comprehensive, mandatory accreditation system, the so-called Danish Quality Model (DDKM), in order to assure the quality of hospital services. So far there is no evidence of DDKM’s positive effects on clinical outcome and it may even be co......, it is argued that the accreditation system is hard to refuse because it promises to increase the quality of hospital services and, more importantly, because the procedural standards espoused by DDKM work through the structured and accountable freedom of medical staff....... be contributing to accountability overload. This article seeks to provide an explanation for why hospital staff seems to accept, albeit grudgingly and partially, the imposition of a new, comprehensive accountability system with questionable clinical merits. Inspired by Michel Foucault’s analytics of government...

  7. Nanomedicine: Governing uncertainties

    Science.gov (United States)

    Trisolino, Antonella

    Nanomedicine is a promising and revolutionary field to improve medical diagnoses and therapies leading to a higher quality of life for everybody. Huge benefits are expected from nanomedicine applications such as in diagnostic and therapeutic field. However, nanomedicine poses several issues on risks to the human health. This thesis aims to defense a perspective of risk governance that sustains scientific knowledge process by developing guidelines and providing the minimum safety standards acceptable to protect the human health. Although nanomedicine is in an early stage of its discovery, some cautious measures are required to provide regulatory mechanisms able to response to the unique set of challenges associated to nanomedicine. Nanotechnology offers an unique opportunity to intensify a major interplay between different disciplines such as science and law. This multidisciplinary approach can positively contributes to find reliable regulatory choices and responsive normative tools in dealing with challenges of novel technologies.

  8. Local Governance and Corruption

    Directory of Open Access Journals (Sweden)

    Marius PROFIROIU

    2006-06-01

    Full Text Available This paper attempts to examine, from the Romanian perspective, the degree to which decentralization process and improvement of local governance contributes to the reduction of corruption in the short and medium term. Through the methodology that is used the paper is consistent with the international trend that endeavors to analyze the impact of corruption on economic and social processes at the local level. In addition, recent research on corruption issues has focused upon the measurement of the level of corruption level and on its impact on the growing rate of the GDP (Mauro [1995]1, Abed and Davoodi2, Krueger [1974]3, on the impact upon some of the national economical sectors (Tanzi [1998]4, Shang-Jin Wei [2001]5, or on the decentralization processes (Shah [2006]6.

  9. Privatization Of Global Governance

    Directory of Open Access Journals (Sweden)

    T. J. Biersteker

    2017-01-01

    Full Text Available Thomas Biersteker graduated from Chicago University (BF in Political Science and MIT (MA in Political Science and got PhD in Political Science in MIT as well. Later professor Biersteker lectured in Yale University (1976-1985, South Carolina University (1985-1992 and Brown University (1992-2006. He could be described as a constructivist focusing his research on global governance, international organizations and transnational policy networks, construction of sovereignty and regimes of targeted sanctions. Professor Birsteker kindly agreed to give an interview to the “MGIMO Review of International Relations” during a seminar within the research project - Grant of RFBR No. 16-23-41004. The seminar was also attended by M.M. Lebedeva, Yu.A. Nikitin, A.I. Nikitin, I.A. Istomin.

  10. Tourism and Governance

    DEFF Research Database (Denmark)

    Dredge, Dianne

    2015-01-01

    This chapter discusses tourism education for sustainability with a particular focus on the challenges and opportunities associated with preparing students to work within complex tourism governance settings. It takes the position that the development of tourism within a sustainability framework...... requires that tourism professionals effectively engage in dynamic social discourses where difficult trade-offs are made between competing demands. The challenge for tourism education is therefore to prepare graduates to work in these complex, value-laden, socio-political environments where they can...... proactively and positively contribute to developing forms of tourism that progress the objectives of sustainable development. This chapter explores this challenge in terms of a philosophic tourism practitioner education, and in doing so, discusses three key dimensions of this education: historical antecedents...

  11. Governing the Conflicted Commons

    DEFF Research Database (Denmark)

    Sareen, Siddharth

    for collective decision-making. This makes them the natural institution of choice to nurture democratic practice among the Ho people of Jharkhand’s West Singhbhum district, whose village communities form the focus of this study. However, Jharkhand’s state laws are at odds with national ones, and decentralisation...... works more along administrative than democratic lines. This limits the extent to which the village assemblies can nurture democratisation in the implementation of development schemes. One village assembly is far more successful at governing natural resources than the other. This is shown to be due...... to proactive leadership, a cohesive community and local social mobilisation within the successful village assembly, in contrast to the co-option of benefits by some village inhabitants in the other. Based on these cases, it is concluded that while a local deliberative institution is essential for nurturing...

  12. Governing Knowledge Processes

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Husted, Kenneth; Michailova, Snejina

    2003-01-01

    An under-researched issue in work within the `knowledge movement' is therelation between organizational issues and knowledge processes (i.e., sharingand creating knowledge). We argue that managers can shape formalorganization structure and organization forms and can influence the moreinformal org...... to Anna Grandori for numerous excellent comments on anearlier draft. The standard disclaimer applies.Keywords: Knowledge creation, knowledge sharing, governance, organizationaleconomics, organizational behavior.......An under-researched issue in work within the `knowledge movement' is therelation between organizational issues and knowledge processes (i.e., sharingand creating knowledge). We argue that managers can shape formalorganization structure and organization forms and can influence the moreinformal...... organizational practices in order to foster knowledge sharing andcreation. Theoretically, we unfold this argument by relying on key ideas oforganizational economics and organizational behaviour studies. We put forwarda number of refutable propositions derived from this reasoning.AcknowledgmentsWe are grateful...

  13. Reinventing government: Reinventing Hanford

    International Nuclear Information System (INIS)

    Mayeda, J.T.

    1994-05-01

    The Hanford Site was established in 1943 as one of the three original Manhattan Project locations involved in the development of atomic weapons. It continued as a defense production center until 1988, when its mission changed to environmental restoration and remediation. The Hanford Site is changing its business strategy and in doing so, is reinventing government. This new development has been significantly influenced by a number of external sources. These include: the change in mission, reduced security requirements, new found partnerships, fiscal budgets, the Tri-Party agreement and stakeholder involvement. Tight budgets and the high cost of cleanup require that the site develop and implement innovative cost saving approaches to its mission. Costeffective progress is necessary to help assure continued funding by Congress

  14. Pension Fund governing board

    CERN Multimedia

    HR Department

    2008-01-01

    On 16 March and 7 May, the Pension Fund Governing Board (PFGB) held its fourth and fifth meetings The first of these meetings was primarily dedicated to the examination of the strategic asset allocation. The PFGB reaffirmed the main goal of the new strategic asset allocation: to improve the Pension Fund’s position with regard to risk by lowering overall portfolio volatility through suitable investments in less volatile asset classes such as real estate and absolute return strategies, where the return does not depend on market trends and negative growth is extremely unlikely. The finalised document will be presented to the Finance Committee and the Council at their June meetings for approval, in accordance with the provisions of the Levaux report. The PFGB also took note of the Internal Audit’s report on Pension Fund operations and decided to refer it to Working Group I as a working document for establishing a control and internal monitoring system for Pension Fund oper...

  15. Knowledge and Governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul

    Assumptions about the knowledge held by economic agents have been an integral part of the theory of economic organization since its inception. However, recent work—here called “knowledge governance”—has more explicitly highlighted knowledge as both an independent and dependent variable. Thus......, knowledge may also be seen as being caused by governance mechanisms and structures; specifically, incentives, allocations of decision rights, organizational structure and so on influence the search for knowledge, and the creation, sharing and integration of knowledge. More philosophically, the concern...... with the role of knowledge in the context of economic organization prompts a reevaluation of a number of the fundamental assumptions that are often used to guide theory-building in the economics of organization (e.g., Bayesian and game theoretical foundations)....

  16. Mediatization and Government Communication

    DEFF Research Database (Denmark)

    Laursen, Bo; Valentini, Chiara

    2015-01-01

    do not tend to get a media coverage that matches the EU’s considerable influence on European citizens’ daily lives. This study, which is based on in-depth interviews with European Parliament press officers, concludes that these professionals are indeed attuned to a “media logic......Social actors see exposure in the news media as attractive for publicity purposes and are under pressure to adapt their press work to a “media logic” to be attractive sources for journalists and editors. This article investigates the European Parliament’s press officers’ professional practices...... in the light of mediatization and government communication theories. Without one pan-European public sphere, the European Parliament, like the other European Union (EU) institutions, competes with national actors for the news media’s attention in the EU’s twenty-eight national public spheres, where EU affairs...

  17. Local Government System in Japan

    Directory of Open Access Journals (Sweden)

    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.

  18. Digital governance and institutional change

    DEFF Research Database (Denmark)

    Schlæger, Jesper

    2010-01-01

    Coal allocation in China is a seminal case of e-government in the political economy. The empirical phenomenon of market supporting e-government has not been systematically analysed. By developing and applying a digital governance model this article examines institutional change in a case of coal...... allocation reform in China. The case shows how the central state used e-government to get rid of planning overload. Coal allocation meetings were abolished in favour of an ecology of online market solutions. The findings suggest that further research on Chinese e-government would benefit from attention...

  19. 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…

  20. Local Government Internal Audit Compliance

    Directory of Open Access Journals (Sweden)

    Greg Jones

    2015-09-01

    Full Text Available Local government councils (LGC rely on a number of funding sources including state and federal governments as well as their community constituents to enable them to provide a range of public services. Given the constraints on these funding sources councils need to have in place a range of strategies and policies capable of providing good governance and must appropriately discharge their financial accountabilities. To assist LGC with meeting their governance and accountability obligations they often seek guidance from their key stakeholders. For example, in the Australian State of New South Wales (NSW, the Office of Local Government has developed a set of guidelines, the Internal Audit Guidelines. In 2010 the NSW Office of Local Government issued revised guidelines emphasising that an internal audit committee is an essential component of good governance. In addition, the guidelines explained that to improve the governance and accountability of the councils, these committees should be composed of a majority of independent members. To maintain committee independence the guidelines indicated that the Mayor should not be a member of the committee. However these are only guidelines, not legislated requirements and as such compliance with the guidelines, before they were revised, has been demonstrated to be quite low (Jones & Bowrey 2013. This study, based on a review of NSW Local Government Councils’ 2012/2013 reports, including Annual Reportsrelation to internal audit committees, to determine if the guidelines are effective in improving local government council governance.

  1. 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

  2. Governing the Nexus for Sustainability

    Directory of Open Access Journals (Sweden)

    Marx Sina

    2015-01-01

    Full Text Available This report summarizes the challenges of and requirements for effective governance of the water, energy and food nexus. With global dynamics such as climate change, urbanization and changing consumption patterns, governing resources in a coherent manner becomes both more complex and more relevant for sustainable development. Governance challenges include nexus economics (costs and benefits of different approaches to resource management, institutional design (like questions of how decision-making should be best distributed and good governance (how to make sure that nexus governance adheres to certain agreed upon principles and values. In terms of economics, a balance between sector specific actions and nexus governance is required. For effective decision-making it is important that power among different institutions is both distributed and coordinated. Good nexus governance requires targets that can be monitored to make sure that basic principles are followed and to examine whether progress toward sustainable development is being made.

  3. 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...

  4. Enabling the hypothesis-driven prioritization of ligand candidates in big databases: Screenlamp and its application to GPCR inhibitor discovery for invasive species control

    Science.gov (United States)

    Raschka, Sebastian; Scott, Anne M.; Liu, Nan; Gunturu, Santosh; Huertas, Mar; Li, Weiming; Kuhn, Leslie A.

    2018-03-01

    While the advantage of screening vast databases of molecules to cover greater molecular diversity is often mentioned, in reality, only a few studies have been published demonstrating inhibitor discovery by screening more than a million compounds for features that mimic a known three-dimensional (3D) ligand. Two factors contribute: the general difficulty of discovering potent inhibitors, and the lack of free, user-friendly software to incorporate project-specific knowledge and user hypotheses into 3D ligand-based screening. The Screenlamp modular toolkit presented here was developed with these needs in mind. We show Screenlamp's ability to screen more than 12 million commercially available molecules and identify potent in vivo inhibitors of a G protein-coupled bile acid receptor within the first year of a discovery project. This pheromone receptor governs sea lamprey reproductive behavior, and to our knowledge, this project is the first to establish the efficacy of computational screening in discovering lead compounds for aquatic invasive species control. Significant enhancement in activity came from selecting compounds based on one of the hypotheses: that matching two distal oxygen groups in the 3D structure of the pheromone is crucial for activity. Six of the 15 most active compounds met these criteria. A second hypothesis—that presence of an alkyl sulfate side chain results in high activity—identified another 6 compounds in the top 10, demonstrating the significant benefits of hypothesis-driven screening.

  5. Project governance: "Schools of thought"

    Directory of Open Access Journals (Sweden)

    Michiel Christiaan Bekker

    2014-02-01

    Full Text Available The terminology, definition and context of project governance have become a focal subject for research and discussions in project management literature. This article reviews literature on the subject of project governance and categorise the arguments into three schools of thought namely the single-firm school, multi-firm school and large capital school. The single-firm school is concerned with governance principles related to internal organisational projects and practice these principles at a technical level. The multi-firm school address the governance principles concerned with two of more organisations participating on a contractual basis on the same project and focus their governance efforts at the technical and strategic level. The large capital school consider projects as temporary organisations, forming their own entity and establishing governance principles at an institutional level. From these schools of thought it can be concluded that the definition of project governance is dependent on the type of project and hierarchical positioning in the organisation. It is also evident that further research is required to incorporate other governance variables and mechanisms such as transaction theory, social networks and agency theory. The development of project governance frameworks should also consider the complexity of projects spanning across international companies, across country borders and incorporating different value systems, legal systems, corporate governance guidelines, religions and business practices.

  6. Democracy over governance

    Directory of Open Access Journals (Sweden)

    Amelia Correa

    2013-12-01

    Full Text Available Varieties of institutional economics are available to evaluate varieties of capitalism. These methodologies dig behind preferences and technology to arrive at the ground on which agents make choices. The individual is at the foundation of these edifices, neoclassical and otherwise. Consequently, the denouement of all these models is that the market knows best in the absence of effective counterfactuals. A natural corollary is that the task of the government is to set effective mechanisms in place in order to approach the best outcomes. In contrast, we propose a framework which contends with the modern economy as an aggregate that evolves in historical time. Problems like effective demand failures are endemic to capitalist economies. Therefore, systematic State intervention is essential to their functioning. In particular, political economy teaches us that intervention must be in the interest of wage earners. In contrast to the earlier model, the fabric of norms and conventions that facilitate the growth and development of economies must emerge from the consciousness and practices of the working class.

  7. Happiness, Sadness and Government

    Directory of Open Access Journals (Sweden)

    G. Duncan

    2013-11-01

    Full Text Available Policy-making that re-presents – as objects of concern and by means of statistics – the suffering or depression and the happiness of populations indicates an evolving form of governance that examines and reshapes subjectivity itself. Never before have states of subjectivity been acted upon, through surveys, statistical and policy analysis, and scientific disciplines, to the extent seen today. This article: Documents changing epistemic co-ordinates, especially in psychology and economics, that first occluded happiness in the interests of objectivity, but, in recent decades, marked out a renewed ‘science’ of happiness.Examines changes in the discursive formulation of depression, as a counterpart to happiness.Argues that, seen in terms of bio-power, contemporary concerns for happiness and depression are consistent – rather than incompatible – with one another. How can so many claim to be happy when so many, we are told, are depressed, anxious or suffering emotional pain? There is no underlying contradiction here, for two reasons: Happiness and depression are manifestations of the same political discourse (or aspects of a political subjectivity characterized by dis-inhibition, consumer self-indulgence and performance anxiety. And, just as we needed madness in order to understand ‘sanity,’ or the prison in order to view ourselves as ‘free,’ so we rely upon concerns about depression in order to understand and act upon ourselves as subjects capable of unlimited happiness.

  8. Global health justice and governance.

    Science.gov (United States)

    Ruger, Jennifer Prah

    2012-01-01

    While there is a growing body of work on moral issues and global governance in the fields of global justice and international relations, little work has connected principles of global health justice with those of global health governance for a theory of global health. Such a theory would enable analysis and evaluation of the current global health system and would ethically and empirically ground proposals for reforming it to more closely align with moral values. Global health governance has been framed as an issue of national security, human security, human rights, and global public goods. The global health governance literature is essentially untethered to a theorized framework to illuminate or evaluate governance. This article ties global health justice and ethics to principles for governing the global health realm, developing a theoretical framework for global and domestic institutions and actors.

  9. INTERNATIONAL GOVERNMENT SECURITIES: SPECIFIC FUNCTIONING

    Directory of Open Access Journals (Sweden)

    N. Versal

    2013-11-01

    Full Text Available It’s disclosed the features of the international government securities market during 1993 – 2012: main players are the developed countries (Western Europe, Canada, USA with the increasing role of developing countries; debt crises have the negative impact as on the development of the international government securities market, but also on the international capital market as a whole; debt crises are not a spontaneous phenomenon, and usually occur as a result of inadequate growth in GDP increasing government debt.

  10. 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...

  11. Corporate Governance Disclosure in Malaysia

    OpenAIRE

    ONG, Wei Jiin

    2006-01-01

    This research provides evidence on corporate governance disclosure in Malaysia based on a sample of 25 Malaysian public listed companies on the Kuala Lumpur Composite Index (KLCI) in the year 1998 and 2005 that are listed on the Bursa Malaysia. The purpose of this dissertation is to examine whether after the launch of the Malaysian Code on Corporate Governance (HLFC, 2000) following the 1997/98 financial crisis, corporate governance in Malaysia has improved in terms of disclosure information ...

  12. Interorganizational Care needs Horizontal Governance

    OpenAIRE

    Spierenburg, Monique; van de Schoot, Rian

    2016-01-01

    Interorganizational Governance isn’t a theme for research yet. Because of the complexity of problems of (new) clients there is an urgent need to cooperate in networks of welfare, care, initiatives of citizens, general practitioners and others. And because of the policy of the (local) government, the transition of the healthcare systems, with the vision to help people close by. In these practice we see new ideas and forms of governance.What’s the problem? Decentralization, integration and pers...

  13. COMPARATIVE STUDY ON CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Gavrea Corina

    2011-12-01

    Full Text Available Corporate governance is a key element of today’s economic reality being more and more present in many countries around the world. This paper has two main objectives. The first one is to offer more insight into the concept of corporate governance by a thorough literature review and by presenting and analyzing a framework of corporate governance. The second objective of this paper is to investigate the corporate governance situation in three developing economies (Romania, Bulgaria and Hungary. The World Bank and the European Bank for Reconstruction and Development published a series of reports on corporate governance. The present study uses data from these reports in order to illustrate how these developing economies are dealing with corporate governance. Based on ROSC Reports a corporate governance score was calculated. As this score shows, there is room for improvement for all three developing economies. This study is important because it shows the differences in corporate governance among developing economies and the need to study these nations at the individual country level. Corporate governance has many benefits for developing economies. It helps developing economies to register sustainable growth rates, to increases investors’ confidence in the national economy, and to increase the ability of capital markets to mobilize savings.

  14. Governance and Foreign Aid Allocation

    National Research Council Canada - National Science Library

    Akramov, Kamiljon T

    2006-01-01

    .... Specifically, the study explores how different categories of aid affect economic growth, whether the quality of governance is significant in explaining differences in economic growth, and whether...

  15. Afghanistan: Government Formation and Performance

    National Research Council Canada - National Science Library

    Katzman, Kenneth

    2009-01-01

    .... However, ethnic disputes remain confined largely to political debate and competition, enabling President Karzai to focus on improving governance, reversing security deterioration, and his re-election...

  16. Dawn of e-government

    DEFF Research Database (Denmark)

    Henriksen, Helle Zinner; Damsgaard, Jan

    2007-01-01

    Most countries have defined strategies for e-government. The objectives for implementing e-government are often defined but the means for fuelling the adoption and diffusion of e-government are typically less well clear in the policy statements. The present study assesses the impact of latest...... internally and externally. The e-Day initiative represents a drastic change in the former policy statements concerning IT adoption and diffusion in Danish government. The policy statements had previously been based on voluntary adoption focusing on visions and pedagogical intervention in governmental...

  17. 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…

  18. 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…

  19. Adopting service governance governing portfolio value for sound corporate citzenship

    CERN Document Server

    AXELOS, AXELOS

    2015-01-01

    Adopting Service Governance provides a useful umbrella for a number of frameworks including ITIL®, TOGAF®, COBIT®, ITSM, BSM, Business Analysis, Programme Management, Management of Value, Management of Portfolios and Management of Risk by establishing the top-down governance of an organisation through services.

  20. 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 ...

  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

  2. Corporate Governance and Equity Returns

    OpenAIRE

    Uchida, Shigeru

    2012-01-01

    This paper analyses the relationship between corporate governance and equity returns from the small investors view point. A primary survey has been conducted to gather the data required to examine the link. Preliminary result of the study shows that the four elements of governance: board structure, transparency, fairness and responsibility are positively related with equity returns.

  3. Introducing Children to Democratic Government

    Science.gov (United States)

    Alleman, Janet; Brophy, Jere

    2006-01-01

    Researchers have been studying children's knowledge, thinking, and attitudes about government for several decades. However, the studies focusing on elementary students, and especially primary students, have little or nothing to say about children's ideas about democracy or democratic government. That is because children at these ages have not yet…

  4. Corporate Governance Frequently Asked Questions

    OpenAIRE

    International Finance Corporation

    2016-01-01

    This guidebook is designed to address common questionson corporate governance that are frequently asked byowners and managers of companies in the Middle Eastand North Africa (MENA) region. It familiarizes readerswith the basic concepts of corporate governance,providing a comprehensive overview of the subject matter,using case studies as practical examples of corporategovernance application...

  5. The Business of Governing Schools

    Science.gov (United States)

    Gann, Nigel

    2015-01-01

    In September 2015, the Secretary of State for Education asked for more business involvement in schools, and in particular for business leaders' help to improve failing schools. This article questions the twenty-year campaign by all governments to engage business expertise and values in the governance of schools.

  6. BOOK REVIEW: Improving Local Government

    Directory of Open Access Journals (Sweden)

    Jaap de Visser

    2009-11-01

    Full Text Available This book is a compilation of ten essays on local government with an introductory and concluding chapter. The themes discussed include metropolitan governance, the role of community leadership, the value of best practice as an administration technique, indigenous knowledge, intergovernmental relations, public-private partnerships and local management.

  7. An international corporate governance index

    NARCIS (Netherlands)

    Martynova, M.; Renneboog, L.D.R.; Wright, M.; Siegel, D.; Keasey, K.; Filatotchev, I.

    2013-01-01

    This chapter presents a comparative analysis of corporate governance regulatory systems and their development since 1990 in the United States and in 30 European countries. It introduces a proposed methodology that would help create detailed corporate governance indices which describe the primary

  8. Faculty Communication with Governing Boards

    Science.gov (United States)

    Tiede, Hans-Joerg

    2013-01-01

    College and university governance works best when every constituency within the institution has a clear understanding of its role with respect to the other constituencies. It works best when communication among the governing board, the administration, and the faculty (not to mention the staff and students) is regular, open, and honest. Too often…

  9. Hungary : Corporate Governance Country Assessment

    OpenAIRE

    World Bank

    2003-01-01

    This report assesses the corporate governance policy framework and enforcement and compliance practices in Hungary. Hungary has already invested considerable resources in upgrading its legislation to meet European Union Directives, and the legislative and regulatory framework dealing with corporate governance issues is robust. The major issues identified by this review include: (1) the gen...

  10. 76 FR 2001 - Government Property

    Science.gov (United States)

    2011-01-12

    ... change ``approval of the NASA Industrial Property Officer to ``approval of the Plant Clearance Officer... equipment), demolition, or management of real property. 0 3. Subpart 1845.3 is added to read as follows...-Government) use of any NASA equipment. 1845.302 Use of Government property on contracts with foreign...

  11. Recent Literature on Government Information

    Science.gov (United States)

    Sleeman, Bill

    2004-01-01

    The purpose of this column is to provide government information scholars and students with a broad overview of recent publications about government information from the literature of librarianship, archives, information technology management, public policy and law. Given the volume of literature produced in this field, a columnist cannot claim…

  12. LOCAL GOVERNMENT AND INTERGOVERNMENTAL RELATIONS ...

    African Journals Online (AJOL)

    GRACE

    issues of tax jurisdiction, revenue allocation, intergovernmental relations ... The 1999 Nigeria constitution stipulates the functions and powers of the ... systems of government, is characterized with diverse ethnic groups, ... states perceived to be an attempt by the federal government to relate directly to ..... excise taxes on oil.

  13. How to govern the cloud?

    NARCIS (Netherlands)

    Prüfer, J.; Diamond, S.; Wainwright, N.

    2013-01-01

    This paper applies economic governance theory to the cloud computing industry. We analyze which governance institution may be best suited to solve the problems stemming from asymmetric information about the true level of data protection, security, and accountability offered by cloud service

  14. 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)

  15. Calvin on church and government

    Directory of Open Access Journals (Sweden)

    W.A. Dreyer

    2010-07-01

    Full Text Available This article examines Calvin’s understanding of civil govern- ment as well as the relationship between church and govern- ment against the background of radical political change during the sixteenth century. It becomes clear that Calvin had an organic understanding of church, government and people. These three entities are interwoven and interact on the basis of the covenant and civil contract. Calvin’s approach, however, is not limited to the covenant, but has a surprising richness and diversity. He integrated theological, juristic and philosophical concepts in his understanding of the state. It is further shown that Calvin’s high regard for civil government, entrenched the corpus christianum, even though he clearly distinguished between ecclesiastical and civil governance. It is also shown that Calvin had a fundamental influence on many of the political concepts which are generally accepted within modern democra- cies.

  16. Practice Governance 101, v. 2013.

    Science.gov (United States)

    Hayes, David F

    2013-03-01

    Consensus governance is a principal weakness leading to group malfunction and failure. Inadequate group governance produces inadequate decisions, leading to inconsistent patient care, inadequate responses to marketplace challenges, and disregard for customers and strategic partners. The effectiveness of consensus management is limited by the pervasive incomplete knowledge and personal biases of partners. Additional structural weaknesses of group behavior include information cascade, the wisdom of the crowd, groupthink, pluralistic ignorance, analysis paralysis, peer pressure, and the herding instinct. Usual corporate governance is, by necessity, the governance model of choice. Full accountability of the decider(s) is the defining requirement of all successful governance models. Copyright © 2013 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  17. 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.

  18. 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…

  19. 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.

  20. 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.

  1. Government Services Information Infrastructure Management

    Energy Technology Data Exchange (ETDEWEB)

    Cavallini, J.S.; Aiken, R.J.

    1995-04-01

    The Government Services Information Infrastructure (GSII) is that portion of the NII used to link Government and its services, enables virtual agency concepts, protects privacy, and supports emergency preparedness needs. The GSII is comprised of the supporting telecommunications technologies, network and information services infrastructure and the applications that use these. The GSII is an enlightened attempt by the Clinton/Gore Administration to form a virtual government crossing agency boundaries to interoperate more closely with industry and with the public to greatly improve the delivery of government services. The GSII and other private sector efforts, will have a significant impact on the design, development, and deployment of the NII, even if only through the procurement of such services. The Federal Government must adopt new mechanisms and new paradigms for the management of the GSII, including improved acquisition and operation of GSII components in order to maximize benefits. Government requirements and applications will continue to evolv. The requirements from government services and users of form affinity groups that more accurately and effectively define these common requirements, that drive the adoption and use of industry standards, and that provide a significant technology marketplace.

  2. Russian Initiatives in Internet Governance

    Directory of Open Access Journals (Sweden)

    Sergey Sergeevich Shirin

    2014-01-01

    Full Text Available The article is devoted to the research of Russian initiatives concerning its participation in international system of Internet governance. In the research, conceptual and theoretic basis for participation of state governments in Internet governance is given, academic discourse of this issue is assessed, the review of main Russian initiatives made from 2005 (since the second stage of the World Summit on Information Society till the present day is carried out. The conclusion is made that the most successful Internet governance initiative of Russia is the implementation of cyrillic top level domains. Much less successful are Russian attempts to reconstruct existing organizational structure of Internet governance. Russian policy is assessed as a policy of preferring loud statements and PR rather than real influence on development of Internet technologies. Russia consideres Internet as political resource and tries to increase its influence on decision making process on a political, not operational level of Internet governance. The author states that federal government of the United States of America has fully lost the control on the domain name systems. These functions are going to be given to the private sector, while ICANN, which was established according to the Memorandum of Understanding/Joint Project Agreement with U.S. Department of Commerce, is becoming a truly independent international organization. Considering this, the author comes to the conclusion that political transformations for the sake of Russia are already made. He also forecast that next initiatives of Russia will be directed to the segmentation of the Internet.

  3. 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...

  4. 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.

  5. GOVERNMENT INVOLVEMENT IN CONSUMPTION BEHAVIOUR

    Directory of Open Access Journals (Sweden)

    CRISTINA ZAMFIR

    2010-01-01

    Full Text Available In this article, we will follow the involvement that the government has,through its expenses, on the consumption behavior. The involvement that the government has inthe consumption behavior is made through fees and taxes that are applied on income. Fees andtaxes are applied to the different forms of income but in this article we will be focused only onthe influence of them on wages. In order to analyze the involvement of government expenses onconsumption behavior an utility model will be used.

  6. Corporate governance cycles during transition

    DEFF Research Database (Denmark)

    Jones, Derek C.; Mygind, Niels

    2004-01-01

    -sures for restructuring produce strong impulses for ownership changes. There is limited possibility for external finance because of the embryonic development of the banking system and the capital markets during early transition. The governance cycle is also influenced by specific features of the institutional, cultural...... is faster in Estonia and this can be explained by the relatively fast pace of institutional change and evolution of important gov-ernance institutions, including tough bankruptcy legislation and advances in the financial system. JEL-codes: G3, J5, P2, P3 Keywords: corporate governance, life...

  7. Governing Individual Knowledge Sharing Behavior

    DEFF Research Database (Denmark)

    Minbaeva, Dana; Pedersen, Torben

    2010-01-01

    The emerging Knowledge Governance Approach asserts the need to build microfoundations grounded in individual action. Toward this goal, using the Theory of Planned Behavior, we aim to explain individual knowledge sharing behavior as being determined by the intention to share knowledge and its...... antecedents: attitude toward knowledge sharing, subjective norms, and perceived behavioral control. In addition, we consider managerial interventions (governance mechanisms) that managers can employ to influence the identified antecedents and thereby govern individual knowledge sharing behavior. We test...... a positive effect on subjective norms and perceived behavioral control, respectively....

  8. IT Management in Local Government

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2010-01-01

    The use of information technology (IT) is increasingly important for local governments (municipalities) in adhering to their responsibilities for providing services to citizens and this requires effective IT management. We present an engaged scholarship approach to formulating the IT management...... problems with local government – not for local government. We define such engaged problem formulation as joint learning and definition of a contemporary and complex problem by researchers and those who experience and know the problem. This engaged problem formulation process was carried out...

  9. Adaptive approaches to biosecurity governance.

    Science.gov (United States)

    Cook, David C; Liu, Shuang; Murphy, Brendan; Lonsdale, W Mark

    2010-09-01

    This article discusses institutional changes that may facilitate an adaptive approach to biosecurity risk management where governance is viewed as a multidisciplinary, interactive experiment acknowledging uncertainty. Using the principles of adaptive governance, evolved from institutional theory, we explore how the concepts of lateral information flows, incentive alignment, and policy experimentation might shape Australia's invasive species defense mechanisms. We suggest design principles for biosecurity policies emphasizing overlapping complementary response capabilities and the sharing of invasive species risks via a polycentric system of governance. © 2010 Society for Risk Analysis

  10. Iraq: Government Formation and Benchmarks

    National Research Council Canada - National Science Library

    Katzman, Kenneth

    2007-01-01

    Elections in 2005 produced a permanent constitution and a broad-based but Shiite-led government that has been unwilling or unable to take major steps to reduce Sunni popular resentment and is showing...

  11. Corporate governance and intellectual capital

    Directory of Open Access Journals (Sweden)

    Rahmat Alizadeh

    2014-01-01

    Full Text Available The purpose of this paper is to examine the association between corporate governance and Intellectual capital in the pharmaceutical companies accepted in Tehran Stock Exchange over the period 2004-2009 using a regression based model. The study investigates the impacts of three some independent variables of the corporate governance (i.e. the number of board members, the relative extent of nonexecutive to executive directors, the auditing committee. The results suggest that corporate governance had no special effect on intellectual capital in the pharmaceutical companies. Furthermore among corporate governance's variables, the first one (i.e. board size had negative impact on firms' intellectual capital and the second and the third variables had no effects on intellectual capital.

  12. Governments plan data grid projects

    CERN Multimedia

    Thibodeau, Patrick

    2007-01-01

    "Some governments and not-for-profit organizations such as hospitals are beginning to look at data grid technology as a means to improve servies, lower operating costs and spur economic development." (1 page)

  13. LOCAL GOVERNMENT AND INTERGOVERNMENTAL RELATIONS ...

    African Journals Online (AJOL)

    GRACE

    study reveals that intergovernmental relations among the levels of government .... International Journal of Development and Management Review (INJODEMAR) Vol.10 June, 2015 ..... Administrative Science Quarterly, 16 (2): 216-229. Jinadu ...

  14. Governance mechanisms for healthcare apps

    DEFF Research Database (Denmark)

    Manikas, Konstantinos; Hansen, Klaus Marius; Kyng, Morten

    2014-01-01

    The introduction of the `app store' concept has challenged the way software is distributed and marketed: developers have easier access to customers, while customers have easy access to innovative applications. Apps today are increasingly focusing on more "mission-critical" areas like healthcare...... with the Apple AppStore counting more than 40,000 apps under the category "health & fitness". This rapid development of healthcare apps increases the necessity of governance as, currently, healthcare apps are not thoroughly governed. The U.S. Food and Drug Administration and the European Commission only have...... policies for apps that are medical devices.In this paper, we approach the problem of how to govern healthcare and medical apps by addressing the risks the use of these apps pose, while at the same time inviting for development of new apps. To do so we (i) analyze four cases of healthcare app governance...

  15. Document Management in Local Government.

    Science.gov (United States)

    Williams, Bernard J. S.

    1998-01-01

    The latest in electronic document management in British local government is discussed. Finance, revenues, and benefits systems of leading vendors to local authorities are highlighted. A planning decisions archive management system and other information services are discussed. (AEF)

  16. HUD Digital Government Strategy Report

    Data.gov (United States)

    Department of Housing and Urban Development — The HUD Digital Strategic Plan clearly articulates the goals of openness and transparency, furthering the innovation economy and meeting more global government wide...

  17. REFORMING CORPORATE GOVERNANCE IN ETHIOPIA ...

    African Journals Online (AJOL)

    milkii

    financial resources on domestic and international capital markets through good corporate governance excited ...... It does not provide for separation of the roles of a chief executive officer (CEO) and board Chairperson;. • Besides, the law does ...

  18. Innovation Across the Federal Government

    Science.gov (United States)

    Innovation happens at EPA, but it also takes place at many other government agencies including NASA, DARPA, HHS, OPM, and USGS through projects such as SBIR, innovation labs, innovation offices, and high-risk, high-reward scientific research.

  19. Corporate governance cycles during transition

    DEFF Research Database (Denmark)

    Mygind, Niels; Demina, Natalia; Gregoric, Aleksandra

    2004-01-01

    -ing or exit stage. During transition the cycle reflects: privatization often with a high proportion of employee ownership like in Russia and in Slovenia; strong pressures for restructuring and owner-ship changes; limited possibility for external finance because of embryonic development of the fi......-nancial system. To provide simple hypothesis tests, we use Russian enterprise data for 1995-2003 and Slovenian data covering 1998-2003. In spite of differences in institutional development, con-cerning privatization and development of corporate governance institutions, we find that govern-ance cycles are broadly...... of ownership on managers, external domestic and foreign owners. JEL-codes: G3, J5, P2, P3 - Keywords: corporate governance, life-cycle, privatization, ownership change, transition economies, Russia and Slovenia....

  20. Innovation in government : workforce practices.

    Science.gov (United States)

    2009-01-01

    A review of the literature on innovation within government provides detailed case studies on innovative practices adopted by transportation agencies across the U.S. These case studies focus on operational innovations adopted by transportation agencie...

  1. Good Governance in the EU

    Directory of Open Access Journals (Sweden)

    Gina Livioara GOGA

    2009-10-01

    Full Text Available Considering the EU adhesion, good governance has been analyzed from different perspectives, in the judicial literature being an analytic model or a normative concept. Some authors have wondered if this concept is a fashion, comprising some older ideas and principles, while other authors have asserted that the reasons why different methods of governance appear in the EU are based on “the complexity and the uncertainty of the problems on the agenda, an irreducible, the new approaches on public administration and law, hidden competencies, legitimacy and subsidiarity”. At a normative level, the White Paper of European Governance consecrated five principles on which good governance is based upon: openness, participation, responsibility, efficiency and coherence.

  2. Minority coalition governance in Denmark

    DEFF Research Database (Denmark)

    Christiansen, Flemming Juul; Pedersen, Helene Helboe

    2014-01-01

    in this share of coalition agreement-based laws. The analyses are based on unique data on legislative as well as governmental coalition agreements entered by three Danish governments with varying parliamentary strength. This study brings the blooming literature on coalition agreements one step further......Coalition governance is a challenge for political parties because it involves cooperation and compromises between parties that have different political goals and are competitors in political elections. Coalition coordination is crucial for the intra-coalitional cooperation of the governing parties....... A key element in coalition coordination is coalition agreements, which to a varying degree constrain the behaviour of the coalition partners. This article explores the share of laws that were precisely defined in government agreements and/or legislative agreements, and sets out to explain variation...

  3. Organizational Enablers for Project Governance

    DEFF Research Database (Denmark)

    Müller, Ralf; Shao, Jingting; Pemsel, Sofia

    and their relationships to organizational success. Based on these results, the authors discovered that organizational enablers (including key factors such as leadership, governance, and influence of project managers) have a critical impact on how organizations operate, adapt to market fluctuations and forces, and make......While corporate culture plays a significant role in the success of any corporation, governance and “governmentality” not only determine how business should be conducted, but also define the policies and procedures organizations follow to achieve business functions and goals. In their book......, Organizational Enablers for Project Governance, Ralf Müller, Jingting Shao, and Sofia Pemsel examine the interaction of governance and governmentality in various types of companies and demonstrate how these factors drive business success and influence project work, efficiency, and profitability. The data...

  4. Afghanistan: Government Formation and Performance

    National Research Council Canada - National Science Library

    Katzman, Kenneth

    2007-01-01

    ...; that body is emerging as a significant force in Afghan politics. However, the Afghan government's limited writ throughout the country and its perceived corruption have contributed to an increase in Taliban violence...

  5. Electronic Freight Management (EFM) Governance

    Science.gov (United States)

    2012-03-01

    The Electronic Freight Management (EFM) initiative is a USDOT-sponsored project that applies web technologies to improve data and message transmissions between supply chain partners. This report describes a new EFM Governance Model and the necessary ...

  6. Environmental Governance in Latin America

    NARCIS (Netherlands)

    de Castro, F.; Hogenboom, B.; Baud, M.

    2016-01-01

    The multiple purposes of nature - livelihood for communities, revenues for states, commodities for companies, and biodiversity for conservationists - have turned environmental governance in Latin America into a highly contested arena. In such a recourse-rich region, unequal power relations,

  7. Governing for the Common Good.

    Science.gov (United States)

    Ruger, Jennifer Prah

    2015-12-01

    The proper object of global health governance (GHG) should be the common good, ensuring that all people have the opportunity to flourish. A well-organized global society that promotes the common good is to everyone's advantage. Enabling people to flourish includes enabling their ability to be healthy. Thus, we must assess health governance by its effectiveness in enhancing health capabilities. Current GHG fails to support human flourishing, diminishes health capabilities and thus does not serve the common good. The provincial globalism theory of health governance proposes a Global Health Constitution and an accompanying Global Institute of Health and Medicine that together propose to transform health governance. Multiple lines of empirical research suggest that these institutions would be effective, offering the most promising path to a healthier, more just world.

  8. Electronic Government and Electronic Participation

    NARCIS (Netherlands)

    Tambouris, E; Scholl, H.J.; Janssen, M.F.W.H.A.; Wimmer, M.A.; Tarabanis, K; Gascó, M; Klievink, A.J.; Lindgren, I; Milano, M; Panagiotopoulos, P; Pardo, T.A.; Parycek, P; Sæbø, Ø

    2016-01-01

    Electronic government and electronic participation continue to transform the public sector and society worldwide and are constantly being transformed themselves by emerging information and communication technologies.This book presents papers from the 14th International Federation for Information

  9. Electronic Government and Electronic Participation

    NARCIS (Netherlands)

    Tambouris, E.; Scholl, H.J.; Janssen, M.F.W.H.A.; Wimmer, M.A.; Tarabanis, K.; Gascó, M.; Klievink, A.J.; Lindgren, I.; Milano, M.; Panagiotopoulos, P.; Pardo, T.A.; Parycek, P.; Sæbø, O.

    2015-01-01

    Electronic government and electronic participation continue to transform the public sector and society worldwide and are constantly being transformed themselves by emerging information and communication technologies. This book presents papers from the 14th International Federation for Information

  10. Local government and climate policy

    International Nuclear Information System (INIS)

    Burger, H.; Menkveld, M.; Coenen, F.H.J.M.

    2000-01-01

    Local government in the Netherlands could play a greater role than they currently do in reducing greenhouse gas emissions in the country. This fact formed the motivation for initiating the research project on Local Government and Climate Policy. Many local climate options are known in theory. Options for reduction that lie within the sphere of influence of Dutch local government are, for example, sustainable building or encouraging the utilisation of sustainable energy. But actual practice turns out to be rather refractory. If such options are to be implemented, then one has to overcome institutional barriers, such as the co-operation between different departments in the same local authority. The objective of this research is to improve the contribution that local government makes to climate policy

  11. Good City Governance in India

    Directory of Open Access Journals (Sweden)

    Raj Kumar Siwach

    2014-06-01

    Full Text Available Good governance is identified as imperative for enhancing the performance of Municipal councils in India. This is against the backdrop of mounting service delivery challenges confronting these Municipalities especially in the Haryana province. Using a case-study design, the study assesses performance in the context of basic elements of participative governance, transparency and accountability. The article contributes to growing literature on public sector issues in the discipline.

  12. Australian Government Balance Sheet Management

    OpenAIRE

    Wilson Au-Yeung; Jason McDonald; Amanda Sayegh

    2006-01-01

    Since almost eliminating net debt, the Australian Government%u2019s attention has turned to the financing of broader balance sheet liabilities, such as public sector superannuation. Australia will be developing a significant financial asset portfolio in the %u2018Future Fund%u2019 to smooth the financing of expenses through time. This raises the significant policy question of how best to manage the government balance sheet to reduce risk. This paper provides a framework for optimal balance sh...

  13. Poverty, governance and economic growth

    Directory of Open Access Journals (Sweden)

    Kefi Mohamed Karim

    2013-07-01

    Full Text Available The objective of this paper is to study the effect of governance and povrety on economic growth of a set of eight developing countries during the period 2000-2009, using a dynamic and static panel data model and a simultaneous equations model. The key findings generated from these three empirical tests stipulate a negative effect of governance on povrety and a positive effect of political instability and corruption on poverty

  14. Business Climate and Good Governance

    OpenAIRE

    Besmira Manaj

    2015-01-01

    This paper consists of three factors, namely: Good Governance, Business Climate and Corruption. How they affect the development product of Albania, not only as a concept, and a principle but mostly as a sensitive aspect in the integration process. There are some interpretations of this concept, but I intend to analyze the key factors and actors, their cooperation and concrete production in society. Improving governance is necessary to have an integrated long term strategy based upon a continu...

  15. Governing the mobility of skills

    OpenAIRE

    Raghuram, Parvati

    2008-01-01

    About the book: This book offers a critical examination of the way in which the nature and governance of international labour migration is changing within a globalizing environment.\\ud \\ud It examines how labour mobility and the governance of labour migration are changing by exploring the links between political economy and differentiated forms of labour migration. Additionally, it considers the effects of new social models of inclusion and exclusion on labour migration. Therefore, the book t...

  16. Governing the carbon offset market

    OpenAIRE

    Lovell, Heather C.

    2010-01-01

    Carbon offsets are produced and sold under the international climate change regime (the United Nations Kyoto Protocol) and also within an expanding voluntary offset market in which companies and individuals can voluntarily opt to compensate for their greenhouse gas emissions. The volume of carbon produced and consumed within compliance and voluntary markets has grown dramatically in the last 5 years, raising a number of governance challenges. This Focus Article gives an overview of the govern...

  17. Audit mode change, corporate governance

    OpenAIRE

    Limei Cao; Wanfu Li; Limin Zhang

    2015-01-01

    This study investigates changes in audit strategy in China following the introduction of risk-based auditing standards rather than an internal control-based audit mode. Specifically, we examine whether auditors are implementing the risk-based audit mode to evaluate corporate governance before distributing audit resources. The results show that under the internal control-based audit mode, the relationship between audit effort and corporate governance was weak. However, implementation of the ri...

  18. Corporate Law and Corporate Governance

    OpenAIRE

    Roberta Romano

    1998-01-01

    We have seen a revival in interest in corporate law and corporate governance since the 1980s, as researchers applied the tools of the new institutional economics and modern corporate finance to analyze the new transactions emerging in the 1980s takeover wave. This article focuses on three mechanisms of corporate governance to illustrate the analytical usefulness of transaction cost economics for corporate law. They are the board of directors; relational investing, a form of block ownership in...

  19. FINANCING DECISION AND CORPORATE GOVERNANCE

    OpenAIRE

    ANDREI STANCULESCU; DAN NICOLAE IVANESCU; PETRE BREZEANU

    2011-01-01

    This paper sustains the existence of a biunivocal link between a company’s financing decision and the corporate governance. On the one hand, the financing decision has an impact on corporate performance, which has been confirmed. According to the agency theory, the financing decision will contribute to solving interest conflicts between shareholders and managers. On the other hand, the corporate governance mechanism provides the proper contractual framework for attracting financing resources....

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Developing Government Renewable Energy Projects

    Energy Technology Data Exchange (ETDEWEB)

    Kurt S. Myers; Thomas L. Baldwin; Jason W. Bush; Jake P. Gentle

    2012-07-01

    The US Army Corps of Engineers has retained Idaho National Laboratory (INL) to conduct a study of past INL experiences and complete a report that identifies the processes that are needed for the development of renewable energy projects on government properties. The INL has always maintained expertise in power systems and applied engineering and INL’s renewable energy experiences date back to the 1980’s when our engineers began performing US Air Force wind energy feasibility studies and development projects. Over the last 20+ years of working with Department of Defense and other government agencies to study, design, and build government renewable projects, INL has experienced the do’s and don’ts for being successful with a project. These compiled guidelines for government renewable energy projects could include wind, hydro, geothermal, solar, biomass, or a variety of hybrid systems; however, for the purpose of narrowing the focus of this report, wind projects are the main topic discussed throughout this report. It is our thought that a lot of what is discussed could be applied, possibly with some modifications, to other areas of renewable energy. It is also important to note that individual projects (regardless the type) vary to some degree depending on location, size, and need but in general these concepts and directions can be carried over to the majority of government renewable energy projects. This report focuses on the initial development that needs to occur for any project to be a successful government renewable energy project.

  3. Result-Based Public Governance

    DEFF Research Database (Denmark)

    Boll, Karen

    Within the public sector, many institutions are either steered by governance by targets or result-based governance. The former sets up quantitative internal production targets, while the latter advocates that production is planned according to outcomes which are defined as institution-produced ef......Within the public sector, many institutions are either steered by governance by targets or result-based governance. The former sets up quantitative internal production targets, while the latter advocates that production is planned according to outcomes which are defined as institution......-produced effects on individuals or businesses in society; effects which are often produced by ‘nudging’ the citizenry in a certain direction. With point of departure in these two governance-systems, the paper explores a case of controversial inspection of businesses’ negative VAT accounts and it describes...... explores how and why this state of affairs appears and problematizes the widespread use of result-based governance and nudging-techniques by public sector institutions....

  4. Business Climate and Good Governance

    Directory of Open Access Journals (Sweden)

    Besmira Manaj

    2015-03-01

    Full Text Available This paper consists of three factors, namely: Good Governance, Business Climate and Corruption. How they affect the development product of Albania, not only as a concept, and a principle but mostly as a sensitive aspect in the integration process. There are some interpretations of this concept, but I intend to analyze the key factors and actors, their cooperation and concrete production in society. Improving governance is necessary to have an integrated long term strategy based upon a continuous cooperation between institutions and citizens. But in developing countries like Albania there are some important questions such as: How can we measure the improvement of Good Governance through policies? Has Good Governance indicated an effective way for the sustainable development? (Meisel, 2008, 6. These question give us the orientation to reflect about the process of development, social economic political behavior and how this multidimensional is transformed in product of good governance. The business cycle is strongly connected with many aspects of political-, social-, juridical aspects and good governance. Despite attempts to draft law regulations, the level of corruption and informality in Albania continues to be a major obstacle. The credibility level in the implementation of law is an indicator that affects democratization and institutional integration. At present, different reports of international institutions, define Albania as the country with the highest level of Corruption in the Balkans, which is a key factor influencing business. The ways with

  5. Spain and the Hamas government

    Directory of Open Access Journals (Sweden)

    Ignacio Álvarez-Ossorio Alvariño

    2007-12-01

    Full Text Available Since the restoration of democracy, Spain’s successive governments have been noted for their favourable stance toward the issue of Palestine and their support for the creation of a sovereign independent state in the territories that Israel occupied during the Six-Day War. Yasser Arafat’s visit to Spain in the time of the UCD, the holding of the Madrid Conference during the term of government of the PSOE and the designation of Miguel Ángel Moratinos as the EU’s special envoy for the Peace Process during the Partido Popular’s term of government are some of the landmarks that have expressed this exemplary relationship between the Spanish State and the Palestine question. However, the victory of Hamas in the legislative elections of 25 January 2006 radically changed the situation, as it led to Rodríguez Zapatero’s government joining the international boycott of the new Islamist executive; even so, the Spanish government clearly maintained its support for restarting the Peace Process, in the form of its backing for Mahmud Abbas, the President of the Palestine Authority. The armed conflict in Gaza in June 2007 which led to the Islamists retaking the Gaza Strip and the formation of a new government in the West Bank led by the technocrat Salam Fayad served to normalise the situation, given that it encouraged the raising of international sanctions and a return to normality in Spanish-Palestine relations.

  6. The Marketplace and Electronic Government Information.

    Science.gov (United States)

    Love, James P.

    1992-01-01

    Discusses the economic impact of government-produced electronic information. Examples of government prices for electronic information products are given; the debate over the privatization of government information dissemination is addressed, including examples from various government agencies; government bulletin board services are described; and…

  7. THE SOUND OF CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    DUMITRASCU LUMINITA MIHAELA

    2012-07-01

    Full Text Available The paper explores the corporate governance and corporate social responsibility in music industry, by reviewing the literature and investigating the aspects in the context of a sample made by top companies in this domain. The paper spotlighting the mutual connections between corporate governance and corporate social responsibility. The research methodology used consists in investigate the corporate governance codes. It’s about a qualitative interpretive research methodology that was adopted. The findings suggest the intercorelation of corporate governance with corporate social responsibility. The main contribution of the author consists in the fact that the added value of this paper and the original contribution leads in the intercorelation of these two aspects of corporate governance and corporate social responsibility, the findings beeing interesting, implying that recent preoccupation with corporate governance in music industry is starting to be equable by some attention to social responsibility aspects, with growing appreciation of their interdependencies. Previous literature has researched corporate governance and corporate social responsibility independently. Due to this fact, this paper is considering them jointly. The paper is important for both practical and theoretical aspects: for managers and also can serve as the basis for future research on this topic. The current paper is realized in the doctoral program entitled “PhD in Economics at the Standards of European Knowledge- DoEsEc”, scientific coordinator Prof. PhD Niculae Feleaga, Institution: The Academy of Economic Studies Bucharest, Faculty of Accounting and Management Informatic System, Department of International Accounting, period of research 2009-2012.

  8. Thematic report on public governance

    International Nuclear Information System (INIS)

    Bouder, F.

    2002-01-01

    The objective of the FSC workshop was to learn from the process that led to the ratification by the Finnish Parliament, on 18 May 2001, of the Decision in Principle on the final disposal facility for spent nuclear fuel in Olkiluoto, Eurajoki. One of the objectives clearly expressed by the NEA was to help government to make the right decisions, including by looking at successful policy making and decision-making practices. This gave 'Public Governance' issues a prominent role in the debates. In addition, the meeting was conceived as a discussion between stakeholders, which, interestingly, also made it an exercise in 'Public Governance'. This purpose of this report is to identify some key governance lessons that emerged from looking at this process in detail. It looks at the difficult policy context in which the Decision in Principle had to be taken. It highlights the governance challenge that emerged and suggests some key findings that could possibly be relevant in other similar circumstances. (author)

  9. Audit mode change, corporate governance

    Directory of Open Access Journals (Sweden)

    Limei Cao

    2015-12-01

    Full Text Available This study investigates changes in audit strategy in China following the introduction of risk-based auditing standards rather than an internal control-based audit mode. Specifically, we examine whether auditors are implementing the risk-based audit mode to evaluate corporate governance before distributing audit resources. The results show that under the internal control-based audit mode, the relationship between audit effort and corporate governance was weak. However, implementation of the risk-based mode required by the new auditing standards has significantly enhanced the relationship between audit effort and corporate governance. Since the change in audit mode, the Big Ten have demonstrated a significantly better grasp of governance risk and allocated their audit effort accordingly, relative to smaller firms. The empirical evidence indicates that auditors have adjusted their audit strategy to meet the regulations, risk-based auditing is being achieved to a degree, reasonable and effective corporate governance helps to optimize audit resource allocation, and smaller auditing firms in particular should urgently strengthen their risk-based auditing capability. Overall, our findings imply that the mandatory switch to risk-based auditing has optimized audit effort in China.

  10. GPCR Interaction: 151 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available hey are close enough to form hetero-oligomers. ... Immunofluorescence Microscopy, De...tection of the Phosphorylated MAPK, MAPK Assay, Inositol Phosphate Assay, Immunogold Electron Microscopy NP_001516.2 ...

  11. GPCR Interaction: 150 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available ey are close enough to form hetero-oligomers. ... Immunofluorescence Microscopy, Det...ection of the Phosphorylated MAPK, MAPK Assay, Inositol Phosphate Assay, Immunogold Electron Microscopy NP_057167.2 ...

  12. GPCR Interaction: 35 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available and alpha2aAR form robust hetero dimer in HEK-293 cells. An interaction between beta1AR and alpha2aAR is reg...ulated by glycosylation. The interaction may play a key role in cross-talk and mu

  13. GPCR Interaction: 207 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available LP2) and secretin (SecR), and interfaces of GLP2 B Glucagon-like peptide Type 2 GLP2 C Secretin ... SecR Experi...ment SecR does not interact with CTR (calcitonin receptor). 18401761 BRET, FRET NP_004237.1 ...

  14. 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

  15. GPCR Interaction: 199 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available ecretin receptor (SecR), and interfaces of VPAC2R B Vasoactive intestinal polypeptide Type 2 VPAC2R C Secret...in ... SecR Experiment SecR does not interact with CTR (calcitonin receptor). 18401761 BRET, FRET NP_003373.2 ...

  16. GPCR Interaction: 158 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available f CCR1 A Chemokine CCR1 CCR1 A Chemokine CCR1 CCR1 Experiment The different oligomeric states are indicated by affinity chromatograph..., dimers and higher order oligomers of CCR1 solubilized in DDM/CHS. 19275940 Affinity chromatography NP_001286.1 ...

  17. GPCR Interaction: 25 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available e of A1R and P2Y1R colocalization was observed in cotransfected cells by double immunofluorescence experiments with confocal laser...2) and Myc-P2Y1R-Rluc was also observed in the co-transfected HEK293T cells by confocal laser microscopy. Th..., 12417330 Double immunofluorescence experiments, confocal laser microscopy Modified BRET NP_001041695.1 ...

  18. GPCR Interaction: 82 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available agonists increase BRET values for MT1BR but not for MT1AR homodimers in living cells and isolated plasma membranes. 11940583 Immunoprecipitation, BRET ... NP_005949.1 ... ... upon agonist and antagonist binding. Agonists, neutral antagonists, and inverse

  19. GPCR Interaction: 83 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available agonists increase BRET values for MT1BR but not for MT1AR homodimers in living cells and isolated plasma membranes. 11940583 Immunoprecipitation, BRET ... NP_005950.1 ... ... upon agonist and antagonist binding. Agonists, neutral antagonists, and inverse

  20. 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 ...

  1. GPCR Interaction: 184 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available tion of C5aR dimers.Upon C5a stimulation, mutant receptors did not internalize when individually express...ed. C5a stimulation of cells that co-expressed wild type C5aR together with either un...terfaces of C5aR A Complement component C5a C5aR A Complement component C5a C5aR Experiment Neither an intact NH2 term...inus nor the presence of COOH-terminal phosphorylation sites appeared to be required for the forma...liganded or phosphorylation-deficient mutant resulted in co-internalization of mutant receptors with C5aR. 18772131 NH2-terminally modified C5aR mutant NP_001727.1 ...

  2. GPCR Interaction: 157 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available ation of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/...one receptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expr...ents using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferas...ession of each receptor. 19896898 BRET NP_000907.2 ...

  3. GPCR Interaction: 156 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available ation of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/...one receptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expr...ents using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferas...ession of each receptor. 19896898 BRET NP_000697.1 ...

  4. GPCR Interaction: 154 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/OTR a...eceptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expression of each receptor. 19896898 BRET NP_000045.1 ... ...using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferase or

  5. GPCR Interaction: 155 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available n of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/OTR ...receptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expression of each receptor. 19896898 BRET NP_000907.2 ... ... using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferase or

  6. GPCR-Mediated Signaling of Metabolites

    DEFF Research Database (Denmark)

    Husted, Anna Sofie; Trauelsen, Mette; Rudenko, Olga

    2017-01-01

    microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals...... and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets....

  7. 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

  8. GPCR Interaction: 30 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available ernalize upon exposure to the agonist. Oxymetazoline (alpha1aAR selective agonist) induces the cointernali...zation of the alpha1aAR and alpha1bAR, whereas the alpha1bAR does not cointernalize

  9. 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

  10. 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 ...

  11. GPCR Interaction: 292 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available Predicted interfaces of Serotonin type 4 by using the SCD with the alignment provided in GPCRDB A Serotonin... Serotonin type 4 Serotonin type 4 ... Prediction ... 15593372 SCD for GPCRDB subtype 001_001_005_004 ...

  12. GPCR Interaction: 293 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available Predicted interfaces of Serotonin type 6 by using the SCD with the alignment provided in GPCRDB A Serotonin... Serotonin type 6 Serotonin type 6 ... Prediction ... 15593372 SCD for GPCRDB subtype 001_001_005_006 ...

  13. GPCR Interaction: 295 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available Predicted interfaces of Serotonin Insect by using the SCD with the alignment provided in GPCRDB A Serotonin... Serotonin Insect Serotonin Insect ... Prediction ... 15593372 SCD for GPCRDB subtype 001_001_005_999 ...

  14. GPCR Interaction: 294 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available Predicted interfaces of Serotonin type 7 by using the SCD with the alignment provided in GPCRDB A Serotonin... Serotonin type 7 Serotonin type 7 ... Prediction ... 15593372 SCD for GPCRDB subtype 001_001_005_007 ...

  15. GPCR Interaction: 160 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available 7412 coimmunoprecipitation,BRET,BRET50,BRETmax,construction of pairs of individua...BRET50, BRETmax and the construction of pairs of individually inactive but potent...ero-oligomerization of the human deltaOPR and CXCR2 could be detected by using coimmunoprecipitation, BRET,

  16. 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 ...

  17. 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 ...

  18. GPCR Interaction: 26 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available ree of A1R and P2Y1R colocalization was observed in cotransfected cells by double immunofluorescence experiments with confocal laser...P(2) and Myc-P2Y1R-Rluc was also observed in the co-transfected HEK293T cells by confocal laser microscopy. ...75, 12417330 Double immunofluorescence experiments, confocal laser microscopy Modified BRET NP_002554.1 ...

  19. Spheres of SA Government, responsibilities and delivery

    CSIR Research Space (South Africa)

    Oelofse, Suzanna HH

    2010-09-01

    Full Text Available The institutional framework for government in South Africa was established in 1996 with the adoption of the first democratic Constitution. National, provincial and local government was established as three elected spheres of government, each...

  20. m-government legal and regulatory framework

    African Journals Online (AJOL)

    Wondwossen Mulugeta

    Legal Framework for Implementation of m-Government in Ethiopia: Best. Practices and Lessons ... opportunity to government and businesses to provide enhanced mobile .... provide effective governance, offer increased service delivery and ...

  1. Corporate Governance Quality in Selected Transition Countries

    Directory of Open Access Journals (Sweden)

    Danila Djokic

    2017-12-01

    Full Text Available Important questions that concern the notion of good corporate governance focus on what good corporate governance is, who benefits from good corporate governance, and how corporate governance quality can be measured. The aim of our study was to broaden our understanding of the role of standards and codes of good corporate governance in improving governance practices.We found that not only formal regulations, standards, and governance codes, but also corporate governance indices-which make the assessment of companies’ governance practices possible-are important in measuring and improving governance quality. The results of the research based on the SEECGAN Index methodology indicated that mandatory requirements and voluntary recommendations of high governance standards had a positive impact on the corporate governance practice in Slovenia.

  2. Recipient government control under pressure

    DEFF Research Database (Denmark)

    Jansson, Johanna

    This paper seeks to contribute to ongoing debates around African countries‟ relations to their external partners. It explores the notion of recipient government control, here defined as the extent to which a recipient government is able to ensure that the outcome of negotiations with its external...... things, cited concerns for debt sustainability. The paper argues that in the early stages of negotiations with China during 2007-2008, the Congolese government exercised control in the sense that the 2008 version of the Sicomines agreement made sizeable amounts of funding available towards large...... relevance here, since it reduced its willingness to push ahead with the criticised version of the Sicomines agreement. Eventually, mid-2009, President Kabila accommodated the concerns of the traditional donors. The agreement was reduced and HIPC completion point was subsequently reached in July 2010...

  3. CORPORATE GOVERNANCE AND STAKEHOLDERS’ ACCOUNTABILITY

    Directory of Open Access Journals (Sweden)

    Elena CHIȚIMUȘ

    2015-04-01

    Full Text Available Corporate governance is the system through which companies are directed and controlled but until today academic environment, regulators, corporations couldn’t reach a unanimous definition. Corporate governance provisions suffered changes after several largely covered financial scandals. Entities incur costs when complying with new regulations but not complying impacts the reputation and investors might think twice before bringing their money into the company. Accountability for business decisions, risk management, control that set the economic path of the company is mandatory for proving that the company is run in a fairly and smart way. This study aims to investigate how corporate governance relates to accountability of all parties involved in the current business of companies as any conflict of interest is detrimental to the company and affects in a negative way its performance.

  4. Towards improvisational governance? Jazz improvisation and networked complex governance

    NARCIS (Netherlands)

    M.W. (Martijn) Hartog

    2014-01-01

    In the past decades considerable amounts of power have shifted away from national governments. These shifts have occurred upwards, towards international organisations, sideways due to privatisation and the creation of quasi non-governmental organisations and downwards due to decentralisation of

  5. Cyber Governance : Challenges, Solutions, and Lessons for Effective Global Governance

    NARCIS (Netherlands)

    Jayawardane, S.; Larik, J.E.; Jackson, E.

    2015-01-01

    Cyberspace permeates global social and economic relations in the 21st Century. It is an integral part of the critical infrastructure on which modern societies depend and has revolutionized how we communicate and socialize. The governance of cyberspace is, therefore, an indispensable component of

  6. Governance in Southeast Asia: Issues and Options

    OpenAIRE

    Gonzalez, Eduardo T.; Mendoza, Magdalena L.

    2003-01-01

    This paper attempts to analyze governance systems in Southeast Asia and proposes some policy suggestions that can improve governance practices in the region. It also discusses the links between governance and official development assistance and the role of the Japan Bank for International Cooperation. To put the discussion on governance systems in a proper context, the paper discusses the governance and growth nexus in Southeast Asia; describes the operating governance systems in Southeast As...

  7. 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...

  8. Measuring interoperability maturity in government networks.

    OpenAIRE

    Huijsman, K.L.L.G.; Plomp, M.G.A.; Batenburg, R.S.

    2012-01-01

    The purpose of this paper is to create a model that describes the development of interorganisational collaboration in government networks that apply eGovernment. Contrary to several models that describe eGovernment from a government-to-citizen perspective, and primarily emphasise on the front office of eGovernment services, this paper focuses on the collaboration that takes place in the back office to enable successful eGovernment services. A maturity model was developed to describe and asses...

  9. Implementing a new governance model.

    Science.gov (United States)

    Stanley-Clarke, Nicky; Sanders, Jackie; Munford, Robyn

    2016-05-16

    Purpose - The purpose of this paper is to discuss the lessons learnt from the process of implementing a new model of governance within Living Well, a New Zealand statutory mental health agency. Design/methodology/approach - It presents the findings from an organisational case study that involved qualitative interviews, meeting observations and document analysis. Archetype theory provided the analytical framework for the research enabling an analysis of both the formal structures and informal value systems that influenced the implementation of the governance model. Findings - The research found that the move to a new governance model did not proceed as planned. It highlighted the importance of staff commitment, the complexity of adopting a new philosophical approach and the undue influence of key personalities as key determining factors in the implementation process. The findings suggest that planners and managers within statutory mental health agencies need to consider the implications of any proposed governance change on existing roles and relationships, thinking strategically about how to secure professional commitment to change. Practical implications - There are ongoing pressures within statutory mental health agencies to improve the efficiency and effectiveness of organisational structures and systems. This paper has implications for how planners and managers think about the process of implementing new governance models within the statutory mental health environment in order to increase the likelihood of sustaining and embedding new approaches to service delivery. Originality/value - The paper presents insights into the process of implementing new governance models within a statutory mental health agency in New Zealand that has relevance for other jurisdictions.

  10. Government

    Science.gov (United States)

    Ministry of Agriculture,...Ministry of Agriculture, Forestry, Fisheries, Rural Transformation, Industry & Labour Ministry of Education,...Ministry of Education, National Reconciliation, Ecclesiastical House of Assembly Office of The DPP CIPO Citizens Culture & Recreation Education Economy Voting

  11. Governance.

    Science.gov (United States)

    McGhehey, M. A.

    This chapter deals with cases on the allocation of authority and responsibility within the educational structure of the several states, as well as with cases arising out of contractual obligations and other sources of legal rights. School board members, administrators, and teachers need to understand their legal rights and responsibilities if they…

  12. Corporate Governance: A Keynote Speech

    DEFF Research Database (Denmark)

    Balling, Morten

    1998-01-01

    In the article, the author gives an overview of the many different aspects of corporate governance to discuss at a conference in Budapest in May 1997 arranged by Société Universitaire Européenne de Recherches Financières (SUERF). Among the subjects dealt with are the relationsship between...... cases of privatization in Western Europe. Almost everywhere, the role of institutional shareholders is increasing. The internationalization proces implies that also the role of the governance systems changes the incentives for corporate managers to demonstrate good financial performance, and there seems...

  13. The Politics of Governance Architectures

    DEFF Research Database (Denmark)

    Borrás, Susana; Radaelli, Claudio M.

    2011-01-01

    Governance architectures are strategic and long-term institutional arrangements of international organizations exhibiting three features; namely, they address strategic and long-term problems in a holistic manner, they set substantive output-oriented goals, and they are implemented through...... not being identified as an object of study on its own right. We define the Lisbon Strategy as a case of governance architecture, raising questions about its creation, evolution and impact at the national level. We tackle these questions by drawing on institutional theories about emergence and change...

  14. Governance in regional development planning?

    DEFF Research Database (Denmark)

    Galland, Daniel

    2008-01-01

    The purpose of this paper is to lay part of the groundwork for a new project aimed at exploring governance aspects concerned with regional development planning (RDP) in Denmark. The fundamental objective is to help establish and clarify a number of research questions to delve into the conditions...... and opportunities for anchoring and implementing such RDP. The paper mainly adopts a descriptive approach to portray tentative pathways to explore and discuss regional governance structures, procedures and practices that are being developed in establishing new RDP processes, strategies and plans....

  15. 3 CFR - Transparency and Open Government

    Science.gov (United States)

    2010-01-01

    ... system of transparency, public participation, and collaboration. Openness will strengthen our democracy... public. Government should be participatory. Public engagement enhances the Government's effectiveness and...

  16. 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...

  17. 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...

  18. Audit Methodology for IT Governance

    Directory of Open Access Journals (Sweden)

    Mirela GHEORGHE

    2010-01-01

    Full Text Available The continuous development of the new IT technologies was followed up by a rapid integration of them at the organization level. The management of the organizations face a new challenge: structural redefinition of the IT component in order to create plus value and to minimize IT risks through an efficient management of all IT resources of the organization. These changes have had a great impact on the governance of the IT component. The paper proposes an audit methodology of the IT Governance at the organization level. From this point of view the developed audit strategy is a strategy based on risks to enable IT auditor to study from the best angle efficiency and effectiveness of the IT Governance structure. The evaluation of the risks associated with IT Governance is a key process in planning the audit mission which will allow the identification of the segments with increased risks. With now ambition for completeness, the proposed methodology provides the auditor a useful tool in the accomplishment of his mission.

  19. Do Kids Need Government Censors?

    Science.gov (United States)

    Rabkin, Rhoda

    2002-01-01

    Fashioning public policies restricting children's access to entertainment glamorizing violence, sex, drugs, and vulgarity is a complex task. The recently introduced Media Marketing Accountability Act would empower the federal government to regulate advertising of entertainment products to youth. Suggests that this power is undesirable compared to…

  20. Corporate Governance, CSR og menneskerettigheder

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2005-01-01

    Artiklen diskuterer om der findes en forbindelse mellem Corporate Governance og Corporate Social Responsibility i forhold til menneskerettigheder. Det konkluderes, at en sådan forbindelse findes, i hvert fald i forhold til arbejdstagerrettigheder og dele af forholdet til eksterne stakeholdere. Me...

  1. IT governance guidelines for directors

    CERN Document Server

    Calder, Alan

    2005-01-01

    This important new book – 'IT Governance: Guidelines for Directors' provides directors, executives, managers and professional advisers with clear, pragmatic guidelines for ensuring that IT and the business work together for the same strategic objectives. 

  2. Gender Play and Good Governance

    Science.gov (United States)

    Powell, Mark

    2008-01-01

    Like good government, thoughtful care of children requires those in power, whether teachers or parents, to recognize when it is appropriate for them to step back from day-to-day decision-making while still working behind the scenes to ensure an organizational structure that supports the independence and equitable development of those they serve.…

  3. Participatory Governance in Social Enterprise

    DEFF Research Database (Denmark)

    Pestoff, Victor Alexis; Hulgård, Lars

    2016-01-01

    This paper emphasizes the importance of participative governance in the study of social enterprise. Furthermore, it argues that social enterprise must be analyzed through a multi-dimensional perspective. The EMES approach is based on three dimensions emphasizing the social, economic, and politica...

  4. Government Spending and Legislative Organization

    DEFF Research Database (Denmark)

    Egger, Peter; Köthenbürger, Marko

    This paper presents empirical evidence of a positive effect of council size on government spending using a data set of 2,056 municipalities in the German state of Bavaria over a period of 21 years. We apply a regression discontinuity design to avoid an endogeneity bias. In particular, we exploit ...

  5. Government spending and legislative organization

    DEFF Research Database (Denmark)

    Egger, Peter; Köthenbürger, Marko

    2010-01-01

    This paper presents empirical evidence of a positive effect of council size on government spending using a dataset of 2,056 municipalities in the German state of Bavaria over a period of 21 years. We apply a regression discontinuity design to avoid an endogeneity bias. In particular, we exploit d...

  6. Governance and European Civil Society

    DEFF Research Database (Denmark)

    Kutay, Acar

    This book provides a critical analysis of the European Union’s approach to ‘governance’, focusing on the way in which civil society is incorporated within the EU decision-making process and arguing that it is not conducive to the democratisation of EU governance.\

  7. Global Trends in Academic Governance

    Science.gov (United States)

    Cummings, William K.; Finkelstein, Martin

    2009-01-01

    Even before the current global economic crisis, discontent with the governance of higher education institutions was widespread among faculty in the United States and throughout the world. Drawing from the 2007 Changing Academic Profession (CAP) survey of faculty in seventeen countries, the authors examine faculty perceptions of the current state…

  8. Introduction 'Governance for Drought Resilience'

    NARCIS (Netherlands)

    Bressers, Nanny; Bressers, Johannes T.A.; Larrue, Corinne; Bressers, Hans; Bressers, Nanny; Larrue, Corinne

    2016-01-01

    This book is about governance for drought resilience. But that simple sentence alone might rouse several questions. Because what do we mean with drought, and how does that relate to water scarcity? And what do we mean with resilience, and why is resilience needed for tackling drought? And how does

  9. GOVERNMENT QUALITY; PROFESSIONALIZE THE SERVICE

    OpenAIRE

    Dr. Gabriela Valderrama Izquierdo; Mtro Jan Fabisiak; Carla Assenth Nava

    2017-01-01

    What do we call good governance and how to go forward with better practices in public administration, it is an important issue in modern societies that require appropriate legal framework in time matter, which are aimed at achieving higher and better levels of social welfare, but also take a shift towards higher levels of citizen engagement.

  10. American National Government: An Overview

    National Research Council Canada - National Science Library

    Kaiser, Frederick M

    2003-01-01

    ...; judicial independence; institutional supports; checks and balances and shared responsibilities in terms of lawmaking, national security policy, executive and judicial appointments, and criminal investigations; and the Federal Government's dispersed and decentralized organization. This report, which examines these characteristics, will be updated as developments require.

  11. The governance of director networks

    NARCIS (Netherlands)

    Renneboog, L.D.R.; Zhou, Y.; Wright, M.; Siegel, D.; Keasey, K.; Filatotchev, I.

    2013-01-01

    This chapter studies director networks, which have gained increasing attention from sociology, finance, and management. It considers the argument that these networks have an interesting role in corporate governance and then reviews their rules in major developed countries. The chapter goes on to

  12. Managing stakeholders in transformational government

    DEFF Research Database (Denmark)

    Reinwald, Anja Kaldahl; Kræmmergaard, Pernille

    2012-01-01

    a stakeholder perspective. The paper reports how they succeeded in involving the most important stakeholders in the process of reaching transformational government. Finally the paper offers six lessons learned, based on the case study, about how to manage the involved stakeholders to reach transformational...

  13. Research Insights About Risk Governance

    Directory of Open Access Journals (Sweden)

    Therese R. Viscelli

    2016-11-01

    Full Text Available In recent years, expectations for increased risk governance have been placed explicitly on boards of directors. In response, boards are being held responsible for not only understanding and approving management’s risk management processes, but they are also being held responsible for assessing the risks identified by those processes as part of overseeing management’s pursuit of value. These increasing responsibilities have led a number of organizations to adopt enterprise risk management (ERM as a holistic approach to risk management that extends beyond traditional silo-based risk management techniques. As boards, often through their audit committee, consider management’s implementation of ERM as part of the board’s risk oversight, a number of questions emerge that can be informed by academic research related to ERM. This article summarizes findings from ERM research to provide insights related to the board’s risk governance responsibilities. We also identify a number of research questions that warrant further analysis by governance scholars. It is our hope that this article will spawn varying types of research about ERM and corporate governance.

  14. Watergate and American Government Textbooks.

    Science.gov (United States)

    Eksterowicz, Anthony J.; Cline, Paul C.

    1993-01-01

    Asserts that the Watergate scandal during the 1972 presidential election altered the U.S. government and the very mood of the United States. Presents a content analysis of 5 middle school, 5 secondary, and 12 college-level textbooks. Finds that the texts exhibit weak historical discussion or analysis of Watergate. (CFR)

  15. Climatic change and world governance

    International Nuclear Information System (INIS)

    Mousel, M.

    1999-01-01

    This paper deals with the problems of international agreements about the greenhouse effect gases control. Even if the prejudice covers the whole world, the implementing of pollution regulations generate conflicts of interest. Solidarity, equity and not historical responsibilities have to govern the discussions. This involves to take into account the place of the developing countries. (A.L.B.)

  16. Tenure, Academic Freedom, and Governance.

    Science.gov (United States)

    Perley, James E.

    1995-01-01

    Tenure itself is not the central issue in the debate over faculty tenure; honest faculty evaluation, adequate faculty development, and termination when appropriate are the real issues as are fears that abandonment of the tenure principle would amount to abandonment of the principles of academic freedom and shared governance. (MSE)

  17. De Ratio van Corporate Governance

    NARCIS (Netherlands)

    A. de Jong (Abe)

    2006-01-01

    textabstractAbe de Jong (1970) is Professor in Corporate Finance and Corporate Governance at RSM Erasmus University. He obtained a PhD in finance at Tilburg University (1999). His research and teaching interests are in the area of empirical corporate finance and include capital structure choice,

  18. Integrated territorial management and governance

    DEFF Research Database (Denmark)

    Galland, Daniel

    This was the last in a series of three postgraduate workshops undertaken by the ENECON project during the period 2012-2014. A total of 28 master’s students, postgraduate students and lecturers from the Nordic-Baltic region gathered at the Utzon Centre in Aalborg to discuss territorial governance...

  19. Private governance of ocean resources

    NARCIS (Netherlands)

    Groeneveld, R.A.; Bush, S.R.; Bailey, M.L.

    2017-01-01

    The United Nations (UN) post-2015 development agenda (United Nations 2015) calls for the establishment of a global partnership for sustainable development, ‘bringing together Governments, civil society, the private sector, the United Nations system and other actors and mobilizing all available

  20. Land governance as grey zone

    DEFF Research Database (Denmark)

    Kjær, Anne Mette

    2017-01-01

    demonstrates that in Uganda, the need to maintain the ruling coalition in a clientelist political settlement to build electoral support, and the desire to attract economic investors, constitute political incentives to maintain land governance as a grey zone, even if there is apparent political...

  1. China's Environmental Governance in Transition

    NARCIS (Netherlands)

    Mol, A.P.J.; Carter, N.T.

    2006-01-01

    In the face of unprecedented economic and industrial growth levels, China is rapidly developing its system of environmental governance. Coming from a conventional command-and-control approach to environmental policy, which fitted well its centrally planned economy, transitional China is swiftly

  2. The hamas government should recognized

    NARCIS (Netherlands)

    Reinhart, T.

    2006-01-01

    In a just and well-ordered world, it would be unthinkable for a government that was elected in this way to be disqualified because Israel does not like the choice of the electorate in question. But in a world in which the U.S. rules, might is right, and might can define democracy as it chooses. Thus

  3. The Nordic Corporate Governance Model

    DEFF Research Database (Denmark)

    Thomsen, Steen

    2016-01-01

    , concentrated ownership, semi two-tier board structures, employee representation and low-powered managerial incentives – has been shaped by the welfare state in ways consistent with systemic corporate governance theories. The article concludes with a skeptical discussion of the Nordic model as a development...

  4. Theorizing government communication with regard

    NARCIS (Netherlands)

    dr. ir. P. (Peter) Jansen

    2018-01-01

    The implementation of a National Ecological Network poses a significant challenge to the Dutch government. The establishment of this ecological network has led to conflicts among various interest groups in the public sphere, each of which defends its own interests. In this struggle for recognition

  5. Distinct cis regulatory elements govern the expression of TAG1 in embryonic sensory ganglia and spinal cord.

    Directory of Open Access Journals (Sweden)

    Yoav Hadas

    Full Text Available Cell fate commitment of spinal progenitor neurons is initiated by long-range, midline-derived, morphogens that regulate an array of transcription factors that, in turn, act sequentially or in parallel to control neuronal differentiation. Included among these are transcription factors that regulate the expression of receptors for guidance cues, thereby determining axonal trajectories. The Ig/FNIII superfamily molecules TAG1/Axonin1/CNTN2 (TAG1 and Neurofascin (Nfasc are co-expressed in numerous neuronal cell types in the CNS and PNS - for example motor, DRG and interneurons - both promote neurite outgrowth and both are required for the architecture and function of nodes of Ranvier. The genes encoding TAG1 and Nfasc are adjacent in the genome, an arrangement which is evolutionarily conserved. To study the transcriptional network that governs TAG1 and Nfasc expression in spinal motor and commissural neurons, we set out to identify cis elements that regulate their expression. Two evolutionarily conserved DNA modules, one located between the Nfasc and TAG1 genes and the second directly 5' to the first exon and encompassing the first intron of TAG1, were identified that direct complementary expression to the CNS and PNS, respectively, of the embryonic hindbrain and spinal cord. Sequential deletions and point mutations of the CNS enhancer element revealed a 130bp element containing three conserved E-boxes required for motor neuron expression. In combination, these two elements appear to recapitulate a major part of the pattern of TAG1 expression in the embryonic nervous system.

  6. Proposal on state affairs and government system for next government

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-11-15

    The contents of this book are introduction of need of study and purpose, building ecosystem to create jobs, consolidation of social innovation to improve life quality, construction of infrastructure to revitalize region, construction of new digital ecosystem, building of effective intellectual property system, creation of future competitiveness with scientific technology, establishment of raising of creative person and comprehensive discussion on reorganization of government system like need, principle, feature, difficulty, and arrangement of discussion.

  7. Proposal on state affairs and government system for next government

    International Nuclear Information System (INIS)

    2012-11-01

    The contents of this book are introduction of need of study and purpose, building ecosystem to create jobs, consolidation of social innovation to improve life quality, construction of infrastructure to revitalize region, construction of new digital ecosystem, building of effective intellectual property system, creation of future competitiveness with scientific technology, establishment of raising of creative person and comprehensive discussion on reorganization of government system like need, principle, feature, difficulty, and arrangement of discussion.

  8. 42 CFR 494.180 - Condition: Governance.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Governance. 494.180 Section 494.180... Administration § 494.180 Condition: Governance. The ESRD facility is under the control of an identifiable governing body, or designated person(s) with full legal authority and responsibility for the governance and...

  9. Measuring interoperability maturity in government networks.

    NARCIS (Netherlands)

    Huijsman, K.L.L.G.; Plomp, M.G.A.; Batenburg, R.S.

    2012-01-01

    The purpose of this paper is to create a model that describes the development of interorganisational collaboration in government networks that apply eGovernment. Contrary to several models that describe eGovernment from a government-to-citizen perspective, and primarily emphasise on the front office

  10. 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.

  11. E-Government: Initiatives, Developments, and Issues.

    Science.gov (United States)

    Aldrich, Duncan; Bertot, John Carlo; McClure, Charles R.

    2002-01-01

    Provides a background of government efforts to incorporate telecommunication and computer technologies to improve government performance and enhance citizen access to government information and services. Describes this symposium issue which discusses key issues that affect the success and implementation of electronic government initiatives. (LRW)

  12. 42 CFR 460.62 - Governing body.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Governing body. 460.62 Section 460.62 Public Health... Administrative Requirements § 460.62 Governing body. (a) Governing body. A PACE organization must be operating under the control of an identifiable governing body (for example, a board of directors) or a designated...

  13. Computerized and Networked Government Information Column

    Science.gov (United States)

    Stratford, Juri

    2004-01-01

    The efforts of the U.S. federal government to develop E-Government services have been the subject of many recent news stories. In February 2002, Arthur Andersen's Office of Government Services released a usability analysis of federal government Web sites. In addition, in February, Vice-President Cheney announced the release of a report detailing…

  14. Measuring interoperability maturity in government networks

    NARCIS (Netherlands)

    Huijsman, K.L.L.G; Plomp, M.G.A.; Batenburg, R.S.

    2012-01-01

    The purpose of this paper is to create a model that describes the development of interorganisational collaboration in government networks that apply eGovernment. Contrary to several models that describe eGovernment from a government-to-citizen perspective, and primarily emphasise on the front office

  15. Governance and Trust in Higher Education

    Science.gov (United States)

    Vidovich, Lesley; Currie, Jan

    2011-01-01

    The adoption of more corporate models of governance is a contemporary trend in higher education. In the early 2000s, the Australian Government legislated national governance protocols for universities, using the policy lever of financial sanctions. These more corporate-style governance protocols followed similar changes in the UK, consistent with…

  16. Convergence of Corporate and Public Governance

    OpenAIRE

    Gérard Hirigoyen; Radhoine Laouer

    2013-01-01

    By analyzing the differences between the corporate and public governance, theoretical and empirical research seems to indicate that the two domains of governance are far too different to share any common aspect. However, in this particular research, it has been argued that public governance is an application of corporate governance. Thus, the research question entails the description and analysis of this possible conve...

  17. 22 CFR 221.43 - Governing law.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Governing law. 221.43 Section 221.43 Foreign... Administration § 221.43 Governing law. This Guarantee shall be governed by and construed in accordance with the laws of the United States of America governing contracts and commercial transactions of the United...

  18. Governing Governance : A formal framework for analysing institutional design and enactment governance

    NARCIS (Netherlands)

    King, T.C.

    2016-01-01

    This dissertation is motivated by the need, in today’s globalist world, for a precise way to enable governments, organisations and other regulatory bodies to evaluate the constraints they place on themselves and others. An organisation’s modus operandi is enacting and fulfilling contracts between

  19. Legitimacy and the Cost of Government

    DEFF Research Database (Denmark)

    Berggren, Niclas; Bjørnskov, Christian; Lipka, David

    2015-01-01

    While previous research documents a negative relationship between government size and economic growth, suggesting an economic cost of big government, a given government size generally affects growth differently in different countries. As a possible explanation of this differential effect, we......, in which two different measures of the size of government are interacted with government legitimacy, reveals that perceived legitimacy exacerbates a negative growth effect of government size in the long run. This could be interpreted as governments taking advantage of being regarded as legitimate in order...... to secure short-term support at a long-term cost to the economy....

  20. Governance and Development: Changing EU Policies

    OpenAIRE

    Hout, Wil

    2010-01-01

    textabstractAbstract This introductory article to the special issue on European Union, development policies and governance discusses how notions of ('good') governance have come to dominate development discourses and policies since the mid-1990s. The article argues that governance was part of the so-called Post-Washington Consensus, which understands governance reform as part of the creation of market societies. Although academics have commonly emphasised the fact that governance concerns the...

  1. Manajemen Perubahan, Tantangan Implementasi E-government

    OpenAIRE

    Prayitno, Edy

    2008-01-01

    Kegagalan implementasi e-government tidak lepas dari kesalahan manusia, para pelaku e-government, dalam menyikapi Perubahan sistem, dari sistem sebelumnya ke sistem e-government yang baru. Makalah ini mencoba menyampaikan hal-hal yang bisa dilakukan untuk mengantisipasi resistensi yang muncul akibat ketidaksiapan para pelaku e-government terhadap Perubahan sistem. Ini penting karena ketidaksiapan menerima Perubahan sistem seringkali menjadi penyebab ditolaknya implementasi e-government. Tidak...

  2. Corporate Governance in Publicly Traded Canadian Companies

    OpenAIRE

    Hu, Jie; Wang, Chong

    2011-01-01

    We investigate the effectiveness of corporate governance practices in this paper, focusing on the corporate governance practices implemented by TSX listed companies in Canada. We analyze the determinants of the effectiveness of corporate governance practices and test whether corporate governance mechanisms relate to quality of accounting earnings and company performance. We obtain mixed results from regression analyses indicating that corporate governance mechanisms are not significantly rela...

  3. Editorial: Open Source in Government

    Directory of Open Access Journals (Sweden)

    Dru Lavigne

    2009-04-01

    Full Text Available Last summer, the Center for Strategic and International Studies published the sixth update to their Open Source Policy survey. The survey "tracks governmental policies on the use of open source software as reported in the press or other media." The report lists 275 open source policy initiatives. It also breaks down by country and by government level whether the policy on the use of open source is considered to be advisory, preferential, or mandatory. The editorial theme for the May issue of the OSBR is "open source in government" and we are pleased that the authors have drawn upon their experiences to provide insight into public policy regarding open source for many parts of the world.

  4. Governing the potentials of life?

    DEFF Research Database (Denmark)

    Staunæs, Dorthe

    2011-01-01

    of perception and neurons. 2) How affectivity becomes synonymous with positive feelings, while more indeterminate parts of affectivity are neglected. 3) How educational leadership becomes a matter of governing the future through simulation and imagination. 4) How affective leadership is energized by a bio......This article explores how educational leadership is increasingly becoming affective in order to cultivate what has been termed “the potentials” of pupils to meet the challenge of bringing schools into “the world class league”. The analysis draws upon the notion of governmentality and the ”affective...... turn”. It highlights four examples of affective educational leadership technologies as they appear in contemporary leadership handbooks in Denmark. 1) How school becomes the managed heart of society. This reshapes educational leadership as ontopower governing through ideas and materialities...

  5. Governing the potentials of life?

    DEFF Research Database (Denmark)

    Staunæs, Dorthe

    of perception and neurons. 2) How affectivity becomes synonymous with positive feelings, while more indeterminate parts of affectivity are neglected. 3) How educational leadership becomes a matter of governing the future through simulation and imagination. 4) How affective leadership is energized by a bio......This article explores how educational leadership is increasingly becoming affective in order to cultivate what has been termed “the potentials” of pupils to meet the challenge of bringing schools into “the world class league”. The analysis draws upon the notion of governmentality and the ”affective...... turn”. It highlights four examples of affective educational leadership technologies as they appear in contemporary leadership handbooks in Denmark. 1) How school becomes the managed heart of society. This reshapes educational leadership as ontopower governing through ideas and materialities...

  6. The Governance of Money Laundering

    DEFF Research Database (Denmark)

    Tsingou, Eleni

    2014-01-01

    What are the drivers behind the anti-money laundering (AML) governance framework? Who are the actors and institutions, and what is the policy content? This chapter provides an overview of the processes and mechanisms of AML policy-making. AML is often presented as a financial problem, and something......, moreover, that is key to debates about international political economy (IPE) since it goes to the heart of the integrity of the financial system and also, at least in principle, aims to impose controls on the movement of money. Yet, as a policy concern, thinking about money laundering was developed away...... from traditional settings for the regulation of global finance. Instead, AML policies were driven by and linked to the public policy objectives of law and order. As a result, the governance of money laundering encompasses a broad set of goals, techniques and professional knowledge. It brings together...

  7. Constructing a European Governance Space

    DEFF Research Database (Denmark)

    Pontoppidan, Caroline Aggestam; Alijarde, Isabel Brusca; Chow, Danny

    Financial crisis has emphasized the need for harmonized public sector accounts in Europe. After a public consultation on the suitability of the IPSAS for EU Member States, the European Commission considers that the proper way is the development of European Union Standards adapted to IPSAS (renaming....... On the basis of that discussion, Eurostat launched another public consultation named; ‘Towards implementing European Public Sector Accounting Standards for EU member states-Public consultation on future EPSAS governance principles and structures’. This paper seeks to provide an in-depth understanding...... of the negotiations and interactions that took place prior to, during and after the issuance of the public consultation on the ‘Suitability of IPSAS’. The focus of this paper is therefore on a systematic analysis of the construction of regional-transnational governance of public sector accounting, using the EPSAS...

  8. Good governance for pension schemes

    CERN Document Server

    Thornton, Paul

    2011-01-01

    Regulatory and market developments have transformed the way in which UK private sector pension schemes operate. This has increased demands on trustees and advisors and the trusteeship governance model must evolve in order to remain fit for purpose. This volume brings together leading practitioners to provide an overview of what today constitutes good governance for pension schemes, from both a legal and a practical perspective. It provides the reader with an appreciation of the distinctive characteristics of UK occupational pension schemes, how they sit within the capital markets and their social and fiduciary responsibilities. Providing a holistic analysis of pension risk, both from the trustee and the corporate perspective, the essays cover the crucial role of the employer covenant, financing and investment risk, developments in longevity risk hedging and insurance de-risking, and best practice scheme administration.

  9. Cultural management and government role

    Directory of Open Access Journals (Sweden)

    Edalat Nemati

    2012-08-01

    Full Text Available Culture plays an important role on human lives and it has been in four ancient civilizations of China, Iran, Egypt and Greece. The civilization achievements are normally categorized in two different groups of material and immaterial. Practical experience of the material, social objective is called as a civilization and the mental aspect of spiritual experiences, spiritual and personal is called culture. The purpose of this research is to find a framework for cross-cultural management. First, we define the cultural planning and we review the existing cultural examples in Iranian society and try to provide an overall analysis. The paper also investigates the role of government on creating adaptive culture within the society and explains that government must act as leadership in creating value added culture.

  10. VALUE CREATION THROUGH CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Elena Chitimus

    2013-12-01

    Full Text Available Companies spend time and money in order to improve their corporate governance (CG system and also do not forget to inform third parties about their efforts in this field. CG studies the separation of power at an entity level and the segregation of responsibilities between shareholders, management, and board of directors. As a mechanism CG helps to align management’s goals with those of the stakeholders in order to avoid conflict and to sustain and develop a healthy company. The objective of this article is to show how corporate governance is defined, what does it stands for and why it is important or maybe better said why companies give it so much importance.

  11. Community Governance and Vocational Education

    Science.gov (United States)

    Martasari, R.; Haryanti, R. H.; Susiloadi, P.

    2018-02-01

    Vocational education is required to create a design of education and training that is friendly and feasible for disabled people. The state has a responsibility for it, but with all the limitations, the state can not always be present. This article aims to analyze the capacity of community governance in passing vocational education for people with disabilities in Ponorogo, Indonesia. Articles are the results of research for approximately two years by using data collection techniques through interviews, documentation and observation. Source Triangulation with analysis technique using interactive model is used for data validation. The results show that there are two large capacities owned by Organisasi Sosial Rumah Kasih Sayang as community governance in conducting vocational education for the disabled person namely community credibility and community vigilance.

  12. The efficiency of government supervision

    International Nuclear Information System (INIS)

    Paetzold, H.

    1992-01-01

    In 1970, fires as events initiating plant failure were included in the accident analyses of nuclear power plant design concepts. In the meantime, they have been expressed in more precise terms and incorporated into the bodies of nuclear technical rules and regulations. Following a suggestion by the Baden-Wuerttemberg State Ministry for the Environment, the efficiency of government supervision has been examined for the example of fire protection measures or the site of Phillipsburg with one BWR and one PWR plant in operation. The result of the examination indicated that pragmatic approaches and the establishment of key areas of supervision could further enhance the efficiency of government supervision under Section 19 of the German Atomic Energy Act and achieve improvements in plant safety. (orig.) [de

  13. Visit of Spanish Government delegation

    CERN Multimedia

    CERN PhotoLab

    1982-01-01

    A Spanish Government delegation visited CERN before Spain rejoined CERN as a Member State(in 1983). Delegates interested in advanced technologies visited the ISR workshop clean room, where Romeo Perin explained fabrication and properties of stainless steel, titanium and inconel components of vacuum chambers for experiments at the ISR. Left to right: Technical Director Giorgio Brianti, the Spanish Minister of Industry and Energy Mr.Ignacio Bayon Marine , Romeo Perin, a delegate and Director-General Herwig Schopper. See also 8202369.

  14. Government spending: an economic boost?

    OpenAIRE

    Daniel J. Wilson

    2012-01-01

    The severe global economic downturn and the large stimulus programs that governments in many countries adopted in response have generated a resurgence in research on the effects of fiscal policy. One key lesson emerging from this research is that there is no single fiscal multiplier that sums up the economic impact of fiscal policy. Rather, the impact varies widely depending on the specific fiscal policies put into effect and the overall economic environment.

  15. Governing cryptocurrencies through forward guidance?

    OpenAIRE

    Goldmann, Matthias; Pustovit, Grygoriy

    2018-01-01

    While the debate about the needs and merits of cryptocurrency regulation is ongoing, the unprecedented price hikes of cryptocurrencies towards the end of 2017 triggered a somewhat unexpected sort of regulation in the form of public statements by governments and financial supervisors. It kicked in rather quickly and turned out to be much more effective than imagined. These interventions can be identified as one of the main factors that drove asset prices down, thereby preventing destabilizing ...

  16. Expert Systems in Government Administration

    OpenAIRE

    Weintraub, Joseph

    1989-01-01

    Artificial Intelligence is solving more and more real world problems, but penetration into the complexities of government administration has been minimal. The author suggests that combining expert system technology with conventional procedural computer systems can lead to substantial efficiencies. Business rules can be removed from business-oriented computer systems and stored in a separate but integrated knowledge base, where maintenance will be centralized. Fourteen specific practical appli...

  17. 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.

  18. Governance in the marine environment

    OpenAIRE

    Appleby, T.

    2015-01-01

    The governance of the UK Overseas Territories and Crown Dependencies is complex, endlessly fascinating and often politically charged. There is no area where this complexity is more demonstrable than in the marine environment, where the issues of extended maritime boundaries granted under the United Nations Convention on the Law of the Sea, fishing and prospecting rights, marine conservation and competing sovereignty mean that the practical application of the law in this area is particularly d...

  19. Ideological Hegemony and Global Governance

    OpenAIRE

    Thomas Ford Brown

    2015-01-01

    In this paper, I analyze libertarian discourse from the perspective of regulation theory, a~ a hegemonic ideology that underlies the emergence of a new mode of regulation. Within this general theoretical approach, I will also employ frames from regime theory as developed by international relations scholars, as well as the "epistemic community" approach from the same discipline. I want to suggest that free-market ideology could engender the emergence of rationalized global governance in order ...

  20. Bioethics as a Governance Practice.

    Science.gov (United States)

    Montgomery, Jonathan

    2016-03-01

    Bioethics can be considered as a topic, an academic discipline (or combination of disciplines), a field of study, an enterprise in persuasion. The historical specificity of the forms bioethics takes is significant, and raises questions about some of these approaches. Bioethics can also be considered as a governance practice, with distinctive institutions and structures. The forms this practice takes are also to a degree country specific, as the paper illustrates by drawing on the author's UK experience. However, the UNESCO Universal Declaration on Bioethics can provide a starting point for comparisons provided that this does not exclude sensitivity to the socio-political context. Bioethics governance practices are explained by various legitimating narratives. These include response to scandal, the need to restrain irresponsible science, the accommodation of pluralist views, and the resistance to the relativist idea that all opinions count equally in bioethics. Each approach raises interesting questions and shows that bioethics should be studied as a governance practice as a complement to other approaches.